Common Cause Of Intellectual Disability Research Articles

INVESTIGATING THE LANGUAGE DEVELOPMENT OF INDIVIDUALS WITH DOWN SYNDROME, AND HIGHLIGHTING THE IMPORTANCE OF SPEECH THERAPY

Down syndrome is the most common viable numerical chromosomal abnormality, affecting one in every 600 births. It is the most common cause of intellectual disability due to genetic factors. Nearly all individuals with this syndrome have an extra copy of the 21st, leading to cognitive and physical disabilities. Down syndrome can be detected through prenatal screening and is classified into three categories: trisomy 21, mosaicism, and translocation. The main aim of this study is to investigate the linguistic characteristics of people with Down syndrome and demonstrate the value of speech therapy. Statistical analysis shows that the linguistic development of individuals with Down syndrome differs in every subsection from normal development. There are deficiencies not only in their linguistic development (i.e., phonology, morphology, syntax, and pragmatics) but also in many cognitive categories (e.g., memory). Furthermore, this study confirmed the value of speech therapy through personalized intervention. However, we found that the speech therapists who participated in this survey did not have the appropriate expertise. Their knowledge of Down syndrome was good, but they needed a deeper understanding of the syndrome.<p> </p><p><strong> Article visualizations:</strong></p><p><img src="/-counters-/edu/0748/a.php" alt="Hit counter" /></p>

Suggestion of creatine as a new neurotransmitter by approaches ranging from chemical analysis and biochemistry to electrophysiology

The discovery of a new neurotransmitter, especially one in the central nervous system, is both important and difficult. We have been searching for new neurotransmitters for 12 y. We detected creatine (Cr) in synaptic vesicles (SVs) at a level lower than glutamate and gamma-aminobutyric acid but higher than acetylcholine and 5-hydroxytryptamine. SV Cr was reduced in mice lacking either arginine:glycine amidinotransferase (a Cr synthetase) or SLC6A8, a Cr transporter with mutations among the most common causes of intellectual disability in men. Calcium-dependent release of Cr was detected after stimulation in brain slices. Cr release was reduced in Slc6a8 and Agat mutants. Cr inhibited neocortical pyramidal neurons. SLC6A8 was necessary for Cr uptake into synaptosomes. Cr was found by us to be taken up into SVs in an ATP-dependent manner. Our biochemical, chemical, genetic, and electrophysiological results are consistent with the possibility of Cr as a neurotransmitter, though not yet reaching the level of proof for the now classic transmitters. Our novel approach to discover neurotransmitters is to begin with analysis of contents in SVs before defining their function and physiology.

Suggestion of creatine as a new neurotransmitter by approaches ranging from chemical analysis and biochemistry to electrophysiology.

The discovery of a new neurotransmitter, especially one in the central nervous system, is both important and difficult. We have been searching for new neurotransmitters for 12 y. We detected creatine (Cr) in synaptic vesicles (SVs) at a level lower than glutamate and gamma-aminobutyric acid but higher than acetylcholine and 5-hydroxytryptamine. SV Cr was reduced in mice lacking either arginine:glycine amidinotransferase (a Cr synthetase) or SLC6A8, a Cr transporter with mutations among the most common causes of intellectual disability in men. Calcium-dependent release of Cr was detected after stimulation in brain slices. Cr release was reduced in Slc6a8 and Agat mutants. Cr inhibited neocortical pyramidal neurons. SLC6A8 was necessary for Cr uptake into synaptosomes. Cr was found by us to be taken up into SVs in an ATP-dependent manner. Our biochemical, chemical, genetic, and electrophysiological results are consistent with the possibility of Cr as a neurotransmitter, though not yet reaching the level of proof for the now classic transmitters. Our novel approach to discover neurotransmitters is to begin with analysis of contents in SVs before defining their function and physiology.

Brain metabolic profile assessed by magnetic resonance spectroscopy in ‎‎children with Down syndrome: Relation to intelligence quotient.

