AEC syndrome

Related Terms

AEC syndrome, ankyloblepharon-ectodermal dysplasia, clefting, Hay-Wells syndrome of ectodermal dysplasia.

Background

Hay-Wells syndrome, also known as ankyloblepharon-ectodermal dysplasia-clefting (AEC) syndrome, is a rare disorder characterized by congenital ectodermal dysplasia. It is one of a group of syndromes that are characterized by abnormalities of the ectodermal structures including, hair, teeth, nails, sweat glands, cranial-facial structure, and hands.
AEC syndrome was first described by researchers Hay and Wells in 1976 when they observed seven individuals from two families with several distinctive features and symptoms. These included sparse hair on the scalp and body, ankyloblepharon (fusing of the upper and lower eyelids), cleft palate (incomplete closure of the roof of the mouth), and cleft lip (an abnormal groove in the upper lip). People with AEC syndrome are generally of normal intelligence.
AEC syndrome is caused by a mutation or defect in the TP73L gene, which produces several variants of the p73-like tumor protein (p73L). AEC syndrome is inherited, or passed down among family members. The syndrome follows an autosomal dominant pattern of inheritance, meaning that only one copy of the defective gene is needed for the disease to occur. However, not all research agrees on the patterns of inheritance.
Several researchers have noted an overlap between AEC syndrome and other forms of ectodermal dysplasia, such as ectrodactyly-ectodermal dysplasia-cleft lip/palate (EEC), limb-mammary syndrome (LMS), acro-dermato-ungual-lacrimal-tooth syndrome (ADULT), and recessive cleft lip/palate-ectodermal dysplasia (CLPED1).

Signs and symptoms

General: Hay-Wells syndrome, also known as ankyloblepharon-ectodermal dysplasia-clefting (AEC) syndrome, was first described by researchers Hay and Wells in 1976 when they observed seven individuals from four families with several distinctive features and symptoms. These included sparse hair on the scalp and body, ankyloblepharon (fusing of the upper and lower eyelids), cleft palate (incomplete closure of the roof of the mouth), and cleft lip (an abnormal groove in the upper lip).
Eyes: Eye problems may include fusion of the upper and lower eyelids or the eyelids to the eyeball, problems with tear ducts, and conjunctivitis (inflammation or infection in the lining of the eye).
Face: Individuals with AEC syndrome tend to have distinctive facial features, including an oval-shaped face, an underdeveloped jaw, a broad bridge of the nose, and ear deformities. They may also have cleft palate or, in rare cases, cleft lip.
Hair: As in most forms of ectodermal dysplasia, the hair tends to be sparse, coarse, wiry, and, in some cases, absent. The eyelashes and eyebrows are usually also sparse or absent.
Nails: The fingernails and toenails may be absent, poorly developed, or spoon-shaped in individuals with AEC syndrome.
Skin: Skin problems observed in people with AEC syndrome include decreased sweating, thickening of the skin on the palms of the hands and soles of the feet, and hyperpigmentation (abnormal coloring). In rare cases, the skin may be eroded, especially on the scalp, predisposing the individual to recurrent scalp infections.
Teeth: As in most forms of ectodermal dysplasia, the teeth may be absent, poorly developed, pointed, cone-shaped, or widely spaced.
Other: Other physical features that have been described in people with AEC syndrome include fusion of the upper and lower jaw, extra nipples, fused fingers and toes, hearing loss, heart problems (e.g., ventricular septal defect and patent ductus arteriosus), and rare problems with sex organs and the urinary system. Because AEC syndrome is so rare, it is difficult to determine how often these symptoms occur. People with AEC syndrome are generally of normal intelligence.

Diagnosis

General: Hay-Wells syndrome, or AEC syndrome, may be suspected based on observation of the distinctive characteristics of the eyes, skin, teeth, nails, and hair. In addition, a detailed family history and complete physical exam should be completed.
Genetic testing: If AEC syndrome is suspected, a cytogenetic test may be performed to confirm a diagnosis. A sample of the patient's blood is taken and analyzed in a laboratory for a particular defect in the TP73L gene. If this is detected, a positive diagnosis is made.
Prenatal DNA testing: Prospective parents who have AEC syndrome may undergo prenatal testing to determine whether a fetus carries the defective TP73L gene. Amniocentesis and chorionic villus sampling (CVS) may be used to diagnose AEC syndrome. However, because there are serious risks associated with these tests, patients should discuss the potential health benefits and risks with a medical professional.
During amniocentesis, a long, thin needle is inserted through the abdominal wall and into the uterus, and a small amount of amniotic fluid is removed from the sac surrounding the fetus. Cells in the fluid are then analyzed for normal and abnormal chromosomes. This test is performed after 15 weeks of pregnancy. The risk of miscarriage is about one in 200-400 patients. Some patients may experience minor complications, such as cramping, leaking fluid, or irritation where the needle was inserted.
During chorionic villus sampling (CVS), a small piece of tissue (chorionic villi) is removed from the placenta between the ninth and 14th weeks of pregnancy. CVS may be performed through the cervix or through the abdomen. The cells in the tissue sample are then analyzed for the mutation in the TP73L gene. Miscarriage occurs in about 0.5-1% of women who undergo this procedure.

Complications

Dental problems: People with Hay-Wells syndrome, or AEC syndrome, may experience dental problems from poorly developed and missing teeth. These may include cavities and tooth loss.
Eye infections: Eye problems may include fusion of the upper and lower eyelids or the eyelids to the eyeball, problems with tear ducts, and conjunctivitis (inflammation or infection in the lining of the eye).
Scalp infections: People with AEC syndrome may have recurrent scalp infections, especially if the skin is eroded or denuded (bare).

