Ozbakir Cagla, Altug Gucenmez Ozge
Department of Pediatrics, University of Health Sciences Dr. Behçet Uz Children's Hospital, İsmet Kaptan District, Sezer Doğan Street, No:11, Konak, İzmir, 35210, Turkey.
Department of Pediatric Rheumatology, University of Health Sciences Dr. Behçet Uz Children's Hospital, İzmir, Turkey.
Eur J Pediatr. 2025 Sep 16;184(10):620. doi: 10.1007/s00431-025-06478-x.
Familial Mediterranean Fever (FMF) is an autoinflammatory disease caused by MEFV gene mutations. Although clinical manifestations and disease severity vary, a clear genotype-phenotype correlation remains unclear. This study aimed to investigate the effect of homozygous mutations in exon 10 mutations of the MEFV gene on musculoskeletal manifestations. This study included pediatric patients diagnosed with FMF who had a mutation detected in exon 10 of the MEFV gene. Patients with homozygous mutations were compared to those with compound heterozygous mutations in terms of age at symptom onset, musculoskeletal manifestations, comorbidities, and response to colchicine treatment. A total of 134 patients (50.7% female) with a median age of 144 months were included. Homozygous mutations were found in 73.9% (n = 99), and compound heterozygous mutations in 26.1% (n = 35). No significant differences were observed between the groups regarding sex distribution, age at symptom onset or diagnosis, and attack frequency or duration (p > 0.05). However, musculoskeletal manifestations were significantly more frequent in the homozygous group (21.2% vs. 5.7%; p = 0.037). Colchicine resistance (p = 0.029) and comorbidities (p = 0.024) were also more common in this group. A lower rate of family history of FMF was detected in patients who developed arthritis (p = 0.047).
Our data suggest that homozygous mutations in exon 10 of the MEFV gene are associated with colchicine resistance and musculoskeletal manifestations. We believe that this group of patients may require earlier interventions aimed at preserving joint health and may have a greater need for alternative treatment options to colchicine.
• Arthritis is a common feature of FMF. • The M694V mutation, the most common and severe form, is associated with increased risk of amyloidosis.
• Pediatric FMF patients with arthritis had a lower rate of family history. • Homozygous MEFV mutations were associated with higher rates of musculoskeletal manifestations and colchicine resistance compared to compound heterozygous mutations, without differences in age at onset, attack duration, or annual attack frequency.
家族性地中海热（FMF）是一种由MEFV基因突变引起的自身炎症性疾病。尽管临床表现和疾病严重程度各不相同，但明确的基因型-表型相关性仍不明确。本研究旨在调查MEFV基因第10外显子突变中的纯合突变对肌肉骨骼表现的影响。本研究纳入了诊断为FMF且在MEFV基因第10外显子检测到突变的儿科患者。将纯合突变患者与复合杂合突变患者在症状发作年龄、肌肉骨骼表现、合并症以及对秋水仙碱治疗的反应方面进行比较。共纳入134例患者（女性占50.7%），中位年龄为144个月。发现73.9%（n = 99）为纯合突变，26.1%（n = 35）为复合杂合突变。两组在性别分布、症状发作或诊断时的年龄、发作频率或持续时间方面未观察到显著差异（p > 0.05）。然而，纯合组的肌肉骨骼表现明显更频繁（21.2%对5.7%；p = 0.037）。该组秋水仙碱耐药（p = 0.029）和合并症（p = 0.024）也更常见。患有关节炎的患者中FMF家族史的发生率较低（p = 0.047）。
我们的数据表明，MEFV基因第10外显子的纯合突变与秋水仙碱耐药和肌肉骨骼表现相关。我们认为，这组患者可能需要更早地采取旨在保护关节健康的干预措施，并且可能更需要秋水仙碱以外的替代治疗选择。
• 关节炎是FMF的常见特征。• M694V突变是最常见和最严重的形式，与淀粉样变性风险增加相关。
• 患有关节炎的儿科FMF患者家族史发生率较低。• 与复合杂合突变相比，MEFV纯合突变与更高的肌肉骨骼表现率和秋水仙碱耐药相关，在发病年龄、发作持续时间或年发作频率方面无差异。
Zotero 插件