PXE & Children
Presentation and Progression of PXE in Children webinar
Sharon Terry, MA
Founder, Executive Director, PXE International, Inc.
It is every parent's nightmare that his or her child will suddenly be diagnosed with a disease. When the doctor diagnoses your child with PXE, it certainly feels awful. Many of the "how, why, what for?" questions surface, and parents can feel very confused and distraught. As a parent of two children with PXE, I offer this bulletin to parents of children with pseudoxanthoma elasticum. I have chosen to make this bulletin more informal than our other bulletins. If you choose to read the original literature from the medical journals, remember that you are reading case histories. These are snapshots of PXE, not the whole picture. There have been few large studies done, and those probably did not have a representative population to study. Having a child with a rare disease is not easy. Often what we as parents need most is correct information with a touch of compassion. I hope I can offer that balance.
Some of the printed medical literature says that doctors diagnose PXE when individuals are in their 20s or 30s. While this is true, it is equally true that many people find out they have PXE when they are children. In addition, many people report having had skin signs for a decade or more, often since childhood, before actual diagnosis. Pediatricians and family practitioners may not recognize these early dermatologic findings and diagnosis may be delayed until middle age, when other symptoms and signs can occur. Case reports of patients diagnosed early include infants and young children. Skin lesions in childhood may be small. Because they are not a medical problem, they are often overlooked.
One of our first questions was, "Will our children have a more severe case since they are diagnosed so young?" There is no definitive answer to this question yet. No long-term studies have been done. At this point, we can hope that the benefits of being diagnosed early will outweigh the chance that the progression of the disorder will be worse.
What is PXE?
Pseudoxanthoma elasticum is a rare genetic disorder that causes mineralization of certain connective tissue. Although there is connective tissue throughout the body, the areas most affected seem to be the skin, retina, cardiovascular, and gastrointestinal systems. The incidence of PXE is said to be about one in 50,000, but is probably much more common since many patients may remain undiagnosed.
The skin is the most obvious site of PXE involvement. This sign probably alerted you to PXE. You may have noticed a rash, or raised bumps. These lesions are small, 1-5 mm yellow-orange papules of varying shapes. They may coalesce (gather) into larger plaques that spread over mainly flexural areas of the body (the areas that bend a great deal). The sides of the neck are often the first sites involved and the first site noticed. Some adults have told us they were teased as children for having a "dirty neck". Other areas of involvement include the underarm, inside the elbows and behind the knees, the navel and groin area. The face may have some lines on the chin in later life.
After many years, as dermatologic lesions progress, the skin may lose its elasticity and hang loosely. The skin may look wrinkled and older than it is. The medical community does not focus much on these skin signs. This is for the good reason that they are not medically significant. However, though no doctor will focus on these changes, sometimes we, as parents, need to lament the loss of the smooth skin our children once had.
Involvement of other areas of the body is medically more significant. The more serious problems associated with PXE tend to happen later in life and involve the ophthalmologic, cardiovascular, and gastrointestinal systems. Ophthalmologic, or eye, changes include peau d'orange, angioid streaks, retinal hemorrhage, and central vision loss. Peau d'orange may occur before any other change. French for 'skin of the orange', this is a rippling of the retina which may occur in children. Later, affected individuals might develop angioid streaks. These are broad, irregular, red to brown to gray lines, which radiate from the area around the optic nerve head under the retina of affected individuals. Some doctors describe them as looking like mud-cracks or lacquer cracks. Ophthalmologists see angioid streaks in at least 50-70% of people affected by PXE. You can ask your ophthalmologist to look for any of these effects. Central vision loss is the effect of PXE that causes the most concern in adults. After the retina has angioid streaks, or cracks, it is possible for blood vessels to grow through the cracks. These vessels sometimes leak. Bleeding in the area of central vision, the macula, may cause vision loss. People affected with PXE almost never lose their peripheral vision. Retinal surgeons try to manage bleeding in some cases by laser surgery. However, the outcome of the surgery is not always positive and sometimes bleeding reoccurs.
People with PXE are never totally blind, and vision loss probably will not start, if at all, until age 40 or so. These points are important, but are also difficult to accept as reassurances when one first hears of the diagnosis. We thought first of our children, somewhere near our present age, being unable to read or drive a car. We have since met many very well adjusted, productive, legally blind, affected individuals. We have also met a number of individuals with PXE who are in their later years and have no vision loss. Nevertheless, like the skin changes, we remind ourselves that it is all right to grieve this potential loss, despite these reassurances. Our hope is founded on the fast pace of major medical advances. Time is on the children's side. Let us hope together.
Another problem that occurs extremely rarely in younger children is gastrointestinal bleeding. The stomach is the most common site for this. In the case histories I have read, I have gleaned that it is important for the physician to know s/he is dealing with PXE so that appropriate measures can be taken. The gastrointestinal effects of PXE have not been studied in detail.
Serious cardiovascular involvement includes coronary artery disease, peripheral artery disease with intermittent claudication (or clogging of arteries), easy fatigability, mitral valve prolapse, and hypertension. These are usually not present in children, although there are reports of a few cases in the medical literature.
