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Cardiac features of Noonan syndrome in Japanese patients

Published online by Cambridge University Press:  27 April 2022

Yasuhiro Ichikawa Open the ORCID record for Yasuhiro Ichikawa [Opens in a new window] ,
Hiroyuki Kuroda Open the ORCID record for Hiroyuki Kuroda [Opens in a new window] ,
Takeshi Ikegawa ,
Shun Kawai ,
Shin Ono ,
Ki-Sung Kim ,
Sadamitsu Yanagi ,
Kenji Kurosawa ,
Yoko Aoki  and
Hideaki Ueda
Yasuhiro Ichikawa*
Affiliation:
Department of Cardiology, Kanagawa Children’s Medical Center, Yokohama, Japan
Hiroyuki Kuroda
Affiliation:
Department of Cardiology, Kanagawa Children’s Medical Center, Yokohama, Japan
Takeshi Ikegawa
Affiliation:
Department of Cardiology, Kanagawa Children’s Medical Center, Yokohama, Japan
Shun Kawai
Affiliation:
Department of Cardiology, Kanagawa Children’s Medical Center, Yokohama, Japan
Shin Ono
Affiliation:
Department of Cardiology, Kanagawa Children’s Medical Center, Yokohama, Japan
Ki-Sung Kim
Affiliation:
Department of Cardiology, Kanagawa Children’s Medical Center, Yokohama, Japan
Sadamitsu Yanagi
Affiliation:
Department of Cardiology, Kanagawa Children’s Medical Center, Yokohama, Japan
Kenji Kurosawa*
Affiliation:
Division of Medical Genetics, Kanagawa Children’s Medical Center, Yokohama, Japan
Yoko Aoki
Affiliation:
Department of Medical Genetics, Tohoku University Graduate School of Medicine, Sendai, Japan
Hideaki Ueda
Affiliation:
Department of Cardiology, Kanagawa Children’s Medical Center, Yokohama, Japan
*
Author for correspondence: Yasuhiro Ichikawa or Kenji Kurosawa, Kanagawa Children’s Medical Center, Yokohama, Japan, 2-138-4 Mutsukawa, Minami-ku, Yokohama 232-8555, Japan. Tel: +81 45 711 2351; Fax: +81-45-721-3324. E-mail: yas1lll@yahoo.co.jp or kkurosawa@kcmc.jp
Author for correspondence: Yasuhiro Ichikawa or Kenji Kurosawa, Kanagawa Children’s Medical Center, Yokohama, Japan, 2-138-4 Mutsukawa, Minami-ku, Yokohama 232-8555, Japan. Tel: +81 45 711 2351; Fax: +81-45-721-3324. E-mail: yas1lll@yahoo.co.jp or kkurosawa@kcmc.jp
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Abstract

Background:

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.

Methods:

This single-centre study evaluated patients who were clinically and genetically diagnosed with Noonan syndrome.

Results:

Forty-three patients diagnosed with Noonan syndrome were analysed. The most prevalent responsible mutation was found in PTPN11 (25/43). The second and third most prevalent causative genes were SOS1 (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 PTPN11 (8/25), SOS1 (4/6), and RIT1 (4/5). Hypertrophic cardiomyopathy was found in two of three patients with mutations in RAF1. There was no difference in the cardiovascular events or cardiovascular disease prevalence in patients with or without PTPN11 mutations. The proportion of RIT1 mutation-positive patients who underwent intervention due to cardiovascular disease was significantly higher than that of patients with PTPN11 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.

Conclusions:

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.

Keywords

Noonan syndromepulmonary valve stenosishypertrophic cardiomyopathyPTPN11RIT1
Type
Original Article
Information
Cardiology in the Young , Volume 33 , Issue 4 , April 2023 , pp. 564 - 569
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Copyright
© The Author(s), 2022. Published by Cambridge University Press

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