NORD gratefully acknowledges Michelle Yanik, NORD Editorial Intern from the University of Notre Dame, and Angela Scheuerle, MD, Department of Pediatrics, Division of Genetics and Metabolism University of Texas, Southwestern Medical Center, for assistance in the preparation of this report.
Incontinentia Pigmenti (IP) is a genetic dermatological disorder affecting the skin, hair, teeth, and central nervous system. Progressive skin changes occur in four stages, the first of which appear in early infancy or can be present at birth. IP is an X-linked dominant genetic disorder caused by mutations in the IKBKG gene.
IP was named based on the appearance of the skin under the microscope during the later stages of the condition.
The skin changes are the most characteristic and common features in IP. They are described in four stages. In all the stages, the lesions appear in lines on the arms and legs or a swirled pattern on the trunk. They can be on the face and scalp.
1) The first stage of IP may be present at birth or appear during early infancy. This phase consists of redness or inflammation of the skin (erythema), blisters, and boils, most often affecting the extremities and the scalp, that last a few weeks to a few months. It can fade and come back again and again for more than a year, commonly when there is an illness with fever.
2) The second stage may overlap the first and may be present at birth. During this phase, the blisters develop a raised, wart-like (verrucous) appearance, and the lesions look like warts. There can be thick crusts or scabs with healing and areas of darkened skin (increased pigmentation). The extremities are involved almost exclusively in this stage, which may last for several months but rarely as long as year.
3) The third stage may be present at birth in a small number of affected individuals, but usually appears between the ages of six and 12 months. In this phase, the skin is darkened (hyperpigmented). On the trunk, the dark is sometimes described as a “marble cake” appearance. The hyperpigmentation does not necessarily happen where the stage I and II rashes happen. The heavy pigmentation tends to fade over time and, in some cases, the pigmented areas thin and widen, leaving streaky diminished color of the skin (hypopigmentation).
4) In the fourth stage, which is known as the “atrophic” stage, scarring appears that often is present before the hyperpigmentation has faded. Scars are seen in adolescents and adults as pale, hairless patches or streaks. Once the affected individuals reach the late teens and adulthood, the skin changes may have faded and may not be visible to the casual observer.
Between 50 to 75 percent of individuals with IP have dental abnormalities. These abnormalities include a delay in the eruption of primary teeth; abnormal contours of teeth, giving them a peg-like or cone-shaped appearance; or the congenital absence of both primary and secondary teeth (anodontia); or small teeth, (microdontia).
Some individuals with IP may have ridged, pitted, thickened (onychogryposis), or missing nails on the hands and/or feet. In some cases, painful growths may develop under the nail.
Approximately 50 percent of individuals with IP may also experience abnormal bald patches on the scalp (alopecia). This usually happens where the stage one and two lesions have left scars. The hair generally may be coarse, wiry, and/or lusterless.
Nearly one-third of individuals have eye (ocular) abnormalities. The most serious, but least frequent, is a congenitally small, abnormal eye. In any patient there can be an abnormality in the growth of blood vessels in the membrane lining the eyes (retina). If it is going to occur, this typically appears before the age of five. This problem may be treated if detected early. If left untreated, it may cause retinal detachment leading to permanent visual impairment or total blindness.
The majority of individuals with IP will have no involvement of the nervous system. Severe neurologic complications can occasionally occur as a consequence of IP, the most serious of which is congenital or neonatal strokes. Some affected individuals may experience episodes of uncontrolled electrical disturbances in the brain (seizures). About 30 percent of children with IP will have slow motor development, muscle weakness in one or both sides of the body, intellectual disability, and/or seizures.
Abnormalities in the development of the breast, ranging from extra nipples to complete absence of the breast, are sometimes seen in individuals with IP.
IP is an X-linked dominant genetic disorder caused by mutations in the IKBKG gene (formerly called NEMO). The IKBKG gene is responsible for the production of a protein that helps regulate other proteins that help protect cells from self-destructing in response to specific triggers.
X-linked dominant disorders are caused by an abnormal gene on the X chromosome and occur mostly in females. Females with these rare conditions are affected when they have an X chromosome with the gene for a particular disease. Males with an abnormal gene for an X-linked dominant disorder are more severely affected than females and often do not survive. Affected males who survive may have an IKBKG gene mutation with relatively mild effects, an IKBKG mutation in only some of the body’s cells (mosaicism), or an extra copy of the X chromosome in each cell.
Approximately 1,200 individuals with IP have been reported in the scientific literature. Most of those affected are female, but several dozen males with IP have also been reported. Public health birth defect surveillance systems put the birth prevalence at 0.6-0.7/1,000,000. The female:male ratio is 20:1.
The diagnosis of IP is based on clinical evaluation, detailed patient history, and molecular genetic testing for mutation in the IKBKG gene. IKBKG is the only gene known to be associated with IP. 65 percent of patients have a specific deletion within the gene. Another 20 percent or so have mutations found by gene sequencing. A skin biopsy to confirm the diagnosis in a female is now rarely needed given the widespread availability and sensitivity of molecular genetic testing. Nonetheless, skin biopsy may be helpful in confirming the diagnosis in a female with borderline or questionable findings in whom molecular genetic testing has not identified a disease-causing mutation.
Clinical Testing and Work-Up
It is very important for babies born with IP to have an eye examination by a pediatric ophthalmologist. This should be done monthly until age four months, then every three months from age four months to one year, every six months from age one to three years, and annually after age three years. The eye problems associated with IP can be severe, but may be effectively managed if recognized early.
The following evaluations may be done to determine the severity of disease in those affected with IP. physical examination with particular emphasis on the skin, hair, nails, and neurologic system, electroencephalography (EEG) and magnetic resonance imaging (MRI) if seizures, other neurologic abnormalities, or retinal abnormalities are present, magnetic resonance angiography to look for cerebrovascular lesions, and developmental screening.
Because IP can be very mild, even in infancy, an affected woman may not know that she has it. It is important that a full evaluation of the mother be done by a geneticist, dermatologist, or other physician after the birth of a child with IP.
Skin abnormalities characteristic of IP usually disappear by adolescence or adulthood without any treatment.
Cryotherapy and laser photocoagulation may be used to treat affected individuals with retinal neovascularization that predisposes to retinal detachment.
Dental abnormalities can often be treated effectively by dentists who may provide dental implants in childhood as needed. Also if dental abnormalities interfere with chewing and/or speech, assistance from a speech pathologist and/or pediatric nutritionist may be necessary.
Hair problems may require the attention of a dermatologist in some cases, although they are usually not severe. Neurological symptoms such as seizures, muscle spasms or mild paralysis may be controlled with various drugs and/or medical devices.
Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov.All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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For information about clinical trials sponsored by private sources, contact:
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Contact for additional information about incontinentia Pigmenti:
Angela Scheuerle, M.D.
University of Texas, Southwestern Medical Center
Department of Pediatrics
Division of Genetics and Metabolism
5323 Harry Hines Blvd.
Dallas TX 75390
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