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At a glance

Rare but second most common lethal recessive disease in the white population. Neurological disorder that leads to loss of motor neurons and progressive muscle wasting and respiratory insufficiency is often noted. Clinical evolution according to the type involved.

Synonyms

SMA Syndrome, Infantile Spinal Muscular Atrophy; Juvenile Muscular Atrophy; Werdnig-Hoffman Disease; Dubowitz Disease; Kugelberg Welander Syndrome; Wohlfart-Kugelberg-Welander Syndrome; Adult Spinal Muscular Atrophy.

Classification

  • Spinal Muscular Atrophy Type I (Werdnig-Hoffman Disease; SMA Infantile Acute Form; Infantile SMA Syndrome)

  • Spinal Muscular Atrophy Type II (Dubowitz Disease; Intermediate Type of SMA; Infantile Chronic Form of SMA)

  • Spinal Muscular Atrophy Type III (Juvenile Muscular Atrophy; Childhood-Onset Proximal SMA; ☞Kugelberg Welander Syndrome; Childhood Isolated SMA; Wohlfart-Kugelberg-Welander Syndrome)

  • Spinal Muscular Atrophy Type IV (Distal Hereditary Motor Neuropathy; Adult Spinal Muscular Atrophy)

Incidence

1/6,000 to 1/10,1000 live births.

Genetic inheritance

Autosomal recessive. However, some forms are believed to be inherited as autosomal dominant and occasionally X-linked.

Pathophysiology

The disorder is characterized by degeneration and loss of anterior horn cells in the spinal cord and sometimes also in the brain stem, leading to symmetrical muscle weakness and wasting of voluntary muscles. There is evidence that at least two identifiable genes are associated with the disease: SMN1 (survival motor neurone) and NAIP (neuronal apoptosis inhibitory protein), the latter being considered a phenotype modifier. The SMN gene is missing in the majority of SMA patients and small, intragenic mutations have also been associated with SMA. Approximately half of the severely affected patients are also missing the NAIP gene, which may affect the severity of the disease.

Diagnosis

Clinical features. CT scan and MRI are used to exclude other pathologies. Electromyography usually shows neurogenic and occasional myogenic pattern. Nerve conduction study is normal. Serum creatine kinase is normal. Muscle biopsy shows a large number of round atrophic fibers and clumps of hypertrophic fibers that are type I by ATPase reaction. Deoxyribonucleic acid (DNA) testing for SMN and NAIP genes is reliable and confirmatory for the phenotype. Prenatal DNA testing is less reliable because a small percentage of population lacks an SMN gene but is not clinically affected.

Clinical aspects

Spinal Muscular Atrophy is the second most common lethal autosomal recessive disease in the white population.

  • Type I (Werdnig-Hoffman Disease): Caused by mutation of SMN1 gene on chromosome 5q13. Early onset and diagnosis (before 3 months), with severe intrauterine growth retardation, polyhydramnios, and tongue fasciculations. Child never sits or walks. There is difficulty with swallowing and feeding. Respiratory function is always severely impaired: diaphragmatic breathing, respiratory infection, and distress. Absent deep tendon reflexes, hypotonia, and weakness, but normal intelligence and no sensory loss are observed. Restricted joint mobility and kyphoscoliosis are ...

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