IntroductionBiallelicPDX1variants are a rare cause of isolated pancreatic agenesis and neonatal diabetes (NDM) without exocrine pancreatic insufficiency, with 17 cases reported in the literature.Research design and methodsTo determine the phenotypic variability caused by this rare genetic aetiology, we investigated 19 individuals with NDM resulting from biallelic disease-causingPDX1variants.ResultsOf the 19 individuals, 8 (42%) were confirmed to have exocrine insufficiency requiring replacement therapy. Twelve individuals (63.2%) had extrapancreatic features, including 8 (42%) with conditions affecting the duodenum and/or hepatobiliary tract. Defects in duodenum development are consistent with previousPdx1ablation studies in mice which showed abnormal rostral duodenum development.ConclusionsOur findings show that recessivePDX1variants can cause a syndromic form of NDM, highlighting the need for clinical assessment of extrapancreatic features in individuals with NDM caused byPDX1variants.