Wilkinson Niamh R, Cervi Elena, Wagner Bart, Morris-Rosendahl Deborah, Baker Duncan, Flora Harpaul, von Klemperer Kate, Andrew Toby, Ghali Neeti, van Dijk Fleur S
National EDS Service, London North West University Healthcare NHS Trust, London, UK.
Department of Metabolism, Digestion and Reproduction, Section of Genetics and Genomics, Imperial College London, London, UK.
Eur J Hum Genet. 2025 Mar;33(3):368-376. doi: 10.1038/s41431-024-01773-x. Epub 2024 Dec 27.
Vascular Ehlers-Danlos syndrome (vEDS) is a rare inherited connective tissue disorder predominantly caused by pathogenic COL3A1 variants. Characteristic arterial and intestinal fragility and generalised severe tissue friability can lead to clinical events from childhood. We highlight a paucity of literature regarding children diagnosed with vEDS, possibly explained by a restraint in predictive testing, and present data on 63 individuals (23 index cases) with a clinical and genetic diagnosis of vEDS in childhood (<18 years) to address this. Patients were identified through the National Ehlers-Danlos Syndrome (EDS) Service London. We report on 18 events in childhood, recorded in 13 individuals. First events occurred at a median age of 11 years (IQR 0-13) and genetic testing was initiated as a direct result of the first event in 11/13 cases. In the cohort majority, diagnosis was the result of familial genetic testing (55%). Our findings emphasise the importance of offering genetic testing in childhood when there is a positive family history of vEDS and/or features suggestive of a potential inherited connective tissue disorder. Diagnosis in childhood allows for follow-up surveillance and informed multi-disciplinary management, in addition to genetic counselling and patient-led management including lifestyle modification. As seen in adult cohorts, we anticipate children with vEDS will experience the same protective benefit afforded by early diagnosis and present preliminary data on follow-up in childhood. Formal evaluation of the impact that diagnosis of vEDS in childhood has on disease management is needed when sufficient data is internationally available.
血管型埃勒斯-当洛综合征（vEDS）是一种罕见的遗传性结缔组织疾病，主要由致病性COL3A1变异引起。其特征性的动脉和肠道脆弱性以及全身性严重组织脆性可导致儿童期出现临床事件。我们强调关于诊断为vEDS的儿童的文献匮乏，这可能是由于预测性检测受限所致，并呈现了63例（23例索引病例）在儿童期（<18岁）临床和基因诊断为vEDS的数据以解决这一问题。患者是通过伦敦国家埃勒斯-当洛综合征（EDS）服务机构确定的。我们报告了13例个体记录的18例儿童期事件。首次事件发生的中位年龄为11岁（四分位间距0 - 13岁），11/13例患者因首次事件直接启动了基因检测。在该队列中，大多数诊断是家族性基因检测的结果（55%）。我们的研究结果强调，当有vEDS家族史阳性和/或有提示潜在遗传性结缔组织疾病的特征时，在儿童期提供基因检测的重要性。儿童期诊断除了进行遗传咨询和患者主导的管理（包括生活方式改变）外，还能进行随访监测和明智的多学科管理。正如在成人队列中所见，我们预计vEDS儿童将从早期诊断中获得同样的保护益处，并呈现儿童期随访的初步数据。当国际上有足够数据时，需要对儿童期vEDS诊断对疾病管理的影响进行正式评估。
