Incontinentia pigmenti (IP) is a rare X-linked dominant genetic disorder that affects the skin, hair, teeth, nails and central nervous system. It is named from its appearance under a microscope.The disease is characterized by skin abnormalities that begin in childhood, usually a blistering rash which heals, followed by the development of harder skin growths. The skin may develop grey or brown patches which fade with time. Other symptoms can include hair loss, dental abnormalities, eye abnormalities that can lead to vision loss and lined or pitted fingernails and toenails. Associated problems can include delayed development, intellectual disability, seizures and other neurological problems. Most males with the disease do not survive to childbirth. Incontinentia pigmenti is caused by a mutation in the IKBKG gene, which encodes the NEMO protein, which serves to protect cells against TNF-alpha-induced apoptosis. A lack of IKBKG therefore makes cells more prone to apoptosis. There is no specific treatment; individual conditions must be managed by specialists. Presentation
The skin lesions evolve through characteristic stages:
blistering (from birth to about four months of age),
a wart-like rash (for several months),
swirling macular hyperpigmentation (from about six months of age into adulthood), followed by
linear hypopigmentation.Alopecia, dental anomalies, and dystrophic nails are observed. Some patients have retinal vascular abnormalities predisposing to retinal detachment in early childhood. Cognitive delays or intellectual disability are occasionally seen.The discolored skin is caused by excessive deposits of melanin (normal skin pigment). Most newborns with IP will develop discolored skin within the first two weeks.
Genetic counseling, prenatal testing, and preimplantation genetic diagnosis is available.In females, the cells expressing the mutated IKBKG gene due to lyonization selectively die around the time of birth, so the X-inactivation is extremely skewed.IP is caused by mutations in a gene called NEMO (NF-κB essential modulator). Diagnosis
The diagnosis of IP is established by clinical findings and occasionally by corroborative skin biopsy. Molecular genetic testing of the NEMO IKBKG gene (chromosomal locus Xq28) reveals disease-causing mutations in about 80% of probands. Such testing is available clinically. In addition, females with IP have skewed X-chromosome inactivation; testing for this can be used to support the diagnosis. Many people in the past were misdiagnosed with a second type of IP, formerly known as IP1. This has now been given its own name: Hypomelanosis of Ito (incontinentia pigmenti achromians). This has a slightly different presentation: swirls or streaks of hypopigmentation and depigmentation. It is not inherited and does not involve skin stages 1 or 2. Some 33–50% of patients have multisystem involvement—eye, skeletal, and neurological abnormalities. Its chromosomal locus is at Xp11, rather than Xq28. Treatment
There does not yet exist a specific treatment for IP. Treatment can only address the individual symptoms. History
This disorder was first reported by Swiss dermatologist Bruno Bloch in 1926 and American dermatologist Marion Sulzberger in 1928. See also
List of cutaneous conditions
List of radiographic findings associated with cutaneous conditions
List of dental abnormalities associated with cutaneous conditions

References
External links
GeneReview/NIH/UW entry on Incontinentia Pigmenti