Congenital myopathy with rhabdomyolysis extends the phenotypic spectrum of DNMT3 gene mutations

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An Australian-Canadian team reported the case of a 25-year-old man with hypotonia at birth, delayed speech and walking at the age of 14 months.

  • During adolescence, he developed exercise intolerance leading to severe myalgias the day after physical exercise, with a first episode of rhabdomyolysis at the age of 16.
  • He had low eyebrow implantation and micrognathia, slight kyphoscoliosis, discrete detachment of the left scapula, hyperextension of the elbows, flat feet and overall low muscle volume.
  • His muscle strength was 5 on manual testing, except for the neck flexors and hip extensors, which were 4.
  • Whole genome sequencing revealed a de novo missense variant in the DNMT3A gene, which encodes DNA methyltranferase 3 alpha and is usually involved in Tatton-Brown-Rahman syndrome, sometimes in Heyn-Sproul-Jackson syndrome or acute myeloid leukaemia.
  • The whole-genome epigenetic signature showed a DNA methylation profile consistent with that of people with a DNMT3A mutation.

 

Expanding the phenotype of DNMT3A as a cause a congenital myopathy with rhabdomyolysis. Ghaoui R, Ha TT, Kerkhof J, McConkey H et al. Neuromuscul Disord. 2023 Apr 4;33(6):484-489.

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