Search

Infantile striatonigral degeneration is caused by a homozygous variant of the nuclear-pore complex (NPC) gene NUP62, involved in nucleo-cytoplasmic trafficking. By querying sequencing-datasets of patients with dystonia and/or Leigh(-like) syndromes, we identified 3 unrelated individuals with biallelic variants in NUP54. All variants clustered in the C-terminal protein region that interacts with NUP62. Associated phenotypes were similar to those of NUP62-related disease, including early-onset dystonia with dysphagia, choreoathetosis, and T2-hyperintense lesions in striatum. In silico and protein-biochemical studies gave further evidence for the argument that the variants were pathogenic. We expand the spectrum of NPC component-associated dystonic conditions with localized basal-ganglia abnormalities. ANN NEUROL 2022.

Although shared genetic factors have been previously reported between dystonia and other neurologic conditions, no sequencing study exploring such links is available. In a large dystonic cohort, we aimed at analyzing the proportions of causative variants in genes associated with disease categories other than dystonia.Gene findings related to whole-exome sequencing-derived diagnoses in 1100 dystonia index cases were compared with expert-curated molecular testing panels for ataxia, parkinsonism, spastic paraplegia, neuropathy, epilepsy, and intellectual disability.Among 220 diagnosed patients, 21% had variants in ataxia-linked genes; 15% in parkinsonism-linked genes; 15% in spastic-paraplegia-linked genes; 12% in neuropathy-linked genes; 32% in epilepsy-linked genes; and 65% in intellectual-disability-linked genes. Most diagnosed presentations (80%) were related to genes listed in ≥1 studied panel; 71% of the involved loci were found in the non-dystonia panels but not in an expert-curated gene list for dystonia.Our study indicates a convergence in the genetics of dystonia and other neurologic phenotypes, informing diagnostic evaluation strategies and pathophysiological considerations.

Background Heterozygous familial hypercholesterolemia (FH) represents the most frequent monogenic disorder with an estimated prevalence of 1:250 in the general population. Diagnosis during childhood enables early initiation of preventive measures, reducing the risk of severe consecutive atherosclerotic manifestations. Nevertheless, population-based screening programs for FH are scarce. Methods In the VRONI study, children aged 5–14 years in Bavaria are invited to participate in an FH screening program during regular pediatric visits. The screening is based on low-density lipoprotein cholesterol measurements from capillary blood. If exceeding 130 mg/dl (3.34 mmol/l), i.e. the expected 95th percentile in this age group, subsequent molecular genetic analysis for FH is performed. Children with FH pathogenic variants enter a registry and are treated by specialized pediatricians. Furthermore, qualified training centers offer FH-focused training courses to affected families. For first-degree relatives, reverse cascade screening is recommended to identify and treat affected family members. Results Implementation of VRONI required intensive prearrangements for addressing ethical, educational, data safety, legal and organizational aspects, which will be outlined in this article. Recruitment started in early 2021, within the first months, more than 380 pediatricians screened over 5200 children. Approximately 50 000 children are expected to be enrolled in the VRONI study until 2024. Conclusions VRONI aims to test the feasibility of a population-based screening for FH in children in Bavaria, intending to set the stage for a nationwide FH screening infrastructure. Furthermore, we aim to validate genetic variants of unclear significance, detect novel causative mutations and contribute to polygenic risk indices (DRKS00022140; August 2020).

Background: Families with young children are particularly vulnerable for the stressors induced by the COVID-19 pandemic. However, studies on their psychosocial situation during the course of the crisis are still sparse.Methods: In a comparison of three survey waves (wave I and III = high incidences), we cross-sectionally investigated the proportion of families (Ntotal = 2,940) with children aged 0-3 years experiencing pandemic burden, parenting stress, and parental and child mental health problems in relation to COVID-19 incidences and restrictions in Southern Germany. Potential influencing factors were also explored.Results: The number of parents with a high pandemic burden decreased from 65.3% to 57.3% in wave II and rose to 62.2% in wave III (significant changes except wave II vs. III). Participants with high parenting stress increased from 38.2% to 46.1% and 51.2% (all significant changes). The number of mothers with affective symptoms remained constant with a maximum of 28.3%. The proportion of affected fathers decreased from 25.4% in wave I to 14.3% in wave II and rose significantly to 28.4% in wave III. Infants with crying sleeping problems increased significantly from 26.4% in wave I to 35.5% in wave III. Toddlers’ emotional and behavioral problems showed a similar trend with 23.9% being affected in wave III (no significant changes after adjusting for child age and gender). Increased family conflicts during the pandemic were the strongest predictor for parenting stress (ß = .355), maternal (ß= .305), infants’ (ß= .149) and toddlers’ (ß= .216) mental health problems.Conclusions: Psychosocial stress factors in families with infants and toddlers remained highly pronounced and even partly increased irrespective of pandemic events. The ongoing heightened support needs of families with young children must remain a focus and promoting infants' mental health as well as strengthening a positive family microclimate should be a top priority in the aftermath of COVID-19.Trial registration: The study was pre-registered in OSF (https://osf.io/search/?q=tksh5&page=1).Keywords: Parent Psychosocial Functioning, Infant Mental Health, COVID-19, Depression, Anxiety, Early Life Adversity, Infancy and Early Childhood, Parenting, Stress, Pandemic

