Impaired Intellectual Functioning Research Articles

Comparative Transcriptomics Data Profiling Reveals E2F Targets as an Important Biological Pathway Overexpressed in Intellectual Disability Disorder.

Intellectual disability (ID) is an early childhood neurodevelopmental disorder that is characterized by impaired intellectual functioning and adaptive behavior. It is one of the major concerns in the field of neurodevelopmental disorders across the globe. Diversified approaches have been put forward to overcome this problem. Among all these approaches, high throughput transcriptomic analysis has taken an important dimension. The identification of genes causing ID rapidly increased over the past 3 to 5 years owing to the use of sophisticated high throughput sequencing platforms. Early monitoring and preventions are much important for such disorder as their progression occurs during fetal development. This study is an attempt to identify differentially expressed genes (DEGs) and upregulated biological processes involved in development of ID patients through comparative analysis of available transcriptomics data. A total of 7 transcriptomic studies were retrieved from National Center for Biotechnology Information (NCBI) and were subjected to quality check and trimming prior to alignment. The normalization and differential expression analysis were carried out using DESeq2 and EdgeR packages of Rstudio to identify DEGs in ID. In progression of the study, functional enrichment analysis of the results obtained from both DESeq2 and EdgeR was done using gene set enrichment analysis (GSEA) tool to identify major upregulated biological processes involved in ID. Our findings concluded that monitoring the level of E2F targets, estrogen, and genes related to oxidative phosphorylation, DNA repair, and glycolysis during the developmental stage of an individual can help in the early detection of ID disorder.

Dihydroxytrimethoxyflavone possess memory improvement effects against scopolamine in mice via modulating multiple pathways: In‐silico and in‐vivo evidences

AbstractBackgroundDementia is a deliberating neurodegenerative disorder which causes impairment of intellectual functions. The USFDA approved drugs has limited efficacy and numerous side effects. Thus, finding newer drugs to manage dementia and cognitive disorders is certainly required. The present study explores the potential of a natural flavone, 5,7‐dihydroxy‐3',4',5'‐trimethoxyflavone (DHF), as memory enhancer drug against scopolamine‐induced cognitive deficit in mice.MethodsAnimals were treated with DHF (5‐10 mg/kg, p.o.) for 7 days after inducing cognitive impairment by scopolamine (1mg/kg,i.p.). Memory functions (passive shock avoidance task and Morris Water Maze), brain acetylcholinesterase (AChE) activity, inflammatory markers, oxidative stress, apoptotic biomarkers and histopathological studies (H&E and congo red staining for beta amyloid) were determined to measure memory improvement effects of DHF. In‐silico (molecular docking) studies were performed to understand the interactions of DHF with key pathological enzymes related to dementia.ResultsTreatment of scopolamine administered mice with DHF improved scopolamine‐induced cognitive impairment and restore brain biochemical parameters (inhibited acetylcholinesterase activity, enhanced glutathione levels, and reduced TBARS, TNF‐α, IL‐6, IL‐1β and caspase‐3 levels). Moreover, histopathological studies showed that DHF treatment reduced the neuronal cell death and amyloid depositions in mice brain. Further, molecular docking studies revealed string interactions of DHF with crucial amino acids of AChE and caspase‐3.ConclusionThese results suggest that DHF was effective in treating scopolamine induced cognitive deficit by improving cerebral cholinergic dysfunction and reducing brain oxidative stress, inflammation, apoptosis and beta‐amyloid depositions in mice. Thus, DHF could be developed as a potential alternative drug to treat memory disorders.

