ESPE Abstracts (2019) 92 P1-97

Familial Neurohypophyseal Diabetes Insipidus and 2 Novel Vasopressin Gene Mutations in 13 Italian Kindreds.

Giuseppa Patti1, Saverio Scianguetta2, Antonio Balsamo3, Marco Cappa4, Sabrina Corbetta5, Rossella Gaudino6, Lorenzo Iughetti7, Maria Carolina Salerno8, Flavia Napoli9, Alessandro Peri10, Mohamad Maghnie1, Silverio Perrotta2, Natascia Di Iorgi1


1Department of Pediatrics, IRCCS Istituto Giannina Gaslini, University of Genova, Genova, Italy. 2Department of Women, Child and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Napoli, Italy. 3Policlinico S. Orsola-Malpighi, Bologna, Italy. 4Bambino Gesù Children's Hospital, Roma, Italy. 5IRCCS Istituto Ortopedico Galeazzi, Milano, Italy. 6Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy. 7Policlinico Universitario Modena, Modena, Italy. 8University of Naples Federico II, Napoli, Italy. 9Department of Pediatrics, IRCCS Istituto Giannina Gaslini, Genova, Italy. 10University of Firenze, Firenze, Italy


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.