Background: Infantile hypotonia with psychomotor retardation and characteristic facies 2 (IHPRF2) is a rare autosomal recessive neurodevelopmental disorder caused by mutations in the UNC80 gene. It is characterized by severe global developmental delay, poor or absent speech and absent or limited walking abilities. The current study explored a case of a Chinese patient with IHPRF2 caused by a novel splicing variant of UNC80. Case Report: The proband is a 8-year-old Chinese male manifested with global developmental delay, severe truncal hypotonia, absent speech and intellectual disability. SNP array analysis revealed a uniparental isodisomy of the entire chromosome 2 [UPD(2)] in the proband. Whole exome sequencing (WES) subsequently identified a novel mutation c.5609-4G>A in the UNC80 gene, which was inherited from his mother and was confirmed by Sanger sequencing, indicating that UPD(2) was of maternal origin. Conclusion: A novel UNC80 homozygous splicing variant c.5609-4G>A associated with maternal UPD(2) was identified. These findings indicate that UPD poses a high risk of autosomal recessive diseases, and provides information on the variant spectrum for UNC80. Our findings elucidate on understanding of the genotype-phenotype associations that occur in IHPRF2 patients.

Autism Spectrum Disorders (ASDs) represent a group of very complex early-onset neurodevelopmental diseases. In this study, we analyzed 5 SNPs (rs2317385, rs5918, rs15908, rs12603582, rs3809865) at the β3 integrin locus (ITGB3), which has been suggested as a possible susceptibility gene, both as single markers and as part of haplotypes in 209 ASD children and their biological parents. We tested for association with the following: a) DSM-IV ASD diagnosis; b) clinical symptoms common in ASD patients (repetitive behaviors, echolalia, seizures and epilepsy, mood instability, aggression, psychomotor agitation, sleep disorders); and c) dimensional scores obtained with the Autism Screening Questionnaire and the Childhood Autism Rating Scale. These hypotheses were investigated using family-based tests, logistic regression models and analysis of covariance. The family-based tests showed an association with the H5 haplotype (composed by GTCGA alleles, the order of SNPs as above), which was transmitted less often than expected by chance (P=0.006; Pcorr=0.036). The analyses of the clinical symptoms showed a trend for an association with rs12603582 (P=0.008; Pcorr=0.064) and positive results for the haplotype composed of rs15908 and rs12603582 (Pglcorr=0.048; Pindcorr=0.015), both in symptoms of echolalia. Other nominal associations with different variants were found and involved epilepsy/seizures, aggression symptoms and higher ASQ scores. Although our positive results are not definitive, they suggest small effect associations of the ITGB3 gene with both ASD diagnosis and symptoms of echolalia. Other studies are nonetheless needed to fully understand the involvement of this locus on the etiology of ASDs and its different clinical aspects.

HIV-associated neurocognitive disorders (HAND) represent a spectrum of cognitive abnormalities affecting attention, concentration, learning, memory, executive function, psychomotor speed, and/or dexterity. Our objectives in this analysis are to determine the prevalence of HAND and the covariates in a Kenyan population.

Iodine deficiency disorders (IDDs) have been recognized as one of the major nutritional disorders throughout the world affecting 200 million people who are at risk and another 71 million suffering from goiter and other IDDs. These groups of disorders can affect every stage of life, but most vulnerable age group is between 6 and 12 years and these disorders together constitute the single largest preventable cause of brain damage leading to learning disabilities and psychomotor impairment. The existence of endemic goiter in an extensive belt along the southern slopes of the Himalayas, Alps, and Andes has long been described, but consistently high prevalence of IDDs outside the endemic zones and failure to attain goals set by the National Iodine Deficiency Disorder Control Program questions the strategy and achievements till date. Therefore, the present article is an attempt to critically examine the program since inception in India.

Mutations in the X-linked MECP2 cause Rett syndrome, a devastating neurological disorder typified by a period of apparently normal development followed by loss of cognitive and psychomotor skills. Data from rare male patients suggest symptom onset and severity can be influenced by the location of the mutation, with amino acids 270 and 273 marking the difference between neonatal encephalopathy and death, on the one hand, and survival with deficits on the other. We therefore generated two mouse models expressing either MeCP2-R270X or MeCP2-G273X. The mice developed phenotypes at strikingly different rates and showed differential ATRX nuclear localization within the nervous system, over time, coinciding with phenotypic progression. We discovered that MeCP2 contains three AT-hook-like domains over a stretch of 250 amino acids, like HMGA DNA-bending proteins; one conserved AT-hook is disrupted in MeCP2-R270X, lending further support to the notion that one of MeCP2's key functions is to alter chromatin structure.

