Clinical Guidance

SCN3A-related neurodevelopmental disorder (SCN3A-NDD) encompasses a spectrum of clinical severity associated with epilepsy and/or malformation of cortical development (MCD). Affected individuals may have developmental and epileptic encephalopathy (DEE) (i.e., intractable seizures with developmental delays associated with ongoing epileptiform EEG activity) with or without MCD, or MCD with or without mild focal epilepsy. To date, 38 individuals from 31 families have been identified with a pathogenic variant in SCN3A [, , , , , , , , , , ]. The following summarizes the clinical findings in these individuals. Table 2. Select Features of SCN3A-Related Neurodevelopmental Disorder

Source: GeneReviews — "SCN3A-Related Neurodevelopmental Disorder"

Differential Diagnosis

The phenotype(s) observed in SCN3A-related neurodevelopmental disorder (SCN3A-NDD) are not sufficient to diagnose an SCN3A-NDD without genetic testing, as other conditions may be associated with clinical features and neuroimaging findings within the same range of phenotypes. Epilepsy. The epilepsy phenotype of SCN3A-NDD cannot be definitively distinguished from other causes of early-infantile epileptic encephalopathies (80 genetic causes have been identified; see OMIM Phenotypic Series). Malformation of cortical development (MCD). A key element of the differential diagnosis is to distinguish SCN3A-NDD from other causes of MCD as these may be associated with a different clinical course and/or mode of inheritance. Other causes of MCD include:

Source: GeneReviews — "SCN3A-Related Neurodevelopmental Disorder"

Clinical Guidance

There is NO evidence that:

• Specific anti-seizure medications can worsen seizures associated with SCN3A-NDD;

• Sleep deprivation or fever exacerbates seizures associated with SCN3A-NDD.

Source: GeneReviews — "SCN3A-Related Neurodevelopmental Disorder"

Therapies Under Investigation

Therapeutic trials of anti-seizure medications that target sodium channels may be indicated in cases of severe, treatment-resistant epilepsy or epileptic encephalopathy associated with SCN3A-NDD based on theoretic considerations [, , , ]. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "SCN3A-Related Neurodevelopmental Disorder"