The yield of family screening in sudden unexplained death in the young

Objectives: When autopsy is performed after sudden death of a young person, cause of death remains undetermined in 6-65%, which is termed sudden unexplained death (SUD). In these cases molecular autopsy and cardiological and genetic examination in surviving first degree relatives is known to unmask its cause, especially primary arrhythmia syndromes. We explored the yield of family screening in a large series of young SUD victims. Methods: We studied all consecutive families who presented to the cardiogenetics department of our university hospital between 1996-2008 for family screening because of ≥1 first degree related SUD victim aged 1-50 years. In the Netherlands autopsy is not mandatory in these cases, and was not performed in 53.8%. It the remainder, autopsy did not reveal a cause of death. First, relatives were questioned on their personal and family medical history and a resting ECG was made. If possible, autopsy of the heart was revised. In most cases, relatives were referred to a cardiologist, who generally performed an exercise test and echocardiography. Other examinations, such as ajmaline drug challenge, Holter monitoring and cardiac MRI, were performed on indication. Genetic analysis of the associated candidate gene(s) was performed in material obtained from the deceased person or in those relatives with clinical abnormalities. Results: Relatives of 115 SUD victims (mean age at death 29.1 years, 67.8% male) were examined. In 52.6% events occurred at rest and in 29.8% upon exertion. Approximately 16% of the victims had experienced an unexplained syncope before the event, mainly at exertion, and one victim had survived a previous out-of-hospital cardiac arrest. A mean of 2.5 (1-8) first-degree relatives were examined per family (N=242). In 28 families another first degree family member age