International collaborative study of the spinal muscular atrophies: Part 1. Analysis of clinical and laboratory data

Abstract

There is considerable variation in age of onset, though in over three-quarters of cases onset is before 4 years of age. A febrile episode, often of viral origin, may be present at the time of onset and might possibly be of aetiological significance, perhaps by precipitating the disease in a genetically predisposed individual. Reduced fetal movements and floppiness at birth are present in about one third of those cases where the onset is in early childhood. It would seem that when the onset is before 4 years of age, and particularly if the child has never been able to sit without support, the prognosis is much worse than in cases where the onset is after the age of 4 years. The proximal limb muscles are predominantly affected and muscle tone is usually reduced but pseudohypertrophy is uncommon. Rarely are the cranial nerves affected. Muscle fasciculations are present in about half the cases. Almost 10% of cases appear to be mentally retarded. With regard to the EMG findings, spontaneous activity, reduced full effort pattern, increased potential amplitude and duration and increased motor unit territory appear to be the most reliable diagnostic criteria. Routine histological evidence of neurogenic atrophy seems to be a more reliable diagnostic criterion than muscle histochemistry. However this may only reflect the way in which the data were selected, that is, from cases where a muscle biopsy showed evidence of neurogenic atrophy on routine histology. Finally the serum level of creatine kinase is rarely very high and in more than half the cases it is normal. The CSF chemistry is always normal.