European Society for the Study of Tourette Syndrome 2022 criteria for clinical diagnosis of functional tic-like behaviours: International consensus from experts in tic disorders.

BACKGROUND AND PURPOSE: In 2020, health professionals witnessed a dramatic increase in referrals of young people with rapid onset of severe tic-like behaviours. We assembled a working group to develop criteria for the clinical diagnosis of functional tic-like behaviours (FTLBs) to help neurologists, pediatricians, psychiatrists, and psychologists recognize and diagnose this condition. METHODS: We used a formal consensus development process, using a multiround, web-based Delphi survey. The survey was based on an in-person discussion at the European Society for the Study of Tourette Syndrome (ESSTS) meeting in Lausanne in June 2022. Members of an invited group with extensive clinical experience working with patients with Tourette syndrome and FTLBs discussed potential clinical criteria for diagnosis of FTLBs. An initial set of criteria were developed based on common clinical experiences and review of the literature on FTLBs and revised through iterative discussions, resulting in the survey items for voting. RESULTS: In total, 24 members of the working group were invited to participate in the Delphi process. We propose that there are three major criteria and two minor criteria to support the clinical diagnosis of FTLBs. A clinically definite diagnosis of FTLBs can be confirmed by the presence of all three major criteria. A clinically probable diagnosis of FTLBs can be confirmed by the presence of two major criteria and one minor criterion. CONCLUSIONS: Distinguishing FTLBs from primary tics is important due to the distinct treatment paths required for these two conditions. A limitation of the ESSTS 2022 criteria is that they lack prospective testing of their sensitivity and specificity.

The spectrum of functional tic-like behaviours: Data from an international registry.

BACKGROUND AND PURPOSE: Between 2019 and 2022, there was a marked rise in adolescents/young adults seeking urgent help for functional tic-like behaviours (FTLBs). Given the global scale of this phenomenon, we aimed to pool cases from different institutions in an international registry to better characterize this spectrum and facilitate future longitudinal observation. METHODS: An international collaborative group from 10 tertiary referral centres for tic disorders collected retrospective data on FTLB patients who sought specialists' attention between the last quarter of 2019 and June 2022. An audit procedure was used for collection of data, which comprised demographics, course of presentation and duration, precipitating and predisposing factors, phenomenology, comorbidities, and pharmacological treatment outcome. RESULTS: During the study period, we collected data on 294 patients with FTLBs, 97% of whom were adolescents and young adults and 87% of whom were female. FTLBs were found to have a peak of severity within 1 month in 70% of patients, with spontaneous remissions in 20%, and a very high frequency of complex movements (85%) and vocalizations (81%). Less than one-fifth of patients had pre-existing primary tic disorder, 66% had comorbid anxiety disorders, 28% comorbid depressive disorders, 24% autism spectrum disorder and 23% attention deficit/hyperactivity disorder. Almost 60% explicitly reported exposure to tic-related social media content. The vast majority of pharmacologically treated patients did not report benefit with tic-suppressing medications. CONCLUSIONS: Our data from the largest multicentre registry of FTLBs to date confirm substantial clinical differences from primary tic disorders. Social modelling was the most relevant contributing factor during the pandemic. Future longitudinal analyses from this database may help understand treatment approaches and responsiveness.

Symptoms compatible with long COVID in an Italian pediatric cohort of Tourette patients with and without SARS­CoV­2 infection: a short-term follow-up assessment.

