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Baraitser-Winter cerebrofrontofacial syndrome is caused by heterozygous missense mutations in one of the two ubiquitous cytoplasmic actin-encoding genes ACTB and ACTG1. Recently, we characterized the large cohort of 41 patients presenting with this condition. Our series contained 34 patients with mutations in ACTB and only nine with ACTG1 mutations. Here, we report on seven unrelated patients with six mutations in ACTG1-four novel and two previously reported. Only one of seven patients was clinically diagnosed with this disorder and underwent ACTB/ACTG1 targeted sequencing, four patients were screened as a part of the large lissencephaly cohort and two were tested with exome sequencing. Retrospectively, facial features were compatible with the diagnosis but significantly milder than previously reported in four patients, and non-specific in one. The pattern of malformations of cortical development was highly similar in four of six patients with available MRI images and encompassed frontal predominant pachygyria merging with the posterior predominant band heterotopia. Two remaining patients showed mild involvement consistent with bilaterally simplified gyration over the frontal lobes. Taken together, we expand the clinical spectrum of the ACTG1-associated Baraitser-Winter cerebrofrontofacial syndrome demonstrating the mild end of the facial and brain manifestations. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Chromosomal abnormalities involving deletions and duplications are known to cause severe developmental disorders, including mental retardation, dysmorphism, and seizures, in children. As the technique of array-based comparative genomic hybridization is being applied more frequently in the diagnostic evaluation of children with developmental disorders, novel pathologic chromosomal abnormalities are being identified. We report the case of a 9-year-old girl with a history of pervasive developmental disorder, growth delay, mild dysmorphic features, and intractable primary generalized epilepsy with a de novo microdeletion of approximately 0.73-0.94 Mb within chromosome 15q26.1. A much larger (5 Mb) but overlapping microdeletion has been previously reported in a 30-month-old child with similar phenotype including intractable myoclonic epilepsy, growth delay, and dysmorphic features. This leads us to propose that a potential candidate gene or genes within the deleted region involved in the pathogenesis of some forms of generalized intractable epilepsy, previously considered to be idiopathic., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Nonketotic hyperglycinemia (NKH) is an inborn error of metabolism characterized by accumulation of glycine in body fluids and various neurological symptoms. NKH is caused by deficiency of the glycine cleavage multi-enzyme system with three specific components encoded by GLDC, AMT, and GCSH. We undertook the first comprehensive screening for GLDC, AMT, and GCSH mutations in 69 families (56, six, and seven families with neonatal, infantile, and late-onset type NKH, respectively). GLDC or AMT mutations were identified in 75% of neonatal and 83% of infantile families, but not in late-onset type NKH. No GCSH mutation was identified in this study. GLDC mutations were identified in 36 families, and AMT mutations were detected in 11 families. In 16 of the 36 families with GLDC mutations, mutations were identified in only one allele despite sequencing of the entire coding regions. The GLDC gene consists of 25 exons. Seven of the 32 GLDC missense mutations were clustered in exon 19, which encodes the cofactor-binding site Lys754. A large deletion involving exon 1 of the GLDC gene was found in Caucasian, Oriental, and black families. Multiple origins of the exon 1 deletion were suggested by haplotype analysis with four GLDC polymorphisms. This study provides a comprehensive picture of the genetic background of NKH as it is known to date., ((c) 2006 Wiley-Liss, Inc.)

Occasionally, but more often than has been reported, true epileptic seizures are triggered by non-epileptic syncopes. This combination of syncope and epileptic seizure has been called an anoxic-epileptic seizure. A few examples of such anoxic-epileptic seizures, including the induction of status epilepticus, have been reported in books and medical journals, but no video-recordings have been published. We show here home video recordings of the first three known examples of the transition from the triggering syncope and anoxic seizure, to the subsequent epileptic seizure. In the first two children, a neurally-mediated syncope, probably mediated by prolonged expiratory apnoea (so-called breath-holding spells), induces a long, clonic epileptic seizure with some features of myoclonic absence. In the third example, a compulsive Valsalva in an older autistic child provokes a vibratory tonic epileptic seizure. In addition, we show two further video clips of the most usual type of epileptic seizure induced by syncopes in very young children. In one, the video recording begins after the end of the triggering syncope and shows a rhythmic clonic seizure that includes repetitive vocalizations. The final recoding is of a spontaneous epileptic seizure with features of myoclonic absence: this child had both epilepsy and identical episodes induced by syncopes, that is, anoxic- epileptic seizures. Not only paediatricians and paediatric neurologists, but also adult neurologists and epileptologists in general, should be aware of the important clinical scenario of true epileptic seizures induced by syncopes. This phenomenon is not considered in any international classification. (Published with videosequences)

