Including Intellectual Disability Research Articles

Intellectual disability and autism in propionic acidemia: a biomarker-behavioral investigation implicating dysregulated mitochondrial biology

Propionic acidemia (PA) is an autosomal recessive condition (OMIM #606054), wherein pathogenic variants in PCCA and PCCB impair the activity of propionyl-CoA carboxylase. PA is associated with neurodevelopmental disorders, including intellectual disability (ID) and autism spectrum disorder (ASD); however, the correlates and mechanisms of these outcomes remain unknown. Using data from a subset of participants with PA enrolled in a dedicated natural history study (n = 33), we explored associations between neurodevelopmental phenotypes and laboratory parameters. Twenty (61%) participants received an ID diagnosis, and 12 of the 31 (39%) who were fully evaluated received the diagnosis of ASD. A diagnosis of ID, lower full-scale IQ (sample mean = 65 ± 26), and lower adaptive behavior composite scores (sample mean = 67 ± 23) were associated with several biomarkers. Higher concentrations of plasma propionylcarnitine, plasma total 2-methylcitrate, serum erythropoietin, and mitochondrial biomarkers plasma FGF21 and GDF15 were associated with a more severe ID profile. Reduced 1-13C-propionate oxidative capacity and decreased levels of plasma and urinary glutamine were also associated with a more severe ID profile. Only two parameters, increased serum erythropoietin and decreased plasma glutamine, were associated with ASD. Plasma glycine, one of the defining features of PA, was not meaningfully associated with either ID or ASD. Thus, while both ID and ASD were commonly observed in our PA cohort, only ID was robustly associated with metabolic parameters. Our results suggest that disease severity and associated mitochondrial dysfunction may play a role in CNS complications of PA and identify potential biomarkers and candidate surrogate endpoints.

The physical and psychosocial impact of a school-based running programme for adolescents with disabilities.

Adolescents with disabilities have fewer opportunities to participate in community-based fitness programmes. The purpose of this study was to examine the impact of a school-based running programme at a local middle school in Lebanon, Pennsylvania, on fitness and quality of life (QoL) in children with physical and cognitive disabilities in a life-skills classroom. Nineteen adolescents with diagnosed disabilities including intellectual disability (ID), autism spectrum disorder and Down syndrome were recruited from three life-skills classrooms to participate in a school-based running programme. The programme was designed to be implemented two times/week for 6weeks by classroom teachers/aides. Physical therapy faculty and students developed the programme and assisted with implementation. Each session lasted 30min, consisting of a warm-up and cooldown, relay races, games and timed runs. Pre- and post-test measures included physiological cost index (PCI) and Paediatric Quality of Life Inventory™ (PedsQL™). Pre- and post-test data were compared using Wilcoxon signed rank tests. Each week participants also completed a training log to reflect on the activity for the day. Participants demonstrated significant improvements in PCI (P=0.028) and the PedsQL™ (P=0.008) following the running programme. Results of this study suggest that participation in a 6-week school-based running programme may improve fitness and QoL in adolescents with disabilities.

Ethical issues of involving people with intellectual disabilities in genomic research: a scoping review protocol.

Background: Psychiatric genomic research is a growing field of research in Africa that is looking at epigenetics of psychiatric disorders; within which a specific focus is neurodevelopmental disorders including intellectual disability (ID). Conducting this type of research is important to identify etiologies and possible interventions or areas for further research. However, genomic research generally, and psychiatric genomic research, faces many social, ethical, cultural, and legal issues; research involving people with ID is particularly challenging. All research stakeholders - researchers, research review bodies, regulators, patient groups - generally agree that involving people with ID require several considerations, including extra protection. It is also recognized that not involving people with ID in research that is relevant to them means that opportunities to learn on specific issues including lived experiences are missed. In this scoping review, we aim to describe the range of ethical and social-cultural issues concerning involvement of people with intellectual disability in genomic research from existing literature. Methods: This scoping review will be conducted based on the Joanna Briggs Institute guidance for scoping review and reported using the PRISMA-ScR guidelines. Iterative review stages will include systematic search of six databases (Embase, Ovid Global Health, PubMed, Scopus, PsycInfo and Web of Science core collection), screening, charting and synthesis of the data. Forward and backward citation screening will also be done for the articles included in the final review. We will include peer reviewed journal articles, guidance documents and reports. Screening and selection of studies based on the eligibility criteria will be done independently by three reviewers; conflicts will be resolved through discussion with a third reviewer and other experts. Results: The results will be included in the scoping review publication. Conclusions: This scoping review will identify key areas of ethical tensions and possible solutions and inform opportunities for empirical ethics studies.

