Severe Intellectual Disability Research Articles

The Clinical and Molecular Spectrum of Trichorhinophalangeal Syndrome Types I and II in a Turkish Cohort Involving 22 Patients.

Trichorhinophalangeal syndrome is a rare autosomal dominant disorder characterized by distinctive craniofacial and skeletal abnormalities. This study aimed to delineate the trichorhinophalangeal syndrome phenotype and to compare the clinical and molecular findings between trichorhinophalangeal syndrome types I and II. A total of 22 trichorhinophalangeal syndrome patients aged 0.9-45 years from 17 families were enrolled. Nineteen patients were diagnosed with trichorhin ophalangeal syndrome I and 3 with trichorhinophalangeal syndrome II. Genetic analyses were made by TRPS1 sequencing and/or chromosomal microarray analyses. A novel frameshift variant (c.531_532del), a known missense variant, and whole-gene deletions were the pathogenic TRPS1 variants detected in trichorhinophalangeal syndrome I. Three trichorhinophalangeal syndrome II patients had large deletions with variable breakpoints involving the TRPS1-EXT1 interval. All patients had the typical craniofacial findings of trichorhinophalangeal syndrome such as a pear-shaped nose, long philtrum, and thin upper lip, as well as cone-shaped epiphyses. Sparse hair and eyebrows (20/22), short metacarpals and metatarsals (20/22), and small hands (19/22) were common. While craniofacial and limb abnormalities were similar in trichorhinophalangeal syndrome I and II, 3 of 19 trichorhinophal angeal syndrome I patients had mild, and 2 of 3 trichorhinophalangeal syndrome II patients had severe intellectual disability. Three trichorhinophalangeal syndrome II patients including the patient with the EXT1 deletion beginning from exon 2 had exostoses. In trichorhinophal angeal syndrome II, although microdeletion sizes and facial or skeletal features were not correlated, patients with larger deletions had severe intellectual disability. This study has expanded the existing knowledge on the phenotype-genotype spectrum in trichorhinophalangeal syndrome. We suggest including the EXT1 gene partially in the minimal critical region for trichorhinophalangeal syndrome II.

Surgery for acute abdomen in adult patients with severe motor and intellectual disabilities.

The present study aimed to examine the characteristics, outcomes, and problems related to surgery for acute abdomen in adult patients with severe motor and intellectual disabilities (MID). The clinical records of 35 adult patients with severe MID who received emergency surgery for acute abdomen between 2011 and 2020 were reviewed. The median duration from onset to surgery was 48 hours. There were 2 cases of in-hospital mortality (5.7%), and all the patients underwent surgery more than 72 hours after onset. The in-hospital mortality rate was significantly higher in patients who received surgery later than 72 hours after onset. Bowel obstruction was the most common disease among the acute abdomen cases (71.4%) and most often involved volvulus of the small bowel and cecum. Of the patients with bowel obstruction with severe MID, 72.0% had abdominal distention, 16.0% had abdominal pain, and 4.0% had vomiting. The median duration from onset to surgery was significantly longer in the patients with bowel obstruction with severe MID than in those without severe MID (24 hours vs. 16 hours). Acute abdomen in patients with severe MID was often due to bowel obstruction caused by volvulus. Because patients with severe MID have few symptoms, they are susceptible to adverse surgical outcomes associated with a prolonged duration from onset to surgery.

Autonomy of adults with intellectual disabilities. A comparative perspective

The main purpose of the research was to determine the level of autonomy of adults with more severe intellectual disabilities (N = 133) living in different environment. The perspective of adults living with their parents (N = 62), residents of nursing homes (N = 40) and residents of LArche homes (N = 31) was considered. The age of the respondents ranged from 18 to 68 years (M = 38.82; SD = 12.71). The diagnostic survey method was used. In order to collect the necessary data, the authors Interview questionnaire with an adult with intellectual disabilities was used. The nonparametric Kruskal-Wallis test and multiple comparison tests (post hoc) were used in the analysis. The obtained results indicate that adults with intellectual disabilities living with their parents, as well as residents of LArche homes have a significantly higher level of autonomy than residents of nursing homes.

