A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Developmental epileptic encephalopathy in DLG4-related synaptopathy
Tekijät: Kassabian Benedetta, Levy Amanda M., Gardella Elena, Aledo-Serrano Angel, Ananth Amitha L., Brea-Fernández Alejandro J., Caumes Roseline, Chatron Nicolas, Dainelli Alice, De Wachter Matthias, Denommé-Pichon Anne-Sophie, Dye Thomas J., Fazzi Elisa, Felt Roxanne, Fernández-Jaén Alberto, Fernández-Prieto Montserrat, Gantz Emily, Gasperowicz Piotr, Gil-Nagel Antonio, Gómez-Andrés David, Greiner Hansel M., Guerrini Renzo, Haanpää Maria K., Helin Minttu, Hoyer Juliane, Hurst Anna C. E., Kallish Staci, Karkare Shefali N., Khan Amjad, Kleinendorst Lotte, Koch Johannes, Kothare Sanjeev V., Koudijs Suzanna V., Lagae Lieven, Lakeman Phillis, Leppig Kathleen A., Lesca Gaetan, Lopergolo Diego, Lusk Laina, Mackenzie Alex, Mei Davide, Møller Rikke S., Pereira Elaine M., Platzer Konrad, Quelin Chloe, Revah-Politi Anya, Rheims Sylvain, Rodríguez-Palmero Agustí, Rossi Andrea, Santorelli Filippo, Seinfeld Syndi, Sell Erick, Stephenson Donna, Szczaluba Krzysztof, Trinka Eugen, Umair Muhammad, Van Esch Hilde, van Haelst Mieke M., Veenma Danielle C. M., Weber Sacha, Weckhuysen Sarah, Zacher Pia, Tümer Zeynep, Rubboli Guido
Julkaisuvuosi: 2023
Journal: Epilepsia
Tietokannassa oleva lehden nimi: Epilepsia
Lehden akronyymi: Epilepsia
ISSN: 0013-9580
eISSN: 1528-1167
DOI: https://doi.org/10.1111/epi.17876
Verkko-osoite: https://onlinelibrary.wiley.com/doi/10.1111/epi.17876
Objective
The postsynaptic density protein of excitatory neurons PSD-95 is encoded by DLG4, de novo pathogenic variants of which lead to DLG4-related synaptopathy. The major clinical features are developmental delay, intellectual disability (ID), hypotonia, sleep disturbances, movement disorders, and epilepsy. Even though epilepsy is present in 50% of the individuals, it has not been investigated in detail. We describe here the phenotypic spectrum of epilepsy and associated comorbidities in patients with DLG4-related synaptopathy.
Methods
We included 35 individuals with a DLG4 variant and epilepsy as part of a multicenter study. The DLG4 variants were detected by the referring laboratories. The degree of ID, hypotonia, developmental delay, and motor disturbances were evaluated by the referring clinician. Data on awake and sleep EEG and/or video-polygraphy and brain MRI were collected. Anti-seizure medication response was retrospectively assessed by the referring clinician.
Results
A large variety of seizure types was reported, though focal seizures were the most common. Encephalopathy related to status epilepticus during slow sleep (ESES)/developmental epileptic encephalopathy with spike-wave activation during sleep (DEE-SWAS) was diagnosed in more than 25% of the individuals. All but one individual presented with neurodevelopmental delay. Regression in verbal and/or motor domains was observed in all individuals who suffered from ESES/DEE-SWAS, as well as some who did not. We could not identify a clear genotype-phenotype relationship even between individuals with the same DLG4 variants.
Significance
Our study shows that a subgroup of individuals with DLG4-related synaptopathy has DEE, and around one fourth of them have ESES/DEE-SWAS. Our study confirms DEE as part of the DLG4-related phenotypic spectrum. Occurrence of ESES/DEE-SWAS in DLG4-related synaptopathy requires to be properly investigated with sleep EEG.
