Familial Cancer DOI 10.1007/s10689-014-9724-5
ORIGINAL ARTICLE
How harmful is genetic testing for familial adenomatous polyposis (FAP) in young children; the parents’ experience Anna A. Kattentidt-Mouravieva • M. den Heijer I. van Kessel • A. Wagner
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Ó Springer Science+Business Media Dordrecht 2014
Abstract Predictive genetic testing for familial adenomatous polyposis (FAP) is routinely offered to children at-risk from the age of 10 years onwards. Predictive testing for FAP at a younger age is debatable, because of absence of medical benefits. However, circumstances may arise when testing at a younger age (\10 years) is appropriate. Currently, there is a lack of published experience with predictive testing of children at this young age. We evaluated 13 children who were tested for FAP at the age younger than 10 years; 7 mutation-carriers and 6 non-carriers. Parents of these children were re-contacted and openended semi-structured interviewed. None of the contacted parents regretted the timing of genetic testing. The major reasons for testing at the young age were (1) testing of all children in the family at the same moment; (2) certainty for the future; and (3) preparing the child for future surveillance. None of the parents observed changes in mental or physical health in their child after testing. Also, young genetic testing did not lead to colon surveillance before it was indicated. Genetic testing for FAP at a young age is experienced as causing no harm by parents. Future studies should evaluate children’s own experiences with early genetic testing. Keywords Children Familial adenomatous polyposis Genetic predictive testing Psychosocial aspects
A. A. Kattentidt-Mouravieva (&) M. den Heijer I. van Kessel A. Wagner Department of Clinical Genetics, Erasmus University Medical Centre Rotterdam, Office Ee2018, PO Box 2040, 3000 CA Rotterdam, The Netherlands e-mail: [email protected]
Introduction FAP is an autosomal dominant predisposition to develop hundreds to thousands of colorectal polyps ultimately leading to colorectal cancer. It is caused by a germline mutation in the APC gene. Untreated, the risk of colorectal cancer in FAP patients is 100 %. When FAP is diagnosed in time, health benefits and increased life expectancy can be achieved. In FAP the average age when colorectal polyps are detected is 15 years [1]. Carriers of a pathogenic APC mutation are recommended to adhere to colonoscopic screening from the age of 10–12 years and to undergo surgery in adolescence in order to prevent colorectal cancer formation. There is a consensus that predictive genetic testing for a hereditary disease in minors is only indicated by a direct medical benefit through either medical intervention or preventive measures [2, 3]. Therefore, predictive genetic testing for FAP is routinely offered to children atrisk from the age of 10 years onwards. Mutation positive children are recommended to adhere to colonoscopic surveillance or may consider surgical intervention, whereas mutation negative children can avoid the unnecessary medical contacts. Occasionally parents request genetic testing in healthy at-risk offspring before the age of 10 years. An important motivation for genetic testing at a young age can be parents’ own uncertainty about the child’s future. Knowing that the child is not a carrier may lead to a relief from worries. While, on the other hand, knowing that the child is a carrier may enable parents to prepare their child for living with FAP. Crawford et al. reported a case when a child was tested for a familial APC mutation at the age of 9 months. In this case, the main motivation for testing at the very young age was to enable better family planning [4]. Depending on the carrier status in the first child the couple would make reproductive
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choices about further children, motivated by the feeling to have a duty to stop the predisposition from being transmitted to future generations. The main arguments against genetic testing at a younger age are respect for the child’s autonomy and potential psychosocial harm [5–8]. Compared to the general population, carriers may experience lower self-esteem [5, 6, 9, 10]. They can feel guilty, abnormal and ‘‘not perfect’’ because of carriership of a heritable disease [9, 10]. Furthermore, a genetic test can lead to not-indicated medical interventions, potential stigmatization and discrimination of a carrier, insurance issues and employment discrimination [11]. Also, the potential for adverse consequences on family dynamics after genetic testing has been frequently discussed in the literature [5, 12, 13]. After a DNA result, a child-carrier can be overprotected or emotionally isolated from his family. The parents and the family may treat a child-carrier and a child-non-carrier differently. In addition, in the case of different DNA result, a child-non-carrier may feel guilty for his/her sibling-carrier about not carrying the predisposition. On the other hand, genetic testing in children may also have positive effects on family relationships. The experience through the process of genetic testing may create closer contact and an increased intimacy between the tested children. Genetic testing for FAP under the age of 10 years has been debated since the advent of predictive genetic testing. Although practice shows that professionals are mostly reluctant in genetic testing of children at the age earlier than first possible onset of the disease, deviations of the recommendations regularly occur. Despite of children being tested for FAP under the age of 10 years, literature on these cases is lacking [4, 14–16]. According to the report on the genetic testing of children of the British Society for Human Genetics [17], for any particular child and family, the benefits of testing in childhood may outweigh the harms. If there are specific reasons, predictive genetic testing for a late onset condition can take place even at a younger age than recommended. Furthermore, the UK alliance of patient organizations Genetic Interest Group [18] claims that parents should be able to decide about the best moment of genetic testing and not professionals according to recommendations such as the rule of the earliest onset’, which implies that genetic testing should be permitted at an age no earlier than the age of first possible onset’ of the disease [19]. Congruently, Michie et al. [20] showed that parents feel strongly about their right to decide about the children’s testing, and that they do not feel that professionals have the relevant experience or right to make this decision. Research data on the consequences of early predictive genetic testing for FAP can contribute to the discussion of testing at the very young age. Currently, published data about predictive testing for FAP in children at the young
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age (\10 years) is scarce [4, 14, 15]. Gjone et al. studied present mental health functioning in a group of 7 adolescents who were tested for FAP at birth and in a group of 11 adolescents who were tested above the age of 9 years [4, 14, 15]. The group tested at birth had better mental health and psychosocial functioning than those tested later, although the differences did not reach statistical significance. These findings suggest no negative influences of early testing on child’s development as compared to later testing. This is of particular clinical interest, given the current guidelines recommending that predictive genetic testing for FAP is routinely offered to children at-risk from the age of 10 years onwards. Further insight is needed on the experiences of predictive testing for FAP in children younger than 10 years. In our centre DNA analysis for FAP is usually offered according to the current guidelines from the 10 years of age, when colon surveillance can be started. In case of parents’ request to perform genetic testing in their child at a younger age, detailed pre-test counselling of parents (and in some cases of children) takes place. Motivations for early genetic testing as well as the psycho-emotional situation within a family are evaluated by a counsellor and a psychologist. The reasons for reluctant policy towards genetic testing for FAP at a young age are always thoroughly discussed with parents. However, in case parents persist in their request after in-depth discussion of the implications, early genetic testing for FAP can be performed in young children in our centre. Also in the posttest period a psychologist is closely involved in counselling of a DNA result. The aims of the present evaluation were to explore parents’ views on (1) reasons for testing children at a younger age than indicated by the current guidelines and (2) physical complaints and psychological consequences of genetic testing in young children. Additionally, we were interested whether parents regretted genetic testing in young children and whether testing before the age of 10 years led to colon surveillance before it was indicated.
Patients and methods In our centre in the period from 1992 until January 2012 predictive genetic testing for FAP was performed in 78 children before the age of 21 years. Seventeen children (22 %), who were asymptomatic for intestinal polyps, were tested at the age younger than 10 years. One child (participant 7) had aspecific abdominal pain from the young age. One child (participant 2) was diagnosed with a hepatoblastoma at the age of 3 years. One child (participant 10) had a (mild) intellectual disability of unknown aetiology. Participants were identified through the Clinical
Familial adenomatous polyposis Table 1 Clinical characteristics of 13 participants, the interviewed parent and the reasons for genetic testing Family no.
