Sleep Spindle-Related EEG Connectivity in Children with Attention-Deficit/Hyperactivity Disorder: An Exploratory Study.

Attention-deficit/hyperactivity disorder (ADHD) is a neurobehavioral disorder with known brain abnormalities but no biomarkers to support clinical diagnosis. Recently, EEG analysis methods such as functional connectivity have rekindled interest in using EEG for ADHD diagnosis. Most studies have focused on resting-state EEG, while connectivity during sleep and spindle activity has been underexplored. Here we present the results of a preliminary study exploring spindle-related connectivity as a possible biomarker for ADHD. We compared sensor-space connectivity parameters in eight children with ADHD and nine age/sex-matched healthy controls during sleep, before, during, and after spindle activity in various frequency bands. All connectivity parameters were significantly different between the two groups in the delta and gamma bands, and Principal Component Analysis (PCA) in the gamma band distinguished ADHD from healthy subjects. Cluster coefficient and path length values in the sigma band were also significantly different between epochs, indicating different spindle-related brain activity in ADHD.

Short-Term Outcomes of an ESDM Intervention in Italian Children with Autism Spectrum Disorder following the COVID-19 Lockdown.

The COVID-19 pandemic caused a temporary lockdown period in Italy, during which the delivery of in-person treatment for children with autism spectrum disorder (ASD) in public health services was discontinued. This occurrence represented a crucial challenge for both families and professionals. We assessed the short-term outcomes of a sample of 18 children who received an early intervention with the Early Start Denver Model (ESDM), delivered at low intensity over one year in the pre-pandemic period, after six months of interruption of in-presence treatment due to lockdown restrictions. Children who received the ESDM treatment maintained their gains in sociocommunicative skills and did not exhibit any developmental regression. Additionally, there was evidence of a decrease in the restrictive and repetitive behavior (RRB) domain. The parents, who were already familiar with the principles of the ESDM, only received telehealth support from therapists that aimed to sustain the gains already achieved. We believe that it is always helpful to support parents in their daily lives by implementing interactional and play skills with their children to integrate and consolidate the results obtained in the individual interventions conducted by experienced therapists.

Gastrointestinal Disorders and Food Selectivity: Relationship with Sleep and Challenging Behavior in Children with Autism Spectrum Disorder.

The aim of this study was to evaluate the interaction between gastrointestinal (GI) disorders, sleep problems, and challenging behaviors in children with a diagnosis of Autism Spectrum Disorder (ASD) and their effect on parental stress. The secondary objective was to assess the frequency and type of GI and feeding disorders in a sample of children with ASD through a multidisciplinary assessment and, finally, to investigate families' perceptions and satisfaction with the proposed multidisciplinary approach. All children underwent a comprehensive gastroenterological and neuropsychiatric evaluation supported by standardized questionnaires. Pediatric gastroenterologists, specifically trained in Applied Behavior Analysis (ABA), provided advice for parent-delivered behavioral intervention for food selectivity. Thirty-six children with an autism diagnosis (29 males, age 4.5 +/-2.2 years, mean +/- SD) were enrolled. A positive correlation between sleep problems and aggressive behavior was found, and this association was stronger in children experiencing more problematic mealtime behaviors (b = 0.788, p = 0.014). Sleep difficulties were associated with stereotyped behaviors and parent-perceived stress. Parents interviewed about the gastroenterology visit perceived this multidisciplinary approach as helpful in addressing food selectivity. This study shows that sleep and mealtime issues can have a synergistic negative impact on ASD symptoms. A multidisciplinary approach and an integrated assessment of GI, feeding problems, and sleep disorders could be helpful in diagnosing comorbidities and to provide targeted advice to parents.

Haploinsufficiency as a Foreground Pathomechanism of Poirer-Bienvenu Syndrome and Novel Insights Underlying the Phenotypic Continuum of CSNK2B-Associated Disorders.

