Huntington's disease: a clinical review

Huntington disease (HD) is a rare neurodegenerative disorder of the central nervous system characterized by unwanted choreatic movements, behavioral and psychiatric disturbances and dementia. Prevalence in the Caucasian population is estimated at 1/10,000-1/20,000. Mean age at onset of symptoms is 30-50 years. In some cases symptoms start before the age of 20 years with behavior disturbances and learning difficulties at school (Juvenile Huntington's disease; JHD). The classic sign is chorea that gradually spreads to all muscles. All psychomotor processes become severely retarded. Patients experience psychiatric symptoms and cognitive decline. HD is an autosomal dominant inherited disease caused by an elongated CAG repeat (36 repeats or more) on the short arm of chromosome 4p16.3 in the Huntingtine gene. The longer the CAG repeat, the earlier the onset of disease. In cases of JHD the repeat often exceeds 55. Diagnosis is based on clinical symptoms and signs in an individual with a parent with proven HD, and is confirmed by DNA determination. Pre-manifest diagnosis should only be performed by multidisciplinary teams in healthy at-risk adult individuals who want to know whether they carry the mutation or not. Differential diagnoses include other causes of chorea including general internal disorders or iatrogenic disorders. Phenocopies (clinically diagnosed cases of HD without the genetic mutation) are observed. Prenatal diagnosis is possible by chorionic villus sampling or amniocentesis. Preimplantation diagnosis with in vitro fertilization is offered in several countries. There is no cure. Management should be multidisciplinary and is based on treating symptoms with a view to improving quality of life. Chorea is treated with dopamine receptor blocking or depleting agents. Medication and non-medical care for depression and aggressive behavior may be required. The progression of the disease leads to a complete dependency in daily life, which results in patients requiring full-time care, and finally death. The most common cause of death is pneumonia, followed by suicide

Prenatal testing for Huntington's disease in the Netherlands from 1998 to 2008

<p>This study aims to give an overview of the number of prenatal tests for Huntington's disease (HD), test results, and pregnancy outcomes in the Netherlands between 1998 and 2008 and to compare them with available data from the period 1987 to 1997. A total of 126 couples underwent prenatal diagnosis (PND) on 216 foetuses: 185 (86%) direct tests and 31 (14%) exclusion tests. In 9% of direct tests the risk for the foetus was 25%. Four at-risk parents (4%) carried intermediate alleles. Ninety-one foetuses had CAG expansions 36% or 50% risk haplotypes: 75 (82%) were terminated for HD, 12 (13%) were carried to term; four pregnancies were miscarried, terminated for other reasons or lost to follow-up. Unaffected pregnancies (122 foetuses) resulted in the birth of 112 children. The estimated uptake of PND was 22% of CAG expansion carriers (36 repeats) at reproductive age. PND was used by two new subgroups: carriers of intermediate alleles and 50% at-risk persons opting for a direct prenatal test of the foetus. A significant number of HD expansion or 50% risk pregnancies were continued. Speculations were made on causative factors contributing to these continuations. Further research on these couples' motives is needed.</p>

Quality issues concerning genetic counselling for presymptomatic testing: a European Delphi study.

Genetic counselling for presymptomatic testing is complex, bringing both ethical and practical questions. There are protocols for counselling but a scarcity of literature regarding quality assessment of such counselling practice. Generic quality assessment tools for genetic services are not specific to presymptomatic testing (PST). Therefore, the aim of this study was to identify aspects of effective counselling practice in PST for late-onset neurological disorders. We used the Delphi method to ascertain the views of relevant European experts in genetic counselling practice, ascertained via published literature and nomination by practitioners. Ethical approval was obtained. Questionnaires were sent electronically to a list of 45 experts, (Medical Doctors, Geneticists, Genetic Counsellors and Genetic Nurses), who each contributed to one to three rounds. In the first round, we provided a list of relevant indicators of quality of practice from a literature review. Experts were requested to evaluate topics in four domains: (a) professional standards; (b) service standards; (c) the consultant's perspective; and (d) protocol standards. We then removed items receiving less than 65% approval and added new issues suggested by experts. The second round was performed for the refinement of issues and the last round was aimed at achieving final consensus on high-standard indicators of quality, for inclusion in the assessment tool. The most relevant indicators were related to (1) consultant-centred practice and (2) advanced counselling and interpersonal skills of professionals. Defined high-standard indicators can be used for the development of a new tool for quality assessment of PST counselling practice