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Diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMS-MFH)

Written1999-12John A. Martignetti
Mount Sinai School of Medicine, Departments of Human Genetics, Pediatrics, 1425 Madison Ave, Box 1498, New York, NY 10029, USA

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Other namesBone dysplasia with medullary fibrosarcoma
Bone dysplasia with malignant fibrous histiocytoma
Hereditary bone dysplasia with malignant change
Atlas_Id 10056
Note DMS-MFH is an hereditary bone dysplasia / cancer syndrome
Inheritance autosomal dominant; rare hereditary cancer syndrome with only four families identified worldwide; etiology unknown


Note radiologic evidence of bone dysplasia not evident in childhood; X-ray findings become apparent during adolescence
Phenotype and clinics
  • main features include:
    • bone dysplasia (100%)
      • cortical growth abnormalities: diaphyseal medullary stenosis with overlying endosteal cortical thickening and scalloping, metaphyseal striations, scattered sclerotic areas symmetrically affecting the long bones; bilateral mandibular radiolucent and sclerotic lesions
      • bone infarctions
      • pathologic fractures: subsequent poor healing or non-union
      • progressive wasting or bowing of the lower extremities
      • bone pain
    • pre-senile cataracts (25%)
  • bone malignant fibrous histiocytoma (MFH) (35%)
  • diagnosis: X-ray skeletal findings are unique; however, there may be some radiologic overlap with other diaphyseal dysplasias including Camurati-Engelman and Kenny-Caffey diseases and radiation osteitis; no hematologic or urinary markers of disease have been identified; 201Thallium chloride radionucleotide scans may offer discrimination between areas of increased metabolic bone activity found in DMS-MFH patients and malignant change.
    Neoplastic risk thirteen cases of osseous MFH; thirty-five per cent of DMS-MFH patients develop MFH; the age distribution has been from the second to fifth decades; no sex predilection; in its sporadic form, MFH represents approximately 6% of all bone cancers and is the most frequently occurring adult soft-tissue sarcoma
    Treatment no known treatment for the dysplasia; the tumors are highly aggressive   treated with surgical ablation and the same chemotherapeutic regimens as osteosarcoma; it is believed that preoperative chemotherapy improves surgical outcome
    Evolution the disease becomes radiologically apparent only in adolescence: however, retrospectively, clinical signs and symptoms may be evident in childhood; these include unexplained bone pain and pathologic fractures; in some, crippling pain and weakness of the lower extremities ensues following the sixth decade; malignancy occurs most frequently between the second to fifth decades and is particularly aggressive; only two long-term survivors, greater than five years, are known.; pre-senile cataracts have been noted as early as in the third decade

    Other findings

    Note collagen fibrils from the endosteal surface of bones appear frayed and unraveled (npublished results); chemical crosslink analysis of bone biopsy samples reveal altered hydroxylysylpyridinolin (HP) / lysylpyridinoline (LP) ratios (unpublished results)

    Genes involved and Proteins

    Note the gene has been mapped by linkage analysis to a 3 cM region on chromosome 9p21-22; all families used in the study generated positive LOD scores in this region and all affecteds had similar phenotypic findings consistent with the syndrome being genetically homogeneous; a number of genes in the region, including p15and p16, have been excluded as the DMS-MFH gene by DNA sequencing analysis; under the hypothesis that hereditary and sporadic MFH tumors are genetically identical, the DMS-MFH tumor-suppressor gene region has been further narrowed to 1.5 cM using loss of heterozygosity analysis; the continued search for the common minimally deleted region in MFH tumors should provide the most powerful method for gene identification


    Hereditary bone dysplasia with sarcomatous degeneration. Study of a family.
    Arnold WH
    Annals of internal medicine. 1973 ; 78 (6) : 902-906.
    PMID 4713573
    Hereditary bone dysplasia with malignant change. Report of three families.
    Hardcastle P, Nade S, Arnold W
    The Journal of bone and joint surgery. American volume. 1986 ; 68 (7) : 1079-1089.
    PMID 3745248
    Malignant fibrous histiocytoma: inherited and sporadic forms have loss of heterozygosity at chromosome bands 9p21-22-evidence for a common genetic defect.
    Martignetti JA, Gelb BD, Pierce H, Picci P, Desnick RJ
    Genes, chromosomes & cancer. 2000 ; 27 (2) : 191-195.
    PMID 10612808
    Diaphyseal medullary stenosis (sclerosis) with bone malignancy (malignant fibrous histiocytoma): Hardcastle syndrome.
    Norton KI, Wagreich JM, Granowetter L, Martignetti JA
    Pediatric radiology. 1996 ; 26 (9) : 675-677.
    PMID 8781110


    This paper should be referenced as such :
    Martignetti, JA
    Diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMS-MFH)
    Atlas Genet Cytogenet Oncol Haematol. 1999;3(4):219-221.
    Free journal version : [ pdf ]   [ DOI ]
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