Variants in HCFC1 and MN1 genes causing intellectual disability in two Pakistani families.

BACKGROUND: Intellectual disability (ID) is a neurodevelopmental condition affecting around 2% of children and young adults worldwide, characterized by deficits in intellectual functioning and adaptive behavior. Genetic factors contribute to the development of ID phenotypes, including mutations and structural changes in chromosomes. Pathogenic variants in the HCFC1 gene cause X-linked mental retardation syndrome, also known as Siderius type X-linked mental retardation. The MN1 gene is necessary for palate development, and mutations in this gene result in a genetic condition called CEBALID syndrome. METHODS: Exome sequencing was used to identify the disease-causing variants in two affected families, A and B, from various regions of Pakistan. Affected individuals in these two families presented ID, developmental delay, and behavioral abnormalities. The validation and co-segregation analysis of the filtered variant was carried out using Sanger sequencing. RESULTS: In an X-linked family A, a novel hemizygous missense variant (c.5705G > A; p.Ser1902Asn) in the HCFC1 gene (NM_005334.3) was identified, while in family B exome sequencing revealed a heterozygous nonsense variant (c.3680 G > A; p. Trp1227Ter) in exon-1 of the MN1 gene (NM_032581.4). Sanger sequencing confirmed the segregation of these variants with ID in each family. CONCLUSIONS: The investigation of two Pakistani families revealed pathogenic genetic variants in the HCFC1 and MN1 genes, which cause ID and expand the mutational spectrum of these genes.

Maternal smoking during pregnancy and offspring risk of intellectual disability: a UK-based cohort study.

Background: Observational studies have described associations of maternal smoking during pregnancy with intellectual disability (ID) in the exposed offspring. Whether these results reflect a causal effect or unmeasured confounding is still unclear. Methods: Using a UK-based prospectively collected birth cohort (the Avon Longitudinal Study of Parents and Children) of 13,479 children born between 1991 and 1992, we assessed the relationship between maternal smoking at 18 weeks' gestation and offspring risk of ID, ascertained through multiple sources of linked information including primary care diagnoses and education records. Using confounder-adjusted logistic regression, we performed observational analyses and a negative control analysis that compared maternal with partner smoking in pregnancy under the assumption that if a causal effect were to exist, maternal effect estimates would be of greater magnitude than estimates for partner smoking if the two exposures suffer from comparable biases. Results: In observational analysis, we found an adjusted odds ratio for ID of 0.75 (95% CI = 0.49-1.13) for any maternal smoking and 0.97 (95% CI = 0.71-1.33) per 10-cigarette increase in number of cigarettes smoked per day. In negative control analysis, comparable effect estimates were found for any partner smoking (OR = 0.94; 95% CI = 0.63-1.40) and number of cigarettes smoked per day (OR = 0.94; 95% CI = 0.74-1.20). Conclusions: The results are not consistent with a causal effect of maternal smoking during pregnancy on offspring ID.

Adult syndromology: challenges, opportunities and perspectives: Illustrated by the description of four adults with Costello syndrome.

Clinical geneticists and syndromologists have traditionally focused on identifying syndromes in children. However, there is a growing acknowledgment of the need to describe adult phenotypes. This article provides an overview of the evolving phenotypes of rare genetic syndromes into adulthood, elucidating its challenges, opportunities, and future perspectives. The clinical phenotypes of four adults with Costello syndrome are described to illustrate these aspects. Phenotypic and genotypic data from four individuals broaden the spectrum of Costello syndrome in adulthood and highlight the high variability in neurocognitive outcome. The clinical data align with previous findings and established genotype-phenotype correlations. Interestingly, two individuals presented with recurrent cancers (bladder cancer and neuroblastoma). Further studies are imperative to provide reliable information for counselling and management to enable comprehensive understanding of the evolving features of rare syndromic diseases and special health issues into adulthood.

Delayed Diagnosis of Spinal Cord Injury in a Patient With Intellectual Disability: A Case Report.

