Degree Of Intellectual Disability Research Articles

Epilepsy and overgrowth-intellectual disability syndromes: a patient organization perspective on collaborating to accelerate pathways to treatment.

Overgrowth-intellectual disability (OGID) syndromes are a collection of rare genetic disorders with overlapping clinical profiles. In addition to the cardinal features of general overgrowth (height and/or head circumference at least two standard deviations above the mean) and some degree of intellectual disability, the OGID syndromes are often associated with neurological anomalies including seizures. In an effort to advance research in directions that will generate meaningful treatments for people with OGID syndromes, a new collaborative partnership called the Overgrowth Syndromes Alliance (OSA) formed in 2023. By taking a phenotype-first approach, OSA aims to unite research and patient communities traditionally siloed by genetic disorder. OSA has galvanized OGID patient organizations around shared interests and developed a research roadmap to identify and address our community's greatest unmet needs. Here, we describe the literature regarding seizures among those with overgrowth syndromes and present the OSA Research Roadmap. This patient-driven guide outlines the milestones essential to reaching the outcome of effective treatments for OGID syndromes and offers resources for reaching those milestones.

Associations of Gait and Cognitive Impairment and Dementia in Individuals with Down Syndrome

AbstractBackgroundLife expectancy of individuals with Down syndrome (DS) has increased considerably over the years. Atypical aging in Down syndrome (DS) is associated with neuropathological characteristics consistent with Alzheimer disease (AD). Significant gait alterations are associated with an increased risk of dementia for the general population. The aim of this study was to determine whether gait performance is associated with cognitive performance and dementia in adults with DS.MethodThis study included 66 individuals with DS over 20 years of age, divided into three diagnostic groups: stable cognition, prodromal dementia, and dementia. They were evaluated with the Performance‐Oriented Mobility Assessment (POMA), Timed Up and Go test, and Cambridge Examination for Mental Disorders of Older People with Down’s Syndrome and Others with Intellectual Disabilities (CAMDEX‐DS), which includes the Cambridge Cognitive Examination (CAMCOG). Logistic regression model was used to assess the effects of gait and balance on the diagnosis (prodromal dementia and dementia versus stable cognition) adjusting for age, sex, body mass index (BMI), degree of intellectual disability and physical inactivity.ResultThe score on the POMA‐Gait subscale score and body mass index (BMI) were found to be independent predictors of prodromal dementia and dementia (Poma‐Gait OR = 0.67, 0.53‐0.85 CI, p<0.001; and BMI OR = 1.12, 1.021.24 CI, p<0.001). A lower POMA‐Total score indicates a higher fall risk. With the exception of perception, all cognitive domains correlated with the POMA total score (P<0.05).ConclusionThese data indicate that poor gait performance, as assessed by the POMA, as well as a high BMI, were associated with a diagnosis of prodromal dementia or dementia. In those individuals, applying the POMA could facilitate the early diagnosis of dementia, help identify fall risks, and promote the adoption of geriatric interventions focused on improving functional mobility. There is a need for longitudinal studies to characterize the true nature of the associations found, to validate gait instruments specifics to this population, and for future analyses in order to clarify the role that gait and balance play in cognitive decline and the development of dementia.

Gait Abnormalities in Children with Phelan-McDermid Syndrome.

