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Background: Macrocephaly is described in almost 15% of children with Autism Spectrum Disorder (ASD). Relationships between head growth trajectories and clinical findings in ASD children show a high degree of variability, highlighting the complex heterogeneity of the disorder. Objectives: The aim of this study was to measure differences of the early growth trajectory of head circumference (HC) in children with ASD and macrocephaly compared to ASD normocephalic children, examining clinical correlates in the two groups of patients. Methods: HC data were collected from birth to 5 years of age in a sample of children with a confirmed diagnosis of ASD. Participants were classified into two groups: ASD macrocephaly (ASD-M, Z-scores =1.88 in at least two consecutive HC measurements), and ASD non-macrocephaly (ASD-N). Based on the distribution of HC measurements (Z-scores), five age groups were identified for the longitudinal study. Developmental and behavioral characteristics of the ASD-M children compared to the ASD-N group were compared by using standardized scores. Results: 20,8% of the children sample met criteria for macrocephaly. HC values became indicative of macrocephaly in the ASD-M group at the age range from 1 to 6 months, and persisted thereafter throughout the first five years of age. ASDM children showed significantly higher developmental quotients of Griffiths III B and D subscales compared to ASD-N group. No significant differences in the severity of ASD symptoms assessed by ADOS-2 were observed between ASD-M and ASD-N groups. Conclusion: In this study HC size from birth to 5 years links to accelerated HC growth rate as early as the first 6 months of age in children with ASD and macrocephaly, preceding the onset and diagnosis of ASD. We found that in early childhood, children with ASD-M may exhibit some advantages in language and social communication and emotional skills without differences in autism severity, when compared with age-matched normocephalic ASD children. Longitudinal analyses are required to catch-up prospectively possible relationships between head size as proxy measure of brain development and neuro-developmental and behavioral features in children with ASD. [ABSTRACT FROM AUTHOR]

Despite the growing interest on how Tourette syndrome (TS) affects social cognition skills, this field remains to date relatively under‐explored. Here, we aim to advance knowledge on the topic by studying moral decision‐making and moral reasoning in a group of adolescents with TS and a group of healthy controls. Overall, we found higher endorsement (i.e. a greater 'yes' response rate) for utilitarian solutions of incidental and instrumental moral dilemmas in TS compared to controls. By contrast, we reported an overall higher tendency of TS individuals to apply principles described in the moral foundation questionnaire to establish whether something is morally right or wrong. Our results document intact moral reasoning in TS and suggest that a deficit in suppressing inappropriate behaviours and/or altered sense of agency might be responsible for their higher utilitarian moral decision‐making. [ABSTRACT FROM AUTHOR]

Background: Tourette syndrome (TS) and autism spectrum disorder (ASD) are two neurodevelopmental disorders with an onset before the age of 18 years. TS patients frequently reported atypical sensory phenomena (SP). Sensory processing abnormalities are also particularly frequent in ASD individuals. Objectives: Considering the higher rate of atypical sensory behaviours in both neurodevelopmental disorders, in the present study we analysed sensory experiences in patients with ASD and in patients with TS. Methods: We enrolled patients with a primary diagnosis of TS or ASD. All participants were assessed for primary diagnosis and associated comorbidities. The presence of sensory behaviours was investigated using the University of Sao Paulo's Sensory Phenomena Scale (USP-SPS). Results: SP were significantly more represented in the ASD-group versus TS-group, except for sound just-right perceptions and energy to released. ASD participants presented higher mean scores in all fields of USP-SPS severity scale respect on TS patients and healthy controls. The USP-SPS total score had significant positive correlations with the CYBOCS and MASC total scores in the TS cohort. In the ASD group, the USP-SPS total score was significantly negative correlated with the total IQ and marginally positive correlated with ADOS total score. Conclusion: SP are a frequently reported characteristic both of ASD and TS. Future studies are needed to better evaluate the differences on their phenomenology in patients with TS and ASD. [ABSTRACT FROM AUTHOR]

