ESPE Abstracts (2016) 86 P-P1-352

A Multicenter Study on Long-Term Outcomes in 56 Males with 45,X/46,XY Mosaicism

Marie Lindhardt Johansena,b, Carlo Acerinic, Juliana Andraded, Antonio Balsamoe, Martine Coolsf, Rieko Tadokoro Cuccaroc, Feyza Darendelilerg, Christa E Flückh, Romina Grinsponi, Tulay Guranj, Sabine Hannemak, Angela K Lucas-Heraldl, Olaf Hiortm, Corina Lichiardopoln, Rita Ortolanoe, Stefan Riedlo, S Faisal Ahmedl & Anders Juula,b


aDepartment of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; bInternational Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; cDepartment of Paediatrics, Addenbrooke’s Hospital, University of Cambridge, Cambridge, UK; dFaculty of Medical Sciences (FCM), Department of Medical Genetics, State University of Campinas (Unicamp), São Paulo, Brazil; eDipartimento di Scienze Mediche e Chirurgiche, Programma di Endocrinologia Pediatrica, Unita Operativa di Pediatria, Universita di Bologna, Policlinico S. Orsola-Malpighi, Bologna, Italy; fUniversity Hospital Ghent and Ghent University, Ghent, Belgium; gIstanbul University, Istanbul, Turkey; hPediatric Endocrinology and Diabetology, Department of Clinical Research, University Children’s Hospital Bern, Bern, Switzerland; iCentro de Investigaciones Endocrinológicas ‘Dr. César Bergadá’ (CEDIE), CONICET – FEI, División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina; jMarmara University, Istanbul, Turkey; kDepartment of Paediatric Endocrinology, Sophia Children’s Hospital, Erasmus MC, Rotterdam, The Netherlands; lDevelopmental Endocrinology Research Group University of Glasgow, Glasgow, UK; mUniversity of Luebeck, Luebeck, Germany; nDepartment of Endocrinology, University of Medicine and Pharmacy Craiova, University Emergency Hospital Craiova, Craiova, Romania; oPediatric Endocrinology, St. Anna Kinderspital, University of Vienna, Vienna, Austria


Background: 45,X/46,XY mosaicism is a rare karyotype with a broad phenotypic variation. In patients with a male or predominantly male phenotype, impaired genital development and statural growth have been observed, but little is known about long-term outcomes. Larger multicenter studies are needed.

Objective and hypotheses: The aim of this study is to investigate long-term outcomes, namely gonadal function, growth and co-morbidities, in a larger group of males with 45,X/46,XY mosaicism.

Method: Using the I-DSD Registry, all centers with males with 45,X/46,XY mosaicism were invited to participate in this multicenter study. Only post-pubertal patients that had reached adult height were included. At the time of writing, inclusion is still ongoing.

Results: In total, 22 centers were invited. Thus far 18 centers have responded positively and 16 centers have supplied data on a total of 56 males. Age at the last evaluation was 26.6 years (13.4–70.2 years). External masculinization score (EMS) at time of diagnosis was 8.5/12 (2–12). Nine (23.7%) patients had a score of 12 (complete external virilization). 38 patients (77.6%) entered puberty spontaneously. 15 (34.1%) had received testosterone treatment. Final height was 157.0 cm (141.1–184.0 cm). 17 patients (38.6%) had received growth hormone. Six patients (11.8%) had renal disease/abnormalities and 10 (19.2%) had congenital cardiac malformations. One patient (2.3%) had a gonadal tumor and 6 (18.2%) had precursor lesions.

Conclusion: These preliminary data show that patients with 45,X/46,XY have varying phenotypes reflected by the EMS. Most of the patients spontaneously entered puberty indicating good Leydig cell function, although 15 did receive testosterone. Patients have short adult stature. The prevalence of gonadal neoplasia in situ and renal and cardiac co-morbidities appears to be high. The study is ongoing, but final data analyses will be presented. It can, however, be concluded that recruiting centers through the iDSD Registry was successful.