As IQ tests are commonly used as key assessment method, we address the question whether our commonly used standardized IQ tests are appropriate for children from families of diverse cultures and different educational levels in a refugee population. We examined 109 refugee children aged 3–7 years (M = 5.10 years, SD = 1.25) with the “Kaufman Assessment Battery for Children “ (KABC-II; Kaufmann & Kaufmann, 2015) on a language-free scale (Scale of Intellectual Functioning, SIF) and learning performance (subtest Atlantis). With a non-verbal IQ of 81.5 (SD = 18.01), the population mean of the refugee children is more than one standard deviation lower than the mean of the German norm population. Standardized scores follow the normal distribution and are not correlated to any of the assessed markers of adversity (flight duration, time spent in Germany, child PTSD in parent rating, parental symptom load, and parental education level).Conclusion: The interpretation of IQ test results for refugee children should be done cautiously as results may underestimate their cognitive capacity. Environmental factors, such as high illiteracy among parents in this study, the lack of institutional education of children and high lifetime stress, may explain our findings.Trial registration: DRKS00021150. What is Known:• There is a high pervasiveness for the use of standardized IQ tests in the German health and education system to determine eligibility for special education and social services. What is New:• Refugee children score significantly lower than German children in a language-free IQ test. As results are normally distributed and not correlated to any of the assessed markers of adversity, the low scores in the refugee group might be due to missing formal education.

Longitudinal studies of the last decades impressively demonstrate the potentially harmful influence of early psychosocial stress on children's physical and mental health (1,2,3). Within the first year of life, children are particularly vulnerable to health-relevant environmental factors, while at the same time their resilience is not yet very robust (4). Children between 1-3 years of age are also still highly dependent on the care provided by and the relationship with their parents. Overall, children aged 0-3 years are considered a special risk group for neglect and other forms of maltreatment (5). Currently, the restrictions caused by the Covid 19 pandemic and the worsening economic conditions lead to multiple psychosocial burdens for young families (parental stress, existential worries, etc.). It can be assumed that this is reflected in both the immediate parental stress and the children's behaviour (6). Early and systematic identification of the needs for psychosocial support in families with children between 0 and 3 years of age enables the prompt initiation of appropriate support services (e.g. early intervention services, so called “Frühe Hilfen”) and can contribute to preventing negative effects on child health. Due to the regular and early access to young families via the well-child visits (so called "U check-ups"), resident paediatricians are particularly suitable for this task (7). Currently, there is no universal standardised procedure in Germany that facilitates a reliable identification of psychosocially burdened families and referral to early intervention services. Within the framework of a Bavaria-wide study, it is to be examined whether the access rate to early prevention services can be positively influenced through a specific "early prevention module". Furthermore, the longitudinal course of psychosocial stress factors in families with children between 0 and 3 years of age during the Covid 19 pandemic will be investigated. A comparison with corresponding historical cohorts will be used to determine the extent to which the psychosocial stress of families with infants and young children has changed under the current crisis conditions, how the stress factors correlate and how effective support measures initiated by the paediatricians are. If psychosocial stress in families is detected at an early stage and support measures are initiated promptly, an escalation of the stressful circumstances (risk to children's well-being) and a chronification of the existing problems can be prevented. If the "early interventions module" proves to be effective, it should be considered to include it in the standard procedure of the paediatric U-check-ups. (1) Werner, E. E. (1993). Risk, resilience, and recovery: Perspectives from the Kauai Longitudinal Study. Development and Psychopathology, 5, 503-515. (2) Laucht, M., Esser, G. & Schmid, M. H. (1997). Developmental Outcome of Infants Born with Biological and Psychosocial Risks. Journal of Child Psychology and Psychiatry, 38(7), 843-854. (3) Laucht, M., Schmidt, M. H. & Esser, G. (2002). Motorische, kognitive und sozial-emotionale Entwicklung von 11-Jährigen mit frühkindlichen Risikobelastungen: späte Folgen. Zeitschrift für Kinder- und Jugendpsychiatrie, 30(1), 5-19. (4) Schlack, H. G. (2009). Sozialpädiatrie: Eine Standortbestimmung. In H. G. Schlack, R. von Kries & U. Thyen (Eds.), Sozialpädiatrie. Gesundheitswissenschaft und pädiatrischer Alltag (pp. 1-8). Berlin, Heidelberg: Springer. (5) Münder J, Mutke B, Schone R: Kindeswohl zwischen Jugendhilfe und Justiz. Münster: Votum-Verlag 2000. (6) Papoušek, M. (2004). Regulationsstörungen der frühen Kindheit: Klinische Evidenz für ein neues diagnostisches Konzept. In: M. Papoušek, M. Schieche, H. Wurmser (Hrsg.), Regulationsstörungen der frühen Kindheit, 77-110. Huber, Bern. (7) Hayutin, L. G., Reed-Knight, B., Blount, R. L., Lewis, J. & McCormick, M. L. (2009). Increasing Parent–Pediatrician Communication about Children’s Psychosocial Problems. Journal of Pediatric Psychology, 34 (10), 1155-1164.