Purpose: Cerebral palsy (CP) is a heterogeneous permanent disorder impacting movement and posture. Investigations aimed at diagnosing this disorder are expensive and time-consuming and can eventually inconclusive. This study aimed to determine the diagnostic yield of next generation sequencing in patients with atypical CP (ACP). Methods: Patient eligibility criteria included impaired motor function with onset at birth or within the first year of life, and one or more of the following conditions: severe intellectual disability, positive family history, brain imaging findings not typical for cerebral palsy, abnormal neurometabolic profile, intractable seizure, normal neuroimaging despite severe psychomotor disability, after pediatric neurologist assessment including neuroimaging and biochemical-metabolic study offered for genetic study. Results: Exome sequencing was done for 66 patients which revealed pathogenic, likely pathogenic, and variants of unknown significance in 36.2, 9, and 43.9%, respectively. We also found 10 new mutations and were able to suggest specific and personalized treatments for nine patients. We also found three different mutations with different phenotypical spectrum in one gene that have not been reported for cerebral palsy. Conclusion: An accurate history and physical examination and determination of patients with atypical cerebral palsy for doing exome sequencing result in improved genetic counseling and personalized management.

Cognitive dysfunction is a prominent feature of psychiatric disorders. Studies have shown that systemic low-grade inflammation is crucial in the development of cognitive deficits across psychiatric disorders. The aim of this study was to further examine the role of inflammation and inflammatory mediators in cognitive function in psychiatric disorders. This study included 364 inpatients (53% females) with International Classification of Diseases (ICD)-10 F3 (affective disorders) and F4 (neurotic, stress-related, and somatoform disorders) diagnoses. The mean age was 52 years (22 to 69 years) and the median body mass index was 27.6. Cognitive function was assessed with the Color-Word Interference Test after Stroop and the Trail-Making Test A/B. Multiple linear regression models were calculated to assess the predictive value of C-reactive protein and the kynurenine/tryptophan ratio on cognitive function controlling for age, sex, education, premorbid verbal intelligence quotient illness duration, depressive symptoms, and obesity-related parameters (e.g., body mass index, high-density lipoprotein). Our data confirm that in patients with psychiatric disorders, C-reactive protein serum concentration is a relevant and important predictor of Trail-Making Test B performance, measuring cognitive flexibility. The effect size of this association did not change much after adding clinical and metabolic variables into the regression model. The kynurenine/tryptophan ratio was not related to cognitive test scores. The involvement of C-reactive protein as a peripheral inflammatory marker in cognitive flexibility and psychomotor processing speed in psychiatric illness can be concluded.

Background: Childhood mortality from infectious diseases has declined steadily in many low and middle-income (LAMIC) countries, with increased recognition of non-communicable diseases such as neurodevelopmental disorders (NDD). There is lack of data on the burden of NDD in LAMIC. Current global burden of these disorders are largely extrapolated from high-income countries. The main objective of the study was therefore to estimate the burden of NDD in LAMIC using meta-analytic techniques. Methods: We systematically searched online databases including Medline/PubMed, PsychoInfo, and Embase for studies that reported prevalence or incidence of NDD. Pooled prevalence, heterogeneity and risk factors for prevalence were determined using meta-analytic techniques.   Results: We identified 4,802 records, but only 51 studies met the eligibility criteria. Most studies were from Asia (52.2%) and most were on neurological disorders (63.1%). The median pooled prevalence per 1,000 for all NDD was 7.6 (95%CI 7.5-7.7), being 11.3 (11.7-12.0) for neurological disorders and 3.2 (95%CI 3.1-3.3) for mental conditions such as attention-deficit hyperactivity disorder (ADHD). The type of NDD was significantly associated with the greatest prevalence ratio in the multivariable model (PR=2.6(95%CI 0.6-11.6) (P>0.05). Incidence was only reported for epilepsy (mean of 447.7 (95%CI 415.3-481.9) per 100,000). Perinatal complications were the commonest risk factor for NDD. Conclusion: The burden of NDD in LAMIC is considerable. Epidemiological surveys on NDD should screen all types of NDD to provide reliable estimates.

Epidemiological studies consistently implicate traffic-related air pollution (TRAP) and/or proximity to heavily trafficked roads as risk factors for developmental delays and neurodevelopmental disorders (NDDs); however, there are limited preclinical data demonstrating a causal relationship. To test the effects of TRAP, pregnant rat dams were transported to a vivarium adjacent to a major freeway tunnel system in northern California where they were exposed to TRAP drawn directly from the face of the tunnel or filtered air (FA). Offspring remained housed under the exposure condition into which they were born and were tested in a variety of behavioral assays between postnatal day 4 and 50. To assess the effects of near roadway exposure, offspring of dams housed in a standard research vivarium were tested at the laboratory. An additional group of dams was transported halfway to the facility and then back to the laboratory to control for the effect of potential transport stress. Near roadway exposure delayed growth and development of psychomotor reflexes and elicited abnormal activity in open field locomotion. Near roadway exposure also reduced isolation-induced 40-kHz pup ultrasonic vocalizations, with the TRAP group having the lowest number of call emissions. TRAP affected some components of social communication, evidenced by reduced neonatal pup ultrasonic calling and altered juvenile reciprocal social interactions. These findings confirm that living in close proximity to highly trafficked roadways during early life alters neurodevelopment.

