The proband, an adopted six-year-old girl, and her four-year-old sister were brought to a pediatric cardiologist for evaluation, largely at the insistence of the natural maternal grandmother (MGM), who had maintained contact with the adoptive parents. At the time of the initial evaluation, the proband's family history, obtained through the natural MGM, was notable for hypertrophic cardiomyopathy (HCM) in her maternal uncle (diagnosed on autopsy following SCD at age 15), maternal grandfather (s/p ICD for HCM), and two maternal great aunts (SCD at age 16 and 36) (Figure 1). At the time of the maternal uncle's death, the cardiac status of the proband's mother was deemed "normal." On initial evaluation, the proband was asymptomatic with a normal physical exam, a normal electrocardiogram (ECG) and a normal echocardiogram. Given their significant family history for HCM, the proband and her sister were followed at 1-2 year intervals.
At 8, 11, and 13 years, the proband was largely asymptomatic. The electrocardiograms showed no evidence of ST changes, left ventricular hypertrophy (LVH), or T-wave changes. The echocardiograms were completely within normal limits. She remained a very active child playing soccer and basketball without any exercise intolerance. At 13 years, the proband experienced a syncopal episode lasting a few minutes that was attributed to a vasovagal event. Her ECG and Holter monitoring at the time did not show any abnormalities. 
At 14 years, the proband continued to be athletic and denied any symptoms. Her physical exam and echocardiogram were normal. However, the proband's ECG did show nonspecific ST-T wave changes (Figure 2(a)). At this time, genetic testing was discussed with her and her adopted parents, but the family opted to defer testing.
At 15 years, the proband's ECG showed right bundle branch block, right posterior fascicular block, and Q waves in the lateral and inferior leads (Figure 2(b)). Subsequent cardiac evaluations, including an exercise stress test, echo, and MRI, however, were normal, without any signs of myocardial ischemia or hypertrophy. The proband denied any symptoms or exercise intolerance. 
At 17 years, the proband's echocardiogram showed very mild concentric LVH (thickness 1.1 cm, Z-Score of 2), with evidence of diastolic dysfunction (maximal E : E' ratio=12). An exercise stress test did not reveal any evidence of ischemia or ectopy, and Holter monitoring was unremarkable. At this time, the proband was restricted from participating in competitive athletics, and genetic testing was performed (see below). An MRI performed two weeks later showed normal overall left ventricular mass at 67 g/m sq and normal interventricular septal and posterior wall thickness, but also revealed a prominent 2.7 cm thickening of the anterior wall at the base of the left ventricle (Figure 3).