Abstract
BACKGROUND: Incontinentia pigmenti (IP) is a rare X-linked dominant genodermatosis that predominantly affects the skin, beginning with a characteristic linear vesicular rash shortly after birth. Multisystem abnormalities can further be seen in hair, nail, ocular, dental, and central nervous system. Although most affected individuals carry a common pathological deletion of the IKBKG gene, approximately 20% have no molecular confirmation. There remains a lack of understanding of phenotypic variations between mutation positive and negative patients with IP. OBJECTIVES: We aim to 1) Describe clinical characteristics, phenotype, and genotype of patients with IP, and 2) Compare clinical differences between mutation positive and negative cohorts. DESIGN/METHODS: A retrospective chart review was conducted at a large tertiary paediatric centre from January 1990 to June 2017, for children under 19 with a clinical diagnosis of IP by a paediatric dermatologist or geneticist. Baseline characteristics, diagnostic history, family history, cutaneous and extracutaneous symptoms were extracted. Further subspecialty reports such as dental and ophthalmology, and available laboratory results including bloodwork, histopathology, and genetic reports were reviewed. Patients who had undergone molecular genetic testing were further divided into either positive (IKBKG mutation) or negative (no identifiable mutation) genetics cohorts for analyses. RESULTS: A total of 44 children with IP were identified, including 79% female, 64% white (non-hispanic), 24% with IP family history, and 85% were confirmed on biopsy. Median age at first dermatology or genetics consult was 6 weeks and 26% had undergone a full septic workup (cultures negative) prior for the IP rash. Extracutaneous involvements were common: dental (49%), ocular (32%), hair (31%), nail (15%), and neurodevelopmental (24%). Compared to the mutation positive (59%) cohort, those with negative mutations (41%) were significantly more likely to be male, have a negative family history of IP, and lower incidences of dental and hair anomalies (P <0.05). CONCLUSION: Clinical approach to IP should involve not only dermatology and genetics evaluation, but may benefit from multidisciplinary monitoring for extracutaneous manifestations. Findings of unique clinical variations between positive and negative mutation cohorts suggests the need for further in-depth evaluation into key differences as they may affect disease counselling and future prognosis.