Determination of Genotype and Phenotypes in Pediatric Patients With Biventricular Noncompaction

Keiichi Hirono; Yukiko Hata; Teruhiko Imamura; Kaori Tsuboi; Shinya Takarada; Mako Okabe; Hideyuki Nakaoka; Keijiro Ibuki; Sayaka Ozawa; Shojiro Ichimata; Naoki Nishida; Hidenori Iwasaki; Susumu Urata; Seigo Okada; Tomoya Hiratsuji; Heima Sakaguchi; Kiyohiro Takigiku; Makoto Nakazawa; Eiki Nishihara; Masako Harada; Osamu Matsuo; Kenji Yasuda; Yoko Yoshida; Hidemasa Namiki; Kazushi Yasuda; Toshinobu Ifuku; Kotaro Urayama; Hideharu Oka; Kayo Ogino; Akio Kato; Nobuhiko Kan; Shunji Seki; Mitsuru Seki; Yutaka Odanaka; Satoru Iwashima; Shuichiro Yoshida; Toyohisa Miyata; Tomoyuki Miyamoto; Ken Watanabe; Naoki Kuwabara; Ryo Inuzuka; Yoshihiro Takahashi; Hisanori Sakazaki; Jun Muneuchi; Shigetoyo Kogaki; Fujito Numano; Sachiko Kido; Masaki Nii; Shinsuke Hoshino; Hidekazu Ishida; Jun Maeda; Yasunobu Hayabuchi; Yoshikazu Otsubo; Kazuyuki Ikeda; Shinya Tsukano; Makoto Watanabe; Nobuo Momoi; Takanari Fujii; Tao Fujioka; Mitsuhiro Fujino; Hiroki Uchiyama; Shigehito Baba; Hitoshi Horigome; Takashi Honda; Kazutaka Suzuki; Fukiko Ichida

doi:10.1161/JAHA.124.035614

Determination of Genotype and Phenotypes in Pediatric Patients With Biventricular Noncompaction

Keiichi Hirono^*, Yukiko Hata, Teruhiko Imamura, Kaori Tsuboi, Shinya Takarada, Mako Okabe, Hideyuki Nakaoka, Keijiro Ibuki, Sayaka Ozawa, Shojiro Ichimata, Naoki Nishida, Hidenori Iwasaki, Susumu Urata, Seigo Okada, Tomoya Hiratsuji, Heima Sakaguchi, Kiyohiro Takigiku, Makoto Nakazawa, Eiki Nishihara, Masako HaradaOsamu Matsuo, Kenji Yasuda, Yoko Yoshida, Hidemasa Namiki, Kazushi Yasuda, Toshinobu Ifuku, Kotaro Urayama, Hideharu Oka, Kayo Ogino, Akio Kato, Nobuhiko Kan, Shunji Seki, Mitsuru Seki, Yutaka Odanaka, Satoru Iwashima, Shuichiro Yoshida, Toyohisa Miyata, Tomoyuki Miyamoto, Ken Watanabe, Naoki Kuwabara, Ryo Inuzuka, Yoshihiro Takahashi, Hisanori Sakazaki, Jun Muneuchi, Shigetoyo Kogaki, Fujito Numano, Sachiko Kido, Masaki Nii, Shinsuke Hoshino, Hidekazu Ishida, Jun Maeda, Yasunobu Hayabuchi, Yoshikazu Otsubo, Kazuyuki Ikeda, Shinya Tsukano, Makoto Watanabe, Nobuo Momoi, Takanari Fujii, Tao Fujioka, Mitsuhiro Fujino, Hiroki Uchiyama, Shigehito Baba, Hitoshi Horigome, Takashi Honda, Kazutaka Suzuki, Fukiko Ichida

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: Left ventricular noncompaction (LVNC) is a hereditary type of cardiomyopathy characterized by prominent tra-beculations. Detailed characteristics of biventricular noncompaction (BiVNC) remain unknown. This study aimed to elucidate the clinical characteristics and genetic landscape of BiVNC.METHODS AND RESULTS: We recruited children with left ventricular noncompaction from Japanese multi-institutional centers from 2013 to 2021. Left ventricular noncompaction was classified as BiVNC, congenital heart disease, arrhythmia, dilated car-diomyopathy, or normal function. In these patients, cardiomyopathy-associated genes were screened. A total of 234 patients (127 male; mean age, 4 months [range, 0–6.6 years]) were enrolled in this study, of whom 25 had BiVNC; 55, normal function; 84, dilated cardiomyopathy; 38, congenital heart disease; and 32, arrhythmia. BiVNC was diagnosed during the perinatal period in 10 patients, in whom the prevalence was higher than that in other patients. A total of 14 patients in the group with BiVNC had congenital heart disease, but not necessarily right heart lesions. Left ventricular dyskinesis was frequently observed in the lateral wall (24%) and apex (28%). Eleven pathogenic variants were found in 11 patients with BiVNC (44.0%). The group with BiVNC had a higher ratio of mitochondrial and developmental gene variants than the other groups. Among all groups, the group with BiVNC had the worst survival rate (P=0.0009). CONCLUSIONS: Pediatric patients with BiVNC had a high rate of ventricular dyskinesis and poor outcome. A comprehensive and careful screening for disease-causing genes and phenotype may help identify specific patients with left ventricular noncom-paction and mortality-related cardiac phenotypes.

