FaCD Online Syndrome Fact Sheet

Last updated: 06 Feb 2008

Name: Bone Dysplasia with Malignant Change, Hereditary

Synonym: Hereditary Bone Dysplasia with Malignant Fibrous Histiocytoma, Diaphyseal Medullary Stenosis with Malignant Fibrous Histiocytoma, DMS-MFH

Mode of Inheritance: AD

OMIM number: 112250  


DMSMFH/BDMF#, mapped to 9p21-p22

Tumor features

bone, malignant fibrous histiocytoma of the

Non-tumor features

skeletal dysplasia

Non-tumor features (possible)

developmental delay/mental deficiency/mental retardation


This disorder is characterized by bone dysplasia presenting with diaphyseal medullary stenosis of bone with overlying cortical bone thickening. The epiphysis is not affected. The bone changes may not appear until the 3d or 4th decade of life. Other features are fractures after minimal trauma and malignant transformation (typically in 2nd-5th decade). The neoplasms were originally classified as fibrosarcomas, but later reclassified as malignant fibrous histiocytomas. Approximately 35 % of the gene carriers develop these malignant tumors. Early-onset cataract was documented in some of the patients and mental retardation was seen in a minority of cases. [1,2]. This syndrome maps to 9p21-22[2,3].


[1] Hardcastle P, Nade S, Arnold W. Hereditary bone dysplasia with malignant change. Report of three families. J Bone Joint Surg Am 1986; 68(7):1079-1089.
[2] Miyake M, Tateishi U, Maeda T, Arai Y, Hasegawa T, Sugimura K. Diaphyseal medullary stenosis with pleomorphic malignant fibrous histiocytoma of the bone: 99mTc hydroxymethylenediphosphonate and 201Tl chloride scintigraphy findings. Annals of nuclear medicine 2006; 20(3):233-6.
[3] Martignetti JA, Desnick RJ, Aliprandis E, Norton KI, Hardcastle P, Nade S, Gelb BD. Diaphyseal medullary stenosis with malignant fibrous histiocytoma: a hereditary bone dysplasia/cancer syndrome maps to 9p21-22. Am J Hum Genet 64[3], 801-807. 1999.
[4] Martignetti JA, Gelb BD, Pierce H, Picci P, Desnick RJ. Malignant fibrous histiocytoma: inherited and sporadic forms have loss of heterozygosity at chromosome bands 9p21-22-evidence for a common genetic defect. Genes, chromosomes & cancer 2000; 27(2):191-5.