BACKGROUND Excessive crying, sleeping, and feeding problems in early childhood are major stressors that can result in parents feeling socially isolated and having low self-efficacy. Affected children are a risk group for being maltreated and developing emotional and behavioral problems. Thus, the development of an innovative and interactive psychoeducational app for parents of children with crying, sleeping, and feeding problems may provide low-threshold access to scientifically based information and reduce negative outcomes in parents and children. OBJECTIVE We aimed to investigate whether following the use of a newly developed psychoeducational app, the parents of children with crying, sleeping, or feeding problems experienced less parenting stress; gained more knowledge about crying, sleeping, and feeding problems; and perceived themselves as more self-effective and as better socially supported and whether their children’s symptoms decreased more than those of the parents who did not use the app. METHODS Our clinical sample consisted of 136 parents of children (aged 0-24 months) who contacted a cry baby outpatient clinic in Bavaria (Southern Germany) for an initial consultation. Using a randomized controlled design, families were randomly allocated to either an intervention group (IG; 73/136, 53.7%) or a waitlist control group (WCG; 63/136, 46.3%) during the usual waiting time until consultation. The IG was given a psychoeducational app that included evidence-based information via text and videos, a child behavior diary function, a parent chat forum and experience report, tips on relaxation, an emergency plan, and a regional directory of specialized counseling centers. Outcome variables were assessed using validated questionnaires at baseline test and posttest. Both groups were compared at posttest regarding changes in parenting stress (primary outcome) and secondary outcomes, namely knowledge about crying, sleeping, and feeding problems; perceived self-efficacy; perceived social support; and child symptoms. RESULTS The mean individual study duration was 23.41 (SD 10.42) days. The IG reported significantly lower levels of parenting stress (mean 83.18, SD 19.94) after app use compared with the WCG (mean 87.46, SD 16.67; P=.03; Cohen d=0.23). Furthermore, parents in the IG reported a higher level of knowledge about crying, sleeping, and feeding (mean 62.91, SD 4.30) than those in the WCG (mean 61.15, SD 4.46; Pd=0.38). No differences at posttest were found between groups in terms of parental efficacy (P=.34; Cohen d=0.05), perceived social support (P=.66; Cohen d=0.04), and child symptoms (P=.35; Cohen d=0.10). CONCLUSIONS This study provides initial evidence of the efficacy of a psychoeducational app for parents with child crying, sleeping, and feeding problems. By reducing parental stress and increasing knowledge of children’s symptoms, the app has the potential to serve as an effective secondary preventive measure. Additional large-scale studies are needed to investigate long-term benefits. CLINICALTRIAL German Clinical Trials Register DRKS00019001; https://drks.de/search/en/trial/DRKS00019001

Inwieweit nutzen jüngere Kinder elektronische Medien? Und überhaupt – welche Bedeutung haben die neuen Medien und die zunehmende Medialisierung der kindlichen Lebenswelt für die Entwicklung und Gesundheit eines Kindes? Ein Überblick über aktuelle Studien und Handlungsempfehlungen.

Background: Physical surroundings of healthcare facilities are suggested to influence young patients’ well-being and hospitalization experiences. Purpose: The current research seeks to understand young patients’ views and perspectives of the hospital lobby and inpatient rooms. Thus, a qualitative study was carried out in a social pediatric clinic for young patients with disabilities, developmental delays, behavioral problems, and chronic health conditions, that is undergoing reconstruction. Method: Operating from a critical realist position, the study employed arts-based methods in conjunction with semi-structured interviews. The data were explored by employing thematic analysis. Results: 37 young people between the age of four and 30 years participated in the study. The analysis illustrates that the built environment should contain comforting and joyful elements, while enabling patients’ autonomy. The ideal lobby was depicted as open and accessible and an ideal patient room as practical and adapted to personal needs. Conclusion: It is suggested that disabling and medicalized spatial arrangements and features may restrict young people’s sense of control and autonomy, while possibly posing a barrier to a health-promoting environment. Large and open spaces with comforting and distracting features are cherished by patients and may be embedded in a comprehensive, yet simple overall design and structural concept.

