Hoshi Kiwamu, Matsuyama Koichi, Oda Yasunori, Shibata Shintaro, Iyo Teruomi, Saito Takeru, Okada Kazuki, Yano Fumiaki, Yamasaki Fumiaki, Nakata Yusuke, Sasaki Tsuyoshi, Niitsu Tomihisa
Department of Psychiatry Chiba University Graduate School of Medicine Chiba Japan.
Department of Child Psychiatry Chiba University Hospital Chiba Japan.
PCN Rep. 2025 Aug 25;4(3):e70195. doi: 10.1002/pcn5.70195. eCollection 2025 Sep.
22q11.2 deletion syndrome is associated with schizophrenia, seizures, and often experience intolerance to antipsychotics. Periventricular nodular heterotopia (PNH) is a neuronal migration disorder that can also be observed in individuals with 22q11.2 deletion syndrome. However, to our knowledge, the use of clozapine in adolescent patients with treatment-resistant schizophrenia and comorbid 22q11.2 deletion syndrome and PNH has not been previously reported.
A 17-year-old female with treatment-resistant schizophrenia was referred to our hospital. She presented with auditory hallucinations, disorganized behavior, and insomnia. Multiple antipsychotics, mood stabilizers, benzodiazepines, and modified electroconvulsive therapy were either ineffective or poorly tolerated due to extrapyramidal symptoms. Brain magnetic resonance imaging (MRI) performed under sedation revealed PNH. Genetic testing confirmed a diagnosis of 22q11.2 deletion syndrome. Clozapine was initiated with close monitoring, and her symptoms gradually improved following a slow titration. She was discharged after approximately 6 months and has remained clinically stable for 15 months.
Brain MRI and genetic testing-even when performed under sedation-may be valuable diagnostic tools in adolescents with treatment-resistant schizophrenia. Furthermore, the presence of structural brain abnormalities does not preclude the efficacy of clozapine, which may remain a viable and effective treatment option in such cases.
22q11.2缺失综合征与精神分裂症、癫痫发作相关，且常对抗精神病药物不耐受。室管膜下结节性异位（PNH）是一种神经元迁移障碍，在22q11.2缺失综合征患者中也可观察到。然而，据我们所知，此前尚未有关于氯氮平用于治疗抵抗性精神分裂症合并22q11.2缺失综合征和PNH的青少年患者的报道。
一名患有治疗抵抗性精神分裂症的17岁女性被转诊至我院。她出现幻听、行为紊乱和失眠症状。多种抗精神病药物、心境稳定剂、苯二氮䓬类药物以及改良电休克治疗要么无效，要么因锥体外系症状而耐受性差。在镇静状态下进行的脑部磁共振成像（MRI）显示存在PNH。基因检测确诊为22q11.2缺失综合征。在密切监测下开始使用氯氮平，经过缓慢滴定后她的症状逐渐改善。大约6个月后她出院，并且在15个月内临床症状保持稳定。
脑部MRI和基因检测——即使是在镇静状态下进行——对于患有治疗抵抗性精神分裂症的青少年可能是有价值的诊断工具。此外，脑部结构异常的存在并不排除氯氮平的疗效；在这种情况下，氯氮平可能仍然是一种可行且有效的治疗选择。
