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 36(4): 334-343 (2020)
doi:10.9794/jspccs.36.334

症例報告Case Report

全エクソン解析によりCACNA1C遺伝子バリアントが同定された心外合併症のない(非Timothy型)QT延長症候群(LQT8)Case Report: P857R CACNA1C Variant Causing Long QT Syndrome Type 8 Without Other Phenotypes Identified on Whole-exome Analysis

1横浜市立大学附属病院小児循環器科Department of Pediatric Cardiology, Yokohama City University Hospital ◇ Kanagawa, Japan

2済生会横浜市東部病院小児科Department of Pediatrics, Saiseikai Yokohamashi Tobu Hospital ◇ Kanagawa, Japan

3国立循環器病研究センター心臓血管内科・不整脈科Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center ◇ Osaka, Japan

受付日:2020年2月6日Received: February 6, 2020
受理日:2020年7月10日Accepted: July 10, 2020
発行日:2020年12月1日Published: December 1, 2020
HTMLPDFEPUB3

Long QT syndrome type 8 (LQT8)は心筋CaチャネルのαサブユニットをエンコードするCACNA1C遺伝子異常が原因で,心電図上QT延長に加えて,合指,先天性心疾患,精神発達遅滞など多臓器に所見を認めるTimothy症候群が知られている.今回我々は心外合併症のない非Timothy症候群型LQT8の親子例を経験したので報告する.症例は18才男性,小学校1年生の学校心臓検診でQT延長を指摘され,9歳時に遺伝子検査を提出したが,LQT1~3の遺伝子変異は認めなかった.18歳時の運動負荷心電図で機能的2 : 1房室ブロックを認めたことを契機に改めて全エクソン遺伝子解析を実施したところ,本患者と父親にLQT8として既報のCACNA1C遺伝子バリアントが同定された.本患者に対してプロプラノロール,メキシレチン,ベラパミルの薬剤負荷試験を施行し,メキシレチン投与後にQT延長の改善を認めた.LQT8に対する明確な治療指針はないが,本症例ではメキシレチンの有効性が示唆された.LQT1~3の遺伝子変異が同定されなかった症例でも,QT延長に加え機能的2 : 1房室ブロックやT wave alternansを認めた場合はLQT8の可能性を疑う必要がある.

Long QT syndrome (LQTS) type 8 is known as Timothy syndrome. It is a multi-systemic disorder involving QT prolongation on electrocardiogram, syndactyly, congenital heart disease, and mental retardation. Herein, we report a case of LQTS type 8 without multi-systemic disorders with a CACNA1C variant identified on whole-exome analysis. An 18-year-old male patient presented with LQTS (QTc=500 msc) at the age of 6 years based on a school health examination. He had been asymptomatic but underwent genetic testing at the age of 9 years. However, via a conventional Sanger screening, no mutations were identified in the following genes: KCNQ1 (LQT1), KCNH2 (LQT2), and SCN5A (LQT3). During follow-up at the age of 18 years, an exercise stress test induced functional 2 : 1 atrioventricular (AV) block with a significant QT prolongation. Whole-exome analysis identified Pro857Arg, a pathogenic variant of the CACNA1C gene, in this patient (proband) and his father. We further performed a drug-provocation study using propranolol, mexiletine, and verapamil, and only mexiletine infusion (2 mg/kg) reduced the QTc interval. In conclusion, when a patient with an unidentified genotype in the major three LQTS genes present with a functional 2 : 1 AV block or T-wave alternans, further genetic screening for the CACNA1C gene might be required. There are no established guidelines on the medical treatment of LQT8. However, our findings showed that propranolol and mexiletine can be effective for the management of LQT8.

Key words: long QT syndrome; CACNA1C; gene; Timothy syndrome

This page was created on 2020-12-09T10:27:31.405+09:00
This page was last modified on 2020-12-22T13:01:43.000+09:00


このサイトは(株)国際文献社によって運用されています。