Coalescing expansile skeletal disease: Delineation of an extraordinary osteopathy involving the IFITM5 mutation of osteogenesis imperfecta type V.

Abstract In 2003, we briefly reported the remarkable osteopathy of a 12-year-old boy who at age two months began fracturing his limbs with subsequent hyperplastic callus formation and expansion and fusion of appendicular bones. By age ten years he had coalesced his lumbosacral spine, pelvis, femurs, and leg and foot bones as a single structure. Computed tomography of expanded bone revealed a thin cortical shell, diminished irregular trabeculae, and cystic areas. Histopathology featured foci of woven bone, densely packed osteocytes, cartilage, fibrovascular tissue, and massive fat deposition in the marrow space lacking hematogenous precursor cells. Bone turnover markers indicated accelerated remodeling and the few radiographically assessable appendicular bones improved during brief adherence to alendronate therapy. Following puberty, serum multiplex biomarker profiling confirmed accelerated bone turnover. At age 23 years, macrospecimens from leg amputation revealed ossification along capsular tissue together with hyaline cartilage degeneration. Concurrently, the life-long course of this same disorder was delineated in an unrelated woman until her death at age 51 years. Both patients demonstrated the radiographic hallmarks and harbored the heterozygous point mutation (c.-14C>T) in the 5′-UTR of IFITM5 associated with osteogenesis imperfecta type V (OI-V). Herein, we detail the clinical, radiological, histopathological, biochemical, and molecular findings and discuss the etiology and pathogenesis of this extraordinary osteopathy that we call coalescing expansile skeletal disease.