Congenital Muscular Dystrophy

Congenital muscular dystrophies are a group of inherited muscle diseases presenting at birth or in the first year with hypotonia, weakness and dystrophic muscle pathology. Main groups are laminin alpha-2 deficiency (merosin deficient, LAMA2), collagen VI-related (Ullrich and Bethlem), alpha dystroglycanopathies (including Walker-Warburg, muscle-eye-brain disease and Fukuyama) and SEPN1-related (rigid spine) disease. Prevalence is about 1 in 100,000.

Pathophysiology. Defects in extracellular matrix proteins or glycosylation of alpha dystroglycan disrupt muscle membrane stability and brain development.

Neonatal hypotonia, weakness, joint contractures, delayed motor milestones, respiratory insufficiency, scoliosis and feeding problems. LAMA2 disease shows white matter change on MRI, with normal intelligence in most and epilepsy in some. Dystroglycanopathies may cause structural brain malformations (cobblestone lissencephaly), intellectual disability, seizures and eye defects. Cardiac involvement occurs in some forms.

Red flags.

• Respiratory insufficiency or hypoventilation.
• Feeding difficulty with aspiration.
• Seizures or rapidly progressive scoliosis.

Creatine kinase is raised (often over 10 times normal in LAMA2 and dystroglycanopathy). Brain MRI shows white matter change (LAMA2) or malformation (dystroglycanopathy). Muscle biopsy shows dystrophic changes with immunostaining of merosin and alpha dystroglycan. Genetic testing (panel or exome) is the key test. Assess respiratory, cardiac and swallowing function.

Differential diagnosis.

• Congenital myopathies, spinal muscular atrophy and congenital myasthenic syndromes.
• Congenital myotonic dystrophy, metabolic myopathies and Prader-Willi syndrome.

There is no curative treatment.

Respiratory. Monitor forced vital capacity and overnight oximetry, give non-invasive ventilation and cough assistance, and vaccinate.

Nutrition. Gastrostomy for unsafe swallowing or poor growth.

Orthopaedic. Stretching, orthoses, scoliosis surgery in selected patients, and contracture care.

Cardiac. Echocardiography and ECG baseline and regular follow up.

Neurological. Treat seizures (levetiracetam 10 mg/kg twice daily, increased to 30 mg/kg twice daily), educational support and ophthalmology.

Steroids. Not shown to help, and not given routinely.

Monitoring. Respiratory, cardiac and growth every 6 to 12 months.

Referral and escalation. Refer to paediatric neuromuscular services and genetics.

Special groups. Genetic counselling for families and prenatal testing.