Non-lethal Raine Syndrome in a Middle-Aged Woman Caused by a Novel FAM20C Mutation

Abstract

Raine syndrome is a rare hereditary disease caused by mutations in the FAM20C gene. Only 18 non-lethal cases have been reported, the majority of them being children and young adults aged up to 30. Due to the rarity of the disease, genotype-phenotype correlations are not available and patient life expectancy is unknown, thus making descriptions of each novel case of particular importance. In this article, we describe a case of an Armenian woman, living in Russia, who was followed-up from age 36 to 39, presenting with pain in the extremities, osteosclerosis with periosteal bone formation, multiple calcifications in solid organs, midface hypoplasia, exophthalmos, amelogenesis imperfecta, shortening of distal phalanges, pectus excavatum, and hypophosphatemia due to renal phosphate wasting. Whole exome sequencing was performed on NextSeq 550 (Illumina, USA) and compound heterozygous variants were identified in the FAM20C gene (reference sequence NM_020223): a frameshift insertion c.1107_1108insTACTG (p.Tyr369fs) and a missense substitution c.1375C > G (p.Arg459Gly). This is the first reported case of a middle-aged patient presenting classical symptoms of Raine syndrome caused by novel compound heterozygous mutations in the conserved C-terminal domain of FAM20C gene.

Keywords: FAM20C; Hypophosphatemia; Osteosclerosis; Raine syndrome.