1. Benitah KC, Kavaliers M, Ossenkopp KP. The enteric metabolite, propionic acid, impairs social behavior and increases anxiety in a rodent ASD model: Examining sex differences and the influence of the estrous cycle. Pharmacol Biochem Behav;2023 (Aug 26):173630.

Research suggests that certain gut and dietary factors may worsen behavioral features of autism spectrum disorder (ASD). Treatment with propionic acid (PPA) has been found to create both brain and behavioral responses in rats that are characteristic of ASD in humans. A consistent male bias in human ASD prevalence has been observed, and several sex-differential genetic and hormonal factors have been suggested to contribute to this bias. The majority of PPA studies in relation to ASD focus on male subjects; research examining the effects of PPA in females is scarce. The present study includes two experiments. Experiment 1 explored sex differences in the effects of systemic administration of PPA (500 mg/kg, ip) on adult rodent social behavior and anxiety (light-dark test). Experiment 2 investigated differential effects of systemic administration of PPA (500 mg/kg) on social behavior and anxiety in relation to fluctuating estrogen and progesterone levels during the adult rodent estrous cycle. PPA treatment impaired social behavior and increased anxiety in females to the same degree in comparison to PPA-treated males. As well, females treated with PPA in their diestrus phase did not differ significantly in comparison to females administered PPA in their proestrus phase, in terms of reduced social behavior and increased anxiety.

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2. Bobos D, Soufla G, Angouras DC, Lekakis I, Georgopoulos S, Melissari E. Investigation of the Role of BMP2 and -4 in ASD, VSD and Complex Congenital Heart Disease. Diagnostics (Basel);2023 (Aug 21);13(16)

Congenital heart malformations (CHMs) make up between 2 and 3% of annual human births. Bone morphogenetic proteins (BMPs) signalling is required for chamber myocardium development. We examined for possible molecular defects in the bone morphogenetic protein 2 and 4 (BMP2, -4) genes by sequencing analysis of all coding exons, as well as possible transcription or protein expression deregulation by real-time PCR and ELISA, respectively, in 52 heart biopsies with congenital malformations (atrial septal defect (ASD), ventricular septal defect (VSD), tetralogy ofFallot (ToF) and complex cases) compared to 10 non-congenital heart disease (CHD) hearts. No loss of function mutations was found; only synonymous single nucleotide polymorphisms (SNPs) in the BMP2 and BMP4 genes were found. Deregulation of the mRNA expression and co-expression profile of the two genes (BMP2/BMP4) was observed in the affected compared to the normal hearts. BMP2 and -4 protein expression levels were similar in normal and affected hearts. This is the first study assessing the role of BMP-2 and 4 in congenital heart malformations. Our analysis did not reveal molecular defects in the BMP2 and -4 genes that could support a causal relationship with the congenital defects present in our patients. Importantly, sustained mRNA and protein expression of BMP2 and -4 in CHD cases compared to controls indicates possible temporal epigenetic, microRNA or post-transcriptional regulation mechanisms governing the initial stages of cardiac malformation.

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3. Burns J, Phung R, McNeill S, Hanlon-Dearman A, Ricci MF. Comorbidities Affecting Children with Autism Spectrum Disorder: A Retrospective Chart Review. Children (Basel);2023 (Aug 19);10(8)

Autism spectrum disorder (ASD) is a developmental disorder characterized by deficits in social interaction/communication, restricted interests, and repetitive behaviors. Recent discussions have emerged worldwide regarding the heterogeneity around presentation/etiology and comorbidities. This study aimed to determine the frequency and characteristics of comorbidities among children diagnosed with ASD in Manitoba and to evaluate differences in presentation between those with and without medical comorbidities. We conducted a retrospective chart review of >1900 electronic charts at the only publicly funded referral site for children ≤6 years requiring evaluation for ASD in Manitoba. All children aged 0-6 years diagnosed with ASD at this site between May 2016 and September 2021 were identified. χ(2) and t-tests were used to compare groups. Of the total of 1858 children identified, 1452 (78.1%) were boys, 251 (13.5%) were prematurely born, and 539 (29.0%) had ≥1 medical comorbidity. Global developmental delay (GDD) was diagnosed in 428 (23.0%). The age of referral and diagnosis did not differ between groups. Comorbidities were more common among premature children (16.0% vs. 12.5%, p: 0.005) and children with comorbid GDD (34.9% vs. 18.2%, p < 0.001). Neurological comorbidities were most common (37.1%). No sex difference in the overall presence of comorbidities was found (boys = 77.1% vs. 78.5%, p: 0.518); however, girls had a higher incidence of neurological comorbidities, e.g., cerebral palsy, seizures, hypotonia (14.8% vs. 9.64%, p: 0.009), as well as genetic comorbidities (4.92% vs. 2.75%, p: 0.04). The high rates of associated neurological conditions, GDD, and prematurity add heterogeneity to this group leading to potential difficulties with prognosis and service allocation. Primary vs. secondary ASD can be a way of separating individuals based on relevant medical comorbidities.

