Ellis–van Creveld syndrome is a recessively inherited single-gene disorder that results in short-limbed dwarfism, polydactyly, cardiac abnormalities in 50% to 60% of cases, fingernail dystrophy, oral frenulae, and defective teeth. It was first described in 1940 (Ellis and van Creveld, 1940). The other name for the condition, chondroectodermal dysplasia, does not adequately describe the extent of tissue involvement. Ellis–van Creveld syndrome is characterized by multisystem abnormalities, encompassing: (1) ectodermal dysplasia, affecting the teeth, nail, hair, gums, and lips but not the skin or sweat glands; (2) mesodermal involvement, affecting bone growth and shape, formation of the heart, and occasionally, the kidneys; and (3) endodermal involvement, affecting formation of the lungs and liver (Blackburn and Belliveau, 1971). At least three of the four following criteria are required for diagnosis: ectodermal dysplasia, chondrodysplasia, polydactyly, or the presence of congenital heart disease (Hill, 1977).

The chondrodystrophy in this condition is manifested by shortening of the extremities, with the distal segments more markedly affected than the proximal segments. In addition, there is metaphyseal thickening of the long bones, and curvature of the weight-bearing bones (Lynch et al., 1968). In Ellis–van Creveld syndrome, the fibula is usually 50% of its normal length (Feingold, 1966). Pathologic studies performed on long bones in affected patients reveal a decreased number of cartilage cells in the cartilage plate and a disorganized columnar arrangement of the chondrocytes (Blackburn and Belliveau, 1971).

Distinctive cardiac abnormalities are found in this syndrome, such as single atrium or large atrioseptal defect (Blackburn and Belliveau, 1971). Other cardiac abnormalities associated with this condition include aortic atresia, hypoplastic ascending aorta, and hypoplastic left ventricle (Blackburn and Belliveau, 1971).

Speculation exists as to whether King Richard III of England (1452-1485) had Ellis–van Creveld syndrome. He was the product of a consanguineous union, which makes an autosomal recessive condition more likely. In their writings, both Shakespeare and Sir Thomas Moore alluded to the presence of neonatal teeth, short stature, a skeletal dysplasia, and a crooked back when describing Richard III (Aird and McIntosh, 1978).

Ellis–van Creveld syndrome has been described in both sexes and all ethnic groups. The incidence of the syndrome is approximately 1 in 60,000 livebirths (Zangwill et al., 1988). It is notable that the syndrome is much more common in highly inbred genetic isolates. The birth frequency of Ellis–van Creveld syndrome is 5 in 1000 livebirths in the old-order Amish population of Pennsylvania (McKusick et al., 1964; Goldblatt et al., 1992). McKusick et al. described 52 cases of Ellis–van Creveld syndrome in 30 sibships in Lancaster County, Pennsylvania. They estimated that 13% of the Amish population was heterozygous for the gene mutation that resulted in Ellis–van Creveld syndrome (McKusick et al., 1964). All affected members can trace their lineage to one founding couple who emigrated to the United States during the 18th century from Southwestern Germany (McKusick, 2000). Other relatively isolated populations have also described an increased incidence of Ellis–van Creveld syndrome. For example, the incidence of Ellis–van Creveld syndrome in Western Australian aborigines is 1 in 6123 livebirths. This population has a calculated carrier frequency of the gene mutation of 1 in 39 individuals, making the Western Australian aborigines the second most common group worldwide to carry the mutation (Goldblatt et al., 1992). Also, a relatively high incidence of the disorder has been reported in an inbred rural Brazilian community (Oliveira da Silva et al., 1980).

Sonographic findings that have been described in fetuses with Ellis–van Creveld syndrome include short long bones with normal density, a narrow thorax, appropriate weight for gestational age, and the presence of hand polydactyly, with the malformed finger usually occurring on the ulnar side (Guschmann et al., 1999; Tongsong and Chanprapaph, 2000) (Figure 94-1). Polydactyly of the feet only occurs in 10% of cases (Bui et al., 1984; Qureshi et al., 1993). Congenital heart disease, manifesting as an atrioseptal defect, ventriculoseptal defect, or a single atrium occurs in 50% to 60% of cases (Oliveira da Silva et al., 1980; Zangwill et al., 1988). Two patients have been described with Ellis–van Creveld syndrome and Dandy–Walker malformation (Zangwill et al., 1988), but, in general, central nervous system defects are not associated with the condition.

The earliest prenatal diagnosis of Ellis–van Creveld syndrome was made at 12 weeks in a family at risk for the condition (Dugoff et al., 2001). Both hands were noted to have polydactyly and there were no normal septal structures in the fetal heart. Increased nuchal translucency (NT) measurement has been reported in association with Ellis–van Creveld syndrome (Venkat-Raman et al., 2005).

The combined use of fetoscopy and ultrasound examination for prenatal diagnosis of Ellis–van Creveld syndrome was described in two families at risk for the condition due to previously affected offspring. In one case, sonography demonstrated a shortened femur and humerus. Fetoscopy permitted the visualization of the left hand, which had a well-formed sixth digit. On the basis of these findings, a presumed diagnosis of Ellis–van Creveld syndrome was made, and the condition was verified after termination (Mahoney and Hobbins, 1977).

The differential diagnosis includes Jeune syndrome (asphyxiating thoracic dystrophy and short-rib polydactyly syndrome (see Chapter 95). Patients with Jeune syndrome may have similar radiologic and sonographic features, but do not have polydactyly, nail dystrophy, or the oral findings that are considered pathognomonic of Ellis–van Creveld syndrome. Also, the narrow chest seen in Jeune syndrome is less severe in Ellis–van Creveld syndrome. Jeune syndrome is also associated with cystic renal dysplasia. Another consideration in the prenatal diagnosis of Ellis–van Creveld syndrome is achon-droplasia (see Chapter 89) but, in achondroplasia, there is more striking proximal shortening of the limbs. Ellis–van Creveld syndrome is characterized by mild micromelia and distal shortening of the limbs. In the postnatal differential diagnosis, ectodermal dysplasia might be considered for a patient with mild features of Ellis–van Creveld syndrome. However, patients affected with ectodermal dysplasia have completely normal bone growth and morphology and their defects are limited to the hair, teeth, nails, and sweat glands. Characteristically, patients with ectodermal dysplasia do not have polydactyly. Finally, Weyers acrodental dyostosis is in the differential diagnosis. It presents with polydactyly and similar heart defects to Ellis–van Creveld but is not associated with short stature.