Prognostic, clinical and demographic features in SCN1A mutation-positive Dravet syndrome
Top Cited Papers
Open Access
- 18 June 2012
- journal article
- research article
- Published by Oxford University Press (OUP) in Brain
- Vol. 135 (8), 2329-2336
- https://doi.org/10.1093/brain/aws151
Abstract
Dravet syndrome is a severe infantile onset epileptic encephalopathy associated with mutations in the sodium channel alpha 1 subunit gene SCN1A. To date no large studies have systematically examined the prognostic, clinical and demographic features of the disease. We prospectively collected data on a UK cohort of individuals with Dravet syndrome during a 5-year study period and analysed demographic information based on UK population and birth figures. From structured referral data we examined a range of clinical characteristics including epilepsy phenotype, seizure precipitants, electroencephalography data, imaging studies, mutation class and response to medication. Predictors of developmental outcome were determined by logistic regression. We identified 241 cases with SCN1A mutation-positive Dravet syndrome, 207 of which were UK-based. The incidence of mutation-positive Dravet syndrome is at least 1:40 900 UK births. Clinical features predicting a worse developmental outcome included status epilepticus (odds ratio = 3.1; confidence interval = 1.5–6.3; P = 0.003), interictal electroencephalography abnormalities in the first year of life (odds ratio = 5.7; confidence interval = 1.9–16.8; P = 0.002) and motor disorder (odds ratio = 3.3; confidence interval = 1.7–6.4; P < 0.001). No significant effect was seen for seizure precipitants, magnetic resonance imaging abnormalities or mutation class (truncating versus missense). Abnormal magnetic resonance imaging was documented in 11% of cases, principally with findings of non-specific brain atrophy or hippocampal changes. Sodium valproate, benzodiazepines and topiramate were reported as being the most helpful medications at the time of referral. Aggravation of seizures was reported for carbamazepine and lamotrigine. The identification of factors influencing prognosis both aids counselling and encourages early, syndrome-specific therapy. Prevention of status epilepticus with regular medication and emergency protocols is important and may influence developmental outcome.Keywords
This publication has 39 references indexed in Scilit:
- Dravet syndrome as epileptic encephalopathy: evidence from long-term course and neuropathologyBrain, 2011
- Comorbidities and predictors of health‐related quality of life in Dravet syndromeEpilepsia, 2011
- Unusual consequences of status epilepticus in Dravet syndromeSeizure, 2010
- TheSCN1Avariant database: a novel research and diagnostic toolHuman Mutation, 2009
- Sporadic Infantile Epileptic Encephalopathy Caused by Mutations in PCDH19 Resembles Dravet Syndrome but Mainly Affects FemalesPLoS Genetics, 2009
- Spectrum of SCN1A gene mutations associated with Dravet syndrome: analysis of 333 patientsJournal of Medical Genetics, 2008
- De-novo mutations of the sodium channel gene SCN1A in alleged vaccine encephalopathy: a retrospective studyThe Lancet Neurology, 2006
- Severe myoclonic epilepsy in infancy: toward an optimal treatment.Journal of Child Neurology, 2004
- De Novo Mutations in the Sodium-Channel Gene SCN1A Cause Severe Myoclonic Epilepsy of InfancyAmerican Journal of Human Genetics, 2001
- Lamotrigine and Seizure Aggravation in Severe Myoclonic EpilepsyEpilepsia, 1998