Down syndrome (DS) is one of the most common causes of intellectual disability. Children with DS have varying intelligence quotient (IQ) that can predict their learning abilities. To assess the brain metabolic profiles of children with DS and compare them to standard controls, using magnetic resonance spectroscopy (MRS) and correlating the results with IQ. This case-control study included 40 children with DS aged 6-15 years and 40 age and sex-matched healthy children as controls. MRS was used to evaluate ratios of choline/creatine (Cho/Cr), N-acetyl aspartic acid/creatine (NAA/Cr), and myoinositol/creatine (MI/Cr (in the frontal, temporal, and occipital lobes and basal ganglia and compared to controls and correlated with IQ. Children with DS showed significant reductions in NAA/Cr and MI/Cr and a non-significant reduction in Cho/Cr in frontal lobes compared to controls. Additionally, we observed significant decreases in NAA/Cr, MI/Cr, and Cho/Cr in the temporal and occipital lobes and basal ganglia in children with DS compared to controls. Furthermore, there was a significant correlation between IQ and metabolic ratios in the brains of children with DS. Brain metabolic profile could be a good predictor of IQ in children with DS.

Next-Generation Sequencing in Unexplained Intellectual Disability.

To determine the diagnostic yield of next generation sequencing (NGS) in patients with moderate/severe/profound intellectual disability (ID) unexplained by conventional tests and to assess the impact of definitive diagnosis on the clinical management and genetic counselling of these families. This was a ambi-directional study conducted at Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi. The study comprised 227 patients (prospective cohort - 126, retrospective cohort - 101) in whom NGS based tests were performed. The mean age of study cohort was 4.5 ± 4.4 y (2.5 mo to 37.3 y). The male: female ratio was 1.6:1. The overall diagnostic yield of NGS was 53.3% (121/227) with causative variants identified in 84 known ID genes. Autosomal recessive intellectual disability (ARID) (23.3%, 53/227) was the most common followed by autosomal dominant intellectual disability (ADID) (20.7%, 47/227) and X-linked intellectual disability (XLID) (9.2%, 21/227). The diagnostic yield was notably higher for ID plus associated condition group (55.6% vs. 20%) (p = 0.0075, Fisher's exact test) compared to isolated ID group. The impact of diagnosis on active or long-term management was observed in 17/121 (14%) and on reproductive outcomes in 26/121 (21.4%) families. There is paucity of data on molecular genetic spectrum of ID from India. The current study identifies extensive genetic heterogeneity and the impact of NGS in patients with ID unexplained by standard genetic tests. The study identified ARID as the most common cause of ID with additional implications for reproductive outcomes. It reiterates the importance of phenotype in genetic testing.

The Need for Psychiatric Assessment in Children with Down Syndrome and Factors Affecting Their Use of Mental Health Services: A Cross-Sectional Study from Turkey

Objective. Down syndrome (DS) is the most common cause of intellectual disability. Children with DS may have difficulty accessing psychiatric services because their mental health problems are often unrecognized. This study aimed to assess the mental health needs of children with Down syndrome and the elements that may affect their access and referral to psychiatric services. Methods. In this single-center cross-sectional study, we evaluated 72 children with Down syndrome and assessed the factors affecting their use of mental health services by using a questionnaire completed by parents. We compared the clinical symptom profiles of young preschool-aged children with Down syndrome (n = 26) with typical (n = 26), developmental delay (n = 15), and autism spectrum disorder (ASD) group (n = 28) to evaluate mental health problems. The Schedule for Affective Disorders and Schizophrenia for School-Aged Children: Present and Lifetime Version DSM-5 (K-SADS-PL) was administered. Parents completed the child behavior check list for ages 6–18 and 1½-5, depending on the child’s age. Results. Although most patients with Down syndrome (51.4%) had psychiatric symptoms reported by parents at the initial assessment, the most frequent reason (62.5%) for applying to our psychiatric clinic was to submit an application for a medical report. The majority of patients with Down syndrome (56%) had a psychiatric disorder, and attention deficit and hyperactivity disorder was the most common diagnosis. Conclusion. Clinicians should not overlook the need for psychiatric assessment, early diagnosis, and collaboration between pediatricians and child psychiatrists, which are crucial during medical evaluation and follow-up of children with Down syndrome.

Fragile X Syndrome and Fetal Alcohol Syndrome: Occurrence of Dual Diagnosis in a Set of Triplets.

