Journal of Genetic Counseling, Vol. 7, No. 2, 1998

Development of the Critical Elements of Genetic Evaluation and Genetic Counseling for Genetic Professionals and Perinatologists in Washington State Kathi Marymee,1,6 Cynthia R. Dolan,1 Roberta A. Pagon,2 Robin L. Bennett,3 Sandra Coe,4 and Nancy L. Fisher5

We present a method for the development of consensus documents describing the components of genetic evaluation and genetic counseling for various diagnoses. These documents were developed to encourage consistency among genetic professionals in Washington State. Other possible uses of these documents are to provide information regarding genetic evaluations for health care practitioners and payers, and to assist in quality assurance and genetic training programs. A working group of six genetic professionals developed two templates for the "critical elements of genetic evaluation and genetic counseling," for clinical (nonprenatal) and prenatal patients. The working group then completed prototype templates for several specific genetic disorders. The templates and prototypes were sent to interested genetic professionals and perinatologists who submitted a total of 76 draft "critical elements" (CE's) to the working group. At two statewide meetings, participating practitioners modified and unanimously approved the CE templates, then unanimously approved the 21 draft CEs that had been finalized in small group discussions. Approved CE's were distributed to genetic professionals and perinatologists within the state. KEY WORDS: practice guidelines; genetic evaluation; genetic counseling.

1

Inland Northwest Genetics Clinic, Spokane, Washington. Children'sHospital and Medical Center, Seattle, Washington. 3 University of Washington, Seattle, Washington. 4 Swedish Medical Center, Seattle, Washington. 5 Washington State Department of Social and Health Services, Office of Managed Care, Olympia, Washington. 6 Correspondence should be directed to Kathi Marymee, Inland Northwest Genetics Clinic, S. 526 Howard, Spokane, Washington 99204. 2

133 1059-7700/98/0400-0133$15.00/1 C 1998 National Society of Genetic Counselors, Inc.

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INTRODUCTION The need for practice guidelines is recognized nationally. Recently, a 2-day conference cosponsored by the Genetic Services Branch, Maternal and Child Health and the Council of Regional Networks for Genetic Services detailed the need for practice guidelines in genetic services (Freeman et al, 1996). The National Society of Genetic Counselors (NSGC) currently has a Practice Guidelines subcommittee. With a grant from the New York State Department of Health, the American College of Medical Genetics is developing practice guidelines for genetic counseling for breast cancer and for the evaluation of a newborn with single or multiple congenital anomalies. Despite the recognition of the need for practice guideline documents, there are few published practice guidelines for genetics professionals. These publications covered specific areas such as guidelines for the medical management of genetic conditions (Committee on Genetics, 1994; Vichinsky and Lubin, 1987), genetic testing (Guidelines, 1994), and risk information (McConkie-Rosell et al., 1995), but do not address the process of developing practice guidelines. In response to the need expressed by genetic professionals in the State of Washington, we undertook a project to develop consensus documents which describe the components of genetic evaluation and genetic counseling. The intent of the Washington State project was to generate practice guidelines for a large number of conditions, utilizing a consistent format reflecting the common components of the genetic evaluation and the genetic counseling process, while highlighting the unique aspects of specific genetic conditions. Rather than being evidence-based, the project was focused to reflect current practices. The project scope was not intended to include laboratory standards for genetic testing or to detail the specifics of medical management of genetic conditions. Under a 15-month, $35,000 contract from the Washington State Department of Health, the project brought together medical geneticists, genetic counselors, and perinatologists to develop a process for establishing broad practice guidelines, as well as specific guidelines for genetic conditions. The contract supported a genetic counselor to serve as a part-time project coordinator, some secretarial support, travel, and meeting expenses for all interested participants, and small honoraria for participants drafting CEs and for meeting attendance. In Washington State, we enjoy a cohesive, stable medical genetics and perinatology community, which has worked cooperatively on projects in the past. Although there are twice yearly statesponsored genetic providers meetings and an active Regional Genetics Group (Pacific Northwest Regional Genetics Group), this project opened

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a new venue for different practice groups within the state to openly discuss their care practices while working toward consensus on issues pertaining to genetic evaluation and genetic counseling.

METHODS In November 1994, the project organizers (CRD and RAP) polled the 38 Washington State genetic professionals about their interest in developing "practice guidelines"; 92% responded positively. Genetic professionals defined as those medical geneticists, genetic counselors, and other health care providers who were actively involved in the medical evaluation and genetic counseling of individuals and families with known or suspected genetic disorders. The medical geneticists were mostly, but not exclusively, Board Certified as Clinical Geneticists by the American Board of Medical Genetics (ABMG). The genetic counselors were exclusively American Board of Genetic Counseling (ABGC) certified or Board eligible genetic counselors. Shortly thereafter, the ten perinatologists in the state were contacted regarding their interest in such a project; five were interested in participating in the process and two were interested in reviewing practice guidelines. A working group was formed comprised of four genetic counselors and two clinical geneticists representing different clinical interests, practice types, and geographic locations. In addition, a nurse from Children's Hospital and Medical Center in Seattle, who had worked with focus groups to develop practice guidelines for certain pediatric conditions, was an ad hoc member. The working group met three times in a 2-month period. As the first item of business, the word "guideline" was eliminated from the project title because of our concerns about confusion with a minimum standard of care. Our goal was to set forth those issues that should be considered in the process of providing genetic services for specific disorders. To accomplish the goal we first developed consensus of the basic issues or "critical elements" underlying all genetic services. The project was renamed the Critical Elements of Genetic Evaluation and Genetic Counseling (CE). The working group developed two templates, one for clinical (nonprenatal) patients and one for prenatal patients (Appendix A). The clinical template reflects the issues to be considered for an individual with a specific disorder or at risk for that disorder. The prenatal template outlines the issues to be considered for a pregnant woman with a given disorder or a family history of that disorder. The templates are concise because they assume a genetic knowledge base.

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Each template is divided into two sections. Part I represents the "information obtained from patient/family" in the process of genetic evaluation, and Part II is the "information to be provided or discussed with the patient/family" during genetic counseling. For example, obtaining a pedigree is included in Part I of both templates (Appendix A). In addition, the templates have blank portions to indicate an area of focus, or directed questions, as appropriate for a specific disorder (e.g., inquiring about "uncontrolled movements and mental illness" are specified as additional information to be sought while obtaining a family history for a patient with a family history of Huntington disease). Using the draft templates, each member of the working group developed prototype CEs for a specific disorder in order to become familiar with the format and to assess the usability and completeness of the templates. The templates were revised throughout this iterative process. By completing prototypes and through group discussion, the working group gained an appreciation of the amount of information needed to complete the blank portions of the templates. Using three mailed surveys, participants were asked to identify and prioritize disorders for which CEs might be developed and to designate three disorders for which s/he would be willing to serve as author. Based on expressed interest and expertise, authors were selected by the working group for 43 conditions (Table I). Four conditions, added later in the project by the project organizers, were assigned in the same manner. Each author was provided copies of the templates, prototype CEs, and the name of a working group member to serve as a contact/advisor. Over the next 9 months, the professionals, representing all of the different genetic centers throughout the state, completed 76 draft documents for 37 conditions. Twenty-one of the 43 invited professionals attended an initial day-long meeting to review, edit, and approve both the templates and CEs. Invitees who were unable to attend were given the opportunity to review materials and comment in writing, to allow incorporation of their input into the review process. The meeting was divided into three parts. First, the group as a whole reviewed, discussed, and edited the templates, eventually approving them unanimously (Appendix A). Second, the participants were divided into five subgroups, which were organized by areas of clinical expertise and led by a member of the working group. The subgroups reviewed, edited, and approved the draft CEs for specific disorders. Third, the group reconvened as a whole to review, discuss, edit, and approve each of the CEs that had been approved by the subgroups. Twenty-four project participants attended a second day-long meeting organized in a similar format to the first. All 21 Critical Elements for specific disorders that were reviewed by the subgroups during the two meetings

