Diffuse subcortical band heterotopia, periodic limb movements during sleep and a novel “de novo” mutation in the DCX gene

2010 ◽  
Vol 32 (6) ◽  
pp. 511-515 ◽  
Author(s):  
Pasquale Parisi ◽  
Silvia Miano ◽  
Davide Mei ◽  
Maria Chiara Paolino ◽  
Rosa Castaldo ◽  
...  
Keyword(s):  
De Novo ◽  
De Novo Mutation ◽  
Periodic Limb Movements ◽  
Limb Movements ◽  
Subcortical Band Heterotopia ◽  
Band Heterotopia

Das Restless-Legs-Syndrom, eine diagnostische und therapeutische Herausforderung bei Kindern und Jugendlichen

2019 ◽  
Vol 19 (03) ◽  
pp. 194-199
Author(s):  
Silvano Vella
Keyword(s):  
Periodic Limb Movements ◽  
Wird Eine ◽  
Limb Movements ◽  
Kognitive Leistungsfähigkeit ◽  
Restless Legs ◽  
Restless Legs Syndrom

ZusammenfassungDas Restless-Legs-Syndrom (RLS) ist eine zentralnervöse, genetisch prädisponierte, durch biochemische Faktoren getriggerte chronisch-progrediente sensomotorische Störung, oft mit Beginn im Kindes- oder Jugendalter. Zugrundeliegend wird eine zerebrale Störung des Eisen- und Dopamin-Stoffwechsels postuliert. Diese manifestiert sich durch den unwiderstehlichen Zwang seine Extremitäten bewegen zu müssen, verbunden mit Parästhesien und Dysästhesien. Die Beschwerden nehmen in Ruhe und in der Nacht zu und bessern sich durch Bewegung. RLS sollte eigentlich mit Restless-Limbs-Syndrome übersetzt werden, da langfristig auch Beschwerden in den Armen auftreten können. Kinder ab 18 Monaten können bereits betroffen sein. Die Prävalenz im Kindes- und Jugendalter beträgt 2–4 %, in Assoziation mit ADHS noch höher. Die Diagnose des RLS beruht auf anamnestischen und somit subjektiv geprägten Aussagen, die bei Kindern mit beschränkten sprachlichen Ausdrucksmöglichkeiten schwierig zu werten sind. Bis zu 75 % der RLS-Betroffenen entwickeln im Schlaf periodische Extremitätenbewegungen, welche die Nachtruhe empfindlich stören können (PLMS, periodic limb movements in sleep). Mitbetroffen sind die kognitive Leistungsfähigkeit, Stimmung und Lebensqualität am Tag. Eisenmangel, Genussmittel und gewisse Medikamente können die Beschwerden verstärken. Im Gegensatz zum RLS können PLMS mit neurophysiologischen Messungen objektiviert werden. Therapeutisch steht an erster Stelle die Behandlung eines allfälligen Eisenmangels. Entwickelt wurden Algorithmen für intravenöse Therapien. Falls angezeigt, kommen L-Dopa oder Dopamin-Agonisten zur Anwendung. Da auch Kinder eine Zunahme der RLS-Symptome unter dieser Therapie erleben (Augmentationen), wird zunehmend eine primäre Gabe von Alpha-2-Liganden bevorzugt.Dieser Artikel möchte auf die wichtige Aufgabe von Kinderärzten und Grundversorgern bei der rechtzeitigen Erkennung und Behandlung von RLS/PLMS hinweisen.

Actimetry-documented persistent Periodic Limb Movements during EEG-confirmed deep General Anesthesia: a case report.

2019 ◽  
Author(s):  
Friedrich Lersch ◽  
Pascal Jerney ◽  
Heiko Kaiser ◽  
Cédric Willi ◽  
Katharina Steck ◽  
...  
Keyword(s):  
Case Report ◽  
Motor Activity ◽  
General Anesthesia ◽  
Burst Suppression ◽  
Periodic Limb Movements ◽  
Deep Sclerectomy ◽  
Limb Movements ◽  
Periodic Leg Movements ◽  
Increase Motor Activity ◽  
Leg Movements

Motor activity during general anesthesia (GA) without curarization is often interpreted as reflecting insufficient analgosedation. Here we present the case of an octogenarian scheduled for deep sclerectomy receiving opioid-sparing electroencephalography-(EEG)-guided anesthesia. Periodic Leg Movements (PLM) made their appearance with ongoing surgery while his raw EEG displayed a pattern of deep GA (burst suppression). To the best of our knowledge, this is the first description of actimetry-documented persisting PLM during EEG-monitored GA. Recognizing PLM in the context of GA is of importance for anesthesiologists, as increasing sedation may increase motor activity.

