Epilepsy and electroencephalography in Pitt-Hopkins syndrome

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.