Ellis-Van Creveld Syndrome

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.

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.

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