Turner Syndrome Group Research Articles

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.

Eye tracking and fear recognition deficits in Turner syndrome

Turner syndrome (TS) is a chromosomal disorder of X-monosomy in females. A minority have impaired social responsiveness, poor discrimination of facial emotions (especially fear), and abnormal amygdala–cortical connectivity. We tested the hypothesis that abnormal gaze fixation, especially with the eye region of faces, would be associated with these features, in a similar pattern to that seen in subjects with autism. Furthermore, since these features tend to be more striking in TS women whose X chromosome is maternal in origin, we also predicted that there may be a difference within the Turner's group according to parental origin of the single X. Adults with 45,X karyotype and age and IQ matched 46,XX women were recruited and tested. Facial fear recognition was significantly worse in 45,X females than controls, but there were no group differences according to parental origin of their single X chromosome. Subsequently, we tested 45,X and 46,XX women using a remote eye-tracking device, as they viewed photographs of emotional human faces. Striking differences in scanpaths were found between the TS and controls, and within the TS group, but not according to parental origin of the X chromosome. These findings provide novel evidence for abnormal face processing in some women with TS, and indicate a potential neural mechanism underlying the difficulties in some key aspects of social cognition.

Metacarpophalangeal pattern profile analysis: useful diagnostic tool for differentiating between dyschondrosteosis, turner syndrome, and hypochondroplasia

To assess the value of the metacarpophalangeal pattern profile (MCPP) analysis as a diagnostic tool for differentiating between patients with dyschondrosteosis, Turner syndrome, and hypochondroplasia. Radiographic and clinical data from 135 patients between 1 and 51 years of age were collected and analyzed. The study included 25 patients with hypochondroplasia (HCP), 39 with dyschondrosteosis (LWD), and 71 with Turner syndrome (TS). Hand pattern profiles were calculated and compared with those of 110 normal individuals. Pearson correlation coefficient (r) and multivariate discriminant analysis were used for pattern profile analysis. Pattern variability index, a measure of dysmorphogenesis, was calculated for LWD, TS, HCP, and normal controls. Our results demonstrate that patients with LWD, TS, or HCP have distinct pattern profiles that are significantly different from each other and from those of normal controls. Discriminant analysis yielded correct classification of normal versus abnormal individuals in 84% of cases. Classification of the patients into LWD, TS, and HCP groups was successful in 75%. The correct classification rate was higher (85%) when differentiating two pathological groups at a time. Pattern variability index was not helpful for differential diagnosis of LWD, TS, and HCP. Patients with LWD, TS, or HCP have distinct MCPPs and can be successfully differentiated from each other using advanced MCPP analysis. Discriminant analysis is to be preferred over Pearson correlation coefficient because it is a more sensitive and specific technique. MCPP analysis is a helpful tool for differentiating between syndromes with similar clinical and radiological abnormalities.

Neurofunctional Differences Associated with Arithmetic Processing in Turner Syndrome

Turner syndrome (TS) is a neurogenetic disorder characterized by the absence of one X chromosome in a phenotypic female. Individuals with TS are at risk for impairments in mathematics. We investigated the neural mechanisms underlying arithmetic processing in TS. Fifteen subjects with TS and 15 age-matched typically developing controls were scanned using functional MRI while they performed easy (two-operand) and difficult (three-operand) versions of an arithmetic processing task. Both groups activated fronto-parietal regions involved in arithmetic processing during the math tasks. Compared with controls, the TS group recruited additional neural resources in frontal and parietal regions during the easier, two-operand math task. During the more difficult three-operand task, individuals with TS demonstrated significantly less activation in frontal, parietal and subcortical regions than controls. However, the TS group's performance on both math tasks was comparable to controls. Individuals with TS demonstrate activation differences in fronto-parietal areas during arithmetic tasks compared with controls. They must recruit additional brain regions during a relatively easy task and demonstrate a potentially inefficient response to increased task difficulty compared with controls.

