Phenotype-genotype correlation in 91 patients with familial Mediterranean fever reveals a high frequency of cutaneomucous features

Objectives. To describe the clinical manifestations of familial Mediterranean fever (FMF) in 91 patients from 47 families and provide data from the genetic study. Patients and methods. We conducted a retrospective chart review of 91 patients (including 83 children aged <15 yr) from 47 families through a questionnaire and a specific database. The genetic analysis included complete screening of known mutations of the MEFV gene on chromosome 16p13.3. A positive diagnosis required at least two mutations, one on each chromosome. Results. Our panel included 52 females and 39 males, with a mean age of 7.27 yr. Of the 47 families, 31 were non-Ashkenazi Jews, 10 were Armenians and six were from other ethnic groups. Clinical features included fever (100%), peritonitis (86%), pleuritis (56%), arthritis (34%) and myalgias (27%). We observed a high rate of cutaneous manifestations (47%); erythema, oedema and recurrent oral ulcers were the most frequent. Phenotype-genotype correlations showed a significant association of M694V homozygosity with earlier age of onset (P = 0.044), fever > 39 degreesC (P = 0.002), pleural crisis (P = 0.0044), splenomegaly (P = 0.0005) and arthritis (P = 0.001). Associations with mucocutaneous features were as follows: erysipelas-like erythema (P = 0.012), oedema (P = 0.61, not significant) and oral ulcers (P = 0.45, not significant). Conclusion. New phenotype-genotype correlations emerged from our study: homozygosity for the M694V mutation was associated with intensity of fever, splenomegaly and with erysipelas-like erythema. Apart from erysipelas-like erythema, no significant association was found between other cutaneous features and the genotype.