Materiały źródłowe

• #1 Definition of multiple endocrine neoplasia type 2 syndrome – NCI Dictionary of Cancer Terms – NCIFacebookFollow on XInstagramYoutubeLinkedin

  https://www.cancer.gov/publications/dictionaries/cancer-terms/def/multiple-endocrine-neoplasia-type-2-syndrome

  A rare, genetic disorder that affects the endocrine glands and can cause tumors in the thyroid gland, parathyroid glands, and adrenal glands. […] Multiple endocrine neoplasia type 2 syndrome is caused by a mutation (change) in a gene called RET, and is divided into three subtypes (MEN2A, MEN2B, and FMTC). […] Multiple endocrine neoplasia 2 (MEN2) syndrome is a rare, inherited disorder that affects the endocrine glands or organs. MEN2 syndrome usually causes thyroid gland, parathyroid gland, or adrenal gland tumors.

• #2 Multiple Endocrine Neoplasias Type 2 – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK519054/

  Multiple endocrine neoplasia type 2 (MEN 2) is a hereditary cancer syndrome associated primarily with tumors of the adrenal gland, thyroid and parathyroid. […] Identify the germline RET mutations in the etiology of multiple endocrine neoplasia type 2. […] The rearranged during transfection (RET) protein is a receptor tyrosine kinase that is localized to chromosome 10q11.2. It appears to transduce growth and differentiate signals in several tissues, particularly those arising from neural crest cells. Some cytogenetic mutations have been reported; these may involve intracellular and extracellular domains of the RET protein signaling pathway. The germline RET mutations in MEN2 result in a gain of function of this tyrosine kinase receptor. This is different from many other inherited predispositions to neoplasia that are due to heritable „loss-of-function” mutations that inactivate tumor suppressor proteins.

• #3 Multiple Endocrine Neoplasia Type 2 (MEN2): Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/123447-overview

  Multiple endocrine neoplasias type 2 (MEN2) is an inherited disorder characterized by the development of medullary thyroid cancer (MTC), parathyroid tumors, and pheochromocytoma. MEN2 results from germline mutations in the RET proto-oncogene and is transmitted in an autosomal dominant fashion. […] Point mutations associated with MEN2A and the FMTC-only subtype have been identified in exons 10 and 11. Evidence of genotype/phenotype correlation exists. Classical MEN2A is associated with germline missense mutations in RET codons 609, 611, 618, or 620 of exon 10 or codon 634 of exon 11, which map to the receptors extracellular cysteine-rich domain. MEN2A with cutaneous lichen amyloidosis is nearly always associated with mutation of codon 634, while patients with MEN2A and Hirschsprung disease typically harbor mutations involving RET exon 10.

• #4 Multiple Endocrine Neoplasia (MEN): Types & Symptoms

  https://my.clevelandclinic.org/health/diseases/23088-multiple-endocrine-neoplasia-men

  Multiple endocrine neoplasia (MEN) is a rare condition caused by a genetic mutation that affects multiple glands in your endocrine system. […] Multiple endocrine neoplasia type 2 (MEN2) is a genetic polyglandular (multiple glands) cancer syndrome. People with MEN2 will develop medullary thyroid cancer (carcinoma) and have an increased risk of developing other tumors that affect other glands in the endocrine system. […] MEN type 2 is caused by mutations of the RET gene, which is a gene that plays a role in the development of cancer. When working as it should, the RET gene helps control cell division and regulation of cell death. Mutations of the RET gene lead to uncontrolled growth of cells, causing tumors to form in certain organs and glands.

• #5 Multiple Endocrine Neoplasias Type 2 – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/sites/books/NBK519054/

  Multiple endocrine neoplasia type 2 (MEN 2) is a hereditary cancer syndrome associated primarily with tumors of the adrenal gland, thyroid and parathyroid. […] Identify the germline RET mutations in the etiology of multiple endocrine neoplasia type 2. […] The rearranged during transfection (RET) protein is a receptor tyrosine kinase that is localized to chromosome 10q11.2. It appears to transduce growth and differentiate signals in several tissues, particularly those arising from neural crest cells. Some cytogenetic mutations have been reported; these may involve intracellular and extracellular domains of the RET protein signaling pathway. The germline RET mutations in MEN2 result in a gain of function of this tyrosine kinase receptor. This is different from many other inherited predispositions to neoplasia that are due to heritable „loss-of-function” mutations that inactivate tumor suppressor proteins.

• #6 Multiple Endocrine Neoplasia Type 2 | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/multiple-endocrine-neoplasia-type-2

  MEN2 is caused by a mutation in the RET gene located on chromosome 10. These mutations can be hereditary or can occur as a new mutation in one of the fathers sperm, mothers eggs or in a cell of the developing fetus. About 95 percent of individuals with MEN2A inherited the condition from their parents, whereas 50 percent of people with MEN2B are the first in their families to be diagnosed with the disease. […] In individuals with either form of MEN2, the RET gene is altered so the protein that is produced is always switched on. With the RET protein (receptor) always active, cells continuously grow (multiply), leading to cancer development and over-production of certain proteins and hormones. […] People with MEN2 carry one normal copy of the RET gene and one abnormal RET gene in all cells throughout their body. These individuals have a 50 percent chance of passing the same genetic alteration onto each of their future children. A disease that is associated with a 50 percent chance of being passed between generations is described as an autosomal dominant condition. Most children who inherit the altered RET gene are born and develop normally, but are at increased risk of developing benign or malignant endocrine tumors during their lifetime.

• #7 Multiple endocrine neoplasia: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/multiple-endocrine-neoplasia/

  Mutations in the RET gene cause multiple endocrine neoplasia type 2. This gene provides instructions for producing a protein that is involved in signaling within cells. The RET protein triggers chemical reactions that instruct cells to respond to their environment, for example by dividing or maturing. Mutations in the RET gene overactivate the protein’s signaling function, which can trigger cell growth and division in the absence of signals from outside the cell. This unchecked cell division can lead to the formation of tumors in endocrine glands and other tissues. […] Mutations in the MEN1 gene cause multiple endocrine neoplasia type 1. […] Mutations in the CDKN1B gene cause multiple endocrine neoplasia type 4.

• #8 Multiple Endocrine Neoplasias Type 2 – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK519054/

  Multiple endocrine neoplasia type 2 (MEN 2) is a hereditary cancer syndrome associated primarily with tumors of the adrenal gland, thyroid and parathyroid. […] Identify the germline RET mutations in the etiology of multiple endocrine neoplasia type 2. […] The rearranged during transfection (RET) protein is a receptor tyrosine kinase that is localized to chromosome 10q11.2. It appears to transduce growth and differentiate signals in several tissues, particularly those arising from neural crest cells. Some cytogenetic mutations have been reported; these may involve intracellular and extracellular domains of the RET protein signaling pathway. The germline RET mutations in MEN2 result in a gain of function of this tyrosine kinase receptor. This is different from many other inherited predispositions to neoplasia that are due to heritable „loss-of-function” mutations that inactivate tumor suppressor proteins.

