Referenced in: none

Automatically associated channels: Kir3.4

Title: Discordant genotype-phenotype correlation in familial hyperaldosteronism type III with KCNJ5 gene mutation: a patient report and review of the literature.

Authors: Masanori Adachi, Koji Muroya, Yumi Asakura, Kenji Sugiyama, Keiko Homma, Tomonobu Hasegawa

Journal, date & volume: Horm Res Paediatr, 2014 , 82, 138-42

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24819081

Abstract
Familial hyperaldosteronism type III (FH-III) is a rare autosomal dominant disease for which five missense mutations in KCNJ5 have been identified. FH-III has a wide phenotypic variability from spironolactone-responsive hyperaldosteronism to massive adrenal hypertrophy with drug-resistant hypertension. This variation has mainly been attributed to genotype, because, in contrast to other genotypes (G151R, T158A, I157S, and Y152C), (1) FH-III patients with G151E have shown milder phenotype, and (2) G151E-harboring cells were found to have rapid lethality due to much larger sodium conductance of the encoded channel (Kir3.4), which prevents adrenal hypertrophy.Here we describe the clinical course of a sporadic case of FH-III, with de novo G151R mutation.The patient developed polyuria at around 1.5 years of age and developed hypertension and hypokalemia by 4 years of age. Thereafter, spironolactone treatment successfully ameliorated hyperaldosteronism for 7 years with no discernible adrenal enlargement.Diverse clinical severity in FH-III cannot be defined solely by KCNJ5 genotype.