Ellis-van Creveld Syndrome (Chondroectodermal Dysplasia)

MS Orthopaedics - 20 Marks Answer

1. INTRODUCTION & HISTORICAL BACKGROUND

1. Short-limb dwarfism (acromesomelic)
2. Polydactyly (postaxial)
3. Ectodermal dysplasia (nail and tooth abnormalities)
4. Congenital heart defects

2. GENETICS & MOLECULAR BASIS

• Rheumatology 2-Volume Set (Elsevier, 2022), p. 1381
• Miller's Review of Orthopaedics 9th Edition, Table 1.27

3. PATHOLOGY / PATHOGENESIS

• Hedgehog signaling (sonic hedgehog pathway) - disrupted chondrocyte differentiation
• Fibroblast growth factor signaling
• Wnt signaling pathway

• Short, poorly formed tubular bones
• Abnormal metaphyseal flaring
• Cone-shaped epiphyses
• Premature fusion of carpal and metacarpal bones
• Defective ectodermal structures (nails, teeth)

4. CLINICAL FEATURES

A. FREQUENCY OF FEATURES (GeneReviews, NCBI)

B. MUSCULOSKELETAL FEATURES (Most Relevant for Orthopaedics)

• Disproportionate short stature with predominantly mesomelic and acromelic limb shortening
• Short forearms and lower legs
• Rhizomelic shortening (proximal limb) less prominent
• Adult height: typically 109-150 cm

• Extra digit on the ulnar/fibular side of the hand/foot
• Usually bilateral (>95% of cases for hands)
• Type A polydactyly - well-formed extra digit articulating with the 5th metacarpal or with a broad bifurcated metacarpal
• Associated anomalies with Type A postaxial polydactyly include chondroectodermal dysplasia (Cornelia de Lange, Schinzel syndrome)
• Campbell's Operative Orthopaedics 15th Ed 2026, block42

• One of the most clinically challenging features to manage
• Caused by lateral slanting/flattening of the tibial plateau (the growth plate on the outer/upper portion of tibia is abnormally flattened)
• Can be very severe and progressive
• Often asymmetric
• The genu valgum tends to recur after correction (high recurrence rate)

• Lateral slanting of the tibial plateau
• Trident acetabulum - medially and laterally projecting "spur" from the acetabular floor (acetabular spur projections)
• Small iliac crests
• Cone-shaped epiphyses of phalanges
• Carpal and metacarpal fusions (especially capitate-hamate)
• Bulbous ends of proximal ulnae and distal radii
• Short tubular bones
• Narrow chest with short ribs

• Short forearms
• Fusion of capitate and hamate bones (most common carpal coalition)
• Hypomobile wrists

• Narrow thorax (thoracic dysplasia)
• Short ribs (can cause respiratory compromise in newborns)
• Normal spine (no vertebral anomalies - key differentiating feature from other dysplasias)
• Brachydactyly (short, stubby fingers)

5. ECTODERMAL DYSPLASIA FEATURES

• Nail dystrophy (hypoplastic, dysplastic nails) - 78%
• Dysplastic nails are noted in chondroectodermal dysplasia per Firestein & Kelley's Textbook of Rheumatology
• Nails may be abnormally hypoplastic or absent
• Andrews' Diseases of the Skin confirms onychoatrophy in EVC syndrome

• Neonatal teeth (teeth present at birth - natal teeth)
• Oligodontia (fewer than normal teeth)
• Delayed eruption
• Malformed teeth (peg-shaped, hypoplastic)
• Upper lip abnormality - partial cleft upper lip (28%), frenula abnormalities, "notched" upper lip
• Accessory frenulae binding the upper lip to the gum
• Partial lip fusion (upper lip frenum may be absent or fused to the gum)

6. CARDIAC DEFECTS

• Present in 66% of patients - most common cardiac defect associated with any skeletal dysplasia
• Atrial septal defect (ASD) in >80% of those with cardiac involvement - particularly a large, single atrium (common atrium / cor triloculare biventriculare) - this is the pathognomonic cardiac lesion
• Also: VSD, patent ductus arteriosus, hypoplastic left heart
• ASD in EVC is specifically listed in Fuster and Hurst's The Heart (15th Ed) among syndromes commonly associated with ASD
• Mortality: Nearly 50% of patients die by 18 months of age from cardiopulmonary complications
• The narrow thorax compound with cardiac defects leads to severe respiratory compromise in neonates