Body mass index changes in children and adolescents with intelectual disability during the COVID-19 pandemic

Introduction: Intellectual disability (ID) is a generalized neurodevelopmental disorder characterized by significantly impaired intellectual and adaptive functioning. Body mass index (BMI) is a value derived from the mass (weight) and height of a person. Due to the COVID-19 pandemic there was a lockdown of all schools and other daily sport activities. Methods: We measured the height and weight of 100 children and adolescents with intellectual disability. The measurements were taken in September 2020 and then six months later, in March 2021. The calculated BMI was transformed into age- and sex-standardized values (zBMI). Mean BMI and zBMI were compared over time and between sexes using a paired t-test and two-way mixed analysis of variance (ANOVA). The effect size was estimated using Cohen’s d. Results: On average across all groups, BMI increased by 0.5kg/m2 in the studied period. The increase in mean BMI was statistically significant for both groups of girls; the difference between girls and boys in BMI increase was marginally statistically significant. The analysis of zBMI confirmed that the observed changes were likely not simply a consequence of maturation. Discussion: One effect of the COVID-19 pandemic and restrictions related to it was the increase of BMI values in children and youth. With our results, we can relate this data also to population with ID. Although we have provided intervention programs and encouraged pupils and their parents to be more physically active during lockdown, the importance of school and after school activities regarding physical fitness status is clearly evident.

Violent Recidivism and Adverse Childhood Experiences in Forensic Psychiatric Patients With Impaired Intellectual Functioning.

Accurate risk assessment and insight into which factors are associated with recidivism are essential for forensic correctional practice. Therefore, we investigated whether the Historical, Clinical, and Future-Revised (HKT-R [Historisch Klinisch Toekomst-Revised]) risk assessment instrument could predict violent recidivism over a 2-year follow-up period in forensic psychiatric patients with intelligence quotient (IQ) < 80. We refer to these patients as intellectually disabled (ID) and patients with IQ ≥ 80 as non-ID. Additionally, the associations of the 14 clinical HKT-R factors with ID versus non-ID group membership were investigated, as well as a possible moderating role of adverse childhood experiences (ACE) in these associations. The final sample encompassed 748 forensic psychiatric patients (15.9% were patients with ID) who were unconditionally released from highly secured Dutch forensic psychiatric institutions between 2004 and 2014. The results showed that the HKT-R total score (AUC = 0.705, 95% confidence interval [CI] [0.527, 0.882]) and the clinical domain (AUC = 0.733, 95% CI [0.579, 0.886]) had a large effect size for predictive validity for 2-year violent recidivism, while the future domain (AUC = 0.653, 95% CI [0.524, 0.781]) and the historical domain (AUC = 0.585, 95% CI [0.397, 0.772]) had a medium effect size for predictive validity for 2-year violent recidivism in ID patients. It was also found that lower levels of self-reliance and social skills were associated with ID, indicating that treatment should prioritize these skills. However, ACE was not associated with ID, nor did it moderate the associations of the clinical HKT-R factors with ID. This study contributes to the understanding of both risk assessment and treatment of forensic psychiatric patients with ID.

A-264 Neurodevelopmental Disorder associated with 8p23.1 Microdeletion Syndrome: A Pediatric Case Study

Abstract Objective: 8p23.1 microdeletion syndrome is a rare genetic disorder involving a partial deletion of chromosome 8. Children with this microdeletion are at increased risk for prenatal growth deficiency, congenital heart defects, craniofacial abnormalities, seizures, intellectual deficits, language impairments, motor deficits, and behavioral disorders which emphasizes the need for comprehensive neuropsychological assessment and intervention for these individuals. Method: This case study presents on the neuropsychological profile of a 9-year-old female with 8p23.1 microdeletion syndrome who had a history of absence seizures, heart valve disease, microcephaly, and developmental delays. The patient previously underwent psychological testing at age 8 and the findings revealed deficits in attention and intellectual functioning; however, her parents now had concerns for her social functioning. Results: Neuropsychological testing showed broad impairments in intellectual functioning, adaptive functioning, language, academic achievement, attention, executive functioning, memory, visuomotor skills, and social cognition. Conclusions: Recommendations were made to modify the patient’s special education academic goals, initiate various interventional services at school (e.g., speech therapy, occupational therapy, and social work), and start private ABA therapy. Continued monitoring and medication management with neurology and psychiatry were recommended as well given the patient’s history of absence seizures and problems with attentional-behavioral regulation. This case demonstrates the importance of comprehensive neuropsychological evaluation and treatment of children with certain rare genetic disorders such as 8p23.1 microdeletion syndrome in order to help improve neurodevelopmental outcomes in these patients.

