<unk>  has an autosomal recessive pattern of inheritance.<unk>  is caused by a genetic mutation in the SMN1 gene. Human chromosome 5 contains two nearly identical genes at location 5q13: a telomeric copy SMN1 and a centromeric copy SMN2. In healthy individuals, the SMN1 gene codes the survival of motor neuron protein (SMN) which, as its name says, plays a crucial role in survival of motor neurons. The SMN2 gene, on the other hand – due to a variation in a single nucleotide (840.C→T) – undergoes alternative splicing at the junction of intron 6 to exon 8, with only 10–20% of SMN2 transcripts coding a fully functional survival of motor neuron protein (SMN-fl) and 80–90% of transcripts resulting in a truncated protein compound (SMNΔ7) which is rapidly degraded in the cell. In individuals affected by<unk> , the SMN1 gene is mutated in such a way that it is unable to correctly code the SMN protein – due to either a deletion occurring at exon 7 or to other point mutations (frequently resulting in the functional conversion of the SMN1 sequence into SMN2). Almost all people, however, have at least one functional copy of the SMN2 gene (with most having 2–4 of them) which still codes 10–20% of the usual level of the SMN protein, allowing some neurons to survive. In the long run, however, the reduced availability of the SMN protein results in gradual death of motor neuron cells in the anterior horn of spinal cord and the brain. Skeletal muscles, which all depend on these motor neurons for neural input, now have decreased innervation (also called denervation), and therefore have decreased input from the central nervous system (CNS). Decreased impulse transmission through the motor neurons leads to decreased contractile activity of the denervated muscle. Consequently, denervated muscles undergo progressive<unk>  (waste away). Muscles of lower extremities are usually affected first, followed by muscles of upper extremities, spine and neck and, in more severe cases, pulmonary and mastication muscles. Proximal muscles are always affected earlier and to a greater degree than distal muscles. The severity of<unk>  symptoms is broadly related to how well the remaining SMN2 genes can make up for the loss of function of SMN1. This partly depends on the number of copies of the SMN2 gene present on the chromosome. Whilst healthy individuals usually carry two SMN2 gene copies, people with<unk>  can have anything between 1 and 5 (or more) of them; the greater the number of SMN2 copies, the milder the disease severity. Thus, most<unk>  type I babies have one or two SMN2 copies; people with<unk>  II and III usually have at least three SMN2 copies; and people with<unk>  IV normally have at least four of them. However, the correlation between symptom severity and SMN2 copy number is not absolute and there seem to exist other factors affecting the disease phenotype.<unk>  is inherited in an autosomal recessive pattern, which means that the defective gene is located on an autosome. Two copies of the defective gene – one from each parent – are required to inherit the disorder: the parents may be carriers and not personally affected.<unk>  seems to appear de novo (i.e., without any hereditary causes) in around 2–4% of cases.<unk>  affects individuals of all ethnic groups, unlike other well known autosomal recessive disorders, such as sickle cell disease and cystic fibrosis, which have significant differences in occurrence rate among ethnic groups. The overall prevalence of<unk> , of all types and across all ethnic groups, is in the range of 1 per 10,000 individuals; the gene frequency is around 1:100, therefore, approximately one in 50 persons are carriers. There are no known health consequences of being a carrier. A person may learn carrier status only if one's child is affected by<unk>  or by having the SMN1 gene sequenced. Affected siblings usually have a very similar form of<unk> . However, occurrences of different<unk>  types among siblings do exist – while rare, these cases might be due to additional de novo deletions of the SMN gene, not involving the NAIP gene, or the differences in SMN2 copy numbers.
Spinal muscular atrophy
Prader–Willi syndrome
Spinal and bulbar muscular atrophy
Duchenne muscular dystrophy
Madras motor neuron disease
Congenital muscular dystrophy
Muscular dystrophy
Distal spinal muscular atrophy type 1