Spinal Muscular Atrophy (SMA) is a congenital neuromuscular disorder characterized most prominently by progressive muscle atrophy and weakness.1 SMA is a neurodegenrative disease and the weakness and loss of muscle tone associated with SMA are the direct result of the death of anterior horn cells in the spinal cord.2 The weakness of SMA is typically proximal more than distal and can involve brainstem motor nuclei in severe forms of the disease.3 The phenotypic spectrum seen in patients with SMA is broad and ranges in age and severity from death in infancy due to absence of any tone including respiratory muscle compromise4 to an insidious loss of muscle mass without functional compromise in adults.5 There are five major subtypes of SMA designated types 0-4 that correspond to the age ranges of onset from prenatal (type 0) through adulthood (type 4).5-7
SMA is a common congenital illness, occurring in an estimated 1 in 11,000 live births.6 SMA is inherited as an autosomal recessive disease, and virtually all patients with SMA have biallelic deletions in exon 7 of the Survival Motor Neuron 1 (SMN1) genes located on chromosome 5q.8 While there is a genotype-phenotype correlation noted in SMA, the presence of other genes can modify the severity of the disease.9 Other diseases can present with similar features to SMA but genetic testing confirms SMA diagnosis and there is increasing advocacy for prenatal testing for early diagnosis and intervention.10,11
Treatment needs for SMA vary by age and phenotype. Infants with SMA require fulltime dedicated care including respiratory, orthopedic, and nutritional support while older children may only physical therapy and require assistive devices for safe ambulation.12
There is one approved therapy for SMA, nusinersen (Spinraza), an antisense oligonuceliotide that increases the production of a homologue of SMN1 and appears to have efficacy as measured by achievement of motor milestones.13
Prognosis in SMA is tied to age of onset and severity of disease. Onsets between prenatal and 6 months of age are associated with severe weakness, respiratory compromise, and early life mortal outcomes.7 Onset of SMA in childhood is not a benign diagnosis but patients can survive into adulthood.3 The adult onset variant of SMA is very rare but appears to confer minimal morbidity and no risk of mortality.5
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13. Maharshi V, Hasan S. Nusinersen: The First Option Beyond Supportive Care for Spinal Muscular Atrophy. Clinical drug investigation. 2017;37(9):807-817.