Editors: Norio Fujiki, M.D. & Darryl R.J. Macer, Ph.D.
Senior Lecturer, Dept. of Medical Genetics, University of Wales College of Medicine, Cardiff, U.K.
Very similar issues are raised by childhood testing for carrier status for recessive disorders or for balanced chromosomal rearrangements; the results are of no immediate health benefit to the child, and only become relevant in the future when consideration is given to plans concerning relationships and reproduction. A summary of issues is given in Table 1.
Possible Advantages of Predictive Testing in Childhood
1 Relieves anxiety about possible early signs of the disorder.
2 Family uncertainty about the future is reduced.
3 More accurate genetic counseling becomes possible.
4 The child's attitude towards reproduction in adulthood will be more responsible.
5 Children who might benefit from genetic counseling in the future will be identified.
6 Practical planning for education, housing and family finances becomes possible.
7 Parental expectations of the child's behaviour become altered.
Possible Disadvantages of Predictive Testing in Childhood
1 Rarely leads to clarification of the genetic status of other family members.
2 Removes the child's right to decide whether or not to be tested in adulthood.
3 Leads to future difficulties in obtaining life insurance.
4 Parental expectations of the child's future reproductive behaviour become altered.
5 Damages the child's sense of self-esteem.
6 Generates unwarranted anxiety about possible early signs, before any genuine manifestation of the disorder.
Concern about predictive genetic testing in childhood for Huntington's disease (HD) was first raised by Craufurd and Harris (2). Subsequently, a consensus was reached by the World Federation of Neurology that children should not be tested for it (3, 4). Now that predictive tests for HD have been available for some years, it is clear that the knowledge of HD gene status can be burdensome for an adult, even when the result is low risk (5), and only a minority of at-risk adults in fact choose to undergo such testing (about 10-15%) (6-8). The right of the child to decide in adult life whether or not to be tested would be removed if their genetic status was determined at the request of parents or others. Such requests have been made on many occasions (9, 10). At least in the case of HD, this knowledge could be harmful, because it might alter the behavioural and intellectual expectations of the child by the family in an unfavourable and self-fulfilling fashion (11). Particular harm could occur if a family have preselected the child, whether as affected or unaffected.
To what extent are these concerns unique to HD testing, and to what extent do these ethical considerations apply to other disorders too? Other neurodegenerative disorders, such as Alzheimer type or prion dementia (12), will clearly raise similar concerns. But the issues of principle - of autonomy and confidentiality - that are raised in this way by concerns over testing for HD could be said to apply across the board to predictive or carrier testing in childhood for any disorder.
Even when an at-risk child develops clinical features compatible with juvenile-onset HD, molecular genetic testing to determine whether or not the child has the HD gene may not necessarily be in the child's best interests (13, 11). Even if the child has the HD mutation, there may be another explanation for the child's neurological signs; the real explanation (perhaps treatable) may then be missed, and an inadvertent predictive test has been performed on a child.
The attitudes of health professionals in Britain to such testing has been investigated in a study carried out on behalf of a Working Party (chair AC) of the Clinical Genetics Society, and a wide range of attitudes and practices has been found. The diagnostic molecular genetic and cytogenetic laboratories in Britain were circulated with a questionnaire. Many of them carry out tests of carrier status on healthy children, although predictive tests are usually performed where some medical intervention may depend upon the result (e.g. screening for bowel tumours in familial polyposis coli).
More than 500 clinicians (predominantly paediatricians, haematologists, geneticists and genetic counsellors) responded to a separate questionnaire requesting information about their attitudes and practice in this area. It emerged that significant numbers of children do have their carrier status determined for a number of recessive disorders, but that practice varies widely and some clinicians regularly suggest that such tests be deferred until the child is older.
Would you test a 5 year-old child whose parents wanted to know the genetic status for the following disorder(s) ?
DISORDERS: PAEDIATRICIANS (n=49): YES; NO;GENETICISTS (n=260) YES; NO;
Adult polycystic kidney disease 27 17 198 29
Charcot-Marie-Tooth 11 28 154 46
Huntington Disease 2 48 100 89
Hyperlipidaemias 40 7 223 16
Polyposis coli 28 16 214 14
Prion-protein dementia 0 42 66 48
Unaffected Carrier Status Testing
Cystic fibrosis 22 27 170 74
Haematological disease 22 28 155 74
Tay-Sachs 20 30 142 88
Adrenoleukodystrophy 12 32 132 74
Becker muscular dystrophy 11 33 136 82
Duchenne muscular dystrophy 14 32 163 75
(Balanced) chromosomal translocation 27 20 146 83
A supplementary questionnaire was circulated to paediatricians and geneticists, asking whether or not the respondent would test an apparently healthy 5-year old child whose parents wanted to know the child's genetic status for a variety of variable dominant disorders (predictive testing) and for a variety of recessive disorders (for carrier status). Geneticists were generally less willing to carry out such tests, particularly for carrier status and for late-onset disorders, than were the paediatricians. The difference was particularly striking for HD and other late-onset dementias where very few geneticists would offer testing while a majority of the paediatricians who answered the question expressed a willingness to oblige the parents.
