Spinal Muscular Atrophies (SMAs)
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; < 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.
A diagnosis of spinal muscular atrophy should be suspected in patients with unexplained muscle wasting and flaccid weakness, particularly in infants and children.
Electromyography (EMG) and nerve conduction studies should be done; muscles innervated by cranial nerves should be included. Conduction is normal, but affected muscles, which are often clinically unaffected, are denervated.
Definitive diagnosis is by genetic testing, which detects the causative mutation in about 95% of patients.
Muscle biopsy is done occasionally to exclude treatable causes and to determine whether the cause is fatal. Serum enzymes (eg, creatine kinase, aldolase) may be slightly increased.
Amniocentesis, done if family history is positive, is often diagnostic.
There is no cure. Treatment of spinal muscular atrophies is mainly supportive.
Physical therapy, braces, and special appliances can benefit patients with static or slowly progressive disease by preventing scoliosis and contractures. Adaptive devices available through physical and occupational therapists may improve children’s independence and self-care by enabling them to feed themselves, write, or use a computer.
Nusinersen is a new antisense oligonucleotide that modulates premessenger RNA splicing of the survival motor neuron 2 (SMN2) gene; this drug may marginally improve motor function and delay disability and death.
If infants and children have unexplained muscle wasting and flaccid weakness, evaluate them for spinal muscular atrophies.
EMG shows muscle denervation.
Use genetic testing to confirm the presence and type of spinal muscular atrophy.
Refer patients to physical and occupational therapists, who may help patients learn to function more independently.
Nusinersen, a new drug, may marginally improve motor function and delay disability and death.
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