A homozygous nonsense HECW2 variant is associated with neurodevelopmental delay and intellectual disability

Intellectual disability is characterized by a significant impaired intellectual and adaptive functioning, affecting approximately 1–3% of the population, which can be caused by a variety of environmental and genetic factors. In this respect, de novo heterozygous HECW2 variants were associated recently with neurodevelopmental disorders associated to hypotonia, seizures, and absent language. HECW2 encodes an E3 ubiquitin-protein ligase that stabilizes and enhances transcriptional activity of p73, a key factor regulating proliferation, apoptosis, and neuronal differentiation, which are together essential for proper brain development.Here, using whole exome sequencing, we identified a homozygous nonsense HECW2 variant: c.736C > T; p.Arg246* in a proband from a Moroccan consanguineous family, with developmental delay, intellectual disability, hypotonia, generalized tonico-clonic seizures and a persistent tilted head.Thus this study describes the first homozygous HECW2 variant, inherited as an autosomal recessive pattern, contrasting with former reported de novo variants found in HECW2 patients.

Exploring the knowledge of social care staff about learning disability: 20 years on

Background It is important for social care staff to understand what a learning disability is so that they can identify people with learning disabilities and provide them with the support they need.Aim To explore whether there have been changes in the knowledge of social care staff about the diagnostic criteria for learning disability more than 20 years after the researchers first explored the topic.Method A sample of 264 social care staff were asked to describe what they understood by ‘learning disability’. Their responses were compared with the three diagnostic criteria of learning disability – that is, significant impairments in intellectual functioning, significant impairments in adaptive functioning and childhood onset.Results Impairments in intellectual functioning was the most commonly identified criterion and childhood onset the least commonly identified criterion. Only 5% of participants (n=13) identified all three criteria, while 57% (n=150) identified none or only one of the criteria.Conclusion While the results are an improvement on those found more than 20 years ago, they still indicate an ongoing need for improved understanding, among social care staff, of what a learning disability is, and learning disability nurses have a role to play in this.

Prevalence of intellectual disability among eight-year-old children from selected communities in the United States, 2014

BackgroundChildren with intellectual disability (ID), characterized by impairments in intellectual functioning and adaptive behavior, benefit from early identification and access to services. Previous U.S. estimates used administrative data or parent report with limited information for demographic subgroups. ObjectiveUsing empiric measures we examined ID characteristics among 8-year-old children and estimated prevalence by sex, race/ethnicity, geographic area and socioeconomic status (SES) area indicators. MethodsWe analyzed data for 8-year-old children in 9 geographic areas participating in the 2014 Autism and Developmental Disabilities Monitoring Network. Children with ID were identified through record review of IQ test data. Census and American Community Survey data were used to estimate the denominator. ResultsOverall, 11.8 per 1,000 (1.2%) had ID (IQ ≤ 70), of whom 39% (n = 998) also had autism spectrum disorder. Among children with ID, 1,823 had adaptive behavior test scores for which 64% were characterized as impaired. ID prevalence per 1,000 was 15.8 (95% confidence interval [95% CI], 15.0–16.5) among males and 7.7 (95% CI, 7.2–8.2) among females. ID prevalence was 17.7 (95% CI, 16.6–18.9) among children who were non-Hispanic black; 12.0 (95% CI, 11.1–13.0), among Hispanic; 8.6 (95% CI, 7.1–10.4), among non-Hispanic Asian; and 8.0 (95% CI, 7.5–8.6), among non-Hispanic white. Prevalence varied across geographic areas and was inversely associated with SES. ConclusionsID prevalence varied substantively among racial, ethnic, geographic, and SES groups. Results can inform strategies to enhance identification and improve access to services particularly for children who are minorities or living in areas with lower SES.

