PMID- 27842554
OWN - NLM
STAT- MEDLINE
DCOM- 20170710
LR  - 20220408
IS  - 1741-7015 (Electronic)
IS  - 1741-7015 (Linking)
VI  - 14
IP  - 1
DP  - 2016 Nov 15
TI  - MEN1 redefined, a clinical comparison of mutation-positive and mutation-negative 
      patients.
PG  - 182
LID - 182
AB  - BACKGROUND: Multiple Endocrine Neoplasia type 1 (MEN1) is diagnosed when two out 
      of the three primary MEN1-associated endocrine tumors occur in a patient. Up to 
      10-30 % of those patients have no mutation in the MEN1 gene. It is unclear if the 
      phenotype and course of the disease of mutation-negative patients is comparable 
      with mutation-positive patients and if these patients have true MEN1. The present 
      study aims to describe and compare the clinical course of MEN1 mutation-negative 
      patients with two out of the three main MEN1 manifestations and mutation-positive 
      patients during long-term follow-up. METHODS: This is a cohort study performed 
      using the Dutch MEN1 database, including > 90 % of the Dutch MEN1 population. 
      RESULTS: A total of 293 (90.7 %) mutation-positive and 30 (9.3 %) 
      mutation-negative MEN1 patients were included. Median age of developing the first 
      main MEN1 manifestation was higher in mutation-negative patients (46 vs. 
      33 years) (P = 0.007). Mutation-negative patients did not develop a third main 
      MEN1 manifestation in the course of follow-up compared to 48.3 % of 
      mutation-positive patients (P < 0.001). Median survival in mutation-positive 
      patients was estimated at 73.0 years (95 % CI, 69.5-76.5) compared to 87.0 years 
      (95 % CI not available) in mutation-negative patients (P = 0.001). CONCLUSIONS: 
      Mutation-positive and mutation-negative MEN1 patients have a different phenotype 
      and clinical course. Mutation-negative patients develop MEN1 manifestations at 
      higher age and have a life expectancy comparable with the general population. The 
      apparent differences in clinical course suggest that MEN1 mutation-negative 
      patients do not have true MEN1, but another MEN1-like syndrome or sporadic 
      co-incidence of two neuro-endocrine tumors.
FAU - de Laat, Joanne M
AU  - de Laat JM
AD  - Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, The 
      Netherlands.
FAU - van der Luijt, Rob B
AU  - van der Luijt RB
AD  - Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The 
      Netherlands.
FAU - Pieterman, Carolina R C
AU  - Pieterman CR
AD  - Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, The 
      Netherlands.
FAU - Oostveen, Maria P
AU  - Oostveen MP
AD  - Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, The 
      Netherlands.
FAU - Hermus, Ad R
AU  - Hermus AR
AD  - Department of Endocrinology, Radboud University Medical Center, Nijmegen, The 
      Netherlands.
FAU - Dekkers, Olaf M
AU  - Dekkers OM
AD  - Departments of Endocrinology and Metabolism & Clinical Epidemiology, Leiden 
      University Medical Center, Leiden, The Netherlands.
FAU - de Herder, Wouter W
AU  - de Herder WW
AD  - Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The 
      Netherlands.
FAU - van der Horst-Schrivers, Anouk N
AU  - van der Horst-Schrivers AN
AD  - Department of Endocrinology, University Medical Center Groningen, Groningen, The 
      Netherlands.
FAU - Drent, Madeleine L
AU  - Drent ML
AD  - Department of Internal Medicine, VU University Medical Center, Amsterdam, The 
      Netherlands.
FAU - Bisschop, Peter H
AU  - Bisschop PH
AD  - Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, 
      The Netherlands.
FAU - Havekes, Bas
AU  - Havekes B
AD  - Department of Internal Medicine, Division of Endocrinology, Maastricht University 
      Medical Center, Maastricht, The Netherlands.
FAU - Vriens, Menno R
AU  - Vriens MR
AD  - Department of Surgery, University Medical Center Utrecht, Utrecht, The 
      Netherlands.
FAU - Valk, Gerlof D
AU  - Valk GD
AD  - Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, The 
      Netherlands. G.D.Valk@umcutrecht.nl.
LA  - eng
PT  - Journal Article
DEP - 20161115
PL  - England
TA  - BMC Med
JT  - BMC medicine
JID - 101190723
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Child
MH  - Cohort Studies
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Molecular Epidemiology
MH  - Multiple Endocrine Neoplasia Type 1/*diagnosis/epidemiology/*genetics/immunology
MH  - Mutation
MH  - Netherlands/epidemiology
MH  - Phenotype
MH  - Proto-Oncogene Proteins/*genetics
MH  - Retrospective Studies
MH  - Young Adult
PMC - PMC5109674
OTO - NOTNLM
OT  - Diagnosis
OT  - MEN1
OT  - Survival
EDAT- 2016/11/16 06:00
MHDA- 2017/07/14 06:00
PMCR- 2016/11/15
CRDT- 2016/11/16 06:00
PHST- 2016/07/12 00:00 [received]
PHST- 2016/09/30 00:00 [accepted]
PHST- 2016/11/16 06:00 [entrez]
PHST- 2016/11/16 06:00 [pubmed]
PHST- 2017/07/14 06:00 [medline]
PHST- 2016/11/15 00:00 [pmc-release]
AID - 10.1186/s12916-016-0708-1 [pii]
AID - 708 [pii]
AID - 10.1186/s12916-016-0708-1 [doi]
PST - epublish
SO  - BMC Med. 2016 Nov 15;14(1):182. doi: 10.1186/s12916-016-0708-1.