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  • Open Access

Impact of MEFV genotype in Caucasian children with periodic fever

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Pediatric Rheumatology20119 (Suppl 1) :P302

  • Published:


  • Cervical Lymph Node
  • Negative Patient
  • Pharyngitis
  • Caucasian Patient
  • Autosomal Recessive Disorder


Despite FMF is considered an autosomal recessive disease caused by mutations of MEFV, one third of patients carries one mutation only.


To analyze the actual impact of MEFV mutations in children with periodic fever.


113 caucasian patients carrying MEFV mutations (46 with mutations in two alleles, 67 heterozygous) and 205 genetically negative patients for MEFV, TNFSF1A and MEFV (70% with a PFAPA phenotype) were analyzed. The following groups were considerd: patients with: i) 2 high penetrance mutations (M694V, M694I, M680I), ii) 1 high, 1 low penetrance mutation, iii) 2 low penetrance mutations, iv) 1 high penetrance mutation, v) one low penetrance mutation, vi) genetically negative.


Patients with two mutations displayed a higher prevalence of chest pain (p = 0.001), pleurisy (p = 0.003) and severe abdominal pain (p = 0.002) in respect to heterozygous patients, which clinical phenotype was more similar to that presented by genetically negative patients, with an higher prevalence of erythematous (p = 0.01) and exudative ( p = 0.009) pharyngitis, enlarged cervical lymph nodes (p = 0.002). The frequency of “FMF-like symptoms” decreases from patients carrying two high penetrance mutations towards patients with a single low penetrance mutation with a specular increase of “PFAPA-like symptoms” (Figure 1).
Figure 1
Figure 1

Prevalence of the clincial manifestations associated to fever attacks in patients with different MEFV genotypes (see text) and in patients with periodic fever negative for mutations of MEFV, MVK and TNFSRF1A genes. P values were assessed by a Chi-square test for trend.


The present study shows a dosage effect of MEFV mutations not consistent with a pure autosomal recessive disorder. A dominant negative or gain of function effects or variants of still unidentified modifier genes may influence the presence of a FMF phenotype in heterozygous patients.

Authors’ Affiliations

Gaslini Institute, Genova, Italy
Sezione di Reumatologia Pediatrica, AOU „G. Martino„, Messina, Italy
Divisione di Immunologia e Reumatologia Pediatrica, università di Messina, Messina, Italy
Dipartimento di Pediatria, Unità di Immunologia e Reumatologia Pediatrica, Spedali Civili E University Of Brescia, Italy
Laboratorio di Genetica Molecolare, Gaslini Institute, Genova, Italy
Dipartimento A.I. di Pediatria, University of Padua, Padova, Italy
IRCCS Burlo Garofolo, Dipartimento di Pediatria, University of Trieste, Trieste, Italy
Divisione di Reumatologia, Ospedale Pediatrico Bambino Gesù, IRCCS, Roma, Italy
Department of Pediatrics, Wilhelmina Children's Hospital,University Medical Center, Utrecht, The Netherlands
Unità di Biostatistica, DISSAL, University of Genoa, Genova, Italy


© Federici et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.