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Delay in Turner syndrome diagnosis from birth. The X-axis indicates the chronologic age at diagnosis of Turner syndrome, with each bar illustrating a 2.5-year period. Data are from the Danish Cytogenetic Central Register from 1910-2000 and include all females with a karyotype that can be associated with Turner syndrome.
Source publication
Turner syndrome (TS) is a common genetic disorder, resulting from the partial or complete absence of one sex chromosome, and occurring in approximately 50 per 100,000 liveborn girls. TS is associated with reduced adult height and with gonadal dysgenesis, leading to insufficient circulating levels of female sex steroids and to infertility. Morbidity...
Context in source publication
Context 1
... postnatal diagnoses are made at birth (15%), during teenage years (26%), and during adulthood (38%), with the remainder being diagnosed during childhood; 8 this represents a substantial delay in diagnosis for the majority of patients (Figure 2). Interestingly, the most common trigger for diagnosis during infancy is lymphedema (97% of cases), and during child- hood and adolescence is short stature (82% of cases). ...
Citations
... Turner syndrome (TS) is a prevalent genetic condition arising from the partial or complete loss of the second X chromosome in phenotypic females. Its occurrence is noted in approximately 1 in 2000-2500 live female births (Gravholt, 2005;Gravholt et al., 2017). Individuals with TS commonly manifest traits such as diminished stature, deferred pubertal onset, ovarian inadequacy, as well as cardiac and renal irregularities, sensorineural hearing impairment, ocular complications, thyroid anomalies, metabolic syndrome, inflammatory bowel disease, and neurocognitive challenges (Gravholt et al., 2019;Huang et al., 2021). ...
Background
Y chromosome material stands as an independent risk determinant for the onset of gonadoblastoma (GB) and subsequent gonadal germ cell tumours in individuals with Turner syndrome (TS). However, the delayed and underestimated identification of Y chromosome material through karyotyping within primary care settings exacerbates the intricacies of managing these patients over the long term.
Methods
We present a case involving TS accompanied by Y chromosome material, wherein puberty delay and GB were identified during prophylactic gonadectomy. Subsequently, we delve into the literature to explore the GB‐related malignancy risk in TS patients with Y chromosome material, the incidence of Y chromosome presence in TS patients using methodologies beyond routine chromosomal testing, and the diagnosis and treatment of puberty delay in TS patients, all based on our case.
Results
A spectrum of more sensitive molecular techniques, including polymerase chain reaction (PCR) and fluorescence in situ hybridisation, effectively augments the detection of Y chromosome material alongside karyotyping. In addition to gonadectomy, the implementation of appropriate oestrogen therapy and a holistic, multidisciplinary approach to care can enhance the quality of life, while mitigating the long‐term morbidity and mortality risks for TS patients harbouring Y chromosome material.
Conclusions
Beyond gonadectomy, adopting a multifaceted approach the Y chromosome material detection, prompt initiation of puberty, tailored oestrogen therapy, and coordinated multidisciplinary management significantly contributes to the comprehensive health oversight of TS patients with Y chromosome material.
... Turner syndrome is a gonadal dysgenesis defined as the total or partial loss of a sex chromosome [1]. The anomalies of Turner syndrome include short stature (95%-100%), primary amenorrhea (85%), infertility (98%), and characteristic stigmata [2]. The variable expressivity of size and other physical characteristics may be only partially related to the chromosomal formula. ...
Turner's syndrome is a rare complex genetic disease characterized by gonadal dysgenesis and sexual chromosomal abnormalities. Half of the patients affected are monosomic, for the X chromosome, and for the remaining patients, a variety of chromosomal abnormalities have been reported. Only a small percentage (3%-4%) of people with Turner syndrome have triple X cell line mosaicism (47, XXX). It has been reported that patients 45, X/47, XXX have normal intelligence, a higher rate of spontaneous menstruation, an increased number of pregnancies, and a lower frequency of short stature (60%) compared to patients 45, X. In this work, we will present a rare and atypical case of a patient who presents a rare chromosomal mosaicism, with three chromosomal lineages, contrasting with a typical clinical picture of Turner syndrome.
... , is caused by the partial or complete deletion of an X-chromosome (Gravholt, 2005;Stochholm et al., 2006). TS is characterized by several physical features, including short stature, heart malformations, and gonadal dysgenesis with ovarian failure and infertility. ...
