Genetic testing can tell how many SMN2 genes a person has and roughly predict the course of SMA that is likely to result.
October is Spinal Muscular Atrophy Awareness Month. In the United States, 1 in every 6,000 to 10,000 people develops spinal muscular atrophy and 1 in 50 is a carrier of the disease. It has been found in people of every race, but is most common in Caucasians, of whom 1 in 35 is a carrier. Carrier rates for other populations include: Ashkenazi Jews (1 in 41 to 62), Asians (1 in 53), African Americans (1 in 66), and Hispanics (1 in 117). Studies done in specific populations have found carrier rates of 1 in 50 in Germany, 1 in 57 in Italy, and 1 in 62 in China.
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. 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.
In SMA types 1 through 4, the muscles closer to the center of the body (proximal muscles) usually are more affected, or at least affected much sooner, than the muscles farther away from the center. For example, the muscles of the thighs are weaker than the muscles of the lower legs and feet. Legs tend to weaken before arms. Hands may weaken eventually, but they usually stay strongest the longest, and, even if they do weaken, they usually remain strong enough for typing on a computer keyboard and other basic functions of modern life. The most serious danger in SMA comes from the weakness of muscles necessary for breathing. Careful attention to respiratory function is needed throughout life, with prompt attention to infections.
The most common form of SMA (types 1-4) is caused by a defect (mutation) in the SMN1 gene on chromosome 5. (People have two SMN1 genes, one on each chromosome 5.) A mutation in the SMN1 gene leads to a deficiency of a motor neuron protein called SMN, for survival of motor neuron. As its name implies, this protein seems to be necessary for normal motor neuron function. Normally, SMN1 genes produce full-length and fully functional SMN protein. But when the SMN1 gene has mutations, as in the chromosome 5-related form of SMA, insufficient levels of SMN protein are produced.
There is a neighboring gene on chromosome 5, called SMN2, which also produces SMN protein. Most of the protein made from instructions carried by SMN2 genes is not functional, but a small percentage is. People can have multiple copies of the SMN2 gene. In the chromosome 5 form of SMA, the more SMN2 genes a person has, the more functional SMN protein is available. And the milder the disease course is likely to be.
Chromosome 5 SMA (types 1 through 4) follows an inheritance pattern known as autosomal recessive, which often takes families by surprise. (The autosomes are the numbered chromosomes, that is, all the chromosomes except the X and the Y, which determine gender.) People who have only one gene flaw for a recessive disease are said to be carriers and usually show no symptoms. Often, a family has no idea that some members are carriers until a child is born with a recessive disorder. If both parents are carriers of the chromosome 5 gene flaw, the risk of each pregnancy producing a child with the disease is 25 percent. This risk doesn’t change no matter how many children a couple has. The “dice are rolled” with each new conception.
Genetic testing can tell how many SMN2 genes a person has and roughly predict the course of SMA that is likely to result. This is done by drawing blood and sending it off to a lab that does genetic testing. Many OB/GYNs are recommending testing at the first prenatal visit or a preconception visit. Contact your provider for more information.
Melissa Waddell, WHNP. is a nurse practitioner at Atlantic Ob/Gyn located in Va. Beach and Chesapeake. Please call 757-463-1234 or visit www.atlanticobgyn.com.