CSNK2B encodes for the regulatory subunit of the casein kinase II, a serine/threonine kinase that is highly expressed in the brain and implicated in development, neuritogenesis, synaptic transmission and plasticity. De novo variants in this gene have been identified as the cause of the Poirier-Bienvenu Neurodevelopmental Syndrome (POBINDS) characterized by seizures and variably impaired intellectual development. More than sixty mutations have been described so far. However, data clarifying their functional impact and the possible pathomechanism are still scarce. Recently, a subset of CSNK2B missense variants affecting the Asp32 in the KEN box-like domain were proposed as the cause of a new intellectual disability-craniodigital syndrome (IDCS). In this study, we combined predictive functional and structural analysis and in vitro experiments to investigate the effect of two CSNK2B mutations, p.Leu39Arg and p.Met132LeufsTer110, identified by WES in two children with POBINDS. Our data prove that loss of the CK2beta protein, due to the instability of mutant CSNK2B mRNA and protein, resulting in a reduced amount of CK2 complex and affecting its kinase activity, may underlie the POBINDS phenotype. In addition, the deep reverse phenotyping of the patient carrying p.Leu39Arg, with an analysis of the available literature for individuals with either POBINDS or IDCS and a mutation in the KEN box-like motif, might suggest the existence of a continuous spectrum of CSNK2B-associated phenotypes rather than a sharp distinction between them.

Case report: A relevant misdiagnosis: Photosensitive epilepsy mimicking a blinking tic.

Blinking in children is most frequently a functional and transient symptom. Nonetheless, sometimes it is the first clinical manifestation of a neurological disorder. The differential diagnosis between voluntary actions, tics and other neurological disorders among which seizures may be challenging and misdiagnosis is common. A 6-year-old girl in good health was admitted for a recent history of bilateral eye blinking. Blinking did not interfere with the girl's activities. The patients reported that blinking seemed to be triggered by sunlight exposure and that girl sometimes seemed to be attracted by the sunlight. Ophthalmological diseases had been already excluded. The girl was addressed to our hospital for neurological consultation, as tic disease was considered the most probable hypothesis. Neurological examination was negative. In the field of differential diagnosis of photosensitive abnormal eyelid movements, the hypothesis of seizures was explored and further investigated with a video-EEG recording with light stimulation. This exam demonstrated a photoparoxysmal response (PPR) to intermittent photic stimulation with appearance on EEG of bilateral spike and polyspike waves associated with eyelid jerks. This girl suffers from generalized epilepsy with photosensitivity. Photosensitivity is a common feature of many epilepsy syndromes, mainly occurring in children and adolescents. To control the seizures, it is essential to avoid the triggering stimulus, by wearing specific glasses. Additional antiseizures treatment is often necessary, at first with valproate and levetiracetam, and ethosuximide, lamotrigine, and benzodiazepines as the second choice. Overlapping phenomenology of seizures and movement disorders is well known in paediatric clinical practice. Moreover, epilepsy and movement disorder may coexist, mainly in children. Seizures with semeiology limited to eye motor manifestations may mimic functional blinking, tics, and other motor events frequently observed in childhood. Differentiating seizures from other non-epileptic paroxysmal movements may be challenging and specialist evaluation is needed for proper treatment and prognostic counselling.

TTC5 syndrome: Clinical and molecular spectrum of a severe and recognizable condition.

Biallelic mutations in the TTC5 gene have been associated with autosomal recessive intellectual disability (ARID) and subsequently with an ID syndrome including severe speech impairment, cerebral atrophy, and hypotonia as clinical cornerstones. A TTC5 role in IDs has been proposed based on the physical interaction of TTC5 with p300, and possibly reducing p300 co-activator complex activity, similarly to what was observed in Menke-Hennekam 1 and 2 patients (MKHK1 and 2) carrying, respectively, mutations in exon 30 and 31 of CREBBP and EP300, which code for the TTC5-binding region. Recently, TTC5-related brain malformation has been linked to tubulinopathies due to the function of TTC5 in tubulins' dynamics. We reported seven new patients with novel or recurrent TTC5 variants. The deep characterization of the molecular and phenotypic spectrum confirmed TTC5-related disorder as a recognizable, very severe neurodevelopmental syndrome. In addition, other relevant clinical aspects, including a severe pre- and postnatal growth retardation, cryptorchidism, and epilepsy, have emerged from the reversal phenotype approach and the review of already published TTC5 cases. Microcephaly and facial dysmorphism resulted in being less variable than that documented before. The TTC5 clinical features have been compared with MKHK1 published cases in the hypothesis that clinical overlap in some characteristics of the two conditions was related to the common p300 molecular pathway.

