The spinal muscular atrophies represent a heterogeneous group of neuromuscular disorders with predominantly autosomal recessive inheritance, characterized by degeneration of the anterior horn cells in the spinal cord and, in some cases, of the motor nuclei in the brain stem, resulting in symmetrical muscle weakness and atrophy. The condition has been divided into several subtypes according to age of onset and clinical severity.

Patients with spinal muscular atrophy type III have a disease onset usually between 2 and 17 years of age. Atrophy and weakness of proximal limb muscles, primarily in the legs, is followed by distal involvement. Usually the cases are diagnosed as limb-girdle muscular dystrophy until they are studied fully. Twitchings (fasciculations) are an important differentiating sign. Muscular biopsy and electromyography show the true nature of the process as a lower motor neuron disease. Pulmonary dysfunction is often a cause of morbidity in these patients.

Linkage studies in families of spinal muscular atrophy patients found that 95% of all cases of spinal muscular atrophy were linked to the 5q13 region of chromosome 5. Two candidate genes within this region were first described: the survival motor neuron (SMN) gene and neuronal apoptosis inhibitory protein gene. Each of these genes was found to be present in at least two copies. Later, the p44 gene (a subunit of the basal transcription factor) was identified as a third candidate gene.

Recently, two candidate genes, namely SMN (survival motor neuron) and NAIP (neuronal apoptosis inhibitory protein), have been suggested as SMA-determining and SMA-modifying genes, respectively. The SMN gene has been found to be homozygously absent or interrupted in 98.6% of childhood SMAs and in at least some patients with the adult form. The frequency of homozygous deletion of the intact NAIP gene was found to be different in SMA type I and type II/III (45% versus 18%), thus leading to the suggestion that the severity of the disease may depend on the deletion of the NAIP gene.