Clinical characteristics: SCN8A-related epilepsy with encephalopathy is characterized by developmental delay, seizure onset in the first 18 months of life (mean 4 months), and intractable epilepsy characterized by multiple seizure types (generalized tonic-clonic seizures, infantile spasms, and absence and focal seizures). Epilepsy syndromes can include Lennox-Gastaut syndrome, West syndrome, and epileptic encephalopathies (e.g., Dravet syndrome). Hypotonia and movement disorders including dystonia, ataxia, and choreoathetosis are common. Psychomotor development varies from normal prior to seizure onset (with subsequent slowing or regression after seizure onset) to abnormal from birth. Intellectual disability, present in all, ranges from mild to severe (in ~50% of affected individuals). Autistic features are noted in some. Sudden unexpected death in epilepsy (SUDEP) of unknown cause has been reported in approximately 10% of published cases. To date SCN8A-related epilepsy with encephalopathy has been reported in the literature in about 50 individuals.
Diagnosis/testing: The diagnosis is established in a proband with encephalopathy and epilepsy and identification of a de novo pathogenic variant in SCN8A on molecular genetic testing.
Management: Treatment of manifestations: Seizure control should be managed by a pediatric neurologist with expertise in epilepsy management who is familiar with the pharmacotherapy for SCN8A-related epilepsy with encephalopathy and aware of how it differs from treatment of similar disorders. Vigorous attempts to control seizures are warranted. Several studies suggest a favorable response to sodium channel blockers.
Surveillance: Periodic evaluation for neurologic, cognitive, and/or behavioral deterioration; monitoring with EEG and other modalities such as video EEG telemetry or ambulatory EEG when new or different seizure types are suspected. Because of the increased risk of SUDEP, some families use oxygen monitoring during sleep.
Agents/circumstances to avoid: Several families of affected individuals report worsening of seizures with levetiracetam.
Genetic counseling: SCN8A-related epilepsy with encephalopathy is expressed in an autosomal dominant manner. Most affected individuals have a de novo pathogenic variant and typically do not reproduce. While the risk to future pregnancies is presumed to be low, some parents of an affected child may wish to consider prenatal testing or preimplantation genetic testing in future pregnancies as the risk may be slightly greater than in the general population because of the possibility of parental germline mosaicism.
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