Treatment

General: There is no cure for Hay-Wells syndrome, or AEC syndrome. Instead, treatment aims to reduce symptoms and prevent or treat complications. Patients with AEC may be seen regularly by a dermatologist, audiologist, ophthalmologist, and various surgeons.
Antibiotics: People with Hay-Wells syndrome may require antibiotics to treat recurrent scalp infections. Depending on the severity and frequency of infections, antibiotic creams or gels may be applied to the skin, or tablets or capsules may be taken by mouth.
Dental care: Patients with Hay-Wells syndrome must practice good oral hygiene including flossing, brushing, and regular visits to the dentist. Dentures may be appropriate for patients who are missing teeth.
Hearing aids: Hay-Wells syndrome patients who experience hearing loss may benefit from hearing aids. These battery-operated devices are available in three basic styles: behind the ear, in the ear, and inside the ear canal. A behind-the-ear device is used for mild-to-profound hearing loss. The device, worn behind the ear, is attached to a plastic ear mold inside the outer ear. In-the-ear hearing aids are worn inside the outer ear and are used for mild-to-severe hearing loss. Canal hearing aids are smaller hearing aids that fit inside the patient's ear canal. They are used for mild-to-moderately severe hearing loss. Patients should talk to their healthcare providers to determine the type of hearing aid that is best for them.
If hearing loss is severe, patients may benefit from cochlear implants. These electronic devices are surgically implanted inside of the ears. Unlike a hearing aid, which amplifies sound, a cochlear implant compensates for damaged parts of the inner ear.
Speech-language therapy: Some patients with Hay-Wells syndrome may have a cleft palate (incomplete closure of the roof of the mouth) or cleft lip (an abnormal groove in the upper lip) and may benefit from speech-language therapy. During speech-language therapy, a qualified speech-language professional (SLP) works with the patient on a one-to-one basis, in a small group, or in a classroom, to help the patient improve speech, language, and communication skills. Programs are tailored to the patient's individual needs.
Speech pathologists use a variety of exercises to improve the patient's communication skills. Exercises typically start simple and become more complex as therapy continues. For instance, the therapist may ask the patient to name objects, tell stories, or explain the purpose of an object.
On average, patients receive five or more hours of therapy per week for three months to several years. Doctors typically recommend that treatment be started early to ensure the best possible outcome for the child.
Surgery: Patients with Hay-Wells syndrome may require reconstructive surgery to correct a cleft palate or cleft lip.

Integrative therapies

Currently there is a lack of scientific evidence on the use of integrative therapies for the treatment or prevention of Hay-Wells syndrome, or AEC syndrome.

Prevention

General: Because Hay-Wells syndrome, or AEC syndrome, is inherited, there is currently no known way to prevent the disease. However, a number of options are available for prospective parents with a family history of AEC syndrome.
Genetic testing and counseling: Individuals who have Hay-Wells syndrome may meet with a genetic counselor to discuss the risks of having children with the disease.
Known carriers of AEC syndrome may undergo genetic counseling before they conceive a child. Genetic counselors can explain the options and the associated risks of various tests, including preimplantation genetic diagnosis (PGD), amniocentesis, and chorionic villus sampling (CVS).
Preimplantation genetic diagnosis (PGD) may be used with in vitro (artificial) fertilization. In PGD, embryos are tested for the defective TP73L gene, and only the embryos that are not affected may be selected for implantation. Because AEC syndrome can be detected in an unborn baby, parents may choose whether to continue the pregnancy. Genetic counselors may assist parents with these difficult decisions.

Author information

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

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Causes

General: Hay-Wells syndrome is believed to be caused by a mutation or defect in the TP73L gene, which produces several variants of the p73-like tumor protein (p73L), known as p40, p51, and p63. The most likely pattern of inheritance is autosomal dominant.
Gene function: The p73-like tumor protein (p73L) may have a tumor suppressor function. The variant proteins p63 and p73 were examined for their roles in deoxyribonucleic acid (DNA) damage-induced apoptosis, or cell death. Researchers found that the combined loss of p63 and p73 results in the failure of cells containing functional p53 to undergo apoptosis in response to DNA damage.
When the TP73L gene is mutated, the protein variants it produces may not function properly. A dysfunction in this protein may cause symptoms of Hay-Wells syndrome, such as ectodermal dysplasia, limb malformations, and cleft lip.
Autosomal dominant inheritance: Hay-Wells syndrome, also known as AEC syndrome, is caused by a mutation or defect in the TP73L gene. Hay-Wells syndrome is inherited as a dominant trait. Individuals receive two copies of most genes, one from the mother and one from the father. For a dominant disorder to occur, only one defective copy of the TP73L gene is necessary. If one parent has the disorder, there is a 50% chance that his or her child will have the disorder. If both parents have the disorder, there is a 75% chance that their child will have the disorder.
Random occurrence: It is unknown whether AEC syndrome can occur as the result of a spontaneous genetic mutation with no family history of the disease.

Risk factors

The only known risk factor for Hay-Wells syndrome is a family history of the disease. Hay-Wells syndrome is believed to be inherited as an autosomal dominant trait. It is extremely rare, and its exact incidence is unknown.
Autosomal dominant inheritance: For a dominant disorder to occur, only one defective copy of the TP73L gene is necessary. Individuals receive two copies of most genes, one from the mother and one from the father. If one parent has the disorder, there is a 50% chance that his or her child will have the disorder. If both parents have the disorder, there is a 75% chance that their child will have the disorder.
Random occurrence: It is unknown whether Hay-Wells syndrome can occur as the result of a spontaneous genetic mutation with no family history of the disease.