Unsuspected hereditary hemochromatosis at forensic autopsy: its presentation, confirmation, and implications

Hereditary hemochromatosis (HH) is one of the most common genetic disorders and may present clinically in a variety of ways. The most common presentation is micronodular cirrhosis with possible associated diabetes. However, HH may also present with cardiac dysfunction and sudden death. The confirmation of unsuspected HH at autopsy is complicated by the growing number of genetic abnormalities, which are not detected by current commercial genetic testing for C282Y and H63D mutations. Consequently, quantitative liver iron studies on fresh or paraffin embedded liver is recommended in confirming HH. The importance of detection and confirmation of HH cannot be overemphasized given the need to screen surviving family members in preventing organ damage of asymptomatic individuals. We present a case of a 38-year-old white woman with micronodular cirrhosis secondary to unsuspected HH that was confirmed by a quantitative liver iron study. The possible presentation of cardiac sudden death from HH, confirmation issues and implications of a HH diagnosis for surviving family members are also discussed.     

Cardiac concussion: definition, differential diagnosis, and cases presentation and the legal ramification of a misdiagnosis

A cardiac concussion is caused by a sudden, nonpenetrating, localized impact to the chest that is theorized to result in almost simultaneous sudden death from a disruption to the conductive system. The detailed external/internal forensic examination of the body reveals no evidence of structural, pathologic, or histologic signs of trauma to the heart. A cardiac concussion is a rare and often overlooked cause of sudden death. This type of sudden death is typically seen among younger individuals participating in sports involving projectiles and, to a lesser degree, where collisions occur. Cardiac concussions are clinically, pathologically, and chemically different from a cardiac contusion. The objective of this paper will be to define cardiac concussion, differentiate between cardiac concussion and cardiac contusion, and describe the clinical and pathologic features of a 32-year-old white male who died of a cardiac concussion following a collision with a catcher during a softball game. The civil ramification of incorrectly diagnosing the manner of death in cases of death involving a cardiac concussion will also be addressed.     

Fatal lung hemorrhage in complex pulmonary angiodysplasia in a case of mongolism

A case of sudden and unexpected death of a boy with Down-Syndrome is reported. Death was due to acute excessive haemorrhage from the lungs. There were no cardiac anomalies. Histology revealed in addition to mediahyperplasia, intimaproliferation and occlusions, multiple foci of anomalous ectatic blood vessels predominantly in the lungs, some of which ruptured and bled into adjacent airways. Evidence of previous less severe bleeding episodes was present. Further investigation showed a familial occurrence of the blood vessel anomaly.     

连接蛋白43与心性猝死的相关性研究进展

部分心性猝死者死后尸检时心脏没有发现明显病理学异常征象,过去均将其归属原因不明的猝死范畴。近年来研究显示,心肌连接蛋白43（connexin43,Cx43）表达对于心性猝死的诊断具有十分重要的意义。本文就Cx43结构、功能以及在心血管疾病发生发展中的作用与法医学意义作一综述。     

Mechanisms of unexpected death in tuberous sclerosis

Tuberous sclerosis complex is a protean autosomal dominant disorder characterized by multifocal tissue lesions arising from defects in cellular migration, proliferation, and differentiation. It has an association with sudden death. In the current study, review of all cases of sudden death due to tuberous sclerosis was undertaken at the Forensic Science Centre in Adelaide, Australia from 1991 to 2001, in addition to an analysis of cases from the literature. There were two local cases where unexpected death had occurred in individuals with known tuberous sclerosis, involving a 31-year-old male (epilepsy), and a 24-year-old female (massive hemorrhage into a renal angiomyolipoma). Fatal mechanisms in cases of tuberous sclerosis may be associated with underlying cardiovascular, renal and cerebral abnormalities. Sudden death may be due to cardiac arrhythmia, epilepsy, and intra-tumoral hemorrhage with additional complications including cardiac outflow obstruction, obstructive hydrocephalus, aneurysm rupture, and spontaneous pneumothorax. An awareness of the highly variable tissue manifestations of tuberous sclerosis and the mechanisms that may be responsible for death is necessary to establish correctly the diagnosis in occult cases (possibly with molecular confirmation), and to chart accurately organ changes in individuals with established disease.     

