A novel FAM20C mutation causing hypophosphatemic osteomalacia with osteosclerosis (mild Raine syndrome) in an elderly man with spontaneous osteonecrosis of the knee

Abstract

Raine syndrome is characterized by FGF23-mediated hypophosphatemic osteomalacia with osteosclerosis caused by mutations in the FAM20C gene. We report a case of a 72-year-old man who presented with rapid progressive spontaneous osteonecrosis of the knee (SONK). A full osteologic assessment including dual energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and serum analyses revealed a high bone mass in the lumbar spine and hip (DXA T-score + 7.5 and + 4.7/+4.2) with increased bone microstructural parameters in the distal radius and tibia (BV/TV 127%, 140% of the age-matched mean, respectively), as well as a low bone turnover state. Phosphate levels were low due to renal phosphate wasting and high FGF23 levels (126.5pg/ml, reference range 23.2-95.4pg/ml). Using gene panel sequencing, we identified a novel FAM20C heterozygous missense mutation in combination with a homozygous duplication that potentially alters splicing. Taken together, this is the first case of mild Raine syndrome with spontaneous osteonecrosis of the knee, phosphate wasting, and a pronounced trabecular high bone mass phenotype.