Table 1.
Disorders Associated With FGF23 and Abnormal Phosphate Regulation
| Disorder | Gene | Phenotype |
|---|---|---|
| General features of all disorders listed below | Hypophosphatemia, renal phosphate wasting, elevated FGF23, low or normal 1,25(OH)2D, variable skeletal deformities due to rickets/osteomalacia, pseudofractures | |
| X‐linked hypophosphatemia (XLH) | PHEX | Dental abscesses, enthesopathy (X‐linked dominant) |
| Autosomal dominant hypophosphatemic rickets (AD) | FGF23 | Dental abscesses, enthesopathy, waxing and waning of clinical phenotype with variable age of onset, association of elevated FGF23 with iron deficiency |
| Autosomal recessive hypophosphatemic rickets (AR) | DMP1 | Dental abscesses, enthesopathy |
| ENPP1 | Can have generalized arterial calcification beginning in infancy | |
| FAM20C | Severe dental disease, intracerebral calcifications, osteosclerosis, additional dysmorphic facies | |
| Fibrous dysplasia | GNAS | One or more skeletal lesions of fibrous dysplasia, may have associated nerve compression, localized skeletal fragility, and may be present as part of McCune‐Albright syndrome with café au lait macules and various hormone hypersecretion (resulting in precocious puberty, acromegaly, hyperthyroidism or other hormone excesses) |
| Cutaneous skeletal hypophosphatemia syndrome (CSHS) | RAS (HRAS, NRAS) | Large epidermal nevi or congenital melanocytic nevi, dysplastic skeletal lesions |
| Tumor‐induced osteomalacia (TIO) | Acquired condition with about half having translocations resulting in fusion proteins FN1‐FGFR1 or FN1‐FGF1; tumors in any location, which may be small and difficult to localize |