Abstracts from the Twenty-First Annual Education Conference of the National Society of Genetic Counselors (Phoenix, Arizona, November 2002).

P1: GRA/GCY/GAY Journal of Genetic Counseling [jgc]

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C 2002) Journal of Genetic Counseling, Vol. 11, No. 6, December 2002 (°

Abstracts From the Twenty-First Annual Education Conference of the National Society of Genetic Counselors (Phoenix, Arizona, November 2002) Cheryl D. Dickerson1 and Catherine A. L. Wicklund2,3

Abstracts have been arranged by the Abstract Committee into the following categories: I. II. III. IV. V. VI. VII. VIII. IX.

Award Papers Adult Cancer Genetics Counseling and Psychosocial Issues Education Pediatrics Pre/Perinatal Genetics Professional Issues Theory-Based I. AWARD PAPERS The Beth Kaplan Student Abstract Award

Impact of Genetic Discrimination on BRCA Testing and Medical Management Decisions M. Merrill, R. Nagy, S. Zyzansky, B. Lamb, G. L. Wiesner, and A. Matthews Case Western Reserve University, Cleveland, Ohio Genetic testing for common adult-onset conditions has resulted in concerns regarding genetic discrimination among patients, health care professionals, 1 Carolinas

Medical Center, Women’s Institute, Charlotte, North Carolina. of Obstetrics, Gynecology & Reproductive Sciences, Houston, Texas. 3 Correspondence should be directed to Catherine A. L. Wicklund, Department of Obstetrics, Gynecology & Reproductive Sciences, University of Texas Medical School at Houston, 6431 Fannin, Suite 3.264, Houston, Texas 77030; e-mail: [email protected]. 2 Department

445 C 2002 National Society of Genetic Counselors, Inc. 1059-7700/02/1200-0445/1 °


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and the media. Despite the potential for misuse of genetic information, there is virtually no evidence of widespread discrimination occurring to date. Concern for insurance discrimination has been cited in several recent reports as a barrier for genetic testing. As a result, this study examined the impact of worry about genetic discrimination on BRCA1/2 testing uptake and medical management decisions among 137 women at risk for hereditary cancer susceptibility using a mailed questionnaire. Responses to seven questions on the survey were used to develop a discrimination scale to quantify each respondent’s overall level of concern regarding genetic discrimination. This scale has both high internal consistency (Cronbach’s alpha = 0.9381) and external validity. Participants with high discrimination scale scores, and thus high concerns about genetic discrimination were more likely to decline BRCA testing ( p = 0.03). Because concern about discrimination was associated with BRCA testing decisions, factors influencing the uptake of testing were examined. Those undergoing BRCA testing were more likely to be Ashkenazi Jewish ( p = 0.006), have a personal history of cancer ( p = 0.001), and have an insurance policy that was not individually rated ( p = 0.013). Despite the fact that concern for genetic discrimination predicted BRCA testing decisions, this study was unable to document any instances of genetic discrimination. A small percentage of respondents reported difficulties with insurance providers unrelated to genetic test results. Furthermore, high concern for genetic discrimination did not predict use of cancer screening, prophylactic surgery, or chemoprevention to lower cancer risk. Finally, the study was unable to document evidence of adverse selection. This study confirms that patient perception is discrepant with actual occurrence of genetic discrimination. Although it appears that patient perception of genetic discrimination is influencing decision making for BRCA testing, it is encouraging that this concern did not prevent high-risk individuals from seeking out options for cancer risk reduction or screening. Best Submission by a Full Member of the National Society of Genetic Counselors Impact of Genetic Risk Assessment for Alzheimer Disease T. Brown, S. Roberts, S. LaRusse, M. Barber, N. Relkin, P. Whitehouse, S. Post, A. D. Sadovnick, K. Quaid, L. Ravdin, and R. Green Boston University Alzheimer’s Disease Center, Boston, Massachusetts The REVEAL Study (Risk Evaluation and Education for Alzheimer’s disease) is the first randomized trial to examine the impact of providing risk assessment, including Apolipoprotein E (APOE) genotyping, for Alzheimer’s disease (AD). REVEAL investigators are using the well-established genetic epidemiology of the disease, including risk attributable to different APOE polymorphisms, to develop risk profiles. Asymptomatic adult children of AD patients are randomized into one arm where risk assessment is based upon age, gender and APOE genotype, or a control arm in which risk assessment is based only upon age and gender.


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Trained genetic counselors communicate these risks (with APOE disclosure) and follow subjects carefully to determine the psychological and practical impact of this information. Outcome variables include measures of anxiety, depression and satisfaction with the risk assessment and counseling protocol, as well as realworld decisions to change retirement planning or insurance coverage. To date, 136 participants (mean age = 52 years (SD = 9); 73% female; 94% White) have completed a 6-week follow-up during which they provided self-report data regarding the impact of the risk assessment they received. Fifty-nine percent said that risk information had a positive overall impact (vs. 15% negative). Participants who learned that they were negative for the APOE e4 allele (n = 50) were more likely to report a positive impact than those who learned that they were e4 positive (n = 46) or controls (n = 40) (84% vs. 45% vs. 43%, p < 0.001). Overall, 38% of participants reported that their anxiety level regarding developing AD had decreased since receiving risk assessment and genetic counseling. No significant group differences were observed in test-related distress as measured by the Impact of Event Scale (IES) or in depression and anxiety levels as measured by the Center for Epidemiological Studies Depression Scale (CES-D) and Beck Anxiety Inventory (BAI), respectively. Moreover, the vast majority of participants scored well below the cut-offs for clinical significance for these validated scales. Eighty-two percent of all participants would recommend risk assessment to family or friends and 95% would choose risk assessment if they had it to do over again (including 96% of those who were disclosed e4+ results). Our preliminary findings suggest that most participants are satisfied with and unharmed by the experience of genetic risk assessment for AD. II. ADULT Reactions Toward Potential Genetic Testing for Bipolar Disorder K. Akin, K. Ormond, and J. Schiffman Northwestern University, Chicago, Illinois Recent attention in genetics has focused on identifying genetic risk factors for common psychiatric conditions, including bipolar disorder (BPD), which affects approximately 1% of the population. The purpose of this study was to assess reactions of unaffected first-degree relatives towards genetic susceptibility testing. Specific issues addressed in this study include (1) experience with BPD in the family, (2) knowledge and attitudes toward BPD, (3) perceived personal risk for BPD, (4) attitudes toward BPD genetic susceptibility testing, and (5) potential risks and benefits of testing. Fifty unaffected adults with a first-degree relative with BPD completed a 36-item multiple-choice questionnaire. Most respondents (57%) had a child with BPD, and generally respondents reported that their relative had a severe form of BPD (72%). Most respondents indicated that they felt BPD, both in their relative and in the general population, was at least in part due to “inherited factors” (91% and 93%, respectively), with stress and other environmental factors being perceived as less of a causal factor. Most respondents believed that the potential


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benefits of genetic testing for BPD outweighed the risks (89.3%), and interest in susceptibility testing was high, with 74.5% of subjects indicating that they would definitely or probably be interested in genetic testing. Individuals who were interested in genetic testing all felt the benefits of testing outweighed the risks, were more likely to be over age 40 ( p = 0.056), and reported that BPD was a severe but treatable condition, at least in part due to inherited factors, and that they felt their personal risks were higher than average. The most commonly cited benefits of testing was to allow for earlier recognition and treatment of BPD (78.7%), to make lifestyle changes (48.9%) and to better understand one’s chances for developing BPD (44.7%). The most commonly stated risks were the fear of others attributing slight changes in mood to the disease after testing (40.4%), personal worry about slight mood changes (38.3%), and concerns regarding insurance discrimination (34%). Finally, 69.6% of respondents felt the optimal time for BPD susceptibility testing was “childhood,” in order to allow earlier treatment and intervention. The high demand expressed for genetic susceptibility testing in our population suggests that individuals will make use of genetic tests for BPD if they become available in the future. Identifying and characterizing populations who could benefit from genetic counseling allows for adequate anticipatory guidance for different patient populations.

Living With Marfan Syndrome: Insurance and Employment Discrimination K. Apse, B. Biesecker, and K. Peters NHGRI/NIH, Bethesda, Maryland Little data on insurance or employment discrimination has been systematically collected from individuals affected with genetic conditions. We offer data from a cross-sectional survey of 174 adults with Marfan syndrome regarding their experiences with employment and insurance discrimination. The majority of respondents had health insurance coverage, 92%, while fewer had life insurance and disability insurance, 66% and 35%, respectively. Notably, a substantial portion of the respondents reported being denied insurance coverage. Eighteen percent of respondents were denied medical insurance, and 26% were denied life or disability insurance. In addition, 20% of respondents indicated that they had experienced employment discrimination due to their diagnosis of Marfan syndrome. Respondents also indicated that being affected with Marfan syndrome directly affected their employment decisions. Forty-seven percent of the cohort reported that having a diagnosis of Marfan syndrome affected their choice of occupation or employer. Due their diagnosis and need for benefits, 24% of respondents remained in a job despite feeling dissatisfied. These data suggest that concerns about discrimination can be validated by those affected with genetic conditions. Genetic counselors should address concerns of clients related to access to insurance and their employment. Letters from genetics providers outlining medical risk status for employers may expand employment opportunities and ultimately job satisfaction for individuals with Marfan syndrome and other genetic conditions.


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Turner Syndrome: Adaptation Across the Lifespan B. Biesecker and A. McInerney-Leo NHGRI/NIH, Bethesda, Maryland Turner syndrome affects girls and women medically, psychologically, and socially across the lifespan. Prior research has focused on the psychological impact of living with short stature and infertility. Yet, few studies have captured the narratives of affected individuals about what has been most useful in helping them to adapt to their condition. We undertook a qualitative interview study of 64 individuals, 54 affected girls and women (ranging in age from 10 to 59 years with an average age of 30 years) and 10 parents of affected girls. The age at diagnosis ranged from the neonatal period to age 35 years. The focus of the study was on family relationships and communication, acceptance and nurturing, and social interactions and stigma. Girls and women were asked what health care providers can do to enhance acceptance and adaptation to their condition. Participants in the study described multiple ways that their families dealt with the diagnosis ranging from secret-keeping to parents disclosing all information to affected daughters. Participants often described experiencing teasing and social isolation as children. Some families provided strategies to resist the hurt that can stem from such treatment. Many of the participants found validation and support through meeting other girls or women with Turner syndrome. Many participants have also successfully identified health care providers who they perceive to be open and receptive to their emotional lives as well as their medical needs. Suggestions given by participants to hypothetical parents of a newborn with Turner syndrome were to treat their daughter “normally” minimizing the condition and focusing on what was unique and interesting about her as a girl. Participants suggested providing sufficient accommodation and medical care to promote independence. Most of the women and girls with Turner syndrome asked not to be stereotyped but rather seen as individuals, while others identified strongly with the label of Turner syndrome and found solidarity and understanding from being viewed as affected with the condition. We present our interpretation of the different roles the diagnosis of Turner syndrome plays in the adaptation of these girls and women. Report of the Fabry International Research Exchange (FIRE) Registry C. Feist Oregon Health and Science University, Portland, Oregon The FIRE Registry collates data on the natural history of the Fabry disease and clinical outcomes in patients receiving enzyme replacement or other therapy. As of June 1, 2002, 68 patients (39 male hemizygotes and 29 female heterozygotes) have been enrolled at 17 centers across the United States and overseas. The mean age of males was 32.0 ± 13.5 years, and of females 39.1 ± 16.9 years. Most (85%) were nonhispanic Caucasians. One male had received enzyme replacement therapy. The majority (54%) of males were diagnosed by gene mutation only, while the majority of the females (59%) were diagnosed by having an affected


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male first-degree relative with the diagnosis confirmed by genotyping. The mean age of onset of Fabry symptoms was 9.2 ± 6.5 years in males and 16.0 ± 16.0 years in females. The mean age of Fabry diagnosis was 18.3 ± 11.9 years in males and 27.0 ± 17.0 years in females. The prevalence in males (m) and females (f ) of the following signs and symptoms were: tinnitus (m-33%, f-30%); vertigo (m-22%, f-22%); hearing loss (m-28%, f-22%); angiokeratoma (m-72%, f-37%); corneal pathology (m-61%, f-41%); and pain (m-67%, f-52%). The prevalence (%) of organ involvement were: stroke (m-11%, f-4%); proteinuria (m-28%, f-41%); renal insufficiency (m-22%, f-7%); hypertension (m-17%, f-11%); and cardiomyopathy (m-6%, f-11%). Analysis of the occurrence of symptoms by age and gender revealed that the earliest symptoms in males 25 years, while renal insufficiency and cardiomyopathy were not reported until >35 years in males and >44 years in females. Thus, males appear to present and be diagnosed almost 10 years sooner than females. Signs of organ involvement, for example, proteinuria, renal insufficiency, and cardiomyopathy, present approximately 10 years sooner, as well. In contrast to the previous characterization of Fabry as an X-linked recessive condition, most, if not all women with a Fabry gene mutation exhibit some signs or symptoms of disease. Continued patient and long-term follow-up will allow more definitive conclusions regarding the natural history of Fabry disease and ultimately possible gender differences in long-term clinical outcomes with enzyme replacement therapy. Applying the Genetic Family History in an Internal Medicine Clinic T. Frezzo, W. Rubinstein, D. Dunham, and K. Ormond Northwestern University, Chicago, Illinois Background: A thorough analysis of the family medical history is typically reserved for patients referred to genetics professionals. Studies have shown that family history analysis often reveals genetic risk factors that are overlooked by other health care providers. There are no previously reported studies comparing family history analysis by genetics professionals to that of an internist. Goals: (1) Determine the proportion of unselected individuals in an internal medicine practice that are at increased risk for common diseases with known genetic components through analysis of their genetic family history. (2) Compare the documentation of family history information and quality of risk assessment between a questionnaire, a pedigree interview and review of medical records. Methods: In 2002, 78 patients seen in the Northwestern Medical Faculty Foundation, Division of Internal Medicine, were randomized into two groups. Group A (n = 39) completed a questionnaire regarding their personal medical and family history. Group B (n = 39) met with a genetic counselor for a 3-generation pedigree interview. Potential risk factors were revealed using a scoring-template, designed from relevant literature and applicable policy statements. For each subject, a review of physician’s chart notes from previous visits was used as an internal


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control for documentation of family history, and relative risk assessment. Areas assessed were mendelian conditions; coronary artery disease (CAD); diabetes; breast/ovarian, colon, and prostate cancer; thrombosis; ethnicity-based disease risks and reproductive risks. Results: Participants were of a range of backgrounds, mostly Caucasian (52.6%), and ranged in age from 21 to 76 years. Sixty-two of the 78 participants (79.5%) scored at increased risk for at least one of the categories assessed: 29 (37.2%) in one disease category; 18 (23.1%) in two disease categories; 10 (12.8%) in three disease categories; four (5.1%) in four disease categories; and one individual (1.3%) was at increased risk for five disease categories. The most frequently reported disease was CAD. The number of participants found at increased risk for an adult-onset disease when using a study tool (47/78, 60.3%) was significantly higher than those categorized as such through chart review (31/78, 39.7%) ( p = 0.01). Conclusions: This investigation indicates a higher prevalence of patients in an unselected internal medicine practice who are at an increased risk for diseases with known genetic components than appreciated by standard medical documentation. Targeted family history analysis reveals patients with indications for increased screening or surveillance, further genetic counseling and/or genetic testing. Awareness of an increased risk for disease provides the opportunity to counsel a patient about preventive measures.

Genetics and Alcoholism Among At Risk Relatives: Interest and Concerns About Hypothetical Genetic Testing for Alcoholism Risk J. Gamm, B. Nussbaum, and B. Biesecker Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio The purpose of this study was to examine interest in predispositional genetic testing for alcoholism among at risk relatives. The possibility of genetic testing in the future elicited comments from participants regarding both hope of benefits and fear about misuses. Qualitative interviews were conducted with 27 individuals who had at least one first-degree relative affected by alcoholism. Data analysis revealed that participants’ interest in genetic testing for susceptibility to alcoholism was moderate. Belief in a genetic etiology for disease has been implicated in lowering individuals’ perceived personal control over health-related behaviors. The concern is that belief in a genetic etiology may lead to a more fatalistic outlook and therefore behavioral choices that are motivated by a sense of genetic determinism. Findings from this study do not support the concern that fatalism is at work in this population. Participants’ concerns about future use of genetic testing ranged from apprehension about side effects to fear of being labeled an alcoholic. Perceived benefits of testing were an increase in education regarding alcoholism as well as a more clear idea of one’s own personal risk. The beliefs that participants held concerning the cause of alcoholism, their interest in testing, and concerns about the hypothetical use of this emerging technology are all important issues for patients behaviorally and psychosocially. Before advent of new genetic tests for alcoholism and other complex conditions we must address the utility, the concerns, and the perceived benefit from the perspective of those patients to whom we would offer testing.


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Genetic Test Results Alter Perception of Risk of Alzheimer’s Disease: Preliminary Results of the REVEAL Study S. LaRusse, H. Katzen, S. Roberts, M. Barber, T. Brown, P. Whitehouse, R. Green, L. Ravdin, A. Cupples, and N. Relkin Weill Medical College of Cornell University, New York, New York Individuals seeking information about their likelihood of developing lateonset Alzheimer’s disease (AD) are typically offered population-based risk estimates. Little is known about the impact of incorporating genetic test results into a risk assessment for a complex disorder such as AD. We sought to determine whether the inclusion of genetic test results affected an individual’s perception of their level of risk. The apolipoprotein E (APOE) e4 allele is currently the only confirmed susceptibility gene for late-onset AD. The REVEAL Study (Risk Evaluation and Education for Alzheimer’s Disease) is an ELSI-funded multicenter study designed to evaluate the impact of providing APOE genotyping and counseling as part of a risk assessment for adult offspring of individuals diagnosed with AD. REVEAL study participants randomized into the Intervention Group learned their APOE genotype and were given a lifetime risk estimate based on genetic test results, family history, and gender. The participants randomized into the Control Group received a risk estimate based only on family history and gender. Six weeks after disclosure, participants completed a series of questionnaires measuring the impact of the risk information. We compared responses of women in the Intervention Group with an e3/e3 genotype (n = 26) to women in the Control Group (n = 29). Both groups received identical numeric estimates of lifetime risk of AD (29%). Chi-square analyses revealed significant group differences in perception of risk, anxiety, and impact of the information ( p < 0.011, p < 0.002, p < 0.007, respectively). Despite the numeric equivalence of the risk estimates they received, women who received genotype information judged their risk to be lower on a Likert scale than those in the Control Group. Women in the Intervention Group also reported a greater reduction in anxiety and indicated that the risk information had a more positive impact. In addition, women who received genotype results reported a greater reduction in uncertainty about their chance of developing AD ( p < 0.003). These results suggest that risk estimates that include genotype results may have a more positive impact on perception of disease susceptibility than estimates based on family history alone. Our study also suggests that individuals view genetic information as more relevant than a numeric risk estimate. Genetic Counseling of Dilated Cardiomyopathy Due to Lamin A/C Gene Mutations M. Taylor, L. Ku, J. Feiger, P. Fain, A. Robertson, E. Carniel, and L. Mestroni Adult Medical Genetics Program, University of Colorado Health Sciences Center, Denver, Colorado Background: Dilated cardiomyopathy (DCM) is a progressive disease of heart muscle that can result in frequent hospitalizations and need for heart


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transplantation, both in children and adults. Early diagnosis and treatment may reduce morbidity and mortality. Familial dilated cardiomyopathy (FDC) is estimated to account for as many as 50% of cases that were initially considered to be “idiopathic.” Extensive genetic and phenotypic heterogeneity exists as there are 10 cytoskeletal/sarcomeric protein-encoding genes and a number of chromosomal loci that have been implicated in FDC. This heterogeneity greatly complicates efforts to provide genetic diagnosis and genetic counseling, as neither the frequency of mutations nor the genotype–phenotype correlations for any given FDC gene is well understood. In addition, while it is anticipated that mutations in some FDC genes might be more or less severe in terms of the natural history of FDC, limited data exists to support this idea. Mutations in the lamin A /C (LMNA) gene have been documented in FDC patients, but the clinical spectrum, prognosis and clinical relevance of LMNA mutations are unknown. Methods: We comprehensively characterized a cohort of 40 consecutive families with familial DCM and nine with sporadic DCM (269 subjects, 105 affected) for genetic mutations in LMNA using denaturing high performance liquid chromatography (DHPLC) and sequence analysis. Results: Heterozygous deleterious LMNA mutations were detected in four families (8%), three with familial and one with sporadic DCM. There was significant phenotypic variability, but the presence of skeletal muscle involvement, supraventricular arrhythmia, conduction defects, and “mildly” dilated cardiomyopathy were predictors of LMNA mutations. LMNA mutation carriers had a significantly poorer cumulative ( p = 0.0034) and event-free ( p = 0.0004) survival compared to noncarrier DCM patients. Conclusions: LMNA mutations are found in a clinically relevant proportion (8%) of patients with DCM. This data has implications for genetic counseling of DCM families, both in testing strategy and anticipatory guidance should a mutation be revealed. In addition, this study indicates that mutation screening can be considered in patients with idiopathic DCM, regardless of family history. III. CANCER GENETICS A Family History Study of Fallopian Tube Carcinoma J. Arseneau, K. Buzaglo, A.-J. Paradis, W. Foulkes, and N. Wong McGill University, Montréal, Québec, Canada Carcinoma of the fallopian tube is the rarest gynecologic cancer, accounting for less than 1% of all cancers of the female genital tract. The international annual incidence of fallopian tube cancer is 3.6 cases per million women. In a recent study in an unselected population of women with fallopian tube cancer, 16% of women carried a germ-line mutation in the two major breast/ovarian cancer susceptibility genes, BRCA1 or BRCA2. The greater hereditary fraction in fallopian tube carcinoma compared to both breast and ovarian cancer supports its inclusion into the disease spectrum of the hereditary breast and ovarian cancer syndrome. The purpose of this study was to evaluate the family histories of women diagnosed with fallopian tube cancer from 2 McGill University teaching hospitals. Pathologically confirmed primary cancers of the fallopian tube (Diagnostic Code


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1832) diagnosed between 1980 and 2001 were identified through hospital tumor board registries. After informed consent, a family history was taken for all cases. A phone questionnaire regarding medical history was administered only to living patients. The family history was evaluated and a relative risk of cancer to firstdegree relatives was determined based on population cancer rates. Subsequent to the study, genetic counseling was offered to all patients on a clinical basis. Ten living and two deceased patients were included in this study from a total of 35 cases identified. Among a total of 96 first-degree relatives, there were 18 cases of cancers. Eight of the 12 women had a history of cancer in their first-degree relatives. Four women reported a first-degree relative with either breast or ovarian cancer. Four of the women had multiple primaries, including two women with a personal history of breast cancer. A statistically significant increase was observed in the risk of female-specific cancer to first-degree female relatives under the age of 60 (relative risk RR = 4.14; 95% confidence interval (CI) = 1.34–9.67). This study supports an important hereditary contribution in fallopian tube carcinoma and identifies another group of patients that may benefit from genetic counseling. As more evidence supports the inclusion of fallopian tube cancer into the disease spectrum of the hereditary breast and ovarian cancer syndrome, current mutation risk models will have to be modified to include this cancer in the calculation of the probability of mutation.

