Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Department of Pediatrics, AZ Maria Middelares Ghent, Ghent, Belgium.
Clin Genet. 2021 Mar;99(3):449-456. doi: 10.1111/cge.13901. Epub 2021 Jan 5.
Pathogenic variants in the RBM10 gene cause a rare X-linked disorder described as TARP (Talipes equinovarus, Atrial septal defect, Robin sequence, and Persistent left vena cava superior) syndrome. We report two novel patients with truncating RBM10 variants in view of the literature, presenting a total of 26 patients from 15 unrelated families. Our results illustrate the highly pleiotropic nature of RBM10 pathogenic variants, beyond the classic TARP syndrome features. Major clinical characteristics include severe developmental delay, failure to thrive, brain malformations, neurological symptoms, respiratory issues, and facial dysmorphism. Minor features are growth retardation, cardiac, gastrointestinal, limb, and skeletal abnormalities. Additional recurrent features include genital and renal abnormalities as well as hearing and visual impairment. Thus, RBM10 loss of function variants typically cause an intellectual disability and congenital malformation syndrome that requires assessment of multiple organ systems at diagnosis and for which provided clinical features might simplify diagnostic assessment. Furthermore, evidence for an RBM10-related genotype-phenotype correlation is emerging, which can be important for prognosis.
RBM10 基因中的致病性变异导致一种罕见的 X 连锁疾病，称为 TARP（马蹄内翻足、房间隔缺损、Robin 序列和永存左上腔静脉）综合征。鉴于文献记载，我们报告了两名新的截断 RBM10 变异患者，总共来自 15 个无关家庭的 26 名患者。我们的结果表明，RBM10 致病性变异除了具有经典的 TARP 综合征特征外，还具有高度的多效性。主要临床特征包括严重的发育迟缓、生长不良、脑畸形、神经症状、呼吸问题和面部畸形。次要特征包括生长迟缓、心脏、胃肠道、四肢和骨骼异常。其他反复出现的特征包括生殖器和肾脏异常以及听力和视力障碍。因此，RBM10 功能丧失变异通常导致智力残疾和先天性畸形综合征，这需要在诊断时评估多个器官系统，并且提供的临床特征可能简化诊断评估。此外，正在出现与 RBM10 相关的基因型-表型相关性的证据，这对于预后很重要。
