Clinical evidence of genetic anticipation in adult-onset idiopathic dystonia

Abstract

Idiopathic dystonia occurs in both hereditary and sporadic forms.In this report, we studied the age of onset and family history of 260 patients (probands) with idiopathic adult-onset dystonia (IAD), cranial or cervical. The mean age at onset of these patients was (45.71 +/- 15.85) years. Forty-nine probands had a positive family history of dystonia or tremor in first- and second-degree relatives, and 7 had affected siblings only. The significance of tremor as a part of clinical manifestation of dystonia was evidenced by a high frequency of postural or action tremor in patients and relatives. Retrospectively, we examined the age of onset of dystonia (cervical or cranial) on successive generations in 49 families. Age of onset of clinical symptoms was earlier, by an average of 21.25 years, in the second generation than in the first generation. The mean age at onset of affected family members differed significantly between successive generations in these 49 families (p = 1.11 times 10 sup -8). Our results suggest a tendency for earlier onset of dystonia and worsening of disease phenotype in succeeding generations in the same family. These findings are most compatible with genetic anticipation and suggest that an unstable trinucleotide repeat is most likely involved in adult-onset primary cranial or cervical dystonia. In addition, tremor as an integral part of dystonia needs further evaluation by molecular genetic studies.NEUROLOGY 1996;47: 215-219