Original language	English
Article number	e035614
Journal	Journal of the American Heart Association
Volume	13
Issue number	21
DOIs	https://doi.org/10.1161/JAHA.124.035614
State	Published - 2024

Keywords

biventricular noncompaction
congenital heart disease
dyskinesis
genetics
heart failure
left ventricular noncompaction

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1161/JAHA.124.035614

Cite this

Hirono, K., Hata, Y., Imamura, T., Tsuboi, K., Takarada, S., Okabe, M., Nakaoka, H., Ibuki, K., Ozawa, S., Ichimata, S., Nishida, N., Iwasaki, H., Urata, S., Okada, S., Hiratsuji, T., Sakaguchi, H., Takigiku, K., Nakazawa, M., Nishihara, E., ... Ichida, F. (2024). Determination of Genotype and Phenotypes in Pediatric Patients With Biventricular Noncompaction. Journal of the American Heart Association, 13(21), Article e035614. https://doi.org/10.1161/JAHA.124.035614

@article{a0d3e79f37b14d7fa54a44c27a2afc85,

title = "Determination of Genotype and Phenotypes in Pediatric Patients With Biventricular Noncompaction",

abstract = "BACKGROUND: Left ventricular noncompaction (LVNC) is a hereditary type of cardiomyopathy characterized by prominent tra-beculations. Detailed characteristics of biventricular noncompaction (BiVNC) remain unknown. This study aimed to elucidate the clinical characteristics and genetic landscape of BiVNC.METHODS AND RESULTS: We recruited children with left ventricular noncompaction from Japanese multi-institutional centers from 2013 to 2021. Left ventricular noncompaction was classified as BiVNC, congenital heart disease, arrhythmia, dilated car-diomyopathy, or normal function. In these patients, cardiomyopathy-associated genes were screened. A total of 234 patients (127 male; mean age, 4 months [range, 0–6.6 years]) were enrolled in this study, of whom 25 had BiVNC; 55, normal function; 84, dilated cardiomyopathy; 38, congenital heart disease; and 32, arrhythmia. BiVNC was diagnosed during the perinatal period in 10 patients, in whom the prevalence was higher than that in other patients. A total of 14 patients in the group with BiVNC had congenital heart disease, but not necessarily right heart lesions. Left ventricular dyskinesis was frequently observed in the lateral wall (24%) and apex (28%). Eleven pathogenic variants were found in 11 patients with BiVNC (44.0%). The group with BiVNC had a higher ratio of mitochondrial and developmental gene variants than the other groups. Among all groups, the group with BiVNC had the worst survival rate (P=0.0009). CONCLUSIONS: Pediatric patients with BiVNC had a high rate of ventricular dyskinesis and poor outcome. A comprehensive and careful screening for disease-causing genes and phenotype may help identify specific patients with left ventricular noncom-paction and mortality-related cardiac phenotypes.",

keywords = "biventricular noncompaction, congenital heart disease, dyskinesis, genetics, heart failure, left ventricular noncompaction",

author = "Keiichi Hirono and Yukiko Hata and Teruhiko Imamura and Kaori Tsuboi and Shinya Takarada and Mako Okabe and Hideyuki Nakaoka and Keijiro Ibuki and Sayaka Ozawa and Shojiro Ichimata and Naoki Nishida and Hidenori Iwasaki and Susumu Urata and Seigo Okada and Tomoya Hiratsuji and Heima Sakaguchi and Kiyohiro Takigiku and Makoto Nakazawa and Eiki Nishihara and Masako Harada and Osamu Matsuo and Kenji Yasuda and Yoko Yoshida and Hidemasa Namiki and Kazushi Yasuda and Toshinobu Ifuku and Kotaro Urayama and Hideharu Oka and Kayo Ogino and Akio Kato and Nobuhiko Kan and Shunji Seki and Mitsuru Seki and Yutaka Odanaka and Satoru Iwashima and Shuichiro Yoshida and Toyohisa Miyata and Tomoyuki Miyamoto and Ken Watanabe and Naoki Kuwabara and Ryo Inuzuka and Yoshihiro Takahashi and Hisanori Sakazaki and Jun Muneuchi and Shigetoyo Kogaki and Fujito Numano and Sachiko Kido and Masaki Nii and Shinsuke Hoshino and Hidekazu Ishida and Jun Maeda and Yasunobu Hayabuchi and Yoshikazu Otsubo and Kazuyuki Ikeda and Shinya Tsukano and Makoto Watanabe and Nobuo Momoi and Takanari Fujii and Tao Fujioka and Mitsuhiro Fujino and Hiroki Uchiyama and Shigehito Baba and Hitoshi Horigome and Takashi Honda and Kazutaka Suzuki and Fukiko Ichida",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s).",

