Neonatal diabetes caused by disrupted pancreatic and β-cell development

Abstract

Neonatal diabetes is diagnosed before the age of 6 months and is usually caused by single-gene mutations. Over 30 genetic causes of neonatal diabetes have been described to date, resulting in severely reduced beta cell number or function. Seven of these genes are known to cause neonatal diabetes through disrupted development of the whole pancreas, resulting in diabetes and exocrine pancreatic insufficiency. Pathogenic variants in 5 transcription factors essential for beta cell development cause neonatal diabetes without other pancreatic phenotypes. However, additional extra-pancreatic features are common. This review will focus on the genes causing neonatal diabetes through disrupted beta cell development, discussing what is currently known about the genetic and phenotypic features of these genetic conditions, and what discoveries may come in the future.