CHKB Muscular Dystrophy (Congenital Megaconial Muscular Dystrophy)

Congenital megaconial muscular dystrophy (OMIM #602541) is a progressive neuromuscular disorder caused by autosomal recessive variants in CHKB, located on chromosome 22q13.33. These variants — including missense, splice-site, stop/gain, and frameshift changes — lead to loss or reduction of CHKB enzyme function. Because choline kinase beta is essential for phospholipid biosynthesis, CHKB deficiency disrupts membrane integrity and mitochondrial structure, resulting in severe muscle pathology.

Children typically present between infancy and early childhood (38 days to 16 years; most commonly ages 2–4) with hypotonia, delayed motor milestones, muscle weakness, and difficulty sitting, standing, or walking. As the disease progresses, fatty infiltration of muscle becomes prominent. Nearly all patients experience muscular dystrophy, and 96 percent present with intellectual disability or speech delay. Thirty percent develop cardiomyopathy, and many ultimately experience respiratory failure — the most common cause of early mortality.

There is currently no cure for CHKB disease. Management includes physical, occupational, and speech therapy, cardiac medications when indicated, and supportive care to address functional decline.