Spinal Muscular Atrophy

Spinal muscular atrophy is a rare genetic disorder that affects the motor neurons in the spinal cord. Dysfunction of motor neurons lead to progressive motor weakness and muscle atrophy.  The prevalence of spinal muscular atrophy is estimated to be 1 in 5,000 to in 10,000 live births. There are several types of spinal muscular atrophy according to age of disease onset and severity. Type 1 and 2 are the most common and are diagnosed in early childhood as the symptoms become noticeable during this period. 

There are several types of spinal muscular atrophy based on the age of onset and SMN2 copy numbers.

• Type 1: Symptom onset occurs before 6 months of age, leading to severe motor dysfunction and respiratory difficulty. Children with this type cannot sit down on their own. These patients have a significantly high risk of life-threatening complications related to respiratory conditions.
• Type 2: Symptom onset occurs between 6 and 18 months of age. Children with this type can sit but cannot walk independently. As the progression of motor weakness, they may loose their motor skills previously acquired.
• Type 3: Symptom onset occurs after 18 months of age, often during childhood and adolescence. Patients with this type can walk independently, but they have difficulty in running or climbing stairs.
• Type 4: Symptom onset is typically in adulthood, often after 30 years old.. Symptoms are mildest among all types of spinal muscular atrophy, it is often delayed or misdiagnosed as other disorders. 

The presenting symptoms of spinal muscular atrophy can be variable according to types and severity of the disease. Most of the common symptoms are related to muscle weakness include:

• Motor weakness, especially in the arms, legs, and trunk
• Difficulty sitting, standing, or walking 
• Loss of motor skills that were previously acquired
• Breathing and swallowing problems in severe cases
• Scoliosis
• Failure to thrive 

Spinal muscular atrophy is caused by mutation of SMN1 gene, which is responsible for producing a protein playing a crucial role in the survival and function of motor neurons. Mutations in the SMN1 gene can vary, and this influences the severity of the disease. Most patients with spinal muscular atrophy have the homozygous deletion of SMN1 gene. The defect of SMN1 gene produce the shortened SMN1 protein, which leads to degeneration of motor neurons. Spinal muscular atrophy is inherited in an autosomal recessive manner, meaning a child with the disease can be born to asymptomatic carrier parents.