Cardiac features of Noonan syndrome in Japanese patients

Cardiovascular disease is one of the most important problems in long-term follow-up for Noonan syndrome. We examined cardiovascular issues and clinical manifestations, with a focus on the cardiovascular disease and prognosis of patients with Noonan syndrome. This single-centre study evaluated patients who were clinically and genetically diagnosed with Noonan syndrome. Forty-three patients diagnosed with Noonan syndrome were analysed. The most prevalent responsible mutation was found in (25/43). The second and third most prevalent causative genes were (6/43) and RIT1 (5/43), respectively, and 67.4% of genetically diagnosed patients with Noonan syndrome had structural cardiovascular abnormalities. Pulmonary valve stenosis was prevalent in patients with mutations in (8/25), (4/6), and (4/5). Hypertrophic cardiomyopathy was found in two of three patients with mutations in . There was no difference in the cardiovascular events or cardiovascular disease prevalence in patients with or without mutations. The proportion of mutation-positive patients who underwent intervention due to cardiovascular disease was significantly higher than that of patients with mutations. Patients who underwent any intervention for pulmonary valve stenosis exhibited significantly higher pulmonary flow velocity than patients who did not undergo intervention, when they visited our hospital for the first time. All patients who underwent intervention for pulmonary valve stenosis had a pulmonary flow velocity of more than 3.0 m/s at first visit. These findings suggest that genetic information can provide a clinical prognosis for cardiovascular disease and may be part of genotype-based follow-up in Noonan syndrome.