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Exp Clin Endocrinol Diabetes 2007; 115(8): 509-517
DOI: 10.1055/s-2007-970160
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG · Stuttgart · New York

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

L. Schaaf 1 , J. Pickel 1 , K. Zinner 1 , U. Hering 1 , M. Höfler 1 , P. E. Goretzki 2 , F. Spelsberg 3 , F. Raue 4 , A. von zur Mühlen 5 , H. Gerl 6 , J. Hensen 7 , D. K. Bartsch 8 , M. Rothmund 8 , U. Schneyer 9 , H. Dralle 9 , M. Engelbach 10 , W. Karges 11 , G. K. Stalla 1 , W. Höppner 12
  • 1Max-Planck-Institute Munich
  • 2University Hospital Düsseldorf
  • 3Martha-Maria Hospital Munich
  • 4Endocrine practice Heidelberg
  • 5MH Hannover
  • 6Charité Berlin
  • 7Klinikum Hannover-Nordstadt
  • 8University Hospital Marburg
  • 9University Hospital Halle
  • 10Endocrine practice, Frankfurt/M
  • 11Medical University Hospital Aachen
  • 12Bioglobe GmbH, Hamburg
Further Information

Publication History

received 29.01.2007 first decision 30.01.2007

accepted 30.01.2007

Publication Date:
12 September 2007 (online)

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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.

Conclusion: 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.

Key words

Multiple endocrine neoplasia type 1 - German MEN 1 Register - MEN 1 phenotype/genotype - endocrine tumors - screening

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Correspondence

Prof. Dr. med. L. Schaaf

Max-Planck-Institute of Psychiatry

Endocrinology and Clinical Chemistry

Kraepelinstr. 10

80804 München and Germany

Phone: +49/89/306 22 454

Fax: +49/89/306 22 454

Email: schaaf@mpipsykl.mpg.de