Analysis of 213 Italian Angelman syndrome patients reveals stark differences in epilepsy prevalence based on genetic subtype. Those with maternal deletions experienced seizures at 88% frequency compared to just 61.9% in non-deletion cases—a 26-percentage-point gap that underscores how the underlying genetic mechanism shapes clinical outcomes. The registry documented universal developmental delays and near-complete absence of speech development (95.8% of cases), with movement disorders affecting 94.8% of patients.
This genotype-phenotype correlation fills a critical gap in rare disease research where small patient populations typically prevent robust statistical analysis. The finding aligns with established understanding that deletion patients lose entire chromosomal regions rather than single gene mutations, potentially disrupting multiple pathways that influence seizure threshold. For families navigating Angelman syndrome care, this data suggests deletion status should inform seizure monitoring intensity and anticonvulsant prophylaxis decisions. The 3.8-year average diagnostic delay remains concerning given the syndrome's distinctive early presentation, though improved genetic testing accessibility may be narrowing this window. While the registry represents meaningful progress in Italian rare disease surveillance, broader international collaboration will be essential to achieve the statistical power needed for precision medicine approaches in ultra-rare conditions.