Association of right coronary artery hypoplasia with sudden death in an eleven-year-old child

Congenital coronary artery abnormalities are a rare but well-documented cause of sudden and unexpected death in the pediatric age group. Most reported cases involve both an aberrant origin and course of the abnormal vessel. A case of unexpected death occurring in an otherwise healthy eleven-year-old boy, who had been previously investigated for sudden collapse, is described. The major finding at autopsy was marked disparity in diameter between the coronary arteries due to diffuse hypoplasia of the right coronary artery. This case demonstrates the importance of meticulous examination of the coronary artery system in cases of sudden death in childhood so that significant reduction in luminal cross section will be adequately documented. The possible role played by this finding in the etiology of sudden death is discussed.     

Impact of Myocardial Infarction and Abnormalities of Cardiac Conduction System on Sudden Cardiac DeathCSCD

Sudden cardiac death (SCD), most commonly seen in coronary heart disease, is a kind of sudden death caused by series of cardiac parameters, which usually combines with myocardial infarction. However, some SCDs (including early myocardial infarction) happen suddenly and cause death in a very short time. In these circumstances, typical morphological changes are lack in macroscopic or microscopic fields, which make such SCDs become the emphasis and difficulty in the present research. SCD caused by myocardial infarction and abnormalities of cardiac conduction system (CCS) is related to atherosclerosis of coronary artery closely. This paper reviews cardiac dysfunction caused by myocardial infarction and diseases of CCS from morphology and molecular biology, and explores potential relationship between them. This paper aims to provide clues to the mechanism of myocardial infarction related sudden death and possible assistance for forensic diagnosis of SCD. © 2017 by the Editorial Department of Journal of Forensic Medicine.     

Molecular genetics of sudden cardiac death

Sudden cardiac death (SCD) is one of the most common causes of death. An important number of sudden deaths, especially in the young, are due to genetic heart disorders, both with structural and arrhythmogenic abnormalities. In recent years, significant advances have been made in understanding the genetic basis of SCD. Identification of the genetic causes of sudden death is important because close relatives are also at potential risk of having a fatal cardiac condition. A comprehensive post-mortem investigation is vital to determine the cause and manner of death and provides the opportunity to assess the potential risk to the family after appropriate genetic counselling. In this paper, we present an update of the different genetic causes of sudden death, emphasizing their importance for the forensic pathologist due to his relevant role in the diagnosis and prevention of SCD.     

Fatal ischemic stroke due to dissecting aneurysm of the intracranial arteries presenting as sudden unexpected death in childhood

Sudden unexpected death is any nontraumatic death in healthy individuals with normal activities for age until acute demise. Whereas not uncommon in adults and infants, it is considered a rarity in children, with most cases due to infection or occult cardiovascular abnormalities. Pathologic intracranial findings are rarely found in sudden unexpected death in childhood, with most cases due to occult intracranial neoplasms. Cerebral arterial dissection is an uncommon cause of arterial ischemic stroke in childhood. Outcome is poor, with more than 20% of patients dying. We report 4 cases of sudden unexpected death due to arterial ischemic stroke after cerebral arterial dissection in childhood and present a review of the literature.     

Cardiac rupture due to severe fatty infiltration in the right ventricular wall

An extremely rare case of sudden death caused by cardiac rupture due to severe fatty infiltration in the right ventricular myocardium is presented. The patient, a 74-year-old woman, had no history of chest trauma, hypertension, or pulmonary disease. The autopsy showed a small tear in the right ventricle and cardiac tamponade, but no coronary artery lesion. In the right ventricular myocardium, muscle fibers were definitely atrophic or absent, with massive fatty replacement. Fatty infiltration of the myocardium, if severe, can be a cause of serious cardiac dysfunction or, occasionally, sudden death.     

Total anomalous pulmonary venous drainage and sudden death in infancy.

The clinicopathologic features of four infants with undiagnosed total anomalous pulmonary venous return who died suddenly and unexpectedly are presented. Two infants were found dead in their beds and two collapsed following very non-specific episodes of mild tachypnoea and tachycardia, respectively. Pulmonary venous blood drained via a common channel to the left innominate vein, the superior vena cava, the inferior vena cava at the junction of the hepatic vein and the supradiaphragmatic portion of the inferior vena cava. All cases demonstrated right atrial and ventricular hypertrophy and in one case there was associated hypoplastic left heart syndrome. Although those mechanisms responsible for sudden infant death syndrome could not definitely be excluded in two cases, the presence of anomalous pulmonary drainage with significant right-sided cardiac cardiac hypertrophy in each patient strongly suggests a contributing role for the vascular malformation in the aetiology of sudden unexpected death. The importance of careful in situ dissection of the major vessels in all cases of paediatric sudden death is emphasised, particularly in the presence of other congenital cardiac anomalies.     

