Ellis–Van Creveld syndrome is an autosomal recessive condition defined by the presence of chondrodysplasia, polydactyly, and ectodermal dysplasia, as well as congenital heart defects [1] [2]. This rare condition is caused by mutations in the ECV 1 or 2 genes located on chromosome 4, which have been identified in approximately two-thirds of patients [3] [4]. Ellis–Van Creveld syndrome predominantly occurs in the Old Order Amish population in Pennsylvania, in which the incidence is about 5 individuals per 1000 live births [5].

The most frequently observed feature is chondrodystrophy, which is secondary to abnormal ossification [6]. This is notable for disproportionate dwarfism and progressive shortening of the forearms and lower legs. Moreover, bilateral postaxial polydactyly of the fingers is consistently observed in patients with Ellis–Van Creveld syndrome [7] whereas the toes are affected in 10% of cases.

Ectodermal dysplasia in these patients includes involvement of the nails and teeth. Specifically, the nails are hypoplastic and dystrophic. With regards to teeth, they may be abnormally shaped and sized, fewer in number, maloccluded, and demonstrative of hypoplastic enamel [8] [9]. Further oral deformities may include partial harelip, multiple labial frena, and maxillary alveolar clefts [9].

Nearly 50% to 60% of individuals with Ellis–Van Creveld syndrome present with a common atrium and an atrioventricular canal [10]. Other anomalies include patent ductus arteriosus (PDA) and septal wall defects [11]. The presence of cardiac malformation and respiratory failure secondary to thoracic dysplasia are predictive of poor prognosis in affected infants.

The clinical phenotype of this syndrome is variable as the patients may exhibit skeletal abnormalities such as a narrow thorax, lumbar lordosis, and valgus deformity of the knee [12]. Other features may include endodermal effects such as problems with the liver and lungs [11]. Finally, some may also have genitourinary malformations. Note that intelligence is usually normal in Ellis–Van Creveld syndrome patients.

Physical exam

Findings on the exam are remarkable for the above described features. Additionally, newborns and infants with heart disease and cardiac failure will exhibit dyspnea, cyanosis, heart murmur, failure to thrive, and other manifestations.

• Nail Abnormality

  We report a family with complex septal cardiac defects, rhizomelic limb shortening, and polydactyly, without the typical lip, dental, and nail abnormalities of EvC. [ncbi.nlm.nih.gov]

  Like Ellis-van Creveld syndrome, Weyers acrofacial dysostosis involves tooth and nail abnormalities, although affected individuals have less pronounced short stature and typically do not have heart defects. [medlineplus.gov]

• Pleural Effusion

  The respiratory system showed bilateral pleural effusion along with pericardial effusion. Arterial blood gas values were measured and showed 7.28 pH (reduced), pCO2 28.5 mmHg (reduced), and pO2 69.7 mmHg (reduced). [cureus.com]

• Failure to Thrive

  We discuss this potentially serious condition with congenital heart malformations that can result in failure to thrive and even death if not recognized early. [ncbi.nlm.nih.gov]

  Additionally, newborns and infants with heart disease and cardiac failure will exhibit dyspnea, cyanosis, heart murmur, failure to thrive, and other manifestations. [symptoma.com]

  We discuss this potentially serious condition with congenital heart malformations that can result in failure to thrive and even death if not recognized early. PDF PD F PDF Download Next Article: Cosmetic Camouflage for Scars [mdedge.com]

  […] to thrive, cyanosis, shortness of breath, or other cardinal signs of heart failure. [emedicine.medscape.com]

• Genu Valgum

  Clinical features were: a marked acromesomelic short stature (135 cm height), narrow thorax, genu valgum, club feet, brachydactyly, malposed toes, hypoplastic nails and teeth, diffuse alopecia, atrioventricular canal, hypoplastic mammary glands and a [ncbi.nlm.nih.gov]

  […] ilia triradiate acetabula cleft lip and/or palate epispadias cryptorchidism polydactyly: tends to be postaxial limb anomalies short limbs: especially forearm and lower leg bowing of humerus and femur hypoplasia of proximal tibial ossification center genu [radiopaedia.org]

  He was being followed up at the orthopedics department of the hospital because of the significant genu valgum. [scielo.br]

• Normal Stature

  However, the patients are often of normal stature and cardiac defects and thoracic dysplasia are generally absent. [ijdvl.com]

• Neuralgia

  Progressive facial hemiatrophy (Parry-Romberg syndrome) is a rare condition which usually starts within the first two decades with altered pigmentation, premonitory muscle spasms or neuralgia at the affected site and may involve skin, subcutis, muscle [ijdvl.com]

Neonates presenting with the above characteristics (i. e, small stature, skeletal abnormalities, cardiac anomalies, etc) warrant a detailed workup consisting of the prenatal and family history (affected family members, parent consanguinity), full physical exam including cardiac evaluation, and the appropriate studies.

