A new genetic variant of the spinal muscular atrophies in infancy.

The proximal spinal muscular atrophies (SMAs) represent clinically and genetically a heterogeneous group of conditions which have in common a more or less slowly progressive degeneration and ultimate disappearance of the anterior horn cells in the spinal cord and to a lesser extent of the motor nuclei in the brainstem. The latter are in most instances not associated with clinical manifestations with the exception of the frequent occurrence of fasciculations in the tongue. The clinical classification of the SMAs meets with difficulties since they form a continuous spectrum from cases with prenatal onset to cases which develop clinical mainifestations after many years (Zellweger et al, 1969a). The rapidity of progression and severity of the clinical picture vary likewise. Classification of the SMAs on the basis of their genetics is possible, however, at least for familial cases, since various patterns of hereditary transmission are encountered (Zellweger, 1971). Autosomal recessive inheritance is most frequent. Autosomal dominant inheritance with complete or with incomplete penetrance is second in frequency, while X-linked recessive inheritance has been observed in very few instances. Several authors described familial SMA affecting more or less distant relatives indicating a hereditary pattern incompatible with any of the above listed types of inheritance (Brandt, 1950; Wohlfart, Fex, and Eliasson, 1955; Kugelberg and Welander, 1956; Kirchhof, Kumral, and Fadiloglu, 1962; Becker, 1964 and 1966; Zellweger, Schneider, and Schuldt, 1969b; White and Blaw, 1971). Becker (1966) analysed this peculiar mode of inheritance and put forward the hypothesis that there are at least 3 allelomorphic genes on the locus of this particular SMA: the wild type gene a, the mutant gene A, and another allele called a' or activator allele. The genotypes Aa and