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.