This review summarizes the state of knowledge of use of new media on the development in early childhood in 6 sections: descriptive utilization data, psychosocial and emotional development, cognition and language, motor development, nutrition and sleep, and influence of parental media consumption.The review is based on a literature search of this topic in peer-reviewed journals. We included 87 articles, books, and book chapters. The used literature data bases were ERIC, PsycARTICLES, PsycINFO and PSYNDEX.Manifold studies describe in young children's utilization data the pervasive nature of digital exposure and impressive usage times and availability. They confirm adverse influences of electronic media use (television, video games) on children's emotional and behavioral problems and well-being, e. g. on physical activity, sleep and obesity. In general a positive effect in sense of knowledge transfer of age could be found for high quality educational media, however predominantly the impact of media use at younger age was negative.High frequent media use in early childhood is likely to have a negative impact on psychosocial development, positive effects such as knowledge transfer may be seen beyond the age of 18 months. As parental media use is a strong predictor of child media habits, reducing parental media use and enhancing parent-child interactions might be important areas to address when trying to change the media behavior of young children. In view of the scarcity of studies for early childhood, it is advisable to use digital play and communication devices cautiously and restrictively in this vulnerable development phase.Dieses Review fasst den aktuellen Wissensstand zum Gebrauch neuer Medien in der frühen Kindheit für 6 Bereiche zusammen: Deskriptive Gebrauchsdaten, psychosoziale und emotionale Entwicklung, Kognition und Sprache, motorische Entwicklung, Ernährung und Schlaf, Einfluss des elterlichen Medienkonsums.Das Review basiert auf einer Literaturrecherche in peer reviewed Zeitschriften. Insgesamt wurden 87 Artikel, Bücher und Buchkapitel eingeschlossen. Durchsucht wurden die Literaturdatenbänke ERIC, PsycARTICLES, PsycINFO und PSYNDEX.Die Studien dokumentieren die Allgegenwärtigkeit der Mediennutzung im frühen Lebensalter und weisen eindrucksvolle Nutzungszeiten und Verfügbarkeiten auf. Sie bestätigen ungünstige Einflüsse der elektronischen Medien (Fernseher, Videospiele) auf emotionale und Verhaltensprobleme und auf das Wohlergehen der Kinder, wie z. B. körperliche Aktivität, Schlaf und Übergewicht. Es konnten auch positive Einflüsse von pädagogisch hochwertigen Medien identifiziert werden. Jedoch überwiegen die negativen Effekte der Mediennutzung im jungen Alter deutlich.Ein hoher Medienkonsum in der frühen Kindheit hat negative Auswirkungen auf die psychosoziale Entwicklung, wohingegen positive Effekte wie bspw. Wissenstransfer erst ab einem Alter von 18 Monaten beobachtet werden können. Eine reduzierte Nutzung seitens der Eltern und eine verbesserte Eltern-Kind Interaktion sind wichtige Bereiche für eine Veränderung der kindlichen Mediennutzung. Wegen des Mangels an Studien ist es ratsam digitale Spiel- und Kommunikationsgeräte nur mit Vorsicht zu nutzen.

Background Psychosocial stress during the COVID-19 pandemic is increasing particularly in parents. Although being specifically vulnerable to negative environmental exposures, research on psychosocial stress factors in infants’ and toddlers’ families during the pandemic is so far sparse. The CoronabaBY study investigates the perceived pandemic burden, parenting stress and parent and child mental health problems in families with children aged 0–3 years in Bavaria, Southern Germany. Further, the relationships between these psychosocial stressors are examined and sociodemographic characteristics that may be predictive of these factors will be explored. Methods Participants were cross-sectionally surveyed via smartphone app. Standardized questionnaires on perceived pandemic burden, parenting stress, parental symptoms of depression and anxiety, infants’ crying, sleeping and feeding problems or toddlers’ emotional and behavioral problems were applied. Results N = 991 parents (Mage = 33.7 years, SD = 4.5; 93.7% mothers, 91.5% born in Germany) with infants (n = 554; Mage = 5.9 months, SD = 3.0) or toddlers (n = 435; Mage = 25.9 months, SD = 6.5) participated in the first half-year of 2021. Sixty-five percent of the parents perceived a high pandemic burden, 37.7% experienced parenting stress and 24.1% showed affective symptoms (anxiety: 30.1%, depression: 18.5%). Feeding problems, crying/ sleeping problems and multiple regulatory problems were found in 34.8%, 26.2% and 13.5% of the infants, respectively. Amongst toddlers, 8.5% showed noticeable behavior and emotional problems. Children`s mental health problems correlated moderately with parenting stress and parental affective symptoms and weakly with perceived pandemic burden. A lower financial status, higher parental education and increasing child age were significant but weak predictors for higher parenting stress, affective symptoms and higher psychological problems in children. Conclusions A majority of the surveyed families with infants and toddlers experience the pandemic as stressful. The main challenges are parental affective symptoms and limited resources for childcare due to parenting stress. Overall, infants and toddlers show similar levels of mental health problems when being compared to pre-pandemic studies, but staggered detrimental effects on children`s mental health might occur if the stressful conditions persist. This is already indicated by correlations between parental and child psychosocial stress factors.

ZUSAMMENFASSUNGDer Einsatz elektronischer Medien in der frühen Kindheit wird häufig kontrovers diskutiert. Der folgende Artikel soll zu dieser Diskussion einen evidenzbasierten Beitrag leisten. Mit dem Ziel konkrete Empfehlungen zur Mediennutzung abzugeben, wird vor allem zwei Fragen nachgegangen: 1. Die Auswirkungen von Mediennutzung in den ersten Lebensjahren auf die Entwicklung und die psychische Gesundheit. 2. Inwiefern „Lernen“ durch moderne elektronische Medien in dieser frühen Entwicklungsphase möglich ist. Die Literaturrecherche ergibt ein klares Bild bezüglich der Auswirkungen von exzessivem Medienkonsum auf die Kindesentwicklung und die psychische Gesundheit. Studien belegen eine verzögerte Sprachentwicklung, verzögerte motorische Fähigkeiten und Erhöhung des Risikos für Aufmerksamkeits- und Angststörung sowie Depression. Für Lerneffekte über digitale Medien gibt es zumindest vor dem 18. Lebensmonat keine Hinweise. Vor diesem Hintergrund wird der frühe Medienkonsum international einheitlich von allen Kinderärzte-Verbänden kritisch gesehen und ein Null-Konsum unter 18 (USA) bzw. 36 (D) Monaten empfohlen.

