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Cardiac manifestations and gene mutations of patients with RASopathies in Taiwan
Author(s) -
Lee ChungLin,
Tan Louis Tan HockCheong,
Lin HsiangYu,
Hwu WuhLiang,
Lee NiChung,
Chien YinHsiu,
Chuang ChihKuang,
Wu MeiHwan,
Wang JouKou,
Chu ShaoYin,
Lin JuLi,
Lo FuSung,
Su PenHua,
Hsu ChiaChi,
Ko YuYuan,
Chen MingRen,
Chiu HuiChing,
Lin ShuanPei
Publication year - 2020
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61429
Subject(s) - noonan syndrome , ptpn11 , medicine , costello syndrome , ductus arteriosus , cardiology , cardiomyopathy , heart disease , heart failure , cancer , colorectal cancer , kras
RASopathies are developmental diseases caused by mutations in rat sarcoma–mitogen‐activated protein kinase pathway genes. These disorders, such as Noonan syndrome (NS) and NS‐related disorders (NSRD), including cardio‐facio‐cutaneous (CFC) syndrome, Costello syndrome (CS), and NS with multiple lentigines (NSML; also known as LEOPARD syndrome), have a similar systemic phenotype. A wide spectrum of congenital heart disease and hypertrophic cardiomyopathy (HCMP) can exhibit major associated characteristics. A retrospective study was conducted at the Mackay Memorial Hospital, National Taiwan University Hospital, Buddhist Tzu‐Chi General Hospital, Chang‐Gung Memorial Hospital, Taichung Veterans General Hospital, and Chung Shan Medical University Hospital from January 2007 to December 2018. We reviewed the clinical records of 76 patients with a confirmed molecular diagnosis of RASopathies, including NS, CS, CFC syndrome, and NSML. We evaluated the demographic data and medical records with clinical phenotypes of cardiac structural anomalies using cross‐sectional and color Doppler echocardiography, electrocardiographic findings, and follow‐up data. A total of 47 (61.8%) patients had cardiac abnormalities. The prevalence of cardiac lesions according to each syndrome was 62.7, 50.0, 60.0, and 66.7% in patients with NS, CFC syndrome, CS, and NSML, respectively. An atrial septal defect was usually combined with other cardiac abnormalities, such as pulmonary stenosis (PS), HCMP, ventricular septal defect, or patent ductus arteriosus. Patients with NS most commonly showed PS. In patients with NSRD and cardiac abnormalities, HCMP (29.4%) was the most commonly observed cardiac lesion. PTPN11 was also the most frequently detected mutation in patients with NS and NSRD. Cardiac abnormalities were the most common symptoms observed in patients with RASopathies at the time of their first hospital visit. Performing precise analyses of genotype–cardiac phenotype correlations in a larger cohort will help us accurately diagnose RASopathy as soon as possible.