Turner syndrome (TS) is a common sex chromosome aneuploidy in females associated with various physical, cognitive, and socio-emotional phenotypes. However, few studies have examined TS-associated alterations in the development of cortical gray matter volume and the two components that comprise this measure-surface area and thickness. Moreover, the longitudinal direct (i.e., genetic) and indirect (i.e., hormonal) effects of X-monosomy on the brain are unclear. Brain structure was assessed in 61 girls with TS (11.3 ± 2.8 years) and 55 typically developing girls (10.8 ± 2.3 years) for up to 4 timepoints. Surface-based analyses of cortical gray matter volume, thickness, and surface area were conducted to examine the direct effects of X-monosomy present before pubertal onset and indirect hormonal effects of estrogen deficiency/X-monosomy emerging after pubertal onset. Longitudinal analyses revealed that, whereas typically developing girls exhibited normative declines in gray matter structure during adolescence, this pattern was reduced or inverted in TS. Further, girls with TS demonstrated smaller total surface area and larger average cortical thickness overall. Regionally, the TS group exhibited decreased volume and surface area in the pericalcarine, postcentral, and parietal regions relative to typically developing girls, as well as larger volume in the caudate, amygdala, and temporal lobe regions and increased thickness in parietal and temporal regions. Surface area alterations were predominant by age 8, while maturational differences in thickness emerged by age 10 or later. Taken together, these results suggest the involvement of both direct and indirect effects of X-chromosome haploinsufficiency on brain development in TS.
... 4,5 In the prenatal period, the ultrasound findings of increased nuchal translucency, cystic hygroma, and left-sided obstructive cardiac anomalies (especially coarctation of the aorta) in any fetus are highly suggestive of TS, and test to confirm the diagnosis prenatally by amniocentesis or chorionic villous sampling is necessary, 6 Webbed neck, lymphedema, or coarctation of the aorta in infancy should prompt a peripheral blood karyotype to rule out TS. 6 However, several girls have delayed diagnosis in late adolescence or early adulthood, with some estimates indicating that up to 38% of TS patients are diagnosed in adulthood. 7 Diagnosis is made by sex chromatin [Barr body] detection, and chromosomal karyotyping is necessary to diagnose and identify the fraction of "Y" chromosome elements. ...
Similar to bronchiectasis, Turner syndrome is possible to have more pathological manifestations or etiologies than what has already been documented. Slower recovery process is expected when treating a patient with several comorbidities like Turner syndrome. Turner syndrome patients are vulnerable and should be extensively monitored to lower late presentation rates.
... Turner syndrome (TS) is a genetic disorder characterized by the absence of all or part of the second X chromosome and occurs in 1/2500 live female births (Baena et al., 2004;Gravholt, 2005). The physical TS phenotypes include short stature and endocrine abnormalities, such as the loss of ovarian function and estrogen deficiency (Dhooge, De Vel, Verhoye, Lemmerling, & Vinck, 2005;Sybert & McCauley, 2004). ...
Gonadal steroids play an important role in brain development, particularly during puberty. Girls with Turner syndrome (TS), a genetic disorder characterized by the absence of all or part of the second X chromosome, mostly present a loss of ovarian function and estrogen deficiency, as well as neuroanatomical abnormalities. However, few studies have attempted to isolate the indirect effects of hormones from the direct genetic effects of X chromosome insufficiency. Brain structural (i.e., gray matter [GM] morphology and white matter [WM] connectivity) and functional phenotypes (i.e., resting‐state functional measures) were investigated in 23 adolescent girls with TS using multimodal MRI to assess the role of hypogonadism in brain development in TS. Specifically, all girls with TS were divided into a hormonally subnormal group and an abnormal subgroup according to their serum follicle‐stimulating hormone (FSH) levels, with the karyotypes approximately matched between the two groups. Statistical analyses revealed significant effects of the “group‐by‐age” interaction on GM volume around the left medial orbitofrontal cortex and WM diffusion parameters around the bilateral corticospinal tract, anterior thalamic radiation, left superior longitudinal fasciculus, and cingulum bundle, but no significant “group‐by‐age” or group differences were observed in resting‐state functional measures. Based on these findings, estrogen deficiency has a nontrivial impact on the development of the brain structure during adolescence in girls with TS. Our present study provides novel insights into the mechanism by which hypogonadism influences brain development during adolescence in girls with TS, and highlights the important role of estrogen replacement therapy in treating TS.
