20 Chondroectodermal Dysplasia
Chondroectodermal Dysplasia 627
Ellis-Van Creveld syndrome, EVC
Dwarfism, acromesomelic shortening of extremities, postaxial polydactyly of hands, cardiac malforma- tions, ectodermal dysplasia of nails and teeth Frequency: 0.9 per 100,000 births.
Genetics
Autosomal recessive (OMIM 225500); gene locus, EVC1 mapped to 4p16; allelic to Weyers acrodental dysostosis. Ellis-van Creveld syndrome can also be caused by mutations in a nonhomologous gene EVC2, located close to the EVC gene in a head-to- head configuration.
Clinical Features
• Disproportionately short-limbed dwarfism identi- fiable at birth (average adult height 109–152 cm)
• Distal limb shortening
• Normal head and facies, except for a mild defect of upper lip (fusion of its middle portion with gingiva)
• Neonatal teeth, hypodontia, premature loss of teeth
• Congenital heart defects (atrial septal defect, sin- gle atrium, atrioventricular canal defect, persist- ent upper left vena cava)
• Pulmonary insufficiency with narrow chest
• Epispadias, hypospadias
• Postaxial polydactyly, brachydactyly
• Hypoplastic, deep-set nails
• Genu valgum Differential Diagnosis
• Asphyxiating thoracic dysplasia
• Heart-hand syndrome IV
• Oculo-cerebro-facial syndrome, Kaufman type
Radiographic Features Hands and Feet
• Postaxial polydactyly, with or without fusion of metacarpals/metatarsals and/or phalanges
• Supernumerary carpal bones
• Cone-shaped epiphyses of middle phalanges (type 37 of Giedion)
• Hypoplasia of distal phalanges
• Carpal fusion (hamate and capitate)
• Missing tarsal bones
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Fig. 20.1. a Patient 1, age 3 years and 5 months. b Patient 2, age 15 years. (Reprinted, with permis- sion, from Mastroiacovo et al.
1990)
a b
Extremities
• Short and broad tubular bones
• Hypoplasia and caudad slant of lateral portion of proximal end of tibia
• Genu valgum
• Exostosis of medial aspect of proximal tibial shaft
• Bony spike in medial side of distal metaphysis of humerus (newborn)
• Enlarged proximal end of ulna and distal end of radius
• Thick, bowed femurs and humeri
• Severe shortening of fibula
Pelvis (Normalization of Pelvic Shape with Age)
• Iliac wings of reduced height
• ‘Trident’ appearance of acetabular margins, with hook-like projections from the medial and lateral borders
• Small sciatic notches
• Premature ossification of capital femoral epiphysis
Chest
• Short ribs, narrow thorax (not mandatory)
• Pectus carinatum
Chondroectodermal Dysplasia 628
Fig. 20.2. Patient 3, age 2 years. Note narrow, elongated thorax, with short and wide ribs, and increased size of the heart.
(Reprinted, with permission, from Canepa et al. 1996)
Fig. 20.3. Patient 4, age 3 months.
The ilia are short in their cranio- caudal diameter, the acetabula have a trident appearance due to downward-directed hook-like projections from the medial and lateral acetabular borders. Note advanced ossification of the femoral heads
Bibliography
Canepa G, Maroteaux P, Pietrogrande V. Sindromi dismorfiche e malattie costituzionali dello scheletro. Piccin, Padova, 1996
Da Silva EO, Janovitz D, de Albuquerque SC. Ellis-van Creveld syndrome: report of 15 cases in an inbred kindred. J Med Genet 1960; 17: 349–56
Digilio MC, Marino B, Giannotti A, Dallapiccola B. Single atrium, atrioventricular canal/postaxial hexadactyly indi- cating Ellis-van Creveld syndrome. Hum Genet 1995; 96:
251–3
Digilio MC, Marino B, Ammirati A, Borzaga U, Giannotti A, Dallapiccola B. Cardiac malformations in patients with oral-facial-skeletal syndromes: clinical similarities with heterotaxia. Am J Med Genet 1999; 84: 350–6
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McKusick VA, Egeland JA, Eldridge R, Krusen DE. Dwarfism in the Amish. I. The Ellis-van Creveld syndrome. Bull Johns Hopkins Hosp 1964; 115: 306–36
Ruiz-Perez VL, Ide SE, Strom TM, Lorenz B, Wilson D, Woods K, King L, Francomano C, Freisinger P, Spranger S, Marino B, Dallapiccola B, Wright M, Meitinger T, Polymeropoulos MH, Goodship J. Mutations in a new gene in Ellis-van Crev- eld syndrome and Weyers acrodental dysostosis. Nat Genet 2000; 24: 283–6.
Ruiz-Perez VL, Tompson SW, Blair HJ, Espinoza-Valdez C, La- punzina P, Silva EO, Hamel B, Gibbs JL,Young ID, Wight MJ, Goodship JA. Mutations in two nonhomologous genes in a head-to-head configuration cause Ellis-van Creveld syn- drome. Am J Hum Genet 2003; 72: 728–32
Taylor GA, Jordan CE, Dorst SK, Dorst JP. Polycarpaly and other abnormalities of the wrist in chondroectodermal dysplasia: the Ellis-van Creveld syndrome. Radiology 1984;
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Chondroectodermal Dysplasia 629
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Fig. 20.4. Patient 3, age 2 years. The long bones are short and heavy, the proximal tibial shafts are wide, with defective ossifi- cation of the lateral portion and subsequent caudad lateral slanting of the tibial plateaus and knock-knee deformity. The fibulas are proximally deficient. (Reprinted, with permission, from Canepa et al. 1996)
Fig. 20.5 a, b. Patient 3, age 2 years.
Note bilateral postaxial poly- dactyly, with widened or bifid 5th metacarpal, and duplicated proxi- mal and middle phalanges. Note also cone-shaped epiphyses of proximal and middle phalanges, hypoplastic middle phalanges, and absent distal phalanges.
(Reprinted, with permission, from Canepa et al. 1996)
a b
