STUDY OBJECTIVES:Data on sleep disorders in Cri du Chat (CdC) syndrome are limited; this study examines their prevalence, clinical features, and age-related patterns in pediatric patients. METHODS:Caregivers of children with CdC syndrome (<18 years), recruited through the Italian CdC Children's Association, completed a structured survey. The questionnaire included four validated sleep assessment tools: the Child's Sleep Habits Questionnaire (CSHQ), the Pediatric Insomnia Severity Index (PISI), the Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD), and the Sleep Questionnaire for Children with Severe Psychomotor Impairment (SNAKE). Analyses were conducted on the overall sample and stratified by age groups (0-6, 7-12, and 13-17 years). RESULTS:Fifty-one participants were included (median age 10 years; IQR 5-14 years). Pathological CSHQ scores were observed in all participants. Younger children exhibited significantly greater insomnia severity on the PISI and higher SNAKE scores for sleep maintenance disorders and daytime sleepiness (p < 0.05). Daytime somnolence assessed by ESS-CHAD was generally mild and showed a decreasing trend with increasing age. Severe intellectual disability was significantly associated with sleep-related arousal and breathing disorders (p = 0.016) and with daytime sleepiness (p = 0.032). Overall, 51% of patients had received pharmacological treatment at least once, with melatonin being the most frequently used medication and reported as effective in 68% of treated cases. CONCLUSIONS:Sleep disturbances are highly prevalent across all pediatric age groups in CdC syndrome and present distinct age-related patterns. Routine screening using standardized questionnaires may facilitate early identification and tailored interventions. CLINICAL TRIAL:The study was approved by the Ethical Committee (Comitato Etico Territoriale Lazio Area 1; study number 7980, Prot. 0481/2025). STATEMENT OF SIGNIFICANCE:Sleep disturbances represent an underrecognized but clinically relevant aspect of Cri du Chat syndrome. This study provides one of the first systematic characterizations of sleep problems across pediatric age groups in this rare neurodevelopmental condition, highlighting age-related patterns and associations with cognitive severity. By integrating multiple caregiver-reported sleep measures, the findings underscore the pervasive impact of sleep disturbances on daily functioning and well-being. The results emphasize the need for routine sleep assessment in clinical practice and support the development of tailored, age-specific management strategies. Future research should focus on longitudinal trajectories, objective sleep measures, and optimized therapeutic approaches to improve outcomes in this population.

BACKGROUND:Sleep disorders are increasingly recognized in individuals with Cri-du-Chat (CdC) syndrome, yet most available data focus on pediatric populations. The present study investigated the prevalence, characteristics, and potential determinants of sleep disturbances in adults with CdC syndrome using standardized and validated scales and questionnaires. Findings were also compared with previously published pediatric data to explore developmental trajectories and persistence of sleep problems into adulthood. METHODS:Adults (≥18 years) with genetically confirmed CdC syndrome were recruited through the Italian Associazione Bambini Cri du Chat ONLUS (A.B.C.). Between September and October 2025, caregivers completed a structured questionnaire comprising general demographic and clinical data, and four standardized sleep assessment instruments: the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), and the Sleep Questionnaire for Children with Severe Psychomotor Impairment (SNAKE). RESULTS:Seventy adults (median age 31 years) were included. Poor sleep quality and insomnia symptoms were detected by using PSQI and ISI in 49% and 35.7% of participants, respectively. According to SNAKE results, disturbances in sleep maintenance were the most frequent (47.1%), followed by sleep-onset difficulties (25.7%) and daytime sleepiness (22.9%). A large proportion of participants with SNAKE scores suggestive of a clinically relevant sleep problem had never undergone a formal diagnostic evaluation for a sleep problem, highlighting a potential gap in clinical recognition. After adjustment for age, sex, and degree of intellectual disability, older age was independently associated with poorer overall sleep quality, greater insomnia severity, and increased daytime sleepiness, while epilepsy was independently associated with greater daytime sleepiness, and severe intellectual disability was associated with more pronounced daytime behavioural disturbances. CONCLUSIONS:Sleep problems are common yet underdiagnosed in adults with CdC syndrome, often persisting from childhood into adulthood. These findings emphasize the need for systematic sleep screening and multidisciplinary management in this population, integrating behavioural, neurological, and environmental factors.