Fragile X syndrome (FXS) and fetal alcohol syndrome disorders are both common causes of intellectual disability in children. When both conditions are present in the same individual, the resultant phenotype may make identification of clinical issues and management challenging. In this case report, we present a case of triplets who had significant in utero alcohol exposure; 2 of whom also have FXS and the other not having the fragile X mutation. The siblings with FXS have subtle differences in the physical phenotype compared with the other one, who has prominent features of partial fetal alcohol syndrome instead. However, all 3 siblings have intellectual impairment (although this is more severe in the 2 with FXS), meet diagnostic criteria for autism spectrum disorder, and present with severe behavioral challenges. The clinical presentation of the 2 siblings with FXS is much more severe as compared to a child with FXS alone, and this is likely due to the additive effect of in utero alcohol exposure and environmental factors. We discuss the combination of these 2 pathologies and how this can affect the overall clinical presentation. In the management of children with FXS, evaluation for other risk factors that can have neurobehavioral sequelae is important, and these can affect clinical presentation and prognosis.

Dementia in people with Down syndrome

Down syndrome (trisomy 21) is one of the most common causes of intellectual disability. It is associated with characteristic physical features and multiple comorbidities, due to the process of accelerated ageing. Improved recognition and access to healthcare in recent decades has dramatically increased life expectancy. However, as a result, people with the syndrome are more at risk of developing conditions associated with ageing, significantly Alzheimer’s dementia. The diagnosis of dementia remains a challenge in the context of intellectual disability, leading to delayed diagnosis and poor outcomes. The importance of recognising early signs is a key to improving management and prognosis.

Hyperthyroidism in Down’s Syndrome – A Rare Association

Trisomy 21 is the most common chromosomal abnormality in paediatric population, and the most common cause of intellectual disability. The most common endocrine disease in these population is hypothyroidism. Hyperthyroidism is rare in patients with Down syndrome, but is likely to be underestimated. Hyperthyroidism treatment strategy is highly important for an undisturbed and balanced development of the children.The objective of this case report is to highlight the importance of hyperthyroidism in Down syndrome which is the rare presentation, to best of our knowledge.

Down syndrome and its screening: knowledge, attitude and practice among pregnant women in Patan Hospital

Introduction: Down syndrome (DS) is the most common cause of intellectual disability among live born children which can be detected prenatally. This study aims to assess the knowledge attitude and practice of pregnant women about Down syndrome and its available prenatal diagnosis.
 
 Method: A study was conducted in Department of Obstetrics and Gynecology of Patan Academy of Health Sciences in 2021.All pregnant ladies who attended the antenatal clinic received a self-administered validated questionnaire to determine their knowledge of Down syndrome, its screening test and willingness to do prenatal testing.
 
 Result: Majority of the participants (88%) belonged to age group of 18 to 35 years.59% were primigravidas. Almost 90% were Hindus and 55% had graduate level education. More than half of the participants had poor knowledge of DS and 60 % had no idea regarding the screening tests. However, more than half (56%) of them were willing to undergo screening for DS. One fifth of the women did not want to continue the pregnancy if baby had DS. Higher income is significantly associated with good knowledge in both domain (knowledge about DS, and knowledge about its screening). Illiterates are found to have better knowledge than educated group which seems a bit contradictory, but this might have been due to our smaller sample size.
 
 Conclusion: There is a significant gap between women’s knowledge and their attitudes and practice, which has to be addressed with local and national policies and protocols. Informed decision making should be the norm after empowering pregnant women with knowledge.

Severity Scoring Cutoff for MLPA and Its Diagnostic Yield in 332 North Indian Children with Developmental Delay.

