目的:PTEN错构瘤综合征(PRTS)是一种公认的遗传性肿瘤综合征,目前也被认为是单基因自闭症谱系障碍的常见原因。PHTS个体之间存在大量的表型变异,除了神经发育方面的挑战,PHTS患者可能会经历各种各样的神经系统挑战,其中许多只是最近才被描述。因此,本系统综述旨在总结目前对PHTS患者神经系统疾病知识的广度.
方法:我们使用MEDLINE和EMBASE数据库进行了系统评价,直至2023年1月。我们纳入了报告神经系统症状的研究,症状,并在诊断为PHTS的患者中进行诊断。两名独立的审阅者从每项研究中提取数据(神经诊断和患者详细信息)。病例报告,案例系列,前瞻性研究,并纳入治疗性试验.我们使用JBI的适当工具评估了证据的质量,取决于研究设计。
结果:筛选了一千九百九十六篇文章,90篇文章符合纳入标准。大多数纳入的研究是病例报告(49/90,54%)或小病例系列(31/90,34%)。继发于脑畸形的癫痫,脊髓或颅动静脉畸形引起的神经功能缺损,和罕见的肿瘤,如发育不良的小脑神经节细胞瘤是在所有PHTS患者中报告的更严重的神经系统特征.一项检查神经认知终点的干预性随机对照试验被确定,但未达到其疗效终点。
结论:我们的系统评价定义了PHTS患者的神经系统合并症的广泛范围。神经系统的发现可以根据PTHS患者的发病年龄进行分类。我们的研究强调需要额外的临床试验终点,了解PHTS患者所面临的神经系统挑战。
OBJECTIVE: PTEN hamartoma tumor syndrome (PHTS) is a well-recognized hereditary tumor syndrome and is now also recognized as a common cause of monogenic autism spectrum disorder. There is a vast spectrum of phenotypic variability across individuals with PHTS, and in addition to neurodevelopmental challenges, patients with PHTS may experience a wide variety of neurologic challenges, many of which have only recently been described. Thus, this systematic
review aimed to summarize the breadth of the current knowledge of neurologic conditions in individuals with PHTS.
METHODS: We conducted a systematic
review using the MEDLINE and EMBASE databases until January 2023. We included studies that reported neurologic signs, symptoms, and diagnoses in patients with a diagnosis of PHTS. Two independent reviewers extracted data (neurologic diagnoses and patient details) from each study. Case reports, case series, prospective studies, and therapeutic trials were included. We assessed the quality of evidence using the appropriate tool from the JBI, depending on study design.
RESULTS: One thousand nine hundred ninety-six articles were screened, and 90 articles met the inclusion criteria. The majority of the included studies were case reports (49/90, 54%) or small case series (31/90, 34%). Epilepsy secondary to cerebral malformations, neurologic deficits from spinal or cranial arteriovenous malformations, and rare tumors such as dysplastic cerebellar gangliocytoma are among the more severe neurologic features reported across patients with PHTS. One interventional randomized control trial examining neurocognitive endpoints was identified and did not meet its efficacy endpoint.
CONCLUSIONS: Our systematic
review defines a broad scope of neurologic comorbidities occurring in individuals with PHTS. Neurologic findings can be categorized by age at onset in individuals with PTHS. Our study highlights the need for additional clinical trial endpoints, informed by the neurologic challenges faced by individuals with PHTS.