New 22q11 Europe Podcast

Episode 1 - Synaptic Dysconnectivity in 22q11

• Featured Research Article: “Synaptic-dependent developmental dysconnectivity in 22q11.2 deletion syndrome” (2025).
• Abstract: Chromosome 22q11.2 deletion increases the risk of neuropsychiatric disorders like autism and schizophrenia. Disruption of large-scale functional connectivity in 22q11 deletion syndrome (22q11DS) has been widely reported, but the biological factors driving these changes remain unclear. We used a cross-species design to uncover the developmental trajectory and neural underpinnings of brain dysconnectivity in 22q11DS. In LgDel mice, a model for 22q11DS, we found age-specific patterns of brain dysconnectivity, with widespread fMRI hyperconnectivity in juvenile mice reconfiguring to hippocampal hypoconnectivity over puberty. These changes correlated with developmental alterations in dendritic spine density, and both were transiently normalized by GSK3β inhibition, suggesting a synaptic origin for this phenomenon. Notably, analogous pubertal hyperconnectivity-to-hypoconnectivity reconfiguration occurs in human 22q11DS, affecting cortical regions enriched for GSK3β-associated synaptic genes and autism-relevant transcripts. This dysconnectivity also predicts age-dependent social alterations in 22q11DS individuals. These results suggest that synaptic mechanisms underlie developmental brain dysconnectivity in 22q11DS.
• Reference : Synaptic‑dependent developmental dysconnectivity in 22q11.2 deletion syndrome Thompson, P. M., Anticevic, A., Burt, J. B., Helmer, M., Shinn, M., Murray, J. D., & others. (2025). Synaptic‑dependent developmental dysconnectivity in 22q11.2 deletion syndrome. Science Advances, 11(11), eadq2807.

Episode 2 - Parkinson and 22q11

• Featured Research Article: Prevalence of Parkinson’s Disease in 22q11.2 Deletion Syndrome: A Multicenter Study (2025)
• Abstract: Microdeletion 22q11.2, associated with 22q11.2 deletion syndrome (22q11.2DS), is a neurodevelopmental disorder with an estimated birth prevalence of 1/2148, that has been identified as a genetic risk factor for early-onset Parkinson’s disease (PD). PD in 22q11.2DS may be indistinguishable from idiopathic PD in terms of its neuropathology, hallmark motor symptoms, findings with dopaminergic imaging, and response to levodopa. Data on the risk of developing PD in 22q11.2DS are however limited to a study from 2013 in 159 adults, with the majority of the study subjects younger than 35 years old (n = 90), hindering the provision of adequate information to affected individuals and their families and the introduction of screening strategies. We therefore aimed to characterize the prevalence and predictors of PD in a large international sample of adults with 22q11.2DS
• Reference : Prevalence of Parkinson’s Disease in 22q11.2 Deletion Syndrome: A Multicenter Study von Scheibler, E. N. M. M., Swillen, A., Repetto, G. M., Reyes, N. G. D., Lang, A. E., Marras, C., Kuijf, M. L., Rouhl, R. P. W., van Eeghen, A. M., Juri, C., Vogels, A., van Amelsvoort, T. A. M. J., Bassett, A. S., & Boot, E. (2025). Prevalence of Parkinson’s Disease in 22q11.2 Deletion Syndrome: A Multicenter Study. Movement Disorders Clinical Practice.

Episode 3 - Scoliosis and 22q11

• Featured Research Article: What can we learn from scoliosis in children with the 22q11.2 deletion syndrome? Prognostic factors at pre‐adolescent age for fast progressive, mild and self‐resolving forms during adolescence (2025)
• Abstract: We found no evidence for the parameters in the coronal, sagittal nor transverse plane before curve onset acting as prognostic factors for curve behavior. In the prediction model on a longitudinal database that starts in many patients before scoliosis, no clear radiographic discriminant for later progressive scoliosis could be identifed. The closure of the triradiate cartilage resulted as the best sign of pubertal spurt onset and scoliosis acceleration.
• Reference : Donzelli, S., Lafranca, P., van Smeden, M., Castelein, R. M., & Schlösser, T. P. C. (2025, mars 20). What can we learn from scoliosis in children with the 22q11.2 deletion syndrome? Prognostic factors at pre‑adolescent age for fast progressive, mild and self‑resolving forms during adolescence. Spine Deformity.

Episode 4 - Sleep, Behavior and 22q11

• Featured Research Article: Children With 22.Q.11.2 Deletion Syndrome: Sleep-Disordered Breathing and Management (2025)
• Abstract: Patients with 22q11.2 deletion syndrome (22q11DS) are predisposed to obstructive sleep apnea (OSA) due to an abnormal craniofacial anatomy with pharyngeal hypotonia, retrognathia, micrognathia, and glossoptosis. The aim of the study was to describe the prevalence and management of OSA in a cohort of children with 22q11DS.
• Reference : La Regina, D. P., Khirani, S., Griffon, L., Poirault, C., Nenna, R., Midulla, F., & Fauroux, B. (2025). Children with 22q11.2 deletion syndrome: Sleep‑disordered breathing and management.