Effects of valproate on seizure-like activity in Drosophila melanogaster with a knockdown of Ube3a in different neuronal populations as a model of Angelman Syndrome

Angelman Syndrome is a rare, genetically induced neurodevelopmental disorder. This disorder stems from a mutation or deletion of the maternal UBE3A gene. Characteristics of this disease include developmental delay, recurring seizures, and severe intellectual disabilities. We studied seizure activity in male Drosophila melanogaster with a knockdown of Ube3a in different neuronal populations (GABAergic, glutamatergic, mushroom body, and all neurons) and investigated the effects of the antiseizure medication (ASM) on seizure-like activity. Epileptiform activity was monitored in individual fruit flies using imaging chambers and mechanically induced seizures using a vortex assay. A positive control was also used: eas (easily shocked seizure phenotype). Seizure activity was analyzed for sums of seizure durations, number of seizures, and total time to return to normal activity.Ube3a knockdowns in GABAergic neurons elicited more seizure-like episodes than knockdowns in glutamatergic neurons and were on par with the positive control group and those with knockdowns in the mushroom bodies. We have established a method whereby valproate could be administered through food rather than through injections to effectively treat epileptiform activity. We demonstrated that if Ube3a is not knocked down pan-neuronally, Angelman Syndrome seizure-like activity can be studied using Drosophila melanogaster and therefore allows for high-throughput drug discovery.

Characteristics and Challenges of Epilepsy in Children with Cerebral Palsy—A Population-Based Study

The aim of this population-based study was to describe the prevalence and characteristics of epilepsy in children with cerebral palsy (CP), focusing on antiseizure medication (ASM) and seizure outcome. Findings were related to CP type, gross motor function and associated impairments. Data on all 140 children with CP born in 2003-2006 were taken from the CP register of Western Sweden. Medical records were reviewed at ages 9-12 and 13-16 years. In total 43% had a diagnosis of epilepsy. Epilepsy was more common in children with dyskinetic CP, who more often had a history of infantile spasms, continuous spike-and-wave during sleep and status epilepticus. Neonatal seizures, severe intellectual disability, severe motor disability and autism were associated with a higher risk of epilepsy. Many children were on polytherapy, and valproate was frequently used, even in girls. At age 13-16 years, 45% of the children with epilepsy were seizure free for at least one year. Onset after 2 years of age, female sex and white matter injury were associated with good seizure outcome. Despite the risk of relapse, reduction or discontinuation of ASM could be an option in selected cases. It is important to optimize ASM and to consider the possibility of epilepsy surgery.

A Case of Surgical Closure of the Larynx (Kano’s Method) After Cricoid Fenestration for Children with Severe Motor and Intellectual Disabilities

A Case of Surgical Closure of the Larynx (Kano’s Method) After Cricoid Fenestration for Children with Severe Motor and Intellectual Disabilities

Family Quality of Life in Children with Severe or Profound Disability: Home Versus Residential Care.

Most children with severe and profound intellectual disability (SPID) are cared for in their homes, according to current recommendations. Yet, their families face marked emotional, health, and economic challenges. The aim of this study was to examine family quality of life (FQOL) along with psychological and health factors among families who raise children with SPID at home versus those residing in residential care. Sixty caregivers of children aged 2 to 18 years (M = 8.81, SD = 4.62) with SPID (developmental quotient/intellectual quotient <35), living at home (38 caregivers-"home group") or in residential care (22 caregivers-"residential group"), completed the FQOL Survey, Beck Depression Inventory, Parental Stress Index, Shame and Guilt Scale, and Health and Demographic questionnaires. FQOL for most domains and dimensions was rated better among families whose child resides in residential care compared with families who raise their child at home. Similarly, parental stress relating to the child was worse among families who raise their children at home. No significant differences between the 2 groups were noted on other psychological or health measures. Family and individual needs for those raising a child with SPID at home should be addressed when planning policy and interventions.

Evaluation of eGFRs to Calculate Kidney Function in Adults with Severe Motor and Intellectual Disabilities

Evaluation of eGFRs to Calculate Kidney Function in Adults with Severe Motor and Intellectual Disabilities

Full Mouth Rehabilitation of a Child with Aicardia-Goutières: A Rare Syndrome

Aicardi-Goutières Syndrome (AGS) is a rare genetic disorder with autosomal recessive inheritance. AGS is characterised by an earlyonset encephalopathy that usually, but not always, results in severe intellectual and physical disability. Involuntary muscular spasms between the ages of four months and four years are the typical starting point for Aicardi syndrome. Hepatosplenomegaly, increased liver enzymes, thrombocytopenia, and abnormal neurologic signs in a subgroup of AGS children at birth strongly imply congenital infection. Agenesis of the corpus callosum, chorioretinal lacunae, and seizures are all symptoms of Aicardi syndrome. They frequently exhibit the subacute onset of a severe encephalopathy that is characterised by intense irritability, sporadic sterile pyrexias, loss of abilities, and slowed head growth. In 40% of cases, skin lesions like chilblains can appear on the fingers, toes, and ears. This disease can be diagnosed with Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) scans with the appearance of calcification of the basal ganglia. The associated behavioral challenges with syndromic patients demand pharmacological management of oral rehabilitation. The literature is scarce regarding the oral manifestations of this syndrome. Hence, authors present the successful fullmouth rehabilitation of severe Early Childhood Caries (ECC) in a 3-year-old child with AGS under General Anaesthesia (GA).

