PT  - JOURNAL ARTICLE
AU  - Balagura, Ganna
AU  - Xian, Julie
AU  - Riva, Antonella
AU  - Marchese, Francesca
AU  - Ben Zeev, Bruria
AU  - Rios, Loreto
AU  - Sirsi, Deepa
AU  - Accorsi, Patrizia
AU  - Amadori, Elisabetta
AU  - Astrea, Guja
AU  - Baldassari, Simona
AU  - Beccaria, Francesca
AU  - Boni, Antonella
AU  - Budetta, Mauro
AU  - Cantalupo, Gaetano
AU  - Capovilla, Giuseppe
AU  - Cesaroni, Elisabetta
AU  - Chiesa, Valentina
AU  - Coppola, Antonietta
AU  - Dilena, Robertino
AU  - Faggioli, Raffaella
AU  - Ferrari, Annarita
AU  - Fiorini, Elena
AU  - Madia, Francesca
AU  - Gennaro, Elena
AU  - Giacomini, Thea
AU  - Giordano, Lucio
AU  - Iacomino, Michele
AU  - Lattanzi, Simona
AU  - Marini, Carla
AU  - Mancardi, Maria Margherita
AU  - Mastrangelo, Massimo
AU  - Messana, Tullio
AU  - Minetti, Carlo
AU  - Nobili, Lino
AU  - Papa, Amanda
AU  - Parmeggiani, Antonia
AU  - Pisano, Tiziana
AU  - Russo, Angelo
AU  - Salpietro, Vincenzo
AU  - Savasta, Salvatore
AU  - Scala, Marcello
AU  - Accogli, Andrea
AU  - Scelsa, Barbara
AU  - Scudieri, Paolo
AU  - Spalice, Alberto
AU  - Specchio, Nicola
AU  - Trivisano, Marina
AU  - Tzadok, Michal
AU  - Valeriani, Massimiliano
AU  - Vari, Maria Stella
AU  - Verrotti, Alberto
AU  - Vigevano, Federico
AU  - Vignoli, Aglaia
AU  - Toonen, Ruud
AU  - Zara, Federico
AU  - Helbig, Ingo
AU  - Striano, Pasquale
TI  - Epilepsy Course and Developmental Trajectories in <em>STXBP1</em>-DEE
AID  - 10.1212/NXG.0000000000000676
DP  - 2022 Jun 01
TA  - Neurology Genetics
PG  - e676
VI  - 8
IP  - 3
4099  - http://ng.neurology.org/content/8/3/e676.short
4100  - http://ng.neurology.org/content/8/3/e676.full
SO  - Neurol Genet2022 Jun 01; 8
AB  - Background and Objectives Clinical manifestations in STXBP1 developmental and epileptic encephalopathy (DEE) vary in severity and outcome, and the genotypic spectrum is diverse. We aim to trace the neurodevelopmental trajectories in individuals with STXBP1-DEE and dissect the relationship between neurodevelopment and epilepsy.Methods Retrospective standardized clinical data were collected through international collaboration. A composite neurodevelopmental score system compared the developmental trajectories in STXBP1-DEE.Results Forty-eight patients with de novo STXBP1 variants and a history of epilepsy were included (age range at the time of the study: 10 months to 35 years, mean 8.5 years). At the time of inclusion, 65% of individuals (31/48) had active epilepsy, whereas 35% (17/48) were seizure free, and 76% of those (13/17) achieved remission within the first year of life. Twenty-two individuals (46%) showed signs of developmental impairment and/or neurologic abnormalities before epilepsy onset. Age at seizure onset correlated with severity of developmental outcome and the developmental milestones achieved, with a later seizure onset associated with better developmental outcome. In contrast, age at seizure remission and epilepsy duration did not affect neurodevelopmental outcomes. Overall, we did not observe a clear genotype-phenotype correlation, but monozygotic twins with de novo STXBP1 variant showed similar phenotype and parallel disease course.Discussion The disease course in STXBP1-DEE presents with 2 main trajectories, with either early seizure remission or drug-resistant epilepsy, and a range of neurodevelopmental outcomes from mild to profound intellectual disability. Age at seizure onset is the only epilepsy-related feature associated with neurodevelopment outcome. These findings can inform future dedicated natural history studies and trial design.ASM=antiseizure medication; DEE=developmental and epileptic encephalopathy; FCD=focal cortical dysplasia; ID=intellectual disability