FAMILIAL PARKINSONS-DISEASE - A CLINICAL GENETIC-ANALYSIS

Objective: To study the frequency, clinical features and clinical gene tics of familial Parkinson's disease (PD). Methods: Family history for PD and tremors was studied in 100 consecutive PD cases, Spouses serve d as controls, Clinical features were compared between personally veri fied familial and sporadic PD cases, from the same consecutive clinica l series. Clinical genetic analysis was performed in a larger group of non-consecutive multicase PD families. Results: Family history for PD was positive in 24% of consecutive PD cases and in 6% of spouse contr ols (p < 0.001). When family history for isolated tremor is also consi dered, the number of positive cases rises to 43% compared with 9% in c ontrols (p < 0.001), Nine of the consecutive cases had at least one li ving affected relative, for a total of 20 familial PD cases. These fam ilial cases showed an earlier onset age when compared with sporadic on es from the same consecutive series. Within 22 non-consecutive PD fami lies with at least two Living and personally examined PD cases (total 52 PD cases), the crude segregation ratios were similar for parents an d siblings and the Lifetime cumulative risks approached 0.4 in sibling s and tended to be comparable, but at later ages, in parents. Ancestra l relatives were all unilaterally distributed, In some families, antic ipation of onset age in new generations was observed. Conclusions: The frequency of positive family history for PD and for PD and tremor is higher among PD cases than controls. Familial and sporadic PD only dif fer in onset age, The clinical genetic analyses support autosomal domi nant inheritance with strongly age-related penetrance as most likely i n familial PD.