Ellis–van Creveld syndrome

Overview

Ellis–van Creveld syndrome (EvC), also known as chondroectodermal dysplasia, is a rare genetic disorder that affects bone growth, teeth, nails, and heart development. It is characterized by short stature, polydactyly (extra fingers or toes), abnormal development of teeth and nails, and congenital heart defects. The condition was first described by Richard Ellis and Simon van Creveld in 1940. It belongs to a group of disorders known as skeletal dysplasias and is particularly prevalent in certain populations, such as the Old Order Amish community.

Causes

Ellis–van Creveld syndrome is caused by mutations in either the EVC or EVC2 gene, both located on chromosome 4p16. These genes are involved in the Hedgehog signaling pathway, which plays a critical role in skeletal development and tissue patterning. The condition is inherited in an autosomal recessive manner, meaning a person must inherit two copies of the defective gene (one from each parent) to be affected. Carriers (with only one mutated gene) typically show no symptoms.

Symptoms

EvC syndrome presents a range of physical and developmental abnormalities, most of which are evident from birth. Common symptoms include:

• Short stature: Disproportionately short limbs and trunk

• Polydactyly: Extra fingers (usually on the ulnar side) or toes

• Dysplastic nails and teeth: Small, malformed, or missing teeth and underdeveloped or absent fingernails and toenails

• Heart defects: Present in about 50–60% of affected individuals, most commonly atrial septal defect

• Thoracic abnormalities: Narrow chest that may impair respiratory function

• Oral anomalies: Fusion of the upper lip to the gum (lip frenula), cleft lip or palate

• Joint stiffness or limited mobility: Especially in the elbows and knees

• Normal intelligence: Cognitive development is typically unaffected

Diagnosis

Diagnosis of Ellis–van Creveld syndrome is based on clinical features, radiographic findings, and genetic testing. Key diagnostic steps include:

• Physical examination: Observation of characteristic skeletal, dental, and nail anomalies

• X-rays: Reveal skeletal dysplasia, shortened long bones, and characteristic hand/foot abnormalities

• Echocardiography: To detect congenital heart defects

• Genetic testing: Confirms mutations in the EVC or EVC2 genes

• Prenatal diagnosis: Possible through ultrasound or genetic testing in families with known carrier status

Treatment

There is no cure for Ellis–van Creveld syndrome. Treatment focuses on managing individual symptoms and improving quality of life through a multidisciplinary approach. Management may include:

• Cardiac surgery: For correction of congenital heart defects

• Orthopedic care: Management of limb deformities, joint issues, and thoracic restrictions

• Dental treatment: To address missing or malformed teeth

• Physical and occupational therapy: To improve mobility and support motor development

• Respiratory support: In cases of severe chest wall narrowing

• Genetic counseling: For affected families to understand inheritance patterns and future reproductive options

Prognosis

The prognosis for individuals with Ellis–van Creveld syndrome varies depending on the severity of the symptoms, especially the presence of congenital heart defects. With proper medical and surgical care, many individuals survive into adulthood and lead functional lives. While short stature and physical anomalies persist, intellectual abilities are typically normal. Early diagnosis and coordinated care can significantly improve the quality of life and long-term outcomes for those affected.