Participant no
Gender
Age at genetic test (years)
Carrier status
Interviewed parent
Carrier status interviewed parent
Tested together with a sibling
Reason for genetic testing, pre-test counselling
Reason for genetic testing, interview
M
2
C
Mother
C
No
a)
a)
F1
1 2
M
4
C
Mother
C
No
a)
a)
F2
3
F
3
N
Mother
N
Yes
a), e)
e)
4
F
6
C
Mother
N
Yes
a), e)
e)
5
M
9
C
Mother
N
Yes
a), e)
a)
F3
6
F
5
C
Father
C
Yes
e)
e)
7
F
8
N
Father
C
Yes
c)
c)
F4
8
M
5
C
Mother
C
Yes
a), b)
b)
9
M
8
N
Mother
C
Yes
a), b)
b)
F5
10
F
7
N
Mother
C
No sibling
a)
d)
F6
11
M
8
N
Mother
N
Yes
b), e)
b)
F7
12
M
9
C
Mother
N
Yes
a)
a)
F8
13
M
9
N
Mother
N
Yes
–
e)
M male, F female, C carrier, N non-carrier Reasons for genetic testing: a) Certainty for the future; b) possibility to prepare a child for future surveillance; c) complaints of a child; d) reproductive choices; e) testing all children in a family at the same moment
Genetic database of our institution. Three parents of four children could not be interviewed; one declined participation, one could not be reached by phone repeatedly and one had insufficient knowledge of the Dutch or English language. Thus, parents from 13 children from the 17 eligible individuals could be re-contacted (Table 1). Since these children originated from 8 families, 8 parents gave informed consent for participating in this study. The parents were interviewed (open-ended semi-structured interview) by a clinical geneticist over the phone between October 2011 and January 2012. We interviewed one parent per child; both carrier-parents as well as non-carrier parents were eligible for this interview study. A parent was chosen randomly, independent on his/her carrier status. A psychologist was closely involved in the development of the questionnaire. The questionnaire was designed based on our own expertise in genetic testing in minors and previous publications on this issue. During the interview, information was collected about motivations for early genetic testing of the child, communication about the genetic test and the DNA result and effects of genetic testing on the child’s well-being, health status of a tested child and family dynamics. Furthermore, the parents were asked about any regrets concerning the testing of their children and suggestions regarding the optimal moment of genetic testing for FAP in childhood. The motivations for early genetic testing form the parent’s interviews were compared with the motivations reported in the medical files during the pre-test counselling. Data from the medical files as well as the interviews were described in detail.
This study was approved by an ethics committee of our centre.
Results The 8 interviewed parents were seven mothers and one father. Three mothers and the father were carrier of the tested APC mutation. The male to female ratio of the 13 tested children was 1.6:1 and the mean age at the moment of testing was 6.4 years (2–9 years) (Table 1). The mean age of these children at the moment of the interview was 13.5 years (9–18 years). Ten of 12 children with a sibling were tested at the same moment as their brother(s) or sister(s). The familial APC mutation was detected in 7 of the 13 tested children. The data from the pre-test counselling in the medical files corresponded largely with the data from the interviews (Table 1). These data were available in 12 children. According to the medical reports, in 9 children parents’ own uncertainty was an important reason for early genetic testing. All parents were satisfied with genetic testing in their children at a young age, and none of them regretted testing their children at a young age. Hereafter we describe in detail the process of genetic testing in every child. Family 1 In this family two children were tested for FAP. The mother, who was a carrier of an APC mutation, was
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interviewed. The oldest son (child 2 in Table 1) had a hepatoblastoma at the age of 3 years old. A hepatoblastoma can occur as a sporadic tumour, but also in association with FAP [16]. The parents intended to obtain certainty about their child’s future by genetic testing through confirming or excluding FAP carriership. Anxiety of the mother about the prognosis of the hepatoblastoma and uncertainty about the relation of the tumour with FAP carriership were the main motivations for no longer deferring genetic testing. Their son was tested for the familial APC mutation at the age of 4 years. The child was informed about the upcoming DNA test as follows: ‘‘It has to be tested whether you have a predisposition for polyps.’’ This child appeared to be a carrier of the familial APC mutation. The communication of the test result was postponed until the later moment at the age of 5.5 years, when he asked his parents about the colon surveillance, which had been discussed during a visit to the paediatric oncologist. The mother could not exactly remember how the parents formulated the explanation of the DNA result, but she did remember that the child stayed calm after the DNA result had been told to him. The parents did not report any complaints or changes in relation with their child after the result was communicated. Shortly after genetic testing in the oldest child, the parents requested genetic testing in their youngest son (child 1 in Table 1), who was 2 years old at that moment. After careful counselling by a clinical geneticist and a psychologist, this child was tested for FAP. Again, the parents’ motivation was to gain more certainty about the child’s future. The parents’ uncertainty about the increased risk of hepatoblastoma in this child was an additional factor to perform genetic testing at a very young age. In view of their previous experience, they perceived the risk of hepatoblastoma in their child-carrier as significant. The youngest child appeared to be a carrier of the familial APC mutation as well. The upcoming DNA test and the result of genetic testing was not (yet) communicated to this child because of his young age. Annually, the ultrasound examination of the abdomen and analysis of alfa-fetoprotein in blood were performed by the paediatric oncologist. Family 2 Within this family three children were tested for the familial APC mutation before the age of 10 years. The father of the children was an APC carrier. The mother was interviewed. All children were tested at the same moment; at the age of respectively 3, 6 and 9 years old (child 3–5 in Table 1). The oldest child was approaching the age at which colonoscopy could be started. Parents’ main motivation for genetic testing in this child was to know whether colon surveillance was indicated. The motivation for testing the two younger children was parents’ request to have all their children being tested at the same moment. Genetic testing was granted after
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counselling by the clinical geneticist and psychologist of both the parents and the children. The children were informed at the same moment about the upcoming DNA test: ‘‘By all of you blood must be drawn to look whether you have the disease of your dad.’’ The two oldest children appeared to be APC carriers; the youngest child was a non-carrier. After the parents received the results of the children from the clinical geneticist, they directly communicated it to their children. The children-carriers got the explanation: ‘‘You will get a sick gut. The doctor says that if the gut is sick, then it has to be removed.’’ Both children became sad and reacted with tears. The parents told to the youngest child: ‘‘You don’t have the disease.’’ The mother reported that this child did not really understand the meaning of the DNA result because of the young age. There were no complaints, changes in the doctor’s visit or changes in the parent–child relation in any of the children, according to the mother. Family 3 Two female siblings (child 6 and 7 in Table 1) were tested for the familial APC mutation simultaneously at the age of 5 and 8 years old. The father, being a FAP carrier himself, was interviewed. The oldest girl was tested because of the persistent abdominal pain. DNA result showed that she was not a FAP carrier. The abdominal complaints appeared to be caused by lactose intolerance. Her asymptomatic sister appeared to be a FAP carrier. Child 6 was tested at a young age together with her sister, because it was important for the parents that both children in the family were tested at the same moment. This was granted after counselling by the clinical geneticist and psychologist. The communication about the upcoming genetic testing occurred in a simplified way, dependent on the level of development and understanding in each child. The parents told the oldest child: ‘‘Something should be tested because of your stomach pain.’’ Only the moment of blood test was communicated to the youngest child: ‘‘Something should be tested in you. Blood must be drawn.’’ Child 7 was informed about the test result by the parents at the age of 10 years. The parents considered their daughter at this age able to understand the consequences of her DNA result. They told: ‘‘The blood test showed that you don’t have the disease. Your stomach pain is not caused by the disease.’’ The child reacted calm. No changes in complaints, frequency of doctor’s visit or relation with the parents were reported. The child 6 is still not informed about the DNA result because of the young age. Family 4 Two boys were tested for the familial APC mutation at the same time at the age of 5 and 8 years (child 8 and 9 in
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Table 1). The interviewed mother was a FAP carrier. During the interview the mother told that a possibility to prepare her children for the future surveillance was the most important reason to initiate early genetic testing in her children. The analysis of the medical records revealed that the parents’ uncertainty about the children’s future together with the possibility to prepare them for future colon surveillance were decisive motivations for genetic testing in children at a young age. This family was counselled by the clinical geneticist and psychologist. Testing was granted because of persistent request of the parents. Granting genetic testing kept the parents positive towards psychological follow-up. The information about the genetic testing was given by mother to both children simultaneously: ‘‘Mom has a strange stomach. This is hereditary. You should be tested for it as well.’’ The youngest child was a FAP carrier, while the oldest was not. Once the DNA result was available, the mother informed the non-carrier child about the test result directly: ‘‘You don’t have the disease that mom has.’’ In mother’s view, the communication of the favourable DNA result led to relief of his stress. Mother told to the child-carrier (child 8) that his test result had been lost by the hospital, in order to protect him from the adverse result. She informed her son about his DNA result 2 years later, at the age of 8 years, when he got symptoms that could be related to FAP. She told: ‘‘Mom has a secret that hurts’’, and subsequently informed the child that he inherited the predisposition. When the DNA result was communicated, the child 8 reacted angry because the truth about his carriership was concealed for years. After a short period this child could understand that mother tried to protect him and accept the delayed communication of his DNA result. The mother reported a reduction of the frequency of doctor’s visits after the communication of the DNA result. Also she reported an easier contact between the parents and their child.
later moment the parents communicated it to their daughter. The parents preferred to postpone communication of the DNA result until their daughter reached a sufficient level of development to understand the result. When the parents told: ‘‘Mom was very ill. You will never get it.’’, the girl remained calm. No behavioural changes, changes in doctor’s visit or alterations in relation between the child and the parents were reported by the mother.
