It’s not enough for us to tell you that scientists and physicians are working on MHE Research. It’s important that you actually see results of some of this work. The following abstracts and listing of recently published papers by members of our Medical and Scientific Advisory Board and/or invited speakers to the Second International MHE Conference speaks louder than our words! (xx) indicates a Board Member; (+) indicates a Conference participant.
Hereditary Cancer in Clinical Practice 2004; 2(4) pp. 161-173
Multiple Osteochondromas: Clinicopathological and Genetic Spectrum and Suggestions for Clinical Management
Hameetman L, Bovee J., Taminiau A, Kroon, H, Hogendoorn P(+).
Departments of Pathology, Orthopaedic Surgery and Radiology, Leiden University Medical Centre, Leiden, The Netherlands
Abstract: Multiple Osteochondromas is an autosomal dominant disorder characterized by the presence of multiple osteochondromas and a variety of orthopaedic deformities. Two genes causative of Multiple Osteochondromas, Exostin-1 (EXT1) and Exostosin-2 (EXT2), have been identified, which act as tumour suppressor genes. Osteochondroma can progress towards its malignant counterpart, secondary peripheral chondrosarcoma and therefore adequate follow-up of Multiple Osteochondroma patients is important in order to detect malignant transformation early.
This review summarizes the considerable recent basic scientific and clinical understanding resulting in a multi-step genetic model for peripheral cartilaginous tumorigenesis. This enabled us to suggest guidelines for clinical management of Multiple Osteochondroma patients. When a patient is suspected to have Multiple Osteochondroma, the radiologic documentation, histology and patient history have to be carefully reviewed, preferably by experts and if indicated for Multiple Osteochondromas, peripheral blood of the patient can be screened for germline mutations in either EXT1 or EXT2. After the Multiple Osteochondroma diagnosis is established and all tumours are identified, a regular follow-up including plain radiographs and base-line bone scan are recommended.
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J Am Acad Orthop Surg. 2005 Mar-Apr;13(2):110-20
Manifestations of hereditary multiple exostoses.
Stieber JR, Dormans JP(**).
Department of Orthopaedic Surgery, Monmouth Medical Center, Long Branch, NJ, USA; Department of Orthopedic Surgery, The Children’s Hospital of Philadelphia, Professor, Department of Orthopaedic Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA
The solitary osteochondroma, a common pediatric bone tumor, is a cartilage-capped exostosis. Hereditary multiple exostosis is an autosomal dominant disorder manifested by the presence of multiple osteochondromas. Linkage analysis has implicated mutations in the EXT gene family, resulting in an error in the regulation of normal chondrocyte proliferation and maturation that leads to abnormal bone growth. Although exostoses are benign lesions, they are often associated with characteristic progressive skeletal deformities and may cause clinical symptoms. The most common deformities include short stature, limb-length discrepancies, valgus deformities of the knee and ankle, asymmetry of the pectoral and pelvic girdles, bowing of the radius with ulnar deviation of the wrist, and subluxation of the radiocapitellar joint. For certain deformities, surgery can prevent progression and provide correction. Patients with hereditary multiple exostosis have a slight risk of sarcomatous transformation of the cartilaginous portion of the exostosis.
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Spine. 2005 Apr 1;30(7):774-80
Spinal exostoses: analysis of twelve cases and review of the literature.
Bess RS, Robbin MR, Bohlman HH, Thompson GH(**).
Department of Orthopaedics, University Hospitals of Cleveland, Case Western Reserve University School of Medicine, OH 44106, USA.