Outcomes of an Intensive Course in Cancer Risk Assessment for Genetic Counselors and Nurses K. Blazer, J. Weitzel, R. Nedelcu, S. Sand, A. Wright, and D. MacDonald City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, California Hereditary Cancer Risk Assessment is an emerging discipline that requires knowledge in genetics and oncology and specialized patient and family counseling skills. There are too few clinicians cross-trained in these specialties. Funded by the California DHS Cancer Research Program, the City of Hope (COH) Center for Cancer Genetics Technology Transfer Research designed and has to date conducted two annual intensive cancer genetics training courses for masters-educated genetic counselors and advanced practice nurses. The goal is to increase access to competent cancer risk assessment services in outlying communities with defined need, while expanding the sphere of COH Cancer Genetics Education Program outreach and Cancer Screening & Prevention Program research. A total of 26 participants (16 GCs, 10 RNs) were competitively selected on the basis of academic merit, demonstrated need in their community and institutional support. The CME/CEU-accredited course (60.25/50 h, respectively) provided didactic and case-based learning modules, workshops, surrogate patient interactions, and wet lab sessions in a format designed to enhance interdisciplinary interactions. All participants have continued access to the COH Cancer Genetics Link web-board, an interactive internet discussion board for continued practice-based learning.


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Knowledge questionnaires administered prior to and immediately after the course reflected an overall increase by 18% ( p < 0.0001) in knowledge of clinical cancer genetics over both sessions. Additional measures included assessment of the effectiveness of teaching methods, participant satisfaction and impact of knowledge gain on practice patterns through the 1-year time point. Overall, the course was well received and resulted in additional clinicians with screening-level competence in cancer risk counseling and access to an interactive informatics-based continuing education link.

The Effects on Patients after Receiving a Result of a Variant of Uncertain Clinical Significance for BRCA1 and BRCA2 Testing C. Chimera, K. Brooks, C. Singletary, and S. Young University of South Carolina, Columbia, South Carolina In approximately 12–14% of patients undergoing BRCA mutation analysis, a variant of uncertain clinical significance is detected for which the effect on protein functioning is unknown. Thus, these results are not conclusive for determining hereditary breast and ovarian cancer risks. Consequently, variants of uncertain clinical significance may pose a dilemma for those patients searching for definitive information. To date, the impact on those receiving an uninformative result due to a variant of uncertain clinical significance has not been assessed separately from those receiving results that are positive or negative for a mutation. In this study, 17 of 22 patients who had received results of a variant of uncertain clinical significance between 1997 and 2001 were interviewed from three different clinics that offer cancer genetic counseling and risk assessment (one patient declined to participate and four could not be located/contacted). The purpose of this study was to identify the effects of a variant on these patients and to provide a framework for genetic counselors to appropriately counsel and follow-up the needs of patients with a variant of uncertain clinical significance. Structured interviews, which included both closed and open-ended questions, were conducted by telephone between September 2001 and January 2002. Interviews were transcribed and analyzed by the development of themes and frequency analysis. The results of this study show that, although variants of uncertain clinical significance create a sense of uncertainty (12/14), approximately half of the patients felt relieved or pleased (9/16) and felt closure (7/14) after completing testing and all were satisfied with the genetic counseling process. However, some patients felt disappointed (7/16), upset and angry (1/16), and continued to feel their risk for cancer was moderate to high (10/17). Therefore, intrinsic emotional values may influence the patient but be unrelated to the content of genetic counseling. Based on these results, pretest genetic counseling should include a discussion of the potential uncertainty that can result from a variant of uncertain clinical significance. Additionally, exploring the emotional impact that a variant of uncertain clinical significance may have on a patient during pre- and posttest counseling will aid genetic counselors in identifying those patients who may need additional follow-up.


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Communication About Colorectal Cancer in Cases and First-Degree Relatives A. Fishbach, D. Bowen, D. Valley, J. Potter, and P. Newcomb Fred Hutchinson Cancer Research Center, Seattle, Washington Little is known about how family members communicate about cancer: who family members talk to about cancer and how much they talk to them. Knowing this information can allow genetic counselors to acquire the most accurate information about family history and assist in helping individuals understand and cope with their risks for cancer. We collected data from 50 pairs of family members, each consisting of a case (defined as a participant who has been diagnosed with colorectal cancer) and a first-degree relative (FDR). Cases were randomly selected from active participants in our Familial Colorectal Cancer (CORE) Registry, a population-based familial registry of colorectal cancer (CRC) patients and their family members. Cases were those who returned the baseline survey instrument or completed a telephone survey of the same instrument. FDRs of participating cases were randomly selected to receive a baseline survey instrument. If an FDR refused to participate, then the next randomly selected FDR of that case would be approached. All participants were asked how much they talked about CRC risk with a specific list of relatives. All participants were asked whether there was a family member who took the lead on dealing with health issues. If they answered yes, participants were asked to choose the individual who is the “Family Health Informant” (“someone who would feel comfortable communicating with other family members about health issues and would know about health issues in your family”). We found that reports of communication with family members about CRC were low: communication frequency with specific relatives ranged from 3 to 50%, depending on relative type. Mothers (46%) were the most frequent relatives to receive communications, followed by siblings (37%). Case and FDR communication frequency differed, with FDRs reporting more frequent communication with relatives. Most participants (80% of cases and 87% of FDRs) named someone in the family as the family health informant. The spouse was the most frequently named informant (25%), followed by daughters (16%). Finally, only 6% of FDRs reported knowing “a lot” about CRC risk, and this was related positively and significantly to perceived cancer risk. Future analyses will relate perceptions of cancer risk and screening intentions for CRC to communication frequency. These data indicate that individuals do not necessarily communicate well with other family members about CRC risk and certain individuals do take responsibility for cancer communication. These data have important implications for counseling and for other intervention settings. Unique Educational Approaches: Hereditary Breast Cancer for Patients and Clinicians K. Huelsman, J. Gamm, D. Rothchild, A. Hafertepen, and J. Everett Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio The demand for updated information regarding hereditary breast cancer is increasing among patients and referring clinicians. Patients who have undergone


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genetic counseling are typically managed by clinicians in other specialties. Both the patient and the clinician need to have access to updated information. This includes new screening practices, testing advances, ongoing supportive resources, and risk reduction strategies. Genetic counselors have a unique opportunity to play a role in management education. To accomplish this goal with limited resources, we set out to develop new approaches. We were fortunate to receive grant funding to support these activities. All patients previously evaluated received an 8-page newsletter designed to highlight recent clinical developments. Patients identified as BRCA1/2 mutation carriers received additional personalized follow-up through contact with a designated Clinical Navigator. The navigator is a breast cancer survivor and mutation carrier with medical genetics training. For clinicians, we developed a management-specific conference to compliment the traditional hereditary breast cancer lectures, and targeted the specialists likely to be involved in management of high-risk women. We utilized the Audience Response System (ARS) so speakers could tailor their lecture to the participants’ preconference knowledge levels. A total of 912 newsletters were distributed, 532 directly to our past patients and the remainder to clinic sites. A feedback postcard solicited patient suggestions for future newsletter topics. A second edition is in progress and samples will be available. The clinical navigator has been assisting patients through the maze of mutation carrier options for 12 months. Patient response is enthusiastic, citing this personalized approach as preferable to a traditional support group. An unanticipated outcome is that many patients have offered to support others in a similar role. Using the ARS, we evaluated audience demographics and general knowledge then analyzed answers. The audience demonstrated a basic understanding of hereditary breast cancer concepts. Using the ARS allowed speakers to focus on complex cases, research screening protocols, and hormone management. Clearly, follow-up education is needed for previous patients and managing clinicians. Patients preferred the convenience of the mailed newsletter to read at their leisure and share with family members. BRCA1/2 carriers have expressed that working with the Clinical Navigator has empowered them to explore all management options and expedited the clinical decision-making process. The ARS promoted active learning among conference participants. These unique educational approaches allow us to maximize our ability to reach significant numbers of patients and clinicians without exhausting limited resources. A Survey of Genetic Counseling and Testing of Early Onset Breast Cancer Survivors R. Hutchison, R. Zinberg, M. McGovern, and K. Brown Mount Sinai School of Medicine, New York, New York Purpose: It is recommended that genetic counseling for BRCA1 and BRCA2 genetic testing be offered to women with a family or personal history suggestive of an inherited breast–ovarian cancer syndrome. This includes women diagnosed before the age of 45, who account for approximately 7% of women with breast cancer in the United States. Genetic testing can provide important information regarding future cancer risks and risk management. The aims of this study were to


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survey the experience of early onset breast cancer survivors to determine their experience with testing and counseling for BRCA1 and BRCA2. Subjects and Methods: The study was a web-based survey administered to 1200 female members of the Young Survival Coalition (YSC) who had been diagnosed with breast cancer at or before the age of 45 and who reside in the United States. The survey included 158 questions divided into the following sections: demographics, quality of life, pregnancy history, family history of cancer, medical history, treatment history, genetic testing, and medical and social support. The study was approved by the Mount Sinai Institutional Review Board (IRB) and was anonymous. Results: Five hundred twenty-nine women responded to the survey for a response rate of 45.8%. Two hundred ninety-eight (56.3%) women were neither referred to see a genetic counselor nor had they discussed genetic testing with their physician. Eighty-six (16.3%) had undergone testing, 19 (22.1%) of whom had tested positive for a BRCA1 or BRCA2 mutation. Fourteen (83%) of the women who tested positive subsequently underwent prophylactic surgery. Women who had been counseled about their genetic risk reported being more satisfied with the process when they were counseled by a genetics provider versus a physician without a specialty in genetics. The cost of the test, having no family history, and not being offered the test were demonstrated as barriers to pursuing testing. Conclusion: A significant number of women are not being appropriately referred to genetic counseling and testing after a diagnosis of early onset breast cancer. However, our study has shown that there is high interest in prophylactic surgery following confirmation of a BRCA1/2 mutation in those individuals that do pursue testing. Since young women may benefit the most from genetic testing, further studies should be conducted to better define these barriers to referral and testing in order to develop strategies to permit increased access to these services.

Pseudonyms in Cancer Risk Assessment Programs—Are They Used? Are They Considered Necessary? Results From Our Survey of Colleagues E. Knell Inherited Cancer Risk Assessment Program, Pasadena, California. Pseudonyms are requested, and sometimes utilized, by an unknown number of clients seeking cancer risk assessment counseling and genetic testing, but there has not been a survey of the frequency of their use. No consensus has been reached on the advisability, or necessity, of this protection, and there is no practice guideline. This raises several questions. What risks do counselors and clients perceive that lead to the desire to use pseudonyms? What are current program practices regarding pseudonyms? Do the risk perceptions align with the program practices? Is there consensus amongst us? To answer these and other questions, a survey of colleagues was conducted to identify and to evaluate cancer risk assessment practices and beliefs regarding the use, acceptance and advisability of pseudonyms for cancer risk assessment counseling and genetic testing. Our NSGC Cancer SIG colleagues received surveys either on-line or at the 2001 AEC meeting and again approximately 6 months later, to assess their policy regarding aliases, and to assess changing practices and beliefs. The questionnaire consisted of 16 questions


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designed to elicit answers to the above questions regarding the use of pseudonyms. Twelve responses were recorded initially, and 24 additional responses have been received to date. All counselors reported fear of discrimination amongst their clientele, and most counselors (77%) felt the fear may be justified, at least some of the time. Despite the perceived fear among clients, most counselors whose programs allow pseudonyms report little usage, most under 5%. Approximately one third of programs allow pseudonyms for counseling, and close to 80% allow either pseudonyms or coded names for genetic testing. Many programs utilize shadow charts and similar mechanisms to protect patients’ identities. Some programs required actual names on all forms, and results are placed in the medical chart. From these results we conclude that at least some programs and individual policies do not reflect the perceptions of risk in clients, as several do not allow pseudonyms or offer other protection via coding or shadow charts. We also find that there is not uniform policy amongst the cancer risk counselors with policy ranging from total acceptance of pseudonyms, even on consent forms, to no allowance for the use of an alias and no protection via shadow chart or similar mechanism.

The Effect of Clinical Practice Location on Physician Referral Practices for Hereditary Breast Cancer C. Krekel, J. Everett, L. Hoechstetter, R. Ricer, R. Wenstrup, and K. Huelsman University of Cincinnati, Cincinnati, Ohio The level of urbanization in an area has been recognized to affect patient access to health services. A study of patient demographics at a hereditary cancer clinic demonstrated that women who reside in rural areas are less likely to be evaluated by genetic services for hereditary breast cancer than urban residents. Genetic counseling for hereditary breast cancer has been shown to be beneficial for patients in regards to decision-making about prophylactic surgery, compliance with cancer screening recommendations, increased knowledge, and accurate risk perception. The purpose of this study was to compare differences in physician referral practices for hereditary breast cancer between clinical practice locations: urban, suburban, and rural. We developed a questionnaire to query physician referral practices, specifically if physicians had ever referred for this indication, frequency of referral, reason for referral or nonreferral, and specialist source of referral. Questionnaires were mailed to 928 physicians in Ohio’s Tristate Region, and the response rate was 25% (n = 214). Physician medical specialties included family practice, general practice, internal medicine, general surgery, obstetrics/gynecology, and oncology. Physicians were grouped retrospectively into clinical practice location groups based on self-reported descriptor of practice location: urban (17%), suburban (39%), and rural (32%). Rural-practice physicians were less likely to have ever referred for hereditary breast cancer than suburban-practice physicians. Ruralpractice physicians were more likely to refer to an oncologist for this indication, whereas urban-practice physicians were more likely to refer to a genetic counselor. Of physicians who reported never referring, 39% reported that barriers exceed motivations and 12% reported not knowing to whom to refer patients in need of genetic services, irrespective of practice location. This study demonstrates that


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women residing in rural areas are less likely to be referred to specialists for genetic services regarding hereditary breast cancer than their suburban counterparts. The decrease in referrals from rural-practice physicians was not shown to be a result of increased overall barriers to referral or decreased awareness of referral source among this clinical practice location group. Further studies are needed to investigate factors that may influence physician referral for hereditary breast cancer, including specialty, knowledge, and attitudes, and to demonstrate the association between genetics services and improved health outcome for women at risk for hereditary breast cancer. A Personalized Risk Assessment & Counseling Model for Menopausal Therapy: The Next Frontier for Genetic Counselors E. Matloff, K. Shannon, A. Moyer, and N. Col Yale Cancer Center Women often overestimate their own risks of developing breast cancer, while underestimating their risks for coronary heart disease (CHD) and osteoporosis. Women with a family history of breast cancer are even more likely to overestimate their risk of developing breast cancer. When these women reach menopause, they are faced with the choices of taking hormone replacement therapy (HRT), a selective estrogen receptor modulator (SERM) (e.g., tamoxifen or raloxifene), no intervention, or agents that treat individual symptoms. This decision is complex, often anxiety provoking, and will likely change their future disease risks. Women currently receive little, if any, assistance in choosing the therapy most suited to their personal risks and preferences. Genetic counselors are expert in conveying risk information in understandable terms, eliciting concerns and questions from patients, and facilitating shared decision-making. The aims of this study were to (a) design a genetic counselor-driven Risk Assessment & Counseling model to aid women in menopausal therapy decision-making and (b) determine if the model would increase subjects’ knowledge of their personal risks and menopausal options, decrease anxiety about decision-making, and increase their confidence and satisfaction with this process. To accomplish the first aim of this study, we conducted a focus group of pre- and perimenopausal women (>40 years of age) who have one first-degree relative with breast cancer and are considering their options for menopausal therapy. Based on recurrent themes from the focus group, we concluded that the model must (a) clarify that the study counselors did not receive funding from any pharmaceutical companies, (b) define menopause and the impact of estrogen on different parts of the body, (c) explain each of the menopausal therapy options and accompanying risks/benefits, and (d) outline the patient’s personalized risk assessment, and the impact of each menopausal therapy on those risks. A counseling model and accompanying flipbook have been created based on these data. This counseling model is currently being used to conduct a 60-patient clinical trial by genetic counselors at two NCI-designated cancer centers. If this model is found to be effective, genetic counseling and risk assessment for menopausal therapy may represent a new, rapidly growing subspecialty in the field of genetic counseling.


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Prostate Cancer Prevention: An Introduction to the Prostate Cancer Prevention Clinic A. Matthew, J. Squire, P. Ritvo, D. Cole, C. Yue, and J. Trachtenberg University Health Network, Toronto, Ontario, Canada Background: Prostate cancer, one of the most common cancers diagnosed in men, is a significant cause of morbidity and mortality. Recent research studies on prostate cancer have suggested that some men have an elevated risk for developing the condition, yet few services for these unaffected at risk men exist. Purpose: In this study we tested the feasibility of developing a clinical and research program focused on early detection and prevention of prostate cancer for unaffected at risk men within an existing cancer treatment facility. Methods: We report our experience to date in the development of the Prostate Cancer Prevention Clinic (PCPC), focusing on the level of interest in this service and the feasibility of the development and operation of this novel clinic. Results: A multidisciplinary model similar to other high-risk cancer clinics was utilized in our development of the PCPC. Services available to the men attending the PCPC included medical surveillance, genetic counseling, psychosocial support, and review of prevention practices. In addition, a comprehensive research program for PCPC patients has been established. Eligibility criteria for unaffected at risk men were broadly defined and include men with (1) a first-degree relative diagnosed with prostate cancer, (2) a known genetic predisposition (e.g., BRCA1/BRCA2 carriers), (3) self-reported African ancestry, (4) an elevated prostate specific antigen (PSA) test result, or (5) prostatic intraepithelial neoplasia (PIN) diagnosed on biopsy. Since the start of the PCPC program in October 2001, 55 eligible men have expressed interest in our clinical services. Of those men interested in clinical services, 32 (58.2%) had a family history of prostate cancer, 14 (25.4%) had an elevated PSA, six (10.9%) had a BRCA1 or BRCA2 mutation, and three (5.5%) had PIN. An additional, 53 men with a diagnosis of prostate cancer expressed interest in our genetic counseling service. Discussion: Although services for men at increased risk to develop prostate cancer are limited, our experience suggests that there is a substantial interest in surveillance, genetic counseling, psychosocial, and prevention services in this population, particularly among men with a family history of prostate cancer. As well, we discovered that it was feasible to integrate this type of program within an already established cancer treatment clinic. Our findings suggest a need for similar clinics to provide care to this population of at risk individuals and to facilitate genetic counseling for affected individuals.

