Multiple endocrine neoplasia type 1 (MEN1)

2000-03-01   Alain Calender 

Service de genetique moleculaire et medicale, hopital Edouard-Herriot, batiment B7, 5, place dArsonval, 69437 Lyon 03, France

Identity

Name

Multiple endocrine neoplasia type 1 (MEN1)

Alias

Wermers syndrome

Note

Multiple Endocrine Neoplasia type 1 or Wermers 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

Omim

131100

Mesh

D018761

Orphanet

652 Multiple endocrine neoplasia type 1

Umls

C0025267

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

    Description

    10 exons

    Transcription

    different splicings

    Description

    610 amino-acids, 67 Kda; contains two nuclear localization signals

    Expression

    wide

    Function

    growth-suppressor gene

    Germinal

    causes multiple endocrine neoplasia type 1

    To be noted

    Hgmd

    120173

    Databases

    http:\/\/umd2.necker.fr:2006\/ MEN1 mutation databasehttp:\/\/rockefeller.univ-lyon1.fr\/GENEM\/ GENEM Scientific network

    Bibliography

    Pubmed IDLast YearTitleAuthors
    99895051999Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription.Agarwal SK et al
    94633361998Characterization of mutations in patients with multiple endocrine neoplasia type 1.Bassett JH et al
    101899861998[Clinicogenetic study of MEN1: recent physiopathological data and clinical applications. Study Group of Multiple Endocrine Neoplasia (GENEM)].Calender A et al
    91031961997Positional cloning of the gene for multiple endocrine neoplasia-type 1.Chandrasekharappa SC et al
    92365231997Multiple facial angiofibromas and collagenomas in patients with multiple endocrine neoplasia type 1.Darling TN et al
    93293901997A large multiple endocrine neoplasia type 1 family with clinical expression suggestive of anticipation.Giraud S et al
    96835851998Germ-line mutation analysis in patients with multiple endocrine neoplasia type 1 and related disorders.Giraud S et al
    100920661999Nuclear/cytoplasmic localization of the multiple endocrine neoplasia type 1 gene product, menin.Huang SC et al
    90692631997AP-1 function and regulation.Karin M et al
    87397831996Multiple endocrine neoplasia type 1 associated with spinal ependymoma.Kato H et al
    28946101988Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma.Larsson C et al
    92156901997Identification of the multiple endocrine neoplasia type 1 (MEN1) gene. The European Consortium on MEN1.Lemmens I et al
    95979231998Late outcome of 304 consecutive patients with multiple gland enlargement in primary hyperparathyroidism treated by conservative surgery.Proye C et al
    16778021991The natural history of multiple endocrine neoplasia type 1. Highly uncommon or highly unrecognized?Shepherd JJ et al
    74915261995Adrenal lesion in multiple endocrine neoplasia type 1.Skogseid B et al
    97099211998Mutation analysis of the MEN1 gene in multiple endocrine neoplasia type 1, familial acromegaly and familial isolated hyperparathyroidism.Teh BT et al
    89177401996Clinical studies of multiple endocrine neoplasia type 1 (MEN1)Trump D et al
    140576231963ENDOCRINE ADENOMATOSIS AND PEPTIC ULCER IN A LARGE KINDRED. INHERITED MULTIPLE TUMORS AND MOSAIC PLEIOTROPISM IN MAN.WERMER P et al