Background: Phelan-McDermid syndrome is a genetic disorder caused by haploinsufficiency of the SHANK3 gene on chromosome 22q13.3 and is characterized by autism spectrum disorder, intellectual disability, speech and language abnormalities, hypotonia, and mild dysmorphic features. Early literature in Phelan-McDermid syndrome did not include gait abnormalities as part of the syndrome although recent prospective studies report that the prevalence of gait abnormalities ranges from 55% to 94%. We compared gait abnormalities in individuals with Phelan-McDermid syndrome, idiopathic autism spectrum disorder, and typically developing controls, and explored associations between gait abnormalities, autism spectrum disorder, and intellectual functioning. Method: The study cohort consists of 67 participants between the ages of 3 and 18 years, divided into 3 groups: Phelan-McDermid syndrome (n = 46), idiopathic autism spectrum disorder (n = 11), and typically developing controls (n = 10). Gait was recorded using a video camera and scored across 26 gait features using a "Gait Clinical Observations scale" designed specifically for this study. Results: Gait abnormalities were significantly higher in the Phelan-McDermid syndrome group as compared to idiopathic autism spectrum disorder or typically developing controls. The number of gait abnormalities across groups was also significantly correlated with Intellectual Quotient/Developmental Quotient (IQ/DQ). In analysis of covariance including IQ/DQ, the effect of group was not significant, but the effect of IQ/DQ was significant. Conclusions: Overall differences in gait abnormalities were determined by the degree of intellectual disability, which was significantly higher in Phelan-McDermid syndrome.

Applications of PET and SPECT in Patients with Autism Spectrum Disorder.

Autism spectrum disorder (ASD) consists of neurological development disorders that manifest before three years of age and affect social interactions, markedly restricting range of interests and activities, often associated with some degree of intellectual disability. Single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are non-invasive imaging tools to investigate the function of the brain in vivo. SPECT and PET studies exploring rCBF and brain glucose metabolism in patients with ASD have been performed, providing important insights into the brain regions involved in ASD. Abnormalities in serotonergic, dopaminergic, GABAergic, cholinergic, and glutamatergic systems have been suggested to contribute to the observed distorted brain circuitry associated with ASD. However, the specificity of such abnormalities needs to be fully clarified because schizophrenia and other psychiatric diseases have been shown to present with comparable changes in neurotransmitter systems. Neuroinflammation could also play a role in the development of autism. Therefore, ASD is a complicated process involving a number of factors. It is mandatory to perform more research studies to determine the molecular cornerstone of ASD and to improve our comprehension of the clinical correlates of ASD.

Reasonable adjustments to the application of the comprehensive care standard within an Australian mainstream internal medicine outpatient clinic attended by adults with Down syndrome

ABSTRACT Background: The Australian Commission on Safety and Quality in Health Care recommends the development of reasonable adjustments to Comprehensive Care Standard to better suit the needs of people with intellectual disability. Method: An audit of adults with Down syndrome attending a mainstream internal medicine outpatient clinic was undertaken to describe their biopsychosocial profile, identify previously developed reasonable adjustments to clinical service and to consider their alignment with comprehensive care. Results: Of 54 adults, 31 (57%) male, average age 36 years (17.5–68 years), there were multiple syndromal and non-syndromal co-morbidities, 10 deaths (9 expected), from dementia. All had some degree of intellectual disability with all requiring disability supports to assist in their healthcare and an active health-disability interface in most cases. Conclusions: Reasonable adjustments to usual clinical content, process, knowledge, and organisation were identified, which appeared to facilitate application of comprehensive care. These were predominantly influenced by intellectual disability, disability supports, and the health-disability interface rather than the disease profile.

Beyond the known phenotype of sotos syndrome: a 31-individuals cohort study.

Sotos Syndrome (SS, OMIM#117550) is a heterogeneous genetic condition, recognized by three main clinical features present in most cases: overgrowth with macrocephaly, typical facial appearance and different degrees of intellectual disability. Three different types are described caused by variants or deletions/duplications in NSD1, NFIX and APC2 genes. We aimed to describe a cohort of pediatric patients reporting the typical and unexpected findings in order to expand the phenotype of this syndrome and trying to find genotype-phenotype correlations. In our referral center, we collected and analyzed clinical and genetic data of 31-patients cohort diagnosed with SS. All of them presented with overgrowth, typical dysmorphic features and different degree of developmental delay. Although structural cardiac defects have been reported in SS, non-structural diseases such as pericarditis were outstanding in our cohort. Moreover, we described here novel oncological malignancies not previously linked to SS such as splenic hamartoma, retinal melanocytoma and acute lymphocytic leukemia. Finally, five patients suffered from recurrent onychocryptosis that required surgical procedures, as an unreported prevalent medical condition. This is the first study focusing on multiple atypical symptoms in SS at the time that revisits the spectrum of clinical and molecular basis of this heterogeneous entity trying to unravel a genotype-phenotype correlation.

