Table 1.

Summary table of genodermatosis-associated hereditary cancer predisposition syndromes

Name	Gene	Mode of inheritance	Age of onset	Dermatological features	Associated tumours	Other features
Hereditary leiomyomatosis and renal cell cancer (HLRCC)	FH	AD	Usually adulthood (youngest renal cancer diagnosed at age 7)	Multiple pilar leiomyomas	HLRCC-associated renal cancer Rarely: Phaeochromocytoma Paraganglioma	Uterine leiomyomas
Birt-Hogg-Dubé syndrome (BHDS)	FLCN	AD	Adulthood	Fibrofolliculomas Trichodiscomas Acrochordons Perifollicular fibromas Less commonly: Angiofibromas Oral papules Cutaneous collagenomas Multiple epidermal cysts	Renal tumours: Oncocytic/chromophobe hybrid Renal oncocytoma Chromophobe, Oncocytoma Clear cell carcinoma, Hybrid clear cell-chromophobe Papillary renal cell carcinomas	Pulmonary cysts and spontaneous pneumothorax Renal cysts
Cowden syndrome/PTEN hamartoma tumour syndrome	PTEN	AD	Childhood or adulthood	Trichilemmomas Oral papillomas Acral keratoses Mucocutaneous neuromas Penile freckling Lipomas Vascular malformations	Breast cancer Endometrial cancer Epithelial thyroid cancer Renal cell cancer Colorectal cancer Melanoma	Cerebellar dysplastic gangliocytoma Macrocephaly Intellectual disability Fibrocystic breast disease, Benign thyroid disease, Hamartomatous gastrointestinal polyps, Genitourinary malformations Uterine fibroids Fibromas
Gorlin syndrome	PTCH1 or SUFU	AD	Childhood or adulthood	Multiple basal cell carcinomas Palmar and/or plantar pits Less commonly: Eyelid meibomian cysts Sebaceous and dermoid cysts Acrochordons	Ovarian fibroma Cardiac fibroma Medulloblastoma Meningioma	Jaw keratocyst Falx calcification Macrocephaly Lympho-mesenteric or pleural cysts Cleft lip or palate Congenital rib or vertebral anomalies Polydactyly (pre/post-axial) Eye anomalies Pigmentary changes in the retinal epithelium Intellectual disability Facial gestalt (frontal bossing, pouting lower lip, coarse facial features)
Peutz-Jegher syndrome	STK11	AD	Childhood or adulthood	Mucocutaneous melanocytic macules	Breast cancer Colorectal cancer Gastric cancer Small bowel cancer Pancreatic cancer Cervical adenocarcinoma (adenoma malignum) Sex cord tumours with annular tubules (SCTAT) Uterine cancer Less commonly: Lung cancer Testicular cancer	Hamartomatous intestinal polyps, especially small intestine Extra-intestinal polyps (renal pelvis, bladder, ureters, gallbladder, nostrils and lungs)
Familial atypical multiple mole melanoma syndrome (FAMMM)	CDKN2A or CDK4	AD	Adulthood	Melanoma	Pancreatic cancer	N/A
BAP1 tumour predisposition syndrome (BAP1-TPDS)	BAP1	AD	Adulthood	BAPoma Melanoma Basal cell carcinoma	Uveal melanoma Malignant mesothelioma (pleural or peritoneal) Renal cell carcinoma	N/A
Carney syndrome	PRKAR1A	AD	Childhood/adulthood	Lentigines Epithelioid-type blue naevi Cutaneous myxomas Less commonly: Freckling Cafe au lait macules Depigmented lesions Skin tags (multiple) Lipomas	Endocrine tumours: Primary pigmented nodular adrenocortical disease (PPNAD) Growth-hormone secreting adenomas Large-cell calcifying Sertoli cell tumours Thyroid follicular adenomas Thyroid cancer (papillary or follicular) Other: Myxomas – cardiac, breast, oropharynx, female genital tract and osteochondromyxomas	May present with symptoms of cardiac outflow obstruction, emboli, hypercortisolism, acromegaly, gynaecomastia, multiple thyroid nodules
Multiple endocrine neoplasia type 1 (MEN)	MEN1	AD	Childhood/adulthood	Facial angiofibromas Collagenomas Lipomas Less commonly: Café au lait macules Hypopigmented macules Gingival papules	Endocrine tumours: Parathyroid Endocrine tumours of the gastro-entero-pancreatic tract Anterior pituitary tumours Carcinoid Adrenocortical Other: Meningioma Ependymoma	May present with symptoms relating to associated tumour hormone secretion and/or mass effect
Multiple endocrine neoplasia type 2B (MEN2B)	RET	AD	Childhood	Mucosal neuromas (tongue, palate, pharynx) Submucosal nodules on lips Eyelid neuromas	Medullary thyroid cancer Phaeochromocytoma	Marfanoid habitus Diffuse intestinal ganglioneuromatosis
APC-associated polyposis	APC	AD	Childhood/adulthood	Lipomas Fibromas Epidermal cysts Multiple pilomatricomas	Colorectal cancer Small bowel (duodenal and peri-ampulla) cancer Cribriform-morular variant of papillary thyroid cancer Hepatoblastoma Medulloblastoma Pancreatic cancer Gastric cancer Desmoid tumours	Colonic polyposis Osteomas Dental anomalies Congenital hypertrophy of retinal pigment epithelium
Lynch syndrome	MLH1, MSH2, MSH6, PMS2, EPCAM	AD	Adulthood	Sebaceous tumours: Adenomas Epitheliomas Carcinoma Keratoacanthomas	Colorectal cancer Endometrial cancer Depending on gene: Ovarian cancer Gastric cancer Small bowel cancer Biliary tract cancer Brain tumours Pancreatic cancer Prostate cancer	N/A

AD autosomal dominant, N/A not applicable