Chromosomal aberrations/rearrangements are the most common cause of intellectual disability (ID), developmental delay (DD), and congenital malformations. Traditionally, karyotyping has been the investigation of choice in such cases, with the advantage of being cheap and easily accessible, but with the caveat of the inability to detect copy number variations of sizes less than 5 Mb. Chromosomal microarray can solve this problem, but again the problems of expense and poor availability are major challenges in developing countries. The purpose of this study is to find the utility of multiplex ligation-dependent probe amplification (MLPA) as a middle ground, in a resource-limited setting. We also attempted to establish an optimum cutoff for the de Vries score, to enable physicians to decide between these tests on a case-to-case basis, using only clinical data. A total of 332 children with DD/ID with or without facial dysmorphism and congenital malformations were studied by MLPA probe sets P245. Assessment of clinical variables concerning birth history, facial dysmorphism, congenital malformations, and family history was done. We also scored the de Vries scoring for all the patients to find a suitable cutoff for MLPA screening. In our study, the overall detection rate of MLPA was 13.5% (45/332). The majority of patients were DiGeorge's syndrome with probe deletion in 22q11.21 in 3.3% (11/332) followed by 15q11.2 del in 3.6% (12/332, split between Angelman's and Prader-Willi's syndromes). Also, 3.0% (10/332) of patients were positive for Williams-Beuren's syndrome 7q11.23, 1.8% (6/332) for Wolf--Hirschhorn's syndrome 4p16.3, 1.2% (4/332) for 1p36 deletion, and 1% for each trichorhinophalangeal syndrome type I 8q23.3 duplication syndrome and cri du chat syndrome. The optimum cutoff of de Vries score for MLPA testing in children with ID and/or dysmorphism came out to be 2.5 (rounded off to 3) with a sensitivity of 82.2% and specificity of 66.7%. This is the largest study from India for the detection of chromosomal aberrations using MLPA common microdeletion kit P245. Our study suggests that de Vries score with a cutoff of 3 or more can be used to offer MLPA as the first tier test for patients with unexplained ID, with or without facial dysmorphism and congenital malformations.

Effects of Cerebrolysin on the Neurodevelopmental Outcomes in Infants with Down Syndrome: A Randomized Controlled Pilot Trial

ABSTRACT Introduction Down syndrome (DS) is a common cause of intellectual disability with a possible glial-neuronal disruption. We assessed the effects of Cerebrolysin on the neurodevelopmental outcomes of infants with DS. Methods This randomized controlled pilot trial included 64 infants with DS. They were allocated into a treatment group (n =32) who received weekly intramuscular Cerebrolysin injections for 12 months and a control group (n =32) who did not receive Cerebrolysin. We assessed the five domains of neurodevelopment (expressive communication, receptive communication, fine motor, gross motor, and cognitive development) for both groups at the ages of 6 months (basal visit), 12 months (first follow-up visit) and 18 months (second follow-up visit), using Bayley Scales of infant and toddler development (third edition). The secondary outcome was to detect the occurrence of Cerebrolysin-related side effects among the treatment group. Kendall’s tau-b correlation coefficient, chi-square test, Fisher’s exact test, Student's t-test, Mann-Whitney and Wilcoxon signed-rank tests were used for the statistical analysis. Results Infants of both groups were matched with respect to gender, maternal level of education, their initial growth parameters, nutritional status, and socioeconomic status. No statistically significant differences existed between both groups regarding all neurodevelopmental domains on the basal visit, while on subsequent visits Z-scores improved in the treatment group, but not in the controls. Within the treatment group, there was a significant improvement in all domains at 12 and 18 months of age (p < .001). The improvement was mainly during the first 6 months of the study (p < .001 for all domains), and was best for fine motor and cognitive development. Only one infant in the treatment group developed fits and was ruled out from the study. Conclusion Weekly intramuscular injections of Cerebrolysin during the first year of life could possibly improve the neurodevelopmental outcomes and mental health in infants with DS. Further, large-scale studies are still needed to evaluate the efficacy and safety of Cerebrolysin among this sector of disabled infants.

Epilepsy and other comorbidities in Down syndrome

AbstractDown syndrome (DS) is the most common cause of intellectual disability. Due to many genetic and biochemical aberrations, people with DS suffer from several somatic disorders and concomitant diseases. Epilepsies occur more often than in the normal population, but less often than with intellectual disability of other causes. Epilepsies in DS have a trimodal distribution with age-related phenotypes, etiologies, and prognosis. The most common epilepsy syndrome in infancy is the often-self-limiting West syndrome; if Lennox–Gastaut syndrome occurs in the later course of development, the seizure prognosis worsens significantly. From the fourth decade of life, myoclonic epilepsy often occurs, which in combination with rapidly progressive Alzheimer’s dementia is life-limiting within a few years.

