ABSTRACT
Spinal muscular atrophy (SMA) was first described in 1891 independently by Guido Werdnig working at the Institute of Pathological Anatomy in Graz, Austria, and Johann Hoffman of Heidelberg University (1,2). Their reports presented the clinical and pathological aspects of infantile SMA, including early onset, occurrence among siblings of unaffected parents, progressive weakness, hand tremor, and death from respiratory failure in early childhood. Since the first description of this disease, a broader range of severity and age of onset has been appreciated, and a few separate disease entities have been defined. In 1991, the International Consortium on Childhood SMA defined three clinical subgroups to reflect the broad range of clinical severity (3). All types of SMA linked to chromosome 5q11 are associated with a relative deficiency in the product of the survival motor neuron (SMN ) gene (described below). SMA is one of the most common autosomal recessive diseases, affecting approximately 1 in 6000-10,000 live births, and is the leading hereditary cause of infant mortality (4-7). De novo mutations in the gene responsible for SMA are relatively frequent, and the carrier frequency for disease-causing mutations is estimated at approximately 1 in 50 (8). For unknown reasons, there is a slight male predominance for SMA, particularly with respect to the later onset forms of the disease.