Trimester-specific ambient PM2.5 exposures and risk of intellectual disability in Utah

Prenatal fine particulate matter (PM2.5) exposure is an understudied risk factor for neurodevelopmental outcomes, including intellectual disability (ID). Associations among prenatal exposures and neurodevelopmental outcomes may vary depending on the timing of exposure. Limited numbers of studies examining PM2.5 and neurodevelopmental outcomes have considered exposures occurring during the preconception period. To address these gaps, we conducted a case-control study of children born in Utah between 2002 and 2008 (n = 1032). Cases were identified using methods developed by the Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring Network and matched with controls on birth year, sex, and birth county. We estimated the daily average PM2.5 concentration during a period spanning 12 weeks before the estimated conception date, as well as during each of the three trimesters at the maternal residential address listed on the child's birth certificate. In a multivariable model, the third (OR: 2.119, CI: 1.123–3.998, p = .021) and fourth (OR: 2.631, CI: 1.750–3.956, p < .001) quartiles for preconception average PM2.5 demonstrated significantly increased risk of ID relative to the first quartile. Second quartile preconception exposure was also associated with increased risk, though it did not reach significance (OR: 1.385, CI: 0.979–1.959, p = .07). The fourth quartile of first trimester average PM2.5 was positive and significant (OR: 2.278, CI: 1.522–3.411, p < .001); the third quartile was positive, but not significant (OR: 1.159, CI: 0.870–1.544, p = .312). Quartiles of second and third trimester were not associated with higher risk of ID. These findings from Utah, which were robust to a variety of sensitivity analyses, provide initial evidence that preconception and prenatal PM2.5 exposure may be associated with ID. Future studies are needed across other geographic locations and populations.

Community services during the COVID-19 pandemic in a Norwegian county: impact on users with multiple, complex needs and their service providers – a qualitative study

PurposeThe purpose of this paper is to investigate how users with particularly complex needs including intellectual disability (ID) reacted to the changes and restrictions during the COVID-19 pandemic in 2020.Design/methodology/approachAs few studies of changes during the pandemic include users with ID and multiple, complex needs, the authors adopted a qualitative approach, using a semistructured interview guide. Ten participants were leading ID nurses in residential facilities in community settings. The interviews were taped, transcribed and analyzed using a thematic analysis.FindingsThe thematic analysis generated six main themes, including both user and staff perspectives: daily routines, activities, facilitation of tasks and well-being, from the users perspectives, and use of working hours and positive staff experiences, from the staff perspectives.Research limitations/implicationsTen residential facilities constituted a convenience sample of services for users with multiple, complex needs. Thus, the authors do not know whether the findings are representative. Further research should include user opinions based on the findings of this study.Practical implicationsThe users represented in this study appeared to experience less stress during the pandemic, contrary to the expectations of professional caregivers. The findings indicated more well-being among users. It was noted that receiving services at home, largely flexible schedules, staying in bed a little longer in the morning and avoiding stressful situations, such as travelling in minibuses, was appreciated by the users.Social implicationsDaily schedules with activities throughout the day should be considered for users as represented in this study. Stressful events should also be considered.Originality/valueThe knowledge about pandemic experiences of users with ID and additional complex conditions and hence comprehensive needs is still sparse. This study may add to this knowledge.

The Usefulness of a Targeted Next Generation Sequencing Gene Panel in Providing Molecular Diagnosis to Patients With a Broad Spectrum of Neurodevelopmental Disorders.

