Recent advances in mechanisms ensuring the pairing, synapsis and segregation of XY chromosomes in mice and humans.

Sex chromosome aneuploidies are among the most common variations in human whole chromosome copy numbers, with an estimated prevalence in the general population of 1:400 to 1:1400 live births. Unlike whole-chromosome aneuploidies of autosomes, those of sex chromosomes, such as the 47, XXY aneuploidy that causes Klinefelter Syndrome (KS), often originate from the paternal side, caused by a lack of crossover (CO) formation between the X and Y chromosomes. COs must form between all chromosome pairs to pass meiotic checkpoints and are the product of meiotic recombination that occurs between homologous sequences of parental chromosomes. Recombination between male sex chromosomes is more challenging compared to both autosomes and sex chromosomes in females, as it is restricted within a short region of homology between X and Y, called the pseudo-autosomal region (PAR). However, in normal individuals, CO formation occurs in PAR with a higher frequency than in any other region, indicating the presence of mechanisms that promote the initiation and processing of recombination in each meiotic division. In recent years, research has made great strides in identifying genes and mechanisms that facilitate CO formation in the PAR. Here, we outline the most recent and relevant findings in this field. XY chromosome aneuploidy in humans has broad-reaching effects, contributing significantly also to Turner syndrome, spontaneous abortions, oligospermia, and even infertility. Thus, in the years to come, the identification of genes and mechanisms beyond XY aneuploidy is expected to have an impact on the genetic counseling of a wide number of families and adults affected by these disorders.

Monosomy X in isogenic human iPSC-derived trophoblast model impacts expression modules preserved in human placenta.

Mammalian sex chromosomes encode homologous X/Y gene pairs that were retained on the Y chromosome in males and escape X chromosome inactivation (XCI) in females. Inferred to reflect X/Y pair dosage sensitivity, monosomy X is a leading cause of miscarriage in humans with near full penetrance. This phenotype is shared with many other mammals but not the mouse, which offers sophisticated genetic tools to generate sex chromosomal aneuploidy but also tolerates its developmental impact. To address this critical gap, we generated X-monosomic human induced pluripotent stem cells (hiPSCs) alongside otherwise isogenic euploid controls from male and female mosaic samples. Phased genomic variants in these hiPSC panels enable systematic investigation of X/Y dosage-sensitive features using in vitro models of human development. Here, we demonstrate the utility of these validated hiPSC lines to test how X/Y-linked gene dosage impacts a widely used model for human syncytiotrophoblast development. While these isogenic panels trigger a GATA2/3- and TFAP2A/C-driven trophoblast gene circuit irrespective of karyotype, differential expression implicates monosomy X in altered levels of placental genes and in secretion of placental growth factor (PlGF) and human chorionic gonadotropin (hCG). Remarkably, weighted gene coexpression network modules that significantly reflect these changes are also preserved in first-trimester chorionic villi and term placenta. Our results suggest monosomy X may skew trophoblast cell type composition and function, and that the combined haploinsufficiency of the pseudoautosomal region likely plays a key role in these changes.

Rare Turner syndrome and lupus coexistence with insights from DNA methylation patterns.

Systemic lupus erythematosus (SLE or lupus) is a complex autoimmune disease that can affect multiple organs. While the exact disease etiology remains incompletely understood, there is a suggested influence of X-chromosome dosage in the pathogenesis of lupus. Here, we report a rare case of a female patient diagnosed with mosaic Turner syndrome and subsequently presenting with juvenile-onset SLE. DNA methylation patterns were analyzed in this patient and compared with age-matched female SLE controls, revealing higher methylation levels in interferon-regulated genes previously shown to be hypomethylated in SLE. These data provide a potential link between a gene-dose effect from the X-chromosome and the lupus-defining epigenotype. We hypothesize that the attenuated demethylation in interferon-regulated genes might provide a protective effect explaining the rarity of SLE in Turner syndrome.

Growth hormone therapy is associated with improved uterine dimensions in girls with Turner syndrome prior to oestrogen replacement.

