FREQUENCY OF FAMILIAL INHERITANCE AMONG 488 INDEX PATIENTS WITH IDIOPATHIC FOCAL DYSTONIA AND CLINICAL VARIABILITY IN A LARGE FAMILY

Idiopathic torsion dystonia is characterized by involuntary twisting m ovements and postures. One molecularly defined form with generalized d ystonia has been shown to be autosomal dominantly inherited with reduc ed penetrance in chromosome 9q34.1, especially in Ashkenazi Jewish fam ilies, while other generalized families from Europe and families with other subtypes of dystonia have been excluded from linkage to this loc us. Genealogical studies suggest that the much more frequent focal dys tonia follows an autosomal dominant inheritance with reduced penetranc e as well. For our study, 388 patients with focal dystonia, without a tendency for generalization, were interviewed for their family history . Evidence for hereditary disposition was found in 88 individuals. In a second step, all available family members of 17 of the 488 index pat ients (chosen for cooperation) were clinically examined. Objective dia gnosis of affected relatives was established in 13 families, whereas o nly 4 of the 17 index patients had previously admitted a positive fami ly history. Furthermore, a large three-generation family with focal dy stonia linked to chromosome 18p (linkage data described elsewhere) was identified. The familial pattern of all reported families is compatib le with autosomal dominant inheritance with reduced penetrance. Assess ment only on patients' report leads to underestimation of the frequenc y of familial idiopathic focal dystonia. Key Words: Focal tors ion dys tonia-Inheritance-Pedigree-Genetics-Phenotypic variability.