Sudden death during struggle in the setting of heterozygosity for a mutation in calsequesterin 2.

Abstract

Instances of sudden and unexpected death while in police custody remain complex and controversial cases in forensic pathology, and provide unique diagnostic challenges. In general, the circumstances of these cases have resulted in two major theories to account for these deaths: "excited delirium syndrome", and positional (restraint) asphyxia. However, some cases that are not easily explained by one of these theories may be best explained by a theory from another emergent area in forensic pathology, non-structural genetic heart disease. We present one such case, a sudden arrhythmic death during struggle/restraint. A 45year old man with developmental delay was walking outdoors as part of his daily routine. He was misidentified as a criminal suspect by police officers, who attempted to take him into custody. He resisted this arrest violently. He was taken to the ground, and restrained in a face-down position. Both police and civilian witness state that he was pushing his chest off the ground with his arms, when he suddenly collapsed and died. The interaction with police lasted approximately 3min. There was no prior excited delirium. At autopsy, minor external blunt force injuries were observed. The heart showed mild cardiomegaly with concentric left ventricular hypertrophy, and sub-occlusive coronary atherosclerosis. Toxicological testing was negative for common drugs, including cocaine and its metabolites. Post-mortem molecular testing demonstrated this man to be heterozygous for a catecholaminergic polymorphic ventricular tachycardia (CPVT) associated mutation (Phe189Leu) in the calsequestrin 2 (CASQ2) gene. This mutation was classified as a class I mutation (deleterious), that may cause disease in a heterozygous state. The cause of death was given as cardiac arrhythmia precipitated by struggle/restraint in a man with CPVT. This case illustrates the difficulty assigning a scientific cause of death in rare and controversial cases, and the value of the molecular autopsy in identifying disease causing mutations.