Abstracts

Rationale: FOXG1-related disorders are associated with severe intellectual disability, absent speech with autistic features, and epilepsy. Children with deletions or intragenic mutations of FOXG1 also have microcephaly, abnormalities of the corpus callosum, and choreiform movements on occasion. Epilepsy has diagnosed in 87% of the affected subjects. Intractable epilepsy was found in a significant number of patients, intractability with severe seizures has been found and response to anti-epileptic medication has been erratic. We wanted to describe the response of 2 previously intractable cases considered to epilepsy palliative surgery in our center and their response to different anti-epileptic medications (AED).

Methods: All subjects had either chromosomal microarray or FOXG1 gene sequencing performed. Development and epilepsy follow-up data was collected from medical records. Given the common occurrence of infantile spasms in children with FOXG1 duplications, the mean age of epilepsy diagnosis was in the first year of life. We evaluated the AED's utilized on their medical records and the response to each one of them in relation to significant seizure reduction. Of all the medications utilized we looked for those that were associated with more than 70 percent in seizure reduction for at least 6 months of follow up.

Results: The medications used in the patients were levatiracetam, topiramate, clobazam, clonazepam, oxcarbazepine, valproic acid, vigabatrin, lamotrigine, and rufinamide. More than 2 AED were used before the first year of life. In the 2 patients studied at least 7 medications were administered, no worsening of seizure frequency was reported. Of the cases followed only 2 AED made them seizure free for more than 6 months with a significant reduction of more than 70 percent. In all the cases the brain imaging findings were similar to those previously reported for FOXG1-related disorders, consistent with frontal lobe and corpus callosum abnormalities. Despite infantile spasms past seizure history, no ACTH was given early in life.

Conclusions: The epilepsy in patients with FOXG1-related disorders is often intractable, and starts in the first year of life. In the patients affected imaging is frequently abnormal, presentation with infantile spasms is usually found. Response to therapy is usually erratic and non sustained.
We conclude that Vigabatrin and Felbamate were the only medications that resulted in seizure reductions of more than 70 percent in patients with FOX1G-related disorders. A large sample of patients is needed to reinforce the described results.

Funding: None.