Is right coronary artery hypoplasia and sudden death an underdiagnosed association?

Determining whether hypoplasia of a coronary artery has caused or contributed to death is often complicated by an absence of histologic evidence of myocardial ischemia in the area of the heart supplied by the affected artery and also by the lack of data for assessing coronary artery size at autopsy. A 45-year-old woman is reported who collapsed and died and who was found at autopsy to have a dominant, small-caliber, right coronary artery, with acute and chronic ischemic changes in the posterior interventricular septum supplied by the diminutive vessel. This case provides evidence that small-caliber coronary arteries may be associated with a lethal outcome. Given the difficulties that may occur in determining whether there is a causal link between small coronary artery caliber and death, it is possible that this may be an underdiagnosed cause of sudden cardiac death, rather than a coincidental finding of minimal significance.     

Cardiac conducting tissue. A simplified technique for examination of the SA and AV nodes

We describe a modified method for examination of the atrioventricular and sinoatrial nodes that displays the major elements of the cardiac conducting system, yet is not time-consuming for the technician. We examined 31 cases in three categories: cases with previous cardiac history, sudden deaths from no known cause, and cases where death was sudden and accidental. All cases showed histologic abnormalities in the cardiac tissue. We contend that our method would permit such examination to be routinely used in the pathology laboratory.     

The clinical problem of occult cardiac amyloidosis. Forensic implications.

A 68-year-old man with known coronary heart disease experienced rapidly progressive cardiac dysfunction and was found to have occult cardiac amyloidosis at autopsy. The amyloidosis was undiagnosed during life and initially at autopsy. Marked diffuse involvement of the intramural coronary arteries by amyloid deposits resulted in severe luminal compromise of numerous medium and small vessels. The myocardium proper was virtually spared from amyloid deposits. Amyloid-related coronary narrowing contributed to cardiac ischemia and sudden death. The significance of amyloid coronary disease in this patient relates primarily to the difficulty in considering the diagnosis when other reasons for cardiac signs and symptoms preexist. Also, the adverse effects of amyloid coronary disease may be profound without direct myocardial involvement.     

Complete Cardiac Rupture Associated with Closed Chest Cardiac Massage: Case Report and Review of the Literature

Chest skeletal injuries are the most frequent complications of external chest massage (ECM) during cardiopulmonary resuscitation, but heart and great vessels lacerations that are indeed very rare. We report the case of a 35‐year‐old workman who collapsed and underwent ECM by his co‐workers for almost 30 min. At autopsy, no external injuries, fractures or bruises of the ribs or sternum, were observed. A hemopericardium with a rupture of the heart was found, with no signs of pre‐existent cardiac disease. Bruises of thoracic aortic wall, lung petechiae, a contusion of the liver, and bruises of lumbar muscles were found. The cause of death was due to sudden cardiac death with an extensive cardiac rupture. This is an unusual report of massive heart damage without any skeletal or muscle chest injuries, secondary to cardiopulmonary resuscitation. This kind of cardiac lesions may be considered when thoracic–abdominal trauma, or medical history, is unclear.     

心脏神经病

目的 研究心源性猝死的病理形态学。方法 用本组建立的CCS检查法对179例心源性猝死者作常规CCS组织学检查。结果 发现8例心脏神经或神经节内有出血、炎症或肿瘤浸润,伴神经组织水肿、变性、坏死,而其他病变不足以解释猝死。结论 一切原发或继发性心脏神经病均可致猝死。     

The role of certain sections of the central nervous system in the genesis of sudden death]

Hypothalamic and hippocampal lipid composition in sudden death from coronary heart disease is studied. Thin-layer chromatography was the main method of biochemical analysis. Disorders in the lipid component of hippocampal cytostructures involved mainly the cholesterol fractions. Metabolic disorders in the hypothalamus involved the phospholipid metabolism. The above-mentioned biochemical changes were paralleled by ultrastructural abnormalities. Analysis of the data demonstrates a probable metabolic basis of a central mechanism of sudden cardiac death.     