• #9 Multiple Endocrine Neoplasias Type 2 – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/sites/books/NBK519054/

  Multiple endocrine neoplasia type 2 (MEN 2) is a hereditary cancer syndrome associated primarily with tumors of the adrenal gland, thyroid and parathyroid. […] Identify the germline RET mutations in the etiology of multiple endocrine neoplasia type 2. […] The rearranged during transfection (RET) protein is a receptor tyrosine kinase that is localized to chromosome 10q11.2. It appears to transduce growth and differentiate signals in several tissues, particularly those arising from neural crest cells. Some cytogenetic mutations have been reported; these may involve intracellular and extracellular domains of the RET protein signaling pathway. The germline RET mutations in MEN2 result in a gain of function of this tyrosine kinase receptor. This is different from many other inherited predispositions to neoplasia that are due to heritable „loss-of-function” mutations that inactivate tumor suppressor proteins.

• #10 Multiple endocrine neoplasia, type 2 (MEN 2) | UM Health-Sparrow

  https://www.uofmhealthsparrow.org/departments-conditions/conditions/multiple-endocrine-neoplasia-type-2-men-2

  Multiple endocrine neoplasia, type 2 is an inherited disorder. This means people who have the changed gene can pass it on to their children. Each child has a 50% chance of getting the disorder. […] MEN 2 is an inherited condition. This means someone who has a changed gene that can cause MEN 2 can pass that gene on to their children. […] Many people also may be the first person in their families to have this disorder.

• #11 Multiple endocrine neoplasia, type 2 (MEN 2) | Beacon Health System

  https://www.beaconhealthsystem.org/library/diseases-and-conditions/multiple-endocrine-neoplasia-type-2-men-2/

  MEN 2 is an inherited disorder. This means people who have the changed gene can pass it on to their children. Each child has a 50% chance of getting the disorder. […] MEN 2 is an inherited condition. This means someone who has a changed gene that can cause MEN 2 can pass that gene on to their children.

• #12 Multiple endocrine neoplasia 2 (MEN2) | Macmillan Cancer Support

  https://www.macmillan.org.uk/cancer-information-and-support/worried-about-cancer/pre-cancerous-and-genetic-conditions/multiple-endocrine-neoplasia-2-men2

  MEN2 is a rare, inherited condition that can run in families. It causes tumours in endocrine (hormone-making) glands. These can be cancerous (malignant) or non-cancerous (benign). […] People with MEN2 have a RET gene variant. If you have this variant, you are more likely to develop certain types of tumour. […] MEN2 causes tumours that usually affect endocrine glands. Endocrine glands produce hormones. […] Tumours caused by MEN2 can be cancerous (malignant) or non-cancerous (benign). Malignant tumours can spread to other parts of the body. […] MEN2A and MEN2B both cause a higher risk of a specific type of thyroid cancer called medullary thyroid carcinoma (MTC). […] A small number of people are the first in their family to have the RET gene variant. This means your parents did not have it. […] If you have MEN, there is a 1 in 2 (50%) chance that your child could inherit it from you.

• #13 Multiple endocrine neoplasia type 2 (MEN 2) | EBSCO Research Starters

  https://www.ebsco.com/research-starters/health-and-medicine/multiple-endocrine-neoplasia-type-2-men-2

  Multiple endocrine neoplasia type 2 (MEN 2) is a hereditary cancer syndrome that affects the endocrine glands, leading to the production of hormones in the body. […] The underlying cause of MEN 2 is typically a mutation in the RET gene, which is necessary for normal cell growth. […] The underlying genetic cause of MEN 2 is a mutation, or a genetic change, in the RET gene. RET is a proto-oncogene, which means it usually functions in cell growth and differentiation. Mutations in RET cause it to become an active oncogene, turning normal cells into cancer cells. […] A mutation in one copy of the gene is sufficient to cause MEN 2, which is why this condition is referred to as autosomal dominant. […] Most mutations are inherited from a parent, but new mutations do occur. […] Mutations in different parts of the RET gene lead to the three subtypes of MEN 2. […] Certain mutations are associated with a higher incidence of pheochromocytoma and hyperparathyroidism.

• #14 Multiple Endocrine Neoplasia Type 2 | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/multiple-endocrine-neoplasia-type-2

  MEN2 is caused by a mutation in the RET gene located on chromosome 10. These mutations can be hereditary or can occur as a new mutation in one of the fathers sperm, mothers eggs or in a cell of the developing fetus. About 95 percent of individuals with MEN2A inherited the condition from their parents, whereas 50 percent of people with MEN2B are the first in their families to be diagnosed with the disease. […] In individuals with either form of MEN2, the RET gene is altered so the protein that is produced is always switched on. With the RET protein (receptor) always active, cells continuously grow (multiply), leading to cancer development and over-production of certain proteins and hormones. […] People with MEN2 carry one normal copy of the RET gene and one abnormal RET gene in all cells throughout their body. These individuals have a 50 percent chance of passing the same genetic alteration onto each of their future children. A disease that is associated with a 50 percent chance of being passed between generations is described as an autosomal dominant condition. Most children who inherit the altered RET gene are born and develop normally, but are at increased risk of developing benign or malignant endocrine tumors during their lifetime.

• #15 Multiple Endocrine Neoplasia Type 2 | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/multiple-endocrine-neoplasia-type-2

  MEN2 is caused by a mutation in the RET gene located on chromosome 10. These mutations can be hereditary or can occur as a new mutation in one of the fathers sperm, mothers eggs or in a cell of the developing fetus. About 95 percent of individuals with MEN2A inherited the condition from their parents, whereas 50 percent of people with MEN2B are the first in their families to be diagnosed with the disease. […] In individuals with either form of MEN2, the RET gene is altered so the protein that is produced is always switched on. With the RET protein (receptor) always active, cells continuously grow (multiply), leading to cancer development and over-production of certain proteins and hormones. […] People with MEN2 carry one normal copy of the RET gene and one abnormal RET gene in all cells throughout their body. These individuals have a 50 percent chance of passing the same genetic alteration onto each of their future children. A disease that is associated with a 50 percent chance of being passed between generations is described as an autosomal dominant condition. Most children who inherit the altered RET gene are born and develop normally, but are at increased risk of developing benign or malignant endocrine tumors during their lifetime.

• #16 Multiple Endocrine Neoplasia Type 2 and the RET gene – Sydney Cancer Genetics

  https://www.sydneycancergenetics.com.au/genes-and-syndromes/multiple-endocrine-neoplasia-type-2-and-the-ret-gene/

  Multiple Endocrine Neoplasia syndrome Type 2 is rare, affecting 1 in 30,000 people. It is caused by a mutation in the RET gene. […] The difference relates to the location of the specific mutation (pathogenic variant) in the DNA code of the RET gene. […] The RET gene is a growth gene. It effects tissues derived from the neural crest cells. […] When the RET gene is mutated, these cells grow when they shouldn’t. This causes problems because of unregulated hormonal production and the cells can become cancerous and spread. […] Multiple Endocrine Neoplasia syndrome type 2 is a hereditary cancer syndrome. There is a 50% chance of a person who carries a germline RET mutation, whether male or female, passing the mutation to their son or daughter. […] 95% of people who meet the clinical criteria for MEN2A or MEN2B will be found to carry a RET mutation. […] In individuals with MEN2a, 5% of the time, they are the first person in their family to carry a RET mutation. For MEN2B it is the majority – 75%. This is called a de novo mutation, meaning „from new”.

• #17 Multiple Endocrine Neoplasia Type 2 (MEN2): Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/123447-overview

  Approximately 75% of MEN2B cases are sporadic and affected patients have de novo RET mutations, while 25% of cases occur in families with previous or current manifestations of MEN2B. Approximately 95% of patients with MEN2B have RET germline mutations in exon 16 (codon M918T) and fewer than 5% have RET germline mutations in exon 15 (codon A883F).

