Comparison of Immune Profiles in Fetal Hearts with Idiopathic Dilated Cardiomyopathy, Maternal Autoimmune-Associated Dilated Cardiomyopathy and the Normal Fetus.

The etiology of idiopathic dilated cardiomyopathy (iDCM) remains unknown. Immune therapies have improved outcome in fetuses with DCM born to mothers with autoimmune disease (aDCM). The purpose of this retrospective study was to compare the myocardial B and T cell profiles in fetuses and neonates with idiopathic DCM (iDCM) versus autoimmune-mediated DCM (aDCM) and to describe the normal cell maturation within the human fetal myocardium.

Combined hereditary and somatic mutations of replication error repair genes result in rapid onset of ultra-hypermutated cancers.

DNA replication-associated mutations are repaired by two components: polymerase proofreading and mismatch repair. The mutation consequences of disruption to both repair components in humans are not well studied. We sequenced cancer genomes from children with inherited biallelic mismatch repair deficiency (bMMRD).

Undiagnosed heart disease leading to sudden unexpected death in childhood: a retrospective study.

Objectives: Heart disease accounts for a significant proportion of sudden unexpected deaths among children. We describe here demographic features, pathological conditions, and the frequency of premonitory symptoms in a retrospective series of cases of sudden unexpected cardiac death (SUCD) attributable to undiagnosed structural heart disease.

Methods: A chart review of autopsies involving children 0 to 17 years of age that were performed at the Hospital for Sick Children (Toronto, Ontario, Canada) between 1984 and 2003 was conducted.

The myocardium of fetuses with endocardial fibroelastosis contains fewer B and T lymphocytes than normal control myocardium.

The observation that endocardial fibroelastosis (EFE) can result from an immune response to maternal autoantibody deposition in the fetal myocardium raises the possibility that the fetal immune system may contribute to the pathogenesis of idiopathic EFE and dilated cardiomyopathy (DCM). This study sought to characterize myocardial immune cell presence in fetuses and neonates with idiopathic EFE + DCM, in those with EFE + structural heart disease, and in normal control subjects. Paraffin tissue sections from fetuses identified from the pathology database were stained for B cell, T cell, macrophage, and general hematopoietic cell surface markers.

Mitogenic cardiomyopathy: a lethal neonatal familial dilated cardiomyopathy characterized by myocyte hyperplasia and proliferation.

Pediatric cardiomyopathies are a heterogenous group of conditions of which dilated cardiomyopathies are the most common clinicomorphologic subtype. However, the etiology and pathogenesis of many cases of dilated cardiomyopathies remain unknown. We describe a series of 5 cases of a rare but clinically and histologically distinctive dilated cardiomyopathy that was uniformly lethal in early infancy.

Abnormal connexin43 in arrhythmogenic right ventricular cardiomyopathy caused by plakophilin-2 mutations.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disorder of cardiomyocyte intercalated disk proteins causing sudden death. Heterozygous mutations of the desmosomal protein plakophilin-2 (PKP-2) are the commonest genetic cause of ARVC. Abnormal gap junction connexin43 expression has been reported in autosomal dominant forms of ARVC (Naxos and Carvajal disease) caused by homozygous mutations of desmosomal plakoglobin and desmoplakin.

Scurvy diagnosed in a pediatric liver transplant patient awaiting combined kidney and liver retransplantation.

First described in the 1500 s, scurvy is infrequently seen in industrialized countries today, although vulnerable patient groups remain. A 15-yr-old girl underwent liver transplantation at age 26 months for a primary diagnosis of biliary hypoplasia, and subsequently developed late allograft failure and progressive renal insufficiency culminating in listing for combined liver retransplantation and kidney transplantation at age 13 yr. She required regular hemodialysis treatment for 12 months prior to deceased donor organ availability, with a complicated clinical course including recurrent septic episodes and severe cachexia.

Presence of periorbital and conjunctival petechial hemorrhages in accidental pediatric drowning.

The pathological findings of drowning are variable and non-specific. Petechial hemorrhages involving the periorbital region and the conjunctiva have been described in many causes of death, but are thought to be exceedingly uncommon in cases of drowning. However, such studies have not specifically addressed the pediatric population.

Decreased left ventricular coronary artery density in pulmonary atresia and intact ventricular septum.

Background: The prognosis for pulmonary atresia and intact ventricular septum (PAIVS) has been poor. Our hypothesis is that intrinsic abnormal left ventricular (LV) intramyocardial circulation might be related to the poor outcomes of these patients.

