What is Spinal Muscular Atrophy?
Learn about Spinal Muscular Atrophy (SMA), its causes, types, symptoms, diagnosis, and treatment options.
Topics
Introduction to Spinal Muscular Atrophy
Neuromuscular disorders that present in the newborn period with hypotonia and weakness can be caused by various conditions that affect the central nervous system (brain or spinal cord), peripheral...
Epidemiology of SMA
The incidence of spinal muscular atrophy ranges from 5 to 13 per 100,000 live births, and the carrier frequency of disease-causing SMN1 mutations ranges from 1:100 to 1:45, with marked interethnic...
Genetics of SMA
The inheritance pattern of chromosome 5q-related SMA is autosomal recessive. The different forms of 5q-SMA are caused by biallelic deletions or mutations in the SMN1 gene on chromosome 5q13.
Clinical Features
SMA disorders are characterized by degeneration of the anterior horn cells in the spinal cord and motor nuclei in the lower brainstem, which results in progressive muscle weakness and atrophy.
Diagnosis of SMA
The diagnosis of SMA should be suspected for any infant with unexplained weakness or hypotonia. Additional clues suggesting the diagnosis in infants, children, or adults include a history of motor...
Differential Diagnosis
The differential diagnosis of SMA varies according to the age of onset.
Supportive Therapy
Supportive therapy is directed at providing nutrition and respiratory assistance as needed and treating or preventing complications of weakness. Recommended evaluations at baseline include...
Disease-modifying Therapy
Treatment for SMA has been mainly supportive, but disease-modifying therapy (DMT) with Nusinersen, Onasemnogene abeparvovec, and Risdiplam is now available.
Genetic Counseling
Affected individuals with SMA and their parents should be referred for genetic counseling, which may be challenging. Occasionally, carriers have normal dosage studies for the SMN1 deletion because...
Pregnancy and SMA
As noted earlier, all SMA types are associated with a restrictive, progressive respiratory insufficiency. Thus, pregnancy in women with SMA is associated with increased risk because of impaired...
Prognosis
SMA encompasses a spectrum of phenotypes ranging from severe forms with early onset to milder forms with later onset. The natural history of SMA according to phenotype is summarized as follows: