Proximal spinal muscular atrophy type 2 (SMA2) is a chronic infantile form of proximal spinal muscular atrophy (see this term) characterized by muscle weakness and hypotonia resulting from the degeneration and loss of the lower motor neurons in the spinal cord and the brain stem nuclei. Prevalence is estimated at around 1/70,000. The disease is slightly more frequent in males than in females. Disease onset occurs between the ages of 6 and 18 months (usually around 15 months). Generally, affected children have difficulty sitting independently and are unable to stand and walk by the age of one year. The muscle weakness (almost always symmetrical) predominantly affects the legs and trunk muscles. Finger trembling is frequent. Respiratory failure, scoliosis, and fractures in response to minimal trauma, are common. As for other forms of SMA, SMA2 is primarily caused by deletions in the SMN1 gene (5q12.2-q13.3) encoding the SMN (survival motor neuron) protein. Although there is some variation, disease severity in SMA is inversely correlated with the number of copies of the second SMN gene (SMN2; 5q13.2), with patients with MSA2 having on average three SMN2copies. Deletions of the NAIP (5q13.1) gene have also been identified in SMA2 patients and may play a role in modifying disease severity. Transmission is autosomal recessive but around 2% of cases are caused by de novo mutations. The diagnosis is based on clinical history and examination, and can be confirmed by genetic testing. Electromyography and muscle biopsy may be necessary. Differential diagnoses include amyotrophic lateral sclerosis, congenital muscular dystrophies, congenital myopathies, primary lateral sclerosis, myasthenia gravis, and carbohydrate metabolism disorders (see these terms). Antenatal diagnosis is possible through molecular analysis of amniocytes or chorionic villus cells. Genetic counseling should be offered to affected families. Clinical trials are ongoing to identify potential drug treatments for SMA2, mainly targeted towards increasing the levels of the full length SMN protein. However, at present, management remains symptomatic, involving a multidisciplinary approach and aiming to improve quality of life. Respiratory support is necessary. Physiotherapy and occupational therapy are recommended. Noninvasive ventilation may be useful. Antibiotic therapy is required in case of pulmonary infection. The scoliosis may require a corset/back brace for support, or need surgical correction. Life expectancy for patients with SMA2 is variable. With adapted treatment, particularly for respiratory insufficiency, the majority of patients survive up to adulthood, although they will never be able to walk independently.
Last update: July 2009