Symptomatic Carrier Frequency of Familial Mediterranean Fever

Purpose: Familial Mediterranean Fever (FMF) is a genetic disorder that is characterized by recurrent episodes of fever and inflammation of the serous membrane affecting mainly Mediterranean and Middle Eastern populations. Five founder mutations of the Mediterranean fever (MEFV) gene, M694V, M694I, V726A, M680I, and E148Q, account for the majority of FMF cases. The disease is considered an autosomal recessive disorder; however, cases of carriers of oneMEFVmutation have been reported to have FMF-like symptoms. The purpose of this review is to investigate the common symptoms of manifesting carriers and determine the symptomatic carrier frequencies for FMF.

Methods: A comprehensive literature search was carried out utilizing three electronic databases (PubMed, ClinVar, and OMIM). The study included published case reports and cohort studies that evaluated FMF carriers. All the included studies underwent assessment and data extraction and analysis.

Results: Data and clinical presentations from 7 studies that met the inclusion criteria were identified. A range of symptomatic carrier frequencies was determined for different FMF-causing mutations, with M694V being the most common at 0.82%, followed by E148Q at 0.37%, V726A at 0.17%, and M680I at 0.16%. The most common symptoms found were abdominal pain, fever, chest pain, and arthritis, with arthritis being the most prevalent symptom among the carriers. None of the carriers developed amyloidosis, a serious complication associated with FMF.

Conclusions: The results data highlight the existence of a substantial group of FMF patients who possess only oneMEFVmutation. These findings have important implications for the medical practice and genetic counseling for FMF patients, especially those from classically affected populations. The results also suggest that detection of a single mutation in conjunction with clinical symptoms appears to be adequate and colchicine treatment should be considered.