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Incontinentia pigmenti

Author
Moise L Levy, MD
Section Editor
Jennifer L Hand, MD
Deputy Editor
Rosamaria Corona, MD, DSc

INTRODUCTION

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 [4].

The disorder is seen almost uniformly in females, although it may occasionally occur in males with somatic mosaicism or XXY karyotype [1]. 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 [2].

EPIDEMIOLOGY

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) [5].

PATHOGENESIS

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 [6]. 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 [9]. 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 [10].

              
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Literature review current through: Oct 2017. | This topic last updated: Feb 16, 2017.
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