Kidney Week

Abstract: SA-PO0190

Unrecognized Nephrogenic Syndrome of Inappropriate Antidiuresis in a Symptomatic Female Patient with an Activating AVPR2 Variant

Session Information

• Tubular, Metabolic, and Systemic Noncystic Genetic Kidney Diseases
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)

Authors

• Conway, Mary E., Natera Inc, Austin, Texas, United States

Mary E. Conway, MS

• Stein, Quinn, Natera Inc, Austin, Texas, United States

Quinn Stein, MS

• Punj, Sumit, Natera Inc, Austin, Texas, United States

Sumit Punj, PhD

• Schneider, Ronen, Natera Inc, Austin, Texas, United States

Ronen Schneider, MD

Introduction

Activating variants in arginine vasopressin receptor 2 gene (AVPR2) cause nephrogenic syndrome of inappropriate antidiuresis (NSIAD), a rare X-linked disorder characterized by impaired water excretion and recurrent hyponatremia. While NSIAD is predominantly described in males, heterozygous females are typically considered asymptomatic carriers potentially due to X chromosome inactivation resulting in variable clinical presentation that may go unrecognized.

Here, we describe a symptomatic female with longstanding features of NSIAD whose diagnosis was established in adulthood using a broad renal gene panel (the Renasight^TM test; Natera, Austin, TX).

Case Description

A 34-year-old female with a prior history of exercise-associated hyponatremic seizure was referred to nephrology for evaluation of hyponatremia identified during pregnancy. She reported self-restricting fluid intake to mitigate symptoms. Family history was notable for a prior hyponatremia episode requiring fluid restriction in her mother and multiple hyponatremic seizures in her brother during childhood that were associated with heat exposure and increased fluid intake. Genetic testing in the proband identified a well-described activating pathogenic variant in AVPR2 [c.409C>T (p.Arg137Cys)] associated with NSIAD.

Discussion

This case illustrates that females with activating variants in AVPR2 may be symptomatic and at risk for hyponatremic seizures. While symptomatic heterozygous females are rarely reported in the literature, the two affected females in this family suggest that clinical expression may be underrecognized. Partial symptoms control, through fluid restriction, as seen in this family, could delay clinical recognition and diagnosis. Importantly, this case shows that genetic testing can establish NSIAD diagnosis in patients with recurrent, unexplained hyponatremia, particularly when associated with exercise, heat exposure, increased fluid intake, or pregnancy as well as to understand the familial clinical phenotype.