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
- PMID: 17853334
- DOI: 10.1055/s-2007-970160
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.
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.
Similar articles
-
MEN1 gene mutations in Hungarian patients with multiple endocrine neoplasia type 1.Clin Endocrinol (Oxf). 2007 Nov;67(5):727-34. doi: 10.1111/j.1365-2265.2007.02953.x. Clin Endocrinol (Oxf). 2007. PMID: 17953629
-
Age-related penetrance of endocrine tumours in multiple endocrine neoplasia type 1 (MEN1): a multicentre study of 258 gene carriers.Clin Endocrinol (Oxf). 2007 Oct;67(4):613-22. doi: 10.1111/j.1365-2265.2007.02934.x. Epub 2007 Jun 21. Clin Endocrinol (Oxf). 2007. PMID: 17590169
-
Pituitary tumors and hyperplasia in multiple endocrine neoplasia type 1 syndrome (MEN1): a case-control study in a series of 77 patients versus 2509 non-MEN1 patients.Am J Surg Pathol. 2008 Apr;32(4):534-43. doi: 10.1097/PAS.0b013e31815ade45. Am J Surg Pathol. 2008. PMID: 18300794
-
[Clinical symptoms, diagnosis and treatment of multiple endocrine neoplasia type 1. Results of genetic screening in Hungarian patients].Orv Hetil. 2005 Oct 23;146(43):2191-7. Orv Hetil. 2005. PMID: 16323565 Review. Hungarian.
-
[Diverse expression of multiple endocrine neoplasia type 1].Ned Tijdschr Geneeskd. 2000 Dec 16;144(51):2437-42. Ned Tijdschr Geneeskd. 2000. PMID: 11151650 Review. Dutch.
Cited by
-
Reconstructed glycosylase base editors GBE2.0 with enhanced C-to-G base editing efficiency and purity.Mol Ther. 2022 Jul 6;30(7):2452-2463. doi: 10.1016/j.ymthe.2022.03.023. Epub 2022 Apr 4. Mol Ther. 2022. PMID: 35381364 Free PMC article.
-
[Indication and performance of endocrine surgery. The significance of molecular genetic examination].Chirurg. 2009 Feb;80(2):122-9. doi: 10.1007/s00104-008-1615-6. Chirurg. 2009. PMID: 19096808 Review. German.
-
Is Routine Screening of Young Asymptomatic MEN1 Patients Necessary?World J Surg. 2017 Aug;41(8):2026-2032. doi: 10.1007/s00268-017-3992-9. World J Surg. 2017. PMID: 28321559
-
Using Structural Analysis In Silico to Assess the Impact of Missense Variants in MEN1.J Endocr Soc. 2019 Sep 27;3(12):2258-2275. doi: 10.1210/js.2019-00260. eCollection 2019 Dec 1. J Endocr Soc. 2019. PMID: 31737856 Free PMC article.
-
Long-term results of surgery for pancreatic neuroendocrine neoplasms in patients with MEN1.Langenbecks Arch Surg. 2011 Dec;396(8):1187-96. doi: 10.1007/s00423-011-0828-1. Epub 2011 Jul 30. Langenbecks Arch Surg. 2011. PMID: 21805182
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials