A heritable microduplication encompassing TBL1XR1 causes a genomic sister-disorder for the 3q26.32 microdeletion syndrome.

Recently, a new syndrome with intellectual disability (ID) and dysmorphic features due to deletions or point mutations within the TBL1XR1 gene located in the chromosomal band 3q26.32 has been described (MRD41, OMIM 616944). One recurrent point mutation in the TBL1XR1 gene has been identified as the cause of Pierpont syndrome (OMIM 602342), a distinct intellectual disability syndrome with plantar lipomatosis. In addition, different de novo point mutations in the TBL1XR1 gene have been found in patients with autism spectrum disorders (ASD) and intellectual disability. Here, we report four patients from two unrelated families in whom array-CGH analysis and real-time quantitative PCR of genomic DNA revealed a TBL1XR1-microduplication. Adjacent genes were not affected. The microduplication occurred as a de novo event in one patient, whereas the other three cases occurred in two generations of a second, unrelated family. We compare and contrast the clinical findings in TBL1XR1 microdeletion, point mutation, and microduplication cases and expand the TBL1XR1-associated phenotypic spectrum. ID, hearing loss, and ASD are common features of TBL1XR1-associated diseases. Our clinical observations add to the increasing evidence of the role of TBL1XR1 in brain development, and they simultaneously demonstrate that different genetic disease mechanisms affecting TBL1XR1 can lead to similar ID phenotypes. The TBL1XR1-microduplication syndrome is an intellectual disability/learning disability syndrome with associated incomplete penetrance ASD, hearing loss, and delay of puberty. Its phenotypic overlap indicates that it is a genomic sister-disorder to the 3q26.32 microdeletion syndrome.

Prevalence of sleep problems and relationship between sleep problems and school refusal behavior in school-aged children in children's and parents' ratings.

OBJECTIVE: This cross-section study investigated the prevalence of sleep disorders and the relationship between sleep problems (insomnias, parasomnias, and daytime sleepiness) and school refusal behavior in school-age children (fourth grade elementary school in Cologne, Germany). METHOD: A sample of 1,490 children (age range: 8-11 years) and their parents each completed a sleep questionnaire and the School Refusal Assessment Scale. RESULTS: The results indicate that sleep problems in childhood are frequent. Furthermore, the results of the study clearly indicate that there is a relationship between sleep problems and school refusal behavior. Children suffering from insomnias (sleep onset problems, difficulties maintaining sleep), parasomnias (nightmares, night terrors), and daytime sleepiness showed without exception significantly higher scores in 3 out of 4 school refusal behavior maintaining conditions compared to children without sleep problems. These three conditions are all associated with anxiety disorders (anxiety or depressive disorder, as well as separation anxiety disorder). Only in the fourth condition, which is associated with oppositional defiant or conduct disorders, truancy, or no disorder at all, were there no significant differences between children with and children without sleep problems. CONCLUSIONS: For research and clinical practice, it is important to view sleep problems and school refusal behavior in relation to each other rather than as isolated phenomena.

Normative values of polysomnographic parameters in childhood and adolescence: arousal events.

OBJECTIVE: This study focused on differences in arousals during sleep, using the arousal rules of the American Academy of Sleep Medicine, by gender, age, and maturity in healthy children. METHODS: One-night polysomnography was performed on 209 healthy German children (age 1-18 years) at their habitual bedtimes in 16 laboratories. Subjects were grouped by gender (112 females, 97 males), age, and Tanner stage. RESULTS: Normative values of arousal events in sleep are presented, including indexes of spontaneous and respiratory arousals, total electroencephalogram (EEG) arousals, phasic increase in submental electromyogram (EMG) in stage R, and leg movements. With increasing age, a decrease was seen in: EEG arousal index ≥1-2.9 s, EEG arousal index ≥3 s, index of total EEG arousals, index of respiratory arousals, chin EMG enhancement in stage R ≥1-2.9 and ≥3 s, index of total leg movements, and leg movements with EEG arousals (p<0.05). Only spontaneous arousals showed no association with age. There was a significant negative correlation between Tanner stage and arousals ≥1-2.9 s, respiratory arousals, leg movements, and leg movements with arousals (p<0.05). Only arousals ≥3 s and total leg movements showed gender differences (p<0.05). CONCLUSIONS: For the diagnosis of pediatric sleep disturbances, the given arousal data enable estimation of the degree of deviation from normal findings for age and maturity. There is need for further research on, and further discussion of, the arousal rules of the American Academy of Sleep Medicine.