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4. Chubick A, Wang E, Au C, Grody WW, Ophoff RA. Large-Scale Whole Genome Sequence Analysis of >22,000 Subjects Provides no Evidence of FMR1 Premutation Allele Involvement in Autism Spectrum Disorder. Genes (Basel);2023 (Jul 25);14(8)

Expansion of a CGG repeat in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene on the X chromosome is the cause of Fragile X Syndrome (FXS). The repeat length of unaffected individuals varies between 5-40 repeats, whereas >200 repeats are observed in cases of FXS. The intermediate range between 55-200 repeats is considered the premutation range and is observed in roughly 1:300 females and 1:900 males in the general population. With the availability of large-scale whole genome sequence (WGS) data and the development of computational tools to detect repeat expansions, we systematically examined the role of FMR1 premutation alleles in autism spectrum disorder (ASD) susceptibility, assess the prevalence, and consider the allelic stability between parents and offspring. We analyzed the WGS data of 22,053 subjects, including 32 FXS positive controls, 1359 population controls, and 5467 ASD families. We observed no FMR1 full mutation range repeats among the ASD parent-offspring families but identified 180 family members with premutation range alleles, which represents a higher prevalence compared to the independent WGS control sample and previous reports in the literature. A sex-specific analysis between probands and unaffected siblings did not reveal a significant increase in the burden of premutation alleles in either males or females with ASD. PCR validation, however, suggests an overestimation of the frequency of FMR1 premutation range alleles through computational analysis of WGS data. Overall, we show the utility of large-scale repeat expansion screening in WGS data and conclude that there is no apparent evidence of FMR1 premutation alleles contributing to ASD susceptibility.

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5. Dell’Osso L, Amatori G, Cremone IM, Massimetti E, Nardi B, Gravina D, Benedetti F, Muscatello MRA, Pompili M, Politi P, Vita A, Maj M, Carpita B. Autistic and Catatonic Spectrum Symptoms in Patients with Borderline Personality Disorder. Brain Sci;2023 (Aug 7);13(8)

BACKGROUND: Recent literature has shown that a considerable percentage of patients with severe mental disorders can develop, over time, full-blown or subthreshold catatonia. Some studies corroborate the model of an illness trajectory in which different mental disorders would be arranged along a continuum of severity until the development of catatonia. In such an illness pathway, autistic traits (AT) and borderline personality disorder (BPD) may represent important steps. In order to further explore the association between AT, BPD, and catatonia, the aim of this study was to compare catatonic spectrum symptoms and AT among patients with major depressive disorder (MDD), BPD, and healthy controls (CTL), also evaluating possible predictive dimensions of the different diagnoses. METHODS: A total of 90 adults affected by BPD, 90 adults with a diagnosis of MDD, and 90 CTL, homogeneous in terms of gender and age, were recruited from six Italian university departments of psychiatry and assessed with the SCID-5-RV, the Catatonia Spectrum (CS), and the Adult Autism Subthreshold Autism Spectrum (AdAS Spectrum). RESULTS: The total CS score was significantly higher in the BPD and MDD groups than in the CTL group, while the majority of CS domain scores were significantly higher in the BPD group than in the MDD group, which scored significantly higher than the CTL group. The total AdAS Spectrum score and the AdAS Spectrum domain scores were significantly higher in the BPD group than in the MDD group, which in turn scored significantly higher than the CTL group. The CS domains « psychomotor activity » and « impulsivity », and AdAS Spectrum domains « verbal communication », « empathy », and « hyper-/hyporeactivity to sensory input » were associated with the risk of presenting a diagnosis of BPD.

