Turner syndrome: a review of genetic and hormonal influences on neuropsychological functioning.

Turner syndrome (TS) is a genetic disorder affecting mainly females that arises from a loss of X chromosome material, most usually one of the two X chromosomes. TS is associated with a number of characteristic physical features such as short stature and absent ovaries as well as a set of common neuropsychological deficits and social and behavioral features. This paper will serve to review the cognitive, social, and psychoeducational abilities of individuals with TS as well as neuroimaging findings. Several putative genetic mechanisms contributing to their particular neurocognitive deficits will also be described including candidate genes. In addition, the available evidence on how hormones affect specific abilities in TS will be reviewed. It will be concluded that the TS neurobehavioral profile arises from an atypical cerebral organization caused by the complex interplay of insufficient expression of certain (unknown) genes on the X chromosome and by abnormal hormonal levels; however, it is still not clear exactly how the specific genes affect broader cognitive abilities. Future research needs to identify the elemental processes that are disturbed in TS and map these both to events in early brain development and subsequent brain function and to specific gene and hormonal contributions.     

COPY AND RECALL PERFORMANCE OF 6–8-YEAR-OLD CHILDREN AFTER STANDARD VS. STEP-BY-STEP ADMINISTRATION OF THE REY-OSTERRIETH COMPLEX FIGURE

Turner syndrome (TS) is a genetic disorder in females characterized by the complete or partial absence of one X chromosome. Its most consistent physical features include short stature and ovarian dysgenesis. TS individuals demonstrate a characteristic neurocognitive profile involving weaknesses in visuospatial processing. The hypothesis of defective right hemisphere specialization has been offered to explain the visuospatial deficits in TS. In contrast, an alternative explanation proposes a more uniform dysfunction of the left and right hemispheres, based on findings of symmetrical abnormalities. This article presents an overview of the two hypotheses, along with relevant findings on hemispheric specialization with respect to TS. The impact of the genetic and hormonal mechanisms on the neurocognitive profile of TS is also discussed and directions for further empirical research are identified.     

Cerebral laterality in Turner syndrome: a critical review of the literature.

Turner syndrome (TS) is a genetic disorder in females characterized by the complete or partial absence of one X chromosome. Its most consistent physical features include short stature and ovarian dysgenesis. TS individuals demonstrate a characteristic neurocognitive profile involving weaknesses in visuospatial processing. The hypothesis of defective right hemisphere specialization has been offered to explain the visuospatial deficits in TS. In contrast, an alternative explanation proposes a more uniform dysfunction of the left and right hemispheres, based on findings of symmetrical abnormalities. This article presents an overview of the two hypotheses, along with relevant findings on hemispheric specialization with respect to TS. The impact of the genetic and hormonal mechanisms on the neurocognitive profile of TS is also discussed and directions for further empirical research are identified.     

Executive Functions in Children and Adolescents with Turner Syndrome: A Systematic Review and Meta-Analysis

Turner syndrome (TS) is a genetic disorder, affecting 1/2500 to 1/3000 live female births, induced by partial or total deletion of one X chromosome. The neurocognitive profile of girls with TS is characterized by a normal Verbal IQ and weaknesses in visual-spatial, mathematics, and social cognitive domains. Executive functions (EFs) impairments have also been reported in these young patients. However, methodological differences across studies do not allow determination of which EFs are impaired and what is the magnitude of these impairments. The aim of this review was to clarify the EF profile of children and adolescents with TS. Sixteen samples, from thirteen studies, were included in the current meta-analysis. EFs measures used in these studies were classified into working memory, inhibitory control, cognitive flexibility, or higher-order EFs tasks in accordance with Diamond’s model, Annual Review of Psychology, 64, 135–168 (2013). Results confirmed that girls with TS had significant executive impairments with effect sizes varying from small (inhibitory control) to medium (cognitive flexibility) and large (working memory, higher-order EFs). Analyses by task revealed that cognitive inhibition may be more impaired than the other inhibitory control abilities. Heterogeneity across cognitive flexibility measures was also highlighted. Between-sample heterogeneity was observed for three tasks and the impact of participants’ characteristics on EFs was discussed. This meta-analysis confirms the necessity to assess, in patients living with TS, each EF by combining both visual and verbal tasks. Results also underline that, when studying girls with TS’ executive profile, it is important to explore the impact of moderator variables, such as IQ, parental socio-economic status, TS karyotype, psychiatric comorbidities, and hormonal treatment status.     

