Spinal Muscular Atrophy

Spinal Muscular Atrophy
Classification and external resources
ICD-10	G12.0
ICD-9	335.1
OMIM	253300
DiseasesDB	14093
MedlinePlus	000996
MeSH	D014180

Spinal Muscular Atrophy (SMA) is a genetic disorder characterized by weakness and wasting (atrophy) in muscles used for movement (skeletal muscles). It is caused by a loss of specialized nerve cells, called motor neurons, in the spinal cord and the part of the brain that connects to the spinal cord (brainstem). The loss of these motor neurons leads to progressive muscle weakness and atrophy.

Causes

SMA is caused by mutations in the SMN1 gene, which encodes the SMN protein essential for the survival of motor neurons. The severity of SMA is related to the amount of SMN protein produced by the SMN2 gene, a copy gene that partially compensates for the loss of SMN1.

Types

There are several types of SMA, classified based on the age of onset and the highest physical milestones achieved:

• Type I (Werdnig-Hoffmann disease): Onset is before 6 months, with severe muscle weakness and poor muscle tone. Most children with Type I SMA do not survive past early childhood due to respiratory failure.
• Type II: Onset is between 6 and 18 months, with some ability to sit but inability to stand or walk independently.
• Type III (Kugelberg-Welander disease): Onset is after 18 months, with the ability to walk but increasing difficulty over time.
• Type IV: Onset is in adulthood, leading to mild motor impairment.

Symptoms

Symptoms of SMA may include hypotonia (reduced muscle tone), muscle weakness, respiratory distress, and difficulties with swallowing and feeding. Motor milestones are delayed or never achieved, depending on the type of SMA.

Diagnosis

Diagnosis of SMA is based on clinical presentation and confirmed by genetic testing showing mutations in the SMN1 gene. Additional tests may include electromyography (EMG), muscle biopsy, and nerve conduction studies.

Treatment

There is no cure for SMA, but treatment options have improved significantly in recent years. Approaches include gene therapy, such as Onasemnogene abeparvovec, which delivers a functional copy of the SMN1 gene to motor neurons. Other treatments involve drugs like Nusinersen and Risdiplam, which enhance the production of the SMN protein from the SMN2 gene. Supportive care includes respiratory support, nutritional support, and physical therapy to manage symptoms and improve quality of life.

Prognosis

The prognosis for SMA depends on the type. Type I SMA has a poor prognosis without intervention, while Types II and III have longer life expectancies, particularly with advances in supportive and targeted therapies.

Epidemiology

SMA affects approximately 1 in 10,000 live births, and it is the leading genetic cause of infant death. Carrier frequency of the SMN1 mutation is about 1 in 50 in the general population.

See also

• Muscular dystrophy
• Gene therapy
• Pediatric neurology

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