Authors :
Presenting Author: Amanda Brand, BS – Institute of Neurology and Neurosurgery at Cooperman Barnabas
Eric Geller, MD – Institute of Neurology and Neurosurgery at St. Barnabas
Robert Gross, MD, PhD – Robert Wood Johnson School of Medicine
Rina Goldberg, MD – Institute of Neurology and Neurosurgery at St. Barnabas
Rationale:
Koolen-de Vries Syndrome (KdVS) is a rare neurodevelopmental disorder caused by microdeletions in 17q21.31 or pathogenic variants and/or deletions in the KANSL1 gene. Clinically, this manifests in developmental delays, distinct physical features, and a variable epilepsy phenotype present in about one-third of those affected. While the epilepsy associated with KdVS has been recognized, there is limited literature focused on treatment outcomes, particularly surgical interventions. Most reported cases are managed with anti-seizure medications (ASMs), though their therapeutic efficacy may vary. We present a unique case of a 28-year-old male with KdVS-associated epilepsy successfully treated with right temporal lobe laser ablation. This case suggests surgical interventions, such as laser ablation, as a potential successful therapeutic option in carefully selected KdVS patients.
Methods:
We present the case of a 28-year-old male with no hand dominance diagnosed with KdVS through genetic testing. In addition to the partial monosomy of 17q21.31, the patient exhibited typical clinical signs such as developmental delays, significant intellectual disability, behavioral tendencies, specific facial features and congenital malformations.
Results:
The patient developed seizures at 10.5 months of age, characterized by behavioral arrest, automatisms, and unilateral hand dystonia evolving to bilateral convulsions. Seizure frequency included one to two breakthrough seizures monthly despite polytherapy with ASMs including clonazepam, zonisamide, and lacosamide. Testing showed persistent right anterior temporal sharp waves and intermittent slowing in the right temporal region across multiple EEGs. MRI testing showed right hippocampal atrophy and T2/FLAIR hyperintense signaling, suggestive of mesial temporal sclerosis. After multiple unsuccessful trials of ASMs and careful risk-benefit analysis, the patient underwent right temporal laser ablation in May 2024, with focus on the right hippocampus.
Following surgery, the patient has remained seizure-free for 12 months to date at the time of submission. No adverse neurological or cognitive side effects were reported post-operatively. This outcome suggests a positive response to surgical intervention in an otherwise pharmacoresistant case. To our knowledge, this represents the first published case of successful temporal laser ablation in a patient with KdVS-associated epilepsy.
Conclusions:
This case demonstrates that surgical interventions done for patients with more common forms of epilepsy, such as temporal lobe laser ablations, can also be effective treatment options for patients with Koolen de-Vries Syndrome (KdVS)-associated epilepsy as well. Our patient achieved seizure freedom for at least 12 months following surgery with no significant adverse effects. These findings suggest that surgical evaluation should be considered in KdVS patients with medication-resistant epilepsy and correlating EEG and MRI abnormalities. As more cases are reported and analyzed, surgical intervention may become a more recognized and reliable option for seizure control in this population.
Funding: n/a