Depression, Levels of Anxiety and Self-Concept in Girls with Turner's Syndrome

Self-esteem, depressive symptoms and anxiety symptoms in girls with Turner's syndrome (TS) were compared to those in girls with familial short stature (FSS) and healthy controls (NC). Eleven girls with TS, 9-17 years of age, all with 45,X0 karyotype, who were matched with 11 girls with FSS and 11 NC girls who had similar socio-demographic characteristics, were enrolled in the study. The Children's Depression Inventory (CDI), State-Trait Anxiety Inventory for Children (STAIC), and Piers-Harris Children's Self Concept Scale (PHSCS) were used to assess the extent of depression, anxiety and self reported self-esteem. The PHSCS means and standard deviations of the TS, FSS and NC groups were 56.2 +/- 6.7, 62.7 +/- 6.9, and 69.3 +/- 6.0, and the STAIC-state anxiety means and standard deviations were 30.6 +/- 4.5, 28.8 +/- 6.1, and 25.7 +/- 3.7, respectively. Study findings showed that girls with TS had lower self-esteem and higher state anxiety levels than NC (p <0.05). In spite of the small sample size, findings showed that girls with TS were at risk of psychological problems. Therefore, in addition to medical treatment and monitoring, girls with TS should also be supported psychologically by social, educational and psychotherapeutic interventions which aim to address their self-esteem and emotional difficulties.

A volumetric study of parietal lobe subregions in Turner syndrome.

Turner syndrome, a genetic disorder that results from the complete or partial absence of an X chromosome in females, has been associated with specific impairment in visuospatial cognition. Previous studies have demonstrated a relationship between parietal lobe abnormalities and visuospatial deficits in Turner syndrome. We used high-resolution magnetic resonance imaging to measure parietal lobe subdivisions in 14 participants with Turner syndrome (mean age 13 years 5 months, SD 5 years) and 14 age-matched controls (mean age 13 years 5 months, SD 4 years 7 months) to localize neuroanatomical variations more closely. Scans were acquired and analyzed for 14 females with Turner syndrome. Analyses of variance were used to investigate differences in regional parietal lobes. Females with Turner syndrome showed a bilateral parietal lobe reduction, specifically in the superior parietal and postcentral gyri. Full-scale IQ scores were significantly positively correlated with postcentral tissue volume in the Turner syndrome group. Structural differences in the parietal lobe are localized specifically to the anterior and superior parietal lobe and might be related to the visuospatial and visuomotor deficits associated with Turner syndrome.

Abnormal prefrontal cortex function during response inhibition in turner syndrome: functional magnetic resonance imaging evidence

Background Turner syndrome (TuS) arises from the partial or complete absence of one X chromosome. Although neuropsychological studies report impaired attentional function and response inhibition in TuS, the neural correlates of these cognitive problems are unknown. Methods Eleven female subjects with TuS and 11 individually matched normal control subjects were imaged using functional magnetic resonance imaging while performing a Go/NoGo task. Results Groups did not differ on accuracy or reaction time; however, the TuS group activated more in the bilateral superior and middle frontal gyri than control subjects. Control subjects did not activate more than the TuS group in any region. Conclusions These findings suggest that female subjects with TuS compensate for executive dysfunction via recruitment of additional prefrontal cortex regions involved in inhibition, attention, and working memory, functions necessary for successful performance of Go/NoGo tasks. Elucidating brain function in TuS will advance our understanding of the influence of X-chromosome genes on neurodevelopment and brain function and contribute to planning future intervention strategies.

X chromosomal abnormalities in Indian adolescent girls.

