350 In 1940, Ellis and van Creveld described a syndrome, char- acterized by ectodermal dysplasia, polydactyly, chondrodyspla- sia, and congenital heart disease. Ellis-van Creveld syndrome, also called chondroectodermal dysplasia, is relatively common in inbred communities, such as the Amish of Lancaster County where it occurs in 1/5000 births compared to 1/60,000 births in the general population.
GENETICS/BASIC DEFECTS
1. Inheritance
a. Autosomal recessive inheritance b. Parental consanguinity in 30% of cases 2. Basic defect
a. Generalized dysplasia of endochondral ossification i. Delayed in the primary centers
ii. Premature in the secondary centers
iii. Leads to short stature with progressive distal shortening of the extremities
b. Caused by mutations in a novel gene, EVC, which is mapped to chromosome 4p16.1
c. Caused by mutations in a second gene, called EVC2, that gives rise to the same phenotype of the syndrome d. May be allelic to Weyers acrodental dysostosis
CLINICAL FEATURES
1. A clinical tetrad a. Chondrodystrophy
i. The most common feature affecting the tubular bones
ii. Disproportionate dwarfism iii. Progressive distal limb shortening
a) Symmetrical
b) Affects the forearms and lower legs b. Polydactyly
i. A constant finding a) Bilateral b) Postaxial
ii. Polydactyly of the hands observed in most cases iii. Polydactyly of the feet observed only in 10% of
cases
c. Ectodermal dysplasia (up to 93%) i. Nails
a) Hypoplastic b) Dystrophic c) Friable
d) Completely absent in some cases ii. Teeth
a) Neonatal teeth b) Partial anodontia c) Small teeth d) Delayed eruption
e) Enamel hypoplasia commonly resulting in abnormally shaped teeth with frequent mal- occlusion
iii. Occasional sparse hair d. Cardiac anomalies (50–60%)
i. A single atrium ii. AV canal
iii. Ventricular septal defect iv. Atrial septal defect
v. Patent ductus arteriosus
vi. The major cause of shortened life expectancy 2. Other clinical findings
a. Other oral lesions
i. A fusion of the anterior portion of the upper lip to the maxillary gingival margin
a) Resulting in absence of mucobuccal fold b) Causing the upper lip to present a slight V-
notch in the middle
ii. Multiple labiogingival frenula frequent iii. Lower alveolar ridge often serrated b. Musculoskeletal anomalies
i. Low-set shoulders ii. A narrow thorax
iii. Frequently lead to respiratory difficulties iv. Knock knees (genu valgum)
v. Lumbar lordosis vi. Broad hands and feet vii. Sausage-shaped fingers c. Genitourinary anomalies (22%)
i. Hypospadias ii. Epispadias iii. Hypoplastic penis
iv. Cryptorchidism v. Vulvar atresia
vi. Focal renal tubular dilation in medullary region vii. Nephrocalcinosis
viii. Renal agenesis ix. Megaureters d. CNS
i. Normal intelligence in most patients
ii. Occasional CNS anomalies or mental retardation
DIAGNOSTIC INVESTIGATIONS
1. Radiography
a. Essential features
i. Postaxial polydactyly
ii. Progressively distal shortening of segments (acromesomelia with relative shortening of the distal and middle segment of the limbs and phalanges)
iii. Generalized thickness and coarseness of bones
b. Other features depending on disease severity and age i. Curvature of the humerus
ii. Enlargement of distal ends of the radii and ulnae iii. Hypoplastic distal phalanges
iv. Short, broad middle phalanges v. Fusion of metacarpals
vi. Fusion of the hamate and capitate bones of the wrists
vii. Supernumerary carpal bone centers viii. Clinodactyly
ix. Synostosis
x. Wedge-shaped tibial epiphyses
xi. Genu valgum with hypoplasia of the upper lateral tibia
xii. Fibula disproportionately smaller than the tibia xiii. Pelvic dysplasia with low iliac wings and spur-
like downward projections at the medial and lateral aspects of the acetabula
xiv. Narrow thorax with short ribs 2. Echocardiography for cardiac malformations
3. Histopathology: disorganization of chondrocytes in the physeal growth zone of the long bones and vertebrae in the prenatal period and retardation of physeal growth zones in the childhood
4. Mutation analysis
GENETIC COUNSELING
1. Recurrence risk a. Patient’s sib: 25%
b. Patient’s offspring: not increased unless the spouse is a carrier
2. Prenatal diagnosis a. Fetoscopy b. Ultrasonography
i. A narrow chest ii. Postaxial polydactyly
iii. Short limbs, especially middle and distal segments iv. A single atrium
c. Molecular genetic testing
i. Using linked microsatellite markers flanking the EVC locus
ii. Mutation analysis of EVC gene 3. Management
a. Dental cares i. Childhood
a) To prevent caries by dietary counseling, plaque control, and oral hygiene instruction b) Crown or composite build-ups for microdonts c) Partial dentures to maintain space and improve mastication, esthetics, and speech because of congenitally missing teeth d) Orthodontic treatment
ii. Adulthood: require implants and prosthetic reha- bilitation to replace congenitally missing teeth b. Cardiac surgery to correct cardiac anomalies c. Urologic management for genitourinary anomalies
d. Orthopedic cares
i. Polydactyly excision ii. Surgery for genu valgum
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Fig. 1. A neonate with small chest and short extremities (Perspect Pediatr Pathol 3:1–40, 1976). The fingernails are small and deformed.
The baby had 6 fingers on each hand. Radiograph of the chest shows short ribs but the vertebral bodies are normal.
Fig. 2. Radiograph of a fetus with Ellis-van Creveld syndrome show- ing short ribs and vertically shortened ilia. The vertebral bodies are unremarkable. Photomicrograph of femoral physeal growth zone shows disorganization of chondrocytes. The physeal growth zone of vertebrae showed better columnization.
Fig. 3. A 10-year-old Lebanese girl, a product of a consanguineous parents, with Ellis-van Creveld syndrome showing oligodontia and malformed teeth, severe nail hypoplasia of the hands and feet, and broad hands with bilateral post-axial polydactyly. Radiographs show polydactyly, fusion of metacarpals and carpal centers, cone epiphyses of the middle and distal phalanges, and genu valgum.
