TL;DR
An early-intervention approach, or combination of approaches, holds significant promise for transforming the lives of individuals affected by AS with outcomes dependent on their age or genotype.
This review evaluates the potential of CRISPR-based editing as a therapeutic strategy for monogenic NDDs and evaluates the limitations that must be addressed before its widespread application in human patients.
The central argument is that UBE3A should not be interpreted as a general explanation for autism, but as a mechanistically informative model for a defined subset of neurodevelopmental disorders in which parent-of-origin effects and copy-number state are central.
This case expands the clinical spectrum associated with RFX3 variants, supporting a potential role in IESS and early neurodevelopmental disruption, and highlights the relevance of including RFX3 in the genetic evaluation of patients with IESS and co-occurring neurodevelopmental disorders.
In two patients with SCN2A epileptic encephalopathy, treatment with personalized allele-selective antisense oligonucleotides led to a decrease in seizure frequency with a positive safety profile, and a pathway from n = 1 to n of more patients with SCN2A-RD and other monogenic disorders is provided.
The biological plausibility of LNX2 as a candidate gene for neurodevelopmental disorders is supported, highlighting its preferential association with neuronal projection-cell networks, synaptic vesicle trafficking pathways, and neuron-specific regulatory programs.
Four major themes are identified, encompassing genetic modifiers, epigenetic modifications, mosaicism, and environmental factors that may act independently or interactively to influence pathogenic burden and functional network balance, ultimately determining whether a pathogenic mutation manifests clinically.