Spinal cord injury (SCI) can cause neurogenic shock accompanied by bradycardia and hypotension. If no preceding traumatic episodes are apparent and the neurological examination is complicated by the patient's intellectual disability, SCI is likely to be overlooked. A 63-year-old man with intellectual disability presented to our hospital. The patient had fallen on the floor; however, no apparent head or neck trauma was observed. The patient returned home after confirming the absence of intracranial hematoma on computed tomography. However, the patient was re-admitted because of hypotension and bradycardia, and sick sinus syndrome was suspected. As the manifestations were motor weakness in the extremities and urinary retention, screening spinal magnetic resonance imaging revealed cervical cord injury and spondylosis. Cervical SCI related to a fall was suspected. Cervical decompression surgery and rehabilitation therapy contributed to the improved patient status. Herein, we report a case of intellectual disability in which SCI was initially overlooked. No severe preceding traumatic episode or intellectual disability of the patient could have led to overlooking SCI in our case. Clinicians should be cautious about this rare condition.

Characterizing the clinical and sociodemographic profiles of hospitalized adolescents with autism spectrum disorder.

The prevalence of autism spectrum disorder (ASD) is increasing worldwide. Youngsters with ASD demonstrate higher rates of intellectual disabilities (IDs), comorbid psychopathology and psychiatric hospitalizations, compared to children in the general population. This study characterizes the demographics and clinical parameters of adolescent psychiatric inpatients with ASD compared to inpatients without ASD, all hospitalized during the study period. Additionally, within the ASD group, those with ID were compared to those without. The rate of males among participants with ASD was significantly higher than among those without ASD, and the duration of hospitalization was longer. In contrast, the rate of cigarette smoking, major depressive disorder and suicidal thoughts among those with ASD was lower. One-third of those with ASD had moderate to severe ID, about 10% had comorbid epilepsy, and about half of them demonstrated aggressive behavior. Most ASD patients showed significant improvement upon discharge, although the extent of improvement was more prominent among ASD patients with no ID. Our findings, consistent with previous research, indicate that hospitalization is beneficial to youths with ASD, both those with and those without ID. Further studies that include long-term follow-up are needed.

Long prodromal symptoms of neuroleptic malignant syndrome in patient with intellectual developmental disorder-A case report.

BACKGROUND: Neuroleptic malignant syndrome (NMS) is a rare and potentially life-threatening condition that may arise at any point during treatment and is often associated with adverse reactions to dopamine-blocking agents. This syndrome is normally characterized by features such as muscle rigidity, alteration in consciousness, autonomic instability, and leukocytosis. AIM: The aim of this study is to investigate a borderline intellectual functioning (BIF) case in which NMS with insidious disease progression and long prodromal symptoms was developed. CASE PRESENTATION: The investigated patient was a 38-year-old female diagnosed with bipolar disorder and a variety of corresponding disorders. The patient exhibited gastrointestinal symptoms and restlessness in the weeks leading up to the study, subsequent to the administration of elevated doses of haloperidol, risperidone, and lithium. In addition, she was hospitalized for restlessness and aggressiveness in the summer of 2023. Furthermore, due to her chief complaint, she received parenteral haloperidol twice in the emergency room, subsequently experiencing fever, altered consciousness, generalized rigidity, and dysphagia. Moreover, the patient's initial creatine phosphokinase (CPK) level was 2550 IU/L, and she was hospitalized in an intensive care unit with the diagnosis of NMS for 8 days. CONCLUSIONS: This case study highlights the necessity of being attentive about prodromal symptoms of NMS and emergent interventions.

Working together with people with intellectual disability to make a difference: a protocol for a mixed-method co-production study to address inequities in cervical screening participation.

Introduction: Cervical cancer is one of the most preventable cancers yet remains a disease of inequity for people with intellectual disability, in part due to low screening rates. The ScreenEQUAL project will use an integrated knowledge translation (iKT) model to co-produce and evaluate accessible cervical screening resources with and for this group. Methods: Stage 1 will qualitatively explore facilitators and barriers to screening participation for people with intellectual disability, families and support people, healthcare providers and disability sector stakeholders (n ≈ 20 in each group). An accessible multimodal screening resource, accompanying supporting materials for families and support people, and trauma-informed healthcare provider training materials will then be co-produced through a series of workshops. Stage 2 will recruit people with intellectual disability aged 25 to 74 who are due or overdue for screening into a single-arm trial (n = 48). Trained support people will provide them with the co-produced resource in accessible workshops (intervention) and support them in completing pre-post questions to assess informed decision-making. A subset will participate in qualitative post-intervention interviews including optional body-mapping (n ≈ 20). Screening uptake in the 9-months following the intervention will be measured through data linkage. Family members and support people (n = 48) and healthcare providers (n = 433) will be recruited into single-arm sub-studies. Over a 4-month period they will, respectively, receive the accompanying supporting materials, and the trauma-informed training materials. Both groups will complete pre-post online surveys. A subset of each group (n ≈ 20) will be invited to participate in post-intervention semi-structured interviews. Outcomes and analysis: Our primary outcome is a change in informed decision-making by people with intellectual disability across the domains of knowledge, attitudes, and screening intention. Secondary outcomes include: (i) uptake of screening in the 9-months following the intervention workshops, (ii) changes in health literacy, attitudes and self-efficacy of family members and support people, and (iii) changes in knowledge, attitudes, self-efficacy and preparedness of screening providers. Each participant group will evaluate acceptability, feasibility and usability of the resources. Discussion: If found to be effective and acceptable, the co-produced cervical screening resources and training materials will be made freely available through the ScreenEQUAL website to support national, and potentially international, scale-up.