BACKGROUND: Tourette Syndrome (TS) is a childhood-onset neurodevelopmental disorder with a worldwide prevalence of about 0.3-1% of the population. During the pandemic caused by SARS-CoV-2 infection, the impact on the mental health of children and adolescents was very important. The persistence of symptoms in the post-acute phase of the disease has been termed Long COVID. The neuropsychiatric symptoms seem to be the most common impairment in children and adolescents with long COVID. OBJECTIVES: Considering the impact of pandemic on mental health, in this study we analyzed the long-term effects of SARS-CoV-2 infection in children and adolescents affected by TS. METHODS: We conducted an online questionnaire covering socio-demographic and clinical data among 158 patients affected by TS or chronic tic disorders (CTD), of which 78 participants reported a positive SARS-CoV-2 infection. Data were collected to investigate tic severity and both the comorbidities, as well as lockdown-related changes to daily life activities and, in case of infection of SARS-CoV-2, possible symptoms of acute infection and long COVID. Markers of systemic inflammation including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), ferritin, iron, electrolytes, white blood cell counts, platelet cell counts levels, markers of liver, kidney and thyroid function were analyzed. First, all patients were screened with the Schedule for affective disorders and Schizophrenia for School age children-present and lifetime (Kiddie-SADS-PL) to rule out primary psychiatric disorders considered as criteria of exclusion. Then, all patients were clinically assessed at baseline (T0), and after three months (T1) through the administration of Yale Global Tic Severity Rating Scale (YGTSS), Multidimensional Anxiety Scale for Children (MASC), Child Depression Inventory (CDI) and Child Behavior Checklist (CBCL). RESULTS: Among the cohort of TS patients that contracted SARS-CoV-2 infection, 84.6% (n = 66) experienced any acute symptoms, and long COVID symptoms occurred in 38.5% (n = 30). A worsening of clinical symptoms of tics and eventually associated comorbidities occurred in 34.6% (n = 27) of TS patients that contracted SARS-CoV-2 infection. TS patients with or without SARS-CoV-2 infection showed an increase in the severity of tics and also behavioral, depressive and anxious symptoms. Instead, this increase was more evident in patients who contracted the infection than in patients who did not contract it. CONCLUSIONS: SARS-CoV-2 infection may have a role in the increase of tics and associated comorbidities in TS patients. Despite of these preliminary results, further investigations are necessary to improve knowledge about the acute and long-term impact of SARS-CoV-2 in TS patients.

European clinical guidelines for Tourette syndrome and other tic disorders-version 2.0. Part I: assessment.

In 2011 a working group of the European Society for the Study of Tourette Syndrome (ESSTS) has developed the first European assessment guidelines for Tourette syndrome (TS). Now, we present an updated version 2.0 of these European clinical guidelines for Tourette syndrome and other tic disorders, part I: assessment. Therefore, the available literature has been thoroughly screened, supplemented with national guidelines across countries and discussions among ESSTS experts. Diagnostic changes between DSM-IV and DSM-5 classifications were taken into account and new information has been added regarding differential diagnoses, with an emphasis on functional movement disorders in both children and adults. Further, recommendations regarding rating scales to evaluate tics, comorbidities, and neuropsychological status are provided. Finally, results from a recently performed survey among ESSTS members on assessment in TS are described. We acknowledge that the Yale Global Tic Severity Scale (YGTSS) is still the gold standard for assessing tics. Recommendations are provided for scales for the assessment of tics and psychiatric comorbidities in patients with TS not only in routine clinical practice, but also in the context of clinical research. Furthermore, assessments supporting the differential diagnosis process are given as well as tests to analyse cognitive abilities, emotional functions and motor skills.

European clinical guidelines for Tourette syndrome and other tic disorders-version 2.0. Part III: pharmacological treatment.

In 2011, the European Society for the Study of Tourette Syndrome (ESSTS) published the first European guidelines for Tourette Syndrome (TS). We now present an update of the part on pharmacological treatment, based on a review of new literature with special attention to other evidence-based guidelines, meta-analyses, and randomized double-blinded studies. Moreover, our revision took into consideration results of a recent survey on treatment preferences conducted among ESSTS experts. The first preference should be given to psychoeducation and to behavioral approaches, as it strengthens the patients' self-regulatory control and thus his/her autonomy. Because behavioral approaches are not effective, available, or feasible in all patients, in a substantial number of patients pharmacological treatment is indicated, alone or in combination with behavioral therapy. The largest amount of evidence supports the use of dopamine blocking agents, preferably aripiprazole because of a more favorable profile of adverse events than first- and second-generation antipsychotics. Other agents that can be considered include tiapride, risperidone, and especially in case of co-existing attention deficit hyperactivity disorder (ADHD), clonidine and guanfacine. This view is supported by the results of our survey on medication preference among members of ESSTS, in which aripiprazole was indicated as the drug of first choice both in children and adults. In treatment resistant cases, treatment with agents with either a limited evidence base or risk of extrapyramidal adverse effects might be considered, including pimozide, haloperidol, topiramate, cannabis-based agents, and botulinum toxin injections. Overall, treatment of TS should be individualized, and decisions based on the patient's needs and preferences, presence of co-existing conditions, latest scientific findings as well as on the physician's preferences, experience, and local regulatory requirements.

Clinical and radiological correlates of activities of daily living in cerebellar atrophy caused by PMM2 mutations (PMM2-CDG).

