EED-Related Overgrowth

Clinical characteristics: EED-related overgrowth is characterized by fetal or early childhood overgrowth (tall stature, macrocephaly, large hands and feet, and advanced bone age) and intellectual disability that ranges from mild to severe. To date, EED-related overgrowth has been reported in eight individuals.

Diagnosis/testing: The diagnosis of EED-related overgrowth is established in a proband with suggestive findings and a heterozygous germline EED pathogenic variant by molecular genetic testing.

Management: Treatment of manifestations: Developmental delay / intellectual disability requires early referral for developmental support and educational interventions tailored to the child's needs. Seizures, cervical spine instability, palatal abnormalities, kyphoscoliosis, congenital heart defects, cryptorchidism, and ophthalmologic findings are treated per standard practice.

Surveillance: Routine assessment of the following: development; spine for scoliosis or deformities; joint range of motion for joint contractures; and eyes for refractive errors, myopia, and strabismus.

Agents/circumstances to avoid: Activities that involve rapid neck motion and/or possible trauma to the head and neck region (e.g., contact sports or thrill rides at amusement parks) because of the possible increased risk for cervical spine instability.

Genetic counseling: EED-related overgrowth is inherited in an autosomal dominant manner. To date all probands whose parents have undergone molecular genetic testing have the disorder as a result of a de novo EED pathogenic variant. The risk to the sibs of the proband depends on the genetic status of the proband's parents: if the EED pathogenic variant found in the proband cannot be detected in the leukocyte DNA of either parent, the recurrence risk to sibs is estimated to be 1% because of the theoretic possibility of parental germline mosaicism. Once a family member has a confirmed molecular diagnosis of EED-related overgrowth, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.