Azma Roxana, Dmytriw Adam A, Biswas Asthik, Pollak Mordechai, Ratjen Felix, Amirabadi Afsaneh, Branson Helen M, Kulkarni Abhaya V, Dirks Peter, Muthusami Prakash
Department of Diagnostic Imaging & Image-Guided Therapy, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Department of Diagnostic Imaging & Image-Guided Therapy, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Pediatr Neurol. 2022 Apr;129:24-30. doi: 10.1016/j.pediatrneurol.2021.12.004. Epub 2021 Dec 30.
Hereditary hemorrhagic telangiectasia (HHT) is a multiorgan vascular dysplasia with limited data regarding its neurovascular manifestations and genotype-phenotype correlation in children. The objective of this study was to describe the neurovascular findings in a large cohort of children with HHT and correlate between phenotype and genotype.
This retrospective study was conducted on 221 children (<18 years) with a definite or possible diagnosis of HHT based on Curacao criteria, or with positive genetics for the mutated genes of ENG, ACVRL-1, and SMAD-4, who also underwent brain MRI and/or conventional angiography. Demographic and clinical information, imaging findings, and follow up information were gathered.
Two hundred twenty-one children with HHT (70.6% genetically confirmed, and 99.5% positive family history) were included, with a median age of 7 years (interquartile range: 3 to 11 years) and 58.8% male predominance. Neurovascular lesions were found in 64 of 221 (28.9%), with 3.1% prevalence of intracranial hemorrhage. The most commonly observed vascular malformations were developmental venous anomalies (48.5%) and brain arteriovenous malformations (AVMs) (31.2%), followed by capillary malformations (14.1%). Multiple AVMs were seen in 10.0% of the cohort. We found no instances of de novo AVM (1281.8 patient-years).A significantly higher proportion of patients with ENG mutations (19.7%) had brain AVM than those with ACVRL-1 (4.9%) and SMAD-4 (0%) mutations (P < 0.01). There was no significant difference in the hemorrhagic risk of shunting lesions associated with ENG (35.3%) or ACVRL-1 (33.3%) positivity (P = 0.9).
We describe the neurovascular imaging and genetic findings from a large pediatric cohort of HHT, to enhance clinical awareness and guide management of patients with HHT.
遗传性出血性毛细血管扩张症（HHT）是一种多器官血管发育异常疾病，关于其在儿童中的神经血管表现及基因型 - 表型相关性的数据有限。本研究的目的是描述一大群HHT儿童的神经血管表现，并将表型与基因型进行关联分析。
本回顾性研究纳入了221名年龄小于18岁的儿童，这些儿童基于库拉索标准被确诊或可能诊断为HHT，或ENG、ACVRL - 1和SMAD - 4基因发生突变且基因检测呈阳性，所有儿童均接受了脑部MRI和/或传统血管造影检查。收集了人口统计学和临床信息、影像学检查结果以及随访信息。
纳入了221名HHT儿童（70.6%经基因确诊，99.5%有家族史阳性），中位年龄为7岁（四分位间距：3至11岁），男性占比58.8%。221名儿童中有64名（28.9%）发现神经血管病变，颅内出血患病率为3.1%。最常见的血管畸形是发育性静脉异常（48.5%）和脑动静脉畸形（AVM）（31.2%），其次是毛细血管畸形（14.1%）。该队列中有10.0%的患者存在多发AVM。未发现新发AVM病例（1281.8患者 - 年）。与ACVRL - 1突变（4.9%）和SMAD - 4突变（0%）的患者相比，ENG突变患者中脑AVM的比例显著更高（19.7%）（P < 0.01）。ENG阳性（35.3%）或ACVRL - 1阳性（33.3%）的分流性病变出血风险无显著差异（P = 0.9）。
我们描述了一大群HHT儿童的神经血管影像学和基因检测结果，以提高临床认识并指导HHT患者的管理。