year = "2024",

doi = "10.1161/JAHA.124.035614",

language = "英語",

volume = "13",

journal = "Journal of the American Heart Association",

issn = "2047-9980",

publisher = "American Heart Association Inc.",

number = "21",

}

Hirono, K , Hata, Y , Imamura, T, Tsuboi, K, Takarada, S, Okabe, M , Nakaoka, H , Ibuki, K , Ozawa, S , Ichimata, S , Nishida, N, Iwasaki, H, Urata, S, Okada, S, Hiratsuji, T, Sakaguchi, H, Takigiku, K, Nakazawa, M, Nishihara, E, Harada, M, Matsuo, O, Yasuda, K, Yoshida, Y, Namiki, H, Yasuda, K, Ifuku, T, Urayama, K, Oka, H, Ogino, K, Kato, A, Kan, N, Seki, S, Seki, M, Odanaka, Y, Iwashima, S, Yoshida, S, Miyata, T, Miyamoto, T, Watanabe, K, Kuwabara, N, Inuzuka, R, Takahashi, Y, Sakazaki, H, Muneuchi, J, Kogaki, S, Numano, F, Kido, S, Nii, M, Hoshino, S, Ishida, H, Maeda, J, Hayabuchi, Y, Otsubo, Y, Ikeda, K, Tsukano, S, Watanabe, M, Momoi, N, Fujii, T, Fujioka, T, Fujino, M, Uchiyama, H, Baba, S, Horigome, H, Honda, T, Suzuki, K & Ichida, F 2024, 'Determination of Genotype and Phenotypes in Pediatric Patients With Biventricular Noncompaction', Journal of the American Heart Association, vol. 13, no. 21, e035614. https://doi.org/10.1161/JAHA.124.035614

TY - JOUR

T1 - Determination of Genotype and Phenotypes in Pediatric Patients With Biventricular Noncompaction

