Table 4.

Syndromic Permanent Neonatal Diabetes Mellitus

GeneDisorderMOIDistinctive Features (in addition to neonatal DM)
CNOT1 Holoprosencephaly ± pancreatic agenesis (OMIM 618500)AD
  • PNDM
  • Pancreatic agenesis
  • Holoprosencephaly
  • Gallbladder agenesis
CTLA4 Immune dysregulation w/autoimmunity, immunodeficiency, & lymphoproliferation (OMIM 616100)AD
  • PNDM
  • Lymphoproliferative syndrome
  • Enteropathy
  • Cytopenias
  • Thyroiditis
EIF2B1 1Neonatal/early-onset DM & transient hepatic dysfunctionAD
  • PNDM
  • Transient hepatitis
FOXP3 IPEX syndrome XL
  • Enteropathy
  • Dermatitis
GATA4 GATA4-related PNDM 2AD
  • Pancreatic exocrine insufficiency/agenesis
  • Cardiac abnormalities
IER3IP1 Neonatal DM, microcephaly, lissencephaly, & epileptic encephalopathy (OMIM 614231)AR
IL2RA Neonatal DM & immune dysfunction (OMIM 606367)AR
  • PNDM
  • Congenital hypothyroidism
  • Sepsis 3
ITCH 4Neonatal DM & systemic autoimmunityAR
  • PNDM
  • Dysmorphic facies
  • Widespread autoimmunity
KCNMA1 Liang-Wang syndrome (OMIM 618729)AD
LRBA 5Common variable immunodeficiency 8 w/autoimmunity (OMIM 614700)AR
  • PNDM
  • Enteropathy
  • Hypothyroidism
  • Hemolytic anemia
NEUROG3 Congenital malabsorptive diarrhea & neonatal DM (OMIM 610370)ARCongenital malabsorptive diarrhea
ONECUT1 6Neonatal DM, non-autoimmune assoc w/pancreatic hypoplasiaAR
  • PNDM
  • IUGR
  • Pancreatic hypoplasia
  • Gall bladder hypoplasia
  • Pancreatic exocrine insufficiency
PAX6 Neonatal DM w/brain malformations, microcephaly, & microphthalmia 7AR
  • Brain malformations
  • Microcephaly
  • Microphthalmia
STAT3 8Neonatal DM assoc w/autoimmunity & pancreatic hypoplasiaAR
  • Leads to early activation of NEUROG3 & premature endocrine activations
  • Critical component of cytokine signaling
WFS1 Classic Wolfram syndrome (See WFS1 Spectrum Disorder.)AR
  • Optic atrophy
  • DM & diabetes insipidus
  • Deafness
YIPF5 9Microcephaly, epilepsy, & DM syndrome (OMIM 619278)AR

AD = autosomal dominant; AR = autosomal recessive; DM = diabetes mellitus; IUGR = intrauterine growth restriction; MOI = mode of inheritance; PNDM = permanent neonatal diabetes mellitus; XL = X-linked

1.

Unfolded protein response and endoplasmic reticulum stress [De Franco et al 2020a]

2.
3.
4.
5.

Neonatal diabetes and beta cell destruction from autoimmunity [Johnson et al 2017]

6.
7.
8.
9.

From: Permanent Neonatal Diabetes Mellitus

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