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Changes in mood and behaviour form the most variable symptoms of the clinical characteristics of Huntington’s disease (HD).1 Although the diagnosis is usually based on motor signs, behavioural changes occur as a first manifestation of HD in up to half of the patients.2,3 Irritable behaviour, aggression, and depression are most commonly seen in the first phase of the disease.4 Anxiety, obsessions, and apathy are also extremely common in HD. In certain families, major affective disorders may appear as early as 20 years before the onset of chorea and dementia.5 However, with regard to the manifestation of psychiatric signs, there is a known difficulty in distinguishing between an intrinsic and a reactive pattern. The action of the disease is often intertwined with the reaction to the disease in diagnosed patients but also in “asymptomatic” (that is, absence of motor signs) subjects carrying the expansion of the CAG triplet repeat (henceforth referred to as “carriers” compared to “non-carriers”). As far as we are aware, only two studies have been reported regarding psychiatric symptoms in asymptomatic carriers compared to non-carriers.6,7 A controlled psychiatric study reported by Shiwach and Norbury7 showed that there was no significant increase in affective disorder in the former group. However, the whole predictive tested group showed a higher prevalence of psychiatric episodes than their partners. According to the authors it is, therefore, not plausible that depression is an early sign of HD in asymptomatic carriers. Depression and feelings of helplessness are indeed usually seen as a consequence of stressful events related to HD, like predictive testing in both carriers and non-carriers, even years after the predictive test result. Many studies have been reported on mood changes as a reactive pattern in both carriers and non-carriers,8,9 but behavioural changes as …

About 5% of colorectal cancers are associated with the autosomal dominantly inherited cancer susceptibility syndrome hereditary non-polyposis colorectal cancer (HNPCC).1,2 HNPCC is characterised by a high risk of developing colorectal cancer and endometrial cancer at a young age (cumulative lifetime risk 80-90% and 30-40%, respectively), and by an increased risk of developing various other tumour types, such as ovarian, uroepithelial, small intestine, biliary tract, stomach, brain, and skin cancers.2–5 Germline mutations in one of three mismatch repair genes ( MSH2 , MLH1 , and MSH6 ) were found to be responsible for a majority of HNPCC families.6–9 Knowledge of the causative mutation in a particular HNPCC family enables the identification of at risk family members by genetic testing. Clearly, the absence or presence of a mutation is of considerable medical and psychological significance. Subjects not carrying the mutation are relieved from a continuous anxiety and can be dismissed from medical surveillance, saving them trouble and reducing health care costs.10 Importantly, subjects with the mutation can benefit from a medical surveillance programme. For HNPCC, colonoscopy has been shown to be a potent tool for the detection and treatment of premalignant adenomas or early colorectal carcinomas in at risk subjects, reducing the risk of developing colorectal cancer and decreasing the overall mortality by about 65%.11,12 The possibility of early detection of colorectal cancer by stool analysis using the genetic markers TP53, BAT26, and K-RAS raises expectations for the development of less invasive surveillance procedures.13 Furthermore, intervention trials with non-steroidal anti-inflammatory drugs (NSAID) in subjects at risk for developing colorectal cancer are in progress.14,15 So far, studies on the use of genetic testing in HNPCC families have used families or subjects who had been registered for research purposes.10,16,17 It is …

The first comparative study on predicting post-test distress (conceptualised by intrusion and avoidance, measured with the Impact of Event Scale) after presymptomatic genetic testing for Huntington's disease (HD, n=25), cancer syndromes (familial adenomatous polyposis (FAP, n=23)), and hereditary breast and ovarian cancer (HBOC, n=10) is reported. The variables with the highest predictive potential of post-test distress are presented. Participants who were depressed before the test were more distressed after testing, but we found that those who were anxious before the test were less distressed, that is, had less intrusive thoughts post-test. Other factors associated with a higher level of post-test intrusion were gender (being a woman), having children, and pre-test intrusion. Religion and being at risk for HBOC were associated with less post-test intrusion. Participants who showed avoidance behaviour before the test and those who had many people available for support showed more avoidance behaviour post-test. The test result did not additionally contribute to post-test distress. The prima facie simple notion that the test result, as such, determines the distress experienced seems to be a misrepresentation of the complex reality.

