SPINAL MUSCULAR ATROPHY (SMA)

(Sara Khan, MD) 

The spinal muscular atrophies or SMA are a group of genetic disorders characterized by diffuse weakness of voluntary muscles. This disease is caused by selective loss of motor nerves called motor neurons or anterior horn cells. These are cells or nerves that control voluntary muscles and instruct the muscles to move. With loss of the motor cells, the muscles become weak and there is loss of muscle bulk (atrophy) when the muscle is not used. The disease is produced by abnormal or missing SMN-1 (survival motor neuron gene) on chromosome 5 which is responsible for producing proteins important for motor neurons. The severity of the disease depends on the number of normal SMN-2 copies present. Due to inherent genetic mutations, there is wide spread degeneration of motor neurons resulting in progressive weakness and loss of muscles.

So far, SMA has been divided in to 4 types. SMA type I-IV are distinguished based on their age of symptom onset, life expectancy and milestones the individual is able to achieve.

SMA -I (also called Werdnig-Hoffman disease) is the most severe form. Symptom onset is within the first 6 months of life. These babies have diffuse weakness and ultimately develop weakness of sucking/swallowing and breathing. They are unable to ever sit because of weakness. Maximum life expectancy is 1-2 years. The most common mutations is a SMN1 deletion with less than 2 functional copies of SMN2.

SMA- II typically begins between 6 to 18 months of age. The child is able to sit independently but never walks. Most survive up to 5 years of age and at times can have prolonged survival up to 25 years of age. In the latter group, development of joint contractures and spinal abnormalities like curved spine (kyphoscoliosis) are common due to long standing muscle weakness. The most common mutations is a SMN1 deletion with 3 functional copies of SMN2.

SMA-III (also called Kugelberg-Welander disease) typically has symptom onset after 18 months of age. These children are able to achieve the milestone of walking. Initial symptoms are usually related to weakness of upper part of arms and legs. Life expectancy extends in to the 60’s and may be normal in many individuals. The most common mutations is a SMN1 deletion with 4 functional copies of SMN2.

SMA-IV is adult onset SMA and is rare. Onset of symptoms is at 30-40 years of age. It starts with weakness of proximal (upper) muscles of arms and legs with difficulty getting up from sitting position, climbing stairs or lifting arms above the head. Life expectancy is normal.

Despite extensive ongoing research, so far there is no cure for SMA. Treatment focuses on managing the symptoms and prevention of development of complications.