Family 5
Family 7
Child 10 underwent predictive genetic testing at the age of 7 years. This girl had a developmental delay and an intellectual disability of unknown origin. The mother, being a carrier of an APC mutation, was interviewed. Retrospective analysis of the medical records showed that the most important reason for predictive testing their child for these parents was to obtain certainty about the child’s future. However, during the interview the mother reported that family planning and the reproductive choices were decisive factors to request APC analysis in her daughter. Due to the intellectual disability of this girl upcoming genetic testing was not prior communicated to her. The girl appeared not to be a carrier. The DNA result was communicated first to the parents by a clinical geneticist. At a
Also in this family two children were tested for the familial APC mutation, of which the oldest girl was 10 years at the moment of testing and therefore not included in the evaluation. She appeared to be a non-carrier. Her brother (child 12 in Table 1) was 9 years old at the moment of genetic testing and was a FAP carrier. The father of the children died from FAP related cancer. The mother was an initiator of genetic testing in both children. The most important motivation was the possibility to get more certainty about the children’s future. During the interview she could not remember how the information about genetic testing and the DNA results was told to her children. The DNA result was communicated by a clinical geneticist directly when it was available. Child 12 reacted calm about his carriership.
Family 6 In this family two children underwent predictive genetic testing for FAP at the age of 8 and 10 years respectively. The youngest child (child 11 in Table 1) was tested at the same time as his older sister, who was approaching the age of colon surveillance and was not included in our evaluation. The father of these children died from colorectal cancer. The mother was interviewed. She and her new partner decided to test the children for the familial APC mutation, and if carrier, to have a possibility to prepare their child for future FAP-related surveillance. To test both children at the same moment was the most important motivation for testing in child 11 at a young age. The upcoming DNA test was communicated to both siblings at the same moment. The mother told about the dad’s disease and the need of genetic testing in the children: ‘‘Your dad died because of a hereditary disease. There is an increased risk that you have got the same predisposition. It has to be tested whether you have this disease or not’’. The child 11 appeared to be a non-carrier, while his sister did carry the familial APC mutation. When the result of genetic testing was available, the parents directly communicated it to both children. The mother reported that child 11 did not really understand the information about his DNA result. No behavioural changes or changes in doctor’s visit were reported.
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The mother did not report any changes in his complaints or frequency of the doctor’s visit. Family 8 Again, two siblings underwent APC mutation analysis in this family, the oldest being 11 years of age at the moment of genetic testing (not included). The youngest child (participant 13 in Table 1) was 9 years old. The father of these children had a clinical diagnosis FAP; however the mutation analysis was not yet preformed. Both children and the father were tested for FAP simultaneously and an APC mutation was found in the father confirming his clinical diagnosis. Both children appeared to be non-carriers. The non-carrier mother was interviewed. The oldest girl was tested because she already reached the age when colon surveillance could start. Her brother (child 13) was tested because the parents wished their children to be tested simultaneously in order to avoid additional stress from genetic testing in every child apart. The upcoming genetic test was introduced by parents to both children: ‘‘You may have inherited the predisposition to polyps from your father. It can be tested to see whether you need surveillance’’. Once the DNA result was available, parents communicated it to the children: ‘‘You did not inherit the predisposition for FAP.’’ This brought relief resulted in more intimate contact between the parents and their children.
Discussion Current guidelines recommend that predictive genetic testing for a hereditary disease in minors is indicated by a direct medical benefit through either medical intervention or preventive measures [2, 3]. Indeed, most European physicians were shown to be in favour of testing a child at risk if a disorder is treatable and early medical intervention is desirable [21]. Accordingly, genetic testing for FAP is presently offered to children at the age of 10–12 years, when endoscopic screening is recommended. Sometimes predictive testing for FAP occurs, however, at a younger age than recommended. Parents are often the initiators of earlier predictive testing in children. Parental decisionmaking on behalf of their children and children’s capacity to make choices can create challenges for genetics professionals [17]. The parents are expected to make the best decision for their children. However, healthcare professionals have the ethical and legal responsibility to intervene in a child’s interests if parents are not able to decide for their child or if parental decisions may harm the child [2]. Plass et al. [21] showed significant international differences in physicians’ attitudes towards testing at a younger age
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than recommended. On the one hand, German and French physicians were more likely to test a younger child on the request of their affected parent; while on the other hand, Dutch physicians are more reluctant in predictive testing of young children. Currently, very little is known about the reasons and implications of deviating from the current guidelines. In our evaluation an important reason for genetic testing at a young age was testing of all children in a family at the same time. According to the recommendations towards predictive genetic testing for FAP in young people formulated by Duncan et al., each individual at risk should be tested separately from other family members, including siblings, allowing an opportunity for individual focus and support [22]. However, genetic testing in children is a stressful moment, which has implications for the whole family. By testing all children at the same moment parents aim to avoid additional stress associated with genetic testing in every child separately. Once parents are aware that children may be confronted with different test results, and all family members should have his/her own way and pace in dealing with different results and the feelings associated with these results, we think testing children at the same time can be an option. A careful counselling of parents enlightening an individual approach and support of every tested child should be offered. Because of the young age of the tested children in our cohort, the communication about the upcoming genetic test occurred in a simplified way. In several cases, when simultaneous genetic testing in siblings was performed, communication about the upcoming DNA test took place at the same moment and the same way in all siblings, also even if a child was too young to understand the parent’s explanation. Although the parents attempted to use simple formulations, we doubt whether their children did understand the meaning of genetic testing. Consequently, it is unlikely that they were autonomous to make an informed decision themselves about this procedure. Nevertheless, we consider it important to communicate about the process of genetic testing and the test results to every single child. Openness can contribute to easier acceptance of the DNA result and probably to better family relationships, whereas secrecy can harm these relations as illustrated by the reaction of child 8 to the delayed communication of his test result. Interestingly, in the families with more than one child being tested it was observed that siblings’ reactions to genetic testing can be similar (Family 2). This similarity may be a consequence of emotional contagion, i.e. the tendency to feel and express feelings that are similar to or influenced by those of others. From a child’s perspective, the parent or sibling may serve as a model on how to process his/her emotions about the own DNA result. Consequently, it may be that, although the child does not
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possess sufficient ability to understand the information of the DNA result, the child is distressed after communication of the results because another sibling or the parent who communicates the result is distressed. Another important motivation for testing their child at a young age reported by parents was relief from parents’ own uncertainty about child’s carrier status. By evaluation of the motivations for genetic testing reported in the medical files, we observed that this parent oriented reason was the most frequently mentioned during the pre-test counselling. The data from the medical files showed that some parents were not only uncertain about the child’s future but even anxious about that. Waiting until the appropriate age for genetic testing in their child would be unbearable for these parents. Relief of parent’s uncertainty has been often raised in the literature as a potential benefit of young testing [23, 24], and was also found to be the most important reason for early genetic testing reported by physicians [2, 21]. It appears that some parents find coping with uncertainty as more burdensome than coping with an unfavourable DNA result. Nevertheless, parents have to be counselled thoroughly about potential anxiety about the child’s health and uncertainty about the future in case of adverse test results. A possibility to prepare a child for the future surveillance was found to be another important argument for initiating early genetic testing. This argument has previously been described in the literature [4]. Some parents describe that they take a child-carrier to their own FAPrelated hospital visits, so that a child can get used to doctor’s visits and accept the surveillance as a part of the FAP carriership. Growing up with the knowledge that one is a carrier and gradual education about FAP may enable children to experience FAP as part of who they are and help to integrate FAP in their self-concept. The communication of a DNA result to a young child can be challenging. One has to be sure that the information suits the understanding of a young child. Most parents preferred to communicate the result themselves without the direct involvement of a professional. Parents have the opportunity to choose the best moment for the communication of the DNA result. It seems that most parents used a gradual approach, led by the children’s developing interest and understanding, which has also been described in one single case-study of the parents of two young girls tested for FAP [20]. By now a booklet for parents on informing children about genetic testing and webpages for children on heredity diseases in generally and FAP particularly (www. ikhebdat.nl, www.bogi.nl) were developed. These may improve the communication of the test results to children and their understanding of these results. In the period after the DNA results, most children did not show any changes in physical or psychological functioning according to the parents’ report. Only in child 8,