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6. do Nascimento P, Oliveira Silva DF, de Morais T, de Rezende AA. Zinc Status and Autism Spectrum Disorder in Children and Adolescents: A Systematic Review. Nutrients;2023 (Aug 21);15(16)

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder, the prevalence of which has increased in children and adolescents over the years. Studies point to deficiency of trace elements as one of the factors involved in the etiology of the disorder, with zinc being one of the main trace elements investigated in individuals with ASD. The aim of this review is to summarize scientific evidence about the relationship between zinc status and ASD in children and adolescents. This review has been registered in the International Prospective Register of Systematic Reviews (registration number CRD42020157907). The methodological guidelines adopted were in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies were selected from an active investigation of the PubMed, Scopus, LILACS, and Google databases to search for observational studies. Fifty-two studies from twenty-two countries were included. The sample sizes ranged from 20 to 2635, and the participants ranged from 2 to 18 years old. Nine types of biological matrices were used, with hair, serum, and plasma being the most frequently used in the evaluation of zinc concentrations. Significant differences in zinc concentrations between the ASD and control groups were observed in 23 studies, of which 19 (36%) showed lower zinc concentrations in the ASD group. The classification of studies according to methodological quality resulted in high, moderate, and low quality in 10, 21, and 21 studies, respectively. In general, we did not observe a significant difference between zinc concentrations of children and adolescents with ASD compared to controls; however, studies point to an occurrence of lower concentrations of Zn in individuals with ASD. This review reveals that more prospective studies with greater methodological rigor should be conducted in order to further characterize this relation.

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7. Hyassat M, Al-Makahleh A, Rahahleh Z, Al-Zyoud N. The Diagnostic Process for Children with Autism Spectrum Disorder: A Preliminary Study of Jordanian Parents’ Perspectives. Children (Basel);2023 (Aug 15);10(8)

Although extensive research has been conducted worldwide to investigate the diagnostic process of Autism Spectrum Disorder (ASD), Jordanian parents’ experiences have been overlooked. This study explored parents’ journeys toward receiving diagnoses for their children with ASD. In particular, it aimed to provide a clear picture of the process for obtaining these diagnoses for children in Jordan. METHODS: Eighteen semi-structured interviews were carried out with 12 mothers and six fathers of children with ASD aged 5 to 11 years old. RESULTS: The coding process was based on a thematic analysis method and resulted in the identification of three overlapping themes: dissatisfaction with professionals’ abilities to approach parents, an unstructured diagnostic process, and perspectives on diagnosis tools. CONCLUSIONS: Our data upheld the idea that parental satisfaction with the diagnostic process is influenced by the duration of the process, the information provided, the support offered, and the communication approach used by professionals. Within the local cultural context, parents were significantly impacted by the societal stigma associated with disability when they sought diagnoses for their children with ASD.

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8. Kéri S. Autism and Religion. Children (Basel);2023 (Aug 20);10(8)

The disease burden of autism spectrum disorder (ASD) is a definitive public health challenge. The quality of life of children with ASD depends on how the cultural environment fits their special needs, including religious and spiritual factors. Does ASD predict low religiosity, and if not, what is the significance for clinical care? To answer this question, we reviewed the literature on the cognitive models of ASD and religious beliefs. We found that the cognitive models of ASD and religious beliefs substantially overlap, which is particularly important from a developmental psychological perspective. These models include Theory of Mind and intentionality, the « broken mirror » hypothesis, central coherence, and the intense world theory. We dispute the assumption that individuals with ASD are inherently less religious and spiritual than the neurotypical population. Religiosity is possibly expressed differently in ASD with unique spiritual experiences and beliefs (« gifted, visionary, and truth-seeker »). In some circumstances, a religious background can be helpful for both children with ASD and their caregivers. These circumstances should not be neglected, and clinicians are encouraged to consider patients’ religious context, resources, and needs.

