Incontinentia pigmenti: A review and update on the molecular basis of pathophysiology - 01/09/11
Abstract |
Incontinentia pigmenti is an uncommon X-linked dominant disorder, lethal in the majority of affected males in utero and variably expressed in females. Cutaneous manifestations are classically subdivided into 4 stages: vesicular, verrucous, hyperpigmented, and atrophic. Various hair and nail abnormalities, dental anomalies, and ophthalmologic and neurologic deficits are associated with the disorder. The gene for incontinentia pigmenti has been mapped to Xq28. Recently, mutations in the NEMO/IKKγ gene located at Xq28 have been found to cause expression of the disease. Knockout mice heterozygous for NEMO/IKKγ gene deficiency develop a clinical phenotype very similar to that of incontinentia pigmenti. NEMO/IKKγ is an essential component of the newly discovered nuclear factor κB (NF-κB) signaling pathway. When activated, NF-κB controls the expression of multiple genes, including cytokines and chemokines, and protects cells against apoptosis. The mechanism by which NEMO/IKKγ deficiency causes, via the NF-κB pathway, the phenotypical expression of the disease has recently been elucidated. In addition, the newest research findings on eosinophil recruitment through eotaxin release by activated keratinocytes are described in the review. Finally, anhidrotic ectodermal dysplasia with immunodeficiency, a disorder allelic to incontinentia pigmenti, is discussed together with implications on the current understanding of NF-κB function. (J Am Acad Dermatol 2002;47:169-87.) Learning objective: At the completion of this learning activity, participants will have a comprehensive and current understanding of incontinentia pigmenti, including its typical and uncommon clinical and histopathologic characteristics, diagnostic assessment, and current management strategies. Additionally, participants will gain the most current knowledge of the genetic and molecular basis of cutaneous pathomechanism.
Le texte complet de cet article est disponible en PDF.Abbreviations : CNS, EDA, EDA-ID, EDAR, GM-CSF, IκB, IKKγ, IKKγ+/−, IL, IP, NEMO, NF-κB, OL-EDA-ID, RANK, RANTES, TNF
Plan
Funding sources: Supported in part by grants from the National Institutes of Health (R01 AR47667, R03 AR47634, and R21 AR48438, to L. S. C.). |
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Conflict of interest: None declared. |
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Reprint requests: Lawrence S. Chan, MD, Department of Dermatology, University of Illinois College of Medicine, 808 S Wood St, Room 376, Chicago, IL 60612. |
Vol 47 - N° 2
P. 169-190 - août 2002 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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