A retrospective cohort study of prescription drug use among youth with intellectual/developmental disabilities in British Columbia.

BACKGROUND: People with intellectual/developmental disabilities (IDD) are known to have high rates of prescription drug use, particularly for psychotropic medications. This is of concern due to the many side effects associated with these medications and because of the risks of polypharmacy. In this paper we compare the most commonly dispensed drugs and all psychotropic medications for youth with IDD compared with youth without IDD. METHODS: Using population-level administrative health data over a 10-year period, this study examined medications dispensed to youth with an IDD aged 15-24 years compared with youth without an IDD. The most common medications dispensed and the number of youth they were dispensed to were determined. As well a wide variety of psychotropic medications were examined. RESULTS: There were a total of 20 591 youth with IDD and 1 293 791 youth without IDD identified. Youth with IDD had higher odds of being dispensed pain medications, amoxicillin, salbutamol, levothyroxine and all the psychotropic medications (antidepressants, antipsychotics, anxiolytics, anti-adrenergic agents, mood stabilisers and stimulants). For youth with IDD, 6558 (31.85%) were dispensed two or more different psychotropic medications within a year, compared with 75 963 (5.87%) of youth without IDD. DISCUSSION: Compared to youth without IDD, youth with IDD had significantly higher odds of being dispensed most of the prescription medications studied, including all of the psychotropic medications. They were also twice as likely to be dispensed two or more medications from different classes of psychotropic drugs within the same year. These findings have important implications for the health of people with IDD and for their health care providers.

Clinical Case of Mild Tatton-Brown-Rahman Syndrome Caused by a Nonsense Variant in DNMT3A Gene.

Tatton-Brown-Rahman syndrome is a rare autosomal dominant hereditary disease caused by pathogenic variants in the DNMT3A gene, which is an important participant in epigenetic regulation, especially during embryonic development, and is highly expressed in all tissues. The main features of the syndrome are high growth, macrocephaly, intellectual disability, and facial dysmorphic features. We present a clinical case of Tatton-Brown-Rahman syndrome in a ten-year-old boy with macrocephaly with learning difficulties, progressive eye impairment, and fatigue suspected by a deep learning-based diagnosis assistance system, Face2Gene. The proband underwent whole-exome sequencing, which revealed a recurrent nonsense variant in the 12th exon of the DNMT3A, leading to the formation of a premature stop codon-NM_022552.5:c.1443C>A (p.Tyr481Ter), in a heterozygous state. This variant was not found in parents, confirming its de novo status. The patient case described here contributes to the understanding of the clinical diversity of Tatton-Brown-Raman syndrome with a mild clinical presentation that expands the phenotypic spectrum of the syndrome. We report the first recurrent nonsense variant in the DNMT3A gene, suggesting a mutational hot-spot. Differential diagnoses of this syndrome with Sotos syndrome, Weaver syndrome, and Cowden syndrome, as well as molecular confirmation, are extremely important, since the presence of certain types of pathogenic variants in the DNMT3A gene significantly increases the risk of developing acute myeloid leukemia.

Strategies for Accessible Breast Screening for People With Intellectual Disability.