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9. Lei J, Leigh E, Charman T, Russell A, Hollocks MJ. Understanding the relationship between social camouflaging in autism and safety behaviours in social anxiety in autistic and non-autistic adolescents. J Child Psychol Psychiatry;2023 (Aug 26)

BACKGROUND: Social camouflaging (hereafter camouflaging) in autism includes factors such as masking and compensating for one’s neurodevelopmental differences, and to assimilate or ‘fit in’ with non-autistic peers. Efforts to hide one’s authentic self and autism traits (masking) resemble impression management (IM) in safety behaviours identified in Clark and Wells’ (1995) cognitive model of social anxiety (SA). This study explores the relationship between camouflaging in autism and safety behaviours in SA among autistic and non-autistic adolescents. METHODS: One hundred fifteen adolescents (14-19 years) with (n = 61; 36 female) and without (n = 54; 37 female) a clinical diagnosis of autism matched on age and SA symptom severity were recruited from clinics, schools and online. Adolescents completed online measures including autism traits, SA symptoms, camouflaging behaviours, SA-related safety behaviours and SA-related negative cognitions. Partial and bivariate Pearson’s correlations and structural equation modelling were used to understand the relationship between camouflaging, safety behaviours, autism traits and SA in both groups. Exploratory factor analysis assessed item-level factor cross-loadings between camouflaging and safety behaviours. RESULTS: Across both groups, masking and IM were significantly associated with SA symptom severity, not autism traits, via SA-related social cognitions. Exploratory factor analysis indicated construct overlap across masking, assimilation, IM and avoidance behaviours and identified factors analogous to self-focused attention, social avoidance and mental rehearsal identified in the Clark and Wells’ (1995) model of SA. CONCLUSIONS: This is the first study using group-matched design to identify that masking (factor in social camouflaging) and IM both relate to SA in autistic and non-autistic adolescents. Assessment and formulation of construct overlap between masking and IM may inform psychoeducation and adaptation of SA treatment for autistic adolescents.

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10. Lewis S, Woroch A, Hatch MK, Lozano R. Autosomal Recessive Limb-Girdle Muscular Dystrophy-3: A Case Report of a Patient with Autism Spectrum Disorder. Genes (Basel);2023 (Aug 5);14(8)

Limb-girdle muscular dystrophies are a group of genetic disorders classically manifesting with progressive proximal muscle weakness. Affected individuals present with atrophy and weakness of the muscles of the shoulders and hips, and in some cases, intellectual disability or developmental delay has also been reported. Limb-girdle muscular dystrophy-3 is a recessive disorder caused by biallelic variants in the SGCA gene. Similarly, symptoms include proximal muscle weakness, elevated CPK, calf muscle pseudohypertrophy, and mobility issues. Cardiac symptoms and respiratory insufficiency are also common symptoms. This case report details a 3-year-old male with muscular weakness, elevated CK, and a neurodevelopmental disorder in whom a homozygous missense variant in c.229C>T (p.Arg77Cys) associated with limb-girdle muscular dystrophy-3 was found. This report shows the association between SGCA c.229C>T and neurodevelopmental disorders as observed in other muscular dystrophies.

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11. Liu T, Tongish M, Li Y, Okuda PMM. Executive and motor function in children with autism spectrum disorder. Cogn Process;2023 (Aug 26)

The purpose of this study was to investigate the relationship between executive function, mainly attention and impulse control, and motor function impairment in children with ASD. Fifteen children with ASD (ages 8-14 years) were examined on their executive function using the Conners continuous performance test-3 and motor function using the movement assessment battery for children-2 (MABC-2). It was found that children with ASD were delayed on executive and motor function. This means that those effects were also observed in male children with Autism Spectrum Disorder (ASD) who had similar characteristics as the participants in the study. This study may have practical implications in the relationship between executive function and motor performance in children with ASD and for clinicians and educators working with children with ASD. Furthermore, the findings suggest that variability in reaction time may be a useful predictor of motor skill performance in children with ASD and may reflect underlying difficulties in executive function and future research is suggested.