Social and emotional characteristics of girls and young women with DDX3X-associated intellectual disability: a descriptive and comparative study

DDX3X variants are a common cause of intellectual disability (ID) in females, and have been associated with autism spectrum disorder and emotional-behavioural difficulties. In this study, we compared phenotypic data for 23 females with DDX3X variants, to 23 females with ID and other genetic diagnoses. We found a wide range of adaptive, social and emotional function within the DDX3X group. Autism characteristics did not differ between DDX3X and comparison groups, while levels of anxiety and self-injurious behaviour (SIB) were significantly higher in the DDX3X group. Within the DDX3X group, adaptive function, autism characteristics, anxiety and SIB scores were positively correlated, with evidence for group-specific associations with SIB. Future work is warranted to explore the multilevel mechanisms contributing to social and emotional development in individuals with DDX3X variants.

Experiences of the Molecular Diagnosis of Fragile X Syndrome in Ecuador.

Fragile X syndrome (FXS) is the most common cause of hereditary intellectual disability and the second most common cause of intellectual disability of genetic etiology. This complex neurodevelopmental disorder is caused by an alteration in the CGG trinucleotide expansion in fragile X mental retardation gene 1 (FMR1) leading to gene silencing and the subsequent loss of its product: fragile X mental retardation protein 1 (FMRP). Molecular diagnosis is based on polymerase chain reaction (PCR) screening followed by Southern blotting (SB) or Triplet primer-PCR (TP-PCR) to determine the number of CGG repeats in the FMR1 gene. We performed, for the first time, screening in 247 Ecuadorian male individuals with clinical criteria to discard FXS. Analysis was carried out by the Genetics Service of the Hospital de Especialidades No. 1 de las Fuerzas Armadas (HE-1), Ecuador. The analysis was performed using endpoint PCR for CGG fragment expansion analysis of the FMR1 gene. Twenty-two affected males were identified as potentially carrying the full mutation in FMR1 and thus diagnosed with FXS that is 8.1% of the sample studied. The average age at diagnosis of the positive cases was 13 years of age, with most cases from the geographical area of Pichincha (63.63%). We confirmed the familial nature of the disease in four cases. The range of CGG variation in the population was 12–43 and followed a modal distribution of 27 repeats. Our results were similar to those reported in the literature; however, since it was not possible to differentiate between premutation and mutation cases, we can only establish a molecular screening approach to identify an expanded CGG repeat, which makes it necessary to generate national strategies to optimize molecular tests and establish proper protocols for the diagnosis, management, and follow-up of patients, families, and communities at risk of presenting FXS.

Senescence biomarkers in adults and elderly with Down syndrome

AbstractBackgroundThe Down syndrome (DS) is a genetic disturb caused for the trisomy of chromosome 21. It is the most common cause of intellectual disability, in addition DS accelerates aging and others development and health problems. Some pathological aspects, common to DS with dementia and Alzheimer disease (AD) suggest common pathogenic aspects. This study aims to investigate biomarkers related to cellular aging and their interrelationship with pathological markers of AD in adults and elderly individuals with DS by determining the expression of apoptotic pathway proteins: β‐catenin plays a role int the cell adhesion, cell survival and cell proliferation, in addition it is a key factor in the Wnt pathway. The activation of Wnt/β‐catenin pathway can protect against neurotoxic effects caused by accumulation of β‐amyloid peptide and the phosphorylation of Tau protein, two neuropathological hallmarks in the AD. The Bcl‐2 protein prevents cell death a promoting the cell survival. The tumoral protein P53 functions in the conservation and stability of DNA. It is normally activated in response of cellular stress, acting in the cell cycle, apoptosis, DNA repairing and the cell metabolism.MethodProteins expressions were measured in platelets from non‐medicated older adults with DS (n=37), and healthy adults and older adults (n=28) by western blotting. The samples were analyzed in duplicate and normalization was done using β‐actin as control.Resultβ‐catenin and P53 expressions were higher in DS samples (p=0.001 and p=0.04 respectively). We found a higher expression of Bcl‐2 in healthy control samples (p=0.05).ConclusionWe concluded that the increased expression of β‐catenin and P53, in addition with the decrease levels of Bcl‐2 might indicate a deregulation in the mechanisms responsible for the cell survival process. It is possible to speculate that these changes are related to the increase in cellular stress related to DS.