Background: Neurodevelopmental disorders comprise a clinically and genetically heterogeneous group of conditions that affect 2%–5% of children and represents a public health challenge due to complexity of the etiology. Only few patients with unexplained syndromic and non-syndromic NDDs receive a diagnosis through first-tier genetic tests as array-CGH and the search for FMR1 CGG expansion. The aim of this study was to evaluate the clinical performance of a targeted next-generation sequencing (NGS) gene panel as a second-tier test in a group of undiagnosed patients with NDDs. Method: A 221-gene next-generation sequencing custom panel was designed and used to analyze a cohort of 338 patients with a broad spectrum of NDDs (202 males and 136 females) including Intellectual Disability (ID), Autism Spectrum Disorders (ASD), Epilepsy, language and motor disorders. Results: A molecular diagnosis was established in 71 patients (21%) and a de novo origin was present in 38 (64.4%) of the available trios. The diagnostic yield was significantly higher in females than in males (29.4% vs. 15.3%; p = 0.0019) in particular in ASD (36.8% vs. 7.6%; p = 0.0026) and Epilepsy (38.9% vs. 14.4% p = 0.001). The most involved genes were SLC2A1, SCN1A, ANKRD11, ATP1A2, CACNA1A, FOXP1, and GNAS altered in more than two patients and accounting for the 19.7% of the diagnosis. Conclusion: Our findings showed that this NGS panel represents a powerful and affordable clinical tool, significantly increasing the diagnostic yield in patients with different form of NDDs in a cost- and time-effective manner without the need of large investments in data storage and bioinformatic analysis.

Prevalence of attention-deficit/hyperactivity disorder and intellectual disability among children with hydrocephalus.

Little is known about the prevalence of attention-deficit/hyperactivity disorder (ADHD) in children with hydrocephalus. In this study, the authors assessed the prevalence of ADHD and its association with clinical and demographic factors, including intellectual disability (ID), a potential factor that can confound the diagnosis of ADHD. The authors conducted a cross-sectional study of children 6-12 years of age with hydrocephalus using parent telephone surveys. The Child and Adolescent Intellectual Disability Screening Questionnaire (CAIDS-Q) and the National Institute for Children's Health Quality (NICHQ) Vanderbilt Assessment Scale were used to screen for ID and ADHD, respectively. Among children without ID, the authors identified those with ADHD and calculated a prevalence estimate and 95% confidence interval (Wald method). Logistic regression analysis was conducted to compare children with ADHD with those without ADHD based on demographics, family income, parental educational, etiology of hydrocephalus, and primary treatment. As a secondary analysis, the authors compared subjects with ID with those without using the same variables. Multivariable analysis was used to identify factors with independent association with ADHD and ID. A total of 147 primary caregivers responded to the telephone questionnaire. Seventy-two children (49%) met the cutoff score for ID (CAIDS-Q). The presence of ID was significantly associated with lower family income (p < 0.001). Hydrocephalus etiology (p = 0.051) and initial treatment (p = 0.06) approached significance. Of children without ID (n = 75), 25 demonstrated a likely diagnosis of ADHD on the NICHQ, yielding a prevalence estimate of 0.33 (95% CI 0.22-0.44). No clinical or demographic variable showed significant association with ADHD. These data indicate that the prevalence of ADHD among children with hydrocephalus (33%) is higher than among the general population (estimated prevalence in Alabama is 12.5%). ID is also common (49%). Routine screening for ADHD and ID in children with hydrocephalus may help to ensure that adequate resources are provided to optimize functional outcomes across development.