Klinefelter syndrome: The characterization of the clinical and sociological features of 51 patients

IntroductionKlinefelter syndrome is the most frequently found aneuploidy among male patients. Its clinical presentation is very heterogeneous, and thus poses a challenge for a timely diagnosis. MethodsA retrospective study was carried out with 51 consecutively selected patients diagnosed with Klinefelter Syndrome from Jan/2010 to Dec/2019. The karyotypes were identified using high resolution GTL banding at the Genetics Department. Multiple clinical and sociological parameters were studied by collecting data from the clinical records. Results44 (86%) of the 51 patients presented a classical karyotype (47,XXY) and 7 (14%) showed evidence of mosaicism. The mean age at diagnosis was 30.2±14.3 years old. Regarding the level of education (N=44), 26 patients (59.1%) had no secondary education, with 5 (11.4%) patients having concluded university studies. Almost two thirds of the sample revealed learning difficulties (25/38) and some degree of intellectual disability was present in 13.6% (6/44). Half of the patients were either non-qualified workers (19.6%) or workers in industry, construction, and trades (30.4%), which are jobs that characteristically require a low level of education. The proportion of unemployed patients was 6.5%. The main complaints were infertility (54.2%), followed by hypogonadism-related issues (18.7%) and gynecomastia (8.3%). 10 patients (23.8%, N=42) were biological parents. With regards the question of fertility, assisted reproductive techniques were used in 39.6% of the studied subjects (N=48), with a success rate (a take home baby) of 57.9% (11/19), 2 with donor sperm and 9 with the patients’ own gametes. Only 41% of the patients (17/41) were treated with testosterone. ConclusionThis study identifies the most important clinical and sociological findings of Klinefelter syndrome patients that should be considered when deciding workout and disease management.

Studying spatial orientation and constructive praxis disorders in normally developing and mentally retarded children aged 8-11 years

The ability to orientate oneself in space is one of the basic requirements for the harmonious development of a person. The problem of human orientation in space is very complex. It includes both ideas about the size and shape of objects and the ability to distinguish the location of objects in space, and understanding different spatial relationships. The concept of spatial orientation includes the evaluation of distances, sizes, shapes, mutual position of objects and their position relative to the orienting object. Spatial orientation is significantly impaired in mentally handicapped children, since the impairment of mental development not only limits their motor activity, but also negatively affects the development of time representations, musculoskeletal functions and leads to a decrease in compensatory processes. The purpose of this study is to identify spatial orientation and constructive praxis disorders in normally developing and mentally retarded children aged 8-11 years. Materials and Methods. The methodological basis of this research investigation was scholarly literature devoted to studying nervous functions in children with mental development disorders and interhemispheric asymmetry of the brain, regulation of these functions, identifying difficulties, modeling the system of work with these children and constructive praxis disorders in normally developing and mentally retarded children aged 8-11 years (Boguslavskaya, Miroshnichenko, 2019, Maryutina, Yermolaev 2001, Reuter-Lorenz and others, 2000, Azatyan2022). The study was conducted in the research laboratory of the Faculty of Special and Inclusive Education at the Armenian State Pedagogical University after Kh. Abovyan and research laboratory in Armenian state institute of physical culture and sport. A total of 131 children aged between 8 and 11 years participated in the study, including 73 healthy schoolchildren and 58 children with mild mental retardation. The degree of intellectual disability was assessed based on medical indications, degree of social adjustment, level of intellectual functioning, and learning outcomes in special education classes. Each category of participants was divided into 2 age groups: 8-9 years old and 10-11 years old. Results. The article discusses the main issues of studies of spatial orientation and constructive praxis in normally developing and mentally retarded children aged between 8 and 11 years, provides a scientific rationale for the problem, taking into account previous research investigations. However, the problem of mentally retarded and normally developing children in this age group remains virtually unexplored. Analysis of research findings allows the authors to identify and summarize the following important points: - mentally handicapped primary school children lag behind their healthy peers in all indicators examined; - 8- and 9-year-olds have less developed practical spatial orientation skills than their older peers; - Intellectually disabled peers have underdeveloped spatial orientation skills and constructive practice, making it difficult to understand spatial relationships between objects. The experimental study of task performance revealed interesting data, which will serve as a basis for developing the necessary means, methods and conditions for the development of elementary practical orientation in mentally disabled primary schoolchildren. The authors have uncovered violations of spatial orientation and constructive praxis in normally developing and intellectually disabled children aged 8-11 years that highlight the limited and incomplete verbalization of spatial relationships of objects in intellectually disabled children. The listed errors in general are reduced to the use by mentally retarded schoolchildren of imprecise, vague spatial characteristics instead of more differentiated ones. Conclusions. Thus, the results of the conducted experimental research testify to the insufficient development of the elementary practical orientation and understanding of the spatial relationships of objects in mentally retarded children of primary school age.

