日本小児循環器学会雑誌 Pediatric Cardiology and Cardiac Surgery

Online ISSN: 2187-2988 Print ISSN: 0911-1794
特定非営利活動法人日本小児循環器学会 Japanese Society of Pediatric Cardiology and Cardiac Surgery
〒162-0801東京都新宿区山吹町358-5アカデミーセンター Japanese Society of Pediatric Cardiology and Cardiac Surgery Academy Center, 358-5 Yamabuki-cho, Shinju-ku, Tokyo 162-0801, Japan
Pediatric Cardiology and Cardiac Surgery 33(6): 431-437 (2017)
doi:10.9794/jspccs.33.431

症例報告Case Report

無症候の両親にそれぞれSCN5AおよびKCNQ1の変異を認め,異なる遺伝伝達および表現型を示したQT延長症候群の三姉妹例A Japanese Family with Long QT Syndrome: Distinct Genetic and Phenotypic Features in Children of Asymptomatic Parents with SCN5A and KCNQ1 Mutations

1市立旭川病院Department of Pediatrics, Asahikawa City Hospital ◇ Hokkaido, Japan

2北海道大学病院小児科Department of Pediatrics, Hokkaido University Graduate School of Medicine ◇ Hokkaido, Japan

3滋賀医科大学呼吸循環器内科Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science ◇ Shiga, Japan

受付日:2017年4月18日Received: April 18, 2017
受理日:2017年11月13日Accepted: November 13, 2017
発行日:2017年11月1日Published: November 1, 2017
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先天性QT延長症候群では遺伝子診断の進歩により,遺伝子変異に基づいた日常診療が可能となってきている.今回複合変異の発端者を含む,QT延長症候群の家族例を経験した.発端者は女児で,6歳時より運動時の失神を繰り返し受診した.補正QT時間(Bazett)0.67 sと延長を認め,失神の既往と合わせQT延長症候群と診断し,β遮断薬および運動制限を開始した.以後無症状だったが,10歳時にβ遮断薬内服中にもかかわらず失神が再発したことを契機に,発端者の遺伝子検査および家族の遺伝子スクリーニングを行った.発端者はKCNQ1 p.K358_Q359delとSCN5A p.A1330Tの複合変異ヘテロ接合体であり,父と姉にはSCN5A p.A1330T,母と妹にはKCNQ1 p.K358_Q359delのヘテロ接合性変異を同定した.その後発端者はβ遮断薬,Naチャネル遮断薬で8か月間失神なく経過しているが,植込み型除細動器を検討している.SCN5Aの変異を有する姉は心電図所見なく経過観察としたが,一方でKCNQ1の変異をもつ妹は運動負荷心電図でQT延長を認めたため,一次予防としてβ遮断薬と運動制限を開始した.遺伝子変異のみならず,臨床検査結果や家族歴等を加え検討することが治療方針決定に重要であった.

Concomitant with advances in genetic diagnosis of congenital long QT syndrome (LQTS), results of genetic analysis in patients with LQTS are becoming increasingly important in clinical practice to design appropriate treatment strategies. The present study reports an LQTS family. The proband was a female patient who exhibited repetitive exercise-induced syncope since the age of six, and her QT interval in ECG was markedly prolonged (0.67 s using Bazett’s formula). Except for her maternal great-grandfather who died suddenly in his 30s, she had no family history of syncope or sudden death. She was diagnosed with LQTS and was treated with a β-blocker. However, the syncope recurred at the age of ten. We performed genetic analysis of the proband and identified the heterozygous compound mutations, KCNQ1 p.K358_Q359del and SCN5A p.A1330T. Her father and elder sister carried heterozygous SCN5A p.A1330T, and her mother and younger sister carried heterozygous KCNQ1 p.K358_Q359del. Although the proband had not exhibited syncope for over 8 months with a β-blocker and a Na channel blocker, we considered placement of an implantable cardioverter-defibrillator as secondary prevention because of the severe phenotype and the compound mutations. Her elder sister who had a normal QT interval was followed without medication. In contrast, we started β-blocker therapy as primary prevention in her younger sister because she exhibited a prolonged QT interval after exercise. Detailed consideration of the gene mutations and evaluation of the phenotype were both important in determining treatment strategies.

Key words: congenital long QT syndrome; compound mutation; genetic screening

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