Familial severe non-ischemic dilated cardiomyopathy with coexisting likely pathogenic BAG3 and FLNC variants: a case report
- 1Department of Cardiology, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine
Abstract
Background: Dilated cardiomyopathy (DCM) is genetically heterogeneous. In severe non-ischemic DCM with familial clustering of heart-failure deaths, genetic testing and pedigree analysis may clarify etiology and guide cascade screening.
Case presentation: A 40-year-old woman presented with progressive dyspnea, chest tightness, and palpitations after an upper respiratory tract infection. Echocardiography showed severe left ventricular systolic dysfunction [left ventricular ejection fraction (LVEF) approximately 20%], left atrial enlargement, functional mitral regurgitation, and a small pericardial effusion. Serial cardiac troponin I and myocardial enzyme measurements remained within the reference ranges. Coronary angiography excluded obstructive coronary disease. Cardiovascular magnetic resonance (CMR) demonstrated global left ventricular hypokinesis and a clinically reported non-ischemic late-gadolinium-enhancement pattern at the papillary-muscle level involving the anterior/lateral wall. Because cardiac biomarkers remained normal and dedicated inflammatory CMR sequences were not acquired, active myocarditis could not be confirmed. Guideline-directed therapy reduced NT-proBNP from 4154 to 828 pg/mL, although angiotensin receptor-neprilysin inhibitor therapy was limited by symptomatic hypotension. At 2 months, symptoms and daily activity tolerance improved, but LVEF remained 25%, QTc was 479 ms, and ventricular premature complexes persisted. Whole-exome sequencing identified heterozygous likely pathogenic variants in BAG3 (NM_004281.4:c.180 + 1G > T) and FLNC [NM_001458.5:c.761_779del, p.(Leu254Profs*14)]. The daughter carried the BAG3 variant, whereas both children were negative for FLNC. The proband reported heart-failure-related deaths in her father and younger brother during adulthood and in a nephew during childhood.
Conclusions: The findings support complex familial non-ischemic DCM with marked variable expressivity. Coexisting BAG3 and FLNC variants should be interpreted as hypothesis-generating rather than proof of dual-gene causality. The infection-associated acute decompensation, persistently normal cardiac injury biomarkers, non-ischemic LGE, and incomplete inflammatory CMR characterization favor cautious interpretation rather than a definitive diagnosis of myocarditis. Serial imaging, rhythm surveillance, individualized device-risk assessment, and follow-up of genotype-positive relatives are essential.
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BibTeX
@article{lili2026familial,
title = {{Familial severe non-ischemic dilated cardiomyopathy with coexisting likely pathogenic BAG3 and FLNC variants: a case report}},
author = {Wang Lili and Wang Youcao and Yao Xiaodong and Wang Zhen},
journal = {Frontiers in Cardiovascular Medicine},
year = {2026},
month = oct,
doi = {10.3389/fcvm.2026.2000926},
url = {https://www.frontiersin.org/articles/10.3389/fcvm.2026.2000926/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Familial severe non-ischemic dilated cardiomyopathy with coexisting likely pathogenic BAG3 and FLNC variants: a case report
AU - Wang Lili
AU - Wang Youcao
AU - Yao Xiaodong
AU - Wang Zhen
PY - 2026
DA - 2026/10/30
JO - Frontiers in Cardiovascular Medicine
DO - 10.3389/fcvm.2026.2000926
UR - https://www.frontiersin.org/articles/10.3389/fcvm.2026.2000926/full
AB - Background: Dilated cardiomyopathy (DCM) is genetically heterogeneous. In severe non-ischemic DCM with familial clustering of heart-failure deaths, genetic testing and pedigree analysis may clarify etiology and guide cascade screening. Case presentation: A 40-year-old woman presented with progressive dyspnea, chest tightness, and palpitations after an upper respiratory tract infection. Echocardiography showed severe left ventricular systolic dysfunction [left ventricular ejection fraction (LVEF) approximately 20%], left atrial enlargement, functional mitral regurgitation, and a small pericardial effusion. Serial cardiac troponin I and myocardial enzyme measurements remained within the reference ranges. Coronary angiography excluded obstructive coronary disease. Cardiovascular magnetic resonance (CMR) demonstrated global left ventricular hypokinesis and a clinically reported non-ischemic late-gadolinium-enhancement pattern at the papillary-muscle level involving the anterior/lateral wall. Because cardiac biomarkers remained normal and dedicated inflammatory CMR sequences were not acquired, active myocarditis could not be confirmed. Guideline-directed therapy reduced NT-proBNP from 4154 to 828 pg/mL, although angiotensin receptor-neprilysin inhibitor therapy was limited by symptomatic hypotension. At 2 months, symptoms and daily activity tolerance improved, but LVEF remained 25%, QTc was 479 ms, and ventricular premature complexes persisted. Whole-exome sequencing identified heterozygous likely pathogenic variants in BAG3 (NM_004281.4:c.180 + 1G > T) and FLNC [NM_001458.5:c.761_779del, p.(Leu254Profs*14)]. The daughter carried the BAG3 variant, whereas both children were negative for FLNC. The proband reported heart-failure-related deaths in her father and younger brother during adulthood and in a nephew during childhood. Conclusions: The findings support complex familial non-ischemic DCM with marked variable expressivity. Coexisting BAG3 and FLNC variants should be interpreted as hypothesis-generating rather than proof of dual-gene causality. The infection-associated acute decompensation, persistently normal cardiac injury biomarkers, non-ischemic LGE, and incomplete inflammatory CMR characterization favor cautious interpretation rather than a definitive diagnosis of myocarditis. Serial imaging, rhythm surveillance, individualized device-risk assessment, and follow-up of genotype-positive relatives are essential.
SN - 2297-055X
ER -