Institute of Human Genetics, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
Center for Rare Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
Genes (Basel). 2023 Mar 15;14(3):724. doi: 10.3390/genes14030724.
Multiple synostoses syndrome (OMIM: #186500, #610017, #612961, #617898) is a genetically heterogeneous group of autosomal dominant diseases characterized by abnormal bone unions. The joint fusions frequently involve the hands, feet, elbows or vertebrae. Pathogenic variants in have been associated with multiple synostoses syndrome type 3 (SYNS3). So far, only five different missense variants in that cause SYNS3 have been reported in 18 affected individuals. Unlike other multiple synostoses syndromes, conductive hearing loss has not been reported in SYNS3. In this report, we describe the clinical and selected radiological findings in a large multigenerational family with a novel missense variant in : c.430T>C, p.(Trp144Arg). We extend the phenotypic spectrum of SYNS3 by suggesting that cleft palate and conductive hearing loss are part of the syndrome and highlight the high degree of intrafamilial phenotypic variability. These findings should be considered when counseling affected individuals.
多发性骨融合综合征（OMIM：#186500、#610017、#612961、#617898）是一组具有遗传异质性的常染色体显性疾病，其特征为异常的骨联合。关节融合常累及手、脚、肘或脊椎。已发现 中的致病变异与多发性骨融合综合征 3 型（SYNS3）有关。到目前为止，已有 18 名受影响的个体报告了 中导致 SYNS3 的 5 种不同的错义变异。与其他多发性骨融合综合征不同，SYNS3 没有报道传导性听力损失。本报告描述了一个大型多代家族中一个新的 错义变异：c.430T>C，p.（Trp144Arg）的临床和部分放射学发现。我们通过提示腭裂和传导性听力损失是该综合征的一部分，扩展了 SYNS3 的表型谱，并强调了家族内表型变异性很大。在对受影响的个体进行咨询时应考虑这些发现。
