Table 1 –

Hereditary renal cell carcinoma syndromes

Gene	Syndrome	Histology	Selected associated extrarenal clinical features	Example initial screening recommendations
VHL	von Hippel-Lindau	ccRCC Clear cell papillary	• Retinal and CNS haemangioblastomas • Pancreatic cysts and neuroendocrine tumours • Endolymphatic sac tumour • Pheochromocytoma • Others	Renal: • Annual abdominal ultrasound • MRI of abdomen every 2 yr 28620007	Other: • Ophthalmological exam • Blood pressure check and neurological assessment • Audiology assessment • Plasma-free metanephrines/urinary metanephrines • MRI of brain and cervical spine
FH	Hereditary leiomyomatosis and renal cell carcinoma (HLRCC)	HLRCC-associated RCC Papillary type 2 Others	• Cutaneous leiomyomas • Uterine leiomyomas • Leiomyosarcomas	Renal: • Annual MRI with renal protocol 28620008	Other: • Dermatological exam Gynaecological exam for women
FLCN	Birt-Hogg-Dubé	Chromophobe Oncocytoma Hybrid Clear cell	• Fibrofolliculomas and other skin findings • Renal and lung cysts	Renal: • CT or MRI of abdomen every 3 yr 23703644	Other: • CT of the chest • Dermatological exam
MET	Hereditary papillary renal cell carcinoma	Papillary type 1	• None	Renal: • Renal ultrasound every 2 yr	Other: • None
TSC1/TSC2	Tuberous sclerosis	Angiomyolipoma ccRCC cystic oncocytoma	• Angiomyofibromas and other dermatological lesions • Cortical dysplasia • Subependymal giant cell astrocytoma • Lymphangioleiomyomatosis • Others	Renal: • MRI of abdomen every 1–3 yr 24053983	Other: • Dermatological exam • Dental exam • Ophthalmological exam • Assessing renal function and blood pressure yearly • Screening neuropsychiatric disorders • Brain MRI • Routine EEG by clinical indication • ECG • CT of the chest every 5–10 yr for asymptomatic patients
BAP1	BAP1 tumour predisposition syndrome	Undefined	• Uveal and cutaneous melanomas • Mesothelioma	Renal: • CT or MRI of abdomen every 2 yr 29413689	Other: • Ophthalmological exam • Dermatological exam • Consider CT or MRI of chest/abdomen
SDHA/B/C/D	Hereditary paraganglioma-pheochromocytoma syndromes	SDH-deficient RCC	• Paragangliomas • Pheochromocytoma • GIST	Renal: • Abdominal MRI every 2 yr 28620007	Other: • Blood pressure • Plasma methoxytyramine, PFM/urine metanephrines • Serum chromogranin A • Complete blood counts • Whole-body MRI (skull base of pelvis)
MITF	MITF predisposition to familial RCC	Undefined	• Melanoma	Renal: • Renal ultrasound every 1–2 yr	Other: • Dermatological exam
PTEN	Cowden syndrome	Papillary Chromophobe ccRCC	•Dermatological lesions • Breast cancer • Thyroid cancer • Endometrial cancer • Others	Renal: • Renal ultrasound every 1–2 yr 28040716	Other: • Thyroid exam • Dermatological exam • Breast exam, mammogram and breast MRI (women) • Thyroid ultrasound • Colonoscopy • Consider endometrial cancer screening (women)
CDC73	Hyperparathyroidism jaw tumour syndrome	Renal cysts Renal hamartomas Wilms tumours Other	• Primary hyperparathyroidism • Ossifying fibromas of the mandible or maxilla • Parathyroid carcinoma • Uterine tumours	Renal: • Renal ultrasound at least every 5 yr 20301744	Other: • Serum calcium, intact parathyroid hormone, and 25-(OH) vitamin D levels • Dental panoramic X-ray with neck shielding • Screening for uterine tumours (women)

ccRCC = clear cell RCC; CNS = central nervous system; CT = computed tomography; ECG = electrocardiography; EEG = electroencephalography; GIST = gastrointestinal stromal tumour; MRI = magnetic resonance imaging; PFM = plasma-free metanephrine; RCC = renal cell carcinoma; SDH = succinate dehydrogenase.

Summary of the known syndromes, genetic alterations, associated histology, and selected associated extrarenal features is given. Example initial screening and surveillance recommendations are also provided.

^*Renal screening recommendations are applicable for initial screening. If a renal tumour or an abnormality is found, then imaging interval and modality should be determined by the treating provider.