Cardiac manifestations and gene mutations of patients with RASopathies in Taiwan
Journal
American Journal of Medical Genetics, Part A
Journal Volume
182
Journal Issue
2
Pages
357-364
Date Issued
2020
Author(s)
Lee C.-L.
Tan L.T.H.-C.
Lin H.-Y.
Chuang C.-K.
Chu S.-Y.
Lin J.-L.
Lo F.-S.
Su P.-H.
Hsu C.-C.
Ko Y.-Y.
Chen M.-R.
Chiu H.-C.
Lin S.-P.
Abstract
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. ? 2019 Wiley Periodicals, Inc.
SDGs
Other Subjects
B Raf kinase; K ras protein; Krev interaction trapped protein 1; protein tyrosine phosphatase SHP 2; SOS protein; tumor necrosis factor receptor associated factor 1; protein tyrosine phosphatase SHP 2; PTPN11 protein, human; Ras protein; adult; aortic valve disease; Article; B Raf kinase gene; color Doppler echocardiography; congenital heart disease; Costello syndrome; electrocardiography; Fallot tetralogy; female; gene; gene mutation; heart atrium septum defect; heart disease; heart ventricle septum defect; HRAS gene; human; hypertrophic cardiomyopathy; infant; Krev interaction trapped protein 1 gene; LEOPARD syndrome; major clinical study; male; MAP2K2 gene; mitral valve regurgitation; molecular diagnosis; NF1 gene; Noonan syndrome; oncogene K ras; patent ductus arteriosus; priority journal; protein tyrosine phosphatase SHP 2 gene; pulmonary valve stenosis; retrospective study; Sanger sequencing; SHOC2 gene; SOS1 gene; SPRED gene; tumor necrosis factor receptor associated factor 1 gene; classification; congenital heart malformation; Costello syndrome; cross-sectional study; developmental disorder; ectodermal dysplasia; facies; failure to thrive; genetics; heart septum defect; LEOPARD syndrome; Noonan syndrome; pathology; pathophysiology; Cardiomyopathy, Hypertrophic; Costello Syndrome; Cross-Sectional Studies; Developmental Disabilities; Ectodermal Dysplasia; Facies; Failure to Thrive; Female; Heart Defects, Congenital; Heart Septal Defects, Atrial; Humans; LEOPARD Syndrome; Male; Noonan Syndrome; Protein Tyrosine Phosphatase, Non-Receptor Type 11; ras Proteins; Retrospective Studies
Publisher
Wiley-Liss Inc.
Type
journal article