Ellis-van Creveld syndrome
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2008-07-14T01:42:34Z
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/* Genetics */ relation to other genetic diseases: ciliopathy
{{Infobox_Disease
| Name = Ellis-van Creveld syndrome
| Image = Polydactyly ECS.jpg
| Caption = Polydactyly in Ellis-van Creveld syndrome
| DiseasesDB = 29309
| ICD10 = {{ICD10|Q|77|6|q|65}}
| ICD9 = {{ICD9|756.55}}
| ICDO =
| OMIM = 225500
| MedlinePlus = 001667
| eMedicineSubj = ped
| eMedicineTopic = 660
| MeshID = D004613
}}
'''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 development|tooth eruption]], [[fingernail]] [[dysplasia]], short-limbed [[dwarfism]], short [[rib]]s, partial [[hare-lip]], and malformation of the [[wrist]] [[bone]]s (fusion of the [[hamate]] and [[capitate]] bones).
==Genetics==
[[Image:autorecessive.jpg|thumb|right|Ellis-van Creveld syndrome has an autosomal recessive pattern of inheritance.]]
Ellis-van Creveld syndrome often is the result of [[founder effect]]s in isolated human [[population]]s, 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 with to the disorder.
Ellis-van Creveld syndrome is caused by a [[mutation]] in the ''[[EVC (gene)|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]], the gene was identified.<ref name="pmid10700184">{{cite journal |author=Ruiz-Perez VL, Ide SE, Strom TM, ''et al'' |title=Mutations in a new gene in Ellis-van Creveld syndrome and Weyers acrodental dysostosis |journal=Nat. Genet. |volume=24 |issue=3 |pages=283–6 |year=2000 |pmid=10700184 |doi=10.1038/73508}}</ref> The EVC gene maps to the [[chromosome]] 4 short arm. The function of a healthy EVC gene is not well understood at this time.
=== Relation to other rare disorders: genetic ciliopathy ===
Until recently, the medical literature did not indicate a connection among many [[genetic disorder]]s, both [[Syndrome|genetic syndromes]] and [[Disease|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 [[genotype|root cause]] despite the widely-varying set of medical [[phenotype|symptoms]] that are clinically visible in the [[Disorder (medicine)|disorders]]. Ellis-van Creveld syndrome is one such disease, part of an [[emergence|emerging]] class of diseases called [[ciliopathy|cilopathies]]. The underlying cause may be a dysfunctional molecular mechanism in the primary [[cilia]] structures of the [[Cell (biology)|cell]], [[organelle]]s 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 [[pleiotropic|multi-symptom]] nature of a large set of syndromes and diseases. Known ciliopathies include [[primary ciliary dyskinesia]], [[Bardet-Biedl syndrome]], [[polycystic kidney disease|polycystic kidney]] and [[polycystic liver disease|liver disease]], [[nephronophthisis]], [[Alstrom syndrome]], [[Meckel-Gruber syndrome]] and some forms of [[retinopathy|retinal degeneration]].<ref>{{cite journal
| last = Badano
| first = Jose L.
| authorlink =
| coauthors = Norimasa Mitsuma, Phil L. Beales, Nicholas Katsanis
| title = The Ciliopathies : An Emerging Class of Human Genetic Disorders
| journal = Annual Review of Genomics and Human Genetics
| volume = 7
| issue =
| pages = 125-148
| publisher =
| location =
| date = September 2006
| url = http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.genom.7.080505.115610
| doi = 10.1146/annurev.genom.7.080505.115610
| id =
| accessdate = 2008-06-15}}</ref>.
==History==
The disorder was described by Richard W. B. Ellis (1902-1966) of [[Edinburgh]] and Simon van Creveld (1895-1971) of [[Amsterdam]].<ref>{{WhoNamedIt|synd|1114}}</ref> 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). <ref>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.</ref>
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 [[inbreeding|inbred]] religious isolate, the ''Old Order Amish'', in [[Lancaster County, Pennsylvania]].<ref name="pmid14217223">{{cite journal |author=McKusick, V. A.; Egeland, J. A.; Eldridge, R.; Krusen, D. E. |title=Dwarfism in the Amish. I. The Ellis-van Creveld syndrome |journal=Bulletin of the Johns Hopkins Hospital |volume=115 |issue= |pages=306–36 |year=1964 |pmid=14217223 |doi=}}</ref> 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<ref name="pmid14217223" /> 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.
==References==
{{reflist}}
==External links ==
* [http://www.ellisvancreveld.co.uk Ellis-van Creveld]
{{Congenital malformations and deformations of musculoskeletal system}}
[[Category:Genetic disorders]]
[[Category:Autosomal recessive disorders]]
[[Category:Syndromes]]
[[Category:Cardiovascular diseases]]
[[Category:Orthopedics]]
[[fr:Syndrome d'Ellis-Van Creveld]]
[[it:Sindrome di Ellis-van Creveld]]
[[pl:Zespół Ellisa-van Crevelda]]
[[pt:Síndrome de Ellis-van Creveld]]
[[uk:Синдром Еліс-ван Кревельда]]
[[zh:埃利偉氏症候群]]