scholarly journals Intranasal oxytocin administration ameliorates social behavioral deficits in a POGZWT/Q1038R mouse model of autism spectrum disorder

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Kohei Kitagawa ◽  
Kensuke Matsumura ◽  
Masayuki Baba ◽  
Momoka Kondo ◽  
Tomoya Takemoto ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Social Behavior ◽  
Mouse Model ◽  
Mouse Models ◽  
De Novo ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
De Novo Mutation ◽  
Behavioral Deficits

AbstractAutism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterized by core symptoms of impaired social behavior and communication. Recent studies have suggested that the oxytocin system, which regulates social behavior in mammals, is potentially involved in ASD. Mouse models of ASD provide a useful system for understanding the associations between an impaired oxytocin system and social behavior deficits. However, limited studies have shown the involvement of the oxytocin system in the behavioral phenotypes in mouse models of ASD. We have previously demonstrated that a mouse model that carries the ASD patient-derived de novo mutation in the pogo transposable element derived with zinc finger domain (POGZWT/Q1038R mice), showed ASD-like social behavioral deficits. Here, we have explored whether oxytocin (OXT) administration improves impaired social behavior in POGZWT/Q1038R mice and found that intranasal oxytocin administration effectively restored the impaired social behavior in POGZWT/Q1038R mice. We also found that the expression level of the oxytocin receptor gene (OXTR) was low in POGZWT/Q1038R mice. However, we did not detect significant changes in the number of OXT-expressing neurons between the paraventricular nucleus of POGZWT/Q1038R mice and that of WT mice. A chromatin immunoprecipitation assay revealed that POGZ binds to the promoter region of OXTR and is involved in the transcriptional regulation of OXTR. In summary, our study demonstrate that the pathogenic mutation in the POGZ, a high-confidence ASD gene, impairs the oxytocin system and social behavior in mice, providing insights into the development of oxytocin-based therapeutics for ASD.

scholarly journals The L1-dependant and Pol III transcribed Alu retrotransposon, from its discovery to innate immunity

2021 ◽  
Vol 48 (3) ◽  
pp. 2775-2789
Author(s):  
Ludwig Stenz
Keyword(s):  
Human Genome ◽  
Viral Infections ◽  
De Novo ◽  
Current Knowledge ◽  
Innate Immune ◽  
De Novo Mutation ◽  
Neuronal Diversity ◽  
Alu Sequences ◽  
Pol Iii ◽  
The Brain

AbstractThe 300 bp dimeric repeats digestible by AluI were discovered in 1979. Since then, Alu were involved in the most fundamental epigenetic mechanisms, namely reprogramming, pluripotency, imprinting and mosaicism. These Alu encode a family of retrotransposons transcribed by the RNA Pol III machinery, notably when the cytosines that constitute their sequences are de-methylated. Then, Alu hijack the functions of ORF2 encoded by another transposons named L1 during reverse transcription and integration into new sites. That mechanism functions as a complex genetic parasite able to copy-paste Alu sequences. Doing that, Alu have modified even the size of the human genome, as well as of other primate genomes, during 65 million years of co-evolution. Actually, one germline retro-transposition still occurs each 20 births. Thus, Alu continue to modify our human genome nowadays and were implicated in de novo mutation causing diseases including deletions, duplications and rearrangements. Most recently, retrotransposons were found to trigger neuronal diversity by inducing mosaicism in the brain. Finally, boosted during viral infections, Alu clearly interact with the innate immune system. The purpose of that review is to give a condensed overview of all these major findings that concern the fascinating physiology of Alu from their discovery up to the current knowledge.

scholarly journals Publisher Correction: Germline de novo mutation clusters arise during oocyte aging in genomic regions with high double-strand-break incidence

2021 ◽  
Author(s):  
Jakob M. Goldmann ◽  
Vladimir B. Seplyarskiy ◽  
Wendy S. W. Wong ◽  
Thierry Vilboux ◽  
Pieter B. Neerincx ◽  
...  
Keyword(s):  
De Novo ◽  
Strand Break ◽  
Double Strand Break ◽  
De Novo Mutation ◽  
Oocyte Aging ◽  
Genomic Regions

523 Characteristics of Patients with REM Sleep without Atonia/Periodic Limb Movements of Sleep without Dream Enactment Behaviors