The dilemmas in counselling a mildly retarded female with the fragile X syndrome and her retarded partner are presented. The fragile X syndrome is an X linked mental retardation disorder that affects males and, often less severely, females. Affected females have an increased risk of having affected offspring. The counselling of this couple was complicated by their impaired comprehension which subsequently impaired their thinking on the different options. The woman became pregnant and underwent CVS, which showed an affected male fetus. The pregnancy was terminated. Whether non-directive counselling for this couple was the appropriate method is discussed and the importance of a system oriented approach, through involving relatives, is stressed. Keywords: fragile X syndrome; counselling; mental retardation; FMR1

The fragile X syndrome is an X linked, semidominant mental retardation disorder caused by the amplification of a CGG repeat in the 5' UTR of the FMR1 gene. Nineteen fragile X families in which the mutated FMR1 gene segregated were evaluated. The implications of the diagnosis for the parents and family were studied through pedigree information, interviews, and questionnaires. Information about the heredity of fragile X syndrome was only disseminated by family members to a third (124/366) of the relatives with an a priori risk of being a carrier of the fragile X syndrome. Twenty-six percent (94/366) of the relatives were tested. Transmission of information among first degree relatives seemed satisfactory but dropped off sharply with increasing distance of the genetic relationship, leaving 66% uninformed. This is particularly disadvantageous in an X linked disease. Of those subjects tested, 42% (39/94) had a premutation and 18% (17/94) had a full mutation. On average, in each family one new fragile X patient and two new carriers were found. When people have the task of transmitting genetic information to their relatives, they usually feel responsible and capable; however, reduced acquaintance and contact with more distant relative severely reduces the effectiveness of such transfer of information in fragile X families.

In a comparative study on the effects of predictive DNA testing for late onset disorders, pre-test psychological distress was assessed in people at risk for Huntington's disease (HD, n = 41), cerebral haemorrhage (HCHWA-D, n = 9), breast and ovarian cancer (HBOC, n = 24), and polyposis coli (FAP, n = 45). Partners, if available, also participated in the study. Distress was measured with the subscales Intrusion and Avoidance of the Impact of Event Scale. People at risk for the neurodegenerative disorders reported more avoidance than those at risk for the cancer syndromes. People at risk for FAP and partners of those at risk for HBOC reported less intrusion than the others at risk and the other partners. Subjects who were more distressed reported more experiences with the disease in close relatives, the disease having a great impact on their lives, having considerations against predictive testing, expecting that being identified as a gene carrier would have adverse effects, and expecting relief after being identified as a non-carrier. Test candidates who expected an increase of personal problems showed higher avoidance, whereas those who could better anticipate future life as a carrier had higher intrusion levels. Generally, subjects with high distress levels are of more concern to the healthcare professional than those with low distress levels. However, high distress may reflect worrying as a mental preparation for the test result, whereas low distress may indicate denial-avoidance behaviour and poor anticipation of the test outcome. In pre-test counselling sessions, this should be acknowledged and addressed.

Editor—Huntington's disease (HD) is an autosomal dominant, progressive, incurable neuropsychiatric disorder, characterised by chorea, changes in personality, mood, and behaviour, and dementia. Because the mean age at onset is 40 years (range 5 to 70 years), the risk for a healthy young adult with an affected parent will remain nearly 50%, making decisions about the future and family planning difficult.1 2 After the localisation of the gene to chromosome 4p16.3 in 1983, predictive testing by linkage analysis became available for subjects at risk for HD3 and was shown to have potential benefits.4 When the mutation in the HD gene was identified in 1993,5 predictive testing became technically simpler, reliable, and available for everyone at risk. HD, like other neurodegenerative disorders (for example, SCA1, 2, 3, 6, and 7, DRPLA, and SBMA), is caused by an expanded CAG repeat. The wild type allele has six to 35 copies but affected subjects have between 36 and 121 repeats.6 7 The HD and normal range have quite distinct peaks but the tails of both curves are close to each other. As in SCA1 and 2 (and as opposed to SCA3 and 6, SBMA, and DRPLA), there is no gap between normal and disease ranges in HD and reduced penetrance is found in the lower range of the disease repeat. The normal repeat segregates simply and stably as a polymorphic locus, but the disease repeat size tends to increase and occasionally decrease in successive generations.8 The limits of the CAG repeat size in the HD gene have been redefined,9 based on the total number of normal and symptomatic subjects assessed. A normal repeat, with less than 27 repeats, has never been associated with a HD phenotype, nor has it shown instability resulting in a HD …