Multiple Endocrine Neoplasia 2A

The clinical diagnosis of MEN2A is made when an individual has two or more specific endocrine tumors: medullary carcinoma of the thyroid (>95%), pheochromocytoma (50%), or parathyroid adenoma/hyperplasia (20-30%). Prophylactic thyroidectomy in childhood is recommended when a RET mutation is identified. FMTC (Familial Medullary Thyroid Carcinoma) is diagnosed in families with four cases of medullary thyroid carcinoma (MTC) in the absence of pheochromocytoma or parathyroid adenoma. The medullary thyroid cancer associated with FMTC is typically later onset and may be subclinical; therefore, in some families RET genetic testing may be necessary to differentiate sporadic medullary thyroid cancer from FMTC. RET gene mutations also are associated with two other distinct disorders, MEN2B and Hirschsprung disease (see separate information sheets for GeneDx testing information), and in approximately 10% of isolated pheochromocytoma. Predisposition to pheochromocytoma is shared by other cancer predisposition syndromes, including Von Hippel Lindau syndrome (VHL gene), Hereditary PGL/PCC syndrome (SDHD, SDHB, SDHC genes), NF1 (NF1 gene) and rarely Carney Complex (PRKAR1A gene). Testing for all of these syndromes, with the exception of NF1, is available at GeneDx.

Tests Available

Forms and Documents

Test Details

RET
  • Confirmation of a clinical diagnosis
  • Determination of appropriate screening and surgical management
  • Identification of at-risk family members
  • Prenatal diagnosis
  • Capillary Sequencing

Ordering

177
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL) | Buccal Swabs

Billing

81405x1
Yes
Yes
  • 227 Benign neoplasm of other endocrine glands and related structures Use additional code to identify any functional activity Excludes: ovary (220) pancreas (211.6) testis (222.0)
  • 193 Malignant neoplasm of thyroid gland, Thyroglossal duct
* For price inquiries please email zebras@genedx.com

References

  1. Mulligan, L.M. et al., Specific mutations of the RET proto-oncogene are related to disease phenotype in MEN 2A and FMTC. Nat Genet. 6: 70-4, 1994
  2. Mulligan, L.M. et al., Genotype-phenotype correlation in multiple endocrine neoplasia type 2: report of the International RET Mutation Consortium. J Intern Med. 238: 343-6, 1995
  3. Elisei, R et al., RET genetic screening in patients with medullary thyroid cancer and their relatives: Experience with 807 individuals at one center. J Clin Endocrinol Metab 92(12)4725-4729, 2007
  4. Heshmati HM, et al. Genetic testing in medullary thyroid carcinoma syndromes: mutation types and clinical significance. Mayo Clin Proc 72(5):430-436, 1997
  5. Wiench M et al. Estimation of risk of inherited medullary thyroid carcinoma in apparent sporadic patients. J Clin Oncol 19(5):1374-1380, 2001
  6. Shirahama S et al. Mutational analysis of the RET proto-oncogene in 71 Japanese patients with medullary thyroid carcinoma. J Hum Genet 43:101-106, 1998
  7. Yip, L. et al., Multiple Endocrine Neoplasia Type 2: Evaluation of the Genotype-Phenotype Relationship. Arch Surg. 138: 409-16, 2003

Forms and Documents

Test Details

RET
  • An individual with a personal history and family history of tumors and features associated with Multiple Endocrine Neoplasia type 2 (MEN2) such as medullary thyroid cancer, hyperparathyroidism, pheochromocytoma, Hirschsprung disease and cutaneous lichen amyloidosis
  • An individual with a personal and/ or family history of a medullary thyroid cancer
  • An individual with a personal history suggestive of MEN2B which may include features such as marfanoid habitus, mucosal neuromas of the lips and tongue and ganglioneuromas of the intestine
  • An individual with apparent non-syndromic Hirschsprung disease
  • An unaffected individual with a family history suggestive of MEN2 (see above) when an affected individual is unavailable for his or her own genetic testing
  • Capillary Sequencing

Ordering

1771
3 weeks
2-5 mL Blood - Lavender Top Tube
Buccal Swab | Fibroblasts (separate charge for cell culture may apply) | Oral Rinse

Billing

81406x1
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Mulligan, L.M. et al., Genotype-phenotype correlation in multiple endocrine neoplasia type 2: report of the International RET Mutation Consortium. J Intern Med. 238: 343-6, 1995.
  2. Elisei, R et al., RET genetic screening in patients with medullary thyroid cancer and their relatives: Experience with 807 individuals at one center. J Clin Endocrinol Metab 92(12)4725-4729, 2007.
  3. Heshmati HM, et al. Genetic testing in medullary thyroid carcinoma syndromes: mutation types and clinical significance. Mayo Clin Proc 72(5):430-436, 1997.
  4. Wiench M et al. Estimation of risk of inherited medullary thyroid carcinoma in apparent sporadic patients. J Clin Oncol 19(5):1374-1380, 2001.
  5. Shirahama S et al. Mutational analysis of the RET proto-oncogene in 71 Japanese patients with medullary thyroid carcinoma. J Hum Genet 43:101-106, 1998.
  6. Mulligan, L.M. et al., Specific mutations of the RET proto-oncogene are related to disease phenotype in MEN 2A and FMTC. Nat Genet. 6: 70-4, 1994.
  7. Eng, C. et al., Point mutation within the tyrosine kinase domain of the RET-proto-oncogene in multiple endocrine neoplasia type 2B and related sporadic tumors. Hum Mol Genet. 3: 237-41, 1994.
  8. Gimm, O. et al., Germline dinucleotide mutation in codon 883 of the RET proto-oncogene in multiple endocrine neoplasia type 2B without codon 918 mutation. J Clin Endocrinol Metab. 82: 3902-4, 1997.
  9. Yip, L. et al., Multiple Endocrine Neoplasia Type 2: Evaluation of the Genotype-Phenotype Relationship. Arch Surg. 138: 409-16, 2003.