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12. Melillo R, Leisman G, Machado C, Machado-Ferrer Y, Chinchilla-Acosta M, Melillo T, Carmeli E. The Relationship between Retained Primitive Reflexes and Hemispheric Connectivity in Autism Spectrum Disorders. Brain Sci;2023 (Jul 30);13(8)

BACKGROUND: Autism Spectrum Disorder (ASD) can be identified by a general tendency toward a reduction in the expression of low-band, widely dispersed integrative activities, which is made up for by an increase in localized, high-frequency, regionally dispersed activity. The study assessed ASD children and adults all possessing retained primitive reflexes (RPRs) compared with a control group that did not attempt to reduce or remove those RPRs and then examined the effects on qEEG and brain network connectivity. METHODS: Analysis of qEEG spectral and functional connectivity was performed, to identify associations with the presence or absence of retained primitive reflexes (RPRs), before and after an intervention based on TENS unilateral stimulation. RESULTS: The results point to abnormal lateralization in ASD, including long-range underconnectivity, a greater left-over-right qEEG functional connectivity ratio, and short-range overconnectivity in ASD. CONCLUSIONS: Clinical improvement and the absence of RPRs may be linked to variations in qEEG frequency bands and more optimized brain networks, resulting in more developmentally appropriate long-range connectivity links, primarily in the right hemisphere.

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13. Raman N, Ringold SM, Jayashankar A, Butera CD, Kilroy E, Harrison L, Cermak SA, Aziz-Zadeh L. Relationships between Affect Recognition, Empathy, Alexithymia, and Co-Occurring Conditions in Autism. Brain Sci;2023 (Aug 3);13(8)

Prior studies show differences in empathy and affect-recognition ability between those with autism spectrum disorder (ASD) and typically developing (TD) individuals. Autistic individuals also exhibit increased behavioral, gastrointestinal, and sleep issues. In the current study, we explored the differences in empathy and affect recognition between the ASD and TD groups; and we investigated their associations with conditions co-occurring in ASD. A total of 54 TD and 56 ASD children (8-17 years) were included. As compared to the TD group, the ASD group showed lower scores for affect recognition and perspective taking (PT) and higher scores for personal distress (PD). Interestingly, results from hierarchical linear regressions suggested that disparities in the PD and PT between the groups were primarily attributable to attenuated levels of alexithymia, rather than being mediated by the presence of an autism diagnosis. Differences in affect-recognition ability, however, were mediated by both an autism diagnosis and alexithymia. We also found significant correlations between empathy and affect recognition and measures of related conditions common in ASD. Alexithymia, hence, contributes to difficulties in empathy while both alexithymia and autism are associated with affect-recognition ability in ASD. Additionally, the association between affect recognition and empathic ability with co-occurring conditions in ASD needs to be considered during assessments and interventions.

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14. Soref B, Robinson GL, Bart O. The Effect of a Short-Term Occupational Therapy Intervention on the Participation and Personal Factors of Preschoolers with Developmental Disabilities. Children (Basel);2023 (Aug 17);10(8)

BACKGROUND: Preschoolers with developmental disabilities are referred to occupational therapy due to their decreased participation in daily life occupations. The purpose of this study was to evaluate the improvement in preschoolers’ participation and sensory-motor abilities following an occupational therapy intervention. MATERIALS AND METHODS: A prospective cohort study of 38 preschoolers and their parents was conducted using an interrupted time-series design, including assessments at three time points: base line (upon referral to an occupational therapy assessment), pre-intervention, and post-intervention after 9-12 sessions of occupational therapy interventions. Children were evaluated with the Developmental Test of Visual-Motor Integration, as well as the balance and fine motor precision sub tests of the Bruininks-Oseretsky Test of Motor Proficiency. Parents completed the Children’s Participation Questionnaire and the Child Performance Skills Questionnaire. Each intervention session was documented by the therapists using the Documentation of Occupational Therapy Session Intervention form. RESULTS: Significant improvement in children’s sensory-motor abilities were found in balance, visual integration, and fine motor precision post-intervention. There were also improvements in the measures of diversity, children’s independence, and parental satisfaction. CONCLUSIONS: A short-term occupational therapy intervention applied to preschoolers with developmental disabilities is effective in improving their sensory-motor abilities, as well as in promoting their participation in daily activities.

