Ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome

Related Terms

Cleft lip, cleft palate, ectrodactyly-ectodermal dysplasia-clefting syndrome, EEC, EEC1, EEC2, EEC3, EEC syndrome 1, EEC syndrome 2, EEC syndrome 3, TP63 gene, TP73L gene.

Background

Ectrodactyly-ectodermal dysplasia-cleft lip/palate (EEC) syndrome is a form of ectodermal dysplasia, a group of disorders that affect the outer layer of the developing embryo. This layer, called the embryonic ectoderm, develops into many parts of a baby's body, including the eyes, skin, nails, and hair. In ectodermal dysplasias, these parts of the body do not develop normally.
Symptoms of EEC syndrome can range from mild to severe and usually include abnormal or absent fingers and toes, hair defects, cleft palate (an incomplete closure of the roof of the mouth), cleft lip (an abnormal groove in the upper lip beneath the nose), and other facial deformities. In addition, the urinary tract may be affected.
Eye problems, such as scarring on the cornea, become more prominent as people with EEC age. The reason for this is unknown. In addition, infections of the eyelids and the lining of the eye are common.
There are two types of the disease, each caused by a different genetic mutation. EEC1 is caused by mutations or defects of the TP63 gene. This is the most common form of the disease and is often referred to simply as EEC. EEC3 is caused by mutations of the TP73L gene. A third form of the disease, EEC2, has been proposed, but researchers do not believe that this is a distinct disorder.
EEC syndrome is an inherited genetic disorder that is passed down in families as an autosomal dominant trait. Individuals receive two copies of most genes from their parents (one from the mother and one from the father). To inherit a dominant trait, an individual needs to inherit only one copy of the defective gene.
EEC syndrome is extremely rare but the exact incidence is unknown. There is currently no known cure for EEC syndrome but treatment aims to reduce symptoms and prevent complications.

Signs and symptoms

General: Ectrodactyly-ectodermal dysplasia-cleft lip/palate (EEC) syndrome is a form of ectodermal dysplasia, a group of disorders that affect the outer layer of the developing embryo. This layer, called the embryonic ectoderm, develops into many parts of a baby's body, including the eyes, skin, nails, and hair. In ectodermal dysplasias, these parts of the body do not develop normally. As in most ectodermal dysplasias, the eyes, hair, and teeth are affected in patients with EEC syndrome. Symptoms of EEC syndrome can range from mild to severe. According to limited available information, the symptoms of EEC3 seem to be limited to the hands, feet, lips and palate, and urinary system.
Cognitive: About 7% of people with EEC syndrome may have intellectual disabilities.
Ears: People with EEC syndrome may have poorly formed ears and hearing loss. The type of hearing loss that occurs in individuals with EEC is called conductive hearing loss, and it is caused by structural problems in the ear canal that do not allow for proper sound conduction.
Eyes: As individuals with EEC syndrome age, eye problems become more prominent. These may include scarring of the corneas and infections of the eyelids and lining of the eyes. Problems with the tear ducts are also common, including the absence of an opening to the tear duct.
Face: People with EEC syndrome may have an abnormal or underdeveloped appearance and structure of the bones in the face, including a flat tip of the nose. Other common facial features found in people with EEC syndrome include cleft palate (an incomplete closure of the roof of the mouth), cleft lip (an abnormal groove in the upper lip beneath the nose), or both.
Hair: As in most ectodermal dysplasias, the hair is affected in EEC syndrome. Scalp hair in patients with EEC syndrome may be sparse and coarse, light colored, and brittle. In addition, the eyelashes and eyebrows also tend to be sparse.
Hands and feet: The most common symptoms seen in EEC syndrome include abnormalities of the hands and feet. These often include abnormal or absent fingers and toes. Hands may appear split or claw-like, and fingers and toes may be fused.
Urinary tract: People with EEC syndrome may have problems with the urinary tract, including abnormal size, structure, or function of parts of the urinary system, such as the kidneys, bladder, ureters, and urinary opening.
Other: As in other forms of ectodermal dysplasia, people with EEC may have reduced or absent sweating ability, poorly developed or missing teeth, underdeveloped or ridged fingernails and toenails, and thickening of the skin on the palms of the hands and soles of the feet. The pituitary gland may be underactive, causing a lowered production of growth hormone and resulting in delays in growth. Nipples may be underdeveloped.

Diagnosis

General: Ectrodactyly-ectodermal dysplasia-cleft lip/palate (EEC) syndrome may be suspected based on the observation of the distinctive characteristics of the head, face, hair, and eyes. In addition, a detailed family history and complete physical exam should be completed.
Imaging: Imaging studies, such as X-rays, may be used to assess the degree and status of skeletal abnormalities in areas such as the hands and feet. An ultrasound, a noninvasive procedure that uses sound waves to create a moving picture of internal structures, has been used during pregnancy to detect features of EEC syndrome in the developing fetus. In particular, fetal ultrasound may detect a cleft lip or palate, as well as finger and toe abnormalities.
Genetic testing: If EEC syndrome is suspected, a genetic test may be performed to confirm a diagnosis. A sample of the patient's blood is analyzed for the defect in the TP63 or TP73L genes. If either is detected, a positive diagnosis is made. Because EEC is so rare, genetic testing may not be widely available or feasible.
Prenatal DNA testing: If there is a family history of EEC, prenatal testing may be performed to determine whether the fetus has the disorder. Because EEC is so rare, prenatal DNA testing may not be available or feasible. Patients should discuss the potential health benefits and risks associated with these procedures 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 TP63 or TP73L genes. Miscarriage occurs in about 0.5-1% of women who undergo this procedure.

