Different Degrees Of Intellectual Disability Research Articles

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.

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.

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.

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.

Rethinking Intellectual Disability from Neuro- to Astro-Pathology.

Neurodevelopmental disorders arise from genetic and/or from environmental factors and are characterized by different degrees of intellectual disability. The mechanisms that govern important processes sustaining learning and memory, which are severely affected in intellectual disability, have classically been thought to be exclusively under neuronal control. However, this vision has recently evolved into a more integrative conception in which astroglia, rather than just acting as metabolic supply and structural anchoring for neurons, interact at distinct levels modulating neuronal communication and possibly also cognitive processes. Recently, genetic tools have made it possible to specifically manipulate astrocyte activity unraveling novel functions that involve astrocytes in memory function in the healthy brain. However, astrocyte manipulation has also underscored potential mechanisms by which dysfunctional astrocytes could contribute to memory deficits in several neurodevelopmental disorders revealing new pathogenic mechanisms in intellectual disability. Here, we review the current knowledge about astrocyte dysfunction that might contribute to learning and memory impairment in neurodevelopmental disorders, with special focus on Fragile X syndrome and Down syndrome.

Danon disease: Two patients with atrial fibrillation in a single family and review of the literature.

The present study reports on a family with two members affected by Danon disease but having different phenotypes. The clinical manifestations of Danon disease include cardiomyopathy, skeletal myopathy and different degrees of intellectual disability that varies greatly among patients. The present case study reports on two siblings, an older sister and a younger brother, with Danon disease from an affected pedigree, presenting with distinctly different phenotypes. The sister was diagnosed with dilated cardiomyopathy at the age of 26 years with an unfavorable outcome, while her younger brother presented with hypertrophic cardiomyopathy in a relatively stable state. The two probands shared the same mutation, c.974delTinsAA in exon 8, in the lysosomal-associated membrane protein-2 gene. Of note, the two patients had a pre-excitation pattern in the electrocardiogram on initial presentation and later developed atrial fibrillation (AF), which markedly aggravated heart failure. To the best of our knowledge, AF has not been widely reported in patients with Danon disease. The development of AF may have a prognostic value under these circumstances.

Video electroencephalogram analysis of 100 cases of intellectual disability children with unexplained pathogenic factor

Objective To observe 100 video-electroencephalogram (EEG)-cases of intellectual disability (ID) children, to analyze their EEG features of different degrees of ID, to explore the relationship between EEG changes and ID. Methods We performed a retrospective analysis of long-range video-EEGs of 100 children with an unexplained reason of ID from July 2016 to May 2018 in the department of pediatrics of Xiangya Hospital of Central South University, summarized their EEG manifestations, and compared their differences among different degrees of ID. We carried out χ2 test according to the degree of ID, and discussed the relationship between the degree of ID and EEG. Results Among 100 cases of ID children with unexplained pathogenic factor, 67 cases (67%) of them were males, 33 cases (33%) of females, 38 cases (38%)of mild ID, 27 cases (27%) of moderate ID and 35 cases (35%) of severe ID. The EEG background of ID patients showed fast waves (11%), slow waves (15%), generalized discharges (14%) and focal discharges (36%), etc. Focal sharp and spike-wave were the most common in children with moderate ID, while background changes and multifocal sharp spike wave were more common in severe ID children. Conclusions The EEG background changes in children with severe ID have significant differences than mild and moderate degree ones. The specific features of EEG in mild and moderate degree ones is focal discharges, while multiple discharges in severe ID patients. Changes in the EEG may be related to the extent of intellectual disability. Key words: Mental retardation; Electroencephalography; Child

3q29 microdeletion syndrome: Cognitive and behavioral phenotype in four patients

The 3q29 microdeletion syndrome is a rare, recurrent genomic disorder, associated with a variable phenotype, despite the same deletion size, consisting in neurodevelopmental features, such as intellectual disability (ID), schizophrenia, autism, bipolar disorder, depression and mild facial morphological anomalies/congenital malformations. A thorough neuropsychiatric evaluation has never been reported in patients with such syndrome. We analyzed the clinical phenotype of four individuals with 3q29 microdeletion syndrome, with special emphasis on the cognitive and behavioral assessment, in order to delineate the neuropsychiatric phenotype related to this condition. We assessed these patients with standardized scales or checklists measuring the cognitive (WISC III or LIPS-R), behavioral (CBCL) and adaptive (VABS) performances. An accurate evaluation in our sample highlights different degrees of ID, variable behavioral disorders, and a preservation of communicative skills among remaining adaptive areas, as the neuropsychiatric hallmark of 3q29 microdeletion syndrome.

