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

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 (), 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 and . As far as we know this is the first description of this syndrome.