A 14-year-old patient with Prader-Willi syndrome: a case report

Prader-Willi Syndrome (PWS) is a disorder resulting from a loss of genetic information on chromosome 15q11.2-q13 inherited from the father. It can be caused by paternal deletions (65-75%) or uniparental maternal disomy (20-30%). The prevalence of PWS is estimated to be 1/10,000 - 1/20,000 births.1 Although its incidence is relatively rare, PWS can cause major health problems for patients and decreased quality of life for their families.
 The course of PWS is characterized by severe hypotonia in the neonatal period, severe feeding problems resulting in growth failure, as well as small hands and feet. Hypogonadism manifests as genital hypoplasia, delayed puberty, and infertility. Children with PWS have delayed motor and language development. Most patients have some degree of intellectual disability. Hyperphagia and obesity occur in early childhood. The patient’s excessive eating behavior affects the patient’s and family’s quality of life, and is often responsible for high morbidity and mortality.

Analysis of Morphological Parameters and Body Composition in Adolescents with and without Intellectual Disability.

Compared to the tremendous volume of studies focusing on children and teenagers without disabilities, research regarding weight and body composition among young populations with an intellectual disability is relatively rare. Their number further decreases when we refer to specific age groups with intellectual deficits, such as children and adolescents younger than 18. In addition, studies are even scarcer when we wish to compare groups of subjects with different degrees of intellectual disability by gender. This study has a constative nature. The research sample comprises 212 subjects-girls and boys with an average age of 17.7 ± 0.2, divided into six groups by gender and type of intellectual disability. The parameters considered within the study include anthropometrical data and body composition determined using a professional device (Tanita MC 580 S). The findings of this study highlight the impact of intellectual disability on body composition in this age category. We hope it will help develop efficient strategies, recommendations, and intervention plans to ensure active participation in physical activities and categorisation within the optimal parameters of body composition indicators.

Methylmalonic acidemia: Neurodevelopment and neuroimaging.

Methylmalonic acidemia (MMA) is a genetic disease of abnormal organic acid metabolism, which is one of the important factors affecting the survival rate and quality of life of newborns or infants. Early detection and diagnosis are particularly important. The diagnosis of MMA mainly depends on clinical symptoms, newborn screening, biochemical detection, gene sequencing and neuroimaging diagnosis. The accumulation of methylmalonic acid and other metabolites in the body of patients causes brain tissue damage, which can manifest as various degrees of intellectual disability and severe neurological dysfunction. Neuroimaging examination has important clinical significance in the diagnosis and prognosis of MMA. This review mainly reviews the etiology, pathogenesis, and nervous system development, especially the neuroimaging features of MMA.

Evaluation of factors affecting body mass index of children with intellectual disability.