A-254 A Pediatric Case Study of Mild Intellectual Disability in the Context of Complex Chiari Malformation, Hydrocephalus, Cleft Palette, and Complex Psychosocial Environment

Abstract Objective Chiari malformation is a congenital condition involving structural skull defects, causing brain tissue herniation and likely resulting in hydrocephalus. People with these medical conditions are at risk for varied cognitive impairments. Recently, emerging evidence has suggested the co-occurrence of Chiari malformation and cleft palette contributing to increased cognitive challenges, highlighting the importance of introducing interventions in a timely manner. Method This case study presents on the neuropsychological profile of an 11-year-old girl with a medical history of complex Chiari malformation with accompanying hydrocephalus and syringomyelia, and lymphangioma born with cleft palette. Relevant social history includes recent parent separation and unstable home life. Presenting concerns included intermittent hand weakness and headaches status post 5 surgeries related to Chiari malformation and hydrocephalus, inattention/impulsivity, learning difficulties, and increased emotional and behavioral dysregulation. Results Neuropsychological testing revealed impairments in intellectual functioning (WISC-V FSIQ = 64), adaptive skills, attention/executive functioning, language, visuomotor skills, memory, and academic skills. Significant emotional and behavior adjustment problems were indicated, secondary to medical treatment, resulting physical limitations, and psychosocial stressors. Finally, staring spells episodes were observed that were concerning for possible seizure activity. Conclusions Recommendations were given to aid in treatment planning for her referring neurosurgeon alongside clinical interventions (e.g., psychotherapy, social work, speech/language, and occupational therapy). Recommendations related to continued intensive special education services were also provided. This case study demonstrates the need for further understanding cognitive impairment in the context of Chiari malformation with co-occurring hydrocephalus and cleft palette. Multidisciplinary collaboration is essential to facilitate the prompt introduction of appropriate clinical interventions.

Structural brain abnormalities in adults with congenital heart disease: Prevalence and association with estimated intelligence quotient

BackgroundLittle is known about the prevalence of structural brain abnormalities and cognitive functioning in the growing population of patients with adult congenital heart disease (ACHD). Thus, our aim was to assess structural abnormalities on brain magnetic resonance imaging (MRI) and their association with intelligence quotient (IQ) in ACHD patients. MethodsCross-sectional study in ACHD patients and healthy controls as comparison group. Brain MRI was performed on a 3 T MR scanner, and inspection of structural abnormalities was performed blinded to ACHD or control status. IQ was estimated using the vocabulary and matrix reasoning subtests from the Wechsler Adult Intelligence Scale, Fourth Edition. ResultsA total number of 67 (55% males) ACHD patients and 55 (51% males) controls were included (mean age 26.9 and 26.0 years respectively). Abnormalities on brain MRI were detected in 29 of 46 (63%) ACHD patients and in none of the controls. Abnormalities consisted of focal infarction or atrophy, white matter lesions, microhemorrhages, and global atrophy. Mean estimated IQ was significantly lower in ACHD patients than in controls (98.51 versus 104.38; 95% CI: −10.09 to −1.66; P value = 0.007). Comparison between patients with and without cerebral abnormalities revealed no significant difference in estimated IQ. ConclusionOur findings indicate a high prevalence and wide spectrum of structural brain abnormalities in ACHD patients. Furthermore, this population is at a higher risk of impaired intellectual functioning than healthy controls. However, the present study could not establish a statistically significant association between MRI findings and estimated IQ. Clinical trial registrationClinicalTrials.gov ID: NCT04041557; URL: https://clinicaltrials.gov/ct2/show/NCT04041557?term=NCT04041557&rank=1.

PGR - 1 A Pediatric Case Study of Autism Spectrum Disorder Associated with Germinal Matrix-Intraventricular Hemorrhage, Periventricular Leukomalacia, and Cerebral Palsy.