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A206-A206
Author(s):  
Lina Barker ◽  
Maja Tippmann-Peikert
Keyword(s):  
Rem Sleep ◽  
Psychiatric Diagnosis ◽  
Neurological Disorders ◽  
Rem Sleep Behavior Disorder ◽  
Control Group ◽  
Periodic Limb Movements ◽  
Limb Movements ◽  
Sleep Behavior ◽  
Rem Sleep Without Atonia ◽  
Antidepressant Use

Abstract Introduction While REM sleep without atonia (RSWA) in REM sleep behavior disorder (RBD) is associated with male sex, age greater than or equal to 50 years, alpha-synucleinopathies, and narcolepsy, the characteristics of patients with RSWA/persistent periodic limb movements of sleep in REM sleep (RSWA/PLMS-REM) without dream enactment behaviors are unexplored. The aim of this study was to compare the demographics, comorbidities, and concomitant medication use between RSWA/PLMS-REM patients and non-RSWA/non-PLMS-REM controls. Based on anecdotal clinical observations, we hypothesized that these patients are more commonly young, women, have psychiatric or neurological diseases, and use antidepressants. Methods We conducted a retrospective review of the Mayo Clinic electronic medical record to identify all patients with RSWA/PLMS-REM between November 2018 and November 2020. After excluding all patients with RBD, restless legs syndrome, narcolepsy, and RSWA/non-PLMS-REM, we identified 27 patients. All in-lab polysomnograms (PSGs) were reviewed to calculate the periodic limb movement index per hour of REM sleep (REM-PLMI). We also identified a control group of 15 individuals without RSWA, reviewed their PSGs, and calculated the REM-PLMI. Results The mean REM-PLMI of patients with RSWA was 64 +/- 8.3 (standard error of mean (SEM)) per hour versus 1 +/- 0.6 (SEM) per hour in non-RSWA controls (p < 0.001). Patients with RSWA/PLMS-REM and non-RSWA controls had similar age and gender, 62 +/- 3 (SEM) versus 58 +/- 3 (SEM) years and 81% versus 87% men, respectively. However, psychiatric diagnosis, neurological disorders, and antidepressants use were more common among RSWA/PLMS-REM patients compared to non-RSWA controls with p = 0.0002, p = 0.0035 and p = 0.0074 respectively (Fisher’s Exact Test). Conclusion Psychiatric diagnosis, neurological disorders, and antidepressant use are more common among RSWA/PLMS-REM patients compared to non-RSWA/non-PLMS-REM controls. Further research to determine the implications of a diagnosis of RSWA/PLMS-REM for the future development of alpha-synucleinopathies are needed and currently ongoing. Support (if any):

Sleep Exacerbations and Facial Twitching: Diagnostic Clues for ADCY5-Related Dyskinesias

2020 ◽  
Author(s):  
Margherita Nosadini ◽  
Gianluca D'Onofrio ◽  
Maria Federica Pelizza ◽  
Concetta Luisi ◽  
Davide Padrin ◽  
...  
Keyword(s):  
Movement Disorder ◽  
Developmental Delay ◽  
De Novo ◽  
Brain Magnetic Resonance Imaging ◽  
Neurological Impairment ◽  
De Novo Mutation ◽  
Oligoclonal Bands ◽  
Emotional Stimuli ◽  
Childhood Onset ◽  
Ataxic Gait

Abstract Background Mutations in the adenylate cyclase 5 (ADCY5) gene are associated with childhood-onset paroxysmal dyskinesia. Methods We report a new video-documented case of pediatric ADCY5-related dyskinesia with de novo ADCY5 mutation. Results A boy born to nonconsanguineous parents after an uneventful pregnancy had developmental delay and hypotonia. At the age of 7 months, he presented with paroxysmal jerky–choreic–dystonic involuntary movements in wakefulness involving limbs, trunk, and face, exacerbated by emotional stimuli. These episodes gradually worsened in duration and frequency: at the age of 2.5 years, they occurred up to six times per day, and appeared also during sleep in prolonged bouts; the boy also had basal choreoathetoid–dystonic movements, hyperactivity, paraparetic–ataxic gait, generalized hypotonia with brisk tendon reflexes, drooling, and language delay with intellectual disability. Brain magnetic resonance imaging, electroencephalogram, electromyogram, eye review, metabolic investigations, oligoclonal bands, and autoantibodies were normal. Extensive genetic testing had not let to a diagnosis, until a heterozygous de novo mutation c.1252C > T (p.Arg418Trp) was identified in the ADCY5 gene. Clonazepam had partial effectiveness. The boy walked at the age of 3.5 years. At the age of 5 years, the paroxysmal movement disorder has slightly improved. Conclusion ADCY5 mutations should be considered among the differential diagnoses of early-onset paroxysmal choreic–athetosic–myoclonic–dystonic movement disorder involving limbs, trunk, and face, in patients with global neurological impairment with hypotonia and developmental delay. Facial dyskinesias and exacerbation by drowsiness/sleep and emotional stimuli are important clues that may allow a timely recognition of the disorder and avoidance of unnecessary diagnostic investigations.