Background/Objectives: Pathogenic variants in the deleted in colorectal cancer gene (DCC), encoding the Netrin-1 receptor, may lead to mirror movements (MMs) associated with agenesis/dysgenesis of the corpus callosum (ACC) and cognitive and/or neuropsychiatric issues. The clinical phenotype is related to the biological function of DCC in the corpus callosum and corticospinal tract development as Netrin-1 is implicated in the guidance of developing axons toward the midline. We report on a child with a novel inherited, monoallelic, pathogenic variant in the DCC gene. Methods: Standardized measures and clinical scales were used to assess psychomotor development, communication and social skills, emotional and behavioural difficulties. MMs were measured via the Woods and Teuber classification. Exome sequencing was performed on affected and healthy family members. Results: The patient's clinical presentation during infancy consisted of paroxysmal dystonic posturing when asleep, mimicking nocturnal leg cramps. A brain magnetic resonance imaging (MRI) showed complete ACC. He developed typical upper limb MMs during childhood and a progressively evolving neuro-phenotype with global development delay and behavioural problems. We found an intrafamilial clinical variability associated with DCC mutations: the proband's father and uncle shared the same DCC variant, with a milder clinical phenotype. The atypical early clinical presentation of the present patient expands the clinical spectrum associated with DCC variants, especially those in the paediatric age. Conclusions: This study underlines the importance of in-depth genetic investigations in young children with ACC and highlights the need for further detailed analyses of early motor symptoms in infants with DCC mutations. [ABSTRACT FROM AUTHOR]

The chromosome 17q21.31 microduplication syndrome is a rare genetic syndrome presenting with craniofacial dysmorphisms, psychomotor delay, microcephaly, behavioral disorders, and poor social interaction. Only ten patients have been reported in the literature until today. All patients share some specific features, including psychomotor delay, behavioral disorders, and autism spectrum disorder (ASD). Here, a new case of this syndrome is reported in an 11-year-old Caucasian child who presented the classical clinical features of the 17q21.31 microduplication syndrome in association with new clinical characteristics previously unreported. The Array-Comparative Genomic Hybridization (aCGH) revealed a partial duplication of the long arm of chromosome 17. A literature review of previously studied patients with 17q21.31 microduplication syndrome is reported. [ABSTRACT FROM AUTHOR]

Tourette syndrome (TS) is a neurodevelopmental disturbance with heterogeneous and not completely known etiology. Clinical and molecular appraisal of affected patients is mandatory for outcome amelioration. The current study aimed to understand the molecular bases underpinning TS in a vast cohort of pediatric patients with TS. Molecular analyses included array-CGH analyses. The primary goal was to define the neurobehavioral phenotype of patients with or without pathogenic copy number variations (CNVs). Moreover, we compared the CNVs with CNVs described in the literature in neuropsychiatric disorders, including TS, to describe an effective clinical and molecular characterization of patients for prognostic purposes and for correctly taking charge. Moreover, this study showed that rare deletions and duplications focusing attention on significant genes for neurodevelopment had a statistically higher occurrence in children with tics and additional comorbidities. In our cohort, we determined an incidence of potentially causative CNVs of about 12%, in line with other literature studies. Clearly, further studies are needed to delineate the genetic background of patients with tic disorders in a superior way to elucidate the complex genetic architecture of these disorders, to describe the outcome, and to identify new possible therapeutic targets. [ABSTRACT FROM AUTHOR]

