Bolton Patrick F
Department of Child Psychiatry and Centre for Social, Genetic and Developmental Psychiatry, The Institute of Psychiatry, Kings College, Denmark Hill, London SE5 8AF, UK.
Ment Retard Dev Disabil Res Rev. 2004;10(2):126-31. doi: 10.1002/mrdd.20024.
Tuberous sclerosis is a genetic condition that is strongly associated with the development of an autism spectrum disorder. However, there is marked variability in expression, and only a subset of children with tuberous sclerosis develop autism spectrum disorder. Clarification of the mechanisms that underlie the association and variability in expression will potentially throw light on the biological processes involved in the etiology of idiopathic forms of autism spectrum disorder. Current evidence indicates that the likelihood of a child with tuberous sclerosis developing an autism spectrum disorder is greater if the child has a mutation in the TSC2 gene, although autism can and does develop in children with TSC1 mutations. The likelihood is also greater if the child has early-onset infantile spasms that are difficult to control, especially if there is an epileptiform focus in the temporal lobes. The emerging evidence is consistent with the notion that early onset electrophysiological disturbances within the temporal lobes (and perhaps other locations) has a deleterious effect on the development and establishment of key social cognitive representations concerned with processing social information, perhaps especially from faces. However, alternative mechanisms to account for the findings cannot yet be ruled out. Future research will have to employ prospective longitudinal designs and treatment trials to clarify the processes involved.
结节性硬化症是一种与自闭症谱系障碍的发展密切相关的遗传性疾病。然而,其表现存在显著差异,只有一部分结节性硬化症患儿会发展为自闭症谱系障碍。阐明这种关联及表现差异背后的机制,可能会为特发性自闭症谱系障碍病因中的生物学过程带来启示。目前的证据表明,如果患有结节性硬化症的儿童TSC2基因发生突变,那么其发展为自闭症谱系障碍的可能性更大,不过TSC1基因突变的儿童也能够且确实会发展出自闭症。如果儿童患有难以控制的早发性婴儿痉挛,尤其是颞叶存在癫痫样病灶,那么其发展为自闭症谱系障碍的可能性也更大。新出现的证据与这样一种观点一致,即颞叶(或许还有其他部位)内的早发性电生理紊乱会对与处理社会信息相关的关键社会认知表征的发展和建立产生有害影响,可能对面部信息的处理影响尤为明显。然而,目前还不能排除其他解释这些发现的机制。未来的研究将必须采用前瞻性纵向设计和治疗试验来阐明其中涉及的过程。