Table I. Prioritized Conditions for Development of Critical Elements of Genetic Evaluation and Genetic Counseling Status Fragile X syndrome Breast cancer Positive maternal serum screeningincreased risk for Down's syndrome Multiple congenital anomalies Positive maternal serum screening —increased risk for open fetal defect Cystic Fibrosis Trisomy 21 Translocation Down syndrome Developmental delay Hemoglobinopathy Advanced maternal age counseling Abnormal fetal ultrasounda Neurofibromatosis

PKU Huntington disease Pseudomosaicism (amnio) Mosaicism (from CVS and amnio) Multiple miscarriages Turner syndrome Ambiguous genitalia Achondroplasia Polycystic kidney disease Trisomy 18 Marfan syndrome Myotonic dystrophy Congenital adrenal hyperplasia DMD-Becker muscular dystrophy Trisomy 13 Structural chromosome abnormality Inborn errors of metabolism-undefined Tuberous sclerosis Prader-Willi syndrome Galactosemia Klinefelter syndrome Tay Sachs disease Gaucher disease Glycogen storage disease Alzheimer disease Von Hippel-Lindau disease Osteogenesis imperfecta Types I, II, III, VI Angelman syndrome Hemophilia Spinocerebellar degeneration Additional conditions Cleft lip/palate Velocardiofacial syndrome Beckwith-Weideman syndrome Retinoblastoma a

approved draft

Prenatal/clinicalb

+/+ na/+ +

approved draft

+/na

approved approved approved approved draft draft approved draft approved approved approved draft not completed draft draft draft not completed draft draft not completed unassigned draft draft draft draft not completed draft not completed not completed draft draft draft draft draft unassigned not completed draft draft not completed

+/na

draft draft draft draft

+/+ +/+ +/+ +/+ +/+ +/+ +/na +/na

+/+ +/+ +/+ + +/na

-/+/+ na/+

+/+ -/+/+ +/+ -/+/+ +/+ +/+ +/+ -/+/+ -/-/+/+ +/+ +/+ +/+ na/+

-/+/+ +/-/+/+ +/+ +/+ -/+

Drafts were completed for 11 different indications. na-not applicable. + draft received. + + two CE's received reflecting different clinical circumstances (e.g., presymtomatic and symptomatic patients for Huntington disease). - draft not received.

b

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were approved unanimously by the group as a whole. These were clinical and prenatal CEs for Fragile X syndrome, multiple congenital anomalies, Cystic fibrosis, Trisomy 21, translocation Down syndrome, Neurofibromatosis type 1, PKU, and Huntington disease. An additional CE was developed for Huntington disease for testing of a symptomatic individual. Prenatal CEs were approved for a positive maternal serum screen indicating an increased risk for Down syndrome, positive maternal serum screen indicating an increased risk for an open fetal defect, advanced maternal age, and an abnormal ultrasound identifying a neural tube defect. These represent CE's for 11 of the top 16 conditions prioritized by the participating practitioners. The CE for Fragile X syndrome is included as an example (Appendix B). Additional examples are included in Appendix D. The practitioners in attendance at the initial meeting expressed concern about the potential for misuse of the Critical Elements. The group agreed that it would be prudent to develop both a disclaimer that would be printed on each CE and a preamble to be distributed along with packets of CEs. The disclaimer would explicitly state that these documents were not intended to define a standard of care, nor to dictate a specific course of treatment/care. Furthermore, the disclaimer would acknowledge that there are variations in the practice of medical genetics. Based on this discussion the working group drafted a disclaimer, modeled on the one used in American College of Obstetricians and Gynecologists (ACOG) bulletins. The disclaimer was subsequently reviewed and approved with minor modifications by the state attorney general. A preamble was drafted by the working group to clarify the intent of the documents (Appendix C). The CEs assume a genetic knowledge base which would not be available to healthcare professionals without training in medical genetics. Use of the CEs is not intended to substitute for evaluation and genetic counseling by a genetic professional. Copies of the approved templates and the 21 specific disease CEs were distributed to all genetics professionals and perinatologists in Washington State. After the remainder of the draft CEs are reviewed and approved, we plan to update approved CEs annually at a statewide meeting.

DISCUSSION We developed a process of formulating and documenting consensus on the current practices of genetic evaluation and genetic counseling in Washington State. This process was not evidence-based and was not intended to define a standard of care. Rather, the materials developed reflect the consensus of the statewide genetic professionals and perinatologists re-

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garding the issues to be considered in a genetics encounter, recognizing that each practitioner must also take into account individual patient needs. These documents have been written by and for genetics professionals as a clinical practice aid to promote consistency. A secondary benefit of the CEs may be to foster an understanding of genetic evaluation and genetic counseling among other healthcare providers and payers. Additional uses of the CE documents, such as for continuous quality improvement (CQI) activities or medical genetics trainee programs are currently under consideration by some of the participants. The intent of this publication is to describe this process and the CE templates developed to other genetic professionals. We are currently evaluating the utility of the CEs, and as part of this process we invite discussion both about the efficacy of the templates and the possible uses of the CEs. A survey of participating practitioners revealed that the documents were being used in clinical care as well as for accreditation, continuous quality improvement, for teaching students, and in presentations for medical and lay audiences regarding genetic services.

