Multiple Endocrine Neoplasia Type 1

Multiple endocrine neoplasia type 1 (MEN1) is a hereditary syndrome caused by pathogenic variants in the MEN1 gene and is associated with a combination of endocrine and nonendocrine tumors. In MEN1, tumors are most often found in the parathyroid gland, islet cells of the pancreas, and pituitary gland. Tumors can also form in other endocrine glands and the digestive tract. The majority of MEN1 tumors are benign but tumors of the gastroenteropancreatic tract and thymic carcinoids may be malignant. Endocrine tumors cause an increased hormone production based on tumor type, resulting in a wide range of symptoms.

Disease Overview

Incidence

1/30,000  

Symptoms

• MEN1 can include development of multiple endocrine and nonendocrine tumors 
• Common endocrine tumors:
  • Parathyroid
  • Gastroenteropancreatic tract (gastrinoma, insulinoma, glucagonoma, pancreatic islet cell tumor)
  • Pituitary (prolactinoma)
  • Gastrinoma
  • Carcinoid (thymic, bronchial, gastric)
  • Adrenal
  • Medullary carcinoma of the thyroid
• Nonendocrine tumors:
  • Facial angiofibromas
  • Collagenomas
  • Lipomas
  • Meningiomas
  • Ependymomas
  • Leiomyomas

Genetics

Gene

MEN1

Inheritance

Autosomal dominant

Penetrance

Variable   

• ~50% by 20 years
• >95% by 40 years

De novo variants: ~10%

Variants

Inactivating variants of MEN1 tumor suppressor gene

Test Interpretation

Clinical Sensitivity

Combined testing: ~94%

• Sequencing: 90% 
• Deletion/duplication: 4% 

Results

• Positive:
  • One pathogenic variant detected in MEN1
  • Confirms diagnosis and etiology of MEN1
• Negative:
  • No detectable pathogenic variant detected in MEN1
  • Reduces, but does not exclude, a diagnosis of MEN1
• Uncertain: variants of unknown clinical significance may be detected

Limitations

• Not evaluated:
  • Regulatory region or deep intronic variants
  • Breakpoints of large deletions/duplications
  • Variants in genes other than MEN1
• Diagnostic errors can occur due to rare sequence variations