For the syndromes listed here, we recommend that you discuss your risk for cancer and other health conditions with a genetic counselor or doctor who is experienced in caring for people with your specific cancer predisposition syndrome.
Multiple Endocrine Neoplasia Type 1 (MEN1)
MEN1 syndrome is a rare condition that is associated with an increased risk for endocrine and nonendocrine tumors. Diagnosis of MEN1 is dependent on the occurrence of two or more MEN1-related tumors (parathyroid, gastro-entero-pancreatic tract, or pituitary). Other features of MEN1 include adrenal cortical tumors, carcinoid tumors, lipomas, and angiofibromas. Mutations in the MEN1 gene are identified in significant proportion of families with a history of MEN1. People with a first-degree relative (a parent, sibling, or child) with MEN1 have a 50% chance of having inherited the same mutation. Biochemical and imaging tests are typically recommended for people with MEN1.
Multiple Endocrine Neoplasia Type 2 (MEN2)
MEN2 is a syndrome characterized by a high risk of developing medullary thyroid cancer. There are three subtypes of MEN2:
- MEN2A, which is also associated with an increased risk for pheochromocytoma and parathyroid adenoma or hyperplasia.
- MEN2B, which is associated with an increased risk for pheochromocytoma and certain facial and body features. Mutations in the RET gene are identified in families with MEN2. People with a first-degree relative (a parent, sibling, or child) with MEN2 have a 50% chance of having inherited the same mutation. Surgical removal of the thyroid (thyroidectomy) and biochemical and imaging tests are typically recommended for people with MEN2.
- Familial medullary thyroid carcinoma (FMTC), which is diagnosed in families with multiple cases of medullary thyroid cancer when there are no cases of pheochromocytoma, parathyroid adenoma, or hyperplasia.
Neurofibromatosis Type 1 (NF1)
Neurofibromatosis type 1 (NF1) is caused by mutations in the NF1 gene. People with a first-degree relative (a parent, sibling, or child) with NF1 have a 50% chance of having inherited the same mutation. NF1 is typically characterized by multiple café au lait spots on the skin, freckles in the armpits and groin area, multiple skin neurofibromas, and Lisch nodules in the eyes. The lifetime risk of cancer (brain tumors, pheochromocytomas, sarcomas, leukemias, and carcinoid tumors) in people with NF1 is approximately 5%. There is also evidence to suggest an increased risk of breast cancer in people with NF1, but the exact level of risk is not clear.
Familial schwannomatosis is a rare condition that is associated with an increased risk of developing schwannomas. Schwannomas affect the nerves in the body and are usually benign tumors (not cancer). These tumors may cause pain depending on their location and size. Familial schwannomatosis can be caused by mutations in the NF2, LZTR1, or SMARCB1 genes. People who have a first-degree relative (a parent, sibling, or child) with one of these gene mutations have a 50% chance of having also inherited the same mutation.
Given clinical similarity between patients with NF2 gene mutations and mutations in the LZTR1 and SMARCB1 genes, neurofibromatosis type 2 (NF2) has been renamed NF2-related schwannomatosis. NF2-related schwannomatosis is typically characterized by tumors called acoustic neuromas, also known as vestibular schwannomas, in both ears. People with NF2 can also develop tumors affecting the nervous system, such as schwannomas, meningiomas, ependymomas, and astrocytomas. Rarely, adrenal gland tumors or carcinoid tumors can occur.
Gorlin Syndrome (Nevoid Basal Cell Carcinoma Syndrome)
Gorlin syndrome, also known as nevoid basal cell carcinoma syndrome, is characterized by early onset and multiple basal cell carcinoma skin cancers. People with Gorlin syndrome can also develop multiple noncancerous tumors of the jaw as well as cardiac fibromas, ovarian fibromas, or medulloblastomas. They often have distinctive physical features, such as a prominent forehead. Gorlin syndrome can be caused by mutations in two genes, PTCH1 and SUFU. People with a first-degree relative (a parent, sibling, or child) with Gorlin syndrome have a 50% chance of having inherited the same mutation.
Familial Atypical Multiple Mole Melanoma (FAMMM) Syndrome
FAMMM is caused by mutations in the CDKN2A (also known as p16) and CDK4 genes. People with a first-degree relative (a parent, sibling, or child) with FAMMM have a 50% chance of having inherited the same mutation. People with FAMMM have multiple atypical moles and melanomas, often at a younger age than is typical. They also have a higher risk of developing pancreatic cancer. Very rarely, certain mutations in the CDKN2A gene can cause an increased risk of other cancer types, including nerve sheath tumors.