ACKNOWLEDGMENTS We would like to thank all of the genetic professionals and perinatologists in Washington State who contributed their time, enthusiasm, and support. They are: Central Washington Genetics Program, Yakima, WA: Susie Ball, MS Children's Hospital and Medical Center, Seattle, WA: Mary Beth Dinulos, MD, Louanne Hudgins, MD, Linda Ramsdell, MS, Darci Sternen, MS, and Virginia Sybert, MD Evergreen Hospital Medical Center, Kirkland, WA: Susan Rutherford, MD and Rebecca Zacharias, MS Group Health Cooperative, Seattle, WA: Ute Ochs, MD Inland Northwest Genetics Clinic, Spokane, WA: Michael Donlan, MD and Lael Hinds, MS Madigan Army Medical Center, Tacoma, WA: Jamilyn Daniels, MS and Mark Stephan, MD Mary Bridge Children's Hospital, Tacoma, WA: Roger Fick, MS Perinatal Associates, Spokane, WA: Cherie Johnson, MD St. Mary Medical Center, Walla Walla, WA:

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Pat Cooper, PhD Southwest Washington Perinatal Services, Tacoma, WA: Gail Hammer, MS Swedish Medical Center, Seattle, WA: Deborah Dunne, MS, David Luthy, MD, and Robert Resta, MS University of Washington, Seattle, WA: Julie Bars, MS, Thomas Bird, MD, Wylie Burke, MD, Leslie Carpenter, MS, Nuhad Dinno, MD, Gail Jarvik, MD, Kathryn Leppig, MD, Linda Mills, MS, Arno Motulsky, MD, Larry Shields, MD, Johanneke Smith, MS, Cris Trahms, MS, RD, and Stefanie Uhrich, MS This project was supported by the Washington State Department of Health, Genetics Services Section. Copies of CEs not contained in this article are available upon request through the Genetic Services Section, 1511 3rd Ave., Suite #323, Seattle, Washington 98101 or e-mail: [email protected].

APPENDIX A. CRITICAL ELEMENTS OF GENETIC EVALUATION AND GENETIC COUNSELING Template: Clinical (nonprenatal) Information obtained from patient/family 1.

Review patient/family questions, reason for referral, knowledge base, perception of disease status and/or risk, what diagnoses have been considered, perceived notion about causation: 2. a) Using standard symbols, obtain family history (1st and 2nd degree relatives to consultand, and further removed as appropriate). Note ethnic background, consanguinity, ongoing pregnancies, and other significant family history. b) Additional directed family history: c) Obtain relevant medical records on patient, including records of a) appropriate tests/evaluations: , b) records bearing on management: , and c) on other family members as needed: 3. Obtain prenatal and perinatal history of patient, including prenatal exposures, pregnancy complications and prenatal testing, when appropriate. 4. Obtain past medical history (including environmental/occupational exposures) focusing on:

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6. 7. 8. 9.

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Obtain information on growth and development, including school placement. For adult, also obtain information on education, employment, and social functioning. Assess family functioning and use of community resources. Assess personal, social, ethnocultural issues: Assess possible ethical concerns, such as confidentiality, nonpaternity, insurability, discrimination, prenatal diagnosis: Perform general physical examination of patient and/or other family members present if indicated, with attention to: Other issues to consider: Information to be provided or discussed with the patient/family

1.

Summarize information obtained and discuss with patient/family the (possible) diagnosis and the degree of certainty of the diagnosis based on available information. 2. a) Recommend relevant tests/evaluations on patient and/or on other relatives which may include: patient: diagnostic: management: other relatives: diagnostic: b) Discuss sensitivity/specificity of test(s)/evaluation(s): 3. Discuss the following issues related to natural history: prognosis, developmental outcome/intellectual functioning, anticipated possible medical complications, including pregnancy related risks for affected women if indicated, and preventive measures: 4. Review inheritance pattern (including penetrance and expressivity): 5.

Assess and discuss recurrence risk for future pregnancies, for affected and at risk individuals. Discuss general background risk for birth defects, including any additional risk based on family history/ethnicity/maternal age/maternal disease/maternal exposure/others: 6. a) Discuss reproductive options (e.g., assisted reproductive technologies, adoption, taking risk and no additional pregnancies) when appropriate: b) Discuss prenatal diagnostic options/issues: (or referral for discussion of): 7. Review management recommendations/options including screening protocols: 8. Consider referral to (medical specialties): 9. Address psychosocial issues including anticipatory guidance, patient and family reaction to diagnosis, need for community support services.

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a) available local/national resources, b) available written resources for families. 10. Address follow-up issues, such as genetic counseling for extended family members, including a plan for relaying test results: 11. Document clinic visit, including persons present, and subsequent substantive contacts (e.g., clinic note, +/- letter to referral source, +/- letter to family, other). 12. Other issues to consider: 13. References and/or other protocols: Template: Prenatal Information to be obtained from patients/family

1.

Review patient/family questions, reason for referral, knowledge base, perception of disease status and/or risk, what diagnoses have been considered, perceived notion of causation: 2. a) Using standard symbols, obtain family history (1st and 2nd degree relatives to consultand, and further removed as appropriate). Note ethnic background, consanguinity, ongoing pregnancies, and other significant family history. b) Additional directed family history: c) Obtain relevant medical records on patient/affected family member(s), including records on appropriate diagnostic testing/evaluation: and on other family members as needed: 3. Obtain patient's past and current pregnancy history; documenting gestational age, Rh, prenatal exposures, pregnancy complications, and pertinent prenatal testing to date. 4. Obtain patient's past medical history. 5. Obtain information on education, employment, and social functioning as appropriate. 6. Assess family functioning and use of community resources, as appropriate. Assess personal (e.g., social, ethnocultural, religious) i s s u e s , i n c l u d i n g f e e l i n g s a b o u t p r e n a t a l testing a n d consequences. 7. Assess ethical issues such as confidentiality, insurability, discrimination, and nonpaternity. 8. Other issues to consider:

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Information to be provided or discussed with patient/family 1. a) Discuss risk of specific condition occurring in current pregnancy based on information available. Arrange for additional tests/evaluations on consultand and/or father of the baby if indicated: b) Discuss sensitivity/specificity of test(s)/evaluation(s): c) Discuss referral of other family members for genetic testing/evaluation if inheritable disease is suspected and confirmation is necessary. 2. a) Discuss general background risk for birth defects, including any additional risk based on family history/ethnicity/maternal age/maternal disease/maternal exposure/others: b) Discuss inheritance pattern of disorder, including risk for future pregnancies: 3. Discuss the following issues related to natural history: prognosis, developmental outcome/intellectual functioning, anticipated possible medical complications, including pregnancy related risks for affected women if indicated, and preventive measures: 4. a) Review prenatal testing options as indicated: a) techniques 1. CVS (10-12 weeks) 2. early amniocentesis (15 weeks) 4. PUB (>18 weeks) 5. ultrasound 6. none

b) laboratory tests 1. karyotype 2. DNA 3. AFAFP/AChE 4. FISH 5. biochemical 6. other

b) Discuss risks and limitations of prenatal testing options, including sensitivity/specificity of test method(s): 5. Explore psychosocial impact of testing vs. nontesting, ethical issues, and discuss the decision making process. Refer to outside resources as appropriate to help with decision making. (Process includes the discussion of outcomes/results, additional testing, option of termination of pregnancy, pediatric follow up, and support groups.) 6. Document status of decision making by patient/family. 7. Make arrangements for testing if desired and plan for relaying results and for follow-up. 8. Consider referral to specific community resources and support groups. 9. Document the clinic visit, including persons present, and subsequent substantive contacts (e.g., clinic note, +/- letter to referring source, +/- letter to family, other). 10. Other issues to consider: 11. References and/or other protocols:

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APPENDIX B. CRITICAL ELEMENTS OF GENETIC EVALUATION AND GENETIC COUNSELING Individual with Fragile X

Date: 7/12/96* Disclaimer

The "Critical Element of Genetic Evaluation and Genetic Counseling" was written and approved by genetic professionals and perinatologists within the State of Washington. The document is to act as an aid to medical geneticists, genetic counselors, and perinatologists who practice within our state. This Critical Element of Genetic Evaluation and Genetic Counseling does not define the applicable standard of care, nor is it intended to dictate an exclusive course for the diagnosis, counseling, treatment or management of genetic conditions or birth defects. The authors acknowledge that appropriate clinical practices may vary depending upon a number of factors including, among others, the needs and choices of the individual patient, the resources available, and limitations unique to the particular institution or type of practice. Information Obtained from patient/family 1.

