Monogenic Forms of Hypertension

Abstract

Monogenic (Mendelian) forms of hypertension provide important insight into mechanisms of blood pressure regulation. Frequently, they are caused by increased salt reabsorption in the kidney via activation of the mineralocorticoid signaling pathway, which includes Liddle syndrome, glucocorticoid-remediable aldosteronism, apparent mineralocorticoid excess, and salt-sensitive congenital adrenal hyperplasia. In pseudohypoaldosteronism type II, salt-sensitive hypertension is linked with a distinctive decrease in renal potassium excretion leading to hyperkalemia. Other mechanisms in monogenic hypertension are sympathetic nervous system hyperactivity (hereditary forms of pheochromocytoma) and altered vascular resistance (hypertension brachydactyly syndrome). Complementary studies examining monogenic forms of lower blood pressure have identified pathways exclusively linked to renal salt wasting due to altered tubular function in the thick ascending limb (Bartter syndrome) or distal nephron (Gitelman syndrome, EAST syndrome). This chapter delineates the genetic mechanisms underlying rare abnormal blood pressure syndromes, providing important implications on improving diagnosis and treatment of blood pressure disorders.