We aimed to identify clinical, molecular and radiological correlates of activities of daily living (ADL) in patients with cerebellar atrophy caused by PMM2 mutations (PMM2-CDG), the most frequent congenital disorder of glycosylation. Twenty-six PMM2-CDG patients (12 males; mean age 13 ± 11.1 years) underwent a standardized assessment to measure ADL, ataxia (brief ataxia rating scale, BARS) and phenotype severity (Nijmegen CDG rating scale, NCRS). MRI biometry of the cerebellum and the brainstem were performed in 23 patients (11 males; aged 5 months-18 years) and 19 control subjects with equal gender and age distributions. The average total ADL score was 15.3 ± 8.5 (range 3-32 out of 36 indicating severe functional disability), representing variable functional outcome in PMM2-CDG patients. Total ADL scores were significantly correlated with NCRS (r2 = 0.55, p < 0.001) and BARS scores (r2 = 0.764; p < 0.001). Severe intellectual disability, peripheral neuropathy, and severe PMM2 variants were all significantly associated with worse functional outcome. Higher ADL scores were significantly associated with decreased diameters of cerebellar vermis (r2 = 0.347; p = 0.004), hemispheres (r2 = 0.436; p = 0.005), and brainstem, particularly the mid-pons (r2 = 0.64; p < 0.001) representing the major radiological predictor of functional disability score in multivariate regression analysis. We show that cerebellar syndrome severity, cognitive level, peripheral neuropathy, and genotype correlate with ADL used to quantify disease-related deficits in PMM2-CDG. Brainstem involvement should be regarded among functional outcome predictors in patients with cerebellar atrophy caused by PMM2-CDG.

Neurodevelopmental outcomes of neonatal non-epileptic paroxysmal events: a prospective study.

AIM: To report on psychomotor development and outcomes in term born neonates with non-epileptic paroxysmal events (NEPEs). METHOD: From October 2017 to March 2019 we enrolled 38 consecutive term born neonates (22 males, 16 females; aged between 0-28d), born at the University Hospital San Marco in Catania, Italy, with NEPEs. We performed the Hammersmith Neonatal Neurological Examination scale (at enrolment), the Hammersmith Infant Neurological Examination (HINE) scale (at age 3, 6, 9, and 12mo), and the Griffiths scale (at age 12mo). RESULTS: The age at onset of first paroxysmal manifestations ranged from birth to 4 days. We recorded a suboptimal global score in 18 out of 38 patients at enrolment and in 10 out of 38 patients at age 3 months (>70% of these infants were male); all events disappeared within 6 months of life. At age 6, 9, and 12 months, all infants scored within normal values on the HINE and Griffiths scale. INTERPRETATION: Patients with NEPEs achieve neurodevelopment optimal scores within their first year of life. WHAT THIS PAPER ADDS: Neonates experiencing non-epileptic paroxysmal events (NEPEs) can be examined with the Hammersmith Neonatal Neurological Examination, Hammersmith Infant Neurological Examination, and Griffiths scale at follow-up. Newborn infants with NEPEs achieve optimal scores within the first year of life.

Expanding the phenotype of Wiedemann-Steiner syndrome: Craniovertebral junction anomalies.

Wiedemann-Steiner syndrome (WDSTS) is a rare autosomal dominant condition caused by heterozygous loss of function variants in the KMT2A (MLL) gene, encoding a lysine N-methyltransferase that mediates a histone methylation pattern specific for epigenetic transcriptional activation. WDSTS is characterized by a distinctive facial phenotype, hypertrichosis, short stature, developmental delay, intellectual disability, congenital malformations, and skeletal anomalies. Recently, a few patients have been reported having abnormal skeletal development of the cervical spine. Here we describe 11 such individuals, all with KMT2A de novo loss-of-function variants: 10 showed craniovertebral junction anomalies, while an 11th patient had a cervical abnormality in C7. By evaluating clinical and diagnostic imaging data we characterized these anomalies, which consist primarily of fused cervical vertebrae, C1 and C2 abnormalities, small foramen magnum and Chiari malformation type I. Craniovertebral anomalies in WDSTS patients have been largely disregarded so far, but the increasing number of reports suggests that they may be an intrinsic feature of this syndrome. Specific investigation strategies should be considered for early identification and prevention of craniovertebral junction complications in WDSTS patients.

Potential Associations Among Alteration of Salivary miRNAs, Saliva Microbiome Structure, and Cognitive Impairments in Autistic Children.