Normative values of polysomnographic parameters in childhood and adolescence: cardiorespiratory parameters.

OBJECTIVE: To provide normative values for pediatric sleep cardiorespiratory parameters following AASM rules, assessing effects of gender, age, and Tanner stage. METHODS: One-night polysomnograhy was performed at subjects' habitual bedtimes in 16 laboratories on 209 healthy German children, 1-18 years old. RESULTS: Normative values of cardiorespiratory parameters in pediatric sleep are presented. No obstructive and mixed apneas occurred. Hypopneas were seldom. Respiratory frequency and apnea-hypopnea-index decreased with age (p<0.001). In all groups central apneas ≥ 20 s were present but uncommon. Oxygen desaturations or respiratory arousals following central apnea were rare. Heart rate showed an inverse correlation to age (p<0.001). Heart rate was lower in sleep, lowest in stage N. The mean heart rate of females was higher than males (p<0.05). Neither Tanner stage nor corresponding age (p<0.05) influenced: mean apnea duration, central apnea index ≥ 20 s, hypopnea index, index of periodic breathing, or oxygen saturation nadir. All other parameters except maximal apnea duration and central apnea index after movements with oxygen desaturation show dependency on both Tanner stage and corresponding age (p<0.05). CONCLUSIONS: Using AASM rules, the development of cardiorespiratory parameters in healthy children, ages 1-18 is shown. Age-related norms may improve sleep pathology identification.

Normative values of polysomnographic parameters in childhood and adolescence: quantitative sleep parameters.

OBJECTIVE: To provide normative values for sleep macroarchitecture of healthy children aged 1-18 years using the AASM sleep scoring criteria, assessing the effects of gender, age, and Tanner pubertal stage. METHODS: One-night polysomnography was performed at subjects' habitual bedtimes in 16 laboratories on 209 healthy German children. RESULTS: Normal values of sleep macrostructure show significant age dependencies (p<0.05). Increasing with age: awakening index, R latency (RL), sleep efficiency (SE) (total sleep time (TST)/sleep period time (SPT)) and SE (TST/time in bed), stage N2, mean sleep cycle duration, number of stage shifts. Decreasing with age: TST, SPT, wake after sleep onset, stage N3, stage R, movement time (MT), number of sleep cycles. The following sleep parameters show a dependency on Tanner stages as well as corresponding age (p<0.05):TST, SPT, awakening index, R latency, stage N2, stage N3, MT, number of sleep cycles, mean sleep cycle duration. No gender dependencies were found. CONCLUSION: The given study, considering AASM rules, shows the development of sleep in normal children ages 1-18. Subject selection criteria and other factors influencing sleep as well AASM guideline modifications including scoring arousals in N2 and scoring MT as a measure of sleep fragmentation are discussed.

Applying principles of good practice for translation and cross-cultural adaptation of sleep-screening instruments in children.

With the increase in the number of international projects in pediatric sleep medicine, the need to adapt sleep-screening tools for use in cross-cultural settings has rapidly grown. However, accepted procedures for translating and adapting existing measures are not uniformly and consistently incorporated in epidemiologic studies, resulting in potential measurement problems. The aims of this brief report are to (a) give an overview of principles for the translation and cultural adaptation of pediatric sleep-screening instruments and (b) illustrate these procedures in describing the translation and adaptation of two widely used pediatric sleep-screening tools for a German population. Challenges in the development of cross-cultural adaptations of parent-report sleep-screening measures for children are also discussed.

Longitudinal study of nightmares in children: stability and effect of emotional symptoms.

