Spinal muscular atrophy: A genetic disease characterized by progressive loss of lower motor neurons (anterior horn cells) in the spinal cord, resulting in symmetric muscle weakness and atrophy. The onset of the progressive muscle weakness ranges greatly in age from before birth to adulthood. The muscle weakness is progressive. Molecular genetics studies have disclosed that spinal muscular atrophy (SMA), irrespective of the age at the onset of symptoms, is due to mutation of one gene called the SMN gene.
Nonetheless, the traditional classification based on age of onset is still useful for diagnosis, prognosis, and management:
- Prenatal onset of SMA: Congenital axonal neuropathy and arthrogryposis multiplex congenita-SMA
- Onset before 6 months of age: SMA1
- Onset between 6 and 12 months: SMA2
- Childhood onset after 12 months: SMA3
- Adult onset: SMA4.
The gene called SMN (SMN = survival of motor neuron) is on chromosome 5 in region 5q11-13. Unaffected individuals have both the SMN gene and a copy of the SMN gene arranged in tandem on each chromosome 5. These are referred to as SMNT (telomeric copy of SMN) and SMNC (centromeric copy of SMN). The mutations in SMN that result in SMA are in SMNT, the telomeric copy of the gene.