Recent evidence has demonstrated that salivary molecules, as well as bacterial populations, can be perturbed by several pathological conditions, including neuro-psychiatric diseases. This relationship between brain functionality and saliva composition could be exploited to unveil new pathological mechanisms of elusive diseases, such as Autistic Spectrum Disorder (ASD). We performed a combined approach of miRNA expression profiling by NanoString technology, followed by validation experiments in qPCR, and 16S rRNA microbiome analysis on saliva from 53 ASD and 27 neurologically unaffected control (NUC) children. MiR-29a-3p and miR-141-3p were upregulated, while miR-16-5p, let-7b-5p, and miR-451a were downregulated in ASD compared to NUCs. Microbiome analysis on the same subjects revealed that Rothia, Filifactor, Actinobacillus, Weeksellaceae, Ralstonia, Pasteurellaceae, and Aggregatibacter increased their abundance in ASD patients, while Tannerella, Moryella and TM7-3 decreased. Variations of both miRNAs and microbes were statistically associated to different neuropsychological scores related to anomalies in social interaction and communication. Among miRNA/bacteria associations, the most relevant was the negative correlation between salivary miR-141-3p expression and Tannerella abundance. MiRNA and microbiome dysregulations found in the saliva of ASD children are potentially associated with cognitive impairments of the subjects. Furthermore, a potential cross-talking between circulating miRNAs and resident bacteria could occur in saliva of ASD.

Use of nutritional supplements based on melatonin, tryptophan and vitamin B6 (Melamil Tripto®) in children with primary chronic headache, with or without sleep disorders: a pilot study.

BACKGROUND: Headache is one of the main complaints in pediatric neurology. Exogenous melatonin has been shown to be useful and safe in improving sleep-wake cycles and sleep quality in children. Tryptophan as well plays a key role in sleep regulation. So far, no studies tried to analyze the effects of a combination of both melatonin and tryptophan in treating chronic headache in children affected also by night-time awakenings. METHODS: Thirty-four children with a diagnosis of chronic headache (with or without sleep disorders) have been enrolled. The study was articulated in two steps: 1) each child was observed for one month without any intervention; 2) children have been then randomized into two groups: the "ME-group", which received the nutritional supplement melatonin for two months and the "MET-group", which received the nutritional supplements melatonin, tryptophan, and vitamin B6 for two months. RESULTS: In terms of changes in number of headache events, responders in the ME-group were 91.7% and those in the MET-group were 66.7% (P=0.113). In terms of changes in number of night awakenings, in the ME group, mean number at baseline, after 30 days, and after 60 days were 3.6±3.2, 3.2±3.5, and 2.7±3.4 (P=0.495). In the MET group, mean number of night awakenings was 7.4±8.1, 4.0±4.4, and 3.3±2.9 (P=0.041). CONCLUSIONS: Using either nutritional supplement for two months can help in decreasing the monthly number of headache episodes and night awakenings. The addition of tryptophan and vitamin B6 appears to have stronger influence on night awakenings reduction than melatonin only.

European Multicentre Tics in Children Studies (EMTICS): protocol for two cohort studies to assess risk factors for tic onset and exacerbation in children and adolescents.

Genetic predisposition, autoimmunity and environmental factors [e.g. pre- and perinatal difficulties, Group A Streptococcal (GAS) and other infections, stress-inducing events] might interact to create a neurobiological vulnerability to the development of tics and associated behaviours. However, the existing evidence for this relies primarily on small prospective or larger retrospective population-based studies, and is therefore still inconclusive. This article describes the design and methodology of the EMTICS study, a longitudinal observational European multicentre study involving 16 clinical centres, with the following objectives: (1) to investigate the association of environmental factors (GAS exposure and psychosocial stress, primarily) with the onset and course of tics and/or obsessive-compulsive symptoms through the prospective observation of at-risk individuals (ONSET cohort: 260 children aged 3-10 years who are tic-free at study entry and have a first-degree relative with a chronic tic disorder) and affected individuals (COURSE cohort: 715 youth aged 3-16 years with a tic disorder); (2) to characterise the immune response to microbial antigens and the host's immune response regulation in association with onset and exacerbations of tics; (3) to increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders; and (4) to develop prediction models for the risk of onset and exacerbations of tic disorders. The EMTICS study is, to our knowledge, the largest prospective cohort assessment of the contribution of different genetic and environmental factors to the risk of developing tics in putatively predisposed individuals and to the risk of exacerbating tics in young individuals with chronic tic disorders.

