Chromosomal abnormalities related to fever of unknown origin in a Chinese pediatric cohort and literature review

Abstract

Background Fever of unknown origin (FUO) has been difficult to diagnose in pediatric clinical practice. With the gradual change in the disease spectrum, genetic factors have received increasing attention. Limited studies have shown an association between FUO and chromosomal abnormalities. In this study, we investigated the clinical and genetic characteristics of patients with FUO presenting with chromosomal abnormalities in a Chinese pediatric cohort. Results Chromosomal abnormalities were detected in 5.5% (8/145) of the patients with FUO. Six patients with inflammatory fever presented with pharyngitis/amygdalitis (4/6), oral aphthous ulcer (2/6), digestive symptoms (3/6), developmental delay (4/6) and elevated C-reactive protein levels (6/6) during fever. These patients were often considered to have systemic inflammatory diseases, such as Behcet’s disease or systemic juvenile idiopathic arthritis. Trisomy 8, 7q11.23 dup, 3p26.3-p26.1 del/17q12 dup, 22q11.21 del, and 6q23.3-q24.1 del were identified in patients with inflammatory fever. The TNFAIP3 gene was included in the 6q23.3-q24.1 deletion fragment. Two patients with central fever were characterized by facial anomalies, developmental delay, seizures and no response to antipyretic drugs and were identified as carrying the de novo 18q22.3-q23 del. By performing a literature review, an additional 19 patients who had FUO and chromosomal abnormalities were identified. Trisomy 8, 6q23.2-q24.3 del and 18q22.3-q23 del were reported to present as fever, similar to the findings of our study. Conclusions We emphasized the important role of detecting chromosomal abnormalities in patients with FUO, especially in patients with systemic inflammatory manifestations or developmental delay. Identifying chromosomal abnormalities may change the diagnosis and management of patients with FUO.

Update on Fever of Unknown Origin in Children: Focus on Etiologies and Clinical Approach

“…In the clinical suspicion of neuroblastoma (e.g., systemic hypertension, spinal or thoracic pain, and opsoclonus-myoclonus syndrome), urinary vanillylmandelic acid should be assayed; and, if in doubt of pheochromocytoma, urinary metanephrines should be tested. Lastly, due to several chromosomal abnormalities that have recently been recognized as potentially related to a fever of an inflammatory nature, some authors suggest that genetic sequencing, using "next-generation sequencing" methods, could be taken into consideration in selected cases [61].…”

Knowledge mapping of paediatric fever—a visual analysis based on CiteSpace

“…Large studies on paediatric fever have been published worldwide, in a wide variety of document types (8,9). However, most of these studies only review knowledge from a certain dimension, and the frontier research has not been sufficiently summarised, making it difficult to find the core contents within the literature quickly.…”