CLINICAL STUDY Shortness: an unknown phenotype of multiple endocrine neoplasia type 1 Caroline L Lo ´pez, Peter Langer, Jens Waldmann, Volker Fendrich, Helmut Sitter 1 , Christoph Nies 2 and Detlef K Bartsch Department of Surgery, University Hospital Giessen and Marburg, Marburg, Germany, 1 Department of Surgical Research, Phillips University, Marburg, Germany and 2 Department of Surgery, Marienhospital Osnabru ¨ck, Osnabru ¨ck, Germany (Correspondence should be addressed to C L Lo ´pez who is now at Department of Surgery, Philipps University Marburg, Baldingerstraße, D-35043 Marburg, Germany; Email: lopez@med.uni-marburg.de) Abstract Objective: An observation of shortness among the female participants of a regular screening program in multiple endocrine neoplasia type 1 (MEN1) patients has raised the question as to whether shortness represents a phenotype characteristic of the disease. Methods: The body height (cm) of genetically confirmed MEN1 patients at the time of diagnosis was compared with the body height of their unaffected relatives (parents, siblings, and children), the mid- parental body height, and the body height of the age-matched German population. Univariate analysis of the clinical variables was performed using the t-test, Mann–Whitney U test, and ANOVA as appropriate, and multivariate analysis was performed as a logistic regression analysis. P values !0.05 were considered statistically significant. Results: The mean body height of 22 female MEN1 patients (mean age 33.5 years) was 161G5 cm and thus significantly lesser than the body heights of their unaffected female relatives (mean 165.5 G7.3 cm, PZ0.027) and the age-matched German female population (mean 167 cm, PZ0.0001) and mid-parental height (177.5 cm, P!0.0001). The mean body height of 24 male MEN1 patients (mean age 34.8 years) was also lesser (177G6.5 cm) than the average body height of German males in this age group (180 cm, PZ0.031) and tended to be lesser than that of their unaffected male relatives (178.5G5.8 cm, PZ0.0915) and the mid-parental body height (177.5 cm, PZ0.124). Conclusions: Small body height is a yet unrecognized phenotype characteristic of MEN1 patients, especially in women. The mechanisms behind this phenotypical characteristic warrant further investigation. European Journal of Endocrinology 169 133–137 Introduction Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited familiar tumor syn- drome with a prevalence ranging from 1 in 10 000 to 1 in 100 000 (1, 2). It is characterized by the occurrence of multiple neoplastic endocrine lesions, including primary hyperparathyroidism, pituitary neo- plasms (mostly prolactinomas), and pancreaticoduode- nal neuroendocrine neoplasms (pNENs) (2, 3). Adrenal lesions are also quite common with an incidence of w50% (4). Neuroendocrine neoplasms of the thymus, lung, or stomach may also occur as well as cutaneous lesions such as lipomas and fibromas (3, 5). The penetrance of the MEN1 syndrome is w100% by the age of 50 years (2, 3). Besides thymic carcinoids, pNENs are the most common disease-related cause of death in MEN1 because all pNENs have the biological ability to develop distant metastases (6, 7). The discovery of causative germline mutations in the MEN1 gene on chromosome 11q13 in 1997 (8) allows a predictive genetic screening to identify the mutation carriers and to include these patients in screening programs. Over 1000 different germline mutations in the MEN1 gene have been described so far (9, 10, 11). The MEN1 gene is a tumor suppressor gene and encodes for the protein menin. Numerous studies have suggested an important role for menin in the regulation of gene transcription, cell proliferation, genome stability, and apoptosis. However, the precise underlying mechanisms that are required to explain the functions of the protein and the endocrine-specific nature in MEN1 patients remain still unexplained (12, 13, 14, 15, 16, 17). During a standardized prospective MEN1 screening program at our institution (18, 19), we got the impression that MEN1 patients might be smaller in body height than both their unaffected relatives and the European Journal of Endocrinology (2013) 169 133–137 ISSN 0804-4643 q 2013 European Society of Endocrinology DOI: 10.1530/EJE-13-0126 Online version via www.eje-online.org Downloaded from Bioscientifica.com at 01/13/2022 09:06:49PM via free access