Department of Pediatric Cardiology and Cardiac Surgery, Bambino Gesù Children's Hospital and Research Institute, Rome, Italy.
Cardiologia SUN, Monaldi Hospital, II University of Naples, Naples, Italy.
Int J Cardiol. 2017 Oct 15;245:92-98. doi: 10.1016/j.ijcard.2017.07.068. Epub 2017 Jul 21.
RASopathies are developmental disease caused by mutations in genes encoding for signal transducers of the RAS-MAPK cascade. The aim of the present study was to provide a comprehensive description of morbidity and mortality in patients with molecularly confirmed RASopathy.
A multicentric, observational, retrospective study was conducted in seven European cardiac centres participating to the CArdiac Rasopathy NETwork (CARNET). Clinical records of 371 patients with confirmed molecular diagnosis of RASopathy were reviewed. Mortality was described as crude mortality, cumulative survival and restricted estimated mean survival. Multivariable regression analysis was used to assess the impact of mutated genes on number of interventions and overall prognosis.
Cardiac defects occurred in 80.3% of cases, almost half of them underwent at least one intervention. Overall, crude mortality was 0.29/100 patients-year. Cumulative survival was 98.8%, 98.2%, 97.7%, 94.3%, at 1, 5, 10, and 20years, respectively. Restricted estimated mean survival at 20years follow-up was 19.6years. Ten patients died (2.7% of the entire cohort; 3.4% of patients with cardiac defect). Patients with hypertrophic cardiomyopathy (HCM) and age <2years or young adults, as well as subjects with biventricular obstruction and PTPN11 mutations had a higher risk of cardiac death.
The risk of intervention was higher in individuals with Noonan syndrome and pulmonary stenosis carrying PTPN11 mutations. Overall, mortality was relatively low, even though the specific association between HCM, biventricular outflow tract obstructions and PTPN11 mutations appeared to be associated with early mortality, including immediate post-operative events and sudden death.
RAS 病是由 RAS-MAPK 级联信号转导蛋白编码基因突变引起的发育性疾病。本研究旨在全面描述经分子证实的 RAS 病患者的发病率和死亡率。
本研究为多中心、观察性、回顾性研究，在参与 CArdiac Rasopathy NETwork（CARNET）的七个欧洲心脏中心进行。对 371 例经分子确诊的 RAS 病患者的临床记录进行了回顾性分析。死亡率描述为粗死亡率、累积生存率和受限估计平均生存率。多变量回归分析用于评估突变基因对干预次数和整体预后的影响。
心脏缺陷发生在 80.3%的病例中，其中近一半的患者至少接受了一次干预。总的来说，粗死亡率为 0.29/100 患者年。累积生存率分别为 98.8%、98.2%、97.7%和 94.3%，随访 1、5、10 和 20 年时。20 年随访时受限估计平均生存率为 19.6 年。10 例患者死亡（整个队列的 2.7%；心脏缺陷患者的 3.4%）。患有肥厚型心肌病（HCM）和年龄<2 岁或年轻成人，以及伴有双心室梗阻和 PTPN11 突变的患者，心脏死亡风险更高。
携带 PTPN11 突变的 Noonan 综合征和肺动脉瓣狭窄患者的干预风险更高。总的来说，死亡率相对较低，尽管 HCM、双心室流出道梗阻和 PTPN11 突变之间的特定关联似乎与早期死亡率相关，包括术后即刻事件和猝死。
