A New Inherited Syndrome Causing Sudden Cardiac Death with Distinct ST-Segment Depression and Ankyrin-2-Mutation

Hubertus von Korn; Cristina Basso; Kalliopi Pilichou; Victor Stefan; Patrick Swojanowsky

doi:10.2147/TACG.S438957

A New Inherited Syndrome Causing Sudden Cardiac Death with Distinct ST-Segment Depression and Ankyrin-2-Mutation

Appl Clin Genet. 2023 Dec 21:16:233-239. doi: 10.2147/TACG.S438957. eCollection 2023.

Authors

Hubertus von Korn¹, Cristina Basso², Kalliopi Pilichou², Victor Stefan¹, Patrick Swojanowsky¹

Affiliations

¹ Department of Cardiology, Marienhaus Klinikum Hetzelstift, Neustadt, Weinstraße, 67434, Germany.
² Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padua Medical School, Padova, 35128, Italy.

Abstract

Introduction: Sudden cardiac death (SCD) is a serious threat. In individuals under the age of 35 years sudden arrhythmic death is the most frequent cause. In younger persons, genetically determined cardiac diseases (eg, cardiomyopathies and ion-channel diseases) account for an important proportion of these cases.

Methods: We investigated the case of a 23-year-old male with SCD, specific ECG changes and left ventricular hypertrophy. Family history was significant for SCD in the paternal line. A precise analysis was performed by an international multidisciplinary expert panel including autopsy of the index patient's heart, molecular autopsy, whole-exome sequencing, analysis of the pedigree and examination of available family members.

Results: Three cases of SCD were reported in paternal relatives. The index patient exhibited specific ECG changes (ST-depression), which were also found in five paternal relatives and the brother of the index patient. Post-mortem analysis of the heart yielded mild idiopathic concentric hypertrophy without myocardial disarray. The genetic analysis of the index patient showed two nucleotide variations in two different genes (ANK2: c.11791G>A, MYO18B: c.3761G>A), which were also expressed in five relatives. Two family members had showed all indicators of the inherited syndrome including distinct ECG changes and genetic changes.

Conclusion: We describe a distinct inheritable syndrome causing SCD, characterized by specific ECG changes and mutations of ANK2 and MYO18. As far as we know this is the first description of this syndrome.

Keywords: MYO18; ST-segment depression; ankyrin 2; inherited syndrome; ion channel disorder; sudden cardiac death.

Grants and funding

The family of the patient paid for the whole exome sequencing. No institutional approval was required to conduct this research and publish the case details. Our hospital is an academic teaching hospital.