I had a patient come to see me last week with the rare disorder, Birt Hogg Dube Syndrome (BHD). She was referred with a mildly elevated serum creatinine and microalbuminuria against a background of a single kidney following nephrectomy for renal cancer, which, along with skin abnormalities, is a feature of the syndrome (see left). She initially presented to dermatology with multiple small papule like lesions on the face, which on biopsy were fibrofolliculomas (skin follicle hamartomas). Her renal cancer presented as an incidental finding in 1993 with a 10cm lower pole tumor attached to small bowel. It was removed and pathology was a chromophobe tumor. It has not recurred despite it's large size and local invasion at presentation.
BHD may present with multiple or bilateral renal cancers; it is also associated with oncocytomas of the kidney, and with pulmonary cysts and spontaneous pneumothorax (which she does not have). It is due to a loss of function mutation of a gene on chromosome 17 which may be a tumor suppressor gene and the gene product is folliculin.
We see a lot of patients (relatively) in our clinic with Tuberous Sclerosis Complex, as we are a referral center. TSC is also rarely associated with renal cancer (in 1-2% of cases). There are numerous skin manifestations of TSC, including facial angiomas. Other major manifestations include lymphangiomyomatosis of the lung, cardiac rhabdomyomas, CNS cerebral tubors and renal angiomyolipomas (AML's), as well as renal cysts. It is an autosomal dominant condition. TSC has two genotypes. The gene defect for TSC1 is on Chromosome 9 (encodes for Hamartin); the gene defect for TSC 2 is on Chromosome 16 (encodes for Tuberin). Hamartin and Tuberin are involved in cell cycle regulation.
Finally, Von Hippel Lindau (VHL) is much more frequently associated with renal cell cancer. It is also autosomal dominant with the loss of function defect on chromosome 3 which is also tumor suppressor gene. VHL is associated with
BHD may present with multiple or bilateral renal cancers; it is also associated with oncocytomas of the kidney, and with pulmonary cysts and spontaneous pneumothorax (which she does not have). It is due to a loss of function mutation of a gene on chromosome 17 which may be a tumor suppressor gene and the gene product is folliculin.
We see a lot of patients (relatively) in our clinic with Tuberous Sclerosis Complex, as we are a referral center. TSC is also rarely associated with renal cancer (in 1-2% of cases). There are numerous skin manifestations of TSC, including facial angiomas. Other major manifestations include lymphangiomyomatosis of the lung, cardiac rhabdomyomas, CNS cerebral tubors and renal angiomyolipomas (AML's), as well as renal cysts. It is an autosomal dominant condition. TSC has two genotypes. The gene defect for TSC1 is on Chromosome 9 (encodes for Hamartin); the gene defect for TSC 2 is on Chromosome 16 (encodes for Tuberin). Hamartin and Tuberin are involved in cell cycle regulation.
Finally, Von Hippel Lindau (VHL) is much more frequently associated with renal cell cancer. It is also autosomal dominant with the loss of function defect on chromosome 3 which is also tumor suppressor gene. VHL is associated with
- Hemangioblasomas of the brain, retinal angiomas
- Pheochromocytoma
- Pancreatic neuroendocrine tumors
- Renal cysts
- Renal cell cancer - usually a clear cell cancer
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