Spinal Muscular Atrophy (SMA) is a genetic disorder characterized by the degeneration of motor neurons, the specialized nerve cells responsible for controlling voluntary muscle movement. It is primarily caused by mutations in the survival motor neuron 1 (SMN1) gene, which is located on chromosome 5.
The SMN1 gene provides instructions for producing the survival motor neuron (SMN) protein, which plays a critical role in the survival and functioning of motor neurons. Motor neurons require sufficient levels of the SMN protein for their development, maintenance, and proper functioning.
In individuals with SMA, mutations in the SMN1 gene lead to a deficiency of the SMN protein. This deficiency affects the stability and health of motor neurons, ultimately resulting in their degeneration. As the motor neurons degenerate, they lose the ability to send signals to the muscles, leading to muscle weakness, atrophy (wasting), and various motor function impairments.
SMA follows an autosomal recessive inheritance pattern. This means that for a person to develop SMA, they must inherit two copies of the mutated SMN1 gene, one from each parent. Carriers of a single copy of the mutated gene typically do not experience symptoms of the condition but can pass it on to their children.
While the SMN1 gene is the main gene associated with SMA, there are also other genes that can modify the severity and progression of the disease. One of these genes is the survival motor neuron 2 (SMN2) gene, which is highly similar to SMN1. However, due to a small genetic variation, the SMN2 gene produces a shorter and less stable form of the SMN protein. Individuals with a higher number of copies of the SMN2 gene tend to have milder forms of SMA due to the increased production of the SMN protein.
The severity of SMA can vary depending on the number of functional copies of the SMN2 gene and other genetic and environmental factors. SMA is classified into different types based on the age of onset and the degree of motor function impairment.