title: An Update on Familial Hyperaldosteronism.
abstract: Familial forms of primary aldosteronism have been suggested to account for up to 6% of cases in referral centers. For many years, the genetics of familial hyperaldosteronism remained unknown, with the notable exception of glucocorticoid-remediable aldosteronism, due to unequal crossing over and formation of a chimeric 11β-hydroxylase/aldosterone synthase gene. Over the past 5 years, mutations in 3 additional genes have been shown to cause familial forms of primary aldosteronism. Gain-of-function heterozygous germline mutations in KCNJ5, which encodes an inward rectifier potassium channel, cause autosomal dominant syndromes of PA and hypertension with or without adrenal hyperplasia. Germline mutations in CACNA1D, which codes for an L-type calcium channel, have so far only been found in 2 cases with a syndrome of primary aldosteronism, seizures, and neurologic abnormalities. Both KCNJ5 and CACNA1D mutations in familial hyperaldosteronism were only discovered following identification of similar or identical somatic mutations in aldosterone-producing adenomas. In contrast, a recent exome sequencing study identified germline mutations in CACNA1H (a T-type calcium channel), previously undescribed in adenomas, in 5 unrelated families with early-onset primary aldosteronism and hypertension, without any additional shared symptoms. Future exome or genome sequencing studies are expected to shed light on the genetic basis of many cases of familial hyperaldosteronism that remain unexplained.
authors.affiliation: Department of Nephrology, Medical School, Heinrich Heine University, University Hospital Düsseldorf, Düsseldorf, Germany.
authors.forename: H E
authors.initials: HE
authors.lastname: Korah
authors.affiliation: Department of Nephrology, Medical School, Heinrich Heine University, University Hospital Düsseldorf, Düsseldorf, Germany.
authors.forename: U I
authors.initials: UI
authors.lastname: Scholl
mesh_terms: D020022:Genetic Predisposition to Disease; D006801:Humans; D006929:Hyperaldosteronism / Q000150:complications / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D010641:Phenotype