Abstract Objective Germinal matrix-intraventricular hemorrhage (GMH-IVH) is a serious complication of prematurity that places infants at risk for damage to important white matter pathways which can result in periventricular leukomalacia (PVL) and ultimately cerebral palsy (CP). GMH-IVH also increases the risk of developmental and intellectual disabilities for preterm infants, highlighting the need for early detection and treatment. Method This case study presents on the neuropsychological profile of a 4-year-old boy who was born micropremature and had a history of multiple hemorrhages, extensive PVL, and CP in the context of significant developmental and social delays. Results Neuropsychological testing revealed severe impairments in intellectual functioning (Stanford Binet-5 FSIQ = 42, Nonverbal IQ = 43, Verbal IQ = 47; Leiter-3 Nonverbal IQ = 41), adaptive skills, language, social cognition, visuomotor abilities, spatial skills, pre-academic skills, and attention/executive functioning. He scored in the significant range on measures specific to Autism Spectrum Disorder (ADOS-2; CARS-2; SCQ) and behavioral-emotional functioning. Lastly, he exhibited intermittent staring behaviors that were concerning for possible seizure activity. Conclusions Recommendations were made to increase special education services for the child and to modify his academic goals. Recommendations were also given to aid in treatment planning for his referring neurologist and clinical interventions (e.g., ABA, social work, speech/language, occupational therapy, and physical therapy). This case study demonstrates the need for early neuropsychological detection and treatment for children with complications of prematurity during this important period of brain development, particularly as there are higher rates of autism in this population. Prompt detection leads to earlier treatment and better outcomes.

Severe neurological impairment: a review of the definition.

Severe neurological impairment (SNI) is a term commonly used in the medical literature, though there is no agreed definition. This limits opportunities for research into healthcare needs, treatment opportunities, resource planning, and outcome. We reviewed the literature to establish consistency of use of the term and to place it in the context of other commonly employed terms used to describe children with severe, complex medical needs. Forty-two articles were included for full-text analysis, with 23 including a definition of SNI. Motor impairment, intellectual disability, communication difficulties, and increased care needs were included in the definition in 80%, 70%, 30%, and 13% of papers respectively. Dependence on others for decision-making, chronicity, and distinction between disorders of the central nervous system and peripheral nervous system were less frequently included. There is wide variation in the use of the term SNI. A consensus-based definition of this term would be useful to facilitate future research. WHAT THIS PAPER ADDS: There is inconsistency in use of the term severe neurological impairment (SNI), limiting research efforts. In defining SNI, considerations are mobility, intellectual disability, communication difficulties, and increased care needs. Distinction between acute and chronic, central and peripheral nervous system disorders, and dependence on others for decision-making were less significant.

Brpf1 Haploinsufficiency Impairs Dendritic Arborization and Spine Formation, Leading to Cognitive Deficits.

Haploinsufficiency of the bromodomain and PHD finger-containing protein 1 (BRPF1) gene causes intellectual disability (ID), which is characterized by impaired intellectual and cognitive function; however, the neurological basis for ID and the neurological function of BRPF1 dosage in the brain remain unclear. Here, by crossing Emx1-cre mice with Brpf1fl/fl mice, we generated Brpf1 heterozygous mice to model BRPF1-related ID. Brpf1 heterozygotes showed reduced dendritic complexity in both hippocampal granule cells and cortical pyramidal neurons, accompanied by reduced spine density and altered spine and synapse morphology. An in vitro study of Brpf1 haploinsufficiency also demonstrated decreased frequency and amplitude of miniature EPSCs that may subsequently contribute to abnormal behaviors, including decreased anxiety levels and defective learning and memory. Our results demonstrate a critical role for Brpf1 dosage in neuron dendrite arborization, spine morphogenesis and behavior and provide insight into the pathogenesis of BRPF1-related ID.

Cognitive impairment in children with CACNA1A mutations.

