Incontinentia pigmenti in a female conceived by in vitro fertilization

Abstract

To the Editor:Incontinentia pigmenti (IP) also known as Bloch-Sulzberger syndrome is an X-chromosome-linkedgenodermatosis caused by mutations of nuclearfactor (NF)-kB essential modulator (NEMO) gene atXq28. The vast majority of NEMO mutations involveidentical deletion of exons 4–10 (DNEMO) causingIP[Aradhyaetal.,2001].TheNEMOlocuscontainsaninversely oriented, truncated and nonfunctionalNEMO pseudogene that plays an essential role indenovorecurrentformationoftheDNEMOmutation[Bardaro et al., 2003].TheNEMOproteinisaregulatorycomponentofaIkB (NF-kB inhibitors) kinase complex required toactivate the NF-kB pathway [Karin and Ben-Neriah,2000]; NEMO gene mutations abolish protein func-tion and eliminate NF-kB activity [Aradhya et al.,2001].NF-kBisfoundinallcelltypesandisinvolvedinactivatinganexceptionallylargenumberofgenesin response to infections, inflammation, and otherstressfulsituationsthatrequirerapidreprogrammingof gene expression and prevention from apoptosis[Karin and Ben-Neriah, 2000]. IP is usually fatal inmale fetuses and thus most IP patients (>95%) arefemale [Cohen and Kurzrock, 1995]. The expressionof IP in female patients can be modulated byselection against the X-chromosome with DNEMOgene causing skewed X-chromosome inactivation(XCI) [Aradhya et al., 2001].The clinical spectrum of IP is broad and highlyvariable, with the skin lesions being the mostprevalentfeatures[Kimetal.,2006].Theyarecausedby the incontinence of melanin from the superficialepidermis into the dermis where it is cleared bymacrophages [Cohen, 1994]. The most significantmedical problems in IP are blindness, immunodefi-ciency and central nervous system defects, whichcan cause mental retardation and/or seizures.Other characteristics are blood eosinophilia, anddental, auricular, musculoskeletal, and cardiovascu-lar anomalies [Kim et al., 2006]. The current reportfocuses on an in vitro fertilization (IVF) newborngirl who manifested IP due to a paternally inheritedpathological NEMO gene. Informed consent forscientific publication was obtained from bothparents.The proposita is the only child of nonconsangui-neous parents born after frozen mixed IVF andintracytoplasmic sperm injection embryo transfer.The mother and father were 34 and 39 years old,respectively, and had experienced infertility due toteratozoospermia for 11 years. The uneventfulpregnancyendedinatermdelivery.Thebirthweightof the female newborn was 3,600 g (0 standarddeviations (SD)), length 48 cm ( 1 SD), and theoccipitofrontalcircumferencewas34cm( 3SD).Atbirth, vesicular lesions of the skin were detectedcovering arms, legs, and buttocks, continuing alongthe lateral side of trunk following Blaschko’s lines;