Authors :
Presenting Author: Kaitlin Angione, MS – Children's Hospital Colorado
Megan Abbott, MD – University of Colorado
Megan Stringfellow, BS – Children's Hospital Colorado
Kristie Malik, MD – University of Colorado
Andrea Miele, PhD – Children's Hospital Colorado
Morgan Jolliffe, Psy.D. – Children's Hospital Colorado
Kaiti Syverson, BS – Project 8p Foundation
Jacob Borello, BS – Project 8p Foundation
Lauren Chaby, PhD, MS – Project 8p Foundation
Bina Maniar, MBA – Project 8p Foundation
Scott Demarest, MD – Children's Hospital Colorado
Rationale:
8p-related disorders are genetic conditions associated with chromosomal rearrangements on the short arm of chromosome 8. These rearrangements—including deletions, duplications, and inverted duplications with deletions (invdupdel(8p))—typically occur de novo and are not inherited. Invdupdel(8p) is the most common of these rearrangements, with an estimated incidence of 1 in 10,000 to 30,000 live births. The phenotype varies with rearrangement type and commonly includes structural brain and cardiac abnormalities, intellectual disability, autism, and epilepsy. While prior studies have described epilepsy in 8p-related disorders, none have provided an in-depth characterization.
Methods:
This study aimed to characterize the epilepsy phenotype in patients with 8p-related disorders seen at Children’s Hospital Colorado (CHCO) and/or participating in the Project 8p Foundation Natural History Study (NHS). Key objectives included determining epilepsy prevalence, age of seizure onset, efficacy of treatment, and EEG features. We also assessed differences in epilepsy presentation and severity among patients with invdupdel(8p), isolated deletions, and isolated duplications. A retrospective chart review was conducted for patients seen in the CHCO Neurogenetics Multidisciplinary Clinic from 2020 to 2024. Clinical data including demographics, genotype, epilepsy history, and EEG findings were collected. Presence of epilepsy and genotype were able to be combined between CHCO patients and those in the Project 8p Natural History Study. Descriptive statistical analysis was performed on the entire group and subgroups.
Results:
The cohort included 162 patients with 8p-related disorders (42 at CHCO, 120 from the Project 8p NHS). Overall, 32% of patients (53/162) had experienced at least one lifetime seizure. Within each rearrangement subgroup, 37% (30/81) of those with invdupdel(8p), 35% (16/46) with 8p deletions, and 15% (4/26) with 8p duplications had at least one seizure. Average age of seizure onset was 3.4 years, with a range from neonatal onset to 16.9 years. Among CHCO patients with epilepsy (11/42), only one had intractable epilepsy, while 9 became seizure-free, including 5 off medications. EEG abnormalities were present in 43% of patients (18/42), most commonly showing generalized background slowing and posterior epileptiform discharges. No cases met criteria for DEE with Spike Wave Activation in Sleep (DEE-SWAS) or infantile epileptic spasms syndrome (IESS).
Conclusions:
This study provides the first detailed analysis of epilepsy in individuals with 8p-related disorders. While epilepsy is relatively common within 8p, it is typically, but not always, well controlled with available medications. Genotype-specific patterns emerged, with invdupdel(8p) associated with the highest epilepsy prevalence and 8p duplication with the lowest. Further research in larger cohorts is warranted to validate these findings.
Funding:
The CHCO Neurogenetics Multidisciplinary Clinic and clinical research involving patients seen in this clinic are partially funded by the Project 8p Foundation.