Phenotype-guided etiologic workup in a prospective cohort of 144 adults with developmental and epileptic encephalopathy.
Phenotype-guided workup found a confirmed cause in most adults with epileptic encephalopathy.
Phenotype-guided etiologic workup in a prospective cohort of 144 adults with developmental and epileptic encephalopathy.
We aimed to assess the clinical utility and diagnostic yield of a structured, phenotype-guided etiologic workup in adults meeting study criteria for developmental and epileptic encephalopathies and to explore associations between electro-clinical phenotype and etiologic category.
Underwent a 4-phase reassessment pathway including critical review of prior documentation, detailed clinical and semiologic phenotyping, prolonged video-EEG monitoring, phenotype-guided genetic testing (targeted resequencing, chromosomal microarray), high-resolution neuroimaging, and multidisciplinary case review to support etiologic clarification and treatment planning.
Structured diagnostic workup identified the underlying cause in 63.2% of patients.
Genetic causes predominated (65 patients, 45.1%), including monogenic (53, 36.8%) and chromosomal (12, 8.3%) disorders, primarily resolved via targeted resequencing gene panels and via chromosomal microarray analysis respectively, while structural-metabolic etiologies accounted for 26 cases (18.1%).
Etiologic clarification changed clinical management in 27.1% of the cohort, including antiseizure medication optimization/precision therapies (25%) and pre-surgical referral (2.1%).
Adults with developmental and epileptic encephalopathy (developmental and epileptic encephalopathies) often reach adult epilepsy services without a clear diagnosis.
In this study, we used a structured approach combining clinical review, video-EEG, MRI, genetic testing, and multidisciplinary discussion in 144 adults with suspected developmental and epileptic encephalopathies.
We identified a confirmed cause in 63.2% of patients. Genetic causes were the most common, but structural and metabolic causes were also important.