The Social Genetic & Developmental Psychiatry Centre and The Department of Child and Adolescent Psychiatry, The Institute of Psychiatry, King's College London, London, England,
J Neurodev Disord. 2009 Jun;1(2):102-13. doi: 10.1007/s11689-009-9021-z. Epub 2009 Jul 7.
Autism spectrum disorder (ASD) is a behaviourally defined syndrome where the etiology and pathophysiology is only partially understood. In a small proportion of children with the condition, a specific medical disorder is identified, but the causal significance in many instances is unclear. Currently, the medical conditions that are best established as probable causes of ASD include Fragile X syndrome, Tuberous Sclerosis and abnormalities of chromosome 15 involving the 15q11-13 region. Various other single gene mutations, genetic syndromes, chromosomal abnormalities and rare de novo copy number variants have been reported as being possibly implicated in etiology, as have several ante and post natal exposures and complications. However, in most instances the evidence base for an association with ASD is very limited and largely derives from case reports or findings from small, highly selected and uncontrolled case series. Not only therefore, is there uncertainty over whether the condition is associated, but the potential basis for the association is very poorly understood. In some cases the medical condition may be a consequence of autism or simply represent an associated feature deriving from an underlying shared etiology. Nevertheless, it is clear that in a growing proportion of individuals potentially causal medical conditions are being identified and clarification of their role in etio-pathogenesis is necessary. Indeed, investigations into the causal mechanisms underlying the association between conditions such as tuberous sclerosis, Fragile X and chromosome 15 abnormalities are beginning to cast light on the molecular and neurobiological pathways involved in the pathophysiology of ASD. It is evident therefore, that much can be learnt from the study of probably causal medical disorders as they represent simpler and more tractable model systems in which to investigate causal mechanisms. Recent advances in genetics, molecular and systems biology and neuroscience now mean that there are unparalleled opportunities to test causal hypotheses and gain fundamental insights into the nature of autism and its development.
自闭症谱系障碍（ASD）是一种行为定义的综合征，其病因和病理生理学仅部分了解。在一小部分患有这种疾病的儿童中，确定了一种特定的医学疾病，但在许多情况下，因果关系尚不清楚。目前，被认为是 ASD 可能原因的医学病症包括脆性 X 综合征、结节性硬化症和涉及 15 号染色体 15q11-13 区域的异常。还报道了各种其他单基因突变、遗传综合征、染色体异常和罕见的新生拷贝数变异可能与病因有关，以及一些产前和产后暴露和并发症。然而，在大多数情况下，与 ASD 相关的证据基础非常有限，主要来自病例报告或从小型、高度选择和不受控制的病例系列中得出的发现。因此，不仅存在不确定性，即该病症是否与 ASD 相关，而且对其相关性的潜在基础也知之甚少。在某些情况下，医学病症可能是自闭症的结果，或者仅仅代表潜在病因的相关特征。然而，越来越多的个体中潜在的因果医学病症正在被确定，阐明它们在发病机制中的作用是必要的。事实上，对结节性硬化症、脆性 X 和 15 号染色体异常等病症之间关联的因果机制的研究，正在开始揭示 ASD 病理生理学中涉及的分子和神经生物学途径。因此，从可能因果性医学病症的研究中可以学到很多东西，因为它们代表了更简单和更易于处理的模型系统，可以在其中研究因果机制。遗传学、分子和系统生物学以及神经科学的最新进展意味着，现在有前所未有的机会来检验因果假设，并深入了解自闭症的本质及其发展。