• #18 Multiple endocrine neoplasia type 2: An overview | Genetics in Medicine

  https://www.nature.com/articles/gim2011127

  With the identification and characterization of RET and genotype-associated phenotypes, it became obvious that all three subtypes are allelic and that MEN 2A and familial MTC (FMTC) are merely manifestations of different penetrances of RET mutations. […] MEN 2A makes up approximately 70-80% of cases of MEN 2. […] As genetic testing for RET mutations has become available, it has become apparent that 70-95% of individuals with MEN 2A develop MTC, approximately 50% develop pheochromocytoma, and approximately 15-30% develop HPT. […] The FMTC subtype comprises approximately 10-20% of cases of MEN 2. […] By operational definition, MTC is the only clinical manifestation of FMTC. […] The MEN 2B subtype comprises approximately 5% of cases of MEN 2. […] MEN 2B is characterized by the early development of an aggressive form of MTC in all affected individuals. […] Individuals with MEN 2B who do not undergo thyroidectomy at an early age (1 year) are likely to develop metastatic MTC at an early age. […] Approximately 50% of individuals with MEN 2B have a de novo germline mutation, and 50% have inherited the mutation from a parent.

• #19 Multiple Endocrine Neoplasia | MD Anderson Cancer Center

  https://www.mdanderson.org/cancer-types/multiple-endocrine-neoplasia.html

  Multiple endocrine neoplasia type 2 (MEN2) is caused by mutations in the RET gene. […] People with multiple endocrine neoplasia type 2 (MEN2) have a 95% chance of developing medullary thyroid cancer. […] MEN2 is divided into three types: […] MEN2A and MEN2B are caused by mutations in the RET gene. […] Multiple Endocrine Neoplasia Type 2A (MEN2A): People with MEN2A often develop medullary thyroid cancer when they are young adults. […] Multiple Endocrine Neoplasia Type 2B (MEN2B) may cause medullary thyroid carcinoma in early childhood. […] Familial Medullary Thyroid Carcinoma (FMTC) is medullary thyroid cancer that develops in multiple members of the same family without the presence of pheochromocytoma and/or hyperparathyroidism. […] Multiple endocrine neoplasia is caused by gene mutations that are handed down in families. […] MEN2 is caused by gene mutations in the RET gene.

• #20 NET Causes – NETRF

  https://netrf.org/old-for-patients/nets-info/net-causes/

  MEN2: Multiple endocrine neoplasia type 2 is associated with MEN2A Syndrome (Familial medullary thyroid cancer, hyperparathyroidism) and MEN2B Syndrome (Cutaneous lichen amyloidosis, Hirschsprung disease). […] The affected gene for MEN2 is RET. […] Related NETs for MEN2 include pheochromocytoma.

• #21 Multiple Endocrine Neoplasias Type 2 – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/sites/books/NBK519054/

  The number of different mutations causes MEN2A. The majority of the mutations in MEN2A variants occur in the cysteine-rich region of RET protein’s extracellular domain (coded by the genes in exon10 and 11), while mutations in the intracellular TK2 domain cause MEN2B-associated tumors. A single 918 Met to Thr mutation (M918T) in exon 16 is responsible for over 95% of cases of MEN2B. Their are other less common mutations associated with both MEN2A and MEN2B divided into high-risk, moderate-risk and low-risk categories. Identification of these specific mutations is very important as it significantly impacts screening, diagnosis, and treatment, for example, the M918T mutation in exon 16 is considered a high-risk mutation for MEN2B cases and needs aggressive screening and prophylactic treatment to decrease morbidity and mortality.

• #22 Multiple Endocrine Neoplasia Type 2 (MEN2): Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/123447-overview

  Multiple endocrine neoplasias type 2 (MEN2) is an inherited disorder characterized by the development of medullary thyroid cancer (MTC), parathyroid tumors, and pheochromocytoma. MEN2 results from germline mutations in the RET proto-oncogene and is transmitted in an autosomal dominant fashion. […] Point mutations associated with MEN2A and the FMTC-only subtype have been identified in exons 10 and 11. Evidence of genotype/phenotype correlation exists. Classical MEN2A is associated with germline missense mutations in RET codons 609, 611, 618, or 620 of exon 10 or codon 634 of exon 11, which map to the receptors extracellular cysteine-rich domain. MEN2A with cutaneous lichen amyloidosis is nearly always associated with mutation of codon 634, while patients with MEN2A and Hirschsprung disease typically harbor mutations involving RET exon 10.

• #23 Multiple endocrine neoplasia type 2: An overview | Genetics in Medicine

  https://www.nature.com/articles/gim2011127

  With the identification and characterization of RET and genotype-associated phenotypes, it became obvious that all three subtypes are allelic and that MEN 2A and familial MTC (FMTC) are merely manifestations of different penetrances of RET mutations. […] MEN 2A makes up approximately 70-80% of cases of MEN 2. […] As genetic testing for RET mutations has become available, it has become apparent that 70-95% of individuals with MEN 2A develop MTC, approximately 50% develop pheochromocytoma, and approximately 15-30% develop HPT. […] The FMTC subtype comprises approximately 10-20% of cases of MEN 2. […] By operational definition, MTC is the only clinical manifestation of FMTC. […] The MEN 2B subtype comprises approximately 5% of cases of MEN 2. […] MEN 2B is characterized by the early development of an aggressive form of MTC in all affected individuals. […] Individuals with MEN 2B who do not undergo thyroidectomy at an early age (1 year) are likely to develop metastatic MTC at an early age. […] Approximately 50% of individuals with MEN 2B have a de novo germline mutation, and 50% have inherited the mutation from a parent.

• #24 Multiple Endocrine Neoplasia (MEN) Symptoms & Treatment

  https://www.myprivia.com/txendocrine/services/endocrine-neoplasia

  Multiple endocrine neoplasia type II – It is caused by a defect in the RET gene. It commonly causes medullary carcinoma in the thyroid gland. Pheochromocytoma (adrenal gland tumor) may be seen in nearly half of the patients and some patients may also have hyperplasia of parathyroid gland. […] The MEN type IIa is most commonly occurring subtype where medullary carcinoma occurs in early stages of adulthood, some of the individuals develop pheochromocytoma and some develop hyperparathyroidism. In MEN type IIb the medullary carcinoma occurs in the early childhood and some individuals develop pheochromocytoma but hyperparathyroidism may not be observed. In FMTC, medullary carcinoma occurs in several members of the same family without the occurrence of pheochromocytoma and hyperparathyroidism.

• #25

  https://omim.org/entry/171400

  A number sign (#) is used with this entry because multiple endocrine neoplasia type IIA (MEN2A) is caused by heterozygous mutation in the RET oncogene (164761) on chromosome 10q11. […] Multiple endocrine neoplasia type IIA is an autosomal dominant syndrome of multiple endocrine neoplasms, including medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid adenomas. […] The mutation for medullary thyroid carcinoma with parathyroid tumors (MTC with PTs) is closely linked to the centromeric region of chromosome 10. […] Each MEN2 index case probably has an activating germline RET mutation. […] RET testing has replaced calcitonin testing to diagnose the MEN2 carrier state. […] The specific RET codon mutation correlates with the MEN2 syndromic variant, the age of onset of MTC, and the aggressiveness of MTC; consequently, that mutation should guide major management decisions, such as whether and when to perform thyroidectomy.