In girls of adolescent age, primary amenorrhea is a major problem and it is often suspected as Turner syndrome (TS), with complete or partial absence of one of the two X chromosomes. The girls who are unable to menstruate are primarily investigated by the gynecologists with the help of a physical examination, sonogram of the pelvis, endocrinologic tests, and ultimately cytogenetic analysis. Chromosomal analyses have been carried out in 280 such cases that were referred from different parts of the country. The standard protocol for peripheral blood lymphocyte culture was followed for metaphase chromosome preparation and conventional analysis of G-banded chromosomes. A total of 29% cases were found to have some chromosomal abnormality, including TS and testicular feminization syndrome involving sex chromosomes. Amongst those with sex chromosomal anomaly, 34% had evidence of a 46,XY karyotype in phenotypic females and 51% had pure line 45,X or mosaic with normal XX or other aberrations in X. The classification of the TS group further showed the spectrum of variant TS in Indian adolescent girls who suffered from absence or delayed menarche to correspond well with the Belgian, Danish, or Russian population. However, it has been reported that only 1% of the pure line 45,X conception is viable, indicating the necessity of mosaicism with X or Y chromosome. It has been understood that conventional banding analysis is absolutely necessary for segregating the variant nature of TS. In addition, molecular genetic or molecular cytogenetic investigations can determine the nature of mosaicism. The present study further indicated the involvement of autosomes in causing improper sexual development in girls of adolescent age.

The Psychological Consequences of Turner Syndrome and Review of the National Cooperative Growth Study Psychological Substudy

To present longitudinal data on the psychological profile of a cohort of girls with and without Turner syndrome (TS) treated for 3 years with growth hormone (GH). Among a sample of 283 children with short stature, 37 girls with TS were recruited at 27 US medical centers. Of the original cohort, 22 girls with TS, 13 girls with isolated growth hormone deficiency (GHD), and 12 girls with idiopathic short stature were followed through 3 years of GH therapy. All were school-age, were below the 3rd percentile for height, had low growth rates, and were naive to GH therapy. Psychological tests (the Wide Range Achievement Test and the Slosson Intelligence Test) were administered to the clinical groups within 24 hours of their first GH injection and yearly thereafter. Control subjects were 25 girls with normal stature matched for age and socioeconomic status, who were tested only at baseline. One parent of each subject also completed the Child Behavior Checklist for that subject. At baseline, the clinical groups had more internalizing behavioral problems, had fewer friends, and participated in fewer activities than did the control subjects. The groups did not differ in mean IQ or academic achievement, but the TS group did have more problems in mathematics achievement. Height and growth rate significantly increased in the clinical groups over the 3 years of GH therapy, but IQ and achievement scores did not. Significant linear reductions were noted in both Internalizing and Externalizing Behavior Problems after GH treatment, with the TS group having fewer behavior problems before and after GH treatment than did the GHD-idiopathic short stature group. Decreases in specific Child Behavior Checklist subscales, including attention, social problems, and withdrawal, also were seen in the clinical groups after GH therapy. The comprehensive treatment of girls with TS should include educational and behavioral interventions in addition to traditional medical therapies.

Growth hormone therapy in pre-pubertal children with Noonan syndrome: first year growth response and comparison with Turner syndrome.

We studied the growth-promoting effect of treatment with recombinant human growth hormone in 23 pre-pubertal children with Noonan syndrome, aged between 5.4 and 14.3 y, and all with a height < 1.4 SD for Tanner standards. The growth response and skeletal maturation after 1 y of recombinant human growth hormone treatment (0.15 U/kg/day given by daily injection) in the Noonan syndrome patients was compared with the auxological changes observed in a group of 17 girls with Turner syndrome with a comparable age and height deficit who were treated with recombinant human growth hormone in a similar way. During 1 y of treatment, the mean +/- SD height velocity increased by 4.0 +/- 1.6 cm/y in the Noonan syndrome group and by 3.6 +/- 1.3 cm/y in the Turner syndrome group. Height SDS for chronological age in the Noonan syndrome group increased by 0.53 +/- 0.46 (p < 0.001). In the Noonan syndrome patients the changes in height velocity were positively related to birthweight (r = 0.48, p < 0.05). The changes in height velocity or height SDS were not related to the age, height deficit or a delay in bone age maturation at start of treatment. In neither the patients with Noonan syndrome nor Turner syndrome was an acceleration of bone maturation found. We conclude that treatment with recombinant human growth hormone in pre-pubertal NS patients induces an increase in height velocity and height SDS comparable to that observed in Turner syndrome girls.

