Hardcastle Syndrome

Hardcastle syndrome refers to diaphyseal medullary stenosis associated with malignant fibrous histiocytoma of the bone. It is a rare autosomal dominant condition that has recently be localized to chromosome 9 (9p21-22).

The major radiographic feature is diaphyseal medullary narrowing with overlying cortical thickening. Some patients also have lucent linear striations in the metaphysis that run parallel to the long axis of the bone and do not extend to the epiphysis. Cyst-like metaphyseal lesions can be seen in isolation or in proximity to these linear striations.

These findings symmetrically affect the long tubular bones of the upper and lower extremities and are not seen in the skull, spine, or pelvis.

Fractures also occur with high frequency and tend to occur with minimum trauma. Delayed union of fractures is typically seen.

There is a high (35%) tendency for transformation into malignant fibrous histiocytoma (originally classified as medullary fibrosarcoma), usually between the second to fifth decades of life. The malignant transformation occurs in the metaphysis or diaphysis, presumably at the sites of bone infarction.

Non-skeletal abnormalities can include early cataracts and mental retardation.

References

• Hardcastle P, Nade S, Arnold W. Hereditary bone dysplasia with malignant change. Report of three families. J Bone Joint Surg Am. 1986 Sep;68(7):1079-89.
• 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. 1999 Mar;64(3):801-7.
• Norton KI, Wagreich JM, Granowetter L, Martignetti JA. Diaphyseal medullary stenosis (sclerosis) with bone malignancy (malignant fibrous histiocytoma): Hardcastle syndrome. Pediatr Radiol. 1996 Sep;26(9):675-7.