同一のバイアレルエクソン10バリアントを持つFMF同胞における臨床的合致の評価

To evaluate the extent of clinical concordance and phenotypic variability among pediatric FMF sibling pairs carrying identical biallelic exon 10 MEFV variants.

This cross-sectional study included 194 pediatric FMF patients from 97 families, all harboring identical biallelic pathogenic exon 10 variants. After excluding four monozygotic twin patients from two families, 190 non-twin siblings from 95 families were analyzed. Demographic information, clinical manifestations, disease severity scores (Pras, ISSF), colchicine response rates and genetic data were collected retrospectively.

In 88 of 95 families, the older sibling was the index case. Older siblings had significantly longer diagnostic delays and higher Pras severity scores at diagnosis. Arthritis was more prevalent among older siblings (30% vs. 13%, p = 0.006), while other FMF symptoms were comparable. Full concordance in clinical features was observed in 41% of pairs, while colchicine response status matched in 79%. Discordance in disease severity scores and attack frequency was also noted. Monozygotic twins exhibited a high degree of clinical concordance.

This study shows that while main clinical features are largely concordant among siblings with identical genotypes, notable differences in disease severity scores and arthritis prevalence exist. These differences are likely attributable to diagnostic delays and age-related disease evolution rather than intrinsic phenotypic divergence.