INTRODUCTION: People with intellectual disability are less likely to participate in breast screening than people without intellectual disability. They experience a range of barriers to accessing breast screening, however, there is no consensus on strategies to overcome these barriers. Our objective was to reach consensus on the strategies required for accessible breast screening for people with intellectual disability. METHODS: Fourteen experts participated in a modified on-line Delphi that used Levesque's model of health care access as the theoretical framework. At the end of each round descriptive and thematic analyses were completed. Data was then triangulated to determine if consensus was reached. RESULTS: After 3 rounds, 9 strategies were modified, 24 strategies were added and consensus was reached for 52 strategies across the 5 dimensions of access. Key areas of action related to (i) decision making and consent, (ii) accessible information, (iii) engagement of peer mentors, (iv) service navigators, and (v) equipping key stakeholders. CONCLUSIONS: The resulting strategies are the first to articulate how to make breast screening accessible and can be used to inform health policy and quality improvement practices.

Variant-specific pathophysiological mechanisms of AFF3 differently influence transcriptome profiles.

BACKGROUND: We previously described the KINSSHIP syndrome, an autosomal dominant disorder associated with intellectual disability (ID), mesomelic dysplasia and horseshoe kidney, caused by de novo variants in the degron of AFF3. Mouse knock-ins and overexpression in zebrafish provided evidence for a dominant-negative mode of action, wherein an increased level of AFF3 resulted in pathological effects. METHODS: Evolutionary constraints suggest that other modes-of-inheritance could be at play. We challenged this hypothesis by screening ID cohorts for individuals with predicted-to-be damaging variants in AFF3. We used both animal and cellular models to assess the deleteriousness of the identified variants. RESULTS: We identified an individual with a KINSSHIP-like phenotype carrying a de novo partial duplication of AFF3 further strengthening the hypothesis that an increased level of AFF3 is pathological. We also detected seventeen individuals displaying a milder syndrome with either heterozygous Loss-of-Function (LoF) or biallelic missense variants in AFF3. Consistent with semi-dominance, we discovered three patients with homozygous LoF and one compound heterozygote for a LoF and a missense variant, who presented more severe phenotypes than their heterozygous parents. Matching zebrafish knockdowns exhibit neurological defects that could be rescued by expressing human AFF3 mRNA, confirming their association with the ablation of aff3. Conversely, some of the human AFF3 mRNAs carrying missense variants identified in affected individuals did not rescue these phenotypes. Overexpression of mutated AFF3 mRNAs in zebrafish embryos produced a significant increase of abnormal larvae compared to wild-type overexpression further demonstrating deleteriousness. To further assess the effect of AFF3 variation, we profiled the transcriptome of fibroblasts from affected individuals and engineered isogenic cells harboring + / + , KINSSHIP/KINSSHIP, LoF/ + , LoF/LoF or KINSSHIP/LoF AFF3 genotypes. The expression of more than a third of the AFF3 bound loci is modified in either the KINSSHIP/KINSSHIP or the LoF/LoF lines. While the same pathways are affected, only about one third of the differentially expressed genes are common to the homozygote datasets, indicating that AFF3 LoF and KINSSHIP variants largely modulate transcriptomes differently, e.g. the DNA repair pathway displayed opposite modulation. CONCLUSIONS: Our results and the high pleiotropy shown by variation at this locus suggest that minute changes in AFF3 function are deleterious.

Knowledge, attitudes and practices related to oral health in participants of the institutional program for the inclusion of people with cognitive disabilities in higher education at the University of Costa Rica / Conocimientos, actitudes y prácticas relacionadas con la salud oral en participantes del Programa Institucional de Inclusión de Personas con Discapacidad Cognitiva a la Educación Superior de la Universidad de Costa Rica

Abstract People with cognitive disabilities face multiple challenges concerning oral health and frequently show oral tissue decay because of the barriers society imposes upon them, and due to financial issues, professional and family lack of knowledge, limitations regarding access to services, lack of empowering-driven actions, among others. Positive knowledge, attitudes and practices regarding oral health, developed during the course of a lifetime, help in preserving good health. The aim of the current study is to describe oral health knowledge, attitudes and practices in people with cognitive disabilities participating in the Institutional Program for the Inclusion of People with Cognitive Disabilities in Higher Education at the University of Costa Rica (PROIN, in Spanish), during 2021. A descriptive study with mixed focus was performed; a representative sample comprised of 86 students enrolled in PROIN was used for the quantitative approach, while the qualitative approach used a criteria sample along with an opinion sample, limiting size due to information overload. The survey, along with its corresponding questionnaire and the semi-structured interview, were used as data gathering techniques. It was evidenced that certain issues need to be readdressed, such as bleeding gums, the importance of preserving dental pieces, as well, the practice of flossing, which many students expressed difficulties doing. Good attitudes were found, such as dentist visits; however, access barriers for this population must be overthrown. This article showed the importance of training professionals in disabilities as well as developing oral health promotion programs aimed at people with cognitive disabilities.

