Presentation: Neonate with cutaneous features consistent with incontinentia pigmenti

The neonatology team is concerned that a two-week-old girl has an underlying genetic condition. She was born with a papulovesicular eruption in a blaschkolinear pattern on her left leg, which has evolved to become warty. She developed seizures on the second day of life and was admitted to NICU for intravenous antibiotics and antivirals, but inflammatory markers and cultures were negative. Her mother notes that she had a rash herself as a baby and has had some dental problems.

• Genomic testing should be considered for female infants presenting with blaschkolinear eruptions (especially if initially vesicular) associated with ocular, neurologic and/or breast anomalies. Dental and hair anomalies may not be present or be obvious in the neonatal period. Very rarely, males can be affected due to somatic mosaicism or concurrent Kleinfelter syndrome (XXY).
• The diagnostic criteria (see the resources section below) are as follows:

Major criteria

• Typical blaschkolinear skin changes associated with incontinentia pigmenti (IP) (each skin manifestation is counted as a separate major criterion):
  • neonatal eruption with erythema and vesicles along Blaschko’s lines (stage one);
  • verrucous papules or plaques along Blaschko’s lines (stage two);
  • typical hyperpigmentation along Blaschko’s lines fading in adolescence (+++) (stage three); and
  • linear, atrophic, hairless lesions along Blaschko lines (stage four).
• Confirmed IKBKG variant typical for IP.

Minor criteria

• Teeth: dental agenesis (hypodontia or oligodontia), shape anomalies (peg-shaped incisors, conical teeth, molar cusp pattern alteration) and delayed eruption.
• Ocular: peripheral retinal neovascularisation, non-retinal anomalies.
• Central nervous system: seizures, microcephaly, developmental delay.
• Hair: scarring alopecia or woolly hair (dull and dry), anomalies of eyebrows and eyelashes.
• Nails: punctuate depressions, onychogryphosis (or ram’s horn nails).
• Palate: cleft or high-arched palate.
• Breast changes (hypoplasia, asymmetry, hypogalactia) and/or nipple involvement (inverted nipples, supernumerary, difficulty in feeding).
• Multiple male miscarriages.
• Characteristic skin histology.

• If there is no evidence of IP in a first-degree female relative:
  • Two or more major criteria or one major and one or more minor criteria are necessary to make a diagnosis of sporadic IP.
• If there is evidence of IP in a first-degree female relative:
  • Any single major or at least two minor criteria are necessary to make a diagnosis of hereditary IP.
• In all cases, eosinophilia and skewed X-chromosome inactivation supports diagnosis.

• Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria, which provides information about individual tests and their associated eligibility criteria. You can also access a spreadsheet containing details of all available tests.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• Decide which of the panels best suits the needs of your patient and/or family. If IP is strongly suspected, the following panel should be considered:
  • R239 Incontinentia pigmenti: this involves IKBKG single gene sequencing and copy number variant analysis to detect the common deletion.
• If there are concerns about other features of ectodermal dysplasia, the following panel should be considered:
  • R163 Ectodermal dysplasia: this currently tests for genes known to cause ectodermal dysplasia, including IKBKG.
• Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• DermNet: Incontinentia pigmenti
• GeneReviews: Incontinentia Pigmenti
• Orphanet: Incontinentia pigmenti

References:

• Bodemer C, Diociaiuti A, Hadj-Rabia S and others. ‘Multidisciplinary consensus recommendations from a European network for the diagnosis and practical management of patients with incontinentia pigmenti‘. Journal of the European Academy of Dermatology 2020: volume 34, issue 7, pages 1,415–1,424. DOI: 10.1111/jdv.16403
• Minić S, Trpinac S and Obradović M. ‘Incontinentia pigmenti diagnostic criteria update‘. Clinical Genetics 2014: volume 85, issue 6, pages 536–542. DOI: 10.1111/cge.12223

For patients

• ED Society: Incontinentia pigmenti
• National Foundation for Ectodermal Dysplasias: Incontinentia pigmenti