Objectives: Mutations disrupting the interaction of extra-cellular ligands and alpha-dystroglycan are responsible for an etiologically heterogeneous group of autosomal recessive congenital muscular dystrophies (CMD) that can have associated brain and eye abnormalities. The objective is to develop a diagnostic test for one of these CMDs, Muscle-Eye-Brain disease (MEB), due to mutations in the gene encoding Protein O-Mannosyl beta-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1)., Design and Methods: POMGnT1 enzyme activity was determined in extracts of muscle biopsies from four MEB patients and various controls using commercially available reagents., Results: All four MEB muscle samples showed a highly significant decrease in POMGnT1 activity relative to controls., Conclusions: The assay of POMGnT1 activity in MEB muscle provides a rapid and relatively simple diagnostic test for this disease. CMDs associated with brain malformations such as MEB, WWS and FCMD are heterogenous in clinical presentation and on radiologic examination, suggesting that POMGnT1 assays of muscle biopsies should be used as a screening procedure for MEB in all CMD patients associated with brain malformations.

Infantile- and juvenile-onset spinal cerebellar ataxia (SCA) is associated with expansion of 130 to more than 200 CAG-repeats in the SCA2 and SCA7 genes. Routine clinical assays for SCA2 and SCA7, which use polymerase chain reaction (PCR) and denaturing PAGE (polyacrylamide gel electrophoresis), will not reliably detect such large expansions. An assay based on separation of PCR products on an agarose gel, blotting, and hybridization with a (CAG)6 oligonucleotide probe was used to test DNA from individuals more than 10 years of age who had a possible diagnosis of SCA. Among 25 cases, the PCR-blot assay confirmed the presence of SCA2 expansions between 230 and 500 repeats in four unrelated individuals, but did not detect any cases of extreme expansion in the SCA7 gene. The PCR-blot assay provides reliable detection of extreme expansion mutations. Routine incorporation of this assay in clinical laboratories may reveal that infantile-juvenile forms of SCA2 and SCA7 are more prevalent than previously recognized., (Copyright 2002 Wiley-Liss, Inc.)

A patient with juvenile Huntington's disease (HD) of probable maternal inheritance is reported. The expanded IT-15 allele was only detected with the use of modified PCR and Southern transfer techniques, which showed a CAG trinucleotide repeat expansion of approximately 250 repeats-the largest CAG expansion reported within the huntingtin gene. This case emphasizes the need for communication between the diagnostic laboratory and the clinician to define the molecular genetics of unusual cases.

Bilateral periventricular nodular heterotopia (BPNH) is a recently recognized malformation of neuronal migration, and perhaps proliferation, in which nodular masses of gray matter line the walls of the lateral ventricles. Most affected individuals have epilepsy and normal intelligence with no other congenital anomalies. A striking skew of the sex ratio has been observed because 31 of 38 probands have been female, and one gene associated with BPNH was recently mapped to chromosome Xq28. We report three unrelated boys with a new multiple congenital anomaly-mental retardation syndrome that consists of BPNH, cerebellar hypoplasia, severe mental retardation, epilepsy, and syndactyly. Variable abnormalities included focal or regional cortical dysplasia, cataracts, and hypospadius. We hypothesize that this syndrome involves the same Xq28 locus as isolated BPNH, and we review the expanding number of syndromes associated with BPNH.

