1. Alhamoudi KM, Barhoumi T, Al-Eidi H, Asiri A, Nashabat M, Alaamery M, Alharbi M, Alhaidan Y, Tabarki B, Umair M, Alfadhel M. A homozygous nonsense mutation in DCBLD2 is a candidate cause of developmental delay, dysmorphic features and restrictive cardiomyopathy. Scientific reports. 2021; 11(1): 12861.

DCBLD2 encodes discodin, CUB and LCCL domain-containing protein 2, a type-I transmembrane receptor that is involved in intracellular receptor signalling pathways and the regulation of cell growth. In this report, we describe a 5-year-old female who presented severe clinical features, including restrictive cardiomyopathy, developmental delay, spasticity and dysmorphic features. Trio-whole-exome sequencing and segregation analysis were performed to identify the genetic cause of the disease within the family. A novel homozygous nonsense variant in the DCBLD2 gene (c.80G > A, p.W27*) was identified as the most likely cause of the patient’s phenotype. This nonsense variant falls in the extracellular N-terminus of DCBLD2 and thus might affect proper protein function of the transmembrane receptor. A number of in vitro investigations were performed on the proband’s skin fibroblasts compared to normal fibroblasts, which allowed a comprehensive assessment resulting in the functional characterization of the identified DCBLD2 nonsense variant in different cellular processes. Our data propose a significant association between the identified variant and the observed reduction in cell proliferation, cell cycle progression, intracellular ROS, and Ca2 + levels, which would likely explain the phenotypic presentation of the patient as associated with lethal restrictive cardiomyopathy.

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2. De La Sablonnière-Griffin M, Paquette G, Hélie S, Dion J. Child maltreatment investigations and substantiations in child protection services: Factors distinguishing children with intellectual disabilities. Disability and health journal. 2021; 14(4): 101128.

BACKGROUND: Children with intellectual disabilities (ID) are more vulnerable to maltreatment than children without ID. Few studies focused on understanding the experiences of maltreatment of children with ID, limiting our capacity to adequately care for them. OBJECTIVE: This study examined the types of maltreatment with which ID is associated among child protection investigations, and identified the individual, environmental, and service-related factors distinguishing children with ID from those without, among children with substantiated maltreatment. METHODS: Secondary data from an incidence study on investigated child maltreatment including 2053 children aged 6-17 years old were analyzed through univariate and multivariate logistic regressions. ID was present for 5.7% (n = 117) of the children. RESULTS: ID was associated with increased odds of being investigated for neglect and decreased odds of being investigated or substantiated for psychological maltreatment. The factors that most distinguished children with ID from other children were physical disabilities (8.45, p < 0.001) and autism spectrum disorder (11.33, p < 0.001) in the child and having at least one parent with ID (16.21, p < 0.001). Two other environmental factors, including having been reported by a professional (2.13, p = 0.047), distinguished children with ID from the other children. CONCLUSIONS: Children with ID who experienced maltreatment present with greater adversity than children without ID. Professionals play a preponderant role in reporting situations of maltreatment for children with ID and need additional training to properly respond to maltreatment of children with ID.

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3. Friedman C. The COVID-19 pandemic and quality of life outcomes of people with intellectual and developmental disabilities. Disability and health journal. 2021; 14(4): 101117.

BACKGROUND: People with intellectual and developmental disabilities (PWIDD) are contracting and dying of COVID-19 at significantly greater rates than nondisabled people and people with other disabilities. Despite the increased risk of COVID-19 for the IDD community, there has been less attention drawn to the impact of the pandemic on people with IDD, especially beyond their health and safety. Yet, PWIDD also face unique challenges as a result of the pandemic compared to other populations. OBJECTIVE: The purpose of this study was to explore the impact of the COVID-19 pandemic on the quality of life outcomes of PWIDD. METHODS: We conducted a secondary analysis of Personal Outcome Measures® interviews from 2019 to 2020 (n = 2284). RESULTS: There were significant differences in the following quality of life outcomes of PWIDD between 2019 and 2020: continuity and security; interact with other members of the community; participate in the life of the community; intimate relationships; and, choose goals. CONCLUSIONS: Our findings suggest the COVID-19 pandemic has negatively hindered the quality of life outcomes of PWIDD in a number of different areas. While the pandemic has been undoubtably hard on the IDD community, in many ways it has simply intensified an underfunded and fractured IDD service system. However the IDD service system evolves during and after the pandemic, it must be done in a way that prioritizes the quality of life of PWIDD and what is most important to them.

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4. Gao Y, Duque-Wilckens N, Aljazi MB, Wu Y, Moeser AJ, Mias GI, Robison AJ, He J. Loss of histone methyltransferase ASH1L in the developing mouse brain causes autistic-like behaviors. Communications biology. 2021; 4(1): 756.

