Preparation and counselling .sx The main centres involved in presymptomatic testing for HD have all taken a cautious and responsible approach to what has universally been recognised to be a difficult situation .sx The testing has been performed initially as a research evaluation , with detailed pre-test counselling sessions and careful arrangements for post-test support and follow up .sx Possibly as a result of this , there have been no serious adverse short term effects in those given a high risk result , though the longer term outcome remains to be seen .sx Should such a thorough procedure , involving many hours of individual counselling , be regarded as the accepted standard for this type of genetic prediction ?sx If so , who will provide the necessary resources once the initial research phase is over ?sx If not , how is the minimal acceptable standard to be defined ?sx Already one major American HD testing centre has had to stop its activities because funding was not renewed ; applicants , in some instances , have had to move their residence to a different part of America where service funding for a testing programme was available .sx As testing becomes more widespread , what restrictions should be placed on those clinicians , laboratories ( and possibly commercial organisations ) offering predictive testing for HD to ensure quality of both counselling and laboratory procedures ?sx A disturbing example of such practice ( not from the UK ) was reported at a recent meeting on the subject , where the applicant was informed of a high risk result for HD by telephone with no adequate prior counselling and no subsequent support .sx Should such practice be regarded as 'negligent' and hence subject to legal pressures , or should there be a voluntary code of practice ?sx Looking to other disorders , it is already clear that the arrangements for counselling often fall far short of those regarded as necessary for HD .sx Perhaps the most obvious example is for the transmissible but non-genetic disorder , acquired immunodeficiency syndrome ( AIDS ) , where counselling and follow up in relation to human immunodeficiency virus ( HIV ) testing is often minimal despite the profound consequences .sx In genetics , a recent report published by the Royal College of Physicians ( 1989 ) has highlighted important shortcomings in the provision of genetic counselling .sx Genetic testing in childhood .sx Our predictive testing programme for HD has , like others so far , only accepted adults , a policy in line with international guidelines drawn up by the International Huntington's Association and World Federation of Neurology ( 1990) .sx We have been surprised , however , how frequently requests for the testing of children have arisen .sx In our series there were 28 such requests , 20 from parents .sx While most parents have accepted the reasons for postponing testing until the child could make its own decision , in one case the mother of a two year old child , whose father was at 50 per cent risk , was insistent on testing and sought a second opinion elsewhere when testing was refused .sx Although it seems logical - for a disorder such as HD where childhood onset is exceptional - to confine testing to those who can consent for themselves , the situation is far from being clear in all circumstances .sx Should DNA testing be done where behaviour or other clinical abnormalities raise a suspicion of the rare juvenile form ?sx Should medical opinion override the wishes of a family which has lived with the disease and is fully aware of its significance ?sx What is the position about testing other late onset disorders whose age range is much more variable ?sx The X-linked muscular dystrophies provide a relevant example here :sx while in the classical Duchenne type the onset is relatively constant in early childhood and severe disability inevitable by late childhood , the sitation is quite different for the later onset 'Becker' type , determined by mutations at the same locus .sx Here onset may vary from late childhood to middle age , while disability varies from minimal to severe .sx An even greater range of disability applies to the autosomal dominant myotonic dystrophy :sx what factors should determine whether molecular genetic testing in childhood is appropriate for such disorders ?sx It is important to look critically at the reasons for requesting testing in childhood .sx The concerns of parents fall into two main categories ; the future health of their child , and the genetic implications .sx Regarding the latter it is surprising , though understandable , how often parents seek to influence their offspring's future reproductive decisions ; this could be seen as analogous socially to parental influence in the choice of marriage partner .sx In discussing this subject with parents we have found it helpful to stress the increasing choice that is likely to be available to their children when adult , in particular that early prenatal ( possibly even preimplantation ) diagnosis may allow them to achieve a healthy family regardless of their own genetic status .sx When the principal reason for requesting testing relates to the health of the child , present or future , the situation may be very much less clear-cut and careful consideration of the individual circumstances is needed .sx One approach that is sometimes underestimated is the value of a careful history and physical examinaton .sx If negative this will allow the question 'is the disorder present now ?sx ' to be answered , even if the future remains unresolved .sx If suspicious or positive clinical features are indeed present , this may make further investigations easier .sx Immediate health problems are not the only reason why parents may request genetic testing .sx Early knowledge that a disorder will develop may be important for educational and future career decisions with such disorders as Becker muscular dystrophy , which might well preclude a physically demanding career , or in retinitis pigmentosa , where future blindness may result .sx Regarding these issues , there is no essential difference between DNA testing for the gene and phenotypic presymptomatic tests such as creatine kinase analysis in the muscular dystrophies , electroretinography in retinitis pigmentosa , and ultrasound examination for adult polycystic kidney disease .sx Indeed it is likely that these more 'clinical' approaches are at present being widely