Technological advancement is constantly evolving, and it is also developing in the mental health field. Various applications, often based on virtual reality, have been implemented to carry out psychological assessments and interventions, using innovative human-machine interaction systems. In this context, the LEAP Motion sensing technology has raised interest, since it allows for more natural interactions with digital contents, via an optical tracking of hand and finger movements. Recent research has considered LEAP Motion features in virtual-reality-based systems, to meet specific needs of different clinical populations, varying in age and type of disorder. The present paper carried out a systematic mini-review of the available literature using Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The inclusion criteria were (i) publication date between 2013 and 2020, (ii) being an empirical study or project report, (iii) written in English or Italian languages, (iv) published in a scholarly peer-reviewed journal and/or conference proceedings, and (v) assessing LEAP Motion intervention for four specific psychological domains (i.e., autism spectrum disorder, attention-deficit/hyperactivity disorder, dementia, and mild cognitive impairment), objectively. Nineteen eligible empirical studies were included. Overall, results show that protocols for attention-deficit hyperactivity disorder and autism spectrum disorder can promote psychomotor and psychosocial rehabilitation in contexts that stimulate learning. Moreover, virtual reality and LEAP Motion seem promising for the assessment and screening of functional abilities in dementia and mild cognitive impairment. As evidence is, however, still limited, deeper investigations are needed to assess the full potential of the LEAP Motion technology, possibly extending its applications. This is relevant, considering the role that virtual reality could have in overcoming barriers to access assessment, therapies, and smart monitoring.

HIV-Associated Neurocognitive Disorder (HAND remains a pronounced consequence of HIV/AIDS despite improved life expectancies. This is often associated with several dysfunctions such as decrease of attention, mood alterations and psychomotor disturbances. Many factors, including age, gender, employment status, and psychiatric disorders, have been associated with HAND. Among the associated psychiatric disorders, depression is often more prevalent. It can influence not only quality of life, relationships and employment but also adherence to medical care. We assessed the prevalence of depression and its association with HAND among people living with HIV in rural Southwestern Uganda.

Mitochondrial diseases (MDs) are a large group of genetically determined multisystem disorders, characterized by extreme phenotypic heterogeneity, attributable in part to the dual genomic control (nuclear and mitochondrial DNA) of the mitochondrial proteome. Advances in next-generation sequencing technologies over the past two decades have presented clinicians with a challenge: to select the candidate disease-causing variants among the huge number of data provided. Unfortunately, the clinical tools available to support genetic interpretations still lack specificity and sensitivity. For this reason, the diagnosis of MDs continues to be difficult, with the new "genotype first" approach still failing to diagnose a large group of patients. With the aim of investigating possible relationships between clinical and/or biochemical phenotypes and definitive molecular diagnoses, we performed a retrospective multicenter study of 111 pediatric patients with clinical suspicion of MD. In this cohort, the strongest predictor of a molecular (in particular an mtDNA-related) diagnosis of MD was neuroimaging evidence of basal ganglia (BG) involvement. Regression analysis confirmed that normal BG imaging predicted negative genetic studies for MD. Psychomotor regression was confirmed as an independent predictor of a definitive diagnosis of MD. The findings of this study corroborate previous data supporting a role for neuroimaging in the diagnostic approach to MDs and reinforce the idea that mtDNA sequencing should be considered for first-line testing, at least in specific groups of children.

The current COVID-19 pandemic has resulted in high rates of infection and death, as well as widespread social disruption and a reduction in access to healthcare services and support. There is growing concern over how the pandemic, as well as measures put in place to curb the pandemic, will impact people with mental disorders. We aim to study the effect of pandemics and epidemics on mental health outcomes for people with premorbid mental disorders.

Rett syndrome (RTT) is a severe progressive neurodevelopmental disease characterized by psychomotor regression. The FOXG1 gene is one of the pathogenic genes associated with the congenital Rett variant, which is less studied. Only a few Chinese patients with FOXG1 mutation have been reported. In this study, we describe a Chinese female patient with congenital Rett variant who presented with psycho-motor retardation, developmental regression, microcephaly, seizure, stereotypic hand movement and hypotonia. Targeted high-throughput sequencing was conducted, and a heterozygous FOXG1 mutation [NM_005249.4: c.506dupG (P.G169Gfs* 286)] was identified. It was a frameshift mutation resulting in alteration of the reading frames downstream of the mutation. SIMILAR CASES PUBLISHED: 10. CONFLICT OF INTEREST: None.

