Hyperphosphatemic familial tumoral calcinosis secondary to fibroblast growth factor 23 (FGF23) mutation: a report of two affected families and review of the literature

• Published in: Osteoporosis international 2018-09, Vol.29 (9), p.1987-2009
• Main Authors: Chakhtoura, M., Ramnitz, M.S., Khoury, N., Nemer, G., Shabb, N., Abchee, A., Berberi, A., Hourani, M., Collins, M., Ichikawa, S., El Hajj Fuleihan, G.
• Format: Article
• Language: English
• Subjects: Calcification; Calcinosis; Endocrinology; Excretion; Fibroblast growth factor 23; Fibroblasts; Genetic disorders; Growth factors; Hyperphosphatemia; Intestinal absorption; Intestine; Literature reviews; Medicine; Medicine & Public Health; Missense mutation; Mutation; Orthopedics; Patients; Point mutation; Renal function; Review; Rheumatology
• ISSN: 0937-941X; 1433-2965
• DOI: 10.1007/s00198-018-4574-x

Hyperphosphatemic familial tumoral calcinosis (HFTC), secondary to fibroblast growth factor 23 (FGF23) gene mutation, is a rare genetic disorder characterized by recurrent calcified masses. We describe young Lebanese cousins presenting with HFTC, based on a retrospective chart review and a prospective case study. In addition, we present a comprehensive review on the topic, based on a literature search conducted in PubMed and Google Scholar, in 2014 and updated in December 2017. While the patients had the same previously reported FGF23 gene mutation (homozygous c.G367T variant in exon 3 leading to a missense mutation), they presented with variable severity and age of disease onset (at 4 years in patient 1 and at 23 years in patient 2). A review of the literature revealed several potential patho-physiologic pathways of HFTC clinical manifestations, some of which may be independent of hyperphosphatemia. Most available treatment options aim at reducing serum phosphate level, by stimulating renal excretion or by inhibiting intestinal absorption. HFTC is a challenging disease. While the available medical treatment has a limited and inconsistent effect on disease symptomatology, surgical resection of calcified masses remains the last resort. Research is needed to determine the safety and efficacy of FGF23 replacement or molecular therapy, targeting the specific genetic aberration. Hyperphosphatemic familial tumoral calcinosis is a rare genetic disorder characterized by recurrent calcified masses, in addition to other visceral, skeletal, and vascular manifestations. It remains a very challenging disease.