The Klinefelter syndrome: current management and research challenges

Following the 1st International Workshop on the Klinefelter Syndrome in 2010 (Juul et al., 2011), the 2nd IWKS took place in Münster, Germany from March 10 to 12, 2016 and was organized by the Centre of Reproductive Medicine and Andrology of the University of Münster. During the program, talks were presented by leading researchers in the field followed by lively discussions among the 120 participants. The talks comprehensively covered basic and clinical aspects of the syndrome. The basic aspects included the mechanisms of X chromosome inactivation (Joost Gribnau, Christine Disteche), sex chromosome evolution in the primate lineage (Gabriel Marais), epigenetics (Joana Viana), gene expression studies (Liborio Stuppia), and animal models (Art Arnold, Armin Raznahan, Joachim Wistuba). Among the clinical aspects, current views on early/prenatal diagnosis (Frank Tüttelmann) and transitional care (Niels E. Skakkebæk, Alan Rogol) were reviewed. A large part of the workshop was devoted to comorbidities – with focus on cardiovascular and metabolic problems (Michael Zitzmann, Anders Bojesen) as well as osteoporosis (Alberto Ferlin). Neuropsychological, behavioral, and socioeconomic aspects were discussed (Hanna Swaab, Anne Skakkebæk, Nicole Tartaglia). Divergent experiences and opinions on fertility preservation and optimal time for TESE were presented (Sabine Kliesch, Hervé Lejeune). Following new findings on testicular steroidogenesis (Manuela Simoni), testosterone replacement in infants and young children (Carole Samango-Sprouse) and age-specific recommendations for management of patients with Klinefelter Syndrome (KS) met with great interest (Anders Juul). Differences and similarities between KS and Turner syndrome provided further insights into disorders of sex chromosome aneuploidies (Claus H. Gravholt). Finally, results of the 'dsd-LIFE study' on quality of life, satisfaction with care and needs of adolescents and men with KS (Birgit Köhler) and the European COST Initiative on DSD including KS (Olaf Hiort) were presented (for details of the program see www.klinefelter2016.de). The purpose of the concluding round table was to discuss – based on the presentations and interactions of this workshop – the shortcomings of current care of patients with KS and to indicate future directions for patient management and research. As an introduction, tribute was paid to Harry F. Klinefelter (1912–1990), who first described this syndrome in 1942 (Klinefelter et al., 1942). Of the 120 workshop participants, only Alan Rogol and Eberhard Nieschlag had met Harry Klinefelter in person, the former as one of his medical teachers at John Hopkins in Baltimore and the latter at an International Klinefelter Symposium in Murnau in the Bavarian Alps in 1983 (Bandmann et al., 1984). The discussion was opened by arguments for and against neonatal screening for KS as this question had come up repeatedly during the workshop. Alan Rogol gave the reasons for screening all male newborns for 47,XXY (and perhaps all children for sex chromosome aneuploidy): primarily in anticipation of services required in childhood, such as early treatment of deficits encountered in speech, behavior/regulation of emotion, physical findings, delayed childhood milestones. Furthermore, for information of parents, doctors, and health care practitioners as well as school and pre-school personnel (as much as parents wish, for there is a risk of stigmatization). An overarching service/education that pediatricians have to offer is anticipatory guidance, and newborn screening would allow pediatricians to provide this guidance to families concerned with KS. However, based on his experience in Denmark, Claus H. Gravholt felt that it was premature to screen large populations for KS, as we do not yet have evidence that the different treatment options that we can provide are efficient and reduce morbidity, mortality, and improve outcome. There is no proof yet that early diagnosis and treatment [truncated]