Background: Chest wall surgery for the correction of pectus excavatum or pectus carinatum has gained increased interest in recent years. Adequate pain treatment, respiratory physiotherapy and early ambulation are key to improving the outcomes. Although thoracic epidural analgesia is highly effective, its safety is controversial, leading to extensive scrutiny and questioning of its role., Objectives: We hypothesise that thoracic epidural analgesia is effective and well tolerated to use in adolescents, with a high success rate and low pain scores., Design: Observational retrospective cohort study., Setting: All adolescent cases in a high-volume academic tertiary chest wall surgery centre between March 1993 and December 2017 were included., Patients: A total of 1117 patients aged from 12 to 19 years of age and receiving either Ravvitch, Nuss or Abramson chest wall reconstruction for pectus excavatum were identified in our institutional chest wall surgery database. After applying selection and exclusion criteria, 532 patients were included in the current analysis., Main Outcome Measures: The primary endpoint of this study was the safety of epidural analgesia, assessed by the incidence of acute adverse events. Secondary endpoints were block success rates using a specific novel definition, and analgesic efficacy using recorded postoperative pain scores., Results: More than 60% of patients experienced one or more adverse events. However, all events were minor and without consequences. No serious or long-term adverse events were detected. The success rate of thoracic epidural placement was 81%. Low postoperative pain scores were observed., Conclusion: Thoracic epidural analgesia is an extremely effective pain control technique, with a surprisingly high number of minor adverse events but safe with regard to serious adverse events., Trial Registration: The local research ethics committee approved and registered this study on 16 May 2022 (registration number: S66594)., (Copyright © 2024 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Background: Neonates with immature auditory function (eg, weak/absent middle ear muscle reflex) could conceivably be vulnerable to noise-induced hearing loss; however, it is unclear if neonates show evidence of hearing loss following MRI acoustic noise exposure., Purpose: To explore the auditory effects of MRI acoustic noise in neonates., Study Type: Prospective., Subjects: Two independent cohorts of neonates (N = 19 and N = 18; mean gestational-age, 38.75 ± 2.18 and 39.01 ± 1.83 weeks)., Field Strength/sequence: T1-weighted three-dimensional gradient-echo sequence, T2-weighted fast spin-echo sequence, single-shot echo-planar imaging-based diffusion-tensor imaging, single-shot echo-planar imaging-based diffusion-kurtosis imaging and T2-weighted fluid-attenuated inversion recovery sequence at 3.0 T., Assessment: All neonates wore ear protection during scan protocols lasted ~40 minutes. Equivalent sound pressure levels (SPLs) were measured for both cohorts. In cohort1, left- and right-ear auditory brainstem response (ABR) was measured before (baseline) and after (follow-up) MRI, included assessment of ABR threshold, wave I, III and V latencies and interpeak interval to determine the functional status of auditory nerve and brainstem. In cohort2, baseline and follow-up left- and right-ear distortion product otoacoustic emission (DPOAE) amplitudes were assessed at 1.2 to 7.0 kHz to determine cochlear function., Statistical Test: Wilcoxon signed-rank or paired t-tests with Bonferroni's correction were used to compare the differences between baseline and follow-up ABR and DPOAE measures., Results: Equivalent SPLs ranged from 103.5 to 113.6 dBA. No significant differences between baseline and follow-up were detected in left- or right-ear ABR measures (P > 0.999, Bonferroni corrected) in cohort1, or in DPOAE levels at 1.2 to 7.0 kHz in cohort2 (all P > 0.999 Bonferroni corrected except for left-ear levels at 3.5 and 7.0 kHz with corrected P = 0.138 and P = 0.533)., Data Conclusion: A single 40-minute 3-T MRI with equivalent SPLs of 103.5-113.6 dBA did not result in significant transient disruption of auditory function, as measured by ABR and DPOAE, in neonates with adequate hearing protection., Evidence Level: 2., Technical Efficacy: Stage 5., (© 2024 International Society for Magnetic Resonance in Medicine.)

Diffuse degeneration of the cerebral cortex and claustrum was found in the brain of a 7-week-old baby with profound psychomotor retardation, multiple ankyloses, seizures, and hypothalamic dysfunction. There was ubiquitous Pick cell formation and gliosis in the affected gray matter. The cortex was not atrophic; in fact, the brain was moderately enlarged. The clinical and pathological findings suggest that the disorder should be distinguished from Pick's disease, as well as from other congenital encephalopathies.