Neugeborenes mit Nasenagenesie: Neonatologische Herausforderungen bei der Versorgung eines Neugeborenen mit Bosma-Arhinie-Mikrophthalmie-Syndrom (BAMS)

2021 ◽  
Vol 100 (04) ◽  
pp. 294-296
Author(s):  
Helen Stromiedel ◽  
Chantal Van Quekelberghe ◽  
Gökhan Yigit ◽  
Ammar Al Naimi ◽  
Franz Bahlmann ◽  
...  
Keyword(s):  
De Novo ◽  
De Novo Mutation ◽  
Intrauterine Wachstumsrestriktion

ZusammenfassungAnhand eines weiblichen Neugeborenen soll das seltene Krankheitsbild der konnatalen Nasenagenesie vorgestellt werden. In der Schwangerschaft fielen eine intrauterine Wachstumsrestriktion mit Polyhydramnion und eine Mittelgesichtshypoplasie auf. Das Atemwegsmanagement nach primärer Sectio in der 38 + 4 SSW gelang mittels Schienung durch einen Güdel- bzw. im Verlauf Rachentubus ohne Zeichen einer respiratorischen Insuffizienz. Neben der vollständigen Nasenagenesie zeigten sich bei unauffälligen zerebralen Strukturen ein Hypertelorismus, ein gotischer Gaumen, ein beidseitiger Mikrophthalmus und Iriskolobom. Die Nahrungsaufnahme wurde mit einer orogastralen Sonde sichergestellt, durch Trinktraining und einen speziellen Schnuller konnten eine bessere Koordination und Trinkleistung erzielt werden. Der sich bei assoziierten Fehlbildungen ergebende Verdacht auf ein Bosma-Arhinie-Mikrophthalmie-Syndrom (BAMS) wurde humangenetisch durch den Nachweis einer heterozygoten de novo Mutation im SMCHD1-Gen, welches eine Schlüsselfunktion in der Embryogenese der menschlichen Nase spielt, bestätigt (c.1043A > G; pHis348Arg). Aus neonatologischer Sicht ist oftmals die initiale Kreißsaal-Versorgung eine Herausforderung: Patienten mit Nasenagenesie werden häufig postpartal intubiert und elektiv tracheotomiert. Bei fehlender respiratorischer Problematik und Nahrungsaufnahme mit perzentilengerechtem Wachstum besteht jedoch keine dringliche Indikation zur frühzeitigen plastisch-chirurgischen Versorgung, insbesondere da diese mit Gefahren wie Sepsis und Wachstumsstörungen im Mittelgesicht behaftet ist.

scholarly journals Enhanced specificity of clinical high-sensitivity tumor mutation profiling in cell-free DNA via paired normal sequencing using MSK-ACCESS

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
A. Rose Brannon ◽  
Gowtham Jayakumaran ◽  
Monica Diosdado ◽  
Juber Patel ◽  
Anna Razumova ◽  
...  
Keyword(s):  
Cancer Patients ◽  
De Novo ◽  
Low Frequency ◽  
High Sensitivity ◽  
Clinical Analysis ◽  
De Novo Mutation ◽  
Cell Free Dna ◽  
Free Dna ◽  
Somatic Alterations ◽  
Mutation Profiling

AbstractCirculating cell-free DNA from blood plasma of cancer patients can be used to non-invasively interrogate somatic tumor alterations. Here we develop MSK-ACCESS (Memorial Sloan Kettering - Analysis of Circulating cfDNA to Examine Somatic Status), an NGS assay for detection of very low frequency somatic alterations in 129 genes. Analytical validation demonstrated 92% sensitivity in de-novo mutation calling down to 0.5% allele frequency and 99% for a priori mutation profiling. To evaluate the performance of MSK-ACCESS, we report results from 681 prospective blood samples that underwent clinical analysis to guide patient management. Somatic alterations are detected in 73% of the samples, 56% of which have clinically actionable alterations. The utilization of matched normal sequencing allows retention of somatic alterations while removing over 10,000 germline and clonal hematopoiesis variants. Our experience illustrates the importance of analyzing matched normal samples when interpreting cfDNA results and highlights the importance of cfDNA as a genomic profiling source for cancer patients.

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