• Hereditary Diffuse Gastric Cancer
• Hereditary Paraganglioma/Pheochromocytoma Syndromes
• Li-Fraumeni Syndrome (p53)
• Melanoma - Pancreatic Cancer Syndrome
• Multiple Endocrine Neoplasias
• Type 1 (MEN1)
• Type 2 (MEN2A, FMTC, MEN2B)
• Polyposis Syndromes
• Familial Adenomatous Polyposis
• Other Polyposis
• von Hippel Lindau Syndrome

• Family member with a confirmed CDH1 gene mutation
• 1 case of diffuse gastric cancer diagnosed < age 35
• 2 or more confirmed cases of gastric cancer in a family, at least 1 of which is diffuse gastric cancer diagnosed < age 50
• 3 or more confirmed cases of gastric cancer in a family at any age, at least 1 of which is diffuse gastric cancer
• colorectal cancer and lobular breast cancer have also been reported in HDGC families

Hereditary Paraganglioma/Pheochromocytoma Syndromes                                               
 top

• Family member with a confirmed SDHD, SDHB, or SDHC gene mutation
• Personal history of, OR a close relative with, multiple (including bilateral and multifocal), recurrent or early onset (< 50 years) paraganglioma and/or pheochromocytomas
• Other associated tumours include gastrointestinal stromal tumours (GISTs) and possibly clear cell renal carcinoma and papillary thyroid carcinoma

1) Classic LFS criteria:   
(Proband refers to the person being referred.)

• Proband with a sarcoma diagnosed before age 45 AND
• 1^st degree relative with any cancer diagnosed before age 45 AND
• 1^st or 2^nd degree relative with any cancer diagnosed before age 45, or a sarcoma at any age

2) Li Fraumeni-like syndrome (Chompret et al., 2000) is suggested by any 1 of the following criteria:
(Proband refers to the person being referred.)

• Proband diagnosed before age 36 with sarcoma, brain tumour, breast cancer or adrenocortical carcinoma (ACC) AND 1^st or 2^nd degree relative with cancer (other than breast if proband has breast cancer) before age 46 OR a relative with multiple primary tumours any age
• Proband with multiple primary tumours,  2 of which are sarcoma, brain tumour, breast cancer, and/or ACC, with the initial cancer diagnosed before age 36
• Proband with adrenocortical carcinoma at any age

Melanoma-Pancreatic Cancer Syndrome                                                                        
top

• Family member with a confirmed CDKN2A gene mutation
• Personal or family history (1st and 2nd degree relatives) that includes:
• 1 melanoma AND 2 pancreatic cancers, OR
• 2 melanomas AND 1 pancreatic cancer

Multiple Endocrine Neoplasia Type 1 (MEN1)                                                                   
 top

• Family member with a confirmed MEN1 gene mutation
• Personal history of two endocrine tumors that are parathyroid, pituitary, or GEP tract in origin
• Non-endocrine tumours associated with MEN1 include: facial angiofibromas, collagenomas, lipomas, meningiomas, ependymomas and leiomyomas.
• Additional cutaneous findings may include: café au lait macules, confetti-like hypopigmented macules and multiple gingival papules

Multiple Endocrine Neoplasia Type 2 (MEN2A, FMTC, MEN2B)

• Family member with a confirmed RET gene mutation
• Personal or family history that includes one or more cases of medullary thyroid cancer
• MEN 2A is suggested by the following additional features: parathyroid hyperplasia or adenoma and pheochromocytoma
• MEN 2B includes: pheochromocytomas, mucosal neuromas of the lips and tongue, and ganglioneuromas of the gastrointestinal tract

Familial Adenomatous Polyposis (FAP)                                       
 top

• Family member with a confirmed APC gene mutation
• Personal history or close relative with a clinical diagnosis of FAP:
• large numbers of adenomatous colorectal polyps (pathology reports required)
• additional features may include: gastric polyps, duodenal adenomatous polyps, osteomas, dental abnormalities (e.g. supernumerary teeth), CHRPE, soft tissue tumours (epidermoid cysts and fibromas), desmoid tumours, and other associated cancers.
• Attenuated FAP is suggested by a personal history, or close relative, with 10 or more histologically confirmed adenomatous polyps

Polyposis Syndromes - Other

• Personal history or close relative with a clinical and/or molecular diagnosis of juvenile polyposis, Peutz-Jeghers syndrome, hereditary mixed polyposis, MYH-associated polyposis

von Hippel Lindau Syndrome                                                                                             
top

• Family member with a confirmed VHL gene mutation
• Hemangioblastomas of the brain, spinal cord, retina (retinal hemangioblastomas may be the initial manifestation and can cause vision loss)
• Renal cysts and clear cell renal cell carcinoma (40% of patients)
• Pheochromocytomas (can be asymptomatic, but may cause sustained or episodic hypertension)
• Endolymphatic sac tumours (can cause hearing loss of varying severity)