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Ellis-Van Creveld Syndrome

Ellis Van Creveld Syndrome

Ellis–Van Creveld syndrome is a rare autosomal recessive disorder remarkable for growth retardation, polydactyly, ectodermal dysplasia, skeletal abnormalities, and heart anomalies. The diagnosis is based on family and prenatal history, detailed physical exam, and other studies.


Presentation

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.

Cervical Lymphadenopathy
  • On examination, the child had multiple congenital anomalies and cervical lymphadenopathy. Cardiac examination revealed a pansystolic murmur grade III/VI in left lower parasternal area.[ncbi.nlm.nih.gov]
Nail Abnormality
  • Our patient had all the major characteristic features consistent with Ellis-van Creveld syndrome including post-axial polydactyly, teeth and nail abnormalities, congenital heart defect and skeletal dysplasia.[ncbi.nlm.nih.gov]
  • 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.[ghr.nlm.nih.gov]
Vietnamese
  • In conclusion, we detected two novel nonsense mutations and a partial deletion of EVC/EVC2 in two Vietnamese families with EvC.[ncbi.nlm.nih.gov]
Chills
  • Author information 1 Department of Pediatric Cardiology, University of Minnesota, MMC 94 Delaware St SE, Minneapolis, MN 55455, USA. chills@chc-pa.org Abstract Ellis-van Creveld (EVC) syndrome is a rare genetic abnormality that has been linked to a mutation[ncbi.nlm.nih.gov]
Lymphadenopathy
  • On examination, the child had multiple congenital anomalies and cervical lymphadenopathy. Cardiac examination revealed a pansystolic murmur grade III/VI in left lower parasternal area.[ncbi.nlm.nih.gov]
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.com]
Abdominal Distension
  • Interestingly, he also had severe developmental delay, and suddenly developed excessive abdominal distension at the age of 2. On surgery, extensive necrotic bowel with chronic intestinal pseudo-obstruction was noted.[ncbi.nlm.nih.gov]
Pansystolic Murmur
  • Cardiac examination revealed a pansystolic murmur grade III/VI in left lower parasternal area. Laboratory evaluation revealed significant hypoalbuminemia and hypercholesterolemia, 24 hours urinary protein was 116 mg/hour/m2.[ncbi.nlm.nih.gov]
Periodontitis
  • Treatment involved non-surgical periodontal management, fabrication of veneers and dentine bonded crowns for maxillary anteriors and fixed-fixed resin retained bridge for mandibular arch.[ncbi.nlm.nih.gov]
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]
  • Acromelic shortening of upper and lower limbs, genu valgum, multiple frenula, deformed teeth, short ribs and narrow thorax and congenital heart diseases complete the picture. The patients with the syndrome rarely survive into adulthood.[ncbi.nlm.nih.gov]
  • Here, we report a consanguineous family with a new variety of OFDS associated with acromelic short stature and genu valgum; the features overlapping with Ellis Van Creveld syndrome.[ncbi.nlm.nih.gov]
  • The lower limbs showed rhizomelic shortening with significant genu valgum (knock-knee deformity), small feet with postaxial polydactyly, syndactyly between the second and third toes and hallux valgus.[ncbi.nlm.nih.gov]
  • Genu valgum is typical and is usually secondary to notching and deepening of the lateral aspect of the tibial epiphysis, as well as a shallow femoral intercondylar notch.[healio.com]
Absent Clavicle
  • Additional findings were ichthyosis and plantar keratoderma in the former and absent clavicles in the latter, which have not been reported previously.[ncbi.nlm.nih.gov]
Long Narrow Thorax
  • Other characteristics are polydactyly (six-fingered dwarfism), a long narrow thorax, hydrotic ectodermal dysplasia, hypoplastic nails and teeth, and congenital heart defects such as atrial and ventricular defects and cleft mitral valve.[whonamedit.com]
Low Self-Esteem
  • A 38 year old female diagnosed with Ellis-Van-Creveld syndrome presented with stained teeth and un-aesthetic smile and related that to her low self-esteem and depression.[ncbi.nlm.nih.gov]
Distractibility
  • Varus osteotomy, distraction osteogenesis, or epiphyseal stapling is one treatment option for valgus malalignment to improve appearance, gait, and function.[ncbi.nlm.nih.gov]
Incontinence
  • One of the sibs has urinary incontinence and growth hormone deficiency, which has not been reported earlier in any type of OFDS in the literature.[ncbi.nlm.nih.gov]
Urinary Incontinence
  • One of the sibs has urinary incontinence and growth hormone deficiency, which has not been reported earlier in any type of OFDS in the literature.[ncbi.nlm.nih.gov]

Workup

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.

