PubMed1978
A genetic study of the subacute spinal muscular atrophies (SMA) of late infancy and early childhood has been undertaken. All such patients with chronic disease (with ages at onset up to 14 years, and excluding SMA Type I) known to 2 large Neurological Centres were reassessed clinically and genetically. There were 124 index patients (67 females and 57 males) and 17 secondary cases, which formed two consecutive unselected series. To investigate the genetic composition of this group, 4 nosological approaches were used; cluster analysis of clinical features of the disease, Haldane's sib-sib analysis on familial cases, interpretation of frequency distribution histograms, and a segregation analysis. A single autosomal recessive gene accounts for over 90% of cases, causes a clinical syndrome which manifests its first clinical signs before 5 years of age and in almost all cases before two years of age, but which is compatible with life into the third decade. Moderate intrafamilial discordance for some clinical features may be observed, but no genetic heterogeneity within this group was demonstrated. A small group of cases is caused by (a) new dominant mutation(s), or (b) is composed of phenocopies, or both. This relatively uncommon form may comprise the majority of late-presenting cases, and may account for all cases which manifest the first signs after 5 years of age. The spectrum of age-at-onset of this group cannot be determined at present, but the disease may be manifest before the age of two years; it is clinically indistinguishable from SMA caused by an autosomal recessive gene. The literature has been reviewed in the light of these findings. Empirical risks for use in genetic counselling are presented.