Background
This study investigated the application of a newly developed neuropsychological assessment, the Wolfenbütteler Dementia Test for Individuals with Intellectual Disabilities (WDTIM) in ...combination with the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID).
Methods
The instruments were evaluated in a prospective 2‐year follow‐up study. A total of 102 people with an intellectual disability were assessed at 6‐month intervals. Data were analysed using qualitative and statistical analyses.
Results
Four groups of individuals emerged from the analysis: (1) confirmed suspicion, (2) no suspicion, (3) questionable suspicion and (4) early suspicion. Significant differences were found between groups 1 and 2. The WDTIM could be administered to 90%–100% of all participants exhibiting mild‐to‐moderate intellectual disability and to 50% with severe intellectual disability .
Conclusions
The WDTIM was shown to have good applicability to people with mild‐to‐moderate intellectual disability and to be appropriate for detecting cognitive changes. Using the two instruments in combination achieved greater accuracy in reinforcing a dementia suspicion than did using the DSQIID alone.
Kabuki syndrome (KS) is a clinically recognisable syndrome in which 70% of patients have a pathogenic variant in
or
. Understanding the function of these genes opens the door to targeted therapies. ...The purpose of this report is to propose diagnostic criteria for KS, particularly when molecular genetic testing is equivocal.
An international group of experts created consensus diagnostic criteria for KS. Systematic PubMed searches returned 70 peer-reviewed publications in which at least one individual with molecularly confirmed KS was reported. The clinical features of individuals with known mutations were reviewed.
The authors propose that a definitive diagnosis can be made in an individual of any age with a history of infantile hypotonia, developmental delay and/or intellectual disability, and one or both of the following major criteria: (1) a pathogenic or likely pathogenic variant in
or
; and (2) typical dysmorphic features (defined below) at some point of life. Typical dysmorphic features include long palpebral fissures with eversion of the lateral third of the lower eyelid and two or more of the following: (1) arched and broad eyebrows with the lateral third displaying notching or sparseness; (2) short columella with depressed nasal tip; (3) large, prominent or cupped ears; and (4) persistent fingertip pads. Further criteria for a probable and possible diagnosis, including a table of suggestive clinical features, are presented.
As targeted therapies for KS are being developed, it is important to be able to make the correct diagnosis, either with or without molecular genetic confirmation.
‘High functioning autism’ is a term often used for individuals with autism spectrum disorder without an intellectual disability. Over time, this term has become synonymous with expectations of ...greater functional skills and better long-term outcomes, despite contradictory clinical observations. This study investigated the relationship between adaptive behaviour, cognitive estimates (intelligence quotient) and age at diagnosis in autism spectrum disorder. Participants (n = 2225, 1–18 years of age) were notified at diagnosis to a prospective register and grouped by presence (n = 1041) or absence (n = 1184) of intellectual disability. Functional abilities were reported using the Vineland Adaptive Behaviour Scales. Regression models suggested that intelligence quotient was a weak predictor of Vineland Adaptive Behaviour Scales after controlling for sex. Whereas the intellectual disability group’s adaptive behaviour estimates were close to reported intelligence quotients, Vineland Adaptive Behaviour Scales scores fell significantly below intelligence quotients for children without intellectual disability. The gap between intelligence quotient and Vineland Adaptive Behaviour Scales scores remained large with increasing age at diagnosis for all children. These data indicate that estimates from intelligence quotient alone are an imprecise proxy for functional abilities when diagnosing autism spectrum disorder, particularly for those without intellectual disability. We argue that ‘high functioning autism’ is an inaccurate clinical descriptor when based solely on intelligence quotient demarcations and this term should be abandoned in research and clinical practice.
