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Sections Ellis-van Creveld Syndrome
Overview
Presentation
- History
- Physical
- Causes
- Show All
DDx
Workup
Treatment
Medication
Media Gallery
References

Workup

Laboratory Studies

In about 66% of patients diagnosed with Ellis-van Creveld (EVC) syndrome, EVC and EVC2 mutations can be identified via sequencing analysis.^[1]

Gene testing for mutational analysis of EVC and EVC2 is available clinically by sequence analysis of the entire coding region, deletion/duplication analysis, and linkage analysis (for up-to-date information on gene testing, see Gene Tests).

Imaging Studies

A radiographic skeletal survey can define skeletal anomalies. Expected findings in patients with Ellis-van Creveld (EVC) syndrome include the following:

Retarded bone maturation
Acromesomelia (relative shortening of the distal and middle segments of the limbs) - Found to be most prominent in the hands, where the distal and middle phalanges are shorter than the proximal phalanx
Postaxial polydactyly (polydactyly on the ulnar side of the hand)
Multiple varieties of carpal fusion - Fusion of the hamate and capitate bones of the wrist; fusion of the 5th and 6th metacarpals
Small iliac crests and sciatic notches (may be revealed on pelvic radiographs)
Valgus deformity of the knee^[3]
Fibula disproportionately smaller than the tibia
Thorax (short ribs, narrow chest wall)
Additional findings - Cubitus valgus, hypoplastic cubitus, supernumerary carpal bone center, clinodactyly of the fifth finger

Chest radiography, electrocardiography, and echocardiography (to evaluate cardiac anatomy) are indicated. Head magnetic resonance imaging (MRI) can be used to reveal structural brain anomalies, while renal ultrasonography can be employed to diagnose renal anomalies.

Prenatal imaging

Ultrasonographic images can detect abnormalities after the 18th week of gestation, including intrauterine growth retardation, skeletal malformations (narrow thorax, marked shortening of the long bones, hexadactyly of the hands and feet), and cardiac defects. These ultrasonographic findings lead to diagnostic discussion of short rib-polydactyly syndromes with the expectant parents.^[4]In addition, increased first-trimester fetal nuchal translucency thickness has been reported as early as the 13th week of gestation.^[38]

Other Tests

Consider ocular examination, as eye anomalies (ie, strabismus) have been described.

Using 235 observations of 101 patients with Ellis-van Creveld (EVC) syndrome (49 males, 52 females), Verbeek et al developed growth charts for males and females, aged 0-20 years.^[39]The growth charts are useful in the continuity of care of patients with EVC syndrome. Most importantly, early detection of and treatment for growth hormone deficiency, known to occur in EVC syndrome patients, can be facilitated. The growth charts, shown below, reveal that 98% of patients with EVC syndrome will exhibit lower height by age 10 years, when compared with unaffected children.

Dutch growth charts for girls and boys. Adapted from Verbeek S, Eilers P, Lawrence K, Hennekam R, Versteegh F. Growth charts for children with Ellis–van Creveld syndrome. European J of Pediatrics. Feb 2011;170(2);207-277.

View Media Gallery

Histologic Findings

Histologic findings include the following:

Disorganization of chondrocytes in the physeal growth zone of the long bones and vertebrae
Retardation of physeal growth zones in childhood

