Nephrogenic Diabetes Insipidus and Nephrogenic Syndrome of Inappropriate Antidiuresis, X-linked (AVPR2)

Pathogenic variants in the AVPR2 gene cause two different disorders, nephrogenic diabetes insipidus (AVPR2-related) and nephrogenic syndrome of inappropriate antidiuresis. These two disorders, which have opposite phenotypes, are inherited in an X-linked recessive manner and are due to different types of pathogenic variants.

  • Nephrogenic diabetes insipidus (AVPR2-related) is caused by the inability of renal collecting ducts to absorb water and concentrate urine in response to arginine vasopressin, resulting in polyuria and polydipsia. Infants affected with this disorder may experience poor feeding, low weight gain, and impaired growth, as well as fever, diarrhea, and vomiting. If left untreated, kidney failure may also develop as a result of damage to the bladder and kidneys. Treatment for this disorder includes thiazide diuretics in combination with indomethacin, as well as a low salt diet with limited potassium and protein intake. The life expectancy for this disorder is normal if detected early and properly managed.
  • Nephrogenic syndrome of inappropriate antidiuresis is caused by the constant activation of the AVPR2 receptor on renal collecting duct cells, resulting in increased free water reabsorption and urine concentration, as well as serum hypo-osmolality and hyponatremia that can lead to cerebral edema. Disease onset occurs in childhood presenting with hyponatremic seizures, as well as nausea, vomiting, dizziness, and gait disturbances. Affected individuals require lifelong treatment including oral urea to correct acute episodes of hyponatremia, as well as fluid restriction in adults (which is not applicable to young infants due to the risk of malnutrition). The life expectancy for this disorder is normal as long as episodes of severe hyponatremia are avoided.

The life expectancy for both disorders may be normal if managed correctly. As the two phenotypes are caused by different types of mutations, the expected phenotype can be predicted based on the inherited pathogenic variant.

For information about carrier frequency and residual risk, please see the residual risk table.

This gene is included on the following panel(s):