Outcomes in West syndrome: Association of genetic and perinatal etiologies with early diagnosis and therapy.

BACKGROUND

West syndrome is a severe epileptic encephalopathy of infancy with heterogeneous etiologies and variable outcomes. The specific influence of genetic and perinatal factors, as well as the impact of early and individualized therapy, remains unclear.

METHODS

We retrospectively reviewed 41 infants diagnosed with West syndrome at a tertiary center between January 2022 and January 2024. Detailed etiological assessment included neuroimaging, metabolic, and genetic analyses. Patients were classified as symptomatic or cryptogenic. Clinical, radiological, and developmental data, along with treatment regimens and 3-month outcomes, were analyzed. Treatment response was categorized as seizure freedom, >50% reduction, or poor response.

RESULTS

Symptomatic etiology was identified in 78% of patients, with genetic mutations (36.6%; including DEPDC5, TUBA1A) and hypoxic-ischemic encephalopathy (HIE) (17.1%) most prevalent. Cryptogenic cases comprised 22%. After 3 months, 24.4% achieved seizure freedom, significantly more common in cryptogenic than symptomatic patients (p = 0.006). Monotherapy was associated with better seizure control (p = 0.002). Severe developmental delay and radiological abnormalities-especially cortical atrophy-were predominant among patients with genetic and perinatal etiologies and correlated with poorer seizure outcomes (p < 0.001). Early intervention improved seizure and neurodevelopmental outcomes. Mortality was observed in 4.9% of the cohort, primarily among patients with homozygous DEPDC5 deletions.

CONCLUSIONS

Genetic and perinatal etiologies fundamentally shape both neurodevelopmental and seizure outcomes in West syndrome. Early diagnosis, comprehensive etiological evaluation, and personalized therapy-favoring monotherapy where feasible-are critical for optimizing prognosis. These findings underscore the necessity of etiological stratification and tailored interventions to improve long-term outcomes in affected infants.