Megaconial congenital muscular dystrophy (CMD) (OMIM#60251) is a rare form of congenital muscular dystrophy characterised by early onset hypotonia, muscle weakness and wasting, global developmental delay, intellectual disability, autistic features, and elevated creatine kinase levels. Some patients also develop cardiomyopathy, ichthyosis-like skin changes, and seizures. The skeletal muscle obtained from biopsy will show abnormal findings with evidence of variation in muscle fibre with muscle fibre degeneration and regeneration, and the appearance of giant mitochondria in the periphery of the muscle fibers but spared in the centre. The disease is caused by loss-of-function mutations in the CHKB gene.
Main clinical features
Early-onset hypotonia, progressive muscle weakness, global developmental delay and intellectual disability with autistic features, and dilated cardiomyopathy.
Prevalence
The prevalence of the megaconial CMD was not known.
Inheritance
Autosomal recessive
Age of onset
Mostly infancy to early childhood
Molecular characteristics
Megaconial CMD is caused by homozygous or compound heterozygous mutations of the CHKB gene including frameshift deletions, non-sense, splice site, and missense mutations or small deletion/insertion.
Genetic counselling
Megaconial CMD has an autosomal recessive disorder. The two asymptomatic parents who each carry one copy of the mutated CHKB gene will have a 25 % chance of having an affected child, and 50% chance of having an unaffected child who is a carrier of the disorder, and a 25% chance of having a child who is not affected and not a carrier. Prenatal diagnosis is available.
Management
Megaconial CMD can affect multiple body systems, and as such treatment should be carried out by a multi-disciplinary team based on the symptoms manifested in the patient. This may include multi-specialty care with teams from the neurology, cardiology, gastrointestinal and nutritional, pulmonary, orthopaedic and rehabilitation subspecialties, and learning support and behavioural management from the educational, child psychology and psychiatry departments. All affected patients should have regular follow-ups to monitor their progress.
CHKB