Background Excessive crying, sleeping, and feeding problems in early childhood are major stressors that can result in parents feeling socially isolated and having low self-efficacy. Affected children are a risk group for being maltreated and developing emotional and behavioral problems. Thus, the development of an innovative and interactive psychoeducational app for parents of children with crying, sleeping, and feeding problems may provide low-threshold access to scientifically based information and reduce negative outcomes in parents and children. Objective We aimed to investigate whether following the use of a newly developed psychoeducational app, the parents of children with crying, sleeping, or feeding problems experienced less parenting stress; gained more knowledge about crying, sleeping, and feeding problems; and perceived themselves as more self-effective and as better socially supported and whether their children’s symptoms decreased more than those of the parents who did not use the app. Methods Our clinical sample consisted of 136 parents of children (aged 0-24 months) who contacted a cry baby outpatient clinic in Bavaria (Southern Germany) for an initial consultation. Using a randomized controlled design, families were randomly allocated to either an intervention group (IG; 73/136, 53.7%) or a waitlist control group (WCG; 63/136, 46.3%) during the usual waiting time until consultation. The IG was given a psychoeducational app that included evidence-based information via text and videos, a child behavior diary function, a parent chat forum and experience report, tips on relaxation, an emergency plan, and a regional directory of specialized counseling centers. Outcome variables were assessed using validated questionnaires at baseline test and posttest. Both groups were compared at posttest regarding changes in parenting stress (primary outcome) and secondary outcomes, namely knowledge about crying, sleeping, and feeding problems; perceived self-efficacy; perceived social support; and child symptoms. Results The mean individual study duration was 23.41 (SD 10.42) days. The IG reported significantly lower levels of parenting stress (mean 83.18, SD 19.94) after app use compared with the WCG (mean 87.46, SD 16.67; P=.03; Cohen d=0.23). Furthermore, parents in the IG reported a higher level of knowledge about crying, sleeping, and feeding (mean 62.91, SD 4.30) than those in the WCG (mean 61.15, SD 4.46; P Conclusions This study provides initial evidence of the efficacy of a psychoeducational app for parents with child crying, sleeping, and feeding problems. By reducing parental stress and increasing knowledge of children’s symptoms, the app has the potential to serve as an effective secondary preventive measure. Additional large-scale studies are needed to investigate long-term benefits. Trial Registration German Clinical Trials Register DRKS00019001; https://drks.de/search/en/trial/DRKS00019001

Dorothee Wein, Volker Mall und Harald Roth: Spuren von Auschwitz ins Gäu. Das KZ-Außenlager Hailfingen/Tailfingen. Marksteinverlag Filderstadt 2007. 266 Seiten mit rund 100 Abbildungen. Gebunden € 19,90. (+ 1,40 € Porto zu bestellen bei Birgit Kipfer, Krebsbachstr.34, 71116 Gärtringen). ISBN 978-3-935129-31-2

Volker Mall und Harald Roth: «Jeder Mensch hat einen Namen» – Gedenkbuch für die 600 jüdischen Häftlinge des KZ-Außenlagers Hailfingen/ Tailfingen. Metropol-Verlag Berlin 2009. 364 Seiten mit 140 Abbildungen, DVD mit zwei Dokumentarfilmen. Gebunden € 24,–. (zu bestellen zuzüglich 2,– € Porto bei Birgit Kipfer, Krebsbachstrraße 34, 71116 Gärtringen. E-Mail: kipfer.rohrau@t-online.de)

As IQ tests are commonly used as key assessment method, we address the question whether our commonly used standardized IQ tests are appropriate for children from families of diverse cultures and different educational levels in a refugee population. We examined 109 refugee children aged 3-7 years (M = 5.10 years, SD = 1.25) with the "Kaufman Assessment Battery for Children " (KABC-II; KaufmannKaufmann, 2015) on a language-free scale (Scale of Intellectual Functioning, SIF) and learning performance (subtest Atlantis). With a non-verbal IQ of 81.5 (SD = 18.01), the population mean of the refugee children is more than one standard deviation lower than the mean of the German norm population. Standardized scores follow the normal distribution and are not correlated to any of the assessed markers of adversity (flight duration, time spent in Germany, child PTSD in parent rating, parental symptom load, and parental education level).Conclusion: The interpretation of IQ test results for refugee children should be done cautiously as results may underestimate their cognitive capacity. Environmental factors, such as high illiteracy among parents in this study, the lack of institutional education of children and high lifetime stress, may explain our findings.Trial registration: DRKS00021150. What is Known: • There is a high pervasiveness for the use of standardized IQ tests in the German health and education system to determine eligibility for special education and social services. What is New: • Refugee children score significantly lower than German children in a language-free IQ test. As results are normally distributed and not correlated to any of the assessed markers of adversity, the low scores in the refugee group might be due to missing formal education.

