Biallelic PKP2 loss of function variants are associated with a lethal perinatal-onset biventricular dilated cardiomyopathy with excessive trabeculations and ventricular septal defects

Jack Gibb; Elizabeth Wall; Ella Fields; Anna Seale; Catherine Armstrong; Andrew Bamber; Piers Daubeney; Makaela Jacobs-Pearson; Tamas Marton; Karen Stals; Karen Low; Juan Pablo Kaski; Georgia Spentzou

doi:10.1136/jmg-2023-109493

Biallelic PKP2 loss of function variants are associated with a lethal perinatal-onset biventricular dilated cardiomyopathy with excessive trabeculations and ventricular septal defects

J Med Genet. 2024 Mar 21;61(4):405-409. doi: 10.1136/jmg-2023-109493.

Authors

Jack Gibb^#¹, Elizabeth Wall^#², Ella Fields^{3

4}, Anna Seale⁵, Catherine Armstrong⁶, Andrew Bamber⁷, Piers Daubeney^{8

9}, Makaela Jacobs-Pearson¹⁰, Tamas Marton^{11

12}, Karen Stals¹³, Karen Low^#^{10

14}, Juan Pablo Kaski^#^{3

4}, Georgia Spentzou^#⁶

Affiliations

¹ Department of Paediatric Cardiology, Bristol Royal Hospital for Children, Bristol, Bristol, UK [email protected].
² Department of Clinical Genetics, Birmingham Women's and Children's Hospitals NHS Foundation Trust, Birmingham, UK.
³ Centre for Paediatric Inherited and Rare Cardiovascular Disease, University College London, London, UK.
⁴ Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital for Children, London, UK.
⁵ Department of Paediatric Cardiology, Birmingham Women's and Children's Hospitals NHS Foundation Trust, Birmingham, UK.
⁶ Department of Paediatric Cardiology, Bristol Royal Hospital for Children, Bristol, Bristol, UK.
⁷ Department of Cellular Pathology, Southmead Hospital, Bristol, City of Bristol, UK.
⁸ Department of Paediatric Cardiology, Royal Brompton and Harefield Hospitals, London, UK.
⁹ Guy's and St Thomas' Hospitals NHS Trust, London, UK.
¹⁰ Department of Clinical Genetics, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK.
¹¹ Department of Obstetrics and Gynecology, Semmelweis University Faculty of Medicine, Budapest, Hungary.
¹² Department of Cellular pathology, Birmingham Women's and Children's Hospitals NHS Foundation Trust, Birmingham, UK.
¹³ Department of Molecular Genetics, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
¹⁴ Department of Academic Child Health, University of Bristol, Bristol, UK.

^# Contributed equally.

PMID: 38050058
DOI: 10.1136/jmg-2023-109493

Abstract

Homozygous plakophilin-2 (PKP2) variants have been identified as a cause of a lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET) in three cases. We report three more cases from two families with homozygous pathogenic PKP2 variants and perinatal-onset, lethal DCM-ET. Identification of the genetic abnormalities played a key role in decision-making and family counselling in these cases. This case series supports the published evidence that biallelic loss of function PKP2 variants cause a lethal, perinatal-onset cardiomyopathy.

Keywords: Cardiomyopathies; Child Health; Congenital, Hereditary, and Neonatal Diseases and Abnormalities.

MeSH terms

Cardiomyopathies* / genetics
Cardiomyopathy, Dilated* / genetics
Heart Septal Defects, Ventricular*
Homozygote
Humans
Plakophilins / genetics

Substances

Plakophilins
PKP2 protein, human