Spinal muscular atrophies (smas)

[Jessica]

Spinal muscular atrophies include several types of hereditary disorders characterized by skeletal muscle wasting due to progressive degeneration of anterior horn cells in the spinal cord and of motor nuclei in the brain stem. Manifestations may begin in infancy or childhood. They vary by the specific type and may include hypotonia; hyporeflexia; difficulty sucking, swallowing, and breathing; unmet developmental milestones; and, in more severe types, very early death. Diagnosis is by genetic testing. Treatment is supportive.
Spinal muscular atrophies usually result from autosomal recessive mutations of a single gene locus on the short arm of chromosome 5, causing a homozygous deletion. They may involve the central nervous system and thus are not purely peripheral nervous system disorders.
There are 4 main types.
Type I spinal muscular atrophy (Werdnig-Hoffmann disease) is present in utero and becomes symptomatic by about age 6 months. Affected infants have hypotonia (often notable at birth), hyporeflexia, tongue fasciculations, and pronounced difficulty sucking, swallowing, and eventually breathing. Death, usually due to respiratory failure, occurs within the first year in 95% and by age 4 years in all.
In type II (intermediate) spinal muscular atrophy, symptoms usually manifest between 3 and 15 months of age; lt; 25% of affected children learn to sit, and none walk or crawl. Children have flaccid muscle weakness and fasciculations, which may be hard to see in young children. Deep tendon reflexes are absent. Dysphagia may be present. Most children are confined to a wheelchair by age 2 to 3 years. The disorder is often fatal in early life, frequently resulting from respiratory complications. However, progression can stop spontaneously, leaving children with permanent, nonprogressive weakness and a high risk of severe scoliosis and its complications.
Type III spinal muscular atrophy (Wohlfart-Kugelberg-Welander disease) usually manifests between age 15 months and 19 years. Findings are similar to those of type I, but progression is slower and life expectancy is longer; some patients have a normal life span. Some familial cases are secondary to specific enzyme defects (eg, hexosaminidase deficiency). Symmetric weakness and wasting progress from proximal to distal areas and are most evident in the legs, beginning in the quadriceps and hip flexors. Later, arms are affected. Life expectancy depends on whether respiratory complications develop.
Type IV spinal muscular atrophy can be recessive, dominant, or X-linked, with adult onset (age 30 to 60 years) and slow progression of primarily proximal muscle weakness and wasting. Differentiating this disorder from amyotrophic lateral sclerosis that involves predominantly lower motor neurons may be difficult.