Pilot Study of a Comprehensive Cancer Family History Screening Questionnaire L. Mays and A. Walker Division of Human Genetics, University of California, Irvine A comprehensive cancer family history screening questionnaire with an easyto-use scoring algorithm was developed to help identify patients who might benefit


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from referral for genetic cancer risk evaluation. The questionnaire asks if specified relatives have ever been diagnosed with cancer, and if so, the location of the primary tumor and age at diagnosis. Sites of tumors more likely to be found in major cancer syndromes were given as possible responses. The scoring algorithm enables a primary care provider or other nongeneticist to determine if the patient may have an increased risk for hereditary cancers. The questionnaire scores “positive” if there are two or more individuals with the same or related cancers on the same side of the family, or if anyone had cancer before age 50. The questionnaire was piloted in the Breast Health Clinic at UC Irvine Medical Center, and offered to all patients presenting for care. Patients were told that the questionnaire was being tested as part of a study, that it was anonymous, and that it would not be entered into their medical record. A Spanish version was also offered. One hundred eighteen questionnaires were returned. Forty-five were screen positive, with nine positive for breast cancer and 22 meeting risk criteria for more than one type of cancer. A chart review of 144 new patients seen at this clinic before the questionnaire was piloted was also conducted to assess the quantity and quality of family history currently recorded in patients’ medical records. One hundred forty-three charts contained at least some family history obtained either by the physician, a patient-completed questionnaire, or both. One hundred seven charts contained sufficient history to apply the pilot questionnaire’s screening algorithm. Using this, 48/107 histories scored “positive” (44.8% of scorable charts). Twenty-five of these were “positive” based on breast cancer history, and nine “positive” for more than one type of cancer. Only one patient had been referred for genetic evaluation. The two groups of patients (those screened via pilot questionnaire and those by chart review) did not differ significantly in the proportions affected by cancer themselves, with breast cancer specifically, or with “positive” family histories. However, the groups did differ significantly in the types of cancers identified in the family, with the questionnaire finding more histories positive for cancers other than breast cancer ( p = 0.0012). The results of this study indicate that the screening questionnaire is effective in identifying patients at possibly increased risk for hereditary cancer.

How BRCA1/2 Test Results Affect Risk Perception and Beliefs Among Members of Hereditary Breast and Ovarian Cancer Families A. McInerney-Leo, B. Biesecker, D. Hadley, R. Kase, T. Giambarresi, E. Johnson, C. Lerman, and J. Struewing NHGRI/NIH, Bethesda, Maryland Purpose: Members of Hereditary Breast and Ovarian Cancer (HBOC) families often have long-held beliefs about their carrier status and the perceived advantages and disadvantages of testing. The extent to which these beliefs affect the decision to undergo testing and the consequences of the receiving results consistent or inconsistent with these beliefs is not known. Methods: Within a randomized trial of breast cancer genetic counseling methods, 212 members of 13 HBOC families were offered BRCA1/2 testing for a known family mutation. Risk perception and perceptions about the advantages and disadvantages of testing


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were assessed at baseline and again at 6–9 months following the receipt of test results, or at the equivalent time for those who declined testing. Comparisons were made between testers and nontesters and as well as between those who tested positive or negative. Results: One hundred eighty-one participants elected to undergo genetic testing (85%) and 47 (26%) were identified as carriers. All individuals who participated believed themselves to be at “a little” to a “much” higher risk of developing breast cancer as compared to another person in the population and all felt it was very likely or definite that they had the mutation, with no difference between testers and nontesters ( p = 0.518). All participants felt that the most important reason to undergo testing would be to learn information about their children’s risk and this was not different between testers and nontesters. The most reason for not wanting to have testing was related to worry about losing insurance and this did not differ between testers and nontesters but nontesters were more likely to be worried about confidentiality than testers. Individuals who tested negative had a significant decrease in their perceived risk for breast cancer, ovarian cancer and their chances of carrying an altered gene ( p < 0.001 for all). Those who tested positive had no change in their perceived risks. Conclusion: Perceived risk and beliefs about testing did not seem to influence the decision to undergo testing. Risk perception was high in these family members to begin with and this perception was unchanged when individuals received a positive test result. However, a negative test result was followed by a significant decrease in perceived risk for developing breast, ovarian cancer and for carrying an altered gene. Therefore, test results have the potential to alter long-held beliefs.

Health Behaviors in Individuals At Risk for Colon Cancer: Follow-Up of Individuals Enrolled in a Colon Cancer Registry M. Moussavi University of Minnesota, Minneapolis, Minnesota Minnesota Colorectal Cancer Initiative Registry (MCCI) is a nonprofit community and professional resource whose aim is to decrease colorectal cancer (CRC) incidence and mortality in the state of Minnesota. Information about cancer and polyp history, CRC screening history, and family history of colorectal polyps, CRC, and other cancers is collected from each participant. A genetic counselor assesses the individual’s risk according to American Cancer Society (ACS) guidelines and assigns them to an average, increased, or high-risk category. Recommendations for screening are made based on ACS guidelines appropriate to their specific situation and included in a letter, along with a summary of their family history and pedigree, recommendations for screening, and information about the early detection and prevention of CRC. The purpose of this study is to assess the value and effectiveness of the MCCI registry in order to evaluate the educational and personalized approach taken with its participants. The participants for the study were randomly selected from the MCCI database according to their risk category. A total of 120 participants, 40 from each risk category, were initially contacted to invite their participation in the study. A total of 50 participants responded, with


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43 participants completing the telephone survey. The anticipated main reasons for participating in CRC screening were determined by answers to Liekert-type factors and open-ended questions derived from the literature on CRC screening. The results showed that the main reasons influencing an individual’s decision to participate in CRC screening were a family history of CRC or polyps (86%, n = 37) and the recommendation of a doctor (81%, n = 35). Membership in MCCI was considered an important factor in continuing with CRC screening to 74% of participants. The participants’ perception of their risk did not have an influence on the decision to participate in CRC screening. Participants did not feel that the fear of health/life insurance discrimination, fear of finding cancer, or the pain/discomfort associated with the screening procedures were adequate reasons for avoiding CRC screening. The majority of the study participants did not have an understanding of genetic counseling and had not visited a genetic counselor. Participants reported the major benefit of membership in MCCI was the personalized risk information they received. MCCI can utilize the results of this study to make improvements in its service and may serve as a model for established registries and for future registries.

A Survey of Women Receiving an Uninformative BRCA1/2 Test Result: Reactions, Risk Perceptions, and Disclosure to Family Members K. Panabaker, C. Azcona, M. McCullum, B. McGillivray, and J. Bottorff BC Cancer Agency, Vancouver, Canada BRCA1 and BRCA2 genetic testing has been offered to members of highrisk breast and ovarian cancer families through the Hereditary Cancer Program of the BC Cancer Agency since 1997. In the majority of patients tested (78%), a deleterious mutation was not detectable in either gene. An extensive literature review demonstrated a lack of research on the experiences of this population. The purpose of this study was to explore the impact of an uninformative BRCA1/2 genetic test result on individuals and their families. All women residing in BC with a personal history of breast cancer, who had received an uninformative BRCA1/2 test result, were invited to complete a questionnaire exploring their experiences after receiving the result. The questionnaire assessed emotional reactions to the test result, risk perceptions, breast cancer worries, knowledge of hereditary cancer genetics, and understanding of the implications of an uninformative test result. Interest in obtaining future genetic testing and disclosure of the test result to family members were also explored. Overall, women reported a strong sense of relief and happiness after receiving their test result. Seventy-six percent (97/128) of women reported low breast cancer worries and 61% (78/123) of respondents felt their risk for a new breast cancer was the same as it was prior to being tested. Most participants were interested in further genetic testing (94%; 121/128) if it becomes available. Only 53% (68/128) of participants achieved a score of 75% or greater in their knowledge of hereditary cancer genetics. However, scores for understanding of the implications of the test result were high, with all participants


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achieving a total score above 80%. Seventy percent (90/128) reported disclosing their test results to “all” family members, citing a concern for family members’ risks of developing cancer as one of the main reasons. Individuals who told only “select” family members preferentially disclosed the result to female relatives. Women’s feelings and breast cancer concerns following an uninformative BRCA1/2 test result appeared similar to those experiences reported in previous studies of women obtaining a true negative test result. Further studies assessing the content of communication about uninformative BRCA1/2 results within families are needed.

p53 Testing Practices of Pediatricians and Pediatric Oncologists in Children of Li-Fraumeni Syndrome Families: Implications for Medical Management D. Patel, J. Tsipis, P. Roche, and K. Shannon Brandeis University, Waltham, Massachusetts Individuals at risk for Li-Fraumeni syndrome (LFS) have the option of being tested for alterations in the causative p53 gene to clarify their cancer risk status. Traditionally, presymptomatic genetic testing of children is generally not of concern if effective treatment and/or management options exist. However, when these options are not available, which is the case with LFS, the rationale for testing minors is less clear. If a child is from an LFS family, their cancer screening options regarding LFS are introduced by the physician who follows them, usually a pediatrician or pediatric oncologist. To assess the attitudes of these types of physicians towards p53 testing in minors at risk for LFS, and to assess how this testing might alter a child’s medical management, a survey was designed and sent to 500 pediatricians and 500 pediatric oncologists. One hundred eighty-six surveys were returned. The majority of pediatricians (91%) and pediatric oncologists (74%) would offer p53 testing to an asymptomatic child from a LFS family. These data are similar to the proportion of physicians that would test a symptomatic child in an LFS family (88% and 86%, respectively). The majority of pediatricians (71%) and pediatric oncologists (86%) believe that a child should be involved in the informed consent/assent process in genetic testing, and genetic counselors were overwhelmingly identified as the primary health care professional who would be best suited to facilitate this process. Regarding alteration of medical management of children, results show that children who are positive for a p53 mutation would have an increase in their medical surveillance while those who have a negative result would have a decrease in medical surveillance. The data obtained here indicate that the attitude of physicians towards presymptomatic testing in minors is not in keeping with many position statements on this issue. We conclude that current statements regarding predisposition testing of minors should be thoughtfully reviewed. We suggest that these statements might be clarified, taking into account current physician practice. We also suggest that physicians are educated about these statements and the reasoning behind them.


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A Study of Genetic Counselor Discussions of Genetic Discrimination With Cancer Risk Patients N. Pfeffer, P. McCarthy Veach, and B. LeRoy Center for Genetic Services, Corpus Christi, Texas Twenty-five genetic counselors from the NSGC cancer SIG who see familial cancer risk patients were interviewed with the purpose of furthering the discussion about how genetic counselors present genetic discrimination issues and ultimately promoting the development of guidelines for the profession. The counselors were asked through phone interviews about their definitions of genetic discrimination, their perceptions of patient risk for discrimination, frequency and type of discrimination experienced by their patients, sources of information about discrimination, and what they tell patients about discrimination. The 25 participants, with a mean of 8 years counseling experience and 5 years cancer counseling experience, all had Master’s degrees and worked primarily in university or private medical centers. They defined genetic discrimination as being treated differently with respect to insurance and employment based on genetic information, genetic test results, and /or family history. Most participants reported always or almost always discussing genetic discrimination with cancer risk patients, and 100% reported typically discussing health and life insurance discrimination risks. The majority considered the actual risk of discrimination to be low to theoretical. The participants mentioned discussing federal and state legislation, lack of documented cases, the actual risk of discrimination, the uncertainty of legal protections, presymptomatic vs. symptomatic testing, and types of insurance in discussions of genetic discrimination with patients. The majority use research and current literature as sources for their information. They all reported discussing strategies to avoid discrimination, including paying for testing out of pocket, confidentiality safeguards, anonymous testing, documentation, obtaining insurance prior to testing, and no guarantee of a strategy’s effectiveness. The majority of participants were knowledgeable about their state laws and reported having a general discussion of the law with patients. Forty percent reported an instance of genetic discrimination, including insurance companies requiring results to cover procedures, denial of life/health insurance, social discrimination, and employment discrimination. There was variability across participants in their definitions of genetic discrimination, perceived risk of genetic discrimination, and their descriptions of discussions with patients. Results suggest that the genetic counseling profession should address topics such as defining genetic discrimination, developing guidelines regarding discrimination issues, and addressing possible ethical issues. Brief Breast Cancer Risk Assessment Can Reduce Distress J. Quillin, E. Fries, D. McClish, E. Shaw de Paredes, and J. Bodurtha Virginia Commonwealth University, Richmond, Virginia Appropriate breast health management depends on an accurate knowledge of cancer risk. Perceptions of breast cancer risk relate to psychological distress,


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and distress can influence screening compliance. To address these concerns, we assessed the psychological impact of Gail model breast cancer risk assessment. We hypothesized that risk-tailored breast health messages could be administered in routine health care without causing distress. Study participants were 299 female patients in a mammography clinic. Participants completed baseline questionnaires and answered questions by phone at 1-month follow-up. Each participant was randomized to either a treatment or control group. Women in the treatment group used a computer to calculate their 5-year and lifetime risks of breast cancer. Depending on their calculated lifetime risks, women received printed breast health messages for “Usual,” “Moderate” or “Strong” breast cancer risk. Each printed message presented appropriate screening and lifestyle recommendations as well as referral information for genetic counseling. Distress was measured using the Brief Symptom Inventory-18 (BSI-18). The BSI-18 assesses somatization (SOM), anxiety (ANX), depression (DEP), and global distress (GSI). Scores of ANX, DEP, and SOM can range from 0 to 36. GSI is a sum of the three subscores. A GSI greater than 21 indicates clinical distress. Changes in distress at baseline and at 1 month were assessed for each group. Because changes in distress scores were not normally distributed, we used nonparametric tests (Wilcoxon Sum/Signed Rank tests). p-values ≤0.05 were considered significant. At baseline, the control and treatment groups had similar scores for GSI, SOM, and ANX (µGSI = 6.6, µSOM = 2.2, µANX = 2.6). Scores for DEP differed significantly between control (µDEP = 2.0) and treatment (µDEP = 1.3) groups at baseline ( p = 0.036). No difference in DEP scores was noted between groups at follow-up (µDEP = 1.5). From baseline to follow-up significant decreases in GSI (µchange = −1.4, p = 0.022), SOM (µchange = −0.8, p < 0.001), and ANX (µchange = −0.6, p = 0.028) were identified in the treatment group. The control group also showed lower SOM at follow-up (µchange = −0.2, p < 0.001), although follow-up SOM scores appeared lower for the treatment group ( p = 0.005). The other distress measures did not change for the control group. We conclude that information about personal breast cancer risk can be supportively incorporated into routine health care without causing distress. In particular, levels of anxiety, somatization, and global distress may be reduced with risk assessment. Satisfaction With and Outcome of Risk Reducing Surgeries Among a Series of BRCA Heterozygotes L. Scheuer, H. Huang, N. Kauff, R. Baum, F. Facio, E. Glogowski, J. Hull, S. Jhanwar, H. Pierce, B. Rapaport, B. Siegel, and K. Offit Memorial Sloan-Kettering Cancer Center, New York, New York Women with mutations in the BRCA1 or BRCA2 genes are at increased risk to develop breast and ovarian cancer. Some of these women elect to undergo risk-reducing salpingo-oophorectomy (RRSO) and /or risk-reducing mastectomy (RRM). We have surveyed women who have undergone RRSO and /or RRM after receiving their genetic test results to assess their satisfaction levels with their decisions to undergo these procedures. Satisfaction with RRSO and RRM were measured using a 5-point Likert scale from 1 (very dissatisfied ) to 5 (very


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satisfied). Among 111 of 129 women on whom data regarding satisfaction with RRSO was available, the mean level of satisfaction was 4.5. There was no significant difference in level of satisfaction among 66 women self-reported as pre- and perimenopausal versus. 44 women reported as postmenopausal at time of RRSO ( p = 0.5). Additionally, there was no significant difference in level of satisfaction among 90 women who underwent RRSO alone and 15 women who underwent hysterectomy at time of RRSO ( p = 0.4). Three out of 129 (2.3%) of women who underwent RRSO were diagnosed with an unsuspected ovarian or fallopian tube cancer at the time of surgery. Among 38 of 51 women on whom RRM satisfaction data was available, the mean level of satisfaction was 4.87. There was no significant difference in mean level of satisfaction among 27 women with and 11 without a previous diagnosis of breast cancer ( p = 0.7). Two out of 51 (3.9%) of women were diagnosed with unsuspected intraductal breast cancers at the time of RRM. Among our series of women with germline BRCA mutations, global levels of satisfaction with RRSO and RRM are high. There was no significant variation in levels of satisfaction associated with type of surgery or menopausal status. No significant difference with RRM satisfaction was detected in women with or without prior breast cancer diagnoses. Further investigations are required in order to determine the effects of these procedures upon specific functional domains and quality of life. From 2 to 4% of women who undergo RRSO and RRM will be diagnosed with unsuspected cancers at the time of these surgeries. Genetic Counseling Reduces Cancer Worry in Mothers of Children With Cancer K. Schneider, T. Brown, C. Medeiros Nancarrow, K. Jensen, E. Casey, C. Recklitis, and L. Diller Dana-Farber Cancer Institute, Boston, Massachusetts In pediatric cancer clinics, the genetic counselor role has not been wellstudied. At our center, mothers of children diagnosed with cancer were enrolled in a genetic counseling (gc) pilot study. All mothers were seen by the same genetic counselor. Participating mothers were asked to complete baseline and follow-up written questionnaires about attitudes towards genetic testing, genetics knowledge, cancer worry, patient satisfaction and emotional well-being. At the visit, the counselor collected detailed family histories and categorized each family as having a low, high or uncertain risk for an underlying inherited predisposition to cancer. Results: Thirty-one mothers enrolled, submitting 31 baseline and 15 follow-up questionnaires. The 31 participating mothers had a mean age of 40 (range: 32–51), 90% were married, 84% had >1 child, and 65% were college graduates. In 53% of cases, mothers had never been asked to provide detailed family history information. Children’s cancer diagnoses were brain tumors (9), lymphoma/non-ALL leukemia (8), Wilms’ tumor (5), neuroblastoma (5), sarcoma (2), and other solid tumors (2). A total of 29/31 (93.5%) cases were assessed as low risk, one case was high risk with concerns about Li-Fraumeni syndrome, and one case was uncertain risk pending documentation of the history. Mothers indicated that the most important reasons to consider genetic testing would be to clarify cancer risks for


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the affected child and other offspring; least important motivator was for family planning purposes. Mothers’ mean scores of genetics knowledge increased significantly following the gc visit (from 20.3 to 23.9; p < 0.05). Mothers were also asked about their level of cancer worry for the affected child. Data showed a significant decrease in cancer worry following the gc visit (8/15 had reduced worry; p < 0.05) and overall, 14/15 (93%) mothers indicated the gc visit was beneficial. Thirteen mothers completed BSI assessments of emotional well-being. The global severity index (GSI) mean scores stayed constant (68.1 baseline/67.9 follow-up), revealing distress levels above population norms but no negative sequelae from the gc encounter. Even if mothers do not express genetic concerns to pediatric oncologists, it is clearly an issue they are worried about. One gc visit has the potential for alleviating these fears as well as identifying the rare family at high risk. A New Perspective Regarding Carrier Status in High-Risk Cancer Patients N. Singer, G. Rosenthal, and S. Fallet Saint Barnabas Medical Center, Livingston, New Jersey Identification of carrier status for disease-causing mutations is an important aspect of genetic counseling services. Traditionally, when a person is identified as a carrier for a particular genetic condition, this is viewed as a negative result necessitating further investigation and posing the possibility of adverse psychological consequences. Screening for predisposition genes, including cancer genes, is a relatively new concept in clinical genetics. We present four families with very strong histories of breast and ovarian cancer. Family members were convinced that there was an inherited predisposition accounting for the cancers in each family. The results of genetic testing in each family and the reaction of family members will be discussed. These and many other experiences screening for BRCA mutations in high-risk cancer families have changed our view regarding the impact of carrier status on family members. We conclude that a positive result may be empowering and, for many women, the answer to years of unanswered questions. Therefore, we have modified our approach to conveying such news to our patients. A more positive outlook during both pre- and posttest counseling can change the dynamic from one of dread to one of constructive management and optimism. As technology advances, more cancer-causing mutations will be identified in families. It is important to keep in mind that the benefit these high-risk families receive from mutation identification may outweigh the negativity traditionally associated with carrier status. IV. COUNSELING AND PSYCHOSOCIAL ISSUES Family Ties: Attitudes Toward Genetic Testing Among Patients With Usher Syndrome, Their Parents, and Siblings A. Bar-Lev, S. Ness, J. Willner, A. Madeo, and R. Zinberg Mount Sinai School of Medicine, New York, New York Research conducted to date has shown the variability in the impact of illness and in attitudes toward genetics—both between and within disease populations.


