ORIGINAL ARTICLE Cardiac manifestations and gene mutations of patients with RASopathies in Taiwan Chung-Lin Lee 1 | Louis Tan Hock-Cheong Tan 1 | Hsiang-Yu Lin 2,3,4,5,6 | Wuh-Liang Hwu 7 | Ni-Chung Lee 7 | Yin-Hsiu Chien 7 | Chih-Kuang Chuang 4,8 | Mei-Hwan Wu 7 | Jou-Kou Wang 7 | Shao-Yin Chu 9 | Ju-Li Lin 10 | Fu-Sung Lo 10 | Pen-Hua Su 11 | Chia-Chi Hsu 12 | Yu-Yuan Ko 12 | Ming-Ren Chen 13 | Hui-Ching Chiu 2 | Shuan-Pei Lin 2,3,4,14 1 Department of Pediatrics, Mackay Memorial Hospital, Hsinchu, Taiwan 2 Department of Pediatrics and Rare Disease Center, Mackay Memorial Hospital, Taipei, Taiwan 3 Department of Medicine, Mackay Medical College, New Taipei City, Taiwan 4 Division of Genetics and Metabolism, Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan 5 Nursing and Management, Mackay Junior College of Medicine, Taipei, Taiwan 6 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan 7 Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan 8 College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan 9 Department of Pediatrics, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan 10 Department of Pediatrics, Chang-Gung Memorial Hospital, Taoyuan, Taiwan 11 Department of Pediatrics, Chung Shan Medical University, Taichung, Taiwan 12 Department of Pediatrics, Taichung Veterans General Hospital, Taichung, Taiwan 13 Pediatric Cardiology Department, Mackay Children's Hospital, Taipei, Taiwan 14 Department of Infant and Child Care, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan Correspondence Shuan-Pei Lin, Department of Pediatrics, Mackay Memorial Hospital, No. 92, Sec. 2, Chung-Shan North Road, Taipei 10449, Taiwan. Email: 4535lin@gmail.com Hsiang-Yu Lin, Division of Genetics and Metabolism, Departments of Pediatrics and Medical Research, Mackay Memorial Hospital, No. 92, Sec. 2, Chung-Shan North Road, Taipei 10449, Taiwan. Email: lxc46199@ms37.hinet.net Funding information Mackay Memorial Hospital, Grant/Award Numbers: MMH-101-111, MMH-103-092, MMH-107-82, MMH-E-108-16; Ministry of Science and Technology, Taiwan, Grant/Award Numbers: MOST-108-2314-B-195-012-MY3, MOST-108-2314-B-195-014, MOST- 105-2314-B-195-013, MOST-105-2628-B- 195-001-MY3, MOST-106-2314-B- 195-015-MY2 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) syn- drome, Costello syndrome (CS), and NS with multiple lentigines (NSML; also known as LEOPARD syndrome), have a similar systemic phenotype. A wide spectrum of congeni- tal 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 Uni- versity 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. Chung-Lin Lee and Louis Tan Hock-Cheong Tan contributed equally to this study. Received: 16 April 2019 Revised: 18 November 2019 Accepted: 20 November 2019 DOI: 10.1002/ajmg.a.61429 Am J Med Genet. 2019;1–8. wileyonlinelibrary.com/journal/ajmga © 2019 Wiley Periodicals, Inc. 1