Genetic investigation of syndromic forms of obesity

Syndromic obesity (SO) refers to obesity with additional phenotypes, including intellectual disability (ID)/developmental delay (DD), dysmorphic features, or organ-specific abnormalities. SO is rare, has high phenotypic variability, and frequently follows a monogenic pattern of inheritance. However, the genetic etiology of most cases of SO has not been elucidated. In this study, we investigated 20 SO patients by whole-exome sequencing (WES) trios to identify causal genetic variants. 4/20 patients had negative results for array comparative genomic hybridization (aCGH) analyses. In the remaining 15 patients, in addition to SNVs and indels, CNVs were also evaluated. Pathogenic/likely pathogenic (P/LP) SNVs/indels were detected in 6/20 patients (involving MED13L, AHDC1, EHMT1, MYT1L, GRIA3, and SETD1A), while two patients carried an inherited VUS. In addition, P/LP CNVs were observed in 3/15 patients (involving SATG2, KIAA0442, and MEIS2). All nine detected P/LP variants involved genes already known to lead to syndromic ID/DD; however, for only two genes (EHMT1 and MYT1L) is the link with obesity well established. This is the first study applying a comprehensive genomic investigation of an SO cohort, showing a high diagnostic yield (~47%). Additionally, our findings suggested that several known ID/DD genes may also predispose individuals to SO.

FarmApp: a new assessment of cognitive control and memory for children and young people with neurodevelopmental difficulties

ABSTRACT We introduce a new touchscreen-based method measuring aspects of cognitive control and memory, in children and young people with neurodevelopmental difficulties, including intellectual disability (ID). FarmApp is a gamified, tablet-based assessment tool measuring go/no-go response speed, response inhibition, visuospatial short-term memory span, and long-term memory. Here, we assessed the feasibility, validity, and utility of the method, including the benefits of measuring change in performance over two weeks. We observed that: 1) a higher proportion of participants completed FarmApp than traditional psychometric tests; 2) this proportion increased when participants had opportunity for two weeks of self-paced testing at home; 3) ADHD-relevant behavioral difficulties were associated with average go/no-go performance across all attempts, and change in go/no-go performance over time, indicating sensitivity of the method to cognitive differences with real-world relevance. We also addressed the potential utility of the FarmApp for exploring links between ID etiology and cognitive processes. We observed differences in go/no-go task between two groups of ID participants stratified by the physiological functions of associated genetic variants (chromatin-related and synaptic-related). Moreover, the synaptic group demonstrated higher degree of improvement in go/no-go performance over time. This outcome is potentially informative of dynamic mechanisms contributing to cognitive difficulties within this group. In sum, FarmApp is a feasible, valid, and useful tool increasing access to cognitive assessment for individuals with neurodevelopmental difficulties of variable severity, with an added opportunity to monitor variation in performance over time and determine capacity to acquire task competence.

A novel KCNQ2 missense variant in non-syndromic intellectual disability causes mild gain-of-function of Kv7.2 channel

BackgroundHeterozygous variants of KCNQ2 can cause KCNQ2 associated neurodevelopmental disorder, mainly are benign (familial) neonatal or infantile epilepsy (B(F)NE or B(F)IE) and developmental epileptic encephalopathy(DEE). Moreover, some intermediate phenotypes, including intellectual disability (ID), and myokymia are related to the gene. MethodsWe collected a non-syndromic ID male patient with a novel KCNQ2 missense variant. Whole cell electrophysiology, western blotting, and immunofluorescence were adopted to analyze the variant’s functional alterations. ResultsThe patient presented with global developmental delay since his infancy. He still had profound ID but did not have epilepsy at the adolescence. The de novo KCNQ2 variant p.R75C (NM_172107) in the NH2 domain identified here showed a slightly hyperpolarized shift of activation curves and larger current density in homomeric configurations, which could be abolished in co-expression with Kv7.2 or Kv7.3 wild-type. Western blotting and immunocytochemistry supported that the expression of variant p.R75C is lower than the Kv7.2 wild-type. The findings indicated variant p.R75C causes mild gain-of-function (GOF) of Kv7.2 channel. ConclusionsWe report a non-syndromic ID patient with a KCNQ2 mild GOF variant, adding evidence for this rare clinical phenotype in the disorder. We propose that individuals with KCNQ2 GOF variants are prone to have cognitive impairments.