Review patient/family questions, reason for referral, knowledge base, perception of disease status and/or risk, what diagnoses have been considered; perceived notion about causation: which individuals in the family are perceived to be affected, carriers, or at risk. 2. a) Using standard symbols, obtain family history (1st and 2nd degree relatives to consultand, and further removed as appropriate). Note ethnic background, consanguinity, ongoing pregnancies, and other significant family history. b) Additional directed family history: maternal relatives with developmental delay/mental retardation, special education, behavior problems, and/ or autism. c) Obtain relevant medical records on patient, including records of a) appropriate tests/evaluations: Fragile X DNA testing, Fragile X cytogenetics, and past genetic evaluations, b) records bearing on management: developmental testing/psychometric and school evaluations, and c) on other family members as needed: Fra X test results. 3. Obtain prenatal and perinatal history of patient, including prenatal exposures, pregnancy complications and prenatal testing, when appropriate.

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4.

5.

6. 7.

8.

9.

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Obtain past medical history (including environmental/occupational exposures) focusing on: Behavior issues (e.g., hand flapping, avoidance of eye contact). Obtain information on growth and development, including school placement. For adults, also obtain information on education, employment, and social functioning. Assess family functioning and use of community resources. Assess personal, social, ethnocultural issues. Assess possible ethical concerns, such as confidentiality, nonpaternity, insurability, discrimination, prenatal diagnosis: informing at risk family members about risk and availability of diagnostic, carrier, and prenatal testing/counseling. Perform general physical examination of patient and/or other family members present if indicated, with attention to: ht, wt, OFC, facial features, testicular size in adolescent and older males, scoliosis, evaluation of joint mobility especially laxity, informal assessment of social skills. Other issues to consider: Information to be provided or discussed with the patient/family

1.

Summarize information obtained and discuss with patient/family the (possible) diagnosis and the degree of certainty of the diagnosis based on available information. 2. a) Recommend relevant tests/evaluations on patient and/or on other relatives which may include: patient: diagnostic: Fra X DNA testing management: psychometric assessment as necessary for appropriate educational placement other relatives: diagnostic: Fra X DNA testing b) Discuss sensitivity/specificity of test(s)/evaluation(s): diagnostic sensitivity of full mutation in males vs. females, predictive aspects of premutation size for expansion in the offspring of females. 3. Discuss the following issues related to natural history: prognosis, developmental outcome/intellectual functioning, anticipated possible medical complications, including pregnancy related risks for affected women if indicated, and preventive measures: males with full mutation, usually moderate MR. Females with full mutation, range of abilities (mild MR to learning difficulties to normal). Premutation carriers are asymptomatic. 4. Review inheritance pattern (including penetrance and expressivity): X-linked, trinucleotide repeat.

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5.

Assess and discuss recurrence risk for future pregnancies for affected and at risk individuals. Discuss general background risk for birth defects, including any additional risk based on family history/ethnicity/maternal age/maternal disease/maternal exposure/others: Males with the full mutation are unlikely to reproduce. Transmitting males have no risk of occurrence, risk to offspring of females with premutation depends on the size of the expansion, females with full mutation have a 50% risk of transmission of full expansion. 6. a) Discuss reproductive options (e.g., assisted reproductive technologies, adoption, taking risk, and no additional pregnancies) when appropriate: b) Discuss prenatal diagnostic options/issues: (or referral for discussion of): amniocentesis for Fragile X DNA mutation analysis; CVS may not be as reliable because of variation in methylation. Risk of mental retardation in female fetuses with the full expansion is 50%. 7. Review management recommendations/options including screening protocols: pharmalocologic intervention for behavioral problems, special education. 8. Consider referral to: developmental pediatrician, OT/PT, psychologist, psychiatrist (medical specialties). 9. Address psychosocial issues including anticipatory guidance, patient and family reaction to diagnosis, need for community support services. a) available local/national resources: National Fragile X Foundation 1441 York St, Suite 303 Denver, CO 80206-2127

b) available written resources for families: Newsletters: National Fragile X Advocate Avanta Media Corporation PO Box 17023, Chapd Hill NC 27516-1702 1-800-434-0322

FRAXA Research Foundation FRAXA P.O. Box 935 West Newbury, MA 01985

FRAXA Research Foundation Newsletter FRAXA P.O. Box 935 West Newbury, MA 01985

Parent to Parent Infant-Toddler Early Intervention Program Family Resources Project (360) 586-2810 (to locate local contact) Children with Special Health Care Needs (CSHCN) Nurse WA Association for Retarded Citizens 10. Address follow up issues, such as genetic counseling for extended family members, including a plan for relaying test results: Genetic

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counseling should be offered to those members of the extended family determined to be at risk by pedigree analysis.

11. Document clinic visit, including persons present, and subsequent substantive contacts (e.g., clinic note, +/- letter to referral source, +/- letter to family, other). 12.

Other issues to consider: Ethical concerns in prenatal diagnosis due to inability to predict phenotype (i.e., MR) in female fetus with full expansion.

13. References and/or other protocols: Hagerman, RJ, Silverman AC (eds.) (1991) Fragile X Syndrome: Diagnosis, treatment and research. Baltimore: Johns Hopkins Press. Tarleton JC, Saul RA (1993) Molecular genetic advances in fragile X syndrome. J Pediatr 122:169. Warren ST, Nelson DT (1994) Advances in molecular analysis Fragile X syndrome. JAMA 271:536.

*This Critical Element of Genetic Evaluation and Genetic Counseling was unanimously approved at a state genetics practitioners meeting on 7/12/96. Pregnant woman with a family history of Fragile X

Date: 7/12/96*

Disclaimer

The "Critical Element of Genetic Evaluation and Genetic Counseling" was written and approved by genetic professionals and perinatologists within the State of Washington. The document is to act as an aid to medical geneticists, genetic counselors, and perinatologists who practice within our state. This Critical Element of Genetic Evaluation and Genetic Counseling does not define the applicable standard of care, nor is it intended to dictate an exclusive course for the diagnosis, counseling, treatment or management of genetic conditions or birth defects. The authors acknowledge that appropriate clinical practices may vary depending upon a number of factors including, among others, the needs and choices of the individual patient, the resources available, and limitations unique to the particular institution or type of practice. Information to be obtained from patients/family

1.

