X-linked Hypohidrotic Ectodermal Dysplasia
Synonyms
1
Overview
X-linked hypohidrotic ectodermal dysplasia (XLHED) is a rare genetic disorder. Children born with XLHED have a reduced ability to sweat (hypohidrosis), abnormally shaped and missing teeth (hypodontia), and fine sparse hair (hypotrichosis). There are a number of additional features of XLHED, which may include dry eyes, eczema, asthma, and dry mucous membranes in the mouth and nose.
In the first years of life, children with XLHED are at risk for severe medical complications. These complications are most often associated with their inability to sweat, which can lead to their bodies overheating. Children with XLHED also have reduced mucous secretion and may be more prone to respiratory infections. Throughout childhood the focus of care may shift to chronic skin issues, medical management, and self-esteem challenges of severe hypodontia—missing and pointed teeth. Dentures may be prescribed as early as age 2-3 years to enhance feeding and growth and to begin to address what are often life-long psychosocial issues.
Incidence
The worldwide incidence of XLHED is estimated to be between 4 to 10/100,000 male births (as many as 200 births annually). Additionally, about 50% of XLHED-carrier females (approximately 400 births annually) are estimated to have symptoms that would warrant therapeutic intervention.
Symptoms
Common symptoms include:
- A reduced ability to sweat. This is because babies born with XLHED have no, or fewer than normal, sweat glands or they don't sweat properly (hypohidrosis)
- Missing and often pointed teeth (hypodontia)
- Sparse and slow-growing hair on both the head and body (hypotrichosis)
- Drier than normal linings or membranes in the nose and mouth
- Dry eyes
- Breathing problems such as asthma
- Increased respiratory tract infections (colds, pneumonias, etc)
- A discharge from the nose that smells bad
- Dry and scaly skin
Causes
XLHED is caused by a change in a gene called EDA. The EDA gene controls the proteins (nutrients the body needs for growth) that work together in directing the development of the skin, hair, nails, teeth, and sweat glands. When this gene is changed, normal protein levels are not able to direct typical development of these tissues and organs.
Inheritance
Chromosomes are threadlike structures in our cells that carry genetic material that tell the body how to grow and develop. X and Y chromosomes are called the sex chromosomes. Women have 2 X chromosomes, while men have one X and one Y chromosome. The EDA gene is carried on the X chromosome. If there is a change to the EDA gene, this can cause XLHED.
Can mothers affected by XLHED pass the gene for XLHED to their children?
Women have 2 X chromosomes. Women who have one changed EDA gene and one working copy of the EDA gene are XLHED carriers. Some of these women may have symptoms of XLHED, which can be mild or, in some cases, severe. This occurs because when one X chromosome is changed, the working X chromosome can compensate and lead to less severe XLHED symptoms.
There is a 50% chance that a woman who is an XLHED carrier will pass the changed gene to her son. Sons who inherit this gene will be affected by XLHED. This is because their only copy of the X chromosome and EDA gene does not work correctly. If the woman who is an XLHED carrier has a daughter, there is a 50% chance that her daughter will inherit the changed gene. She can then also pass XLHED to a future child like her mother did.
Can fathers affected by XLHED pass the gene for XLHED to their children?
Fathers pass their X chromosome to their daughters and the Y chromosome to their sons. Because the changed gene for XLHED is only on the X chromosome, fathers with XLHED will pass the changed gene to all of their daughters. Daughters may then pass the changed gene to their children. Fathers cannot pass this gene to their sons because they can only pass the Y chromosome onto their sons, and the Y chromosome does not contain the EDA gene. Please see the diagram for more information about how XLHED is passed from parents to their children.
Fathers with XLHED will pass the gene to all of their daughters, who will be carriers for XLHED. A mother who is a carrier of XLHED has a 1 in 4 chance of having an affected son and a 1 in 4 chance of having a carrier/affected daughter. Women who are carriers for XLHED may have no symptoms of XLHED, or they may have mild or even severe versions of them.
Diagnosis
XLHED is diagnosed clinically based on these common signs and symptoms:
- A reduced ability to sweat
- Missing and often pointed teeth
- Sparse hair on both the head and body
In some cases, a parent or doctor may only begin to suspect a problem when teeth fail to develop normally. Other ways diagnosis is made depends on what part of the body is affected, mainly how it is developing and functioning as the child grows. There is also a genetic test available (which uses a blood sample) to diagnose certain forms of XLHED.
Treatment
There are currently no specific treatments available for XLHED. However, doctors and patients have found ways to manage the challenges of living with XLHED. Edimer is developing EDI200 as a potential treatment that may improve the health and quality of life of future generations living with XLHED.
What is ED1200?
EDI200 is being developed as a potential treatment to replace the missing protein in newborn boys with XLHED. Animal studies have shown that use of EDI200 leads to more normal development of hair, teeth, skin, and sweat glands in XLHED-affected animals. A clinical trial of EDI200 for newborn boys affected by XLHED is starting in 2013. Edimer will begin enrolling participants in 2013. EDI200 will only be available to newborn boys enrolled in this trial. If you are pregnant and may be an XLHED carrier, contact Edimer to learn more.
Resources
For more information on XLHED and managing its symptoms, please refer to the following resources:
Provides information and education for the global community of patients and families affected by XLHED.
This site helps answer questions for those affected by XLHED who are thinking of starting a family or having another child so you can have informed conversations with your spouse or partner, family members, and genetic counselor.
A global online community of those impacted by XLHED dedicated to providing information, education, and support.
www.clinicaltrials.gov
Find out about current and upcoming clinical trials, including the Edimer neonate study.