Department of Clinical Immunology, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China.
Department of Pediatric, Xiamen Children's Hospital, Xiamen, 361000, China.
Orphanet J Rare Dis. 2022 Jul 27;17(1):292. doi: 10.1186/s13023-022-02444-0.
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.
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.
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.
发热原因不明（FUO）在儿科临床实践中一直难以诊断。随着疾病谱的逐渐变化，遗传因素受到越来越多的关注。有限的研究表明，FUO 与染色体异常之间存在关联。在这项研究中，我们调查了在中国儿科队列中出现染色体异常的 FUO 患者的临床和遗传特征。
在 145 例 FUO 患者中，检测到染色体异常 5.5%（8/145）。6 例炎症性发热患者表现为咽炎/扁桃体炎（4/6）、口腔阿弗他溃疡（2/6）、消化道症状（3/6）、发育迟缓（4/6）和 C 反应蛋白升高（6/6）在发热期间。这些患者通常被认为患有全身炎症性疾病，如贝切特病或全身青少年特发性关节炎。在炎症性发热患者中发现了三体 8、7q11.23dup、3p26.3-p26.1del/17q12dup、22q11.21del 和 6q23.3-q24.1del。TNFAIP3 基因包含在 6q23.3-q24.1 缺失片段中。2 例中枢性发热患者表现为面部异常、发育迟缓、癫痫发作，对退热药物无反应，被鉴定为携带从头发生的 18q22.3-q23del。通过进行文献复习，又确定了 19 例 FUO 伴染色体异常的患者。三体 8、6q23.2-q24.3del 和 18q22.3-q23del 被报道为发热，与本研究的发现相似。
我们强调了在 FUO 患者中检测染色体异常的重要作用，特别是在有全身炎症表现或发育迟缓的患者中。确定染色体异常可能会改变 FUO 患者的诊断和治疗。
