Ellis-Van Creveld syndrome

 Ellis-Van Creveld syndrome

DISEASE OVERVIEW

Ellis-Van Creveld syndrome is a rare genetic disorder characterized by short limb dwarfism, additional fingers and/or toes (polydactyly), abnormal development of fingernails and, in over half of the cases, congenital heart defects. Motor development and intelligence are normal. This disorder is inherited as an autosomal recessive condition.

SIGNS & SYMPTOMS

Individuals with Ellis-Van Creveld syndrome typically have arms and legs that are abnormally short while the head and trunk are normal. Extra fingers (polydactyly) are present in all patients with this condition and both hands are usually affected. Ectodermal abnormalities include abnormal development of hair, nails and teeth.

More than fifty percent of the patients with Ellis-Van Creveld syndrome are born with malformations of the heart. The most common heart defect is an abnormal opening in the wall between the two upper heart chambers (atrial septal defect). Other types of heart defects have also been reported including ventricular septal defects and patent ductus arteriosis.

Some boys with this condition have been described with undescended testicles (cryptorchidism) or an abnormally located opening of the urine canal in the penis (epispadias). Abnormalities in the chest wall, spine and respiratory system have also been reported.

CAUSES

Ellis-Van Creveld syndrome is associated with abnormalities (mutations) in two genes on the number 4 chromosome called EVC and EVC2. These gene mutations result in the production of abnormally small EVC and EVC2 proteins. Some affected individuals do not have mutations in these genes, so it is likely that other unknown genes are also responsible for EVC.

Ellis-Van Creveld syndrome is inherited as an autosomal recessive genetic condition. Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease. Some individuals who carry one copy of the EVC or EVC2 gene have a condition called Weyers acrofacial dysostosis, described in the Related Disorders section of this report. The risk for two carrier parents to both pass the defective gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry a number of abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

DISORDERS WITH SIMILAR SYMPTOMS

Ellis Van-Creveld syndrome is in the category of rare skeletal disorders called short rib-polydactyly syndromes, belonging to the ciliopathies group.

These disorders are characterized by growth deficiency resulting in short stature, abnormally short ribs, extra fingers and toes (polydactyly) and variable visceral manifestations. These additional findings may include polycystic kidneys, underdevelopment (hypoplasia) of the lungs, vertebral and genitourinary abnormalities, central nervous system abnormalities, and cleft lip and cleft palate. They are inherited as autosomal recessive genetic conditions.

The short rib-polydactyly group includes 4 antenatal lethal types, Saldino-Noonan, Majewski, Verma-Naumoff and Beemer-Langer syndromes, and 2 types compatible with life, EVC and Asphyxiating Thoracic Dystrophy (ATD) or Jeune syndrome.

ATD is characterized by variable respiratory insufficiency due to the thorax narrowness, kidney, liver and retinal abnormalities, and inconstant short stature. (For more information about this condition, choose “asphyxiating thoracic dystrophy” as you search term in the Rare Disease Database.). At least two genes are associated with this condition (IFT80, DYNC2H1). The neonatal clinical presentation overlap with EVC features, especially in absence of heart abnormalities.

Weyers acrofacial dysostosis is another genetic disorder associated with polydactyly, dental and nail abnormalities, short stature and abnormal facial features. This condition has been found to be associated with a single mutation in either the EVC or EVC2 gene and follows autosomal dominant inheritance.

DIAGNOSIS

Ellis-Van-Creveld syndrome is diagnosed by the observation of short stature, slow growth, skeletal abnormalities determined by imaging techniques and sometimes teeth present at birth (natal teeth). Molecular genetic testing for the EVC and EVC2 genes is available on a research basis only. Prenatal diagnosis is possible by ultrasound.

Treatment

It is often necessary to treat respiratory distress shortly after birth that results from a narrow chest and/or heart failure. Natal teeth should be removed because they can interfere with feeding.

The treatment of Ellis-Van Creveld syndrome is directed toward the specific symptoms that are apparent in each individual. Such treatment may require the coordinated efforts of a team of medical professionals, such as pediatricians, surgeons, cardiologists, dentists, pulmonologists, orthopedists, urologists, physical and occupational therapists and/or other health care professionals.

Genetic counseling is recommended for affected individuals and their families.

TYPE OF DOCTOR AND DEPARTMENT: Child and Adolescent Neurology SPECIALIST CAN DIAGNOSE THIS DISEASE.