BACKGROUND: Adult women with Turner syndrome (TS) have high rates of miscarriage, presumably due to the abnormal size and shape of the uterus. There is a paucity of data regarding the determinants of uterine volume (UtVol) in young girls with TS before the initiation of oestrogen replacement therapy (ERT). METHODS: We performed a cross-sectional study on premenarchal girls with TS, aged 5-15 years, pubertal stage B1-B3, not having received ERT (n = 73) and 50 age-matched healthy controls. Anthropometric parameters and a history of growth hormone (GH) therapy (≥1 year) were noted. Uterine length (UtL), UtVol, and mean-ovarian-volume (MOV) standard-deviation scores (SDS) were determined from transabdominal ultrasonography data. RESULTS: Girls with TS had lower median UtVol-SDS (-1.07 vs. 0.86; p < .001), UtL-SDS (-3.72 vs. -0.41; p < .001) and MOV-SDS (-5.53 vs. 1.96; p < .001) compared to age-matched controls. Among TS girls, recipients of GH (n = 38) had higher UtVol-SDS (-0.63 vs. -1.39; p = .0001), UtL-SDS (-1.73 vs. -6.49; p < .0001) but similar MOV-SDS compared to nonrecipients (n = 35). Those with normal uterine volume for age (NUVA, n = 29) had earlier initiation (7.8 vs. 9.3 years; p = .03) and a longer duration of GH (3.71 vs. 2.14 years; p = .002) than those with low UtVol for age (n = 44). UtVol-SDS correlated with duration of GH (ρ = 0.411, p = .01) and negatively with age at GH initiation (ρ = -0.479, p = .003). In a model adjusted for pubertal status, karyotype and height-SDS, GH use could independently predict having NUVA (odds ratio: 5.09, confidence interval: 1.63-15.94, p = .005). CONCLUSION: GH therapy has a stimulatory effect on uterine dimensions in pre-and peripubertal girls with TS. Earlier initiation and longer duration of GH is important in TS girls before ERT.

Anti-Mullerian hormone and spontaneous puberty in a diverse US Turner syndrome clinic cohort: A cross-sectional study.

OBJECTIVE: Serum Anti-Mullerian Hormone (AMH) concentrations have been proposed as a marker of spontaneous puberty and future fertility in Turner syndrome (TS). Gonadotropins during minipuberty may also provide a clue to ovarian function but there is insufficient data to inform utility in the routine clinical management of TS. Our objective was to describe the distribution of AMH in a cross-sectional cohort of patients in a TS specialty clinic, and correlate with spontaneous puberty and karyotype, as well as gonadotropins during the minipuberty of infancy in a smaller subset of patients aged 2-9 months. DESIGN: Retrospective chart review of patients seen in the TS clinic at Children's National Hospital from 1/1/2019 to 8/24/2022, to assess AMH and correlate with karyotype and spontaneous puberty. RESULTS: Among 114 patients (median age 9.6 year, 0.08-22 year), AMH values were detectable in only (40/104) 38%, and higher mean AMH (2.7 ± 0.95 ng/mL) was seen in mosaic 45,X/46,XX karyotype compared to 45,X (0.03 ± 0.14 ng/mL) (p < .001), and structurally abnormal-X karyotype (0.11 ± 0.5) (p = .0003). Mean AMH was higher (1.4 ± 1.6 ng/mL) among those with spontaneous menarche compared with spontaneous thelarche but no menarche. AMH was detectable in 2/10 during minipuberty in those with the lowest luteinizing hormone (LH). CONCLUSIONS: Our institutional data reflects a diverse cohort of patients seen in a TS specialty clinic in the United States, showing correlation of AMH with karyotype and spontaneous menarche, as well as description of gonadotropins during minipuberty highlighting their clinical relevance. Studies in larger, prospective longitudinal cohorts will help determine their predictive value and role in the care of TS.

Fertility and pregnancy outcomes in women with Turner syndrome: A single centre experience.

OBJECTIVE: Many women with Turner syndrome (TS) will consider fertility options and pregnancy. We wished to examine the fertility and pregnancy outcomes in women with TS undergoing oocyte donation (OD) treatment or spontaneous pregnancy in a large single-centre cohort. General population reference data or data from those with idiopathic premature ovarian insufficiency were used as comparators. DESIGN: A retrospective single-centre cross-sectional study. PATIENTS AND MEASUREMENTS: Seventy-four women with TS underwent OD treatment with a total of 105 pregnancies, and 31 women with TS had 71 spontaneous conceptions. Fertility outcomes included clinical pregnancy and live birth rate. Pregnancy outcomes included miscarriage rate, prevalence of hypertension, gestational diabetes, lower segment caesarean section (LSCS), small for gestational age (SGA), prematurity and vertical transmission of TS. RESULTS: In those with TS, OD pregnancies were associated with increased rates of LSCS and SGA compared to spontaneous pregnancies; LSCS (OR: 4.19, 95% CI: 1.6-10.8, p = .003) and SGA (OR: 2.92, 95% CI: 1.02-8.38, p = .04). There were no recorded cardiac events but 5 (17.2%) cases of vertical transmissions of TS in daughters were identified. OD in those with TS was associated with a lower live birth rate per cycle started (OR: 0.53, 95% CI: 0.34-0.84, p = .008) and a higher rate of miscarriage compared to women with POI (40% vs. 26.2%, p = .04). CONCLUSIONS: We show that pregnancy in women with TS, whether OD or spontaneously conceived, carries obstetric risks, and therefore, women with TS, considering pregnancy, should receive comprehensive pre-pregnancy counselling and optimal obstetric care.

