Incontinentia pigmenti

Incontinentia pigmenti (IP) is usually a lethal condition for males. There are some rare exceptions. The gene for incontinentia pigmenti is located on the X chromosome. IP is caused by mutations in a gene called IKBKG. This gene is found on the X chromosome. Chromosomes are the structures that hold all of our genetic information. We have 23 pairs of chromosomes and one of these pairs determines a baby’s sex. The pair that determines sex are the X and Y chromosomes. Females usually have two X chromosomes and males have one X and one Y chromosome. Since females have an extra copy of the X chromosome, they have an extra copy of the IKBKG gene. If one copy is not working correctly, they have a backup copy. This is why females with IP survive and are less severely affected. Males, however, have only one X chromosome. If his one X chromosome has a mutation in this gene, he does not have a backup copy. The effect will be abnormal development of the male very early in a pregnancy leading to miscarriage. This is called "male-lethal". Talk to a genetic counselor to learn more about IP. A genetic counselor can explain how certain diseases occur and how they run in families. To find a genetic counselor near you, visit the Find a Genetic Counselor tool on the National Society of Genetic Counselors website.

There are a handful of support groups – both in the United States and internationally. One of the more prominent groups is the Incontinentia Pigmenti International Foundation (IPIF). They can be found online at http://www.ipif.org/index.html

The National Foundation for Ectodermal Dysplasias is another organization that supports people with IP. They can be found at http://nfed.org/index.php/about_ed/types_of_ectodermal_dysplasias

Since incontinentia pigmenti is a rare health condition, it may be difficult to find extensive information about the condition online. It is important to understand that not every online resource will have accurate information regarding incontinentia pigmenti. The more reputable sources will be national foundations and medical centers. However, disease specific support groups may be more up to date when it comes to current and ongoing research. Support groups also often provide a means for families affected with incontinentia pigmenti to connect directly or through community blogs.

At the time of diagnosis, a person with incontinentia pigmenti should see the following types of doctors:

Skin
Care should be taken of blisters in a standard manner. They should not be opened. Topical treatments such as creams, medications, and oatmeal baths may help to relieve discomfort. If the skin gets infected, it should be treated the same as any other skin infection. This includes using antibiotic creams and bandages as needed.
Eyes
Some individuals may have retinal detachment (tissue pulls away from the blood vessels in the back of the eye). Standard treatment is needed. These treatments can include laser therapy to “weld” the retina back into place. They may also include a treatment called cryopexy. In this treatment the area around the hole is frozen to help reattach the retina. Other surgical treatments may be needed.
Teeth
Individuals with incontinentia pigmenti should see a child’s dentist (pedodontist) at six months of age or when teeth erupt, whichever comes first. If the child has hypodontia (too few teeth), dental implants may be considered. Referral to a speech pathologist should be considered if delayed teeth prevent normal speech. Referral to a nutritionist should be considered if delayed teeth cause problems with chewing and normal eating.
Neurology
Some people with IP have learning problems or seizures. They may also have problems with controlling their muscles. Referral to a neurologist is needed if any of these problems are present. A brain MRI may be needed to see if there are any brain abnormalities. Special education may be needed if there are learning problems.
A medical geneticist can help determine which types of doctors you need to see. To find a medical geneticist near you, visit the Genetic Services Search Engine on the American College of Medical Genetics website.

A diagnosis of incontinentia pigmenti (IP) can be made clinically. This means that a doctor can do an exam and make a diagnosis based on your symptoms. Genetic testing can be done to confirm a diagnosis. Genetic testing is usually done on blood. The blood sample is sent to a genetics laboratory that can test the IKBKG gene for mutations. A genetic counselor can help to interpret genetic testing results. To find a genetic counselor near you, visit the Find a Genetic Counselor tool on the National Society of Genetic Counselors website.

When a child is diagnosed with incontinentia pigmenti (IP), the following exams are recommended. This can help to establish the extent of symptoms in the child:

Incontinentia pigmenti is usually abbreviated IP.