Resumen La población con discapacidad cognitiva enfrenta múltiples retos en cuanto a la salud oral, presentado comúnmente un deterioro de los tejidos orales; esto como consecuencia a las barreras impuestas por la sociedad, factores económicos, desconocimiento de los profesionales y familiares, limitaciones en el acceso a la atención, falta de acciones para fomentar su autonomía, entre otras. Los conocimientos, actitudes y prácticas favorables en salud oral ayudan a conservar una buena salud, los cuales se desarrollan a lo largo de la vida. El objetivo del presente estudio es describir los conocimientos, actitudes y prácticas de salud oral en las personas con discapacidad cognitiva que participaron en el Programa Institucional de Inclusión de Personas con Discapacidad Cognitiva a la Educación Superior de la Universidad de Costa Rica (PROIN) durante el año 2021. Se realizó un estudio descriptivo con un enfoque mixto, para el enfoque cuantitativo se utilizó una muestra representativa de 86 estudiantes matriculados en PROIN y para la parte cualitativa se utilizó una muestra por criterio con un muestreo opinático, estableciendo el tamaño por saturación de la información. Se utilizaron como técnicas de recolección de datos la encuesta con su respectivo cuestionario y la entrevista semiestructurada. Se evidenció que existen temas que se deben reforzar, como lo es el sangrado de encías, la importancia de conservar las piezas dentales, así como la práctica de uso de hilo dental, donde la mayoría de los estudiantes expresaron tener dificultades para su utilización. Además, se encontró buenas actitudes con respecto a la visita al odontólogo, sin embargo, se debe derribar barreras de acceso que se presentan para esta población. Este estudio demostró la necesidad de capacitar a los profesionales en el tema de discapacidad y desarrollar programas de promoción de la salud oral específicos para personas con discapacidad cognitiva.

La superación del profesor de Educación Física para desarrollar la autodeterminación, en educandos con discapacidad intelectual

La superación continua de los profesores de Educación Física constituye una necesidad que ha transcendido diferentes generaciones de docentes, determinada por el desarrollo creciente de la ciencia y la técnica, las exigencias del tercer perfeccionamiento educacional cubano, las demandas en la preparación y capacitación del profesorado y la necesidad de su incidencia en la formación de un egresado apto y capaz de desarrollar no solo habilidades y capacidades físicas, sino también para la vida, que les permitan actuar en el medio social, familiar y laboral. El objetivo de esta investigación consistió en diseñar una estrategia pedagógica de superación para transformar los modos de actuación de los profesores de Educación Física, en la dirección del proceso de enseñanza-aprendizaje, en función del desarrollo de habilidades de autodeterminación en los educandos en situación de discapacidad intelectual. Los métodos investigativos utilizados en el orden teórico y empírico fueron el análisis y síntesis, el histórico-lógico, el inductivo-deductivo, la modelación y el sistémico-estructural-funcional; además de la entrevista, la observación, la encuesta, el análisis de documentos, el criterio de expertos y la triangulación múltiple, los que permitieron revelar las causales que inciden en el normal desarrollo de las habilidades de autodeterminación, así como elaborar la estrategia. Con su implementación se perfeccionó el desempeño profesional y personal de los profesores y los educandos, quienes egresaron con el empoderamiento de habilidades para la toma de decisiones, la realización de elecciones, la resolución de problemas y el establecimiento de metas y objetivos.

O aperfeiçoamento contínuo dos professores de Educação Física constitui uma necessidade que transcendeu as diferentes gerações de professores, determinada pelo crescente desenvolvimento da ciência e da tecnologia, pelas exigências do terceiro melhoramento educacional cubano, pelas exigências na preparação e formação de professores e pela necessidade de seu impacto na formação de um egresso qualificado, capaz de desenvolver não apenas competências e habilidades físicas, mas também para a vida, que lhe permitam atuar no ambiente social, familiar e de trabalho. Discapacidade intelectual. Os métodos investigativos utilizados na ordem teórica e empírica foram análise e síntese, histórico-lógico, indutivo-dedutivo, modelagem e sistêmico-estrutural-funcional; Além da entrevista, observação, inquérito, análise documental, peritagem e triangulação múltipla, que permitiram revelar as causas que afetam o normal desenvolvimento das competências de autodeterminação, bem como desenvolver a estratégia. Com a sua implementação melhorou-se o desempenho profissional e pessoal de professores e alunos, que se formaram com a capacitação de competências para tomar decisões, fazer escolhas, resolver problemas e estabelecer metas e objetivos.