Safety of Off-Label Pharmacological Treatment in Pediatric Neuropsychiatric Disorders: A Global Perspective From an Observational Study at an Italian Third Level Children's Hospital.

Background: The acquisition of proper and relevant pediatric clinical data is essential to ensure tolerable and effective pediatric drug therapies. In the field of pharmacological treatment of neuropsychiatric disorders, the lack of sufficient high quality scientific evidence for pediatric age results in the frequent need to prescribe off-label drugs. With the aim of improving knowledge about safety profile of off-label drug prescription in children and adolescent with neurological and/or psychiatric disorders, we realized a multidisciplinary pharmacovigilance study. Materials and methods: An observational retrospective study was conducted to assess the safety of off-label pharmacological therapies in patients aged 0-18 years, admitted to the Neuropsychiatry Unit of the Institute for Maternal and Child Health - IRCCS "Burlo Garofolo" between January 2016 and December 2018. Prescription patterns and adverse drug reactions were evaluated by a multidisciplinary team. Results: Overall, 230 patients were enrolled, 48% boys (N = 111), 52% girls (N = 119), average age of 10 years, and a total of 534 prescriptions was analyzed. 54.5% (N = 125) of patients had epilepsy, 37.5% (N = 86) suffered from psychiatric disorders, 8% (N = 19) had other neurological disorders. The prevalence of off-label prescriptions was 32% and 50% of the study population received at least one off-label drug. A total of 106 ADRs was detected: 57% of ADRs were due to drug-drug interactions, 30% were due to off-label prescriptions, 10% were due to overdose and 3% were due to improper use. No significant association between emerged ADRs and off label prescriptions was found (Fisher's exact two-tailed test, p = 1.000). There was significant association between increasing number of administrated drugs and risk of ADRs (OR 1.99; IC95% 1.58-2.5; p = 0.000). Psychiatric disorders were associated with at least three times higher risk to be treated with an off-label drug (OR 3.30; IC95% 2.26-4.83; p = 0.000). Conclusions: This study shows that off-label prescribing in neuropsychiatric disorders does not pose a greater risk of ADRs than on-label prescribing and highlights unmet clinical needs in pediatric neuropsychopharmacology. The multidisciplinary approach can provide important contributions to improve therapeutic path of these already complex pathologies by careful monitoring of therapeutic appropriateness and drug interactions.

Early factors associated with risk of developmental coordination disorder in very preterm children: A prospective area-based cohort study in Italy.

BACKGROUND: Developmental coordination disorder (DCD) is a motor disorder of unknown aetiology that may have long-term consequences on daily activities, and psychological and physical health. Studies investigating risk factors for DCD have so far provided inconsistent results. OBJECTIVES: To assess, using a parent-report screening tool, risk of DCD in school-age very preterm children born in Italy, and investigate the associated early biomedical and sociodemographic factors. METHODS: A prospective area-based cohort (804 children, response rate 73.4%) was assessed at 8-11 years of age in three Italian regions. Perinatal data were abstracted from medical records. DCD risk was measured using the Italian-validated version of the Developmental Coordination Disorder Questionnaire (DCDQ-IT). For this study, children with cognitive deficit (i.e. intelligence quotient <70), cerebral palsy, severe vision and hearing disabilities, and other impairments affecting movement were excluded. A total of 629 children were analysed. We used inverse probability weighting to account for loss to follow-up, and multilevel, multivariable modified Poisson models to obtain adjusted risk ratio (aRR) and 95% confidence interval (CI). Missing values in the covariates were imputed. RESULTS: 195 children (weighted proportion 31.8%, 95% CI 28.2, 35.6) scored positive on the DCDQ-IT, corresponding to the 15th centile of the reference Movement-ABC test. Factors associated with overall DCD risk were male sex (aRR 1.35, 95% CI 1.05, 1.73), intrauterine growth restriction (aRR 1.45, 95% CI 1.14, 1.85), retinopathy of prematurity (aRR 1.62, 95% CI 1.07, 2.45), and older maternal age at delivery (aRR 1.39, 95% CI 1.09, 1.77). Complete maternal milk feeding at discharge from the neonatal unit and higher parental socio-economic status were associated with decreased risk. CONCLUSIONS: Both biomedical and sociodemographic factors increase DCD risk. These findings can contribute to elucidating the origins of this disorder, and assist in the identification of children at risk for early referral and intervention.

