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BRIEF RESEARCH REPORT article

Front. Neurol.
Sec. Neurogenetics
Volume 15 - 2024 | doi: 10.3389/fneur.2024.1428076
This article is part of the Research Topic Genetics in Rare Neurological Diseases: From Discovery to Targeted Treatment View all 10 articles

Clinical characteristics of patients with P4HTM variant-associated epilepsy and therapeutic exploration: a case report and literature review

Provisionally accepted
Yan-Juan Wang Yan-Juan Wang Wen-Guang Hu Wen-Guang Hu Li-Li Zhao Li-Li Zhao Lan Mingping Lan Mingping Jia-Lei Chen Jia-Lei Chen Si-Xiu Li Si-Xiu Li *
  • Chengdu Women and Children’s Central Hospital, Chengdu, China

The final, formatted version of the article will be published soon.

    The P4HTM gene encodes a transmembrane prolyl 4-hydroxylase, which is responsible for the degradation of hypoxia-inducible transcription factors (HIF) under normoxia. Clinically, biallelic P4HTM variants have been identified in patients with hypotonia, hypoventilation, intellectual disabilities, dysautonomia, epilepsy, and eye abnormalities (HIDEA syndrome). Seizure was one of the most prominent symptoms.However, the clinical features of patients with epilepsy associated with P4HTM variants remain unclear. In this report, we describe a one-month-old infant with HIDEA syndrome caused by compound heterozygous P4HTM variants (c.300dupG/p.Gly103Argfs*22 and c.488C>T/p.Ala163Val). The infant presented with clonic seizures of focal onset that responded well to valproate, but with profound intellectual disability and global developmental delay at the last follow-up at three years old. A review of the existing literature indicates that seizures in this population typically begin early in infancy, manifest in multiple types, and are relatively well controlled. Epilepsy seemed unrelated to developmental outcomes or disease progression. Valproate, which has HIF-1α inhibiting properties, may be a promising treatment avenue for this population.

    Keywords: P4HTM gene, Epilepsy, HIDEA syndrome, HIF-1α inhibitor, valproate, case report, review

    Received: 05 May 2024; Accepted: 23 Oct 2024.

    Copyright: © 2024 Wang, Hu, Zhao, Mingping, Chen and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Si-Xiu Li, Chengdu Women and Children’s Central Hospital, Chengdu, China

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