Ellis-van Creveld Syndrome

Excerpt

Clinical characteristics: Ellis-van Creveld (EVC) syndrome is characterized by postaxial polydactyly of the hands, disproportionate short stature with short limbs, dystrophic and/or hypoplastic nails, dental and oral manifestations, congenital heart disease, and radiologic abnormalities (narrow chest, short ribs, short tubular bones, bulbous ends of the proximal ulnae and distal radii, carpal and metacarpal fusions, cone-shaped epiphyses of phalanges, small iliac crests, acetabular spur projections [trident ilia], and lateral slanting of the tibial plateau). Other less common and more variable features include postaxial polydactyly of the feet, upper lip defect, and developmental delay.

Diagnosis/testing: The diagnosis of EVC syndrome is established in a proband with characteristic clinical and radiographic findings and biallelic pathogenic variants in DYNC2H1, DYNC2LI1, EVC, EVC2, GLI, SMO, or WDR35 or a heterozygous pathogenic variant in PRKACA or PRKACB identified by molecular genetic testing.

Management: Treatment of manifestations: Surgical amputation for polydactyly if desired; surgical correction of genu valgum as needed; physical therapy as needed; mechanical ventilation may be required in the neonatal period in those with severe restrictive lung disease; orthodontic and/or surgical treatment of dental anomalies; standard treatment for congenital heart disease; developmental services as needed; surgical correction of genital urinary malformations as needed; standard treatment for hearing loss.

Surveillance: Monitor growth at least annually throughout childhood; orthopedic evaluation with radiographic assessment as needed; physical and rehabilitation medicine evaluation as needed; assessment for manifestations of respiratory failure and/or restrictive lung disease as needed; monitor for dental eruption, overcrowding, and dental morphology annually throughout childhood; echocardiogram as needed; monitor developmental progress and educational needs at each visit until adulthood; hearing evaluation as needed if hearing loss is present.

Pregnancy management: Cesarean delivery is recommended in pregnant women with EVC syndrome who have pelvic/hip abnormalities.

Genetic counseling: EVC syndrome caused by pathogenic variants in DYNC2H1, DYNC2LI1, EVC, EVC2, GLI, SMO, or WDR35 is inherited in an autosomal recessive manner. EVC syndrome caused by pathogenic variants in PRKACA or PRKACB (accounting for 2% of affected individuals) is inherited in an autosomal dominant manner.

Autosomal recessive inheritance: If both parents are known to be heterozygous for an EVC syndrome-related pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being heterozygous, and a 25% chance of inheriting neither of the familial pathogenic variants. Once the EVC syndrome-related pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal and preimplantation genetic testing are possible.