Utility of genetic testing in suspected familial cranial diabetes insipidus

AIM: Differentiating familial cranial diabetes insipidus (CDI) from primary polydipsia can be difficult. We report the diagnostic utility of genetic testing as a means of confirming or excluding this diagnosis. PATIENT AND METHODS: The index case presented at 3 months with polydipsia. He was diagnosed with familial CDI based on a positive family history combined with what was considered to be suspicious symptomatology and biochemistry. He was treated with desmopressin (DDAVP) but re-presented at 5 months of age with hyponatraemia and the DDAVP was stopped. Gene sequencing of the vasopressin gene in father and his offspring was undertaken to establish the underlying molecular defect. RESULTS: Both father and daughter were found to have the pathogenic mutation c.242T>C (p.Leu81Pro) in exon 2 of the AVP gene consistent with a diagnosis of familial diabetes insipidus. The index case did not have the pathogenic mutation and the family could be reassured that he would not require intervention with DDAVP. CONCLUSIONS: Gene sequencing of AVP gene can have a valuable role in predicting whether or not a child is at risk of developing CDI in future. This can help to prevent family uncertainty and unnecessary treatment with its associated risks. LEARNING POINTS: Differentiating patients with familial cranial diabetes insipidus from those with primary polydipsia is not always straightforward. Molecular genetic analysis of the vasopressin gene is a valuable way of confirming or refuting a diagnosis of familial CDI in difficult cases and is a valuable way of identifying individuals who will develop CDI in later childhood. This information can be of great value to families.