To define further the electroclinical manifestations of frontal lobe epilepsy (FLE), we studied 150 seizures manifested by 24 patients; 18 patients had subdural electrode arrays (SEA). The findings in these patients clearly overlapped presumably reflecting the interconnections between functionally related frontal zones; yet the manner in which the symptoms clustered and the sequence in which they occurred generally indicated the anatomic site of the epileptogenic zone. We divided the patients into three major groups: (a) those with supplementary motor seizures, (b) those with focal motor seizures, and (c) those with complex partial seizures (CPS, psychomotor seizures). Supplementary motor seizures began with tonic posturing of the extremities. Focal motor seizures generally began with conscious contralateral version or unilateral clonic focal motor activity; tonic posturing was noted only late in the seizure. CPS (psychomotor) began with unresponsiveness at onset, followed by staring or unconscious contraversion. We compared frontal lobe seizures with temporal lobe seizures reported previously; oral-alimentary automatisms, repetitive hand movements, or looking around, were more common in temporal lobe seizures, whereas tonic posturing and bicycling movements were more common in frontal lobe psychomotor seizures.

Ribonucleases (RNases) are crucial for degradation of ribosomal RNA (rRNA). RNASET2 as a subtype of RNASEs is a 256 amino acid protein, encoded by RNASET2 gene located on chromosome six. Defective RNASET2 leads to RNASET2-deficient leukoencephalopathy, a rare autosomal recessive neurogenetic disorder with psychomotor delay as its main clinical symptom. The clinical findings can be similar to congenital cytomegalovirus (CMV) infection and Aicardi-Goutieres syndrome (AGS).

Evidence from clinical and preclinical studies has demonstrated that stress can cause depressive-like symptoms including anhedonia and psychomotor retardation, namely, the manifestation of motivational deficits in depression. The proximate mediator of linking social-environmental stress with internal motivational deficits remains elusive, although substantial studies proposed neural endocrine mechanisms. As an endogenous danger-associated molecule, high mobility group box-1 (HMGB1) is necessary and sufficient for stress-induced sensitization of innate immune cells and subsequent (neuro)inflammation.

Skeletal muscle function can be affected by multiple disorders in dogs of which cranial cruciate ligament rupture or disease (CCLD) is one of the most common. Despite the significance of this condition only sparse research exists regarding assessment of muscle function in dogs. This scoping review aimed to identify the non-invasive methods for canine muscle function assessments that have been reported in the literature in the past 10 years. A systematic literature search was conducted 1st March 2022 across six databases. After screening, 139 studies were considered eligible for inclusion. Among the included studies, 18 different muscle function assessment categories were identified, and the most frequently reported disease state was CCLD. We included an attempt to elucidate the clinical applicability of the 18 reported methods, as experts were asked to subjectively assess the methods for their clinical relevance as well as their practical applicability in dogs with CCLD.

The striatum comprises a mosaic structure of striosomal and matrix compartments. Imbalanced neuronal activity between striosomes and matrix is implicated in neurological deficits in psychomotor and limbic functions. Because patients with autism spectrum disorder (ASD) are impaired in social communication and psychomotor function, it raises the possibility that abnormal striatal compartments may contribute to ASD pathogenesis. Here, we provide pathological evidence from human postmortem brains to support this hypothesis. Because ASD is a neurodevelopmental disease that emerges early in childhood, we analyzed juvenile and adolescent brains. Distinct patterns of PRODYNORPHIN-positive and calbindin-poor striosomes were detected in the caudate nucleus of control brains by in situ hybridization and immunohistochemistry. By contrast, PRODYNORPHIN-positive and calbindin-poor striosomes were decreased in the caudate nucleus of young ASD brains. Moreover, calbindin, a matrix marker, was aberrantly increased in the striosomal compartment, obscuring the boundaries between calbindin-poor striosomes and calbindin-rich matrix in ASD caudate nucleus. Calbindin-positive cells were decreased in the ASD matrix compartment. Collectively, our study has uncovered for the first time that aberrant striatal compartments occur in the caudate nucleus of human ASD brains, which suggests abnormal striatal compartmentation as a pathological signature that has previously been underestimated in ASD pathogenesis.

Adolescents' health-related behavior varies from weekday to weekend. Only few studies, however, have examined to which degree such variation will affect markers of cardiometabolic health. Therefore, the primary aim of this study is to examine if markers of cardiometabolic health differ between different days of the week in adolescents.