A clinical and genetic study of spinal muscular atrophy of adult onset: the autosomal recessive form as a discrete disease entity.

A clinical and genetic study of spinal muscular atrophy (SMA) of adult onset is reported. A genetic analysis of all cases of SMA occurring over a ten-year period in North-east England (48 index cases) has shown that chronic proximal SMA of adult onset is a distinct clinical and genetic entity, and is not a variant of the more common and relatively benign late juvenile cases. Nine cases of SMA of adult onset have been studied, occurring in 6 families. The median age of clinical onset was 35 years and the mean age at initial medical presentation was 37 years. The sex ratio was 5:4 (males:females). The condition is relatively benign and there is no evidence to date that life expectancy is shortened; there is usually no premonitory evidence of muscular weakness in early adult life. The muscular involvement is relatively symmetrical and the distal musculature is well preserved; clinical progression of the disease is interrupted by periods of apparent arrest. No patient was able to walk completely unaided twenty years after the initial clinical onset; the median age of patients in the study was 61 years but only one was confined to a wheelchair. In the early stages the recessive form of familial motor neuron disease must be excluded. A segregation analysis of sibs born after index cases was undertaken (segregation ratio of 0.20). This finding is consistent with autosomal recessive inheritance with an extended period during which the disease might initially present. The presence of new dominant mutations cannot be excluded, but is unlikely to account for more than 10% of cases. The carrier rate in the English population is estimated to be 1 in 300, with a gene frequency q = 0.00165. Prevalence is 0.32 per 100,000 in the general population. Empirical risks for genetic counselling are presented.