Ellis-Van Creveld Syndrome

Related Terms

Autosomal recessive inheritance, chondroectodermal dysplasia, common atrium, disproportionate dwarfism, ectodermal dysplasia, EVC syndrome, EVC gene, EVC2 gene, mesoectodermal dysplasia.

Background

Ellis-van Creveld (EVC) syndrome is one form of the ectodermal dysplasias, a group of disorders that affect the embryonic ectoderm, which is the outer layer of the developing embryo. The ectodermal layer develops into many parts of a baby's body, including the eyes, skin, teeth, and bones, so in EVC syndrome these parts may not develop normally.
EVC syndrome primarily affects the bones. Symptoms associated with this disorder include short stature, short forearms and lower legs, and short ribs. Additional features may include extra fingers, toes, (called polydactyly), or both, and poorly developed nails and teeth. People with EVC syndrome also have a high incidence of certain heart problems, such as a single atrium.
EVC syndrome is caused by mutations or defects in the EVC or EVC2 gene. The normal functions of these genes are not yet known, but mutations result in abnormal protein synthesis.
Humans have 23 sets of chromosomes: 22 pairs of autosomes and one pair of sex chromosomes (females have two X chromosomes and males have one X and one Y chromosome). EVC syndrome is inherited, or passed down in families, as an autosomal recessive trait. This means that the defective genes are located on one of the 22 pairs of autosomes. In addition, two copies of the defective gene (one from each parent) must be inherited for the disease to appear. Individuals who inherit only one copy of the defective gene do not have the disease but are called carriers because they can pass the disorder to their children.
EVC syndrome is a rare disorder, occurring in about one out of 60,000-200,000 newborns worldwide. Males and females are affected in equal numbers. Incidence tends to be higher among the Old Order Amish in Lancaster County, Pennsylvania, where it occurs in about five out of 1,000 live births and two out of 1,000 living people. The prevalence of carriers in this population may be as high as 13%.
Other populations with a higher incidence of EVC syndrome include the indigenous people of Western Australia and people with English, Dutch, Jewish, Turkish, or French-Canadian heritage.
About half of patients with EVC syndrome die during infancy because of heart and breathing problems. Patients who survive infancy may have a normal life span. Those who survive tend to have normal intelligence. Maximum adult height is generally about 43-60 inches.

Signs and symptoms

General: As in most ectodermal dysplasias, the bones, teeth, and nails are affected in patients with Ellis-van Creveld (EVC) syndrome. Symptoms of EVC syndrome, which primarily affect the bones, are generally present at birth. Babies with EVC syndrome tend to be small for their age and to have growth delays.
Bones: People with EVC syndrome tend to be of short stature. The pattern of skeletal development is such that the lower legs and forearms are more severely affected than the upper legs and upper arms. This is known as disproportionate dwarfism. The hands and feet may be affected in a similar way in that the bones farthest away from the palm of the hand (i.e., the fingertips) are disproportionately smaller than the bones closest to the palm.
About 10% of people with EVC syndrome have extra fingers and toes (called polydactyly). Other skeletal symptoms may include sloped shoulders, a narrow windpipe, knock knees, broad hands and feet, poorly developed pelvis, and spinal curvature.
Hair: As in many forms of ectodermal dysplasia, people with EVC syndrome may have sparse or brittle scalp hair.
Heart: About 50-60% of people with EVC syndrome have heart problems. The most common type of heart problem seen in EVC syndrome is a single atrium. A normal heart has two atria, which in patients with EVC syndrome may be combined into one. Therefore the heart, which normally has four chambers (two atria and two ventricles), has only three (one atrium and two ventricles).
Mouth: People with EVC syndrome may have structural problems in the mouth. In particular, the upper lip may be short, giving the impression of a partially cleft lip.
Nails: In people with EVC syndrome, the fingernails and toenails tend to be underdeveloped, misshapen, and fragile. In some cases, the nails are absent.
Teeth: Dental problems in people with EVC syndrome may include poorly developed teeth, small or abnormally shaped teeth, missing teeth, and poor alignment of the upper and lower jaws. In some cases, babies are born with visible teeth, called natal teeth.
Other: In rare cases, people with EVC syndrome may have symptoms that affect the genitals, urinary system, kidneys, or central nervous system (CNS). Problems with the CNS, which includes the brain and spinal cord, may be associated with intellectual disabilities.

