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This study was designed to describe the spectrum of epilepsy phenotypes in Koolen-de Vries syndrome (KdVS), a genetic syndrome involving dysmorphic features, intellectual disability, hypotonia, and congenital malformations, that occurs secondary to 17q21.31 microdeletions and heterozygous mutations in KANSL1.

We were invited to attend a large gathering of individuals with KdVS and their families. While there, we recruited individuals with KdVS and seizures, and performed thorough phenotyping. Additional subjects were included who approached us after the family support group brought attention to our research via social media. Inclusion criteria were genetic testing results demonstrating 17q21.31 deletion or KANSL1 mutation, and at least one seizure.

Thirty-one individuals were studied, aged 2–35 years. Median age at seizure onset was 3.5 years, and 9 of 22 had refractory seizures 2 years after onset. Focal impaired awareness seizures were the most frequent seizure type occurring in 20 of 31, usually with prominent autonomic features. Twenty-one patients had prolonged seizures and, at times, refractory status epilepticus. Electroencephalography (EEG) showed focal/multifocal epileptiform discharges in 20 of 26. MRI studies of 13 patients were reviewed, and all had structural anomalies. Corpus callosum dysgenesis, abnormal hippocampi, and dilated ventricles were the most common, although periventricular nodular heterotopia, focal cortical dysplasia, abnormal sulcation, and brainstem and cerebellum abnormalities were also observed. One patient underwent epilepsy surgery for a lesion that proved to be an angiocentric glioma.

The typical epilepsy phenotype of KdVS involves childhood-onset focal seizures that are prolonged and have prominent autonomic features. Multifocal epileptiform discharges are the typical EEG pattern. Structural brain abnormalities may be universal, including signs of abnormal neuroblast migration and abnormal axonal guidance. Epilepsy surgery should be undertaken with care given the widespread neuroanatomic abnormalities; however, tumors are a rare, yet important, occurrence.