Turner syndrome and schizophrenia: A further hint for the role of the X-chromosome in the pathogenesis of schizophrenic disorders

Abnormalities of sex chromosomes are associated with various forms of neuropsychiatric disorders, such as schizophrenia. Turner syndrome occurs approximately threefold more frequently in female schizophrenics compared to the general female population. A single case is reported. We report on a case of a 41-year-old woman with Turner syndrome, schizophrenia, mental retardation, and hypothyroidism. A polymorphism of the HOPA gene within Xq13 termed HOPA^12bp is associated with schizophrenia, mental retardation, and hypothyroidism. Interestingly, Xq13 is the X-chromosome region that contains the X-inactivation center and a gene escaping X-inactivation whose gene product may be involved in the X-inactivation process as well as in the pathogenesis of sex chromosome anomalies such as Turner syndrome. These genes that escape X-inactivation may produce their gene products in excess, influencing normal brain growth and differentiation. Our case gives a further hint for an involvement of the X-chromosome in the pathogenesis of schizophrenia.     

Ischemic stroke in a young adult with Turner syndrome

A 37-year-old woman suffered from sudden hemiparesis due to an ischemic stroke. Physical examination revealed dysmorphic features, cognitive impairment, and emotional lability. Radiological studies showed multiple intracranial arterial stenoses, and laboratory examination revealed diabetes mellitus, dyslipidemia, and endocrinological abnormalities consistent with secondary amenorrhea. Karyotyping disclosed partial monosomy of the short arm of the X chromosome. We diagnosed the patient with Turner syndrome and concluded that premature atherosclerosis was a cause of stroke. We emphasize a possible relationship between strokes and Turner syndrome. Physicians need to manage adult Turner patients carefully, especially with regard to metabolic dysfunctions, to prevent strokes.     

Turner syndrome

Turner syndrome is a neurogenetic disorder characterized by partial or complete monosomy-X. It is associated with certain physical and medical features, including estrogen deficiency, short stature, and increased risk for several diseases, with cardiac conditions being among the most serious. The cognitive-behavioral phenotype associated with the syndrome includes strengths in verbal domains with impairments in visuospatial, executive function, and emotion processing. Less is known regarding psychosocial and psychiatric functioning in Turner syndrome, but essential aspects of psychotherapeutic treatment plans are suggested. Future investigations should include continued genetic studies and determination of candidate genes for physical and cognitive features. Multimodal, interdisciplinary studies are essential for identifying optimal, syndrome-specific interventions for improving the lives of individuals who have Turner syndrome.     

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.     

Agenesis of the corpus cállosum in Turner syndrome with ring X

An 8-year-old girl with Turner syndrome and 45,X/48,X,r (X) mosaicism was found to have agenesis of the corpus callosum and various other characteristics including 'kabuki makeup' facial features and mild learning disability. Only two other cases of Turner syndrome associated with agenesis of the corpus callosum have been reported, both in patients with a 45,X karyotype. In both of those patients the constellation of signs differed from those of the present patient in a number of ways. It remains to be confirmed whether there is a higher incidence of CNS malformation in girls who have Turner syndrome with a ring X than has been reported for girls with Turner syndrome in general.     

Girl with partial Turner syndrome and absence epilepsy

This report describes a 16-year-old girl with short stature (-5 standard deviations), normal puberty, panic attacks, absence epilepsy, some stigmata of Turner syndrome, and a Madelung deformity. Routine chromosomal analysis revealed a female karyotype with one abnormal chromosome X, with the suspicion of additional material on the short arm. With fluorescent in situ hybridization and array-multiplex amplifiable probe hybridization methodology, a complex aberration was detected, with a deletion of the distal part of Xp22.33 (including the short-stature homeobox gene) and a duplication of Xp22.32-p22.12 proximal to the deleted segment. The deletion in our patient involves the Xp22.33 region. Two genes in this region may contribute to the patient's phenotype: short-stature homeobox, and visuospatial/perceptual abilities. The duplication in our patient involves the Xp22.12-p22.32 region, which, according to the Online Mendelian Inheritance in Man database, contains at least 93 genes, 49 of which are of unknown function. It is difficult to conjecture which gene overexpression in this region may have contributed to the phenotype of our patient. To our knowledge, this small, complex chromosome X aberration was not described previously.     