Autism spectrum disorder (ASD) is a neurodevelopmental disease associated with various gene mutations. Recent genetic and clinical studies report that mutations of the epigenetic gene ASH1L are highly associated with human ASD and intellectual disability (ID). However, the causality and underlying molecular mechanisms linking ASH1L mutations to genesis of ASD/ID remain undetermined. Here we show loss of ASH1L in the developing mouse brain is sufficient to cause multiple developmental defects, core autistic-like behaviors, and impaired cognitive memory. Gene expression analyses uncover critical roles of ASH1L in regulating gene expression during neural cell development. Thus, our study establishes an ASD/ID mouse model revealing the critical function of an epigenetic factor ASH1L in normal brain development, a causality between Ash1L mutations and ASD/ID-like behaviors in mice, and potential molecular mechanisms linking Ash1L mutations to brain functional abnormalities.

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5. Gunderson J, Worthley E, Grzadzinski R, Burrows C, Estes A, Zwaigenbaum L, Botteron K, Dager S, Hazlett H, Schultz R, Piven J, Wolff J. Social and non-social sensory responsivity in toddlers at high-risk for autism spectrum disorder. Autism research : official journal of the International Society for Autism Research. 2021; 14(10): 2143-55.

Empirical evidence concerning sensory responsivity in young children who later develop autism spectrum disorder (ASD) remains relatively limited. It is unclear whether specific patterns or aspects of sensory responsivity underlay the emergence of the disorder. The goals of this study were to (a) examine whether social versus non-social context impacted the expression of sensory responsivity in infants at high risk for ASD, and (b) examine if sensory responsivity in social or non-social contexts was associated with severity of ASD symptoms. The Sensory Experiences Questionnaire 2.1 was collected for 338 infants (131 females, 207 males) at high-risk for ASD at 12 and/or 24 months of age. High-risk toddlers meeting diagnostic criteria for ASD (n = 75) showed elevated sensory responsivity in both social and non-social contexts at 12 months of age and differences widened over the second year of life. Individuals with ASD demonstrate higher responsivity in both contexts suggestive of generalized atypical sensory responsivity in ASD. LAY SUMMARY: Behaviors such as avoiding or noticing sensory input (e.g., sounds, touches) are often different in individuals with autism spectrum disorder (ASD) than those without. The reason for this is widely unknown. The findings from this study show that in toddlers, sensory responsivity increased in both social and non-social situations. Therefore, the setting of sensory input does not explain these differences.

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6. Kengne Kamga K, De Vries J, Nguefack S, Munung NS, Wonkam A. Explanatory models for the cause of Fragile X Syndrome in rural Cameroon. Journal of genetic counseling. 2021; 30(6): 1727-36.

Among the myriad causes of intellectual disability (ID), Fragile X Syndrome (FXS) is the leading genetic cause. Yet, little is known of how people affected by this condition make sense of it. The present study aimed to investigate the explanatory models for the causes of FXS in an extended family mainly affected by this condition and members of the village from which they originated in Cameroon. Using an ethnographic approach, 92 participants were interviewed (59 females and 33 males) through 10 focus group discussions and 23 in-depth interviews between April 2018 and February 2020. Data analysis revealed four explanatory models regarding the etiologies of FXS in the community. Firstly, the curse model described a curse from the chief because of the belief that his wives did not mourn his intellectually disabled servant. Secondly, the spiritual model relates FXS to a punishment from God. Thirdly, the socioeconomic model attributes FXS to events in the prenatal and perinatal periods. Finally, the genetic model describes the pattern of inheritance of the disease in the family. This paper helps to understand the explanatory disease models that exist for FXS in rural Cameroon and could inform genetic counseling practices, community genetic education, and policymakers when drafting protocols for public engagement activities.

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7. Miyoshi G, Ueta Y, Natsubori A, Hiraga K, Osaki H, Yagasaki Y, Kishi Y, Yanagawa Y, Fishell G, Machold RP, Miyata M. FoxG1 regulates the formation of cortical GABAergic circuit during an early postnatal critical period resulting in autism spectrum disorder-like phenotypes. Nature communications. 2021; 12(1): 3773.

Abnormalities in GABAergic inhibitory circuits have been implicated in the aetiology of autism spectrum disorder (ASD). ASD is caused by genetic and environmental factors. Several genes have been associated with syndromic forms of ASD, including FOXG1. However, when and how dysregulation of FOXG1 can result in defects in inhibitory circuit development and ASD-like social impairments is unclear. Here, we show that increased or decreased FoxG1 expression in both excitatory and inhibitory neurons results in ASD-related circuit and social behavior deficits in our mouse models. We observe that the second postnatal week is the critical period when regulation of FoxG1 expression is required to prevent subsequent ASD-like social impairments. Transplantation of GABAergic precursor cells prior to this critical period and reduction in GABAergic tone via Gad2 mutation ameliorates and exacerbates circuit functionality and social behavioral defects, respectively. Our results provide mechanistic insight into the developmental timing of inhibitory circuit formation underlying ASD-like phenotypes in mouse models.