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Usher syndrome is an autosomal recessive condition characterized by hearing loss and retinitis pigmentosa; it accounts for approximately 50% of deaf-blindness. Recognition that unique mutations may be prevalent in individuals of Ashkenazi Jewish descent has initiated current family linkage studies. In anticipation of possible genetic testing, we examined psychosocial issues among affected families in this population. An understanding of these issues would be critical to meeting the needs of such families when genetic services become available. Thirty-two participants, including patients with Usher syndrome, their parents and siblings, completed anonymous and confidential questionnaires assessing: (1) the familial experience in adaptation to Usher syndrome, (2) understanding of autosomal recessive inheritance, and (3) attitudes toward carrier testing, prenatal diagnosis, and termination of pregnancy. This protocol was approved by the Institutional Review Board of the Mount Sinai School of Medicine. Over 46% of patients and parents indicated “feeling very unhappy or depressed” over the past few weeks; a comparable proportion of patients felt “very lonely or remote from other people.” Involvement in the deaf, blind, and deaf-blind communities was found to be very low. Understanding of autosomal recessive inheritance was poor, with 43% of multiple choice questions answered correctly. Those who indicated having had some interaction with a health care professional scored better (52%) than those who had no such interaction (25%), yet room for improvement in the process of providing education is clearly shown. While interest in prenatal diagnosis of Usher syndrome did exist, interest in seeking termination of pregnancy for this indication was significantly lower ( p < 0.01). Interest in seeking termination was also significantly lower for a diagnosis of Usher syndrome than for Down syndrome ( p < 0.01) or Tay-Sachs disease ( p < 0.01). Our data further suggests that religious conviction did not significantly alter interest in seeking carrier testing, prenatal diagnosis, or termination of pregnancy; however, greater religious conviction was significantly associated with lower actual and anticipated support for the individual pursuing these services. Implications for genetic counseling and future research will be discussed, with attention to the role of the counselor in facilitating family and community support, improving family education, and addressing the benefits and limitations of genetic services specific to this condition.

Uncertainty in a Family at High Risk for a BRCA1 Mutation B. Baty, A. Kinney, W. Dudley, and E. Marshall University of Utah Health Sciences Center, Salt Lake City, Utah The commonly held notion that genetic testing reduces uncertainty has not been empirically tested. Sources of uncertainty include test results, whether and when the feared condition develops after a positive test, possible medical actions, potential loss of insurance as “payment” for medical knowledge, and inheritance of the trait. Based on anecdotal information, we predicted that genetic testing would decrease some types of uncertainty but increase other types of uncertainty. We examined baseline levels of uncertainty and tested our predictions in the Family


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Health Study, which offers genetic counseling and testing to adults in a single African American kindred with over 30 cases of breast, ovarian, prostate, and colon cancer, and an identified BRCA1 mutation (1775T → G). Questionnaires were administered to study participants (62 women and 26 men) before genetic counseling and testing, and approximately 6 weeks after testing (25 women and 10 men to date). Participants rated questions regarding uncertainty about genetic testing and cancer risk reduction on a 1–5 scale with 1 indicating very uncertain and 5 indicating very certain. On the baseline questionnaire the majority of participants had a high degree of certainty (4–5 on the scale) that they will follow through with recommended cancer detection check-ups (88%), they can obtain cancer screening (84%), their health care provider can detect cancer early (71%), they can obtain medical care for risk reduction (62%) and they can cope well with genetic testing results (57%). Fewer participants were certain that they can detect cancer early (45%), they want prophylactic surgery (29%), they are unlikely to have insurance problems (19%), and their daughters (11%) and sons (10%) will inherit a BRCA1 mutation. Fifty-six percent were certain they would have positive changes after learning their test result but only 17% were certain that learning their chances of getting cancer would negatively affect their lives. Comparing the baseline responses to responses after counseling and testing, participants became more uncertain that testing will result in a negative effect on their lives (mean 2.6 vs. 1.8; p < 0.01), more confident that they can detect cancer early (3.1 vs. 3.8; p < 0.01), and more confident that they can cope well with genetic testing results (3.5 vs. 4.4; p < 0.01). Preliminary results document differing levels of uncertainty regarding various aspects of genetic testing and complex changes in the level of uncertainty experienced by individuals participating in genetic counseling and testing for a BRCA1 mutation. Genetic Counseling Clients’ Perception of Different Numeric Formats of Probabilistic Risk Figures: A Pilot Study M. Cantwell and D. Punales-Morejon ˜ University of Utah Health Sciences Center, Salt Lake City, Utah A fundamental aspect of genetic counseling is client education regarding probabilistic information such as incidences, recurrence risks, and procedural risks. Studies indicate clients transform actual risk into perceived risk and tend to make decisions in accordance with the latter. Therefore, it is crucial that the best methods for promoting accurate risk perception be delineated. The purpose of this study was to (1) Develop a questionnaire assessing clients’ level of numeracy and perception of different numeric formats of probabilistic risk figures. A visual analog scale was designed to evaluate clients’ perceived likelihood of percentages, proportions, rates, and odds. Equivalents of 0.5% (specifically 0.5%, 1/200, 5 per 1000, and 1–199), 4%, 96%, 25%, and 75% were used, which are values commonly encountered in sessions. (2) Evaluate the questionnaire’s readability and comprehensibility. Our results indicate that the lowest values tended to be overestimated, and their converse values underestimated. Many clients


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interpreted particular figures very differently. Overall, percentages and proportions were the most accurately perceived, and odds were the most disparately interpreted. Data from all 22 participants’ questionnaires are appropriate for inclusion in a large-scale study, the next phase of this project. The large-scale study will address these questions: (1) Do genetic counseling clients perceive the different formats of equivalent numeric risk figures as having different levels of risk? (2) For which format of risk figure is clients’ perception most accurate? (3) Among genetic counseling clients, is level of numeracy related to ability to perceive risk figures accurately? Unlike previous studies, this study allows ranking of the perceived risk level of the four numeric formats and investigates whether level of numeracy affects perception of the different formats. In summary, the pilot study data show interesting trends that warrant further investigation in a large-scale study.

What Factors Influence At Risk African American Family Members to Undergo Predictive Testing for Type 1 Diabetes? D. Dorsainville, V. Headings, N. Burka, B. Harrison, and F. Ampy Howard University, Washington, District of Columbia Type 1 Diabetes is a lifelong chronic illness that typically affects children and young adults. It is caused by autoimmune destruction of the insulin producing beta cells of the pancreas. Currently one of the screening methods being utilized to determine whether an individual is at increased risk for developing Type 1 diabetes is the Islet Cell Antibody (ICA) test. This screening method can be especially helpful for detecting at risk family members of affected individuals months or even years before symptoms manifest. ICA screening measures the levels of islet cell antibodies in the blood, which may precede the development of Type 1 diabetes by months or years. The purpose of this study was to identify factors that influence decision-making about screening for islet cell antibodies in at risk African American families. These families were approached moments after they were informed about the testing process. A total of 21 African American families were recruited for the study. Questionnaires were utilized to ascertain decisionmaking practices. The resulting data was compared with factors such as time of the proband’s diagnosis, relationship to affected family member, income, education, sex, and age. The identified factor most associated with decision-making was a strong relationship with the health care team. Neither income, educational level, spiritual beliefs, elapsed time since diagnosis in proband, and burden of illness presented an association with decision-making in this population. There was a relationship established between the importance placed on pursing ICA testing and the family member’s fear of developing diabetes, that is, family members who were worried that they or another relative may develop diabetes were more likely to consider or pursue screening. We concluded that the population we surveyed held different beliefs about research than previous African American groups studied in the literature. This group of African Americans was willing to partake in the research process.


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Prenatal Genetic Testing and Pregnancy Termination: Perceptions of pastors in the Church of the Nazarene S. Ellingwood, D. Lea, D. Shea, A. Truesdale, and J. Tsipis Brandeis University, Waltham, Massachusetts When a fetal anomaly is detected prenatally, a woman or couple may seek the guidance of a trusted spiritual leader when making a decision about termination of the pregnancy. Very few studies, however, assess religious leaders’ perceptions of prenatal genetic counseling and pregnancy termination, and this information may be helpful to genetic counselors to understand what guidance a spiritual leader might provide to their patients. To assess their perceptions of the value of prenatal genetic testing, the acceptability of pregnancy termination, their support of a parishioner in this situation, and their willingness to provide pastoral counseling, a survey was devised and sent to 400 pastors of the Eastern Educational Region of the Church of the Nazarene, a conservative Protestant denomination made up of 1.4 million members. One hundred twenty-five surveys were returned. In the survey, the pastors were asked to indicate their level of agreement with six attitude statements following four previously published vignettes dealing with situations of prenatal diagnosis of Down syndrome, Huntington disease, trisomy 18, and anencephaly (Stuck et al.,• • • J. Genet. Counsel. 10:251–263). Results suggest that some Nazarene pastors will support a woman’s/couples’ decision to terminate a pregnancy, particularly if the diagnosis is not compatible with life; 0.8–14.5% of pastors thought that termination of the pregnancy was an acceptable option in one or more of the given situations presented. Over 25% of pastors commented that even if they could not support a decision to terminate, they could still provide spiritual and emotional support to the individuals involved. The great majority of pastors (97–99%) responded that pastoral counseling was indicated in these situation, and many pastors commented that they would like more training in bioethical counseling to better prepare them for this role. Furthermore, the majority of pastors (91–94%) agreed that information obtained from genetic counseling is important to the woman or couple. The responses of the Nazarene pastors were more conservative than the responses of ELCA Lutheran pastors, a group previously studied using the same vignettes (Stuck et al.,• • • ) even though both denominations fall into the broad category of Protestantism. The Role of Genetics Professionals in Counseling Individuals With Factor V Leiden Thrombophilia E. Hellmann, S. Moll, and N. Leslie University of Cincinnati, Cincinnati, Ohio Genetic susceptibility testing for factor V Leiden (FVL) is widely utilized by health care providers in an effort to better treat those with a history of venous thrombosis or prevent thromboembolism in family members. Testing is rarely performed under the guidance of genetics professionals. To assess patient experience of genetic testing and identify unmet needs of this population, we studied


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knowledge, satisfaction with information received from health care providers, health perception, information needs and opinions on genetic testing. Individuals who tested positive for the FVL mutation between 1995 and 2001 at an academic medical center were ascertained (N = 303). Those cases that could be contacted were offered participation in the study (153); 110/153 (72%) of these individuals completed a 5-page, written questionnaire. Unexpectedly, 14 individuals (13%) did not recall being informed of genetic test results for FVL. Informed consent for testing was given by 61%. Questions used to assess knowledge of FVL revealed many uncertainties and misconceptions among patients. The most striking was misperception of thrombotic risk associated with FVL. Fewer than 1% of individuals with factor V Leiden develop a blood clot during their lifetime, however, only 21% of those surveyed recognized that the statement “approximately 70% of individuals with factor V Leiden will develop a blood clot in their lifetime” was incorrect. Participants also indicated uncertainty regarding inheritance; 85% did not recognize that the inheritance pattern was unrelated to gender. Patients were not content with the quantity of information they received about factor V Leiden; 64% stated that they were not given much information and 68% still had many questions. A minority of patients (47%) were satisfied with their health care providers’ knowledge of FVL. Participants commonly expressed the need for more information and specifically, information pertaining to genetics and testing of family members. From a psychosocial standpoint, knowledge of FVL status increased worry in 43% of patients and caused 53% to believe that they were at increased risk to develop health problems. There is a need for genetics professionals to become involved in the care of individuals with FVL and possibly, other tests of genetic susceptibility. Genetic counselors are needed to increase awareness of the complex issues surrounding genetic susceptibility testing among health care providers and the public; clarify concepts of gene-environment interaction, inheritance, and issues of genetic testing for patients; identify appropriate support resources; and develop educational tools to be utilized in mainstream medicine. Regional Sickle Cell Consumer/Provider Workshop: A Strategy for Understanding Consumer Experiences and Perspectives S. Iden, R. Austin, H. Britton, M. Wilborn, V. Tsegah-Teye, D. Dixon, J. Hutter, and P. Lane for the Mountain States-Texas Hemoglobinopathy Working Group University of Arizona, Tucson, Arizona Since 1997, sickle cell providers in the Mountain States and Texas have collaborated on the development and implementation of Regional Clinical Care Guidelines and Protocols to improve the quality of health care for children with sickle cell disease. These guidelines have provided detailed information about medical issues but have not specifically addressed psychosocial issues. Federal Healthy People 2010 Objectives for Children With Special Health Care Needs specify that patients and families should participate in decision-making about their health care services and be satisfied with the services they receive. To better understand patient and family perspectives we convened a 2-day regional workshop


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in June 2000. Seventeen consumers from Colorado, Arizona and Texas, including patients and parents of patients with sickle cell disease, shared their personal experiences and perspectives with 12 sickle cell health care providers and seven observers from government and advocacy organizations, and academic institutions. Critical to the workshop’s success was its organization, which included the use of an experienced group facilitator. By design, consumers did most of the talking and providers most of the listening. Important issues identified by consumers included the need for more education and community awareness about sickle cell disease, stigmatization of patients and families, barriers to quality health care, problems in managing pain, the impact of chronic illness on normal family functioning (including adjustment issues for nonaffected siblings), patient/provider relationships, and school and other educational issues. Insights gleaned from the workshop are being incorporated into a new section on psychosocial care that will be added to the next edition of our Regional Guidelines and Protocols and are being used to develop regional strategies to achieve the Healthy People 2010 Objectives. These new strategies will be tested to determine their effect on patient/family satisfaction, quality of life and other outcomes. We believe that the successful format of this workshop provides a model that can facilitate better understanding of consumer perspectives and greater involvement of consumers in the organization of sickle cell services, both locally and regionally. Influence of Culture and Gender on Communication of Medical Family History H. Kim, L. Murrelle, J. Silberg, P. Board, and J. Bodurtha Virginia Commonwealth University, Richmond, Virginia Background: Knowledge of medical family history may be an important factor in health care decision-making and family planning because health conditions often run in families and have a genetic component. This knowledge, which is important for accurate genetic counseling, depends upon its communication within a family. This communication may have several influences. Purpose: To assess and characterize the influence of culture and gender on communication of medical family history. Methodology: Sixty-four question survey administered to college students. Forty percent response rate: 70 males, 238 females. Results: Those with bicultural, multicultural, or “other” cultural identity (designated multi) as compared with those of “American” cultural identity (designated Amer) were significantly less likely to know some health knowledge items, less comfortable discussing medical family history with extended family members, more likely to find certain personal factors and health beliefs to be barriers, and more likely to associate shame or embarrassment with specific aspects of health status. For example, 44.7% of the multigroup found not wanting to burden other family members very limiting to communication of medical family history while 23.5% of the Amer group did ( p = 0.0058). Also, 42.6% of the multigroup had some shame/embarrassment with physical disabilities or deformities, while 22.7% of the Amer group did ( p = 0.0048). Race (Caucasian, African American, or Asian) also had a statistically significant influence on these groups of items. For example,


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96.5% of Caucasians and 95.4% of African Americans reported that it was important to know one’s medical family history before having a child while 80.6% of Asians did ( p = 0.0037). Also, Asians were significantly more likely to find not wanting to pry ( p = 0.0009) and the importance of privacy ( p = 0.0008) to be barriers to communication of medical family history. Gender was not found to be significantly associated with any of the above groups of items. The level of general communication within a family was found to be the only independent variable influencing familiarity with medical family history. Ethnic background was one of the independent variables influencing general communication within a family. Conclusions: Culture has a multifaceted influence on communication of medical family. When obtaining a family history, awareness of this cultural influence, assessment of general communication within a family, and assessment of comfort level discussing medical family history information may be beneficial. Given that inaccurate and incomplete medical family history reports are not uncommon, pedigree analysis and confirmation of diagnoses through review of medical records is essential. Genetic Counseling for Double BRCA Mutation Carriers: A Case Series R. Klatt, H. Saal, E. Schorry, and K. Huelsman University of Cincinnati, Cincinnati, Ohio Although rare, it appears that the presence of two BRCA mutations does not significantly increase the risk of breast, ovarian, or other types of cancer compared to the presence of one mutation. To date there have been no known studies examining the psychosocial impact of receiving double positive BRCA results. Although single mutation carriers generally have not had serious short-term negative psychosocial consequences, carriers who did not expect to receive positive results have been found to be at higher risk for distress. Therefore, the purpose of this case series was to assess levels of distress by examining the perception of cancer risk and the coping strategies of two women of Ashkenazi Jewish descent who each had two BRCA mutations. Chapter 8 of K. Schneider’s textbook, “Counseling for Cancer: Strategies for Genetic Counselors, Second Edition” (2002) examines the psychological aspects of cancer counseling and was used as a model. This case series revealed that receiving an unexpected result of two BRCA mutations may result in increased feelings of anxiety, fear, and uncertainty in the short-term. The degree to which a patient might experience these feelings can be assessed by examining the patient’s personal cancer experience, family history, other cancer experiences, timing issues, and family structure and communication style. These are described and evaluated for each patient. It is also important to examine patient coping responses to evaluate whether or not they are adaptive or maladaptive. Using these criteria, the two patients reported here did not appear to be significantly distressed. In addition, several issues should be emphasized in a posttest counseling session for double BRCA mutation carriers: (1) The cancer risks do not appear to be increased over those for single mutation carriers. Thus, the standard BRCA surveillance and management options are still appropriate; (2) The risk for


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siblings and offspring to have inherited one or both mutations is 75% versus 50%; (3) Double mutation carriers who initially had a Multisite 3 BRACAnalysis may still desire full sequencing of the BRCA genes, despite the unlikely possibility of finding further mutations. Therefore, genetic counselors need to address the unique counseling issues that arise when counseling women of Ashkenazi Jewish descent with two BRCA mutations.

Health Beliefs and Attitudes of Individuals Affected With PKU and Diabetes S. Manzo, H. Northrup, P. Brosnan, J. Fletcher, D. Johnston, and C. Wicklund The University of Texas Health Science Center, Houston, Texas PKU is a metabolic disorder resulting in the inability to convert phenylalanine into tyrosine. Because individuals affected with PKU must maintain a strict and difficult diet for life, compliance becomes an issue for many. Dietary compliance is thought to be influenced by many factors: knowledge, complexity of the treatment, social barriers, cost, palatability, and accessibility of dietary substitutions. Many studies have attempted to assess some of these factors to determine the largest predictor of adherence to the diet. However, few studies have attempted to assess whether these children, both boys and girls, believe that strict dietary compliance is essential. We propose two hypotheses: (1) children with PKU do not believe strict dietary compliance is necessary to maintain a healthy lifestyle; (2) there is a difference in health beliefs of individuals with PKU compared to individuals with Type 1 diabetes. The study population consisted of individuals affected with PKU or Type 1 diabetes and their primary caregiver. The PKU population (56 children, 48 parents) was ascertained at two camps as well as The University of Texas Medical School at Houston—Medical Genetics Clinic. The diabetes population (55 children, 49 parents) was ascertained through The University of Texas Medical School at Houston—Endocrinology Clinic. The questionnaire was based on the Health Belief Model and validated by Dr. Rani Singh at Emory University. Our study found that although the majority of children believed that following the diet was important the positive aspects did not outweigh the negative aspects, which may contribute to decreased dietary compliance. The majority of children also felt that adherence is important because of parental and health professional satisfaction rather than an internal motivation for dietary adherence. In comparing the PKU and diabetes populations, the study found that both parent and child of the PKU population perceived higher levels of barriers and peer rejection than the diabetes population. Perceived levels of support and self-efficacy were similar among parents and children of both populations. Parents of both populations perceived the same levels of isolation whereas children with PKU perceived higher level of isolation than children with diabetes. However, children of both populations perceived the same amount of benefits whereas parent PKU population perceived higher benefits than parent diabetes population. Based on our results, future studies should focus on finding a correlation between health beliefs and compliance.