used in an uncritical and at times inappropriate manner by paediatricians and others , though no clear evidence on this exists .sx However the power of molecular testing to make a prediction in disorders where no previous tests were available , together with its independence of age , makes it especially important to apply it only after careful thought and in the context of ethical guidelines .sx Perhaps a widespread debate is needed on this neglected topic ( Harper and Clarke , 1990) ?sx Preadoption testing .sx In our HD prediction study we were surprised to receive five requests for predictive tests to be done on children at risk for HD who were being placed for adoption , and we are aware of two others .sx This represents the extreme situation of genetic testing in childhood discussed above , and brings up additional issues such as the rights of the child in relation to those of the potential adoptive parents .sx We have not undertaken such testing for reasons set out briefly elsewhere ( Morris et al. , 1988 ) , which include the removal from the child of future choice regarding testing , the possible ( indeed likely ) stigmatisation from the knowledge that HD would develop in later life , together with the general uncertainty of the long-term effects of prediction even in adults , and the current lack of effective treatment .sx Our experience has however raised serious questions over the legal situation , and over what tests for genetic disorders in general are appropriate both now and in the future when adoption placement is being considered .sx Currently some tests are already mandatory ( for example phenylketonuria ) , while others would be generally advised ( such as Duchenne muscular dystrophy in a child at risk ) , but the question of testing for disorders of adult life has not been addressed .sx Studies have shown that there is considerable variation in the standard of the pre-placement examinations and investigations .sx 'INADVERTENT' GENETIC TESTING .sx In most medical situations it is an individual who seeks advice and is tested ; in genetic disorders it is often the entire family , nuclear or extended , that is under consideration .sx Testing on one member may prove to have major implications for others , and these should be considered before the testing is done , rather than afterwards .sx While the discovery of a genetic disorder in an individual may put relatives at risk , it rarely gives conclusive evidence as to whether or not they will be affected .sx An exceptional situation is provided by identical twins , where a diagnosis ( or predictive test ) in one twin for a disorder such as HD would give certainty that the co-twin would also become affected at some time .sx We have not so far encountered this problem .sx A more frequent difficulty , and one that is easy to overlook , is the inadvertent prediction that may result from samples being tested of relatives who themselves do not wish for prediction .sx Molecular genetic testing for most disorders currently remains dependent on family testing for polymorphisms , whether gene-specific or linked .sx Pedigree structures are frequently far from perfect in disorders such as HD , and testing of sibs may be the only way by which parental genotypes can be inferred to allow prediction .sx Figure 10.1 shows an example of this situation .sx Unless great care is taken a laboratory may find itself testing samples from a relative where the results may have major implications for that relative , as well as for the person who has sought prediction .sx The only way to avoid such a problem is to prevent it occurring in the first place .sx To begin with , no sample should be taken without careful review of the pedigree to be sure that it is really necessary .sx There is often a temptation to take a blood sample from relatives attending a clinic or on a home visit 'just in case' it might be needed in the future .sx Such samples should not be taken , or if they are , the samples should not be tested .sx When such a sample is really needed it must be made completely clear to the donor ( preferably in writing ) that the sample is being taken for the benefit of the relative and that no result is to be expected .sx To avoid the laboratory being placed in the invidious position of knowing information that is not known to the individual , we insist on such samples being made anonymous before testing .sx figure&caption .sx How far is this a general policy outside the rigorous situation of HD testing ?sx Our own experience suggests that it is not , and that laboratories commonly test all samples sent to them without clarifying who has requested prediction and who not .sx We have found ourselves in this sitation for such disorders as myotonic dystrophy , and it is likely that a careful audit of requests for genetic testing would uncover an appreciable number of comparable situations .sx While the consequences may be less extreme than for HD , the principle remains the same .sx THE USE OF RESEARCH RESULTS AND SAMPLES .sx Most major advances in human molecular genetics have come from the study of DNA from affected families who have donated blood samples in the hope that this will help research .sx Not unnaturally , when the promised breakthrough occurs they will wish to know what implications it will have for them personally ; they may enquire about the results that a research worker has obtained , or about the samples that remain stored for future use .sx Despite the recent tightening of ethical constraints for research projects , this is probably the area of genetic prediction that has been least carefully thought out and is most open to abuse .sx Part of the problem results from the very simplicity of the material needed .sx Whereas ethical committees may query the value of a brain biopsy or a potentially hazardous neuropharmacological test in a disorder like HD , few will cavil at the taking of a single blood sample .sx The stability of DNA also compounds the problem , as does the responsible and far-sighted behaviour of most geneticists who insist ( rightly ) on banking DNA for its possible future service use .sx Such a policy has already had direct benefits in allowing testing for HD and other disorders such as Duchenne dystrophy after the death of the affected family member .sx The same policy however creates difficulty for decisions on the use of what was initially collected as research material .sx