A reassessment of Jackson\u2019s checklist and identification of two Down syndrome sub-phenotypes

Down syndrome (DS) is characterised by several clinical features including intellectual disability (ID) and craniofacial dysmorphisms. In 1976, Jackson and coll. identified a checklist of signs for clinical diagnosis of DS; the utility of these checklists in improving the accuracy of clinical diagnosis has been recently reaffirmed, but they have rarely been revised. The purpose of this work is to reassess the characteristic phenotypic signs and their frequencies in 233 DS subjects, following Jackson's checklist. 63.77% of the subjects showed more than 12 signs while none showed less than 5, confirming the effectiveness of Jackson's checklist for the clinical diagnosis of DS. An association between three phenotypic signs emerged, allowing us to distinguish two sub-phenotypes: Brachycephaly, short and broad Hands, short Neck (BHN), which is more frequent, and "non-BHN". The strong association of these signs might be interpreted in the context of the growth defects observed in DS children suggesting decreased cell proliferation. Lastly, cognitive assessments were investigated for 114 subjects. The lack of association between the presence of a physical sign or the number of signs present in a subject and cognitive skills disproves the stereotype that physical characteristics are predictive of degree of ID.

Neurodevelopmental disorders: 2022 update.

With a prevalence of 2-4% of the worldwide population, neurodevelopmental disorders (NDDs) comprise a heterogeneous group of disorders associated with neurodevelopmental dysfunction, including intellectual disability (ID), autism spectrum disorder (ASD), Down syndrome (DS) and attention-deficit/hyperactivity disorder (ADHD) among others. However, due to their heterogeneity and overlapping clinical features, NDDs such as ASD are often misdiagnosed, while for others with more distinct symptoms, such as Rett syndrome or DS, the mechanisms underlying their pathogenesis remain elusive. Last year, important steps in the mechanistic understanding of several NDDs have been achieved. New preclinical models demonstrated causality between PAK3 mutations and disorders associated with social deficiencies. ARID1B mutations have been linked to neuroectoderm specification in Coffin-Siris syndrome and DNA damage was established as an important pathologic mechanism in Aicardi-Goutières syndrome. Moreover, alterations in basic molecular processes including translation and histone acetylation have been established as major traits in the pathology of X-linked ID and Rett syndrome, revealing new pathogenetic mechanisms. Last year, advances in bioinformatics have begun to shed light on the human repeatome, a largely unexplored part of our genome, and how alterations in these sequences have a central role in ASD. The role of mitochondria in neuropathology was clarified last year with the discovery of previously unknown vesicles derived from mitochondria with a putative role in DS. An interesting discovery in the field of basic neurodevelopment showed that during postnatal brain development, changes in genome architecture and transcriptional dynamics progress independently of sensory experience. Finally, our neurocentric views of NDDs are changing as new players such as astrocytes are revealed to be crucial in neuropathology. The role of astrocytes has been clarified for some pathologies such as ASD and DS, linking well-known genetic mutations to impaired astrocyte function.

Identification of three novel pathogenic mutations in cystathionine beta-synthase gene of Pakistani intellectually disabled patients.

Classical homocystinuria (HCU) is an autosomal recessive inborn error of metabolism, which is caused by the cystathionine-β-synthase (CBS: encoded by CBS) deficiency. Symptoms of untreated classical HCU patients include intellectual disability (ID), ectopia lentis and long limbs, along with elevated plasma methionine, and homocysteine. A total of 429 ID patients (age range: 1.6-23 years) were sampled from Northern areas of Punjab, Pakistan. Biochemical and genetic analyses were performed to find classical HCU disease in ID patients. Biochemically, nine patients from seven unrelated families were identified with high levels of plasma methionine and homocysteine. Targeted exonic analysis of CBS confirmed seven causative homozygous mutations; of which three were novel missense mutations (c.451G>T; p.Gly151Trp, c.975G>C; p.Lys325Asn and c.1039+1G>T splicing), and four were recurrent variants (c.451+1G>A; IVS4+1 splicing, c.770C>T; p.Thr257Met, c.808_810del GAG; p.Glu270del and c.752T>C; p.Leu251Pro). Treatment of patients was initiated without further delay with pyridoxine, folic acid, cobalamin, and betaine as well as dietary protein restriction. The immediate impact was noticed in behavioral improvement, decreased irritability, improved black hair color, and socialization. Overall, health outcomes in this disorder depend on the age and symptomatology at the time of treatment initiation. With personalized treatment and care, such patients can reach their full potential of living as healthy a life as possible. This screening study is one of the pioneering initiatives in Pakistan which would help to minimize the burden of such treatable inborn errors of metabolism in the intellectually disabled patients.

