Wang Yan-Juan, Li Si-Xiu, Hu Wen-Guang, Zhao Li-Li, Lan Mingping, Chen Jia-Lei
Department of Pediatric Neurology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Institute of Electronic and Information Engineering of UESTC in Guangdong, Dongguan, China.
Front Neurol. 2024 Nov 8;15:1428076. doi: 10.3389/fneur.2024.1428076. eCollection 2024.
The gene encodes a transmembrane prolyl 4-hydroxylase, which is responsible for the degradation of hypoxia-inducible transcription factors (HIF) under normoxia. Clinically, biallelic 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 variants remain unclear. In this report, we describe a one-month-old infant with HIDEA syndrome caused by compound heterozygous 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 3 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.
该基因编码一种跨膜脯氨酰4-羟化酶，其在常氧条件下负责缺氧诱导转录因子（HIF）的降解。临床上，已在患有肌张力减退、通气不足、智力残疾、自主神经功能障碍、癫痫和眼部异常（HIDEA综合征）的患者中鉴定出双等位基因变异。癫痫发作是最突出的症状之一。然而，与这些变异相关的癫痫患者的临床特征仍不清楚。在本报告中，我们描述了一名1个月大的婴儿，其患有由复合杂合变异（c.300dupG/p.Gly103Argfs*22和c.488C>T/p.Ala163Val）引起的HIDEA综合征。该婴儿出现局灶性发作的阵挛性癫痫发作，对丙戊酸盐反应良好，但在3岁的最后一次随访时存在严重智力残疾和全面发育迟缓。对现有文献进行回顾表明，该人群中的癫痫发作通常在婴儿期早期开始，表现为多种类型，且相对易于控制。癫痫似乎与发育结局或疾病进展无关。具有HIF-1α抑制特性的丙戊酸盐可能是该人群有前景的治疗途径。