The continuous improvement of Physical Education teachers constitutes a need that has transcended different generations of teachers, determined by the growing development of science and technology, the demands of the third Cuban educational improvement, the demands in the preparation and training of teachers and the need for its impact on the training of a qualified graduate capable of developing not only physical skills and abilities, but also for life, which allow them to act in the social, family and work environment. The objective of this research was to design a pedagogical improvement strategy to transform the modes of action of Physical Education teachers, in the direction of the teaching-learning process, based on the development of self-determination skills in students in situations of intellectual disability. The investigative methods used in the theoretical and empirical order were analysis and synthesis, historical-logical, inductive-deductive, modeling and systemic-structural-functional; In addition to the interview, observation, survey, document analysis, expert judgment and multiple triangulations, which allowed us to reveal the causes that affect the normal development of self-determination skills, as well as to develop the strategy. With its implementation, the professional and personal performance of teachers and students was improved, who graduated with the empowerment of skills for making decisions, making choices, solving problems and establishing goals and objectives.

A novel framework for functional annotation of variants of uncertain significance in ID/ASD risk gene CC2D1A.

Intellectual disability (ID) and autism spectrum disorder (ASD) are genetically heterogeneous with hundreds of identified risk genes, most affecting only a few patients. Novel missense variants in these genes are being discovered as clinical exome sequencing is now routinely integrated into diagnosis, yet most of them are annotated as variants of uncertain significance (VUS). VUSs are a major roadblock in using patient genetics to inform clinical action. We developed a framework to characterize VUSs in Coiled-coil and C2 domain containing 1A (CC2D1A), a gene causing autosomal recessive ID with comorbid ASD in 40% of cases. We analyzed seven VUSs (p.Pro319Leu, p.Ser327Leu, p.Gly441Val, p.Val449Met, p.Thr580Ile, p.Arg886His and p.Glu910Lys) from four cases of individuals with ID and ASD. Variants were cloned and overexpressed in HEK293 individually and in their respective heterozygous combination. CC2D1A is a signaling scaffold that positively regulates PKA-CREB signaling by repressing phosphodiesterase 4D (PDE4D) to prevent cAMP degradation. After testing multiple parameters including direct interaction between PDE4D and CC2D1A, cAMP levels and CREB activation, we found that the most sensitive readout was CREB transcriptional activity using a luciferase assay. Compared to WT CC2D1A, five VUSs (p.Pro319Leu, p.Gly441Val, p.Val449Met, p.Thr580Ile, and p.Arg886His) led to significantly blunted response to forskolin induced CREB activation. This luciferase assay approach can be scaled up to annotate ~150 CC2D1A VUSs that are currently listed in ClinVar. Since CREB activation is a common denominator for multiple ASD/ID genes, our paradigm can also be adapted for their VUSs.

Missed opportunities for HIV testing and sexual health-related challenges in an individual with intellectual disability: a case report.

BACKGROUND: HIV testing remains an important tool in identifying people living with HIV/AIDS (PLWHA). An early diagnosis of HIV can lead to a prolonged life expectancy if treatment is initiated promptly. Indicator conditions can be the first sign of an HIV infection and should therefore be recognised and consequently a HIV test should be carried out. Testing should occur in all individuals as sexuality can be experienced by everyone, and stigma can lead to the exclusion of vulnerable groups, leading to a gap in diagnosis and treatment [1, 2]. CASE PRESENTATION: A 63-year-old man, who identifies as bisexual and has had an intellectual disability since birth, presented at our health care centre for HIV testing. A decade ago, the patient was diagnosed with Stage III Diffuse Large B-cell Non-Hodgkin Lymphoma, an AIDS defining cancer. The patient presented at a Haematology and Oncology department 3 months prior, due to a weight loss of 10 kg over the past 5 months. Oral thrush, an HIV-indicator condition, had been diagnosed by the otolaryngologists shortly before. During this medical evaluation, pancytopenia was identified. Despite the presence of indicator conditions, the patient was never tested for HIV in the past. Staff members from the care facility for intellectually disabled suggested conducting a HIV test in our clinic through the public health department, where HIV positivity was revealed. The AIDS-defining diagnosis, along with a CD4 + cell count of 41/µl, suggests a prolonged period of HIV positivity. CONCLUSION: Due to the presence of existing indicator conditions, an earlier HIV diagnosis was possible. We contend that most of the recent illnesses could have been prevented if earlier testing had been carried out. Therefore, patients presenting with AIDS indicator conditions, including those with mental disabilities, should be given the opportunity to be tested for HIV. HIV/AIDS trainings should be made available to health care professionals as well as to personnel interacting with vulnerable groups.

