Spinal muscular atrophies (SMAs) are hereditary degenerative disorders of lower motor neurons associated with progressive muscle weakness and atrophy. Proximal 5q SMA is caused by decreased levels of the survival of motor neuron (SMN) protein and is the most common genetic cause of infant mortality. Its inheritance pattern is autosomal recessive, resulting from mutations involving the SMN1 gene on chromosome 5q13. Unlike other autosomal recessive diseases, the SMN gene has a unique structure (an inverted duplication) that presents potential therapeutic targets. Although there is currently no effective treatment of SMA, the field of translational research in this disorder is active and clinical trials are ongoing. Advances in the multidisciplinary supportive care of children with SMA also offer hope for improved life expectancy and quality of life.
Key points
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Spinal muscular atrophies (SMAs) are hereditary degenerative disorders of lower motor neurons associated with progressive muscle weakness and atrophy.
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SMA subtypes are classified by severity of weakness: type I nonsitters, type II sitters, type III walkers, and type IV adult-onset patients with mild phenotype.
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The survival of motor neuron (SMN) gene is present in 2 copies on each chromosome 5, designated SMN1 and SMN2 . A majority of cases are caused by homozygous deletions of exon 7 of the telomeric SMN1 gene on chromosome 5q.
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An approximate inverse correlation exists between SMN2 gene copy number, which varies normally in the population, the level of SMN protein, and severity of disease; however, the role of the SMN protein is still under active investigation.
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No cure exists for SMA. Treatment consists of multidisciplinary management of symptoms. Trials are under way to identify agents for therapy.
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