title: Developing effective screening strategies in multiple endocrine neoplasia type 1 (MEN 1) on the basis of clinical and sequencing data of German patients with MEN 1.
abstract: BACKGROUND
  Multiple-endocrine-neoplasia-type-1 (MEN1) is an autosomal-dominant inherited disorder characterized by the combined occurrence of primary hyperparathyroidism (pHPT), gastroenteropancreatic neuroendocrine tumors (GEP), adenomas of the pituitary gland (APA), adrenal cortical tumors (ADR) and other tumors. As the tumors appear in an unpredictable schedule, uncertainty about screening programs is persisting.
  
  
  OBJECTIVE
  To optimize screening and to analyze possible differences in sporadic versus familial cases.
  
  
  METHODS
  We analyzed data of 419 individuals including 306 MEN-1 patients (138 isolated and168 familial cases out of 102 unrelated families).
  
  
  RESULTS
  A total of 683 tumors occurred consisting of 273 pHPT, 138 APA, 166 GEP, 57 ADR, 24 thymic- and bronchial-carcinoids as well as 25 neoplasms of other tissues. The age-related penetrance was determined as 10%, 35%, 67%, 81% and 100% at 20, 30, 40, 50 and 65 years respectively. Although pHPT being the most frequent first manifestation (41%), also GEP (22%) or APA (21%) were found to be the first presentation. APA occurred significantly more frequent (p<0,05) in isolated (n=138) than in familial (n=168) cases, whereas GEP showed a tendency to occur more often in familial cases. Genotype/phenotype correlation in 140 clinically affected MEN-1 cases showed a tendency for truncating mutations, especially nonsense mutations to be associated to GEP and carcinoids of the lungs and thymus.
  
  
  CONCLUSIONS
  In view of the morbidity and frequency in familial cases an effective screening programme should aim at an early diagnosis of GEP particularly when truncating, especially nonsense mutations are found.
authors.affiliation: Endocrinology and Clinical Chemistry, Max-Planck-Institute of Psychiatry, Kraepelinstrasse 10, 80804 Munich, Germany. schaaf@mpipsykl.mpg.de
authors.forename: L
authors.initials: L
authors.lastname: Schaaf
authors.forename: J
authors.initials: J
authors.lastname: Pickel
authors.forename: K
authors.initials: K
authors.lastname: Zinner
authors.forename: U
authors.initials: U
authors.lastname: Hering
authors.forename: M
authors.initials: M
authors.lastname: Höfler
authors.forename: P E
authors.initials: PE
authors.lastname: Goretzki
authors.forename: F
authors.initials: F
authors.lastname: Spelsberg
authors.forename: F
authors.initials: F
authors.lastname: Raue
authors.forename: A
authors.initials: A
authors.lastname: von zur Mühlen
authors.forename: H
authors.initials: H
authors.lastname: Gerl
authors.forename: J
authors.initials: J
authors.lastname: Hensen
authors.forename: D K
authors.initials: DK
authors.lastname: Bartsch
authors.forename: M
authors.initials: M
authors.lastname: Rothmund
authors.forename: U
authors.initials: U
authors.lastname: Schneyer
authors.forename: H
authors.initials: H
authors.lastname: Dralle
authors.forename: M
authors.initials: M
authors.lastname: Engelbach
authors.forename: W
authors.initials: W
authors.lastname: Karges
authors.forename: G K
authors.initials: GK
authors.lastname: Stalla
authors.forename: W
authors.initials: W
authors.lastname: Höppner
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D004247:DNA / Q000097:blood / Q000235:genetics; D005260:Female; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000453:epidemiology* / Q000235:genetics; D009679:Nuclear Family; D010641:Phenotype; D016133:Polymerase Chain Reaction
chemical_list: D004247:DNA