• #26 Multiple Endocrine Neoplasia, Type 2A (MEN 2A) – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/multiple-endocrine-neoplasia-men-syndromes/multiple-endocrine-neoplasia-type-2a-men-2a

  Mutations in the RET proto-oncogene on chromosome 10 have been identified in MEN 2A, MEN 2B, and familial medullary thyroid carcinoma. […] The RET protein is a receptor tyrosine kinase; MEN 2A and familial medullary thyroid carcinoma mutations result in activation of certain intracellular pathways. […] Once genetic testing identifies a child as having a RET mutation, prophylactic thyroidectomy is recommended. Depending on the particular mutation, prophylactic thyroidectomy as early as the first months of life may be indicated. Medullary thyroid cancer can be cured or prevented by early thyroidectomy. […] There is a genotype-phenotype correlation for patients with RET mutations that may provide information about age of onset and clinical course of medullary thyroid cancer and this impact the timing of surgery for an affected child.

• #27

  https://www.singhealth.com.sg/patient-care/conditions-treatments/multiple-endocrine-neoplasia-type-2

  Multiple Endocrine Neoplasia Type 2 is a hereditary cancer syndrome. […] People with MEN2 are born with a faulty (i.e., disease-causing) RET gene. […] If there is a fault (i.e., mutation) within the RET gene, it can become dysfunctional, resulting in the production of an overactive protein which can signal cells to grow and divide uncontrollably, resulting in tumour formation and cancer. […] The location of the fault within the RET gene can determine the age, likelihood and aggressiveness of the medullary thyroid cancer that may develop. […] MEN2 follows a dominant inheritance pattern. This means that having one faulty copy of the RET gene can result in an increased risk of tumours/cancer. […] A parent with a faulty gene(s) has a 50% chance of passing down their faulty gene(s) to their children. […] The conditions associated with a faulty RET gene and their risk estimates may change as more information is available.

• #28 Multiple Endocrine Neoplasias Type 2 – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/sites/books/NBK519054/

  The number of different mutations causes MEN2A. The majority of the mutations in MEN2A variants occur in the cysteine-rich region of RET protein’s extracellular domain (coded by the genes in exon10 and 11), while mutations in the intracellular TK2 domain cause MEN2B-associated tumors. A single 918 Met to Thr mutation (M918T) in exon 16 is responsible for over 95% of cases of MEN2B. Their are other less common mutations associated with both MEN2A and MEN2B divided into high-risk, moderate-risk and low-risk categories. Identification of these specific mutations is very important as it significantly impacts screening, diagnosis, and treatment, for example, the M918T mutation in exon 16 is considered a high-risk mutation for MEN2B cases and needs aggressive screening and prophylactic treatment to decrease morbidity and mortality.

• #29 Multiple Endocrine Neoplasia, Type 2A (MEN 2A) – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/multiple-endocrine-neoplasia-men-syndromes/multiple-endocrine-neoplasia-type-2a-men-2a

  Mutations in the RET proto-oncogene on chromosome 10 have been identified in MEN 2A, MEN 2B, and familial medullary thyroid carcinoma. […] The RET protein is a receptor tyrosine kinase; MEN 2A and familial medullary thyroid carcinoma mutations result in activation of certain intracellular pathways. […] Once genetic testing identifies a child as having a RET mutation, prophylactic thyroidectomy is recommended. Depending on the particular mutation, prophylactic thyroidectomy as early as the first months of life may be indicated. Medullary thyroid cancer can be cured or prevented by early thyroidectomy. […] There is a genotype-phenotype correlation for patients with RET mutations that may provide information about age of onset and clinical course of medullary thyroid cancer and this impact the timing of surgery for an affected child.

• #30 Multiple Endocrine Neoplasias Type 2 – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK519054/

  The number of different mutations causes MEN2A. The majority of the mutations in MEN2A variants occur in the cysteine-rich region of RET protein’s extracellular domain (coded by the genes in exon10 and 11), while mutations in the intracellular TK2 domain cause MEN2B-associated tumors. A single 918 Met to Thr mutation (M918T) in exon 16 is responsible for over 95% of cases of MEN2B. Their are other less common mutations associated with both MEN2A and MEN2B divided into high-risk, moderate-risk and low-risk categories. Identification of these specific mutations is very important as it significantly impacts screening, diagnosis, and treatment, for example, the M918T mutation in exon 16 is considered a high-risk mutation for MEN2B cases and needs aggressive screening and prophylactic treatment to decrease morbidity and mortality. […] The prevalence of all MEN2 worldwide is 1 in 35,000, while in the United States, it is 1 in 30,000 to 50,000. The epidemiology of MEN2B is unknown. The prevalence of MEN2B is estimated to be between 1 in 600,000 to 1 in 4 million.

• #31 Clinical manifestations and diagnosis of multiple endocrine neoplasia type 2 – UpToDate

  https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-multiple-endocrine-neoplasia-type-2

  Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant disorder with an estimated prevalence of 1 per 30,000 in the general population. […] The genetic defect in these disorders involves the RET proto-oncogene on chromosome 10. MEN2A and 2B are inherited in an autosomal dominant pattern with very high penetrance. […] In both syndromes, there is an occurrence of multicentric tumor formation in all organs where the RET proto-oncogene is expressed.

• #32 Orphanet: Multiple endocrine neoplasia type 2

  https://www.orpha.net/en/disease/detail/653

  MEN2 is caused by a heterozygote germline activating mutation in the RET proto-oncogene (10q11.2), encoding a membrane tyrosine kinase receptor. The clinical subtypes depend on which functional domain the mutations affect. […] The total prevalence of all variants of multiple endocrine neoplasia type 2 (MEN2) is approximately 1/35,000. MEN2A, accounts for 95% of MEN2 cases.

• #33 Multiple endocrine neoplasia type 2 – Wikipedia

  https://en.wikipedia.org/wiki/Multiple_endocrine_neoplasia_type_2

  Multiple endocrine neoplasia type 2 (also known as „Pheochromocytoma (codons 630 and 634) and amyloid producing medullary thyroid carcinoma,” „PTC syndrome,” and „Sipple syndrome”) is a group of medical disorders associated with tumors of the endocrine system. […] Most cases of MEN2 derive from a variation in the RET proto-oncogene, and are specific for cells of neural crest origin. […] The protein produced by the RET gene plays an important role in the TGF-beta (transforming growth factor beta) signaling system. Because the TGF-beta system operates in nervous tissues throughout the body, variations in the RET gene can have effects in nervous tissues throughout the body. MEN2 generally results from a gain-of-function variant of a RET gene. […] When inherited, multiple endocrine neoplasia type 2 is transmitted in an autosomal dominant pattern, which means affected people have one affected parent, and possibly affected siblings and children. Some cases, however, result from spontaneous new mutations in the RET gene.

• #34 Multiple Endocrine Neoplasias Type 2 – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK519054/

  Multiple endocrine neoplasia type 2 (MEN 2) is a hereditary cancer syndrome associated primarily with tumors of the adrenal gland, thyroid and parathyroid. […] Identify the germline RET mutations in the etiology of multiple endocrine neoplasia type 2. […] The rearranged during transfection (RET) protein is a receptor tyrosine kinase that is localized to chromosome 10q11.2. It appears to transduce growth and differentiate signals in several tissues, particularly those arising from neural crest cells. Some cytogenetic mutations have been reported; these may involve intracellular and extracellular domains of the RET protein signaling pathway. The germline RET mutations in MEN2 result in a gain of function of this tyrosine kinase receptor. This is different from many other inherited predispositions to neoplasia that are due to heritable „loss-of-function” mutations that inactivate tumor suppressor proteins.