Nuclear Peroxisome Proliferator-Activated Receptors (PPARs) as Therapeutic Targets of Resveratrol for Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by defective social communication and interaction and restricted, repetitive behavior with a complex, multifactorial etiology. Despite an increasing worldwide prevalence of ASD, there is currently no pharmacological cure to treat core symptoms of ASD. Clinical evidence and molecular data support the role of impaired mitochondrial fatty acid oxidation (FAO) in ASD. The recognition of defects in energy metabolism in ASD may be important for better understanding ASD and developing therapeutic intervention. The nuclear peroxisome proliferator-activated receptors (PPAR) α, δ, and γ are ligand-activated receptors with distinct physiological functions in regulating lipid and glucose metabolism, as well as inflammatory response. PPAR activation allows a coordinated up-regulation of numerous FAO enzymes, resulting in significant PPAR-driven increases in mitochondrial FAO flux. Resveratrol (RSV) is a polyphenolic compound which exhibits metabolic, antioxidant, and anti-inflammatory properties, pointing to possible applications in ASD therapeutics. In this study, we review the evidence for the existing links between ASD and impaired mitochondrial FAO and review the potential implications for regulation of mitochondrial FAO in ASD by PPAR activators, including RSV.

Familial 18q12.2 deletion supports the role of RNA-binding protein CELF4 in autism spectrum disorders.

Deletion of 18q12.2 is an increasingly recognized condition with a distinct neuropsychiatric phenotype. Twenty-two patients have been described with overlapping neurobehavioral disturbances including developmental delay, intellectual disability of variable degree, seizures, motor coordination disorder, behavioral/emotional disturbances, and autism spectrum disorders. The CUGBP Elav-like family member 4 (CELF4) gene at 18q12.2 encodes a RNA-binding protein that links to RNA subsets involved in pre- and postsynaptic neurotransmission including almost 30% of potential autism-related genes. Haploinsufficiency of CELF4 was associated with an autism or autistic behavior diagnosis in two adult patients with de novo 18q12.2 deletions. We report on a girl and her mildly affected mother with a 275 kb deletion at 18q12.2 involving CELF4 and KIAA1328 whose disruption is not associated with any known disease. The child was diagnosed with syndromic intellectual disability and autism at 6 years of age. Her mother had minor dysmorphisms, mild intellectual disability, and autistic behavior. The deleted region reported in this family is one of the smallest so far reported at 18q12.2. This is also the first full clinical description of maternally inherited CELF4 haploinsufficiency. The present study refines the molecular and neuropsychiatric phenotype associated with 18q12.2 deletion leading to CELF4 haploinsufficiency and provides evidence for a role for CELF4 in brain development and autism spectrum disorders.

Resuming the obsolete term "small head": when microcephaly occurs without cognitive impairment.

Microcephaly is defined as a head circumference measurement of 2 or 3 standard deviations below the mean for age and sex. However, distinguishing the value of -2 or -3 standard deviations as a cutoff is relevant in the clinical practice, since the limit of -3 standard deviations is more frequently associated with cognitive impairment. The use of ultrasound scans in pregnancy has allowed the identification of subjects with a measurement of the head circumference at the limit of the cutoff for gestational age, but who do not subsequently show cognitive delay. The same is true for newborns with a -2 to -3 standard deviations cutoff, and without anomalous clinical signs, for which a cognitive delay is not easily diagnosed. In this case, to define an infant as being affected by microcephaly (with a prognosis usually recognized as harmful) may be unnecessarily distressful for parents or caregivers. In the cases mentioned, resuming the word "small head" instead of microcephaly to define such subjects could be more appropriate and more appreciated.

Parsing the phenotype of obsessive-compulsive tic disorder (OCTD): a multidisciplinary consensus.

Obsessive-Compulsive Disorder (OCD) and Tic Disorder (TD) are highly disabling and often comorbid conditions. Of note, the DSM-5 acknowledged a new 'tic-related' specifier for OCD, which might be referred to as Obsessive-Compulsive Tic Disorder (OCTD), raising new interest toward a better clinical characterisation of affected patients. Available literature indicates that early onset, male gender, sensory phenomena and obsessions of symmetry, aggressiveness, hoarding, exactness and sounds as well as comorbidity with Attention Deficit Hyperactivity Disorder (ADHD) may be of more frequent observation in patients with OCTD. In order to share expertise in the field from different perspectives, a multidisciplinary panel of Italian clinicians, specifically involved in the clinical care of OCD and TD patients, participated into a consensus initiative, aimed to produce a shared document. As a result, after having examined the most relevant literature, authors sought to critically identify and discuss main epidemiologic, socio-demographic and clinical features characterising OCTD patients, along with other specific aspects including Health-Related Quality-of-Life (HRQoL), economic consequences related with the condition and its management, as well as treatment-related issues, that need to be further investigated.

