Two types of early epileptic encephalopathy in a Pitt-Hopkins syndrome patient with a novel TCF4 mutation

Kirikae, Hinako; Uematsu, Mitsugu; Numata‐Uematsu, Yurika; Saijo, Naoya; Katata, Yu; Oikawa, Yoshitsugu; Kikuchi, Atsuo; Yanagi, Kumiko; Kaname, Tadashi; Haginoya, Kazuhiro; Kure, Shigeo

doi:10.1016/j.braindev.2021.09.003

Cited by 3 publications

(3 citation statements)

References 16 publications

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“…Although there is a report of topiramate's effective treatment of epilepsy in PTHS, 7 there are no prior reports in the literature about the use of topiramate for respiratory dysrhythmia in PTHS. There are reports of its use for these symptoms in Rett Syndrome, which can be associated with similar episodes of hyperventilation, apnea, and cyanosis.…”

Section: Discussion/conclusionmentioning

confidence: 99%

A Case Report of Topiramate for Severe Breath Holding Spells in a Teenage Boy with Pitt-Hopkins Syndrome

Bone

Goodspeed

2022

Child Neurology Open

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Pitt-Hopkins syndrome is a rare genetic neurodevelopmental disorder characterized by intellectual disability, delayed motor development, and absent speech. Patients often show symptoms of respiratory dysrhythmia, including episodes of hyperpnea followed by apnea with cyanosis. These spells occur while awake and do not have ictal correlate on electroencephalogram (EEG). The episodes can become quite frequent and can be challenging to treat. We present a case of a teenage patient with Pitt-Hopkins syndrome who had very frequent apneic spells that responded well to treatment with topiramate after limited response to acetazolamide.

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Section: Discussion/conclusionmentioning

confidence: 99%

A Case Report of Topiramate for Severe Breath Holding Spells in a Teenage Boy with Pitt-Hopkins Syndrome

Bone

Goodspeed

2022

Child Neurology Open

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“…This transcription factor is mainly characterized by its regulatory role for the proliferation and differentiation of neuronal and glial progenitor cells (Ross et al, 2003 ). Besides impaired emotion processing, mutations in TCF4 may lead to Pitt‐Hopkins syndrome, characterized by intellectual disabilities as well as altered brain morphology (Kirikae et al, 2021 ; Liu et al, 2018 ). The regulatory role of TCF4 was further demonstrated in schizophrenia by Torshizi et al ( 2019 ) in two independent datasets by means of transcriptional network analysis.…”

Section: Discussionmentioning

confidence: 99%

Regional gene expression patterns are associated with task‐specific brain activation during reward and emotion processing measured with functional MRI

Komorowski

Murgaš

Vidal

et al. 2022

Human Brain Mapping

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The exploration of the spatial relationship between gene expression profiles and taskevoked response patterns known to be altered in neuropsychiatric disorders, for example depression, can guide the development of more targeted therapies. Here, we estimated the correlation between human transcriptome data and two different brain activation maps measured with functional magnetic resonance imaging (fMRI) in healthy subjects. Whole-brain activation patterns evoked during an emotional face recognition task were associated with topological mRNA expression of genes involved in cellular transport. In contrast, fMRI activation patterns related to the acceptance of monetary rewards were associated with genes implicated in cellular localization processes, metabolism, translation, and synapse regulation. An overlap of these genes with risk genes from major depressive disorder genome-wide association studies revealed the involvement of the master regulators TCF4 and PAX6 in emotion and reward processing. Overall, the identification of stable relationships between spatial gene expression profiles and fMRI data may reshape the prospects for imaging transcriptomics studies.

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“…Nearly half of patients with PTHS have spells of abnormal breathing, including hyperventilation, which may be followed by apnea with rapid onset of cyanosis [1] . Breathing spells are consistently only observed while awake and do not have an ictal electroencephalogram (EEG) correlate [11] . This suggests that breathing spells are not epileptic events but could be a behavioral phenomenon or related to autonomic dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Epilepsy and electroencephalography in Pitt-Hopkins syndrome

Bone¹,

Goodspeed²,

Sirsi³

2022

J Transl Genet Genom

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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.

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Two types of early epileptic encephalopathy in a Pitt-Hopkins syndrome patient with a novel TCF4 mutation

Cited by 3 publications

References 16 publications

A Case Report of Topiramate for Severe Breath Holding Spells in a Teenage Boy with Pitt-Hopkins Syndrome

A Case Report of Topiramate for Severe Breath Holding Spells in a Teenage Boy with Pitt-Hopkins Syndrome

Regional gene expression patterns are associated with task‐specific brain activation during reward and emotion processing measured with functional MRI

Epilepsy and electroencephalography in Pitt-Hopkins syndrome

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