Incontinentia pigmenti, or IP, is an inherited disorder of skin coloring (pigmentation). Other symptoms involve the teeth, skeletal system, eyes, and brain. The defining symptom in IP is skin problems that change over time. Many affected infants have a blistering rash at birth. The rash heals and is followed by the development of wart-like skin growths. The skin develops grey or brown patches (hyperpigmentation) in early childhood. These patches occur in a swirled patterns and fade with time. Adults with IP usually have lines of unusually light-colored skin (hypopigmentation) on their arms and legs.
Other signs and symptoms of incontinentia pigmenti can include:

People with incontinentia pigmenti (IP) may have symptoms that involve vision, brain development and the teeth. Your doctor should monitor these areas.

In most cases, incontinentia pigmenti is caused by mutations in a gene called IKBKG. This gene has also been called NEMO. About 80% of people who are diagnosed with IP have a mutation in IKBKG. This gene is responsible for making a protein that helps protect cells from self-destructing. If the gene is not working, then it cannot make the protein correctly. The cells in the body will be more likely to self-destruct when they get certain signals. The symptoms of IP are probably caused by the cell death that occurs without this protective protein. Mutations in the IKBKG gene can occur randomly or they can be inherited. Sometimes a mutation can not be found in the IKBKG gene. This could be because the person has a mutation in a part of the gene that was not examined. There could also be a gene that has not yet been discovered that also causes IP. Talk to a genetic counselor to learn more about the causes of IP. To find a genetic counselor near you, visit the Find a Genetic Counselor tool on the National Society of Genetic Counselors website.

A "variant" or "variant of unknown significance" (VUS) means that a genetic test result is unclear. A variant is a DNA change that has limited information. Doctors do not know if this type of change is disease causing (pathogenic) or not (benign). Having a variant does not mean that your child is affected with incontinentia pigmenti. Having a variant does not mean that your child is unaffected. It just means that there is not enough information to tell if your child is affected. Sometimes a variant can be reclassified when more information is gathered. If you have a VUS, talk to your doctor to see if there is new information available. A genetic counselor can help research variants to see if they are disease causing or not. To find a genetic counselor near you, visit the Find a Genetic Counselor tool on the National Society of Genetic Counselors website.

Visit www.clinicaltrials.gov to find clinical studies on incontinentia pigmenti. As of 6/9/2016, there were no current studies. However, studies may be added at any time.

The main symptoms of incontinentia pigmenti are skin abnormalities that change throughout childhood and young adulthood. There are four stages of the skin changes:

Incontinentia pigmenti (IP) mostly affects skin coloring, but it also has other symptoms. These symptoms can include abnormalities of the teeth, eyes, and brain.
The skin abnormalities in IP occur in stages although not all affected people experience all of the stages. The skin of the trunk and limbs is usually affected. The first stage is called the bullous stage. It occurs in the newborn and involves a rash with blisters. The second stage is called the verrucous stage. In this stage, there are wart like growths. It usually occurs as the first stage rash is disappearing. Stage III is called the hyperpigmentation stage. In this stage the skin begins to show discolored lines and swirls. These lines are usually a gray or brown color and can fade over time. The final stage is called the atretic stage. In this stage there are areas of the skin that show less pigment. Hair loss can also occur. This stage does not occur until the lines in stage 3 fade.
Brain abnormalities are not common and occur early in life if they occur at all. They can include: loss of brain tissue, extra folds in the brain, and brain cells in the wrong locations of the brain. About 30% of children with incontinentia pigmenti will have slow motor development, muscle weakness in one or both sides of the body, impaired intellect, and seizures. Males with incontinentia pigmenti are more likely than females to have neurologic abnormalities. About 7% of people with IP will experience one or more seizures. Most seizures occur within the first year of life. Most people with incontinentia pigmenti, have normal intelligence.
Eye problems in IP can include: crossed eyes, cataracts, and severe vision loss. Retinal hypervascularization (abnormal blood vessels in the back of the eye) is most common. When untreated, this leads to retinal detachment. The greatest risk for retinal detachment is in infancy and childhood; it almost never occurs after age six years.
Dental abnormalities are also common. These include: hypodontia (too few teeth), microdontia (small teeth), abnormally shaped teeth, delayed eruption, or impaction. Other findings of IP can include hair loss, brittle nails, extra nipples, and underdeveloped breasts. Life expectancy in IP is usually normal. Women with IP do have an increased chance for miscarriage. This is probably due to the fact that affected male pregnancies typically cannot survive. A medical geneticist is the type of doctor who treats incontinentia pigmenti. Talk to a medical geneticist to find out more about the symptoms of IP. To find a medical geneticist near you, visit the Genetic Services Search Engine on the American College of Medical Genetics website.