• #35 Multiple endocrine neoplasia type 2 – Wikipedia

  https://en.wikipedia.org/wiki/Multiple_endocrine_neoplasia_type_2

  Multiple endocrine neoplasia type 2 (also known as „Pheochromocytoma (codons 630 and 634) and amyloid producing medullary thyroid carcinoma,” „PTC syndrome,” and „Sipple syndrome”) is a group of medical disorders associated with tumors of the endocrine system. […] Most cases of MEN2 derive from a variation in the RET proto-oncogene, and are specific for cells of neural crest origin. […] The protein produced by the RET gene plays an important role in the TGF-beta (transforming growth factor beta) signaling system. Because the TGF-beta system operates in nervous tissues throughout the body, variations in the RET gene can have effects in nervous tissues throughout the body. MEN2 generally results from a gain-of-function variant of a RET gene. […] When inherited, multiple endocrine neoplasia type 2 is transmitted in an autosomal dominant pattern, which means affected people have one affected parent, and possibly affected siblings and children. Some cases, however, result from spontaneous new mutations in the RET gene.

• #36 Multiple Endocrine Neoplasias Type 2 – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/sites/books/NBK519054/

  Multiple endocrine neoplasia type 2 (MEN 2) is a hereditary cancer syndrome associated primarily with tumors of the adrenal gland, thyroid and parathyroid. […] Identify the germline RET mutations in the etiology of multiple endocrine neoplasia type 2. […] The rearranged during transfection (RET) protein is a receptor tyrosine kinase that is localized to chromosome 10q11.2. It appears to transduce growth and differentiate signals in several tissues, particularly those arising from neural crest cells. Some cytogenetic mutations have been reported; these may involve intracellular and extracellular domains of the RET protein signaling pathway. The germline RET mutations in MEN2 result in a gain of function of this tyrosine kinase receptor. This is different from many other inherited predispositions to neoplasia that are due to heritable „loss-of-function” mutations that inactivate tumor suppressor proteins.

• #37 Multiple Endocrine Neoplasia Type 2 | St. Jude Care & Treatment

  https://www.stjude.org/care-treatment/treatment/genetic-syndromes/multiple-endocrine-neoplasia-type-2.html

  Multiple endocrine neoplasia type 2 (MEN2) is a rare genetic disorder that is passed down from parents to their children (inherited). […] MEN2 is caused by changes in a gene known as RET. This gene carries important information that controls cell growth and function. A change that causes the gene to not work correctly is called a mutation. […] Children who have MEN2 inherit 1 normal copy of the RET gene and 1 copy that is changed (mutated). This change makes the gene not work correctly. It is called a RET mutation. […] Nearly all children with MEN2A and about 50% (1 in 2) of children with MEN2B inherit the RET gene mutation from a parent who also has the syndrome. […] Because people with MEN2 have only 1 normal copy of RET in their cells, those cells are harder to control. They tend to grow and divide more than usual, which can cause a tumor. This happens most often in certain cells of the endocrine system, especially thyroid cells. This may be why people with MEN2 have a higher risk of developing tumors than people who do not have this condition.

• #38 Multiple Endocrine Neoplasia Type 2 | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/multiple-endocrine-neoplasia-type-2

  MEN2 is caused by a mutation in the RET gene located on chromosome 10. These mutations can be hereditary or can occur as a new mutation in one of the fathers sperm, mothers eggs or in a cell of the developing fetus. About 95 percent of individuals with MEN2A inherited the condition from their parents, whereas 50 percent of people with MEN2B are the first in their families to be diagnosed with the disease. […] In individuals with either form of MEN2, the RET gene is altered so the protein that is produced is always switched on. With the RET protein (receptor) always active, cells continuously grow (multiply), leading to cancer development and over-production of certain proteins and hormones. […] People with MEN2 carry one normal copy of the RET gene and one abnormal RET gene in all cells throughout their body. These individuals have a 50 percent chance of passing the same genetic alteration onto each of their future children. A disease that is associated with a 50 percent chance of being passed between generations is described as an autosomal dominant condition. Most children who inherit the altered RET gene are born and develop normally, but are at increased risk of developing benign or malignant endocrine tumors during their lifetime.

• #39 Clinical manifestations and diagnosis of multiple endocrine neoplasia type 2 – UpToDate

  https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-multiple-endocrine-neoplasia-type-2

  Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant disorder with an estimated prevalence of 1 per 30,000 in the general population. […] The genetic defect in these disorders involves the RET proto-oncogene on chromosome 10. MEN2A and 2B are inherited in an autosomal dominant pattern with very high penetrance. […] In both syndromes, there is an occurrence of multicentric tumor formation in all organs where the RET proto-oncogene is expressed.

• #40 Multiple endocrine neoplasia type 2 – Knowledge and References – Taylor & Francis

  https://taylorandfrancis.com/knowledge/Medicine_and_healthcare/Endocrinology/Multiple_endocrine_neoplasia_type_2/

  Multiple endocrine neoplasia type 2 (MEN2) is a genetic disorder caused by mutations in a proto-oncogene, specifically the RET gene, which plays a role in normal cellular growth and differentiation. […] Multiple endocrine neoplasia type 2 (MEN2) is due to mutations in the RET gene. […] The RET (REarranged during Transfection) proto-oncogene (OMIM: 164761) is mapped on chromosome 10q11.2, which contains 21 exons and encodes a tyrosine kinase receptor. RET is expressed in a variety of neural crest derived cells, branchial arches, and urogenital system. Germline mutations of RET leads to multiple endocrine neoplasia type 2 (MEN 2) in an autosomal dominant pattern. […] Multiple endocrine neoplasia type 2 (MEN 2) includes three subtypes: MEN 2A, familial medullary thyroid carcinoma (FMTC), and MEN 2B. All entities show medullary thyroid carcinoma (MTC) with typical onset in young adulthood, middle age, or early childhood, respectively. They are caused by heterozygous germline gain-of-function mutations in the RET proto-oncogene.

• #41 Multiple Endocrine Neoplasia in Childhood: An Update on Diagnosis, Screening, Management and Treatment

  https://www.mdpi.com/2673-396X/3/1/7

  Multiple endocrine neoplasia (MEN) is a group of heterogenous syndromes characterized by the occurrence of two or more endocrine gland tumors in a patient or related individuals in the same family. They are inherited in an autosomal dominant fashion and are highly penetrant. There are three types of MEN syndromes: MEN type 1 (MEN1), MEN type 2 (MEN2), and MEN type 4 (MEN4). MEN2 is further divided into MEN2A, MEN2B (formerly known MEN3), and familial medullary thyroid carcinoma (FMTC). […] MEN2 occurs due to mutations in the tyrosine kinase receptor encoded by the REarranged during Transfection (RET) proto-oncogene on 10q11.2. […] All types of MEN2 are due to a mutation in the RET gene. The estimated prevalence of MEN2—including MEN2A, MEN2B, FMTC, and other subtypes—is 1 in 30,000. […] In all variants of MEN2, the lifetime risk of developing MTC is nearly 100%. […] For this reason, guidelines recommend that all patients in whom MTC is identified receive routine genetic screening for RET mutations.