Volker Mall: Die Häftlinge des KZ-Außenlagers Hailfingen/Tailfingen. Daten und Porträts aller Häftlinge. BoD-Books on Demand Norderstedt 2014. 420 Seiten mit einigen Abbildungen. Broschur €13,99. ISBN 978-3-7386-0332-3

More than 1 million Syrian refugees have sought asylum in Europe since 2011. Disastrous conditions in their country and an arduous flight increased the risk for the emergence of physical and mental problems, especially in children. We performed a comprehensive medical and psychological examination in 96 Syrian refugee children aged 0–14 years in a German reception camp. Parents were interviewed and answered questions on health, flight and living conditions. In the children, we found most frequently somatic and in particular dental problems, incomplete immunization state and mental disorders. Post-traumatic stress disorder (PTSD) was diagnosed in 30.2 per cent of the children. Fifty-seven per cent of the parents reported somatic complaints; most of them were neurological (e.g. headache) and sleep disorders. Syrian refugee children show a significant rate of PTSD, somatic disorders and incomplete immunization state. The separation from family members during flight and physical complaints of the parents were identified as risk factors for PTSD in the children of our study. Early combined acute and preventive health-care management for children and their parents is indicated.

Background Despite the established value of genomic testing strategies, practice guidelines for their use do not exist in many indications. Objectives We sought to validate a recently introduced scoring algorithm for dystonia, predicting the diagnostic utility of whole-exome sequencing (WES) based on individual phenotypic aspects (age-at-onset, body distribution, presenting comorbidity). Methods We prospectively enrolled a set of 209 dystonia-affected families and obtained summary scores (0-5 points) according to the algorithm. Singleton (N = 146), duo (N = 11), and trio (N = 52) WES data were generated to identify genetic diagnoses. Results Diagnostic yield was highest (51%) among individuals with a summary score of 5, corresponding to a manifestation of early-onset segmental or generalized dystonia with coexisting non-movement disorder-related neurological symptoms. Sensitivity and specificity at the previously suggested threshold for implementation of WES (3 points) was 96% and 52%, with area under the curve of 0.81. Conclusions The algorithm is a useful predictive tool and could be integrated into dystonia routine diagnostic protocols. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

Introduction Next-generation sequencing is now used on a routine basis for molecular testing but studies on copy-number variant (CNV) detection from next-generation sequencing data are underrepresented. Utilizing an existing whole-exome sequencing (WES) dataset, we sought to investigate the contribution of rare CNVs to the genetic causality of dystonia. Methods The CNV read-depth analysis tool ExomeDepth was applied to the exome sequences of 953 unrelated patients with dystonia (600 with isolated dystonia and 353 with combined dystonia; 33% with additional neurological involvement). We prioritized rare CNVs that affected known disease genes and/or were known to be associated with defined microdeletion/microduplication syndromes. Pathogenicity assessment of CNVs was based on recently published standards of the American College of Medical Genetics and Genomics and the Clinical Genome Resource. Results We identified pathogenic or likely pathogenic CNVs in 14 of 953 patients (1.5%). Of the 14 different CNVs, 12 were deletions and 2 were duplications, ranging in predicted size from 124bp to 17 Mb. Within the deletion intervals, BRPF1, CHD8, DJ1, EFTUD2, FGF14, GCH1, PANK2, SGCE, UBE3A, VPS16, WARS2, and WDR45 were determined as the most clinically relevant genes. The duplications involved chromosomal regions 6q21-q22 and 15q11-q13. CNV analysis increased the diagnostic yield in the total cohort from 18.4% to 19.8%, as compared to the assessment of single-nucleotide variants and small insertions and deletions alone. Conclusions WES-based CNV analysis in dystonia is feasible, increases the diagnostic yield, and should be combined with the assessment of single-nucleotide variants and small insertions and deletions.

PURPOSEBi-allelic TECPR2 variants have been associated with a complex syndrome with features of both a neurodevelopmental and neurodegenerative disorder. Here, we provide a comprehensive clinical description and variant interpretation framework for this genetic locus.METHODSThrough an international collaboration, we identified 17 individuals from 15 families with bi-allelic TECPR2-variants. We systemically reviewed clinical and molecular data from this cohort and 11 cases previously reported. Phenotypes were standardized using Human Phenotype Ontology terms.RESULTSA cross-sectional analysis revealed global developmental delay/intellectual disability, muscular hypotonia, ataxia, hyporeflexia, respiratory infections and central/nocturnal hypopnea as core manifestations. A review of brain MRI scans demonstrated a thin corpus callosum in 52%. We evaluated 17 distinct variants. Missense variants in TECPR2 are predominantly located in the N- and C-terminal regions containing β-propeller repeats. Despite constituting nearly half of disease associated TECPR2 variants, classifying missense variants as (likely) pathogenic according to ACMG criteria remains challenging. We estimate a pathogenic variant carrier frequency of 1/1,221 in the general and 1/155 in the Jewish Ashkenazi populations.CONCLUSIONBased on clinical, neuroimaging and genetic data, we provide recommendations for variant reporting, clinical assessment, and surveillance/treatment of individuals with TECPR2-associated disorder. This sets the stage for future prospective natural history studies.CONFLICTS OF INTERESTAll authors involved in the study declare no conflicts of interest relevant to this study.

