Whole Exome Sequencing in Incontinentia Pigmenti: A ROP Mimicker and the Genetic Detection Dilemma

J Pediatr Ophthalmol Strabismus. 2025 Nov-Dec;62(6):e74-e80. doi: 10.3928/01913913-20250724-07. Epub 2025 Nov 1.

Abstract

Incontinentia pigmenti is an X-linked dominant multisystemic disorder caused by pathogenic variants in the inhibitor of nuclear factor kappa B kinase regulatory subunit gamma (IKBKG) gene. Mutations in the IKBKG gene, encoding the NF-kappa-B essential modulator protein, underlie its pathogenesis, leading to inflammation-driven vascular ischemia and significant ocular manifestations. The authors report a case of an Asian-Indian infant diagnosed as having stage 3 incontinentia pigmenti in both eyes treated with anti-vascular endothelial growth factor and laser photocoagulation where standard whole exome sequencing failed to reveal pathogenic variants. This case emphasizes the need for a multi-disciplinary approach to early diagnosis and intervention, and the challenges in genetic testing when dealing with rare diseases in resource-limited settings.

Publication types

  • Case Reports

MeSH terms

  • Diagnosis, Differential
  • Exome Sequencing* / methods
  • Genetic Testing* / methods
  • Humans
  • I-kappa B Kinase* / genetics
  • I-kappa B Kinase* / metabolism
  • Incontinentia Pigmenti* / diagnosis
  • Incontinentia Pigmenti* / genetics
  • Infant
  • Mutation*

Substances

  • I-kappa B Kinase
  • IKBKG protein, human