Technological Improvements in the Genetic Diagnosis of Rett Syndrome Spectrum Disorders.

Rett syndrome (RTT) is a severe neurodevelopmental disorder that constitutes the second most common cause of intellectual disability in females worldwide. In the past few years, the advancements in genetic diagnosis brought by next generation sequencing (NGS), have made it possible to identify more than 90 causative genes for RTT and significantly overlapping phenotypes (RTT spectrum disorders). Therefore, the clinical entity known as RTT is evolving towards a spectrum of overlapping phenotypes with great genetic heterogeneity. Hence, simultaneous multiple gene testing and thorough phenotypic characterization are mandatory to achieve a fast and accurate genetic diagnosis. In this review, we revise the evolution of the diagnostic process of RTT spectrum disorders in the past decades, and we discuss the effectiveness of state-of-the-art genetic testing options, such as clinical exome sequencing and whole exome sequencing. Moreover, we introduce recent technological advancements that will very soon contribute to the increase in diagnostic yield in patients with RTT spectrum disorders. Techniques such as whole genome sequencing, integration of data from several “omics”, and mosaicism assessment will provide the tools for the detection and interpretation of genomic variants that will not only increase the diagnostic yield but also widen knowledge about the pathophysiology of these disorders.

Parental stress and adjustment in the context of rare genetic syndromes: A scoping review.

Chromosomal abnormalities are now considered a common cause of intellectual disability. With increased genetic testing, phenotyping and technological advancements, many new syndromes have been identified. This review sought to explore parental stress and adjustment in the context of rare genetic syndromes to evaluate their clinical impact. A systematic review of English peer-reviewed literature across three databases (PsycINFO, Medline, CINAHL) was completed and 69 articles were included. Parents of children with rare genetic syndromes experienced greater distress relative to other disabilities. Differences in parental wellbeing were syndrome-specific relative to ASD thus demonstrating the need to consider the contribution of syndrome-specific phenotypes. Child emotional and behavioural difficulties were the most consistent predictor of parental distress. Research reflecting other factors such as physical health, syndrome-specific behaviours, benefit finding and, parental appraisal in the context of a rare genetic aetiology is required in order to support parental adjustment in these conditions.

Maternal Prenatal History And Consanguinity Among Families Of Children With Down Syndrome: A Retrospective Case Control Study

Introduction: Down syndrome (DS) is one of the most common causes of intellectual disability. Many studies reported the relationship between antenatal history of spontaneous abortion and the risk of having DS children. Consanguineous marriage is common and preferrable in most of the Arabic countries, but its relation to DS remains controversial. Objective: Evaluating the association between antenatal maternal history, spontaneous abortions and consanguineous marriage in relation to the risk of giving DS live births. Subjects and Methods: This case control study included 306 patients diagnosed as DS, and their caregivers, presented to Clinical Genetics clinic, Cairo University Children Hospitals, from February 2018 to February 2020. The patients’ ages ranged from 1 to 5 years old and 306 families with healthy children as controls. They were evaluated by full history and examination. Results: Among DS children 67.6% were males, 22% of mothers of DS gave history of antenatal illness. History of previous spontaneous abortions was statistically significant higher among mothers with DS children with P- value

Normal Pressure Hydrocephalus in Down Syndrome: The Report of Two Cases

Down syndrome (DS) is the most common cause of intellectual disability in infants and has a well-known relationship with the Alzheimer's disease. The association between DS and the other pathologies of senescence, such as normal pressure hydrocephalus (NPH), has been poorly investigated. This series included two DS patients with NPH. In both cases, NPH symptoms were initially misdiagnosed as DS associated senescence. Patients were treated with ventricular-peritoneal shunt, showing a sustained improvement (1 and 4 years of follow-up). To our knowledge, this is the first description of the occurrence of NPH in adult patients with DS and surgical outcomes.