Megaconial congenital muscular dystrophy secondary to novel CHKB mutations resemble atypical Rett syndrome

J Hum Genet. 2021 Aug;66(8):813-823. doi: 10.1038/s10038-021-00913-1. Epub 2021 Mar 12.


Megaconial congenital muscular dystrophy (CMD)(OMIM #602541), related to CHKB mutation, is a rare autosomal recessive disorder. To date, only 35 confirmed patients are recorded. We present a detailed description of the clinical, histopathological, imaging, and genetic findings of five children from four Indian families. The children had moderate-to-severe autistic behavior, hand stereotypies, and global developmental delay mimicking atypical Rett syndrome. In addition, generalized hypotonia was a common initial finding. The progression of muscle weakness was variable, with two patients having a milder phenotype and three having a severe form. Interestingly, the majority did not attain sphincter control. Only patient 1 had classical ichthyotic skin changes. Muscle biopsy in two patients showed a myopathic pattern with characteristic peripherally placed enlarged mitochondria on modified Gomori trichrome stain and electron microscopy. Genetic analysis in these patients identified three novel null mutations in CHKB [c.1027dupA (p.Ser343LysfsTer86);c.224 + 1G > T (5' splice site); c.1123C > T (p.Gln375Ter)] and one reported missense mutation, c.581G > A (p.Arg194Gln), all in the homozygous state. Megaconial CMD, although rare, forms an important group with a complex phenotypic presentation and accounted for 5.5% of our genetically confirmed CMD patients. Atypical Rett syndrome-like presentation may be a clue towards CHKB-related disorder.

MeSH terms

  • Child
  • Child, Preschool
  • Choline Kinase / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Humans
  • Infant
  • Male
  • Mitochondria / enzymology
  • Mitochondria / genetics*
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / pathology
  • Muscular Dystrophies / congenital
  • Muscular Dystrophies / genetics*
  • Muscular Dystrophies / pathology*
  • Mutation
  • Phenotype
  • Retrospective Studies
  • Rett Syndrome / genetics*


  • CHKB protein, human
  • Choline Kinase

Supplementary concepts

  • Rett Syndrome, Atypical