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Multiple Endocrine Neoplasia Type 1, MEN 1 - MEN1

Clinical Features

The characteristical feature of multiple endocrine neoplasia type 1 (MEN1) syndrome is the occurance of a variable combination of more than 20 endocrine and non-endocrine tumors. The group of endocrine tumors, which became evident by the overproduction of hormons include parathyroide tumors (almost all patients show a primary hyperparathyreoidism by age of 50 years), pituitary tumors, well-differentiated endocrine tumors of the gastro-entero-pancreatic tract, neuro-endocrine tumors and adrenocortical tumors. The group of non-endocrine tumors include facial angiofibromas, collagenomas, lipomas, meningiomas, ependymonas, and leiomyomas. The parathyroid tumors manifest as hypercalcemia by age 50 years and may cause lethargy, depression, anorexia, constipation, vomiting, diuresis, dehydration, hypertension and a shortened QT interval.

Genetic Information

The MEN1-syndrome follows an autosomal dominant pattern of inheritance. In up to 90% of all patients with a clinically well defined MEN1-syndrome germline mutations in the MEN1-gene (chromosom 11, 11q13) can be detected (90% of the mutations are inherited by one affected parent, 10% of mutations arise de novo). The penetrance to develop a parathyroide tumor by the age of 50 years is almost 100%. Menin, the gene product of the MEN1-gene is a tumorsuppressor protein of 615 aminoacid length, it functions as a transcriptional repressor.

Prevalence

A prevalence of about one in 30.000 has been reported

 

Diagnostic

 

Indication

The MEN1 can is characterized by various endocrine and not endocrine tumors.  MEN1 can be expected when two of the following three endocrine tumors occurred in a patient:

Endocrine tumors associated with MEN1:

  •  Parathyroid glands: primary hyperparathyroidism (PHPT) with hypercalzaemia resulting from an overproduction of parathyroid hormone.
  • Pituitary tumor: prolactinoma, which may manifest as oligomenorrhea / amenorrhea in women. In men, a gynecomastia occurs in rare cases.
  • Differentiated endocrine tumors of the gastrointestinal tract: These tumors can manifest as (in descending order of frequency):

· Zollinger-Ellison syndrome (ZES) caused by a gastrin-secreting tumor (gastrinoma)
· hypoglycemia due to an insulin-secreting pancreatic tumor
· hyperglycaemia, anorexia, glossitis and anemia due to a glucagon-secreting pancreatic tumor
· WDHA syndrome (Watery Diarrhea Hypokalemia and Achlorhydria)

Non-endocrine tumors are associated with MEN1 include:

  •  Skin: Up to 88% of MEN1 patients have multiple angiofibromas of the face and 72% of patients develop collagenoma. Café-au-lait spots are observed in 38% of MEN1 patients, lipoma in 34%.
  • CNS: meningiomas and ependymomas are rarely observed
  • Leiomyoma: rare
Method

All exons and their flanking regions are analyzed by DNA sequencing.
To detect deletions / duplications of one or several exons of the MEN1 gene, a MLPA analysis is performed.

Sample Requirement

2 - 4 ml of EDTA-blood

Duration

approx. 3 weeks

OMIM

131100 MEN1



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