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Chapter 55: Mendelian Basis of Congenital and Other Cardiovascular Diseases

A 54-year-old man presents to your office to establish care. His family history is notable for hypertrophic cardio­myopathy in his grandfather, paternal uncle, and sister. His father and his two other brothers are unaffected. He has previously undergone genetic testing and is a carrier for a mutation in the MYH6 gene that is associated with hypertrophic cardiomyopathy. He is otherwise healthy and denies any functional limitation. His electrocardiogram and echocardiogram are essentially normal. Which of the following concepts explains your patient’s lack of a phenotype?

A. Low expressivity

B. Variable penetrance

C. Genetic heterogeneity

D. Spontaneous mutation to a wild type allele

E. The allele is recessive

The answer is B. (Hurst’s The Heart, 14th Edition, Chap. 55) This patient carries a disease allele but does not have signs or symptoms of the disease, suggesting that the allele is not fully penetrant (option B). Expressivity refers to variable degrees of disease severity in carriers of the disease allele, but all carriers exhibit some signs of the disease (option A). Genetic heterogeneity refers to different disease alleles at different loci that can result in the same phenotypic disease (option C). For instance, multiple mutations in different genes can result in hypertrophic cardiomyopathy. The pattern of inheritance here is consistent with an autosomal dominant allele (option E). Like your patient, his father is likely to also carry the disease allele but not have phenotypic disease. This patient tested positive for the disease allele, so spontaneous mutation to a wild type allele is unlikely (option D).

A 62-year-old woman presents to your office to establish care. Her past medical history is notable for aortic valve replacement with arch repair for a thoracic aortic aneurysm. Her exam is notable for short stature and low-set ears. She was unable to have children despite trying to become pregnant. Karyotype analysis would likely reveal which of the following?

A. Trisomy 21

B. Trisomy 18

C. Trisomy 13

D. Monosomy of the X chromosome

E. A deletion in the long arm of chromosome 22

The answer is D. (Hurst’s The Heart, 14th Edition, Chap. 55) This patient has Turner syndrome, which is associated with monosomy of the X chromosome (option D). Patients with Turner syndrome can have a bicuspid aortic valve, often associated with aortic aneurysms.1 Trisomy 21 is associated with Down syndrome (option A). Trisomy 18 is associated ...

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