Review Question - QID 108871

The most likely diagnosis in this patient is hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy occurs due to mutations in sarcomere proteins such as myosin heavy chain.

The clinical presentation of sudden cardiac death during exertion in an otherwise healthy individual suggests a diagnosis of hypertrophic cardiomyopathy. This diagnosis is supported by the finding of a childhood murmur and a family history of sudden death. Hypertrophic cardiomyopathy is caused by autosomal dominant mutations in various sarcomere proteins such as myosin heavy chain and troponin. Structurally, this mutation leads to an asymmetrically thickened left ventricular wall and enlarged septum. Disordered myofibrils will be seen on histologic examination of hearts in patients with this condition. Clinically, hypertrophic cardiomyopathy presents as sudden death in young athletes due to either fatal arrhythmias or severe left ventricular outflow tract obstruction.

Incorrect Answers:
Answer 2: Dystrophin gene mutations are associated with muscular dystrophy syndromes. However, these syndromes can also present with dilated cardiomyopathy. Dilated cardiomyopathy presents with systolic dysfunction due to decreased contractility and slowly progressive heart failure.

Answer 3: Tropomyosin is a coiled protein that regulates interactions between actin and myosin in the muscle sarcomere. It forms part of the sarcomeric thin filament along with actin and troponin. Though it is a cause of hypertrophic cardiomyopathy, it is a less frequent mutation (< 5%) as compared to myosin heavy chain (15-25%).

Answer 4: Fibrillin is a glycoprotein that contributes to the formation of connective tissue. Fibrillin mutations are associated with Marfan’s syndrome and adolescent idiopathic scoliosis.

Answer 5: Elastin is a highly elastic protein in connective tissue. Alpha-1-antitrypsin deficiency leads to excess breakdown of elastin, leading to panacinar emphysema and cirrhosis.

Bullet Summary:
Hypertrophic cardiomyopathy causes sudden death in young athletes due to arrhythmias or left ventricular outflow obstruction. It is caused by mutations in sarcomeric proteins like myosin heavy chain and troponin.