Niceta Marcello, Barresi Sabina, Pantaleoni Francesca, Capolino Rossella, Dentici Maria Lisa, Ciolfi Andrea, Pizzi Simone, Bartuli Andrea, Dallapiccola Bruno, Tartaglia Marco, Digilio Maria Cristina
Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Rome, Italy.
Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Rome, Italy.
Eur J Med Genet. 2019 Jun;62(6):103534. doi: 10.1016/j.ejmg.2018.09.001. Epub 2018 Sep 3.
TARP syndrome (TARPS) is an X-linked syndromic condition including Robin sequence, congenital heart defects, developmental delay, feeding difficulties and talipes equinovarus, as major features. The disease is caused by inactivating mutations in RBM10 which encodes for a RNA binding motif protein involved in transcript processing. We herein report a male born from healthy and non-consanguineous parents, presenting prenatal record of intrauterine fetal growth retardation, and postnatal features including growth and developmental delays, CNS abnormalities, facial dysmorphisms, bilateral syndactyly at the hands, talipes equinovarus and congenital heart defects. By using trio-based Whole Exome Sequencing approach, a maternally inherited RBM10 frameshift variant causing decay of the RBM10 transcript was identified. Despite the syndrome is considered lethal in affected males, our subject with molecularly confirmed TARPS is still alive at 11 years of age supporting the chance of surviving. Long-term surviving in TARPS is extremely rare and should be considered in genetic counselling and clinical follow up of the syndrome. We provide the natural history of the syndrome, reviewing the major clinical characteristics. Congenital heart defects are confirmed as specific diagnostic markers for the syndrome. In addition, cardiac anatomical details are defining a possible clinical overlap with syndromic conditions related to the hedgehog pathway and/or primary cilium anomalies as Oral-Facial-Digital or Smith-Lemli-Opitz syndromes.
TARP综合征（TARPS）是一种X连锁综合征性疾病，主要特征包括罗宾序列、先天性心脏缺陷、发育迟缓、喂养困难和马蹄内翻足。该疾病由RBM10基因的失活突变引起，RBM10编码一种参与转录加工的RNA结合基序蛋白。我们在此报告一例男性患儿，其父母健康且非近亲结婚，产前记录显示宫内胎儿生长受限，出生后具有生长发育迟缓、中枢神经系统异常、面部畸形、双手双侧并指、马蹄内翻足和先天性心脏缺陷等特征。通过基于三联体的全外显子测序方法，鉴定出一个母系遗传的RBM10移码变异，该变异导致RBM10转录本降解。尽管该综合征在受影响的男性中被认为是致死性的，但我们这位经分子确诊为TARPS的患者在11岁时仍然存活，这表明存在存活的可能性。TARPS患者长期存活极为罕见，在该综合征的遗传咨询和临床随访中应予以考虑。我们提供了该综合征的自然病史，回顾了主要临床特征。先天性心脏缺陷被确认为该综合征的特异性诊断标志物。此外，心脏解剖细节确定了其与与刺猬通路和/或原发性纤毛异常相关的综合征性疾病（如口面指综合征或史密斯-勒米-奥皮茨综合征）可能存在临床重叠。
