Inheritance: autosomal dominant, with incomplete penetrance; however, new mutations may occur without an affected parent.
Genetic locus: 12p13
Affected molecule: fibroblast growth factor 23 (FDF-23). The mutated molecule is more difficult to degrade, and so has a prolonged effect. This results in inhibition of renal tubular reabsorption of phosphate and reduced renal 1-alpha hydroxylase activity with reduced 1,25-dihydroxyvitamin D.
Clinical findings:
(1) rickets in childhood and osteomalacia in the adult (may show a delayed onset as an adult or childhood onset with reversion after puberty)
(2) dental abscesses
(3) muscle weakness
(4) bone pain
(5) short stature and lower limb deformities if childhood onset
(6) pathologic fractures
Laboratory findings:
(1) hypophosphatemia
(2) normal serum and urine calcium levels
(3) low to normal serum 1,25-dihydroxyvitamin D
(4) a normal serum parathyroid hormone level
(5) decreased renal threshold phosphate concentration (TmPO4/GFR)
(6) absence of glycosuria and aminoaciduria
