Diagnostic Yield of Genetic Testing in Young Patients With Atrioventricular Block of Unknown Cause

Johnni Resdal Dyssekilde; Tanja Charlotte Frederiksen; Morten Krogh Christiansen; Rikke Hasle Sørensen; Lisbeth Nørum Pedersen; Peter Loof Møller; Lene Svendstrup Christensen; Jacob Moesgaard Larsen; Kristian Korsgaard Thomsen; Tommi Bo Lindhardt; Morten Böttcher; Stig Molsted; Ole Havndrup; Thomas Fischer; Dorthe Svenstrup Møller; Finn Lund Henriksen; Jens Brock Johansen; Jens Cosedis Nielsen; Henning Bundgaard; Mette Nygaard; Henrik Kjærulf Jensen

doi:10.1161/JAHA.121.025643

Diagnostic Yield of Genetic Testing in Young Patients With Atrioventricular Block of Unknown Cause

Johnni Resdal Dyssekilde, Tanja Charlotte Frederiksen^*, Morten Krogh Christiansen, Rikke Hasle Sørensen, Lisbeth Nørum Pedersen, Peter Loof Møller, Lene Svendstrup Christensen, Jacob Moesgaard Larsen, Kristian Korsgaard Thomsen, Tommi Bo Lindhardt, Morten Böttcher, Stig Molsted, Ole Havndrup, Thomas Fischer, Dorthe Svenstrup Møller, Finn Lund Henriksen, Jens Brock Johansen, Jens Cosedis Nielsen, Henning Bundgaard, Mette NygaardHenrik Kjærulf Jensen

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

3 Citations (Scopus)

Abstract

Background The cause of atrioventricular block (AVB) remains unknown in approximately half of young patients with the diagnosis. Although variants in several genes associated with cardiac conduction diseases have been identified, the contribution of genetic variants in younger patients with AVB is unknown. Methods and Results Using the Danish Pacemaker and Implantable Cardioverter Defibrillator (ICD) Registry, we identified all patients younger than 50 years receiving a pacemaker because of AVB in Denmark in the period from January 1, 1996 to December 31, 2015. From medical records, we identified patients with unknown cause of AVB at time of pacemaker implantation. These patients were invited to a genetic screening using a panel of 102 genes associated with inherited cardiac diseases. We identified 471 living patients with AVB of unknown cause, of whom 226 (48%) accepted participation. Median age at the time of pacemaker implantation was 39 years (interquartile range, 32-45 years), and 123 (54%) were men. We found pathogenic or likely pathogenic variants in genes associated with or possibly associated with AVB in 12 patients (5%). Most variants were found in the LMNA gene (n=5). LMNA variant carriers all had a family history of either AVB and/or sudden cardiac death. Conclusions In young patients with AVB of unknown cause, we found a possible genetic cause in 1 out of 20 participating patients. Variants in the LMNA gene were most common and associated with a family history of AVB and/or sudden cardiac death, suggesting that genetic testing should be a part of the diagnostic workup in these patients to stratify risk and screen family members.

Original language	English
Article number	e025643
Journal	Journal of the American Heart Association
Volume	11
Issue	9
ISSN	2047-9980
DOIs	https://doi.org/10.1161/JAHA.121.025643
Publication status	Published - 3 May 2022

Keywords

LMNA
conduction
diagnostic testing
inherited heart diseases

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10.1161/JAHA.121.025643Licence: CC BY-NC-ND

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Dyssekilde, J. R., Frederiksen, T. C., Christiansen, M. K., Hasle Sørensen, R., Pedersen, L. N., Loof Møller, P., Christensen, L. S., Larsen, J. M., Thomsen, K. K., Lindhardt, T. B., Böttcher, M., Molsted, S., Havndrup, O., Fischer, T., Møller, D. S., Henriksen, F. L., Johansen, J. B., Nielsen, J. C., Bundgaard, H., ... Jensen, H. K. (2022). Diagnostic Yield of Genetic Testing in Young Patients With Atrioventricular Block of Unknown Cause. Journal of the American Heart Association, 11(9), Article e025643. https://doi.org/10.1161/JAHA.121.025643