7. RADIOLOGY

Plain Radiographs (X-rays)

Prenatal Ultrasound Findings

• Bowing of long bones (EvC is listed among conditions with bowing of long bones on fetal ultrasound per Creasy & Resnik's Maternal-Fetal Medicine)
• Fetal limb shortening (prenatal limb shortening in 36%)
• Polydactyly
• Congenital heart defect
• Narrow thorax
• Associated with increased risk of Down syndrome workup and differentials including: Meckel-Gruber syndrome, oral-facial-digital syndrome, skeletal dysplasias (EvC, short rib-polydactyly), VACTERL

8. DIFFERENTIAL DIAGNOSIS

9. DIAGNOSIS

• Classic tetrad of features
• Physical examination
• X-rays of lower extremities (to monitor genu valgum)

• Sequencing of EVC1 and EVC2 genes identifies mutations in approximately two-thirds of patients
• Additional gene panel: DYNC2LI1, GLI1, WDR35, DYNC2H1, PRKACA, PRKACB, SMO

• Fetal ultrasound (limb shortening, polydactyly, cardiac defects, narrow thorax)
• Molecular genetic testing of chorionic villus sample or amniocentesis if family history known

10. ORTHOPEDIC MANAGEMENT

A. Polydactyly

• Surgical amputation of the extra digit - typically performed at 6-12 months of age
• Goal: functional hand with 5 digits
• The extra digit shares a bifurcated metacarpal in many cases - requires careful surgical planning
• Delay surgery until adequate tissue and bone development

B. Genu Valgum (Knock-knee)

• Medial physeal stapling or 8-plate (tension band plate) on the medial tibial physis and/or medial distal femoral physis
• Slows growth on the medial side, allowing gradual correction
• High recurrence rate is a key issue - additional surgeries often required
• Must be done before skeletal maturity

• For severe deformity or skeletally mature patients
• High tibial osteotomy (varus producing) or distal femoral osteotomy
• Must account for the abnormal tibial plateau morphology
• Again, recurrence is a known complication

• Per physical and rehabilitation medicine assessment
• Strengthening quadriceps and hip abductors
• Gait training and orthotic support (knee-ankle-foot orthoses)

C. Respiratory Support

• Neonatal period: may require mechanical ventilation for severe restrictive lung disease due to narrow thorax
• Ongoing pulmonology follow-up

D. Cardiac Surgery

• Standard cardiac surgery per cardiologist for ASD/VSD closure
• ASD closure (catheter-based or open) as indicated

E. Dental Treatment

• Orthodontic and surgical treatment of dental anomalies
• Extraction of natal teeth if causing feeding difficulties

F. Genitourinary

• Surgical correction of genitourinary malformations (e.g., hypospadias) if indicated

G. Hearing Loss

• Standard audiological assessment and treatment

11. PROGNOSIS

• Nearly 50% die by 18 months from cardiopulmonary complications (narrow thorax + cardiac defects)
• Survivors have normal intelligence (developmental delay only in 9%)
• Motor development generally normal
• Adult height severely reduced: 109-150 cm
• Genu valgum progressively worsens during growth and often recurs post-operatively
• Quality of life improved with timely orthopedic and cardiac intervention

12. GENETIC COUNSELING

• Both parents must be carriers (autosomal recessive) - 25% recurrence risk with each pregnancy
• Prenatal diagnosis available via ultrasound + molecular testing
• EVC syndrome has particularly high prevalence in consanguineous communities and the Old Order Amish
• Carrier testing available for at-risk family members

SUMMARY TABLE (Quick Revision)

• Firestein & Kelley's Textbook of Rheumatology, 2-Volume Set - Skeletal dysplasias section
• Rheumatology, 2-Volume Set (Elsevier, 2022) - Noncollagen gene mutations and skeletal dysplasias
• Campbell's Operative Orthopaedics 15th Ed (2026) - Postaxial polydactyly and associated anomalies
• Miller's Review of Orthopaedics 9th Edition - Inheritance pattern and gene table
• Creasy & Resnik's Maternal-Fetal Medicine - Prenatal skeletal anomalies
• Fuster & Hurst's The Heart, 15th Edition - ASD genetics
• GeneReviews (NCBI NBK596643) - Frequency data and management table
• NORD (rarediseases.org) - Clinical overview