Novel Genetic and Phenotypic Expansion in -Related Progressive Myoclonus Epilepsy.

Biallelic variants in the Golgi SNAP receptor complex member 2 gene () have been reported in progressive myoclonus epilepsy with neurodegeneration. Typical clinical features include ataxia and areflexia during early childhood, followed by seizures, scoliosis, dysarthria, and myoclonus. Here, we report two novel patients from unrelated families with a -related disorder and novel genetic and clinical findings.

Responsive Neurostimulation for the Treatment of Children With Drug-Resistant Epilepsy in Tuberous Sclerosis Complex.

Background: To review seizure outcomes in children with tuberous sclerosis complex (TSC) and drug-resistant epilepsy (DRE) treated with the responsive neurostimulation (RNS) System.

Methods: We retrospectively reviewed children (<21 years old) with TSC implanted with the RNS System at Texas Children's Hospital between July 2016 and May 2022.

Results: Five patients meeting the search criteria were identified (all female).

An Initial Experience of Completion Hemispherotomy via Magnetic Resonance-Guided Laser Interstitial Therapy.

Introduction: In carefully selected patients with medically refractory epilepsy, disconnective hemispherotomy can result in significant seizure freedom; however, incomplete disconnection can result in ongoing seizures and poses a significant challenge. Completion hemispherotomy provides an opportunity to finish the disconnection. We describe the use of magnetic resonance-guided laser interstitial thermal ablation (MRgLITT) for completion hemispherotomy.

KCNA1 gain-of-function epileptic encephalopathy treated with 4-aminopyridine.

Precision medicine for Mendelian epilepsy is rapidly developing. We describe an early infant with severely pharmacoresistant multifocal epilepsy. Exome sequencing revealed the de novo variant p.

Epilepsy Surgery in Young Children With Tuberous Sclerosis Complex: A Novel Hybrid Multimodal Surgical Approach.

Background: Surgery has become integral in treating children with tuberous sclerosis complex (TSC)-related drug-resistant epilepsy (DRE).

Objective: To describe outcomes of a multimodal diagnostic and therapeutic approach comprising invasive intracranial monitoring and surgical treatment and compare the complementary techniques of open resection and magnetic resonance-guided laser interstitial thermal therapy.

Methods: Clinical and radiographic data were prospectively collected for pediatric patients undergoing surgical evaluation for TSC-related DRE at our tertiary academic hospital.

Koolen-de Vries syndrome associated with continuous spike-wave in sleep.

Koolen-de Vries syndrome (KdVS) is a genetic condition caused by 17q21.31 microdeletions or pathogenic variants in KANSL1. Affected patients most commonly exhibit some or all of the following: neonatal hypotonia, developmental impairment, facial dysmorphic features, and congenital malformations.

Gain-of-function variants in GABRD reveal a novel pathway for neurodevelopmental disorders and epilepsy.

A potential link between GABRD encoding the δ subunit of extrasynaptic GABAA receptors and neurodevelopmental disorders has largely been disregarded due to conflicting conclusions from early studies. However, we identified seven heterozygous missense GABRD variants in 10 patients with neurodevelopmental disorders and generalized epilepsy. One variant occurred in two sibs of healthy parents with presumed somatic mosaicism, another segregated with the disease in three affected family members, and the remaining five occurred de novo in sporadic patients.

Epilepsy Surgery: Monitoring and Novel Surgical Techniques.

Drug-resistant epilepsy warrants referral to an epilepsy surgery center for consideration of alternative treatments including epilepsy surgery. Advances in technology now allow for minimally invasive neurophysiologic monitoring and surgical interventions, approaches that are attractive to families because large craniotomies and associated morbidity are avoided. This work reviews the presurgical evaluation process and discusses the use of invasive stereo-electroencephalography monitoring to localize seizure onset zones.

Phenotypic characterization of individuals with SYNGAP1 pathogenic variants reveals a potential correlation between posterior dominant rhythm and developmental progression.

Background: The SYNGAP1 gene encodes for a small GTPase-regulating protein critical to dendritic spine maturation and synaptic plasticity. Mutations have recently been identified to cause a breadth of neurodevelopmental disorders including autism, intellectual disability, and epilepsy. The purpose of this work is to define the phenotypic spectrum of SYNGAP1 gene mutations and identify potential biomarkers of clinical severity and developmental progression.

Successful Treatment of Electrographic Status Epilepticus of Sleep With Felbamate in a Patient With SLC9A6 Mutation.

Background: Mutations of SLC9A6 may cause an X-linked clinical syndrome first described by Christianson in 1999 in which affected males exhibited profound intellectual disability, autism, drug-resistant epilepsy, ophthalmoplegia, mild craniofacial dysmorphism, microcephaly, and ataxia.

Methods: We describe a child with an SLC9A6 mutation and an electroencephalographic pattern consistent with electrographic status epilepticus of sleep.

Results: Our patient's electrographic status epilepticus of sleep resolved after treatment with felbamate.

Clinical neurogenetics: recent advances in the genetics of epilepsy.

Epilepsy represents a diverse group of disorders with primary and secondary genetic etiologies, as well as non-genetic causes. As more causative genes are identified, genetic testing is becoming increasingly important in the evaluation and management of epilepsy. This article outlines the clinical approach to epilepsy patients, with emphasis on genetic testing.