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Communicating Cancer Risk Information and Assessing Risk Perception R. Ruzicka, K. Blazer, P. Gambol, and J. Weitzel City of Hope Cancer Center A key aim of cancer risk counseling is to ensure that patients understand complex numerical information. Patients possess varying facility with numerical abstraction and counselors are challenged to find the most effective methods for communicating numerical risk information. A survey of counselors’ experience in communicating numerical information to patients undergoing cancer risk counseling was conducted on-line via the NSGC cancer SIG listserv. Use of graphic displays of risk information and various frequency and probability formats was ascertained. Twenty-nine cancer risk counselors completed the survey. Twenty-five counselors (86%) reported sometimes or always assessing their patients’ perceived risk for cancer during the counseling session. Variation was noted among the formats employed for assessing perceived risk: 55% of respondents use a qualitative estimate (e.g., very unlikely, unlikely . . . likely, very likely) and 45% ask patients to express risk as a percent. A minority of counselors assess risk as an odds ratio (e.g., one in 10) or by other means (e.g., numerical Likert scale). Most counselors (62%) incorporate graphic presentations of numeric risk information (e.g., bar or pie graphs, obtained from a variety of sources) into counseling sessions. Almost all counselors (93%) provide patients with a written summary of risks for cancer and risk-reduction options. Sixty-five percent of these counselors create a summary letter specifically for the patient, 28% send the patient a copy of the letter written to the referring doctor, and 7% do both. Of the counselors who write separate letters for the patient, most create customized letters after the counseling session, while a minority fill in templates at the time of counseling. When asked which method they would be most comfortable using to indicate their own perceived risk for cancer, 55% of respondents would use a percent and 21% would use a qualitative measure. Many counselors commented favorably on the utility of both graphics and presenting numeric risk information in a variety of formats to aid comprehension. Several counselors reported that they found using odds ratios and providing a comparison between the patient’s risk and other people’s risk to be most understandable to patients. However, some counselors believe that graphs may be frightening to patients, and others expressed concern over how to know whether a patient truly understands the risk information presented. The results of this study have prompted an investigation of the most effective methods for the communication and comprehension of numerical risk information for patients undergoing cancer risk counseling. An Assessment of Understanding in Genetic Counseling Hispanic Patients J. Seifert, H. Northrup, D. A. Johnston, and A. Tucker Williams University of Texas Health Science Center, Houston Introduction: It has been proposed that the use of culturally sensitive counseling techniques can result in improved understanding and integration of genetic


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counseling information by those of varied cultural and educational backgrounds. There have been no systematic studies assessing the impact of said counseling on understanding in the Hispanic population. Study aims: The development and administration of questionnaires to Hispanic and Caucasian women assessing patient understanding of genetic counseling information and identifying factors affecting understanding. Areas assessed: (a) demographic variables and (b) four areas of genetic counseling comprehension: (i) knowledge, (ii) risk comprehension and specific format understanding, (iii) beliefs, and (iv) interpretation of commonly used metaphors. Hypothesis: Hispanic women differ in their understanding of genetic counseling information as compared to Caucasian women. Results: A total of 107 questionnaires were collected, 56 questionnaires from Hispanic patients receiving counseling for advanced maternal age (AMA) and 51 from Caucasian controls. Responses were scored for understanding and scores were analyzed in context of demographic data collected. Overall, Hispanics demonstrated lesser understanding of genetic counseling information compared to Caucasians. Areas of significant difference between study and control population scores included: total questionnaire, knowledge section, risk section, and beliefs. Demographic variables affecting understanding were education levels, income, primary language, number of family members born outside the United States, and number of years living in the United States. Both groups had difficulties with risk understanding, with the expression of risks in percentages being the least understood format. This finding suggests that percentages may not be optimal for conveying risk information to a majority of patients. While the use of qualitative words was effective in counseling controls, Hispanic women greatly misinterpreted their use, implying a danger in attempting to qualify risk for this population. Metaphor answers were not determined to be significantly different between ethnic groups, and were therefore generally understood. In addition, there were no appreciable differences between Hispanic patients of differing countries of origin except in the belief category, which may be explained by the large proportion of Mexican individuals represented in the study. However, the ability to conduct a comparison of Hispanics from differing countries of origin is limited due to insufficient number of patients from countries other than Mexico. Conclusion and Significance: Demographic factors associated with ethnicity clearly influence understanding of genetic counseling information by Hispanic patients. Awareness of said influences will affect the selection of counseling techniques and strategies utilized by genetic counselors.

Genetic Conditions During Adolescence: Communication Patterns of Parents and Teens C. Turansky, A. Matthews, M. Drumm, D. Drotar, J. Scott, and N. Robin Case Western Reserve University, Cleveland, Ohio The purpose of this descriptive study was to explore the communication that occurs between parents and teens, with regard to an adolescent’s genetic disorder (Marfan syndrome or hemophilia). When an infant or child is diagnosed with a chronic condition, pertinent information is typically discussed with the parents.


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Little is known about how this information is ultimately conveyed to the child, and what questions remain unanswered during adolescence. Participants included 18 adolescents (12–19 years) with Marfan syndrome, 12 with hemophilia and at least one of their parents (N = 25 and 24). Using a mailed survey, teens were asked to recall how and when they first learned about their condition; how often they and their parents discuss their diagnosis; to describe their emotions when first told about the diagnosis, versus their current feelings; and to answer knowledge questions regarding the genetic component of their disorder. Most teens recalled learning about their diagnosis from their parents. However, 80% of parents did not receive any guidance on how to explain this information. Interestingly, many teens did not recall a specific conversation in which they first learned about their condition. Forty-one percent of teens with Marfan syndrome recalled feeling confused and 65% were scared or worried. In addition, 41% of teens with Marfan and 44% of teens with hemophilia recalled having questions they were afraid to ask. All participants reported discussing their disorder when necessary but did not want these conversations to monopolize daily interactions. Topics most often discussed included physical restrictions, body image, medical management, and the latest research. Participants were asked whether genetics played a role in ongoing care. Forty-four percent of parents from families with Marfan syndrome received their child’s diagnosis from a geneticist and 50% of these teens met with genetics to discuss their condition. The majority described their visit as informative. However, no child with hemophilia was diagnosed by a geneticist, and although 75% of these parents ultimately met with a geneticist or counselor, only 3/12 teens had this opportunity. Genetic counselors are uniquely qualified to meet with adolescents to review information regarding inheritance and discuss the psychosocial impact of their diagnosis during this life stage. These results suggest that families discuss the condition rarely and are pleased with this arrangement. Still, some teens have unanswered questions and counseling should be encouraged during this period especially if not routinely followed by genetic counselors. V. EDUCATION Knowledge and Attitudes of Modern Orthodox Jewish High School Students Toward Carrier Screening P. Cottrell Sarah Lawrence College, Bronxville, New York This study evaluated the knowledge and attitudes of Modern Orthodox high school juniors and seniors about Ashkenazi Jewish carrier screening. Survey questions were asked both before and after educational sessions provided at two Modern Orthodox high schools. Two hundred forty-one students completed pretests and posttests. This population was chosen to study because their needs are not well met by the screening models currently in place. Most Ashkenazi Jews are screened as part of routine care during pregnancy. In this model, the health care system is responsible to initiate screening. Many Orthodox Jews are screened by


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an organization called Dor Yeshorim, which screens high school students anonymously. In this model, the Jewish community is responsible to initiate screening. Carriers are not notified of their carrier status unless they are part of a carrier couple. The screening needs of many Modern Orthodox Jews fall between these two models. Knowledge scores improved significantly from 46 to 87%. For most attitude questions, no clear direction of change from pretest to posttest could be documented as a group, but individual responses changed in both directions. Over 60% of students wanted carrier screening, and more than 90% would want the screening done before pregnancy. Fewer students were opposed to anonymous testing on the posttest, although 76% still felt they would want to know their carrier test result. Students were more likely to agree that being a carrier of a genetic disease is not harmful, with 43% pretest increasing to 78% on the posttest. They were more likely to disagree with the statement that rabbis should require genetic testing before marrying a couple, with 45% disagreement increasing to 55% on the posttest. While the majority of respondents were unsure on both the pretest and posttest if they would marry someone if they knew both members of the couple were carriers, 18% were willing to become a member of a carrier couple, increasing to 27% on the posttest. In asking an open ended question about how they would feel if they found out they were carriers, there was a subtle shift from “scared,” “sad” or “bad” toward “cautious” or “better to know.” Providing information during high school about carrier screening may be the best way to assure that each individual in this population has the opportunity to select the personally appropriate screening method.

The Effect of Message Framing on Folic Acid Intake Knowledge, Attitudes, and Intentions S. Hashimoto, M. Levitt, E. Schorry, and N. Warren University of Cincinnati, Cincinnati, Ohio The U.S. Public Health Services recommends that all women of childbearing age who are capable of becoming pregnant consume 400 µg of folic acid daily. However, only 32% of women report taking a multivitamin with folic acid daily. Message framing, or the way information is presented, is one potential factor influencing women’s decisions to consume folic acid. Published studies suggest that gain-framed messages are more effective in promoting preventive behaviors while loss-framed messages are more effective in promoting detection behaviors. The purpose of this study is to evaluate the effect of message framing on women’s FAI knowledge, attitudes, and intentions. Since FAI is a preventive behavior, this study tested the hypothesis that a reading pamphlet emphasizing the benefits of taking folic acid daily would result in higher FAI knowledge, attitudes, and behavior scores than a pamphlet emphasizing the risks of not taking folic acid daily. Subjects were 237 women enrolled in undergraduate psychology courses. Subjects were randomly assigned to one of three conditions: gain-framed pamphlet, loss-framed pamphlet, or no pamphlet. Subjects’ baseline FAI behavior was assessed prior to the intervention, then immediately after the pamphlet/no-pamphlet intervention,


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their FAI knowledge, attitudes, and intentions were assessed. Compared to the no-pamphlet group, both gain- and loss-framed groups scored higher in knowledge by 22% ( p = 0.0001) and 21% ( p = 0.0004), respectively. Also, both gainand loss-framed groups agreed more than the no pamphlet group that FAI prevents birth defects ( p < 0.0001), must start preconceptionally ( p = 0.015), and prevents adult diseases ( p < 0.0001). However, there was no statistical difference between the two pamphlet groups’ knowledge ( p = 0.66) or attitude scores ( p > 0.5). Although there was no difference in FAI intentions among the groups ( p = 0.065), all three groups reported FAI intentions that were higher than their baseline FAI behavior. On average, subjects reported intending FAI 3–4 times/week, while their reported baseline behavior was 1–2 times/week. One possible explanation for this finding is that answering questions regarding “folic acid/multivitamin” alone may increase the intentions. In conclusion, a pamphlet intervention had positive effects on FAI knowledge and attitudes but no immediate effect on FAI intentions. Message framing had no effect on knowledge, attitudes, or intentions. The results of this study imply that improving knowledge and attitudes alone may not be sufficient to overcome the barriers to daily FAI.

The Relationship Between Genetic Counselors and Support Groups E. Kramer, J. Lewis, T. Pollin, and M. A. Wilson University of Maryland, Baltimore, Maryland As genetic technology rapidly advances, the number of genetic support groups is growing at an equally rapid rate. These groups play an important role in educating patients, professionals and the public about genetic conditions. For support groups to provide all the services they have the potential to offer, health care professionals need both to provide information to them, and to learn from them. This give-and-take relationship gives support groups life. The purpose of this pilot study was to gather information about the current state of the relationship between genetic counselors and support groups and to look more closely at factors thought to influence this relationship. The study was based on surveys of genetic counselors and support group leaders and members. It found that each group has a generally positive opinion and considerable awareness and use of the other group’s services. All of the genetic counselor respondents reported that they provide support group information to their clients. The pilot study also found that the vast majority of genetic counselors surveyed have a positive or somewhat positive opinion of genetic support groups. Although the results indicate that genetic counselors are aware of most support group functions, the data show that there are two functions (education and contribution to research) about which counselors could be better informed. The study found that there is a good flow of information from support groups to genetic counselors, but that genetic counselors could be more aware of the resources support groups have to offer and could make more use of them. Several characteristics of genetic counselors (including counselor’s specialty and use of the Internet to locate resources) seem to influence their knowledge about and use of support groups. In looking at support group respondents, the pilot study


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found that most have had a generally positive experience with genetic counseling. However, the data show that many support group respondents are not aware of all of the services genetic counselors are trained to provide. There are several features of support groups that seem to influence respondents’ level of knowledge about and use of genetic counseling services (including having seen a genetic counselor and having a genetic counselor on an advisory board). Because of the small size and limited nature of this pilot study, more research is needed to determine if its findings are truly representative of genetic counselors and support groups.

Recruitment Strategies and Perceptions of Genetics in an Epilepsy Family Database J. Mak, S. Vohra, and B. Minassian The Hospital for Sick Children, Toronto, Ontario, Canada Background: Rapidly increasing knowledge about the genetic basis of idiopathic epilepsy has created the need for more extensive and informed interactions between people with epilepsy and professionals in the field of genetics. Idiopathic epilepsy can be inherited as either a Mendelian or multifactorial trait. Although the identification of loci involved in epilepsy continues to progress, the role of clinical genetics in epilepsy care remains limited. Objectives: We established an Epilepsy Family Database containing clinical and family history information to serve as a resource for future research in genetics and genetic counseling. As part of this process, we compared several strategies for identifying subjects and also examined the knowledge and perceptions of genetics among research participants. This project represented the collaboration of professionals specializing in genetics, epidemiology, and neurology. Methods: Recruitment strategies included mailings to patients of a community-based neurologist, referrals from neurologists, and publicity through local epilepsy organizations. One hundred twenty-nine people with epilepsy and parents of children with epilepsy completed a survey combining previously published tools and specifically-designed questions to assess knowledge and perceptions of genetics, as well as clinical characteristics and experiences. Results: Direct mailing to patients was the most sensitive recruitment strategy, although this approach was also the most expensive and time-consuming. Analysis of the survey responses indicated that respondents overestimate the population prevalence and recurrence risks for epilepsy. The mean estimate for prevalence was 15%, and the mean estimates for recurrence were 23% with an affected sibling and 29% with an affected parent. Perception of risk was associated with the history of epilepsy in the respondent’s family. Sixty-seven percent of respondents indicated they thought genetic factors were a major cause of epilepsy, and a family history of epilepsy was found to also be associated with this belief. Fifty-three percent of respondents expressed a desire for more information on the genetics of epilepsy. Other areas of interest included improved diagnosis and prognosis and the development of treatments with less side effects. Conclusions: Informed collaboration between genetics professionals and epilepsy patients is critical to furthering scientific knowledge and clinical management in this area. The value


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of this relationship appears to be recognized by many epilepsy patients. However, further education and counseling are needed, as evidenced by the limitations in survey respondents’ knowledge and by their stated interest in genetics and in areas of epilepsy care which may be indirectly benefited by genetic research. Evaluating Health Care Providers: What Do They Know About the Genetics of Autism? E. Neumeister, S. Folstein, B. Lerner, C. Wolpert, and B. Rosen-Sheidley Brandeis University, Waltham, Massachusetts Pediatricians and child psychiatrists are the health care providers likely to first encounter children with autism spectrum disorders. Previous research suggests that a subset of these providers, identified primarily as autism specialists, provide genetic counseling despite a lack of basic knowledge about the genetic basis of autism. For example, the majority were unable to correctly identify the recurrence risk for siblings of autistic probands. We hypothesized that health care providers who are not autism specialists would also have limited knowledge of autism genetics. To investigate this question, we mailed a 44-item survey to members of the American Medical Association (AMA) with a specialty in pediatrics or child/adolescent psychiatry. The survey included questions about demographic information, education and employment, clinical evaluation practices, genetic counseling for autism, general genetics, and the genetic basis of autism. Survey questions were either multiple choice, true/false, yes/no, or Likert scaled. Five hundred surveys were sent to pediatricians and 499 were sent to child/adolescent psychiatrists. Sixtyeight surveys were returned and 63 were included in the data analysis, for a return rate of 6.9%. Overall, performance on knowledge-based questions was poor. Only 19.7% of respondents correctly identified the sibling recurrence risk as 6–8% and only 18% correctly identified the sibling recurrence risk for multiplex families as 25%. Only 10.9% of the respondents knew that 10–15% of individuals with autism have an underlying genetic syndrome or chromosome abnormality. None of the respondents correctly identified all of the genetic syndromes associated with autism (Joubert syndrome, Tourette’s syndrome, neurofibromatosis, tuberous sclerosis complex, phenylketonuria, fragile X syndrome, and Rett syndrome) and 41% indicated that they were “Not Sure.” Unlike the autism specialists previously surveyed, the majority of respondents do not provide genetic counseling themselves. Seventy-two percent indicated that they were uncomfortable with their ability to provide genetic counseling for autism and 87% indicated that they refer families for genetic counseling. Sixty-six percent of respondents always or sometimes refer families for a genetics evaluation. Therefore, although pediatricians and child/adolescent psychiatrists appear to have limited knowledge of autism genetics, they are aware of the need for a genetics referral. Although based on a small sample size, these preliminary results suggest that these health care providers would benefit from education regarding the genetics of autism. In addition, as the public becomes increasingly aware of the genetic factors involved in autism, genetic counselors will need to be prepared to provide genetic counseling.


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A Pilot Study on Psychiatric Genetic Counseling: Counselors’ Needs H. Peay and J. McInerney National Coalition for Health Professional Education in Genetics (NCHPEG) Researchers are getting closer to understanding the genetic components of psychiatric disorders, and the need to educate genetics professionals about psychiatric genetics is critical. NCHPEG is producing a CD-ROM, funded by the U.S. Department of Energy, to educate genetic counselors about psychiatric genetics. In the fall of 2002 NCHPEG will provide CD-ROMs to NSGC members and to each genetic counseling training program. To guide development we surveyed two groups of counselors about their perceived needs and comfort. Few such data exist in the literature. While both survey populations were small and self-selected, and may not reflect NSGC membership as a whole, the results provide insights into counselors’ knowledge of, and comfort with, psychiatric genetics. In the first phase, 209 NSGC members completed an on-line survey. Counselors overwhelmingly identified a need for information on: schizophrenia, bipolar disorder, and major depression; major psychosocial issues; evaluating psychiatric diagnoses; the etiology of psychiatric disorders; risk assessment; evaluating multiplex families and genetic subtypes; managing uncertainty; teratogenicity of psychotropic medications; and counseling for those at risk. During field-testing 41 practicing genetic counselors (PGC) and 28 second-year genetic counseling students (GCS) completed a pretest survey. Students indicated less preparedness to provide psychiatric counseling, but practicing counselors also indicated deficits. When asked how prepared they feel to raise the issue of psychiatric disease with their clients, 32% (PGC) and 67% (GCS) felt either very unprepared or somewhat unprepared; when asked how prepared they feel to answer questions about psychiatric disease from their clients, 44% (PGC) and 96% (GCS) felt either very unprepared or somewhat unprepared; when asked how comfortable they feel providing psychosocial counseling for psychiatric disease, 54% (PGC) and 78% (GCS) felt either very uncomfortable or somewhat uncomfortable. When asked how often they raise issues related to psychiatric disease when they take a family history, 22% (PGC) and 46% (GCS) responded never or seldom. When asked what limits their ability to provide psychiatric genetic counseling, 59% (PGC) and 93% (GCS) chose “My understanding of psychiatric diagnoses,” 83% (PGC) and 82% (GCS) chose “My knowledge of research in psychiatric genetics,” and 39% (PGC) and 75% (GCS) chose “My lack of knowledge/experience with psychosocial issues involved in psychiatric genetic counseling.” These results suggest a need for education on psychiatric genetics within the genetic counseling community. Educating the Teenage Population About Genetic Services and Careers in Genetic Counseling: A Needs Assessment S. Randall, N. Lazarciuc, and S. Cook University Health Network, Toronto, Ontario, Canada A questionnaire was administered to a group of 45 high school students following a career day presentation about genetic counseling. The goal of the survey


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was to address the importance of educating high school students regarding careers in genetic counseling, to assess their perceptions about the need for genetic services and their opinions of genetic testing and genetic discrimination. Of the 45 students attending the career seminar, 31 completed the survey for an overall response rate of 69%. Prior to the presentation, 90% had not previously heard of genetic counseling. However, 71% expressed interest in learning about careers in genetics during high school. When asked about the relevance of genetic services in society, 83% of students indicated that genetic services were important and 20% expressed interest in pursuing a career in genetic counseling. To explore their opinions about genetic testing and genetic discrimination, two case scenarios were presented. When asked to assume that they were at a 50% risk to inherit Huntington’s disease, 81% of the students indicated that they would undergo genetic testing. Planning for the future was specified as the most important reason for testing. Furthermore, the majority indicated a preference to testing now rather than in the future. In a similar scenario for inheriting a BRCA1 mutation, 73% indicated they would want genetic testing, the majority for purposes of planning their health care or for the “sake of knowing.” Likewise, most identified a preference to have testing now. To examine issues of genetic discrimination, students were requested to rate their concern that an employer or an insurance company could use results against them. Forty-eight percent expressed concern regarding discrimination by an employer and 75% by an insurance company. Preliminary results from this pilot study demonstrate the importance of shifting the focus of educational efforts from university to high school students. By targeting this population, we will not only attract more individuals to the field, but will also educate many others about the availability of genetic services. Currently, minimal information is available regarding the needs of teenagers confronted with the option of genetic testing for adult onset diseases. This study suggests that teenagers are interested in pursuing testing for reasons similarly sited by adults and also have concerns regarding genetic discrimination. Future research with a larger sample size is required to assess the results obtained from this study with greater accuracy.

Educational Practices About Folic Acid Supplementation—Doomed to Failure? A March of Dimes Sponsored Project R. Resta, A. Hoffman, and A. Roche Swedish Medical Center, Seattle, Washington Objective: It has been about a decade since researchers first showed that folic acid supplementation prior to pregnancy is a key factor in preventing neural tube defects. However, studies have shown that most fertile women have inadequate folic acid intake to prevent neural tube defects. This may in part be due to the educational practices of their health care providers. To determine if health care providers are properly educating women about the importance of folic acid, we assessed the educational practices of obstetricians and family practitioners about folic acid supplementation, and compared these practices with patient


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recall. Methods: Surveys were distributed in six rural and urban medical clinics in Washington state. Physicians were asked about their educational practices on pregnancy-related topics, including folic acid. A similar survey was provided to a convenience sample of their female patients who read English or Spanish, asking them to recall if these topics were discussed either before or during pregnancy. To determine validity, a random sample of patient charts was surveyed for documentation of education. Results: Thirty-four physicians and 196 patients completed surveys. Two hundred fifty-six charts were reviewed. The interobserver agreement on chart reviews was >0.95. During pregnancy, the majority (>80%) of patients remembered their physician discussing folic acid supplementation, and over 80% of physicians recalled discussing folic acid supplementation with their pregnant patients. Critically, however, about 70% of nonpregnant patients did not recall a discussion about folic acid, and more than 80% of physicians stated they did not discuss folic acid with their nonpregnant patients. Documentation of patient education was inconsistently recorded in charts, but generally supported the results of the survey. Conclusions: For most of these women, education about folic acid supplementation occurred at an inappropriate time, that is, after conception, when supplementation will not prevent neural tube defects. To rectify this situation, we initiated a multipronged effort to improve folic acid educational practices in Washington state, including a state wide mailing, advising physicians of the importance of preconception folic acid supplementation; a web site containing physician and patient information; articles in medical organizations’ newsletters; focus groups with medical practices to help develop useful educational materials; and development of a “Well Woman Visit” form to document educational efforts.