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15. Stancioiu F, Bogdan R, Dumitrescu R. Neuron-Specific Enolase (NSE) as a Biomarker for Autistic Spectrum Disease (ASD). Life (Basel);2023 (Aug 13);13(8)

Autistic spectrum disease (ASD) is an increasingly common diagnosis nowadays with a prevalence of 1-2% in most countries. Its complex causality-a combination of genetic, immune, metabolic, and environmental factors-is translated into pleiomorphic developmental disorders of various severity, which have two main aspects in common: repetitive, restrictive behaviors and difficulties in social interaction varying from awkward habits and verbalization to a complete lack of interest for the outside world. The wide variety of ASD causes also makes it very difficult to find a common denominator-a disease biomarker and medication-and currently, there is no commonly used diagnostic and therapeutic strategy besides clinical evaluation and psychotherapy. In the CORDUS clinical study, we have administered autologous cord blood to ASD kids who had little or no improvement after other treatments and searched for a biomarker which could help predict the degree of improvement in each patient. We have found that the neuron-specific enolase (NSE) was elevated above the normal clinical range (less than 16.3 ng/mL) in the vast majority of ASD kids tested in our study (40 of 41, or 97.5%). This finding opens up a new direction for diagnostic confirmation, dynamic evaluation, and therapeutic intervention for ASD kids.

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16. Tiberi A, Borgonovo G, Testa G, Pacifico P, Jacob A, Di Caprio M, Totaro V, Calvello M, Cattaneo A, Capsoni S. Reversal of neurological deficits by painless nerve growth factor in a mouse model of Rett syndrome. Brain;2023 (Aug 26)

Rett syndrome is a rare genetic neurodevelopmental disease, affecting 1 in over 10,000 females born worldwide, caused by de novo mutations in the X-chromosome-located methyl-CpG-binding protein 2 (MeCP2) gene. Despite the great effort put forth by the scientific community, a therapy for this devastating disease is still needed. Here, we tested the therapeutic effects of a painless mutein of the Nerve Growth Factor, called human NGF painless (hNGFp), via a non-invasive intranasal delivery in female MeCP2+/- mice. Of note, previous work had demonstrated a broad biodistribution of hNGFp in the mouse brain by the nasal delivery route. We report that (1) the long-term lifelong treatment of MeCP2+/- mice with hNGFp, starting at 2 months of age, increased the chance of survival while also greatly improving behavioral parameters. Furthermore, when we assessed the phenotypic changes brought forth by (2) a short-term 1-month-long hNGFp-treatment, starting at 3 months of age (right after the initial presentation of symptoms), we observed the rescue of a well-known neuronal target population of NGF, cholinergic neurons in the medial septum. Moreover, we reveal a deficit in microglial morphology in MeCP2+/- mice, completely reversed in treated animals. This effect on microglia is in line with reports showing microglia to be a TrkA-dependent non-neuronal target cell population of NGF in the brain. To understand the immunomodulatory activity of hNGFp, we analyzed the cytokine profile after hNGFp treatment in MeCP2+/- mice, to discover that the treatment recovered the altered expression of key neuroimmune-communication molecules, such as fractalkine. The overall conclusion is that hNGFp delivered intranasally can ameliorate symptoms in the MeCP2+/- model of Rett syndrome, by exerting strong neuroprotection with a dual mechanism of action: directly on target neurons and indirectly via microglia.

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17. Veneruso I, Ranieri A, Falcone N, Tripodi L, Scarano C, La Monica I, Pastore L, Lombardo B, D’Argenio V. The Potential Usefulness of the Expanded Carrier Screening to Identify Hereditary Genetic Diseases: A Case Report from Real-World Data. Genes (Basel);2023 (Aug 19);14(8)

Expanded carrier screening (ECS) means a comprehensive genetic analysis to evaluate an individual’s carrier status. ECS is becoming more frequently used, thanks to the availability of techniques such as next generation sequencing (NGS) and array comparative genomic hybridization (aCGH), allowing for extensive genome-scale analyses. Here, we report the case of a couple who underwent ECS for a case of autism spectrum disorder in the male partner family. aCGH and whole-exome sequencing (WES) were performed in the couple. aCGH analysis identified in the female partner two deletions involving genes associated to behavioral and neurodevelopment disorders. No clinically relevant alterations were identified in the husband. Interestingly, WES analysis identified in the male partner a pathogenic variant in the LPL gene that is emerging as a novel candidate gene for autism. This case shows that ECS may be useful in clinical contexts, especially when both the partners are analyzed before conception, thus allowing the estimation of their risk to transmit an inherited condition. On the other side, there are several concerns related to possible incidental findings and difficult-to-interpret results. Once these limits are defined by the establishment of specific guidelines, ECS may have a greater diffusion.

