Atypical Presentation of Raine Syndrome in a Middle-aged Lady

Raine syndrome (OMIM # 259775) is a rare disorder characterized by osteosclerotic bone dysplasia and autosomal recessive inheritance due to mutations in FAM20C. Classic clinical features include generalized osteosclerosis, dysmorphic facies, and thoracic hypoplasia. FGF23-mediated hypophosphatemic rickets/osteomalacia, besides osteosclerosis, occurs due to mutations in the FAM20C gene that encodes a Golgi-enriched fraction casein kinase involved in the mineralization of bone. Most cases were reported to be fatal during the neonatal period; however, some nonlethal variants have also been identified. Here, we report a middle-aged lady presenting with proximal myopathy. On evaluation, she was found to have hypophosphatemia due to increased renal tubular wasting with low TMP/GFR. Radiological evaluation showed findings suggestive of osteomalacia and osteosclerosis. On molecular analysis, a novel homozygous mutation, the FAM20C variant c.1375C>T (p.Arg459Cys) located on chromosome 7p22.3, was identified. The current case expands the phenotypic and genetic spectrum of the adult cases of nonlethal variants of Raine syndrome with hypophosphatemic osteomalacia caused by the FAM20C mutation.