Survival motor neuron spinal muscular atrophy is characterized by progressive muscle weakness resulting from degeneration and loss of the anterior horn cells (i.e., lower motor neurons) in the spinal cord and the brain stem nuclei. Onset ranges from before birth to adolescence or young adulthood. Poor weight gain, sleep difficulties, pneumonia, scoliosis, and joint contractures are common complications. Prior to identification of the genetic basis of SMA, it was classified into clinical subtypes on the basis of age of onset and maximum function achieved; however, SMA phenotypes associated with mutations in the gene SMN1 span a continuum without a clear delineation of subtypes. These phenotypically defined subtypes include SMA 0 (proposed), with prenatal onset and severe joint contractures, facial diplegia, and respiratory failure; SMA I, with onset before age six months; SMA II, with onset between age six and 12 months; SMA III, with onset in childhood after age 12 months and ability to walk at least 25 meters achieved; and SMA IV, with adult onset. [From GeneReviews, Spinal Muscular Atrophy, pubmed:20301526 2016.07.29]

Spinal muscular atrophy refers to a group of autosomal recessive neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. (Wirth, 2000, pubmed:10679938). Four types of SMA are recognized depending on the age of onset, the maximum muscular activity achieved, and survivorship: type I, severe infantile acute SMA, or Werdnig-Hoffman disease (MIM:253300; FBhh0000354); type II (MIM:253550; FBhh0000355), or infantile chronic SMA; type III (MIM:253400; FBhh0000356), juvenile SMA, or Wohlfart-Kugelberg-Welander disease; and type IV (MIM:271150; FBhh0000357), or adult-onset SMA. All types are caused by recessive mutations in the SMN1 gene. Many groups have observed the occurrence of different SMA subtypes within the same family, suggesting different manifestations of a single disease entity. [From MIM:253300, 2016.08.08]

The SMN complex plays a catalyst role in the assembly of small nuclear ribonucleoproteins (snRNPs) into the spliceosome. [Gene Cards, SMN1; 2016.04.16]

The SMN1 and SMN2 genes lie within the telomeric and centromeric halves, respectively, of a large, inverted duplication on chromosome 5q13. These genes share more than 99% nucleotide identity, and both are capable of encoding a 294-amino acid RNA-binding protein, SMN, that is required for efficient assembly of small nuclear ribonucleoprotein (snRNP) complexes. Homozygous loss of the SMN1 gene causes spinal muscular atrophy (SMA; MIM:253300). Absence of SMN1 is partially compensated for by SMN2, which produces enough SMN protein to allow for relatively normal development in cell types other than motor neurons. However, SMN2 cannot fully compensate for loss of SMN1 because, although SMN2 is transcribed at a level comparable to that of SMN1, a large majority of SMN2 transcripts lack exon 7, resulting in production of a truncated, less stable SMN protein (Lefebvre et al., 1995, pubmed:7813012; Kashima et al., 2007, pubmed:17884807). A small proportion of SMN1 associates with polyribosomes and represses translation of target mRNAs (Sanchez et al., 2013, pubmed:23136128). [From MIM:600354, 2016.08.08]