Autosomal dominant spinal muscular atrophy: A clinical and genetic study

Abstract

A clinical and genetic study of 6 kindreds (13 patients) with autosomal dominant spinal muscular atrophy is presented. Evidence is presented to indicate that two separate autosomal dominant genes are involved. One of these causes clinical disease with onset in early childhood (birth-8 years), which is relatively benign and in which proximal selectivity of muscle involvement is not marked. A separate autosomal dominant gene causes a disease with onset in adult life (median age 37 years), showing marked initial proximal selectivity; this disease may be more rapid in its clinical progression. Penetrance of both genes approaches 100%. Incidence figures are presented; less than 2% of all cases of childhood onset spinal muscular atrophy, but 30% of adult onset cases, are due to an autosomal dominant gene transmitted from an affected parent. Implications for prognosis, diagnosis and genetic counselling are discussed. A review of 11 kindreds of dominant spinal muscular atrophy in the literature is presented.