Turner Syndrome: A Review of Genetic and Hormonal Influences on Neuropsychological Functioning

Turner syndrome (TS) is a genetic disorder in females that arises from the loss of X chromosome material. Affected individuals demonstrate a characteristic neuropsychological profile of strengths in verbal processing and weaknesses in visuospatial processing, consistent with the Nonverbal Learning Disabilities syndrome. Previous research has described a wide range of visuospatial deficits in TS; however, their verbal abilities are less extensively studied. The present paper describes the processing difficulties of a 9-year-old girl with TS who demonstrated problems in integrating details of a complex visual display and using organizational terms to describe visual scenes or events. Her specific cognitive disabilities were thought to underlie some of the social and behavioral problems she was currently experiencing. Her pattern of results is consonant with the neuropsychological pattern that others have attributed to right hemisphere dysfunction and/or white matter abnormality.     

Visual integration difficulties in a 9-year-old girl with Turner syndrome: parallel verbal disabilities?

Turner syndrome (TS) is a genetic disorder in females that arises from the loss of X chromosome material. Affected individuals demonstrate a characteristic neuropsychological profile of strengths in verbal processing and weaknesses in visuospatial processing, consistent with the Nonverbal Learning Disabilities syndrome. Previous research has described a wide range of visuospatial deficits in TS; however, their verbal abilities are less extensively studied. The present paper describes the processing difficulties of a 9-year-old girl with TS who demonstrated problems in integrating details of a complex visual display and using organizational terms to describe visual scenes or events. Her specific cognitive disabilities were thought to underlie some of the social and behavioral problems she was currently experiencing. Her pattern of results is consonant with the neuropsychological pattern that others have attributed to right hemisphere dysfunction and/or white matter abnormality.     

Indices of Laterality in Turner Syndrome

The present study explored the utility of manual laterality in predicting verbal and visual-spatial functioning and educational placement among girls and adolescents with Turner syndrome (TS). A significant curvilinear relationship emerged between derived Performance Intelligence Quotient (PIQ) and motor skill laterality such that either very strong or very weak laterality was less advantageous for visual-spatial skills than moderate laterality. A significant negative correlation, but no curvilinear relation, emerged between derived Verbal Intelligence Quotient (VIQ) and degree of motor skill laterality, with more strongly lateralized participants showing lower verbal skills than weakly lateralized participants. Hand preference category showed no significant relationships with VIQ, PIQ, or educational placement.     

Neuropsychological Aspects of Pediatric Sickle Cell Disease

Sickle cell disease (SCD), a class of genetic disorders characterized by abnormal, sickled red blood cells, is a chronic illness that results in progressive cerebrovascular disease. Neurocognitive sequelae of clinically apparent cerebrovascular accidents in children with SCD are characterized by pervasive impairments, including decrements in general intellectual functioning, language and verbal abilities, visual-motor and visual-spatial processing, memory, academic achievement, and processing of subtle prosodic information. In contrast, subtle neurocognitive deficits in the areas of attention and concentration, executive function, and visual-motor speed and coordination appear to be associated with silent infarcts that are not necessarily detected on physical examination. Investigation of the disease course and associated neurocognitive sequelae suggest a disease-specific model of neuropsychological impairment. Recommendations are made for clinical and research efforts in the field of pediatric neuropsychology.     

