Phenotype-guided etiologic workup in a prospective cohort of 144 adults with developmental and epileptic encephalopathy.

Four-phase aetiologic reassessment pathway: critical review of prior documentation, clinical and semiologic phenotyping, prolonged video-EEG and high-resolution neuroimaging, then phenotype-guided genetic testing (targeted resequencing, chromosomal microarray).

Adults with developmental and epileptic encephalopathy often reach adult neurology services without an established aetiology, because of incomplete paediatric transition, outdated investigations and attenuation of childhood electro-clinical features. The authors prospectively enrolled 144 consecutive adults (mean age 28.4 years; 57.6% male) with drug-resistant epilepsy meeting the ILAE operational definition of DEE at a tertiary epilepsy centre between May 2022 and December 2025, and applied a four-phase reassessment pathway combining review of prior documentation, semiologic phenotyping, prolonged video-EEG, high-resolution neuroimaging, phenotype-guided genetic testing and multidisciplinary case review. A confirmed aetiology was identified in 91 patients (63.2%): genetic in 65 cases (45.1%, comprising 53 monogenic disorders at 36.8% and 12 chromosomal disorders at 8.3%), resolved respectively by targeted resequencing panels and chromosomal microarray, and structural-metabolic in 26 cases (18.1%). Lennox-Gastaut syndrome was significantly associated with structural-metabolic and chromosomal aetiologies (69.2% and 58.3% versus 9.4% among monogenic cases; p < 0.0001), whereas absence seizures occurred exclusively in monogenic cases (p = 0.024). Aetiologic clarification changed clinical management in 27.1% of the cohort, through antiseizure medication optimisation or precision therapy (25%) and pre-surgical referral (2.1%).

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The figure to circulate among adult neurologists is that 27.1% of management changes: revisiting aetiology ten or fifteen years after paediatric transition is not an academic exercise. The limitation lies in the genetic strategy itself, targeted panels and chromosomal microarray with no exome or genome, so the 36.8% left without a cause reflects the ceiling of the method as much as the difficulty of the cases; in 2026 this workup should open with exome or genome sequencing. Single-centre and unreplicated, but the logic of prioritising investigations by electro-clinical phenotype transfers directly.

Analysis by Dr Thibaut Benquey