Radiology Clinic of Tartu University Hospital; Department of Radiology, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.
Department of Laboratory Genetics, Genetics and Personalized Medicine Clinic, Tartu University Hospital, Tartu, Estonia.
J Child Neurol. 2023 May;38(6-7):373-388. doi: 10.1177/08830738231186233. Epub 2023 Jul 10.
The aim of this study was to evaluate genetic risk factors in term-born children with antenatal periventricular hemorrhagic infarction (PVHI), presumed antenatal periventricular venous infarction and periventricular hemorrhagic infarction in preterm neonates.
Genetic analysis and magnetic resonance imaging were performed in 85 children: term-born children (≥36 gestational weeks) with antenatal periventricular hemorrhagic infarction (n = 6) or presumed antenatal (n = 40) periventricular venous infarction and preterm children (<36 gestational weeks) with periventricular hemorrhagic infarction (n = 39). Genetic testing was performed using exome or large gene panel (n = 6700 genes) sequencing.
Pathogenic variants associated with stroke were found in 11 of 85 (12.9%) children with periventricular hemorrhagic infarction/periventricular venous infarction. Among the pathogenic variants, and variants were found in 7 of 11 (63%) children. Additionally, 2 children had pathogenic variants associated with coagulopathy, whereas 2 other children had other variants associated with stroke. Children with collagenopathies had significantly more often bilateral multifocal stroke with severe white matter loss and diffuse hyperintensities in the white matter, moderate to severe hydrocephalus, moderate to severe decrease in size of the ipsilesional basal ganglia and thalamus compared to children with periventricular hemorrhagic infarction/periventricular venous infarction without genetic changes in the studied genes ( ≤ .01). Severe motor deficit and epilepsy developed more often in children with collagenopathies compared to children without genetic variants ( = .0013, odds ratio [OR] = 233, 95% confidence interval [CI]: 2.8-531; and = .025, OR = 7.3, 95% CI: 1.3-41, respectively).
Children with periventricular hemorrhagic infarction/periventricular venous infarction have high prevalence of pathogenic variants in collagene genes ( and . Genetic testing should be considered for all children with periventricular hemorrhagic infarction/periventricular venous infarction; and genes should be investigated first.
本研究旨在评估产前脑室内出血性梗死（PVHI）、产前脑室内静脉梗死和早产儿脑室内出血性梗死患儿的遗传危险因素。
对 85 名儿童进行了基因分析和磁共振成像检查：足月产儿（≥36 孕周）伴产前脑室内出血性梗死（n=6）或疑似产前脑室内静脉梗死（n=40），早产儿（<36 孕周）伴脑室内出血性梗死（n=39）。基因检测采用外显子或大基因panel（n=6700 个基因）测序。
在 85 例脑室内出血性梗死/脑室内静脉梗死患儿中，发现了 11 例（12.9%）与卒中相关的致病性变异。在这些致病性变异中，7 例（63%）患儿存在 或 变异。此外，2 例患儿存在与凝血障碍相关的致病性变异，另有 2 例患儿存在与卒中相关的其他变异。胶原病患儿更常发生双侧多灶性卒中，伴有严重的白质丢失和白质弥漫性高信号，中重度脑积水，对侧基底节和丘脑体积中度至重度缩小，与研究基因无遗传改变的脑室内出血性梗死/脑室内静脉梗死患儿相比（ ≤ .01）。胶原病患儿更常出现严重运动障碍和癫痫，与无遗传变异的患儿相比（ = .0013，比值比[OR] = 233，95%置信区间[CI]：2.8-531； = .025，OR = 7.3，95% CI：1.3-41）。
脑室内出血性梗死/脑室内静脉梗死患儿胶原基因（ 和 ）致病性变异的发生率较高。应考虑对所有脑室内出血性梗死/脑室内静脉梗死患儿进行基因检测；首先应检测 和 基因。
