Longitudinal Associations Between COVID-19 Stress and the Mental Health of Children With ADHD.

Objective: To investigate the longitudinal associations between COVID-19 induced stress (related to COVID-19 restrictions/changes), attention-deficit/hyperactivity disorder (ADHD) symptoms, oppositional symptoms, and mental health outcomes (negative affect, anxiety, depression, and irritability) in children with ADHD during the COVID-19 pandemic.

Method: Parents of 140 Australian children with ADHD (aged 5-17 years) completed an online survey in May 2020 during stay-at-home restrictions and 12-months later.

Results: Baseline COVID-19 stress was associated with increased total ADHD symptom severity (β = .

Randomised Controlled Trial of a Behavioural Sleep Intervention, 'Sleeping Sound', for Autistic Children: 12-Month Outcomes and Moderators of Treatment.

This study examined the sustained and moderating effects of a behavioural sleep intervention for autistic children in a randomised controlled trial. Autistic children (5-13 years) with sleep problems were randomised to the Sleeping Sound intervention or Treatment as Usual (TAU). At 12-month follow-up (n = 150), caregivers of children in the Sleeping Sound group reported greater reduction in child sleep problems compared to TAU (p < .

Sleeping Sound Autism Spectrum Disorder (ASD): a randomised controlled trial of a brief behavioural sleep intervention in primary school-aged autistic children.

Background: Behavioural sleep problems are common in children with autism spectrum disorder (ASD); however, evidence for the efficacy of behavioural sleep interventions is limited. This study examined the efficacy of a brief behavioural sleep intervention in autistic children. It was hypothesised that the intervention would reduce overall child sleep problems (primary outcome), in addition to improvements in children's social, emotional, cognitive, academic functioning, and quality of life, and parent/caregivers' stress, quality of life, and mental health (secondary outcomes).

Physical Health, Media Use, and Mental Health in Children and Adolescents With ADHD During the COVID-19 Pandemic in Australia.

Objective: To examine the impact of COVID-19 restrictions among children with attention-deficit/hyperactivity disorder (ADHD).

Methods: Parents of 213 Australian children (5-17 years) with ADHD completed a survey in May 2020 when COVID-19 restrictions were in place (i.e.

Familial adult myoclonic epilepsy type 1 SAMD12 TTTCA repeat expansion arose 17,000 years ago and is present in Sri Lankan and Indian families.

Familial adult myoclonic epilepsy 1 (FAME1), first recognised in Japanese families, was recently shown to be caused by a TTTCA repeat insertion in intron 4 of SAMD12 on chromosome 8. We performed whole genome sequencing on two families with FAME, one of Sri Lankan origin and the other of Indian origin, and identified a TTTCA repeat insertion in SAMD12 in both families. Haplotype analysis revealed that both families shared the same core ancestral haplotype reported in Japanese and Chinese families with FAME1.

Sleeping sound with autism spectrum disorder (ASD): study protocol for an efficacy randomised controlled trial of a tailored brief behavioural sleep intervention for ASD.

Introduction: Sleep problems are a characteristic feature of children with autism spectrum disorder (ASD) with 40% to 80% of children experiencing sleep difficulties. Sleep problems have been found to have a pervasive impact on a child's socio-emotional functioning, as well as on parents' psychological functioning. The project aims to evaluate the efficacy of a brief behavioural sleep intervention in reducing ASD children's sleep problems in a fully powered randomised controlled trial (RCT).

Epilepsy in families: Age at onset is a familial trait, independent of syndrome.

Objective: We tested 2 hypotheses regarding age at onset within familial epilepsies: (1) family members with epilepsy tend to have similar ages at onset, independent of epilepsy syndrome; and (2) age at onset is younger in successive generations after controlling for sampling bias.

Methods: We analyzed clinical data collected by the Epi4K Consortium (303 multiplex families, 1,120 individuals). To test hypothesis 1, we used both linear mixed models commonly used for heritability analysis and Cox regression models with frailty terms to assess clustering of onset within families after controlling for other predictors.

No evidence for a BRD2 promoter hypermethylation in blood leukocytes of Europeans with juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is a common syndrome of genetic generalized epilepsies (GGEs). Linkage and association studies suggest that the gene encoding the bromodomain-containing protein 2 (BRD2) may increase risk of JME. The present methylation and association study followed up a recent report highlighting that the BRD2 promoter CpG island (CpG76) is differentially hypermethylated in lymphoblastoid cells from Caucasian patients with JME compared to patients with other GGE subtypes and unaffected relatives.

Familial mesial temporal lobe epilepsy and the borderland of déjà vu.

Objective: The cause of mesial temporal lobe epilepsy (MTLE) is often unknown. We ascertained to what extent newly diagnosed nonlesional MTLE actually represents familial MTLE (FMTLE).

Methods: We identified all consecutive patients presenting to the Austin Health First Seizure Clinic with MTLE and normal magnetic resonance imaging (MRI) or MRI evidence of hippocampal sclerosis over a 10-year period.

Evaluation of GLUT1 variation in non-acquired focal epilepsy.

Brain glucose transport is dependent on glucose transporter 1 (GLUT1), encoded by the solute carrier family 2 member 1 (SLC2A1) gene. Mutations in SLC2A1 cause GLUT1 deficiency which is characterized by a broad spectrum of neurological phenotypes including generalized epilepsy, motor disorders, developmental delay and microcephaly. Recent case reports suggest SLC2A1 mutations can contribute to non-acquired focal epilepsy (NAFE) but interrogation of a large patient cohort has not been reported.