[Non-therapeutic hysterectomy in Mexican young females with intellectual disability: a problematized reality]. / Histerectomía no terapéutica en jóvenes mexicanas con discapacidad intelectual: una realidad problematizada.

Background: Non-therapeutic hysterectomy in girls and adolescents with intellectual disability (ID) is an acceptable practice, even when there is a lack of prescriptive ethical reason. Objectives: To determine the magnitude of the practice of hysterectomy in girls and adolescents with ID, and explore the emic factors associated with this procedure. Material and methods: Multicenter, intersectoral study with a mixed methods design. Results: The quantitative results showed that 50 of 234 reported hysterectomies corresponded to females with ID. Average age at the time of surgery was 15 ± 2.9 years. Prophylactic abdominal hysterectomy was the most common procedure, and the justifications for it were "fertility control", "menstrual hygiene management", and "risk of sexual abuse". A qualitative analysis of 15 focus groups revealed that parents' main concern was how to manage their daughters' index disease and reproductive health; they perceived menstruation positively; they expressed their fear of dying and leaving them without support, and emphasized fertility control; none of them approved hysterectomy. Conclusions: The bodies that define health policies need to create a new philosophy that avoids the reductionist approach of current biomedical model, which separates (in the health-disease process) our interdependence with other humans.

Antecedentes: La histerectomía no terapéutica en niñas y adolescentes con discapacidad intelectual (DI) es una práctica aceptable, aun cuando se carece de razón ética prescriptiva. Objetivos: Determinar la magnitud de la práctica de la histerectomía en niñas y adolescentes con DI, y explorar los factores emic asociados a esta práctica. Material y métodos: Estudio multicéntrico e intersectorial con método mixto. Resultados: Los resultados cuantitativos mostraron que 50 de 234 histerectomías reportadas correspondieron a mujeres con DI. El promedio de edad a la cirugía fue de 15 ± 2.9 años. La histerectomía abdominal profiláctica fue el procedimiento predominante y las justificaciones fueron control de fertilidad, manejo de la higiene menstrual y riesgo de abuso sexual. El análisis cualitativo de 15 grupos focales reveló que la principal preocupación de los padres fue cómo manejar la enfermedad índice y la salud reproductiva de sus hijas; percibieron positivamente la menstruación, expresaron su miedo a morir y dejarlas sin ayuda, resaltaron el control de la fertilidad y ninguno aprobó la histerectomía. Conclusiones: Los organismos que definen políticas de salud necesitan crear una nueva filosofía que evite el enfoque reduccionista del actual modelo biomédico, el cual separa (en el proceso salud-enfermedad) la interdependencia entre los seres humanos.

Tic-Related Obsessive-Compulsive and Eating Disorders in Dandy-Walker Variant: A Case Report and Systematic Reappraisal of Psychiatric Profiles.

Dandy-Walker complex (DWC) consists of a continuum of brain malformations involving the posterior fossa, often leading to psychiatric manifestations during adulthood. We discussed the case of a young woman with Dandy-Walker variant (DWV) and a comorbid complex neuropsychiatric presentation, who was diagnosed with an eating disorder, obsessive-compulsive disorder, and a tic disorder. Afterwards, we conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020-compliant systematic review reappraising all evidence of psychiatric outcomes in adults with DWC. Overall, 34 studies were eligible for data extraction, comprising 36 patients. Psychiatric profiles were more common among young adult males, with DWC lesions, especially DWV subtype, being often discovered incidentally after admission to mental health inpatient facilities. Most patients were diagnosed with psychosis and bipolar disorder, often comorbid with cognitive impairment. Psychotropic polypharmacy was frequently prescribed, generally leading to complete recovery. Evidence from our case report and systematic review indicates the importance of monitoring long-term psychiatric sequelae among adult patients with DWC malformations.

