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Familial Mediterranean fever, autosomal dominant

MedGen UID:
341987
Concept ID:
C1851347
Disease or Syndrome
Synonyms: Dominant Familial Mediterranean Fever; FMF, AUTOSOMAL DOMINANT
 
Gene (location): MEFV (16p13.3)
 
Monarch Initiative: MONDO:0007601
OMIM®: 134610

Disease characteristics

Excerpted from the GeneReview: Familial Mediterranean Fever
Familial Mediterranean fever (FMF) is divided into two phenotypes: type 1 and type 2. FMF type 1 is characterized by recurrent short episodes of inflammation and serositis including fever, peritonitis, synovitis, pleuritis, and, rarely, pericarditis and meningitis. The symptoms and severity vary among affected individuals, sometimes even among members of the same family. Amyloidosis, which can lead to kidney failure, is the most severe complication, if untreated. FMF type 2 is characterized by amyloidosis as the first clinical manifestation of FMF in an otherwise asymptomatic individual. [from GeneReviews]
Authors:
Mordechai Shohat   view full author information

Additional description

From MedlinePlus Genetics
The first episode of illness in familial Mediterranean fever usually occurs in childhood or the teenage years, but in some cases, the initial attack occurs much later in life. Typically, episodes last 12 to 72 hours and can vary in severity. Episodes generally occur once a month, and in affected women of reproductive age, attacks often correspond with menstruation or ovulation. However, the length of time between episodes can range from days to years. During these periods, affected individuals usually have no signs or symptoms related to the condition. However, without treatment to help prevent attacks and complications, a buildup of protein deposits (amyloidosis) in the body's organs and tissues may occur, especially in the kidneys, which can lead to kidney failure.

Familial Mediterranean fever is an inherited condition characterized by recurrent episodes of painful inflammation in the abdomen, chest, or joints.  These episodes are often accompanied by fever and sometimes a rash or headache. Occasionally inflammation may occur in other parts of the body, such as the heart; the membrane surrounding the brain and spinal cord; and in males, the testicles. In about half of affected individuals, attacks are preceded by mild signs and symptoms known as a prodrome. Prodromal symptoms include mildly uncomfortable sensations in the area that will later become inflamed, or more general feelings of discomfort.  https://medlineplus.gov/genetics/condition/familial-mediterranean-fever

Clinical features

From HPO
Abdominal pain
MedGen UID:
7803
Concept ID:
C0000737
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen.
Arthralgia
MedGen UID:
13917
Concept ID:
C0003862
Sign or Symptom
Joint pain.
Chest pain
MedGen UID:
2992
Concept ID:
C0008031
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the chest.
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
Increased levels of protein in the urine.
Renal amyloidosis
MedGen UID:
120633
Concept ID:
C0268382
Disease or Syndrome
A form of amyloidosis that affects the kidney. On hematoxylin and eosin stain, amyloid is identified as extracellular amorphous material that is lightly eosinophilic. These deposits often stain weakly for periodic acid Schiff (PAS), demonstrate a blue-to-gray hue on the trichrome stain and are typically negative on the Jones methenamine silver (JMS) stain. These tinctorial properties contrast with the histologic appearance of collagen, a major component of basement membranes, mesangial matrix and areas of sclerosis, which demonstrates strong positivity for PAS and JMS (See Figure 1 of PMID:25852856).
Renal insufficiency
MedGen UID:
332529
Concept ID:
C1565489
Disease or Syndrome
A reduction in the level of performance of the kidneys in areas of function comprising the concentration of urine, removal of wastes, the maintenance of electrolyte balance, homeostasis of blood pressure, and calcium metabolism.
Polyarticular arthritis
MedGen UID:
56408
Concept ID:
C0162323
Disease or Syndrome
An arthritis affecting five or more separate joints.
Pleuritis
MedGen UID:
10807
Concept ID:
C0032231
Disease or Syndrome
Inflammation of the pleura.
Erysipelas
MedGen UID:
41855
Concept ID:
C0014733
Disease or Syndrome
Increased susceptibility to erysipelas, as manifested by a medical history of repeated episodes of erysipelas, which is a superficial infection of the skin, typically involving the lymphatic system.
Peritonitis
MedGen UID:
14697
Concept ID:
C0031154
Pathologic Function
Inflammation of the peritoneum.
Recurrent fever
MedGen UID:
811468
Concept ID:
C3714772
Sign or Symptom
Periodic (episodic or recurrent) bouts of fever.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Tufan A, Lachmann HJ
Turk J Med Sci 2020 Nov 3;50(SI-2):1591-1610. doi: 10.3906/sag-2008-11. PMID: 32806879Free PMC Article
Gattorno M, Hofer M, Federici S, Vanoni F, Bovis F, Aksentijevich I, Anton J, Arostegui JI, Barron K, Ben-Cherit E, Brogan PA, Cantarini L, Ceccherini I, De Benedetti F, Dedeoglu F, Demirkaya E, Frenkel J, Goldbach-Mansky R, Gul A, Hentgen V, Hoffman H, Kallinich T, Kone-Paut I, Kuemmerle-Deschner J, Lachmann HJ, Laxer RM, Livneh A, Obici L, Ozen S, Rowczenio D, Russo R, Shinar Y, Simon A, Toplak N, Touitou I, Uziel Y, van Gijn M, Foell D, Garassino C, Kastner D, Martini A, Sormani MP, Ruperto N; Eurofever Registry and the Paediatric Rheumatology International Trials Organisation (PRINTO)
Ann Rheum Dis 2019 Aug;78(8):1025-1032. Epub 2019 Apr 24 doi: 10.1136/annrheumdis-2019-215048. PMID: 31018962
Ozen S, Demirkaya E, Erer B, Livneh A, Ben-Chetrit E, Giancane G, Ozdogan H, Abu I, Gattorno M, Hawkins PN, Yuce S, Kallinich T, Bilginer Y, Kastner D, Carmona L
Ann Rheum Dis 2016 Apr;75(4):644-51. Epub 2016 Jan 22 doi: 10.1136/annrheumdis-2015-208690. PMID: 26802180

