SETD2 belongs to the family of histone methyltransferase proteins and has been associated with three nosologically distinct entities with different clinical and molecular features: Luscan-Lumish syndrome (LLS), intellectual developmental disorder, autosomal dominant 70 (MRD70), and Rabin-Pappas syndrome (RAPAS). LLS [MIM #616831] is an overgrowth disorder with multisystem involvement including intellectual disability, speech delay, autism spectrum disorder (ASD), macrocephaly, tall stature, and motor delay. RAPAS [MIM #6201551] is a recently reported multisystemic disorder characterized by severely impaired global and intellectual development, hypotonia, feeding difficulties with failure to thrive, microcephaly, and dysmorphic facial features. Other neurologic findings may include seizures, hearing loss, ophthalmologic defects, and brain imaging abnormalities. There is variable involvement of other organ systems, including skeletal, genitourinary, cardiac, and potentially endocrine. Three patients who carried the missense variant p.Arg1740Gln in SETD2 were reported with a moderately impaired intellectual disability, speech difficulties, and behavioral abnormalities. More variable findings included hypotonia and dysmorphic features. Due to the differences with the two previous phenotypes, this association was then named intellectual developmental disorder, autosomal dominant 70 [MIM 620157]. These three disorders seem to be allelic and are caused either by loss-of-function, gain-of-function, or missense variants in the SETD2 gene. Here we describe 18 new patients with variants in SETD2, most of them with the LLS phenotype, and reviewed 33 additional patients with variants in SETD2 that have been previously reported in the scientific literature. This article offers an expansion of the number of reported individuals with LLS and highlights the clinical features and the similarities and differences among the three phenotypes associated with SETD2.

UNASSIGNED: To verify the effects of multi-domain computerized cognitive training on intellectual function and adaptive functioning in children with intellectual developmental disorder (IDD).
UNASSIGNED: Children with IDD were randomized to a multi-domain computerized cognitive training (CCT) group (n = 30) and control group (n = 30). Both groups received a 5-week training program. Intellectual function was assessed by Chinese-Wechsler Young Children scale (C-WYCSI) and adaptive functioning was assessed by the Chinese Vineland Adaptive Behavior Rating Scale (VABS-C), which were used at baseline, post-training, and 3-month follow-up.
UNASSIGNED: There were significant differences for intellectual function and adaptive functioning between the two groups. The CCT group showed significant improvements in total full-scale intelligence quotient (FSIQ) score the Wechsler Intelligence Scale (F[60] = 31.97, p < 0.01) and its subdomain VIQ score (F[60] = 33.83, p < 0.01). For adaptive functioning, CCT had a better adaptive developmental quotient (ADQ) score (F[60] = 28.05, p < 0.01), and subdomain communication (F[60] = 10.86, p < 0.01) and socialization scores (F[60] = 4.35, p < 0.015). Moreover, there was a positive correlation between FSIQ changes and ADQ changes in the CCT group (rs = 0.74, p < 0.01). A greater increase in VIQ score was associated with a greater increase in adaptive functioning (bootstrapping CI: [0.16, 3.30]) in the CCT group.
UNASSIGNED: Multi-domain CCT improves the intellectual function and adaptive functioning of children with IDD.

Aims: Athletes in the general population report higher satisfaction of basic needs when coaches are providing an autonomy supportive sport climate (ASSC). Our study aims at investigating whether ASSC is associated with satisfaction with life in athletes with intellectual disabilities (ID) and whether this association is mediated by basic need satisfaction. Method: During the Special Olympics World Winter Games 2017, 168 athletes with ID (M = 33.86 years; SD = 10.47) completed questionnaires measuring ASSC, basic need satisfaction (autonomy, competence, and relatedness), and satisfaction with life. Multiple linear regression analyses and mediation analyses were performed. The mediation model was controlled for the potential impact of participating in team vs. individual sports. Additionally, gender effects were explored. Results: ASSC was significantly associated with satisfaction with life (β = .38, p < .001). This association was mediated by competence (indirect effect: ab1 = .15; CI [.05; .32]) but not by autonomy or relatedness. No effects were found related to participating in team vs. individual sports or gender. Conclusions: Our study provides evidence that an ASSC is associated with athletes perceiving themselves as more competent and reporting more satisfaction with life.

