Overview
Incontinentia pigmenti (IP) is an X-linked dominant multisystem disorder caused by mutations in IKBKG (NEMO), affecting NF-κB signaling. It is typically lethal in males and presents in females with characteristic skin lesions progressing through four stages, dental anomalies, neurological features, and in ~35% of cases, proliferative retinopathy resembling retinopathy of prematurity. Retinal involvement is the most serious complication, potentially causing retinal detachment and blindness.
Genetics
Caused by IKBKG (NEMO) mutations. ~80% are de novo deletions of exons 4–10. X-linked dominant; typically lethal in hemizygous males.
| Gene | Locus | Inheritance | Notes |
|---|---|---|---|
| IKBKG (NEMO) | Xq28 | X-linked dominant | NF-κB essential modulator; ~80% exon 4–10 deletion |
Clinical Presentation
Neonatal (Stage 1)
- Vesicular skin lesions along Blaschko lines
- Eosinophilia
Infancy (Stages 2–3)
- Verrucous then hyperpigmented skin lesions
- Dental anomalies (pegged teeth, delayed eruption)
- Neurological features (seizures, developmental delay) in some
Retinal (35% of cases)
- Peripheral retinal avascularity
- Fibrovascular proliferation
- Retinal detachment and blindness if untreated
Diagnosis
- Skin biopsy: Stage-specific histopathology
- Genetic testing: IKBKG deletion/sequencing
- RetCam/wide-field fundus imaging: Essential for all affected females
- Fluorescein angiography: Peripheral avascular retina
- Neuroimaging: MRI brain if neurological features
Current Research & Treatment
Laser photocoagulation and anti-VEGF therapy for proliferative retinopathy. Early screening and treatment are critical to prevent retinal detachment. The IP International Foundation supports research and patient advocacy.
Active Clinical Trials
The following active clinical trials are investigating treatments for Incontinentia Pigmenti. Trial status and enrollment may change; always verify directly on ClinicalTrials.gov.