Risk assessment for aortic dissection in Turner syndrome: The role of the aortic growth rate.

OBJECTIVE: The risk of aortic dissection (AoD) is increased in Turner syndrome (TS) but predicting those at risk is difficult. Based on scarce evidence, preventive aortic surgery is recommended when aortic diameter increases >5 mm/year. To investigate the aortic growth rate in TS and TS-related conditions associated with aortic growth. We also reported our experience of women who suffered aortic dissection (AoD), and who had preventive aortic replacement. METHODS: 151 adult TS were retrospectively identified. Women who had more than one transthoracic echocardiogram (TTE) after age 16 years were included in the aortic growth study. Aortic diameters at sinuses of Valsalva (SoV) and ascending aorta (AA) were analysed by two experts. RESULTS: 70/151 women had more than one TTE (interscan interval 4.7 years). Mean aortic growth was 0.13 ± 0.59 mm/year at SoV and 0.23 ± 0.82 mm/year at AA. Known risk factors for aortic dilatation and TS-related conditions were not associated with aortic growth. 4/151 women experienced AoD (age 25±8 years): two had paired scans for aortic growth, which was 0.67 mm/year at both SoV and AA in the first woman, and 11 mm/year (SoV) and 4 mm/year (AA) in the second. Only 1/4 of women with AoD survived; she used a TS cardiac-alert card to inform emergency personnel about her risk of AoD. 5/151 had a preventive aortic replacement, but one died post-operatively. CONCLUSIONS: Mean aortic growth in our TS population was increased compared to non-TS women and was not associated with currently known risk factors for AoD, suggesting that aortic growth rate itself could be a useful variable to stratify who is at risk for AoD.

Microcystic lymphatic malformations in Turner syndrome are due to somatic mosaicism of PIK3CA.

Turner syndrome (45,X) is caused by a complete or partial absence of a single X chromosome. Vascular malformations occur due to abnormal development of blood and/or lymphatic vessels. They arise from either somatic or germline pathogenic variants in the genes regulating growth and apoptosis of vascular channels. Aortic abnormalities are a common, known vascular anomaly of Turner syndrome. However, previous studies have described other vascular malformations as a rare feature of Turner syndrome and suggested that vascular abnormalities in individuals with Turner syndrome may be more generalized. In this study, we describe two individuals with co-occurrence of Turner syndrome and vascular malformations with a lymphatic component. In these individuals, genetic testing of the lesional tissue revealed a somatic pathogenic variant in PIK3CA-a known and common cause of lymphatic malformations. Based on this finding, we conclude that the vascular malformations presented here and likely those previously in the literature are not a rare part of the clinical spectrum of Turner syndrome, but rather a separate clinical entity that may or may not co-occur in individuals with Turner syndrome.

Development and validation of a computable phenotype for Turner syndrome utilizing electronic health records from a national pediatric network.

Turner syndrome (TS) is a genetic condition occurring in ~1 in 2000 females characterized by the complete or partial absence of the second sex chromosome. TS research faces similar challenges to many other pediatric rare disease conditions, with homogenous, single-center, underpowered studies. Secondary data analyses utilizing electronic health record (EHR) have the potential to address these limitations; however, an algorithm to accurately identify TS cases in EHR data is needed. We developed a computable phenotype to identify patients with TS using PEDSnet, a pediatric research network. This computable phenotype was validated through chart review; true positives and negatives and false positives and negatives were used to assess accuracy at both primary and external validation sites. The optimal algorithm consisted of the following criteria: female sex, ≥1 outpatient encounter, and ≥3 encounters with a diagnosis code that maps to TS, yielding an average sensitivity of 0.97, specificity of 0.88, and C-statistic of 0.93 across all sites. The accuracy of any estradiol prescriptions yielded an average C-statistic of 0.91 across sites and 0.80 for transdermal and oral formulations separately. PEDSnet and computable phenotyping are powerful tools in providing large, diverse samples to pragmatically study rare pediatric conditions like TS.

45,X/46,XY mosaicism: Clinical manifestations and long term follow-up.

