What is spinal muscular atrophy?
Spinal muscular atrophy (SMA) is a genetic disease affecting the central nervous system, peripheral nervous system, and voluntary muscle movement (skeletal muscle).
Most of the nerve cells that control muscles are located in the spinal cord, which accounts for the word spinal in the name of the disease. SMA is muscular because its primary effect is on muscles, which don’t receive signals from these nerve cells. Atrophy is the medical term for getting smaller, which is what generally happens to muscles when they’re not stimulated by nerve cells.
SMA involves the loss of nerve cells called motor neurons in the spinal cord and is classified as a motor neuron disease.
In the most common form of SMA (chromosome 5 SMA, or SMN-related SMA), there is wide variability in age of onset, symptoms, and rate of progression. In order to account for these differences, chromosome 5-related SMA, which often is autosomal recessive, is classified into types 1 through 4.
The age at which SMA symptoms begin roughly correlates with the degree to which motor function is affected: The earlier the age of onset, the greater the impact on motor function. Children who display symptoms at birth or in infancy typically have the lowest level of functioning (type 1). Later-onset SMA with a less severe course (types 2 and 3, and in teens or adults, type 4) generally correlates with increasingly higher levels of motor function.
What causes SMA?
Chromosome 5 SMA is caused by a deficiency of a motor neuron protein called SMN, for “survival of motor neuron.” This protein, as its name implies, seems to be necessary for normal motor neuron function. SMN plays a pivotal role in gene expression in motor neurons. Its deficiency is caused by genetic flaws (mutations) on chromosome 5 in a gene called SMN1. The most common mutation in the SMN1 gene within patients diagnosed with SMA is a deletion of a whole segment, called exon 7.1 Neighboring SMN2 genes can in part compensate for nonfunctional SMN1 genes as there is 99% identity between these two genes.2
What are the symptoms of SMA?
SMA symptoms cover a broad spectrum, ranging from mild to severe.
The muscles closer to the center of the body (proximal muscles) are usually more affected in SMA than are the muscles farther from the center (distal muscles).
The primary symptom of chromosome 5-related (SMN-related) SMA is weakness of the voluntary muscles. The muscles most affected are those closest to the center of the body, such as those of the shoulders, hips, thighs, and upper back. The lower limbs seem to be affected more than the upper limbs, and deep tendon reflexes are decreased.4
Special complications occur if the muscles used for breathing and swallowing are affected, resulting in abnormalities in these functions. If the muscles of the back weaken, spinal curvatures can develop.