Nightmares are defined as dreams with strong negative emotions which awaken the dreamer and are common during childhood: cross-sectional data shows the highest prevalence rates between the ages of five and ten. The present longitudinal study was designed to study the stability of nightmares over the course of 2 years. Sleep questionnaires and Strengths and Difficulties Questionnaires were completed by 851 10-years-old children and their parents, separately. In the total sample, nightmares occurred often in 2.5% (parental estimates) to 3.5% (self estimates of the children). The findings indicate that nightmare stability is considerably high, i.e., nightmare occurrence was predicted by the prevalence the year before (in addition to the concurrent amount of emotional symptoms). Children with 'chronic' nightmares showed more psychopathological symptoms. It would be interesting to follow-up these children in order to investigate whether childhood nightmares are also predictive for adult psychopathology.

Factors affecting nightmares in children: parents' vs. children's ratings.

OBJECTIVE: The present study investigated the relationship between daytime symptomatology and nightmare frequency in school-aged children by eliciting daytime symptoms and nightmare frequency from children directly in addition to questionnaires completed by their parents. METHODS: A sample of 4,834 parents and 4,531 of their children (age range: 8-11 years) completed each a sleep questionnaire and the strengths and difficulties questionnaire (SDQ). RESULTS: The results of the study clearly indicate that there is an underestimation of nightmare frequency in the parents' ratings compared to the children's data (effect size: d = 0.30) and the closeness between influencing factors and nightmare frequency is considerably higher for the data based on the children's responses; the proportion of explained variance was twice as high. CONCLUSIONS: Therefore, it seems important for research and clinical practice to not to rely on parents' information but to ask the children about the occurrence of nightmares.

Sleep disorders in children beginning school: their causes and effects.

BACKGROUND: Sleep disorders are a common problem among children beginning school and may be associated both with impaired school performance and with behavioral difficulties. Because these disorders manifest themselves highly variably among children of any given age, and even in an individual affected child, they need an appropriate diagnostic evaluation so that the many environmental and background factors that may be relevant to the further course of the problem can be assessed. METHODS: Extensive data were obtained on approximately 1400 children who were tested before beginning school in 2005 by means of a special sleep questionnaire and another screening instrument that is used to assess behavioral strengths and difficulties (the SDQ, Strengths and Difficulties Questionnaire). RESULTS: Five percent of the children were found to have difficulty falling asleep, difficulty staying asleep, or nocturnal awakening. Less frequent problems included parasomnias such as pavor nocturnus (0.5%), sleepwalking (0.1%), and frequent nightmares (1.7%). CONCLUSION: Sleep disorders increase the risk of daytime fatigue and of psychological problems in general, including both hyperactivity and excessive emotional stress. These results imply that sleep problems and emotional disturbances are intimately connected and underscore the importance of diagnosing sleep problems in young children.

Increased slow wave sleep and reduced stage 2 sleep in children depending on exercise intensity.

BACKGROUND: There is controversy about the consequences of physical exercise on human sleeping behaviors. Evidence suggests that voluntary physical exercise affects brain structures and functions. However, there are inconsistent data regarding the effects of exercise on sleep architecture and sleep continuity, especially the amounts of slow wave sleep (SWS) and rapid eye movement (REM) sleep. OBJECTIVE: The aim of the present study was to investigate the effects of moderate and high intense physical exercise on vigilance state and sleep patterns in school-aged children. METHODS: Eleven healthy children (12.6+/-0.8 years old) were recruited for this polysomnographic study and underwent two exercise sessions. The two exercise sessions on a bicycle ergometer were performed 3-4h prior to bedtime, lasted 30min and varied in intensity. The moderate-intensity exercise was at 65-70% of maximal heart rate (HR(max)) while the high-intensity exercise was at 85-90% HR(max) to exhaustion. Polysomnographic and physiological measurements, including oximetry, were made on three nights in random order and separated by 1 week. Vigilance tests were carried out before and after the three sleep periods. RESULTS: Only high-intensity exercise resulted in a significantly elevated SWS proportion and less sleep in stage 2 as well as a higher sleep efficiency and shorter sleep onset latency. No significant effects on REM sleep were found. CONCLUSION: The results suggest that exercise intensity is responsible for the effects on stage 2 sleep and SWS in children and support the hypothesis of homeostatic sleep regulation.

Prevalence and course of sleep problems in childhood.

