# Neonatal Diabetes Mellitus Due to Homozygous ZNF808 Mutation Associated With Skeletal Anomalies: A Novel Presentation of Pancreatic Agenesis-3

## TL;DR

A rare case of neonatal diabetes caused by a ZNF808 gene mutation is linked to skeletal anomalies, highlighting the need for early genetic testing in infants with diabetes and birth defects.

## Contribution

This paper reports a novel association between ZNF808 mutations and skeletal anomalies in neonatal diabetes.

## Key findings

- A homozygous ZNF808 mutation was identified in a Saudi infant with neonatal diabetes and skeletal anomalies.
- Skeletal anomalies associated with ZNF808 mutations have not been previously reported.
- Early genetic testing is emphasized for neonatal diabetes cases with congenital anomalies and consanguinity.

## Abstract

Neonatal diabetes mellitus (NDM) is a rare genetic condition characterized by persistent hyperglycemia presenting within the first six months of life. It is most commonly caused by mutations affecting pancreatic development or β-cell function. ZNF808 is a recently identified gene that plays an essential role in human pancreatic development, with biallelic pathogenic variants causing autosomal recessive pancreatic agenesis.

We report the case of a seven-month-old Saudi male infant with a history of intrauterine growth restriction who presented at 2.5 months of age with severe hyperglycemia and polyuria. Clinical examination revealed congenital skeletal anomalies, including a fixed flexion deformity of the right knee and oligodactyly of the right foot. Whole-genome sequencing identified a homozygous likely pathogenic variant in the ZNF808 gene, confirming a diagnosis of pancreatic agenesis-3.

This case highlights a rare genetic cause of neonatal diabetes and suggests a novel association between ZNF808 mutations and skeletal anomalies, a feature not previously reported. These findings emphasize the importance of early genetic testing in neonatal diabetes, particularly in the presence of congenital anomalies and parental consanguinity.