Biological bases of autism spectrum disorder (ASD) include both genetic and epigenetic causes. Patients with ASD show anomalies in the profile of certain plasma amino acids, including neuroactive amino acids. Monitoring plasma amino acids may be relevant for patient care and interventions. We evaluated the plasma amino acid profile in samples extracted from dry blood spots by electrospray ionization-tandem mass spectrometry. Fourteen amino acids and eleven amino acid ratios were examined in patients with ASD and intellectual disability (ID), and neurotypical control subjects (TD). The amino acid profile in the ASD group showed reduced levels of ornithine (p = 0.008), phenylalanine (p = 0.042) and tyrosine (p = 0.013). The statistically significant amino acid ratios were Leu+Val/Phe+Tyr (p = 0.002), Tyr/Leu (p = 0.007) and Val/Phe (p = 0.028), such differences remaining significant only in the comparison between ASD and TD. Finally, a positive correlation emerged between the score of the restricted and repetitive behavior on ADOS-2 and the citrulline levels in the ASD group (p = 0.0047). To conclude, patients with ASD may show a distinguishable metabolic profile useful for studying their metabolic pathways in order to develop screening tests and targeted therapies. [ABSTRACT FROM AUTHOR]

Epilepsy is rarely associated with Joubert's syndrome and related disorders (JSRD), being reported only in 3% of cases. Few patients have been described, moreover, with poor evidences of specific seizures' semiology or standard of practice for pharmacological treatment. Epilepsy is likely to be related to brain malformations in ciliopathies. Beyond the typical hindbrain malformation, the molar tooth sign, other cerebral anomalies variably reported in JSRD, such as generalized polymicrogyria, hamartomas, periventricular nodular heterotopia, and hippocampal defects, have been described. Herein, we aimed to revise the main clinical and etiopathogenetic characteristics of epilepsy associated with JSRD. [ABSTRACT FROM AUTHOR]

Alström syndrome (ALMS) is a rare ciliopathy with pleiotropic and wide spectrum of clinical features. It is autosomal recessively inherited and associated with mutations in ALMS1 , a gene involved in cilia functioning. High clinical heterogeneity is the main feature of ALMS. Cone-rod dystrophy with blindness, hearing loss, obesity, insulin resistance and hyperinsulinemia, type 2 diabetes mellitus, hypertriglyceridemia, endocrine abnormalities, cardiomyopathy, and renal, hepatic, and pulmonary anomalies are the most common signs and symptoms. [ABSTRACT FROM AUTHOR]

Joubert syndrome (JS) is a rare inherited disorder of central nervous system with neonatal/infantile onset, mainly affecting cerebellum and brainstem, and clinically characterized by agenesis or dysgenesis of the cerebellar vermis with accompanying brainstem malformations. More than 20 disease-causing genes have been associated with JS but a clear genotype–phenotype correlation has not been assessed yet. Diagnosis is usually confirmed by detection of the JS neuroradiological hallmark, the molar tooth sign. Patients with JS typically present with neurological manifestations, moreover, a heterogeneous spectrum of multisystemic anomalies may be observed. Signs and symptoms onset varies according to the age range and clinical diagnosis might become complicated. Moreover, specific neurodevelopmental disorders can be associated with JS such as autism spectrum disorders, attention deficit with hyperactivity, and a wide range of behavioral disturbances. Here, we examined the main neurological and neurodevelopmental features of JS according to an age-dependent mode of presentation. Furthermore, differential diagnosis with other neurological syndromes was closely reviewed. [ABSTRACT FROM AUTHOR]

Bardet–Biedl syndrome is a genetically pleiotropic disorder characterized by high clinical heterogeneity with severe multiorgan impairment. Clinically, it encompasses primary and secondary manifestations, mainly including retinal dystrophy, mental retardation, obesity, polydactyly, hypogonadism in male, and renal abnormalities. At least 21 different genes have been identified, all involved into primary cilium structure or function. To date, genotype–phenotype correlation is still poor. [ABSTRACT FROM AUTHOR]

Zhu‐Tokita‐Tachenouchi‐Kim syndrome (ZTTK) is a recently recognized malformation syndrome presenting with craniofacial dysmorphism, developmental delay/intellectual disability, seizures, anomalies involving brain white matter, and other body‐organs. In humans, the disorder is linked to the loss‐of‐function variants in the SON gene (MIM# 617140). Herewith, a new case of this syndrome is reported in a 2‐year‐old Caucasian child who presented the classical clinical features of the ZTTK syndrome in association with hydrocephalus and Chiari malformations type 1 an anomaly previously unreported. Exome analysis showed a de novo heterozygous variant in SON gene. Literature review of similar cases is reported. [ABSTRACT FROM AUTHOR]

