Separate developmental slowing from loss of acquired skills
Longitudinal reports on ST3GAL5 deficiency, PACS1-NDD, and TLK2-related disorder create an opportunity to distinguish two explanations for changing developmental profiles: progressive disruption causing genuine loss of previously acquired skills, versus an early neurodevelopmental constraint that becomes more apparent as age-dependent demands increase. These are not equivalent mechanisms.
The discriminating evidence would be domain-specific trajectories: documented skill loss after stable acquisition, plateau without loss, seizure timing relative to change, and whether motor, language, adaptive, or behavioral domains diverge. Repeated measures anchored to developmental age—and contemporaneous neurologic events—would help determine which explanation better fits each genotype rather than treating “regression” as a single phenotype.
