Ellis-van Creveld Syndrome

Updated: Nov 06, 2017
  • Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Maria Descartes, MD  more...
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Overview

Background

Ellis-van Creveld (EVC) syndrome was first described by physicians Richard WB Ellis (1902-1966) of Edinburgh, Scotland, and Simon van Creveld (1895-1971) of Amsterdam, Netherlands. In the late 1930s, the two pediatricians met on a train while traveling to a pediatrics conference in England and discovered that each had a patient with a similarly distinctive phenotype. In 1940, they formally described the genetic syndrome that bears their names, although they initially called it chondroectodermal dysplasia or mesoectodermal dysplasia. [1]

EVC syndrome, a skeletal dysplasia with an autosomal recessive inheritance pattern, is characterized by disproportionate dwarfism; ectodermal dysplasia; short ribs with a long, narrow chest; postaxial polydactyly; the presence of natal teeth; and a high frequency of congenital heart defects. The images below illustrate some of the syndrome's salient phenotypic features. 

Newborn with Ellis–van Creveld syndrome. Note the Newborn with Ellis–van Creveld syndrome. Note the narrow chest.
Postaxial polydactyly. Postaxial polydactyly.
Newborn with Ellis–van Creveld syndrome. Note the Newborn with Ellis–van Creveld syndrome. Note the narrow chest and disproportionate dwarfism.
Natal teeth and lip tie. Natal teeth and lip tie.
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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 diagnosed with EVC syndrome revealed that in the long bones of patients with this condition, chondrocyte disorganization exists in the cartilage's physeal growth zone. In addition, variable chondrocyte disorganization was seen in the central physeal growth zone of the vertebrae.

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Epidemiology

Frequency

Ellis-van Creveld (EVC) syndrome is a rare disease.  As of 2007, only about 150 cases had been reported since the syndrome's description in the medical literature by Ellis and van Creveld. [3]  In the world population, the frequency of EVC syndrome is 1 per 60,000 to 1 per 200,000 newborns.

Among persons from the Old Order Amish in Lancaster, Pa, however, the incidence is estimated to be 1 case per 200 livebirths. [4]  The frequency of carriers in this population may be as high as 13%.

Mortality/Morbidity

Neonatal phenotypic findings include disproportionate small stature and noted increased severity, with progression from the proximal to distal parts of the limbs; shortening of the middle and distal phalanges; polydactyly affecting the hands (unilateral or bilateral) and, sometimes, feet; and hidrotic ectodermal dysplasia primarily affecting the nails, hair, and teeth. Dental problems are frequent, and natal teeth may be present. [5]

In the neonatal period, the leading causes of death are cardiac anomalies and thoracic dysplasia (with a narrow chest wall), with the latter causing severe respiratory compromise. Approximately 50% of patients with Ellis-van Creveld (EVC) syndrome die in early infancy as a consequence of cardiorespiratory problems.

Congenital cardiac malformations occur in 50-60% of cases and include a number of possible defects, such as a single atrium, patent ductus, defects of the mitral and tricuspid valves, ventricular septal defects (VSD), atrial septal defects (ASD), and hypoplastic left heart syndrome. [3] Significant heart disease may manifest as cardiac murmur, along with failure to thrive, cyanosis, shortness of breath, or other cardinal signs of heart failure.

Limitation of hand function, such as the inability to form a clenched fist, is frequently observed.

Potential end-organ system impact may include the following [6] :

  • Renal diagnoses include  nephrotic syndrome, nephronophthisis, and renal failure [7, 8, 9]
  • Hepatic abnormalities, such as a congenital paucity of bile ducts, can lead to progressive fibrosis and hepatic failure [7, 10]
  • Hematologic/oncologic impact can range from myelodysplastic changes with dyserythropoiesis to acute leukemia [11, 12]

Patients who survive infancy with non–life-threatening pulmonary or cardiac conditions are expected to have a normal life span.

Race

The highest frequency of Ellis-van Creveld (EVC) syndrome has been noted in one particular inbred population, the Old Order Amish community in Lancaster County, Pa, where, as based on research by McKusick, the largest pedigree has been described (52 cases in 30 sibships). [4]  This very high incidence (1 in 200) is due to a founder effect. The Old Order Amish population in Lancaster stems from the 1742 immigration of about 200 Europeans, with the abnormal gene having been traced back to one immigrant couple, Samuel King and his wife. 

The incidence of EVC syndrome also appears to be more common in the native aboriginal population of Western Australia.

Sex

The frequency of Ellis-van Creveld (EVC) syndrome is equal in males and females. The EVC gene is located on autosome #4 and not on the sex chromosomes; hence, the occurrence is independent of the affected patient's sex.

Age

Clinical findings, such as disproportionate extremities, narrow thorax, polydactyly, cardiac defects, and hidrotic ectodermal dysplasia affecting the nails, hair and teeth, are observed and diagnosable at birth.

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Prognosis

A poor prognosis is declared in the neonatal period. Congenital cardiac anomalies and thoracic dysplasia (with a narrow chest wall) causing severe respiratory compromise are leading causes of death at this time.

Patients who survive infancy with non–life-threatening pulmonary or cardiac conditions are expected to have a normal life span. Final adult skeletal height has been difficult to predict. Publications have cited an adult height range of 119 cm (3'11") to 161 cm (5'3"). [13]

Developmentally, most patients have normal intelligence. [3] Case reports have cited patients with associated brain malformations (Dandy-Walker anomaly, hydrocephalus, cerebral heterotopias) and developmental delay. [14]

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Patient Education

The following organizations may provide helpful information for patients and their families:

Little People of America, Inc.

617 Broadway #518

Sonoma, CA 95476

Toll free: (888) LPA-2001 or (888) 572-2001

Direct: (714) 368-3689

Fax: (707) 721-1896

E-mail: info@lpaonline.org

Website: http://www.lpaonline.org/

 

Genetic and Rare Diseases Information Center (GARD), of the National Institutes of Health

PO Box 8126

Gaithersburg, Md 20898-8126

Toll free: (888) 205-2311

Fax: (301) 251-4911

Website: https://rarediseases.info.nih.gov

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