Kreowanie upośledzonej tożsamości Innego w środowisku edukacyjnym (psychiatryzowanie)

The aim of the article, based on a qualitative study, is to identify and interpret the meanings parents assign to messages conveyed by school personnel about the behavior of students with moderate and severe intellectual disabilities coupled with autism. The main research objective is to present the mechanism of impairment of the identity of pupils in special education, known as psychiatricization. The phenomenon of psychiatricization occurs in situations where school staff abuse and misinterpret the behaviour of people with intellectual disabilities, looking for mental illness in the behaviours they present. One of the reasons for this phenomenon is the misunderstood, behavioural-coded communication of pupils perceived as mentally ill by teachers who are convinced they should be diagnosed and treated with appropriate psychotropic drugs in order to subdue and quieten the awkward pupil. A consequence of the activities and discourse of school staff, i.e. psychiatricization, including stigmatization, harm, abuse of power-knowledge, is falsifying the identity of students, depriving them of opportunities and opportunities for optimal development and satisfying their special educational needs. The presented qualitative research is located in the constructivistinterpretative paradigm, and the mainstream of the scientific narrative is the critical theory.

P212: A familial case of CAMK2B mutation: Two brothers with severe intellectual disability inherited from healthy father

P212: A familial case of CAMK2B mutation: Two brothers with severe intellectual disability inherited from healthy father

До питання про тяжкий ступінь порушення інтелектуального розвитку

The article analyzes the peculiarities of theтpsychophysical development of children with severe intellectual disabilities. In Ukraine, there are four degrees of persistent intellectual development disorders, and one of the conditions for assigning a child to one of them is the determination of the intellectual quotient (IQ) based on conducting standardized tests of mental abilities. However, at the same time, the quantitative determination of the degree of intellectual disability does not reflect the entire structure of the disorder and the features of clinical manifestations. Emphasis is placed on such mental processes as thinking, speech, attention, memory, perception, and reflection. Particular attention is focused on these children's emotional and motivational spheres and the development of the motor and kinesthetic spheres. At the same time, their psychophysical development directly affects the formation of socially valuable behavioral qualities and the formation of their sphere. The problems that exist in psychophysical development and that are caused by significant negative organic influences have a direct impact on the educational process,on the process of transmitting socially significant information, and, accordingly, its receipt by children with a severe degree of intellectual impairment. Organizing the educational process for children with severe intellectual disabilities, like for those with neurotypical development, is practically impossible. However, at the same time, the training conducted with them gives positive results in their development, allowing them to form the skills and habits necessary in the social environment. It positively affects their psychophysical development, improving it and making it, to a certain extent, appropriate to the social conditions in which such a person will live. Nevertheless, they cannot live independently.

Hemispherotomy in Infants with Hemimegalencephaly: Long-Term Seizure and Developmental Outcome in Early Treated Patients.

Hemimegalencephaly (HME) is a rare brain congenital malformation, consisting in altered neuronal migration and proliferation within one hemisphere, which is responsible for early onset drug-resistant epilepsy. Hemispherotomy is an effective treatment option for patients with HME and drug-resistant epilepsy. Surgical outcome may be variable among different surgical series, and the long-term neuropsychological trajectory has been rarely defined using a standardized neurocognitive test. We report the epileptological and neuropsychological long-term outcomes of four consecutive HME patients, operated on before the age of three years. All patients were seizure-free and drug-free, and the minimum follow-up duration was of five years. Despite the excellent post-surgical seizure outcome, the long-term developmental outcome is quite variable between patients, ranging from mild to severe intellectual disabilities. Patients showed improvement mainly in communication skills, while visuo-perceptive and coordination abilities were more impaired. Epileptological outcome seems to be improved in early treated patients; however, neuropsychological outcome in HME patients may be highly variable despite early surgery.

Ap4b1-knockout mouse model of hereditary spastic paraplegia type 47 displays motor dysfunction, aberrant brain morphology and ATG9A mislocalization.