Sudden unexpected death due to a previously undiagnosed plasma cell dyscrasia

The plasma cell dyscrasias are a diverse group of disorders characterized by the production of a clonal paraprotein. Sudden death is a recognized complication of the plasma cell dyscrasias, most commonly in individuals with cardiac involvement by amyloidosis. However, the current forensic literature has no reported cases in which sudden death resulted from complications of a plasma cell dyscrasia that was first diagnosed by postmortem histologic examination. We present the case of a woman whose sudden and unexpected death resulted from a seizure. Postmortem examination revealed no evidence of trauma or a grossly identifiable natural disease process that would have accounted for her death. However, microscopic and immunohistologic studies revealed a previously undiagnosed plasma cell dyscrasia, the clonality of which was determined by immunohistochemical studies for immunoglobulin light chains, that was not associated with amyloid deposition. This case elucidates a previously unrecognized cause of sudden unexpected death and illustrates the importance of microscopic studies in selected cases examined in medical examiner/coroner offices.     

Asymmetric septal hypertrophy of the heart. New findings concerning the possible etiology of sudden deaths in five males

This report describes certain interesting postmortem findings in the hearts of five subjects who died suddenly, silently, and unexpectedly, and in whom the only significant abnormality at autopsy was asymmetric septal hypertrophy (ASH) of the heart. Deep clefts, cystic faults, and dilated vascular channels were not only seen within the septal myocardium in all the hearts, but also within the left ventricular free walls of two hearts. The septal myocardium and the left ventricular free walls of two hearts and the A-V node and His bundle of one heart demonstrated mural and luminal thrombi of several dilated vascular channels. In another heart, foci of cardiocytic myofibrillar degeneration were seen, especially close to narrowed small coronary vessels. Fetal dispersion and fibrosis of the A-V node and His bundle were evident in one heart. These abnormalities in the conducting system and the ventricular myocardium suggest that the hearts of subjects with ASH are not only excellent anatomic substrates for lethal arrhythmias, but also are bound to be hemodynamically impaired. We believe that conditions such as hypoxia, increased oxygen demand by the heart or abnormal sympathetic stimulus may easily trigger fatal arrhythmias in such individuals, thereby causing sudden death.     

Is there progress in the autopsy diagnosis of sudden unexpected death in adults?

Sudden death is now currently described as natural unexpected death occurring within 1h of new symptoms. Most studies on the subject focused on cardiac causes of death because most of the cases are related to cardiovascular disease, especially coronary artery disease. The incidence of sudden death varies largely as a function of coronary heart disease prevalence and is underestimated. Although cardiac causes are the leading cause of sudden death, the exact incidence of the other causes is not well established because in some countries, many sudden deaths are not autopsied. Many risk factors of sudden cardiac death are identified: age, gender, heredity factors such as malignant mutations, left ventricular hypertrophy and left ventricle function impairment. The role of the police surgeon in the investigation of sudden death is very important. This investigation requires the interrogation of witnesses and of the family members of the deceased. The interrogation of physicians of the rescue team who attempted resuscitation is also useful. Recent symptoms before death and past medical history must be searched. Other sudden deaths in the family must be noted. The distinction between sudden death at rest and during effort is very important because some lethal arrhythmia are triggered by catecholamines during stressful activity. The type of drugs taken by the deceased may indicate a particular disease linked with sudden death. Sudden death in the young always requires systematic forensic autopsy performed by at least one forensic pathologist. According to recent autopsy studies, coronary artery disease is still the major cause of death in people aged more than 35 years. Cardiomyopathies are more frequently encountered in people aged less than 35 years. The most frequent cardiomyopathy revealed by sudden death is now arrhythmogenic right ventricular cardiomyopathy also known simply as right ventricular cardiomyopathy (RVC). The postmortem diagnosis of cardiomyopathies is very important because the family of the deceased will need counseling and the first-degree relatives may undergo a possible screening to prevent other sudden deaths. In each case of sudden death, one important duty of the forensic pathologist is to inform the family of all autopsy results within 1 month after the autopsy. Most of the recent progress in autopsy diagnosis of sudden unexpected death in the adults comes from molecular biology, especially in case of sudden death without significant morphological anomalies. Searching mutations linked with functional cardiac pathology such as long-QT syndrome, Brugada syndrome or idiopathic ventricular fibrillation is now the best way in order to explain such sudden death. Moreover, new syndromes have been described by cardiologists, such as short-QT syndrome and revealed in some cases by a sudden death. Molecular biology is now needed when limits of morphological diagnosis have been reached.