Introduction

Ellis-Van Creveld Syndrome is a very rare genetic condition, marked by four main signs, as listed below.¹ It is caused by mutations in the EVC and EVC2 genes, and so a diagnosis can be reached according to a series of genetic testing criteria. According to this criterion, individuals tested either have the EVC phenotype (showing signs of the condition) or a family history suggestive of autosomal recessive inheritance.² Management for Ellis-Van Creveld syndrome generally requires a broad approach across a range of specialities, as each symptom requires specific and distinct care.³

Clinical Features

Ellis-Van Creveld syndrome generally presents with the following four symptoms, although patients may not show all (or any) of these:¹

• Chondrodystrophy - more simply, this is abnormal development of cartilage, leading to affected bone growth. This generally presents as shortened ribs
• Postaxial polydactyly - an extra digit on the side of the little finger or little toe
• Ectodermal dysplasia-  abnormal development of skin, hair, nails, teeth and sweat glands. This often shows up as underdeveloped nails and teeth⁴
• Cardiac anomalies - most frequently, an atrial septal defect (commonly referred to as ‘hole in the heart’)³

Less commonly, individuals with Ellis-Van Creveld syndrome have also reported:³

• Undescended testicles (cryptorchidism), or an abnormally located opening of the urine canal in the penis (epispadias)
• Abnormalities in the chest wall, spine or respiratory system
• Restriction of foetal growth, otherwise known as intrauterine growth delay
• Abnormality of the tongue mucous membrane, incisor teeth or missing teeth
• Underdeveloped teeth (microdontia) or missing teeth (hypodontia)
• Underdeveloped lungs
• Abnormality of the kidney
• Abnormality of the urine duct
• Abnormal opening of the urine canal on the underside of the penis (hypospadias)
• Fusion of the wrist bones (capitate-hamate fusion)
• Abnormality of the bones in the pelvis

Very rare symptoms also include:³

• Abnormalities of female genitalia
• Abnormal elbow positioning, referred to as cubitus valgus
• Delayed eruption of teeth
• Delayed skeletal maturation
• Wide ureter (or hydroureter)
• Intellectual disability
• Abnormality of the lips (seen as a thin red border)

The most commonly seen symptoms are related to the mouth or heart. Oral manifestations are found in 70% of cases, although they vary in presentation.⁵ Furthermore, the life expectancy of patients with Ellis-Van Creveld syndrome is generally determined by the progression of their congenital heart disease- almost 50% of patients die during childhood due to cardiopulmonary defects.⁴ 

Diagnosis

Ellis-Van Creveld syndrome can be diagnosed during the prenatal period, from the 18th week of gestation, using a technique called ultrasonography.⁴ This uses high-frequency sound waves to create real-time images of what is happening inside the body. After birth, Ellis-Van Creveld syndrome can also be diagnosed using clinical examinations- this will generally follow the usual tetrad of features outlined above. In order to prevent misdiagnosis, however, it should be noted that the clinical presentation is variable, and each individual will present with a different set of symptoms.⁴ 

In one case history, for example, genetic counselling was used (suggested due to a pre-existing family history of ‘skeletal dysplasia’, otherwise known as malformation of the skeleton).⁶ Following this, a prenatal transabdominal ultrasound showed extra fluid at the back of the neck, a hole in the middle of the heart, extra fingers and shortened middle parts of the arms and legs (where long bones should ordinarily be).⁶ At roughly 13 weeks, techniques known as amniocentesis and cytogenetic analysis were carried out, revealing a mutation in the EVC2 gene.⁶ At 16 weeks, a prenatal ultrasound was carried out, revealing a fetus with short limbs, a poorly formed heart and extra fingers on both hands.⁶ This case study gives an insight into the multiple techniques that can be used to reach a diagnosis of Ellis-Van Creveld syndrome. 

Despite this, there are several  prenatal differential diagnoses that should be considered, along with Ellis-Van Creveld syndrome:⁶

• Short rib polydactyly syndrome
• Bardet-Biedl syndrome
• Orofaciodigital syndrome
• Smith-Lemli-Opitz syndrome
• Hydrolethalus syndrome

Management

Treatment for Ellis-Van Creveld syndrome is symptom-specific, depending on the presentation of each patient.³ It will generally require a large, multidisciplinary approach- this often involves paediatricians, surgeons, cardiologists, dentists, pulmonologists, orthopaedists, urologists, physical and occupational therapists and other medical professionals.³ Following diagnosis, genetic counselling is often recommended for affected individuals and their families.³

Due to the typical symptoms of shortened ribs and narrow chest formations, treatment for respiratory distress is often urgent in patients with Ellis-Van Creveld syndrome, especially as heart failure can present shortly after birth.³ In addition, ectodermal dysplasia can result in natal teeth (teeth present at birth) and extra fingers; natal teeth should be removed due to the likelihood of interrupted feeding, and surgery to remove extra fingers may also be needed.³ 

Other surgical corrections may include:³

• Surgical correction of genu valgum (knock-knees), if required by orthopaedic assessment
• Surgery to correct any heart, genital or urinary abnormalities, if medically indicated

Summary

Ellis-van Creveld syndrome is a rare autosomal recessive disorder caused by mutations in the EVC or EVC2 genes. It classically presents with a tetrad of symptoms: short ribs and short stature (chondrodystrophy), extra fingers or toes (postaxial polydactyly), malformed teeth, nails, and hair (ectodermal dysplasia), and congenital heart defects (most often an atrial septal defect). Although these are typical features, there is a wide array of less likely, but possible presentations, such as respiratory, skeletal and urinary difficulties. Diagnosis can be made prenatally through ultrasound and confirmed with genetic testing, or after birth through the use of clinical examinations. Management is multidisciplinary and extremely individual to each individual’s symptoms, with prognosis depending largely on cardiac and respiratory complications.