Testing for SMA and Fragile X
SPINAL MUSCULAR ATROPHY (SMA)
What is SMA?
SMA is a rare, inherited disease characterized by muscle atrophy and loss of motor function, caused by the absence of or defect in the Survival Motor Neuron 1 (SMN1) gene. This gene ensures the survival of a motor neuron protein (called SMN) and this protein is critical to the survival and health of motor neurons, which are nerve cells in the spinal cord responsible for muscle function. As the muscle motor neurons become unhealthy due to the reduced levels of the SMN protein, muscles progressively weaken and eventually become paralyzed.
What happens if someone is born with SMA?
The clinical spectrum of SMA ranges from early infant death to normal adult life with only mild weakness. There is a wide range of severity of SMA; however, even in its moderate form, SMA can limit function and mobility. People with SMA either never acquire, or progressively lose, the ability to walk, stand, sit and eventually move.
Genetics of SMA
Spinal Muscular Atrophy (SMA) is a recessive genetic disease that a fetus can inherit if both parents are carriers. There is a blood test to determine if someone is a carrier for this genetic disease. A carrier has no symptoms, so there is no way to know if someone is a carrier unless they have the blood test done.
SMA is caused by the deletion of, or a mutation in, the survival motor neuron 1 (SMN1) gene on chromosome 5. SMA affects between 1 in 6,000 and 1 in 10,000 babies, and approximately 1 out of every 50 individuals is a carrier of the mutation in the SMN1 gene. These statistics mean that SMA is one of the more common human genetic disorders.
According to the American College of Medical Genetics, SMA meets established criteria for population-based genetics screening. It is a severe disease, there is a relatively high frequency of gene carriers in the population, and an accurate genetic test is available, along with prenatal diagnosis and genetic counseling. Therefore, this test should be made available to all families. It is included in all of the genetic carrier testing panels.
FRAGILE X SYNDROME (FXS)
What is Fragile X Syndrome?
Fragile X syndrome (FXS) is the most common cause of inherited mental impairment (or mental retardation). This impairment can range from learning disabilities to more severe cognitive or intellectual disabilities. FXS is the most common known cause of autism or "autistic-like" behaviors. Symptoms can also include characteristic physical and behavioral features and delays in speech and language development.
FXS is due to a mutation in the X-linked FMR1 gene. Males with Fragile X Syndrome almost always exhibit mental retardation. One well recognized consequence for women who carry the mutation is an increased risk for premature ovarian failure (POF), defined as the cessation of menses before the age of 40. Among women who carry the mutation, approximately 21% have POF compared to only 1% in the general population.
Fragile X Syndrome is an X-linked genetic disease
This means that the mutation exists on the X-chromosome. X-linked conditions are more severe in males than females, because males have only a single X-chromosome (males are 46 XY) and females (who are 46 XX) have two, so one gene might have the mutation but the other gene will be normal. Other common X-linked genetic diseases are hemophilia and color blindness, also much more common in males.
The Fragile X mutation follows the traditional rules of X-linked inheritance: Half of the children of carrier mothers will receive the mutation. If the father is the carrier of the mutation, none of the sons and all of the daughters will receive the mutation. Approximately 1/350 females and 1/1,000 males carry the FXS mutation. Also about 4% of males and 8% of females of Northern European descent will carry the mutation. Approximately 1/4,000 males have Fragile X Syndrome.
Universal testing for this disorder is NOT the standard. Testing for FXS is recommended for individuals seeking reproductive counseling who have a family history of fragile X syndrome, a family history of undiagnosed mental retardation or a woman with a family history of premature ovarian failure.