To describe the clinico-radiological phenotype of children with a CACNA1A mutation and to precisely evaluate their learning ability and cognitive status. Children between the ages of 3 and 18years harboring a pathogenic CACNA1A mutation associated with episodic ataxia, hemiplegic migraine, benign paroxysmal torticollis, benign paroxysmal vertigo, or benign paroxysmal tonic upgaze, were enrolled in this cross-sectional study. Data concerning psychomotor development, academic performance, educational management, clinical examination at inclusion, and brain imaging were collected. Cognitive assessment was performed using age-standardized scales. Eighteen patients (nine males, nine females; mean age at inclusion: 11y 7mo [SD 4y 5mo; range 3y-17y 11mo]) from 14 families were enrolled. Eleven patients displayed the coexistence or consecutive occurrence of more than one type of episodic event. Nine patients exhibited abnormal neurological examination at inclusion. Brain magnetic resonance imaging (MRI) showed cerebellar atrophy in five patients. Psychomotor development was delayed in nine patients and academic difficulties were reported by the parents in 15 patients; nine patients were in special education. Impairment of intellectual function was assessed in six of the 12 patients with interpretable Full-scale IQ scores and was more frequent when cerebellar atrophy was present on MRI. Cognitive impairment is commonly associated with CACNA1A mutations. We suggest that CACNA1A-associated phenotype should be considered a neurodevelopmental disorder. Cognitive disabilities and academic difficulties are common in children with CACNA1A mutations associated with episodic syndromes. Cognitive function ranges from normal to moderate intellectual disorder in wheelchair-dependent children. Patients with vermian atrophy are at a higher risk of cognitive impairment.

Biallelic loss of EEF1D function links heat shock response pathway to autosomal recessive intellectual disability.

Intellectual disability (ID) is a genetically heterogeneous neurodevelopmental disorder characterised by significantly impaired intellectual and adaptive functioning. ID is commonly syndromic and associated with developmental, metabolic and/or neurological findings. Autosomal recessive ID (ARID) is a significant component of ID especially in the presence of parental consanguinity. Several ultra rare ARID associated variants in numerous genes specific almost to single families have been identified by unbiased next generation sequencing technologies. However, most of these new candidate ARID genes have not been replicated in new families due to the rarity of associated alleles in this highly heterogeneous condition. To determine the genetic component of ARID in a consanguineous family from Turkey, we have performed SNP-based linkage analysis in the family along with whole exome sequencing (WES) in an affected sibling. Eventually, we have identified a novel pathogenic variant in EEF1D, which has recently been recognised as a novel candidate gene for ARID in a single family. EEF1D encodes a ubiquitously expressed translational elongation factor functioning in the cytoplasm. Herein, we suggest that the loss of function variants exclusively targeting the long EEF1D isoform may explicate the ARID phenotype through the heat shock response pathway, rather than interfering with the canonical translational elongation.

Relationship between the Vineland Adaptive Behaviour Scales and the Wechsler Adult Intelligence Scale IV in adults with intellectual disabilities.

Diagnoses of intellectual disability (ID) are based on three criteria: significant impairments in intellectual functioning, concurrent deficits in adaptive behaviour, and both being acquired in the developmental period. Adaptive behaviour was formally incorporated into the diagnosis in 1959; the rationale being that IQ and adaptive behaviour were different constructs that independently contribute to the diagnosis. However, there are limited data on the relationship between IQ and adaptive behaviour and especially so for adults who have ID. The aim of this study was to investigate this relationship on two widely used assessment tools: the Wechsler Adult Intelligence Scale - fourth edition (WAIS-IV) and the Vineland Adaptive Behaviour Scales (VABS). Data were extracted from the case files of 147 adults who had a formal diagnosis of ID based on the WAIS-IV and VABS. Internal consistency was computed and compared to general population data. Correlations between the WAIS-IV and the VABS were computed. Internal consistencies for the tests when used with adults who have ID were generally good. The correlations between the WAIS-IV and VABS composite and subdomain scores were all low and similar to those reported for the general population. These results suggest that the WAIS-IV and VABS are measuring different constructs that contribute to the diagnosis of ID. Unfortunately, by the time such data have been collected, tests are being revised. The Vineland has now been revised and is in its third edition, but no data on the relationship between IQ and the VABS were collected during test development. The WAIS-V is now in development, and so it is recommended that such work be incorporated into this process or shortly thereafter to ensure that the tools continue to access independent constructs.

Clinical Practice Guidelines for Assessment and Management of intellectual disability.

