Covers spinal muscular atrophy as a group of disorders sharing an SMN1 defect, starting with its definition and genetic basis, including the role of the nearby SMN2 gene and how its copy number affects severity. It then explains the function of the SMN protein, the stepwise pathophysiology, and a table classifying the four types by age of onset, severity and SMN2 copies. Clinical features, diagnostic tests, disease-modifying and supportive treatments, and prognosis by type close the note.
Topic 28 of 65 in the MU Sofia syllabus for Genetics (Medicine, Year 3). The free AceMed note covers it in 9 sections, about 405 words (4 min of reading), with 14 flashcards.
Spinal Muscular Atrophy (SMA) is a hereditary neuromuscular disease characterized by progressive degeneration of α-motor neurons in the anterior horn of the spinal cord, leading to muscle weakness and atrophy.
It is one of the most common genetic causes of infant mortality due to neuromuscular failure.
SMA represents a group of disorders that differ in age of onset and severity, but share the same molecular defect involving the SMN1 gene.
Genetic and Molecular Basis
Causative gene:
SMN1 (Survival Motor Neuron 1) gene located on chromosome 5q13.2.
Inheritance: Autosomal recessive.
Molecular mechanism:
Homozygous deletion or mutation of SMN1 → deficiency of SMN protein, which is essential for motor neuron survival.
A nearby gene, SMN2, produces limited amounts of functional SMN protein.
Disease severity depends on the number of SMN2 copies (more copies → milder phenotype).
Function of SMN Protein
The SMN protein is part of a complex involved in RNA splicing and assembly of small nuclear ribonucleoproteins (snRNPs).
It is critical for the maintenance of motor neurons.
Loss of SMN → defective RNA processing → motor neuron degeneration → denervation of skeletal muscle fibers.
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