The Application of Clinical Genetics (Dec 2023)
A New Inherited Syndrome Causing Sudden Cardiac Death with Distinct ST-Segment Depression and Ankyrin-2-Mutation
Abstract
Hubertus von Korn,1 Cristina Basso,2 Kalliopi Pilichou,2 Victor Stefan,1 Patrick Swojanowsky1 1Department of Cardiology, Marienhaus Klinikum Hetzelstift, Neustadt, Weinstraße, 67434, Germany; 2Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padua Medical School, Padova, 35128, ItalyCorrespondence: Hubertus von Korn, Department of Cardiology, Stiftstr. 10, Neustadt, 67434, Germany, Tel +496321 859 400, Fax +496321 859 4009, Email [email protected]: 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: sudden cardiac death, inherited syndrome, ion channel disorder, ankyrin 2, ST-segment depression, MYO18
