Infantile Appendicitis: A Deceptive Challenge with Disastrous Consequences.

Acute appendicitis (AA) in neonates and infants is an infrequent event. In day-to-day practice, death due to AA is hardly ever reported to a coroner or a medical examiner. Here, we report on an 8-month-old infant assigned to the medical examiner as the death occurred within 10 days of a surgical procedure. The cause of death was undetermined. Autopsy revealed gross and histologic features of AA. A postmortem review of the medical records showed signs and symptoms consistent with AA. On the other hand, a recent history of upper respiratory tract infection followed by clinical diagnosis and treatment by a community pediatrician probably blindsided the hospital physicians. This case illustrates the challenges of AA in infancy. The literature review revealed that a misdiagnosis of AA is more likely to occur on several occasions. They include patients who present "atypically," patients who are not thoroughly examined, patients receiving antipyretic or analgesic medication and discharged, those diagnosed as having gastroenteritis, and patients who do not receive an appropriate discharge or follow-up instructions.

Investigating the Genetic Causes of Sudden Unexpected Death in Children Through Targeted Next-Generation Sequencing Analysis.

BACKGROUND: Inherited arrhythmia syndromes are responsible for a significant portion of autopsy-negative sudden unexpected death (SUD) cases, but molecular autopsy used to identify potentially causal variants is not routinely included in SUD investigations. We collaborated with a medical examiner's office to assist in finding a diagnosis for their autopsy-negative child SUD cases. METHODS AND RESULTS: 191 child SUD cases (<5 years of age) were selected for analyses. Our next generation sequencing panel incorporated 38 inherited arrhythmia syndrome candidate genes and another 33 genes not previously investigated for variants that may underlie SUDY pathophysiology. Overall, we identified 11 potentially causal disease-associated variants in 12 cases, for an overall yield of 6.3%. We also identified 31 variants of uncertain significance in 36 cases and 16 novel variants predicted to be pathogenic in silico in 15 cases. The disease-associated variants were reported to the medical examiner to notify surviving relatives and recommend clinical assessment. CONCLUSIONS: We have identified variants that may assist in the diagnosis of at least 6.3% of autopsy-negative child SUD cases and reduce risk of future SUD in surviving relatives. We recommend a cautious approach to variant interpretation. We also suggest inclusion of cardiomyopathy genes as well as other candidate SUD genes in molecular autopsy analyses.