What is spinal muscular atrophy?

Muscles affected in SMA
The muscles closer to the center of the body (proximal muscles) are usually more affected in spinal muscular atrophy than are the muscles farther from the center (distal muscles).

Spinal muscular atrophy (SMA) is a genetic disease affecting the part of the nervous system that controls voluntary muscle movement.

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 active.

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, the chromosome 5 SMA often 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). SMA onset in children (types 2 and 3), teens or adults (type 4) generally correlates with increasingly higher levels of motor function.

For more, see Forms of SMA.

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. Its deficiency is caused by genetic flaws (mutations) on chromosome 5 in a gene called SMN1. Neighboring SMN2 genes can in part compensate for nonfunctional SMN1 genes.

Other rare forms of SMA (non-chromosome 5) are caused by mutations in genes besides SMN.  

For more information including detailed reading on rare, non-chromosome 5-linked SMA, see Forms of SMA and Causes/Inheritance.

What are the symptoms of SMA?

SMA symptoms cover a broad spectrum ranging from mild to severe.

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. 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.

There's a great deal of variation in the age of onset and level of motor function achieved in chromosome 5-related SMA. These are roughly correlated with how much functional SMN protein is present in the motor neurons, which in turn is correlated with how many SMN2 genes a person has.

Sensory, mental and emotional functioning are entirely normal in chromosome-5 SMA.

Some forms of SMA are not linked to chromosome 5 or SMN deficiency. These forms vary greatly in severity and in the muscles most affected. While most forms, like the chromosome 5-related form, affect mostly the proximal muscles, other forms exist that affect mostly the distal muscles (those farther away from the body’s center) — at least in the beginning.

For more, see Signs and Symptoms.

What is the progression of SMA?

In chromosome 5-related SMA, the later the symptoms begin and the more SMN protein there is, the milder the course of the disease is likely to be. While in the past, infants with SMA typically did not survive more than two years, today most doctors now consider SMN-related SMA to be a continuum and prefer not to make rigid predictions about life expectancy or weakness based strictly on age of onset.

What is the status of research on SMA?

Research has focused on strategies to increase the body's production of SMN protein, lacking in the chromosome 5-related forms of the disease. Approaches in this and other forms of SMA include methods to help motor neurons survive in adverse circumstances.

For more, see Research, SMA: Full Speed Ahead and In Focus: Spinal Muscular Atrophy (SMA)