Outcomes and comorbidities of SCN1A-related seizure disorders

• Published in: Epilepsy & behavior 2019-01, Vol.90, p.252-259
• Main Authors: de Lange, Iris M., Gunning, Boudewijn, Sonsma, Anja C.M., van Gemert, Lisette, van Kempen, Marjan, Verbeek, Nienke E., Sinoo, Claudia, Nicolai, Joost, Knoers, Nine V.A.M., Koeleman, Bobby P.C., Brilstra, Eva H.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Behavioral problems; Child; Child, Preschool; Cohort Studies; Comorbidities; Comorbidity; Cross-Sectional Studies; Dravet; Epilepsies, Myoclonic - diagnosis; Epilepsies, Myoclonic - epidemiology; Epilepsies, Myoclonic - genetics; Epilepsy - diagnosis; Epilepsy - epidemiology; Epilepsy - genetics; Epileptic Syndromes - diagnosis; Epileptic Syndromes - epidemiology; Epileptic Syndromes - genetics; Female; GEFS; Humans; Male; Middle Aged; NAV1.1 Voltage-Gated Sodium Channel - genetics; Quality of Life; Retrospective Studies; SCN1A; Seizures, Febrile - diagnosis; Seizures, Febrile - epidemiology; Seizures, Febrile - genetics; Spasms, Infantile - diagnosis; Spasms, Infantile - epidemiology; Spasms, Infantile - genetics; Surveys and Questionnaires; Treatment Outcome; Young Adult
• ISSN: 1525-5050; 1525-5069
• DOI: 10.1016/j.yebeh.2018.09.041

Differentiating between Dravet syndrome and non-Dravet SCN1A-related phenotypes is important for prognosis regarding epilepsy severity, cognitive development, and comorbidities. When a child is diagnosed with genetic epilepsy with febrile seizures plus (GEFS+) or febrile seizures (FS), accurate prognostic information is essential as well, but detailed information on seizure course, seizure freedom, medication use, and comorbidities is lacking for this milder patient group. In this cross-sectional study, we explore disease characteristics in milder SCN1A-related phenotypes and the nature, occurrence, and relationships of SCN1A-related comorbidities in both patients with Dravet and non-Dravet syndromes. A cohort of 164 Dutch participants with SCN1A-related seizures was evaluated, consisting of 116 patients with Dravet syndrome and 48 patients with either GEFS+, febrile seizures plus (FS+), or FS. Clinical data were collected from medical records, semi-structured telephone interviews, and three questionnaires: the Functional Mobility Scale (FMS), the Pediatric Quality of Life Inventory (PedsQL) Measurement Model, and the Child or Adult Behavior Checklists (CBCL/ABCL). Walking disabilities and severe behavioral problems affect 71% and 43% of patients with Dravet syndrome respectively and are almost never present in patients with non-Dravet syndromes. These comorbidities are strongly correlated to lower quality-of-life (QoL) scores. Less severe comorbidities occur in patients with non-Dravet syndromes: learning problems and psychological/behavioral problems are reported for 27% and 38% respectively. The average QoL score of the non-Dravet group was comparable with that of the general population. The majority of patients with non-Dravet syndromes becomes seizure-free after 10 years of age (85%). Severe behavioral problems and walking disabilities are common in patients with Dravet syndrome and should receive specific attention during clinical management. Although the epilepsy course of patients with non-Dravet syndromes is much more favorable, milder comorbidities frequently occur in this group as well. Our results may be of great value for clinical care and informing newly diagnosed patients and their parents about prognosis. •Walking disabilities and severe behavioral problems are specific for Dravet syndrome and can already occur between 4-7 years of age.•These comorbidities should receive specific attention during clinical management.•A substantial part of n