Unravelling the Genetic Basis of Primary Aldosteronism

Abstract

Primary aldosteronism (PA), a condition characterized by autonomous aldosterone hypersecretion, constitutes the most common cause of secondary hypertension. Over the last decade, major breakthroughs have been made in the field of genetics underpinning PA. The advent and wide application of Next Generation Sequencing (NGS) technology led to the identification of several somatic and germline mutations associated with sporadic and familial forms of PA. Somatic mutations in ion-channel genes that participate in aldosterone biosynthesis, including KCNJ5, CACNA1D, ATP1A1, and ATP2B3, have been implicated in the development of aldosterone-producing adenomas (APAs). On the other hand, germline variants in CLCN2, KCNJ5, CACNA1H, and CACNA1D genes have been implicated in the pathogenesis of the familial forms of PA, FH-II, FH-III, and F-IV, as well as PA associated with seizures and neurological abnormalities. However, recent studies have shown that the prevalence of PA is higher than previously thought, indicating the need for an improvement of our diagnostic tools. Further research is required to recognize mild forms of PA and to investigate the underlying molecular mechanisms.

Low renin forms of monogenic hypertension: review of the evidence

“…Diagnosis is made using genetic testing and adrenal computed tomography [26]. Owing to the variety of phenotypes these patients may present with, bilateral adrenalectomy is recommended in these patients if MR blockers cannot stabilize the blood pressure [25,27]. Unilateral adrenalectomy has been erroneously trialled in the management of markedly elevated blood pressure and plasma aldosterone in a patient with FH-III [25].…”