Incontinentia pigmenti: a review and update on the molecular basis of pathophysiology

J Am Acad Dermatol. 2002 Aug;47(2):169-87; quiz 188-90. doi: 10.1067/mjd.2002.125949.


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/IKKgamma gene located at Xq28 have been found to cause expression of the disease. Knockout mice heterozygous for NEMO/IKKgamma gene deficiency develop a clinical phenotype very similar to that of incontinentia pigmenti. NEMO/IKKgamma is an essential component of the newly discovered nuclear factor kappaB (NF-kappaB) signaling pathway. When activated, NF-kappaB controls the expression of multiple genes, including cytokines and chemokines, and protects cells against apoptosis. The mechanism by which NEMO/IKKgamma deficiency causes, via the NF-kappaB 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-kappaB 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Chemokine CCL11
  • Chemokines, CC / metabolism
  • Diagnosis, Differential
  • Disease Models, Animal
  • Humans
  • Immunohistochemistry
  • Incontinentia Pigmenti / diagnosis
  • Incontinentia Pigmenti / genetics
  • Incontinentia Pigmenti / physiopathology*
  • Incontinentia Pigmenti / therapy
  • Mice
  • Mice, Knockout
  • Mutation
  • NF-kappa B / physiology
  • Signal Transduction
  • Skin / metabolism
  • Skin / pathology
  • Skin Diseases / diagnosis
  • X Chromosome


  • CCL11 protein, human
  • Ccl11 protein, mouse
  • Chemokine CCL11
  • Chemokines, CC
  • NF-kappa B