Myers KA, Mandelstam SA, Ramantani G, Rushing EJ, de Vries
BB, Koolen DA, Scheffer IE. The epileptology of Koolen-de Vries syndrome: Electro-clinico-radiologic findings in 31 patients.
Epilepsia. 2017 Apr 25. doi:10.1111/epi.13746. [Epub ahead of print]
Abstract
OBJECTIVE:
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.
METHODS:
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.
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 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.
_____________________________________________________________________________
This study's goal was to explain 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. The authors concluded that the typical
epilepsy phenotype of KdVS involves childhood–onset focal seizures that are
prolonged and have prominent autonomic features. The typical EEG pattern is
multifocal epileptiform discharges and structural brain abnormalities may be
universal, including signs of abnormal neuroblast migration and abnormal axonal
guidance. Epilepsy surgery ought to be undertaken with care given the
widespread neuroanatomic abnormalities; though, tumors are a rare, yet
important, occurrence.
Methods
The authors were welcomed to take part in a large gathering
of individuals with KdVS and their families.
At that time, they enlisted individuals with KdVS and
seizures and performed thorough phenotyping.
Extra subjects were included who approached them after the
family support group brought attention to the research via social media.
In this study, inclusion criteria were genetic testing
results demonstrating 17q21.31 deletion or KANSL1 mutation, and at least 1
seizure.
Results
The authors studied 31 individuals, aged 2–35 years.
At seizure onset, median age was 3.5 years, and 9 of 22 had
refractory seizures 2 years after onset.
The most frequent seizure type were focal impaired awareness
seizures occurring in 20 of 31, usually with prominent autonomic features.
They found prolonged seizures in 21 patients and, at times,
refractory status epilepticus.
Electroencephalography (EEG) demonstrated focal/multifocal
epileptiform discharges in 20 of 26.
They reviewed MRI studies of 13 patients, and all had
structural anomalies.
Corpus callosum dysgenesis, abnormal hippocampi, and dilated
ventricles were the most common, while periventricular nodular heterotopia,
focal cortical dysplasia, abnormal sulcation, and brainstem and cerebellum
abnormalities were also seen.
For a lesion, 1 patient underwent epilepsy surgery that
proved to be an angiocentric glioma.
______________________________________________________________________
About 10 percent of people diagnosed with Angelman syndrome
do not have a clear genetic cause, even with the availability of advanced
genomic technologies. A study published 29 January in the American Journal of
Medical Genetics2 encourages clinicians to consider similar disorders, which
all present with speech difficulties and delays, when diagnosing these
children.
For example, Koolen-de Vries syndrome has some
characteristics in common with Angelman syndrome: developmental delay,
intellectual disability, severe speech and language delays and a friendly,
happy demeanor. However, people with Koolen-de Vries syndrome have more
advanced language skills than those with Angelman syndrome, and distinctive
physical features such as a broad forehead and unusually loose joints.
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