@article{d96ac6b5de654453a8e13056e1d02a71,

title = "Diagnostic Yield of Genetic Testing in Young Patients With Atrioventricular Block of Unknown Cause",

abstract = "Background The cause of atrioventricular block (AVB) remains unknown in approximately half of young patients with the diagnosis. Although variants in several genes associated with cardiac conduction diseases have been identified, the contribution of genetic variants in younger patients with AVB is unknown. Methods and Results Using the Danish Pacemaker and Implantable Cardioverter Defibrillator (ICD) Registry, we identified all patients younger than 50 years receiving a pacemaker because of AVB in Denmark in the period from January 1, 1996 to December 31, 2015. From medical records, we identified patients with unknown cause of AVB at time of pacemaker implantation. These patients were invited to a genetic screening using a panel of 102 genes associated with inherited cardiac diseases. We identified 471 living patients with AVB of unknown cause, of whom 226 (48%) accepted participation. Median age at the time of pacemaker implantation was 39 years (interquartile range, 32-45 years), and 123 (54%) were men. We found pathogenic or likely pathogenic variants in genes associated with or possibly associated with AVB in 12 patients (5%). Most variants were found in the LMNA gene (n=5). LMNA variant carriers all had a family history of either AVB and/or sudden cardiac death. Conclusions In young patients with AVB of unknown cause, we found a possible genetic cause in 1 out of 20 participating patients. Variants in the LMNA gene were most common and associated with a family history of AVB and/or sudden cardiac death, suggesting that genetic testing should be a part of the diagnostic workup in these patients to stratify risk and screen family members. ",

keywords = "LMNA, conduction, diagnostic testing, inherited heart diseases",

author = "Dyssekilde, {Johnni Resdal} and Frederiksen, {Tanja Charlotte} and Christiansen, {Morten Krogh} and {Hasle S{\o}rensen}, Rikke and Pedersen, {Lisbeth N{\o}rum} and {Loof M{\o}ller}, Peter and Christensen, {Lene Svendstrup} and Larsen, {Jacob Moesgaard} and Thomsen, {Kristian Korsgaard} and Lindhardt, {Tommi Bo} and Morten B{\"o}ttcher and Stig Molsted and Ole Havndrup and Thomas Fischer and M{\o}ller, {Dorthe Svenstrup} and Henriksen, {Finn Lund} and Johansen, {Jens Brock} and Nielsen, {Jens Cosedis} and Henning Bundgaard and Mette Nygaard and Jensen, {Henrik Kj{\ae}rulf}",

year = "2022",

month = may,

day = "3",

doi = "10.1161/JAHA.121.025643",

language = "English",

volume = "11",

journal = "Journal of the American Heart Association",

issn = "2047-9980",

publisher = "American Heart Association Inc.",

number = "9",

}

Dyssekilde, JR , Frederiksen, TC , Christiansen, MK , Hasle Sørensen, R, Pedersen, LN, Loof Møller, P, Christensen, LS, Larsen, JM, Thomsen, KK, Lindhardt, TB, Böttcher, M, Molsted, S, Havndrup, O, Fischer, T, Møller, DS, Henriksen, FL, Johansen, JB, Nielsen, JC, Bundgaard, H, Nygaard, M & Jensen, HK 2022, 'Diagnostic Yield of Genetic Testing in Young Patients With Atrioventricular Block of Unknown Cause', Journal of the American Heart Association, vol. 11, no. 9, e025643. https://doi.org/10.1161/JAHA.121.025643

Diagnostic Yield of Genetic Testing in Young Patients With Atrioventricular Block of Unknown Cause. / Dyssekilde, Johnni Resdal ; Frederiksen, Tanja Charlotte ; Christiansen, Morten Krogh et al.
In: Journal of the American Heart Association, Vol. 11, No. 9, e025643, 03.05.2022.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Diagnostic Yield of Genetic Testing in Young Patients With Atrioventricular Block of Unknown Cause