Ocular motor indicators of executive dysfunction in fragile X and Turner syndromes

Fragile X and Turner syndromes are two X-chromosome-related disorders associated with executive function and visual spatial deficits. In the present study, we used ocular motor paradigms to examine evidence that disruption to different neurological pathways underlies these deficits. We tested 17 females with fragile X, 19 females with Turner syndrome, and 40 females with neither disorder who comprised the comparison group. Group differences emerged for both the fragile X and Turner syndrome groups, each relative to the comparison group: Females with fragile X had deficits in generating memory-guided saccades, predictive saccades, and saccades made in the overlap condition of a gap/overlap task. Females with Turner syndrome showed deficits in generating memory-guided saccades, but not during either the predictive saccade or gap/overlap task. Females with Turner syndrome, but not females with fragile X, showed deficits in visually guided saccades and anti-saccades. These findings indicate that different brain regions are affected in the two disorders, and suggest that different pathways lead to the similar cognitive phenotypes described for fragile X and Turner syndromes.     

Exploring Visual–Spatial Working Memory: A Critical Review of Concepts and Models

The ability to retain and process an object's identity and spatial location is essential for many daily tasks, often referred to as visual-spatial working memory. Research investigating visual-spatial processing has concentrated on three aspects or mechanisms thought to sub-serve this process; perceptual processes, anatomical correlates and working memory functions. An approach integrating all three areas has largely been neglected. Hence, this review sought to (1) outline some of the advances made to the understanding by these three concepts or models of visual-spatial processing, (2) establish the relationship between these processes, and discuss the challenges faced by researchers attempting to dissociate this functions from other visual-spatial processes as well as other working memory functions. It is suggested that a more comprehensive and integrative understanding of visual-spatial working memory has implications for research seeking to investigate visual-spatial memory, and to relate visual-spatial memory to other cognitive functions, such as executive function and attention.     

Neuropsychological, learning and psychosocial profile of primary school aged children with the velo-cardio-facial syndrome (22q11 deletion): evidence for a nonverbal learning disability?

In this exploratory study, the neuropsychological and learning profile of nine primary school age children with velo-cardio-facial syndrome (VCFS) was studied by systematic neuropsychological testing. In five out of nine children, the following profile was found: a VIQ-PIQ discrepancy (in favor of the VIQ), significantly better scores (.05 level) for reading (decoding) and spelling compared to arithmetic, deficient tactile-perceptual skills (difficulties mainly on the left side of the body), weak but not deficient visual-perceptual abilities, deficient visual-spatial skills, extremely poor psychomotor skills (gross motor skills more deficient than fine motor skills), problems with processing of new and complex material, poor visual attention, good auditory memory and relatively good language skills. These findings correspond to the pattern of neuropsychological assets and deficits that has been described for the syndrome of nonverbal learning disabilities (NLD) (Rourke, 1987, 1988, 1989, 1995). The psychosocial profile of all nine children with VCFS also correspond to that of children with NLD. Further studies on the relationship between cognitive function, behavior, psychiatric disorder and abnormalities in brain anatomy in young people with VCFS will be needed. In clinical practice, it is worthwhile exploring in greater depth the neuropsychological functions of children with VCFS to rule out NLD, since they may benefit from specific remediation following the learning principles of the NLD-treatment.     

Working Memory Interference Control Deficit in Children Referred by Teachers for ADHD Symptoms

In this exploratory study, the neuropsychological and learning profile of nine primary school age children with velo-cardio-facial syndrome (VCFS) was studied by systematic neuropsychological testing. In five out of nine children, the following profile was found: a VIQ-PIQ discrepancy (in favor of the VIQ), significantly better scores (.05 level) for reading (decoding) and spelling compared to arithmetic, deficient tactile-perceptual skills (difficulties mainly on the left side of the body), weak but not deficient visual-perceptual abilities, deficient visual-spatial skills, extremely poor psychomotor skills (gross motor skills more deficient than fine motor skills), problems with processing of new and complex material, poor visual attention, good auditory memory and relatively good language skills. These findings correspond to the pattern of neuropsychological assets and deficits that has been described for the syndrome of nonverbal learning disabilities (NLD) (Rourke, 1987, 1988, 1989, 1995). The psychosocial profile of all nine children with VCFS also correspond to that of children with NLD. Further studies on the relationship between cognitive function, behavior, psychiatric disorder and abnormalities in brain anatomy in young people with VCFS will be needed. In clinical practice, it is worthwhile exploring in greater depth the neuropsychological functions of children with VCFS to rule out NLD, since they may benefit from specific remediation following the learning principles of the NLD-treatment.     

