Definition
The term spinal muscular atrophy (SMA) comprises a clinically and genetically heterogeneous group of diseases characterized by degeneration and loss of the anterior horn cells in the spinal cord, and – depending on type and severity – sometimes also in the brainstem nuclei, resulting in muscle weakness and atrophy. The sensory neurons are always clinically spared, and there are no signs of upper motor neuron (pyramidal tract) involvement (Emery, 1971).
The subdivision of the SMAs into separate genetic and clinical entities (Table 55.1) is still controversial unless biochemical or molecular genetic criteria are available to define distinct pathomechanisms. The criteria used are age of onset, severity (progression, age of death), distribution of weakness, the inclusion of additional features, and different modes of inheritance.
Epidemiology
Autosomal recessive proximal SMA is one of the most common inherited diseases leading to death in early infancy. According to a rough estimate, less than 2% of cases with an onset before 10 years of age show a parent-to-child transmission (Emery, 1971). While vertical transmission of childhood-onset proximal SMA is an exception, autosomal dominant transmission can be found in about two-thirds of the adult-onset proximal SMA families (Pearn, 1978a). Assuming an incidence of about 1:10000 for all types of autosomal recessive SMA, it has been estimated that adult SMA accounts for 8% of all SMA cases, with a prevalence of 0.32 per 100 000 of the population (Pearn, 1978b). Distal SMA accounts for about 10% of all SMAs (Pearn & Hudgson, 1979).