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Anxiety, social responsiveness, and grit among patients with KCNJ11-related neonatal diabetes compared to unaffected

Jui M Desai1, Lisa R Letourneau-Freiberg1, Kristen E Wroblewski2

  • 1Kovler Diabetes Center, Department of Medicine, University of Chicago, Chicago, IL, 60637, USA.

Acta Diabetologica
|January 27, 2026
PubMed

Insights

Neonatal diabetes mellitus (NDM) linked to KCNJ11 mutations shows significant social challenges, with many affected individuals exhibiting autism spectrum disorder traits. However, both affected and unaffected children display resilience, despite high anxiety levels in families.

Area of Science:

  • Endocrinology
  • Neurodevelopmental disorders
  • Genetics

Background:

  • Neonatal diabetes mellitus (NDM) is a rare condition diagnosed in the first six months of life, often caused by mutations in KCNJ11 or ABCC8 genes.
  • Mutations in KCNJ11 (KCNJ11-NDM) affect ATP-dependent potassium channels, which are expressed in the brain, leading to neurodevelopmental issues like epilepsy and developmental delay (DEND syndrome).
  • Limited data exists on the prevalence of anxiety, social responsiveness, and grit in individuals with KCNJ11-NDM.

Purpose of the Study:

  • To investigate social responsiveness, anxiety, and grit in children with KCNJ11-NDM.
  • To compare these outcomes in affected children with their unaffected siblings.
  • To enhance understanding of the neurodevelopmental profile associated with KCNJ11-NDM.

Main Methods:

  • A cohort of 12 individuals with KCNJ11-NDM and 12 unaffected siblings was recruited.
  • Participants or their caregivers completed the Screen for Adult/Child Anxiety Related Disorder (SCAARED/SCARED), the Social Responsiveness Scale, Second Edition (SRS-2), and the Grit Scale.
  • Statistical analyses were performed to compare scores between the KCNJ11-NDM group and the sibling control group.

Main Results:

  • Social Responsiveness Scale (SRS-2) scores were significantly higher in the KCNJ11-NDM group compared to controls (P < 0.001).
  • Seven out of ten KCNJ11-NDM participants scored suggestively of autism spectrum disorder (ASD), while no siblings did.
  • No significant differences in anxiety or grit scores were found between groups, though a high percentage in both groups reported anxiety symptoms.

Conclusions:

  • Individuals with KCNJ11-NDM exhibit significant social functioning difficulties, with a notable proportion showing traits suggestive of ASD, underscoring the need for early screening.
  • While anxiety disorders are prevalent in families with KCNJ11-NDM, both affected and unaffected children demonstrate robust grit and self-resiliency.
  • Further research with larger cohorts is needed to fully elucidate long-term outcomes and optimal support strategies for this population.
Abstract

Keywords:
AnxietyBrainDiabetes mellitusGeneticsPotassium channelsResilience

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