Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Familial Mediterranean Fever (FMF) [E85.0]

OMIM numbers: 249100, 608107 (MEFV)

Dr. rer. nat. Christoph Marschall, Dr. rer. nat. Barbara Bangol

Scientific Background

FMF is the most frequently occurring familial form of periodic recurrent episodes of fever, mainly occurring among the population around the Southern Mediterranean Sea. Inheritance of the common, classic type of familial Mediterranean fever is autosomal recessive with reduced penetrance. Northern Africans, Anatolian Turks, Iraqi Jews and Armenians are most frequently affected. Incidence is 1 in 2,000 among Northern Africans; heterozygous frequency can reach up to 20% in certain regions. In 70% of all cases first signs and symptoms of the disease already appear before the age of ten and are characterized by temporary fever attacks lasting 3-5 days, pleuritis and peritonitis accompanied by joint, muscular and abdominal pain. If not treated, a secondary amyloidosis causes renal insufficiency followed by death in 12-40% of all cases. Prophylactic administration of Colchicine seems to reduce the signs and symptoms and the risk of amyloidosis.

In the case of the classic form of Mediterranean fever, mutations were identified in the marenostrin/pyrine (MEFV) gene on chromosome 16, which enables early diagnosis and appropriate treatment. Most cases are caused by a small number of frequently occuring mutations (founder effect), which are detected in the first step of the diagnostic procedure. Despite searching for mutations within the entire coding region of the MEFV gene, no mutation can be found in approx. 30% of all chromosomes of FMF patients. The detection of a heterozygous MEFV mutation, however, supports the clinical diagnosis of FMF if there are clear clinical signs and symptoms.