The children with T21 and IS were diagnosed and treated similarly to those patients with idiopathic IS. There were no significant differences in the age of onset, time between the onset and diagnosis of IS, or acute treatment response of IS between the T21 and control groups. However those with T21 and IS had a lower risk of subsequent epilepsy following IS than those with idiopathic IS. IS in the T21 population appears to be inherently different from IS of unknown etiology.

BACKGROUND Channelopathies are a group of monogenic disorders that affect a single ion channel and can result in neurologic disease. While a rare cause of epilepsy, channelopathies offer unique insight to the molecular basis of epilepsy and treatment opportunities. Calcium homeostasis is tightly regulated by a series of interacting subunits. CACNA1A encodes the principal pore-forming subunit of the voltage-gated P/Q-type calcium channel, alpha1. Patients with epileptic encephalopathy due to pathogenic variants in CACNA1A have been previously described and are challenging to treat. METHODS Case report of a child with epileptic encephalopathy, ataxia, cognitive impairment and significant social behavioral abnormalities due to a de novo pathogenic variant, p.S1373L in the CACNA1A gene. RESULTS After failing zonisamide and divalproex sodium, the child had a dramatic response to lamotrigine with a precipitous decrease in seizure frequency and severity. This improvement has persisted over one year. CONCLUSION While classically thought to act at sodium channels, lamotrigine also modulates the activity of the P/Q-type calcium channel, making it a candidate for precision therapy for patients with epileptic encephalopathy due to CACNA1A pathogenic variants. The rarity and clinical heterogeneity of epilepsy due to variants in CACNA1A presents challenges to clinical diagnosis. However, genetic analysis for patients with epilepsy continues to expand, additional patients are likely to be identified molecularly. Lamotrigine should be considered as a first line treatment in patients with epileptic encephalopathy due to pathogenic variants in CACNA1A.

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