Abstract
PurposeDifferentiating 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. MethodsA 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). ResultsWalking 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%). ConclusionsSevere 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.
Highlights
Pathogenic variants in SCN1A can cause several different epilepsy syndromes, with varying disease severities [1,2,3,4,5]
The Dravet syndrome subgroup consisted of 116 patients belonging to 112 different families, and the non-Dravet group consisted of 48 patients belonging to 28 different families
Behavioral problems in the clinical range were most frequently seen between 4 and 11 years of age, when assessed by CBCL/Adult Behavior Checklist 18–59 years (ABCL) questionnaires. This is in contrast to previous studies that have found an increase of behavioral problems with age [7,19]
Summary
Pathogenic variants in SCN1A can cause several different epilepsy syndromes, with varying disease severities [1,2,3,4,5]. The most common and severe associated condition is Dravet syndrome, which is characterized by intractable epileptic seizures and a slowing of the psychomotor development in the second year of life, which results in mild to severe intellectual disability (ID). Milder phenotypes include genetic epilepsy with febrile seizures plus (GEFS +) syndrome and febrile seizures (FS and febrile seizures plus (FS+)), in which usually no ID is present, and the epilepsy has a milder course [4,10]. The majority of school-aged, adolescent, and adult patients with SCN1Arelated disease can be classified as having Dravet syndrome or not, these different phenotypes may have a similar presentation at onset [11,12].
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