The Genetic Diagnosis of Ultrarare DEEs: An Ongoing Challenge.

Epileptic encephalopathies (EEs) and developmental and epileptic encephalopathies (DEEs) are a group of severe early-onset neurodevelopmental disorders (NDDs). In recent years, next-generation equencing (NGS) technologies enabled the discovery of numerous genes involved in these conditions. However, more than 50% of patients remained undiagnosed. A major obstacle lies in the high degree of genetic heterogeneity and the wide phenotypic variability that has characterized these disorders. Interpreting a large amount of NGS data is also a crucial challenge. This study describes a dynamic diagnostic procedure used to investigate 17 patients with DEE or EE with previous negative or inconclusive genetic testing by whole-exome sequencing (WES), leading to a definite diagnosis in about 59% of participants. Biallelic mutations caused most of the diagnosed cases (50%), and a pathogenic somatic mutation resulted in 10% of the subjects. The high diagnostic yield reached highlights the relevance of the scientific approach, the importance of the reverse phenotyping strategy, and the involvement of a dedicated multidisciplinary team. The study emphasizes the role of recessive and somatic variants, new genetic mechanisms, and the complexity of genotype-phenotype associations. In older patients, WES results could end invasive diagnostic procedures and allow a more accurate transition. Finally, an early pursued diagnosis is essential for comprehensive care of patients, precision approach, knowledge of prognosis, patient and family planning, and quality of life.

Feasibility and Outcomes of the Early Start Denver Model Delivered within the Public Health System of the Friuli Venezia Giulia Italian Region.

The Early Start Denver Model (ESDM) is an evidence-based early intervention model for young children with autism spectrum disorder (ASD). It is crucial to investigate the feasibility of the ESDM in community settings in contexts that are culturally different from American universities in which the model was originally developed. The aim was to further evaluate the effectiveness of the ESDM delivered within the Italian community setting at low intensity. We compared a group aged 19 to 43 months receiving the ESDM for 2 h per week over the course of 1 year with a concurrent, comparable, non-randomized control group receiving treatment as usual (TAU). Children were evaluated at baseline (T0) and after 6 months (T1) and 12 months (T2) of intervention. Feasibility was evaluated by parent and therapist questionnaires, retention rate, and therapist treatment fidelity. Both groups made similar gains in cognition and language abilities. The ESDM group made larger improvement in domains measured by the ESDM Curriculum Checklist, including communication, social skills, and maladaptive behaviors. Feasibility seemed well supported by retentions, therapists and parent satisfaction, and treatment fidelity. Our study further supports the feasibility of the ESDM implemented within the Italian public health system and suggests a better response in the ESDM-treated group than in the control group.

Severe onset of inflammatory myositis in a child: think to paraneoplastic myositis.

BACKGROUND: Juvenile idiopathic inflammatory myopathies (JIIMs) are a group of heterogenous, acquired, autoimmune disorders that affect the muscle. While the association between IIMs and malignancy has been widely reported in adults, cancer-associated myositis (CAM) is rare in children, so that routine malignancy screening is not generally performed. This report shows a case of severe CAM in a child. CASE PRESENTATION: An 11-years-old girl presented with worsening dyspnea after a 3-weeks history of progressive proximal weakness, myalgia, dysphagia, and weight loss. Her past history was remarkable for a type I Arnold-Chiari malformation associated with an anterior sacral meningocele. Physical examination showed severe hypotony and hypotrophy. Pulse oximetry and blood test showed a type II respiratory failure (SpO2 88%, pCO2 68 mmHg) and increased muscle enzyme levels (CPK 8479 U/L, AST 715 U/L, ALT 383 U/L, LDH 1795 U/L). The patient needed invasive mechanical ventilation. Inflammatory myositis was considered and treatment with intravenous methylprednisolone (30 mg/Kg/day for 3 days followed by 2 mg/Kg/day) and IVIG (1 g/kg/day for 2 days) was started. Muscle biopsy showed endomysial and perimysial necrosis and inflammation. The presence of serum anti-TIF1-γ antibody positivity led to a malignancy screening. Whole-body MRI showed a mature teratoma underneath sacral meningocele and both lesions were surgically removed. Given the histological and clinical severity of the myopathy, mycophenolate (500 mg twice a day) and rituximab (360 mg/m2, 4 weekly infusions) were added. Due to extreme muscular wasting, severe malnutrition and intolerance to enteral feeding the patient needed a transient tracheostomy and parenteral nutrition, followed by physiotherapy, speech therapy and nocturnal non-invasive ventilation. A complete remission was achieved 3 months after. CONCLUSIONS: Among cancer-associated autoantibodies (CAAs) in adult patients, anti-TIF1-γ carries the highest risk of CAM, which recognizes with a high likelihood a paraneoplastic pathogenesis. In children, anti-TIF1-γ antibody has been associated with severe cutaneous disease, lipodystrophy, and chronic disease course, but not with CAM, which is overall rare in younger patients. Severe onset of a JIIM, especially if anti-TIF1-γ antibody positive, should prompt suspect of a CAM and lead to a screening for malignancy.