Cognitive profile of adolescents with math disabilities: are the profiles different from those with reading disabilities?

Adolescents (ages 14-17) with math disabilities (MD, n=12), reading disabilities (RD, n=19), math+reading disabilities (MD+RD, n=12), and average achievers (n=15) were compared on measures of visual-spatial processing, random generation (inhibition), writing speed, short-term memory (STM), and working memory (WM). Adolescents with MD performed significantly lower than adolescents with RD on measures of visual-spatial processing and visual WM. Adolescents with MD outperformed adolescents with RD +MD on measures of random generation and motor speed. Performance of all three low-achieving groups was inferior to average achievers on measures of random generation, motor speed, and verbal WM. The results were interpreted within a multicomponent model that attributed deficits related to MD in adolescents to deficits related the visual-spatial sketchpad of WM.     

Obstructive Sleep Apnea Syndrome in Prader-Willi Syndrome: An Unrecognized and Untreated Cause of Cognitive and Behavioral Deficits?

Prader-Willi Syndrome (PWS) is a rare genetic disorder characterized by a range of physical, psychological, and physiological abnormalities. It is also distinguished by the high prevalence of obstructive sleep apnea syndrome (OSAS), i.e., repetitive upper airway collapse during sleep resulting in hypoxia and sleep fragmentation. In non-PWS populations, OSAS is associated with a range of neurocognitive and psychosocial deficits. Importantly, these deficits are at least partly reversible following treatment. Given the findings in non-PWS populations, it is possible that OSAS may contribute to neurocognitive and psychosocial deficits in PWS. The present review examines this possibility. While acknowledging a primary contribution from the primary genetic abnormality to central neural dysfunction in PWS, we conclude that OSAS may be an important secondary contributing factor to reduced neurocognitive and psychosocial performance. Treatment of OSAS may have potential benefits in improving neurocognitive performance and behavior in PWS, but this awaits confirmatory investigation.     

人类颞叶皮层与视、听信息加工:Ⅰ、神经心理模型和左颞叶癫痫病人的认知功能

对37名被试的18项神经心理测验结果进行因素分析后得到4个主要因素:知觉组织、感觉注意、记忆和知觉运动。对比组t 考验发现左颞叶瘢痫病人的节律跟随和说话人识别测验得分明显低于普通外科病人,说明左颞叶癫痫病可能影响听觉运动和非言语复杂听觉信息加工的能力。     

Memory abilities in Williams syndrome: Dissociation or developmental delay hypothesis?

Williams syndrome (WS) is a neurodevelopmental genetic disorder often described as being characterized by a dissociative cognitive architecture, in which profound impairments of visuo-spatial cognition contrast with relative preservation of linguistic, face recognition and auditory short-memory abilities. This asymmetric and dissociative cognition has been also proposed to characterize WS memory ability, with sparing of auditory short-term memory and impairment of spatial and long-term memory abilities. In this study, we explored the possibility of a double memory dissociation in WS (short- versus long-term memory; verbal versus visual memory). Thus, verbal memory abilities were assessed using California Verbal Learning Test and Digit Span and Rey-Osterrieth Complex Figure and Corsi Blocks was used to assess visual-spatial memory abilities. Overall, WS subjects were found to present a generalized significant impairment in verbal and visuo-spatial components either in short- or long-term memory. In sum, data from this study brings support for a developmental delay hypothesis, rather than a double dissociation within memory systems in WS.     

Exploring inhibitory deficits in female premutation carriers of fragile X syndrome: Through eye movements

There is evidence which demonstrates that a subset of males with a premutation CGG repeat expansion (between 55 and 200 repeats) of the fragile X mental retardation 1 gene exhibit subtle deficits of executive function that progressively deteriorate with increasing age and CGG repeat length. However, it remains unclear whether similar deficits, which may indicate the onset of more severe degeneration, are evident in female PM-carriers. In the present study we explore whether female PM-carriers exhibit deficits of executive function which parallel those of male PM-carriers. Fourteen female fragile X premutation carriers without fragile X-associated tremor/ataxia syndrome and fourteen age, sex, and IQ matched controls underwent ocular motor and neuropsychological tests of select executive processes, specifically of response inhibition and working memory. Group comparisons revealed poorer inhibitory control for female premutation carriers on ocular motor tasks, in addition to demonstrating some difficulties in behaviour self-regulation, when compared to controls. A negative correlation between CGG repeat length and antisaccade error rates for premutation carriers was also found. Our preliminary findings indicate that impaired inhibitory control may represent a phenotype characteristic which may be a sensitive risk biomarker within this female fragile X premutation population.     

