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A 16-year-old athlete collapses during basketball practice and cannot be resuscitated. Autopsy reveals asymmetric septal hypertrophy. Family screening reveals his father has a thickened septum on echo.

AD; sarcomeric protein genes

  • MYH7 (β-myosin heavy chain) and MYBPC3 (myosin-binding protein C) account for ~70%
  • Also: TNNT2, TNNI3, TPM1, ACTC1, etc.
  • LV hypertrophy (≥15 mm) without other cause
  • Often asymmetric septal hypertrophy
  • Dynamic LVOT obstruction (some)
  • Diastolic dysfunction
  • Leading cause of sudden cardiac death in young athletes
  • Echo or cardiac MRI showing LV wall thickness ≥15 mm (≥13 mm in a relative of an affected person or with a positive genotype) not explained by abnormal loading conditions
  • ECG is almost always abnormal; cardiac MRI characterizes fibrosis and apical or focal hypertrophy
  • Sarcomeric gene testing confirms the diagnosis and enables cascade screening; at-risk relatives need serial clinical evaluation even when the genotype is unknown
  • Risk stratification for ICD, beta-blockers, septal reduction (myectomy or alcohol ablation), activity restrictions

Arrhythmias vs cardiomyopathies: Arrhythmias are mostly due to ion channels; cardiomyopathies are mostly due to sarcomere protein mutations. HCM is the classic example: MYH7 and MYBPC3 are sarcomere genes