slight behavioural changes in the first period after communication of the result were noticed, most likely as a consequence of the suboptimal communication of the DNA result. Child 8 also started with colonoscopic screening at a younger age because of early symptoms of FAP (polyps). Apart from child 1, who underwent additional abdominal surveillance for hepatoblastoma, the parents accepted the surveillance protocols and did not insist on earlier surveillance in their children than indicated. In the current evaluation focusing on a parent’s perspective, we did not find evidence for adverse consequences of genetic testing in children younger than 10 years. Previous studies focusing on the short term [9, 15] as well as the long term [25] psychological consequences of genetic testing for FAP in children did not report any adverse psychological consequences as well. However, these previous studies did not distinguish between the children tested at a very young age (\10 years) and children being 10 years or older. We hypothesized that this particular group may differ in response to genetic testing because of lack of communication of the result and lack of understanding of the consequences of genetic testing and DNA results. Furthermore, it could be that the children did have signs of psychical or physical distress, which were not observed or reported by the parents. Another concern about genetic testing in children raised in the literature is about potential harm to the parent–child relationship and to the bond between siblings [23, 26, 27]. A child-carrier may be emotionally isolated and/or overprotected by the parents, while a child-non-carrier can experience a lack of attention from the parents and even feel isolated from carrier-relatives. In the current study, parents did not report negative effects on the parent–child relation. In contrast, a closer relation between the parents and children as well as between tested siblings was reported. This may suggest that the process of genetic testing may increase intimacy between relatives. However, these results must be interpreted with caution, while it may be difficult for parents to reflect on their relationship with their children. Moreover, whether the interviewed parent was a carrier him/herself may also influence the relationship with the child. Although testing of children for FAP at a young age deviates from the current guidelines, none of the parents experienced regret about testing at the very young age. According to the parents’ reports there were no disadvantages of young testing. If a child appears to be a carrier, he/ she will grow up with the knowledge of being a carrier and will better accept FAP as a part of him/herself. If a child does not have a mutation, earlier testing will relief the family from anxiety and stress about the children’s future health. Although the perception of no regret by the parents could be a true feeling, it could be also an expression of a cognitive dissonance. In our cohort, the parents might rationalize their choice to perform genetic
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testing in their minor children by claiming that they never wanted any other option. Various reports and guidelines recommend to postpone predictive testing in children until the age when they can be involved in the decision-making process if possible, in order to respect their developing anatomy and self-confidence. According to the recent ethical policy in genetic testing of children, decision whether to offer genetic testing should be driven by the best interest of the child [28], which, for FAP may imply genetic testing at the age of 10–12 years. However, it is of question whether this is a valid argument to postpone testing of children at-risk for FAP until this age, while the delay of genetic testing until the age of 10 years may still not lead to complete participation of a child in the decision process about genetic testing, because of the still young age. Observing the families in our cohort, we doubt whether the deviation in testing strategy would cause more harm than an expectant policy. Although the experiences of the tested children have not been evaluated in this study, we assume that a satisfaction of parents can have positive effects on family dynamics and a child’s psychosocial well-being. Genetic testing in these families may reduce a psychosocial burden for a whole family and for a child particular as well. The current evaluation focused specifically on this particular cohort of children tested for FAP at an age earlier than the recommended guidelines (10 years). Earlier studies that described testing of children for FAP may also have included children \10 years old as part of the larger cohort [14, 15, 25, 29], however, this group was not further specified. Therefore, the characteristics of the children \10 years and the attitudes towards genetic testing of these children have not been well described until now. Some limitations, however, should be considered. First, the cohort of the participants is small. Nevertheless, this is the biggest cohort of children tested for FAP at a young age described in the literature. Second, we performed a retrospective study. In some families there is a time gap of some years between the moment of genetic testing and the moment when the parents were interviewed. Therefore, some details about the communication of the result could have been forgotten by the parents. Furthermore, in this study we describe parents’ experiences with genetic testing in their children at a young age. This can differ from the experience of the children. It is possible that the children did have signs of psychical or physical distress, which were not observed or reported by the parents. Future (prospective) studies should evaluate both the parents’ and the children’s own experience with early genetic testing, and explore whether the moment of testing affects present well-being of a tested child and influences the family dynamic, in order to discover the possible pitfalls of testing for FAP at a young age.
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In conclusion, testing of children for FAP at a young age is desired by some parents and is experienced by parents as causing no harm. Although the children’s perspective must be explored in the future, our results may help genetic counsellors in decisions around genetic testing of children at a younger age than the current guidelines. Acknowledgement
This project is funded by Fonds NutsOhra.
Conflict of interest
There were no conflicts of interest.
References 1. Croner RS, Brueckl WM, Reingruber B, Hohenberger W, Guenther K (2005) Age and manifestation related symptoms in familial adenomatous polyposis. BMC Cancer 5:24 2. Borry P, Stultiens L, Nys H, Cassiman JJ, Dierickx K (2006) Presymptomatic and predictive genetic testing in minors: a systematic review of guidelines and position papers. Clin Genet 70(5):374–381 3. Borry P, Evers-Kiebooms G, Cornel MC, Clarke A, Dierickx K (2009) Genetic testing in asymptomatic minors: background considerations towards ESHG Recommendations. Eur J Hum Genet 17(6):711–719 4. Crawford G, Lucassen A (2010) Predictive genetic testing in a young child: a case report. Fam Cancer 9(1):61–64 5. Wertz DC, Fanos JH, Reilly PR (1994) Genetic testing for children and adolescents. Who decides? J Am Med Assoc 272(11):875–881 6. Fanos JH (1997) Developmental tasks of childhood and adolescence: implications for genetic testing. Am J Med Genet 71(1):22–28 7. Lowden J (2002) Children’s rights: a decade of dispute. J Adv Nurs 37(1):100–107 8. Davis DS (1997) Genetic dilemmas and the child’s right to an open future. Hastings Center Report 27(2):7–15 9. Michie S, Bobrow M, Marteau TM (2001) Predictive genetic testing in children and adults: a study of emotional impact. J Med Genet 38(8):519–526 10. Douma KF, Aaronson NK, Vasen HF, Bleiker EM (2008) Psychosocial issues in genetic testing for familial adenomatous polyposis: a review of the literature. Psycho-oncology 17(8):737–745 11. Holland J (1997) Should parents be permitted to authorize genetic testing for their children? Fam Law Q 31(2):321–353 12. Ross LF, Moon MR (2000) Ethical issues in genetic testing of children. Arch Pediatr Adolesc Med 154(9):873–879 13. Lessick M, Faux S (1998) Implications of genetic testing of children and adolescents. Holist Nurs Pract 12(3):38–46 14. Gjone H, Diseth TH, Fausa O, Novik TS, Heiberg A (2011) Familial adenomatous polyposis: mental health, psychosocial functioning and reactions to genetic risk in adolescents. Clin Genet 79(1):35–43 15. Codori AM, Petersen GM, Boyd PA, Brandt J, Giardiello FM (1996) Genetic testing for cancer in children. Short-term psychological effect. Arch Pediatr Adolesc Med 150(11):1131–1138 16. Kattentidt-Mouravieva AA, Escher JC, Kessel Iv, Beishuizen A, Vanheusden K, Wagner A (2010) Familiaire adenomateuze polyposis coli op de kinderleeftijd. Tijdschr Kindergeneeskd 78(1):28–33 17. The British Society for Human Genetics (2010) Report on the Genetic Testing of Children 2010, British Society for Human Genetics 18. Dalby S (1995) GIG response to the UK Clinical Genetics Society report ‘‘The genetic testing of children’’. J Med Genet 32(6):490–491