Electrophysiologic studies, echocardiograms, cardiac catheterizations and histologic and biochemical analyses of skeletal muscle biopsies were performed in 10 patients (aged 10 to 37 years, mean 21) who had dysrhythmias as the initial manifestation of cardiomyopathy. Presenting symptoms and signs attributable to dysrhythmias included sudden cardiac arrest in 2 patients, syncope in 3, presyncope in 3 and palpitations in 2. There was no clinical evidence of skeletal muscle weakness in any patient. Multicatheter electrophysiologic evaluation established diagnoses of ventricular tachycardia in 6 patients, primary atrial tachycardia in 2 and third degree infra-Hisian heart block in 1 patient. One patient presenting with palpitations had no inducible arrhythmia or conduction disturbance. Echocardiographic, angiographic and hemodynamic studies demonstrated previously unsuspected dilated cardiomyopathy in 7 patients and restrictive cardiomyopathy in 3. Skeletal muscle histologic characteristics were abnormal in all 10 patients; increases in lipid droplets and endomysial fibrosis were the characteristic findings. Serum free carnitine and short- and long-chain acylcarnitine were normal in 9 patients. However, skeletal muscle long-chain acylcarnitine was reduced in 9 patients. These findings support the concept that in certain patients presenting with dysrhythmias, the dysrhythmia may be a manifestation of cardiac and skeletal (that is, generalized) myopathy.

One hundred ninety-nine infants (birth to 15 weeks) were administered an impedance battery to describe emerging characteristics of the acoustic reflex in this age range. Tympanometry results suggest that the middle ear system changes from a highly flaccid state at birth to a relatively normal compliance by 15 weeks. Acoustic reflexes were observed infrequently in the newborn population and gradually increased as a function of age, but never exceeding 43% of the ears tested. A conservative approach regarding the relevance of the presence of the reflex in young children is warranted.

Background: Breath-holding spells (BHS) are common in infancy and early childhood and may appear like seizures. Factors such as autonomic dysfunction and iron deficiency anemia are thought to contribute to the incidence of BHS. In this study, electrocardiographic (ECG) parameters of patients with BHS were compared to those of healthy, normal children. Logistic regression and machine-learning (ML) models were then created to predict these spells based on ECG characteristics., Methods: In this case-control study, 52 BHS children have included as the case and 150 healthy children as the control group. ECG was taken from all children along with clinical examinations. Multivariate logistic regression model was used to predict BHS occurrence based on ECG parameters. ML model was trained and validated using the Gradient-Boosting algorithm, in the R programming language., Results: In BHS and control groups, the average age was 11.90 ± 6.63 and 11.33 ± 6.17 months, respectively (p = .58). Mean heart rate, PR interval, and QRS interval on ECGs did not differ significantly between the two groups. BHS patients had significantly higher QTc, QTd, TpTe, and TpTe/QT (all p-values < .001). Evaluation of the ML model for prediction of BHS, fitting on the testing data showed AUC, specificity, and sensitivity of 0.94, 0.90, and 0.94 respectively., Conclusion: There are repolarization changes in patients with BHS, as the QTc, QTd, TpTe, and TpTe/QT ratio were significantly higher in these patients, which might be noticeable for future arrhythmia occurrence. In this regard, we developed a successful ML model to predict the possibility of BHS in suspected subjects., (© 2023 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Chromatin, a protein-DNA complex, is a dynamic structure that stores genetic information within the nucleus and responds to molecular/cellular changes in its structure, providing conditional access to the genetic machinery. ATP-dependent chromatin modifiers regulate access of transcription factors and RNA polymerases to DNA by either "opening" or "closing" the structure of chromatin, and its aberrant regulation leads to a variety of neurodevelopmental disorders. The chromodomain helicase DNA-binding (CHD) proteins are ATP-dependent chromatin modifiers involved in the organization of chromatin structure, act as gatekeepers of genomic access, and deposit histone variants required for gene regulation. In this review, we first discuss the structural and functional domains of the CHD proteins, and their binding sites, and phosphorylation, acetylation, and methylation sites. The conservation of important amino acids in SWItch/sucrose non-fermenting (SWI/SNF) domains, and their protein and mRNA tissue expression profiles are discussed. Next, we convey the important binding partners of CHD proteins, their protein complexes and activities, and their involvements in epigenetic regulation. We also show the ChIP-seq binding dynamics for CHD1, CHD2, CHD4, and CHD7 proteins at promoter regions of histone genes, as well as several genes that are critical for neurodevelopment. The role of CHD proteins in development is also discussed. Finally, this review provides information about CHD protein mutations reported in autism and neurodevelopmental disorders, and their pathogenicity. Overall, this review provides information on the progress of research into CHD proteins, their structural and functional domains, epigenetics, and their role in stem cell, development, and neurological disorders., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Epilepsy and syncope can be difficult to distinguish, with misdiagnosis resulting in unnecessary or incorrect treatment and disability. Combined tilt-table and video EEG (vEEG) testing (tilt-vEEG) is infrequently used to parse these entities even at large centers. Because of the discovery of a rare case of epileptic seizure induced by head-up tilt (HUT) (no prior cases have been published), the authors sought to verify the rarity of this phenomenon., Methods: An observational, retrospective case series study of all combined tilt-vEEG studies performed at Stanford Health Care over a 2-year period was performed. Studies were grouped into categories: (1) abnormal tilt and normal vEEG; (2) abnormal vEEG and normal tilt; (3) abnormal vEEG and abnormal tilt; (4) normal tilt and normal vEEG, with neurologic symptoms; and (5) normal tilt and normal vEEG without neurologic symptoms., Results: Sixty-eight percent of patients had an abnormal study (categories A-C), with only 3% having both an abnormal tilt and an abnormal EEG (category C). Of these, one patient had a focal epileptic seizure induced by HUT. With HUT positioning, the patient stopped answering questions and vEEG showed a left temporal seizure; systolic blood pressure abruptly dropped to 89 mm Hg (64 mm Hg below baseline); heart rate did not change, but pacemaker showed increased firing (threshold: <60 bpm)., Conclusions: Combined tilt-table and vEEG evaluation was able to identify a previously unreported scenario-head-up tilt provocation of an epileptic seizure-and improve treatment. Combined tilt and vEEG testing should be considered for episodes that persist despite treatment to confirm proper diagnosis., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 by the American Clinical Neurophysiology Society.)

