Clinical features and genotype-phenotype correlations in epilepsy patients with de novo DYNC1H1 variants.
Claudia CuccurulloEmanuele Cerulli IrelliLorenzo UggaAntonella RivaAlessandra D'AmicoSara CabetGaëtan LescaLeonilda BiloFederico ZaraCatrinel IliescuDiana BarcaFrance W FungKatherine L HelbigXilma Ortiz-GonzalezHelenius J SchelhaasMarjolein H WillemsenInge van der LindenCanafoglia LauraCarolina CourageSamuele GommaraschiPedro Gonzalez-AlegreTanya BardakjianSteffen SyrbeElisabeth SchulerJohannes R LemkeStella VariGitte RoendeMads BakMahbulul HuqZoe PowisKatrine Marie JohannesenTrine Bjørg HammerRikke Steensjerre MollerRachel RabinJohn PappasMary L ZupancNeda ZadehJulie CohenSakkubai NaiduIlona KreyRussell SanetoJenny ThiesLaura LicchettaPaolo TinuperFrancesca BisulliRaffaella MinardiCarolina AlvarezNathalie VilleneuveFlorence MolinariHormos Salimi DafsariBirk MollerMarie Le RouxClara HoudayerMarilena VecchiIsabella MammiElena FioriniJacopo ProiettiSofia FerriGaetano CantalupoDomenica Immacolata BattagliaMaria Luigia GambardellaIlaria ContaldoClaudia BrognaMarina TrivisanoAngela De DominicisStefania Maria BovaElena GardellaPasquale StrianoAntonietta CoppolaPublished in: Epilepsia (2024)
We propose a classification in which pathogenic de novo DYNC1H1 variants feature drug-resistant IESS in half of cases with potential evolution to LGS (Class 1), developmental and epileptic encephalopathy other than IESS and LGS (Class 2), or less severe focal or genetic generalized epilepsy including a progressive phenotype (Class 3). We observed an association between stalk domain variants and Class 1 phenotypes. The variants p.Arg309His and p.Arg1962His were common and associated with Class 1 subphenotype in our cohort. These findings may aid genetic counseling of patients with DYNC1H1-related epilepsy.