Premium
The epileptology of Koolen‐de Vries syndrome: Electro‐clinico‐radiologic findings in 31 patients
Author(s) -
Myers Kenneth A.,
Mandelstam Simone A.,
Ramantani Georgia,
Rushing Elisabeth J.,
Vries Bert B.,
Koolen David A.,
Scheffer Ingrid E.
Publication year - 2017
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.13746
Subject(s) - epilepsy , cortical dysplasia , corpus callosum , medicine , epileptic spasms , pediatrics , electroencephalography , status epilepticus , polymicrogyria , seizure types , hypotonia , dysgenesis , psychology , pathology , anatomy , psychiatry
Summary Objective This study was designed to describe the spectrum of epilepsy phenotypes in Koolen‐de Vries syndrome (Kd VS ), a genetic syndrome involving dysmorphic features, intellectual disability, hypotonia, and congenital malformations, that occurs secondary to 17q21.31 microdeletions and heterozygous mutations in KANSL 1 . Methods We were invited to attend a large gathering of individuals with Kd VS and their families. While there, we recruited individuals with Kd VS 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 KANSL 1 mutation, and at least one seizure. Results 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. Significance The typical epilepsy phenotype of Kd VS 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.