Background: Abnormal sensory reactivity is considered one of the diagnostic criteria for autism spectrum disorders (ASD) and has been associated with autism severity, poorer functional outcomes, and behavioral difficulties across the lifespan. Its early characterization could provide valuable insights into the processes favoring the instantiation of maladaptive behaviors. Objectives: The present study has two aims: (1) to describe the sensory profile of preschool children with ASD compared with an age-matched population of children with a diagnosis of language disorder (DLD) and typically developing (TD) control peers; (2) to explore within each group whether the sensory alterations play a predictive role in the instantiation of emotional and behavioral issues. Methods: The parents of 42 ASD, 18 DLD, and 56 TD filled out the Sensory Processing Measure—Preschool (SPM-P). To gather information on competencies, behaviors, and emotional problems of children, the Child Behavior Checklist 1½-5 (CBCL 1½-5) was also administered. Results: On the SPM-P, ASD and DLD samples generally had scores more compromised than control peers. The contrast between ASD and DLD was reflected in a higher (and highly significant) impairment on the social participation and hearing subscales, suggesting a greater sensitivity and a possible specificity of these scores for ASD. More importantly, linear regression analyses revealed a strong and predictive association for ASD children with SPM total scores explaining more than 50% of the variance of the CBCL 1½-5 total scores (p < 0.001). Conclusions: Our findings reinforce the need to detect the abnormal sensory profiles of ASD already at an early stage and during clinical evaluations. Due to the impact on the emotional and behavioral manifestations, such a procedure has significant clinical and social implications, potentially guiding the development of new interventions relying on multisensory strategies. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical effectiveness of online remote behavior therapy, compared with face-to-face therapy in reducing tics and co-occurring disorders associated with the tics in a sample of youths with Tourette Syndrome. Design: A randomized controlled trial. TS patients were randomized to receive face-to-face or online remote behavior therapy. Participants: 40 children aged between 9 and 16 years affected by Tourette Syndrome. Results: Online remote and face-to-face behavior therapy are equally effective in the treatment of tics and co-occurring disorders in children and adolescents affected by Tourette Syndrome. Both groups showed an improvement in the severity of tics, obsessive-compulsive symptoms, and anxiety symptoms, as assessed by neuropsychological findings. Online remote behavior therapy was more effective for reducing depressive symptoms than face-to-face behavior therapy. Conclusions: Online remote behavior therapy is a promising tool for behavioral therapies for patients with Tourette Syndrome and may represents an alternative treatment option. [ABSTRACT FROM AUTHOR]

Background: Sensory reactivity is considered one of the diagnostic criteria for Autism Spectrum Disorders (ASD) and has been associated with poorer functional outcomes, behavioral difficulties, and autism severity across the lifespan. The characterization of the sensory processing in ASD has thus become crucial to identify the sensory and motor features influencing the development of personal autonomy. Objectives: The present study has two aims: (1) to compare the sensory processing between school-aged children with ASD and typically developing peers (TD); (2) to evaluate whether, within the ASD sample, the cognitive level and reported sensory symptoms explain the scores exhibited at the Sensory Processing Measure (SPM-2). Methods: The SPM-2 test was administered to the parents of 105 children with ASD and 70 TD. The ASD group was further subdivided into two groups, namely high and low functioning based on their cognitive level (High Functioning (HF), IQ > 80; Low Functioning (LF), IQ < 80). Results: ASD children exhibited higher scores throughout the SPM-2 total score and its multiple subscales. Within ASD, while HF and LF children did not differ in terms of the SPM-2 total score, a significant difference was found for the hearing, social participation, and balance and motion subscales. Conclusions: Aside from classical knowledge that the ASD population suffers from sensory processing disorders, we revealed that different sensory patterns are associated with high or low cognitive functioning. Beyond its neurobiological interest, such knowledge may be of fundamental importance for individualizing psychoeducational interventions in preschool- and school-aged children and later developmental stages. [ABSTRACT FROM AUTHOR]