Therapeutic drug monitoring of second-generation antipsychotics in pediatric patients: an observational study in real-life settings.

PURPOSE: Available guidelines on therapeutic drug monitoring of second-generation antipsychotics were designed for adults; therefore, they cannot be transferred as such in pediatric patients, who may have different drug absorption, distribution, metabolism, and elimination. Moreover, available tools that guide dosing in neuropsychiatric pediatric patients are scant, leading to the possibility of reduced efficacy and/or increased risks of toxicity. Here we describe the results of observational therapeutic drug monitoring conducted in three pediatric neuropsychiatry units across Italy in 2012-2014, with the following aims: (1) to describe the distribution of plasma concentrations of second-generation antipsychotics in our pediatric patients and (2) to identify clinical covariates associated with plasma drug levels. METHODS: Five hundred fifty-six plasma trough concentrations of the second-generation antipsychotics risperidone (plus 9-hydroxy-risperidone), aripiprazole, olanzapine, and quetiapine were measured from 172 pediatric outpatients overall. The distribution of drug concentrations was described and correlated with drug doses and clinical variables. RESULTS: Risperidone plasma levels were lower than in adults (median 13.6 ng/ml), with a high inter-patient (78.9%) but lower intra-patient (34.2%) variability. In multiple regression analyses, risperidone plasma levels depended only on drug dose (p < 0.001). Aripiprazole plasma levels were similar to those described in adults (median 165.8 ng/ml) and were widely distributed, with an inter-patient variability of 81.1%, while the intra-patient variability was much lower (29.3%). Multiple regression analyses indicated that aripiprazole plasma levels were influenced by the daily doses (p < 0.001) and by the number of concomitant drugs (p < 0.01). CONCLUSION: Our study described the distribution of plasma levels of SGAs in a real-life setting involving pediatric patients, significantly increasing the amount of available data for this fragile population. If confirmed in larger dataset, these data may contribute to the definition of optimal therapeutic window for risperidone and aripiprazole plasma levels in pediatric patients.

Genetic association signal near NTN4 in Tourette syndrome.

Tourette syndrome (TS) is a neurodevelopmental disorder with a complex genetic etiology. Through an international collaboration, we genotyped 42 single nucleotide polymorphisms (p < 10(-3) ) from the recent TS genomewide association study (GWAS) in 609 independent cases and 610 ancestry-matched controls. Only rs2060546 on chromosome 12q22 (p = 3.3 × 10(-4) ) remained significant after Bonferroni correction. Meta-analysis with the original GWAS yielded the strongest association to date (p = 5.8 × 10(-7) ). Although its functional significance is unclear, rs2060546 lies closest to NTN4, an axon guidance molecule expressed in developing striatum. Risk score analysis significantly predicted case-control status (p = 0.042), suggesting that many of these variants are true TS risk alleles.

TBR1 is the candidate gene for intellectual disability in patients with a 2q24.2 interstitial deletion.

Interstitial deletion of 2q24.2 is a rarely described cytogenetic aberration in patients with intellectual disability (ID). Previously reported genotype-phenotype correlation identified a minimum deleted region of 2.65 Mb including 15 genes. Recently, a patient with a de novo 2q24.2 microdeletion of 0.4 Mb encompassing only three genes was described. However, the precise relationship between most deleted genes and the clinical features remains unclear. Here we describe a 12-year-old male patient diagnosed with growth retardation and ID. He also showed microcephaly, right palpebral ptosis, scapular winging, and pectus excavatum. Single nucleotide polymorphisms (SNP) array analysis showed a de novo interstitial deletion of 0.122 Mb at 2q24.2 region harboring only TBR1 (T-box, brain, 1; OMIM: 604616), which encodes a T-box family transcription factor expressed in post-mitotic projection neurons and functionally significant in embryologic corticogenesis. This is the first case of a deletion at 2q24.2 involving only TBR1. This finding narrows the smallest region of overlap (SRO) for deletions in this region and strengthens the previously suggested hypothesis that this gene is a strong candidate for the ID phenotype. The identification of TBR1 as candidate for ID encourages further molecular studies to identify novel mutations to understand the pathogenic effects of its haploinsufficiency. Finally, this report provides a review on 10 2q24.2 microdeletion patients.