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.

中文翻译：

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超越经典 TARP 综合征特征的 RBM10 介导的智力障碍和先天性畸形综合征的表型谱

RBM10基因的致病性变异导致一种罕见的 X 连锁疾病，称为 TARP（马蹄足、房间隔缺损、Robin 序列和持续性左上腔静脉）综合征。鉴于文献，我们报告了两名具有截断RBM10变体的新患者，共有来自 15 个无关家庭的 26 名患者。我们的结果说明了RBM10的高度多效性致病变异，超出了经典的 TARP 综合征特征。主要临床特征包括严重的发育迟缓、发育迟缓、脑畸形、神经系统症状、呼吸问题和面部畸形。次要特征是生长迟缓、心脏、胃肠道、肢体和骨骼异常。其他复发特征包括生殖器和肾脏异常以及听力和视力障碍。因此，RBM10功能变异的丧失通常会导致智力障碍和先天性畸形综合征，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会简化诊断评估。此外，正在出现 RBM10 相关基因型-表型相关性的证据，这对预后可能很重要。