Cell-to-cell communication is essential for proper embryonic development and its dysfunction may lead to disease. Recent research has drawn attention to a new group of molecules called connexins (Cxs) and pannexins (Panxs). Cxs have been described for more than forty years as pivotal regulators of embryogenesis; however, the exact mechanism by which they provide this regulation has not been clearly elucidated. Consequently, Cxs and Panxs have been linked to congenital neurodegenerative diseases such as Charcot-Marie-Tooth disease and, more recently, chronic hemichannel opening has been associated with adult neurodegenerative diseases (e.g., Alzheimer’s disease). Cell-to-cell communication via gap junctions formed by hexameric assemblies of Cxs, known as connexons, is believed to be a crucial component in developmental regulation. As for Panxs, despite being topologically similar to Cxs, they predominantly seem to form channels connecting the cytoplasm to the extracellular space and, despite recent research into Panx1 (Pannexin 1) expression in different regions of the brain during the embryonic phase, it has been studied to a lesser degree. When it comes to the nervous system, Cxs and Panxs play an important role in early stages of neuronal development with a wide span of action ranging from cellular migration during early stages to neuronal differentiation and system circuitry formation. In this review, we describe the most recent available evidence regarding the molecular and structural aspects of Cx and Panx channels, their role in neurodevelopment, congenital and adult neurological diseases, and finally propose how pharmacological modulation of these channels could modify the pathogenesis of some diseases.

Background Down syndrome (DS, also known as Trisomy 21) is a condition associated with abnormal neurodevelopment and a higher risk for sleep apnea. Our study sought to better understand and characterize the age‐related developmental differences in sleep architecture and obstructive sleep apnea (OSA) severity in children with DS compared to euploid individuals. Methods Retrospective review of polysomnograms in over 4151 infants, children, and adolescents in the pediatric sleep center at Children's National Hospital in Washington D.C. (0–18 years) including 218 individuals with DS. Results The primary findings of our study are that: (1) severe OSA (obstructive apnea‐hypopnea index ≥ 10/h) was more prevalent in the DS group (euploid 18% vs. DS 34%, p < 0.001) with the highest OSA severity being present in young children (<3 years old) and adolescents (>10 years old), (2) abnormalities in sleep architecture in children with DS were characterized by a prolonged rapid‐eye movement (REM) sleep onset latency (SOL) (euploid 119 min vs. DS 144 min, p < 0.001) and greater arousal indexes (euploid 10.7/h vs. DS 12.2/h, p < 0.001), (3) developmental changes in the amount of REM sleep or slow wave sleep were not different in DS individuals relative to euploid children, (4) multivariate analyses showed that OSA and REM sleep latency differences between DS and euploid individuals were still present after adjusting by age, biological sex, and body mass index. Conclusion Severe OSA is highly prevalent in children with DS and follows an age‐dependent “U” distribution with peaks in newborns/infants and children >10 years of age. Children with DS also have disturbances in sleep architecture characterized by a longer REM SOL and elevated arousal indexes. As sleep cycle generation and continuity play crucial roles in neuroplasticity and cognitive development, these findings offer clinically relevant insights to guide anticipatory guidance for infants, children, and adolescents with DS.

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