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Conditions

Incontinentia pigmenti

Incontinentia pigmenti is a rare X-linked dominant genetic disorder, principally affecting females. It is characterised by distinct and changing skin lesions with or without associated teeth, hair, nail, eye and central nervous system findings.

Overview

Incontinentia pigmenti (IP) is a rare and variable genetic disorder that principally affects females, as it is typically embryonically lethal in males. The condition is characterised by distinct and evolving skin lesions that manifest in four stages (vesicular, wart-like, hyperpigmented and atrophic), with or without associated dental, hair, nail, breast, eye and central nervous system findings. IP is caused by dominant variants in the IKBKG gene.

Clinical features

IP causes characteristic evolving skin changes in at least 90% of affected individuals.

Stage Skin lesion  Age of onset Presentation
1 Erythema Two weeks to 24 months Redness and vesicles over body (sparing face), often linear
2 Verrucous Two weeks to 24 months Mainly on the limbs and respecting Blaschko’s lines
3 Hyperpigmented Four months to 16 years

(some adults)

 Streaky pigmentation in a swirling pattern, respecting Blaschko’s lines
4 Atrophic Adolescence to adulthood Streaked linear or patchy areas of low pigmentation that are often hairless

In addition to the changes seen in the skin, IP can also affect other parts of the body, as listed below.

  • Teeth: hypo/oligodonia (reduced number) and altered shape (peg-shaped incisors, conical teeth, molar cusp pattern alteration) and delayed eruption.
  • Hair: patches of hair loss or hair with a dull, coarse and/or wiry appearance.
  • Nails: pitted, ridged and/or thickened.
  • Breast: hypoplasia, asymmetry, inverted or supernumerary nipples (often not noted until post-puberty).
  • Eyes: peripheral neovascularisation of the retina and retinal detachment.
  • Neurological: intellectual disability and/or developmental delay, seizures.
  • Family history: incidents of recurrent miscarriage (due to the loss of male affected fetuses).

Genomics

IP is caused by changes in one copy of the IKBKG gene (sometimes referred to as NEMO). The majority (>80%) are due to recurrent or nonrecurrent deletions, though small insertion-deletion and sequence variants are reported.

Genomic testing involves IKBKG single gene sequencing and copy number variant analysis to detect a common deletion recognised in IP.

Diagnosis

Initial suspicion of the diagnosis of IP is based on the patient history and clinical appearance of the skin lesions, which often occur in a linear or whorled pattern and progress through the stages outlined in the above table.

Diagnosis criteria have been proposed (see ‘Resources for clinicians’). Major criteria includes skin lesions in any of the stages. Minor criteria includes anomalies in other related systems, including dental, ocular, central nervous system, hair, nail, palate, breast and nipple.

A skin biopsy is not essential to diagnose IP, but may be performed. Histological features will depend on the stage of skin involvement and are not specific to the condition. The occurrence of multiple male miscarriages can add weight to the diagnosis.

Confirmation of the diagnosis is best achieved through molecular genomic testing. For information about testing, see Neonate with cutaneous features consistent with incontinentia pigmenti.

Inheritance and genomic counselling

IP is an X-linked dominant condition. 65% of cases are caused by new (de novo) gene changes in IKBKG and so, in these cases, the recurrence risk is low. The remainder are inherited from an affected mother.

As male conceptuses typically miscarry (unless somatic mosaic or Klinefelter syndrome (47,XXY)), the expected ratio among liveborn children of a mother with IP is about 33% unaffected females, 33% affected females and 33% unaffected males.

Management

Management of children with IP is complex and should be delivered via a specialist multidisciplinary team, which includes dermatology, dentistry, ophthalmology and neurology. Recommended guidelines have been published – see ‘Resources for clinicians’.

Resources

For clinicians

References:

For patients

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  • Last reviewed: 28/08/2025
  • Next review due: 28/08/2027
  • Authors: Dr Alexander Ross
  • Reviewers: Dr Danielle Anthony, Dr Eleanor Hay, Dr Gabriela Petrof