AU - Dyssekilde, Johnni Resdal

AU - Frederiksen, Tanja Charlotte

AU - Christiansen, Morten Krogh

AU - Hasle Sørensen, Rikke

AU - Pedersen, Lisbeth Nørum

AU - Loof Møller, Peter

AU - Christensen, Lene Svendstrup

AU - Larsen, Jacob Moesgaard

AU - Thomsen, Kristian Korsgaard

AU - Lindhardt, Tommi Bo

AU - Böttcher, Morten

AU - Molsted, Stig

AU - Havndrup, Ole

AU - Fischer, Thomas

AU - Møller, Dorthe Svenstrup

AU - Henriksen, Finn Lund

AU - Johansen, Jens Brock

AU - Nielsen, Jens Cosedis

AU - Bundgaard, Henning

AU - Nygaard, Mette

AU - Jensen, Henrik Kjærulf

PY - 2022/5/3

Y1 - 2022/5/3

N2 - Background The cause of atrioventricular block (AVB) remains unknown in approximately half of young patients with the diagnosis. Although variants in several genes associated with cardiac conduction diseases have been identified, the contribution of genetic variants in younger patients with AVB is unknown. Methods and Results Using the Danish Pacemaker and Implantable Cardioverter Defibrillator (ICD) Registry, we identified all patients younger than 50 years receiving a pacemaker because of AVB in Denmark in the period from January 1, 1996 to December 31, 2015. From medical records, we identified patients with unknown cause of AVB at time of pacemaker implantation. These patients were invited to a genetic screening using a panel of 102 genes associated with inherited cardiac diseases. We identified 471 living patients with AVB of unknown cause, of whom 226 (48%) accepted participation. Median age at the time of pacemaker implantation was 39 years (interquartile range, 32-45 years), and 123 (54%) were men. We found pathogenic or likely pathogenic variants in genes associated with or possibly associated with AVB in 12 patients (5%). Most variants were found in the LMNA gene (n=5). LMNA variant carriers all had a family history of either AVB and/or sudden cardiac death. Conclusions In young patients with AVB of unknown cause, we found a possible genetic cause in 1 out of 20 participating patients. Variants in the LMNA gene were most common and associated with a family history of AVB and/or sudden cardiac death, suggesting that genetic testing should be a part of the diagnostic workup in these patients to stratify risk and screen family members.

AB - Background The cause of atrioventricular block (AVB) remains unknown in approximately half of young patients with the diagnosis. Although variants in several genes associated with cardiac conduction diseases have been identified, the contribution of genetic variants in younger patients with AVB is unknown. Methods and Results Using the Danish Pacemaker and Implantable Cardioverter Defibrillator (ICD) Registry, we identified all patients younger than 50 years receiving a pacemaker because of AVB in Denmark in the period from January 1, 1996 to December 31, 2015. From medical records, we identified patients with unknown cause of AVB at time of pacemaker implantation. These patients were invited to a genetic screening using a panel of 102 genes associated with inherited cardiac diseases. We identified 471 living patients with AVB of unknown cause, of whom 226 (48%) accepted participation. Median age at the time of pacemaker implantation was 39 years (interquartile range, 32-45 years), and 123 (54%) were men. We found pathogenic or likely pathogenic variants in genes associated with or possibly associated with AVB in 12 patients (5%). Most variants were found in the LMNA gene (n=5). LMNA variant carriers all had a family history of either AVB and/or sudden cardiac death. Conclusions In young patients with AVB of unknown cause, we found a possible genetic cause in 1 out of 20 participating patients. Variants in the LMNA gene were most common and associated with a family history of AVB and/or sudden cardiac death, suggesting that genetic testing should be a part of the diagnostic workup in these patients to stratify risk and screen family members.

KW - LMNA

KW - conduction

KW - diagnostic testing

KW - inherited heart diseases

UR - http://www.scopus.com/inward/record.url?scp=85129781151&partnerID=8YFLogxK

U2 - 10.1161/JAHA.121.025643

DO - 10.1161/JAHA.121.025643

M3 - Journal article

C2 - 35470684

SN - 2047-9980

VL - 11

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

IS - 9

M1 - e025643

ER -

Diagnostic Yield of Genetic Testing in Young Patients With Atrioventricular Block of Unknown Cause

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