Spinal Muscular Atrophy Carrier Screening

This test is designed to detect carriers of spinal muscular atrophy. Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder characterized by muscle weakness and atrophy resulting from progressive loss of motor neurons in the spinal cord and brain stem (MIM 253300, 253550, 253400, 271150). The age of onset and severity of the disorder are highly variable. The more common early onset forms, when treated with only supportive care, typically result in death due to respiratory failure by the age of two. Later onset forms are associated with a slower decline in motor function and, in some cases, normal life expectancy. Targeted therapies have recently become available and will likely improve the clinical course of this disorder. In most affected individuals, SMA is due to homozygous loss (0 copies) of the SMN1 gene (NM_022874). Individuals with milder presentations often have an increase in the number of copies (>2 copies) of the highly homologous SMN2 gene (NM_022876). Individuals with one copy of SMN1 are carriers of SMA and are at risk of having a child with SMA. Individuals with two or more copies of SMN1 generally have a low carrier risk. Most individuals with two copies of SMN1 have one copy on each chromosome [1+1]; however, some individuals have two copies of SMN1 on one chromosome and zero copies on the other chromosome [2+0]. Individuals with a [2+0] configuration are known as silent carriers and are at risk of having a child with SMA. The presence of the SMN1 c.*3+80T>G SNP correlates in certain populations with increased risk of being a silent carrier of SMA (g.27134T>G, see Luo: PMID 23788250). If both reproductive partners are SMA carriers/silent carriers, the risk for SMA in their children is 25%. SMA is the most common genetic cause of infant death and the American College of Obstetrics and Gynecology (ACOG) recommends offering SMA carrier screening to all women who are pregnant of considering pregnancy. This test is intended for pre/post-conception carrier screening and is not intended for diagnostic testing.