Hyperkinetic stereotyped movements in a boy with biallelic CNTNAP2 variants

BackgroundHeterozygous variants in CNTNAP2 have been implicated in a wide range of neurological phenotypes, including intellectual disability (ID), epilepsy, autistic spectrum disorder (ASD), and impaired language. However, heterozygous variants can also be found in unaffected individuals. Biallelic CNTNAP2 variants are rarer and cause a well-defined genetic syndrome known as CASPR2 deficiency disorder, a condition characterised by ID, early-onset refractory epilepsy, language impairment, and autistic features.Case-reportA 7-year-old boy presented with hyperkinetic stereotyped movements that started during early infancy and persisted over childhood. Abnormal movements consisted of rhythmic and repetitive shaking of the four limbs, with evident stereotypic features. Additional clinical features included ID, attention deficit-hyperactivity disorder (ADHD), ASD, and speech impairment, consistent with CASPR2 deficiency disorder. Whole-genome array comparative genomic hybridization detected a maternally inherited 0.402 Mb duplication, which involved intron 1, exon 2, and intron 2 of CNTNAP2 (c.97 +?_209-?dup). The affected region in intron 1 contains a binding site for the transcription factor FOXP2, potentially leading to abnormal CNTNAP2 expression regulation. Sanger sequencing of the coding region of CNTNAP2 also identified a paternally-inherited missense variant c.2752C > T, p.(Leu918Phe).ConclusionThis case expands the molecular and phenotypic spectrum of CASPR2 deficiency disorder, suggesting that Hyperkinetic stereotyped movements may be a rare, yet significant, clinical feature of this complex neurological disorder. Furthermore, the identification of an in-frame, largely non-coding duplication in CNTNAP2 points to a sophisticated underlying molecular mechanism, likely involving impaired FOXP2 binding.

Protein phosphatase 2A - structure, function and role in neurodevelopmental disorders.

Neurodevelopmental disorders (NDDs), including intellectual disability (ID), autism and schizophrenia, have high socioeconomic impact, yet poorly understood etiologies. A recent surge of large-scale genome or exome sequencing studies has identified a multitude of mostly de novo mutations in subunits of the protein phosphatase 2A (PP2A) holoenzyme that are strongly associated with NDDs. PP2A is responsible for at least 50% of total Ser/Thr dephosphorylation in most cell types and is predominantly found as trimeric holoenzymes composed of catalytic (C), scaffolding (A) and variable regulatory (B) subunits. PP2A can exist in nearly 100 different subunit combinations in mammalian cells, dictating distinct localizations, substrates and regulatory mechanisms. PP2A is well established as a regulator of cell division, growth, and differentiation, and the roles of PP2A in cancer and various neurodegenerative disorders, such as Alzheimer's disease, have been reviewed in detail. This Review summarizes and discusses recent reports on NDDs associated with mutations of PP2A subunits and PP2A-associated proteins. We also discuss the potential impact of these mutations on the structure and function of the PP2A holoenzymes and the etiology of NDDs.

JARID2 haploinsufficiency is associated with a clinically distinct neurodevelopmental syndrome

PurposeJARID2, located on chromosome 6p22.3, is a regulator of histone methyltransferase complexes that is expressed in human neurons. So far, 13 individuals sharing clinical features including intellectual disability (ID) were reported with de novo heterozygous deletions in 6p22–p24 encompassing the full length JARID2 gene (OMIM 601594). However, all published individuals to date have a deletion of at least one other adjoining gene, making it difficult to determine if JARID2 is the critical gene responsible for the shared features. We aim to confirm JARID2 as a human disease gene and further elucidate the associated clinical phenotype. MethodsChromosome microarray analysis, exome sequencing, and an online matching platform (GeneMatcher) were used to identify individuals with single-nucleotide variants or deletions involving JARID2. ResultsWe report 16 individuals in 15 families with a deletion or single-nucleotide variant in JARID2. Several of these variants are likely to result in haploinsufficiency due to nonsense-mediated messenger RNA (mRNA) decay. All individuals have developmental delay and/or ID and share some overlapping clinical characteristics such as facial features with those who have larger deletions involving JARID2. ConclusionWe report that JARID2 haploinsufficiency leads to a clinically distinct neurodevelopmental syndrome, thus establishing gene–disease validity for the purpose of diagnostic reporting.

