Angwin C, Zschocke J, Kammin T, Björck E, Bowen J, Brady A F, Burns H, Cummings C, Gardner R, Ghali N, Gröbner R, Harris J, Higgins M, Johnson D, Lepperdinger U, Milnes D, Pope F M, Sehra R, Kapferer-Seebacher I, Sobey G, Van Dijk F S
National EDS Service, London North West University Healthcare NHS Trust, London, United Kingdom.
Department of Metabolism, Digestion and Reproduction, Section of Genetics and Genomics, Imperial College London, London, United Kingdom.
Front Genet. 2023 May 31;14:1136339. doi: 10.3389/fgene.2023.1136339. eCollection 2023.
Periodontal Ehlers-Danlos Syndrome (pEDS) is a rare autosomal dominant type of EDS characterised by severe early-onset periodontitis, lack of attached gingiva, pretibial plaques, joint hypermobility and skin hyperextensibility as per the 2017 International EDS Classification. In 2016, deleterious pathogenic heterozygous variants were identified in and , which encode components of the complement system. Individuals with a clinical suspicion of pEDS were clinically and molecularly assessed through the National EDS Service in London and Sheffield and in genetic services in Austria, Sweden and Australia. Transmission electron microscopy and fibroblast studies were performed in a small subset of patients. A total of 21 adults from 12 families were clinically and molecularly diagnosed with pEDS, with variants in all families. The age at molecular diagnosis ranged from 21-73 years (mean 45 years), male: female ratio 5:16. Features of easy bruising (90%), pretibial plaques (81%), skin fragility (71%), joint hypermobility (24%) and vocal changes (38%) were identified as well as leukodystrophy in 89% of those imaged. This cohort highlights the clinical features of pEDS in adults and contributes several important additional clinical features as well as novel deleterious variants to current knowledge. Hypothetical pathogenic mechanisms which may help to progress understanding and management of pEDS are also discussed.
根据2017年国际埃勒斯-当洛综合征（EDS）分类，牙周埃勒斯-当洛综合征（pEDS）是一种罕见的常染色体显性类型的EDS，其特征为严重的早发性牙周炎、无附着龈、胫前斑块、关节活动过度和皮肤过度伸展。2016年，在编码补体系统成分的 和 中发现了有害的致病杂合变异。临床怀疑患有pEDS的个体通过伦敦和谢菲尔德的国家EDS服务机构以及奥地利、瑞典和澳大利亚的基因服务机构进行了临床和分子评估。对一小部分患者进行了透射电子显微镜检查和成纤维细胞研究。共有来自12个家庭的21名成年人被临床和分子诊断为pEDS，所有家庭均存在变异。分子诊断时的年龄范围为21至73岁（平均45岁），男女比例为5:16。发现了易瘀伤（90%）、胫前斑块（81%）、皮肤脆弱（71%）、关节活动过度（24%）和嗓音变化（38%）等特征，以及在89%的成像患者中发现了脑白质营养不良。该队列突出了成人pEDS的临床特征，并为当前知识贡献了几个重要的额外临床特征以及新的有害变异。还讨论了可能有助于推进对pEDS理解和管理的假设致病机制。
