SMA is a monogenic disease, that is, a disease caused by a single gene abnormality. It is currently known that the genetic disease pattern of SMA is autosomal recessive (AR).

The causative gene for SMA is the survival motor neuron (SMN) gene located at 5q13, a region with a complex structure, repetitive sequences and numerous pseudogene clusters, which are prone to gene deletion and conversion. The telomeric and centromeric copies of the gene are almost identical and encode the same protein, however, mutations in the gene, the telomeric copy, are associated with spinal muscular atrophy, and mutations in the centromeric copy do not cause disease. The centromeric copy can be a modifier of diseases caused by mutations in the telomeric

The human genome contains two highly homologous SMN genes, namely the SMN1 pathogenic gene of SMA and the SMN2 modifier gene. These two genes are arranged in tandem on the chromosome. SMN1 is also called SMNT because it is close to the telomere, and SMN2 is also called SMNC because it is located on the centromere. There are only 5 nucleotide sites different between the two genes (and only 2 in the coding region) and they encode the same protein. About 95% of SMA patients are caused by homozygous deletion of exon 7 of the SMN1 gene, 3% are caused by heterozygous mutations of the SMN1 allele, and the rest are caused by other mutations. SMN2 also has similar functions to SMN1, but its transcription products are usually degraded quickly, and only 10-20% can eventually become functional motor neuron proteins. Therefore, if SMN1 is homozygous missing, no matter how small the number of SMN2 copies is, it will cause the disease; however, the more copies of SMN2, the more the relative compensation dose, and the condition will be relatively mild. The mutation of SMN2 alone will not cause the disease.