Coexistent MEFV and CIAS1 mutations manifesting as familial Mediterranean fever plus deafness

The worldwide incidence of severe sensorineural deafness is approximately 1:2000 and at least 50% of cases are hereditary. 2 Of these, 70% are non-syndromic and autosomal recessive. 2 Mutations of the connexin 26 gene are thought to account for the majority of such deafness. 2 The aetiology of progressive deafness in Cryopyrin associated periodic syndromes (CAPS) is unknown, but recent work showing that CIAS1 is highly expressed in chondrocytes 3 and cochlear enhancement on MRI scan in patients with CAPS suggests an inflammatory cause. 4 We propose that synergistic heterozygosity between disease causing mutations in the MEFV gene and non-disease causing or low penetrance sequence variations of the CIAS1 gene may have resulted in the clinical phenotype of FMF with progressive sensorineural deafness as seen in CAPS, possibly due to the role of both genes in the regulation of interleukin-1.