Genetic analysis

Sequencing analysis for the EVC and EVC2 genes is available.

Imaging

Skeletal survey in these patients reveals abnormalities such as short ribs, narrow thorax, shortened long bones, and proximal phalanges that are longer than the distal and middle phalanges. Additionally the diaphyses and metaphyses are widened while the epiphyses appear cone-shaped [13]. Furthermore, various types of bone fusions may be present as well. Pelvic X-rays may demonstrate smaller sized iliac crests and sciatic notches.

Cardiac assessment is crucial, and should consist of echocardiography, electrocardiography (EKG), and chest X-ray. Other studies include renal ultrasonography and brain magnetic resonance imaging (MRI). Finally, physicians should employ the use of growth charts to track the growth of the child [14].

Prenatal studies

On prenatal ultrasonography, findings include inadequate fetal growth, skeletal abnormalities, and heart anomalies. This should warrant further investigation.

• Pericardial Effusion

  The respiratory system showed bilateral pleural effusion along with pericardial effusion. Arterial blood gas values were measured and showed 7.28 pH (reduced), pCO2 28.5 mmHg (reduced), and pO2 69.7 mmHg (reduced). [cureus.com]

• T Wave Abnormality

  The ECG showed abnormalities in leads V1, V2, and aVR, T wave abnormality, and severity of left axis deviation (25mm/sec; Figure 11). [cureus.com]

• Pleural Effusion

  The respiratory system showed bilateral pleural effusion along with pericardial effusion. Arterial blood gas values were measured and showed 7.28 pH (reduced), pCO2 28.5 mmHg (reduced), and pO2 69.7 mmHg (reduced). [cureus.com]

Ellis van Creveld syndrome DIAGNOSIS AND TREATMENT A diagnosis of Ellis van Creveld syndrome can be made using clinical assessments, radiological imaging and genetic testing. [muhealth.org]

Early treatment can help the patient to prevent various problems and undue psychological trauma. After completion of the treatment, esthetics, function and phonetics improved remarkably. [hindawi.com]

[…] to take care of the possible bacteremia resulting from the treatment. [jomos.org]

There is no cure for the underlying cause of this condition, and treatment is based on symptoms. In the neonatal period, treatment is based on management of respiratory and cardiac symptoms. [myriad.com]

Prognosis is linked to the respiratory difficulties in the first months of life due to thoracic narrowness and possible heart defects. Prognosis of the final body height is difficult to predict. [ncbi.nlm.nih.gov]

Prognosis: Neonatal mortality: 50% due to pulmonary hypoplasia and cardiac problems. The overall prognosis for affected patients is related to the presence or absence of cardiac abnormalities. Intelligence is normal. [fetalmedicine.org]

Surgical data is lacking on the prognosis and life expectancy of EvC patients. Herein, we report the case of a 38-year-old man with EvC syndrome who underwent two surgical corrections for cardiac anomalies. [smj.org.sg]

The etiology of the condition is obscure, and there is nothing to suggest an hereditary factor. [pubs.rsna.org]

( 12100513 ) Association hydrometrocolpos (not linked to chromosome arm 4p or 20p) ( 15054850 ) thymic hypoplasia ( 12538281 ) nephronophtisis ( 9502561 ) situs inversus totalis (#5770269 #) Cytogenetics segmental uniparental disomy of chromosome 4 Etiology [humpath.com]

The dental literature describing the oral manifestations and etiology of both syndromes is scarce. [researchgate.net]

Etiology The EVC gene was previously localized by linkage analysis to the distal short arm of chromosome 4 [25, 26], in an area proximal to other chondrodystrophias. [ojrd.biomedcentral.com]

These may not explain the disease etiology of the proband; however, they may bring an extra layer of complexity to genetic counseling because all intrafamily members will have an increased risk of having offspring with these recessive conditions due to [karger.com]

Relevant External Links for EVC Genetic Association Database (GAD) EVC Human Genome Epidemiology (HuGE) Navigator EVC Atlas of Genetics and Cytogenetics in Oncology and Haematology: EVC No data available for Genatlas for EVC Gene Mutations in a new gene [genecards.org]

DISCUSSION: Epidemiology Chondroectodermal dysplasia, also known as the Ellis-van Creveld Syndrome, is an autosomal recessive skeletal dysplasia that results in short-limbed disproportionate dwarfism. [gait.aidi.udel.edu]

