Children with SCN2A-associated infantile epileptic encephalopathy (IEE)
Infantile epileptic encephalopathy (IEE) generally presents with seizures in the neonatal period but seizure onset after 3 months is also possible (20–40% of cases). The type of seizures varies a lot depending on the case, and very often more than one type of seizure is observed. Depending on how early seizure onset is, different syndromes are given to the patients – Ohtahara for the earliest age of seizure onset or epilepsy of infancy with migrating focal seizures; West syndrome for onset after 3 months; Lennox–Gastaut syndrome for multiple seizure types in older children.
Developmental delay can be between moderate to severe, often together with comorbidities like hypotonia, microcephaly, cerebral and/or cerebellar atrophy, cortical visual impairment and movement disorders (dystonia, chorea or episodic ataxia).
In general, these children show a gain-of-function in the sodium channel.
Children with SCN2A-associated autism spectrum disorder (ASD)/intellectual Disability (ID)
Children with ASD/ID generally show a normal early development (up to about 6 months of age). Then, motor and verbal delay follow, and some children develop seizures with 1-2 to 4 years, which may bring more relevant developmental delay, especially if the seizures are severe.
These children seem to share several behavioural characteristics: placid and enjoying physical contact; repeating actions like chewing objects or hand gestures; rarely initiating social interactions or making eye contact; avoiding hand contact with people or novel objects. Motor skills seem to be less delayed than social skills. Hypotonia, high pain threshold, increased sensitivity to heat, cortical visual impairment, disrupted sleep and gastrointestinal issues are other comorbidities.
In general, these children show a loss-of-function in the sodium channel.
Text based on learnings from: Progress in Understanding and Treating
SCN2A-Mediated Disorders, Sanders, Stephan J. & Co.; Trends in Neurosciences, July 2018, Vol. 41, No. 7