... When patients enter puberty spontaneously, progressive premature ovarian failure will follow in most cases (Mortensen et al., 2009). Nonetheless, nearly 20% of patients will present spontaneous menarche, with nonassisted pregnancy rate being 2%-5% (Gravholt, 2005). ...
In everyday practice, a pediatric endocrinologist will face a variety of different endocrine issues (such as short or tall stature, dysthyroidism, abnormal pubertal timing or impaired glucose metabolism), which relevantly contribute to the global care of a number of syndromic conditions. On the other hand, the presence of endocrine features may assist in the diagnostic process, leading to final diagnosis of a syndromic disorder. The intention of this review is to provide a referenced overview of different genetic syndromes characterized by endocrine features, and to present a possible classification, based on whether the endocrinopathy or the syndrome is typically recognized first. Thus, the first part of the manuscript deals with the most common syndromes associated with endocrine dysfunctions, while the second part describes the conditions by which a syndrome is most frequently diagnosed after an endocrine finding. The aim is to provide a practical overview of the assessment of syndromic patients, so that they can be recognized and managed in an integrated, multidisciplinary fashion.
... Turner syndrome (TS) is a common genetic disorder occurring in approximately 1/2500 live births (Gravholt CH, 2005;Baena N, De Vigan C, Cariati E, et al. 2004). The physical phenotype is often characterized by short stature, cardiac, renal and endocrine abnormalities, including loss of ovarian function and estrogen deficiency (Dhooge IJ, De Vel E, Verhoye C, Lemmerling M, Vinck B, 2004;Sybert VP, McCauley E, 2004;Bondy CA, Bakalov VK, 2006). ...
There is increasing evidence that Turner syndrome is associated with a distinct pattern of cognitive and neurophysiological characteristics. Typically this has been characterized by relative strengths in verbal skills, contrasting with relative weaknesses in arithmetic, visuospatial and executive function domains. Potential differences in social cognitive processing have also been identified. More recently, applications of neuroimaging techniques have further elucidated underlying differences in brain structure, function and connectivity in individuals with Turner syndrome. Ongoing research in this area is focused on establishing a unified mechanistic model incorporating genetic influences from the X chromosome, sex hormone contributions, neuroanatomical variation and differences in cognitive processes. This review broadly covers current understanding of how X-monosomy impacts neurocognitive phenotype both from the perspective of cognitive-behavioral and neuroimaging studies. Furthermore, relevant clinical aspects of identifying potential learning difficulties and providing anticipatory guidance for affected individuals with TS, are briefly discussed.
... Genetic and developmental disorders are commonly characterized by a unique cognitivebehavioral phenotype. Turner syndrome (TS), a common X-chromosome aneuploidy syndrome affecting approximately 1/2000 live female births (Gravholt, 2005), is caused by the partial or complete deletion of an X-chromosome. Individuals with TS are at risk for developing impairments in social awareness and fear recognition Mazzocco et al., 1998), as well as cognitive deficits related to attention, memory, and visuospatial and executive processing (Kesler et al., 2006;Tamm et al., 2003). ...