Complications

Dry eyes: Because of structural problems with the tear ducts, people with ectrodactyly-ectodermal dysplasia-cleft lip/palate (EEC) syndrome may experience dry eyes. Tears protect and lubricate the eyes. Lack of tears may cause itching, burning, irritation, redness, and blurred vision.
Recurrent infections: People with EEC syndrome may be likely to get recurrent infections, particularly of the eyes. Researchers believe that this tendency is the result of structural problems of the body, rather than problems with the immune system.
Vision problems: Severe corneal scarring, which is common in EEC syndrome, may cause partial or total vision loss.
Heatstroke: Patients who are unable to sweat have an increased risk of developing heatstroke. This is a serious life-threatening condition because the body's internal organs start to shut down in response to extreme temperatures. Patients who experience decreased or no sweating, rapid heartbeat, rapid and shallow breathing, increased blood pressure, irritability, confusion, unconsciousness, and fainting, should receive immediate medical care.

Treatment

General: There is currently no known no cure for ectrodactyly-ectodermal dysplasia-cleft lip/palate (EEC) syndrome. Instead, treatment aims to reduce symptoms and prevent complications. People with EEC syndrome should be seen regularly by geneticists, psychologists, urologists, ophthalmologists, audiologists, orthopedists, and dermatologists, depending on individual symptoms.
Antibiotics: Antibiotics taken by mouth or applied to the eyes may be used to treat infections of the eyelids and lining of the eyes. Some people regularly take antibiotics to prevent these infections. Commonly used medications include nitrofurantoin (Furadantin?) and trimethoprim/sulfamethoxazole (Bactrim?, Septra?).
Artificial tears: Some people with EEC syndrome may benefit from the use of artificial tears to lubricate the eyes.
Dental care: People with EEC syndrome should practice good preventive dental care, including brushing their teeth at least twice a day and flossing once a day, getting a dental checkup every six months, and avoiding cavity-causing foods and beverages.
Surgery: Orthopedic surgery may be performed to treat or correct various skeletal problems that may be present in people with EEC syndrome, including split hands and feet. Surgery may also be used to correct a cleft lip or palate.
Laser surgery may be used to remove scarring from the corneas and to improve vision. A procedure known as dacryocystorhinostomy may be done to improve the condition of the tear ducts. During this procedure, the location of the lacrimal sac (where tears come from) is moved into the nasal passages.

Integrative therapies

Note: Currently, there is a lack of scientific evidence on the use of integrative therapies for the treatment or prevention of ectodermal dysplasia-cleft lip/palate (EEC) syndrome. The therapies listed below have been studied for related conditions, such as dry eye and eye infections, should be used only under the supervision of a qualified healthcare provider, and should not be used in replacement of other proven therapies.
Strong scientific evidence:
Vitamin A: Oral vitamin A is the treatment of choice for dry eye caused by prolonged vitamin A deficiency, and should be given immediately once the disorder is established. It is not known, however, whether vitamin A affects dry eye from other causes.
Avoid if allergic or hypersensitive to vitamin A. Vitamin A toxicity can occur if taken at high doses. Use cautiously with liver disease or alcoholism. Smokers who consume alcohol and beta-carotene may be at an increased risk for lung cancer or heart disease. Vitamin A appears safe in pregnant women if taken at recommended doses. Use cautiously if breastfeeding because the benefits or dangers to nursing infants have not been clearly established.
Good scientific evidence:
Iodine: Povidone-iodine solutions have been used in the management of childhood bacterial conjunctivitis, and may be as effective as other anti-bacterial solutions such as neomycin-polymyxin B-gramicidin. This is not an effective treatment for viral conjunctivitis. Medical supervision is recommended.
Reactions can be severe, and deaths have occurred with exposure to iodine. Avoid iodine-based products if allergic or hypersensitive to iodine. Do not use for more than 14 consecutive days. Avoid Lugol solution and saturated solution of potassium iodide (SSKI, PIMA) with hyperkalemia (high amounts of potassium in the blood), pulmonary edema (fluid in the lungs), bronchitis, or tuberculosis. Use cautiously when applying to the skin because it may irritate or burn tissues. Use sodium iodide cautiously with kidney failure. Avoid sodium iodide with gastrointestinal obstruction. Iodine is safe in recommended doses for pregnant or breastfeeding women. Avoid povidone-iodine for perianal preparation during delivery or postpartum antisepsis.
Unclear or conflicting scientific evidence:
Acupuncture: There is insufficient evidence on which to base recommendations for use of acupuncture for keratoconjunctivitis sicca (dryness of the lining of the eye) at this time. Needles must be sterile in order to avoid disease transmission. Avoid with valvular heart disease, infections, bleeding disorders or with drugs that increase the risk of bleeding (anticoagulants), medical conditions of unknown origin, and neurological disorders. Avoid on areas that have received radiation therapy. Avoid during pregnancy. Use cautiously with pulmonary disease, such as asthma or emphysema. Use cautiously in elderly or medically compromised patients, diabetics, or with a history of seizures. Avoid electroacupuncture with arrhythmia (irregular heartbeat) or in patients with pacemakers.
Eyebright: In Europe, eyebright (Euphrasia officinalis) has been used for centuries to treat eye infections and other eye-related irritations. When taken by mouth, eyebright has been used to treat sinusitis and swelling of nasal membranes. Currently there is not enough evidence to determine whether eyebright effectively treats viral conjunctivitis.
Avoid if allergic to eyebright, any of its constituents, or members of the Scrophulariaceae family. Use cautiously as an eye treatment, particularly homemade preparations, because of the risk of infection if the preparation is not sterile. Use cautiously with diabetes or if taking drugs that are broken down by the liver. Avoid if pregnant or breastfeeding.

