Megaconial congenital muscular dystrophy is a multi-system disorder with spectrum of severity.
Muscular dystrophy with skeletal muscle weakness
• Floppiness after birth is common
• Delay in motor development is common - unable to stand or walk, or delayed in walking.
• For those who can walk independently, limb girdle muscle weakness is common, and Gower’s sign is typically present.
• With progressive weakness, some patients may lose their ability to walk at a later age.
• For those with a milder disease, their muscle weakness only become apparent at later age.
Cognitive and behavioral problems
• Global developmental delay and intellectual disability are the most prominent features of megaconial CMD. It can vary from mild, moderate to severe and profound range.
• Autism / autistic features are most common.
• Language impairment is frequently associated.
• Aggressive behavior or attention deficit and hyperactive behavior can occur.
Other neurological dysfunctions
• Seizures can start at any age and can be without any precipitating cause.
• Hearing problems have been reported.
Dilated cardiomyopathy
• Cardiac muscle weakness leading to dilated cardiomyopathy with decreased left ventricular function is common and can present at any age.
• Dilated cardiomyopathy is one of the major causes of early death in megaconial CMD.
Skin problem
• Ichthyosis-like skin changes and white scaling of the skin may occur.
Secondary musculoskeletal problems
• Joint contractures, hip subluxation or dislocation, foot deformities and scoliosis may develop and progress over time in the presence of significant muscle weakness.
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Increase level of Creatine Kinases (CK)
• Most patients have elevated serum CK levels from 2 to 9 times of the normal range.
• Patients with milder disease may have normal CK levels, though this is less common.
• During episodes of rhabdomyolysis, very high CK levels over 10,000 u/L can occur.
Characteristic findings of skeletal muscle biopsy
All patients have dystrophic changes in the muscle biopsies with variations in fibre , interstitial fibrosis, and evidence of necrosis and regeneration in muscle fibers. There is also mitochondrial depletion in the centre of the sarcoplasm and enlarged mitochondria (“megaconial” appearance) at the peripheral of most fibers.
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