Patterns of genetic mutations explored by systematic screening of patients with aortopathy and their family membersCentral MessagePerspective
Jihoon Kim, MD, PhD,
Jae Suk Yoo, MD, PhD,
Hee-Jung Kim, MD, PhD,
Ho Jin Kim, MD,
Dae-Hee Kim, MD, PhD,
Suk Jung Choo, MD, PhD,
Joon Bum Kim, MD, PhD
Affiliations
Jihoon Kim, MD, PhD
Department of Thoracic and Cardiovascular Surgery, Hallym University Kangnam Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, Republic of Korea
Jae Suk Yoo, MD, PhD
Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Asan Genetic Aortopathy Clinic, Asan Aortic Disease Center, Asan Medical Center, Seoul, Republic of Korea
Hee-Jung Kim, MD, PhD
Department of Thoracic and Cardiovascular Surgery, Korea University Anam Hospital, Korea University, Seoul, Republic of Korea
Ho Jin Kim, MD
Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Asan Genetic Aortopathy Clinic, Asan Aortic Disease Center, Asan Medical Center, Seoul, Republic of Korea
Dae-Hee Kim, MD, PhD
Asan Genetic Aortopathy Clinic, Asan Aortic Disease Center, Asan Medical Center, Seoul, Republic of Korea; Division of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
Suk Jung Choo, MD, PhD
Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Asan Genetic Aortopathy Clinic, Asan Aortic Disease Center, Asan Medical Center, Seoul, Republic of Korea
Joon Bum Kim, MD, PhD
Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Asan Genetic Aortopathy Clinic, Asan Aortic Disease Center, Asan Medical Center, Seoul, Republic of Korea; Address for reprints: Joon Bum Kim, MD, PhD, Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea.
Objective: Genetic aortopathy, if left untreated, leads to aortic catastrophe in most affected individuals. We sought to determine the genetic mutation patterns and detection rates in patients with aortopathy and their families with a systematic screening protocol. Methods: In 2016 to 2020, patients with aortic dissection or root aneurysm (Z score ≥2) and their first-degree relatives were enrolled in a prospective registry at a tertiary referral center. The individuals underwent systematic single- or multi-gene panel testing depending on clinical presentations. Results: Among 575 enrolled individuals (mean age, 46.6 ± 14.5 years; 203 women), 346 (60.2%) underwent genetic testing. Rates of relevant gene mutations identified were 39.4% (91/231), 27.1% (54/199) and 72.4% (n = 105) in aneurysm, dissection, and family screening groups, respectively (P < .001). Mutated genes frequently identified were FBN1 (n = 199; Marfan), TGFBR1/2 or SMAD3 (n = 14; Loeys-Dietz), COL3A1/COL5A2 (n = 15; Ehlers-Danlos), and ACTA2 (n = 10). After enrollment, 123 aortic surgeries were performed in 117 patients (20.3%) including 15 family members, with resultant operative mortality of 0.8% (n = 1). In logistic regression analysis, systemic score in Ghent nosology was the only significant factor associated with positive gene mutation (odds ratio, 14.81; 95% confidence interval, 6.87-31.96), and its 3.5 point cutoff showed the best predictive value with 78.2% sensitivity and 87.2% specificity. Conclusions: Genetic aortopathy was identified in a considerable proportion of patients with aortopathy and their family members by systematic genetic testing. This strategy is recommended for timely diagnosis and proactive management of genetic aortopathy.
