Familial Mediterranean Fever, Autosomal Dominant

A number sign (#) is used with this entry because autosomal dominant familial Mediterranean fever is associated with heterozygous mutation in the MEFV gene (608107).

Homozygous or compound heterozygous mutations in the MEFV gene result in classic familial Mediterranean fever (FMF; 249100), which shows autosomal recessive inheritance.

Bergman and Warmenius (1968) described a Swedish family in which 4 individuals had recurrent fever and abdominal pain that persisted for 7 to 14 days. Death from renal failure occurred at ages 19, 21, 33, and 58 years. Renal deposition of amyloid was demonstrated in 2 of the 4 patients in whom postmortem examination was performed. The amyloid was described as perireticular and morphologically identical to that seen in FMF. The inheritance pattern was autosomal dominant.

Reich and Franklin (1970) described a 79-year-old Sicilian man with intestinal amyloidosis whose daughter and granddaughter had attacks of fever and abdominal pain. The daughter died at age 26 years and the granddaughter at age 8 years.

Gertz et al. (1987) described a nonconsanguineous, non-Jewish, American family of German descent in which in 4 persons in 3 generations developed amyloidosis with onset of symptoms between the ages of 15 and 34 years. The 4 individuals involved were grandmother, mother, and son and daughter. They had attacks of a character entirely consistent with FMF. Unlike typical FMF, colchicine had no influence on the attacks and did not prevent amyloidosis in the 3 patients who received this treatment.

Karenko et al. (1992) described a 23-year-old Finnish man with an 8-year history of recurrent bouts of fever and abdominal pain. His father had been repeatedly investigated because of similar episodes beginning at the age of 24 years, and one of the father's sisters was reported to have had recurrent episodes of fever. No signs of amyloidosis were detected. The authors commented on another Finnish family in which a father and son and possibly the paternal grandmother had an FMF-like syndrome. They also referred to the German family reported by Hawle et al. (1989) in which a father and son and 3 cousins had this disorder. Karenko et al. (1992) suggested that amyloidosis may not be an invariant feature.

Aldea et al. (2004) reported a Spanish family in which 5 members spanning 3 generations had a severe form of a FMF-like periodic inflammatory disorder with autosomal dominant inheritance. Age at onset ranged from 9 to 13 years of age with symptom-free intervals ranging from 6 to 12 weeks. Clinical features included high fever, abdominal pain, pleuritis, polyarticular and migratory arthritis, and erysipelas. C-reactive protein (CRP; 123260) was persistently high in all affected individuals and increased significantly during attacks. Two older individuals developed renal amyloidosis at age 50 and end-stage renal disease 3 years later. Females tended to have a more severe disease course. There was not a favorable response to colchicine, but some patients showed a good response to monoclonal antibodies against TNF-alpha (TNFA; 191160).

Booth et al. (2000) reported autosomal dominant inheritance of FMF in 5 unrelated families. A Turkish and an Indian family each had a heterozygous double mutation in the MEFV gene (608107.0018) on the same allele, and 3 unrelated British families had a heterozygous deletion in the MEFV gene (608107.0019). All affected individuals had the classic FMF phenotype, including favorable response to colchicine. Incomplete penetrance was observed.

In affected members of a Spanish kindred with an autosomal dominant FMF, Aldea et al. (2004) identified a heterozygous mutation in the MEFV gene (608107.0020). No additional mutations were detected in the MEFV gene or in the TNFRSF1A (191190) or CIAS1 (606416) genes.

Shohat et al. (1999) studied the association between amyloidosis and the 4 common mutations in exon 10 of the MEFV gene in a total of 83 FMF families from 3 ethnic groups, North African Jews, Armenians, and Turks. A significant association was found between amyloidosis and the M694V mutation (608107.0001). Amyloidosis was present in 18 of 87 homozygous FMF patients (20.7%) and in only 2 of the 41 compound heterozygous FMF patients (4.9%). No patients carrying other mutations had amyloidosis. There was no significant association between the various mutations and the type or severity of the FMF symptoms.