Incontinentia pigmenti is caused by mutations in the IKBKG gene. Once a mutation in the gene has been found in an affected person, targeted genetic testing is available for family members. This is also called known mutation testing.
The mother of an affected person should be offered genetic testing for the known mutation. This can establish whether the mutation was inherited from the mother or if the mutation is new in the child. New mutations are called de novo mutations. If the mother also has the IKBKG gene mutation, then her other children should be offered genetic testing for the known mutation.
The mother’s relatives can also be offered genetic testing for the known mutation. This can determine if they may also be at risk to have children affected with IP. Males are not usually born with IP. They usually do not survive to be born. Therefore, IP is typically only inherited from the mother. Testing the father of an affected person or his family members is usually not needed. A genetic counselor can help arrange for genetic testing and explain results. To find a genetic counselor near you, visit the Find a Genetic Counselor tool on the National Society of Genetic Counselors website.

Expressivity is the degree to which an affected person will show symptoms. It is highly variable in incontinentia pigmenti. In addition, the skin findings can resolve over time. They may look similar to other skin conditions with age. Some individuals may lose hair and have problems with their teeth or nails. Other individuals will not have all of these symptoms. A medical geneticist is the type of doctor who treats incontinentia pigmenti. Talk to a medical geneticist to find out more about the symptoms of IP. To find a medical geneticist near you, visit the Genetic Services Search Engine on the American College of Medical Genetics website.

There is no routine newborn screening that tests for incontinentia pigmenti (IP). A baby with IP can have a normal newborn screening test as IP is not included. A genetic counselor can help arrange for genetic testing. To find a genetic counselor near you, visit the Find a Genetic Counselor tool on the National Society of Genetic Counselors website.

Incontinentia pigmenti (IP) has high penetrance. This means that most individuals with the disorder will have some symptoms of the disease. The majority of affected individuals will show skin changes within a few months after birth. However, not all affected people show all of the skin findings. Some people with IP do not show hypopigmentation (lighter than normal patches of skin). Some people do not show hair loss or dental findings. About a third of affected people have intellectual problems. The exact findings can vary between affected individuals. A medical geneticist is the type of doctor who treats incontinentia pigmenti. Talk to a medical geneticist to find out more about the symptoms of IP. To find a medical geneticist near you, visit the Genetic Services Search Engine on the American College of Medical Genetics website.

Incontinentia pigmenti is inherited in a pattern called X linked dominant. This means that only one copy of the gene needs to have a mutation in order for someone to be affected. The gene for incontinentia pigmenti is located on the X chromosome. IP is caused by mutations in a gene called IKBKG. This gene is also known as NEMO. It is found on the X chromosome. Chromosomes are the structures that hold all of our genetic information. We have 23 pairs of chromosomes and one of these pairs determines a baby’s sex. The pair that determines sex are the X and Y chromosomes. Females usually have two X chromosomes and males have one X and one Y chromosome. Since females have an extra copy of the X chromosome, they have an extra copy of the IKBKG gene. If one copy is not working correctly, they have a backup copy. This is why females with IP survive and are less severely affected. Males, however, have only one X chromosome. If his one X chromosome has a mutation in this gene, he does not have a backup copy. The effect will be abnormal development of the male very early in a pregnancy leading to miscarriage. This is called "male-lethal". Therefore, since males do not usually survive, this disorder is typically passed on through the mother. An affected woman will have an affected liveborn child about 33% of the time. Talk to a genetic counselor to learn more about IP. A genetic counselor can explain how certain diseases occur and how they run in families. To find a genetic counselor near you, visit the Find a Genetic Counselor tool on the National Society of Genetic Counselors website.

