Journal Article

Discordant Genotype-Phenotype Correlation in Familial Hyperaldosteronism Type III with KCNJ5 Gene Mutation: A Patient Report and Review of the Literature

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

2014

Overview

Background: 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. Methods: Here we describe the clinical course of a sporadic case of FH-III, with de novo G151R mutation. Results: 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. Conclusion: Diverse clinical severity in FH-III cannot be defined solely by KCNJ5 genotype.

• Publisher: S. Karger AG
• Subject: Adrenal Glands - pathology / Amino Acid Substitution / Child, Preschool / G Protein-Coupled Inwardly-Rectifying Potassium Channels - genetics / Humans / Hyperaldosteronism - drug therapy / Hyperaldosteronism - genetics / Hyperaldosteronism - pathology / Male / Mineralocorticoid Receptor Antagonists - administration & dosage / Mutation, Missense / Novel Insights from Clinical Practice / Polyuria - drug therapy / Polyuria - genetics / Polyuria - pathology / Spironolactone - administration & dosage