Leukodystrophies are a diverse group of genetically established disorders categorized by unusual white matter changes on brain imaging. Hypomyelinating leukodystrophies (HLDs) are a group of neurodevelopmental disorders that affect myelin sheath development in the brain. These disorders are categorized as developmental delay, spasticity, hypotonia, and intellectual disabilities. We describe a patient with developmental delay, cerebellar ataxia, spasticity, hypotonia, and intellectual disability from a healthy family member. Whole exome sequencing (WES) was performed to identify causative variants, which were further analyzed by bioinformatic analysis. WES was performed, and Sanger sequencing-based segregation analysis confirmed the presence of the homozygous missense variants of NM_203290.3 c.934T > C p.Ser312Pro of RNA polymerase I and III subunit C (POLR1C) gene in this patient and heterozygous variant in the unaffected carrier father and mother, supporting the pathogenicity and inheritance pattern of this variant. Furthermore, the variant identified by WES was validated in healthy controls (n = 100) using Sanger sequencing analysis. Finally, our study explained the important use of WES in disease diagnosis and provided further evidence that the variant in the POLR1C gene may play an important role in the development of hypomyelinating leukodystrophy in Saudi families.

OBJECTIVE: To critically appraise relevant literature on the lived experiences of registered nurses caring for adults with intellectual disability in the acute care setting in Australia to determine current knowledge and gaps in the literature.
BACKGROUND: People with intellectual disability have the right to the highest attainable health care the same as everyone else. However, inequities still exist in the delivery of health care across the globe, including Australia that result in poorer health outcomes for this population group. Part of the problem is a lack of understanding of the complexities of ID care due to an absence of ID specific content in undergraduate curricula.
METHODS: Integrative literature review.
METHODS: Electronic databases were searched for relevant empirical and theoretical literature. Additional articles were found by reviewing reference lists of selected articles resulting in ten articles for review. Selected articles were critically appraised using JBI critical appraisal tools. Data were analysed using comparative thematic analysis. PRISMA checklist completed the review.
RESULTS: Two main themes emerged from the data that informed the gap in knowledge: (a) Defining nursing practice; and (b) Confidence to practice.
CONCLUSIONS: There was limited qualitative research published on the topic. International studies revealed that a lack of understanding of the ID condition due to inadequate education left registered nurses feeling underprepared, unsupported and struggling to provide optimal care. No studies were located on the phenomenon within the Australian context. A study exploring the lived experiences of RNs in Australia is needed to offer a deeper understanding of the phenomenon that will help inform practice.
CONCLUSIONS: Including ID care in national undergraduate and postgraduate nursing curricula must become a nursing educational and professional priority to support nurses more fully in their practice to ensure patients with ID receive the highest attainable standard of nursing care.

UNASSIGNED: Mental disability is a common condition but is considered as an invisible disability. The disability certificate in psychiatry remains underexplored. Some reasons are issues of confidentiality, stigma, lack of awareness in the public, and the hesitancy in the mental health professionals. We aim to provide a brief profile of patients with mental illness issued disability certificates from a psychiatric unit over a five-year period (2013-2017).
UNASSIGNED: Our retrospective study is based on the data available from the copies of the issued disability certificates from a psychiatric unit that functions in a multispecialty tertiary care teaching government hospital in Southern India. Patients undergoing treatment in psychiatry apply for a disability certificate to the medical superintendent of the hospital. Each applicant undergoes a detailed workup to ascertain the diagnosis, and the mental disability is assessed using Indian Disability Evaluation and Assessment Scale (IDEAS). Those with intellectual developmental disorder (IDD) are assessed by a clinical psychologist for quantifying intelligence quotient, based on which the disability certificate is issued. Data were extracted and analyzed using SPSS. Descriptive statistics were used.
UNASSIGNED: Over five years, 258 disability certificates were issued. A total of 218 were for mental illness and 40 were for IDD. Schizophrenia was the commonest primary diagnosis. There was no gender predominance, nor the influence of gender on different domains of IDEAS except on work domain dysfunction due to mental illness. The validity period was not mentioned in 81% of the issued certificates for mental illness.
UNASSIGNED: This descriptive study found a lower number of certificates issued from the psychiatric unit. Schizophrenia remains the main psychiatric diagnosis for which a disability certificate was issued. We did not assess the utilization pattern of the issued certificates.

