Incontinentia pigmenti
Definition
Incontinentia pigmenti is a rare genetic disease resulting in a neurocutaneous disorder. Neurocutaneous means that the disorder affects the nervous system and that clinical abnormalities can involve the skin, hair, and teeth of affected individuals.
Description
Incontinentia pigmenti patients develop discolored, abnormally pigmented skin that is distributed randomly and asymmetrically. Occasionally, persons with incontinentia pigmenti experience cognitive delays (including mental retardation), but most have normal intelligence. Muscle weakness in one or both sides of the body is also characteristic of the disorder. Incontinentia pigmenti is also known as Bloch-Sulzberger syndrome, as well as incontinentia pigmenti, type 2.
Demographics
Incontinentia pigmenti is considered rare, with only about 1,000 affected individuals reported in medical literature. The gene that is defective in this disease is located on the X chromosome and is inherited as a dominant disorder, meaning that each child of an affected mother has a 50% risk of inheriting the faulty gene and the disorder. Most male fetuses affected with incontinentia pigmenti die before birth; more females are affected with the disorder.
Causes and symptoms
Incontinentia pigmenti results in defects in the skin, nails, hair, and teeth. The disorder is caused by mutations in the IKBKG gene, located on the X chromosome. This gene encodes a protein that is important during human development. Approximately 80% of affected individuals have mutations in this gene. Cases can be caused by inherited mutations or spontaneous mutation that occur randomly in families; therefore, there is an absence of a family history.
Defects in the skin usually develop at birth in four distinct stages. The first stage usually occurs before four months old when the blisters appear in the skin. The second stage involves a wart-like rash that eventually turns into the third stage, in which regions of swirling, darkened pigmentation (skin color) appear after six month of age (and into adulthood). The last stage is characterized by linear hypopigmentation, or areas of the body that are less darkly pigmented.
Neurological problems associated with incontinentia pigmenti occur in about 25% of cases and include cerebral atrophy (deterioration and loss of brain cells), leading to poor muscle control and weakness. Mental retardation and seizures are also similarly present.
Other symptoms include defects in the teeth, with too few or too many present. The finger and toenails can often be brittle or pitted, often resembling fungal infections. Patients often have alopecia (hair loss) that occurs on the scalp or body trunk and extremities. Hair can appear patchy and hair loss can occur in areas that blistered during the first stage of the disease. Some patients have been reported to have defects in blood flow in the retina of the eye, predisposing them to retinal detachment during childhood.
Diagnosis
Diagnosis is achieved first by a clinical diagnosis from a clinical geneticist, followed by molecular genetic testing in a CLIA-approved diagnostic laboratory. This test usually supports DNA sequencing of the IKBKG gene. A mutation in this gene can confirm the clinical diagnosis. The clinical diagnosis requires the presence of involved skin that displays any or all the following symptoms, including blisters anywhere on the body except the face, usually before four months of age, hyperpigmentation (increased areas of pigment) occurring on the trunk of the body that fades during adolescence, and/or hairless streaks or patches that occur after adolescence.
Treatment team
The treatment team consists of a neurologist, clinical geneticist, genetic counselor, speech pathologist, ophthalmologist, and a dermatologist. A specialist that deals with learning disorders or developmentally delayed children may be necessary in certain cases.
Treatment
As there is no cure for incontinentia pigmenti, treatment is based on symptoms. The risk of infection from blisters is a consideration, and topical medications can often be used to lessen the associated pain. Corrective dentistry might be necessary to help with eating and talking.
Recovery and rehabilitation
There is no cure for incontinentia pigmenti. A speech pathologist and a nutritionist can often help with rehabilitation to address problems associated with speech difficulties and difficulties eating.
Clinical trials
As of mid-2004, there were no ongoing clinical trials specific for the study or treatment of incontinentia pigmenti.
Prognosis
The skin abnormalities can improve with age and in some instances disappear completely. The prognosis for neurological abnormalities depends on each case, but is often permanent and significant. Life expectancy, however, is considered normal.
Special concerns
Genetic counseling is important in cases in which there is a family history of incontinentia pigmenti, or in which there is a clinical diagnosis.
Resources
BOOKS
Staff. The Official Parent's Sourcebook on Incontinentia Pigmenti: A Revised and Updated Directory for the Internet Age. San Diego: Icon Group International, 2002.
OTHER
"Incontinentia Pigmenti." Incontinentia Pigmenti International Foundation (IPIF). April 23, 2004 (June 2, 2004). http://imgen.bcm.tmc.edu/IPIF/nipfchar.htm#Top%20of%20page.
"NINDS Incontinentia Pigmenti Information Page." National Institute of Neurological Disorders and Stroke. April 23, 2004 (June 2, 2004). http://www.ninds.nih.gov/health_and_medical/disorders/inconpig_doc.htm.
ORGANIZATIONS
Incontinentia Pigmenti International Foundation (IPIF). 30 East 72nd Street, 16th Floor, New York, NY 10021. (212) 452-1231; Fax: (212) 452-1406. ipif@ipif.org. http://www.imgen.bcm.tmc.edu/IPIF.
Bryan Richard Cobb, PhD
