Elucidating the Genetic Landscape of Cerebral Palsy Following Perinatal Cerebrovascular Events

IF 2 3区医学 Q2 CLINICAL NEUROLOGY

Pediatric neurology Pub Date : 2026-01-01 Epub Date: 2025-10-07 DOI:10.1016/j.pediatrneurol.2025.09.023

Liene Thys MD , Diane Beysen MD, PhD , Sandra Kenis MD , Lieve Verstraete MD , Sabine Laroche MD , Sven Dekeyzer MD , Katrien Janssens PhD , Marije Meuwissen MD, PhD

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引用次数: 0

Abstract

Background

Cerebral palsy (CP) is a heterogeneous neurodevelopmental disorder resulting from damage to the developing brain. While perinatal ischemic and hemorrhagic cerebrovascular events are well-established causes, the potential genetic contribution to these injuries remains underexplored. This study investigated the role of genetic factors in a selected CP cohort secondary to perinatal cerebrovascular injury and explored helpful clinical characteristics that may guide genetic evaluation.

Methods

Chromosomal microarray and exome sequencing were performed in 61 individuals diagnosed with CP secondary to perinatal cerebrovascular injury, of which 37 with ischemic and 24 with hemorrhagic brain injury.

Results

A genetic diagnosis was established in five out of 61 cases (8.2%) with a striking difference between the hemorrhagic and ischemic groups: four out of 24 cases (16.7%) with hemorrhagic injury had a confirmed genetic diagnosis compared to only one out of 37 (2.7%) in the ischemic group. Three hemorrhagic cases carried (likely) pathogenic variants in COL4A1. One additional case carried a de novo 12pter duplication, a previously unreported association with perinatal brain hemorrhage. The single diagnosis in the ischemic group was a mosaic JAG1 variant related to Alagille syndrome.

Conclusions

Our findings underscore the value of genetic testing in children with CP due to perinatal hemorrhagic brain injury, with a seemingly important role for COL4A1. Less diagnoses were made in the ischemic group, suggesting a potential multifactorial underlying pathophysiology. Further research in larger cohorts and by using genome-wide technologies is essential in further elucidating the genetic architecture of perinatal cerebrovascular injury.

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阐明围生期脑血管事件后脑瘫的遗传格局

背景：脑瘫（CP）是一种由发育中的大脑损伤引起的异质神经发育障碍。虽然围产期缺血性和出血性脑血管事件是公认的原因，但这些损伤的潜在遗传贡献仍未得到充分探讨。本研究探讨遗传因素在围生期脑血管损伤继发CP队列中的作用，并探讨可能指导遗传评价的有益临床特征。方法对61例围生期脑血管损伤继发CP患者进行染色体微阵列和外显子组测序，其中缺血性脑损伤37例，出血性脑损伤24例。结果61例出血性损伤患者中有5例（8.2%）有基因诊断，出血性损伤患者24例（16.7%）有基因诊断，而缺血性损伤患者37例（2.7%）只有1例。三例出血性病例携带（可能）COL4A1致病性变异。另外一个病例携带新生12pter复制，这是以前未报道的与围产期脑出血的关联。缺血性组的单一诊断是与Alagille综合征相关的马赛克JAG1变异。结论基因检测在围产儿出血性脑损伤CP患儿中具有重要意义，COL4A1基因可能发挥重要作用。缺血组的诊断较少，提示潜在的多因素病理生理。在更大的队列中进行进一步的研究，并使用全基因组技术，对于进一步阐明围产期脑血管损伤的遗传结构至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pediatric neurology 医学-临床神经学

CiteScore

4.80

自引率

2.60%

发文量

176

审稿时长

78 days

期刊介绍： Pediatric Neurology publishes timely peer-reviewed clinical and research articles covering all aspects of the developing nervous system. Pediatric Neurology features up-to-the-minute publication of the latest advances in the diagnosis, management, and treatment of pediatric neurologic disorders. The journal''s editor, E. Steve Roach, in conjunction with the team of Associate Editors, heads an internationally recognized editorial board, ensuring the most authoritative and extensive coverage of the field. Among the topics covered are: epilepsy, mitochondrial diseases, congenital malformations, chromosomopathies, peripheral neuropathies, perinatal and childhood stroke, cerebral palsy, as well as other diseases affecting the developing nervous system.