Definition

Disorders that may begin in infancy or childhood, characterized by skeletal muscle wasting due to progressive degeneration of anterior horn cells in the spinal cord and motor nuclei in the brain stem.

Most cases are autosomal recessive and appear to be allelic mutations of a single gene locus on chromosome 5. Four main variants are recognized.

Type I spinal muscular atrophy (Werdnig-Hoffmann disease) is present in utero or becomes symptomatic by 2 to 4 mo of age. Most affected infants are hypotonic at birth; all have delayed motor milestones by 6 mo. Death occurs in 95% by age 1-1/2 yr and in all by age 4 yr, usually from respiratory failure.

In type II (intermediate) spinal muscular atrophy, most infants and children are symptomatic by about age 6 to 12 mo, and all by 2 yr; < 25% learn to sit, and none walk or crawl. Children are hypotonic with flaccid muscle weakness, absent deep tendon reflexes, and fasciculations, which may be hard to see in young children. Dysphagia may be present. The disorder is often fatal in early life, frequently from respiratory complications. However, progression can stop spontaneously, leaving the child with permanent, nonprogressive weakness.

Type III spinal muscular atrophy (Wohlfart-Kugelberg-Welander disease) begins between 2 and 30 yr of age. Pathologic findings and mode of inheritance are similar to the acute form, but disease evolution is slower and life expectancy longer. Weakness and wasting are most evident in the legs, beginning in the quadriceps and hip flexors. Later, the arms are affected. Weakness often progresses from proximal to distal parts. Some familial cases are secondary to specific enzyme defects (eg, hexosaminidase deficiency).

Type IV spinal muscular atrophy has a variable inheritance pattern (recessive, dominant, X-linked), with adult onset (age 30 to 60 yr) and slow progression. Differentiating it from the lower motor neuron form of amyotrophic lateral sclerosis may be impossible.

Diagnosis and Treatment

Diagnosis is usually confirmed by demonstrating denervation without peripheral nerve involvement, chiefly with electromyography; nerve conduction velocity studies are normal. Muscle biopsy is performed occasionally. Serum enzymes (CK, aldolase) may be slightly increased. Amniocentesis is not diagnostic.

There is no specific treatment. Physical therapy, bracing, and special appliances can benefit patients with static or slowly progressive disease by preventing scoliosis and contractures.

Disorders Of The Peripheral Nervous System

spinal muscular atrophy-microcephaly-mental retardation syndrome

spinal muscular atrophy-mental retardation syndrome