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).Conclusion: 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.<Table Float="No" ID="Taba"> <tgroup cols="1"> <colspec align="left" colname="c1" colnum="1" /> <tbody> <row> <entry align="left" colname="c1"> What is known: • Arthritis is a common feature of FMF. • The M694V mutation, the most common and severe form, is associated with increased risk of amyloidosis. </entry> </row> <row> <entry align="left" colname="c1"> What is new: • 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. </entry> </row> </tbody> </tgroup> </Table>

The impact of homozygous mutations in exon 10 on musculoskeletal findings in children with familial mediterranean fever

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发表日期：

2025年9月16日

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Cagla Ozbakir,
Ozge Altug Gucenmez

摘要

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).

Conclusion: 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.

What is known:

• Arthritis is a common feature of FMF.

• The M694V mutation, the most common and severe form, is associated with increased risk of amyloidosis.

What is new:

• 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.