Familial tumoral calcinosis (TC) is an extremely rare disease characterized by multilobulated calcific masses most commonly occurring within the periarticular soft regions of large joints. Two forms of TC have been reported according to the literature. Normophosphatemic TC (NTC) is a genetically determined disorder caused by mutations in the sterile alpha motif domain containing 9 gene (SAMD9). Instead, hyperphosphatemic TC (HTC) is caused by variations in FGF23 (the gene encoding fibroblast growth factor 23, a phosphaturic protein and important hormone regulator of phosphate homeostasis), in GALNT3 (the gene encoding N-acetylgalactosaminyltransferase 3, which is responsible for FGF23 O-glycosylation serving to protect intact FGF23 from proteolytic processing), or in α-Klotho (a co-receptor for FGF23 whose alteration leads to FGF23 deficiency or resistance and consequently hyperphosphatemia and ectopic calcification). A variety of treatment approaches have been attempted to manage blood phosphate levels, reduce pain and inflammation, and treat HTC-associated calcifications and their complications. Unfortunately, efficacy data are limited to clinical case reports and small cohorts of patients, and no clearly effective treatment approaches have been identified so far. This concise review aims to provide a brief overview of current understanding of the etiopathogenesis, diagnostic modalities, and treatment options for HTC, and to discuss the currently available experimental models for studying the biological mechanisms underlying TC.
KEY WORDS: Tumoral calcinosis, ectopic calcifications, rare bone disorder.
