Pediatric paroxysmal movement disorders - A clinical epidemiological study in an Irish cohort.

Background: Paroxysmal movement disorders (PxMD) are characterized by episodic involuntary movements and include paroxysmal dyskinesias (PD) and episodic ataxias (EA). Although reported in the medical literature since 1892, the exact prevalence in children is unknown.

Objectives: To determine the prevalence and clinical characteristics of PxMD in the pediatric population in the Republic of Ireland.

-related disorders: expansion of the phenotypic spectrum and long-term efficacy of deep brain stimulation.

Heterozygous mutations in are associated with an early-onset, progressive and often complex dystonia (DYT28). Key characteristics of typical disease include focal motor features at disease presentation, evolving through a caudocranial pattern into generalized dystonia, with prominent oromandibular, laryngeal and cervical involvement. Although -related disease is emerging as one of the most common causes of early-onset genetic dystonia, much remains to be understood about the full spectrum of the disease.

Neurodevelopmental and Epilepsy Phenotypes in Individuals With Missense Variants in the Voltage-Sensing and Pore Domains of .

Background And Objectives: encodes the voltage-gated potassium channel EAG2/Kv10.2. We aimed to delineate the neurodevelopmental and epilepsy phenotypic spectrum associated with de novo variants.

Response to treatment and outcomes of infantile spasms in Down syndrome.

Aim: To estimate the prevalence, and evaluate presentation, treatment response, treatment side effects, and long-term seizure outcomes in all known cases of children with Down syndrome and infantile spasms on the island of Ireland.

Method: This was a 10-year retrospective multicentre review of clinical records and investigations, focusing on treatment response, side effects, and long-term outcomes.

Results: The prevalence of infantile spasms in Down syndrome was 3.

Persistent sodium currents in developmental and degenerative epileptic dyskinetic encephalopathy.

Pathogenic variants in the voltage-gated sodium channel gene () are amongst the most common genetic causes of childhood epilepsies. There is considerable heterogeneity in both the types of causative variants and associated phenotypes; a recent expansion of the phenotypic spectrum of associated epilepsies now includes an early onset severe developmental and epileptic encephalopathy with regression and a hyperkinetic movement disorder. Herein, we report a female with a developmental and degenerative epileptic-dyskinetic encephalopathy, distinct and more severe than classic Dravet syndrome.

4-Aminopyridine is a promising treatment option for patients with gain-of-function -encephalopathy.

Developmental and epileptic encephalopathies are devastating disorders characterized by epilepsy, intellectual disability, and other neuropsychiatric symptoms, for which available treatments are largely ineffective. Following a precision medicine approach, we show for -encephalopathy that the K channel blocker 4-aminopyridine can antagonize gain-of-function defects caused by variants in the K1.2 subunit in vitro, by reducing current amplitudes and negative shifts of steady-state activation and increasing the firing rate of transfected neurons.

Paroxysmal Movement Disorders.

Paroxysmal movement disorders (PxMDs) are a clinical and genetically heterogeneous group of movement disorders characterized by episodic involuntary movements (dystonia, dyskinesia, chorea and/or ataxia). Historically, PxMDs were classified clinically (triggers and characteristics of the movements) and this directed single-gene testing. With the advent of next-generation sequencing (NGS), how we classify and investigate PxMDs has been transformed.

Mutations Expand the Phenotypic Spectrum of Alternating Hemiplegia of Childhood.

Objective: To explore the phenotypic spectrum of -related disorders and specifically to determine whether patients fulfill criteria for alternating hemiplegia of childhood (AHC), we report the clinical features of 11 affected individuals.

Methods: Individuals with -related disorders were identified through a movement disorder clinic at a specialist pediatric center, with additional cases identified through collaboration with other centers internationally. Clinical data were acquired through retrospective case-note review.

FBXO28 causes developmental and epileptic encephalopathy with profound intellectual disability.

Chromosome 1q41-q42 deletion syndrome is a rare cause of intellectual disability, seizures, dysmorphology, and multiple anomalies. Two genes in the 1q41-q42 microdeletion, WDR26 and FBXO28, have been implicated in monogenic disease. Patients with WDR26 encephalopathy overlap clinically with those with 1q41-q42 deletion syndrome, whereas only one patient with FBXO28 encephalopathy has been described.

