Growth retardation in untreated autosomal dominant familial neurohypophyseal diabetes insipidus caused by one recurring and two novel mutations in the vasopressin-neurophysin II gene

Abstract

Objective: Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI), a disorder caused by mutations in the vasopressin (AVP)-neurophysin II (NPII) gene, manifests gradually during early childhood with progressive polyuria and polydipsia. Patients are usually treated with synthetic AVP analog. If unlimited access to water is provided, prognosis is usually good even in the absence of specific treatment.In this study, we describe three families with adFNDI, in which growth failure was a prominent complaint, on the clinical and molecular level. Design/methods: Histories from affected and unaffected family members were taken. Height and weight of index patients were recorded longitudinally. Patients underwent water deprivation tests, magnetic resonance imaging, and genetic analysis. One mutant was studied by heterologous expression in cell culture. Results: A total of ten affected individuals were studied. In two of the three pedigrees, a novel mutation in the AVP-NPII gene was found. The index children in each pedigree showed growth retardation, which was the reason for referral in two. In these cases, water intake was tightly restricted by the parents in an attempt to overcome suspected psychogenic polydipsia and to improve appetite. Once the children were treated by hormone replacement, they rapidly caught up to normal weight and height. Conclusions: Genetic testing and appropriate parent counseling should be enforced in adFNDI families to ensure adequate treatment and avoid chronic water deprivation, which causes failure to thrive.

Identification of five novel arginine vasopressin gene mutations in patients with familial neurohypophyseal diabetes insipidus

“…Theoretically, plain MRI of the posterior pituitary reveals short T1 and high-intensity signals in normal individuals, while such signals are absent in patients with FNDI; however, a study of 79 patients with CDI with a median follow-up of 1.5 years (0.2-7.5 years) demonstrated that posterior pituitary MRI hyper-intensity signals disappeared in 6% of the patients (9). Thus, CDI cannot be excluded based on MRI alone (10).…”

“…This relatively high rate of mental retardation may result from the stress placed on the hypothalamus-pituitary axis due to excessive water consumption, which causes a persistent chronic hyperosmotic state, leading to anorexia, insufficient energy supply and impeded developmental processes (9). Due to the risk of developmental disorders, early intervention with medications, such as desmopressin acetate is essential to achieve good clinical outcomes (9). This further highlights the need for early diagnosis and symptoms prediction, which requires careful cataloguing of FNDI genetic components.…”

Early-Onset Central Diabetes Insipidus due to Compound Heterozygosity for AVP Mutations

“…It may very well be present at birth but difficult to recognize. Failure to thrive in infancy may be the presenting sign, and inappropriate fluid restriction may be advised [15], as was done in our case. However, once the child became old enough to have free access to water, growth improved, so that auxological parameters were within normal limits by the time of diagnosis.…”

AVP-NPII gene mutations and clinical characteristics of the patients with autosomal dominant familial central diabetes insipidus

“…Growth retardation and delayed bone age are commonly reported in patients with central DI with an incidence of 20-35 %, and effectively corrected by desmopressin treatment [22]. However, some patients with unlimited and unrestricted fluid intake can thrive normally, which causes a difficulty in creating a clear genotype-phenotype correlation [23]. Nevertheless, in the present report, earlier age of onset of symptoms in family B can be a predictive clue in determining the severity of the mutation (p.G45C) as evidenced by the molecular studies mentioned previously.…”