The relationship between migraines and allergies is controversial. Though they are epidemiologically linked, the underlying pathophysiological connection between them remains unclear. Migraines and allergic disorders have various underlying genetic and biological causes. As per the literature, these conditions are epidemiologically linked, and some common pathophysiological pathways have been hypothesized. The histaminergic system may be the clue to understanding the correlation among these diseases. As a neurotransmitter in the central nervous system with a vasodilatory effect, histamine has a well-documented influence on the allergic response and could be involved in the pathophysiology of migraines. Histamine may influence hypothalamic activity, which may play a major role in migraines or may simply influence their severity. In both cases, antihistamine drugs could prove useful. This review examines whether the histaminergic system, particularly H3 and H4 receptors, may provide a mechanistic link between the pathophysiology of migraines and allergic disorders, two common and debilitating conditions. Identifying their connection could help identify novel therapeutic strategies.

Background: Oxidative stress is a condition characterized by an imbalance between the production of pro-oxidant factors (i.e. ROS) and the ability of biological systems to counteract them with antioxidant mechanisms. In patients with OSAS, the oxidative stress induced by intermittet hypoxia generates the release of proinflammatory factors responsible for the onset of systemic damage, which occurs primarily through endothelial damage. Objectives: The aim of this study was to investigate blood levels of oxidative stress in children with obstructive sleep apnea syndrome (OSAS). Methods: Children with sleep disordered breathing (SDB) were recruited. OSAS patients were diagnosed based on polysomnography (PSG). A blood sample was collected in children with OSAS to evaluate oxidative stress markers: total antioxidant status, biological antioxidant potential test, diacron reactive oxygen metabolites (d-ROMs test). Results: Children with OSAS showed significant differences in Total Antioxidant Status (2.13 ±0.2 vs 0.93-1.33 mmol/L, p=0.0001) and d-ROMs test (25.4 ±1.2 vs<24 mgH2O2/dL, p=0.0001) when compared to normal pediatric values. Conclusions: Total Antioxidant Status and d-ROMs test proved to be reliable and useful as early markers of systemic oxidative stress in children with OSAS.

Background: Circadian rhythm dysregulation and sleep fragmentation could induce changes in intestinal microbiota. Aim: In our study we compared the intestinal microbiota between children with obstructive sleep apnea syndrome (OSAS) and healthy children. Methods: Children with OSAS performed standard polysomnography and sleep clinical record. Exclusion criteria were: genetic or neurologic diseases,prematurity,allergy or asthma,gastrointestinal or metabolic or chronic diseases. Every children performed a stool examination analyzed by next-generation sequencing technologies for microbiota composition using 16SrRNA sequences. Results: Sixteen children were recruited, 9 healthy children (mean age 6.9± 1.0 y) and 7 children with OSAS (mean age 5.6± 1.2 y).In children with OSAS we obtained an elevated concentrations in Parabacteroides (p:0.05) and Eubacterium hadrum (p:0.04) and asignificant negative correlation between mean oxygen saturation (SpO2) and Bifidobacterium longum (p:0.02) and Eubacterium eligens (p:0.04). Conclusions: Sleep fragmentation and intermittent hypoxia produce alterations in intestinal microbiota. Studies on a larger population are needed for further microbiological and clinical details.