AU - Hirono, Keiichi

AU - Hata, Yukiko

AU - Imamura, Teruhiko

AU - Tsuboi, Kaori

AU - Takarada, Shinya

AU - Okabe, Mako

AU - Nakaoka, Hideyuki

AU - Ibuki, Keijiro

AU - Ozawa, Sayaka

AU - Ichimata, Shojiro

AU - Nishida, Naoki

AU - Iwasaki, Hidenori

AU - Urata, Susumu

AU - Okada, Seigo

AU - Hiratsuji, Tomoya

AU - Sakaguchi, Heima

AU - Takigiku, Kiyohiro

AU - Nakazawa, Makoto

AU - Nishihara, Eiki

AU - Harada, Masako

AU - Matsuo, Osamu

AU - Yasuda, Kenji

AU - Yoshida, Yoko

AU - Namiki, Hidemasa

AU - Yasuda, Kazushi

AU - Ifuku, Toshinobu

AU - Urayama, Kotaro

AU - Oka, Hideharu

AU - Ogino, Kayo

AU - Kato, Akio

AU - Kan, Nobuhiko

AU - Seki, Shunji

AU - Seki, Mitsuru

AU - Odanaka, Yutaka

AU - Iwashima, Satoru

AU - Yoshida, Shuichiro

AU - Miyata, Toyohisa

AU - Miyamoto, Tomoyuki

AU - Watanabe, Ken

AU - Kuwabara, Naoki

AU - Inuzuka, Ryo

AU - Takahashi, Yoshihiro

AU - Sakazaki, Hisanori

AU - Muneuchi, Jun

AU - Kogaki, Shigetoyo

AU - Numano, Fujito

AU - Kido, Sachiko

AU - Nii, Masaki

AU - Hoshino, Shinsuke

AU - Ishida, Hidekazu

AU - Maeda, Jun

AU - Hayabuchi, Yasunobu

AU - Otsubo, Yoshikazu

AU - Ikeda, Kazuyuki

AU - Tsukano, Shinya

AU - Watanabe, Makoto

AU - Momoi, Nobuo

AU - Fujii, Takanari

AU - Fujioka, Tao

AU - Fujino, Mitsuhiro

AU - Uchiyama, Hiroki

AU - Baba, Shigehito

AU - Horigome, Hitoshi

AU - Honda, Takashi

AU - Suzuki, Kazutaka

AU - Ichida, Fukiko

PY - 2024

Y1 - 2024

N2 - BACKGROUND: Left ventricular noncompaction (LVNC) is a hereditary type of cardiomyopathy characterized by prominent tra-beculations. Detailed characteristics of biventricular noncompaction (BiVNC) remain unknown. This study aimed to elucidate the clinical characteristics and genetic landscape of BiVNC.METHODS AND RESULTS: We recruited children with left ventricular noncompaction from Japanese multi-institutional centers from 2013 to 2021. Left ventricular noncompaction was classified as BiVNC, congenital heart disease, arrhythmia, dilated car-diomyopathy, or normal function. In these patients, cardiomyopathy-associated genes were screened. A total of 234 patients (127 male; mean age, 4 months [range, 0–6.6 years]) were enrolled in this study, of whom 25 had BiVNC; 55, normal function; 84, dilated cardiomyopathy; 38, congenital heart disease; and 32, arrhythmia. BiVNC was diagnosed during the perinatal period in 10 patients, in whom the prevalence was higher than that in other patients. A total of 14 patients in the group with BiVNC had congenital heart disease, but not necessarily right heart lesions. Left ventricular dyskinesis was frequently observed in the lateral wall (24%) and apex (28%). Eleven pathogenic variants were found in 11 patients with BiVNC (44.0%). The group with BiVNC had a higher ratio of mitochondrial and developmental gene variants than the other groups. Among all groups, the group with BiVNC had the worst survival rate (P=0.0009). CONCLUSIONS: Pediatric patients with BiVNC had a high rate of ventricular dyskinesis and poor outcome. A comprehensive and careful screening for disease-causing genes and phenotype may help identify specific patients with left ventricular noncom-paction and mortality-related cardiac phenotypes.

AB - BACKGROUND: Left ventricular noncompaction (LVNC) is a hereditary type of cardiomyopathy characterized by prominent tra-beculations. Detailed characteristics of biventricular noncompaction (BiVNC) remain unknown. This study aimed to elucidate the clinical characteristics and genetic landscape of BiVNC.METHODS AND RESULTS: We recruited children with left ventricular noncompaction from Japanese multi-institutional centers from 2013 to 2021. Left ventricular noncompaction was classified as BiVNC, congenital heart disease, arrhythmia, dilated car-diomyopathy, or normal function. In these patients, cardiomyopathy-associated genes were screened. A total of 234 patients (127 male; mean age, 4 months [range, 0–6.6 years]) were enrolled in this study, of whom 25 had BiVNC; 55, normal function; 84, dilated cardiomyopathy; 38, congenital heart disease; and 32, arrhythmia. BiVNC was diagnosed during the perinatal period in 10 patients, in whom the prevalence was higher than that in other patients. A total of 14 patients in the group with BiVNC had congenital heart disease, but not necessarily right heart lesions. Left ventricular dyskinesis was frequently observed in the lateral wall (24%) and apex (28%). Eleven pathogenic variants were found in 11 patients with BiVNC (44.0%). The group with BiVNC had a higher ratio of mitochondrial and developmental gene variants than the other groups. Among all groups, the group with BiVNC had the worst survival rate (P=0.0009). CONCLUSIONS: Pediatric patients with BiVNC had a high rate of ventricular dyskinesis and poor outcome. A comprehensive and careful screening for disease-causing genes and phenotype may help identify specific patients with left ventricular noncom-paction and mortality-related cardiac phenotypes.

KW - biventricular noncompaction

KW - congenital heart disease

KW - dyskinesis

KW - genetics

KW - heart failure

KW - left ventricular noncompaction

UR - http://www.scopus.com/inward/record.url?scp=85208601810&partnerID=8YFLogxK

U2 - 10.1161/JAHA.124.035614

DO - 10.1161/JAHA.124.035614

M3 - 学術論文

C2 - 39494597

AN - SCOPUS:85208601810

SN - 2047-9980

VL - 13

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

IS - 21

M1 - e035614

ER -

Determination of Genotype and Phenotypes in Pediatric Patients With Biventricular Noncompaction

Abstract

Keywords

ASJC Scopus subject areas

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