Assumptions About Patients Based on Their Socioeconomic Status—An Invisible Barrier to the Prevention of Birth Defects: A March of Dimes Sponsored Project R. Resta, A. Roche, and A. Hoffman Swedish Medical Center, Seattle, Washington Objectives: Previous research by the CDC’s Pregnancy Risk Assessment Monitoring System (PRAMS) has suggested that a woman’s socioeconomic status influenced the educational issues that her physician discussed with her during prenatal visits. We therefore sought to determine the extent to which the socioeconomic status of patients influences physicians’ educational efforts. Methods: We surveyed physicians about their prenatal educational practices on several pregnancy-related topics. We also surveyed a convenience sample of patients in these clinics to determine if patient recall matched the stated educational practices of the physicians. Surveys were distributed in six Washington state rural and urban clinics (four family practice, two Ob/Gyn). A similar survey was provided to a convenience sample of their fertile female patients who read English or Spanish, asking them to recall if these topics were discussed before or during pregnancy. To determine validity, a random sample of patient charts was surveyed for


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documentation of educational activities. Chi-square analysis was used to analyze data by patient race and socioeconomic status. Results: Thirty-four physicians and 196 patients completed surveys. Two hundred fifty-six charts were reviewed. The interobserver agreement on chart reviews was >0.95. Physician surveys showed that they said they discussed all prenatal topics with all of their patients. However, patient surveys indicated that physicians were more likely to discuss alcohol use and cigarette smoking with pregnant patients who were less educated and on government assistance than they were with women were better educated and had private insurance ( p > 0.01). Socioeconomic status did not influence educational activities by physicians about other prenatal issues. Chart documentation of education was poor, but generally supported the results of the patient survey. Conclusions: The socioeconomic status of a woman influences which topics her physician will discuss with her during pregnancy. Either physicians inappropriately assume that better-educated, upper socioeconomic status women are less likely to use alcohol and cigarettes during pregnancy, or physicians are less comfortable talking about such topics with patients who are socially similar to physicians. Given that alcohol is the most common preventable cause of mental deficit and cigarette smoking is the most common preventable cause of low birth weight, such invisible barriers to education can have important medical and economic consequences.

Web-Based Survey of Families With Autism: Reassessing the Need for Genetic Education B. Rosen-Sheidley, C. Wolpert, J. Feigon-Schiffman, C. Palmer, S. Folstein, and M. Pericak-Vance New England Medical Center, Boston, Massachusetts Determining the genetic basis of autism has been the focus of multiple international research efforts. As a result of this progress, we identified a need to educate the public about research findings and their potential clinical application. Previously we reported the results of a pilot survey mailed to families participating in our collaborative autism research projects. These families all had children diagnosed with autism or related disorders. Based on the pilot data an educational web site, www.exploringautism.org, was developed for families to inform them about the genetic basis of autism. Since the pilot data were generated from a small number of families participating in autism genetics research, we hypothesized that a larger, nonresearch oriented population would yield different results. Therefore, an on-line version of the survey was made available on the exploringautism.org web site, which was launched in February of 2002. Since then, more than 9500 people have visited the web site, and 433 surveys have been submitted. Similar to our pilot population, 387 (89%) of the respondents have a family member with autism, with the majority (81%) having an affected child. However, in contrast to the pilot study sample, a majority of the respondents (93%) indicated that they are not currently participating in research. When asked about possible causes of autism, 85% of respondents identified genetic factors, while 31% cited vaccinations and


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33% cited other environmental factors (despite the lack of medical evidence for the latter). Although 24% of respondents correctly identified the recurrence risk for autism among siblings, 38% of respondents grossly overestimated the risk and 32% were unsure. Most respondents favored genetic testing to confirm a diagnosis of autism (92%) and genetic testing for prenatal diagnosis of autism (75%). Most respondents (97%) indicated an interest in learning more about the genetic basis of autism. Of note, 70% of respondents indicated that learning about the genetic basis of autism would reduce their anxiety, and could potentially help them with family planning. In summary, the responses obtained from this follow-up survey were remarkably similar to those obtained from our pilot survey. This suggests that a need and desire for education regarding the genetics of autism is not limited to families participating in genetic research. Additionally, our data indicate that web-based tools are an effective method to reach families, for whom obtaining up-to-date knowledge might otherwise be difficult for logistical and financial reasons.

Severe Osteogenesis Imperfecta: Evolving Roles of Genetic Counselors L. Terry, M. Berry, and T. Jewett Wake Forest University School of Medicine, Winston Salem, North Carolina Osteogenesis imperfecta (OI) is a connective tissue disorder that displays significant clinical heterogeneity with outcomes ranging from mild bone fragility to perinatal death. Severe OI was historically classified into types II and III by a system based on radiographic and physical evidence. Although this classification system was helpful in distinguishing severe types of OI from mild, it was not as helpful in delineating the severe types from each other because of significant overlap of features. Advances in biochemical and molecular testing have helped to differentiate types of severe OI and have shown that the vast majority of cases result from new dominant mutations within the genes for type I collagen. Although autosomal recessive inheritance is rare, these tests can also help clarify recurrence risks in some cases. We present a case that illustrates that although advances in testing strategies have provided helpful information for genetic counseling, they are also elucidating the complex nature of this disorder and adding new challenges and roles for genetic counselors. L.H. was prenatally diagnosed as having bowed, foreshortened long bones with decreased mineralization, polyhydramnios and edema of the scalp and chest. OI was highly suspected, and amniocytes were sent for COL1A1 and COL1A2 mutational analysis. Results were negative. At birth, radiographs and physical examination findings were consistent with OI, either mild type II or severe type III. Fibroblasts were sent for collagen analysis in order to confirm the diagnosis since almost all cases of severe OI result in abnormalities of type I collagen. Surprisingly, collagen results were normal. L.H. is very unusual in that she presents radiographic and clinical evidence of OI but has normal molecular and collagen analyses. Her case raises the possibility that that she has OI due to a different locus, which could potentially be autosomal recessive. Given this information, L.H.’s parents have chosen to involve her in bisphosphonate therapy


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to increase bone density and decrease fracture rate. This case illustrates how the role of the genetic counselor in cases of severe OI has evolved to include not only meeting the psychosocial needs of the family and basic knowledge of etiology of the disorder, but also being able to interpret results of complex testing strategies, integrating that information with the clinical information and applying it to the clinical genetic counseling setting. In addition, it stresses the need for genetic counselors to be current in the newly developing treatment modalities for genetic disease.

Monitoring Genetic Counseling Students’ Progress in Developing PracticeBased Competencies Through Standardized Patient Encounters A. Trepanier, A. Greb, and M. Kavanaugh Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigam We have incorporated standardized patient (SP) encounters into the curriculum of our genetic counseling graduate program to help monitor students’ progress in developing the American Board of Genetic Counseling practice-based competencies. The first SP encounter, which occurred at the end of the first semester of training, assessed whether students had acquired the skills necessary to begin clinical internships. This encounter involved a pregnant woman who presents for genetic counseling because she is at risk for carrying a dystrophin gene mutation. Students were expected to prepare the case, take a complete history, conduct a risk assessment, explain the genetics and natural history of the condition, and offer genetic testing in a nonbiased manner. The SP’s were trained to reveal specific psychosocial and family history information only if asked appropriate questions. The sessions were videotaped and later evaluated by the program directors. The results revealed that the students’ communication skills were on target. However, their skills related to taking a targeted family history, understanding the importance of reviewing medical records, and nondirective counseling were not, prompting specific curriculum adjustments. The encounter also allowed the instructors to assess students’ counseling skills prior to their entry into a two-semester psychosocial course. The second encounter occurred at the end of the second semester. In this encounter, the SP returns for genetic counseling to review her carrier results. Students were expected to perform a psychosocial assessment, present prenatal diagnosis and pregnancy management options in a nonbiased manner, and facilitate decision-making. Psychosocial factors incorporated into the case (unplanned pregnancy, resulting marital tension, patient’s recent experience with a support group) were only revealed if the student asked specific questions. Immediately after the session, students received feedback from the SP on a number of variables including whether the student balanced information sharing with attention to the patient’s emotional reactions. The sessions were again videotaped and evaluated by the program directors. Individual strengths and weaknesses were identified. Plans for addressing these during the clinical internships were implemented. In summary, SP encounters provide a powerful method for assessing and guiding


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the development of genetic counseling skills for students in training. They also allow program faculty to assess whether curriculum goals are being met. The benefit of SP versus “real” patient encounters is that cases can be developed to specifically and consistently assess different components of the practice-based competencies.

Involving Health Care Providers Personally and Professionally in Birth Defects Prevention N. Warren, K. Augustine, S. Hashimoto, and M. Wojtasiak University of Cincinnati, Cincinnati, Ohio Neural tube defects (NTDs) affect 4000 pregnancies in the United States each year, with costs exceeding 2 billion dollars annually due to associated morbidity and mortality. Although NTDs are a substantial public health concern, most individuals are not aware that 50–70% of neural tube defects can be prevented when women take 0.4 mg of folic acid daily. Prevention efforts are currently limited because few health care providers routinely discuss the benefits of folic acid with their clients. By educating providers about the benefits of folic acid ingestion, providing client education materials, and encouraging providers to take a multivitamin daily, we develop a network of providers who routinely promote folic acid ingestion in clinical practice. The purpose of this study was to design and implement a program to involve health care providers personally and professionally in birth defects prevention. Our project educated 71 (37%) nurses, 45 (23%) family support workers/home visitors, 29 (16%) social workers, 24 (12%) administrators, 12 (6%) dieticians, 9 (5%) counselors, who serve 2699 clients through local public health care agencies. The average provider age was 37 years; 85% were females of reproductive age. Each provider participated in 30–60 min inservices on the benefits of folic acid ingestion and received several “tools” for educating clients about birth defects prevention in their daily practice. Surveys were administered prior to the intervention, following the inservice, and 1–5 months later to assess knowledge level, personal folic acid habits, personal behavior changes, and client interest level. Knowledge of folic acid increased significantly (35%; p < 0.0001) between the pretest and posttest for all professions. Prior to the intervention, 41% (78/190) of providers reported taking a daily multivitamin. End point evaluation data collected 1–5 months later demonstrated that 80% of providers were taking a daily multivitamin ( p = 0.071). Prior to the inservice, 38% (69/190) of providers reported discussing folic acid and NTDs with at least one client weekly; however, 1–5 months postintervention, 88% of providers reported discussing folic acid with their clients. End point evaluations also indicated a positive correlation between providers taking a multivitamin daily and routinely discussing folic acid with their clients ( p = 0.074). Providers who participate in an educational inservice and either have access to resources about the impact of folic acid ingestion on birth defects prevention or who themselves take a multivitamin daily are more likely to educate their clients about folic acid and birth defects prevention.


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VI. PEDIATRICS Mosaicism for Deletion of 15q11.2q13 in a Patient With Atypical Angelman Syndrome Phenotype: A Second Case L. Berkheim, S. O. Lewin, and J. C. Carey University of Utah, Salt Lake City, Utah We report a child with mosaicism for a deletion 15q11.2q13 involving the PWS/AS critical region. Our patient has global developmental delay with language more severely impaired than motor skills, normal growth with head circumference at the 95th centile, unusual gait and sleep disturbance. Her facial features include a long philtrum with a thin upper lip, prominent forehead and wide mouth. A seizure disorder was recognized at 3.5 years of age with an EEG pattern consistent with Angelman syndrome (AS). Chromosome analysis on peripheral blood lymphocytes indicated mosaicism for a visible deletion at 15q11.2q13 at 550 band level in 35% of cells. FISH studies showed mosaicism for a deletion in the AS critical region in 50% of scored cells. PCR-based methylation studies indicated a normal biparental methylation pattern, although the sample showed slightly reduced amplification of the maternal signal, supporting that the deletion is maternally derived. Tekin et al. (2000) reported a similar case with normal methylation pattern and mosaic deletion of the AS critical region detected by FISH. Our patient closely resembles the reported case in facial features and developmental profile. Both cases appear to have a milder presentation compared to typical AS patients. In summary, methylation studies are commonly used as an initial screening for AS because most cases show only paternal methylation regardless of the molecular explanation for the condition. However, these two cases demonstrate that methylation studies alone are not sufficient to rule out AS. Chromosome analysis with FISH should also be performed in patients with clinical features of AS despite a normal methylation pattern. Down Syndrome and Autistic Spectrum Disorder: Prenatal, Neonatal, and Neurological Risk Factors K. Borman University of Maryland Baltimore, Baltimore, Maryland The prevalence of Autistic Spectrum Disorder (ASD) in the Down syndrome (DS) population has been estimated to be between 5 and 10%. A growing number of DS children are being identified with features of ASD. Children with DS and ASD have impairments in social interactions, verbal and nonverbal communication, an intolerance to change, restricted activities and stereotypies. The goal of this study is to identify any known prenatal, perinatal, and neurologic risk factors that may be associated with the development of ASD in children with DS. Subjects with DS/ASD have been identified using the Autistic Behavior Checklist (abc) and DSM-IV criteria. Medical records were obtained and reviewed for 55 DS/ASD subjects and 44 DS subjects. Prenatal findings were recorded and perinatal and


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neurological risk factors were scored using an existing perinatal risk inventory and a devised neurological risk inventory. This study found no significant differences in pre- and perinatal events between the DS/ASD and DS control group. However, there was a significant difference in neurological score between the DS/ASD and DS group. Furthermore, the presence of pathologic reflexes and developmental regression was a positive predictor of abc score. These findings suggest a greater frequency of underlying changes in neuronal organization in individuals with ASD. At this point, nothing can be done to prevent ASD but the accurate identification and recognition of DS/ASD is critical. If potential “risk factors” can be identified in the DS population to alert physicians and families to the development of a severe behavioral disturbance, a targeted group of children may be monitored closely and earlier intervention techniques may be used. Fanconi Anemia: What Happens When Pediatric Patients Grow Up? A. Carr, J. Peters, B. Alter, L. Leathwood, J. Loud, N. Weissman, I. Velazquez, K. Briand, and M. Greene Westat, Inc., Rockville, Maryland Fanconi anemia (FA) is one of a group of genetic conditions known as the inherited bone marrow failure syndromes (IBMFS). FA affects the development and function of diverse organ systems. Children with this disorder may be referred to pediatric genetics clinics because of dysmorphic features apparent at birth or during childhood. Among the characteristic physical findings in Fanconi anemia are short stature, café-au-lait spots, and radial ray anomalies. However, at least 25% of reported cases have no such physical findings. Some people with FA are not diagnosed until they develop progressive bone marrow failure, which may require bone marrow transplantation, and which may be complicated by myelodysplastic syndrome or acute leukemia. Others develop aerodigestive or gynecological carcinomas as young adults. Some patients are first identified while they are being evaluated as a potential bone marrow donor for an affected sibling. As treatment of hematologic and other problems of early life has improved, these patients are beginning to be seen in adult clinical settings. It is the purpose of ongoing research to discover what the genetic counseling, medical, and psychosocial needs of these adult patients are. We present two patients evaluated through our National Cancer Institute IBMFS epidemiological research protocol (http://marrowfailure.cancer.gov), which is investigating the increased risk of malignancies in patients with IBMFS, including FA. These patients must deal with FA-specific health problems as well as those common in the general population. Patient #1 is a 30 year-old man who had hand anomalies at birth that were partially repaired as a toddler but who was not diagnosed with FA until age 7. During his study-related clinical evaluation, this man learned that he had a long list of unexpected medical problems including orthopedic, endocrine, dental, hematologic, ophthalmologic, audiologic, and psychosocial difficulties. Patient #2 is a 33-year-old woman who was diagnosed with FA at age 7 after her older brother was diagnosed with FA and leukemia, and siblings were being evaluated as possible bone marrow donors. She is currently dealing with the aftermath of extensive surgery for gynecological cancer, has oral


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leukoplakia (a precursor to oral cancer), and complex hematological problems. These cases will be used to illustrate how genetic counselors may participate in developing a new model for helping FA patients make the transition from pediatric to adult care.

The Clinical Significance of DG Heterozygosity: Literature Review and MetaAnalysis H. Creswick, M. Barnes, L. Lawson, and V. Proud Children’s Hospital of The King’s Daughters, Norfolk, Virginia Newborn screening permits identification and treatment of infants with genetic disorders. Test results imply genetic information and can have implications on future insurability. We report a 16-month-old female identified by newborn screening to be a Duarte/galactosemia (DG) heterozygote who was denied insurance because of potential medical complications resulting from her genotype. Classic galactosemia (GG) has essentially zero Galactose-1-Phosphate Uridyltransferase (GALT) enzyme activity and, despite dietary lactose restriction, may cause clinical complications including cataracts, liver problems or ovarian dysfunction. The DG variant; however, is heterogeneous with approximately 25% GALT activity. Theoretically, this level should minimize risks for medical problems. To investigate this, we performed a comprehensive literature review and meta-analysis. Hypothesis: DG heterozygosity should cause no medical complications that would limit insurability or impact medical management. Methods: Initial review began with 701 references from PubMed (1965–2002) with a search strategy that included “galactosemia OR Duarte OR genotype OR phenotype.” We reviewed the titles and abstracts and identified 33 articles that met study inclusion criteria addressing: (i) phenotype, (ii) molecular studies, (iii) biochemical studies, or (iv) genotype/phenotype correlation in GG or DG individuals. Articles included cases, case-control, and cohort studies. Information from two independent reviewers was compiled in a database for analysis. Results: With regard to medical complications in DG heterozygotes: 12/33 articles clearly support; 10/33 completely deny; 7/33 neither support nor deny; and 4/33 both support and deny. Nineteen articles specifically studied DG heterozygotes. Seven supported a clinical phenotype with four reporting cases of cataracts, jaundice, hepatomegaly, lethargy, feeding problems, increased FSH or decreased ovarian function. One article found an increased number of Duarte heterozygotes in families with ovarian cancer. In contrast, 7/19 articles completely denied any clinical phenotype in DG individuals. The remainder were mixed or neutral. Ten out of 19 articles addressed in vivo galactose metabolism in DG heterozygotes. Six articles supported abnormal galactose metabolism with increased urinary galactitol or RBC Gal-1-P; while four articles denied abnormal galactose metabolism primarily citing normal in vivo galactose breath testing. Conclusions: While there is biochemical data and case reports to suggest possible pathogenesis in DG heterozygotes, there are many conflicting reports in the literature. Our case highlights that with current insurance and privacy issues, such conflicting information can


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be detrimental. Clearly, a prospective study or comprehensive analysis of longitudinal registry data needs to be performed in order to define the actual risk of DG heterozygosity. Perception of Disease Severity in Adolescents Diagnosed With Neurofibromatosis Type 1 C. Drake, A. Lovell, R. Hopkin, R. Noll, and E. Schorry Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio Neurofibromatosis type 1 (NF1) is an autosomal dominant condition whose features include a number of cutaneous, systemic, cognitive, and behavioral problems. The degree to which NF1 impacts an adolescent’s daily life depends on the clinical features of the condition as well as on social and emotional influences, including the adolescent’s perception of the condition’s severity. The purpose of this study was to examine the relationship between adolescent and parental perception of disease severity and the clinical severity of NF1 as perceived by health care providers. The Perception of Severity of Chronic Illness (PSCI) questionnaire was administered to 56 parents and 47 adolescents with NF1. Scores assessing the clinical severity of the adolescent’s condition were assigned. Correlation coefficients and the paired t test were used to evaluate the relationship between the clinical features of NF1 and the families’ perceptions. Parental perceptions were significantly correlated with the degree of systemic (r = 0.3116, p < 0.05), cognitive (r = 0.4911, p < 0.0001), and behavioral (r = 0.3341, p < 0.05) impairment of the adolescent. Adolescent perception was correlated only with the degree of cognitive impairment (r = 0.5429, p < 0.0001). Parental and adolescent perceptions were closely correlated (r = 0.6724, p < 0.0001); however, adolescents consistently viewed the condition’s impact as being less than the parents’ perceptions ( p < 0.001). The results of this study have implications for the clinical care and counseling of families of adolescents with NF1. First, families dealing with more systemic, cognitive, and behavioral complications of NF1 perceive the impact of the condition on daily life as being greater than those families facing fewer complications. Ongoing psychosocial assessment is important in understanding how the family is coping with the perceived impact of the condition. Secondly, parents and adolescents do not necessarily perceive the condition’s impact in a similar manner, emphasizing the importance of eliciting concerns from both during clinic visits. MECP2 Mutations Found in Patients Initially Referred for Angelman Syndrome Testing R. Heleski, M. Friez, R. Best, and K. Corning University of South Carolina, Columbia, South Carolina The phenotypic overlap in girls with Angelman syndrome (AS) and those with Rett syndrome (RTT) has been recognized for years. However, only recently


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has the relationship between testing negative upon methylation studies for AS and subsequently testing positive for mutations in MECP2, the gene associated with RTT, been studied. Unidentified samples were obtained and MECP2 was sequenced from a relatively large cohort of unrelated female patients who were initially referred to the Greenwood Genetic Center or Fullerton Genetics for AS methylation analysis and found to be negative. Of the 61 samples studied, nine were found to have mutations (14.75%) in MECP2. One sample revealed a base pair change not previously described as causing the RTT phenotype. (1) This study nearly doubles the number of female samples that have been analyzed to determine the significance of this specific relationship and has demonstrated consistent findings in comparison to the previous reports. The cumulative total determined by three independent studies is approximately 14%. This indicates a significant number of females with a clinical diagnosis of AS in the absence of molecular confirmation may actually be misdiagnosed. Therefore, MECP2 testing should be considered in females with an AS presentation who do not have molecular confirmation of their diagnosis. (2) We present a cost analysis and recommend a stepwise molecular testing protocol for girls with overlapping features of both syndromes in which AS methylation analysis is followed by MECP2 sequencing. (3) Furthermore, we evaluate the phenotypic findings of the females that tested negative for AS and positive for RTT and present the consistencies among them. These include microcephaly, ataxia, repetitive hand movements as well as an absence of growth retardation and hyperventilation. We recommend that the phenotypic features of the females who fall into this particular group of patients continue to be described in order to further define each of the two syndromes. In addition, continuing analysis of the features of females testing negative for both tests may be beneficial in determining the etiology of their phenotypic presentation.

