Spinal Muscle Atrophy

Spinal muscular atrophy (SMA) denotes a collection of inherited clinical syndromes causing degeneration of anterior horn cells in the spinal cord with associated destruction of alpha motor cells and presents clinically with characteristic proximal muscle weakness and atrophy. Homozygous deletion at 5q13 (the coding region for the survival motor neuron (SMN1) gene) is responsible for 95% of cases of SMA, and after cystic fibrosis is the second most common cause of autosomal recessive inherited related mortality with an estimated incidence of 1 in 6000 to 11000. Homozygous deletion at 5q13 is also referred to as classical proximal SMA and will be the focus of this article with differentials and other causes of SMA discussed below. SMA is heterogeneous in presentation and ranges from death within weeks of birth to mild proximal weakness developing during adulthood. Earlier presentations are typically associated with poorer function and prognosis: classification of SMA subtypes are determined by the age of onset as well as clinical severity and life expectancy.  SMA was first described in the 1890s, first by Guido Werdnig in describing intermediate and severe SMA in 2 brothers and then 7 cases by Johan Hoffmann; type I SMA is sometimes eponymously referred to as Werdnig-Hoffmann disease. Similarly, milder forms of SMA (type III) detailed by Kugelberg and Welander is sometimes eponymously referred to as Kugelberg-Welander disease.