Alomarı Omar, Bebek Ogun, Turkyilmaz Ayberk, Sager Safiye Gunes
Hamidiye International School of Medicine, University of Health Sciences, 3400, Istanbul, Türkiye.
Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey.
Seizure. 2025 Jan;124:35-38. doi: 10.1016/j.seizure.2024.11.009. Epub 2024 Nov 17.
HIDEA syndrome (MIM: #618493) is a rare autosomal recessive disorder characterized by hypotonia, hypoventilation, intellectual disability, dysautonomia, epilepsy, and eye anomalies. We present the case of a Turkish female with developmental and epileptic encephalopathy, highlighting a novel compound heterozygous variation in the P4HTM gene.
A 6-year and 11-month-old girl with early infantile epileptic encephalopathy and abnormal eye movements since the neonatal period has been presented to our clinic. Despite severe developmental delays and a happy demeanor, she showed significant hypotonia and autistic behaviors. Genetic testing revealed a novel heterozygous splice-site variant (c.436+1G>T) in intron 2 and a previously reported missense variant (c.934G>A; p.E312 K) in exon 6 of the P4HTM gene. Imaging showed cortical atrophy and thin corpus callosum, but no dystonia was observed. The patient's phenotype aligns with most reported cases of HIDEA syndrome, yet developmental epileptic encephalopathy had not been documented previously in such patients, emphasizing the uniqueness of this case.
This case is the first to associate P4HTM gene variants with epileptic encephalopathy, expanding the phenotypic spectrum of HIDEA syndrome. It underscores the importance of genetic testing and reanalysis in undiagnosed developmental and epileptic encephalopathies. The novel genetic variations identified in this study underscore the necessity for continuous genetic exploration and personalized clinical management to improve outcomes for patients with this rare but impactful syndrome. Finally, the association between developmental epileptic encephalopathy, the patient's clinical presentation, and EEG findings suggests a compelling link to the P4HTM gene.
HIDEA综合征（MIM：#618493）是一种罕见的常染色体隐性疾病，其特征为肌张力减退、通气不足、智力残疾、自主神经功能障碍、癫痫和眼部异常。我们报告了一例患有发育性和癫痫性脑病的土耳其女性病例，突出了P4HTM基因中的一种新的复合杂合变异。
一名6岁11个月大的女孩自新生儿期起就患有早期婴儿癫痫性脑病和异常眼动，已被转诊至我们的诊所。尽管存在严重的发育迟缓且性格开朗，但她表现出明显的肌张力减退和自闭症行为。基因检测显示，P4HTM基因第2内含子中有一个新的杂合剪接位点变异（c.436+1G>T），第6外显子中有一个先前报道的错义变异（c.934G>A；p.E312K）。影像学检查显示皮质萎缩和胼胝体变薄，但未观察到肌张力障碍。该患者的表型与大多数报道的HIDEA综合征病例一致，但此前此类患者中尚未记录到发育性癫痫性脑病，强调了该病例的独特性。
该病例首次将P4HTM基因变异与癫痫性脑病相关联，扩展了HIDEA综合征的表型谱。它强调了基因检测和重新分析在未确诊的发育性和癫痫性脑病中的重要性。本研究中鉴定出的新基因变异强调了持续进行基因探索和个性化临床管理的必要性，以改善这种罕见但有影响的综合征患者的治疗效果。最后，发育性癫痫性脑病、患者的临床表现和脑电图结果之间的关联表明与P4HTM基因存在令人信服的联系。
