EBF3 Neurodevelopmental Disorder

Excerpt

Clinical characteristics: EBF3 neurodevelopmental disorder (EBF3-NDD) is associated with developmental delay (DD) / intellectual disability (ID), speech delay, gait or truncal ataxia, hypotonia, behavioral problems, and facial dysmorphism. Variability between individuals with EBF3-NDD is significant. Although all affected children have DD noted in early infancy, intellect generally ranges from mild to severe ID, with two individuals functioning in the low normal range. Less common issues can include genitourinary abnormalities and gastrointestinal and/or musculoskeletal involvement. To date, 42 symptomatic individuals from 39 families have been reported.

Diagnosis/testing: The diagnosis of EBF3-NDD is established in a proband with suggestive findings and a heterozygous pathogenic variant in EBF3 identified by molecular genetic testing.

Management: Treatment of manifestations: Developmental delay / intellectual disability, speech delay, hypotonia and ataxia, behavioral issues, genitourinary abnormalities, gastrointestinal involvement, and musculoskeletal involvement are managed as per standard care.

Surveillance: Follow up of manifestations at each clinic visit.

Genetic counseling: EBF3-NDD is an autosomal dominant disorder typically caused by a de novo pathogenic variant. If a parent is known to have the EBF3 pathogenic variant identified in the proband, the risk to the sibs of inheriting the pathogenic variant is 50%. If the EBF3 pathogenic variant identified in the proband cannot be detected in the leukocyte DNA of either parent, the recurrence risk to sibs is slightly greater than that of the general population because of the possibility of parental germline mosaicism. Once the EBF3 pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.