Mental retardation is a developmental disorder and is associated with significant limitations in intellectual functioning and adaptive behaviors. Currently, it is widely referred to as “intellectual disability (ID)” and “intellectual developmental disorders (IDDs).” In India, the Rights of Persons with Disabilities Act (2016) has introduced the term “intellectual disability” in the place of “mental retardation.” However, India being a signatory country to the World Health Organization (WHO), where the International Classification of Diseases, 10th revision (ICD-10) guidelines are adopted in the clinical practice, the term “mental retardation” is still in clinical use (The WHO Working Group on the Classification of Intellectual Disabilities has recommended replacing the term “mental retardation” with “IDD” in ICD-11 [Salvador-Carulla et al., 2011]. Thus, both the terms, intellectual disability and mental retardation, are in use in India. Despite variation in the terminology and the differences in the criteria for diagnosis (e.g., ICD-10; Diagnostic and Statistical Manual of Mental Disorders, 5th Edition [DSM-5]) and assessment of disability (as notified in the guidelines in January 2018, which are based on the RPD Act), it is commonly agreed that significant impairments in intellectual functioning and adaptive behavior during the developmental period is the hallmark of the condition [Table 1]. Table 1 Terminology and conceptual issues related to intellectual disability among different diagnostic systems

A HS6ST2 gene variant associated with X-linked intellectual disability and severe myopia in two male twins.

X‐linked intellectual disability (XLID) refers to a clinically and genetically heterogeneous neurodevelopmental disorder, in which males are more heavily affected than females. Among the syndromic forms of XLID, identified by additional clinical signs as part of the disease spectrum, the association between XLID and severe myopia has been poorly characterized. We used whole exome sequencing (WES) to study two Italian male twins presenting impaired intellectual function and adaptive behavior, in association with severe myopia and mild facial dysmorphisms. WES analysis detected the novel, maternally inherited, mutation c.916G > C (G306R) in the X‐linked heparan sulfate 6‐O‐sulfotransferase 2 (HS6ST2) gene. HS6ST2 transfers sulfate from adenosine 3′‐phosphate, 5′‐phosphosulfate to the sixth position of the N‐sulphoglucosamine residue in heparan sulfate (HS) proteoglycans. Low HS sulfation levels are associated with defective optic disc and stalk morphogenesis during mammalian visual system development. The c.916G>C variant affects the HS6ST2 substrate binding site, and its effect was considered “deleterious” by in‐silico tools. An in‐vitro enzymatic assay showed that the HS6ST2 mutant isoform had significantly reduced sulphotransferase activity. Taken together, the results suggest that mutant HS6ST2 is possibly involved in the development of myopia and cognitive impairment, characteristics of the probands reported here.

A case report of the neurocognitive and behavioral phenotype of mosaic trisomy 14

ABSTRACTMosaic trisomy 14 is associated with impaired intellectual functioning, although no study has examined the cognitive-behavioral profile associated with the syndrome. This study provides the first case description of the cognitive-behavioral phenotype associated with mosaic trisomy 14 by contrasting the performance an adolescent female (T14) with a group of females with Down syndrome (DS; n=9). T14 performed below age expectations on most direct assessments and demonstrated weaknesses relative to the DS group on aspects of language, adaptive functioning, and executive functioning. T14 also demonstrated strengths in delayed visual recall and social skills relative to the DS group.

Quality improvement in neurology: Epilepsy Quality Measurement Set 2017 update.

Epilepsy is a common condition in the United States. It is estimated that 1.2% of the population or 3.4 million people have epilepsy. This figure may be underestimated because of potential repercussions and stigma in disclosing epilepsy.1 Studies have shown that people with epilepsy are more likely to be unemployed or unable to work, have lower annual household incomes, be obese and physically inactive, and be less likely to marry.2,3 People with epilepsy can have poor overall health status, impaired intellectual and physical functioning, elevated risk of accidents and injuries, and negative side effects from antiseizure medications.2,3 It is estimated the annual direct medical cost of epilepsy in the United States is $9.6 billion; combined with indirect costs, the total rises to $15.5 billion yearly.2