Neuropsychological characteristics of children with the 22q11 Deletion Syndrome: a descriptive analysis.

Previous reports of cognitive functioning in children with the 22q11 Deletion Syndrome have reported marked variability in IQ and achievement subtest scores. Studies have begun to explore neuropsychological function in 22q11 DS however results are inconsistent and the profile incomplete. We assessed 40 children ages 5-12 with 22q11 DS. Consistent with past results, visual-spatial memory was significantly lower than verbal memory. Differentially lowered scores were found only in visual attention, working memory and motor function. Contrary with some past results quantitative, verbal ability, and visual spatial memory scores were within 1 SD from the standardization sample mean. Motor behavior, not typically discussed with regard to 22q11 DS school-age children, may be critical to incorporate in neurocognitive studies of children with 22q11 DS. Implications of these findings are considered with regard to past results.     

Functional neuroimaging of working memory in survivors of childhood brain tumors and healthy children: Associations with coping and psychosocial outcomes

Purpose: Pediatric brain tumors are the second most common cancer diagnosis in individuals under age 20 and research has documented significant neurocognitive, psychosocial, and emotional late effects. Associations among these deficits have not been adequately considered and the role of survivors’ coping with stress in relation to deficits is unknown. Further, research has yet to examine neurobiological processes related to neurocognitive, psychosocial, and emotional difficulties in survivors through the use of functional neuroimaging. Method: Questionnaire measures and functional neuroimaging were used to examine the neurocognitive, psychosocial, and emotional functioning and coping responses of survivors of pediatric brain tumors (N = 17; age 8–16) and healthy children (N = 15). Results: Survivors experienced elevated levels of psychosocial and behavioral/emotional difficulties relative to healthy controls and normative data. Increases in brain activation in prefrontal and other anterior regions in response to a working memory task were associated with better psychosocial functioning, use of engagement coping strategies, and less use of disengagement coping strategies. Regression analyses suggest coping accounts for a significant portion of the association between brain activation and behavioral/emotional functioning. Conclusions: This study extends late-effects research by examining neurobiological processes associated with psychosocial and emotional difficulties. These findings contribute to our understanding of difficulties in survivors and provide a foundation for research exploring these associations and mediators of deficits in future longitudinal studies.     

Are there pre-existing neural, cognitive, or motoric markers for musical ability?

Adult musician's brains show structural enlargements, but it is not known whether these are inborn or a consequence of long-term training. In addition, music training in childhood has been shown to have positive effects on visual-spatial and verbal outcomes. However, it is not known whether pre-existing advantages in these skills are found in children who choose to study a musical instrument nor is it known whether there are pre-existing associations between music and any of these outcome measures that could help explain the training effects. To answer these questions, we compared 5- to 7-year-olds beginning piano or string lessons (n=39) with 5- to 7-year-olds not beginning instrumental training (n=31). All children received a series of tests (visual-spatial, non-verbal reasoning, verbal, motor, and musical) and underwent magnetic resonance imaging. We found no pre-existing neural, cognitive, motor, or musical differences between groups and no correlations (after correction for multiple analyses) between music perceptual skills and any brain or visual-spatial measures. However, correlations were found between music perceptual skills and both non-verbal reasoning and phonemic awareness. Such pre-existing correlations suggest similarities in auditory and visual pattern recognition as well a sharing of the neural substrates for language and music processing, most likely due to innate abilities or implicit learning during early development. This baseline study lays the groundwork for an ongoing longitudinal study addressing the effects of intensive musical training on brain and cognitive development, and making it possible to look retroactively at the brain and cognitive development of those children who emerge showing exceptional musical talent.