Rober, Ann-Kathrin (2025) A multi-centre analysis of the genotype-phenotype correlation in patients with Dravet syndrome and an SCN1A mutation. thesis, Medicine.
Full text available on request.Abstract
Dravet syndrome (DS) is a severe genetic epileptic encephalopathy predominantly caused by SCN1A mutations, characterised by refractory seizures and a highly heterogeneous disease course. While previous studies suggest that truncating mutations are linked to a more severe phenotype, recent evidence indicates that missense mutation localisation within SCN1A may also play a critical role. This study investigates genotype-phenotype correlations in DS and the impact of genotype on antiseizure medication effectiveness. Data from 51 included patients were collected using a standardised questionnaire. We explored relationships between mutation type (missense vs. truncating), localisations of missense mutations, clinical parameters and effectiveness of antiseizure medications. No statistically significant correlation between genotype and phenotype or medication response was found. However, a trend suggested that patients with missense mutations experienced an earlier median seizure onset than those with truncating mutations (4 months vs. 5 months, p = 0.066), had more epileptic states in the first year of life (8 vs. 5, p = 0.058), and required more antiseizure medications (3 vs. 2, p = 0.056). An explanation for this trend may be that 69% of the missense mutations were located in the pore-forming regions (S5-S6) of the SCN1A protein, previously linked to earlier seizure onset and more severe phenotypes. Although statistical significance was not reached, these findings suggest that mutation localisation within SCN1A may be more relevant for disease severity than mutation type alone. Future studies with larger cohorts are needed to confirm these observations and improve prognostic models in DS.
| Item Type: | Thesis (UNSPECIFIED) |
|---|---|
| Supervisor name: | Muhle, Prof. Dr. H. and Portier, Drs. R.P. |
| Faculty: | Medical Sciences |
| Date Deposited: | 29 Apr 2026 12:31 |
| Last Modified: | 29 Apr 2026 12:31 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/3937 |
Actions (login required)
 |
View Item |