Prevention

General: Because ectodermal dysplasia-cleft lip/palate (EEC) syndrome is an inherited condition, there is currently no known way to prevent the disease.
Genetic testing and counseling: Individuals who have EEC syndrome may meet with a genetic counselor to discuss the risks of having children with the disease. Individuals with family histories of EEC syndrome may meet with a genetic counselor to determine whether they carry the defective genes. Genetic counselors can explain the options and the associated risks of various tests, including pre-implantation genetic diagnosis (PGD), amniocentesis, and chorionic villus sampling (CVS).
Pre-implantation genetic diagnosis (PGD) may be used with in vitro (artificial) fertilization. In PGD, embryos are tested for the defective genes, and only the embryos that are not affected are selected for implantation. Because EEC syndrome can be detected in a fetus, 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

Anneren G, Andersson T, Lindgren PG, et al. Ectrodactyly-ectodermal dysplasia-clefting syndrome (EEC): the clinical variation and prenatal diagnosis. Clin Genet. 1991;40:257-62.
Buss PW, Hughes HE, Clarke A. Twenty-four cases of the EEC syndrome: clinical presentation and management. J Med Genet. 1995;32:716-23.
Knudtzon J, Aarskog D. Growth hormone deficiency associated with the ectrodactyly-ectodermal dysplasia-clefting syndrome and isolated absent septum pellucidum. Pediatrics. 1987;79:410-2.
London R, Heredia RM, Israel J. Urinary tract involvement in EEC syndrome. Am J Dis Child. 1985;139:1191-3.
Nardi AC, Ferreira U, Netto NR, et al. Urinary tract involvement in EEC syndrome: a clinical study in 25 Brazilian patients. Am J Med Genet. 1992;44:803-6.
National Center for Biotechnology Information: Online Mendelian Inheritance in Man. .
Natural Standard: The Authority on Integrative Medicine. .
Tse K, Temple IK, Baraitser M. Dilemmas in counseling: the EEC syndrome. J Med Genet. 1990;27:752-5.

Causes

Genetic mutations: Researchers have proposed three types of ectrodactyly-ectodermal dysplasia-cleft lip/palate (EEC) syndrome, each caused by a different genetic mutation. EEC1 is caused by mutations or defects of the TP63 gene. This is the most common form of the disease and is often referred to simply as EEC. EEC3 is caused by mutations of the TP73L gene. Both the TP63 and the TP73L gene appear to play a role in the regulation of cell growth.
Autosomal dominant inheritance: EEC syndrome is inherited, or passed down in families, as an autosomal dominant trait. Individuals receive two copies of most genes (one from the mother and one from the father). For a dominant disorder to appear, only one copy of the defective geneis 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 EEC syndrome can occur as the result of a spontaneous genetic mutation in the egg or sperm cells or in the developing embryo in individuals with no family history of the disorder.

Risk factors

Because ectrodactyly-ectodermal dysplasia-cleft lip/palate (EEC) syndrome is inherited, the only known risk factor is a family history of the disease. EEC syndrome is extremely rare. It is not known whether this condition affects any gender or ethnicity more than any other.

Types of the disease

General: There are two main types of ectrodactyly-ectodermal dysplasia-cleft lip/palate (EEC) syndrome. A third form of the disease, EEC2, has been proposed, but researchers have determined that this is not a distinct form of the disease.
EEC1: EEC1 is the most common form of EEC syndrome and is often referred to simply as EEC. This form of the disease is caused by a mutation in the TP63 gene.
EEC3: A second form of the disease, EEC3, is caused by a mutation in the TP73L gene. According to limited available information, the symptoms of EEC3 seem to be limited to the hands, feet, lips and palate, and urinary system.