Incontinentia pigmenti (IP), is an X linked dominant disorder featuring blistering and hyperpigmentation along the lines of Blaschko. Genetically, a single large intragenic deletion spanning exons 4–10 of the IKBKG gene has been identified as the cause of IP in ~80% of all cases. Females with IP usually survive due to X chromosome inactivation. However, nearly all males with IP typically die in utero. Survival of males with IP can be explained by somatic mosaicism, co-existing Klinefelter syndrome or the presence of less damaging (hypomorphic) mutations in IKBKG. We describe a living male child with IP resulting from a somatic IKBKG mutation, and propose a diagnostic algorithm for assessing such individuals. A full term male infant was seen at birth to have blisters on both legs along the lines of Blaschko. Histological examination of a skin biopsy revealed mild eosinophilic spongiosis and perivascular dermatitis with increased eosinophils. Based on the clinicopathological features, vesicular stage IP was diagnosed. Using an established three primer PCR reaction protocol, we searched for the recurrent IKBKG intragenic deletion in DNA from both blood and lesional skin from the proband. The common recurrent intragenic deletion in IKBKG was identified in lesional skin DNA but not in blood genomic DNA, consistent with a somatic mosaicism and a diagnosis of IP. Cytogenetic analysis revealed a normal male karyotype (46,XY). It is extremely rare for males with IP to survive. Based on our experience, we summarize a diagnostic evaluation protocol for such individuals to provide an explanation for male survival. Clinically, although IP is diagnosed mainly by the cutaneous manifestations, some extracutaneous defects may appear gradually; therefore, accurate genetic diagnosis and profiling, as well as regular follow up and evaluations, are necessary. Genetic counselling of surviving males with IP should also include the possibility of the somatic IKBKG mutation also being present in sperm, as there are reports of such individuals having daughters with IP with germline IKBKG pathology.

ESDR544 - Incontinentia pigmenti in a male infant and a proposed diagnostic algorithm

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.