Unraveling incontinentia pigmenti: A comparison of phenotype and genotype variants.

Abstract

Incontinentia pigmenti (IP) is a rare X-linked dominant genodermatosis that affects multiple systems with highly variable phenotypic expressivity. Although most affected individuals carry a common pathogenic variant on the IKBKG gene, approximately 20% have no identifiable mutation. To describe clinical characteristics and genotype of IP patients and compare clinical differences between IKBKG pathogenic variant positive and negative cohorts. Retrospective cohort study conducted at a large tertiary pediatric center from 1990 to 2017, for children with a clinical diagnosis of IP. Forty-two children with IP were identified, including 33 of 42 (79%) females. Most presented with cutaneous stage I findings (31 of 42; 74%). Extracutaneous involvements were common: dental (50%), ocular (31%), hair (31%), nail (15%), and neurodevelopmental (26%). An IKBKG pathogenic variant was detected in 20 of 34 (59%) patients. Compared with these, 14 of 34 (41%) patients who tested negative were significantly more likely (P < .05) to be male, have no family history of IP, and have lower incidences of dental and hair anomalies. Retrospective methodology limits clear determination of the temporality of symptoms. Clinical differences between IKBKG pathogenic variant positive and negative IP cohorts support the prognostic utility of molecular genetic evaluation.