ObjectivesThis study explores the hospital journey of patients with intellectual disabilities (IDs) compared with the general population after admission for COVID-19 during the first wave of the ...pandemic (when demand on inpatient resources was high) to identify disparities in treatment and outcomes.DesignMatched cohort study; an ID cohort of 506 patients were matched based on age, sex and ethnicity with a control group using a 1:3 ratio to compare outcomes from the International Severe Acute Respiratory and emerging Infections Consortium WHO Clinical Characterisation Protocol UK.SettingAdmissions for COVID-19 from UK hospitals; data on symptoms, severity, access to interventions, complications, mortality and length of stay were extracted.InterventionsNon-invasive respiratory support, intubation, tracheostomy, ventilation and admission to intensive care units (ICU).ResultsSubjective presenting symptoms such as loss of taste/smell were less frequently reported in ID patients, whereas indicators of more severe disease such as altered consciousness and seizures were more common. Controls had higher rates of cardiovascular risk factors, asthma, rheumatological disorder and smoking. ID patients were admitted with higher respiratory rates (median=22, range=10–48) and were more likely to require oxygen therapy (35.1% vs 28.9%). Despite this, ID patients were 37% (95% CI 13% to 57%) less likely to receive non-invasive respiratory support, 40% (95% CI 7% to 63%) less likely to receive intubation and 50% (95% CI 30% to 66%) less likely to be admitted to the ICU while in hospital. They had a 56% (95% CI 17% to 102%) increased risk of dying from COVID-19 after they were hospitalised and were dying 1.44 times faster (95% CI 1.13 to 1.84) compared with controls.ConclusionsThere have been significant disparities in healthcare between people with ID and the general population during the COVID-19 pandemic, which may have contributed to excess mortality in this group.
One of the recently described syndromes emerging from the massive study of cohorts of undiagnosed patients with autism spectrum disorders (ASD) and syndromic intellectual disability (ID) is ...White-Sutton syndrome (WHSUS) (MIM #616364), caused by variants in the
gene (MIM *614787), located on the long arm of chromosome 1 (1q21.3). So far, more than 50 individuals have been reported worldwide, although phenotypic features and natural history have not been exhaustively characterized yet. The phenotypic spectrum of the WHSUS is broad and includes moderate to severe ID, microcephaly, variable cerebral malformations, short stature, brachydactyly, visual abnormalities, sensorineural hearing loss, hypotonia, sleep difficulties, autistic features, self-injurious behaviour, feeding difficulties, gastroesophageal reflux, and other less frequent features. Here, we report the case of a girl with microcephaly, brain malformations, developmental delay (DD), peripheral polyneuropathy, and adducted thumb-a remarkable clinical feature in the first years of life-and heterozygous for a previously unreported, de novo splicing variant in
. This report contributes to strengthen and expand the knowledge of the clinical spectrum of WHSUS, pointing out the importance of less frequent clinical signs as diagnostic handles in suspecting this condition.
To describe the outcome of Dravet syndrome (DS) in adolescents and adults we conducted a longitudinal retrospective study of two independent cohorts of 34 adolescents (group 1) and 50 adults (group ...2). In both cohorts, we collected information about genetic mutation, and semiology of seizures at onset and during disease course. At the last evaluation, we considered the following features: epilepsy (distinguishing myoclonic/complete and nonmyoclonic/incomplete phenotype), neurologic signs, intellectual disability (ID), and behavioral disorders. Moreover, in both cohorts, we performed a correlation analysis between early characteristics of the disease and the outcome of DS with regard to seizure persistence, ID, behavioral disorder, and neurologic impairment at last evaluation. Group 1 includes 22 adolescents with complete form of DS and 12 with incomplete form; group 2 includes 35 adults with complete form and 15 with incomplete form. The seizures persisted in 73.6% of adolescents and in 80% of adults, but epilepsy severity progressively decreased through age. Seizure persistence correlated with the complete phenotype and with the occurrence of reflex seizures. At last evaluation, ID was moderate or severe in 70.5% of adolescents and in 80% of adults. The most severe cognitive and motor impairment was observed in patients with persisting seizures. The severity of cognition, language, and neurologic impairment at last evaluation correlated statistically with the complete phenotype. The study confirms that the global outcome of DS is poor in most cases, albeit epilepsy severity decreases throughout adulthood. The improvement of epilepsy throughout ages is not associated with improvement in intellectual abilities and motor skills; this confirms that the unfavorable outcome is not a pure consequence of epilepsy.
Purpose
Recently, efforts have been made to quantify frailty among older adults with intellectual disability (ID). Medication exposure is associated with frailty among older adults without ID. ...However, there is little research on this association among older adults with ID. The aim of this study was to examine specifically in people with ID the association between frailty and medication exposure, including anticholinergic and sedative medication exposure.
Methods
Data were drawn from Wave 2 (2013/2014) of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS‐TILDA), a nationally representative study of older adults with ID in Ireland. A modified version of Fried's frailty phenotype was constructed. Drug burden measures were polypharmacy, Drug Burden Index (DBI), Anticholinergic Cognitive Burden (ACB) and Sedative Load Model. Multinomial logistic regression was used to calculate odds ratios (ORs) and identify associations between frailty and drug burden.