Familial adenomatous polyposis 19. Kodish ED (1999) Testing children for cancer genes: the rule of earliest onset. J Pediatr 135(3):390–395 20. Michie S, McDonald V, Bobrow M, McKeown C, Marteau T (1996) Parents’ responses to predictive genetic testing in their children: report of a single case study. J Med Genet 33(4):313–318 21. Plass AM, Baars MJ, Cornel MC et al (2009) Testing the children: do non-genetic health-care providers differ in their decision to advise genetic presymptomatic testing on minors? A crosssectional study in five countries in the European Union. Genet Test Mol Biomark 13(3):367–376 22. Duncan RE, Gillam L, Savulescu J, Williamson R, Rogers JG, Delatycki MB (2010) The challenge of developmentally appropriate care: predictive genetic testing in young people for familial adenomatous polyposis. Fam Cancer 9(1):27–35 23. Duncan RE, Gillam L, Savulescu J, Williamson R, Rogers JG, Delatycki MB (2008) ‘‘You’re one of us now’’: young people describe their experiences of predictive genetic testing for Huntington disease (HD) and familial adenomatous polyposis (FAP). Am J Med Genet C Semin Med Genet 148C(1):47–55
24. Robertson SSJ (2001) Is there a case in favour of predictive genetic testing in young children? Bioethics 15(1):26–49 25. Codori AM, Zawacki KL, Petersen GM et al (2003) Genetic testing for hereditary colorectal cancer in children: long-term psychological effects. Am J Med Genet A 116A(2):117–128 26. Duncan RE, Delatycki MB (2006) Predictive genetic testing in young people for adult-onset conditions: where is the empirical evidence? Clin Genet 69(1):8–16; discussion 7–20 27. Fryer A (2000) Inappropriate genetic testing of children. Arch Dis Child 83(4):283–285 28. Committee on Bioethics, Committee on Genetics, The American College of Medical Genetics and Genomics Social, Ethical, and Legal Issues Committee (2013) POLICY STATEMENT: Ethical and policy issues in genetic testing and screening of children. Pediatrics 131(3):620–622 29. Levine FR, Coxworth JE, Stevenson DA, Tuohy T, Burt RW, Kinney AY (2010) Parental attitudes, beliefs, and perceptions about genetic testing for FAP and colorectal cancer surveillance in minors. J Genet Couns 19(3):269–279
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ORIGINAL ARTICLE
How harmful is genetic testing for familial adenomatous polyposis (FAP) in young children; the parents’ experience Anna A. Kattentidt-Mouravieva • M. den Heijer I. van Kessel • A. Wagner
•
Ó Springer Science+Business Media Dordrecht 2014
Abstract Predictive genetic testing for familial adenomatous polyposis (FAP) is routinely offered to children at-risk from the age of 10 years onwards. Predictive testing for FAP at a younger age is debatable, because of absence of medical benefits. However, circumstances may arise when testing at a younger age (\10 years) is appropriate. Currently, there is a lack of published experience with predictive testing of children at this young age. We evaluated 13 children who were tested for FAP at the age younger than 10 years; 7 mutation-carriers and 6 non-carriers. Parents of these children were re-contacted and openended semi-structured interviewed. None of the contacted parents regretted the timing of genetic testing. The major reasons for testing at the young age were (1) testing of all children in the family at the same moment; (2) certainty for the future; and (3) preparing the child for future surveillance. None of the parents observed changes in mental or physical health in their child after testing. Also, young genetic testing did not lead to colon surveillance before it was indicated. Genetic testing for FAP at a young age is experienced as causing no harm by parents. Future studies should evaluate children’s own experiences with early genetic testing. Keywords Children Familial adenomatous polyposis Genetic predictive testing Psychosocial aspects
A. A. Kattentidt-Mouravieva (&) M. den Heijer I. van Kessel A. Wagner Department of Clinical Genetics, Erasmus University Medical Centre Rotterdam, Office Ee2018, PO Box 2040, 3000 CA Rotterdam, The Netherlands e-mail: [email protected]
Introduction FAP is an autosomal dominant predisposition to develop hundreds to thousands of colorectal polyps ultimately leading to colorectal cancer. It is caused by a germline mutation in the APC gene. Untreated, the risk of colorectal cancer in FAP patients is 100 %. When FAP is diagnosed in time, health benefits and increased life expectancy can be achieved. In FAP the average age when colorectal polyps are detected is 15 years [1]. Carriers of a pathogenic APC mutation are recommended to adhere to colonoscopic screening from the age of 10–12 years and to undergo surgery in adolescence in order to prevent colorectal cancer formation. There is a consensus that predictive genetic testing for a hereditary disease in minors is only indicated by a direct medical benefit through either medical intervention or preventive measures [2, 3]. Therefore, predictive genetic testing for FAP is routinely offered to children atrisk from the age of 10 years onwards. Mutation positive children are recommended to adhere to colonoscopic surveillance or may consider surgical intervention, whereas mutation negative children can avoid the unnecessary medical contacts. Occasionally parents request genetic testing in healthy at-risk offspring before the age of 10 years. An important motivation for genetic testing at a young age can be parents’ own uncertainty about the child’s future. Knowing that the child is not a carrier may lead to a relief from worries. While, on the other hand, knowing that the child is a carrier may enable parents to prepare their child for living with FAP. Crawford et al. reported a case when a child was tested for a familial APC mutation at the age of 9 months. In this case, the main motivation for testing at the very young age was to enable better family planning [4]. Depending on the carrier status in the first child the couple would make reproductive
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choices about further children, motivated by the feeling to have a duty to stop the predisposition from being transmitted to future generations. The main arguments against genetic testing at a younger age are respect for the child’s autonomy and potential psychosocial harm [5–8]. Compared to the general population, carriers may experience lower self-esteem [5, 6, 9, 10]. They can feel guilty, abnormal and ‘‘not perfect’’ because of carriership of a heritable disease [9, 10]. Furthermore, a genetic test can lead to not-indicated medical interventions, potential stigmatization and discrimination of a carrier, insurance issues and employment discrimination [11]. Also, the potential for adverse consequences on family dynamics after genetic testing has been frequently discussed in the literature [5, 12, 13]. After a DNA result, a child-carrier can be overprotected or emotionally isolated from his family. The parents and the family may treat a child-carrier and a child-non-carrier differently. In addition, in the case of different DNA result, a child-non-carrier may feel guilty for his/her sibling-carrier about not carrying the predisposition. On the other hand, genetic testing in children may also have positive effects on family relationships. The experience through the process of genetic testing may create closer contact and an increased intimacy between the tested children. Genetic testing for FAP under the age of 10 years has been debated since the advent of predictive genetic testing. Although practice shows that professionals are mostly reluctant in genetic testing of children at the age earlier than first possible onset of the disease, deviations of the recommendations regularly occur. Despite of children being tested for FAP under the age of 10 years, literature on these cases is lacking [4, 14–16]. According to the report on the genetic testing of children of the British Society for Human Genetics [17], for any particular child and family, the benefits of testing in childhood may outweigh the harms. If there are specific reasons, predictive genetic testing for a late onset condition can take place even at a younger age than recommended. Furthermore, the UK alliance of patient organizations Genetic Interest Group [18] claims that parents should be able to decide about the best moment of genetic testing and not professionals according to recommendations such as the rule of the earliest onset’, which implies that genetic testing should be permitted at an age no earlier than the age of first possible onset’ of the disease [19]. Congruently, Michie et al. [20] showed that parents feel strongly about their right to decide about the children’s testing, and that they do not feel that professionals have the relevant experience or right to make this decision. Research data on the consequences of early predictive genetic testing for FAP can contribute to the discussion of testing at the very young age. Currently, published data about predictive testing for FAP in children at the young
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age (\10 years) is scarce [4, 14, 15]. Gjone et al. studied present mental health functioning in a group of 7 adolescents who were tested for FAP at birth and in a group of 11 adolescents who were tested above the age of 9 years [4, 14, 15]. The group tested at birth had better mental health and psychosocial functioning than those tested later, although the differences did not reach statistical significance. These findings suggest no negative influences of early testing on child’s development as compared to later testing. This is of particular clinical interest, given the current guidelines recommending that predictive genetic testing for FAP is routinely offered to children at-risk from the age of 10 years onwards. Further insight is needed on the experiences of predictive testing for FAP in children younger than 10 years. In our centre DNA analysis for FAP is usually offered according to the current guidelines from the 10 years of age, when colon surveillance can be started. In case of parents’ request to perform genetic testing in their child at a younger age, detailed pre-test counselling of parents (and in some cases of children) takes place. Motivations for early genetic testing as well as the psycho-emotional situation within a family are evaluated by a counsellor and a psychologist. The reasons for reluctant policy towards genetic testing for FAP at a young age are always thoroughly discussed with parents. However, in case parents persist in their request after in-depth discussion of the implications, early genetic testing for FAP can be performed in young children in our centre. Also in the posttest period a psychologist is closely involved in counselling of a DNA result. The aims of the present evaluation were to explore parents’ views on (1) reasons for testing children at a younger age than indicated by the current guidelines and (2) physical complaints and psychological consequences of genetic testing in young children. Additionally, we were interested whether parents regretted genetic testing in young children and whether testing before the age of 10 years led to colon surveillance before it was indicated.
