AUTOSOMAL RECESSIVE PROXIMAL SPINAL MUSCULAR-ATROPHY IN 101 SIBS OUT OF 48 FAMILIES - CLINICAL PICTURE, INFLUENCE OF GENDER, AND GENETIC-IMPLICATIONS

We analysed the clinical picture of 101 sibs (43 sib pairs, 5 triplets ) with autosomal recessive proximal spinal muscular atrophy (SMA). Lin kage data of 20 sibships, which were available for analysis, were in a greement with chromosome 5q linkage. The patients were classified acco rding to the motor development into SMA I (never sat), SMA II (sitting without support), and SMA III (walking without aids). Three sibs with adult onset (>30 years = SMA IV) were discussed as a separate entity. Age-of-onset of the 101 patients showed a wide spectrum (prenatal to 47 years). Among sib pairs with SMA I and SMA II the ages-of-onset app eared to be very similar except of one atypically discordant sib pair. With regard to SMA III, 3 out of 13 sibships (23%) showed a marked va riation in age-of-onset ranging from 5-15 years within a family. Conce rning acquired motor development (ability to sit and walk), 7 sibships (15%) belonged to different SMA types. Ages of death in 29 sib pairs in whom at least one sib had died before the age of 20 years were stri kingly discordant. Neither the degree of disability nor the respirator y deficits are reliable predictors of life expectancy. Although a pred ominance of males can be observed, no significant effect of gender has been established in familial cases. The existence of multiple allelis m seems to be the most suitable explanation for the high interfamilial variability considering the clinical concordance in most affected sib pairs. (C) 1994 Wiley-Liss, Inc.