Evidence-based recommendations for genetic diagnosis of familial Mediterranean fever

Abstract

Familial Mediterranean fever (FMF) is a disease of early onset which can lead to significant morbidity. In 2012, Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) was launched with the aim of optimising and disseminating diagnostic and management regimens for children and young adults with rheumatic diseases. The objective was to establish recommendations for FMF focusing on provision of diagnostic tools for inexperienced clinicians particularly regarding interpretation of MEFV mutations. Evidence-based recommendations were developed using the European League against Rheumatism standard operating procedure. An expert committee of paediatric rheumatologists defined search terms for the systematic literature review. Two independent experts scored articles for validity and level of evidence. Recommendations derived from the literature were evaluated by an online survey and statements with less than 80% agreement were reformulated. Subsequently, all recommendations were discussed at a consensus meeting using the nominal group technique and were accepted if more than 80% agreement was reached. The literature search yielded 3386 articles, of which 25 were considered relevant and scored for validity and level of evidence. In total, 17 articles were scored valid and used to formulate the recommendations. Eight recommendations were accepted with 100% agreement after the consensus meeting. Topics covered were clinical versus genetic diagnosis of FMF, genotype-phenotype correlation, genotype-age at onset correlation, silent carriers and risk of amyloid A (AA) amyloidosis, and role of the specialist in FMF diagnosis. The SHARE initiative provides recommendations for diagnosing FMF aimed at facilitating improved and uniform care throughout Europe

EULAR recommendations for the management of familial Mediterranean fever

“…SHARE, which is a mainly European paediatric initiative, has suggested recommendations for the diagnosis and genetic understanding of the disease 85. In addition, in 2012, a group of clinicians and geneticists had developed guidelines for the analysis and reporting of the genetic results in the main AIDs, including FMF 86…”

New workflow for classification of genetic variants’ pathogenicity applied to hereditary recurrent fevers by the International Study Group for Systemic Autoinflammatory Diseases (INSAID)

“…A need for consensus evidence-based criteria on the basis of the combination of clinical and genetic features was proposed for the diagnosis of FMF 11. Hence, disease classification and diagnosis may strictly rely on the conclusion given in the report issued by the geneticist.…”

MEFV Mutation Frequency in Pediatric Patients with Familial Mediterranean Fever and its Relationship with Clinical Phenotypes in Marmara Region of Turkey

“…While R202Q (37.2%) was observed to be the mutation with the highest frequency, this was followed by E148Q (23.4%), M694V (21.9%), V726A (5.1%), M680I (2.9%), R761H (2.2%), A744S, F479L, R408Q, G304R (1.5%), M694I, and E167D (0.7%). In the study carried out in Turkey by the FMF study group in 2005, M694V (51.4%), M680I (14.4%), V726A (8.6%) were found to be most prevalent in the patients whose gene mutation analysis was performed (10,26). In our study, R202Q mutation was identified as the most common mutation.…”