A PET study of turner's syndrome: Effects of sex steroids and the X chromosome on brain

Women with Turner's syndrome (TS) allow us to study the neurobiological associates of cognitive and behavioral abnormalities because they lack one/part of one X chromosome, and endogenous estrogen. We studied 13 healthy controls (mean age +/- SD, 28 +/- 6 years) and 16 TS subjects (mean age +/- SD, 26 +/- 6 years). We measured cognitive abilities using neuropsychological tests, and cerebral metabolic rates for glucose with positron emission tomography. Compared to controls, TS subjects had significant absolute hypermetabolism in most brain areas; however, normalized metabolism was significantly lower in TS subjects than controls in the insula and association neocortices bilaterally, and there were significant differences in functional metabolic associations of brain region pairs originating in occipital cortex bilaterally, and within the right hemisphere. There were significant correlations between right-left cognitive and metabolic asymmetries in the TS group. Also, within TS a preliminary analysis demonstrated "X chromosome dosage" effects in language ability and left temporal metabolism, asymmetry of right-left test scores, and parietal metabolism. We hypothesize that within TS: i) generalized brain hypermetabolism reflects global abnormalities in neuron packing; ii) neuronal abnormalities occur in association neocortex that differ in nature or extent from whole brain and are associated with significant differences in normalized metabolism; iii) cognitive deficits are related to brain metabolic abnormalities; and iv) social-behavioral problems may be related to abnormalities of brain metabolism. Moreover, in human brain the X chromosome involved in development of the association neocortices.

Executive function in girls with turner's syndrome

Turner's syndrome (TS), a genetic disorder affecting girls, has a well‐described neurocognitive profile including difficulty with visuospatial processing and attention skills. The goal of this study was to investigate executive function and attention abilities in girls with TS. Executive skills include the ability to plan, organize, monitor, and execute multistep problem‐solving processes. Measures of attention and executive function were analyzed from 105 girls with TS and from 153 female controls matched for age, IQ, and socioeconomic status. Three age groups were evaluated in order to assess developmental patterns in executive skills. The TS group (all ages) performed significantly less well than did controls on measures of attention, including the Freedom From Distractibility factor of the Wechsler Intelligence Scale for Children‐Revised and the Test of Variables of Attention. In the executive function domain, girls with TS performed at levels comparable to controls on the Wisconsin Card Sort Test and on measures of semantic clustering, but they exhibited significant deficits on the Rey‐Osterrieth organizational component and the Tower of Hanoi. In summary, girls with TS showed evidence of increased impulsivity at all ages studied. Their performance on tests of executive function with complex spatial demands showed similar impairment at all ages studied. Further exploration of the contribution of multimodal factors and the resulting neurocognitive profile in individuals with TS is warranted.

Developmental changes in motor function in girls with Turner syndrome

The Turner syndrome phenotype is characterized by a particular neurocognitive profile of normal verbal skills, impaired visuospatial and/or visuoperceptual abilities, and difficulty with motor function. We investigated motor function in non-estrogen-treated girls (ages 7–9 and 10–12 years) with Turner syndrome and age-matched female controls. Our goal was to delineate the differences in motor performance between girls with Turner syndrome (n = 78) and control girls (n = 145). Cognitive and motor tasks were administered, as well as nonspatial, repetitive motor tasks, and spatially mediated motor tasks. Questionnaires were also administered. Turner subjects performed less well than the controls on the motor tasks with the greatest spatial demands, particularly in the older age group (age 10–12.9 years). The older control group, unlike the older Turner syndrome group, had significantly increased speed on most of the motor tasks, suggesting a Turner syndrome-associated deficiency in motoric development. The superior performance of the dominant (right) versus the nondominant (left) hand was similar for the Turner syndrome and control groups. In general, the girls with Turner syndrome had evidence of a decreased sense of athletic ability and physical self-image. A likely explanation for motoric deficiency in the older Turner syndrome group relates to their gonadal dysgenesis and estrogen deficiency. In addition to the obvious physical benefits of estrogen replacement, estrogen treatment may have a positive impact on motor function; this will be the subject of future investigations.

