Clinical Characteristics of Seizures and Epilepsy in Individuals With Recurrent Deletions and Duplications in the 16p11.2 Region

Christelle Moufawad El Achkar; Alyssa Rosen; Sudha Kilaru Kessler; Kyle J Steinman; Sarah J Spence; Melissa Ramocki; Elysa Jill Marco; LeeAnne Green Snyder; John E Spiro; Wendy K Chung; Poduri Annapurna; Elliott H Sherr

doi:10.1212/NXG.0000000000200018

Clinical Characteristics of Seizures and Epilepsy in Individuals With Recurrent Deletions and Duplications in the 16p11.2 Region

Neurol Genet. 2022 Aug 5;8(5):e200018. doi: 10.1212/NXG.0000000000200018. eCollection 2022 Oct.

Affiliation

¹ Department of Neurology (C.M.E.A., S.J.S., P.A.), Boston Children's Hospital, Harvard Medical School, MA; Departments of Neurology and Pediatrics (A.R., S.K.K.S.C.E.), Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia; Department of Neurology (K.J.S.), Seattle Children's Hospital, University of Washington, Seattle; Center for Vestibular and Balance Disorders (M.R.), University Otolaryngology Inc., East Greenwich; Children's Neurodevelopmental Center (M.R.), Hasbro Children's Hospital, Brown University, Providence, RI; Department of Neurodevelopmental Medicine (E.J.M.), Cortica Healthcare, San Rafael; Department of Radiology (E.J.M.), University of California San Francisco; Simons Foundation (L.G.S., J.E.S.); Department of Pediatrics (W.K.C.), Columbia University Irving Medical Center, New York; Department of Neurology (E.H.S.), University of California, San Francisco; and Weil Institute of Human Genetics and Neurosciences (E.H.S.), University of California, San Francisco.

Abstract

Background and objectives: Deletions and duplications at 16p11.2 (BP4 to BP5; 29.5-30.1 Mb) have been associated with several neurodevelopmental and neuropsychiatric disorders including autism spectrum disorder, intellectual disability (ID), and schizophrenia. Seizures have also been reported in individuals with these particular copy number variants, but the epilepsy phenotypes have not been well-delineated. We aimed to systematically characterize the seizure types, epilepsy syndromes, and epilepsy severity in a large cohort of individuals with these 16p11.2 deletions and duplications.

Methods: The cohort of ascertained participants with the recurrent 16p11.2 copy number variant was assembled through the multicenter Simons Variation in Individuals Project. Detailed data on individuals identified as having a history of seizures were obtained using a semistructured phone interview and review of medical records, EEG, and MRI studies obtained clinically or as part of the Simons Variation in Individuals Project.

Results: Among 129 individuals with the 16p11.2 deletion, 31 (24%) had at least one seizure, including 23 (18%) who met criteria for epilepsy; 42% of them fit the phenotype of classic or atypical Self-limited (Familial) Infantile Epilepsy (Se(F)IE). Among 106 individuals with 16p11.2 duplications, 16 (15%) had at least one seizure, including 11 (10%) who met criteria for epilepsy. The seizure types and epilepsy syndromes were heterogeneous in this group. Most of the individuals in both the deletion and duplication groups had well-controlled seizures with subsequent remission. Pharmacoresistant epilepsy was uncommon. Seizures responded favorably to phenobarbital, carbamazepine, and oxcarbazepine in the deletion group, specifically in the Se(F)IE, and to various antiseizure medications in the duplication group.

Discussion: These findings delineate the spectrum of seizures and epilepsies in the recurrent 16p11.2 deletions and duplications and provide potential diagnostic, therapeutic, and prognostic information.

Grants and funding

P50 HD105354/HD/NICHD NIH HHS/United States