Review patient/family questions, reason for referral, knowledge base, perception of disease status and/or risk, what diagnoses have been considered, perceived notion of causation: which individuals in the family are perceived to be affected, carriers, or at risk.

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2. a) Using standard symbols, obtain family history (1st and 2nd degree relatives to consultand, and further removed as appropriate). Note ethnic background, consanguinity, ongoing pregnancies, and other significant family history. b) Additional directed family history: maternal relatives with developmental delay/mental retardation, special education, behavior problems, and/or autism. c) Obtain relevant medical records on patient/affected family member(s), including records on appropriate diagnostic testing/evaluation: Fragile X DNA analysis, Fragile X cytogenetics and on other family members as needed: either Fragile X DNA analysis or Fragile X cytogenetics on at least one affected individual and Fragile X DNA testing on consultand if he/she is determined to be at risk by pedigree analysis. 3. Obtain patient's past and current pregnancy history, documenting gestational age, Rh, prenatal exposures, pregnancy complications, and pertinent prenatal testing to date. 4. Obtain patient's past medical history. 5. Obtain information on education, employment, and social functioning as appropriate. 6. Assess family functioning and use of community resources, as appropriate. Assess personal (e.g., social, ethnocultural, religious) issues, including feelings about prenatal testing and consequences. 7. Assess ethical issues, such as confidentiality, insurability, discrimination, and nonpaternity. 8. Other issues to consider: Information to be provided or discussed with patient/family 1. a) Discuss risk of specific condition occurring in current pregnancy based on information available. Arrange for additional tests/evaluations on consultand and/or father of the baby if indicated: Fragile X DNA analysis on consultand or father of the baby as appropriate. b) Discuss sensitivity/specificity of test(s)/evaluation(s): diagnostic sensitivity of full mutation in males vs. females, predictive aspects of premutation size for expansion in the offspring of females. c) Discuss referral of other family members for genetic testing/evaluation if inheritable disease is suspected and confirmation is necessary. 2. a) Discuss general background risk for birth defects, including any additional risk based on family history/ethnicity/maternal age/maternal disease/maternal exposure/others. b) Discuss inheritance pattern of disorder, including risk for future pregnancies.

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3.

Discuss the following issues related to natural history: prognosis, developmental outcome/intellectual functioning, anticipated possible medical complications, including pregnancy related risks for affected women if indicated, and preventive measures: males with full mutation, usually moderate MR. Females with full mutation, range of abilities (mild MR to learning difficulties to normal). Premutation carriers are asymptomatic. 4. a) Review prenatal testing options as indicated: a) techniques amniocentesis (>15 weeks) early amniocentesis (15 weeks) PUB (>22 weeks)* *Depending on gestational age at the time of referral. b) Discuss risks and limitations of prenatal testing options, including sensitivity/specificity of test method(s). Option of: 1. multiple maternal analyte screen (if prenatal chromosome analysis declined) 2. directed U/S 5. Explore psychosocial impact of testing vs. nontesting, ethical issues, and discuss the decision-making process. Refer to outside resources as appropriate to help with decision making. (Process includes the discussion of outcomes/results, additional testing, option of termination of pregnancy, pediatric follow-up, and support groups.) 6. Document status of decision-making by patient/family. 7. Make arrangements for testing if desired and plan for relaying results and for follow-up. 8. Consider referral to specific community resources and support groups. 9. Document the clinic visit, including persons present, and subsequent substantive contacts (e.g., clinic note, +/- letter to referring source, +/- letter to family, other). 10. Other issues to consider: 11. References and/or other protocols: Beirkowit GS et al. (1990) Delayed childbearing and the outcome of pregnancy. NEJM 322:659-664.

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*This Critical Element of Genetic Evaluation and Genetic Counseling was unanimously approved at a state genetics practitioners meeting on 12/6/96. Date: 7/12/96* Pregnant woman with a positive serum screening for Down syndrome Disclaimer The "Critical Element of Genetic Evaluation and Genetic Counseling" was written and approved by genetic professionals and perinatologists within the State of Washington. The document is to act as an aid to medical geneticists, genetic counselors, and perinatologists who practice within our state. This Critical Element of Genetic Evaluation and Genetic Counseling does not define the applicable standard of care, nor is it intended to dictate an exclusive course for the diagnosis, counseling, treatment or management of genetic conditions or birth defects. The authors acknowledge that appropriate clinical practices may vary depending upon a number of factors including, among others, the needs and choices of the individual patient, the resources available, and limitations unique to the particular institution or type of practice. Information to be obtained from patients/family 1.

Review patient/family questions, reason for referral, knowledge base, perception of disease status and/or risk, what diagnoses have been considered, perceived notion of causation: understanding that risk is for Down syndrome, rather than neural tube defects, understanding of the meaning of "screening" test. 2. a) Using standard symbols, obtain family history (1st and 2nd degree relatives to consultand, and further removed as appropriate). Note ethnic background, consanguinity, ongoing pregnancies, and other significant family history. b) Additional directed family history: Down syndrome, miscarriage/ stillbirth. c) Obtain relevant medical records on patient/affected family member(s), including records on appropriate diagnostic testing/evaluation: lab report to check screening results and US to confirm gestational age, karyotype if history of Down syndrome or pregnancy loss, and on other family members as needed: karyotypes if history of Down syndrome or pregnancy loss. 3. Obtain patient's past and current pregnancy history; documenting gestational age, Rh, prenatal exposures, pregnancy complications, and pertinent prenatal testing to date: history of preeclampsia/eclampsia.

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4. 5. 6.

7. 8.

Obtain patient's past medical history: Obtain information on education, employment, and social functioning as appropriate. Assess family functioning and use of community resources, as appropriate. Assess personal (e.g., social, ethnocultural, religious) issues, including feelings about prenatal testing and consequences. Assess ethical issues such as confidentiality, insurability, discrimination, and nonpaternity. Other issues to consider: Correct gestational age, accuracy of ultrasound dating vs. menstrual dating, short femur/humerus in Down syndrome and effect on gestational dating, screen should be repeated only if ultrasound shows initial sample was drawn too early in pregnancy, recalculate risk if > = 2 week dating discrepancy but patient still at least 15 weeks, screen may be invalid in the presence of twins or maternal IDDM, awareness of statistical limitations of screening related to specific combination of analytes and specific criteria for screen positive results. Information to be provided or discussed with patient/family