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18. Vilvarajan S, McDonald M, Douglas L, Newham J, Kirkland R, Tzannes G, Tay D, Christodoulou J, Thompson S, Ellaway C. Multidisciplinary Management of Rett Syndrome: Twenty Years’ Experience. Genes (Basel);2023 (Aug 11);14(8)

Over the last 20 years, the understanding and natural history of Rett syndrome has advanced, but to date no cure has emerged, with multidisciplinary management being symptomatic and supportive. This study provides a comprehensive review of the clinical features, comorbidities and multidisciplinary management of a well-characterized cohort of females with classical Rett syndrome. We aim to improve awareness and understanding of Rett syndrome amongst pediatricians, pediatric subspecialists and allied health professionals to enable early diagnosis and a streamlined enrolment approach for future clinical trials. Rett syndrome, a complex X-linked condition, affecting mainly females, is due to pathogenic variants of the MECP2 gene in most affected individuals. The Rett syndrome Multidisciplinary Management clinic at The Children’s Hospital at Westmead, Sydney, Australia, was established in 2000. This retrospective analysis of individuals who attended the clinic from 2000 to 2020 was performed to identify the incidence and predicted age of onset of Rett syndrome related comorbidities, disease progression and to review management principles. Data collected included age of Rett syndrome diagnosis, MECP2 genotype, clinical features and medical comorbidities, such as sleep disturbance, seizures, breathing irregularities, scoliosis, mobility, hand stereotypies, hand function, constipation, feeding ability, use of gastrostomy, communication skills, QTc prolongation, anthropometry, and bruxism. Analysis of 103 girls who fulfilled the clinical diagnostic criteria for classical Rett syndrome with a pathogenic variant of the MECP2 gene showed a median age of diagnosis of 3 years. The most frequent MECP2 variant was c.502 C>T.

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19. Wu CS, Tsai TH, Chen WL, Tsai HJ, Chien YL. Ophthalmologic diagnoses in youths with autism spectrum disorder: Prevalence and clinical correlates. Autism Res;2023 (Aug 26)

Autism spectrum disorder (ASD) is associated with a high prevalence of visual dysfunction. This study aimed to investigate the rates of amblyopia, refractive errors, and strabismus, as well as their clinical correlates in ASD. This population-based matched-cohort study used data from the Taiwan National Health Insurance Research Database. A total of 3,551 youths with ASD and 35,510 non-autistic control participants matched by age and sex were included. All the participants were followed-up until they were 18 years old. The prevalence of amblyopia, refractive errors, and strabismus was compared between the ASD and control groups. Effect modifiers, including sex, ASD subgroup, and co-diagnosis of intelligence disability, were examined. Compared to the control group, youths with ASD had a significantly increased risk of amblyopia (adjusted odds ratio [aOR] = 1.75), anisometropia (aOR = 1.66), astigmatism (aOR = 1.51), hypermetropia (aOR = 2.08), exotropia (aOR = 2.86), and esotropia (aOR = 2.63), but a comparable likelihood of myopia according to age. Males with ASD had a significantly lower likelihood of exotropia, but a higher likelihood of myopia than females with ASD. The autism subgroup had a higher OR for hypermetropia, but a lower OR for myopia than the other ASD subgroups. ASD youths with intelligence disabilities demonstrated significantly higher ORs for amblyopia, hypermetropia, and all types of strabismus and lower OR for myopia than those without intelligence disabilities. In conclusion, the rates of amblyopia, refractive errors, and strabismus were higher in youths with ASD. Ocular abnormalities in youths with ASD require a comprehensive assessment and management.

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