The relationship between clinical presentation and the nature of care in adults with intellectual disability and epilepsy - national comparative cohort study.

BACKGROUND: A quarter of People with Intellectual Disabilities (PwID) have epilepsy compared with 1% of the general population. Epilepsy in PwID is a bellwether for premature mortality, multimorbidity and polypharmacy. This group depends on their care provider to give relevant information for management, especially epilepsy. There is no research on care status relationship and clinical characteristics of PwID and epilepsy. AIM: Explore and compare the clinical characteristics of PwID with epilepsy across different care settings. METHOD: A retrospective multicentre cohort study across England and Wales collected information on seizure characteristics, intellectual disability severity, neurodevelopmental/biological/psychiatric comorbidities, medication including psychotropics/anti-seizure medication, and care status. Clinical characteristics were compared across different care settings, and those aged over and younger than 40 years. RESULTS: Of 618 adult PwID across six centres (male:female = 61%:39%), 338 (55%) received professional care whereas 258 (42%) lived with family. Significant differences between the care groups existed in intellectual disability severity (P = 0.01), autism presence (P < 0.001), challenging behaviour (P < 0.001) and comorbid physical conditions (P = 0.008). The two groups did not vary in intellectual disability severity/genetic conditions/seizure type and frequency/psychiatric disorders. The professional care cohort experienced increased polypharmacy (P < 0.001) and antipsychotic/psychotropic use (P < 0.001/P = 0.008).The over-40s cohort had lower autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) comorbidity (P < 0.001/P = 0.007), increased psychiatric comorbidity and challenging behaviour (P < 0.05), physical multimorbidity (P < 0.001), polypharmacy (P < 0.001) and antipsychotic use (P < 0.001) but reduced numbers of seizures (P = 0.007). CONCLUSION: PwID and epilepsy over 40 years in professional care have more complex clinical characteristics, increased polypharmacy and antipsychotic prescribing but fewer seizures.

Report of a Novel Homozygous Intragenic DCC Duplication and a Review of Literature of Developmental Split-Brain Syndrome aka Horizontal Gaze Palsy with Progressive Scoliosis-2 with Impaired Intellectual Development Syndrome.

Introduction: Horizontal gaze palsy with progressive scoliosis-2 (HGPPS2, MIM 617542) with impaired intellectual development aka developmental split-brain syndrome is an ultra-rare congenital disorder caused by pathogenic biallelic variants in the deleted in colorectal cancer (DCC) gene. Case Presentation: We report the clinical and genetic characterization of a Syrian patient with a HGPPS2 phenotype and review the previously published cases of HGPPS2. The genetic screening was performed using exome sequencing on Illumina platform. Genetic analysis revealed a novel DCC c.(?_1912)_(2359_?)dup, p.(Ser788Tyrfs*4) variant segregating recessively in the family. This type of variant has not been described previously in the HGPPS2 patients. To date, including the case reported here, three different homozygous pathogenic frameshift variants, one homozygous missense variant, and an intragenic duplication in the DCC gene have been reported in 8 patients with the HGPPS2 syndrome. Conclusion: The analysis of duplications and deletions in the DCC should be included in the routine genetic diagnostic evaluation of patients with suspected HGPPS2. This report expands the knowledge of phenotypic and genotypic spectrum of pathogenic variants causing HGPPS2.

Improvement of palliative care for people with intellectual disabilities: A multi-site evaluation.

BACKGROUND: To improve the quality of palliative care, six evidence-based tools were implemented in 10 care services specialised in care for people with intellectual disabilities. Contextual differences were taken into account by using a participatory action research approach. METHOD: The RE-AIM framework (Reach, Effectiveness, Adoption, Implementation and Maintenance) structured the evaluation. Data sources were online questionnaires completed by 299 professionals at baseline (response 45.2%) and 250 professionals after 2.5 years (35.1%), 11 semi-structured group interviews with 43 professionals, field notes and implementation plans. RESULTS: A total of 767 professionals and 43 teams were reached. The effectiveness of the intervention was demonstrated in an improved knowledge of palliative care policy and increased competences among professionals. 79% of the professionals adopted tools in the toolbox. The participatory action research method was perceived as valuable in driving change. CONCLUSIONS: Improving palliative care needs a context-specific, flexible approach, with involvement of all stakeholders.