What Is Spinal Muscular Atrophy?

Spinal muscular atrophy (SMA) is a motor weakness disease caused by a mutation in the survival motor neuron (SMN) gene on chromosome 5. In over 95% of cases, the defect is a homozygous deletion of exon 7 resulting in a lack of SMN protein. The SMN protein is essential for normal functioning of the motor neuron, including the neuromuscular junction. The protein is involved in transport of mRNA along axons and local RNA processing. This deletion leads to loss of anterior horn cells of the spinal cord despite the presence of normal numbers of motor neurons. Its incidence is approximately 1 in 6,000–10,000 live births, and it is inherited in an autosomal recessive fashion. Sensation is generally intact. This disorder is heterogeneous in clinical presentation and has therefore been subcategorized for prognostic utility. Muscle weakness affects most major muscle groups as well as the intercostal muscles, but the diaphragm is spared.

What Are the Different Types of SMA?

SMA type 1 (Werdnig–Hoffmann) has onset at birth or shortly thereafter. Without ventilatory support, 90% of these infants will succumb to respiratory failure before 1 year of age, and none will survive to two years. Noninvasive artificial ventilation (e.g., CPAP) may lead to survival past five years of age, and invasive ventilation via tracheostomy may increase lifespan into adulthood.

Often, the infant has no spontaneous movements of extremities except tremor of the fingers and tongue fasciculations. Intercostal muscles are so weak that diaphragmatic breathing is required.

SMA type 2 (juvenile spinal muscular atrophy) usually presents between 6–18 months of age. While infants are weak, motor milestones such as sitting unassisted are often achieved but walking is never achieved. In less severe cases, spirometry may be unaffected. If untreated, about 70% will reach adulthood, but modern medical care improves the situation considerably.

SMA type 3 (Wohlfart–Kugelberg–Welander syndrome) usually presents after two years of age with abnormal gait. Most of these children will eventually be able to walk, and survival into adulthood is not unusual.

Electromyography shows denervation with fibrillation potentials and muscle biopsy often shows neurogenic atrophy, but diagnosis of SMA is confirmed by genetic testing for the SMN mutation.