Summary Background Dystonia is a clinically and genetically heterogeneous condition that occurs in isolation (isolated dystonia), in combination with other movement disorders (combined dystonia), or in the context of multisymptomatic phenotypes (isolated or combined dystonia with other neurological involvement). However, our understanding of its aetiology is still incomplete. We aimed to elucidate the monogenic causes for the major clinical categories of dystonia. Methods For this exome-wide sequencing study, study participants were identified at 33 movement-disorder and neuropaediatric specialty centres in Austria, Czech Republic, France, Germany, Poland, Slovakia, and Switzerland. Each individual with dystonia was diagnosed in accordance with the dystonia consensus definition. Index cases were eligible for this study if they had no previous genetic diagnosis and no indication of an acquired cause of their illness. The second criterion was not applied to a subset of participants with a working clinical diagnosis of dystonic cerebral palsy. Genomic DNA was extracted from blood of participants and whole-exome sequenced. To find causative variants in known disorder-associated genes, all variants were filtered, and unreported variants were classified according to American College of Medical Genetics and Genomics guidelines. All considered variants were reviewed in expert round-table sessions to validate their clinical significance. Variants that survived filtering and interpretation procedures were defined as diagnostic variants. In the cases that went undiagnosed, candidate dystonia-causing genes were prioritised in a stepwise workflow. Findings We sequenced the exomes of 764 individuals with dystonia and 346 healthy parents who were recruited between June 1, 2015, and July 31, 2019. We identified causative or probable causative variants in 135 (19%) of 728 families, involving 78 distinct monogenic disorders. We observed a larger proportion of individuals with diagnostic variants in those with dystonia (either isolated or combined) with coexisting non-movement disorder-related neurological symptoms (100 [45%] of 222; excepting cases with evidence of perinatal brain injury) than in those with combined (19 [19%] of 98) or isolated (16 [4%] of 388) dystonia. Across all categories of dystonia, 104 (65%) of the 160 detected variants affected genes which are associated with neurodevelopmental disorders. We found diagnostic variants in 11 genes not previously linked to dystonia, and propose a predictive clinical score that could guide the implementation of exome sequencing in routine diagnostics. In cases without perinatal sentinel events, genomic alterations contributed substantively to the diagnosis of dystonic cerebral palsy. In 15 families, we delineated 12 candidate genes. These include IMPDH2, encoding a key purine biosynthetic enzyme, for which robust evidence existed for its involvement in a neurodevelopmental disorder with dystonia. We identified six variants in IMPDH2, collected from four independent cohorts, that were predicted to be deleterious de-novo variants and expected to result in deregulation of purine metabolism. Interpretation In this study, we have determined the role of monogenic variants across the range of dystonic disorders, providing guidance for the introduction of personalised care strategies and fostering follow-up pathophysiological explorations. Funding Else Kroner-Fresenius-Stiftung, Technische Universitat Munchen, Helmholtz Zentrum Munchen, Medizinische Universitat Innsbruck, Charles University in Prague, Czech Ministry of Education, the Slovak Grant and Development Agency, the Slovak Research and Grant Agency.

Next-generation sequencing (NGS) technologies in clinical diagnostics open vast opportunities through the ability to sequence all genes simultaneously at a cost and speed that is superior to traditional sequencing approaches. On the other hand, the practical implementation of NGS in routine diagnostics involves a variety of challenges, which need to be overcome. Among these are the generation, analysis and storage of large amounts of data, strict control of sequencing performance, validation of results, interpretation of detected variants and reporting. Here, we outline the Multiple Integration and Data Annotation Study, an approach for data integration in clinical diagnostics based on genotype-phenotype correlations. MIDAS aims to accelerate NGS data analysis and to enhance the validity of the results by computer-based variant prioritization using the clinical data of the patient. In this context, we present the MIDAS case reports of one patient with intellectual disability caused by a novel de novo loss-of-function variant in theGATAD2Bgene [NM_020699.3: c.1426G>T (p.Glu476*)] identified by trio whole-exome sequencing, as well as two cardiac disease patients with severe phenotype and multiple variants in genes linked to cardiac arrhythmogenic disorders analyzed with multi-gene panel sequencing. Based on the data collected in the MIDAS cohort, the MIDAS software will be tested and optimized. Moreover, the MIDAS software concept can be extended modularly to include further data resources for improved data handling and interpretation in the broad field of diagnostics.

Purpose: This study characterizes the clinical and genetic features of nine unrelated patients with de novo variants in the NR4A2 gene. Methods: Variants were identified and de novo origins were confirmed through trio exome sequencing in all but one patient. Targeted RNA sequencing was performed for one variant to confirm its splicing effect. Independent discoveries were shared through GeneMatcher. Results: Missense and loss-of-function variants in NR4A2 were identified in patients from eight unrelated families. One patient carried a larger deletion including adjacent genes. The cases presented with developmental delay, hypotonia (six cases), and epilepsy (six cases). De novo status was confirmed for eight patients. One variant was demonstrated to affect splicing and result in expression of abnormal transcripts likely subject to nonsense-mediated decay. Conclusion: Our study underscores the importance of NR4A2 as a disease gene for neurodevelopmental disorders and epilepsy. The identified variants are likely causative of the seizures and additional developmental phenotypes in these patients.

