Ellis–van Creveld syndrome

Ellis–van Creveld syndrome
Polydactyly in Ellis–van Creveld syndrome
Classification and external resources
Specialty medical genetics
ICD-10 Q77.6
ICD-9-CM 756.55
OMIM 225500
DiseasesDB 29309
MedlinePlus 001667
eMedicine ped/660
MeSH D004613

Ellis–van Creveld Syndrome (also called chondroectodermal dysplasia or mesoectodermal dysplasia but see 'Nomenclature' section below) is a rare genetic disorder of the skeletal dysplasia type.

Symptoms

Patient with Ellis–Van Creveld syndrome at the age of 5 years showing long narrow chest and shortness of the limbs
Anterior view of the mouth of EVC patient showing absence of upper incisors and conical lower incisors

It involves numerous anomalies including:

Genetics

Ellis–van Creveld syndrome often 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 for an individual to be affected by the disorder.[3]

Ellis–van Creveld syndrome is 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. The gene was identified by positional cloning.[4] The EVC gene maps to the chromosome 4 short arm. The function of a healthy EVC gene is not well understood at this time.[3]

Relation to other rare disorders: genetic ciliopathy

Until recently, the medical literature did not indicate a connection among many genetic disorders, both genetic syndromes and genetic diseases, that are now being found to be related. As a result of new genetic research, some of these are, in fact, highly related in their root cause despite the widely varying set of medical symptoms that are clinically visible in the disorders. Ellis–van Creveld syndrome is one such disease, part of an emerging class of diseases called ciliopathies. The underlying cause may be a dysfunctional molecular mechanism in the primary cilia structures of the cell, organelles which are present in many cellular types throughout the human body. The cilia defects adversely affect "numerous critical developmental signaling pathways" essential to cellular development and thus offer a plausible hypothesis for the often multi-symptom nature of a large set of syndromes and diseases. Known ciliopathies include primary ciliary dyskinesia, Bardet–Biedl syndrome, polycystic kidney and liver disease, nephronophthisis, Alstrom syndrome, Meckel–Gruber syndrome and some forms of retinal degeneration.[5]

Weyers acrofacial dysostosis is due to another mutation in the EVC gene and hence is allelic with Ellis–van Creveld syndrome.[6]

History

The disorder was described by Richard W. B. Ellis (1902–1966) of Edinburgh and Simon van Creveld (1895–1971) of Amsterdam.[7] 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).[8]

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.[9] Almost as many persons were known in this one kindred 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[9] 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 initialism, 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 otherwise.

References

  1. ↑ "Natal teeth". MedlinePlus : U.S. National Library of Medicine. Retrieved 7 April 2013.
  2. 1 2 3 "Ellis-van Creveld syndrome". MedlinePlus : U.S. National Library of Medicine. Retrieved 7 April 2013.
  3. 1 2 "Ellis–van Creveld syndrome". Genes and Diseases. NCBI. 1998. Retrieved November 8, 2010.
  4. ↑ Ruiz-Perez VL, Ide SE, Strom TM, et al. (2000). "Mutations in a new gene in Ellis–van Creveld syndrome and Weyers acrodental dysostosis". Nat. Genet. 24 (3): 283–6. doi:10.1038/73508. PMID 10700184.
  5. ↑ Badano, Jose L.; Norimasa Mitsuma; Phil L. Beales; Nicholas Katsanis (September 2006). "The Ciliopathies : An Emerging Class of Human Genetic Disorders". Annual Review of Genomics and Human Genetics. 7: 125–148. doi:10.1146/annurev.genom.7.080505.115610. PMID 16722803. Retrieved 2008-06-15.
  6. ↑ Shi L, Luo C, Ahmed MK, Attaie AB, Ye X (2015) Novel mutations in EVC cause aberrant splicing in Ellis-van Creveld syndrome. Mol Genet Genomics
  7. ↑ synd/1114 at Who Named It?
  8. ↑ Ellis, R. W. B.; van Creveld, S.: A syndrome characterized by ectodermal dysplasia, polydactyly, chondro-dysplasia and congenital morbus cordis: report of three cases. Arch. Dis. Child. 15: 65–84, 1940.
  9. 1 2 McKusick, V. A.; Egeland, J. A.; Eldridge, R.; Krusen, D. E. (1964). "Dwarfism in the Amish. I. The Ellis–van Creveld syndrome". Bulletin of the Johns Hopkins Hospital. 115: 306–36. PMID 14217223.
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