Methods: Neonatal heart specimens were examined microscopically in four groups of 6 cases each.

Piloting a novel porcine model for endolaryngeal injury following prolonged intubation.

Objectives: (1) To develop a practical animal model of endolaryngeal damage secondary to prolonged endotracheal intubation. (2) To demonstrate the contribution of chronic hypoxia to laryngeal injury in the context of this model.

Methods: Four Sus scrofa piglets were anaesthetized and intubated for 24h.

Sudden unexpected death in infancy and childhood due to undiagnosed neoplasia: an autopsy study.

Sudden unexpected death due to clinically undiagnosed neoplasia in infancy and childhood (SUDNIC) is a rare phenomenon, with only small numbers of cases reported in the literature. In the majority of instances, the tumors involve critical structures within the heart or central nervous system and include gliomas, medulloblastomas, rhabdomyomas, and neoplasms of stromal elements. A 20-year retrospective review of autopsy records from the Hospital for Sick Children, Toronto, was performed (1984-2003, n = 4926), and 7 cases of SUDNIC were identified (0.

Association of drowning and myocarditis in a pediatric population: an autopsy-based study.

Context: Drowning is a frequent cause of accidental death in childhood, but the association of myocarditis and drowning has only rarely been reported.

Objective: To report 5 cases of drowning in children with coexistent myocarditis.

Design: A retrospective review of autopsy records of patients 0 years to 18 years of age was performed during a 6-year period (1998-2003, total cases reviewed = 1431).

Abnormal pericyte recruitment as a cause for pulmonary hypertension in Adams-Oliver syndrome.

Adams-Oliver syndrome (AOS) consists of congenital scalp defects with variable limb defects of unknown pathogenesis. We report on two children with AOS plus additional features including intrauterine growth retardation (IUGR), cutis marmorata telangiectatica congenita (CMTC), pulmonary hypertension (PH), intracranial densities shown in one case to be sites of active bleeding and osteopenia. Autopsy in one case revealed defective vascular smooth muscle cell/pericyte coverage of the vasculature associated with two blood vessel abnormalities.

Intrascrotal lipoblastoma with a complex karyotype: a case report and review of the literature.

Lipoblastoma is a tumor of adipose tissue that usually occurs in young children. Most lipoblastomas occur on the extremities, trunk, and head and neck, and most have rearrangements of the 8q region. We describe a lipoblastoma in a 12-month-old boy who presented with a rapidly enlarging scrotal mass.

Supravalvar aortic stenosis with supravalvar pulmonary stenosis and peripheral vascular stenoses.

A non-dysmorphic 10 month old female was discovered at surgery to have severe vasculopathy of both the systemic and pulmonary arteries. These findings were confirmed by pathologic examination. Follow-up angiography has confirmed multiple sites of vascular obstruction which appear to be worsening.

Endocardial fibroelastosis associated with maternal anti-Ro and anti-La antibodies in the absence of atrioventricular block.

Objectives: This study was designed to document the association of endocardial fibroelastosis (EFE) and maternal autoantibodies.

Background: Neonatal lupus erythematosus is associated with the transplacental passage of maternal anti-Ro and anti-La antibodies, leading to complete atrioventricular block (CAVB). In some cases, CAVB is associated with EFE.

Fetal cardiomyopathies: pathogenic mechanisms, hemodynamic findings, and clinical outcome.

Background: Although the prenatal diagnosis of most fetal structural heart defects and dysrhythmias has been described, there is a paucity of information about cardiomyopathies (CMs) in prenatal life.

Methods And Results: To determine the pathogenic mechanisms, hemodynamic findings, and outcome of fetal CM, we reviewed the fetal echocardiograms and perinatal histories of 55 affected fetuses. Dilated CM was diagnosed in 22 cases, including 2 with congenital infections, 5 familial cases, 6 with endocardial fibroelastosis related to maternal anti-Ro/La antibodies, and 9 idiopathic cases.

Maternal anti-Ro and anti-La antibody-associated endocardial fibroelastosis.

Background: Maternal anti-Ro and anti-La antibodies are associated with congenital heart block (CHB). Although endocardial fibroelastosis (EFE) has been described in isolated cases of autoantibody-mediated CHB, the natural history and pathogenesis of this disease are poorly understood.

Methods And Results: We retrospectively reviewed the clinical history, echocardiography, and pathology of fetuses and children with EFE associated with CHB born to mothers positive for anti-Ro or anti-La antibodies at 5 centers.