Mitchell Rebecca, Barton Sarah, Harvey A Simon, Williams Katrina
Developmental Medicine, The Royal Children's Hospital, 50 Flemington Road, Parkville, Victoria, 3052, Australia.
Department of Neurology, The Royal Children's Hospital, 50 Flemington Road, Parkville, Victoria, 3052, Australia.
Syst Rev. 2017 Mar 8;6(1):49. doi: 10.1186/s13643-017-0448-0.
Tuberous sclerosis complex (TSC) is an autosomal dominant condition, caused by mutations in either the TSC1 or TSC2 gene. It has widespread systemic manifestations and is associated with significant neurological morbidity. In addition to seizures and cerebral pathology including cortical tubers, subependymal nodules, subependymal giant cell astrocytoma and abnormal white matter, there are recognised neuropsychiatric difficulties including intellectual disability, autism spectrum disorder (ASD) and a range of learning and behaviour problems, recently conceptualised as "tuberous sclerosis-associated neuropsychiatric disorders", or "TAND". ASD in TSC is of particular importance because (1) it affects up to 50% of people with TSC and is a source of considerable difficulty for them and their families and (2) it provides a model for considering neurobiological pathways involved in ASD. Multiple factors are implicated in the development of ASD in TSC, including (1) seizures and related electrophysiological factors, (2) cerebral pathology, (3) genotype and (4) child characteristics. However, the neurobiological pathway remains unclear. We will conduct a systematic review to investigate and synthesise existing evidence about the role of these risk factors, individually and in combination, in leading to the development of ASD.
Our review will report on all studies that include one or more of four predefined risk factors in the development of ASD in children with TSC. We will search five databases: MEDLINE, EMBASE, PubMed, The Cochrane Library and Web of Science (Conference Proceedings Citation Index). Studies will be selected for reporting after two authors independently (1) review all titles and abstracts, (2) read full text of all appropriate papers and (3) assess for bias using the Newcastle-Ottawa Scale recommended by the Guidelines for Meta-Analysis and Systematic Reviews of Observational Studies (MOOSE guidelines) and the ROBINS-I.
To our knowledge, this is the first systematic review investigating multiple risk factors in the development of ASD in children with TSC. Clarifying the evidence in this area will be important to researchers in the field and to clinicians providing prognostic information to families.
PROSPERO CRD42016042841.
结节性硬化症（TSC）是一种常染色体显性疾病，由TSC1或TSC2基因突变引起。它具有广泛的全身表现，并伴有严重的神经功能障碍。除了癫痫发作和脑部病变，包括皮质结节、室管膜下结节、室管膜下巨细胞星形细胞瘤和白质异常外，还存在公认的神经精神问题，包括智力残疾、自闭症谱系障碍（ASD）以及一系列学习和行为问题，最近被概念化为“结节性硬化症相关神经精神障碍”，或“TAND”。TSC中的ASD尤为重要，因为（1）它影响高达50%的TSC患者，给他们及其家庭带来了相当大的困难；（2）它为研究ASD涉及的神经生物学途径提供了一个模型。TSC中ASD的发展涉及多种因素，包括（1）癫痫发作及相关电生理因素，（2）脑部病变，（3）基因型，以及（4）儿童特征。然而，神经生物学途径仍不清楚。我们将进行一项系统综述，以调查和综合现有证据，了解这些风险因素单独或共同作用导致ASD发展的作用。
我们的综述将报告所有包含TSC儿童ASD发展中四个预定义风险因素中一个或多个因素的研究。我们将检索五个数据库：MEDLINE、EMBASE、PubMed、Cochrane图书馆和科学网（会议论文引文索引）。在两位作者独立（1）审查所有标题和摘要，（2）阅读所有合适论文的全文，以及（3）使用观察性研究的Meta分析和系统评价指南（MOOSE指南）和ROBINS-I推荐的纽卡斯尔-渥太华量表评估偏倚后，将选择研究进行报告。
据我们所知，这是第一项调查TSC儿童ASD发展中多种风险因素的系统综述。阐明该领域的证据对该领域的研究人员以及向家庭提供预后信息的临床医生来说都很重要。
PROSPERO CRD42016042841。