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8. Strang JF, Chen D, Nelson E, Leibowitz SF, Nahata L, Anthony LG, Song A, Grannis C, Graham E, Henise S, Vilain E, Sadikova E, Freeman A, Pugliese C, Khawaja A, Maisashvili T, Mancilla M, Kenworthy L. Transgender Youth Executive Functioning: Relationships with Anxiety Symptoms, Autism Spectrum Disorder, and Gender-Affirming Medical Treatment Status. Child psychiatry and human development. 2021.

Executive function (EF) underlies broad health and adaptive outcomes. For transgender youth, navigating gender discernment and gender affirmation demand EF. Yet, factors associated with transgender youth EF are unknown. We investigate hypothesized predictors of EF: over-represented conditions among transgender youth (anxiety and depression symptoms, autism spectrum disorder [ASD]) and gender-affirming care. One-hundred twenty-four transgender 11-21-year-olds participated. Parents/caregivers completed EF and mental health report measures. ASD diagnostics and gender-affirming medication histories were collected. 21 % of non-autistic and 69 % of autistic transgender youth had clinically elevated EF problems. Membership in the gender-affirming hormone treatment group was associated with better EF. ASD, anxiety symptoms, and membership in the long-duration pubertal suppression group were associated with poorer EF. Given the importance of EF skills for multiple outcomes, and the unique and additional EF demands specific to transgender youths’ experiences, EF skill monitoring-and when appropriate, supports-should be considered for transgender youth.

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9. Synnes AR, Petrie J, Grunau RE, Church P, Kelly E, Moddemann D, Ye X, Lee SK, O’Brien K. Family integrated care: very preterm neurodevelopmental outcomes at 18 months. Archives of disease in childhood Fetal and neonatal edition. 2022; 107(1): 76-81.

OBJECTIVE: To examine whether the family integrated care (FICare) programme, a multifaceted approach which enables parents to be engaged as primary caregivers in the neonatal intensive care unit, impacts infant neurodevelopment and growth at 18 months’ corrected age. DESIGN/METHODS: Prospective cohort study of infants born <29 weeks' gestational age (GA) who participated in the FICare cluster randomised control trial (cRCT) and were assessed in the Canadian Neonatal Follow-Up Network (CNFUN). The primary outcome measure, Cognitive or Language composite score <85 on the Bayley-III, was compared between FICare exposed and routine care children using logistic regression, adjusted for potential confounders and employing generalised estimation equations to account for clustering of infants within sites. RESULTS: Of 756 infants <29 weeks' GA in the FICare cRCT, 505 were enrolled in CNFUN and 455 were assessed (238 FICare, 217 control). Compared with controls, FICare infants had significantly higher incidence of intraventricular haemorrhage (IVH) (19.5% vs 11.7%, p=0.024) and higher proportion of employed mothers (76.6% vs 73.6%, p=0.043). There was no significant difference in the odds of the primary outcome (adjusted OR: 0.92 (0.59 to 1.42) FiCare vs Control) on multivariable analyses adjusted for GA, IVH and maternal employment. However, Bayley-III Motor scores (adjusted difference in mean (95% CI) 3.87 (1.22 to 6.53) and body mass index 0.67 (0.36 to 0.99) were higher in the FICare group. CONCLUSIONS: Very preterm infants exposed to FICare had no significant difference in incidence of cognitive or language delay but had better motor development. TRIAL REGISTRATION NUMBER: Participants in this cohort study were previously enrolled in a registered trial: NCT01852695.

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10. Vieira T, Schlittler LXC, Vieira LC, Celeri E, Banzato CEM. Effective Electroconvulsive Therapy for Catatonia in a Patient With Pitt-Hopkins Syndrome and Autism Spectrum Disorder. The journal of ECT. 2021; 37(3): e33-e4.

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11. Williams ZJ. Commentary: The construct validity of ‘camouflaging’ in autism: psychometric considerations and recommendations for future research – reflection on Lai et al. (2020). Journal of child psychology and psychiatry, and allied disciplines. 2022; 63(1): 118-21.

Research on the construct of ‘camouflaging’ in autism and its sociodemographic/clinical correlates has far outpaced the work being done to establish the construct validity of camouflaging and its distinction from other similar constructs. The imprecision with which camouflaging is defined and measured has serious implications for future research on this topic, and unless additional effort is made to produce reliable and valid measurements of this construct, researchers will not be able to meaningfully assess important questions such as whether the effort of camouflaging one’s behavior contributes to increased mental health difficulties. By reviewing the psychometric strengths and weaknesses of various operationalizations of camouflaging, this commentary highlights a pressing need for further measure validation in this area. Specific methodological guidance is provided for researchers interested in rigorously testing the validity of putative camouflaging measures.

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