Pseudotumour cerebri and the Turner syndrome.

One of 170 patients with karyotype-proven Turner syndrome from our institution has had pseudotumour cerebri. This patient and one previous report suggest that patients with Turner syndrome may be predisposed to increased intracranial pressure. Fourteen patients with pseudotumour cerebri were ascertained from hospital records; karyotypes of four were obtained and were normal. Karyotyping may be appropriate in women with pseudotumour cerebri who also have infertility, short stature, multiple pregnancy losses, or other features suggestive of Turner syndrome.     

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.     

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.     

Behavioral assessment of social anxiety in females with Turner or fragile X syndrome

Social skills impairment in children with Turner or fragile X syndrome has been documented using parental reports. Anxiety, shyness, and difficulty understanding social cues have been reported for females with Turner syndrome; whereas social withdrawal, avoidance of social interactions, and anxiety are often reported for females with fragile X syndrome. Social interaction anxiety in these two populations may be a framework for understanding the difficulty these children experience in social situations. In the present study, 29 females with Turner syndrome and 21 females with fragile X syndrome ages 6–22 years were compared to females in a comparison group, on a videotaped role-play interaction. Behavioral indices examined included eye-contact maintenance, duration of speech, and body discomfort as observed during the brief interaction. Three of eight such behavioral measures of social skills differentiated the participant groups from each other. Specifically, participants with fragile X required more time to initiate interactions than did participants in either of the remaining groups; and females with Turner syndrome made fewer facial movements than did females in the fragile X or comparison group. Self-report and parental ratings did not suggest higher levels of anxiety in females with Turner or fragile X syndrome, but did reflect higher levels of social difficulty. The authors discuss these findings in terms of understanding the nature of social dysfunction in females with Turner or fragile X syndrome.     

Coffin-Lowry syndrome and schizophrenia: a family report

ABSTRACT. A family is reported in which the mother and 4 of her 6 children are affected by a constellation of abnormalities including mental handicap, abnormal facies, short stature, soft fleshy hands with sapering fingers and skeletal abnormalities. The family is believed to represent a further group of individuals with Coffin-Lowry syndrome. Additionally, one affected daughter has symptoms suggestive of schizophrenia and one affected son has severe sensorineural deafness.     

Photosensitivity in electroencephalogram of a child with 45, X/46, X,mar (X) Turner Syndrome

We report an 11-year-old girl with Turner syndrome with 45, X/46, X, mar (X) who had mental retardation. EEG showed remarkable provocation of paroxysmal activity by photic stimulation. Diffuse irregular poly-spike and wave bursts were elicited by photic stimuli, without accompanying by clinical seizure.     

Unusual Parsonage–Turner syndrome with relapses and bilateral simultaneous anterior interosseous neuropathy

We report an unusual case of Parsonage–Turner syndrome with relapses and simultaneous bilateral anterior interosseous neuropathy (AIN). A 66-year-old man, after a typical right brachial amyotrophic neuralgia few months previously, underwent surgery for left carpal tunnel syndrome. The day following surgery, wrist aching and bilateral weakness, even if prevalent on the right side, on thumb and index finger flexion appeared. Neurophysiology was consistent with bilateral AIN neuropathy and serology revealed anti-nucleus antibody positivity. Association of relapses with bilateral acute AIN involvement in the subject with autoantibody detection can suggest an immunological pathogenesis.     

Lateralized neurologic deficits and psychopathology in a Turner syndrome patient.

A Turner syndrome patient has been studied by more extensive neuropsychological testing than has previously been reported with such patients. Testing indicates impairment of a variety of functions normally subserved by the right cerebral hemisphere. If replicated with other Turner patients, a lateralized neurologic deficit is implicated as part of the syndrome. Also, this case illustrates the importance of family support and sensitive professional treatment in determining the psychological outcome of this disorder. As an important therapeutic consideration, we describe psychologically detrimental effects of delayed estrogen treatment with an older Turner syndrome patient.     

