Muerte súbita de jóvenes: rendimiento diagnóstico de un programa autonómico de autopsia molecular con secuenciación masiva / Sudden cardiac death in persons aged 50 years or younger: diagnostic yield of a regional molecular autopsy program using massive sequencing

Introducción y objetivos La muerte súbita (MS) de personas jóvenes suele tener una causa genética, por lo cual la «autopsia molecular» puede tener implicaciones importantes para los familiares. El objetivo del estudio es evaluar el rendimiento diagnóstico de un programa de autopsia molecular mediante secuenciación masiva. Métodos Estudio prospectivo de una cohorte de pacientes consecutivos de edad ≤ 50 años y fallecidos por MS no violenta, a los que se realizó autopsia molecular mediante paneles amplios por secuenciación masiva, con posterior cribado familiar clínico y genético. Se analizan datos demográficos, clínicos, toxicológicos y genéticos. Resultados Se estudiaron 123 casos consecutivos de MS a edades ≤ 50 años. La incidencia de MS fue de 5,8 casos/100.000 individuos/año, a una media de edad de 36,15±12,7 años; 95 (77%) eran varones. La causa fue cardiaca en el 53%; MS inexplicada en el 24%, tóxicos en el 10,6% y MS del lactante en el 4%. De las cardiacas, el 38% por cardiopatía isquémica, el 7% por miocardiopatía arritmogénica, el 5% por miocardiopatía hipertrófica y el 11% por hipertrofia ventricular izquierda idiopática. Se indicó análisis genético en 62 casos (50,4%). Se hallaron variantes genéticas en 42 (67,7%), con una media de 3,4±4 variantes/paciente, que se consideraron patogénicas o probablemente patogénicas en el 30,6%. De las MS inexplicadas, hasta el 70% presentó alguna variante genética. El estudio familiar permitió detectar a 21 portadores o afectos, 5 de ellos estaban en riesgo, por lo que se indicó implante de desfibrilador. Conclusiones El estudio protocolizado y exhaustivo de la MS cardiaca de personas jóvenes es factible y necesario. En un alto porcentaje la causa es genética y, por lo tanto, existen familiares en riesgo que pueden beneficiarse de un diagnóstico y un tratamiento precoces para evitar complicaciones. (AU)

Introduction and objectives Sudden cardiac death (SCD) in young people often has a genetic cause. Consequently, the results of “molecular autopsy” may have important implications for their relatives. Our objective was to evaluate the diagnostic yield of a molecular autopsy program using next-generation sequencing. Methods We performed a prospective study of a cohort of consecutive patients who died from nonviolent SCD, aged ≤ 50 years, and who underwent molecular autopsy using large panels of next-generation sequencing, with subsequent clinical and genetic family screening. We analyzed demographic, clinical, toxicological, and genetic data. Results We studied 123 consecutive cases of SCD in persons aged ≤ 50 years. The incidence of SCD was 5.8 cases/100 000 individuals/y, mean age was 36.15±12.7 years, and 95 were men (77%). The cause was cardiac in 53%, unexplained SCD in 24%, toxic in 10.6%, and infant SCD in 4%. Among cardiac causes, ischemic heart disease accounted for 38% of deaths, arrhythmogenic cardiomyopathy for 7%, hypertrophic cardiomyopathy for 5%, and idiopathic left ventricular hypertrophy for 11%. Genetic analysis was performed in 62 cases (50.4%). Genetic variants were found in 42 cases (67.7%), with a mean of 3.4±4 genetic variants/patient, and the variant found was considered to be pathogenic or probably pathogenic in 30.6%. In unexplained SCD, 70% showed some genetic variant. Family screening diagnosed 21 carriers or affected individuals, 5 of whom were at risk, indicating an implantable cardiac defibrillator. Conclusions Protocol-based and exhaustive study of SCD from cardiac causes in persons aged ≤ 50 years is feasible and necessary. In a high percentage of cases, the cause is genetic, indicating the existence of relatives at risk who could benefit from early diagnosis and treatment to avoid complications. (AU)

Sudden cardiac death in persons aged 50 years or younger: diagnostic yield of a regional molecular autopsy program using massive sequencing.