Cornelia de Lange Syndrome: Parental Preferences Regarding the Provision of Medical Information D. Hinkson, S. Vohra, S. Kennedy, and A. Levin The Hospital for Sick Children, Toronto, Ontario, Canada Published studies and anecdotal reports have highlighted parental dissatisfaction with quantity or quality of information provided at the time of their child’s diagnosis. We surveyed 57 caregivers of children with Cornelia de Lange syndrome (CdLS) using a self-report questionnaire designed to elicit their experiences with receiving information regarding health concerns associated with this multisystem disorder. Caregivers were surveyed at two CdLS family conferences (n = 50) as well as by mail (n = 7). The most frequent sources of information at the time of diagnosis were a health care provider (86%) and the CdLS Foundation (72%). These were also the most frequently used current information sources (77% and 93%, respectively). Health problems most often reported by caregivers were problems with speech and language (95%), mental development (86%), or growth (83%). At the time of diagnosis, information was most commonly available on mental development (88%), growth (88%), and feeding problems (70%). Most caregivers


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(81%) indicated a desire to receive information about all possible health concerns related to CdLS, whether or not their child would develop them. On average, caregivers recalled receiving information on 64% of the of health concerns that their child already had or went on to develop. Caregivers ranked problems with gastroesophageal reflux, feeding and behavior as the most important health concerns. Information on two of these three main concerns (gastroesophageal reflux and behavior) was available to fewer than half of the caregivers at diagnosis. Only 40% of caregivers were satisfied with the amount of information received at diagnosis and only 46% felt that the information they received was useful. Caregivers indicated a preference for receiving information in written format (59%) or verbally (39%). Our results indicate that caregivers of children with CdLS report a high need for information at diagnosis, regarding their child’s actual or potential health concerns. Dissatisfaction may result from both a deficiency in information provided, as well as a mismatch between issues mentioned and those that caregivers deem most important. Caregivers may benefit maximally from receiving information in person at the time of diagnosis as well as having an additional written source of information (such as the CdLS Foundation’s information booklet). These findings highlight the value of disease specific support groups and may have relevance to other multisystem disorders.

Diagnosis and Infant Screening for Duchenne Muscular Dystrophy: Parents’ Experiences and Attitudes C. Hoffman, J. Tsipis, and P. Hawley Brandeis University, Waltham, Massachusetts Duchenne muscular dystrophy (DMD) is the most common and severe form of the hereditary childhood myopathies. There have been widespread infant screening programs for DMD in countries other than the United States, growing partially out of a concern about delayed diagnosis. In contrast, there has been little available information about delay of diagnosis and attitudes about infant screening for DMD in the United States. The purpose of the current study was to gain a better understanding of parents’ diagnostic experiences and attitudes about infant screening in this country. Parents of boys diagnosed with DMD were asked to complete an on-line survey containing questions about demographic information, family history, diagnostic experience and attitudes about infant screening. Participants were solicited through the Parent Project Muscular Dystrophy and Muscular Dystrophy Association web sites. Data from 93 participants who resided in the United States were analyzed. The average age of diagnosis of DMD was 4.5 years, comparable to that reported for other countries. The time to diagnose DMD was shorter in this sample than reported for other countries, but there still existed a considerable average delay of diagnosis of 1.2 years, and this delay was increased when boys presented as infants or toddlers (1.8 years). Parents who were satisfied versus dissatisfied with the diagnostic process tended to have a first consult when their son was older, waited a shorter amount of time for a definitive diagnosis, and initially consulted a medical professional who took direct action. Parents reported


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more perceived benefits of early diagnosis in infancy than negative consequences. The most frequently reported benefits included the opportunity to start medical services and therapies early and the option to prepare emotionally, financially, and domestically. Parents cited prolonged distress as the most frequent perceived negative consequence of early diagnosis in infancy. Parents overwhelmingly supported widespread infant screening for DMD (92.4%), but differed in their endorsement of a voluntary (63.4%) versus a mandatory program (29%). In conclusion, results suggested that there exists a considerable delay in diagnosis for DMD in the United States. In addition, if widespread infant screening for DMD was to be implemented in the United States, the program would likely need to be voluntary, emphasizing parental choice and informed consent, and to provide continuing education and support for families. Finally, current findings also underscored the important role played by the primary care physician in recognizing the early signs of DMD and in influencing parents’ satisfaction with the diagnostic process.

Enrollment of Craniosynostosis Research Participants On-Site and via the Web N. Isaac, T. Beaty, B. Carson, E. Jabs, J. Richtsmeier, A. Scott, C. Vander Kolk, and S. Boyadjiev Johns Hopkins Institute of Genetic Medicine, School of Medicine, Baltimore, Maryland Over the past 18 months, we have utilized two approaches to enroll families into a study of the genetic and nongenetic causes of craniosynostosis. The first method involved recruitment of 249 families through the Johns Hopkins Hospital. Of these 32 families (13%), 16 of whom were recruited retrospectively through multidisciplinary pediatric neurosurgery, plastic surgery, and genetics clinics, were enrolled on-site. A clinical genetics evaluation was done and medical information, photographs, and blood samples for DNA mutation analysis were obtained during a scheduled General Clinical Research Center visit. Craniosynostosis was verified by CAT scan and/or surgical reports. Four of the 32 probands examined on-site were syndromic (Saethre-Chotzen syndrome, Apert syndrome, fragile X syndrome, aqueductal stenosis) with one or more sutural synostoses. Twenty-one probands had one sutural synostosis (12 sagittal, three coronal, four lambdoidal, two metopic) and seven probands had multiple (two or more) sutural synostoses. The alternative method of recruitment was web based. Seven peer support groups were contacted with the request to post information about the study. Four of 7 Web based groups (Craniosynostosis and Positional Plagiocephaly, Inc., CRANIOSUPPORT, FACES and Let’s Face It USA) agreed to post this information on their web sites. The study information was also posted on the Hopkins Center for Craniofacial and Development and Disorders web site. A total of 152 families responded. Families recruited via the Web completed an e-mail based questionnaire to determine eligibility. After review of the initial screening questionnaire, a sample collection kit was mailed to the family. Once the samples, photographs and medical records were received, medical and family history information was


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collected through a phone interview. Genetic evaluation and CAT scan reports were requested to confirm the diagnosis. Thirty-one families were enrolled (21%). Two of the 31 probands recruited via the web were syndromic (Crouzon syndrome and craniofrontonasal dysplasia) with one or more sutural synostoses. Twenty-two probands had one sutural synostosis fusion (seven sagittal, six coronal, five lambdoidal, four metopic) and seven probands had multiple sutural synostoses. Web based enrollment was as efficient as on-site enrollment. No significant differences in sutural involvement were apparent between participants enrolled on-site or via the web.

Deletion 3p25.3 in a Mother and Daughter With Normal Phenotype G. Jervis, P. Newkirk, and B. Kousseff University of South Florida Regional Genetics program, Tampa, Florida JT, a 36-year-old Caucasian woman, G2P1001, had an amniocentesis during her first pregnancy which revealed 46,XX,del(3)(p25.3). JT was found to have the same terminal deletion. JT had FISH analysis using multiple probes for chromosome 3 to rule out a translocation or inversion involving band 3p25. Five metaphase cells were scored using a whole chromosome 3 paint probe (Oncor, Inc) and all cells showed complete hybridization over the entire length. No other hybridization signals were seen on any of the other chromosomes. These results suggested that chromosome 3 was not involved in a translocation. To rule out a subtle rearrangement or inversion, two different sets of subtelomeric probes specific for the short arm of chromosome 3 were hybridized independently to metaphase cells (D3S1443/D3S1444, Oncor, Inc; D3S4559, Vysis) using a chromosome 3 centromere probe (D3Z1) to identify the chromosome in each hybridization reaction. Ten cells were analyzed with each probe set and all cells demonstrated a terminal deletion of 3p. Skin biopsy revealed the same result without mosaicism. JT’s parents had normal karyotypes. Of interest, JT’s mentally retarded sister had a de novo unbalanced translocation, 46,XX,add(8).ishder(8)t(4;8)(q31.1-23.2 (wcp4+,wcp+8). JT is a pediatrician, without dysmorphic features. JT’s daughter, AT, is a beautiful Eurasian girl, developing normally at 15 months with weight at 25th centile, height at 30th centile and head circumference at 50th centile. With her current pregnancy, JT is having CVS due to 50% risk for her fetus to have 3p deletion and advanced maternal age. The phenotypic expression of this deletion may vary due to genomic imprinting and there may be physical consequences (Am. J. Med. Genet. 44, p. 573, 1992). Without genomic imprinting, the deleted segment may be genetically inert and of no clinical significance. Terminal deletions of 3p have been reported and most involved loss of the 3p25 band. The most common features included low birth weight (70%), severe postnatal growth retardation (100%), severe mental retardation (100%), microcephaly (80%), brachycephaly, and unusual facies (Gorlin, 2001). We present a mother and daughter with 3p25.3 deletion and apparently normal phenotype. This suggests that the critical region for the phenotype of 3p deletion syndrome lies within the region 3p25 to 3p25.3.


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Severe Psychomotor Retardation Associated With Mosaic Down Syndrome and Mosaic Turner Syndrome Involving Trisomy 21, Monosomy X and Ring X Cell lines M. Jodah, L. Estabrooks, K. Clark, and B. Kousseff University of South Florida, Tampa, Florida Case report: A 3-year-old, Mexican female (IV) was referred to the genetic clinic with a diagnosis of Down syndrome, diagnosed prenatally via amniocentesis for advanced maternal age; the cytogenetic report was unavailable. The phenotype of IV consisted of intermittent nystagmus, synophrys, patent ductus arteriosus, minimal upslant to the palpebral fissures, epicanthal folds, Brushfield spots, large ears with a pit on the right, short neck with redundant skin, bilateral simian creases, and fifth finger clinodactyly. She was wheelchair bound, had cortical blindness, bilateral profound hearing loss, severe speech delay and myoclonic seizures. The facial gestalt of IV was suggestive of Cornelia de Lange syndrome rather than Down syndrome. Repeat chromosome analysis on peripheral lymphocytes showed 46,X,+mar[14]/47,XX,+21[12]/45,X[4]. Fluorescence In-Situ Hybridization (FISH) analysis revealed the marker was a ring X and lacked the X inactivation locus (XIST). At least three possible mechanisms could result in the observed cell lines. The first assumes the original cell line was 47,XX,+21 with loss of the 21 giving a 46,XX cell line; a subsequent break in the X chromosome results in the 46,X,r(X) cell line. As ring chromosomes are inherently unstable, they may be lost creating the 45,X cell line. Although a 46,XX cell line was not observed in this analysis, its presence cannot be completely ruled out, as it may be confined to a specific tissue. The second mechanism is a possible reabsorbed twin, one with a 47,XX,+21 karotype and the other with a 46,X,r(X) and subsequent loss of the ring X. The third possibility is that this represents a true chimera. The phenotype in cases involving a ring X depends on the presence of the XIST locus and euchromatic regions. If gene-coding material is present, in the absence of the XIST locus, this will be expressed, along with genes on the normal X chromosome. It results in a lack of dosage compensation for the X-linked genes and leads to an abnormal phenotype that may include mental retardation, growth retardation, and multiple congenital anomalies. The phenotype suggests the predominant cell line in this individual is 46,X,r(X). However, it was not possible to assess the amount of euchromatic material that might be present on the ring X. Neonatal Screening for Muscular Dystrophy: A Retrospective Study of Parents’ Perceptions N. Johnson, H. Wessel, and N. Holtzman Johns Hopkins University, Baltimore, MD Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder that often results in death within the third decade of life. It is a relatively common disorder that affects approximately 1:3500 live born males. As there is currently no cure for DMD; medical intervention focuses on supportive care. Between 1985 and 1997, a Western Pennsylvania pilot neonatal muscular dystrophy screening project was


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conducted in Pennsylvania, Texas, and Puerto Rico that identified a total of 58 affected neonates. In this study we explored the experience of the parents of children identified in Pennsylvania and how this presymptomatic diagnostic testing affected their families. Seventeen parents, from 12 families, completed a semistructured interview. The interviews were analyzed for common themes that emerged from the parents’ experiences. Results indicate that the parents perceived the presymptomatic diagnosis as beneficial for helping to emotionally prepare themselves and their family prior to their son’s own awareness of his disorder, time to prepare their house for a “handicapped” child, and for planning future reproductive decisions. Negative perspectives on screening centered on the process by which parents learned of their son’s potential diagnosis of muscular dystrophy. Some parents described feelings of detachment or interference with bonding as a result of learning their child’s diagnosis during the neonatal period. While all families believed that learning their son’s diagnosis prior to a later clinical diagnosis was beneficial, many families expressed ambivalence about whether the neonatal period was the most appropriate time to be given their son’s diagnosis of an untreatable disorder. In the absence of presymptomatic clinical trials for treatment of muscular dystrophy, heightened awareness about the early signs and symptoms of muscular dystrophy for pediatricians and the general public may be a better alternative than neonatal screening in achieving early diagnosis. Protocols should be developed for any future neonatal screening programs for untreatable conditions that create accurate as well as sensitive means for pediatricians to disclose results to parents. Genetic counselors familiar with the condition should be involved with the initial disclosure and available to families on both an immediate and long-term basis after they receive their child’s screening results. In addition, screening of newborns in pilot neonatal screening programs should remain optional. Pilot programs should include an evaluative component to monitor and assess parents’ experiences so that programs can be altered in response to their experiences. Supplemental Newborn Screening: Attitudes of Parents, Pediatricians, and the Public of Maryland R. Kern and T. Cowan University of Maryland, Baltimore, Maryland Tandem mass spectrometry (MS/MS) is being implemented into newborn screening programs across the United States and around the world. It has many obvious benefits, but there are also concerns that need to be addressed prior to its implementation. This study is a qualitative assessment of the attitudes of pediatricians, parents, and the general public pertaining to the implementation of MS/MS technology for newborn screening in the state of Maryland. It also includes some quantitative analysis of how attitudes related to demographics. Cover letters, educational brochures, and surveys were designed and subjects were recruited from three groups: parents affected directly by newborn screening (either by having a child who was diagnosed via current screening or having a child with a genetic condition that was not diagnosed by current screening, but would have been picked up by MS/MS); pediatricians practicing in the state of Maryland; and general public parents. Subjects were asked to read an informational brochure describing


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current newborn screening and expanded newborn screening and then complete a survey. Qualitative data was analyzed using an editing approach. The majority of parents, pediatricians, and the public are in favor of implementing MS/MS and appreciate the many benefits it has to offer, however, the study also elucidated serious concerns with implementation such as creating unnecessary parental anxiety, detecting nontreatable conditions, and preparedness of follow-up. The study also showed a definite need for education for both health professionals dealing with the explanation of and outcomes of expanded newborn screening, as well as quality parent education both before testing is conducted and quickly following an abnormal result. Overall, the outcome of the study showed that the groups surveyed were overall in favor of implementing MS/MS into newborn screening, but that concerns must be addressed prior to offering testing clinically. Parent & Teacher Concerns of School-Age Children With Isolated Cleft Lip and Palate or Cleft Palate R. Klatt, J. Schultz, L. Lee, and H. Saal University of Cincinnati, Cincinnati, Ohio Isolated cleft lip and palate (CLP) and isolated cleft palate (CP) are among the most common congenital anomalies, occurring in approximately one in 700 children. Quantitative data show that school-age children with an isolated CLP or CP may be at increased risk for conduct disorders, anxiety and depression, cognitive problems, low self-esteem, poor socialization skills, and overall behavior problems and psychosocial maladjustment. However, little qualitative data regarding the concerns of parents and teachers have been published. Both parents and teachers of children with isolated CLP or CP aged 6–11 were mailed a validated scale, the Achenbach Child Behavior Checklist (CBCL). The scale included openended questions asking the parents and teachers what concerned them most about the child with CLP or CP. Of the initial 97 eligible families ascertained from the Craniofacial Center of Cincinnati Children’s Hospital Medical Center, 90 could be contacted by mail. Of those returning the CBCL, 45 of 51 parents and 33 of 35 teachers completed the open-ended questions. Children with a known genetic syndrome (aside from Stickler’s syndrome) or other chronic medical conditions were excluded. Of the participating children, 64.5% had CLP while 34.5% had CP. The male to female ratio was 1.9:1. Based on the responses, themes were found for both the parent and teacher data. The most frequently reported parental concerns were for academic issues in school (22.2%), the child’s self-esteem or self-confidence (20.0%), teasing by peers or adults (11.1%), hyperactive or inattentive behavior (11.1%), and poor social interactions with peers (8.9%). Only 4 of 45 parents (8.9%) stated that they had no major concerns. Teachers were most concerned with the child’s hyperactive or inattentive behavior (25.7%), academic performance (22.9%), and poor social interactions with their peers (14.3%). Of participating teachers, 12 of 35 (34.3%) specifically indicated that they had no major concerns. These results show that the concerns expressed by parents and teachers reflect the cognitive and psychosocial problems found using quantitative methods. Pediatric genetic counselors are in an ideal position to provide anticipatory guidance by addressing these issues with families in clinic.