Mutations in any one of the four subunits (ɛ4, β4, μ4 and σ4) comprising the adaptor protein Complex 4 results in a complex form of hereditary spastic paraplegia, often termed adaptor protein Complex 4 deficiency syndrome. Deficits in adaptor protein Complex 4 complex function have been shown to disrupt intracellular trafficking, resulting in a broad phenotypic spectrum encompassing severe intellectual disability and progressive spastic paraplegia of the lower limbs in patients. Here we report the presence of neuropathological hallmarks of adaptor protein Complex 4 deficiency syndrome in a clustered regularly interspaced short palindromic repeats-mediated Ap4b1-knockout mouse model. Mice lacking the β4 subunit, and therefore lacking functional adaptor protein Complex 4, have a thin corpus callosum, enlarged lateral ventricles, motor co-ordination deficits, hyperactivity, a hindlimb clasping phenotype associated with neurodegeneration, and an abnormal gait. Analysis of autophagy-related protein 9A (a known cargo of the adaptor protein Complex 4 in these mice shows both upregulation of autophagy-related protein 9A protein levels across multiple tissues, as well as a striking mislocalization of autophagy-related protein 9A from a generalized cytoplasmic distribution to a marked accumulation in the trans-Golgi network within cells. This mislocalization is present in mature animals but is also in E15.5 embryonic cortical neurons. Histological examination of brain regions also shows an accumulation of calbindin-positive spheroid aggregates in the deep cerebellar nuclei of adaptor protein Complex 4-deficient mice, at the site of Purkinje cell axonal projections. Taken together, these findings show a definitive link between loss-of-function mutations in murine Ap4b1 and the development of symptoms consistent with adaptor protein Complex 4 deficiency disease in humans. Furthermore, this study provides strong evidence for the use of this model for further research into the aetiology of adaptor protein Complex 4 deficiency in humans, as well as its use for the development and testing of new therapeutic modalities.

Whole-Exome Sequencing of Pakistani Consanguineous Families Identified Pathogenic Variants in Genes of Intellectual Disability.

Intellectual disability (ID) is a condition of significant limitation of cognitive functioning and adaptive behavior, with 50% of etiology attributed to genetic predisposition. We recruited two consanguineous Pakistani families manifesting severe ID and developmental delay. The probands were subjected to whole exome sequencing (WES) and variants were further prioritized based on population frequency, predicted pathogenicity and functional relevance. The WES data analysis identified homozygous pathogenic variants in genes MBOAT7 and TRAPPC9. The pathogenicity of the variants was supported by co-segregation analysis and in silico tool. The findings of this study expand mutation spectrum and provide additional evidence to the role of MBOAT7 and TRAPPC9 in causation of ID.

PARK2 microdeletion in a multiplex family with Autism Spectrum Disorder.

PARK2 (PRKN; MIM*602544) encodes Parkin protein, an ubiquitin-protein ligase required for proteasomal degradation and operating in the synaptic compartments. Copy Number Variations (CNV) involving PARK2 have been associated with autism spectrum disorder (ASD). We report on a family with ASD (multiplex family) harbouring a microdeletion at chr. 6q26 causing PARK2 disruption. CNV analyses was performed using CGH/SNP-array platforms and the detected microdeletion was confirmed by real-time quantitative PCR. Standardized psychometric evaluation was used for neurobehavioral characterization. We found an intragenic ~ 157 kb microdeletion of the chromosomal region 6q26 causing PARK2 disruption in two male sibs with ASD and syndromic phenotype. They both had dysmorphic facial features with coarse faces, deeply set eyes with long horizontal palpebral fissures, long eyelashes and thick eyebrows, fleshy lips, and mild skeletal problems. We found an intra-familial clinical heterogeneity owing to different severity of the autism symptoms between the affected sibs: the younger one had minimally verbal autism and severe intellectual disability while his older brother presented high-functioning autism and preserved speech. Parental analysis and real-time PCR using a PRKN fragment mapping within the deletion demonstrated that the deletion was inherited from their father having subthreshold features of ASD consisting with broad autism phenotype. The study corroborates the hypothesis that PARK2 aberrations may be associated with ASD and highlights correlations between CNV affecting PARK2 and ASD in a multiplex family. We show remarkable intrafamilial variability in the severity of inherited ASD associated with PARK2 microdeletion.

Depressive symptoms, social support, cognitive function, and stigma: predictors of resilience in caregivers of children with intellectual disabilities

Abstract Objective: Family plays an important role in taking care of children with intellectual disabilities (IDs). Resilience supports coping strategies for caregivers with their children caring. However, factors influencing the resilience of caregivers with ID in Thailand are yet to be identified. Therefore, the aim of this study was to identify the predictors of resilience in caregivers of children with moderate to severe ID. Methods: A cross-sectional study was implemented in caregivers of children with ID aged 18 years and older who had children diagnosed with ID aged 6–18 years and classified as moderate to severe ID. Descriptive statistic and multiple linear regression were used for data analysis. Results: The study sample consisted of 85 caregivers who took care of their children older than 5 years (95.30%). Depression, social support, cognitive function, and stigma could predict the resilience (F [4, 80] = 26.79, P &lt; 0.001) and explain the variability of resilience by 57.3%. Conclusions: Caregivers have to take care of their children for a long period, which could develop a burden to the caregivers. The resilience and influencing factors should be monitored and managed by developing a campaign to promote caregivers’ health and well-being.

