Studies of penetrance and anticipation in five autosomal-dominant restlesslegs syndrome pedigrees

Restless legs syndrome (RLS) can occur with an autosomal-dominant mode of i nheritance. To determine if there are distinguishing features of RLS pedigr ees which might clarify molecular mechanisms of pathogenesis, five pedigree s with 81 affected members were analyzed for age of onset, sex ratio, and t ransmission pattern. One-factor analysis of variance of ages of onset betwe en generations was carried out, and segregation ratios were calculated for each generation. These kindreds showed an autosomal-dominant mode of inheri tance and a male:female ratio of 1:1.4 (p = 0.15). One of the five analyzed pedigrees shows some evidence of reduced penetrance. In two of the five an alyzed pedigrees, there is statistical support for anticipation (p < 0.05). These variations in penetrance and anticipation suggest possible genetic h eterogeneity.