High-school students and self-injurious thoughts and behaviours: clues of emotion dysregulation.

BACKGROUND: Suicide attempts and self-harm in adolescence are a major public health concern: they are among the main causes of disability-adjusted life-years worldwide, with severe long-term health consequences in terms of mental illness and psychiatric hospitalisation and a significantly increased risk of suicide. Several studies recently focused on the hypothesis that adolescents may be particularly vulnerable to emotional dysregulation and on the relation between problems with emotion regulation and suicidal and self-harming behaviours. Italian epidemiological data about prevalence of these behaviours at the community level are lacking. Our study aimed to estimate the prevalence of self-injurious thoughts and behaviours (SITBs) in a representative sample of community adolescents, and to examine the association between SITBs and the emotional and behavioural profiles. METHODS: Anonymous self-report questionnaires were completed by 1507 students aged 11-18 years from 24 high schools in the North-eastern Italian region of Friuli Venezia Giulia. Information was collected on SITBs, on the socio-environmental context, and on the psychological profile ('Achenbach's YSR questionnaire 11-18, Multidimensional Test of Self-harm and Multi-Attitude Suicide Tendency Scale). RESULTS: Overall, 11.1% of adolescents reported self-harming behaviours without suicide ideation or attempts, 6.4% declared having thought to suicide without acting a suicide attempt or self-harm, 1.4% declared having attempted suicide and really thought to take away their life. Access to health services following a suicide thought, a self-harming behaviour or suicide attempt was infrequent, particularly for suicide ideation. At the YSR, all the SITBs groups reported high scores in almost all scales, with the most evident differences in the self-harming groups in which adolescents reported significantly higher scores in all scales, both internalising and externalising. An emotion dysregulation profile was found in almost all the groups. CONCLUSIONS: This study provides us with an estimate of the prevalence of SITBs in the adolescent population and confirms the importance of further investigating the association between SITBs and emotion dysregulation. The naturalistic setting of community studies appears to be useful for studies in this field, and it allows to approach the onerous and often neglected issue of adolescent suicidality.

Description of a peculiar alternating ictal electroclinical pattern in a young boy with a novel SPATA5 mutation.

Heterozygous variants in the SPATA5 gene have recently been described to be associated with epileptic encephalopathy. As of 2019, 37 patients have been described in the published literature. We report a patient with a novel autosomal recessive pathogenic variant in SPATA5 and a clinical phenotype consistent with SPATA5 syndrome, including severe neurological impairment, intellectual disability (ID), generalized intractable epilepsy, microcephaly, abnormal muscle tone, and sensorineural hearing loss. The epileptic clinical features were characterized by infantile spasms associated with seizures with a complex ocular movement; a predominant involvement of the posterior cerebral area and cortical visual impairment were also noticed. This phenotype is highlighted with a review of the literature showing other patients with SPATA5-related disease. This report aims to contribute to further understanding phenotype/genotype correlations, which are fundamental for the interpretation of data made available by exome sequencing for the diagnosis of epileptic encephalopathies. [Published with video sequence].

Rebound of Severe Alcoholic Intoxications in Adolescents and Young Adults After COVID-19 Lockdown.