The effects of sex steroids, and the X chromosome, on female brain function: A study of the neuropsychology of adult turner syndrome

Sex steroids and the X chromosome can independently affect cognitive abilities. Because subjects with Turner syndrome (TS) have gonadal aplasia, and various alterations in X chromosome structure and number, they provide a model to study the effects of sex steroids and of the X chromosome on human brain function. We used neuropsychological tests to study the cognitive abilities of 18 TS adults and 19 age/sex matched healthy controls. Nine TS subjects were mosaic for the 45,X karyotype, and 9 were non-mosaic 45,X (full TS). The TS group as a whole, compared to controls, had (i) significantly lower scores in tests of language and visual-spatial function, attention and memory, and (ii) a significantly greater discrepancy between verbal and performance scores. Mosaic TS subjects were intermediate between full TS and controls in some tests of verbal ability, but did not differ significantly from controls in others. Visuospatial ability was significantly lower than controls in both mosaic and full TS. Within the mosaic TS group, there was a significant negative correlation between visuospatial ability and % lymphocytes having a 45,X karyotype. Memory test scores were reduced independently of “X chromosome dosage” in all TS subjects. We conclude that in humans, the X chromosome is involved in development of both cerebral hemispheres, but moreso of the association neocortices. Also, sex steroids may modulate this effect— particularly in hippocampus.

X-chromosome effects on female brain: a magnetic resonance imaging study of Turner's syndrome

Summary Many neuropsychiatric disorders differ between the sexes in incidence, symptoms, and age at onset. To investigate the effects of X-chromosome aneuploidy and of sex steroid deficiency during childhood on brain structure and function, we used neuropsychological tests and quantitative magnetic resonance imaging (MRI) to study the brains of eighteen women with Turner's syndrome (TS) and nineteen healthy control women of similar age. Nine TS subjects had mosaic 45,X karyotypes, and 9 had non-mosaic 45,X. The TS group had significantly lower scores than the controls for all the Wechsler adult intelligence scale tests, except verbal comprehension and reading level. The greatest difference was in visuospatial construction (mean 90 [SD 12] vs 118 [13], p < 0·0001). The TS subjects also had a greater discrepancy than controls between verbal and performance intelligence quotients (9 [8] vs -5 [9], p<0 001). We found that TS subjects had significantly smaller values than controls in MRI-measured volumes of hippocampus, caudate, lenticular, and thalamic nuclei, and parieto-occipital brain matter, on both sides. Women with mosaic TS had values between the full TS and control groups for cerebral hemisphere and lenticular and thalamic nuclei volume and for verbal ability. Within the mosaic TS group, visuospatial ability was significantly correlated with the percentage of lymphocytes that had the 45,X karyotype. Hippocampal volume and memory test scores were significantly lower in mosaic and non-mosaic 45,XTS subjects than in controls. We postulate that in human beings the X chromosome plays an important part in the development and ageing of grey matter in striatum, diencephalon, and cerebral hemispheres.

Altered brain development in Turner's syndrome: an event-related potential study.

We compared event-related brain potentials (ERPs) and reaction time (RT) measures from untreated young (prepubertal and peripubertal; ages 9 to 14) and old (postpubertal; ages 15 to 20) Turner's syndrome (TS) subjects with those from normal age-matched controls. Comparisons among groups permitted the assessment of the relative roles of congenital and maturational brain alterations as possible bases of the cognitive deficits in TS. All subjects were presented with series of auditory stimuli, and they either counted one of the two stimuli or made rapid discriminative button presses to both. The results indicated that, whereas the ERPs in young TS females were essentially the same as those in their age-matched controls, the ERPs in old TS females more closely resembled those in both young groups than those in their age-matched controls. Specifically, a late (400 to 900 msec) frontal negative slow wave (Nc) in the old TS subjects failed to show the normal maturational course in which the amplitude and duration of this component steadily decreases with age. Except for slightly greater amounts of N1 amplitude in the young TS group, the latencies, amplitudes, and scalp distributions of the other ERP components (N1, P2, N2, P300) were all the same at all ages in the TS subjects and their controls. Behaviorally, both TS groups had longer RTs than their controls but, consistent with the ERP results, they did not make more errors.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of growth hormone (GH) axis in Turner's syndrome using 24-hour integrated concentrations of GH, insulin-like growth factor-I, plasma GH-binding activity, GH binding to IM9 cells, and GH response to pharmacological stimulation.

