Incontinentia Pigmenti

Incontinentia pigmenti (IP) (OMIM#308300) is a rare (0.7/100000) X-linked dominant neuroectodermal disorder, usually lethal in males and affecting females. IP manifests with an extreme variety of symptoms, including skin, hair, dental, hair, eye, and central nervous system (CNS) abnormalities. The diagnosis is usually based on clinical features, such as the characteristic skin manifestations, and confirmed by genetic testing to identify the IKBKG/NEMO gene mutation. Approximately 70% of IP patients have a sporadic condition with no IP family history, and the mutation arises as a de novo event. In the majority of IP cases, the genomic deletion (IKBKG/NEMOdel4–10) is found; in the remaining cases, IKBKG/NEMO point mutations and rare rearrangements in the IP locus are reported. Although IP is lethal in hemizygous males, rare cases of IP males with abnormal karyotype (Klinefelter syndrome) or IKBKG/NEMO postzygotic mutation have been reported. The phenotypic and genotypic variability in IP makes it a rare disease that models the importance of multidisciplinary approaches to care through the collaboration between pediatric dermatologists, ophthalmologists, neurologists, and developmental specialists to address the developmental delay and geneticists whose role is essential to provide early molecular diagnosis and more appropriate counseling based on molecular subtype and explanation of recurrence risk.