Prognostic, clinical and demographic features in SCN1A mutation-positive Dravet syndrome

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.

Quality of life and comorbidities associated with Dravet syndrome severity: a multinational cohort survey

“…The proportion of patients reporting a diagnosis of autism, ADHD, other behavioural problems or learning disabilities aligns with those reported by Brunklaus et al for a cohort of 241 patients with SCN1A mutation-positive Dravet syndrome. 13,14 However, the proportion with motor impairments (including ataxia) was higher than described by others, 14 and may be owing to the difference between parents' perceptions and clinical criteria applied by the authors. Similar to the study findings of Brunklaus et al, 13,14 the proportion of patients reporting each comorbidity increased with age, although these plateaued or even decreased in adults for diagnoses of autism (51% in adolescents, 38% in adults), ADHD (22% in adolescents and 19% in adults), or other behavioural problems (55% in adolescents and 51% in adults) (Table II), possibly reflecting a difference in the cohort makeup (age distribution was not reported in Brunklaus et al 13 ).…”

“…13,14 However, the proportion with motor impairments (including ataxia) was higher than described by others, 14 and may be owing to the difference between parents' perceptions and clinical criteria applied by the authors. Similar to the study findings of Brunklaus et al, 13,14 the proportion of patients reporting each comorbidity increased with age, although these plateaued or even decreased in adults for diagnoses of autism (51% in adolescents, 38% in adults), ADHD (22% in adolescents and 19% in adults), or other behavioural problems (55% in adolescents and 51% in adults) (Table II), possibly reflecting a difference in the cohort makeup (age distribution was not reported in Brunklaus et al 13 ). Dravet syndrome exhibits a range of severities in terms of seizure frequency and comorbidities, 15 and there is evidence that in addition to the SCN1A phenotype, 5 the magnitude of cognitive and behavioural impairment in Dravet syndrome is related to seizure frequency.…”

The role of focal versus generalized epilepsy classification and EEG features on antiepileptic drug choice

“…Lamotrijin JME'de etkili bir ilaç olmakla birlikte bazı epilepsilerde miyoklonileri artırmaktadır. [10,11] Lamotirijinin Doose sendromunda etkisinin sendrom spesifik olduğuna dikkati çekilmektedir. [12] Vigabatrin özellikle tubero skleroz ile ilişkili West sendromunda gündemdedir.…”

Pitfalls in genetic testing: the story of missed SCN1A mutations

“…During the second year of life however, developmental delay and other neurological defects become apparent (Brunklaus et al. 2012). …”