Spinal muscular atrophy
Spinal muscular atrophy is an autosomal recessive degeneration of anterior horn cells caused by SMN1 mutation, producing symmetric, proximal-greater-than-distal flaccid weakness with tongue fasciculations and preserved cognition; diagnosis is by genetic testing for SMN1 deletion, and management centers on respiratory, nutritional, and orthopedic supportive care, since there is no disease-modifying therapy.
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What this article covers
- Overview
Definition: spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by congenital degeneration of the anterior horn cells of the spinal cord, producing progressive…
- Epidemiology
Autosomal recessive inheritance: both parents are typically asymptomatic carriers of a single mutated SMN1 allele, and an affected child inherits a nonfunctional copy from each parent.
- Risk factors
Family history of SMA or known carrier status in both parents: the dominant risk factor, since the disease requires inheritance of a nonfunctional SMN1 allele from each parent.
- Pathophysiology
SMN1 mutation: a mutation, usually a deletion, in the SMN1 gene on chromosome 5 reduces production of the survival motor neuron protein.
- Clinical features
Diagnostic clinical pattern: symmetric, predominantly proximal, lower motor neuron weakness (flaccid paralysis, hypotonia, and areflexia) with tongue fasciculations and preserved cognition is the…
- Differential diagnosis
Cerebral palsy: presents with hypertonia and upper motor neuron signs (hyperreflexia, positive Babinski response) from a static prenatal or perinatal insult, unlike the hypotonic, areflexic, lower motor neuron pattern of SMA.
- Diagnosis
First, establish the diagnosis with genetic testing: confirmatory diagnosis rests on genetic testing demonstrating a homozygous SMN1 deletion or mutation, which should be pursued as soon as SMA is…
- Management
First, confirm that supportive care is the mainstay: there is no cure, so management centers on a multidisciplinary team addressing respiratory, nutritional, and orthopedic needs as soon as the diagnosis is made.
- Complications
Respiratory failure: the leading cause of morbidity and mortality in the most severe, earliest-onset form, from progressive weakness of the respiratory muscles.
- Prognosis
Severity correlates with age of onset and SMN2 copy number: the earliest-onset, most severe form carries the worst prognosis, historically with death in infancy from respiratory failure without…
- Prevention
Carrier screening: offered to prospective parents, particularly those with a family history of SMA, to identify carrier status of an SMN1 mutation before or during pregnancy.
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