Aberrant alternative splicing (AS) events are frequently observed in lung cancer, which can be attributed to aberrant gene AS, alterations in splicing regulatory factors, or changes in splicing regulatory mechanisms. Consequently, the dysregulation of alternative RNA splicing is the fundamental cause of lung cancer. In this review, we have summarized the pivotal role of AS in the development, progression, invasion, metastasis, angiogenesis, and drug resistance of lung cancer. Ultimately, this review emphasizes the potential of AS as biomarkers in lung cancer prognosis and diagnosis, and introduces some applications of AS isoform in the treatment of lung cancer. The comprehension of the AS may provide a glimmer of hope for the eradication of lung cancer., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

CHD2 encodes the chromodomain helicase DNA-binding protein 2, an ATP-dependent enzyme that acts as a chromatin remodeler. CHD2 pathogenic variants have been associated with various early onset phenotypes including developmental and epileptic encephalopathy, self-limiting or pharmacoresponsive epilepsies and neurodevelopmental disorders without epilepsy. We reviewed 84 previously reported patients carrying 76 different CHD2 pathogenic or likely pathogenic variants and describe 18 unreported patients carrying 12 novel pathogenic or likely pathogenic variants, two recurrent likely pathogenic variants (in two patients each), three previously reported pathogenic variants, one gross deletion. We also describe a novel phenotype of adult-onset pharmacoresistant epilepsy, associated with a novel CHD2 missense likely pathogenic variant, located in an interdomain region. A combined review of previously published and our own observations indicates that although most patients (72.5%) carry truncating CHD2 pathogenic variants, CHD2-related phenotypes encompass a wide spectrum of conditions with developmental delay/intellectual disability (ID), including prominent language impairment, attention deficit hyperactivity disorder and autistic spectrum disorder. Epilepsy is present in 92% of patients with a median age at seizure onset of 2 years and 6 months. Generalized epilepsy types are prevalent and account for 75.5% of all epilepsies, with photosensitivity being a common feature and adult-onset nonsyndromic epilepsy a rare presentation. No clear genotype-phenotype correlation has emerged., (© 2021 Wiley Periodicals LLC.)

