Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Aug;38(6):1262-1268.
doi: 10.1007/s00246-017-1655-0. Epub 2017 Jul 1.

Novel Genetic Variants in BAG3 and TNNT2 in a Swedish Family with a History of Dilated Cardiomyopathy and Sudden Cardiac Death

Eva Fernlund  1   2 , A Wålinder Österberg  3 , E Kuchinskaya  4 , M Gustafsson  5 , K Jansson  5   6 , C Gunnarsson  4   7
Affiliations

Novel Genetic Variants in BAG3 and TNNT2 in a Swedish Family with a History of Dilated Cardiomyopathy and Sudden Cardiac Death

Eva Fernlund et al. Pediatr Cardiol. 2017 Aug.

Abstract

Familial dilated cardiomyopathy is a rare cause of dilated cardiomyopathy (DCM), especially in childhood. Our aim was to describe the clinical course and the genetic variants in a family where the proband was a four-month-old infant presenting with respiratory problems due to DCM. In the family, there was a strong family history of DCM and sudden cardiac death in four generations. DNA was analyzed initially from the deceased girl using next-generation sequencing including 50 genes involved in cardiomyopathy. A cascade family screening was performed in the family after identification of the TNNT2 and the BAG3 variants in the proband. The first-degree relatives underwent clinical examination including biochemistry panel, cardiac ultrasound, Holter ECG, exercise stress test, and targeted genetic testing. The index patient presented with advanced DCM. After a severe clinical course, the baby had external left ventricular assist as a bridge to heart transplantation. 1.5 months after transplantation, the baby suffered sudden cardiac death (SCD) despite maximal treatment in the pediatric intensive care unit. The patient was shown to carry two heterozygous genetic variants in the TNNT2 gene [TNNT2 c.518G>A(p.Arg173Gln)] and BAG3 [BAG3 c.785C>T(p.Ala262Val)]. Two of the screened individuals (two females) appeared to carry both the familial variants. All the individuals carrying the TNNT2 variant presented with DCM, the two adult patients had mild or moderate symptoms of heart failure and reported palpitations but no syncope or presyncopal attacks prior to the genetic diagnosis. The female carriers of TNNT2 and BAG3 variants had more advanced DCM. In the family history, there were three additional cases of SCD due to DCM, diagnosed by autopsy, but no genetic analysis was possible in these cases. Our findings suggest that the variants in TNNT2 and BAG3 are associated with a high propensity to life-threatening cardiomyopathy presenting from childhood and young adulthood.

Keywords: BAG3; DCM; Familial DCM; SCD; TNNT2.

PubMed Disclaimer

Conflict of interest statement

The authors do not have any conflict of interest.

Figures

Fig. 1
Fig. 1
The first ECG in the proband (V:3) at the time of presentation, 4 months old, showing a picture of electrocardiographic hypertrophy and ST-depression over left ventricle
Fig. 2
Fig. 2
The chest X-ray at the time of presentation in the 4 month old proband, showing the severely enlarged heart
Fig. 3
Fig. 3
The echocardiogram at the time of presentation in the proband. a Apical four-chamber view showing the enlarged left ventricle. b Short-axis view showing the enlarged left chamber
Fig. 4
Fig. 4
The pedigree of the family. The proband V:3 developed DCM at 4 months of age, V:1 developed clinical DCM at the age of 18 years, and IV:1 and IV:2 at the early thirties. In the older generations, SCD due to DCM in their early forties (II:1, III:2, III:3)
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Elliott PM, Anastasakis A, Borger MA, et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC) Eur Heart J. 2014;35(39):2733–2779. doi: 10.1093/eurheartj/ehu284. - DOI - PubMed
    1. Wilkinson JD, Landy DC, Colan SD, et al. The pediatric cardiomyopathy registry and heart failure: key results from the first 15 years. Heart Fail Clin. 2010;6(4):401–413. doi: 10.1016/j.hfc.2010.05.002. - DOI - PMC - PubMed
    1. Kirk R, Dipchand AI, Rosenthal DN, et al. The International Society for Heart and Lung Transplantation Guidelines for the management of pediatric heart failure: executive summary. [Corrected] J Heart Lung Transplant. 2014;33(9):888–909. doi: 10.1016/j.healun.2014.06.002. - DOI - PubMed
    1. Taylor MR, Carniel E, Mestroni L. Cardiomyopathy, familial dilated. Orphanet J Rare Dis. 2006;1:27. doi: 10.1186/1750-1172-1-27. - DOI - PMC - PubMed
    1. Wren C. Screening children with a family history of sudden cardiac death. Heart. 2006;92(7):1001–1006. doi: 10.1136/hrt.2005.069757. - DOI - PMC - PubMed

Supplementary concepts