Background
The MEN1 gene was identified on chromosome 11 in 1997 (Lemmens 1997). Mutations in the MEN1 gene cause MEN1 syndrome, an endocrinopathy syndrome which is primarily characterized by primary hyperparathyroidism (PHPT), pancreatic neuroendocrine tumors (PNET) or pancreatic islet tumors, and pituitary adenomas (Brandi 2001). Other endocrine tumors in MEN1 syndrome include adrenocortical tumors (Skogseid 1992), pheochromocytoma (Brandi 2001), and thyroid tumors (Marx 1998).
Non-endocrine tumors in MEN1 syndrome include collagenomas, facial angiofibromas, thymic carcinoids, lipomas, leiomyomas, and central nervous system tumors, namely meningiomas and ependymomas (Darling 1997; Teh 1998; Asgharian 2004; Kato 1996; McKeeby 2001; Ikota 2004.
Penetrance classes were taken from literature on families that have been comprehensively phenotyped and ascertained based on strong family history. Because of this the penetrance may be higher than observed in clinically ascertined families. This could lead to falsely low cosegregation likelihood ratio results.
Affected Phenotypes Included in Penetrance Model
Primary hyperparathyroidism (PHPT)
Pituitary adenoma
Pancreatic neuroendocrine tumor (PNET)
Adrenocortical carcinoma
Note: Neoplasms and other tumors not listed above, such as lipomas and paragangliomas, are not counted in this model.
Coding the Pedigree
Code affected individuals in column 5 of the Excel or plain text file used to build your pedigree.
- Code "2" (affected) for individuals with primary hyperparathyroidism, pituitary adenoma, pancreatic neuroendocrine tumor, or adrenocortical carcinoma.
- Code "1" (unaffected) for individuals who have not had any of the clinical features listed above.
- Code "0" for individuals with uncertain or unknown affected status.
More information on formatting pedigrees can be found here.
Penetrance classes for MEN1
Penetrance is gender-specific.
| Female | Male | |||
|---|---|---|---|---|
| Age Range | Homozygous Normal | Heterozygous | Homozygous Normal | Heterozygous |
| [0,20) | 0.00054 | 0.06851 | 0.00049 | 0.06851 |
| [20,30) | 0.00197 | 0.30529 | 0.002247 | 0.30529 |
| [30,40) | 0.00388 | 0.71125 | 0.00501 | 0.71125 |
| [40,50) | 0.0069 | 0.90842 | 0.00802 | 0.90842 |
| [50,60) | 0.01564 | 0.96661 | 0.01276 | 0.96661 |
| [60,70) | 0.02971 | 0.99672 | 0.02031 | 0.99672 |
| [70,∞) | 0.10412 | 0.99891 | 0.03135 | 0.99891 |
References
- Lemmens I, et al. Identification of the multiple endocrine neoplasia type 1 (MEN1) gene. The European Consortium on MEN1. Hum Mol Genet. 1997, 6:1177. PMID: 9215690
- Brandi ML, et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab. 2001, 86:5658. PMID: 11739416
- Skogseid B, et al. Clinical and genetic features of adrenocortical lesions in multiple endocrine neoplasia type 1. J Clin Endocrinol Metab. 1992, 75:76. PMID: 1352309
- Marx S, et al. Multiple endocrine neoplasia 1: clinical and genetic topics. Ann Intern Med. 1998, 129:484. PMID: 9735087
- Darling TN, et al. Multiple facial angiofibromas and collagenomas in patients with multiple endocrine neoplasia type 1. Arch Dermatol. 1997, 133:853. PMID: 9236523
- Teh BT. Thymic carcinoids in multiple endocrine neoplasia type 1. J Intern Med. 1998, 243:501. PMID: 9681849
- Asgharian B, et al. Meningiomas may be a component tumor of multiple endocrine neoplasia type 1. Clin Cancer Res. 2004, 10:869. PMID: 14871962
- Kato H, et al. Multiple endocrine neoplasia type 1 associated with spinal ependymoma. Intern Med. 1996, 35:285. PMID: 8739783
- McKeeby JL, et al. Multiple leiomyomas of the esophagus, lung, and uterus in multiple endocrine neoplasia type 1. Am J Pathol. 2001, 159:1121. PMID: 11549605
- Ikota H, et al. Ureteral leiomyoma causing hydronephrosis in Type 1 multiple endocrine neoplasia. Pathol Int. 2004, 54:457–9. PMID: 15144407