Treatment & Management

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Ellis RW, van Crefeld S. A syndrome characterized by ectodermaldysplasia, polydactyly, chondrodysplasia and congenital morbus cardia. Arch Dis Child. 1940. 15:65.
Shibata T, Kawabata H, Yasui N, et al. Correction of knee deformity in patients with Ellis-van Creveld syndrome. J Pediatr Orthop B. 1999 Oct. 8(4):282-4. [QxMD MEDLINE Link].
Baujat G, Le Merrer M. Ellis-van Creveld syndrome. Orphanet J Rare Dis. 2007 Jun 4. 2:27. [QxMD MEDLINE Link]. [Full Text].
McKusick VA. Ellis-van Creveld syndrome and the Amish. Nat Genet. 2000 Mar. 24(3):203-4. [QxMD MEDLINE Link].
Tuna EB, Koruyucu M, Kurklu E, et al. Oral and craniofacial manifestations of Ellis-van Creveld syndrome: Case series. J Craniomaxillofac Surg. 2016 Aug. 44 (8):919-24. [QxMD MEDLINE Link].
Abeles AI, Tobias JD. Anesthetic implications of Ellis-van Creveld syndrome. J Clin Anesth. 2008 Dec. 20(8):618-21. [QxMD MEDLINE Link].
Böhm N, Fukuda M, Staudt R, Helwig H. Chondroectodermal dysplasia (Ellis--van Creveld syndrome) with dysplasia of renal medulla and bile ducts. Histopathology. 1978 Jul. 2(4):267-81. [QxMD MEDLINE Link].
Moudgil A, Bagga A, Kamil ES, et al. Nephronophthisis associated with Ellis-van Creveld syndrome. Pediatr Nephrol. 1998 Jan. 12(1):20-2. [QxMD MEDLINE Link].
Datta V, Chaturvedi P. Ellis-Van Creveld syndrome associated with nodular sclerosing Hodgkin's disease and nephrotic syndrome. Indian J Pediatr. 2000 Dec. 67(12):929-30. [QxMD MEDLINE Link].
Black D, Reutter J, Johnson M, Fair J, Woosley J, Gerber D. Liver transplantation in Ellis-van Creveld syndrome: a case report. Pediatr Transplant. 2002 Jun. 6(3):255-9. [QxMD MEDLINE Link].
Miller DR, Newstead GJ, Young LW. Perinatal leukemia with a possible variant of the Ellis-van Greveld syndrome. J Pediatr. 1969 Feb. 74(2):300-3. [QxMD MEDLINE Link].
Scurlock D, Ostler D, Nguyen A, Wahed A. Ellis-van Creveld syndrome and dyserythropoiesis. Arch Pathol Lab Med. 2005 May. 129(5):680-2. [QxMD MEDLINE Link].
da Silva EO, Janovitz D, de Albuquerque SC. Ellis-van Creveld syndrome: report of 15 cases in an inbred kindred. J Med Genet. 1980 Oct. 17 (5):349-56. [QxMD MEDLINE Link]. [Full Text].
ELLIS-VAN CREVELD SYNDROME; EVC. Online Mendelian Inheritance in Man. Available at https://www.omim.org/entry/225500. Updated Sep 30, 2011; Accessed: Nov 3, 2017.
Rao MS, Sahu D, Kareem H, Devasia T, Shetty KK. Adult Survival in Ellis-van Creveld Syndrome with Common Atrium - A Rare Case Report. J Clin Diagn Res. 2017 Aug. 11 (8):OD12-OD13. [QxMD MEDLINE Link]. [Full Text].
Hills CB, Kochilas L, Schimmenti LA, Moller JH. Ellis-van Creveld syndrome and congenital heart defects: presentation of an additional 32 cases. Pediatr Cardiol. 2011 Oct. 32(7):977-82. [QxMD MEDLINE Link].
Blackburn MG, Belliveau RE. Ellis-van Creveld syndrome. A report of previously undescribed anomalies in two siblings. Am J Dis Child. 1971 Sep. 122(3):267-70. [QxMD MEDLINE Link].
Kalaskar R, Kalaskar AR. Oral manifestations of Ellis-van Creveld syndrome. Contemp Clin Dent. 2012 Apr. 3(Suppl 1):S55-9. [QxMD MEDLINE Link].
Fryns JP. Postaxial polydactyly as heterozygote manifestation in Ellis-Van Creveld syndrome?. Am J Med Genet. 1991 Jun 15. 39(4):500-1. [QxMD MEDLINE Link].
Goldblatt J, Minutillo C, Pemberton PJ, Hurst J. Ellis-van Creveld syndrome in a Western Australian aboriginal community. Postaxial polydactyly as a heterozygous manifestation?. Med J Aust. 1992 Aug 17. 157(4):271-2. [QxMD MEDLINE Link].
Spranger S, Tariverdian G. Symptomatic heterozygosity in the Ellis-van Creveld syndrome?. Clin Genet. 1995 Apr. 47(4):217-20. [QxMD MEDLINE Link].
Ruiz-Perez VL, Ide SE, Strom TM, et al. Mutations in a new gene in Ellis-van Creveld syndrome and Weyers acrodental dysostosis. Nat Genet. 2000 Mar. 24(3):283-6. [QxMD MEDLINE Link].
Ruiz-Perez VL, Ide SE, Strom TM, et al. Mutations in a new gene in Ellis-van Creveld syndrome and Weyers acrodental dysostosis. Nature Genet. 2000. 24:283-286.