More than a Physical Problem: The Effects of Physical and Sensory Impairments on the Emotional Development of Adults with Intellectual Disabilities.

With the introduction of the ICD-11 and DSM-5, indicators of adaptive behavior, including social-emotional skills, are in focus for a more comprehensive understanding of neurodevelopmental disorders. Emotional skills can be assessed with the Scale of Emotional Development-Short (SED-S). To date, little is known about the effects of physical disorders and sensory impairments on a person's developmental trajectory. The SED-S was applied in 724 adults with intellectual disabilities, of whom 246 persons had an additional physical and/or sensory impairment. Ordinal regression analyses revealed an association of movement disorders with more severe intellectual disability and lower levels of emotional development (ED) on the overall and domain levels (Others, Body, Material, and Communication). Visual impairments predicted lower levels of ED in the SED-S domains Material and Body, but not the overall level of ED. Hearing impairments were not associated with intellectual disability or ED. Epilepsy correlated only with the severity of intellectual disability. Multiple impairments predicted more severe intellectual disabilities and lower levels of overall ED. In conclusion, physical and sensory impairments may not only affect physical development but may also compromise intellectual and emotional development, which should be addressed in early interventions.

Preferred outcome measures in treatments for challenging behaviour in individuals with intellectual disabilities: Results of an inclusive Delphi method.

Interventions for challenging behaviours in individuals with intellectual disabilities benefit from outcome monitoring that takes clients' preferences into account. We determined clients' and representatives' preferred outcome domains and measures to secure their involvement in treatment decisions for challenging behaviours. We used an inclusive Delphi method. A focus group of individuals with mild intellectual disabilities and representatives of those with moderate and severe intellectual disabilities prepared the first round by assisting us in collecting possible outcomes. Panels of individuals with intellectual disabilities and representatives were composed to achieve consensus on instruments for preferred outcome domains. Preferred outcome domains were behaviour, side-effects of psychotropic drugs, quality of life, daily functioning, caregiver burden and family quality of life. Corresponding outcome measures included self-report, interview and proxy-scales, including spoken versions. Including the preferred domains on outcomes of interventions for challenging behaviours is recommended. Research on corresponding outcome measures is necessary.

Intellectual functioning and adaptive behaviour in children with Dravet syndrome: A population-based study.

To identify, on a population basis, the prevalence of intellectual disability in children with Dravet syndrome, profiles on a measure of adaptive behaviour, and factors associated with intellectual functioning and adaptive behaviour. Forty-two out of 48 children with Dravet syndrome living in Sweden, born between 1st January 2000 and 31st December 2018, underwent assessment of intellectual functioning and adaptive behaviour. Factors associated with level of intellectual functioning and adaptive behaviour were analysed. Eight-six per cent (n= 36) of the children fulfilled DSM-5 criteria for intellectual disability (29% [n= 12] mild intellectual disability, 24% [n= 10] moderate intellectual disability, 33% [n= 14] severe intellectual disability, 0% profound intellectual disability) and 93% (n= 39) had an adaptive behaviour composite more than two standard deviations below the mean. Communication was a significant weakness compared with daily living skills (p< 0.001; mean difference 95% confidence interval [CI] -8.193 to -4.092) and socialization (p= 0.001; mean difference 95% CI 6.511 to -1.775) on the Vineland Adaptive Behavior Scales, Second Edition. The only factors significantly associated with both decreased adaptive behaviour and presence of severe intellectual disability was the presence of increased autistic symptoms and younger age. Children with Dravet syndrome have a very high level of intellectual disability and almost all have significant deficits in adaptive behaviour. Greater deficits in adaptive behaviour and greater severity of intellectual disability are associated with the presence of increased autistic symptoms, highlighting the need for comprehensive neurodevelopmental assessment for all affected children. Eighty-six per cent (n=36) of children with Dravet syndrome fulfilled criteria for intellectual disability. Ninety-three per cent (n=39) of children with Dravet syndrome had significant deficits in adaptive behaviour. Communication was a significant weakness on a measure of adaptive behaviour. Increased autistic symptoms were associated with greater deficits in cognition/adaptive behaviour. Older age and earlier status epilepticus were associated with decreased adaptive behaviour.