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.

中文翻译：

---

种系 PTEN 突变携带者的小脑表型

PTEN错构瘤综合征 (PHTS) 包括由种系引起的不同遗传性疾病PTEN突变，容易在许多身体组织中形成多种错构瘤，并增加某些类型癌症的风险。由于特有的小脑错构瘤（称为小脑发育不良神经节细胞瘤）的发展，PHTS 患者的小脑受累早已为人所知。或 Lhermitte-Duclos 病）。最近，小脑在自闭症谱系障碍的发病机制中的关键作用被强调，现在被认为是在不同比例的 PHTS 儿童中表达的一种表型。此外，罕见的PTEN确实在髓母细胞瘤中也发现了变异，即使它们比其他种系基因突变频率较低。PTEN及其下游信号传导酶通路 PI3K/AKT/mTOR 已在人类临床环境和动物模型中进行了不同水平的研究，不仅可以更好地了解不同疾病的发病机制，而且最重要的是，可以确定潜在的靶点用于特定疗法。尤其，PTEN完整性对神经系统（包括小脑）组织结构的正常发育做出重要贡献。因此，在患者中PTEN由于种系突变，小脑是一个受影响的器官，在不同的疾病中越来越多地被认识到，而在动物模型中，小脑普滕损失导致各种功能和组织学改变。在这篇综述中，我们总结了在 PHTS 中观察到的小脑受累范围及其与种系的关系PTEN突变，以及小鼠模型表达的表型PTEN小脑组织缺乏。