Basu Anna P, Low Karen, Ratnaike Thiloka, Rowitch David
Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Paediatric Neurology, Great North Children's Hospital, Newcastle upon Tyne, UK.
Dev Med Child Neurol. 2025 Feb;67(2):177-185. doi: 10.1111/dmcn.16080. Epub 2024 Aug 29.
The original description of cerebral palsy (CP) contained case histories suggesting that perinatal environmental stressors resulted in brain injury and neurodevelopmental disability. While there are clear associations between environmental impact on brain development and CP, recent studies indicate an 11% to 40% incidence of monogenic conditions in patients given a diagnosis of CP. A genetic diagnosis supports the delivery of personalized medicine. In this review, we describe how the Wnt pathway exemplifies our understanding of pathophysiology related to a gene variant (CTNNB1) found in some children diagnosed with CP. We cover studies undertaken to establish the baseline prevalence of monogenic conditions in populations attending CP clinics. We list factors indicating increased likelihood of a genomic diagnosis; and we highlight the need for a comprehensive, accurate, genotype-phenotype reference data set to aid variant interpretation in CP cohorts. We also consider the wider societal implications of genomic management of CP including significance of the diagnostic label, benefits and pitfalls of a genetic diagnosis, logistics, and cost.
脑性瘫痪（CP）最初的描述包含一些病例史，提示围产期环境应激源会导致脑损伤和神经发育障碍。虽然环境对脑发育的影响与CP之间存在明确关联，但最近的研究表明，被诊断为CP的患者中，单基因疾病的发病率为11%至40%。基因诊断有助于提供个性化医疗。在这篇综述中，我们描述了Wnt信号通路如何体现我们对与某些被诊断为CP的儿童中发现的基因变异（CTNNB1）相关的病理生理学的理解。我们涵盖了为确定CP诊所就诊人群中单基因疾病的基线患病率而开展的研究。我们列出了表明基因组诊断可能性增加的因素；并强调需要一个全面、准确的基因型-表型参考数据集，以帮助解释CP队列中的变异。我们还考虑了CP基因组管理的更广泛社会影响，包括诊断标签的意义、基因诊断的益处和陷阱、后勤以及成本。
