Ellis-van Creveld syndrome

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Ellis-van Creveld Syndrome (also called chondroectodermal dysplasia or mesoectodermal dysplasia) is a rare genetic disorder of the skeletal dysplasia type.

Symptoms
It involves numerous anomalies including post-axial polydactyly, congenital heart defects (most commonly an atrial septal defect producing a common atrium, occurring in 60% of affected individuals), pre-natal tooth eruption, fingernail dysplasia, short-limbed dwarfism, short ribs, partial hare-lip, and malformation of the wrist bones (fusion of the hamate and capitate bones).

Genetics
Typically this disorder is the result of founder effects in isolated human populations, such as the Amish and some small island inhabitants. Although relatively rare, this disorder does occur with higher incidence within founder-effect populations due to lack of genetic variability. Observation of the inheritance pattern has illustrated that the disease is autosomal recessive, meaning that both parents have to carry the gene in order to transmit it to offspring for the signs to become noticeable.

Ellis-van Creveld syndrome can be caused by a mutation in the EVC gene, as well as by a mutation in a nonhomologous gene, EVC2, located close to the EVC gene in a head-to-head configuration. By positional cloning, Ruiz-Perez et al. (2000) were able to identify the gene. The EVC gene maps to the chromosome 4 short arm. The function of a healthy EVC gene is not well understood at this time.

History
The disorder was described by Richard W. B. Ellis (1902-1966) of Edinburgh and Simon van Creveld (1895-1971) of Amsterdam. Each had a patient with this syndrome, as they had discovered when they met in the same train compartment on the way to a pediatrics conference in England in the late 1930s. A third patient had been referred to by L. Emmett Holt, Jr. and Rustin McIntosh in a textbook of pediatrics (Holt and McIntosh, 1933) and was included in full in the paper by Ellis and van Creveld (1940).

McCusick et al.(1964) followed up with a study of its incidence in the Amish population. He observed the largest pedigree so far, in an inbred religious isolate, the Old Order Amish, in Lancaster County, Pennsylvania. Almost as many persons were known in this one as hundreds as had been reported in all the medical literature up to that time.

Nomenclature
'Six-fingered dwarfism' ('digital integer deficiency') was an alternative designation used for this condition when it was being studied in the Amish and may have served a useful function in defining this then little known condition for the medical profession, as well as the lay public. The term, however, has been found offensive by some, apparently not because of 'dwarfism,' but because of the reference to the polydactyly, which is seen as a 'freakish' labeling. For this reason, 6-fingered dwarfism has been removed as an alternative name for this entry. This leaves Ellis-van Creveld syndrome with its felicitous abbreviation, EVC, as the only satisfactory designation. Chondroectodermal dysplasia and mesoectodermal dysplasia do not well define the entity and are not satisfactory for general usage, either medical or lay.