Turner syndrome (TS) is a highly prevalent genetic condition caused by partial or complete absence of one X-chromosome in a female and is associated with a lack of endogenous estrogen during development secondary to gonadal dysgenesis. Prominent cognitive weaknesses in executive and visuospatial functions in the context of normal overall IQ also occur in affected individuals. Previous neuroimaging studies of TS point to a profile of neuroanatomical variation relative to age and sex matched controls. However, there are no neuroimaging studies focusing on young girls with TS before they receive exogenous estrogen treatment to induce puberty. Information obtained from young girls with TS may help to establish an early neural correlate of the cognitive phenotype associated with the disorder. Further, univariate analysis has predominantly been the method of choice in prior neuroimaging studies of TS. Univariate approaches examine between-group differences on the basis of individual image elements (i.e., a single voxel's intensity or the volume of an a priori defined brain region). This is in contrast to multivariate methods that can elucidate complex neuroanatomical profiles in a clinical population by determining the pattern of between-group differences from many image elements evaluated simultaneously. In this case, individual image elements might not be significantly different between groups but can still contribute to a significantly different overall spatial pattern. In this study, voxel-based morphometry (VBM) of high-resolution magnetic resonance images was used to investigate differences in brain morphology between 13 pediatric, pre-estrogen girls with monosomic TS and 13 age-matched typically developing controls (3.0 T imaging: mean age 9.1±2.1). A similar analysis was performed with an older cohort of 13 girls with monosomic TS and 13 age-matched typically developing controls (1.5 T imaging: mean age 15.8±4.5). A multivariate, linear support vector machine analysis using leave-one-out cross-validation was then employed to discriminate girls with TS from typically developing controls based on differences in neuroanatomical spatial patterns and to assess how accurately such patterns translate across heterogeneous cohorts. VBM indicated that both TS cohorts had significantly reduced gray matter volume in the precentral, postcentral, and supramarginal gyri and enlargement of the left middle and superior temporal gyri. Support vector machine (SVM) classifiers achieved high accuracy for discriminating brain morphology patterns in TS from typically developing controls and also displayed spatial patterns consistent with the VBM results. Furthermore, the SVM classifiers identified additional neuroanatomical variations in individuals with TS, localized in the hippocampus, orbitofrontal cortex, insula, caudate, and cuneus. Our results demonstrate robust spatial patterns of altered brain morphology in developmentally dynamic populations with TS, providing further insight into the neuroanatomical correlates of cognitive-behavioral features in this condition.
... Turner Syndrome, occurring in approximately 1:2500 female births, is caused by a sex chromosome abnormality involving the presence of only one normal X chromosome and the complete or partial absence of the second. 1 Short stature and/ or ovarian failure are the most common clinical presentations and the majority of women never produce ovarian hormones. Typical congenital malformations are pterygium colli, horse shoe kidney, and coarctation of the aorta, as well as less severe heart defects, especially associated with the 45, XO karyotype. ...
... There is epidemiological evidence for increased morbidity due to ischemic heart disease, hypertension, and stroke. 1 Progress made in proteomics over the past few years was rendered possible through the development of protein separation approaches and mass spectrometry (MS). Two-dimensional electrophoresis (2DE) is an excellent tool for proteomic analysis and can be used to compare patterns of protein expression in various biological materials under physiological and pathological conditions. ...
Turner syndrome, occurring in 1:2500 female births, is caused by the complete or partial absence of one X chromosome. Amniotic fluid supernatant proteins from five second trimester pregnancies with Turner syndrome fetuses and five normal ones were analyzed by 2DE, MALDI-TOF-MS, and Western blot. Serotransferin, lumican, plasma retinol-binding protein, and apolipoprotein A-I were increased in Turner syndrome, while kininogen, prothrombin, and apolipoprotein A-IV were decreased. Since differentially expressed proteins are likely to cross the placenta barrier and be detected in maternal plasma, proteomic analysis may enhance research for noninvasive prenatal diagnosis of Turner syndrome.
... The most common (i.e. frequency of 50% or greater) physical abnormalities affecting girls with TS include short stature, infertility, estrogen deficiency, hypertension, elevated hepatic enzymes, middle ear infection, micrognathia, bone age retardation, decreased bone mineral content, cubitus valgus, and poor thriving during the first postnatal year [1]. Females with TS also have significantly higher risks for certain diseases compared to the general population including hypothyroidism, diabetes, heart disease, osteoporosis, congenital malformations (heart, urinary system, face, neck, ears), neurovascular disease and cirrhosis of the liver as well as colon and rectal cancers [1]. ...
... frequency of 50% or greater) physical abnormalities affecting girls with TS include short stature, infertility, estrogen deficiency, hypertension, elevated hepatic enzymes, middle ear infection, micrognathia, bone age retardation, decreased bone mineral content, cubitus valgus, and poor thriving during the first postnatal year [1]. Females with TS also have significantly higher risks for certain diseases compared to the general population including hypothyroidism, diabetes, heart disease, osteoporosis, congenital malformations (heart, urinary system, face, neck, ears), neurovascular disease and cirrhosis of the liver as well as colon and rectal cancers [1]. ...
... Cardiac abnormalities are considered the most serious medical problems associated with TS. There exists a high rate of morbidity among the TS population, primarily due to congenital and acquired heart conditions such as coarctation of the aorta, biscuspid aortic valves, mitral valve prolapse, hypertension, ischemic heart disease and arteriosclerosis [1,4,[31][32][33]. ...
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.
