Inheritance: autosomal recessive
Genes: EVC1
EVC2

Chondroectodermal dysplasia
Mesoectodermal dysplasia
EVC

Dwarfism
Short limbs
Skeletal dysplasia
Short ribs
Ectodermal dysplasia
Polydactyly
Congenital heart defects
Single atrium
Bone age
Early dentition

Ellis-van Creveld Syndrome

Clinical Characteristics

General description (for patients):   

This is primarily a skeletal disorder causing dwarfism .  The signs are highly variable but the main features are short ribs, short limbs, extra digits, and abnormally formed teeth and nails. Heart defects are common.  Teeth  may be present at birth but are soon lost.  The upper lip sometimes resembles a partial “harelip”.

Medical description:  

EvC has both inter and intra-familial variability with effects on multiple organs. Prenatal abnormalities can be detected after the 18th week of gestation based on a narrow thorax, marked shortening of the long bones, hexadactyly of the hands and feet.  Increased first trimester fetal nuchal translucency has also been described.  Post-natally, the hallmark features are: 1) disproportionate small stature with increasing severity from the proximal to the distal portions of the limbs, 2) shortening of the middle and distal phalanges, 3) post-axial polydactyly affecting the hands and occasionally the feet, 4) hidrosis, 5) ectodermal dysplasia affecting mainly the hands, nails and teeth, 6) congenital heart malformations, e.g., mitral/tricuspid valve defects, atrial and ventricular septal defects, and single chambers.   Dental abnormalities include malocclusion, conical teeth, enamel hypoplasia and hypodontia.  Teeth may erupt prenatally and exfoliate early.  Head circumference and mental development in EvC are normal.  Diagnosis is based on the clinical findings and symptoms and supported by a skeletal survey, showing retarded bone maturation, fusion of the hamate and capitate bones of the wrist, cubitus valgus (increased carrying angle of the arms), and disturbances in bone remodeling with retarded bone age. Cardiac defects are present in 60% of patients.  EvC syndrome was first described by Richard W. B. Ellis (1902-1966) of Edinburgh and Simon van Creveld (1895-1971) of Amsterdam.  They had independently examined a patient with the syndrome and later met in a train carriage on their way to a pediatrics conference in England in the 1930s.

Genetics:

This is an autosomal recessive disorder.  The mutation specifically encountered in the Lancaster County, Pennsylvania Amish community is believed to cause aberrant splicing of the protein product.  This mutation ( IVS13+5G>T) occurs in intron 13 of EVC1 located on chromosome 4 (4p16).  Mutations in an adjacent gene, EVC2, cause a similar disorder.  This EVC1 is found in especially high prevalence among the Amish of Lancaster Co., PA.   The lineage of the parents in this population can be traced to Samuel King and his wife, who immigrated to Eastern Pennsylvania in 1744, thus demonstrating the ‘founder effect’.

Treatment: 

There is no known treatment other than mutidisciplinatry supportive management. This is mostly required in the first year of life including treatment of respiratory distress resulting from a narriw chest and heart failure. It is recommended that neonatal teeth be removed as they can impair feeding.   Orthopedic  intervention  to reduce or limit the impact of bone deformities can be helpful. 

Prognosis: 

Longevity is dependent in most cases on the severity of the cardiac defects.

Ancillary treatments and support:

Dental treatment should be accompanied by prophylactic antibiotics in view of the fact that a significant proportion of EvC patients have heart anomalies.

Specialists and specialty centers:

Orthopedist, dentist, cardiologist.

References:

Baujat, B., and Merrer, M.L.:  Ellis-van Creveld syndrome. Orphanet J. Rare dis.  2: 2731, 2007. PubMed ID: 17547743

Mckusick, V.A.:  Ellis-van Creveld syndrome and the Amish:  Nat. Genet. 24:203-204, 2000. PubMed ID: 10700162

McKusick, V.A., Egeland, J.A., Eldridge, R., and Krusen, D.E.:  Dwarfism in the Amish I The Ellis-van Creveld syndrome. Bull. Johns Hopkins Hosp. 115: 306-336, 1964. PubMed ID: 14217223

Ruiz-Perez, V.L., Tompson, S.W.J., Blair, H.J., Espinoza-Valdez, C., Lapunzina, P., Silva, E.O., Hamel, B., Gibbs, J.L., Young, I.D., Wright, M.J., and Goodship, J.A.:  Mutations in two nonhomologous genes in a head-to-head configuration cause Ellis-van Creveld syndrome.  Am. J. Med. Genet. 72: 728-732, 2003.  PubMed ID: 12571802

Resources:

Ellis-van Creveld for parents
Little People of America