PURPOSE: The coronavirus lockdown in Italy ended, but the postlockdown phase may be even more challenging than the outbreak itself if the impact on mental health is considered. To date, little evidence is available about the effect of lockdown release in terms of adolescent health from the perspective of an emergency department (ED). METHODS: We reviewed data on ED arrivals of adolescents and young adults (aged 13-24 years) in the weeks immediately before and after the Italian lockdown release in 2020, and in the same periods in 2019, with a focus on cases of severe alcohol abuse, psychomotor agitation, and other mental issues. RESULTS: The relative frequency of severe alcohol intoxications increased from .88% during the last part of the lockdown to 11.3% after lockdown release. When comparing these data with the same period in 2019, a highly significant difference emerged, with severe alcohol intoxications accounting for 11.31% of ED visits versus 2.96%, respectively. The relative frequency of ED arrivals related to psychomotor agitation or other mental health issues was not significantly increased after lockdown release. CONCLUSIONS: This report suggests that emergency services should be prepared for a possible peak of alcohol intoxication-related emergencies in adolescents and young adults. The connection between alcohol abuse and mental health should not be overlooked.

A Two-Stage Screening Approach with I-TC and Q-CHAT to Identify Toddlers at Risk for Autism Spectrum Disorder within the Italian Public Health System.

Standardized screening programs ensure that children are monitored for early signs of autism spectrum disorder (ASD) in order to promote earlier diagnosis and intervention. The aim of this study is to identify early signs of atypical development consistent with ASD or other developmental disorders in a population of 224 low-risk toddlers through a two-stage screening approach applied at 12 and 18 months of age. We adopted two screening tools combined: 1. the Communication and Symbolic Behavior Scales Developmental Profile (CSBS DP) Infant-Toddler Checklist (I-TC) and 2. The Quantitative Checklist for Autism in Toddlers (Q-CHAT). We assessed their sensitivity and specificity related to the diagnostic outcome at 36 months. The results showed that autistic signs can be detected as early as the first year even through a few questions extrapolated from both screeners and that our model could be used as a screening procedure in the Italian public health system.

Epileptic encephalopathy with microcephaly in a patient with asparagine synthetase deficiency: a video-EEG report.

Asparagine synthetase deficiency is a rare autosomal recessive neurometabolic disorder caused by mutations in the asparagine synthetase gene. It is characterized by congenital microcephaly, intellectual disability, progressive cerebral atrophy, and intractable seizures. A decrease in asparagine in CSF or plasma guides subsequent investigations in some cases, but normal values are described in other cases. Therefore, reaching a diagnosis is challenging and relies on exome sequencing. We report the case of a child with progressive microcephaly, irritability, startle reflexes, and jitteriness since birth. Focal clonic and myoclonic seizures, status epilepticus, and infantile spasms appeared in the first months of life. At first, the EEG showed multifocal epileptic activity which later turned into modified hypsarrhythmia and discontinuous activity. Brain MRI showed brain atrophy, a simplified gyral pattern, and poor myelination. Plasma asparagine levels were normal. Due to remote parental consanguinity, a study of contiguous regions of runs of homozygosity was performed, showing a 5-Mb region (chr7:95629078-100679007) including the asparagine synthetase gene. The molecular analysis of this gene led to identification of a novel homozygous missense mutation, c.761G>T(p.Gly254Val), in our patient. The peculiar electroclinical phenotype may lead to diagnostic suspicion and molecular analysis which may benefit genetic counselling. [Published with video sequence].

Risk of Developmental Coordination Disorder in Italian very preterm children at school age compared to general population controls.

BACKGROUND: Developmental Coordination Disorder (DCD) is a neurodevelopmental disorder that involves difficulties in goal-directed motor coordination, with ineffective control of fine and gross motor movements in the absence of sensory impairment or neurological condition. DCD is frequently reported in children born very preterm (VP) who survive without CP. AIMS: To measure the risk of DCD at school age in a large area-based cohort of VP children and general population controls, adjusting for gender, birth weight by gestational age and age at assessment. METHODS: VP children (N = 608) were part of a prospective cohort study in Italy. Controls (N = 370) were participants in the DCDQ-Italian validation study in the same age range. The Italian version of Developmental Coordination Disorder Questionnaire (DCDQ-Italian) was used to measure the performances in motor coordination during ordinary activities from the parental point of view. Multivariable regression analysis was used to obtain adjusted risk ratios of screening positive for DCD. RESULTS: VP children had scores significantly lower than peers, and about 30% of them appeared at risk of DCD using the 15th percentile cut-off of the Italian validation study. Birth-weight <10th percentile for gestational age and male gender were significant predictors. A slight trend effect was present, with extremely preterm children (<28 weeks gestation) showing the highest risk. CONCLUSIONS: Our study confirmed the higher DCD risk in VP children, particularly when males and SGA.