1. a) Discuss risk of specific condition occurring in current pregnancy based on information available. Arrange for additional tests/evaluations on consultand and/or father of the baby if indicated: karyotypes if family history suggestive of Down syndrome or translocation: b) Discuss sensitivity/specificity of test(s)/evaluation(s): c) Discuss referral of other family members for genetic testing/evaluation if inheritable disease is suspected and confirmation is necessary: 2. a) Discuss general background risk for birth defects, including any additional risk based on family history/ethnicity/maternal age/maternal disease/maternal exposure/others: b) Discuss inheritance pattern of disorder, including risk for future pregnancies: 3. Discuss the following issues related to natural history: prognosis, developmental outcome/intellectual functioning, anticipated possible medical complications, including pregnancy related risks for affected women if indicated, and preventive measures: 4. a) Review prenatal testing options as indicated: a) techniques amniocentesis (>15 weeks) PUB (>18 weeks)

b) laboratory tests karyotype

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b)

Discuss risks and limitations of prenatal testing options, including sensitivity/specificity of test method(s): Include discussion of limitations of sonographic detection of abnormalities associated with Down syndrome: 5. Explore psychosocial impact of testing vs. nontesting, ethical issues, and discuss the decision-making process. Refer to outside resources as appropriate to help with decision making. (Process includes the discussion of outcomes/results, additional testing, option of termination of pregnancy, pediatric follow up, and support groups.) 6. Document status of decision-making by patient/family. 7. Make arrangements for testing if desired and plan for relaying results and for follow up: If fetus has Down syndrome offer fetal echocardiogram > 20 weeks and third trimester scan to rule out duodenal atresia which usually does not manifest until third trimester (see Down syndrome CE). 8. Consider referral to specific community resources and support groups. 9. Document the clinic visit, including persons present, and subsequent substantive contacts (e.g., clinic note, +/- letter to referring source, +/- letter to family). 10. Other issues to consider: If normal fetal karyotype variety of other pregnancy complications have been associated with high and low levels of analytes (e.g., high hCG and preeclampsia). If fetal translocation offer parental karyotypes (see Translocation Down syndrome CE). 11. References and/or other protocols: Cuckle H, Densen J, Wald N (1994). Repeat maternal serum testing in multiple marker Down's syndrome screening programmes. Prenatal Diag 14:603-607. Haddow JE, Palomaki GE, Knight GJ et al. (1992) Prenatal screening for Down's syndrome with use of maternal serum markers. NEJM 327:588-593. Cheng EY, Luthy DA, Zebelraan AM et al. (1993) A prospective evaluation of a second-trimester test for fetal Down syndrome using maternal serum alpha-fetoprotein, hCG, and unconjugated estriol. Obstet Gynecol 81:72-77. Haddow JE, Palomaki GE, Knight GJ et al. (1994) Reducing the need for amniocentesis in women 36 years of age or older with maternal serum markers for screening. NEJM 330:1114-1118. Sorensen TK, Williams MA, Zingheim RW, Clement SJ, Hickok DE (1993) Elevated second-trimester human chorionic gonadotropin and subsequent pregnancy-induced hypertension. Am J Obstet Gynecol 169:834-838.

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Lieppman RE, Williams MA, Cheng EY, Resta R, Zingheim R, Hickok DE, Luthy DA (1993) An association between elevated levels of human chorionic gonadotropin in the midtrimester and adverse pregnancy outcome. Am J Obstet Gynecol 168:1852-1857. PacNoRGG Fact Sheet: Maternal Serum Multiple Marker Screening for Chromosome Abnormalities and Open Neural Tube Defects. This Critical Element of Genetic Evaluation and Genetic Counseling was unanimously approved at a state genetics practitioners meeting on 7/12/96. Date: 7/12/96* Individual with Trisomy 21 Down syndrome or individual with chromosomes pending Disclaimer The "Critical Element of Genetic Evaluation and Genetic Counseling" was written and approved by genetic professionals and perinatologists within the State of Washington. The document is to act as an aid to medical geneticists, genetic counselors, and perinatologists who practice within our state. This Critical Element of Genetic Evaluation and Genetic Counseling does not define the applicable standard of care, nor is it intended to dictate an exclusive course for the diagnosis, counseling, treatment or management of genetic conditions or birth defects. The authors acknowledge that appropriate clinical practices may vary depending upon a number of factors including, among others, the needs and choices of the individual patient, the resources available, and limitations unique to the particular institution or type of practice. Information Obtained from patient/family 1.

Review patient/family questions, reason for referral, knowledge base, perception of disease status and/or risk, what diagnoses have been considered, perceived notion about causation: 2. a) Using standard symbols, obtain family history (1st and 2nd degree relatives to consultand, and further removed as appropriate). Note ethnic background, consanguinity, ongoing pregnancies, and other significant family history. b) Additional directed family history: miscarriages, neonatal death, known or suspected chromosome abnormalities, Down Syndrome, individuals with multiple anomalies/MR. c) Obtain relevant medical records on patient, including records of a) appropriate tests/evaluations: karyotype, genetic evaluations, b)

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3.

4.

5.

6. 7. 8.

9.

1S7

records bearing on management: thyroid, CBC, echocardiogram, and c) on other family members as needed: karyotype. Obtain prenatal and perinatal history of patient, including prenatal exposures, pregnancy complications and prenatal testing, when appropriate: Obtain past medical history (including environmental/occupational exposures) focusing on: congenital heart disease, GI, hematology, development, vision, hearing/ear infections. Obtain information on growth and development, including school placement. For adults, also obtain information on education, employment, and social functioning: Assess family functioning and use of community resources. Assess personal, social ethnocultural issues: Assess possible ethical concerns, such as confidentiality, nonpaternity, insurability, discrimination, prenatal diagnosis: Perform general physical examination of patient and/or other family members present if indicated, with attention to: physical stigmata of Down syndrome, heart, growth (ht, wt, OFC), informal developmental assessment. Other issues to consider: Information to be provided or discussed with the patient/family

1.

Summarize information obtained and discuss with patient/family the (possible) diagnosis and the degree of certainty of the diagnosis based on available information. 2. a) Recommend relevant tests/evaluations on patient and/or on other relatives which may include: patient: diagnostic: karyotype management: age dependent other relatives: diagnostic: b) Discuss sensitivity/specificity of test(s)/evaluation(s): Discuss the following issues related to natural history: prognosis, developmental outcome/intellectual functioning, anticipated possible medical complications, including pregnancy related risks for affected women if indicated, and preventive measures: reproductive issues. 4. Review inheritance pattern (including penetrance and expressivity): sporadic chromosomal 5. Assess and discuss recurrence risk for future pregnancies, for affected and at risk individuals. Discuss general background risk for birth defects, including any a d d i t i o n a l risk based on family 3.

