Hereditary renal cell carcinoma syndromes

Hereditary Renal Carcinoma syndromes

Hereditary Renal Carcinoma syndromes- Currently, there are 8 syndromes associated with an increased risk of all types of renal cancer.

1.Von Hippel Lindau (vHL) Disease

Salient features:  Patients with type 1 mutations (in general, truncating mutations) have a decreased incidence of pheochromocytoma as compared to those with type 2 mutations (in general, missense mutations). Families with type 2 mutations have either a high (type 2A) or low risk of ccRCC (type 2B); type 2C families only develop pheochromocytoma. 

2. Hereditary papillary renal cancer

Hereditary papillary renal cell carcinoma (HPRCC) is an autosomal dominant syndrome characterized by multifocal, bilateral type I papillary renal cell carcinomas.  Mutations of the MET gene on 7q31 have been causally associated with HPRCC, but MET is mutated in less than 10% of sporadic type papillary renal cancers. 

3. Hereditary leiomyomatosis and renal cell cancer (type 2 papillary)

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal cancer susceptibility syndrome characterized by the development of cutaneous and uterine leiomyomas and renal cancer. Papillary type 2 renal cancer is the pathological type most commonly associated with HLRCC, and tends to have an early age of onset, be high grade and have an aggressive course. The gene fumarate hydratase (FH), which encodes the enzyme which converts fumarate to malate in the Kreb’s cycle, is mutated in HLRCC.

4. BAP1 mutations and familial renal cancer

BAP1 mutations predispose to familial clear cell renal cancer, along with uveal and cutaneous melanoma and mesothelioma.

5. Chromosome 3 translocations

Increased loss of one allele leads to an increased risk of clear cell renal cancer.

6. PTEN hamartoma tumor syndrome (Cowden disease)

PTEN is associated with an increased risk of benign and malignant tumors of the thyroid, breast and endometrium caused by mutations in PTEN. Clear cell renal cancer has been reported as a observed in patients with Cowden syndrome.

7. SDH- associated paraganglioma/pheochromocytoma

Germline SDHB mutations are associated with increased risk of developing a variety of RCCs including clear cell, chromophobe, and oncocytomas.

8. Tuberous Sclerosis Complex

The 50 to 80% of patients with TSC who develop renal lesions can have angiomyolipomas (AMLs), cysts, oncocytomas, and renal cell carcinomas.


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