- Moise L Levy, MD
Moise L Levy, MD
- Section Editor — Pediatric Dermatology
- Professor of Pediatrics and Medicine (Dermatology)
- Dell Medical School, University of Texas, Austin
- Clinical Professor of Dermatology and Pediatrics
- Baylor College of Medicine
Incontinentia pigmenti (IP, Bloch-Sulzberger syndrome, MIM #308300) is an X-linked dominant genodermatosis that is usually lethal in males before birth [1-3]. IP is caused by loss-of-function mutations in the IKBKG/NEMO (inhibitor of kappa polypeptide gene enhancer in B-cells, kinase gamma/nuclear factor-kappa B essential modulator) gene, encoding the nuclear factor-kappa-B essential modulator, a regulatory protein that activates genes involved in cell survival, inflammation, and immunity .
The disorder is seen almost uniformly in females, although it may occasionally occur in males with somatic mosaicism or XXY karyotype . In females, IP typically presents with a staged, linear cutaneous eruption and anomalies of teeth, hair, and nails. Approximately one-third of patients have ocular and neurologic abnormalities. Because of the involvement of skin, hair, nails, and teeth, IP can be considered a form of ectodermal dysplasia .
IP occurs in approximately 1:40,000 to 1:50,000 births [1,3]. Virtually all cases are seen in females because affected males usually do not survive until birth. Males born with the condition have either somatic mosaicism or a XXY karyotype (Klinefelter syndrome) .
In the majority of cases, IP is due to mutations in the IKBKG/NEMO (inhibitor of kappa polypeptide gene enhancer in B-cells, kinase gamma/nuclear factor-kappa B essential modulator) gene, located at Xq28 . These mutations occur "de novo" in approximately 65 percent of the IP cases. IKBKG/NEMO encodes the NEMO/I-kappa-B kinase (IKK)-gamma protein, a regulatory subunit of the inhibitor of the IKK complex, which activates NF-kappa B, leading to the activation of genes involved in cell survival, inflammation, and immunity. (See "Combined immunodeficiencies", section on 'Defects of NF-kappa-B regulation'.)
Approximately 90 percent of the IKBKG/NEMO mutations in IP are recurrent or nonrecurrent deletions of exons 4 to 10 resulting in complete loss of NEMO/IKK-gamma function [7-9]. Microdeletions, missense, frameshift, nonsense, and splice-site mutations leading to complete or partial loss of NEMO/IKK-gamma activity account for the remaining cases . Milder (hypomorphic) IKBKG/NEMO mutations that impair but do not abolish NF-kappa B signaling result in males with a rare form of X-linked hypohidrotic ectodermal dysplasia associated with immunodeficiency .To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
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