New developments and future trajectories in supernumerary sex chromosome abnormalities: a summary of the 2022 3rd International Workshop on Klinefelter Syndrome, Trisomy X, and XYY

Abstract

The 3rd International Workshop on Klinefelter Syndrome, Trisomy X, and 47,XYY syndrome was held in Leiden, the Netherlands, on September 12–14, 2022. Here, we review new data presented at the workshop and discuss scientific and clinical trajectories. We focus on shortcomings in knowledge and therefore point out future areas for research. We focus on the genetics and genomics of supernumerary sex chromosome syndromes with new data being presented. Most knowledge centre specifically on Klinefelter syndrome, where aspects on testosterone deficiency and the relation to bone, muscle and fat were discussed, as was infertility and the treatment thereof. Both trisomy X and 47,XYY syndrome are frequently affected by infertility. Transitioning of males with Klinefelter syndrome was addressed, as this seemingly simple process in practise is often difficult. It is now realized that neurocognitive changes are pervasive in all supernumerary sex chromosome syndromes, which were extensively discussed. New intervention projects were also described, and exciting new data concerning these were presented. Advocacy organizations were present, describing the enormous burden carried by parents when having to explain their child’s specific syndrome to most professionals whenever in contact with health care and education systems. It was also pointed out that most countries do not have health care systems that diagnose patients with supernumerary sex chromosome syndromes, thus pinpointing a clear deficiency in the current genetic testing and care models. At the end of the workshop, a roadmap towards the development of new international clinical care guidelines for Klinefelter syndrome was decided.