title: Nephrogenic syndrome of inappropriate antidiuresis in adults: high phenotypic variability in men and women from a large pedigree.
abstract: Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a recently described genetic cause of hyponatremia in male infants. Whether this X-linked condition could be detected in the adult or also could affect women is unknown. A large five-generation family was identified in which the recently described arginine-vasopressin receptor type 2 (AVPR2) mutation that is responsible for NSIAD was segregated. The proband was a 74-yr-old patient who had a syndrome of inappropriate antidiuresis and whose hyponatremia resisted administration of two AVPR2 antagonists. The phenotype of family members who carry the mutation was investigated. Patients with normal serum sodium were subjected to a water-load test. The previously reported activating missense R137C mutation in the AVPR2 gene in three hemizygous male and four heterozygous female individuals was identified. Except in one woman, spontaneous episodes of hyponatremia or abnormal water-load test were identified in all patients with the mutation, whether male or female. Skewed X inactivation was evidenced in the blood of the asymptomatic woman, which is compatible with preferential inactivation of her mutated allele. NSIAD is not limited to male infants. The diagnosis also should be considered in both male and female adults.
authors.affiliation: General Internal Medicine, University Hospital Erasme, Route de Lennik, 808, B-1070 Brussels, Belgium. guy.decaux@skynet.be
authors.forename: Guy
authors.initials: G
authors.lastname: Decaux
authors.forename: Frédéric
authors.initials: F
authors.lastname: Vandergheynst
authors.forename: Yasmina
authors.initials: Y
authors.lastname: Bouko
authors.forename: Jasmine
authors.initials: J
authors.lastname: Parma
authors.forename: Gilbert
authors.initials: G
authors.lastname: Vassart
authors.forename: Catheline
authors.initials: C
authors.lastname: Vilain
mesh_terms: D000328:Adult; D000368:Aged; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines / Q000627:therapeutic use; D001921:Brain / Q000002:abnormalities; D002648:Child; D002986:Clinical Trials as Topic; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007177:Inappropriate ADH Syndrome / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D010375:Pedigree; D010641:Phenotype; D017483:Receptors, Vasopressin / Q000235:genetics*; D000077602:Tolvaptan
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D017483:Receptors, Vasopressin; D000077602:Tolvaptan