Results
This study included 570 participants with ID. Excessive polypharmacy (use of ≥10 medications) was significantly associated with being pre‐frail (P = .017; OR = 2.56; 95% confidence interval CI 1.19‐5.50) and frail (P < .001; OR 7.13; 95% CI 2.81‐18.12), but DBI, ACB or Sedative Load score were not significantly associated with frailty status (P > .05).
Conclusions
This is the first study to examine frailty and its association with medication use including anticholinergic and sedative medication burden among older adults with ID. Further research is required to investigate frailty as measured by other frailty models in relation to medication burden in older adults with ID.
The aim of this article is to present explicit and implicit attitudes of occupational therapy (OT) staff towards people with intellectual disabilities. The study was conducted on a group of 77 OT ...employees. To explore the explicit attitude, the Conditional Respect for Persons with Disabilities Questionnaire (Kurtek, Roczniki Psychologiczne, 2018, 4, 327–344) was used, while to estimate the implicit attitude, the Intellectual Disability Attitudes Implicit Association Test was applied (Kurtek, Roczniki Psychologiczne, 2021, 1, 43–64). At the explicit level, OT staff tended to tolerate negative and overrate positive behaviours of people with intellectual disabilities, which indicates a tendency to favour the individuals. However, the opposite devalorizing tendency was observed at the implicit dimension, which indicates aversive ableism. Although the study confirmed the independence of the two dimensions of the personnel's attitude, relationships were observed between the disclosure of negativity towards antagonistic behaviours of the people with intellectual disabilities and a decrease in the level of their implicit devaluation.
KDM4B (MIM*609765, NM_015015.3, formerly JMJD2B) encodes a histone demethylase and regulates gene expression via demethylation, mainly of H3K9 tri‐methylation. Heterozygous KDM4B loss‐of‐function ...variants cause autosomal dominant intellectual developmental disorder 65 (MIM#619320), which is characterized by global developmental delay, intellectual disability, language and gross motor delays, structural brain anomalies, characteristic facial features, and clinodactyly. Although the majority of reported patients have de novo pathogenic variants, some patients inherit pathogenic variants from affected parents. To our knowledge, only 23 patients with heterozygous KDM4B variants have been reported to date, and there are no reports of patients with biallelic KDM4B pathogenic variants. Herein, we report a female patient with a biallelic KDM4B frameshift variant (NM_015015.3: c.1384_1394delinsGGG, p.(Leu462Glyfs*43)) located at exon 12 of 23 protein‐coding exons, which is thought to be subject to nonsense‐mediated mRNA decay and no protein production. She presented developmental and language delays and a hypotonic and characteristic face. The patient's phenotype was more obvious than that of her mother, who is heterozygous for the same variant. Although declining birth rate (embryonic lethality in male mice) in homozygous knockout mice has been demonstrated, our report suggests that homozygous KDM4B frameshift variants can be viable in humans at least female.
We report a patient with a homozygous frameshift variant in KDM4B, who shows global developmental delay, severe speech impairment, and a hypotonic and characteristic face. Heterozygous pathogenic KDM4B variants have been known to cause intellectual developmental disorder, autosomal dominant 65, but this is the first report identifying homozygous KDM4B loss‐of‐function variant as far as we know.
SYNCRIP encodes for the Synaptotagmin‐binding cytoplasmic RNA‐interacting protein, involved in RNA‐binding and regulation of multiple cellular pathways. It has been proposed as a candidate gene for ...neurodevelopmental disorders (NDDs) with autism spectrum disorder (ASD), intellectual disability (ID), and epilepsy. We ascertained genetic, clinical, and neuroradiological data of three additional individuals with novel de novo SYNCRIP variants. All individuals had ID. Autistic features were observed in two. One individual showed myoclonic‐atonic epilepsy. Neuroradiological features comprised periventricular nodular heterotopia and widening of subarachnoid spaces. Two frameshift variants in the more severely affected individuals, likely result in haploinsufficiency. The third missense variant lies in the conserved RNA recognition motif (RRM) 2 domain likely affecting RNA‐binding. Our findings support the importance of RRM domains for SYNCRIP functionality and suggest genotype‐phenotype correlations. Our study provides further evidence for a SYNCRIP‐associated NDD characterized by ID and ASD sporadically accompanied by malformations of cortical development and myoclonic‐atonic epilepsy.
PDF