Recent clinical studies

Etiology

Seyahi E, Ugurlu S, Amikishiyev S, Gul A
Clin Immunol 2023 Jun;251:109630. Epub 2023 Apr 30 doi: 10.1016/j.clim.2023.109630. PMID: 37216220
Ozen S
Curr Opin Rheumatol 2021 Sep 1;33(5):398-402. doi: 10.1097/BOR.0000000000000821. PMID: 34397603
Ozdogan H, Ugurlu S
Presse Med 2019 Feb;48(1 Pt 2):e61-e76. Epub 2019 Jan 25 doi: 10.1016/j.lpm.2018.08.014. PMID: 30686512
Onen F
Rheumatol Int 2006 Apr;26(6):489-96. Epub 2005 Nov 10 doi: 10.1007/s00296-005-0074-3. PMID: 16283319
Bakkaloglu A
Pediatr Nephrol 2003 Sep;18(9):853-9. Epub 2003 Jun 27 doi: 10.1007/s00467-003-1185-2. PMID: 12836090

Diagnosis

Lancieri M, Bustaffa M, Palmeri S, Prigione I, Penco F, Papa R, Volpi S, Caorsi R, Gattorno M
Int J Mol Sci 2023 May 31;24(11) doi: 10.3390/ijms24119584. PMID: 37298536Free PMC Article
Batu ED, Basaran O, Bilginer Y, Ozen S
Curr Rheumatol Rep 2022 Jun;24(6):206-212. Epub 2022 Apr 18 doi: 10.1007/s11926-022-01073-7. PMID: 35435612
Tufan A, Lachmann HJ
Turk J Med Sci 2020 Nov 3;50(SI-2):1591-1610. doi: 10.3906/sag-2008-11. PMID: 32806879Free PMC Article
Ozdogan H, Ugurlu S
Presse Med 2019 Feb;48(1 Pt 2):e61-e76. Epub 2019 Jan 25 doi: 10.1016/j.lpm.2018.08.014. PMID: 30686512
Lachmann HJ
Best Pract Res Clin Rheumatol 2017 Aug;31(4):596-609. Epub 2018 Jan 11 doi: 10.1016/j.berh.2017.12.001. PMID: 29773275

Therapy

Lancieri M, Bustaffa M, Palmeri S, Prigione I, Penco F, Papa R, Volpi S, Caorsi R, Gattorno M
Int J Mol Sci 2023 May 31;24(11) doi: 10.3390/ijms24119584. PMID: 37298536Free PMC Article
Ozdogan H, Ugurlu S
Presse Med 2019 Feb;48(1 Pt 2):e61-e76. Epub 2019 Jan 25 doi: 10.1016/j.lpm.2018.08.014. PMID: 30686512
De Benedetti F, Gattorno M, Anton J, Ben-Chetrit E, Frenkel J, Hoffman HM, Koné-Paut I, Lachmann HJ, Ozen S, Simon A, Zeft A, Calvo Penades I, Moutschen M, Quartier P, Kasapcopur O, Shcherbina A, Hofer M, Hashkes PJ, Van der Hilst J, Hara R, Bujan-Rivas S, Constantin T, Gul A, Livneh A, Brogan P, Cattalini M, Obici L, Lheritier K, Speziale A, Junge G
N Engl J Med 2018 May 17;378(20):1908-1919. doi: 10.1056/NEJMoa1706314. PMID: 29768139
Lachmann HJ
Best Pract Res Clin Rheumatol 2017 Aug;31(4):596-609. Epub 2018 Jan 11 doi: 10.1016/j.berh.2017.12.001. PMID: 29773275
Kucuk A, Gezer IA, Ucar R, Karahan AY
Acta Medica (Hradec Kralove) 2014;57(3):97-104. doi: 10.14712/18059694.2014.47. PMID: 25649364

