FLNB相关脊椎腕骨融合综合征：系统文献综述与新病例报告

文献信息

中文摘要

背景： 脊椎腕骨融合综合征（SCT）是一种罕见的常染色体隐性遗传骨骼发育不良，由FLNB双等位基因功能丧失变异引起，其特征为不成比例的身材矮小、进行性椎体融合、脊柱侧弯以及腕骨（通常为头状骨-钩骨）融合，典型情况下不伴肋骨异常。方法：我们按照PRISMA 2020声明，对PubMed/MEDLINE和Scopus进行了系统性文献检索，并辅以引文检索，以识别所有提供经分子确诊的FLNB相关SCT患者原始数据的报告。结果：共纳入11篇符合条件的出版物，涵盖台湾、阿根廷、巴基斯坦、意大利、德国和印度队列，并与一例新病例一起进行定性综合。该新患者为一名印度裔领养儿童，表现为严重的不成比例身材矮小、多节段椎体融合以及从颈椎延伸至骶椎的后弓裂、尾骨发育不全、头状骨-钩骨融合和全面性发育迟缓；靶向外显子组测序发现了一个新的纯合移码FLNB变异。将该病例与所综述的文献整合后证实，不成比例的身材矮小、连续性椎体融合和腕骨融合是几乎普遍存在的核心特征，而跗骨融合、听力损失和面部畸形则表现不一。结论：我们患者中轴向受累的范围和多节段模式似乎比大多数既往报告的病例更为严重，拓宽了FLNB相关SCT的已知表型谱，并强化了进行结构化、多学科长期随访的必要性。

英文摘要

Spondylocarpotarsal synostosis syndrome (SCT) is a rare autosomal recessive skeletal dysplasia caused by biallelic loss-of-function variants in FLNB, characterized by disproportionate short stature, progressive vertebral fusion, scoliosis, and carpal (typically capitate-hamate) synostosis, classically without rib anomalies. We performed a systematic literature search of PubMed/MEDLINE and Scopus, supplemented by citation searching, following the PRISMA 2020 statement, to identify all reports providing original, molecularly confirmed FLNB-related SCT patient data. Eleven eligible publications, spanning Taiwanese, Argentinian, Pakistani, Italian, German and Indian cohorts, were included in a qualitative synthesis together with a novel case. The novel patient, an adopted child of Indian origin, presented with severe disproportionate short stature, multisegmental vertebral fusion and posterior arch clefts extending from the cervical to the sacral spine, coccygeal dysgenesis, capitate-hamate fusion, and global developmental delay; targeted exome sequencing identified a novel homozygous frameshift FLNB variant. Integration of this case with the reviewed literature confirms disproportionate short stature, contiguous vertebral fusion, and carpal synostosis as near-universal core features, while tarsal fusion, hearing loss, and facial dysmorphism are variably present. The extent and multisegmental pattern of axial involvement in our patient appear more severe than in most previously reported cases, broadening the recognized phenotypic spectrum of FLNB-related SCT and reinforcing the need for structured, multidisciplinary long-term follow-up.