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Chapter 9: Genetic Basis of Cardiovascular Disease

A 23-year-old woman presents with a long history of muscle weakness. Her past medical history is notable for “hypertrophic” cardiomyopathy (HCM), cryptogenic stroke, and optic neuritis. She was told that she had a dilated cardiomyopathy prior to developing a hypertrophic cardiomyopathy. Physical examination, in addition to findings of HCM, are remarkable for short stature and hearing loss. Labs are notable for an elevated CPK. Her family history includes multiple family members with cardiac problems. Her pedigree is shown in Figure 9-1. Her brother has a similar constellation of findings of similar severity. Her mother, her maternal grandmother, and her maternal uncle also have a similar set of findings but with milder severity. Based on the presentation and pedigree, what is the likely mode of inheritance?



FIGURE 9-1. Pedigree for question 9-1.

A. Autosomal recessive

B. Spontaneous somatic mutation

C. X-linked

D. Mitochondrial inheritance

E. Spontaneous chromosomal translocation

The answer is D. (Hurst’s The Heart, 14th Edition, Chap. 9) The patient has a syndrome of mitochondrial encephalomyopathy with lactic acidosis and strokelike episodes (MELAS). MELAS patients can have a dilated cardiomyopathy that transitions to a HCM.1 MELAS is a mitochondrial myopathy and often is the result of a mutation in transfer RNA (option D). The pedigree shows the phenotype in every generation. Spontaneous mutations would not be in each generation (options B and E). Autosomal recessive mutations skip every generation (option A). Similarly, X-linked mutations tend to involve males because males have a single X chromosome (option C). Autosomal dominant mutations result in affected family members in each generation, but this is not a choice. Mitochondrial DNA is maternally derived, so the disease can only be passed by females. The penetrance of the disease is related to the amount of abnormal mitochondrial DNA that is inherited.

Which of the following is true of heritable cardiomyopathies?

A. About 1 in 500 people carry a gene associated with HCM

B. Patients with sarcomeric mutations can have either a hypertrophic, dilated, or restrictive cardiomyopathy

C. Most heritable cardiomyopathies are autosomal recessive

D. Heritable cardiomyopathies are rare

E. Patients with heritable cardiomyopathies only have mutations in sarcomeric genes

The answer is B. (Hurst’s The Heart, 14th Edition, Chap. 9) Hypertrophic cardiomyopathy is the most common heritable cardiomyopathy. One in 500 young adults are affected, and 1 in ...

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