Left Axis Deviation
  • Electrocardiography showed features of left axis deviation, bi-atrial enlargement and right ventricular hypertrophy.[ncbi.nlm.nih.gov]
Hypercholesterolemia
  • Laboratory evaluation revealed significant hypoalbuminemia and hypercholesterolemia, 24 hours urinary protein was 116 mg/hour/m2.[ncbi.nlm.nih.gov]
Left Anterior Fascicular Block
  • Echocardiogram showed absence of the atrial sept and the basal portion of the ventricular sept and electrochardiogram--right bundle branch block, left anterior fascicular block and left ventricular hypertrophy.[ncbi.nlm.nih.gov]
Ventricular Hypertrophy
  • Echocardiogram showed absence of the atrial sept and the basal portion of the ventricular sept and electrochardiogram--right bundle branch block, left anterior fascicular block and left ventricular hypertrophy.[ncbi.nlm.nih.gov]
  • Electrocardiography showed features of left axis deviation, bi-atrial enlargement and right ventricular hypertrophy.[ncbi.nlm.nih.gov]
Liver Biopsy
  • Sequential liver biopsies during the patient's childhood demonstrated progressive fibrosis that can occur in other chondrodysplastic malformations.[ncbi.nlm.nih.gov]

Treatment

  • The treatment was divided into three stages: growth observation during which the patient wore acrylic plates with artificial anterior teeth; surgical-orthodontic treatment with sagittal split ramus osteotomy; and prosthodontic treatment with removable[ncbi.nlm.nih.gov]
  • Little is known on growth, growth hormone (GH) levels and GH treatment in patients with Ellis-van Creveld syndrome (EvC).[ncbi.nlm.nih.gov]
  • Aesthetics are a major concern with limited manual dexterity, making choice of treatment critical.[ncbi.nlm.nih.gov]
  • The authors report two cases of EVC syndrome with different manifestations, which underwent surgical treatment for polydactyly.[ncbi.nlm.nih.gov]
  • The presence of a variety of oral manifestations, such as fusion of upper lip to the gingival margin, presence of multiple frenula, abnormally shaped and microdontic teeth and congenitally missing teeth requires multidisciplinary dental treatment, with[ncbi.nlm.nih.gov]

Prognosis

  • 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]
  • 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.[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]

Etiology

  • ( 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.[ncbi.nlm.nih.gov]
  • 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]

Epidemiology

  • 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]
  • Epidemiology Frequency Ellis-van Creveld (EVC) syndrome is a rare disease.[emedicine.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]
Sex distribution
Age distribution

Pathophysiology

  • 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]

Prevention

  • Year : 2010 Volume : 21 Issue : 1 Page : 143-145 Oral abnormalities in the Ellis-van Creveld syndrome Department of Pedodontics and Preventive Dentistry, SPPGIDMS, Lucknow, Uttar Pradesh, India Click here for correspondence address and email Date of Submission[ijdr.in]
  • SYNDROME Year : 2007 Volume : 25 Issue : 5 Page : 5-7 Ellis Van Creveld syndrome Department of Pedodontics and Preventive Dentistry, Govt.[jisppd.com]
  • Prevention Genetic counseling is recommended for prospective parents from a high-risk group, or who have a family history of EVC syndrome. References Horton WA, Hecht JT. Disorders for which defects are poorly understood or unknown.[mclarenhealthplan.org]
  • Studies suggest that they prevent normal Sonic Hedgehog signaling in the developing embryo, disrupting the formation and growth of the bones, teeth, and other parts of the body.[ghr.nlm.nih.gov]

References

Article

  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.

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Last updated: 2019-07-11 20:27