Ellis-van Creveld and Weyers acrofacial dysostosis

Abstract

I read with great interest the report of Ghosh et al., “Report of a new syndrome: focus on differential diagnosis and review of Ellis-van Creveld, Curry-Hall, acrofacial dysostosis, and orofacial digital syndromes.”1Ghosh S. Setty S. Sivakumar A. Pai K.M. Report of a new syndrome: focus on differential diagnosis and review of Ellis-van Creveld, Curry-Hall, acrofacial dysostosis, and orofacial digital syndromes.Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007; 103: 670-676Google Scholar Their findings in the affected patient do not provide a firm base for categorizing it as a new syndromic entity. The authors have assumed that the features they have listed for Ellis-van Creveld (EvC) in Table I are constant without providing the relative frequencies of these manifestations, and the absence or existence of these features in their patient make their case either unique or somewhat different from EvC. In fact, congenital heart defects occur in only 50% to 60% and natal teeth occur in at least 25% of cases of EvC, and are not constant or obligatory features of the disorder. Also, Gorlin et al.2Gorlin R.J. Cohen M.M.J. Hennekam R.C.M. Syndromes of the head and neck. Oxford University Press, New York2001: 239-241Google Scholar states that hair changes, although reported in EvC, are not a feature.3Hunter M.L. Roberts G.J. Oral and dental anomalies in Ellis van Creveld syndrome (chondroectodermal dysplasia): report of a case.Int J Paediatr Dent. 1998; 8: 153-157Google Scholar High arched palate has also been reported to occur in EvC.3Hunter M.L. Roberts G.J. Oral and dental anomalies in Ellis van Creveld syndrome (chondroectodermal dysplasia): report of a case.Int J Paediatr Dent. 1998; 8: 153-157Google Scholar Hamate and capitate syncarpalism, synmetacarpalism, and polymetacarpalism are frequent in EvC. The combination of these congenital hand anomalies with metatarsal anomalies do occur in some cases with EvC.2Gorlin R.J. Cohen M.M.J. Hennekam R.C.M. Syndromes of the head and neck. Oxford University Press, New York2001: 239-241Google Scholar, 4Okten A. Cakir M. Orhan F. Mungan I. Atypical crossed polydactyly in two siblings with Ellis-van Creveld Syndrome and mild clinical manifestations in close relatives.Pediatr Int. 2004; 46: 184-187Google Scholar In addition, cone-shaped epiphyses of middle phalanges of the index to the fifth fingers in both hands are evident in Figure 4, which are pathognomonic for EvC.2Gorlin R.J. Cohen M.M.J. Hennekam R.C.M. Syndromes of the head and neck. Oxford University Press, New York2001: 239-241Google Scholar The features they have listed in Tables II and III and shared with other syndromes are part of the clinical spectrum of EvC.2Gorlin R.J. Cohen M.M.J. Hennekam R.C.M. Syndromes of the head and neck. Oxford University Press, New York2001: 239-241Google Scholar These different clinical patterns seen in different patients with EvC, which express variable phenotypic expression of the same genetic entity, might be due to mutations in the two adjacent genes EVC and EVC2 on chromosome 4p16, which have a head-to-head configuration and may be functionally related. Furthermore, evidence is present that EvC and Curry-Hall (CH) syndrome (Weyers acrofacial dysostosis) are allelic, and that CH syndrome is the heterozygous expression of a mutation in its homozygous form that causes the autosomal recessive disorder EvC syndrome, which further extends the spectrum of clinical manifestations.5Galdzicka M. Patnala S. Hirshman M.G. Cai J.F. Nitowsky H. Egeland J.A. et al.A new gene, EVC2, is mutated in Ellis-van Creveld syndrome.Mol Genet Metab. 2002; 77: 291-295Google Scholar, 6Ye X. Song G. Fan M. Shi L. Jabs E.W. Huang S. et al.A novel heterozygous deletion in the EVC2 gene causes Weyers acrofacial dysostosis.Hum Genet. 2006; 119: 199-205Google Scholar The case presented by the authors carries all the classical stigmata that EvC has, which leaves no doubt that the patient is merely a typical case of EvC and not a new syndromic entity.