Dravet syndrome: patients with co-morbid SCN1A gene mutations and mitochondrial electron transport chain defects

Abstract

Purpose: To review our cohort of patients with Dravet syndrome and determine if patients with SCN1A mutations can also express mitochondrial disease due to electron transport chain dysfunction.

Methods: A retrospective chart review was used to describe clinical manifestations and retrieve biochemical testing, neuroimaging, gene sequencing, and electroencephalographic results of patients expressing both mitochondrial disease and Dravet syndrome.

Results: Two children were found to have pathological mutations in the SCN1A gene and defects in mitochondrial electron transport chain complex activity. Both developed early febrile and medically intractable afebrile seizures with resulting neurocognitive decline. In the first patient, a muscle biopsy demonstrated complex IV dysfunction and in the second patient, complex III dysfunction. Patient 1 had more difficult to control seizures, and had features consistent with severe autism. Patient 2, who had earlier control and less severe seizures, did not have features of autism. Patient 1 had SCN1A missense mutation, c. 3734 G>A and patient 2 had a mutation, c. 3733 C>T, which produces a truncation mutation.

Conclusion: Our two patients underscore the need to rule out possible co-morbid mitochondrial disease and Dravet syndrome. The treatment of seizures for each is different, with valproic acid being first line treatment in Dravet syndrome and contraindicated in many mitochondrial diseases, due to possible induction of liver failure and death. Failure to pursue complete diagnostic evaluation might influence medication choice, possible seizure control, and developmental outcomes.