At this point in time, we do not fully understand how pseudoxanthoma elasticum (PXE) is inherited. Current research suggests that PXE is inherited in an autosomal recessive manner. This means that both copies of the gene for PXE must be altered or changed in order for a person to have signs and symptoms of PXE. A person with one altered gene is called a carrier. Having only one changed gene does not make much of a difference clinically and the carrier doesn't usually have PXE, since the working gene can still perform its function. A child inherits PXE when both parents are carriers of the changed PXE gene and have both passed it on to the child. Your child may have siblings who are affected, or they might be carriers, or their PXE gene might not be altered at all. It is possible for all the children to be affected. For each pregnancy, the odds are 25% that the conception will result in two altered PXE genes coming together. These are the odds for each pregnancy, so you may have more than one child with PXE. We have 2 out of 2!
If PXE is autosomal recessive, how is it possible that there are families with more than one generation of people with PXE? There are three obvious situations in which this is possible, and they are described in detail below:
- A High Carrier Frequency. This means that there are many people in the general population with only one changed copy of the PXE gene. In some families, people who have PXE have had children with people who are carriers. In this situation, there is a 50% chance to have a child with PXE, but it is still autosomal recessive inheritance.
- Parental Consanguinity. This means that the parents of the child with PXE are related to each other. When people are related, they have a higher chance to have the same changed gene that has been passed down to them from their common ancestor. This situation puts them at higher risk to have a child who may inherit the same changed gene and have a recessive problem like PXE.
- Manifesting Carrier. This means that a person who has only one changed copy of the gene has some mild symptoms of PXE. If they have children with another PXE carrier they may have a child with PXE and it appears that there are two generations of people with PXE.
For some parents, the idea that they have passed a genetic disorder on to their children is uncomfortable or difficult. It is important to remember that we all influence our children in a number of genetic and psychological ways. Some of these things we can control and others we cannot. What we pass on genetically is something we cannot control.
Once the doctor diagnoses your child with PXE, siblings, parents, and grandparents if possible should have careful eye and skin examinations to search for characteristic signs of PXE. Include multiple generations, if possible, as there may be others affected with more subtle signs. It is important to note that PXE has varied symptoms, with different degrees of severity.
Scientists have discovered the PXE gene with the help of PXE International, Inc. Within a year or so, there will be a blood test for PXE. At that time, it will be easier to test family members for PXE. No prenatal diagnosis currently exists, but in the future this may be possible. A good genetic counselor can explain genetic and prenatal testing further to you in greater detail.
Caring for Your Child
There is no cure or specific therapy for PXE. The only treatment that exists, at present, is living a healthy lifestyle. It is important that you find specialists familiar with PXE. Ask your primary care practitioner, or call PXE International for information. We maintain a database of physicians who are working with people affected by PXE.
First, a dermatologist should examine the child. After a positive biopsy (a punch the size of a pencil eraser is used to take a small bit of skin, usually from the neck), the dermatologist will usually suggest that your child see an ophthalmologist and a cardiologist. (We have a bulletin for your primary care practitioner if you would like to share this information, written by physicians, with him/her.)
The ophthalmologist will look for peau d'orange and/or angioid streaks. Sometimes in young children these do not appear. It is good, however, to get a baseline examination and then to follow up yearly with your ophthalmologist.
The cardiologist should also do a baseline examination including a stress sonogram, and a check for the pulse in the extremities. He or she should measure cholesterol, HDL, and triglycerides and suggest appropriate dietary changes when indicated. Your primary care practitioner and cardiologist will emphasize the importance of a heart-healthy diet. They should suggest a low fat diet, with plenty of exercise. Controlling weight and blood pressure should also be suggested.
A child should not engage in sports that might result in head or eye trauma. A blow to the eye might encourage bleeding. Therefore, baseball, basketball, weightlifting, soccer, and football are probably not good choices for a child with PXE. Biking with a helmet, swimming, and walking are all very good choices.
Gastrointestinal bleeding is one complication that may occur in younger patients. Your primary care practitioner may advise avoiding aspirin and non-steroidal medications such as ibuprofen (Motrin, Advil), that may promote gastric irritation. Acetaminophen (Tylenol) may be the safest medication for the pediatric patient who requires pain or fever control.
Probably the greatest early complication will be the emotional one. It hurts to have a child diagnosed with PXE. Give yourself and your family the time and space you need to deal with this revelation. Ignore the people who say, "Oh, thank goodness it isn't cancer". That does not make this different right now. No, your child probably is not going to die from PXE (so far it seems that life expectancy is the same for PXE affected individuals as it is for the general population). However, life is not the same now that you have this diagnosis. Find good friends who are willing to talk with you about your fears and anxieties. Help your child to deal with this on whatever level they are capable of handling. Mostly, celebrate life; it is more fragile than we often remember. Life is so much more valuable and important than all those other things that creep in and overwhelm us. The money problems, our jobs, the house in need of cleaning, can all wait while we enjoy our children and the life we have been given.