General
- A congenital lower motor neuron disorder manifesting as progressive, symmetric proximal muscular weakness
- Leading inherited cause of infant death.
Numbers
- Occurring in 1 in 6000 to 1 in 10,000 births (second most common autosomal recessive disease in humans after cystic fibrosis).
Classified clinically by the age at symptom onset and disease severity
- Type I (Werdnig-Hoffman disease, acute)
- Type II (intermediate form, usually 7-18 months old and can sit unsupported but can’t walk independently),
- Type III (Kugelberg-Welander disease, mildest form, presents > 18 months and able to achieve independent walking)
- Type IV SMA (adult-onset).
Genetic
- Autosomal recessive fashion or is sporadic.
- Mutations or deletions in the telomeric SMN (survival of motor neuron) gene occur in most patients.
- The loss of functional SMN protein results in premature neuronal cell death.
- The SMN protein has a role in cardiac development.
Investigation
- If the history and physical examination suggest spinal muscular atrophy, a positive DNA test for deletion of the survival motor neuron gene eliminates the need for electrophysiological testing and muscle biopsy.
- However, the SMN gene is deleted only in 96% of patients, serum creatine kinase activity may be 1 to 2 times normal.
- Electromyography reveals large motor units;
- Nerve conduction velocities and sensory conduction times are normal, ruling out motor neuropathies.
- Muscle biopsy reveals group atrophy of type 1 and type 2 muscle fibers as opposed to the normal checkerboard pattern.
Outcome
- Most severe cases (Type I), children never gain the ability to sit unsupported and severe respiratory problems mean children rarely survive beyond two years of age.
- Type II SMA may shorten life expectancy, but improvements in care standards mean the majority of people can live long, fulfilling, and productive lives.
- Survival into adulthood is now expected.
- Life expectancy is usually unaffected in Types III and IV.
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