Spinal Muscular Atrophy (SMA) is a severe disease with a prevalence of 1 in 6,000-10,000 births. This disease has an autosomal recessive inheritance pattern. This means that a child must inherit a mutated copy of the relevant gene from each of their parents to develop this condition. However, in rare cases (less than 5 percent of patients) a gene mutation may occur after birth.
Symptoms include symmetrical and widespread muscle weakness that gradually progresses to muscle atrophy that develops first in the proximal muscles and later in the distal muscles.
There are several types of SMA that differ by age of onset:
- SMA type 1 – SMA type I (Werdnig-Hoffman disease) is the most severe type of this disease. This is an infantile-onset type of SMA, symptoms develop during the first six months of life and include generalized muscle weakness and breathing impairments. Babies do not reach their developmental milestones such as walking or even sitting. Lifespan is around two years, although there have been documented cases of children surviving to five years of age.
- SMA type 2 – SMA type II is also known as intermediate SMA. Age of onset is around six months to eighteen months. Babies with this type can sit up but usually cannot walk. Most people live into adolescence, but their lifespan usually does not exceed young adulthood, since motor impairments are severe.
- SMA type 3 – Babies with SMA type III (also known as juvenile-onset SMA) can walk and sit up to a certain age. When the age of onset is after three years of age, this is known as type 3b. Cases with an age of onset before three years of age are known as type 3a. Only around 44% of people with SMA type 3a can still walk unaided during their twenties, while 90% of people with type 3b can still walk at that age. People with type III have a normal life expectancy.
- SMA type 4 – In SMA type IV (also known as adult-onset SMA), symptoms appear during people’s early thirties. Symptoms are usually very mild and do not affect patients’ quality of life. People with type IV have a normal life expectancy.
There are other types of SMA, but these are considered rare.
SMA is caused by mutations to the gene SMN1. The most common gene mutation is actually a missing gene. 95% of mutations known today result from missing genes.
In most cases, a baby will inherit the defective gene copies from both their parents, but as mentioned above, gene mutations can also occur during one’s life, in these cases a person may inherit only one mutated gene copy and develop the mutation later.
The homologous gene for SMN1 is called SMN2. However, SMN2 is encoded to produce only 10 percent of the protein coded to SMN1. Therefore, the more copies of SMN2 a person inherits, the milder the disease will become.
People with the most severe form of SMA (type 1) have two copies of SMN2, while people with type IV have around 4-6 copies of SMN2.
Diagnosis and genetic testing
Genetic testing can help identify SMN1 mutations when infants show symptoms resembling neuromuscular disorders. Women with a family history of SMA, or women who are SMA carriers, are often referred to prenatal testing that may include methods such as amniocentesis or CVS (chorionic villus sampling). In addition, carrier screening via blood tests is available to couples with a family history of this disease.
Enzyme and protein blood tests, and occasionally muscle biopsies, can also be used to diagnose SMA.