Familial DI and Genetic Workup

There are familial forms of both neurohypophyseal and nephrogenic diabetes insipidus (Table 13.1). Familial neurohypophyseal DI is most often due to autosomal dominant arginine vasopressin (AVP) mutations, with gradual onset in childhood due to progressive neuronal destruction that make early diagnosis challenging. Recessive mutations in AVP have rarely been described. Wolfram’s syndrome or DIDMOAD (diabetes insipidus, diabetes mellitus, obesity and optic atrophy), caused by mutations in WSF, is also autosomal recessive in inheritance; 70% develop DI in the 2nd or 3rd decade of life. Familial nephrogenic DI is most commonly due to X-linked mutations in AVPR2 or autosomal recessive mutations in AQP2 and presents in early infancy. In all familial forms, phenotype can be variable, even within a family. Treatment of familial DI is similar to that of other forms of DI, with desmopressin for nephrogenic DI and thiazide diuretics or indomethacin in nephrogenic disease.