Abstract Details

SCN1A mutations were first identified as an underlying cause of epilepsy in 2001. The gene codes for the alpha subunit of the voltage gated sodium channels, which are responsible for the creation and propagation of action potentials throughout the nervous system. A loss-of-function mutation in SCN1A is commonly known for causing Dravet syndrome, a form of epilepsy in which children have refractory seizures beginning in the first 1-2 years of life. The mutation seen in Dravet syndrome is believed to cause a complete loss of function in the sodium channel’s inhibitory circuitry in GABAergic interneurons as well as reduced expression on the plasma membrane. This leads to an imbalance of inhibitory to excitatory neurotransmission and thus a hyperexcitable state and higher risk of seizures. Due to this, it is advised to avoid sodium channel blocking antiepileptics as they can exacerbate symptoms by further inhibiting the remainder of the functioning sodium channels.

We describe a case in which an SCN1A missense mutation of unknown significance was found, however the patient did not exhibit typical Dravet syndrome characteristics and showed response to the typically avoided sodium channel blocking antiepileptics. 

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Due to initial poor treatment response, it was suggested that our patient’s mutation may have resulted in a gain-of-function. Treatment with sodium channel blocking epileptics were initiated and our patient showed improvements in seizure frequency.

This case further demonstrates the variability of SCN1A mutations that occur in infantile epilepsy syndromes and the importance of considering alternative treatment options in patients with mutations of unknown significance.