This study was conducted to evaluate the BMI of the children with intellectual disability and the factors affecting their BMI. This descriptive and cross-sectional study was carried out between March 2016 and April 2016 in Turkey and consisted of 135 children. Children's anthropometric measurements were and their BMI values were calculated. Categorization of children by BMI percentile according to AAP reference values was performed. There was a significant difference between the BMI categories of the children (p < 0.05) and the education level of children's father (x2 = 8.960; p = 0.028), the degree of intellectual disability (x2 = 16.113; p = 0.008), the presence of other disabilities (x2 = 22.013; p = 0.000), type of disability (x2 = 21.359; p = 0.001), the nutrient intake (x2 = 38.935; p = 0.000) and the presence of nutritional problems (x2 = 7.687; p = 0.042). Father's education level, children's degree of disability, child's having presence of other disabilities, child's being dependent in the view of nutrient intake, and child's having nutritional problems were determined as factors affecting BMI.

Clinical features of epilepsy in 5 children with Mowat-Wilson syndrome

Objective: To summarize and investigate the clinical characters of epilepsy in children with Mowat-Wilson syndrome (MWS), thus to improve the understanding of this disease. Methods: Clinical characters of epilepsy episodes in 5 children with MWS admitted to Department of Pediatrics, Peking University First Hospital from June to December 2020 were retrospectively reviewed. Clinical data including onset age of seizures, clinical features, characters of electroencephalogram (EEG), magnetic resonance imaging (MRI) findings, results of ZEB2 gene testing and responses to the anti-seizure medications (ASM) were summarized. Results: The onset age of seizures in the 5 patients (3 males and 2 females) ranged from 6 months to 4 years. Four patients showed focal motor seizures with diverse expressions, while the other 1 patient had epileptic spasms. All the 5 patients showed distinctive face, different degrees of intellectual disability, development delay and other congenital malformations. EEG of 4 patients presented the slowing of background rhythm and epileptiform discharges mainly occurred in the posterior region of the brain. The other 1 patient showed hypsarrhythmia at the beginning of the disease, changing into multifocal discharges mainly occurred in posterior region later. Corpus callosum abnormality and white matter disability were found from investigations of MRI in 2 patients, respectively. All the 5 patients carried a de novo heterozygous variation in the ZEB2 gene, 4 were nonsense variants and 1 was frame-shift variant. Within the follow-up of 14 months to 20 months, 3 patients achieved seizure-free more than 1 year, 2 patients achieved seizure-free more than 6 months. Two patients used valproate only and 2 patients received valproate combined with other ASM. Conclusions: Epileptic seizures are common clinical phenotype of MWS. Focal motor seizure may be the most common seizure type and epileptic spasms exist. The manifestations of EEG can be age-related. The most common type of variation of the ZEB2 gene is de novo nonsense variation. Valproate might be the first-line ASM for patients with MWS.

The Analysis of the Correlations between BMI and Body Composition among Children with and without Intellectual Disability.

Background: Compared to the great volume of studies focusing on children and adolescents without intellectual disability, research regarding body mass index among young populations (13–17 years old) with intellectual disability is scarce, mostly when we refer to the comparisons between various degrees of intellectual disability and gender. Methods: The purpose of this study was to assess a series of morphofunctional parameters among children with and without intellectual disability to characterise the morphofunctional normality and its perturbations. Within the study, we included 101 subjects from several educational institutions, distributed on five groups, by their gender and degree of intellectual disability. Results: The average values of body mass index exceed the values recommended by the WHO among all the five groups (boys and girls with and without intellectual disabilities) prone to obesity. Upon analysing the values of BMI by gender and type of intellectual disability, we note that the prevalence of obesity among boys is 28.07% (BMI > 24), while 19.29% are overweight (BMI ranging between 21.5 and 24). Conclusions: The prevalence of excess weight and obesity among persons with intellectual disabilities was similar among the male and female subjects. It shows an increasing trend by age.

The relationship between parents' oral hygiene knowledge and children with Down Syndrome's oral hygiene via OHI-S.

