Background: Autosomal dominant neurohypophyseal diabetes insipidus (adNDI) is characterized by arginine vasopressin (AVP) deficiency resulting from mutations in the AVP-NPII gene
Patients and Methods: We analyzed AVP-NPII gene in 13 kindreds with familial NDI
Aim: To describe the clinical and molecular features of Italian kindreds with adNDI
Results: Twenty-two patients had a pathogenic AVP-NPII gene mutation. Two novel c.173 G>C (p.Cys58Ser), c.215 C>A (p.Ala72Glu) missense mutations and additional 8 different mutations previously described were identified; nine were missense and 1 non sense mutation. 8 out of 10 mutations occurred in the region encoding for the NPII moiety; 2 mutations were detected in exon 1. No mutations were found in exon 3. Median age of onset was 32.5 months with a variability within the same mutation (3 to 360 months). No clear genotype-phenotype correlation has been observed, except for the c.55 G>A (p.Ala19Thr) mutation, which led to a later onset of disease (median age 120 months). Brain magnetic resonance imaging (MRI) revealed absence of posterior pituitary hyperintensity in 8 out of 15 subjects, hypointense signal in 4 and normal signal in 2. Follow-up MRI showed the disappearance of the posterior pituitary hyperintensity after 6 years in one case.
Conclusion: adNDI is a progressive disease with a variable age of onset. Molecular diagnosis and counseling should be provided to avoid unnecessary investigations and to ensure an appropriate treatment.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology