From variome to phenome: Pathogenesis, diagnosis and management of ectopic mineralization disorders

Table 7 Differential diagnosis of hyperphosphatemic familial tumoral calcinosis[149,151,158-166]

Disease	Distinct differences with HFTC
Calcinosis universalis	Calcium depositions in tendons and muscle tissues Normophosphatemia High hemosedimentation Microcytic and hypochromic anemia
Calcinosis circumscripta	Adult onset Local calcinosis Fingers symmetrically affected
Calcific tendinitis	Adult onset Calcification limited to tendons
Synovial chondromatosis	Lesions arising from synovial tissue Widespread throughout the body Not all lesions are calcified
Osteosarcoma	Long bone malignant tumor 2nd life decade or late adulthood No subcutaneous/skin lesions
Fibrodysplasia ossificans progressiva (AD; ACVR1 gene)	Hallux valgus, monophalangism and/or malformed first metatarsal Sporadic episodes of painful soft tissue swellings (flare-ups) in 1st life decade
Tophaceous gout	Severe form of gout Severe joint deformity, chronic pain and functional decline More prominent in Asian population (slow metabolizers) and in young men with strong genetic predisposition
Calcific myonecrosis	Post-traumatic (time interval of several years possible) Lower limbs only
NFTC (AR; SAMD9 gene)	Reddish-to-hyperpigmented skin lesions during the first year of life (preceding calcified nodules) Severe conjunctivitis and gingivitis Normophosphatemia
Secondary tumoral calcinosis	Renal insufficiency, hyperparathyroidism, or hypervitaminosis D
Rheumatological diseases	Usually normophosphatemia and - calcemia Possibly positive results in antinuclear, anti-Smith, anti-centromere and anti-scleroderma antibodies, which should all be negative

ACVR1: Activin A receptor, type 1; AD: Autosomal dominant; AR: autosomal recessive; HFTC: Hyperphosphatemic familial tumoral calcinosis; NFTC: Normophosphatemic familial tumoral calcinosis; SAMD9: Sterile alpha motif domain-containing protein 9.