Diagnosis

General: Ellis-van Creveld (EVC) syndrome may be suspected based on the observation of short stature, disproportionate growth of the arms and legs, and qualities of the hands, feet, and mouth. In addition, a detailed family history and thorough physical exam should be completed.
Imaging studies: X-rays may be used to assess the presence and degree of skeletal problems. Magnetic resonance imaging (MRI) of the brain may reveal brain problems. Ultrasound of the kidneys may also be done.
An echocardiogram may be done to assess the health of the heart and the presence of a common or single atrium. An echocardiogram is a painless and noninvasive procedure during which sound waves are used to create a moving picture of the heart. Reflected sound waves allow the clinician to observe the heart's structure and function.
Prenatal diagnosis: After 18 weeks of gestation, an ultrasound may be used to check for symptoms associated with EVC syndrome, including problems with the hands, feet, arms, legs, and heart. An echocardiogram may also be performed on the fetus to assess heart health.
Genetic testing: If EVC syndrome is suspected, a test may be performed to confirm a diagnosis. A sample of the patient's blood is analyzed for the defect in the EVC or EVC2 gene. If this defect is detected, a positive diagnosis is made.
Prenatal DNA testing: If there is a family history of EVC syndrome, prenatal testing may be performed to determine whether the fetus has the disorder. Amniocentesis and chorionic villus sampling (CVS) can confirm a diagnosis of EVC 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 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 EVC or EVC2 gene. Miscarriage occurs in about 0.5-1% of women who undergo this procedure.

Complications

Heart problems: About 50-60% of people with Ellis-van Creveld (EVC) have heart problems. The most common type of heart problem seen in EVC syndrome is a single atrium. A normal heart has two atria that in a patient with EVC syndrome may be combined into one. Therefore the heart, which normally has four chambers (two atria and two ventricles), has only three (one atrium and two ventricles). This condition may not cause any problems or it may predispose people with EVC syndrome to abnormal heart rhythms, high blood pressure, or heart failure.
Limited mobility: Complications seen in EVC syndrome are generally related to functional problems caused by short limbs and other skeletal issues.

Treatment

General: There is currently no known cure for Ellis-van Creveld (EVC) syndrome. Instead, treatment aims to reduce symptoms and prevent complications. Based on individual symptoms and complications, patients with EVC syndrome may be seen regularly by a geneticist, cardiologist, pulmonologist, orthopedist, urologist, physical and occupational therapist, dentist, and psychologist.
Dental care: People with EVC syndrome should practice good preventive dental care, including brushing their teeth at least twice a day and flossing once a day, seeing a dentist every six months, and avoiding cavity-causing foods and beverages. In addition, crowns or composite fillings may be used on small teeth. Partial or full dentures, implants, or dental surgery may be needed for absent teeth.
Physical and occupational therapy: EVC syndrome patients may also benefit from occupational therapy and physiotherapy. These therapies may help patients with EVC syndrome improve their physical abilities and perform daily functions in order to increase their independence.
Surgery: Surgery may be needed to improve the appearance and functionality of the hands and feet by removing extra fingers and toes. The extent of surgery depends on the severity of the bone problem. Surgery may also be needed to correct heart problems. The common atrium, for example, may be corrected by building a division between the two atria and restoring the heart to normal functioning.

