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DOI: 10.1055/s-2007-970160
© 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
Publikationsverlauf
received 29.01.2007
first decision 30.01.2007
accepted 30.01.2007
Publikationsdatum:
12. September 2007 (online)
![](https://www.thieme-connect.de/media/eced/200708/lookinside/thumbnails/10.1055-s-2007-970160-1.jpg)
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
Telefon: +49/89/306 22 454
Fax: +49/89/306 22 454
eMail: schaaf@mpipsykl.mpg.de