Multiple Endocrine Neoplasia Type1 (MEN1)
Multiple Endocrine Neoplasia Type 1(MEN1) is an inherited cancer syndrome characterized by the occurrence of endocrine and non-endocrine tumors mainly involving the parathyroid gland, anterior pituitary gland, and the pancreas.
PrintMultiple Endocrine Neoplasia Type 1(MEN1) is an inherited cancer syndrome characterized by the occurrence of endocrine and non-endocrine tumors mainly involving the parathyroid gland, anterior pituitary gland, and the pancreas.
Germline mutations in the MEN1 gene cause a predisposition to develop tumors associated with this condition. Mutations in MEN1 are detected in approximately 80-90% of affected individuals.
Multiple endocrine neoplasia type 1 (MEN1), also known as Wermer syndrome, is an inherited cancer syndrome characterized by the occurrence of endocrine and non-endocrine tumors mainly involving the parathyroid, anterior pituitary and the pancreas. The most common endocrine tumors include, parathyroid adenomas, prolactinomas, and gastrinomas.1 Non-endocrine features include facial angiofibromas, collagenomas, and lipomas.1-3 Generally, primary hyperparathyroidism is the first clinical manifestation in up to 100% of patients by the age of 40, with a typical age of onset between 20-25 years old.4,5 Twenty percent of individuals diagnosed with familial isolated hyperparathyroidism have mutations in the MEN1 gene.
MEN1 is inherited in an autosomal dominant manner and is caused by germline mutations in the tumor suppressor gene MEN1. Germline mutations in this gene cause a predisposition to develop tumors associated with this condition. The incidence of MEN1 is estimated to be 1/30,000, affecting all ethnic backgrounds worldwide.
Gene sequence and gross deletion/duplication analyses are available. Mutations in MEN1 are detected in approximately 80-90% of affected individuals. To date, partial and whole-gene deletions/duplications have accounted for up to 4-6% of pathogenic mutations identified in large MEN1 cohorts and over 5% of all MEN1 mutations listed in The Human Gene Mutation Database (HGMD).6-8
Genetic testing enables identification of individuals who are at increased risk of cancer associated with MEN1 mutations. It is useful in the confirmation of diagnosis in symptomatic individuals. Although approximately one-third of MEN1 patients will die from an MEN1-related cancer, treatment options are available for disease management, including surgical removal of endocrine tumors, various drug treatments and radiation therapy.9,10 Specific mutation analysis for individual MEN1 mutations is available for relatives of patients with known mutations in MEN1.
MEN1 analysis includes gene sequence analysis performed by PCR-based double-stranded automated sequencing in the sense and antisense directions for exons 2-10 of the MEN1 gene, plus at least 20 bases into the 5’ and 3’ ends of all the introns and deletion/duplication analysis performed by multiplex ligation-dependent probe amplification (MLPA). Specific mutation analysis for individual MEN1 mutations known to be in the family is also available.
Mutations in the MEN1 gene account for approximately 80-90% of individuals affected with MEN.1 The analytic sensitivity of full gene sequencing combined with deletion/duplication analyses exceeds 99% of described mutations in MEN1.
Blood: Collect 3-5 cc from adult or 2 cc minimum from child into EDTA purple-top tube (preferred) or ACD yellow-top tube. Store at room temperature or refrigerate. Ship at room temperature.
Blood Spot: Call for availability.
Saliva: Collect 2 ml into Oragene™ DNA Self-Collection container. Store and ship at room temperature.
DNA: Minimum DNA Amount of 5μg of DNA at a concentration of ~100ng/μl in 50μl TE (10mM Tris-Cl pH 8.0, 1mM EDTA); preferred 20μg. Store frozen and ship on ice or dry ice.
Prenatal: Prenatal testing is available. Please call to discuss your case with an Ambry Genetic Counselor.
| Test Code | Technique |
|---|---|
| 2646 | MEN Type 1 (MEN1 Gene Sequence and Deletion/Duplication Analysis) |
| 2644 | MEN Type 1 (MEN1 Deletion/Duplication Analysis) |
| 2640 | MEN Type 1 (MEN1 Gene Sequence Analysis) |
| Technique | Days |
|---|---|
| MEN Type 1 (MEN1 Gene Sequence and Deletion/Duplication Analysis) | 7-21 |
| MEN Type 1 (Deletion/Duplication Analysis) | 7-14 |
| MEN Type 1 (MEN1 Gene Sequence Analysis) | 7-21 |
1. Brandi ML et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab. 2001; 86: 5658-5671. [PMID: 11739416]
2. Asgharian et al. Cutaneous tumors in patients with multiple endocrine neoplasm type 1 (MEN1) and gastrinomas: prospective study of frequency and development of criteria with high sensitivity and specificity for MEN1. J Clin Endocrinol Metab. 2004; 89 (11): 5328-5336. [PMID: 15531478]
3. Darling et al. Multiple facial angiofibromas and collagenomas in patients with multiple endocrine neoplasia type 1. J Arch Dermatol. 1997; 133: 853-857. [PMID: 9236523]
4. Burgess et al. Osteoporosis in multiple endocrine neoplasia type 1: severity, clinical significance, relationship to primary hyperparathyroidism, and response to parathyroidectomy. Arch Surg.1999; 134: 1119-1123. [PMID: 10522858]
5. Tichomirowa et al. Familial pituitary adenomas. J Intern Med. 2009; 266: 5-18. [PMID: 19522822]
6. Cebrian A et al. Mutational and gross deletion study of the MEN1 gene and correlation with clinical features in Spanish patients. J Med Genet. 2003;40(5):e72. [PMID: 12746426]
7. Tham E et al. Clinical testing for mutations in the MEN1 gene in Sweden: a report on 200 unrelated cases. J Clin Endocrinol Metab. 2007;92(9):3389-95. [PMID: 17623761]
8. Stenson et al. Human Gene Mutation Database (HGMD): 2003 update. Hum Mutat. 2003;21:577-581). [PMID: 12754702]
9. Agarwal et al. The MEN1 gene and pituitary tumours. J Horm Res. 2009; 71: 131-138. [PMID: 19407509]
10. Gagel et al. Williams Textbook of Endocrinology. 2007:1705-1746.