A cognitive characterization of dyscalculia in Turner syndrome

Current theories of number processing postulate that the human abilities for arithmetic are based on cerebral circuits that are partially laid down under genetic control and later modified by schooling and education. This view predicts the existence of genetic diseases that interfere specifically with components of the number system. Here, we investigate whether Turner syndrome (TS) corresponds to this definition. TS is a genetic disorder which affects one woman in 2500 and is characterized by partial or complete absence of one X chromosome. In addition to well-characterized physical and hormonal dysfunction, TS patients exhibit cognitive deficits including dyscalculia. We tested 12 women with Turner syndrome and 13 control subjects on a cognitive battery including arithmetical tests (addition, subtraction, multiplication, division) as well as tests of the understanding of numerosity and quantity (cognitive estimation, estimation, comparison, bisection, subitizing/counting). Impairments were observed in cognitive estimation, subitizing, and calculation. We examine whether these deficits can be attributed to a single source, and discuss the possible implications of hormonal and genetic factors in the neuropsychological profile of TS patients.     

Mapping the effect of the X chromosome on the human brain: Neuroimaging evidence from Turner syndrome

In addition to determining sex, the X chromosome has long been considered to play a crucial role in brain development and intelligence. Turner syndrome (TS) is caused by the congenital absence of all or part of one of the X chromosomes in females. Thus, Turner syndrome provides a unique “knock-out model” for investigating how the X chromosome influences the human brain in vivo. Numerous cutting-edge neuroimaging techniques and analyses have been applied to investigate various brain phenotypes in women with TS, which have yielded valuable evidence toward elucidating the causal relationship between the X chromosome and human brain structure and function. In this review, we comprehensively summarize the recent progress made in TS-related neuroimaging studies and emphasize how these findings have enhanced our understanding of X chromosome function with respect to the human brain. Future investigations are encouraged to address the issues of previous TS neuroimaging studies and to further identify the biological mechanisms that underlie the function of specific X-linked genes in the human brain.     

Arousal Modulation in Females with Fragile X or Turner Syndrome

The present study was carried out to examine physiological arousal modulation (heart activity and skin conductance, across baseline and cognitive tasks, in females with fragile X or Turner syndrome and a comparison group of females with neither syndrome. Relative to the comparison group, for whom a greater increase in skin conductance was associated with poor arithmetic performance and less risk taking behavior, females with fragile X displayed a minimal increase in heart activity that was nevertheless associated with poor performance on mental arithmetic. In contrast, no arousal–cognitive performance relationship emerged for the group with Turner syndrome. Taken together, our findings suggest that distinct profiles of arousal modulation might be associated with cognitive deficits in these syndrome populations.     

Intractable epilepsy in Turner syndrome associated with bilateral perisylvian hypoplasia: one case report

Turner syndrome (TS) is the most frequent sex abnormality in females, generally associated with a 45,X0 karyotype. Although neurological complications are frequently part of the clinical picture, serious brain abnormalities are quite rare in TS. Epilepsy in TS is not frequent and so far only few cases have been reported, usually associated with cortical dysplasias. We report a Turner patient showing severe neurological impairment, refractory epilepsy and MRI finding of bilateral perisylvian hypoplasia. The possible dysgenetic role of X-chromosome on cortical morphogenesis is also discussed.     

Development and treatment of anorexia nervosa in patients with Turner syndrome. A case study

summary We describe the case of a girl with Turner syndrome who has also developed anorexia nervosa. According to the available literature, patients with Turner syndrome do not have an increased risk of developing anorexia nervosa. However, if such comorbidity should occur, as it did in our case, then some aspects of treatment will have to be adjusted.     

Psychiatric manifestations in Turner Syndrome: a brief survey

Turner Syndrome (TS) is a relatively common genetic syndrome in which a woman has a 45XO or 45XO/46XX mosaic karyotype. Although it is not associated with any psychiatric syndrome, several case reports in the literature describe a similar constellation of symptoms in TS that may represent a biologically-based entity. This article reviews existing case reports and seeks common characteristics among them, which may include mild psychosis with stress-precipitated onset, prominent mood features, and some features that may resemble organic disease.