Incontinentia pigmenti

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Incontinentia pigmenti is a condition that can affect many body systems, particularly the skin. This condition occurs much more often in females than in males.

Incontinentia pigmenti is characterized by skin abnormalities that typically evolve throughout childhood and young adulthood. Many affected infants have a blistering rash at birth and in early infancy. Though this blistering heals spontaneously, it can recur during illnesses with high fever. This blistering stage is followed by the development of wart-like (verrucous) lesions that also heal spontaneously. The blisters and wart-like lesions primarily occur on the arms and legs.

In infancy and early childhood, the skin develops grey or brown patches (hyperpigmentation) that occur in a swirled pattern. These patches, which can occur anywhere on the body, fade with time. Adults with incontinentia pigmenti usually have lines of unusually light-colored skin (hypopigmentation) on their arms and legs. These markings follow the paths along which cells migrate as the skin develops before birth (called the lines of Blaschko).

Individuals with incontinentia pigmenti are at risk of stroke and vision loss, especially within the first year of life. These risks are due to abnormalities in blood vessels in the brain and in the light-sensitive tissue that lines the back of the eye (retina). Affected individuals at risk often have developmental delays, intellectual disabilities, seizures, or other neurological problems. In the absence of stroke or another brain abnormality, most people with incontinentia pigmenti have normal intelligence.

Other signs and symptoms of incontinentia pigmenti can include hair loss (alopecia) on the scalp and other parts of the body, dental abnormalities (such as small teeth or few teeth), and lined or pitted fingernails and toenails. The features of incontinentia pigmenti may be mild or gone by the time affected individuals reach adulthood.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Variants (also called mutations) in the IKBKG gene cause incontinentia pigmenti. The IKBKG gene provides instructions for making a protein that helps regulate nuclear factor-kappa-B. Nuclear factor-kappa-B is a group of related proteins that helps protect cells from self-destructing (undergoing apoptosis) in response to certain signals.

Sixty to 80 percent of affected individuals have a change in the IKBKG gene that deletes some genetic material from the gene. This deletion probably leads to the production of an abnormally small, nonfunctional version of the IKBKG protein. Other people with incontinentia pigmenti have variants that prevent the production of any IKBKG protein. Without this protein, nuclear factor-kappa-B is not regulated properly, and cells are more sensitive to signals that trigger them to self-destruct. Researchers believe that this abnormal cell death leads to the signs and symptoms of incontinentia pigmenti.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an X-linked dominant pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a variant in one of the two copies of the gene in each cell is sufficient to cause the disorder. Some cells produce a normal amount of IKBKG protein, and other cells produce none. The resulting imbalance in cells producing this protein leads to the signs and symptoms of incontinentia pigmenti.

In males (who have only one X chromosome), most IKBKG variants result in a total loss of the IKBKG protein. A lack of this protein appears to be lethal early in development, so few males are born with incontinentia pigmenti. Affected males who survive may have an IKBKG variant with relatively mild effects, an IKBKG variant in only some of the body's cells (mosaicism), or an extra copy of the X chromosome in each cell.

Some people with incontinentia pigmenti inherit an IKBKG variant from one affected parent. Other cases result from new variants in the gene and occur in people with no history of the disorder in their family.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Incontinentia pigmenti is estimated to affect 1.2 in 100,000 individuals worldwide. Between 900 and 1,200 affected individuals have been reported in the scientific literature. Most of the individuals affected are female, but several dozen males with incontinentia pigmenti have also been identified.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormality of skin pigmentation · Very frequent (99-80%)

An abnormality of the pigmentation of the skin.

Erythema · Very frequent (99-80%)

Redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin.

Pustular rash · Very frequent (99-80%)

A rash composed of pustular lesions. A pustule is defined as a vesicle or bulla containing purulent material. It varies in size and may occur at different levels within the epidermis: subcorneal, intraepidermal, or basement membrane zones. The pustules may or may not be sterile and are normally filled with neutrophils.

Verrucous papule · Very frequent (99-80%)

A wartlike (with multiple small elevated projections) papule.

Vesicular eruption · Very frequent (99-80%)

A type of acute-onset skin rash characterized by multiple vesicles, which are circumscribed, fluid-containing, epidermal elevation generally considered less than 10mm in diameter at the widest point. The fluid contained in a vesicle may be clear, serous, or hemorrhagic.

Abnormal dental morphology · Frequent (79-30%)

An abnormality of the morphology of the tooth.

Alopecia · Frequent (79-30%)

A noncongenital process of hair loss, which may progress to partial or complete baldness.

Corneal opacity · Frequent (79-30%)

A reduction of corneal clarity.

Other findings in the same source

From: Orphanet

Additional reported features include Delayed eruption of primary teeth (Frequent (79-30%)); Delayed eruption of teeth (Frequent (79-30%)); Hypodontia (Frequent (79-30%)); Nail dystrophy (Frequent (79-30%)); Seizure (Frequent (79-30%)); Abnormal breast morphology (Occasional (29-5%)); Abnormal nipple morphology (Occasional (29-5%)); Cataract (Occasional (29-5%)); Cerebral cortical atrophy (Occasional (29-5%)); Cleft palate (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Incontinentia pigmenti is Dermatology, with a dermatologist as the relevant type of clinician. Dermatologist; paediatric services for children as appropriate.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which features of the skin, hair or nails distinguish the possibilities?
• Would photographs over time help document the changes?
• What should be expected from treatment, and how will irritation or other adverse effects be managed?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Incontinentia pigmenti. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.