These differences of response are likely to reflect the different experiences of the professional groups. The caution of the geneticists might well arise from their experiences of the difficulties of dealing with such requests, while most paediatricians will never have been confronted with these issues (at least in the extreme case of testing for HD) in their clinical practice. The importance of the survey result is that the sudden availability of these tests through commercial laboratories might result in children being tested for these conditions because neither the families nor the clinicians involved have ever thought the issues through. It is therefore necessary to promote an awareness of these issues amongst the wider medical world outside clinical genetics.
For testing to identify carriers of recessive disorders in childhood the balance of the argument is less clear. While testing in childhood does ensure that the opportunity to perform the test is not lost, it does not ensure that the correct information will be given to the child in an appropriate fashion and at an appropriate age. Parents may have many different motives for requesting carrier status tests on their healthy children, and these may need to be explored before testing is performed. There are other, perhaps more satisfactory, ways in which carrier testing can be offered to children as they mature the maintenance of an active contact genetic register is one such way.
It can be argued that it is better for a child to know about their genetic status in childhood: this may then be accepted as a simple matter of fact, without the emotional problems that could arise from a later disclosure. An alternative view is that children should be encouraged to discuss the family's potential genetic problem at this early stage, but that the testing be deferred until the child is sufficiently mature to request the testing in their own right. This explicit granting of control to the child may actually be helpful in enhancing their self-esteem, and in allowing them to come to terms with possibly unfavourable results once they are adult.
We canvassed the views of genetic disease support groups - lay associations - and their members also expressed a great variety of different views ranging from the full "parental right to test" stance to the opinion that children should never be tested for such conditions. Several respondents voiced concerns about stigmatisation of the disabled and the poor social provision for them, and the harmful effects of genetic screening programmes aimed at "wiping out" (those with) genetic disorders.
There is little evidence available as to the practical effects of testing for genetic status, or refusing to test, in childhood; this is true for HD as well as for tests of carrier status. However, there is some evidence that knowledge of carrier status can have adverse effects in adults. Problems may arise with carrier testing because of stigmatisation or the fear of stigmatisation, even in an area where the carrier frequency is high (14). Adult carriers of Tay-Sachs have been shown to be less optimistic about their future health (15). An earlier study has shown that as many as 19% of Tay-Sachs carriers were worried about their carrier status (16), as were 10% of carriers of sickle cell and thalassaemia in Rochester, New York (17). The wider issues of social stigma have also caused concern even in the recent past, particularly in relation to population screening for sickle cell carrier status in the USA (18, 19). The limited experience with population screening for cystic fibrosis in Britain indicates that many adults, even those related to known carriers, decline the offer of screening tests (20).
In contrast to the situation in USA, where some authorities would grant parents the right to full genetic information on their offspring (21, 22), the law in Britain appears to be unlikely to impose childhood testing at parental request, so that rational policy development remains a possibility. Empirical studies are needed to assess the effects on families of disclosing predictive and carrier status genetic information about children to their parents. Accordingly, we (in Cardiff) are setting up studies to examine: 1) the effects of presymptomatic predictive testing for autosomal dominant polycystic kidney disease, where the medical benefits of testing are uncertain but potentially significant (a prospective study); 2) the long-term psychosocial effects of carrier status determination on children (in families with balanced chromosomal translocations and certain sex-linked disorders - a retrospective, qualitative study); 3) an in-depth examination of the conflicting attitudes towards childhood genetic testing discovered in the questionnaire study. It is hoped that this will help in the development of a professional consensus, which is needed to avoid arbitrary inconsistencies of practice between different clinicians, centres and disciplines.
Such empirical studies do not displace the consideration of the ethical issues, but they are certainly required if society is to arrive at a just consensus on these issues. One related area that will need to be monitored most carefully will be diagnostic screening of those with educational difficulties for fragile X or other causes of learning difficulties. The psychosocial and educational effects on children who are identified as carrying a fragile X; mutation will need to be studied carefully. For those who are already known to have moderate or severe learning difficulties, there may be little harm done; however, for those who are tested by screening because of minor learning problems or difficult classroom behaviour, there could be considerable damage from the stigmatising effects of this diagnostic label.
In concluding, I should add that I value the responses to this paper, particularly from my colleagues from Asia, Africa and South America. Perhaps the concerns felt in Britain about the possible harm done to children whose genetic status is determined in childhood appear bizarre to people from less individualistic, more family-focussed societies.
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