A genetic study of idiopathic torsion dystonia in the United Kingdom.

The inheritance of idiopathic torsion dystonia (ITD) was investigated in 100 British families containing 107 index cases with generalized, multifocal or segmental dystonia, and 79 secondary cases. Fifty-eight index cases had affected relatives, usually in two or more generations. Nearly half of the secondary cases were asymptomatic. Paternal age was increased among the 49 single cases, parental consanguinity was not increased and there was no evidence of genetic heterogeneity. Eleven cases (10.3%) were Jewish, which exceeded the number expected, but they did not differ clinically or genetically from non-Jewish cases. The most likely explanation for the excess of Jewish cases is a founder effect in Eastern Europe. We conclude that, in the UK, approximately 85% of cases of ITD are due to an autosomal dominant gene with about 40% penetrance and highly variable expression, possibly reflecting environmental influences. Approximately 14% of these inherited cases may represent new mutations. The remaining 15% are probably nongenetic phenocopies, but are not clinically distinguishable. There was no evidence in this study for the existence of autosomal recessive or X-linked forms of ITD. The estimated recurrence risk for first degree relatives of familial cases is 21%; the risk is lower for single cases. Of affected individuals, 75% will have developed symptoms or signs of dystonia by the age of 30 yrs.