During neuronal diseases, neuronal proteins get disturbed due to changes in the connections of neurons. As a result, neuronal proteins get disturbed and cause epilepsy. At the genetic level, many mutations may take place in proteins like axon guidance proteins, leucine-rich glioma inactivated 1 protein, microtubular protein, pore-forming, chromatin remodeling, and chemokine proteins which may lead toward temporal lobe epilepsy. These proteins can be targeted in the future for the treatment purpose of epilepsy. Novel avenues can be developed for therapeutic interventions by these new insights., (© 2021 John Wiley & Sons A/S.)

Background: The aim of the present systematic revision is to analyze existing published reports about the use of home-videos recordings (HVRs) to support physicians in the differential diagnosis of paroxysmal seizure-like episodes (PSLE). We also developed practical recommendations in order to ensure adequate quality standards and safety advice for HVRs., Material and Methods: A comprehensive search of PubMed, Medline, Scopus, and Google Scholar was performed, and results were included up to July 2020. All studies concerning the use of HVRs as a diagnostic tool for patients presenting PSLE were included., Results: Seventeen studies satisfied all inclusion and exclusion criteria and were considered for the review. A consistent boost in diagnostic and clinical decision-making was reported across all studies in the literature. One study found that HVRs decreased the stress level in many families and improved their quality of life. Training in performing good-quality videos is necessary and increases the diagnostic value of HVRs., Conclusions: HVRs can be of diagnostic value in epilepsy diagnosis and management. HVRs are low cost, widespread, and may provide great support for neurologists. It is important to train patients and caregivers in performing good quality videos to optimize this useful tool and to guarantee safety standards during the recording.

Background and Purpose: Some epilepsy syndromes (sleep-related epilepsies, SREs) have a strong link with sleep. Comorbid sleep disorders are common in patients with SRE and can exert a negative impact on seizure control and quality of life. Our purpose was to define the standard procedures for the diagnostic pathway of patients with possible SRE (scenario 1) and the general management of patients with SRE and comorbidity with sleep disorders (scenario 2)., Methods: The project was conducted under the auspices of the European Academy of Neurology, the European Sleep Research Society and the International League Against Epilepsy Europe. The framework entailed the following phases: conception of the clinical scenarios; literature review; statements regarding the standard procedures. For the literature search a stepwise approach starting from systematic reviews to primary studies was applied. Published studies were identified from the National Library of Medicine's MEDLINE database and Cochrane Library., Results: Scenario 1: Despite a low quality of evidence, recommendations on anamnestic evaluation and tools for capturing the event at home or in the laboratory are provided for specific SREs. Scenario 2: Early diagnosis and treatment of sleep disorders (especially respiratory disorders) in patients with SRE are likely to be beneficial for seizure control., Conclusions: Definitive procedures for evaluating patients with SRE are lacking. Advice is provided that could be of help for standardizing and improving the diagnostic approach of specific SREs. The importance of identifying and treating specific sleep disorders for the management and outcome of patients with SRE is underlined., (© 2020 European Academy of Neurology and European Sleep Research Society.)

Background: Some epilepsy syndromes (sleep-related epilepsies [SRE]) have a strong link with sleep. Comorbid sleep disorders are common in patients with SRE and can exert a negative impact on seizure control and quality of life., Purposes: To define the standard procedures for the diagnostic pathway of patients with possible SRE (scenario 1) and the general management of patients with SRE and comorbidity with sleep disorders (scenario 2)., Methods: The project was conducted under the auspices of the European Academy of Neurology (EAN), the European Sleep Research Society (ESRS) and the International League against Epilepsy (ILAE) Europe. The framework of the document entailed the following phases: conception of the clinical scenarios; literature review; statements regarding the standard procedures. For literature search a step-wise approach starting from systematic reviews to primary studies was applied. Published studies were identified from the National Library of Medicine's MEDLINE database and Cochrane Library., Results: Scenario 1: despite a low quality of evidence, recommendations on anamnestic evaluation, tools for capturing the event at home or in the laboratory are provided for specific SRE. Scenario 2: Early diagnosis and treatment of sleep disorders (especially respiratory disorders) in patients with SRE are likely to be beneficial for seizures control., Conclusions: Definitive procedures for evaluating patients with SRE are lacking. We provide advice that could be of help for standardising and improving the diagnostic approach of specific SRE. The importance of identifying and treating specific sleep disorders for the management and outcome of patients with SRE is underlined., (© 2020 European Academy of Neurology and European Sleep Research Society.)