Prognosis

Tsur AM, Watad A, Gendelman O, Nissan D, Cohen AD, Amital H
Rheumatology (Oxford) 2021 Dec 1;60(12):5642-5646. doi: 10.1093/rheumatology/keab159. PMID: 33590869
Tufan A, Lachmann HJ
Turk J Med Sci 2020 Nov 3;50(SI-2):1591-1610. doi: 10.3906/sag-2008-11. PMID: 32806879Free PMC Article
Kucuk A, Gezer IA, Ucar R, Karahan AY
Acta Medica (Hradec Kralove) 2014;57(3):97-104. doi: 10.14712/18059694.2014.47. PMID: 25649364
Finkelstein Y, Aks SE, Hutson JR, Juurlink DN, Nguyen P, Dubnov-Raz G, Pollak U, Koren G, Bentur Y
Clin Toxicol (Phila) 2010 Jun;48(5):407-14. doi: 10.3109/15563650.2010.495348. PMID: 20586571
Br Med J 1980 Jul 5;281(6232):2-3. PMID: 7407479Free PMC Article

Clinical prediction guides

Baspinar SN, Kilic B, Azman FN, Guler Y, Gunay UB, Tanin MK, Can G, Ugurlu S
Semin Arthritis Rheum 2023 Dec;63:152284. Epub 2023 Nov 2 doi: 10.1016/j.semarthrit.2023.152284. PMID: 37979399
Siligato R, Gembillo G, Calabrese V, Conti G, Santoro D
Medicina (Kaunas) 2021 Oct 1;57(10) doi: 10.3390/medicina57101049. PMID: 34684086Free PMC Article
Atas N, Armagan B, Bodakci E, Satis H, Sari A, Bilge NSY, Salman RB, Yardımcı GK, Babaoglu H, Kilic L, Ozturk MA, Goker B, Haznedaroglu S, Kasifoglu T, Kalyoncu U, Tufan A
Clin Rheumatol 2020 Jan;39(1):255-261. Epub 2019 Sep 9 doi: 10.1007/s10067-019-04773-1. PMID: 31502094
Padeh S, Berkun Y
Curr Opin Rheumatol 2016 Sep;28(5):523-9. doi: 10.1097/BOR.0000000000000315. PMID: 27286236
Soriano A, Manna R
Autoimmun Rev 2012 Nov;12(1):31-7. Epub 2012 Aug 2 doi: 10.1016/j.autrev.2012.07.019. PMID: 22878273

Recent systematic reviews

Hirahara Y, Yamaguchi M, Takase-Minegishi K, Kirino Y, Aoki S, Hirahara L, Obata S, Kasai M, Maeda A, Tsuchida N, Yoshimi R, Horita N, Nakajima H, Miyagi E
Rheumatology (Oxford) 2024 Feb 1;63(2):277-284. doi: 10.1093/rheumatology/kead417. PMID: 37594755
Arnold DD, Yalamanoglu A, Boyman O
Front Immunol 2022;13:888392. Epub 2022 Jul 6 doi: 10.3389/fimmu.2022.888392. PMID: 35874710Free PMC Article
Abbara S, Grateau G, Ducharme-Bénard S, Saadoun D, Georgin-Lavialle S
Front Immunol 2019;10:763. Epub 2019 Apr 12 doi: 10.3389/fimmu.2019.00763. PMID: 31031761Free PMC Article
Demirkaya E, Erer B, Ozen S, Ben-Chetrit E
Rheumatol Int 2016 Mar;36(3):325-31. Epub 2015 Dec 19 doi: 10.1007/s00296-015-3408-9. PMID: 26687683
Finkelstein Y, Aks SE, Hutson JR, Juurlink DN, Nguyen P, Dubnov-Raz G, Pollak U, Koren G, Bentur Y
Clin Toxicol (Phila) 2010 Jun;48(5):407-14. doi: 10.3109/15563650.2010.495348. PMID: 20586571

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