• #42 Multiple endocrine neoplasia type 2: An overview | Genetics in Medicine

  https://www.nature.com/articles/gim2011127

  With the identification and characterization of RET and genotype-associated phenotypes, it became obvious that all three subtypes are allelic and that MEN 2A and familial MTC (FMTC) are merely manifestations of different penetrances of RET mutations. […] MEN 2A makes up approximately 70-80% of cases of MEN 2. […] As genetic testing for RET mutations has become available, it has become apparent that 70-95% of individuals with MEN 2A develop MTC, approximately 50% develop pheochromocytoma, and approximately 15-30% develop HPT. […] The FMTC subtype comprises approximately 10-20% of cases of MEN 2. […] By operational definition, MTC is the only clinical manifestation of FMTC. […] The MEN 2B subtype comprises approximately 5% of cases of MEN 2. […] MEN 2B is characterized by the early development of an aggressive form of MTC in all affected individuals. […] Individuals with MEN 2B who do not undergo thyroidectomy at an early age (1 year) are likely to develop metastatic MTC at an early age. […] Approximately 50% of individuals with MEN 2B have a de novo germline mutation, and 50% have inherited the mutation from a parent.

• #43 Multiple Endocrine Neoplasias Type 2 – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/sites/books/NBK519054/

  The number of different mutations causes MEN2A. The majority of the mutations in MEN2A variants occur in the cysteine-rich region of RET protein’s extracellular domain (coded by the genes in exon10 and 11), while mutations in the intracellular TK2 domain cause MEN2B-associated tumors. A single 918 Met to Thr mutation (M918T) in exon 16 is responsible for over 95% of cases of MEN2B. Their are other less common mutations associated with both MEN2A and MEN2B divided into high-risk, moderate-risk and low-risk categories. Identification of these specific mutations is very important as it significantly impacts screening, diagnosis, and treatment, for example, the M918T mutation in exon 16 is considered a high-risk mutation for MEN2B cases and needs aggressive screening and prophylactic treatment to decrease morbidity and mortality.

• #44 Multiple Endocrine Neoplasia, Type 2A (MEN 2A) – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/multiple-endocrine-neoplasia-men-syndromes/multiple-endocrine-neoplasia-type-2a-men-2a

  Mutations in the RET proto-oncogene on chromosome 10 have been identified in MEN 2A, MEN 2B, and familial medullary thyroid carcinoma. […] The RET protein is a receptor tyrosine kinase; MEN 2A and familial medullary thyroid carcinoma mutations result in activation of certain intracellular pathways. […] Once genetic testing identifies a child as having a RET mutation, prophylactic thyroidectomy is recommended. Depending on the particular mutation, prophylactic thyroidectomy as early as the first months of life may be indicated. Medullary thyroid cancer can be cured or prevented by early thyroidectomy. […] There is a genotype-phenotype correlation for patients with RET mutations that may provide information about age of onset and clinical course of medullary thyroid cancer and this impact the timing of surgery for an affected child.

• #45

  https://omim.org/entry/171400

  A number sign (#) is used with this entry because multiple endocrine neoplasia type IIA (MEN2A) is caused by heterozygous mutation in the RET oncogene (164761) on chromosome 10q11. […] Multiple endocrine neoplasia type IIA is an autosomal dominant syndrome of multiple endocrine neoplasms, including medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid adenomas. […] The mutation for medullary thyroid carcinoma with parathyroid tumors (MTC with PTs) is closely linked to the centromeric region of chromosome 10. […] Each MEN2 index case probably has an activating germline RET mutation. […] RET testing has replaced calcitonin testing to diagnose the MEN2 carrier state. […] The specific RET codon mutation correlates with the MEN2 syndromic variant, the age of onset of MTC, and the aggressiveness of MTC; consequently, that mutation should guide major management decisions, such as whether and when to perform thyroidectomy.

• #46 Multiple Endocrine Neoplasia (MEN) Type 2 | American Thyroid Association

  https://www.thyroid.org/multiple-endocrine-neoplasia-men-type-2/

  MEN 2 (Multiple Endocrine Neoplasia Syndrome type 2) is due to a change (mutation) in a gene called RET. […] If you have changes in this gene, you [and your family members] are at a higher risk of getting MTC and other tumors. […] It is important for your doctor to know the exact change you have in the RET gene to know your risk for getting the diseases in MEN2. […] In MEN 2, PHEO is usually a benign tumor and not cancer.

• #47 Multiple Endocrine Neoplasias Type 2 – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/sites/books/NBK519054/

  The number of different mutations causes MEN2A. The majority of the mutations in MEN2A variants occur in the cysteine-rich region of RET protein’s extracellular domain (coded by the genes in exon10 and 11), while mutations in the intracellular TK2 domain cause MEN2B-associated tumors. A single 918 Met to Thr mutation (M918T) in exon 16 is responsible for over 95% of cases of MEN2B. Their are other less common mutations associated with both MEN2A and MEN2B divided into high-risk, moderate-risk and low-risk categories. Identification of these specific mutations is very important as it significantly impacts screening, diagnosis, and treatment, for example, the M918T mutation in exon 16 is considered a high-risk mutation for MEN2B cases and needs aggressive screening and prophylactic treatment to decrease morbidity and mortality.

• #48 Multiple Endocrine Neoplasia Type 2 – Endocrine Surgery | UCLA Health

  https://www.uclahealth.org/medical-services/surgery/endocrine-surgery/patient-resources/patient-education/endocrine-surgery-encyclopedia/multiple-endocrine-neoplasia-type-2

  Multiple Endocrine Neoplasia II (MEN II) is a hereditary disorder in which a type of thyroid cancer accompanied by recurring cancer of the adrenal glands. […] The cause of MEN II is genetic — a mutation in a gene called RET. […] The main risk factor is a family history of MEN II. […] Diagnosis depends on identification of mutation of the RET gene. […] Family members should be screened for the RET gene mutation.

• #49 Multiple endocrine neoplasia 2 (MEN2) | Macmillan Cancer Support

  https://www.macmillan.org.uk/cancer-information-and-support/worried-about-cancer/pre-cancerous-and-genetic-conditions/multiple-endocrine-neoplasia-2-men2

  MEN2 is a rare, inherited condition that can run in families. It causes tumours in endocrine (hormone-making) glands. These can be cancerous (malignant) or non-cancerous (benign). […] People with MEN2 have a RET gene variant. If you have this variant, you are more likely to develop certain types of tumour. […] MEN2 causes tumours that usually affect endocrine glands. Endocrine glands produce hormones. […] Tumours caused by MEN2 can be cancerous (malignant) or non-cancerous (benign). Malignant tumours can spread to other parts of the body. […] MEN2A and MEN2B both cause a higher risk of a specific type of thyroid cancer called medullary thyroid carcinoma (MTC). […] A small number of people are the first in their family to have the RET gene variant. This means your parents did not have it. […] If you have MEN, there is a 1 in 2 (50%) chance that your child could inherit it from you.