Integrative therapies

Currently, there is a lack of scientific evidence on the use of integrative therapies for the treatment or prevention of Ellis-van Creveld (EVC) syndrome. The therapies listed below have been studied for related conditions, should be used only under the supervision of a qualified healthcare provider, and should not be used in place of other proven therapies or preventive measures.
Traditional or theoretical uses lacking sufficient evidence:
Physical therapy: Several studies have used physical therapy techniques to improve joint function, reduce pain, and improve muscle strength and range of motion. Physical therapy may help some individuals with Ellis-van Creveld (EVC) syndrome to increase mobility and independence. However, there is limited evidence in this area and more data are needed before a recommendation may be made. Not all physical therapy programs are suited for everyone, and patients should discuss their medical history with a qualified healthcare professional before beginning any treatment. Based on the available literature, physical therapy appears generally safe when practiced by a qualified physical therapist, however, complications are possible.
Treatment options should be considered carefully. Physical therapy may aggravate pre-existing conditions. Persistent pain and fractures of unknown origin have been reported. Physical therapy may increase the duration of pain or limit range of motion. Pain and anxiety may occur during the rehabilitation of patients with burns. Both morning stiffness and bone erosion have been reported in the physical therapy literature, although the cause is unclear. Erectile dysfunction has also been reported. Physical therapy has been used in pregnancy, specifically to treat women with pelvic girdle pain during pregnancy and at three, six, and 12 months postpartum. Reports of major adverse effects are lacking in the available literature, but caution is advised nonetheless. All therapies during pregnancy and breastfeeding should be discussed with a licensed obstetrician/gynecologist before initiation.

Prevention

General: Because Ellis-van Creveld (EVC) syndrome is inherited, there is currently no known way to prevent the disease.
Genetic testing and counseling: Individuals who have EVC syndrome may meet with a genetic counselor to discuss the risks of having children with the disease. Individuals with family histories of EVC syndrome may meet with a genetic counselor to determine whether they carry the defective EVC or EVC2 gene. Carriers can be determined through detailed family histories or genetic testing.
Known carriers of EVC syndrome may undergo genetic counseling before they conceive a child. 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 EVC or EVC2 gene, and only the embryos that are not affected are selected for implantation. Because EVC 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

Baujat G, LeMerrer M. Ellis-van Creveld syndrome. Orphanet J Rare Dis. 2007;2:27.
Cahuana A, Palma C, Gonzales W, et al. Oral manifestations in Ellis-van Creveld syndrome: report of 5 cases. Pediatr Dent. 2004;26(3):277-82.
Ellis van Creveld syndrome Web site. .
Galdzicka M, Patnala S, Hirshman MG, et al. A new gene, EVC2, is mutated in Ellis-van Creveld syndrome. Mol Genet Metab. 2002;77(4):291-5.
McKusick VA. Ellis-van Creveld syndrome and the Amish. Nat Genet. 2000;24(3):203-4.
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Torrente I, Mangino M, De Luca A, et al. First-trimester prenatal diagnosis of Ellis-van Creveld syndrome using linked microsatellite markers. Prenat Diagn. 1998;18(5):504-6.

Causes

Genetic mutations: Ellis-van Creveld (EVC) syndrome is caused by mutations or defects in the EVC or EVC2 genes. The normal functions of these genes are not yet known, but mutations result in abnormal protein synthesis.
Autosomal recessive: EVC syndrome follows an autosomal recessive pattern of inheritance. Therefore, a person must inherit two copies of the defective gene (one from each parent) in order to have the disease. Individuals who inherit only one copy of the defective EVC or EVC2 gene generally have no symptoms and are called carriers because they can pass the disorder to their children.
If one parent is a carrier, or has only one copy of the defective gene, then each child will have a 50% chance of inheriting one defective gene and of being a carrier. If both parents are carriers, each child has a 25% chance of inheriting two defective genes, a 50% chance of inheriting only one defective gene, and a 25% chance of inheriting neither defective gene. Therefore, if both parents are carriers, about one out of four children will have EVC syndrome.
Random occurrence: It is unknown whether EVC syndrome can occur as the result of a spontaneous genetic mutation without a family history of the disease.

Risk factors

Because Ellis-van Creveld (EVC) syndrome is inherited, the only known risk factor is a family history of the disease. EVC syndrome is a rare disorder, occurring in about one out of 60,000-200,000 newborns worldwide. Males and females are affected in equal numbers.
As with most recessive disorders, EVC syndrome occurs more often in certain populations, especially in isolated or closely related populations. Incidence tends to be higher among the Old Order Amish in Lancaster County, Pennsylvania, where it occurs in about five out of 1,000 live births and two out of 1,000 living people. Incidence of carriers in this population may be as high as 13%. Other populations with a higher incidence of EVC syndrome include the indigenous people of Western Australia and people with English, Dutch, Jewish, Turkish, or French-Canadian heritage.