BACKGROUND:Recent evidence has emphasized the role of a short lingual frenulum in the pathogenesis of sleep-disordered breathing (SDB) in childhood. The oral dysfunction induced by a short frenulum may promote oral-facial dysmorphism, decreasing the size of upper airway lumen and increasing the risk of upper airway collapsibility during sleep. The aim of this study was to evaluate the presence of a short lingual frenulum as risk factor for SDB in children of school age, with and without snoring, who were recruited from the community. METHODS:Children aged 6-14 years were recruited from a school in Rome. For all participants, the previously described Sleep Clinical Record (SCR) was completed, and orthodontic evaluation and measurement of lingual frenulum were performed. Tongue strength and endurance were evaluated in all participants using the Iowa Oral Performance Instrument (IOPI). SDB was defined as positive SCR (≥6.5). RESULTS:We assessed 504 children with mean age of 9.6 ± 2.3 years, and in 114 of them (22.6%) a short frenulum was identified. Children with a short lingual frenulum were at significantly higher risk for a positive SCR compared to those with a frenulum of normal length (odds ratio = 2.980, 95% confidence interval = 1.260-6.997). Participants with positive or negative SCR did not differ in tongue strength or endurance. CONCLUSION:Short lingual frenulum is a risk factor for SDB. An early multidisciplinary approach and screening for SDB are indicated when this anatomical abnormality is recognized.

Objective: Airway oxidative stress and inflammation are likely to be involved in sleep disordered breathing (SDB) in children. We aimed to measure concentrations of 8-isoprostane (8-IsoP) in the exhaled breath condensate (EBC) and exhaled nitric oxide (FENO) in patients with SBD and healthy children, in order to assess the relationship between these two biomarkers, disease severity, and overnight changes.& para;& para;Methods: Patients with SDB (n = 46) and healthy controls (n = 20) aged 4.5-15.1 years (M/F: 36/30) underwent exhaled measurements. Patients with SDB underwent standard polysomnography to define primary snoring (PS: AHI < 1) and obstructive sleep apnea (OSA). Upon awakening the following morning, FENO was measured and EBC was collected for the measurement of EBC 8-IsoP.& para;& para;Results: OSA patients yielded higher awakening levels of 8-IsoP in EBC than PS patients and control subjects. The 8-IsoP levels, though not FENO , correlated with AHI (r = 0.40, p = 0.003) and SaO2 (r = -0.50, p = 0.001). Cut-off levels of 8-IsoP predicted OSA with a high AUC value (0.84, p = 0.000). Sensitivity and specificity for 8-IsoP levels above the percentile 50 (33.3 pg/mL) were 76.5% and 78.1%, respectively. 8-IsoP levels did not change from the evening to morning session, whereas morning FENO levels rose significantly only in patients with mild OSA (p = 0.03).& para;& para;Conclusion: Levels of 8-IsoP, though not FENO, distinguish children with OSA from those with PS or healthy, correlate with disease severity and closely predict OSA in the whole sample. (C) 2018 Elsevier B.V. All rights reserved.

Background: A recent study suggested that the presence of short lingual frenulum could be a “new phenotype” for paediatric sleep apnoea. Aims: In an epidemiological study we analyzed the presence of short lingual frenulum related to sleep disordered breathing (SDB) in school age children. Methods: We studied 504 school age children. Sleep clinical record (SCR) was obtained for all children. Moreover every child received orthodontic and lingual frenulum evaluation. Tongue strength, tongue peak pressure and endurance, using the Iowa Oral Performance Instrument (IOPI), were obtained in all patients. Results: We evaluated 504 children, mean age 9.6 ± 2.3 years, 277 were male. Forty-two children (8.3 %) obtained a positive SCR. Short lingual frenulum was found in 114 (22.6%) children. Children with short lingual frenulum, when compared to children with normal lingual frenulum, had a higher prevalence of male gender (54.4 vs 41%, p= 0.01), SDB (15.4 vs 6.1 %, p=0.003) and dento-skeletal malocclusions (67.5 vs 42.8%, p=0.0001). Moreover children with SDB and short lingual frenulum showed lower tongue strength measured by IOPI when compared to children without SDB (42.6±9.6 vs 47.2±10.4, p=0.04). Children with malocclusion and short lingual frenulum showed an higher odds ratio for the presence of obstructive sleep apnea (OSA) related symptoms [p<0.000, odds ratio=10.40, 95% CI 2.80-39.00]. Conclusion: A short lingual frenulum, associated with dento-skeletal malocclusion, is a major risk factor for SDB in school age children. An early multidisciplinary approach, including lingual frenulum evaluation, should be conducted for screening SDB.

