Congenital pancreatic hypoplasia is a rare cause of neonatal diabetes. We report on a series of three patients with pancreatic agenesis and congenital heart defects. All had abdominal scan evidence of pancreatic agenesis. In addition, Patient 1 had a ventricular septal defect, patent ductus arteriosus and pulmonary artery stenosis; Patient 2 had a truncus arteriosus and Patient 3 had tetralogy of Fallot. Two of the three patients have developmental delay. All three patients were isolated cases within the family. Investigations included sequencing of GCK, ABCC8, IPF1, NEUROD1, PTF1A, HNF1B, INS, ISL1, NGN3, HHEX, G6PC2, TCF7L2, SOX4, FOXP3 (Patients 1 and 2), GATA4 and KCNJ11 genes (all three patients), but no mutations were found. Genetic investigation to exclude paternal UPD 6, methylation aberrations and duplications of 6q24 was also negative in all three. 22q11 deletion was excluded in all three patients. Array CGH in Patient (1) showed a approximately 250 kb, paternally inherited duplication of chromosome 12q [arr cgh 12q24.33 (B35:CHR12:131808577-132057649++) pat], not found in the other two patients. Permanent neonatal diabetes mellitus due to pancreatic hypoplasia with congenital heart defects has been reported before and may represent a distinct condition. We discuss this rare association and review previously reported literature.
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