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Multiple endocrine neoplasia type 1 (MEN1)

Identity

Other namesWermer's syndrome
Note Multiple Endocrine Neoplasia type 1 or Wermer's syndrome (MEN1) is a complex disease predisposing to a variety of endocrine tumors multifocal and/or bilateral localization and uncommonly to non-endocrine tumors mainly of the skin and central nervous system
Inheritance an autosomal dominant disorder with high penetrance (increasing with age: 90% by age 50 yrs) but variable expressivity (with phenotype/genotype correlations); frequency is unkown but estimated between 1/50000 and 1/30000

Clinics

Phenotype and clinics Onset of the disease occurs commonly between 15 and 40 yrs and most patients (90-100%) present primary hyperparathyroidism related to multiglandular hyperplasia and/or adenomas; other endocrine lesions and relative percentages are neuroendocrine tumors of the pancreas (either functionnal such as gastrinomas, insulinoma, and more rarely glucagonoma, VIPoma or non functionnal) (50-70%), pituitary adenoma (20-40%), adrenocortical hyperplasia, adenomas or cancers (20-70%) and thymic/bronchial neuroendocrine tumors (5-10%); cutaneous lesions, such as angiofibromas, collagenomas, lentiginosis, melanocytic lesions and lipoma might occur in 5-10% of MEN1 patients; less common lesions are infratentorial papillary ependymoma, rhabdomyosarcoma and leiomyosarcoma, and renal and thyroid cancers
Neoplastic risk
  • pancreatic neuroendocrine tumors such as gastrinoma have malignant evolution in 30 to 50% of the cases. Insulinoma might be frequently benign. Most agressive tumors are glucagonoma and VIPoma (VIP: vasoactive intestinal peptide) in pancreas and some tumors occuring in the adrenal cortex.
  • pituitary adenomas in MEN1 are classicla benign lesions but complications might be related to local nervous compression by the tumor.
  • parathyroid adenomas in MEN1 remain benign lesions
  • cutaneous and CNS (Central Nervos System) lesions in MEN1 might be malignant in a few cases. Strikingly , melanomas, ependymomas and rare astrocytomas observed in the MEN1 context have better prognosis than the same lesions occuring sporadically
  • Treatment
  • parathyroids : the recommended procedure is 3 and half parathyroidectomy and cautious exploration of the thymic tissues in which ectopic adenomas and/or carcinoids (neuroendocrine tumors) have been described
  • pancreas : in most cases (insulinoma, glucagonomas, > 2cm non functionnal tumors, surgery is a best procedure and might be duodenopancreactomy in the heavy cases; nevertheless, in gastrinomas and non functionnal small tumors identified by US endoscopy, the best procedure is the medical (antiacid) treatment and a careful follow-up of patients.
  • pituitary adenomas : the treatment is the same as for sporadic lesions
  • adrenal glands tumors : surgery is the best recommended procedure when lesions are clearly identified by imagery
  • thymic/bronchial carcinoids : they must be cured by surgery because they are malignant and alter prognosis in MEN1 patients
  • Prognosis according to the severity of the disease in a given patient, and to the quality of a regular follow up; mean age at death is relatively similar to that of the general population; nevertheless, death may occur early in life (10 to 50yr) due to the complications of hormonal secretions by tumors (hemorrhagic ulcers, malignant hypercalcaemia, carcinoid syndromes) or evolution of the maligant process (pancreatic neuroendocrine tumors and thoracic carcinoids): 50 yrs; a presymptomatic diagnosis improves survival data and might prevent earlier the main causes of death in this disease

    Genes involved and Proteins

     
    Gene NameMEN1
    Location 11q13
    DNA/RNA
    Description 10 exons
    Transcription different splicings
    Protein
    Description 610 amino-acids, 67 Kda; contains two nuclear localization signals
    Expression wide
    Function growth-suppressor gene
    Mutations
    Germinal causes multiple endocrine neoplasia type 1

    External links

    OMIM131100
    OrphanetMultiple endocrine neoplasia type 1
    HGMD120173
    Other databaseMEN1 mutation database
    Other databaseGENEM Scientific network

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    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed

    Contributor(s)

    Written03-2000Alain Calender

    Citation

    This paper should be referenced as such :
    Calender A . Multiple endocrine neoplasia type 1 (MEN1). Atlas Genet Cytogenet Oncol Haematol. March 2000 .
    URL : http://AtlasGeneticsOncology.org/Kprones/MEN1KproneID10008.html

    The various updated versions of this paper are referenced and archived by INIST as such :
    http://documents.irevues.inist.fr/bitstream/2042/37630/1/03-2000-MEN1KproneID10008.pdf   [ Bibliographic record ]

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