NORD is very grateful to Michelle Yanik, NORD Editorial Intern from the University of Notre Dame, and Angela Scheuerle, MD, Tesserae Genetics, for assistance in the preparation of this report.
Synonyms of Incontinentia Pigmenti
- Bloch-Siemens incontinentia pigmenti melanoblastosis cutis linearis
- Bloch-Sulzberger syndrome
- pigmented dermatosis, Siemens-Bloch type
- No subdivisions found.
Incontinentia Pigmenti (IP) is a rare 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.
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 a illness with fever. The second stage may overlap the first and may be present at birth. During this phase, the blisters develop a raised, wart-like (verrous) appearance, and the lesions look like pustules. 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. 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 areas appear in a swirled pattern sometimes described as a "marble cake" appearance. On the extremities it is linear. Dark areas can appear on the face: 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). 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). The hair generally may be coarse, wiry, and/or lusterless.
Nearly one-third of individuals have eye (ocular) abnormalities. This can include a congenitally small, abnormal eye. An abnormality in the growth of blood vessels in the membrane lining the eyes (retina), which typically appears before the age of five, may be treated if detected early but may cause retinal detachment leading to permanent visual impairment or total blindness if left untreated.
Although 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. Some affected individuals may experience episodes of uncontrolled electrical disturbances in the brain (seizures). About 20 percent of children with IP will have slow motor development, muscle weakness in one or both sides of the body, intellectual disability, and 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. The IKBKG gene is responsible for the production of a protein that helps regulate other proteins called nuclear factor-kappa-B 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 900 to 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.
Symptoms of the following disorders can be similar to IP (IP). Comparisons may be useful for a differential diagnosis:
IP Achromians is characterized by diminished skin pigmentations similar only in pattern to discolorations of IP (IP). The lack of skin coloration is easily contrasted with the excess discoloration characteristic of IP although diminished skin pigmentations can appear late in the course of some cases of IP. Associated neurological problems are similar. This disorder is inherited as an autosomal dominant trait. A variety of other developmental abnormalities and/or conditions may also occur in conjunction with this illness. Skin color tends to normalize with aging.
Franceschetti-Jadassohn syndrome is marked by skin pigmentation changes similar to those of IP (IP), but symptoms begin during adolescence and do not follow inflammatory skin changes. Additionally, skin may thicken on the hands and/or feet, ability to sweat may become impaired and yellow mottling of the teeth may occur. This disorder appears to be inherited as an autosomal dominant trait.
Caffey disease is characterized by discolorations accompanied by soft tissue swellings over benign bone growths typically capped by cartilage. Fever and irritability may also occur. Symptoms tend to fluctuate in severity. This disorder, also known as infantile cortical hyperostosis, primarily affects infants under six months of age and often resolves with age. The exact cause is unknown although it is assumed to be genetic.
The term hypomelanosis of Ito (HI) encompasses a heterogeneous group of disorders characterized by hypopigmented whorls and streaks. It may be associated with other symptoms such as mental retardation, seizures, a lack of sweating on the areas of hypopigmentation, crossed eyes (strabismus), nearsightedness, a cleft along the edge of the eyeball (coloboma), overgrowth of brain tissue, and/or a small head. Hypomelanosis of Ito may occur sporadically or it may be inherited as an autosomal dominant trait. (For more information on this disorder, choose "Hypomelanosis of Ito" as your search term in the Rare Disease Database.)
The diagnosis of IP is based on clinical evaluation, detailed patient history, and molecular genetic testing for mutation in the IKBKG (previously called NEMO) gene. IKBKG is the only gene known to be associated with IP. Mutations in this gene are present in about 80% of affected individuals. 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 an 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 (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:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
For information about clinical trials conducted in Europe, contact:
Contact for additional information about incontinentia Pigmenti:
Angela Scheuerle, M.D.
7777 Forest Lane, B240
Dallas TX 75230
Phone: 972 566 6524
Fax: 972 566 2024
Organizations related to Incontinentia Pigmenti
Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 18th edNew York, NY: McGraw-Hill; 2011.
Ruggieri M, Pascual-Castroviejo I, Di Rocco C, eds. Neurocutaneous Disorders: Phakomatoses & Hamartoneoplastic Syndromes. New York, NY: Springer; 2007: 363.
Kanski JJ, ed. Clinical Ophthalmology. 4th ed Woburn, MA: Butterworth-Heinemann; 1999: 342.
Adams RD, Victor M, Ropper AA, eds. Principles of Neurology. 6th ed. New York, NY: McGraw-Hill, Inc.; 1997:1002.
Jones KL, ed. Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia,. PA: W. B. Saunders Co.; 1997: 502-03.
Behrman RE, ed. Nelson Textbook of Pediatrics. 15th ed. Philadelphia, PA: W.B. Saunders Company; 1996:1846-47.
Champion JL, Ebling FJG, eds. Textbook of Dermatology. 5th ed. Dover, MA: Blackwell Scientific Publications; 1992: 213, 1580-82, 2744.
Newell FW. Ophthalmology: Principles and Concepts. 7th ed.Mosby Year Book; 1991: 482.
Buyse ML, ed. Birth Defects Encyclopedia.Dover, MA: Blackwell Scientific Publications; 1990: 969-70.
Nelson DL. NEMO, NFkappaB signaling and incontinentia pigmenti. Curr Opin Genet Dev. 2006;16(3):282-8.
Käsmann-Kellner B, Jurin-Bunte B, Ruprecht KW. Incontinentia pigmenti (Bloch-Sulzberger-syndrome): case report and differential diagnosisto related dermato-ocular syndromes. Ophthalmologica. 1999;213(1):63-9.
Goldberg MF. Macular vasculopathy and its evolution in incontinentia pigmenti. Ophthalmic Genet. 1998;19(3):141-8.
Happle R. Incontinentia pigmenti versus hypomelanosis of Ito: the whys and wherefores of a confusing issue. Am J Med Genet. 1998;79(1):64-5.
Kegel MF. Dominant disorders with multiple organ involvement. Dermatol Clin. 1987;5(1):205-19.
Garcia-Bravo B, Rodriguez-Pichardo A, Camacho-Martinez F. Incontinentia pigmenti. Study of 3 families. Ann Dermatol Venereol. 1986;113(4):301-8.
Scheuerle A, Ursini MV. (Updated October 28, 2010). Incontinentia Pigmenti. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2012. Available at http://www.genetests.org. Accessed November 16, 2012.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Incontinentia Pigmenti; IP. Entry No: 308300. Last Edited December 16, 2011. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed November 16, 2012.
Incontinentia Pigmenti. Genetics Home Reference.
http://ghr.nlm.nih.gov/condition/incontinentia-pigment. Reviewed June 2008. Accessed November 16, 2012.
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