NeurometPlus

Incidence

Autosomal recessive. Although precise epidemiological data are not available, this is one of the most common variants of congenital muscular dystrophy.

Clinical Characteristics

This is the most common CMD and accounts for about 40% of all cases. Reduced fetal movements in utero may be noted. At birth or in the first few months of life, patients may have severe hypotonia, weakness, feeding difficulty, and respiratory insufficiency. Contractures are common. External ophthalmoplegia may occur late. Most infants eventually sit unsupported, but standing is rare. Weakness is static or minimally progressive. Complications are related to respiratory compromise, feeding difficulty, scoliosis, and (in about one third) cardiopulmonary disease. A motor-to-sensory demyelinating neuropathy is present in many patients, but it may not be clinically relevant. CNS manifestations may be present. Mild mental retardation or perceptual-motor difficulties are observed in a few cases. Seizures occur in up to 30% of patients. White-matter changes, most often in periventricular areas, as noted on MRI, are invariably present after 6 months of age, even in patients with normal intelligence. White-matter changes are not correlated with the amount of laminin-alpha2, the patient\'s intelligence, or the presence of seizures. Structural brain changes have been reported in a few patients and include enlargement of the lateral ventricles, focal cortical dysplasia, occipital polymicrogyria and/or agyria, and hypoplasia of the pons and/or cerebellum. Clinical variants of MDC1A occur with some mutations when only partial laminin-alpha2 deficiency is present. Patients may present with hypotonia during infancy, but they become ambulatory and maintain ambulation for many years. The phenotype of limb-girdle dystrophy may also be present; this includes RSMD1 or Emery-Dreifuss muscular dystrophy-type syndrome. Clues to the presence of laminin-alpha2 deficiency include MRI abnormalities, seizures, and demyelinating neuropathy. This condition is due to defects of proteins of the extracellular matrix of peripheral membrane proteins.

Precipitants

None. There is no report of malignant hyperthermia in patients with muscular dystrophy congenital type 1A.

Provocation Tests

None

Diagnostic Procedures

Supportive clinical features are the presence of the classical white matter brain changes and a mild demyelinating peripheral motor neuropathy. Serum CK levels are typically elevated (more than 10 times normal values). A muscle biopsy is necessary to look at laminin alpha2 chain expression; this protein is also expressed in skin. The identification of the causative mutation in the laminin alpha2 chain gene will be necessary to confirm the diagnosis.