Identifying Microdeletion Syndromes in Patients with Intellectual Disability Using Molecular Genetic Testing: An Example for the Brazilian Public Health Care System

Unexplained intellectual disability is a clinical situation in which molecular diagnostic techniques should be indicated. The diagnostic yield of Multiplex Ligation-dependent Probe Amplification (MLPA) in a cohort of patients with intellectual disability and dysmorphic features was investigated to identify microdeletion syndromes. We aimed to provide an example of the utilization of MLPA method in the medical care routine that can be useful for planning the inclusion of molecular genetic testing in the Brazilian public health care system. This study was based on 57 patients who had different degrees of intellectual disability with etiology not determined. All patients had normal brain CT scan or MRI and normal karyotype, and patients with environmental damage history were not included. Two of the 57 patients were referred to molecular genetic testing as they were clinically diagnosed as having Williams syndrome. MLPA test costs were calculated (human resources and equipment costs were not included in the calculation). MLPA revealed chromosomal imbalance in 4 out of 57 patients (7%). These imbalances were associated with well-described microdeletion syndromes: 3 patients had Williams syndrome (1 without clinical diagnosis) and 1 patient had 22q11.21 deletion syndrome. The MLPA analysis cost per individual, considering DNA extraction and laboratory reagents, was US$66.40. In this study, MLPA confirmed its value as a promising technique as it has adequate feasible characteristics to identify microdeletion syndromes in patients who had unexplained intellectual disability. This work suggests that MLPA can be a viable alternative to implement molecular genetic testing in the Brazilian public health care system, considering its cost-effectiveness.

Working memory functions in children with different degrees of intellectual disability

In recent years, there has been increased research interest in the functioning of working memory in people with intellectual disabilities. Although studies have repeatedly found these individuals to have weak working memory skills, few investigations have distinguished between different degrees of intellectual disability. This study aims to help close this research gap and, in so doing, to examine whether the deficits observed reflect a developmental lag or a qualitative deviation from normal development. In a 5-group design, the working memory performance of a group of 15-year-olds with mild intellectual disability (IQ 50-69) was compared with that of two groups of children (aged 10 and 15 years) with borderline intellectual disability (IQ 70-84) and with that of two groups of children with average intellectual abilities (IQ 90-115) matched for mental and chronological age (aged 7 and 15 years). All children were administered a comprehensive battery of tests assessing the central executive, the visual-spatial sketchpad, and the phonological loop. The results showed deficits in all three components of working memory, and revealed that these deficits increased with the degree of intellectual disability. The findings indicate that, relative to their mental age peers, children with learning difficulties show structural abnormalities in the phonological store of the phonological loop, but developmental lags in the other two subsystems. Similar patterns of results emerged for both subgroups of children with intellectual disability, indicating that problems with phonological information processing seem to be one of the causes of cognitive impairment in individuals with intellectual disability.

Calidad de vida relacionada con la salud en personas con discapacidad intelectual en España

To measure health-related quality-of-life (HRQL) among people with intellectual disabilities in the province of Salamanca, Spain.A population-based, cross-sectional descriptive study. The SF-36 Health Survey, adapted and validated for the Spanish population, was selected and administered to 265 people with intellectual disabilities in the province of Salamanca, Spain. Personal interviews were also conducted with the participants in the presence of their parents, tutors, or close family. Eight quality-of-life scales were explored: general health, physical functioning, role-physical, bodily pain, role-emotional, social functioning, vitality, and mental health, based on questions on sociodemographic and lifestyle variables, health services utilization, support needs, and health status and HRQL.Of the 265 people studied, 69.8% were men and 30.2% were women (median age: 35 years; minimum: 16; maximum: 72). The highest number of points pertained to role-physical and physical functioning (more than 85 points), and the lowest, to general health and vitality (less than 70 points). No significant differences were found between men and women for any of the eight components. The independent variables, age, family income, level of education, and support needs showed the greatest number of independent associations with the general health, physical functioning, and social functioning components. Of the participants, 41.5% indicated that they felt their health was good.The study participants perceived their HRQL to be good, especially on the role-physical and physical functioning scales. Additional studies should be designed to evaluate HRQL in people with different degrees of intellectual disability to further contribute to intervention efforts and health and social programs designed specifically for this population group and to evaluate the interventions and program already underway.

