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

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.