Clinical Guidance

The natural history of SCN1A seizure disorders is strongly influenced by seizure phenotype, which can range from simple febrile seizures and generalized epilepsy with febrile seizures plus (GEFS+) at the mild end to Dravet syndrome and intractable childhood epilepsy with generalized tonic-clonic seizures (ICE-GTC) at the severe end [, , , ]. The phenotype varies even among family members with the same pathogenic variant . As a result of this variable expressivity, long-term prognosis is difficult to determine. Features associated with poor cognitive outcome include early myoclonic and absence seizures . Phenotypes with intractable seizures (e.g., Dravet syndrome) usually cause epileptic encephalopathy, a form of progressive dementia.

Source: GeneReviews — "SCN1A Seizure Disorders"

Differential Diagnosis

The phenotypes typically seen in individuals with an SCN1A pathogenic variant are neither necessary nor sufficient to diagnose an SCN1A seizure disorder. Other conditions (including those caused by pathogenic variants in other genes) may be associated with the same phenotypes. It is most important to distinguish SCN1A seizure disorders from potentially treatable conditions, including the following :

Source: GeneReviews — "SCN1A Seizure Disorders"

Clinical Guidance

Several ASMs that are effective for most forms of epilepsy can worsen SCN1A-related seizures:

• Carbamazepine, lamotrigine, and vigabatrin, which can induce or increase myoclonic seizures

• Phenytoin, which may worsen seizures and can induce choreoathetosis

• Rufinamide, which has a pharmacologic mechanism similar to carbamazepine and phenytoin and may exacerbate seizures as well

• Acetaminophen, which is hepatotoxic in overdose. Given the possibility of interaction with anticonvulsant medications, especially valproate and topiramate , acetaminophen should be avoided. Any of the NSAIDs are effective as antipyretics, and represent much lower risk.

Activities in which a sudden loss of consciousness could lead to injury or death should be avoided (e.g., bathing, swimming, driving, or working/playing at heights).

Source: GeneReviews — "SCN1A Seizure Disorders"

Therapies Under Investigation

Thalamic deep brain stimulation (DBS) was reported by in two children with Dravet syndrome with ten-year follow up. One showed "marked improvement" after implantation, whereas the other received no benefit. Lacosamide has not been studied in SCN1A seizure disorders; however, there are theoretic reasons why it may be effective . Verapamil was reported to help two girls with severe epilepsy resulting from SCN1A pathogenic variants ; however, it has not been formally studied. Search ClinicalTrials.gov in the US for access to information on clinical studies for SCN1A seizure disorders and a wide range of other diseases and conditions. Search EU Clinical Trials Register in Europe.

Source: GeneReviews — "SCN1A Seizure Disorders"