Patients and methods In our centre in the period from 1992 until January 2012 predictive genetic testing for FAP was performed in 78 children before the age of 21 years. Seventeen children (22 %), who were asymptomatic for intestinal polyps, were tested at the age younger than 10 years. One child (participant 7) had aspecific abdominal pain from the young age. One child (participant 2) was diagnosed with a hepatoblastoma at the age of 3 years. One child (participant 10) had a (mild) intellectual disability of unknown aetiology. Participants were identified through the Clinical
Familial adenomatous polyposis Table 1 Clinical characteristics of 13 participants, the interviewed parent and the reasons for genetic testing Family no.
Participant no
Gender
Age at genetic test (years)
Carrier status
Interviewed parent
Carrier status interviewed parent
Tested together with a sibling
Reason for genetic testing, pre-test counselling
Reason for genetic testing, interview
M
2
C
Mother
C
No
a)
a)
F1
1 2
M
4
C
Mother
C
No
a)
a)
F2
3
F
3
N
Mother
N
Yes
a), e)
e)
4
F
6
C
Mother
N
Yes
a), e)
e)
5
M
9
C
Mother
N
Yes
a), e)
a)
F3
6
F
5
C
Father
C
Yes
e)
e)
7
F
8
N
Father
C
Yes
c)
c)
F4
8
M
5
C
Mother
C
Yes
a), b)
b)
9
M
8
N
Mother
C
Yes
a), b)
b)
F5
10
F
7
N
Mother
C
No sibling
a)
d)
F6
11
M
8
N
Mother
N
Yes
b), e)
b)
F7
12
M
9
C
Mother
N
Yes
a)
a)
F8
13
M
9
N
Mother
N
Yes
–
e)
M male, F female, C carrier, N non-carrier Reasons for genetic testing: a) Certainty for the future; b) possibility to prepare a child for future surveillance; c) complaints of a child; d) reproductive choices; e) testing all children in a family at the same moment
Genetic database of our institution. Three parents of four children could not be interviewed; one declined participation, one could not be reached by phone repeatedly and one had insufficient knowledge of the Dutch or English language. Thus, parents from 13 children from the 17 eligible individuals could be re-contacted (Table 1). Since these children originated from 8 families, 8 parents gave informed consent for participating in this study. The parents were interviewed (open-ended semi-structured interview) by a clinical geneticist over the phone between October 2011 and January 2012. We interviewed one parent per child; both carrier-parents as well as non-carrier parents were eligible for this interview study. A parent was chosen randomly, independent on his/her carrier status. A psychologist was closely involved in the development of the questionnaire. The questionnaire was designed based on our own expertise in genetic testing in minors and previous publications on this issue. During the interview, information was collected about motivations for early genetic testing of the child, communication about the genetic test and the DNA result and effects of genetic testing on the child’s well-being, health status of a tested child and family dynamics. Furthermore, the parents were asked about any regrets concerning the testing of their children and suggestions regarding the optimal moment of genetic testing for FAP in childhood. The motivations for early genetic testing form the parent’s interviews were compared with the motivations reported in the medical files during the pre-test counselling. Data from the medical files as well as the interviews were described in detail.
This study was approved by an ethics committee of our centre.
Results The 8 interviewed parents were seven mothers and one father. Three mothers and the father were carrier of the tested APC mutation. The male to female ratio of the 13 tested children was 1.6:1 and the mean age at the moment of testing was 6.4 years (2–9 years) (Table 1). The mean age of these children at the moment of the interview was 13.5 years (9–18 years). Ten of 12 children with a sibling were tested at the same moment as their brother(s) or sister(s). The familial APC mutation was detected in 7 of the 13 tested children. The data from the pre-test counselling in the medical files corresponded largely with the data from the interviews (Table 1). These data were available in 12 children. According to the medical reports, in 9 children parents’ own uncertainty was an important reason for early genetic testing. All parents were satisfied with genetic testing in their children at a young age, and none of them regretted testing their children at a young age. Hereafter we describe in detail the process of genetic testing in every child. Family 1 In this family two children were tested for FAP. The mother, who was a carrier of an APC mutation, was
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interviewed. The oldest son (child 2 in Table 1) had a hepatoblastoma at the age of 3 years old. A hepatoblastoma can occur as a sporadic tumour, but also in association with FAP [16]. The parents intended to obtain certainty about their child’s future by genetic testing through confirming or excluding FAP carriership. Anxiety of the mother about the prognosis of the hepatoblastoma and uncertainty about the relation of the tumour with FAP carriership were the main motivations for no longer deferring genetic testing. Their son was tested for the familial APC mutation at the age of 4 years. The child was informed about the upcoming DNA test as follows: ‘‘It has to be tested whether you have a predisposition for polyps.’’ This child appeared to be a carrier of the familial APC mutation. The communication of the test result was postponed until the later moment at the age of 5.5 years, when he asked his parents about the colon surveillance, which had been discussed during a visit to the paediatric oncologist. The mother could not exactly remember how the parents formulated the explanation of the DNA result, but she did remember that the child stayed calm after the DNA result had been told to him. The parents did not report any complaints or changes in relation with their child after the result was communicated. Shortly after genetic testing in the oldest child, the parents requested genetic testing in their youngest son (child 1 in Table 1), who was 2 years old at that moment. After careful counselling by a clinical geneticist and a psychologist, this child was tested for FAP. Again, the parents’ motivation was to gain more certainty about the child’s future. The parents’ uncertainty about the increased risk of hepatoblastoma in this child was an additional factor to perform genetic testing at a very young age. In view of their previous experience, they perceived the risk of hepatoblastoma in their child-carrier as significant. The youngest child appeared to be a carrier of the familial APC mutation as well. The upcoming DNA test and the result of genetic testing was not (yet) communicated to this child because of his young age. Annually, the ultrasound examination of the abdomen and analysis of alfa-fetoprotein in blood were performed by the paediatric oncologist. Family 2 Within this family three children were tested for the familial APC mutation before the age of 10 years. The father of the children was an APC carrier. The mother was interviewed. All children were tested at the same moment; at the age of respectively 3, 6 and 9 years old (child 3–5 in Table 1). The oldest child was approaching the age at which colonoscopy could be started. Parents’ main motivation for genetic testing in this child was to know whether colon surveillance was indicated. The motivation for testing the two younger children was parents’ request to have all their children being tested at the same moment. Genetic testing was granted after