Dominant KCNA2 mutation causes episodic ataxia and pharmacoresponsive epilepsy.

Objective: To identify the genetic basis of a family segregating episodic ataxia, infantile seizures, and heterogeneous epilepsies and to study the phenotypic spectrum of KCNA2 mutations.

Methods: A family with 7 affected individuals over 3 generations underwent detailed phenotyping. Whole genome sequencing was performed on a mildly affected grandmother and her grandson with epileptic encephalopathy (EE).

Evaluation of non-coding variation in GLUT1 deficiency.

Aim: Loss-of-function mutations in SLC2A1, encoding glucose transporter-1 (GLUT-1), lead to dysfunction of glucose transport across the blood-brain barrier. Ten percent of cases with hypoglycorrhachia (fasting cerebrospinal fluid [CSF] glucose <2.2mmol/L) do not have mutations.

Loss of synaptic Zn2+ transporter function increases risk of febrile seizures.

Febrile seizures (FS) are the most common seizure syndrome and are potentially a prelude to more severe epilepsy. Although zinc (Zn(2+)) metabolism has previously been implicated in FS, whether or not variation in proteins essential for Zn(2+) homeostasis contributes to susceptibility is unknown. Synaptic Zn(2+) is co-released with glutamate and modulates neuronal excitability.

Evaluation of multiple putative risk alleles within the 15q13.3 region for genetic generalized epilepsy.

The chromosome 15q13.3 region has been implicated in epilepsy, intellectual disability and neuropsychiatric disorders, especially schizophrenia. Deficiency of the acetylcholine receptor gene CHRNA7 and the partial duplication, CHRFAM7A, may contribute to these phenotypes and we sought to comprehensively analyze these genes in genetic generalized epilepsy.

Glucose metabolism transporters and epilepsy: only GLUT1 has an established role.

The availability of glucose, and its glycolytic product lactate, for cerebral energy metabolism is regulated by specific brain transporters. Inadequate energy delivery leads to neurologic impairment. Haploinsufficiency of the glucose transporter GLUT1 causes a characteristic early onset encephalopathy, and has recently emerged as an important cause of a variety of childhood or later-onset generalized epilepsies and paroxysmal exercise-induced dyskinesia.

Atypical multifocal Dravet syndrome lacks generalized seizures and may show later cognitive decline.

Aim: To show that atypical multifocal Dravet syndrome is a recognizable, electroclinical syndrome associated with sodium channel gene (SCN1A) mutations that readily escapes diagnosis owing to later cognitive decline and tonic seizures.

Method: Eight patients underwent electroclinical characterization. SCN1A was sequenced and copy number variations sought by multiplex ligation-dependent probe amplification.

Seizure semiology in autosomal dominant epilepsy with auditory features, due to novel LGI1 mutations.

Mutations in LGI1 are found in 50% of families with autosomal dominant epilepsy with auditory features (ADEAF). In ADEAF, family members have predominantly lateral temporal lobe seizures but mesial temporal lobe semiology may also occur. We report here three families with novel LGI1 mutations (p.

Copy number variants are frequent in genetic generalized epilepsy with intellectual disability.

Objective: We examined whether copy number variants (CNVs) were more common in those with a combination of intellectual disability (ID) and genetic generalized epilepsy (GGE) than in those with either phenotype alone via a case-control study.

Methods: CNVs contribute to the genetics of multiple neurodevelopmental disorders with complex inheritance, including GGE and ID. Three hundred fifty-nine probands with GGE and 60 probands with ID-GGE were screened for GGE-associated recurrent microdeletions at 15q13.

Role of the sodium channel SCN9A in genetic epilepsy with febrile seizures plus and Dravet syndrome.

Mutations of the SCN1A subunit of the sodium channel is a cause of genetic epilepsy with febrile seizures plus (GEFS(+) ) in multiplex families and accounts for 70-80% of Dravet syndrome (DS). DS cases without SCN1A mutation inherited have predicted SCN9A susceptibility variants, which may contribute to complex inheritance for these unexplained cases of DS. Compared with controls, DS cases were significantly enriched for rare SCN9A genetic variants.

Mutations in DEPDC5 cause familial focal epilepsy with variable foci.

The majority of epilepsies are focal in origin, with seizures emanating from one brain region. Although focal epilepsies often arise from structural brain lesions, many affected individuals have normal brain imaging. The etiology is unknown in the majority of individuals, although genetic factors are increasingly recognized.

Genome-wide association analysis of genetic generalized epilepsies implicates susceptibility loci at 1q43, 2p16.1, 2q22.3 and 17q21.32.

Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% and account for 20-30% of all epilepsies. Despite their high heritability of 80%, the genetic factors predisposing to GGEs remain elusive.

Familial adult myoclonic epilepsy: recognition of mild phenotypes and refinement of the 2q locus.

Background: Familial adult myoclonic epilepsy (FAME) is an autosomal dominant syndrome characterized by a core triad of cortical tremor, multifocal myoclonus, and generalized tonic-clonic seizures.

Objectives: To expand the phenotypic spectrum of FAME, to highlight diagnostic pointers to this underrecognized disorder, and to refine the FAME2 genetic locus.

Design: Observational family study.