The aim of this report was to refine the genotypes and phenotypes of chromodomain helicase DNA-binding protein 2 (CHD2)-related epilepsy. Seventeen patients with CHD2 mutations were enrolled. CHD2 mutations were identified by application of next-generation sequencing of epilepsy or whole exome sequencing. Sixteen mutations were identified, among which 15 have not yet been reported. Thirteen mutations were de novo. Age at seizure onset ranged from 3 months to 10 years 5 months. Seizures observed were generalized tonic-clonic, myoclonic, atonic, atypical absence, focal, and myoclonic-atonic. Epileptic spasms occurred in two patients. Developmental disability was present in 14 patients. Autism features were observed in seven patients. Video electroencephalogram was abnormal in 15 patients. Five patients were diagnosed with non-specific epileptic encephalopathy, two with epilepsy with myoclonic-atonic seizures, two with Lennox-Gastaut syndrome, two with febrile seizures plus, and one with West syndrome. Seizures were controlled in nine patients. Q1392TfsX17 may be a hot-spot mutation of CHD2. West syndrome was observed as a new phenotype of CHD2 mutation. The severity of the phenotypes of CHD2 mutations ranged from mild febrile seizures to severe epileptic encephalopathy. WHAT THIS PAPER ADDS: Q1392TfsX17 maybe the hot-spot mutation of CHD2. West syndrome could be a new phenotype of CHD2 mutation., (© 2019 Mac Keith Press.)

Introduction: The purposes of this study were to develop an instructional leaflet on home video recording for the General Movement Assessment (GMA) and to examine the concurrent and predictive validity of the GMA completed by physical therapists (PTs) and completed by parents., Methods: The GMA and the Alberta Infant Motor Scale (AIMS) were completed by PTs in the clinic. Parents completed the GMA following the instructional leaflet., Results: The content validity of the leaflet was 0.83. The consistency of the GMA results between sources was κ = 0.869. The concurrent validity of the GMA at a corrected age of 3 months was κ = 0.266 (PT) versus 0.525 (parent) using the 10th-percentile cutoffs of the AIMS. The positive likelihood ratio was 26 (PT) versus 25 (parents) at a corrected age of 12 months based on 5th-percentile cutoffs of the AIMS., Conclusions: Home GMA videos are valid for clinical assessment following the instructional leaflet.

Spinocerebellar ataxia type 2 (SCA2) is caused by an unstable expanded CAG repeat tract (CAGexp) at ATXN2. Although prone to selective forces such as anticipation, SCA2 frequency seems to be stable in populations. Our aim was to estimate reproductive success, segregation patterns, and role of anticipation in SCA2. Adult subjects from families with molecular diagnosis provided data about all his/her relatives. Affected and unaffected sibs older than 65.7 years of age were used to estimate reproductive success and segregation patterns. Twenty-one SCA2 families were studied, including 1017 individuals (164 affected) who were born from 1840 to 2012. The median number of children of the non-carriers and carriers, among 99 subjects included in the reproductive success analysis, were 2 and 3 (p < 0.025), respectively. Therefore, the reproductive success of carriers was 1.5. There were 137 non-carriers (59.6%) and 93 carriers (40.4%) (p = 0.04), among subjects included in the segregation analysis. Age at onset across generations pointed to anticipation as a frequent phenomenon. We raised evidence in favor of increased reproductive success related to the carrier state at ATXN2, and segregation distortion favoring normal alleles. Since majority of normal alleles analyzed carried 22 repeats, we propose that this distortion segregation can be related to the high frequency of this allele in human chromosomes.