STUDY DESIGN: Retrospective review of spinal exostoses treated at our institution and literature review. OBJECTIVES: Review of 12 cases of spinal exostoses treated at our institution compared with 165 cases of spinal exostoses reported in the literature. SUMMARY OF BACKGROUND DATA: Spinal exostoses are uncommon. Most reports consist of 1 to 3 cases. The relationship between solitary exostoses and those associated with multiple hereditary exostoses (MHE), as well as the incidence of intraspinal and extraspinal location, symptoms presentation, and results of treatment are unclear. METHODS: The medical records, operative reports, and diagnostic imaging of 12 patients with spinal exostoses treated at our institution between 1972 and 2002 were reviewed. The literature was reviewed using MEDLINE search of English literature and bibliographies of published manuscripts. RESULTS: Solitary spinal exostoses were more common than those associated with MHE. Lesions were most common in the upper cervical spine and originated from the posterior elements. Patients with exostoses associated with MHE were significantly younger and had a higher incidence of symptoms consistent with neural structure compression than patients with solitary exostoses. Complete excision resulted in resolution of preoperative symptoms. Intralesional excision resulted in recurrence in all cases. CONCLUSIONS: Spinal exostoses are more common than reported previously. Patients with MHE that present with back pain or neurological symptoms should produce a high index of suspicion. Evaluation should include both computed tomography and magnetic resonance imaging to define the origin of the exostosis and the presence of neural structure compression. Surgical excision should be preformed en bloc.
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Scientific
Bone 36 (2005) 379-386
EXT1 regulates chondrocyte proliferation and differentiation during enchondral bone development
Hilton MJ (a,b.c,*), Gutierrez L (b.c), Martinez, DA (b,d), Wells DE (b,c)(**)
(a) Department of Internal Medicine, Division of Bone and Mineral Diseases, Washington University School of Medicine, St. Louis, MO 63110,USA; (b) Department of Biology and Biochemistry, University of Houston, Texas 77204-5001, USA, (c) Institute for Molecular Biology, University of Houston, Houston, TX 77204-5001, USA, (d) Connective Tissue Physiology Laboratory, University of Houston, Houston, TX 77204-5001, USA, (*) Corresponding author. Barnes-Jewish Hospital, North.
Cytokine Growth Factor Rev. 2005 Apr; 16(2):205-13. Epub 2005 Apr 1.
FGF signaling in the developing endochondral skeleton.
Ornitz DM(+).
Department of Molecular Biology and Pharmacology, Washington University Medical School, Campus Box 8103, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
Crit Rev Eukaryot Gene Expr. 2005;15(1):29-48
Heparan sulfate proteoglycans: key players in cartilage biology.
Farach-Carson MC, Hecht JT(**), Carson DD (+)
Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA.
Dev Growth Differ. 2005 Feb;47(2):59-63.
Localization of Indian hedgehog and PTH/PTHrP receptor expression in relation to chondrocyte proliferation during mouse bone development.
MacLean HE, Kronenberg HM(+).
Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
J Biol Chem. 2004 Jul 30; 279(31):32134-41. Epub 2004 May 25.
Embryonic fibroblasts with a gene trap mutation in Ext1 produce short heparan sulfate chains.
Yamada S, Busse M, Ueno M, Kelly OG, Skarnes WC, Sugahara K, Kusche-Gullberg M (+).
Department of Medical Biochemistry and Microbiology, Uppsala University, Biomedical Center, P.O. Box 582, SE-751 23 Uppsala, Sweden.
Dev Cell. 2004 Jun;6(6):801-13.
Ext1-dependent heparan sulfate regulates the range of Ihh signaling during endochondral ossification.
Koziel L, Kunath M, Kelly OG, Vortkamp A(+).
Otto-Warburg-Laboratory, Max-Planck-Institute for Molecular Genetics, Ihnestrasse 73, 14195 Berlin, Germany.
Development. 2004 May;131(9):1927-38. Epub 2004 Mar 31.
Abrogation of heparan sulfate synthesis in Drosophila disrupts the Wingless, Hedgehog and Decapentaplegic signaling pathways.
Bornemann DJ, Duncan JE, Staatz W, Selleck S(**), Warrior R(+).
Developmental and Cell Biology, University of California Irvine, Irvine, CA 92697, USA.
