Table 1 The genetics and clinical characteristics of autosomal dominant hereditary renal cell carcinoma (RCC)-associated disorders that can be associated with MPRT.
Hereditary RCC-associated syndrome | Genetic cause | RCC histopathology | Major extra-renal features | Risk of RCC | Frequency of multicentric or bilateral RCC |
|---|---|---|---|---|---|
Von Hippel-Lindau (VHL) disease | VHL gene | Clear cell RCC and renal cysts | Retinal and cerebellar hemangioblastomas, paraganglioma, pheochromocytoma, pancreatic cyst and neuroendocrine tumours, epididymal cysts, endolymphatic sac tumours | 70% [19] | 44% [59] |
Birt-Hogg- Dubé (BHD) syndrome | FLCN gene | Hybrid chromophobe and oncocytic RCC | Fibrofolliculomas, trichodiscomas, pulmonary cysts, pneumothorax | 25–30% [60, 61] | 18–60% [62, 63] |
Hereditary leiomyomatosis and RCC syndrome | FH gene | Type 2 papillary RCC, collecting duct RCC | Cutaneous leiomyomas, uterine leiomyomas | 21% [24] | 4% [24] |
Succinate dehydrogenase (SDH) deficiency | SDHA/B /C/D genes | SDH- deficient RCC | Head and neck paragangliomas, extra-adrenal sympathetic paragangliomas, wild-type gastrointestinal stromal tumours, pituitary tumours | <10% [64, 65] | 11% [66] |
Hereditary papillary RCC | MET gene | Type 1 Papillary RCC | / | 54% [67] | 47% [68] |
Chromosome 3 translocation | Chromo some 3 | Clear cell RCC | / | Up to 70% [69] | / |
Tuberous sclerosis complex | TSC1 and TSC2 genes | RCC, angiomyolipoma, oncocytoma | Learning disability, cutaneous fibromas and other skin lesions, subependymal giant cell astrocytoma, hamartomas, pulmonary lymphangioleiomyomatosis, cardiac rhabdomyomas | 4% [70] | / |
BAP1 tumour predisposition syndrome | BAP1 gene | RCC | Uveal and cutaneous melanoma, mesothelioma | 10% [71, 72] | / |
Cowden syndrome | PTEN gene | RCC | Breast, endometrium and follicular thyroid cancer, hamartoma, macrocephaly, mucocutaneous papules/keratosis, facial trichilemmomas | 4–35% [73] | 11% [74] |
