Spinal Muscular Atrophy (SMA)

Epidemiology and Etiology:

· Autosomal recessive

· Presents in childhood or adolescence

· SMN1 gene on chromosome 5

· SMA type 1 is most common (Werdnig-Hoffman)

· Onset at birth or within 4 mo.

· Death in first 3 years

· SMA type 2

· Presents at 3-15 mo.

· Death at > 4 y.

· SMA type 3

· Presents at > 2 y.

· Survive to adulthood often

Common sites:

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Gross features:

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Histologic features:

· Muscle:

· Atrophic fibres in large number

· Panfascicular atrophy

· Scattered large fibers 2-4x normal size

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Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

· SMN1 gene on chromosome 5

· Homozygous deletions most common

· Contiguous deletion of NAIP (neuronal apoptosis inhibitory gene) may be associated with a severe clinical phenotype

· Intragenic mutations less common

· Tudor homology region is highly conserved motif involved in splicing the RNA of the gene

Other features:

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References:

· Kumar V, Fausto N, Abbas A. Robbins & Cotran Pathologic Basis of Disease, Seventh Edition. 7th ed. Saunders; 2004:1552.