The sleep clinical record (SCR) may be a valid method for detecting children with obstructive sleep apnoea (OSA). This study aimed to evaluate whether there were differences in SCR depending on age and to identify the possible risk factors for OSA development. We enrolled children with sleep disordered breathing between 2013 and 2015, and divided them according to age into preschool- and school-age groups. All patients underwent SCR and polysomnography. OSA was detected in 81.1% and 83.6% of preschool- and school-age groups, respectively. Obesity, malocclusions, nasal septal deviation and inferior turbinate hypertrophy were significantly more prevalent in school-age children (p<0.05); however, only tonsillar hypertrophy had significant hazard ratio (2.3) for OSA development. Saddle nose, nasal hypotonia, oral breathing and tonsillar hypertrophy were significantly more prevalent for development of OSA in preschoolers (p<0.03). The SCR score was significantly higher among preschool children than in school-age children (8.4±2.22 versus 7.9±2.6; p=0.044). Further, SCR score >6.5 had a sensitivity of 74% in predicting OSA in preschool children with positive predictive value of 86% (p=0.0001). Our study confirms the validity of the SCR as a screening tool for patient candidates for a PSG study for suspected OSA, in both school and preschool children.

OBJECTIVES:The objectives of this study were to confirm the efficacy of rapid maxillary expansion in children with moderate adenotonsillar hypertrophy in a larger sample and to evaluate retrospectively its long-term benefits in a group of children who underwent orthodontic treatment 10 years ago. METHODS:After general clinical examination and overnight polysomnography, all eligible children underwent cephalometric evaluation and started 12 months of therapy with rapid maxillary expansion. A new polysomnography was performed at the end of treatment (T1). Fourteen children underwent clinical evaluation and Brouilette questionnaire, 10 years after the end of treatment (T2). RESULTS:Forty patients were eligible for recruitment. At T1, 34/40 (85%) patients showed a decrease of apnea-hypopnea index (AHI) greater than 20% (ΔAHI 67.45% ± 25.73%) and were defined responders. Only 6/40 (15%) showed a decrease <20% of AHI at T1 and were defined as non-responders (ΔAHI -53.47% ± 61.57%). Moreover, 57.5% of patients presented residual OSA (AHI > 1 ev/h) after treatment. Disease duration was significantly lower (2.5 ± 1.4 years vs 4.8 ± 1.9 years, p <0.005) and age at disease onset was higher in responder patients compared to non-responders (3.8 ± 1.5 years vs 2.3 ± 1.9 years, p <0.05). Cephalometric variables showed an increase of cranial base angle in non-responder patients (p <0.05). Fourteen children (mean age 17.0 ± 1.9 years) who ended orthodontic treatment 10 years previously showed improvement of Brouilette score. CONCLUSION:Starting an orthodontic treatment as early as symptoms appear is important in order to increase the efficacy of treatment. An integrated therapy is needed.

Rapid maxillary expansion (RME) is an additional treatment in pediatric obstructive sleep apnea (OSA). The aim of this study was to present data about the outcome of adenotonsillectomy (AT) and of RME in a clinical sample of pediatric OSA.

