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Bone et al. J Transl Genet Genom 2022;6:169-78 Journal of Translational
DOI: 10.20517/jtgg.2021.56
Genetics and Genomics

Original Article Open Access

Epilepsy and electroencephalography in Pitt-
Hopkins syndrome

Megan Bone, Kimberly Goodspeed, Deepa Sirsi

Department Pediatrics, Division Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Correspondence to: Dr. Deepa Sirsi, Department Pediatrics, Division Neurology, University of Texas Southwestern Medical
Center, 5323, Harry Hines Blvd, Dallas, TX 75390, USA. E-mail: Deepa.Sirsi@utsouthwestern.edu

How to cite this article: Bone M, Goodspeed K, Sirsi D. Epilepsy and electroencephalography in Pitt-Hopkins syndrome. J Transl
Genet Genom 2022;6:169-78. https://dx.doi.org/10.20517/jtgg.2021.56

Received: 29 Oct 2021 First Decision: 13 Jan 2022 Revised: 21 Jan 2022 Accepted: 17 Mar 2022 Published: 26 Apr 2022

Academic Editors: Sanjay Gupta, Richard E. Frye Copy Editor: Tiantian Shi Production Editor: Tiantian Shi

Abstract
Aim: Pitt-Hopkins syndrome (PTHS) is a rare neurodevelopmental disorder caused by mono-allelic loss of function
variants of transcription factor 4 (TCF4), which plays a key role in early brain developmental and neuronal
differentiation. Up to one-half of patients with PTHS will have epilepsy; however, little is known about the
characteristic electroencephalogram (EEG) findings in this population. Because there is significant phenotypic
overlap between PTHS and other neurodevelopmental disorders such as Angelman syndrome and Rett syndrome,
which have characteristic EEG patterns, exploration of a potential EEG signature in patients with PTHS was
warranted.

Methods: We conducted a retrospective review of clinical EEGs in patients with PTHS.

Results: In this cohort of patients with PTHS (n = 16), over half had abnormal EEGs; however, no characteristic EEG
signature was identified. Further, all patients with epilepsy (5/16) had focal onset seizures with or without
secondary generalization, and all five had focal abnormalities on EEG. There was no specific correlation between
EEG results and developmental trajectories or age in our patient group, and there was no clear genotype-phenotype
correlation.

Conclusion: Although a distinctive EEG signature was not identified, all individuals with epilepsy in our cohort had
focal onset seizures with corresponding focal epileptiform discharges or focal slowing on EEG. Future studies are
needed to fully elucidate the spectrum of EEG findings in PTHS and explore the pathogenesis of focal seizures in a
disorder of neuronal differentiation and development.

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

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