The lost children: The underdiagnosis of dyslexia in Italy. A cross-sectional national study.

BACKGROUND: Developmental dyslexia is one of the most common neurobehavioral disorders affecting children, but prevalence data on this condition are poor. The objective of the present study is to determine the prevalence of dyslexia in Italy in an unselected school population, using clearly defined diagnostic criteria and methods. METHODS: Cross-sectional study carried out in nine Italian Regions: two located in Northern Italy (Friuli Venezia Giulia and Veneto), three in Central Italy (Marche, Lazio and Umbria) and four in Southern Italy (Abruzzo, Molise, Puglia and Sardegna). Three consecutive levels of screening were carried out: the first two at school, to screen the population and identify children with suspect dyslexia; the last in centers with multi-professional staff specialized in learning disabilities to confirm the diagnosis. The key outcome measure is the prevalence of dyslexia, defined as the ratio between the number of children confirmed positive at the third level of screening and the total number of children enrolled in the study. RESULTS: We finally recruited 11094 children aged 8-10 years, of which 9964 constituted the final working sample after applying exclusion criteria and including only children who received parents' consent to participate. The prevalence of dyslexia in the whole sample was 3.5% (95% CI 3.2-3.9%), with little differences between Northern, Central and Southern Italy (respectively 3.6%, 3.2% and 3.7%). In almost two out of three children with dyslexia the disorder had not been previously diagnosed. CONCLUSIONS: This study confirms that in primary school children at the age of 8-10 years in Italy dyslexia is widely underestimated. Reliable data on dyslexia prevalence are needed to allocate necessary human and financial resources both to Health Services and Schools, ensuring timely support to children and families.

An evaluation of the Movement ABC-2 Test for use in Italy: A comparison of data from Italy and the UK.

BACKGROUND: The standardized test within the Movement Assessment Battery for Children-2nd edition (MABC-2) is used worldwide to assess motor problems in children. Ideally, any country using a test developed in another country should produce national norms to ensure that it functions effectively in the new context. AIM: The first objective of this study was to explore the differences in motor performance between Italian and British children. The second was to examine the structural validity of the test for the Italian sample. METHOD: A total of 718 Italian (IT) and 765 British (UK) children, aged 3-10 years, were individually tested on the age-appropriate items of the MABC-2 Test. RESULTS: Developmental trends emerged on every task and differences between IT and UK children were obtained on 11 of 27 task comparisons. Interactions between age and country indicated that differences were not consistently in favor of one culture. Confirmatory factor analysis generally supported the proposed structure of the MABC-2 Test. CONCLUSION: Although the differences between the IT and the UK children were relatively few, those that did emerge emphasize the need for population specific norms and suggest that cultural diversity in motor experiences should be considered when evaluating motor abilities in children.

19p13 microduplications encompassing NFIX are responsible for intellectual disability, short stature and small head circumference.

Syndromes caused by copy number variations are described as reciprocal when they result from deletions or duplications of the same chromosomal region. When comparing the phenotypes of these syndromes, various clinical features could be described as reversed, probably due to the opposite effect of these imbalances on the expression of genes located at this locus. The NFIX gene codes for a transcription factor implicated in neurogenesis and chondrocyte differentiation. Microdeletions and loss of function variants of NFIX are responsible for Sotos syndrome-2 (also described as Malan syndrome), a syndromic form of intellectual disability associated with overgrowth and macrocephaly. Here, we report a cohort of nine patients harboring microduplications encompassing NFIX. These patients exhibit variable intellectual disability, short stature and small head circumference, which can be described as a reversed Sotos syndrome-2 phenotype. Strikingly, such a reversed phenotype has already been described in patients harboring microduplications encompassing NSD1, the gene whose deletions and loss-of-function variants are responsible for classical Sotos syndrome. Even though the type/contre-type concept has been criticized, this model seems to give a plausible explanation for the pathogenicity of 19p13 microduplications, and the common phenotype observed in our cohort.