Long-term course of epilepsy in a large cohort of intellectually disabled patients

This study was designed to describe the course of epilepsy (in terms of seizure frequency) and to assess the variables (antiepileptic therapy regimens and others) correlated to improvement. Seizure frequency (categories: seizure free, more than one seizure/year, monthly seizures, weekly seizures and daily seizures) and antiepileptic medication were retrospectively compared between 1992 and 2002 in a large cohort of 550 inpatients with chronic epilepsy and different degrees of intellectual disability or multiple handicaps. Seizure frequency decreased significantly (p<0.001). 218 of the 394 patients (55.3%) not seizure free in 1992 improved (changed into a better frequency category). The improvement rate was marginally higher in patients who had undergone a medication change (p=0.08). A high seizure frequency in 1992 (p=0.016) and older age (p=0.006), but not epilepsy syndrome or degree of intellectual disability, were predictors for improvement (stepwise logistic regression analysis). 56.4% of the improved patients were on combinations of two AEDs (17.4%, monotherapy; 20.2%, triple therapy). The most frequent therapy regimens in the improved patients were lamotrigine/valproate (48 patients), carbamazepine/phenobarbital (21) and carbamazepine only (19). Lamotrigine/valproate was effective in all kinds of epileptic syndromes. Most patients on lamotrigine had serum concentrations above 10microg/ml, approximately one half had dosages above 200mg/day. The rate of seizure freedom increased from 28.4 to 37.6%. The 84% of the patients seizure free in 1992 remained seizure free. Predictors for seizure freedom in 2002 were higher age (stepwise logistic regression, p<0.0005) and seizure freedom in 1992 (p<0.0005). Substantial improvement can be achieved even in intellectually disabled patients with chronic epilepsy. Although the rate of seizure freedom is reduced in comparison with a non-ID population, once seizure freedom has been achieved it is most likely to continue. For a majority of this patient population, monotherapy may not be sufficient. Lamotrigine/valproate appears to be a major therapeutic innovation.

What am I doing in Timbuktu: person–environment picture recognition for persons with intellectual disability

The aim of this study was to examine the effects of familiarity of depicted persons and environments in recognition of photographs for pupils with different degrees of intellectual disability (ID). Forty-five pupils with ID participated. An interaction effect between the two variables, person and environment, was found in addition to main effects for both the variables. Pictures of the test person himself or herself in familiar environments were easier to recognize than in unfamiliar environments, whereas the opposite was found for pictures of other familiar persons. No interaction effects of degree of ID were found. The interaction pattern is explained in terms of absent, present or implausible semantic associations between the person and the environmental context. The results are discussed in relation to augmentative and alternative communication with photographs.

Self‐Injury and Präder–Willi Syndrome

Abstract Präder–Willi syndrome (PWS) is predominantly a genetic disorder resulting from the absence of normally active paternally expressed genes from the 15q11–q13 chromosome region. The principal characteristics are developmental psychomotor delay, generalized hypotonia, intellectual delay, behavioral and emotional problems, hyperphagia, and consequent obesity. There are frequent problems in the emotional affective sphere, with significant emotional instability, irascibility, scarce tolerance to frustrations, rigidity of thoughts, repetitive behaviors, and self‐injury. This study evaluated self‐injurious behaviors (SIBs) prevalent among persons with PWS, by their localization in relation to different degrees of intellectual disability, and their evolution in time by using a specially designed interview questionnaire with families and providers. The subjects were drawn from referrals to the Diagnostic and Rehabilitation Departments of the OASI Institute, Troina, Italy and consisted of the 15 known persons with PWS (7 males; 8 females) residing in Sicily (Italy). SIBs were found in 73% of the subjects, and the body areas most affected were hands, arms, and legs. The most frequent SIB observed was skin‐picking (64%). Our data substantially agree with what has been reported in the literature, although we found slightly lower rates of SIBs in the Sicilian sample.