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history/ethnicity/maternal age/maternal disease/maternal exposure/others. 6. a) Discuss reproductive options (e.g., assisted reproductive technologies, adoption, taking risk, and no additional pregnancies) when appropriate: pregnancy with or without prenatal diagnosis. b) Discuss prenatal diagnostic options/issues: refer to prenatal CE (or referral for discussion of). 7. Review management recommendations/options including screening protocols: As outlined in the American Academy of Pediatrics Health supervision for child with Down syndrome. 8. Consider referral to: cardiology, ophthalmology, developmental pediatrician, audiologist, PT/OT(medical specialties). 9. Address psychosocial issues including anticipatory guidance, patient and family reaction to diagnosis, need for community support services. a) available local/national resources: Infant Stimulation Program

Infant-Toddler Early Intervention Program Family Resources Project (360) 586-2810 (to identify local contact)

Association for Children with Down Syndrome, Inc. (ACDS) 2616 Martin Avenue, Bellmore, NY 11710-3169 (516) 221-4700 Fax: (516) 221-4311 National Down Syndrome Congress (NDSC) 1605 Chantilly Drive, Suite 250, Atlanta, GA 30324-3269 (404) 633-1555 1-800-232-6372 Fax: (404) 633-2817

National Down Syndrome Society (NDSS) 666 Broadway, New York, NY 10012 (212) 460-9330 1-800-221-4602 Fax: (212) 979-2873

Parent Assistance Committee on Down Syndrome (PACDS) 208 Lafayette Avenue, Peekskill, NY 10566 (914) 739-4085 b) available written resources for families: Pueschel, S (1990) A Parents Guide to Down Syndrome. Baltimore: Brookes Publishing Co. Stray-Gunderson (ed) (1986) Babies with Down syndrome: A New parent's guide. Rockville, MD: Woodine House.

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10.

Address follow up issues, such as genetic counseling for extended family members, including a plan for relaying test results: 11. Document clinic visit, including persons present, and subsequent substantive contacts (e.g., clinic note, +/- letter to referral source, +/- letter to family; other). 12. Other issues to consider: 13. References and/or other protocols: 1. Health Supervision for children with Down syndrome (Committee on Genetics) (1994) Pediatrics 93(5): May. 2. Atlantoaxial instability in Down syndrome: Subject review (Committee on Sports Medicine and Fitness) (1995) Pediatrics 96(1): July. 3. Lott IT, McCoy EE (eds) (1993) Down syndrome advances in medical care. New York: Wiley-Liss. *This Critical Element of Genetic Evaluation and Genetic Counseling was unanimously approved at a state genetics practitioners meeting on 7/12/96. Date: 7/12/96* Pregnant woman with a family history of Trisomy 21 or Down syndrome Disclaimer The "Critical Element of Genetic Evaluation and Genetic Counseling" was written and approved by genetic professionals and perinatologists within the State of Washington. The document is to act as an aid to medical geneticists, genetic counselors, and perinatologists who practice within our state. This Critical Element of Genetic Evaluation and Genetic Counseling does not define the applicable standard of care, nor is it intended to dictate an exclusive course for the diagnosis, counseling, treatment or management of genetic conditions or birth defects. The authors acknowledge that appropriate clinical practices may vary depending upon a number of factors including, among others, the needs and choices of the individual patient, the resources available, and limitations unique to the particular institution or type of practice. Information to be obtained from patients/family 1.

Review patient/family questions, reason for referral, knowledge base, perception of disease status and/or risk, what diagnoses have been considered, perceived notion of causation: 2. a) Using standard symbols, obtain family history (1st and 2nd degree relatives to consultand, and further removed as appropriate). Note

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ethnic background, consanguinity, ongoing pregnancies, and other significant family history. b) Additional directed family history: miscarriages, neonatal death, known or suspected chromosome abnormalities, Down syndrome, individuals with multiple anomalies/MR. c) Obtain relevant medical records on patient/affected family member(s), including records on appropriate diagnostic testing/evaluation: karyotype and genetic evaluations and on other family members as needed: 3. Obtain patient's past and current pregnancy history, documenting gestational age, Rh, prenatal exposures, pregnancy complications, and pertinent prenatal testing to date: 4. Obtain patient's past medical history: 5. Obtain information on education, employment, and social functioning as appropriate: 6. Assess family functioning and use of community resources, as appropriate. Assess personal (e.g., social, ethnocultural, religious) issues, including feelings about prenatal testing and consequences: 7. Assess ethical issues, such as confidentiality, insurability, discrimination, and nonpaternity: 8. Other issues to consider: Information to be provided or discussed with patient/family

1. a) Discuss risk of specific condition occurring in current pregnancy based on information available. Arrange for additional tests/evaluations on consultand and/or father of the baby if indicated: increased recurrence risk for trisomies is identified for couple with a child with Trisomy 21, all other family members have the maternal age related risk for chromosome abnormalities. b) Discuss sensitivity/specificity of test(s)/evaluation(s). c) Discuss referral of other family members for genetic testing/evaluation if inheritable disease is suspected and confirmation is necessary. 2. a) Discuss general background risk for birth defects, including any additional risk based on family history/ethnicity/maternal age/maternal disease/maternal exposure/others. b) Discuss inheritance pattern of disorder, including risk for future pregnancies. 3. Discuss the following issues related to natural history: prognosis, developmental outcome/intellectual functioning, anticipated possible medical complications, including pregnancy related risks for affected women if indicated, and preventive measures.

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4. a) Review prenatal testing options as indicated: a) techniques CVS (10-12 weeks) early amniocentesis (15 weeks)

b) laboratory tests karyotype

b) Discuss risks and limitations of prenatal testing options, including sensitivity/specificity of test method(s). 5. Explore psychosocial impact of testing vs. nontesting, ethical issues, and discuss the decision-making process. Refer to outside resources as appropriate to help with decision making. (Process includes the discussion of outcomes/results, additional testing, option of termination of pregnancy, pediatric follow up, and support groups.) 6. Document status of decision making by patient/family. 7. Make arrangements for testing if desired and plan for relaying results and for follow up. 8. Consider referral to specific community resources and support groups. 9. Document the clinic visit, including persons present, and subsequent substantive contacts (e.g., clinic note, +/- letter to referring source, +/- letter to family). 10. Other issues to consider: Triple Marker Maternal Serum Screening 11. References and/or other protocols: This Critical Element of Genetic Evaluation and Genetic Counseling was unanimously approved at a state genetics practitioners meeting on 7/12/96. Adult Presymptomatic for Huntington Disease

Date: 7/12/96*

Disclaimer The "Critical Element of Genetic Evaluation and Genetic Counseling" was written and approved by genetic professionals and perinatologists within the State of Washington. The document is to act as an aid to medical geneticists, genetic counselors, and perinatologists who practice within our state. This Critical Element of Genetic Evaluation and Genetic Counseling does not define the applicable standard of care, nor is it intended to dictate an exclusive course for the diagnosis, counseling, treatment or management of genetic conditions or birth defects. The authors acknowledge that appropriate clinical practices may vary depending upon a number of factors including, among others, the needs and choices of the individual patient, the resources available, and limitations unique to the particular institution or type of practice.

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Information obtained from patient/famify 1.