Ye X, Song G, Fan M, et al. A novel heterozygous deletion in the EVC2 gene causes Weyers acrofacial dysostosis. Hum Genet. 2006 Mar. 119(1-2):199-205. [QxMD MEDLINE Link].
WEYERS ACROFACIAL DYSOSTOSIS; WAD. Online Mendelian Inheritance in Man. Available at https://www.omim.org/entry/193530. Updated May 16, 2006; Accessed: Nov 3, 2017.
Howard TD, Guttmacher AE, McKinnon W, Sharma M, McKusick VA, Jabs EW. Autosomal dominant postaxial polydactyly, nail dystrophy, and dental abnormalities map to chromosome 4p16, in the region containing the Ellis-van Creveld syndrome locus. Am J Hum Genet. 1997 Dec. 61(6):1405-12. [QxMD MEDLINE Link]. [Full Text].
EVC GENE; EVC. Online Mendelian Inheritance in Man. Available at https://www.omim.org/entry/604831. Updated Aug 16, 2017; Accessed: Nov 3, 2017.
Ruiz-Perez VL, Blair HJ, Rodriguez-Andres ME, et al. Evc is a positive mediator of Ihh-regulated bone growth that localises at the base of chondrocyte cilia. Development. 2007 Aug. 134(16):2903-12. [QxMD MEDLINE Link].
Galdzicka M, Patnala S, Hirshman MG, et al. A new gene, EVC2, is mutated in Ellis-van Creveld syndrome. Mol Genet Metab. 2002 Dec. 77(4):291-5. [QxMD MEDLINE Link].
Waters AM, Beales PL. Ciliopathies: an expanding disease spectrum. Pediatr Nephrol. 2011 Jul. 26(7):1039-56. [QxMD MEDLINE Link]. [Full Text].
Huber C, Cormier-Daire V. Ciliary disorder of the skeleton. Am J Med Genet C Semin Med Genet. 2012 Aug 15. 160C(3):165-74. [QxMD MEDLINE Link].
Warman ML, Cormier-Daire V, Hall C, Krakow D, Lachman R, LeMerrer M. Nosology and classification of genetic skeletal disorders: 2010 revision. Am J Med Genet A. 2011 May. 155A(5):943-68. [QxMD MEDLINE Link].
Ginns EI, Galdzicka M, Elston RC, et al. Disruption of sonic hedgehog signaling in Ellis-van Creveld dwarfism confers protection against bipolar affective disorder. Mol Psychiatry. 2014 Oct 14. [QxMD MEDLINE Link].
Hu Z, Hong S, Zhang Y, et al. Down-regulated WDR35 contributes to fetal anomaly via regulation of osteogenic differentiation. Gene. 2019 May 20. 697:48-56. [QxMD MEDLINE Link].
Ellis-Van Creveld syndrome. Alliance of Genome Resources. Available at https://www.alliancegenome.org/disease/DOID:12714. Accessed: Sep 6, 2019.
SHORT-RIB THORACIC DYSPLASIA 3 WITH OR WITHOUT POLYDACTYLY; SRTD3. Online Mendelian Inheritance in Man. Available at https://www.omim.org/entry/613091. Updated Feb 10, 2014; Accessed: Nov 3, 2017.
Venkat-Raman N, Sebire NJ, Murphy KW, Carvalho JS, Hall CM. Increased first-trimester fetal nuchal translucency thickness in association with chondroectodermal dysplasia (Ellis-Van Creveld syndrome). Ultrasound Obstet Gynecol. 2005 Apr. 25(4):412-4. [QxMD MEDLINE Link].
Verbeek S, Eilers PH, Lawrence K, Hennekam RC, Versteegh FG. Growth charts for children with Ellis-van Creveld syndrome. Eur J Pediatr. 2011 Feb. 170(2):207-11. [QxMD MEDLINE Link]. [Full Text].
Pirazzoli P, Mazzanti L, Mandini M, Cau M, Ravagli L, Cacciari E. GH-deficiency in Ellis-van Creveld Syndrome: response to replacement therapy. Growth Abnormalities. 1989. 56:391-3.
Weiner DS, Tank JC, Jonah D, et al. An operative approach to address severe genu valgum deformity in the Ellis-van Creveld syndrome. J Child Orthop. 2014 Feb. 8(1):61-9. [QxMD MEDLINE Link]. [Full Text].
O'Connor MJ, Rider NL, Thomas Collins R, Hanna BD, Holmes Morton D, Strauss KA. Contemporary management of congenital malformations of the heart in infants with Ellis - van Creveld syndrome: a report of nine cases. Cardiol Young. 2011 Apr. 21(2):145-52. [QxMD MEDLINE Link].
Susami T, Kuroda T, Yoshimasu H, Suzuki R. Ellis-van Creveld syndrome: craniofacial morphology and multidisciplinary treatment. Cleft Palate Craniofac J. 1999 Jul. 36(4):345-52. [QxMD MEDLINE Link].
Cahuana A, Palma C, Gonzales W, Gean E. Oral manifestations in Ellis-van Creveld syndrome: report of five cases. Pediatr Dent. 2004 May-Jun. 26(3):277-82. [QxMD MEDLINE Link].
Digoy GP, Greenberg M, Magit A. Congenital stridor secondary to an upper airway cyst in a patient with Ellis-van Creveld syndrome. Int J Pediatr Otorhinolaryngol. 2005 Oct. 69(10):1433-5. [QxMD MEDLINE Link].