• #50 Multiple Endocrine Neoplasia in Childhood: An Update on Diagnosis, Screening, Management and Treatment

  https://www.mdpi.com/2673-396X/3/1/7

  Multiple endocrine neoplasia (MEN) is a group of heterogenous syndromes characterized by the occurrence of two or more endocrine gland tumors in a patient or related individuals in the same family. They are inherited in an autosomal dominant fashion and are highly penetrant. There are three types of MEN syndromes: MEN type 1 (MEN1), MEN type 2 (MEN2), and MEN type 4 (MEN4). MEN2 is further divided into MEN2A, MEN2B (formerly known MEN3), and familial medullary thyroid carcinoma (FMTC). […] MEN2 occurs due to mutations in the tyrosine kinase receptor encoded by the REarranged during Transfection (RET) proto-oncogene on 10q11.2. […] All types of MEN2 are due to a mutation in the RET gene. The estimated prevalence of MEN2—including MEN2A, MEN2B, FMTC, and other subtypes—is 1 in 30,000. […] In all variants of MEN2, the lifetime risk of developing MTC is nearly 100%. […] For this reason, guidelines recommend that all patients in whom MTC is identified receive routine genetic screening for RET mutations.

• #51 Multiple endocrine neoplasia type 2B | Endocrine Conditions

  https://www.yourhormones.info/endocrine-conditions/multiple-endocrine-neoplasia-type-2b/

  Multiple endocrine neoplasia type 2B (MEN2B) is a rare inherited disease causing the development of tumours in the thyroid, adrenal and parathyroid glands, and mucosal tumours. […] MEN2B is caused by a defect in the RET gene, found on chromosome 10. Knowing the exact abnormality in the RET gene can help predict the types of tumours/cancers a patient is at risk of developing. […] MEN2B is an inherited conditions due to an abnormality or spelling mistake in the RET gene, which can be passed on from parent to child. It is inherited in an 'autosomal dominant’ way. This means it is not a sex-linked condition and that there is a 50% (1 in 2) chance that a child will inherit the abnormal gene, and therefore, MEN2B. […] Other members of the families of patients with MEN2B should be offered genetic tests to see if they also carry the defect in the RET gene.

• #52 Multiple endocrine neoplasia type 2A | Endocrine Conditions

  https://www.yourhormones.info/endocrine-conditions/multiple-endocrine-neoplasia-type-2a/

  Multiple endocrine neoplasia type 2 (MEN2) is a rare inherited disorder in which medullary thyroid cancer, phaeochromocytoma and overactive parathyroid glands develop. […] MEN2A is caused by an abnormality in the RET gene, found on chromosome 10. Knowing the exact abnormality in the RET gene can help predict the types of tumours/cancers a patient is at risk of developing. […] MEN2A is an inherited condition due to an abnormality or spelling mistake (mutation) in the RET gene, which can be passed on from parent to child. It is inherited in an 'autosomal dominant’ way. […] Other members of the families of patients with MEN2A should be offered genetic tests to see if they also carry the abnormality in the RET gene.

• #53

  https://omim.org/entry/171400

  A number sign (#) is used with this entry because multiple endocrine neoplasia type IIA (MEN2A) is caused by heterozygous mutation in the RET oncogene (164761) on chromosome 10q11. […] Multiple endocrine neoplasia type IIA is an autosomal dominant syndrome of multiple endocrine neoplasms, including medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid adenomas. […] The mutation for medullary thyroid carcinoma with parathyroid tumors (MTC with PTs) is closely linked to the centromeric region of chromosome 10. […] Each MEN2 index case probably has an activating germline RET mutation. […] RET testing has replaced calcitonin testing to diagnose the MEN2 carrier state. […] The specific RET codon mutation correlates with the MEN2 syndromic variant, the age of onset of MTC, and the aggressiveness of MTC; consequently, that mutation should guide major management decisions, such as whether and when to perform thyroidectomy.

• #54 Multiple Endocrine Neoplasia, Type 2A (MEN 2A) – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/multiple-endocrine-neoplasia-men-syndromes/multiple-endocrine-neoplasia-type-2a-men-2a

  Mutations in the RET proto-oncogene on chromosome 10 have been identified in MEN 2A, MEN 2B, and familial medullary thyroid carcinoma. […] The RET protein is a receptor tyrosine kinase; MEN 2A and familial medullary thyroid carcinoma mutations result in activation of certain intracellular pathways. […] Once genetic testing identifies a child as having a RET mutation, prophylactic thyroidectomy is recommended. Depending on the particular mutation, prophylactic thyroidectomy as early as the first months of life may be indicated. Medullary thyroid cancer can be cured or prevented by early thyroidectomy. […] There is a genotype-phenotype correlation for patients with RET mutations that may provide information about age of onset and clinical course of medullary thyroid cancer and this impact the timing of surgery for an affected child.

• #55 Comprehensive Guide on Multiple Endocrine Neoplasia Type 2: Causes, Symptoms, and Treatment – The Kingsley Clinic

  https://thekingsleyclinic.com/thyroid-and-parathyroid/comprehensive-guide-on-multiple-endocrine-neoplasia-type-2-causes-symptoms-and-treatment/

  Vandetanib and Cabozantinib are medications used to slow the growth of medullary thyroid cancer cells. These medications are typically used when surgery isn’t an option or in more advanced cases. […] Thyroidectomy, the surgical removal of the thyroid gland, is a common procedure in MEN2 to prevent or treat thyroid cancer. This surgery is often performed early after diagnosis, and can prevent or cure medullary thyroid carcinoma.

• #56 Multiple endocrine neoplasia – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/multiple-endocrine-neoplasia/

  Multiple endocrine neoplasia (MEN) is a term used to describe three autosomal dominant syndromes that are associated with certain hormone-producing neoplasias. […] MEN 2A and MEN 2B are caused by a mutated RET proto-oncogene and both present with medullary thyroid carcinoma and sometimes pheochromocytoma. […] Those positive for mutated genes should be closely monitored and should undergo a total thyroidectomy if positive for the RET proto-oncogene.

• #57 Comprehensive Guide on Multiple Endocrine Neoplasia Type 2: Causes, Symptoms, and Treatment – The Kingsley Clinic

  https://thekingsleyclinic.com/thyroid-and-parathyroid/comprehensive-guide-on-multiple-endocrine-neoplasia-type-2-causes-symptoms-and-treatment/

  Vandetanib and Cabozantinib are medications used to slow the growth of medullary thyroid cancer cells. These medications are typically used when surgery isn’t an option or in more advanced cases. […] Thyroidectomy, the surgical removal of the thyroid gland, is a common procedure in MEN2 to prevent or treat thyroid cancer. This surgery is often performed early after diagnosis, and can prevent or cure medullary thyroid carcinoma.

• #58 Multiple Endocrine Neoplasia, Type 2A (MEN 2A) – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/multiple-endocrine-neoplasia-men-syndromes/multiple-endocrine-neoplasia-type-2a-men-2a

  Mutations in the RET proto-oncogene on chromosome 10 have been identified in MEN 2A, MEN 2B, and familial medullary thyroid carcinoma. […] The RET protein is a receptor tyrosine kinase; MEN 2A and familial medullary thyroid carcinoma mutations result in activation of certain intracellular pathways. […] Once genetic testing identifies a child as having a RET mutation, prophylactic thyroidectomy is recommended. Depending on the particular mutation, prophylactic thyroidectomy as early as the first months of life may be indicated. Medullary thyroid cancer can be cured or prevented by early thyroidectomy. […] There is a genotype-phenotype correlation for patients with RET mutations that may provide information about age of onset and clinical course of medullary thyroid cancer and this impact the timing of surgery for an affected child.

