Severe myoclonic epilepsy (Dravet syndrome)

Severe myoclonic epilepsy (SMEI or Dravet syndrome) is an epilepsy syndrome beginning in infancy (usually in the first year of life) with generalized or unilateral febrile clonic seizure which tend to be prolonged. After the first year of life, seizures also appear without fever, although the precipitating role of fever or high body temperature is still present in older children. Myoclonic jerks, absence and partial seizures appear subsequently in most children. Episodes of status epilepticus or seizures in clusters are often observed. The interictal EEG does not show a highly characteristic pattern. However, generalized spike and wave discharges and early photosensitivity can be present and be associated with focal or multifocal abnormalities. Brain imaging is usually normal. Cognitive and psychomotor development, initially normal, tend to be retarded from the second year of life.
Most children have frequent seizures and severe cognitive problems, however, some may present with an attenuated form of the disorder and be mildly impaired (borderline SMEI or SMEB). Treatment with antiepileptic drugs is scarcely effective, although some associations of drugs have significantly reduced seizure frequency. No alternative treatment has shown any definite efficacy. About 80% of patients show a mutation or deletion of the sodium channel alpha 1 subunit (SCN1A) gene. SCN1A  is the most relevant epilepsy gene with the largest number of epilepsy-related mutations so far identified. The high correlation between SMEI/SMEB and SCN1A mutations suggests a phenotypic specificity of SCN1A. The high rate of epilepsy in families of probands with SMEI suggests that, in addition to SCN1A  mutations, other genetic factors might play a role in the expression of the epilepsy phenotypes. SCN1A mosaic mutations should also be taken into account, at least in some cases, as a possible explanation for familial phenotypic variability. What causes SMEI when there is no detectable SCN1A  involvement remains to be identified.

We  have characterized  mutations and genomic abnormalities and established phenotype genotype correlations  in a large series of patients and identified familial SMEI in relation to inherited mosaic mutations. We are continuing to enroll patients/families with SMEI or SMEB in our clinical research unit to continue these studies and establish the yield of new diagnostic methods.

If you have a child who you think may have this condition and you would like us to review the diagnosis or provide genetic testing please contact us at neuroscience@meyer.it.