PTEN错构瘤综合征(PHTS)包括由种系PTEN突变引起的不同遗传性疾病,在许多身体组织中易诱发多发性错构瘤的发展,也增加了某些类型癌症的风险。由于病理性小脑错构瘤(称为小脑发育不良神经节细胞瘤或Lhermitte-Duclos病)的发展,人们早就知道小脑受累。最近,小脑在自闭症谱系障碍的发病机制中的关键作用已被强调,现在被认为是在可变百分比的PHTS儿童中表达的表型。此外,确实在髓母细胞瘤中也发现了罕见的PTEN变异,即使它们比其他种系基因突变频率低。PTEN及其下游信号酶途径的重要性,PI3K/AKT/mTOR,在人类临床环境和动物模型中都进行了不同程度的研究,不仅导致更好地了解不同疾病的发病机制,而且,最重要的是,确定特定疗法的潜在目标。特别是,PTEN完整性对神经系统组织结构的正常发育做出了重要贡献,包括小脑.因此,在PTEN种系突变患者中,小脑是一个受影响的器官,在不同的疾病中越来越被认识到,然而,在动物模型中,小脑Pten缺失会导致各种功能和组织学改变。在这次审查中,我们总结了在PHTS中观察到的小脑受累的范围及其与种系PTEN突变的关系,以及小脑组织中PTEN缺乏的小鼠模型表达的表型。
PTEN hamartoma tumour syndrome (PHTS) comprises different hereditary conditions caused by germline PTEN mutations, predisposing to the development of multiple hamartomas in many body tissues and also increasing the risk of some types of cancer. Cerebellar involvement in PHTS patients has been long known due to the development of a pathognomonic cerebellar hamartoma (known as dysplastic gangliocytoma of the cerebellum or Lhermitte-Duclos disease). Recently, a crucial role of the cerebellum has been highlighted in the pathogenesis of autism spectrum disorders, now recognised as a phenotype expressed in a variable percentage of PHTS children. In addition, rare PTEN variants are indeed identified in medulloblastoma as well, even if they are less frequent than other germline gene mutations. The importance of PTEN and its downstream signalling enzymatic pathways, PI3K/AKT/mTOR, has been studied at different levels in both human clinical settings and animal models, not only leading to a better understanding of the pathogenesis of different disorders but, most importantly, to identify potential targets for specific therapies. In particular, PTEN integrity makes an important contribution to the normal development of tissue architecture in the nervous system, including the cerebellum. Thus, in patients with PTEN germline mutations, the cerebellum is an affected organ that is increasingly recognised in different disorders, whereas, in animal models, cerebellar Pten loss causes a variety of functional and histological alterations. In this review, we summarise the range of cerebellar involvement observed in PHTS and its relationships with germline PTEN mutations, along with the phenotypes expressed by murine models with PTEN deficiency in cerebellar tissue.