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De Novo 46,XX,del(4)(q12q13.3) in a 3-Year-Old With Piebald Trait D. LaGrave, M. S. Eswara, S. Yang, M. Tomlinson, and N. Qin Department of Cytogenetics, Quest Diagnostics at Nichols Intitute, San Juan Capistrano, California We describe a 3-year-old girl born at term to a 24-year-old gravida 5, para 2, phenotypically normal mother. Amniocentesis was performed due to two previous pregnancies with neural tube defects, which had resulted in intrauterine fetal demises at 32 weeks and 37 weeks, respectively. Chromosome studies on the amniocytes revealed an interstitial deletion in the long arm of one chromosome 4. A series of ultrasounds were reportedly negative for any adverse findings. At birth, the infant weighed 6 lb, 15 oz, was 20 in. in length, and had an OFC of 33 cm. No neonatal problems were reported. CT scan of the head and EKG were reportedly normal. The child has had no significant medical problems or surgeries. Hearing and vision were checked soon after birth and were normal, although glasses were prescribed at 18 months of age for esotropia. The patient shows delay in all milestones (sat at 8 months, walked at 2 years, and is saying “mama” nonspecifically at almost 3 years). She is estimated to be functioning at a 6-month level for speech and communication and at a 1-year level socially. She cannot yet eat solid foods so her diet consists of purees and liquids. Her weight is at the 97th percentile, her height is at the 75th percentile, and her OFC is at the 50th percentile. She displays subtle dysmorphic features including a high forehead, hypertelorism, a short nose, and a small midface. Her ears are low-set and posteriorly rotated, but with normal morphology. Her teeth were late in erupting; they are yellowish in color and seem to have abnormal enamel. She has a midline white forelock and several large hypopigmented areas on her trunk and lower extremities. A few smaller areas of hyperpigmentation are present as well. Repeat karyotype of peripheral blood lymphocytes was performed at 3 years of age. This confirmed the previous finding of an interstitial deletion on 4q and identified the breakpoints as 4q12q13.3. FISH analysis using a whole chromosome paint probe specific for chromosome 4 revealed that the missing segment from 4 was not present on any other chromosome. Parental chromosome studies were normal. In summary, we discuss a case with a rare deletion on 4q12q13.3 that resulted in developmental delay, mild dysmorphic features, and piebald trait. Literature review and genotype/phenotype correlation will be discussed. Is Having an Etiology for a Child’s Developmental Delay Beneficial to Families? A Comparison Study of Children With Unexplained Developmental Delay Versus Children With Developmental Delay of Known Etiology S. Nix and A. Toburen University of South Carolina School of Medicine, Department of Obstetrics and Gynecology Columbia, South Carolina One goal of genetic evaluation is to provide families with a diagnosis for their child’s disability. Multiple benefits of having a diagnosis are assumed in medical literature, yet few studies have assessed parents’ opinions on this issue. This study


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first sought to determine which elements of a medical diagnosis are considered useful by parents of children with developmental delay. Second, we sought to determine whether differences exist between parents of children with unexplained and etiologic developmental delay when comparing these topics: medical management, reproductive decision making, parental psychosocial issues, and accessibility to social services. Participants were recruited from three Greenwood Genetic Center offices located in South Carolina over 5 months. Study subjects included children with unexplained developmental delay and those with a specific diagnosis for their delay. Parents of 33 children (76.7% of recruited population) completed questionnaires consisting of demographic, closed, and open-ended questions. Data analysis c and SPSS. Several results were found that support was completed using Excel° and contradict current understanding of the utility of a diagnosis. As suggested in the literature, the majority of parents reported a diagnosis is helpful because it aids treatment plan creation, increases access to information, gives a name to their child’s condition, aids in understanding abilities and limitations, and helps in receiving support from national organizations. As expected, a difference in support group participation was found between the two groups. Contrary to the literature, most parents did not agree that a diagnosis decreases anxiety. Specifically, parents of diagnosed children felt a diagnosis had less impact on anxiety than parents of undiagnosed children. The factors suggested in the literature as influencing reproductive decision making were not statistically significant in our study, though trends were seen. No statistical correlation was found between the choice to have further children and parental perception of severity or the numerical recurrence risk. Data also suggested recurrence risks are less likely to be given when an etiology is not known. This research demonstrates that overall parents feel a diagnosis is useful, but that differences exist between parents whose children have a diagnosis and those who do not. It is imperative for medical professionals to explore parents’ views on how diagnostic information may be helpful as a means to individualize and improve patient care.

Genetic Counselors and Autism: Assessment of the Knowledge Base M. Novak, B. Lerner, S. Parrott, and B. Rosen-Sheidley Brandeis University, Waltham, Massachusetts Very little research has yet been conducted regarding genetic counseling for autism and pervasive developmental disorders. As genetic counselors are trained to provide genetic information and psychosocial support, they could be a valuable resource for families seeking genetic information about autism. However, previous research has suggested that autism care providers may be unlikely to refer patients for genetic counseling, in part due to a belief that genetic counselors are not knowledgeable about autism spectrum disorders. The goal of this study was therefore to assess what genetic counselors know about autism and other pervasive developmental disorders, and to examine current practices regarding autism genetic counseling. We designed an on-line survey consisting of 33 questions to assess counselors’ understanding of the clinical symptoms of autism spectrum disorders,


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understanding of autism genetics, and current clinical practices. Subjects were recruited through the NSGC listserv, and 220 completed surveys were returned for a response rate of 19.7%. The majority of respondents indicated that they are involved in clinical work (73%), and approximately half work in a prenatal setting. As expected, results showed that counselors working in clinical prenatal and pediatric settings are more knowledgeable about autism than are counselors in other specialty areas, such as cancer genetics ( p = 0.000). However, even among the pediatric and prenatal counselors, roughly half (44.6%) were unable to correctly identify the current estimated prevalence of autistic disorder, which is approximately 1 in 1000. Approximately 42% of all respondents believed incorrectly that autistic disorder is always accompanied by developmental regression, and only 26.9% knew that most individuals with autistic disorder also have mental retardation. Only 61.4% of respondents correctly identified the current estimate for recurrence in the sibling of a single affected proband, and only 64.1% correctly identified the recurrence risk for the sibling of two affected individuals. Almost all (94.5%) were aware that fragile X syndrome is associated with autism, and most (67.3%) were aware of the association with chromosome anomalies. Almost half of respondents (49%) reported feeling somewhat or very uncomfortable about providing autism genetic counseling, and stated that this discomfort is due to lack of knowledge about PDDs and autism genetics. In summary, the data suggest that genetic counselors could benefit from education regarding the natural history and genetics of pervasive developmental disorders. Such education would increase their comfort levels in providing counseling, and may then in turn increase the frequency of referral from autism care providers.

An Assessment of Needs for Families and Patients With Bladder Exstrophy: Implications for Genetic Counseling J. Pierre-Louis, R. Babul-Hirji, D. Chitayat, J. Clarke, and B. Neilson Hospital for Sick Children, Toronto, Ontario, Canada Bladder exstrophy is a congenital anomaly of complex inheritance where the lower abdominal wall, bladder, pubic bones, and urethra are incompletely fused during fetal development. Although surgery has improved the medical outcome for these children, little is known about the day-to-day challenges of parenting a child with bladder exstrophy. The aim of this study was to identify the needs of parents of children with bladder exstrophy and to assess if these needs could be addressed through the addition of genetic counseling services. We conducted an IRB-reviewed exploratory, qualitative study that consisted of two focus groups (n = 10) with parents of children with bladder exstrophy held in November 2001, and a web-based questionnaire distributed in February 2002 to 189 members of an on-line bladder exstrophy parents group (n = 20). The focus group transcripts were independently analyzed for themes by three coinvestigators and underwent external review by an experienced group of qualitative researchers. The questionnaire posed a series of open-ended questions to elicit the respondents’ perceived need within the categories medical and health care needs, social and community


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needs, psychological needs and information and education needs. Medical needs identified by both the focus group participants and the questionnaire respondents included achieving continence, kidney health, surgeries, and the challenges of catheterization. Social and community needs commonly identified included community knowledge of the disorder, financial support and greater understanding and accommodations at the child’s school. Psychological needs commonly identified included peer acceptance, normalcy, emotional support for the child, emotional support for the parent and fertility concerns. Information and education needs commonly identified included discussion of medical options, age appropriate information, noninternet-based resources, cause, recurrence risk, and anticipatory guidance. In general, medical and health care needs were described as better dealt with (60% satisfied) than social and community needs (35% satisfied), psychological needs (30% satisfied) and information and educational needs (35% satisfied). As genetic counselors are specially trained to translate complex medical information and to provide psychosocial support, a number of the identified information and education needs and psychological needs could be addressed through genetic counseling. Insight gained from this study should be useful for genetic counselors and other health care providers involved with families who have received a prenatal or neonatal diagnosis of bladder exstrophy. Parents’ Use of the Internet as a Source of Genetic Information M. Roche, D. Skinner, K. Kuczynski, and R. Schaffer University of North Carolina, Chapel Hill Clinical experience suggests that parental use of the Internet to obtain genetic information is widespread but influencing factors have largely been unexplored. Two previous studies, Taylor (2001) and Christian (2001) surveyed families prior to their genetics clinic visit. Over 75% had Internet access but fewer than half had searched prior to their visit. Locating information about their relative’s condition in “layperson’s terms” ranked as the main goal. The frequency of searching increased if a child was the proband and if a specific diagnosis had been made. As part of a longitudinal study to determine how families seek out, interpret, and use genetic information, parents were specifically queried about their Internet use. The first of four semistructured interviews, conducted after the initial clinic visit, sought to determine the searching methods used, types of information sought, and families’ appraisals of their searches prior to and following their visit to the Pediatric Genetics and Metabolism Clinic at the University of North Carolina, Chapel Hill. Sixty-nine interviews were audiotaped, transcribed, and entered into the program, NUD∗ IST 4.0 for data coding and analysis. The keywords searched were “Internet,” “web,” and “computer.” Participating families were representative of the ethnic distribution of the clinic population: Caucasian, 69%; African American, 18%; Latino, 7%; and Native American, 6%. Internet searching occurred both prior to and after the visit in four fifths of the families. Preparatory searches using broad terms occurred prior to the visit and enabled families to build a genetic vocabulary, anticipate what to expect during the session, and construct pertinent questions. Following a specific diagnosis, searches focused on potential


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treatments, services, and support. Parental assessments of their Internet searching were laudatory but guarded and the uncertain validity of the information was recognized. Twenty percent of families did not use the Internet; African American families comprised nearly half of this group. Parents’ use of the Internet as a source of genetic information was widespread in our population, occurred more frequently in Caucasian families, and augmented traditional methods such as personal contact with health professionals and other service providers. Awareness of the type of information families seek and obtain by Internet searching as well as the barriers to this source of information can enhance the genetic counseling process. (Supported by NHGRI/ELSI grant HG02164-03) Clinical Characterization of Psychotic Patients With a 22q11 Deletion: A Descriptive Study C. Tichnell, E. Wulfsberg, P. Wolyniec, and A. Pulver University of Maryland, Baltimore, Maryland Velo-cardio-facial syndrome (VCFS) is a congenital disorder characterized by cardiac and palatal abnormalities, learning disabilities, hypernasal speech, and a characteristic facial appearance. Most individuals diagnosed with VCFS possess a detectable microdeletion on chromosome 22q11.2. In 1992, Robert Shprintzen observed that approximately 10% of his VCFS patients developed psychiatric disorders, including schizophrenia and bipolar disorder. Additional studies have investigated the relationship between VCFS and psychiatric manifestations. Some focused on psychiatric findings among VCFS individuals concluding that VCFS patients are at increased risk for developing psychiatric disorders (Goldberg et al., 1993; Pulver et al., 1994; Chow et al., 1994; Papolos et al., 1996; Carlson et al., 1997; Murphy et al., 1999). Others investigated the presence of VCFS clinical features among psychiatric patients concluding that some psychiatric patients have an undiagnosed 22q deletion, as well as mild VCFS clinical facial features (Karayiorgou et al., 1995; Bassett et al., 1998; Sugama et al., 1999). We clinically described 10 psychotic patients with a confirmed 22q11 deletion by reviewing previous data collected through an in-person interview, family history, medical records, and photographs. Four subjects were identified through a craniofacial clinic and the remaining six were identified through various psychiatric studies. Nine of the 10 subjects were diagnosed with schizophrenia (VCFS/SZ group) and were compared to a control group of 123 schizophrenic patients (SZ group) in an attempt to differentiate a subtype of schizophrenia that is associated with a 22q11 deletion syndrome. Results from this study concluded that the VCFS/SZ group and the SZ group are quite similar with respect to the onset, course, and symptoms of their psychiatric illness. However, individuals in the VCFS/SZ group were more likely to have attended a special education class (63%) compared with the SZ group (25%). In addition, individuals in the VCFS/SZ group were more likely to suffer from anxiety disorders (71%) compared with the SZ group (28%). There were also trends toward significance with respect to attendance at a special school (VCFS/SZ = 25%, SZ = 4.1%), presence of affective symptoms early in the course of illness (VCFS/SZ = 100%, SZ = 61.7%) and


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Pre/Perinatal Genetics

substance abuse/dependence (VCFS/SZ = 22.2%, SZ = 54.9%). This hypothesisgenerating study indicates the need for additional studies using larger sample sizes to further investigate similarities and differences among those diagnosed with a 22q deletion and psychotic disorder compared with those diagnosed with only a psychotic disorder. VII. PRE/PERINATAL GENETICS Alternative Applications and Findings of Subtelomeric FISH in the Clinical Setting M. Berry and M. Pettenati Wake Forest University School of Medicine, Winston-Salem, North Carolina Many chromosome abnormalities are visible with routine cytogenetic analysis. Advances in molecular cytogenetics using subtelomeric probes have allowed for the identification of submicroscopic abnormalities that can be associated with various syndromes and mental retardation. Thus far, subtelomeric FISH is primarily used to identify minute deletions, duplications, or cryptic translocations in children with moderate to severe MR. We have pursued alternative applications for subtelomeric FISH, and encountered successful and unexpected results. Prenatal FISH analysis for chromosomal aneuploidy is available; however it may not be of primary benefit to a translocation carrier. By using subtelomeric probes, we could rapidly detect the carrier status of a fetus when a parent carries a known chromosome translocation. Prospective prenatal interphase subtelomeric FISH analyses were performed on six uncultured amniocytes and one CVS sample. Appropriate translocation probes were selected. Three cases were abnormal, all verified by cytogenetic analysis. Abnormalities included partial trisomies for 4q and 15q, and trisomy 13 (Robertsonian). These analyses demonstrated the utility of FISH using subtelomeric probes to rapidly and correctly identify balanced/unbalanced chromosome anomalies prenatally that can result from parental translocations. Thus, subtelomeric FISH analysis represents a new, rapid prenatal test available for known chromosome translocation carriers whose primary concern is the presence of a chromosomally balanced or unbalanced fetus. Caution is recommended with regard to insuring a careful cytogenetic analysis/review of the parental chromosome anomaly prior to the prenatal analysis. Routine FISH analyses using subtelomeric probes uncovered unexpected results in four of six normal individuals with apparently balanced chromosome anomalies and a history of miscarriages and/or abnormal outcomes. Three cases involved reciprocal translocations: t(9;11)(q12;q25); t(4;15)(q21;q26.3); t(11;16)(p15.5;q22); and one a paracentric inversion: inv(4)(q33q35.2). In the three translocation cases, two subtelomere probes were identified on one chromosome while the reciprocal chromosome lacked its subtelomere signal. In the paracentric inversion case, the subtelomeric 4q probe was identified within the q-arm at 4q33. Thus, while the rearrangements were apparently cytogenetically balanced and present in normal individuals, the FISH results were unexpected. Our serendipitous finding of an


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unusual relocation of subtelomeric probes in four cases with terminal band chromosome rearrangement regions and abnormal reproductive histories suggests that such individuals could be at increased risk for miscarriages and /or abnormal outcomes. Further studies to evaluate terminal band chromosome rearrangements utilizing subtelomeric FISH are needed to fully evaluate any association with clinical history. Additional uses for subtelomeric FISH reported or under investigation include cancer rearrangements and preimplantation diagnosis.

Initial Findings Using Gene Sequence Analysis for CFTR Mutations in At Risk Fertility Patients L. Black and P. Turek California Pacific Medical Center, San Francisco, California Men with an infertility diagnosis of congenital bilateral absence of the vas deferens (CBAVD) have up to an 80% risk to carry at least one Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene mutation. Common mutation DNA analysis typically provides adequate detection rates for mutations in individuals of Northern European Caucasian or Eastern European Jewish ancestry (90% and 97%, respectively). However, for Caucasian or Jewish men with CBAVD who have had negative common mutation analysis, or for men in whom common mutation screening does not provide high detection rates, offering testing with a maximum detection rate can be critical to a couple’s assisted reproduction decision making. In a male infertility clinic, we offered six men with CBAVD sequencing of the CFTR gene, which provides approximately a 99% detection rate regardless of ancestry. Indications for sequencing included (1) a negative CFTR mutation analysis by other methods, (2) assumed low detection rates with other methods due to ancestry, and (3) patient choice. Five of the six men tested for CFTR mutations by sequencing were found to have mutations, with a total of seven mutations on 12 chromosomes. Five of the seven mutations identified were those which would not have been detected by common mutation screening. Three were rare mutations previously described, and two were novel variations in DNA sequence. Taking into consideration the female partner’s CFTR results, these couples were able to make more informed decisions about their assisted reproduction and embryo testing options based on accurate cystic fibrosis risk assessment. Inherited Terminal Deletion of 4q34 Without Apparent Phenotypic Effect S. Cooper and D. Saxe Department of Pediatrics, Division of Medical Genetics, Emory School of Medicine, Atlanta, Georgia. Multiple cases of terminal deletions from 4q34 to 34.2 have been reported with phenotypic effects similar to velocardiofacial syndrome or with mild phenotypic effects. We describe a familial case with an inherited terminal deletion without


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apparent abnormalities in one family member. The patient was originally referred for advanced maternal age and elected to undergo amniocentesis at 19 weeks gestation after a congenital diaphragmatic hernia was noted on ultrasound. Chromosome analysis revealed the fetus carried a terminal deletion at 4q34 and the common pericentric inversion for chromosome 2. The phenotypically normal mother carried the same deletion of chromosome 4. Subtelomeric FISH for chromosome 4 showed that the subtelomeric probe for 4q was deleted in both the mother and fetus. Chromosome 4 paint showed identical patterns for both 4 homologs and no chromosome 4 material on any other chromosome. The baby was delivered prematurely at 27 weeks gestation and died shortly after birth. Postnatal examination revealed a diaphragmatic hernia and situs inversus. Echocardiogram showed a right aortic arch, patent ductus arteriosus with moderate tricuspid regurgitation and a dilated left ventricle. This case report emphasizes that small deletions at specific sights may have little phenotypic effect as in the mother. Identification of such chromosome regions has strong implication in genetic counseling and prenatal diagnosis.

Comparison of Genetic Counselors in Prenatal and Assisted Reproductive Technology Specialties Regarding Their Counseling Practices Prior to Intracytoplasmic Sperm Injection E. Crocker, J. Edwards, C. Singletary, and J. Busowski University of South Carolina, Columbia, SC The potential risks of intracytoplasmic sperm injection (ICSI) for male infertility due to azoo/oligospermia have been raised because preliminary data on children born after ICSI have shown an increased incidence of sex chromosome abnormalities. Additionally, the incidence of genetic conditions and risk of infertility in offspring conceived via ICSI are as yet unknown. Standards for counseling and laboratory testing remain open questions. The purpose of this study was to determine what risks are being quoted and which tests are being offered among genetic counselors seeing patients prior to and during pregnancies conceived via ICSI. Members of the Prenatal and Assisted Reproductive Technology (ART) Special Interest Groups (SIG) of the National Society of Genetic Counselors were surveyed on (1) what risks are being presented to patients regarding the ICSI procedure, (2) what genetic conditions are being discussed in men with azoo/oligospermia, and (3) what risks are being presented for possible infertility in offspring. Twenty-six of 42 members of the ART SIG (70.0%) and 73 out of 162 members of the Prenatal SIG surveyed responded (45.1%). Both groups report discussing sex chromosome aneuploidy, translocations, and Y chromosome microdeletions. However, a significantly increased number of ART SIG members discuss translocations ( p = 0.001,

Abstracts from the Twentieth Annual Education Conference of the National Society of Genetic Counselors (Washington, DC, November 2001).

Abstracts from the Nineteenth Annual Education Conference of the National Society of Genetic Counselors (Savannah, Georgia, November 2000).

Abstracts from the Seventeenth Annual Education Conference of the National Society of Genetic Counselors (Denver, Colorado, October 1998).

Abstracts from the Twenty-Second Annual Education Conference of the National Society of Genetic Counselors (Charlotte, NC, September 2003).

Abstracts of papers and posters presented at the Fifteenth Annual Education Conference of the National Society of Genetic Counselors.

The 53rd Annual Meeting of The Society of Toxicology . . . from Phoenix, Arizona.

An Oral History of the National Society of Genetic Counselors.

Leading Voices and the Power of One: 2002 Presidential Address to the National Society of Genetic Counselors.

Abstracts of the Caribbean Urological Association 16th Annual Conference, November 7-8, 2014, Montego Bay, Jamaica.

Society of Critical Care Medicine presidential address-44th annual congress, January 2015, Phoenix, Arizona.

The American Society for Cell Biology 32nd annual meeting. November 15-19, 1992, Denver, Colorado. Abstracts.

Abstracts of the 54th Annual Conference of the Indian Society of Gastroenterology in association with the Indian National Association for Study of the Liver and the Society of Gastrointestinal Endoscopy of India. November 28-December 1, 2013. Gujarat, India.

Abstracts of the RCOG National Trainees Conference (NTC) 2014, 27-28 November 2014, Manchester, United Kingdom.

Abstracts of papers presented at the Thirteenth Annual Education Conference : 25 years of genetic counseling Expanding roles, extending horizons.

Abstracts of the British Psychosocial Oncology Society, 2015 Annual Conference, 19 - 20 March 2015, England, UK.

Embedded research to improve health: the 20th annual HMO Research Network conference, March 31-April 3, 2014, Phoenix, Arizona.

Abstracts of the British Psychosocial Oncology Society, 2014 Annual Conference, 27 - 28 February 2014, Preston, UK.

Abstracts of the 48th Annual Scientific Meeting of the Vascular Society of Great Britain and Ireland, 27–29 November 2013.

Abstracts of papers presented at the Fourteenth Annual Education Conference : Conditions that affect adults.

Abstracts of the 41st Annual Meeting of the Austrian Diabetes Society. November 21-23, 2013. Salzburg, Austria.

Abstracts of the 2013 Annual Scientific Meeting of the Irish Thoracic Society (ITS). November 15-16, 2013. Derry, Ireland.

Pancreatic Society of Great Britain and Ireland. 14th annual meeting. 17 November 1989. Abstracts.

Abstracts of the 49th Annual Scientific Meeting of the Vascular Society of Great Britain and Ireland, November 26-28, 2015.

The College of Podiatry Annual Conference 2014: meeting abstracts.