Review patient/family questions, reason for referral, knowledge base, perception of disease status and/or risk, what diagnoses have been considered, perceived notion of causation: Recommend support person be present at all visits. If asymptomatic minor, testing should be deferred until legal adult (see Neurology 1994, Bloch 1993, ASHG position statement on testing children, 1995). 2. a) Using standard symbols, obtain family history (1st and 2nd degree relatives to consultand, and further removed as appropriate). Note ethnic background, consanguinity, ongoing pregnancies, and other significant family history. b) Additional directed family history: neurological diseases, uncontrolled movements, mental illness, age of onset of symptoms, ages and causes of death. c) Obtain relevant medical records on patient, including records of a) appropriate tests/evaluations: prior neurological exams, neuro/psych evaluations, genetic evaluations, b) records bearing on management, and c) on other family members as needed: HD testing, neurological exams, brain imaging, autopsy (brain). 3. Obtain prenatal and perinatal history of patient, including prenatal exposures, pregnancy complications and prenatal testing, when appropriate. 4. Obtain past medical history (including environmental/occupational exposures) focusing on: changes in mental and physical functioning, depression, traumatic head injury, drug and alcohol use. 5. Obtain information on growth and development, including school placement. For adult, also obtain information on education, employment and social functioning: assess changes in job and driving performance, social/family functioning. 6. Assess family functioning and use of community resources. Assess personal, social ethnocultural issues. 7. Assess possible ethical concerns, such as confidentiality, nonpaternity, insurability, discrimination, prenatal diagnosis: evaluation of symptomatic minor, genetic counseling for any additional family members being tested concurrently, evaluation of individuals at 25% risk, prenatal testing. 8. Perform general physical examination of patient and/or other family members present if indicated, with attention to: neurological exam, mental status exam. 9. Other issues to consider: consider documentation of diagnosis in an affected family member by HD DNA testing. If testing is done in

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another asymptomatic family member—that family member needs genetic services as outlined in this document.

Information to be provided or discussed with the patient/family 1.

Summarize information obtained and discuss with patient/family the (possible) diagnosis and the degree of certainty of the diagnosis based on available information: Symptomatic individuals should follow symptomatic critical elements. Before HD DNA testing, counseling should explore the impact of positive, negative, and uncertain DNA results on the following areas:

• • • •

relationships with significant partner, children, extended family, friends career decisions, and telling colleagues at work impact on financial planning, including insurance (life, medical, disability) "survival guilt" (i.e., perceive increased burden of taking care of affected family members) • optimal timing of testing (assess if other stressful life events occurring), plan for giving results to whom (i.e., phone, in person). see references below: Bennett (1996), Bennett et al. (1993), Guidelines (1994), and Quaid (1992)

2. a) Recommend relevant tests/evaluations on patient and/or on other relatives which may include: patient: diagnostic: HD DNA testing (if requested) management: other relatives: diagnostic: HD DNA testing with informed consent after counseling b) Discuss sensitivity/specificity of test(s)/evaluation(s): Discuss the following issues related to natural history: prognosis, developmental outcome/intellectual functioning, anticipated possible medical complications, including pregnancy related risks for affected women if indicated, and preventive measures: a positive HD DNA test result does not give information about age of onset of symptoms, severity of symptoms nor prognosis. 4. Review inheritance pattern (including penetrance and expressivity): autosomal dominant, trinucleotide repeat, age related penetrance. 5. Assess and discuss recurrence risk for future pregnancies, for affected and at risk individuals. Discuss general background risk for birth defects, including any additional risk based on family history/ethnicity/maternal age/maternal disease/maternal exposure/others: 3.

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6. a) Discuss reproductive options (e.g., assisted reproductive technologies, adoption, taking risk, and no additional pregnancies) when appropriate: male affected: artificial insemination by donor semen, female affected: donor ovum. b) Discuss prenatal diagnostic options/issues: in pregnancies at 50% risk: amniocentesis, CVS, option of non-disclosing prenatal diagnosis by DNA linkage for pregnancies at 25% risk (or referral for discussion of). 7. Review management recommendations/options including screening protocols: 8. Consider referral to: neurologist, professional psychological support (medical specialties). 9. Address psychosocial issues including anticipatory guidance, patient and family reaction to diagnosis, need for community support services. a) available local/national resources: HDSA, 140 W. 22nd Street 6th floor Northwest Chapter Helpline: 206-469-6512 New York, NY 10011-2420

b) available written resources for families: Testing for Huntington Disease: Making an Informed Choice (available from PacNoRGG) 10. Address follow up issues, such as genetic counseling for extended family members, including a plan for relaying test results: individual with positive results should be contacted shortly after being given results and offered a return clinic visit. 11. Document clinic visit, including persons present, and subsequent substantive contacts (e.g., clinic note, +/- letter to referral source, +/- letter to family, other). 12. Other issues to consider: presymtomatic testing usually requires more that one visit. Visit 1: information and counseling, visit 2: neurological examination with additional counseling, Visit 3: results 13. References and/or other protocols: Bennett RL (1996) Testing for Huntington Disease: Making an Informed Choice. Available through PacNoRGG, CDRC-Clinical Services Bldg, 901 E. 18th Ave., Eugene, OR 97403-5254. Bennett RL, Bird TD, Teri L (1993) Offering predictive testing for Huntington disease in a medical genetics clinic: Practical applications. J Genet Counsel 2:123-137. Bloch M, Hayden MR (1990) Opinion: Predictive testing for Huntington disease in childhood: Challenges and implications. Am J Hum Genet 46:1-4.

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Folstein SE (1989) Huntington disease: A disorder of families. Baltimore: Johns Hopkins University Press. Goldberg YP, Telenius H, Hayden MR (1994) The molecular genetics of Huntington's disease. Curr Opin Neural 7(4):325-332. Guidelines for the molecular genetics predictive test in Huntington's disease (1994) Neurology 44:1533-1536. Hayden MR, Kremer B (1995) Huntington disease In: Scriver CR et al. (eds) The metabolic and molecular bases of inherited disease. New York: McGraw-Hill pp 4483-4510. Quaid KA (1992) Presymptomatic testing for Huntington disease: Recommendations for counseling. J Genet Counsel 1(4):277-302.

Wexler A (1995) Mapping fate: A memoir of family, risk and genetic research. New York: Times Books Wiggins S, Whyte P, Huggins M (1992) The psychological consequences of predictive testing for Huntington's disease. N Engl J Med 327:1401-1405. This Critical Element of Genetic Evaluation and Genetic Counseling was unanimously approved at a state genetics practitioners meeting on 7/12/96.

REFERENCES Committee on Genetics (1994) Health supervision for children with Down syndrome. Pediatrics 93:855-859. Freeman SB, Hinton CF, Elsas LJ (eds) (1996) Genetic Services: Developing Guidelines for the Public's Health. Conference Proceedings, The Council of Regional Networks for Genetic Services. Guidelines for the molecular genetics predictive test in Huntington's disease (1994) Neurology 44:1533-1536. McConkie-Rosell A, Robinson H, Wake S, Staley LW, Heller K, Cronister A (1995) Dissemination of genetic risk information to relatives in the Fragile X syndrome: Guidelines for genetic counselor. Am J Med Genet 59:426-430. Vichinsky E, Lubin BH (1987) Suggested guidelines for the treatment of children with Sickle Cell Anemia. Pediat. Hematol. 1:483-501.