Background: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by tics and co-occurring disorders. It has been suggested that anxiety occurs in 2–45% patients affected by Tourette syndrome. Despite dietary and nutritional factors have been found to affect a range of neurological conditions, no more studies have investigated the relationship between nutritional supplements and tics. Objective: To evaluate the effectiveness of supplementation of both L-Theanine and Vitamin B6 in reducing tics and co-occurring disorders in a sample of youth with chronic tic disorder (CTD) or Tourette syndrome with anxiety symptoms. Design: A open-label trial. Patients affected by Tourette syndrome were randomized to receive nutritional supplements based on L-Theanine and vitamin B6, or psychoeducation (PE). Participants: 34 children (30 boys and 4 girls) aged between 4 and 17 years affected by Tourette syndrome or chronic tic disorder, associated with anxiety symptoms. Results: Patients in both groups showed a reduction in the severity of tic and anxiety symptoms. Supplementation with L-Theanine and vitamin B6 was significantly more effective than psychoeducation in reducing tics and co-occurring disorders, as measured by neuropsychological findings. Conclusions: Supplementation of both L-Theanine and Vitamin B6 may help in the treatment of tic disorders associated with anxious symptoms. Between-group differences in clinician-rated severity did reach statistical significance only for tics. Despite this finding, further placebo-controlled trials are needed. [ABSTRACT FROM AUTHOR]

Background: Functional tics are included in the wide spectrum of functional movement disorders (FMDs). Their distinction from organic tics is challenging because they both phenomenologically present common features. During the COVID-19 pandemic, there has been an increase in functional tic-like behaviours in vulnerable children and adolescents after social media exposure. This study explores the phenomenology and course of a cohort of newly diagnosed functional tic-like behaviors., Methods: We analysed clinical data of 243 patients affected by tic disorders collected at outpatient Tourette Clinic, Child and Adolescent Neurology and Psychiatry Unit, Catania University. Among the clinical cohort with functional tic-like behaviors, we evaluated the clinical course of symptoms at follow-up visits after 6 and 12 months., Results: Among the cohort of 243 patients referred for evaluation at our centre, 11 were diagnosed with functional tic-like behaviours. The majority of participants with functional tic-like behaviours were female with a mean age of 15 years old and presented an explosive symptom's onset. At follow-up visit after 12 months, patients with functional tic-like behaviors showed a significant variation in the severity of tics and anxiety symptoms. Conversely, depressive, and obsessive-compulsive symptoms did not significantly differ during the follow-up., Conclusion: Our data suggest that several characteristics in clinical course and their phenomenology can help clinicians to distinguish functional tic-like behaviours from organic tics. Our results also suggest a better outcome for tics and anxiety symptoms respect on other comorbidities. A prompt diagnosis and management not only of tics but also comorbidities are recommended, as generally conventional pharmacotherapy for tics does not have positive effects on these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Prato, Saia, Milana, Scerbo, Barone and Rizzo.)

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are clinical conditions characterized by the sudden onset of obsessive-compulsive disorder and/or tics, often accompanied by other behavioral symptoms in a group of children with streptococcal infection. PANDAS-related disorders, including pediatric acute-onset neuropsychiatric syndrome (PANS), childhood acute neuropsychiatric symptoms (CANS), and pediatric infection triggered autoimmune neuropsychiatric disorders (PITANDs), have also been described. Since first defined in 1998, PANDAS has been considered a controversial diagnosis. A comprehensive review of the literature was performed on PubMed and Scopus databases, searching for diagnostic criteria and diagnostic procedures of PANDAS and related disorders. We propose a test panel to support clinicians in the workout of PANDAS/PANS patients establishing an appropriate treatment. However, further studies are needed to improve our knowledge on these acute-onset neuropsychiatric conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Prato, Gulisano, Scerbo, Barone, Vicario and Rizzo.)