Ellis-van Creveld Syndrome

Ellis-van Creveld Syndrome

Ellis-van Creveld (EvC) syndrome, also known as chondroectodermal dysplasia, is a rare genetic disorder characterized by short-limb dwarfism, polydactyly, ectodermal dysplasia, and congenital heart defects. It was first described in 1940 by Richard W. B. Ellis and Simon van Creveld.

Epidemiology

  • Rare disorder with an estimated prevalence of 1 in 60,000 to 1 in 200,000 live births
  • Higher prevalence in certain populations, such as the Amish community of Lancaster County, Pennsylvania (1 in 5,000)
  • No gender predilection
  • Present at birth

Historical Context

EvC syndrome is named after Richard W. B. Ellis and Simon van Creveld, who independently described the condition in the 1940s. It is one of a group of genetic disorders known as ciliopathies, which are caused by defects in the structure or function of cilia.

Genetics of Ellis-van Creveld Syndrome

Inheritance Pattern

EvC syndrome is inherited in an autosomal recessive manner. This means:

  • Both parents must be carriers of a mutated gene to have an affected child
  • Each child of carrier parents has a 25% chance of being affected
  • Siblings of an affected individual have a 25% chance of being affected, even if they are asymptomatic

Causative Genes

Two genes have been identified as causative for EvC syndrome:

  1. EVC gene: Located on chromosome 4p16
  2. EVC2 gene: Also located on chromosome 4p16, in close proximity to EVC

These genes encode proteins that are involved in hedgehog signaling pathways, which are crucial for proper embryonic development.

Molecular Mechanisms

  • EVC and EVC2 proteins localize to the basal bodies of primary cilia
  • They play a role in transducing hedgehog signals during development
  • Mutations in these genes disrupt hedgehog signaling, leading to the characteristic features of EvC syndrome

Genotype-Phenotype Correlations

While genotype-phenotype correlations are not fully established, some observations include:

  • Mutations in either EVC or EVC2 can cause the full spectrum of EvC syndrome
  • Some EVC2 mutations have been associated with a milder phenotype called Weyers acrofacial dysostosis

Clinical Features of Ellis-van Creveld Syndrome

Skeletal Abnormalities

  • Short-limb dwarfism (disproportionate short stature)
    • Adult height typically ranges from 109 to 155 cm
  • Postaxial polydactyly of the hands (rarely of the feet)
  • Short ribs
  • Narrow chest
  • Knock knees (genu valgum)
  • Fusion of the wrist bones (carpal fusion)

Ectodermal Dysplasia

  • Hypoplastic fingernails and toenails
  • Sparse, fine hair
  • Dental abnormalities
    • Natal teeth (present at birth)
    • Partial anodontia (missing teeth)
    • Peg-shaped teeth
    • Enamel hypoplasia

Cardiovascular Abnormalities

  • Present in about 60% of cases
  • Most common: atrial septal defects, particularly common atrium
  • Other defects may include:
    • Ventricular septal defects
    • Patent ductus arteriosus
    • Hypoplastic left heart syndrome

Other Features

  • Respiratory problems due to narrow chest
  • Genitourinary abnormalities (e.g., epispadias, cryptorchidism)
  • Strabismus
  • Normal intelligence in most cases

Diagnosis of Ellis-van Creveld Syndrome

Clinical Diagnosis

Diagnosis is primarily based on clinical features. The presence of the following suggests EvC syndrome:

  1. Short-limb dwarfism
  2. Postaxial polydactyly
  3. Ectodermal dysplasia (particularly dental and nail abnormalities)
  4. Congenital heart defects (especially common atrium)

Imaging Studies

  • Skeletal radiographs: To assess bone abnormalities
  • Echocardiography: To evaluate cardiac defects
  • Chest X-ray: To assess rib and chest wall abnormalities

Genetic Testing

  • Molecular genetic testing of EVC and EVC2 genes
    • Sequence analysis
    • Deletion/duplication analysis
  • Useful for confirming diagnosis and genetic counseling

Prenatal Diagnosis

  • Possible in families with known mutations
  • Ultrasound can detect some features (e.g., short limbs, polydactyly) as early as 18 weeks gestation

Differential Diagnosis

  • Jeune syndrome (asphyxiating thoracic dystrophy)
  • Short rib-polydactyly syndromes
  • McKusick-Kaufman syndrome
  • Weyers acrofacial dysostosis

Management of Ellis-van Creveld Syndrome

Management of EvC syndrome is multidisciplinary and focused on treating specific symptoms and complications.

Orthopedic Management

  • Surgical correction of polydactyly
  • Treatment of genu valgum if severe
  • Potential limb lengthening procedures
  • Physical therapy to improve mobility

Dental Care

  • Regular dental check-ups
  • Orthodontic treatment as needed
  • Prosthetic teeth for missing dentition

Cardiac Care

  • Surgical repair of congenital heart defects
  • Regular cardiac follow-up
  • Antibiotic prophylaxis for endocarditis when indicated

Respiratory Management

  • Monitoring for respiratory complications
  • Treatment of respiratory infections
  • Potential need for oxygen supplementation

Other Interventions

  • Genetic counseling for families
  • Psychosocial support
  • Regular developmental assessments
  • Ophthalmological follow-up for strabismus

Prognosis

Prognosis varies depending on the severity of symptoms, particularly cardiac involvement:

  • Early mortality is often due to cardiorespiratory problems
  • Those surviving infancy often have a normal life expectancy
  • Quality of life can be good with appropriate management


Further Reading
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