STUDY OBJECTIVES: The Cologne Children's Sleep Study intended to provide information on prevalence and course of difficulties of initiating and maintaining sleep in childhood. DESIGN: Longitudinal study. SETTING: Children of the fourth grade of elementary schools in Cologne. PARTICIPANTS: 832 children and their parents; the mean age of the children was 9.4, 10.7, and 11.7 years at the 3 assessments. MEASUREMENTS AND RESULTS: Children and parents were surveyed using questionnaires 3 times on an annual basis. In self- and parental reports, about 30%-40% of the children of the longitudinal sample had problems falling asleep at the first assessment. One year later, about 30% to 40% of these children did not describe any difficulties initiating sleep, whereas about 60% did report continuing difficulties initiating sleep. Difficulties maintaining sleep are less common in childhood. The analysis of self- and parental reports revealed that in general children described significantly more difficulties initiating and maintaining sleep than their parents report. CONCLUSIONS: Difficulties initiating and maintaining sleep may be transient or persistent. In practice, children and adolescents should be included in the diagnostic and therapeutic process.

[A new treatment program for children with sleep disorders--concept, practicability, and first empirical results]. / Kölner Behandlungsprogramm für Kinder mit Schlafstörungen--Konzept, praktische Durchführung und erste empirische Ergebnisse.

Sleep disorders are common in childhood. We introduce a new psychological treatment program for children with sleep disorders. The program consists of different educational modules and can be conducted in single and group setting. In this case study, the program was implemented with a small group of parents (4 participants) in order to receive information on the efficacy of treatment. Sleep behaviour and children's well-being were improved in all cases. Moreover, the assessment of the treatment concept was extremely positively rated without any exception.

[Sleep disorders in children with attention-deficit hyperactivity disorder--results of a polysomnographic study]. / Schlafstörungen bei hyperkinetischen Kindern--Polysomnografische Untersuchungen zur Schlafstruktur und -architektur.

OBJECTIVES: We report results of a polysomnographic study carried out with children aged 6 to 12 years with either ADHD or a sleep disorder. The study focussed on whether the sleep structure and architecture of n = 36 ADHD children with and without sleep disorders differed from that of either n=15 children with sleep disorders or n=87 children without sleep disorders. Moreover, we assessed whether there was an increased risk for co-morbid sleep-related breathing disorders among ADHD children. METHODS: All children underwent polysomnography in a paediatric clinic. Principal variables of the sleep structure and architecture as well as cardiorespirographic measures were analysed. RESULTS: Our findings demonstrate that sleep problems in children with ADHD seem to be unspecific concurrent symptoms since the sleep structure of sleep-disordered ADHD children and children with sleep disorders was similar. Only minor differences were found between non-sleep-disturbed ADHD children and healthy children without sleep problems. CONCLUSIONS: We conclude that sleep problems in ADHD are independent co-morbid symptoms without any pathogenetic relationship to vigilance functions in ADHD. The cardiorespirographic analyses showed that a subgroup of ADHD children with sleep problems may be at increased risk for co-morbid sleep-related breathing disorder. This finding is potentially important for differential diagnostic considerations in ADHD.

[Prevalence and stress factors of sleep disorders in children starting school]. / Häufigkeit und Belastungsfaktoren bei Schlafstörungen im Einschulalter.

Epidemiological studies of sleep disturbances in preschool and school-aged children are under-represented in international clinical research. Based on this fact we investigated the prevalence of insomnia and parasomnia in a representative sample of school-novices in Cologne in 2002 (Cologne Children's Sleep Study). We have also considered the relationship between sleep problems on the one hand and sleep hygienic variables, physical and somatic healthy factors and behavioral problems on the other. A high prevalence of insomnia problems (15%) and repeated nightmares (14%) in children of this age were found in parent's report. Thereas sleep-walking, night terrors and daytime sleepiness were reported less frequently. Children having a solid sleep-wake-schedule show significant less problems to fall into sleep and feel sleepy during the day. Moreover we focused the correlation between disturbed sleep and multiple influencing, as light irritating and noise. We found a two- to three times elevated risk for hyperactive and emotional problems for children with insomnia or parasomnia complaints with regard to the comorbidity of behavioural difficulties. These findings underline the necessity for diagnostic clarifying of sleep disturbances and intervention programs for behavioural disturbed and isolated sleep impaired children.