Incontinentia pigmenti (IP) is a rare disorder. About 1,000 people have been reported with IP. There are about 20 affected girls for every boy. Because this disorder is so rare, your doctor may not be familiar with it. IP is often treated by a type of doctor called a medical geneticist. To find a medical geneticist near you, visit the Genetic Services Search Engine on the American College of Medical Genetics website.

There is no information available to suggest that any substances or exposures will make the symptoms worse. However, you should talk to a doctor if you have any concerns. The type of doctor that treats incontinentia pigmenti is called a medical geneticist. To find a medical geneticist near you, visit the Genetic Services Search Engine on the American College of Medical Genetics website.

Most people with incontinentia pigmenti should be expected to have a normal life expectancy. Some people may have more severe problems in infancy that lead to a shortened life span. Most male pregnancies that are affected by IP are miscarried. A medical geneticist can help explain the risks associated with IP. To find a medical geneticist near you, visit the Genetic Services Search Engine on the American College of Medical Genetics website.

In rare cases boys can have incontinentia pigmenti. Although most male pregnancies with IP are miscarried, there are some cases of boys that have survived. There are two ways that a male can be affected with incontinentia pigmenti. They can have a 47, XXY karyotype or somatic mosaicism. IP is caused by mutations in a gene called IKBKG. This gene is found on the X chromosome. Chromosomes are the structures that hold all of our genetic information. We have 23 pairs of chromosomes and one of these pairs determines a baby’s sex. The pair that determines sex are the X and Y chromosomes. Females usually have two X chromosomes and males have one X and one Y chromosome.
Sometimes an error happens during development of the sperm or egg and an extra sex chromosome is packaged into one of these sex cells. When the embryo is formed, the baby has three sex chromosomes instead of just two. If there is at least one Y chromosome, the baby will develop into a male. Therefore, a baby with two Xs and one Y (XXY) will be a male. However, since this baby has an extra X chromosome, it will also have a backup copy of the mutated IKBKG gene just like females do. There have been several reported cases of boys with XXY and IP. The second way that a boy can have incontinentia pigmenti is through somatic mosaicism. Somatic mosaicism occurs when there are two different cell lines in the body. This means that some cells in the body have different genetic makeup than others. It is possible that some of the cells in a boy’s body may have a working IKBKG gene and others do not. If there are enough cells with a working gene, then the boy will survive. Only the parts of the body with the gene that is not working will show symptoms of IP. For instance, some parts of the skin may show the pigment changes of IP, while others do not. A genetic counselor is someone who can explain how genes work and are inherited. Talk to a genetic counselor to learn more about how IP is inherited. To find a genetic counselor near you, visit the Find a Genetic Counselor tool on the National Society of Genetic Counselors website.

Other names for incontinentia pigmenti include:

Other disorders may have symptoms that resemble incontinentia pigmenti (IP). Some examples are:

The skin findings are the most distinguishing feature of incontinentia pigmenti. The 4 stages of IP are unique to this disorder. These stages include a blistering stage, warty growth stage, swirling pigmented skin, and lighter skin patches. The swirling brown skin pattern is a defining feature. This disorder is also unique in that it is rarely seen in males. This is due to the way it is inherited. A medical geneticist is the type of doctor who treats IP. Talk to a medical geneticist to find out more about the symptoms of IP. To find a medical geneticist near you, visit the Genetic Services Search Engine on the American College of Medical Genetics website.