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counselling by the clinical geneticist and psychologist of both the parents and the children. The children were informed at the same moment about the upcoming DNA test: ‘‘By all of you blood must be drawn to look whether you have the disease of your dad.’’ The two oldest children appeared to be APC carriers; the youngest child was a non-carrier. After the parents received the results of the children from the clinical geneticist, they directly communicated it to their children. The children-carriers got the explanation: ‘‘You will get a sick gut. The doctor says that if the gut is sick, then it has to be removed.’’ Both children became sad and reacted with tears. The parents told to the youngest child: ‘‘You don’t have the disease.’’ The mother reported that this child did not really understand the meaning of the DNA result because of the young age. There were no complaints, changes in the doctor’s visit or changes in the parent–child relation in any of the children, according to the mother. Family 3 Two female siblings (child 6 and 7 in Table 1) were tested for the familial APC mutation simultaneously at the age of 5 and 8 years old. The father, being a FAP carrier himself, was interviewed. The oldest girl was tested because of the persistent abdominal pain. DNA result showed that she was not a FAP carrier. The abdominal complaints appeared to be caused by lactose intolerance. Her asymptomatic sister appeared to be a FAP carrier. Child 6 was tested at a young age together with her sister, because it was important for the parents that both children in the family were tested at the same moment. This was granted after counselling by the clinical geneticist and psychologist. The communication about the upcoming genetic testing occurred in a simplified way, dependent on the level of development and understanding in each child. The parents told the oldest child: ‘‘Something should be tested because of your stomach pain.’’ Only the moment of blood test was communicated to the youngest child: ‘‘Something should be tested in you. Blood must be drawn.’’ Child 7 was informed about the test result by the parents at the age of 10 years. The parents considered their daughter at this age able to understand the consequences of her DNA result. They told: ‘‘The blood test showed that you don’t have the disease. Your stomach pain is not caused by the disease.’’ The child reacted calm. No changes in complaints, frequency of doctor’s visit or relation with the parents were reported. The child 6 is still not informed about the DNA result because of the young age. Family 4 Two boys were tested for the familial APC mutation at the same time at the age of 5 and 8 years (child 8 and 9 in
Familial adenomatous polyposis
Table 1). The interviewed mother was a FAP carrier. During the interview the mother told that a possibility to prepare her children for the future surveillance was the most important reason to initiate early genetic testing in her children. The analysis of the medical records revealed that the parents’ uncertainty about the children’s future together with the possibility to prepare them for future colon surveillance were decisive motivations for genetic testing in children at a young age. This family was counselled by the clinical geneticist and psychologist. Testing was granted because of persistent request of the parents. Granting genetic testing kept the parents positive towards psychological follow-up. The information about the genetic testing was given by mother to both children simultaneously: ‘‘Mom has a strange stomach. This is hereditary. You should be tested for it as well.’’ The youngest child was a FAP carrier, while the oldest was not. Once the DNA result was available, the mother informed the non-carrier child about the test result directly: ‘‘You don’t have the disease that mom has.’’ In mother’s view, the communication of the favourable DNA result led to relief of his stress. Mother told to the child-carrier (child 8) that his test result had been lost by the hospital, in order to protect him from the adverse result. She informed her son about his DNA result 2 years later, at the age of 8 years, when he got symptoms that could be related to FAP. She told: ‘‘Mom has a secret that hurts’’, and subsequently informed the child that he inherited the predisposition. When the DNA result was communicated, the child 8 reacted angry because the truth about his carriership was concealed for years. After a short period this child could understand that mother tried to protect him and accept the delayed communication of his DNA result. The mother reported a reduction of the frequency of doctor’s visits after the communication of the DNA result. Also she reported an easier contact between the parents and their child.
later moment the parents communicated it to their daughter. The parents preferred to postpone communication of the DNA result until their daughter reached a sufficient level of development to understand the result. When the parents told: ‘‘Mom was very ill. You will never get it.’’, the girl remained calm. No behavioural changes, changes in doctor’s visit or alterations in relation between the child and the parents were reported by the mother.
Family 5
Family 7
Child 10 underwent predictive genetic testing at the age of 7 years. This girl had a developmental delay and an intellectual disability of unknown origin. The mother, being a carrier of an APC mutation, was interviewed. Retrospective analysis of the medical records showed that the most important reason for predictive testing their child for these parents was to obtain certainty about the child’s future. However, during the interview the mother reported that family planning and the reproductive choices were decisive factors to request APC analysis in her daughter. Due to the intellectual disability of this girl upcoming genetic testing was not prior communicated to her. The girl appeared not to be a carrier. The DNA result was communicated first to the parents by a clinical geneticist. At a
Also in this family two children were tested for the familial APC mutation, of which the oldest girl was 10 years at the moment of testing and therefore not included in the evaluation. She appeared to be a non-carrier. Her brother (child 12 in Table 1) was 9 years old at the moment of genetic testing and was a FAP carrier. The father of the children died from FAP related cancer. The mother was an initiator of genetic testing in both children. The most important motivation was the possibility to get more certainty about the children’s future. During the interview she could not remember how the information about genetic testing and the DNA results was told to her children. The DNA result was communicated by a clinical geneticist directly when it was available. Child 12 reacted calm about his carriership.
Family 6 In this family two children underwent predictive genetic testing for FAP at the age of 8 and 10 years respectively. The youngest child (child 11 in Table 1) was tested at the same time as his older sister, who was approaching the age of colon surveillance and was not included in our evaluation. The father of these children died from colorectal cancer. The mother was interviewed. She and her new partner decided to test the children for the familial APC mutation, and if carrier, to have a possibility to prepare their child for future FAP-related surveillance. To test both children at the same moment was the most important motivation for testing in child 11 at a young age. The upcoming DNA test was communicated to both siblings at the same moment. The mother told about the dad’s disease and the need of genetic testing in the children: ‘‘Your dad died because of a hereditary disease. There is an increased risk that you have got the same predisposition. It has to be tested whether you have this disease or not’’. The child 11 appeared to be a non-carrier, while his sister did carry the familial APC mutation. When the result of genetic testing was available, the parents directly communicated it to both children. The mother reported that child 11 did not really understand the information about his DNA result. No behavioural changes or changes in doctor’s visit were reported.
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The mother did not report any changes in his complaints or frequency of the doctor’s visit. Family 8 Again, two siblings underwent APC mutation analysis in this family, the oldest being 11 years of age at the moment of genetic testing (not included). The youngest child (participant 13 in Table 1) was 9 years old. The father of these children had a clinical diagnosis FAP; however the mutation analysis was not yet preformed. Both children and the father were tested for FAP simultaneously and an APC mutation was found in the father confirming his clinical diagnosis. Both children appeared to be non-carriers. The non-carrier mother was interviewed. The oldest girl was tested because she already reached the age when colon surveillance could start. Her brother (child 13) was tested because the parents wished their children to be tested simultaneously in order to avoid additional stress from genetic testing in every child apart. The upcoming genetic test was introduced by parents to both children: ‘‘You may have inherited the predisposition to polyps from your father. It can be tested to see whether you need surveillance’’. Once the DNA result was available, parents communicated it to the children: ‘‘You did not inherit the predisposition for FAP.’’ This brought relief resulted in more intimate contact between the parents and their children.
