Discrete subaortic stenosis (DSS) accounts for 8% to 20% of all cases of left ventricular outflow tract (LVOT) obstruction. 1 Familial incidence of DSS, although very rare, signifies the importance of screening in family members. Thus far, a clear inheritance pattern has not been reported in any single pedigree. We have described a family with 2 affected children (out of 3) and have also reviewed the inheritance patterns observed in the reported familial cases of DSS. Most cases of DSS present with systolic murmurs and with time progress to systolic dysfunction. Therefore we also explored the relationship between age and the peak LVOT pressure gradient in the familial cases. Clinical Summary PATIENT 1. A 3-month-old infant presented with recurrent pulmonary infections, congestive heart failure, and failure to thrive. On examination, he had a machinery murmur. Echocardiography revealed a large patent ductus arteriosus, mild pericardial effusion, severe left ventricular hypertrophy (LVH), moderate-to-severe subaortic stenosis, a normal aortic valve, and the presence of a subaortic membrane (Figure E1, A). The peak pressure gradient was 70 mm Hg, and the mean pressure gradient was 45 mm Hg. The child underwent surgical intervention for closure of the patent ductus arteriosus during the same admission and an elective operation for subaortic membrane removal at the age of 21 months. The subaortic membrane, surrounding hypertrophied muscles, and free wall were excised. Histopathology showed fibromuscular tissue fragments exhibiting secondary regenerative changes on a myxoid background. A follow-up echocardiogram showed moderate LVH, a peak pressure gradient of 51 mm Hg, and a mean pressure gradient of 32 mm Hg. PATIENT 2. A 5-year-old, otherwise healthy sister of the proband was found to have a heart murmur. Echocardiography showed the presence of a subaortic membrane (Figure E1, B), moderate aortic stenosis, and moderate LVH. The LVOT pressure gradient was 90 mm Hg, and the mean pressure gradient was 55 mm Hg. She underwent elective surgical excision of the subaortic membrane, hypertrophied muscles, and free wall. Histopathology revealed fibromuscular tissue showing spindle-shaped cells with abundant intercellular connective tissue stroma. Postoperative echocardiography showed moderate aortic valvular stenosis and a peak pressure gradient of 72 mm Hg.