• #59 Multiple Endocrine Neoplasia, Type 2A (MEN 2A) – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/multiple-endocrine-neoplasia-men-syndromes/multiple-endocrine-neoplasia-type-2a-men-2a

  Mutations in the RET proto-oncogene on chromosome 10 have been identified in MEN 2A, MEN 2B, and familial medullary thyroid carcinoma. […] The RET protein is a receptor tyrosine kinase; MEN 2A and familial medullary thyroid carcinoma mutations result in activation of certain intracellular pathways. […] Once genetic testing identifies a child as having a RET mutation, prophylactic thyroidectomy is recommended. Depending on the particular mutation, prophylactic thyroidectomy as early as the first months of life may be indicated. Medullary thyroid cancer can be cured or prevented by early thyroidectomy. […] There is a genotype-phenotype correlation for patients with RET mutations that may provide information about age of onset and clinical course of medullary thyroid cancer and this impact the timing of surgery for an affected child.

• #60 Multiple Endocrine Neoplasias Type 2 – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK519054/

  Multiple endocrine neoplasia type 2 (MEN 2) is a hereditary cancer syndrome associated primarily with tumors of the adrenal gland, thyroid and parathyroid. […] Identify the germline RET mutations in the etiology of multiple endocrine neoplasia type 2. […] The rearranged during transfection (RET) protein is a receptor tyrosine kinase that is localized to chromosome 10q11.2. It appears to transduce growth and differentiate signals in several tissues, particularly those arising from neural crest cells. Some cytogenetic mutations have been reported; these may involve intracellular and extracellular domains of the RET protein signaling pathway. The germline RET mutations in MEN2 result in a gain of function of this tyrosine kinase receptor. This is different from many other inherited predispositions to neoplasia that are due to heritable „loss-of-function” mutations that inactivate tumor suppressor proteins.

• #61 Multiple Endocrine Neoplasias Type 2 – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/sites/books/NBK519054/

  Multiple endocrine neoplasia type 2 (MEN 2) is a hereditary cancer syndrome associated primarily with tumors of the adrenal gland, thyroid and parathyroid. […] Identify the germline RET mutations in the etiology of multiple endocrine neoplasia type 2. […] The rearranged during transfection (RET) protein is a receptor tyrosine kinase that is localized to chromosome 10q11.2. It appears to transduce growth and differentiate signals in several tissues, particularly those arising from neural crest cells. Some cytogenetic mutations have been reported; these may involve intracellular and extracellular domains of the RET protein signaling pathway. The germline RET mutations in MEN2 result in a gain of function of this tyrosine kinase receptor. This is different from many other inherited predispositions to neoplasia that are due to heritable „loss-of-function” mutations that inactivate tumor suppressor proteins.

• #62 Multiple endocrine neoplasia, type 2 (MEN 2) | UM Health-Sparrow

  https://www.uofmhealthsparrow.org/departments-conditions/conditions/multiple-endocrine-neoplasia-type-2-men-2

  Multiple endocrine neoplasia, type 2 is an inherited disorder. This means people who have the changed gene can pass it on to their children. Each child has a 50% chance of getting the disorder. […] MEN 2 is an inherited condition. This means someone who has a changed gene that can cause MEN 2 can pass that gene on to their children. […] Many people also may be the first person in their families to have this disorder.

• #63 Multiple Endocrine Neoplasia Type 2 | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/multiple-endocrine-neoplasia-type-2

  MEN2 is caused by a mutation in the RET gene located on chromosome 10. These mutations can be hereditary or can occur as a new mutation in one of the fathers sperm, mothers eggs or in a cell of the developing fetus. About 95 percent of individuals with MEN2A inherited the condition from their parents, whereas 50 percent of people with MEN2B are the first in their families to be diagnosed with the disease. […] In individuals with either form of MEN2, the RET gene is altered so the protein that is produced is always switched on. With the RET protein (receptor) always active, cells continuously grow (multiply), leading to cancer development and over-production of certain proteins and hormones. […] People with MEN2 carry one normal copy of the RET gene and one abnormal RET gene in all cells throughout their body. These individuals have a 50 percent chance of passing the same genetic alteration onto each of their future children. A disease that is associated with a 50 percent chance of being passed between generations is described as an autosomal dominant condition. Most children who inherit the altered RET gene are born and develop normally, but are at increased risk of developing benign or malignant endocrine tumors during their lifetime.

• #64 Multiple endocrine neoplasia type 2: An overview | Genetics in Medicine

  https://www.nature.com/articles/gim2011127

  With the identification and characterization of RET and genotype-associated phenotypes, it became obvious that all three subtypes are allelic and that MEN 2A and familial MTC (FMTC) are merely manifestations of different penetrances of RET mutations. […] MEN 2A makes up approximately 70-80% of cases of MEN 2. […] As genetic testing for RET mutations has become available, it has become apparent that 70-95% of individuals with MEN 2A develop MTC, approximately 50% develop pheochromocytoma, and approximately 15-30% develop HPT. […] The FMTC subtype comprises approximately 10-20% of cases of MEN 2. […] By operational definition, MTC is the only clinical manifestation of FMTC. […] The MEN 2B subtype comprises approximately 5% of cases of MEN 2. […] MEN 2B is characterized by the early development of an aggressive form of MTC in all affected individuals. […] Individuals with MEN 2B who do not undergo thyroidectomy at an early age (1 year) are likely to develop metastatic MTC at an early age. […] Approximately 50% of individuals with MEN 2B have a de novo germline mutation, and 50% have inherited the mutation from a parent.

• #65

  https://omim.org/entry/171400

  A number sign (#) is used with this entry because multiple endocrine neoplasia type IIA (MEN2A) is caused by heterozygous mutation in the RET oncogene (164761) on chromosome 10q11. […] Multiple endocrine neoplasia type IIA is an autosomal dominant syndrome of multiple endocrine neoplasms, including medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid adenomas. […] The mutation for medullary thyroid carcinoma with parathyroid tumors (MTC with PTs) is closely linked to the centromeric region of chromosome 10. […] Each MEN2 index case probably has an activating germline RET mutation. […] RET testing has replaced calcitonin testing to diagnose the MEN2 carrier state. […] The specific RET codon mutation correlates with the MEN2 syndromic variant, the age of onset of MTC, and the aggressiveness of MTC; consequently, that mutation should guide major management decisions, such as whether and when to perform thyroidectomy.

• #66 Multiple Endocrine Neoplasia, Type 2A (MEN 2A) – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/multiple-endocrine-neoplasia-men-syndromes/multiple-endocrine-neoplasia-type-2a-men-2a

  Mutations in the RET proto-oncogene on chromosome 10 have been identified in MEN 2A, MEN 2B, and familial medullary thyroid carcinoma. […] The RET protein is a receptor tyrosine kinase; MEN 2A and familial medullary thyroid carcinoma mutations result in activation of certain intracellular pathways. […] Once genetic testing identifies a child as having a RET mutation, prophylactic thyroidectomy is recommended. Depending on the particular mutation, prophylactic thyroidectomy as early as the first months of life may be indicated. Medullary thyroid cancer can be cured or prevented by early thyroidectomy. […] There is a genotype-phenotype correlation for patients with RET mutations that may provide information about age of onset and clinical course of medullary thyroid cancer and this impact the timing of surgery for an affected child.

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