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Incontinentia Pigmenti

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Neurocutaneous Disorders

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Abstract

Incontinentia pigmenti (IP) is an X-linked genodermatosis caused by loss-of-function mutations in the IKBKG gene (previously known as the NEMO gene). De novo mutations are responsible for the majority of IKBKG pathogenic variants, and a common recurrent rearrangement (deletion of exons 4–10) accounts for 80% of cases. The disorder is seen primarily in heterozygous females as the moderating effects of X-chromosome mosaicism allow for survival, although males can also be affected in rare circumstances. Incontinentia pigmenti is a multisystemic disorder with highly variable phenotypic expressivity. It is characterized by distinct cutaneous features which occur in four successive and overlapping stages (vesicular, verrucous, hyperpigmented, hypopigmented) with linear arrangements along Blaschko lines.

Additional neuroectodermal manifestations include varying degrees of involvement of the eyes, nails, hair, teeth, and central nervous system. These extracutaneous manifestations, particularly the ophthalmologic and neurologic, have potentially serious long-term sequelae including retinal detachment, seizures, and ischemic stroke leading to motor and/or cognitive impairment. Early recognition and diagnosis of incontinentia pigmenti are therefore critical so that appropriate monitoring, treatment, and support for these patients can be established.

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Abbreviations

CBCT:

Cone beam computed tomography

CNS:

Central nervous system

DWI:

Diffusion-weighted imaging

EEG:

Electroencephalography

IKBKG:

Inhibitor of κB kinase gamma

IP:

Incontinentia pigmenti

IV:

Intravenous

MDT:

Multidisciplinary team

MRI:

Magnetic resonance imaging

NEMO:

Nuclear factor-κB essential modulator

NF-κB:

Nuclear factor-κB

OCT:

Optical coherence tomography

OT:

Occupational therapy

PCR:

Polymerase chain reaction

PT:

Physiotherapy

RPE:

Retinal pigment epithelium

SLT:

Speech and language therapy

STIPs:

Subungual tumors of IP

SWI:

Susceptibility-weighted imaging

TNF:

Tumor necrosis factor

VGEF:

Vascular endothelial growth factor

XR:

X-ray

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Authors and Affiliations

  1. Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

    Lukas Kieswetter & Elena Pope

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  1. Lukas Kieswetter
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Correspondence to Elena Pope .

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Editors and Affiliations

  1. Department of Paediatric Neurology and Developmental Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Christos P. Panteliadis

  2. Department of Neurology, University of Washington, Seattle, WA, USA

    Ramsis Benjamin

  3. Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Christian Hagel

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Kieswetter, L., Pope, E. (2022). Incontinentia Pigmenti. In: Panteliadis, C.P., Benjamin, R., Hagel, C. (eds) Neurocutaneous Disorders. Springer, Cham. https://doi.org/10.1007/978-3-030-87893-1_8

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