WBR282

Author	PageAuthor::Gerald Chi (Reviewed by Serge Korjian)
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pathology
Sub Category	SubCategory::Cardiology
Prompt	[[Prompt::A 29-year-old woman presents with a three-year history of increasing dyspnea on exertion associated with chest tightness and lightheadedness. Physical examination is notable for palpable double apical impulses, fourth heart sounds, and systolic murmurs at the left lower sternal border. Echocardiography demonstrates systolic anterior motion of the mitral valve. Which of the following disorders has the same pattern of inheritance as the disorder likely to be present in this patient?]]
Answer A	AnswerA::Huntington disease
Answer A Explanation	AnswerAExp::Huntington disease has an autosomal dominant mode of inheritance similar to familial hypertrophic cardiomyopathy (HCM).
Answer B	AnswerB::Cystic fibrosis
Answer B Explanation	AnswerBExp::Cystic fibrosis has an autosomal recessive mode of inheritance.
Answer C	AnswerC::Kartagener syndrome
Answer C Explanation	AnswerCExp::Kartagener syndrome has an autosomal recessive mode of inheritance.
Answer D	AnswerD::Tay-Sachs disease
Answer D Explanation	AnswerDExp::Tay-Sachs disease has an autosomal recessive mode of inheritance.
Answer E	AnswerE::Leber hereditary optic neuropathy
Answer E Explanation	AnswerEExp::Leber hereditary optic neuropathy has a mitochondrial mode of inheritance.
Right Answer	RightAnswer::A
Explanation	[[Explanation::Familial hypertrophic cardiomyopathy (HCM) is an autosomal dominant disorder due to one or more of 11 identified missense mutations in genes that encode the thick and thin contractile myofilament protein components of the sarcomere (specifically the beta-myosin heavy chain and myosin-binding protein C) which are exclusive to the heart. Phenotypically, not all patients with the mutation manifest the disease, although phenotypic conversion is possible at any point in the disease. Diagnosis requires phenotypic confirmation with imaging, which demonstrates unexplained LV wall thickness >15 mm. Patients generally have a normal life expectancy-, but have a higher risk of sudden death, progressive heart failure, and paroxysmal or chronic atrial fibrillation. The typical murmur of HCM is a systolic ejection murmur that is intensified with conditions of decreased preload or after long cardiac cycles and softened with conditions of increased afterload. The hypertrophied interventricular septum with systolic anterior motion of the mitral valve among patients with phenotypically manifest disease may result in subaortic obstruction of the left ventricular outflow tract that produces a "double-tap" apical impulse as well as pulsus bisferiens (biphasic or beating twice). Treatment of HCM depends on the extent of symptoms. Beta-blockers are the first-line for outflow tract obstruction to decrease the flow gradient (same mechanism as decreased murmurs). Patients with siginificant obstruction may benefit from surgical septal myectomy. Implantable cardioverter-defibrillators are the only strategy shown to reduce the risk of sudden death. Educational Objective: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disorder due to one or more of 11 identified missense mutations in genes that encode the thick and thin contractile myofilament protein components of the sarcomere. References: Maron BJ, Ommen SR, Semsarian C, Spirito P, Olivotto I, Maron MS. Hypertrophic cardiomyopathy: present and future, with translation into contemporary cardiovascular medicine. J Am Coll Cardiol. 2014;64(1):83-99.]]
Approved	Approved::Yes
Keyword	WBRKeyword::Hypertrophic cardiomyopathy, WBRKeyword::Huntington's disease, WBRKeyword::Autosomal dominant, WBRKeyword::Inheritance, WBRKeyword::Cardiomyopathy
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::