Kukulka Natalie A, Singh Shriya, Whitehead Matthew T, Dobyns William B, Chang Taeun, Kousa Youssef A
Division of Neurology, Children's National Hospital, Washington, DC 20010, USA.
Department of Radiology, Children's National Hospital, Washington, DC 20010, USA.
Brain Commun. 2025 Aug 17;7(5):fcaf298. doi: 10.1093/braincomms/fcaf298. eCollection 2025.
Pontocerebellar hypoplasia is a rare neurodevelopmental disorder that results from differences in formation and function of the pons, cerebellum and cerebrum. It can be diagnosed prenatally or postnatally with a combination of clinical, neuroimaging and genetic data obtained over time. The diagnosis of pontocerebellar hypoplasia usually portends severe developmental delay, epilepsy and/or neurodegeneration in childhood. Here we perform a comprehensive review with the primary goal of evaluating published evidence addressing the clinical and genetic features of pontocerebellar hypoplasia by type and subtype. Secondly, we summarize neurodiagnostic patterns of pontocerebellar hypoplasia and demonstrate its spectrum. Finally, we provide recommendations in diagnosis, prognosis and management for the neurologist. To address these goals, we performed an extensive review of published literature from 1912 to 2022. We identified 191 publications by combining search results from PubMed, OMIM and cross-referenced bibliographies. Publications on developmental neuroanatomy, not pertaining to pontocerebellar hypoplasia or published in a foreign language were excluded. We performed both qualitative (1912-1993) and quantitative (1993-2022) analyses to understand the current classification of this disease as it pertains to genetic and neurodiagnostic features of pontocerebellar hypoplasia by type and subtype. Our review shows that the most reported types of pontocerebellar hypoplasia are 1, 2 and 6; less frequently described are 3, 4 and 9. Very few cases are described for all other subsequent pontocerebellar hypoplasia types. Mutations in , , and (genes that regulate RNA processing and basic cellular metabolism) are the most frequently reported pathological mutations in pontocerebellar hypoplasia. The neuroradiographic features of pontocerebellar hypoplasia are complex and evolve over time, affecting the pons, cerebellum, vermis, cortex and cerebral white matter. In conclusion, pontocerebellar hypoplasia is a rare neurodevelopmental disorder, often the result of genetic dysfunction in basic neural metabolism. The diagnosis conveys significant implications for the affected individual and their families and requires a combination of clinical, neuroradiographic, and genetic testing to best inform type/subtype categorization of pontocerebellar hypoplasia.
脑桥小脑发育不全是一种罕见的神经发育障碍，由脑桥、小脑和大脑的形成及功能差异所致。它可通过综合一段时间内获取的临床、神经影像学和基因数据在产前或产后进行诊断。脑桥小脑发育不全的诊断通常预示着儿童期严重的发育迟缓、癫痫和/或神经退行性变。在此，我们进行了一项全面综述，主要目的是评估已发表的证据，按类型和亚型阐述脑桥小脑发育不全的临床和基因特征。其次，我们总结了脑桥小脑发育不全的神经诊断模式并展示其范围。最后，我们为神经科医生提供诊断、预后和管理方面的建议。为实现这些目标，我们对1912年至2022年发表的文献进行了广泛综述。通过合并来自PubMed、OMIM的搜索结果及交叉引用的参考文献，我们确定了191篇出版物。排除了与脑桥小脑发育不全无关或以外语发表的发育神经解剖学方面的出版物。我们进行了定性分析（1912 - 1993年）和定量分析（1993 - 2022年），以了解该病目前与脑桥小脑发育不全按类型和亚型划分的基因及神经诊断特征相关的分类情况。我们的综述表明，报道最多的脑桥小脑发育不全类型是1型、2型和6型；较少描述的是3型、4型和9型。所有其他后续脑桥小脑发育不全类型的病例描述极少。在 、 、 和 （调控RNA加工及基本细胞代谢 的基因）中的突变是脑桥小脑发育不全中最常报道的病理性突变。脑桥小脑发育不全的神经影像学特征复杂且随时间演变，影响脑桥、小脑、蚓部、皮质和脑白质。总之，脑桥小脑发育不全是一种罕见的神经发育障碍，通常是基本神经代谢中基因功能障碍的结果。该诊断对受影响的个体及其家庭具有重大意义，需要结合临床、神经影像学和基因检测，以最好地为脑桥小脑发育不全的类型/亚型分类提供信息。