Discussion Current guidelines recommend that predictive genetic testing for a hereditary disease in minors is indicated by a direct medical benefit through either medical intervention or preventive measures [2, 3]. Indeed, most European physicians were shown to be in favour of testing a child at risk if a disorder is treatable and early medical intervention is desirable [21]. Accordingly, genetic testing for FAP is presently offered to children at the age of 10–12 years, when endoscopic screening is recommended. Sometimes predictive testing for FAP occurs, however, at a younger age than recommended. Parents are often the initiators of earlier predictive testing in children. Parental decisionmaking on behalf of their children and children’s capacity to make choices can create challenges for genetics professionals [17]. The parents are expected to make the best decision for their children. However, healthcare professionals have the ethical and legal responsibility to intervene in a child’s interests if parents are not able to decide for their child or if parental decisions may harm the child [2]. Plass et al. [21] showed significant international differences in physicians’ attitudes towards testing at a younger age
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than recommended. On the one hand, German and French physicians were more likely to test a younger child on the request of their affected parent; while on the other hand, Dutch physicians are more reluctant in predictive testing of young children. Currently, very little is known about the reasons and implications of deviating from the current guidelines. In our evaluation an important reason for genetic testing at a young age was testing of all children in a family at the same time. According to the recommendations towards predictive genetic testing for FAP in young people formulated by Duncan et al., each individual at risk should be tested separately from other family members, including siblings, allowing an opportunity for individual focus and support [22]. However, genetic testing in children is a stressful moment, which has implications for the whole family. By testing all children at the same moment parents aim to avoid additional stress associated with genetic testing in every child separately. Once parents are aware that children may be confronted with different test results, and all family members should have his/her own way and pace in dealing with different results and the feelings associated with these results, we think testing children at the same time can be an option. A careful counselling of parents enlightening an individual approach and support of every tested child should be offered. Because of the young age of the tested children in our cohort, the communication about the upcoming genetic test occurred in a simplified way. In several cases, when simultaneous genetic testing in siblings was performed, communication about the upcoming DNA test took place at the same moment and the same way in all siblings, also even if a child was too young to understand the parent’s explanation. Although the parents attempted to use simple formulations, we doubt whether their children did understand the meaning of genetic testing. Consequently, it is unlikely that they were autonomous to make an informed decision themselves about this procedure. Nevertheless, we consider it important to communicate about the process of genetic testing and the test results to every single child. Openness can contribute to easier acceptance of the DNA result and probably to better family relationships, whereas secrecy can harm these relations as illustrated by the reaction of child 8 to the delayed communication of his test result. Interestingly, in the families with more than one child being tested it was observed that siblings’ reactions to genetic testing can be similar (Family 2). This similarity may be a consequence of emotional contagion, i.e. the tendency to feel and express feelings that are similar to or influenced by those of others. From a child’s perspective, the parent or sibling may serve as a model on how to process his/her emotions about the own DNA result. Consequently, it may be that, although the child does not
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possess sufficient ability to understand the information of the DNA result, the child is distressed after communication of the results because another sibling or the parent who communicates the result is distressed. Another important motivation for testing their child at a young age reported by parents was relief from parents’ own uncertainty about child’s carrier status. By evaluation of the motivations for genetic testing reported in the medical files, we observed that this parent oriented reason was the most frequently mentioned during the pre-test counselling. The data from the medical files showed that some parents were not only uncertain about the child’s future but even anxious about that. Waiting until the appropriate age for genetic testing in their child would be unbearable for these parents. Relief of parent’s uncertainty has been often raised in the literature as a potential benefit of young testing [23, 24], and was also found to be the most important reason for early genetic testing reported by physicians [2, 21]. It appears that some parents find coping with uncertainty as more burdensome than coping with an unfavourable DNA result. Nevertheless, parents have to be counselled thoroughly about potential anxiety about the child’s health and uncertainty about the future in case of adverse test results. A possibility to prepare a child for the future surveillance was found to be another important argument for initiating early genetic testing. This argument has previously been described in the literature [4]. Some parents describe that they take a child-carrier to their own FAPrelated hospital visits, so that a child can get used to doctor’s visits and accept the surveillance as a part of the FAP carriership. Growing up with the knowledge that one is a carrier and gradual education about FAP may enable children to experience FAP as part of who they are and help to integrate FAP in their self-concept. The communication of a DNA result to a young child can be challenging. One has to be sure that the information suits the understanding of a young child. Most parents preferred to communicate the result themselves without the direct involvement of a professional. Parents have the opportunity to choose the best moment for the communication of the DNA result. It seems that most parents used a gradual approach, led by the children’s developing interest and understanding, which has also been described in one single case-study of the parents of two young girls tested for FAP [20]. By now a booklet for parents on informing children about genetic testing and webpages for children on heredity diseases in generally and FAP particularly (www. ikhebdat.nl, www.bogi.nl) were developed. These may improve the communication of the test results to children and their understanding of these results. In the period after the DNA results, most children did not show any changes in physical or psychological functioning according to the parents’ report. Only in child 8,
slight behavioural changes in the first period after communication of the result were noticed, most likely as a consequence of the suboptimal communication of the DNA result. Child 8 also started with colonoscopic screening at a younger age because of early symptoms of FAP (polyps). Apart from child 1, who underwent additional abdominal surveillance for hepatoblastoma, the parents accepted the surveillance protocols and did not insist on earlier surveillance in their children than indicated. In the current evaluation focusing on a parent’s perspective, we did not find evidence for adverse consequences of genetic testing in children younger than 10 years. Previous studies focusing on the short term [9, 15] as well as the long term [25] psychological consequences of genetic testing for FAP in children did not report any adverse psychological consequences as well. However, these previous studies did not distinguish between the children tested at a very young age (\10 years) and children being 10 years or older. We hypothesized that this particular group may differ in response to genetic testing because of lack of communication of the result and lack of understanding of the consequences of genetic testing and DNA results. Furthermore, it could be that the children did have signs of psychical or physical distress, which were not observed or reported by the parents. Another concern about genetic testing in children raised in the literature is about potential harm to the parent–child relationship and to the bond between siblings [23, 26, 27]. A child-carrier may be emotionally isolated and/or overprotected by the parents, while a child-non-carrier can experience a lack of attention from the parents and even feel isolated from carrier-relatives. In the current study, parents did not report negative effects on the parent–child relation. In contrast, a closer relation between the parents and children as well as between tested siblings was reported. This may suggest that the process of genetic testing may increase intimacy between relatives. However, these results must be interpreted with caution, while it may be difficult for parents to reflect on their relationship with their children. Moreover, whether the interviewed parent was a carrier him/herself may also influence the relationship with the child. Although testing of children for FAP at a young age deviates from the current guidelines, none of the parents experienced regret about testing at the very young age. According to the parents’ reports there were no disadvantages of young testing. If a child appears to be a carrier, he/ she will grow up with the knowledge of being a carrier and will better accept FAP as a part of him/herself. If a child does not have a mutation, earlier testing will relief the family from anxiety and stress about the children’s future health. Although the perception of no regret by the parents could be a true feeling, it could be also an expression of a cognitive dissonance. In our cohort, the parents might rationalize their choice to perform genetic
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testing in their minor children by claiming that they never wanted any other option. Various reports and guidelines recommend to postpone predictive testing in children until the age when they can be involved in the decision-making process if possible, in order to respect their developing anatomy and self-confidence. According to the recent ethical policy in genetic testing of children, decision whether to offer genetic testing should be driven by the best interest of the child [28], which, for FAP may imply genetic testing at the age of 10–12 years. However, it is of question whether this is a valid argument to postpone testing of children at-risk for FAP until this age, while the delay of genetic testing until the age of 10 years may still not lead to complete participation of a child in the decision process about genetic testing, because of the still young age. Observing the families in our cohort, we doubt whether the deviation in testing strategy would cause more harm than an expectant policy. Although the experiences of the tested children have not been evaluated in this study, we assume that a satisfaction of parents can have positive effects on family dynamics and a child’s psychosocial well-being. Genetic testing in these families may reduce a psychosocial burden for a whole family and for a child particular as well. The current evaluation focused specifically on this particular cohort of children tested for FAP at an age earlier than the recommended guidelines (10 years). Earlier studies that described testing of children for FAP may also have included children \10 years old as part of the larger cohort [14, 15, 25, 29], however, this group was not further specified. Therefore, the characteristics of the children \10 years and the attitudes towards genetic testing of these children have not been well described until now. Some limitations, however, should be considered. First, the cohort of the participants is small. Nevertheless, this is the biggest cohort of children tested for FAP at a young age described in the literature. Second, we performed a retrospective study. In some families there is a time gap of some years between the moment of genetic testing and the moment when the parents were interviewed. Therefore, some details about the communication of the result could have been forgotten by the parents. Furthermore, in this study we describe parents’ experiences with genetic testing in their children at a young age. This can differ from the experience of the children. It is possible that the children did have signs of psychical or physical distress, which were not observed or reported by the parents. Future (prospective) studies should evaluate both the parents’ and the children’s own experience with early genetic testing, and explore whether the moment of testing affects present well-being of a tested child and influences the family dynamic, in order to discover the possible pitfalls of testing for FAP at a young age.
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In conclusion, testing of children for FAP at a young age is desired by some parents and is experienced by parents as causing no harm. Although the children’s perspective must be explored in the future, our results may help genetic counsellors in decisions around genetic testing of children at a younger age than the current guidelines. Acknowledgement
This project is funded by Fonds NutsOhra.
Conflict of interest
There were no conflicts of interest.
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