Abstract
Hypertension is an important public health problem affecting more than 50 million individuals in the US alone. The most common form, essential hypertension, results from the complex interplay between genetic predisposition and environmental influences. In contrast, monogenic (mendelian) forms of hypertension are caused by single gene mutations that are influenced little, if at all, by environmental factors. Most monogenic forms of hypertension affect either electrolyte transport in the distal nephron, or the synthesis or activity of mineralocorticoid hormones, leading to the common pathogenic mechanisms of increased distal tubular reabsorption of sodium and chloride, volume expansion and hypertension. In young patients with a family history of hypertension who present with severe or refractory hypertension and characteristic hormonal and biochemical abnormalities, the differential diagnosis should include monogenic forms of hypertension. Genetic testing, which is increasingly available, can facilitate timely diagnosis and treatment of these relatively uncommon disorders, such that the underlying defect can be corrected or ameliorated and the long-term consequences of poorly controlled hypertension prevented.
Key Points
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Monogenic hypertension is caused by single gene mutations and accounts for a spectrum of familial forms of elevated blood pressure
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Monogenic forms of hypertension share a common pathway of increased reabsorption of sodium and chloride in distal tubules and volume expansion, which suppresses plasma renin activity
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These disorders should be suspected in young patients with a family history of hypertension who present with severe or refractory hypertension and characteristic hormonal and biochemical abnormalities
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Timely diagnosis using genetic tests might enhance the success of therapies that target the underlying defects and thus prevent long-term consequences of uncontrolled hypertension
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Garovic, V., Hilliard, A. & Turner, S. Monogenic forms of low-renin hypertension. Nat Rev Nephrol 2, 624–630 (2006). https://doi.org/10.1038/ncpneph0309
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DOI: https://doi.org/10.1038/ncpneph0309
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