Intellectual developmental disorder with abnormal behavior, microcephaly and short stature (IDDABS), (OMIM# 618342) is an autosomal recessive condition described as developmental delay, poor or absent speech, intellectual disability, short stature, mild to progressive microcephaly, delayed psychomotor development, hyperactivity, seizure, along with mild to swear aggressive behavior. Homozygous frameshift mutation in Pseudouridine Synthase 7, Putative; (PUS7) OMIM# 616,261 NM_019042.3 and splice acceptor variants in Alpha-Aminoadipic Semialdehyde Synthase; (AASS) OMIM# 605,113 NM_005763.3 was funded. Whole exome sequencing (WES) technique was used as tool to identify the molecular diagnostic test. Different bioinformatics analysis done for WES data and we identified two novel mutations one as frameshift mutation c.606_607delGA, p.Ser282CysfsTer9 in the PUS7 gene and splice acceptor variants c.1767-1 G > A in the AASS gene has been reported. The pattern of family segregation maintained the pathogenicity of this variation associated with abnormal behavior, intellectual developmental disorder, microcephaly along with short stature IDDABS. Further, the WES data was validated in the family having other affected individuals and healthy controls (n = 100) was done using Sanger sequencing. Finally, our results further explained the role of WES in the disease diagnosis and elucidated that the mutation in PUS7 and AASS genes may lead an important role for the development of IDDABS in Saudi family.

BACKGROUND: Aneuploids, copy number variations (CNVs), and single nucleotide variants in specific genes are the main genetic causes of developmental delay (DD) and intellectual disability disorder (IDD). These genetic changes can be detected using chromosome analysis, chromosomal microarray (CMA), and next-generation DNA sequencing techniques. Therefore; In this study, we aimed to investigate the importance of CMA in determining the genomic etiology of unexplained DD and IDD in 123 patients.
METHODS: For 123 patients, chromosome analysis, DNA fragment analysis and microarray were performed. Conventional G-band karyotype analysis from peripheral blood was performed as part of the initial screening tests. FMR1 gene CGG repeat number and methylation analysis were carried out to exclude fragile X syndrome.
RESULTS: CMA analysis was performed in 123 unexplained IDD/DD patients with normal karyotypes and fragile X screening, which were evaluated by conventional cytogenetics. Forty-four CNVs were detected in 39 (39/123=31.7%) patients. Twelve CNV variant of unknown significance (VUS) (9.75%) patients and 7 CNV benign (5.69%) patients were reported. In 6 patients, one or more pathogenic CNVs were determined. Therefore, the diagnostic efficiency of CMA was found to be 31.7% (39/123).
CONCLUSIONS: Today, genetic analysis is still not part of the routine in the evaluation of IDD patients who present to psychiatry clinics. A genetic diagnosis from CMA can eliminate genetic question marks and thus alter the clinical management of patients. Approximately one-third of the positive CMA findings are clinically intervenable. However, the emergence of CNVs as important risk factors for multiple disorders increases the need for individuals with comorbid neurodevelopmental conditions to be the priority where the CMA test is recommended.

Intellectual developmental disorder with dysmorphic facies and ptosis is an autosomal dominant condition characterized by delayed psychomotor development, intellectual disability, delayed speech, and dysmorphic facial features, mostly ptosis. Heterozygous mutations in bromodomain and plant homeodomain (PHD) finger containing one (BRPF1) gene have been reported. In this study, whole exome sequencing (WES) was performed as a molecular diagnostic test. Bioinformatics of WES data and candidate gene prioritization identified a novel variant in heterozygous state in the exon 3 of BRPF1 gene (ENST383829: c.1054G > C and p.Val352Leu). Autosomal dominant inheritance in the family affected individuals and exclusion of non-pathogenicity in the ethnically matched healthy controls (n = 100) were performed by Sanger sequencing. To the best of our knowledge, this is the first evidence of BRPF1 variant in a Saudi family. Whole exome sequencing analysis has been proven as a valuable tool in the molecular diagnostics. Our findings further expand the role of WES in efficient disease diagnosis in Arab families and explained that the mutation in BRPF1 gene plays an important role for the development of IDDFP syndrome.

Two community-based cohorts of children with autism spectrum disorder, examined using similar assessment protocols, were pooled (n = 301) and subdivided according to history of regression. Those with regression (n = 62), 20.5% of the combined cohort, were contrasted with those without regression (n = 241) at first assessment (age range 19-60 months) and at 2-year follow-up on a range of measures. The regression group was significantly more functionally impaired, with regard to intellectual function (p < .001), language development (p < .001), and to severity of autism (p < .01) at both T1 and T2. Only 14 (23.3%) had a clearly identified underlying etiology [24 (18.6%) in the non-regressive group]. There were no significant differences between those who had regressed \'from normal\' and those who had regressed \'from low\' functioning.