Sudden death in childhood and adolescence

Sudden death in childhood and adolescence is fortunately rare. However, when it occurs, it can have a devastating effect on the family. Therefore, these cases should be thoroughly investigated, including a complete post mortem examination by a specialist in paediatric pathology. The aim is to identify the cause of death, and potentially prevent future deaths. This review will provide an overview of the epidemiology of sudden death in childhood and adolescence and will outline the wide range of causes of death identified. Certain aspects of the paediatric post mortem examination will be discussed, and will finish with a section on deaths in children with chronic medical conditions.     

A de novo BRPF1 variant in a case of Sudden Unexplained Death in Childhood

Sudden Unexplained Death in Childhood (SUDC), the death of a child that remains unexplained after a complete autopsy and investigation, is a rare and poorly understood entity. This case report describes a 3-year-old boy with history of language delay and ptosis, who died suddenly in his sleep without known cause. A pathogenic de novo frameshift mutation in BRPF1, a gene which has been associated with the syndrome of Intellectual Developmental Disorder with Dysmorphic Facies and Ptosis (IDDDFP), was identified during a post-mortem evaluation. The finding of a pathogenic variant in BRPF1, which has not previously been associated with sudden death, in an SUDC case has implications for this child's family and contributes to the broader field of SUDC research. This case demonstrates the utility of post-mortem genetic testing in SUDC.     

Tumors Associated with Sudden Infant and Childhood Death

Tumors are rare causes of sudden death in infancy and early childhood. The goals of this study were to determine the types and frequency of the tumors associated with sudden death occurring in cases between birth and age 3 years. The San Diego Sudden Infant Death Syndrome/sudden unexplained death in childhool (SUDC) Research Project database and the literature were reviewed retrospectively. Sixty-eight cases, with the most (84%) affecting the heart and brain, were identified. Tumors are a rare but significant cause of sudden death in infancy and early childhood, and their diagnosis may have significant genetic implications for planning future pregnancies. The diagnosis of these lesions can be established only after thorough postmortem examination.     

Are brief febrile seizures benign? A systematic review and narrative synthesis

Febrile seizures affect 2%–5% of U.S. children and are considered benign although associated with an increased risk of epilepsy and, rarely, with sudden unexplained death. We compared rates of mortality, neurodevelopmental disorders, and neuropathology in young children with simple and complex febrile seizures to healthy controls. We systematically reviewed studies of 3- to 72-month-old children with simple or complex febrile seizures ≤30 min. We searched studies with outcome measures on mortality, neurodevelopment, or neuropathology through July 18, 2022. Bias risk was assessed per study design. Each outcome measure was stratified by study design. PROSPERO registration is CRD42022361645. Twenty-six studies met criteria reporting mortality (11), neurodevelopment (11), and neuropathology (13), including 2665 children with febrile seizures and 1206 seizure-free controls. Study designs varied: 15 cohort, 2 cross-sectional, 3 case–control, 5 series, and 1 case report. Mortality outcomes showed stark contrasts. Six cohort studies following children after febrile seizure (n = 1348) reported no deaths, whereas four child death series and 1 case report identified 24.1% (108/449) deaths associated with simple (n = 104) and complex (n = 3) febrile seizures ≤30 min. Minor hippocampal histopathological anomalies were common in sudden deaths with or without febrile seizure history. Most electroencephalography (EEG) studies were normal. Neuroimaging studies suggested increased right hippocampal volumes. When present, neurodevelopmental problems usually preexisted febrile-seizure onset. Risk bias was medium or high in 95% (18/19) of cohort and case–control studies vs medium to low across remaining study designs. Research on outcomes after simple or brief complex febrile seizures is limited. Cohort studies suffered from inadequate sample size, bias risk, and limited follow-up durations to make valid conclusions on mortality, neurodevelopment, and neuropathology. Sudden death registries, focused on a very small percentage of all cases, strongly suggest that simple febrile seizures are associated with increased mortality. Although most children with febrile seizures have favorable outcomes, longer-term prospective studies are needed.