Ellis-van Creveld (EVC) syndrome or chondroectodermal dysplasia is a rare autosomal recessive disorder characterized by a variable spectrum of clinical findings. Classical Ellis-van Creveld syndrome comprises a tetrad of clinical manifestations of chondrodystrophy, polydactyly, ectodermal dysplasia, and cardiac defects. In several case reports, dysplasia involving other organs has also been identified. Oral manifestations tend to be pathognomonic such as multiple broad labial frenula and congenital missing teeth. Hematologic abnormalities have been rarely reported in patients with Ellis-van Creveld syndrome. Ellis-van Creveld syndrome and Jeune's asphyxiating thoracic dystrophy are related disorders. Some patients have overlapping features of both disorders, indicating that these syndromes may be a part of a disease spectrum.
Mutations in the EVC and EVC2 genes have been reported in many individuals with Ellis-van Creveld syndrome.
Mostafa et al. (2005) reported three Egyptian families with six cases of Ellis-Van Creveld syndrome. Mostafa et al. (2005) observed an unusual pattern of inheritance with father to son or to daughter transmission in two consanguineous families; thus, demonstrating pseudo-dominant inheritance, probably for the first time in the literature. A new consistent orodental anomaly found in all our cases was bifid tip of the tongue. Mostafa et al. (2005) emphasized the study of orodental anomalies in future cases for accurate diagnosis of Ellis-van Creveld syndrome and its probable differential diagnosis from Weyers acrodental dysostosis.
Temtamy et al. (2008) reported affected individuals with both the EVC and EVC2 genes inactivated on each allele. Affected subjects were born to a consanguineous family diagnosed with EvC and borderline intelligence. In the affected members from this family, Temtamy et al. (2008) detected a 520-kb homozygous deletion comprising EVC, EVC2, C4orf6, and STK32B, caused by recombination between long interspersed nuclear element-1 (LINE-1 or L1) elements. Patients homozygous for the deletion are deficient in EVC and EVC2 and have no increase in the severity of the EvC typical features. Similarly, deletion carriers demonstrate absence of digenic inheritance in EvC. The phenotype of these patients led Temtamy et al. (2008) to suggest that the EVC-STK32B deletion also leads to mild mental retardation and reveals that loss of the novel genes C4orf6 and STK32B causes at most mild mental deficit. In an EvC compound heterozygote of different ethnic origin, Temtamy et al. (2008) identified the same LINE-to-LINE rearrangement due to a different recombination event.
[See also: United Arab Emirates > Ali et al., 2010].
Hattab et al. (1998) presented two siblings with Ellis-Van Creveld, a boy aged 9 years and a girl aged 7 1/2 years, a product of unaffected first cousin parents. The patients exhibited chondrodysplasia of tubular bones resulting in disproportionate dwarfism, polydactyly and syndactyly of hands and feet, severe dystrophic nails, multiple broad labial frenula with abnormal attachments, congenital missing incisors, anomalous teeth, bilateral partial clefts of the alveolar bone, and malocclusion. Other features noted in either cases were: congenital heart defect, median notch of the upper lip, shovel-shaped incisors and taurodontism. Of the unusual dental findings observed in the patients of Hattab et al. (1998) were talon cusp, reduced crown size, supernumerary tooth, and early eruption of teeth. Hattab et al. (1998) pointed that because half of the cases with Ellis-Van Creveld syndrome have cardiac malformation, dental treatment must be performed under prophylactic antibiotic coverage. They also emphasized the important role of dentists in early diagnosis and control of dental problem of this condition.
Rajab et al. (2005) undertook a study to estimate the prevalence of commonly diagnosed autosomal recessive diseases in Oman from a hospital-based register in years 1993 to 2002. The study revealed that Ellis-Van-Creveld syndrome was diagnosed in 18 patients, with an observed incidence of 1 in 25,000 births.
Sawardekar (2005) conducted a study to establish the prevalence of major congenital malformations in children born during a 10-year period in an Omani hospital in Nizwa. Of the 21,988 total births in the hospital, four children were born with Ellis-van Creveld syndrome. Sawardekar (2005) hinted for a possible genetic contribution in these children.
Reddy and Madelioglu (1967) reported two cases of Ellis-Van Creveld syndrome from Saudi Arabia. No further details could be obtained on these patients.
[See: United Arab Emirates > Ali et al., 2010].
Al Talabani et al. (1998) studied the pattern of major congenital malformations in 24,233 consecutive live and stillbirth at Corniche hospital, which is the only maternity hospital in Abu Dhabi, between January 1992 and January 1995. A total of 401 babies (16.6/1,000), including 289 Arabs, were seen with major malformation. Single gene disorders accounted for 24% of the cases, 76% were due to autosomal recessive disorders. In their study, Al Talabani et al. (1998) observed one case of Ellis-Van Creveld syndrome born to a first cousin couple from the United Arab Emirates with no recurrent case in their family. Al Talabani et al. (1998) concluded that their study was very close to representing the true incidence of congenital abnormalities in the whole United Arab Emirates, as they investigated over 98% of deliveries in Abu Dhabi, the capital of United Arab Emirates.
In a 5-year prospective study for newborns at Al Ain Medical District, Al-Gazali et al. (2003) defined the pattern and birth prevalence of the different types of osteochondrodysplasias in the United Arab Emirates. Among the 38,048 births during the study period, 36 (9.46/10,000 births) had some type of skeletal dysplasia of which two had Ellis-Van Creveld syndrome. In one of these two cases, the parents were consanguineous. Al-Gazali et al. (2003) calculated the birth rate of this type of osteochondrodysplasia in the United Arab Emirates to be 0.52/10,000 births.
Ali et al. (2010) described six children from four families residing in the UAE and suffering from EvC syndrome. All patients clinically displayed narrow chests, short limbs, postaxial polydactyly, and with the exception of one, hypoplastic nails. All patients also had congenital cardiac defects. Radiological assessment, wherever possible, also supported the diagnosis of EvC. The first patient was born to consanguineous Emirati parents of Yemeni origin. Apart form the usual clinical features, he was found to have a common atrium with dilated coronary sinus. The infant died within 2-months of birth due to pulmonary hypertension secondary to lung hypoplasia. There was no family history in this case. The second family had two affected children born to consanguineous Sudanese parents. Both children died within 2-days of birth. Three other siblings were unaffected. The third family was Egyptian in origin and had a single affected child born to unrelated parents. ECG in this case showed a complete AV canal defect, which corrected. The fourth family was Emirati of Afghani origin. In this highly inbred family, two children in two separate branches were affected. The proband was also noted to have as atrial septal defect. She died at 3-years of age due to respiratory complications. Her uncle was the second affected child. He died in his first few weeks of life, again due to respiratory complications. Mutation analysis in these patients identified a novel mutation in the ECV2 gene in the first family, and other known mutations in the ECV and ECV2 genes in the second and third families, confirming the diagnosis of EvC Syndrome. However, no such mutations could be detected in the fourth family. Ali et al. (2010), therefore, referred to the condition in this family as 'EvC-Like' Syndrome.