Background: Down Syndrome (DS) is a genetic disorder responsible for mental and development retardation. DS occurs when a person has an extra chromosome (47 instead of 46), the third copy of the Trisomy 21 chromosome. This causes structural and functional anomalies in the human body and some degree of intellectual disability. Children with DS have poor oral hygiene as they are unable to understand and are unaware of its importance. Oral hygiene problems commonly found in children with DS are gingivitis, periodontal problems, pain, infection, and problems with the masticatory system. This study explored the relationship between parents' knowledge and maintenance of the oral hygiene of children with DS through the OHI-S (Oral Hygiene Index Simplified) Index Score. Method: This study was conducted by distributing 25 questions via Google Form to 100 subjects that belong to POTADS (Down Syndrome Parents Association. The participants were children diagnosed with Down Syndrome and their parents. Questionnaires were used to assess parents' knowledge about their child's oral hygiene. To assess the children's oral hygiene, dental exams were performed with the OHI-S on six tooth surfaces. To calculate the OHI-S score for each individual, the debris and calculus scores from the 6 surfaces of the teeth were totalled and divided by six. Results: The relationship between parents' knowledge and the maintenance of oral hygiene of children with DS was found by conducting a linear regression analysis and hypothetical test. The equation of Y = 77.734 + (-7.377) X was achieved through linear regression analysis, and indicated that a 1% increase in parents' knowledge caused a reduction in OHI-S score to 7.377. The hypothetical test showed that parents' knowledge affected their children's OHI-S score significantly. Conclusion: There was a significant contradictive relationship between parents' knowledge and the maintenance of oral hygiene of children with DS .

Influence of COVID-19 pandemic lockdown on a sample of Egyptian children with Down syndrome

BackgroundDown syndrome (DS) is characterized by variable degrees of intellectual disability (ID). The coronavirus disease-2019 (COVID-19) lockdown prevented children with DS from reaching their rehabilitation facilities. This could have led to deterioration of their abilities and mental health hazards. The aim of this cohort study was to investigate frequency of COVID-19, the influence of COVID-19 pandemic on health, and some abilities of children with DS, and to explore factors that could have governed receiving home-based training during the lockdown. A survey of 150 individuals with Down syndrome was answered by their caregivers. Additionally, 135 participants were subjected to assessment of cognitive, language, and motor abilities using Portage program. They were divided into 2 groups: group I who received online therapy sessions during the lockdown and group II who did not receive sessions. Logistic regression was used to determine the factors which influenced getting home-based training.ResultsThe percentage of COVID-19 cases was 3.3%. All evaluated abilities were reduced despite receiving online sessions particularly language performance (P < 0.001). Male gender, having severe ID and low parental education were among the factors which encouraged parents to get virtual training.ConclusionCOVID-19 pandemic had a negative impact on the abilities of DS children even those who got rehabilitation sessions. Their dependence on social interaction could have limited the benefit of virtual sessions. Factors that influence a parent’s decision to get home-based training should be monitored and targeted in order to overcome obstacles or concepts that may prevent families from enduring home-based intervention.

Moral Sensitivity of Young People with Intellectual Disability – Its Role in The Process of Their Education

According to Heller and Życiński (1980) the primary regulator of human behaviour is the system of values therefore its development should be in the centre of all educational and upbringing measures. Our focus here is on moral sensitivity understood as the ability of an individual to see social situations from the perspective of moral good and moral evil that represent values embodied in moral norms adopted by the world and internalised by humans as the principles of conduct. The main research question was the following: How morally sensitive are persons with ID and how is their sensitivity associated with the degree of intellectual disability and gender? A non-probability sample 267 of Polish residents aged 16-30 years with mild (58.42%) or moderate (41.58%) intellectual disability was assembled. Men and women were almost in equal proportion. The Moral Sensitivity Inventory (MSI; Otrębski, Sudoł, 2020) has been used to measure the moral sensitivity of people with ID. It consists of 10 illustrated stories presenting typical social situations containing moral dilemmas, and an evaluation form. The tested person’s task is to answer the following question “Who, in this story, did something right or wrong, and what was that?” and to indicate as many moral elements in the story and the picture as they can. The results imply that the study participants had different ability to discern moral good and moral evil. They were more sensitive to the manifestations of good and evil bad associated with Understanding one’s behaviour and its impact on others (more than one-fourth of them had high scores) and less perceptive of those relating to Respect for others’ property and Conformance to principles and norms. The results of the study expand the knowledge of the overall moral sensitivity of persons with intellectual disabilities.

