Lessons Learned from 17 Years of Multidisciplinary Care for DSD Patients at A Single Indonesian Center

Background: Our Multidisciplinary Team (MDT) is a large specialized team based in Semarang,Indonesia that cares for a wide variety of pediatric and adult individuals with Differences of SexDevelopment (DSD) from across Indonesia. Here we describe our work over the last 17 years.Methods: We analyzed phenotypic, hormonal and genetic findings from clinical records for allpatients referred to our MDT during the period 2004 to 2020.Results: Among 1184 DSD patients, 10% had sex chromosome DSD, 67% had 46,XY DSD and 23% had46,XX DSD. The most common sex chromosome anomaly was Turner syndrome (45,X) (55 cases). Forpatients with 46,XY DSD under-masculinization was the most common diagnosis (311 cases) and for46,XX DSD a defect of Müllerian development was most common (131 cases) followed by CongenitalAdrenal Hyperplasia (CAH) (116 cases). Sanger sequencing, MLPA and targeted gene sequencing ofDownloaded from http://karger.com/sxd/article-pdf/doi/10.1159/000534085/3998946/000534085.pdf by guest on 03 October 2023257 patients with 46,XY DSD found likely causative variants in 21% (55 cases), with 13 diagnosticgenes implicated. The most affected gene coded for the Androgen Receptor. Molecular analysisidentified a diagnosis for 69 of 116 patients with CAH, with 62 carrying variants in CYP21A2 includingfour novel variants, and seven patients carrying variants in CYP11B1. In many cases these geneticdiagnoses influenced the clinical management of patients and families.Conclusions: Our work has highlighted the occurrence of different DSDs in Indonesia. By applyingsequencing technologies as part of our clinical care, we have delivered a number of geneticdiagnoses and identified novel pathogenic variants in some genes, which may be clinically specific toIndonesia. Genetics can inform many aspects of DSD clinical management, and whilst many of ourpatients remain undiagnosed, we hope that future testing may provide answers for even more

Gonadal development and tumor formation at the crossroads of male and female sex determination

Malignant germ cell tumor (GCT) formation is a well-known complication in the management of patients with a disorder of sex development (DSD). DSDs are defined as congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical. DSD patients in whom the karyotype – at least at the gonadal level – contains (a part of) the Y chromosome are at increased risk for neoplastic transformation of germ cells, leading to the development of the so-called ‘type II germ cell tumors’. However, tumor risk in the various forms of DSD varies considerably between the different diagnostic groups. This contribution integrates our actual knowledge on the pathophysiology of tumor development in DSDs, recent findings on gonadal (mal)development in DSD patients, and possible correlations between the patient’s phenotype and his/her risk for germ cell tumor development.</jats:p

Multilingual Global E-Learning Pediatric Endocrinology and Diabetes Curriculum for Front Line Health Care Providers in Resource-Limited Countries: Development Study.

BACKGROUND: Electronic learning (e-learning) is a widely accessible, low-cost option for learning remotely in various settings that allows interaction between an instructor and a learner. OBJECTIVE: We describe the development of a free and globally accessible multilingual e-learning module that provides education material on topics in pediatric endocrinology and diabetes and that is intended for first-line physicians and health workers but also trainees or medical specialists in resource-limited countries. METHODS: As complements to concise chapters, interactive vignettes were constructed, exemplifying clinical issues and pitfalls, with specific attention to the 3 levels of medical health care in resource-limited countries. The module is part of a large e-learning portal, ESPE e-learning, which is based on ILIAS (Integriertes Lern-, Informations- und Arbeitskooperations-System), an open-source web-based learning management system. Following a review by global experts, the content was translated by native French, Spanish, Swahili, and Chinese-speaking colleagues into their respective languages using a commercial web-based translation tool (SDL Trados Studio). RESULTS: Preliminary data suggest that the module is well received, particularly in targeted parts of the world and that active promotion to inform target users is warranted. CONCLUSIONS: The e-learning module is a free globally accessible multilingual up-to-date tool for use in resource-limited countries that has been utilized thus far with success. Widespread use will require dissemination of the tool on a global scale

New insights into type II germ cell tumor pathogenesis based on studies of patients with various forms of disorders of sex development (DSD)

International audienc