CLINICAL-EVIDENCE OF GENETIC ANTICIPATION IN ADULT-ONSET IDIOPATHIC DYSTONIA

Idiopathic dystonia occurs in both hereditary and sporadic forms. In t his report, we studied the age of onset and family history of 260 pati ents (probands) with idiopathic adult-onset dystonia (IAD), cranial or cervical. The mean age at onset of these patients was (45.71 +/- 15.8 5) years. Forty-nine probands had a positive family history of dystoni a or tremor in first- and second-degree relatives, and 7 had affected siblings only. The significance of tremor as a part of clinical manife station of dystonia was evidenced by a high frequency of postural or a ction tremor in patients and relatives. Retrospectively, we examined t he age of onset of dystonia (cervical or cranial) on successive genera tions in 49 families. Age of onset of clinical symptoms was earlier, b y an average of 21.25 years, in the second generation than in the firs t generation. The mean age at onset of affected family members differe d significantly between successive generations in these 49 families (p = 1.11 x 10(-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 a nticipation and suggest that an unstable trinucleotide repeat is most likely involved in adult-onset primary cranial or cervical dystonia. I n addition, tremor as an integral part of dystonia needs further evalu ation by molecular genetic studies.