Media Gallery

Newborn with Ellis–van Creveld syndrome. Note the narrow chest.
Natal teeth and lip tie.
Postaxial polydactyly.
Newborn with Ellis–van Creveld syndrome. Note the narrow chest and disproportionate dwarfism.
Dutch growth charts for girls and boys. Adapted from Verbeek S, Eilers P, Lawrence K, Hennekam R, Versteegh F. Growth charts for children with Ellis–van Creveld syndrome. European J of Pediatrics. Feb 2011;170(2);207-277.

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Author

Germaine L Defendi, MD, MS, FAAP Associate Clinical Professor, Department of Pediatrics, Olive View-UCLA Medical Center

Germaine L Defendi, MD, MS, FAAP is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Maria Descartes, MD Professor, Department of Human Genetics and Department of Pediatrics, University of Alabama at Birmingham School of Medicine

Maria Descartes, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics, Society for Inherited Metabolic Disorders, International Skeletal Dysplasia Society, Southeastern Regional Genetics Group

Disclosure: Nothing to disclose.

Additional Contributors

Michael Fasullo, PhD Senior Scientist, Ordway Research Institute; Associate Professor, State University of New York at Albany; Adjunct Associate Professor, Center for Immunology and Microbial Disease, Albany Medical College

Michael Fasullo, PhD is a member of the following medical societies: Radiation Research Society, American Society for Biochemistry and Molecular Biology, Genetics Society of America, Environmental Mutagenesis and Genomics Society

Disclosure: Nothing to disclose.

Harold Chen, MD, MS, FAAP, FACMG Professor, Department of Pediatrics, Louisiana State University Medical Center

Harold Chen, MD, MS, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics

Disclosure: Nothing to disclose.

David Flannery, MD, FAAP, FACMG Vice Chair of Education, Chief, Section of Medical Genetics, Professor, Department of Pediatrics, Medical College of Georgia

David Flannery, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Ayala Laufer-Cahana, MD, to the original writing and development of this article.

Sections Ellis-van Creveld Syndrome
Overview
Presentation
- History
- Physical
- Causes
- Show All
DDx
Workup
Treatment
Medication
Media Gallery
References

Ellis-van Creveld Syndrome Workup

Laboratory Studies

Imaging Studies

Prenatal imaging

Other Tests

Histologic Findings

References

Tables

Contributor Information and Disclosures

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