We report new genetic diagnoses of Dravet syndrome in a group of adults with complex epilepsy of unknown cause, under follow-up at a tertiary epilepsy center. Individuals with epilepsy and other features of unknown cause from our unit underwent whole-genome sequencing through the 100 000 Genomes Project. Virtual gene panels were applied to frequency-filtered variants based on phenotype summary. Of 1078 individuals recruited, 8 (0.74%) were identified to have a pathogenic or likely pathogenic variant in SCN1A. Variant types were as follows: nonsense (stopgain) in five (62.5%) and missense in three (37.5%). Detailed review of childhood history confirmed a phenotype compatible with Dravet syndrome. Median age at genetic diagnosis was 44.5 years (range 28-52 years). Tonic-clonic seizures were ongoing in all despite polytherapy including valproate. All had a history of fever sensitivity and myoclonic seizures, which were ongoing in two (25%) and three (37.5%) individuals, respectively. Salient features of Dravet syndrome may be less apparent in adulthood, making clinical diagnosis difficult. Regardless of age, benefits of a genetic diagnosis include access to syndrome-specific treatment options, avoidance of harmful drugs, and monitoring for common complications.
Late diagnoses of Dravet syndrome: How many individuals are we missing? / Silvennoinen K.; Puvirajasinghe C.; Hudgell K.; Sidhu M.K.; Martins Custodio H.; Jones W.D.; Balestrini S.; Sisodiya S.M.; Ambrose J.C.; Arumugam P.; Baple E.L.; Bleda M.; Boardman-Pretty F.; Boissiere J.M.; Boustred C.R.; Caulfield M.J.; Chan G.C.; Craig C.E.H.; Daugherty L.C.; de Burca A.; Devereau A.; Elgar G.; Foulger R.E.; Fowler T.; Furio-Tari P.; Hackett J.M.; Halai D.; Hamblin A.; Henderson S.; Holman J.E.; Hubbard T.J.P.; Ibanez K.; Jackson R.; Jones L.J.; Kasperaviciute D.; Kayikci M.; Lahnstein L.; Lawson K.; Leigh S.E.A.; Leong I.U.S.; Lopez F.J.; Maleady-Crowe F.; Mason J.; McDonagh E.M.; Moutsianas L.; Mueller M.; Murugaesu N.; Need A.C.; Odhams C.A.; Patch C.; Perez-Gil D.; Polychronopoulos D.; Pullinger J.; Rahim T.; Rendon A.; Riesgo-Ferreiro P.; Rogers T.; Ryten M.; Savage K.; Sawant K.; Scott R.H.; Siddiq A.; Sieghart A.; Smedley D.; Smith K.R.; Sosinsky A.; Spooner W.; Stevens H.E.; Stuckey A.; Sultana R.; Thomas E.R.A.; Thompson S.R.; Tucci A.; Walsh E.; Watters S.A.; Welland M.J.; Williams E.; Witkowska K.. - In: EPILEPSIA OPEN. - ISSN 2470-9239. - ELETTRONICO. - 6:(2021), pp. 770-776. [10.1002/epi4.12525]
Late diagnoses of Dravet syndrome: How many individuals are we missing?
Balestrini S.;
2021
Abstract
We report new genetic diagnoses of Dravet syndrome in a group of adults with complex epilepsy of unknown cause, under follow-up at a tertiary epilepsy center. Individuals with epilepsy and other features of unknown cause from our unit underwent whole-genome sequencing through the 100 000 Genomes Project. Virtual gene panels were applied to frequency-filtered variants based on phenotype summary. Of 1078 individuals recruited, 8 (0.74%) were identified to have a pathogenic or likely pathogenic variant in SCN1A. Variant types were as follows: nonsense (stopgain) in five (62.5%) and missense in three (37.5%). Detailed review of childhood history confirmed a phenotype compatible with Dravet syndrome. Median age at genetic diagnosis was 44.5 years (range 28-52 years). Tonic-clonic seizures were ongoing in all despite polytherapy including valproate. All had a history of fever sensitivity and myoclonic seizures, which were ongoing in two (25%) and three (37.5%) individuals, respectively. Salient features of Dravet syndrome may be less apparent in adulthood, making clinical diagnosis difficult. Regardless of age, benefits of a genetic diagnosis include access to syndrome-specific treatment options, avoidance of harmful drugs, and monitoring for common complications.
I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
