What is Incontinentia pigmenti?

Incontinentia pigmenti (IP) is one of the genetic diseases collectively known as neurocutaneous disorders. These neurocutaneous disorders cause characteristic patterns of discolored skin and invariably involve other systems like brain, eyes, nails, and hair.

IP is caused by genetic alteration of the IKBKG gene. Genetic transmission is such that it occurs primarily in females and on occasion in males. Male fetuses generally do not survive.

Symptoms include characteristic skin discolorations that appear within the first few weeks of life. Neurological abnormalities include seizures, slow development, mental retardation, and stroke. Other key features include visual problems, dental, and nail anomalies.

How is IP inherited?

IP is a rare disorder and until 2010 only 1,200 cases have been reported. IP is due to a mutation in IKBKG gene that is located on the X chromosome. It is inherited in an X-linked dominant manner.  This means that it is inherited maternally and affected woman have a 50% chance of transmitting the mutant IKBKG at conception. Spontaneous mutation of the IKBKG gene also occurs. IP is embryonic lethal in most of the male pregnancies.

How it is diagnosed?

Diagnosis of IP should be suspected in individuals with characteristic clinical finding, family history, and genetic testing. The clinical characteristics include major and minor criteria.

Major criteria (skin findings that evolve from infancy to adulthood)

  • Stage 1: Vesicular Stage - marked redness with linear vesicles (blisters), bullae, and pustules seen in linear distribution (1 week to 24 months of life). Figure-1.
  • Stage 2: Verrucous lesions - wart like papules and thick skin patches that respect Blaschko’s line (normal swirling pattern on skin) (seen between 1 week to 24 months of life).
  • Stage 3: Hyperpigmented Stage - swirling or whirling macular patches of hyperpigmentation (age 4 months to 16 years). Figure-2
  • Stage 4: Hypopigmented Stage - patchy areas of hypopigmentation (light color), usually arranged in streaks or whorls (present by early adulthood).
Incontinentia pigmenti in an affected female Stage 1: the blistering stage
Figure-1. IP in an affected female
Stage 1: blistering
Incontinentia pigmenti in an affected female Stage 3: rash
Figure-2. IP in an affected female
Stage 3: rash

Figures courtesy of GeneReviews® [Internet].Pagon RA, Adam MP, Ardinger HH, et al., editors. Seattle (WA): University of Washington, Seattle; 1993-2015.

Minor criteria

  • Teeth: partial or complete absence of teeth, small teeth, and abnormally shaped teeth
  • Hair: lusterless, wiry, and coarse hair, alopecia
  • Nails: mild ridging or pitting
  • Eyes:  retinal detachment
  • Family history: consistent with X-linked inheritance or history of multiple miscarriages
  • Other suggested minor criteria: CNS, palate, and breast anomalies

The diagnosis of IP is established with identification of pathogenic IKBKG gene.

What are clinical findings?

  1. Skin: as described in the diagnosis criteria.
  2. Central nervous system: seizures, strokes, intellectual disability, and CNS structural abnormalities have been reported in approximately 30% of the individuals with IP.
    • Epilepsy: patients with IP whose nervous system is effected by the disease have a high incidence of epilepsy. It has been reported that almost 77% of these IP patient had seizures.  Seizures in IP can range from few episodes to lifetime chronic epilepsy.  Focal clonic type seizures are most frequently observed in patients with IP. There are reports of patients presenting with severe form of infantile epilepsy called infantile spasms or West syndrome. Others have reported cases where epilepsy was severe in infancy, moderate during early childhood and later resolved.
    • EEG: IP has no typical signature electroencephalogram (EEG) changes. Often the EEG shows presence of an underlying neuronal injury caused by brain vasculopathy (inflammation of brain blood vessels). These changes on EEG would be seen as either localized spikes/sharp waves or focal delta slowing. Localized spikes/sharp waves would indicate presence of an underlying brain cortex that has been injured and can be a potential source for a seizure onset. Similarly focal delta slowing is indicative of underlying neuronal dysfunction.
    • Intellect: the majority of patients with IP, both male and female, are intellectually normal. 25 to 35% of male patients known to have IP were found to have intellectual disability.
    • Brain anomalies: in general, neurological problems in patients with IP appear to be associated with underlying brain vasculopathy. This leads to blood vessel occlusion, transient ischemic attacks, and stroke.
  3. Eye findings: patients with IP have a high susceptibility (20 to 70%) for eye abnormalities. Vasculopathy at an early age can lead to increase in growth of retinal blood vessels with resultant retinal detachment or hemorrhage. Additional non-retinal presentations include cataract, strabismus, optic atrophy, and nystagmus. Regular and frequent eye examination by an ophthalmologist is recommended until the patient is 3 years old.
  4. Teeth: the abnormalities include small teeth (microdontia), too few teeth (hypodontia), and abnormal shaped teeth.
  5. Hair: alopecia can be seen on the scalp as well as on the body. Hair may also be lusterless and coarse.

How is the condition treated?

It is mostly limited to treatment of symptoms:

  • Routine management of blisters and skin infections.  
  • Laser surgery of retina to prevent retinal detachment.
  • Neurological assessment for seizures, spasticity, and acute focal deficits.
  • Brain MRI for structural neurological abnormalities.
  • Dental care by pedodontist.
  • Developmental programs and special education as needed for developmental delay.
  • Surveillance and eye examination: monthly until age 4 months; then every 3 months from age 4 months to 1 year; followed by every 6 months from age 1 to three years; and annually after age 3 years.

What is the life expectancy of someone with IP?

For a person without major complications during neonatal or infancy period, life expectancy is considered normal.

Authored By: 
Saleem I. Malik MD and Angel W. Hernandez MD