Introduction Polysomnography (PSG) is the gold standard for the diagnosis of Obstructive Sleep Apnea (OSA). However, it is expensive and not available everywhere. For these reasons, alternatives to full PSG for the evaluation of suspected OSAS are often sought. The aim of our study is to develop a simple tool to screen OSA, thus reducing the use of PSG. Methods Children with suspected OSA referred to our Pediatric Sleep Centre from September 2012 to September 2013 were included. Each patient underwent Sleep Clinical Record (SCR), full PSG, and nocturnal pulse oximetry. A diagnosis of OSA was made in children with an Apnea/Hypopnea Index (AHI) ≥1 ev/h. A SCR score ≥ 6.5 and a McGill Oximetry Score (MOS) ≥ 2 were considered positive. Results We enrolled 285 children, mean age 6.2 ± 3.1, 187 (65.6%) male. 52 children (18.2%) showed MOS ≥ 2 with a sensitivity of 20.5% and specificity of 97.2%. 227 children (79.6%) had SCR score ≥ 6.5 with a sensitivity of 81.1% and specificity of 30.5%. 48 children (16.8%) showed positive SCR and MOS; all of them received a diagnosis of OSA at the PSG, reaching a specificity of 100%. Sensitivity was 52%; positive and negative predictive value were respectively 100% and 18.5%. Conclusion The combined use of SCR and nocturnal pulse oximetry with MOS may represent a valid alternative to full PSG.

Background: In Obstructive Sleep Apnea Syndrome (OSAS), the key role of airway inflammation is confirmed. Studies about noninvasive methods and new markers of inflammation in diagnosis and management of pediatric OSAS are increasing. 8-IsoP is an oxidative stress marker.The study of this marker in urines of children with OSAS could be promising. Aim: To evaluate urinary 8-IsoP values in children with OSAS Methods: Twenty children (mean age 6.33±2.06, M/F:12/8), with referred OSAS, underwent urinary collection at the morning after the polysomnography, sleep questionnaire, medical examination. 8-IsoP was assessed in urinary sample. Results: According to the AHI (Apnoea/Hypopnea index) obtained from the polysomnography, we found 13 subjects (group1) with primary snoring/minimum OSAS (mean AHI 1.89±1.80; mean SaO2 97.59±0.59) and 7 subjects (group2) with moderate/severe OSAS (mean AHI 14.65±11.09; mean SaO2 96.04±2.98). The urinary 8-IsoP values is higher in Group 2 (respectively Group1:0,72±0,57 ng/ml vs Group2: 2.19±1.29 ng/ml, p=0.01). Moreover we found a positive correlation between AHI and urinary 8Iso-P (r= 0,5; p=0,02). The linear regression analysis, performed using as dependent variable values of urinary 8-Isop and as independent variables severity of OSAS, age, sex, AHI, SaO2, Prick test, BMI percentile, adenotonsillar ipertrophy, showed that the severity of OSAS was the only predictor for levels of urinary 8-Isop (R Square: 0.415). Conclusion: Our data show that values of urinary 8-IsoP are related to OSAS severity. Further studies are needed to assess the utility of urinary 8-Isop as marker of inflammation likely due to oxidative stress.

OBJECTIVE:To analyze sleep architecture and NREM sleep instability by means of the cyclic alternating pattern (CAP) in children with benign epilepsy with rolandic spikes (BERS). METHODS:Ten children with BERS, drug free at the time of the study and 10 age-matched normal controls were included in this study. Sleep was visually scored for sleep architecture and CAP using standard criteria. RESULTS:Sleep architecture in BERS showed only few significant differences vs. controls with a reduction of total sleep time, sleep efficiency, and REM sleep percentage. CAP analysis revealed several significant differences: reduced total CAP rate, mainly in sleep stage 2, and reduced EEG slow oscillations and arousals during stages N1 and N2. CONCLUSIONS:Sleep architecture is not importantly affected in BERS but CAP analysis reveals a decrease of NREM instability, mainly in sleep stage 2. Since there is a spindle-related spike activation in BERS, we speculate that the decrease of CAP and of EEG slow oscillations and arousals might be linked with the inhibitory action of spindling activity and spikes on arousals. SIGNIFICANCE:CAP analysis discloses sleep structure abnormalities in children with BERS not shown by the classical sleep scoring. Spike activity and CAP A1 subtypes seem to be mutually exclusive probably because centro-temporal spikes disturb the physiological synchronization mechanisms needed for the generation of slow-wave components of CAP.