Novel Gene-Environment Regulatory Circuit in Chamber-Specific Growth of Perinatal Heart

We report a case of hypertrophic cardiomyopathy and lactic acidosis in a 3-year-old female. Cardiac and skeletal muscle biopsies exhibited mitochondrial hyperplasia with decreased complex VI activity. Whole exome sequencing identified compound heterozygous variants, p.Arg333Trp and p.Val119Leu, in TSFM, a nuclear gene that encodes a mitochondrial translation elongation factor, resulting in impaired oxidative phosphorylation and juvenile hypertrophic cardiomyopathy.]]>
The proband is a previously healthy 3-year-old female of nonconsanguineous Caucasian parents, who presented with a 10-day history of cough, rhinorrhea, fever, and diarrhea and a 2-day history of emesis, found to have severe cardiomegaly on X-ray. She had no prior history of shortness of breath, syncope or chest pain. She was born at term without complications after an uneventful pregnancy. Early growth and development were typical (able to walk by 14 months) and she reported no difficulty with running and keeping up with peers. Her older sister and both parents were healthy. The family history was significant for a paternal grandfather with adult-onset coronary artery disease, but otherwise non-contributory. There was no history of congenital disease or sudden infant deaths in the family. Physical examination was largely unremarkable.]]>