Spinal muscular atrophy (SMA) is a potentially fatal genetic disorder whose onset ranges from infancy to adulthood. After onset, the affected individual suffers symmetric and gradual degeneration as well as muscle atrophy. SMA patients thus slowly lose voluntary control over muscles involved in walking, crawling, swallowing, breathing, and controlling the head and neck. Depending on the age of onset, the severity of the disorder, and the impact on muscles, SMA can generally be divided into three types.

■Severe

• Type I SMA: Werdning-Hoffmann Disease

Type I SMA is characterized by severe, generalized muscle weakness and hypotonia at birth or before the baby is 6 months old. Most of affected individuals do not survive past early childhood due to respiratory failure.

■Intermediate

• Type II SMA: Dubowitz Disease

Type II SMA occurs between the ages of 6 and 18 months. Affected individuals display symmetric muscle weakness in the lower extremities, which makes them unable to stand or walk unaided. On occasion, the upper limbs are affected, causing trembling in the hands. The head muscles are rarely affected, allowing normal facial expressions. A small portion of affected individuals die of complications during childhood, but most can survive to adulthood with external support and health care.

■Milder

• Type III SMA: Kugelberg-Welander Disease

Type III SMA may begin anytime between 18 months and adulthood, and is characterized by mild weakness in the proximal limb muscles, which only causes slight inconvenience during physical activities such as running or stair climbing. People with this type usually have a normal life expectancy.

SMA is an autosomal recessive disorder, so carriers are not affected. However, when both parents are carriers, there is a 25% chance that their baby will get the disease. In Taiwan, the carrier frequency of SMA is approximately 1 in 40, making SMA the most common genetic disorder after thalassemia.

■Dual-platform (DHPLC+MLPA) Testing System

In 2003, SOFIVA Genomics developed the first spinal muscular atrophy (SMA) carrier screening test. In subsequent years, we made a great effort to improve this test and established the first SMA carrier screening system in the world. After continuing research and enhancement tests, we became the first research team to develop a dual-platform (DHPLC+MLPA) testing system.

• Screening Method

Approximately 2 - 3 c.c. of whole blood is collected in EDTA tube for DNA extraction.

• Screening Time

The results are available in 10 working days.

Recommendations from the American College of Medical Genetics (ACMG)

1. Because SMA is present in all populations, carrier testing should be offered to all couples regardless of race or ethnicity. Ideally, testing should be performed before conception or early in pregnancy.

2. Formal genetic counseling services must be made available to anyone requesting this testing. It is important that all individuals undergoing testing understand that a carrier is a healthy individual who is not at risk of developing the disease but has a risk of passing the gene mutation to his/her offspring.

3. All identified carriers should be referred for follow-up genetic counseling to discuss risks to the fetus or future pregnancies. Prenatal and preimplantation diagnosis should be offered.

4. The sensitivity of the test is not 100% and the detection rate is 90%. Therefore, a negative result reduces the possibility of giving birth to a child with SMA, but does not eliminate it.

5. As other carrier screening programs, this screening is voluntary. Informed consent is required and patient concerns must be addressed.

Reference: Carrier screening for spinal muscular atrophy. ACMG practice guidelines. November 2008 Vol. 10, No. 11, Page 840-842.