Faculty of Medicine, Vilnius University, M.K. Ciurlionio st. 21, Vilnius, Lithuania.
Center of Cardiothoracic Surgery, Clinic of Cardiovascular Diseases, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Santariskiu St. 2, Vilnius, Lithuania.
BMC Pediatr. 2023 Oct 28;23(1):539. doi: 10.1186/s12887-023-04357-8.
Marfan syndrome is a genetic connective tissue disorder affecting skeletal, ocular, and cardiovascular organ systems. Previous research found that pathogenic variants clustered in exons 24-32 of fibrillin-1 (FBN1) gene result in more severe clinical phenotypes. Furthermore, genotype-phenotype correlation studies suggested that more severe cardiovascular phenotypes were related to variants held responsible for haploinsufficiency. Our objective was to analyze the differences in clinical manifestations and genotypes of individuals with early-onset Marfan syndrome and to assess their impact on management strategies.
We analyzed clinical and genetic data of a new patient with early-onset Marfan syndrome together with 51 previously reported ones in the PubMed database between 1991 and 2022.
Analysis showed 94% (49/52) of pathogenic variants clustered in exons 24-32 of the FBN1. The most common skeletal features were arachnodactyly (98%), reduced elbow extension (48%), pectus deformity (40%), and scoliosis (39%). Haploinsufficiency variants were reported as having poor outcome in 87.5% of the cases. Among patients carrying variants that substitute a cysteine for another amino acid and those that do not change cysteine content, cardiac intervention was found to be associated with a better outcome (p = 0.035 vs. p = 0.002). Variants that create an extra cysteine residue were found to be associated with a higher risk of ectopia lentis. Additionally, children up to 36-months-old were more often reported as still alive at the time of publication compared to newborns (p < 0.01).
Our findings have implications for prognosis, because different genotype groups and their resulting phenotype may require personalized care and management.
马凡综合征是一种遗传性结缔组织疾病，影响骨骼、眼部和心血管器官系统。先前的研究发现，纤连蛋白 1（FBN1）基因外显子 24-32 中的致病变异导致更严重的临床表型。此外，基因型-表型相关性研究表明，更严重的心血管表型与导致单倍体不足的变异有关。我们的目的是分析早发性马凡综合征患者的临床表现和基因型差异，并评估其对管理策略的影响。
我们分析了一名新的早发性马凡综合征患者的临床和遗传数据，以及 1991 年至 2022 年期间在 PubMed 数据库中报告的 51 例先前患者的数据。
分析显示，94%（49/52）的致病变异集中在 FBN1 的外显子 24-32 中。最常见的骨骼特征是蜘蛛指（98%）、肘部伸展减少（48%）、鸡胸畸形（40%）和脊柱侧凸（39%）。报道称，单倍体不足变异的病例中有 87.5%预后不良。在携带替代另一种氨基酸的半胱氨酸的变异和不改变半胱氨酸含量的变异的患者中，发现心脏介入与更好的结果相关（p=0.035 比 p=0.002）。发现产生额外半胱氨酸残基的变异与晶状体异位的风险增加相关。此外，与新生儿相比，在发布时报告的 36 个月以下儿童更常存活（p<0.01）。
我们的研究结果对预后有影响，因为不同的基因型组及其导致的表型可能需要个性化的护理和管理。