INTRODUCTION AND OBJECTIVES: Sudden cardiac death (SCD) in young people often has a genetic cause. Consequently, the results of "molecular autopsy" may have important implications for their relatives. Our objective was to evaluate the diagnostic yield of a molecular autopsy program using next-generation sequencing. METHODS: We performed a prospective study of a cohort of consecutive patients who died from nonviolent SCD, aged ≤ 50 years, and who underwent molecular autopsy using large panels of next-generation sequencing, with subsequent clinical and genetic family screening. We analyzed demographic, clinical, toxicological, and genetic data. RESULTS: We studied 123 consecutive cases of SCD in persons aged ≤ 50 years. The incidence of SCD was 5.8 cases/100 000 individuals/y, mean age was 36.15±12.7 years, and 95 were men (77%). The cause was cardiac in 53%, unexplained SCD in 24%, toxic in 10.6%, and infant SCD in 4%. Among cardiac causes, ischemic heart disease accounted for 38% of deaths, arrhythmogenic cardiomyopathy for 7%, hypertrophic cardiomyopathy for 5%, and idiopathic left ventricular hypertrophy for 11%. Genetic analysis was performed in 62 cases (50.4%). Genetic variants were found in 42 cases (67.7%), with a mean of 3.4±4 genetic variants/patient, and the variant found was considered to be pathogenic or probably pathogenic in 30.6%. In unexplained SCD, 70% showed some genetic variant. Family screening diagnosed 21 carriers or affected individuals, 5 of whom were at risk, indicating an implantable cardiac defibrillator. CONCLUSIONS: Protocol-based and exhaustive study of SCD from cardiac causes in persons aged ≤ 50 years is feasible and necessary. In a high percentage of cases, the cause is genetic, indicating the existence of relatives at risk who could benefit from early diagnosis and treatment to avoid complications.

Lesiones y muerte por balconing en Baleares / Injuries and death by balconing from the Balearic Islands

Introducción. El balconing es un fenómeno relativamente reciente en las Islas Baleares (España), protagonizado típicamente por jóvenes turistas en establecimientos hoteleros, que consiste en pasar de balcón a balcón o en saltar desde el balcón a la piscina, y que se ha asociado al consumo de alcohol o drogas. El objetivo del presente trabajo es describir los casos de lesiones y muerte por supuesto balconing. Material y métodos. Estudio descriptivo retrospectivo de fallecidos y heridos por precipitación que fueron tratados como balconing por los medios de comunicación durante el año 2010 en la isla de Mallorca. Fuentes de información: autopsias del Instituto de Medicina Legal de las Islas Baleares y atestados de la Guardia Civil. Resultados. Se identificaron 11 casos, constituidos por 5 fallecimientos y 6 supervivientes. La mayoría fueron varones (8 casos), de 30 años de edad o menos (8 casos), y de nacionalidad extranjera (10 casos). La etiología medicolegal fue accidental en 8 casos, solo uno de ellos con características propias de balconing, suicida en 2 casos, e indeterminada en uno. Conclusiones. A pesar del impacto mediático del balconing, las precipitaciones en establecimientos turísticos no siempre se corresponden con este fenómeno. Como en otros tipos de lesiones no intencionales, las fuentes medicoforenses pueden aportar una información muy valiosa(AU)

Introduction. Balconing is a relatively recent phenomenon in Balearic Islands (Spain), featuring typically young people in tourist resorts, who jump from balcony to balcony or from the balcony to the swimming pool, under the influence of alcohol or drugs of abuse. This article aims to describe the cases of death or injury attributed to balconing. Material and methods. Descriptive and retrospective study of fatalities and injuries as a result of falls which were presented as balconing events by the media during the year 2010 in the island of Majorca. Information sources: autopsies from the Institute of Legal Medicine of the Balearic Islands and police reports from the Guardia Civil. Results. Eleven cases were identified: 5 were deaths and 6 were survivors. Most of the cases were men (8 cases), aged 30 years or less (8 cases), and foreigners (10 cases). The manner of death or injury was accident for 8 cases, of which only 1 had balconing characteristics, suicide for 2 cases, and undetermined for 1 case. Conclusions. In spite of the media impact of balconing, the falls in tourist resorts do not always fit its definition. As with other non-intentional injuries, clinical forensic medicine or forensic pathology are a valuable source of information(AU)