Elston, professor of epidemiology and biostatistics at Case Western Reserve University. [sciencedaily.com]

Epidemiology Frequency Ellis-van Creveld (EVC) syndrome is a rare disease. [emedicine.medscape.com]

Pathophysiology is unknown. Recently two EVC genes were identified. This may through some light on pathophysiology in future. Morbidity and mortality is related to the thoracic dysplasia, respiratory insufficiency and cardiac anomalies. [ispub.com]

Bone deformity, such as knee valgus with lateral tibial plateau depression and patella dislocation, requires ongoing orthopedic follow-up and care. [4] Pathophysiology The pathophysiology of Ellis-van Creveld (EVC) syndrome is unknown; however, a better [emedicine.medscape.com]

Pathophysiology The pathophysiology of Ellis-van Creveld (EVC) syndrome is unknown; however, a better understanding may be achieved now that the genes EVC (MIM #604831) and EVC2 (MIM #607261) have been identified. [2] Histopathologic examination of fetuses [emedicine.com]

Ellis-van Creveld syndrome Shilpa S Sasalawad1, Shivayogi M Hugar1, K S Poonacha2, http://orcid.org/0000-0001-8793-5842Rachappa Mallikarjuna2http://orcid.org/0000-0001-8793-5842 1Department of Pedodontics and Preventive Dentistry, KLE VK Institute of [casereports.bmj.com]

Albeit there are numerous articles penned on the EVC, the treatise from an oral perspective is inadequate, covering only oral exhibitions and the preventive treatments. [hindawi.com]

To achieve satisfactory functional and aesthetic results, multidisciplinary care planning is necessary for preventing and providing conservative or surgical care to ensure oral health, and to refer patients to the appropriate specialists to prevent cardiac [jomos.org]

Preventive measures were planned with professional care and home oral hygiene instruction. [ijdr.in]

How can I prevent it? The gene must be present in both the parents for the child to get it. However, prenatal diagnosis is possible by gene sequencing of the affected gene (by checking the fetus during pregnancy) by advanced molecular techniques. [pediatriconcall.com]

1. Ruiz-Perez VL, Tompson SW, Blair HJ, et al. Mutations in two nonhomologous genes in a head-to-head configuration cause Ellis-van Creveld syndrome. Am J Hum Genet. 2003;72(3):728–732.
2. Baujat G, Le Merrer M. Ellis-van Creveld syndrome. Orphanet J Rare Dis. 2007;2:27.
3. Beeghton P, ed. MC-Kusick's Heritable Disorders of Connective Tissue. St. Louis, Missouri: Mosby-Year Book, Inc; 1993:590–595.
4. Tompson SW, Ruiz-Perez VL, Blair HJ, et al. Sequencing EVC and EVC2 identifies mutations in two-thirds of Ellis-van Creveld syndrome patients. Hum Genet. 2007;120(5):663-670.
5. McKusick VA. Ellis-van Creveld syndrome and the Amish. Nat Genet. 2000; 24(3):203-204.
6. Varela M, Ramos C. Chondroectodermal dysplasia (Ellis-van Creveld syndrome): A case report. Eur J Orthod. 1996;18(4):313–318.
7. Sharma OP, Saraf R, Gupta B. EVC syndrome (a case report) Indian J Radiol Imaging. 2006;(16)3:325–327.
8. Kalaskar R, Kalaskar AR. Oral manifestations of Ellis-van Creveld syndrome. Contemp Clin Dent. 2012;3(Suppl 1):S55-S59.
9. Popli MB, Popli V. EVC syndrome. Indian J Radiol. 2002;12(4):549–550.
10. Grainger RG, Allis DJ. Diagnostic Radiology. 11th ed. III. London, UK: Churchill Livingstone; 1992:651–652.
11. Gokulraj S, Mohan N, Raj JB, et al. Ellis–Van Creveld syndrome in siblings: A rare case report. J Pharm Bioallied Sci. 2016;8(Suppl 1):S179-S181.
12. Shibata T, Kawabata H, Yasui N, et al. Correction of knee deformity in patients with Ellis-van Creveld syndrome. J Pediatr Orthop B. 1999;8(4):282-284.
13. Brueton LA, Dillon MJ, Winter RM. Ellis-van Creveld syndrome, Jeune syndrome, and renal-hepatic-pancreatic dysplasia: Separate entities or disease spectrum? J Med Genet. 1990;27(4):252–255.
14. Verbeek S, Eilers PH, Lawrence K, Hennekam RC, Versteegh FG. Growth charts for children with Ellis-van Creveld syndrome. Eur J Pediatr. 2011;170(2):207-211.