This study aims to evaluate the effectiveness of a prefabricated carbon-composite ankle foot orthoses (c-AFOs) on gait parameters in children with unilateral spastic cerebral palsy (USCP) exhibiting a drop foot pattern.Sixteen ambulatory children with USCP and a drop foot pattern were included (mean age: 9 years; gross motor function classification system: I = 14, II = 2) and three-dimensional gait analysis was applied under randomly assigned conditions (barefoot; shoe; c-AFO). Kinematics, kinetics, time-distance parameters and gait indices were investigated.Effects on the drop foot pattern were investigated while the children walked in shoes only. The shoes already increased the maximum ankle dorsiflexion in swing (p= 0.004) and initiated more knee flexion during single support (p⩽ 0.013). Compared to shoe walking, the c-AFO led to additional benefits regarding further ankle dorsiflexion during swing (p⩽ 0.001) and initial contact (p0.001), ankle movement during loading response (p= 0.002), improved the sole angle during initial contact (p0.001) and during mid stance (p= 0.015). Plantarflexion and ankle power generation during push-off decreased when wearing the c-AFO (p⩽ 0.008).Investigated c-AFOs are beneficial for improving drop foot patterns in children with USCP. Significant effects on pathological barefoot pattern were already achieved with the child's regular shoes. This could be considered in clinical decision processes. In comparison to shoe walking, c-AFO additionally improved foot clearance and normalized initial heel contact. The third rocker deteriorates with the c-AFO. Since kinematics improved with the orthoses during swing and early stance phase, c-AFOs might reduce tripping and falling caused by a drop foot during long distance walking.

Mitochondrial dynamics such as fission and fusion play a vital role in normal brain development and neuronal activity. DNM1L encodes a dynamin-related protein 1 (Drp1), which is a GTPase essential for proper mitochondrial fission. The clinical phenotype of DNM1L mutations depends on the degree of mitochondrial fission deficiency, ranging from severe encephalopathy and death shortly after birth to initially normal development and then sudden onset of refractory status epilepticus with very poor neurologic outcome. We describe a case of a previously healthy 3-year-old boy with a mild delay in speech development until the acute onset of a refractory status epilepticus with subsequent epileptic encephalopathy and very poor neurologic outcome. The de novo missense mutation in DNM1L (c.1207C > T, p.R403C), which we identified in this case, seems to determine a unique clinical course, strikingly similar to four previously described patients in literature with the identical de novo heterozygous missense mutation in DNM1L.

Synaptic plasticity in the form of long-term potentiation (LTP) and long-term depression (LTD) is considered to be the neurophysiological correlate of learning and memory. Impairments are discussed to be one of the underlying pathophysiological mechanisms of developmental disorders. In so-called RASopathies [e.g., neurofibromatosis 1 (NF1)], neurocognitive impairments are frequent and are affected by components of the RAS pathway which lead to impairments in synaptic plasticity. Transcranial magnetic stimulation (TMS) provides a non-invasive method to investigate synaptic plasticity in humans. Here, we review studies using TMS to evaluate synaptic plasticity in patients with RASopathies. Patients with NF1 and Noonan syndrome (NS) showed reduced cortical LTP-like synaptic plasticity. In contrast, increased LTP-like synaptic plasticity has been shown in Costello syndrome. Notably, lovastatin normalized impaired LTP-like plasticity and increased intracortical inhibition in patients with NF1. TMS has been shown to be a safe and efficient method to investigate synaptic plasticity and intracortical inhibition in patients with RASopathies. Deeper insights in impairments of synaptic plasticity in RASopathies could help to develop new options for the therapy of learning deficits in these patients.

Sozialpadiatrie beschaftigt sich mit sozialen Determinanten fur Erkrankungen. Diese konnen die Inzidenz bzw. Pravalenz von Morbiditat und Mortalitat verandern. Epidemiologie beschreibt zeitliche Trends in Populationen und untersucht deren Ursachen. Durch Pravention sollen Erkrankungsraten reduziert bzw. deren Prognose verbessert werden. Psychische Storungen sind haufige Phanomene und betreffen bis zu 20% der Kinder und Jugendlichen bis zum Erreichen des Erwachsenenalters. Die Besonderheit der Phanomenologie psychischer Storungen im Kindes- und Jugendalters ist ihre enge Verbindung zur Entwicklung des Individuums und ihre haufig starke Wechselwirkung mit korperlichen Funktionen und dem Auftreten somatischer Symptome. Aus diesem Grund bewahrt sich fur das Verstandnis und die Versorgung zahlreicher psychischer Storungen ein biopsychosomatischer Ansatz im Kindes- und Jugendalter. Dieser Ansatz kann als Wechsel der Perspektive von einer primar auf das Organ zu einer mehr psychisch zentrierten Betrachtung in der Diagnostik und Behandlung von Storungen mit einer primar korperlichen Symptomatik verstanden werden. Dieser Vorstellung liegt zugrunde, dass keine somatische Symptomatik isoliert aufritt, ohne dass ein psychisches Korrelat besteht, was dann als somato-psychisches Phanomen beschrieben werden kann. Psychosomatische Erkrankungen sind z. B. die Essstorungen, die dissoziativen und die somatoformen Storungen.