The GH axis was studied in Turner's syndrome (TS) patients. Thirty-seven prepubertal TS patients and 42 normally growing girls (NGG; 5.5-16.3 yr old), of whom 13 were prepubertal, were studied by 24-h continuous blood withdrawal and provocative tests. The 24-h integrated concentrations of GH (IC-GH), FSH (IC-FSH), and insulin-like growth factor-I (IC-IGF-I) as well as the IC-IGF-I/IC-GH ratio were determined. An increase in IC-GH with age and progression of puberty was found in NGG, but not in TS. IC-GH in the NGG was significantly higher than that in age-matched TS patients. Estrogen replacement therapy normalized IC-GH levels in 6 TS patients in whom these levels were subnormal for age. A positive correlation between IC-GH and IC-FSH or IC-estradiol was found in NGG (r = 0.462; P less than 0.01), but not in TS patients. The IC-IGF-I/IC-GH ratio was significantly higher in the TS than in the NGG group. Serum GH-binding activity and serum GH binding to IM9 cells in the TS group did not differ from those in the normal group. We hypothesize that the growth retardation of TS results from a combination of insufficient GH secretion, mainly due to sex steroid deficiency, and an end-organ resistance to IGF-I. IGF-I receptor studies are needed to test this speculation about IGF-I resistance.

Effect of obesity on endogenous secretion of growth hormone in Turner's syndrome.

Nocturnal growth hormone secretion over a 12 hour period was assessed at 20 minute intervals in 25 prepubertal subjects with Turner's syndrome and 11 normal prepubertal girls of short stature to try and elucidate the relationship between body weight and endogenous secretion of growth hormone in Turner's syndrome. There were no differences in mean growth hormone concentration, age, height, or growth velocity between the two groups. There was an age related decline in mean growth hormone concentration in patient's with Turner's syndrome in contrast to the age related increase in controls. Mean percentage of ideal body weight was significantly higher in the Turner's syndrome group than among controls and it increased with age. There was a strong inverse relationship between mean growth hormone concentration and percentage of ideal body weight in those with Turner's syndrome. Covariate analysis of the multiple linear regression of mean growth hormone concentration on age and percentage of ideal body weight in Turner's syndrome indicated that percentage of ideal body weight had a significant effect on endogenous secretion of growth hormone when age was held constant, but not the other way round. We conclude that the age related decline in endogenous secretion of growth hormone in Turner's syndrome is partly the result of increasing body weight with age. The significant influences of biological variables such as age and body weight in the interpretation of measurements of endogenous secretion of growth hormone in Turner's syndrome should be emphasised.

A Comparison of Memory and Attention in Turner Syndrome and Learning Disability

Compared short-term verbal memory, sustained attention, and impulsivity in 13 children with Turner syndrome to 13 females and 14 males with learning disability who had neuropsychological patterns similar to the children with Turner syndrome. Similar patterns of short-term memory deficits were found in all three groups. There were no significant differences among the groups on computer measures of sustained attention and impulsivity. However, extreme variability of the attention and impulsivity scores for the Turner syndrome group may reflect atypical attention deficit disorder in some of these children.

Changes of serum protein and immunoglobulins in ovarian agenesis

The levels of serum proteins and immunoglobulins were determined in five cases of Turner's syndrome, in five secondary amenorrheic patients who responded to progesterone, and in five healthy women as controls. Compared with the controls, the patients with secondary amenorrhea showed significantly lower albumin, but higher α 1- and β-globulins; IgG was also lower. In the Turner's syndrome group, gamma globulin, IgG and IgM levels were significantly lower. These results support the suggestion that at least some of the serum proteins and immunoglobulins are related to estrogen.