Psychiatric disorders in adults with cerebral palsy

BackgroundCerebral palsy (CP) is one of the most common neurological conditions in childhood. Individuals with CP often experience various secondary conditions, including intellectual disability (ID), medical conditions, and psychiatric issues. A large number of youth with CP have psychiatric disorders; however, few studies have examined the prevalence of psychiatric issues in adults with CP at the population-level. AimsTo investigate the prevalence and co-occurrence of psychiatric disorders at the population-level in adults with CP only, and adults with CP and ID. Method and proceduresUsing clinical information from seven Canadian data sources, we conducted a retrospective cross-sectional analysis of adults with CP, with and without ID. Outcomes and resultsAdults with CP were more likely than the general population to have a psychiatric diagnosis, independent of ID status. All psychiatric disorders were more common in individuals with CP than the general population, with the exception of addiction related disorders. In most cases, having an ID substantially increased the risk of having a psychiatric disorder. ConclusionsAdults with CP are at heightened risk for experiencing psychiatric disorders. Current findings highlight the important role health care providers play in screening for psychiatric issues in individuals with CP.

Why Does Intellectual Disability Matter to Philosophy?: Toward a Transformative Pedagogy

This article explores what it means to include intellectual disability (ID) in philosophical discourse and in the philosophy classroom. Taking Audre Lorde’s claim that “the master’s tools will never dismantle the master’s house” as a starting point, it asks how certain forms of cognitive ableism have excluded ID from the “philosopher’s house.” Drawing upon Michel Foucault’s work as a theoretical framework, part one critically examines the ways that ID has been included, excluded, and constructed within philosophical discourse. Part two then considers what it would mean for ID and people with an ID to be included in the philosophy classroom. It offers some examples of how the work in disability studies, philosophies of disability, and philosophy of art can lead to a more inclusive and transformative pedagogy that will generate new critical questions and expand our philosophical dwelling places.

A Japanese boy with NAA10-related syndrome and hypertrophic cardiomyopathy

NAA10-related syndrome is an extremely rare X-chromosomal disorder, the symptoms of which include intellectual disability (ID), ocular anomalies, or congenital heart diseases, such as hypertrophic cardiomyopathy (HCM). Here, we describe a 4-year-old Japanese male patient who exhibited mild ID, HCM, and specific facial features. A hemizygous mutation (NM_003491.3: c.455_458del, p. Thr152Argfs*6) in exon 7 of NAA10 was detected. We recommend that patients undergo precise medical follow-up considering the characteristics of NAA10-related syndrome.

Neurodevelopmental disorders-the history and future of a diagnostic concept .

This article describes the history of the diagnostic class of neurodevelopmental disorders (NDDs) up to DSM-5. We further analyze how the development of genetics will transform the classification and diagnosis of NDDs. In DSM-5, NDDs include intellectual disability (ID), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). Physicians in German-, French- and English-speaking countries (eg, Weikard, Georget, Esquirol, Down, Asperger, and Kanner) contributed to the phenomenological definitions of these disorders throughout the 18th and 20th centuries. These diagnostic categories show considerable comorbidity and phenotypic overlap. NDDs are one of the chapters of psychiatric nosology most likely to benefit from the approach advocated by the National Institute of Mental Health’s Research Domain Criteria project. Genetic research supports the hypothesis that ID, ASD, ADHD, schizophrenia, and bipolar disorder lie on a neurodevelopmental continuum. The identification of recurrently observed copy number variants and disruptive gene variants in ASD (eg, CDH8, 16p11.2, SCN2A) led to the adoption of the genotype-first approach to characterize individuals at the etiological level.