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.

Calcificación miocárdica y muerte súbita: posible relación etiopatogénica. A propósito de 2 casos / Myocardial calcification and sudden death: Possible aetiopathogenic relationship. Report of two cases

Se describen 2 casos de muerte súbita con hallazgo autópsico de una calcificación miocárdica difusa. El primer caso en posible relación a un hiperparatiroidismo primario por adenoma de paratiroides, y el segundo de origen indeterminado por autopsia incompleta. Se comentan los antecedentes clínicos y la descripción histopatológica de ambos casos, las posibles causas de la calcificación, y el mecanismo por el que pudo ocurrir la muerte súbita de ambos pacientes

Two cases are described of sudden death with an autopsy finding of significant myocardial calcification. The first case was in possibly due to primary hyperparathyroidism caused by parathyroid adenoma. The second case was of indeterminate origin due to incomplete autopsy. The clinical background and histopathological description of both cases, as well as the possible causes of the calcification, that have to be taken into account in the study of sudden death, are discussed

Arteriosclerosis in paleopathology. Are macroscopic findings well known?

Although clinical atherosclerosis is fairly common, it is a surprisingly uncommon finding in anthropology. Several cases have been reported in the anthropological literature but most of them are referred to X-ray studies and to computerized tomographic imaging but, as far as we know, no macroscopic findings useful to anthropologists have been published before. We present a case of an adult male skeleton scattered on a wooded area with remains of partially mummified soft tissues between right tibia and fibula in which macroscopic findings showed a cylindrical structure that could be confused with a root or a branch. This cylindrical structure was diagnosed as an arterial segment and microscopic findings revealed calcified eccentric fibroatheromatosis. We hope this case will improve the knowledge of this macroscopic appearance and thus be useful to anthropologists.

Aspectos médico-forenses de la muerte súbita del adulto / Forensic medicine issues of sudden cardiac death

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