West syndrome in patients with Kabuki syndrome (literature review and case report)

Kabuki syndrome (KS) is a rare genetic disorder that has facial phenotypic descriptors, retarded growth, various malformations and different degrees of intellectual disability. Objective: to study the characteristic features of KS comorbid with West syndrome according to literature review and data collection together with KS described clinically, and treatment success rates by the clinical case study research. There was conducting literature review on the topic in the databases OMIM, PubMed, Scopus, and e-library. The articles describing cases of epilepsy in patients with KS were analyzed. We conducted our own observation of KS in the male patient with epilepsy and West syndrome in a patient with KS was analyzed by the clinical case study research. Kabuki syndrome comorbid with West syndrome increases neurological deficits and leads to the formation of a marked delay in mental and speech development and psychomotor development retardation. Peculiarities of the treatment of KS comorbid with West syndrome are the lack of efficacy of antiepileptic drugs, and the very visible effectiveness of the ketogenic diet, together with an atypical response to hormone replacement therapy in the form of distinct positive dynamics – a clinically meaningful reduction in seizure frequency along with elevated liver enzymes.

Expanding Phenotype of Poirier-Bienvenu Syndrome: New Evidence from an Italian Multicentrical Cohort of Patients.

Background: Poirier–Bienvenu Neurodevelopmental Syndrome (POBINDS) is a rare disease linked to mutations of the CSNK2B gene, which encodes for a subunit of caseinkinase CK2 involved in neuronal growth and synaptic transmission. Its main features include early-onset epilepsy and intellectual disability. Despite the lack of cases described, it appears that POBINDS could manifest with a wide range of phenotypes, possibly related to the different mutations of CSNK2B. Methods: Our multicentric, retrospective study recruited nine patients with POBINDS, detected using next-generation sequencing panels and whole-exome sequencing. Clinical, laboratory, and neuroimaging data were reported for each patient in order to assess the severity of phenotype, and eventually, a correlation with the type of CSNK2B mutation. Results: We reported nine unrelated patients with heterozygous de novo mutations of the CSNK2B gene. All cases presented epilepsy, and eight patients were associated with a different degree of intellectual disability. Other features detected included endocrinological and vascular abnormalities and dysmorphisms. Genetic analysis revealed six new variants of CSNK2B that have not been reported previously. Conclusion: Although it was not possible to assess a genotype–phenotype correlation in our patients, our research further expands the phenotype spectrum of POBINDS patients, identifying new mutations occurring in the CSNK2B gene.

Acquired mild cognitive impairment in adults with Down syndrome: Age-related prevalence derived from single point assessment data normed by degree of intellectual disability.

BackgroundIndividuals with Down syndrome (DS) are at significant risk for early onset Alzheimer's disease (AD), likely due to the triplication of genes on chromosome 21 that facilitate AD neuropathology. To aid the effective early diagnosis of dementia in DS, we demonstrate the strategy of using single point assessment of cognitive performance with scoring normed for degree of intellectual disability to generate age related prevalence data for acquired mild cognitive impairment (AMCI).MethodsFour hundred and twelve adults with DS were assessed using the Neuropsychological Assessment of dementia in adults with Intellectual Disability. Normative data, banded by degree of intellectual disability, allowed identification of AMCI by atypical deviation from expected performance.ResultsAMCI was evident in approximately 20% of adults with DS aged 40 and under, 40% aged 41–50 and 45% aged 51 and over. Relative risk increased significantly in those aged 46 and over. Analysis of prevalence by 5‐year age bands revealed two peaks for higher prevalence of AMCI.ConclusionsPsychometric data indicate single point assessment of AMCI is possible for the majority of adults with DS. Two peaks for age‐related prevalence of AMCI suggest the risk for onset of AD conferred by trisomy of chromosome 21 is moderated by another factor, possibly ApoE status.