Fifteen-minute consultation: Approach to investigation and management of childhood dystonia.

Dystonia is a hyperkinetic movement disorder characterised by sustained or intermittent muscle contractions causing abnormal movements, postures or both. Dystonia is a challenging condition to diagnose and treat. Dystonia is often under-recognised in children, particularly in cerebral palsy, and frequently coexists with spasticity.

Catatonic features in children and adolescents with -methyl-d-aspartate receptor antibody encephalitis.

Catatonia is a psychomotor dysregulation syndrome of diverse aetiology, increasingly recognised as a prominent feature of -methyl-d-aspartate receptor antibody encephalitis (NMDARE) in adults. No study to date has systematically assessed the prevalence and symptomatology of catatonia in children with NMDARE. We analysed 57 paediatric patients with NMDARE from the literature using the Bush-Francis Catatonia Rating Scale.

Moyamoya disease and moyamoya syndrome in Ireland: patient demographics, mode of presentation and outcomes of EC-IC bypass surgery.

Background: There are no previously published reports regarding the epidemiology and characteristics of moyamoya disease or syndrome in Ireland.

Aims: To examine patient demographics, mode of presentation and the outcomes of extracranial-intracranial bypass surgery in the treatment of moyamoya disease and syndrome in Ireland.

Methods: All patients with moyamoya disease and syndrome referred to the National Neurosurgical Centre during January 2012-January 2019 were identified through a prospective database.

Generation of three induced pluripotent stem cell (iPSC) lines from a patient with developmental epileptic encephalopathy due to the pathogenic KCNA2 variant c.869T>G; p.Leu290Arg (NUIGi052-A, NUIGi052-B, NUIGi052-C).

De novo pathogenic variants in KCNA2 are implicated in causing a spectrum of human neurological disorders, in particular developmental and epileptic encephalopathies. KCNA2 encodes the voltage-gated delayed rectifier potassium channel K1.2, which is vital in regulating neuronal membrane potential and repolarization.

Genetic potassium channel-associated epilepsies: Clinical review of the K family.

Next-generation sequencing has enhanced discovery of many disease-associated genes in previously unexplained epilepsies, mainly in developmental and epileptic encephalopathies and familial epilepsies. We now classify these disorders according to the underlying molecular pathways, which encompass a diverse array of cellular and sub-cellular compartments/signalling processes including voltage-gated ion-channel defects. With the aim to develop and increase the use of precision medicine therapies, understanding the pathogenic mechanisms and consequences of disease-causing variants has gained major relevance in clinical care.

The phenotypic spectrum of SCN2A-related epilepsy.

Pathogenic variants in SCN2A are reported in a spectrum of neurodevelopmental disorders including developmental and epileptic encephalopathies, benign familial neonatal-infantile seizures, episodic ataxia, and autism spectrum disorder and intellectual disability with and without seizures. To date, more than 300 patients with SCN2A variants have been published, the majority presenting with epilepsy. Large cohort studies and variant-specific electrophysiology, have enabled the delineation of different SCN2A-epilepsy phenotypes, phenotype-genotype correlations, prediction of pharmacosensitivity to sodium channel blockers and long-term prognostication for clinicians and families.

Causing Complex Hereditary Spastic Paraplegia With Dysphonia: Expanding the Disease Spectrum.

Herein we present two siblings with hereditary spastic paraplegia caused by novel compound heterozygous variant and deletion in and expansion of the disease spectrum to include dysphonia.

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome.

Hearing impairment and hypoxia ischaemic encephalopathy: Incidence and associated factors.

Objective: To establish the local incidence of hearing loss in newborns with Hypoxic Ischaemic Encephalopathy (HIE) and to identify associated risk factors.

Study Design: Retrospective Cohort Study. Neonatal Intensive Care Unit (NICU) dual stage hearing screening protocol, including automated otoacoustic emissions (AOAE) and automated auditory brainstem response (AABR) testing.