TY - JOUR
T1 - Coalescing expansile skeletal disease
T2 - Delineation of an extraordinary osteopathy involving the IFITM5 mutation of osteogenesis imperfecta type V
AU - Whyte, Michael P.
AU - Aronson, James
AU - McAlister, William H.
AU - Weinstein, Robert S.
AU - Wenkert, Deborah
AU - Clements, Karen L.
AU - Gottesman, Gary S.
AU - Madson, Katherine L.
AU - Stolina, Marina
AU - Bijanki, Vinieth N.
AU - Plotkin, Horacio
AU - Huskey, Margaret
AU - Duan, Shenghui
AU - Mumm, Steven
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
KW - Adipogenesis
KW - Bone-restricted ifitm-like protein
KW - Ectopic calcification
KW - Heterotopic ossification
KW - Hyperostosis
KW - Hyperplastic callus
KW - Interferon
KW - Interferon-induced transmembrane protein 5
KW - Osteoblast
KW - Osteocyte
KW - Osteogenesis
KW - Osteosarcoma
KW - Periosteum
KW - Sarcopenia
KW - Serum multiplex biomarker profiling
KW - Skeletal dysplasia
UR - http://www.scopus.com/inward/record.url?scp=85099616448&partnerID=8YFLogxK
U2 - 10.1016/j.bone.2020.115835
DO - 10.1016/j.bone.2020.115835
M3 - Article
C2 - 33360005
AN - SCOPUS:85099616448
SN - 8756-3282
VL - 145
JO - Bone
JF - Bone
M1 - 115835
ER -