45,X/46,XY chromosomal mosaicism presents a range of clinical manifestations, including phenotypes from Turner syndrome through genital abnormalities to apparently unaffected phenotypic males; however, the full clinical spectrum has not yet been fully delineated since prior studies on the clinical phenotype and associated risk of gonadal tumors included small cohorts and limited follow-up. To better describe the clinical manifestations and long-term outcome of patients with 45,X/46,XY mosaicism. We conducted a retrospective chart review of patients with 45,X/46,XY from three health centers (Hospital for Sick Children and Mount Sinai Hospital in Canada, and University of Pittsburgh Medical Center in United States). Of 100 patients with 45,X/46,XY karyotype, 47 were raised as females and 53 as males. Females were significantly shorter than males (p = 0.04) and height Z-score was significantly decreased with age for both genders (p = 0.02). Growth hormone (GH) treatment did not result in a significant height increase compared to the untreated group (p = 0.5). All females required puberty induction in contrast to majority of males. Five females were diagnosed with gonadal tumors, while no males were affected. Around 58% of patients exhibited at least one Turner syndrome stigmata. This study expands the clinical spectrum, long-term outcomes, and associated tumor risk in a large cohort of patients with 45,X/46,XY mosaicism. Additionally, it highlights our experience with GH therapy and prophylactic gonadectomy.

Inspiring New Science to Guide Healthcare in Turner Syndrome: Rationale, design, and methods for the InsighTS Registry.

Inspiring New Science to Guide Healthcare in Turner Syndrome (InsighTS) Registry is a national, multicenter registry for individuals with Turner syndrome (TS) designed to collect and store validated longitudinal clinical data from a diverse cohort of patients with TS. Herein, we describe the rationale, design, and approach used to develop the InsighTS registry, as well as the demographics of the initial participants to illustrate the registry's diversity and future utility. Multiple stakeholder groups have been involved from project conceptualization through dissemination, ensuring the registry serves the priorities of the TS community. Key features of InsighTS include recruitment strategies to facilitate enrollment of participants that appropriately reflect the population of individuals with TS receiving care in the US, clarity of data ownership and sharing, and sustainability of this resource. The registry gathers clinical data on diagnosis, treatment, comorbidities, health care utilization, clinical practices, and quality of life with the goal of improving health outcomes for this population. Future directions include multiple patient-centered clinical-translational research projects that will use the InsighTS platform. This thorough and thoughtful planning will ensure InsighTS is a valuable and sustainable resource for the TS community for decades to come.

Anxiety in Turner syndrome: Engaging community to address barriers and facilitators to diagnosis and care.

Turner syndrome (TS), caused by complete or partial loss of the second sex chromosome, is associated with complex medical manifestations. The TS community identifies anxiety as a major contributor to reduced quality of life. The study aimed to improve understanding of anxiety symptomatology, diagnosis, and care in individuals with TS. A mixed methods design integrated community engagement, including community leaders as co-investigators and a community advisory board, an online survey (N = 135), and in-depth interviews (N = 10). The majority of respondents reported that anxiety symptoms occur two or more days per week, with self-advocates reporting more frequent symptoms than caregivers (p = 0.03). Self-advocates reported feeling anxious more often at school/work; both rater groups reported anxiety-related behaviors were most likely to be expressed at home. Insomnia was the most common symptom of anxiety endorsed across age and rater groups (>70%). Anxiety symptoms and triggers changed with age and often were undiagnosed or untreated during childhood. Therapy and medication were reported as helpful by most respondents who had tried these strategies. Qualitative themes included: 'Triggers for anxiety are related to TS', 'Anxiety impacts the whole family', and 'Opportunities for early identification and intervention'.

Prevalence, diagnostic features, and medical outcomes of females with Turner syndrome with a trisomy X cell line (45,X/47,XXX): Results from the InsighTS Registry.

Turner syndrome (TS) is defined by partial or complete absence of a sex chromosome. Little is known about the phenotype of individuals with TS mosaic with trisomy X (45,X/47,XXX or 45,X/46,XX/47,XXX) (~3% of TS). We compared the diagnostic, perinatal, medical, and neurodevelopmental comorbidities of mosaic 45,X/47,XXX (n = 35, 9.4%) with nonmosaic 45,X (n = 142) and mosaic 45,X/46,XX (n = 66). Females with 45,X/47,XXX had fewer neonatal concerns and lower prevalence of several TS-related diagnoses compared with 45,X; however the prevalence of neurodevelopmental and psychiatric diagnoses were not different. Compared to females with 45,X/46,XX, the 45,X/47,XXX group was significantly more likely to have structural renal anomalies (18% vs. 3%; p = 0.03). They were twice as likely to have congenital heart disease (32% vs. 15%, p = 0.08) and less likely to experience spontaneous menarche (46% vs. 75% of those over age 10, p = 0.06), although not statistically significant. Congenital anomalies, hypertension, and hearing loss were primarily attributable to a higher proportion of 45,X cells, while preserved ovarian function was most associated with a higher proportion of 46,XX cells. In this large TS cohort, 45,X/47,XXX was more common than previously reported, individuals were phenotypically less affected than those with 45,X, but did have trends for several more TS-related diagnoses than individuals with 45,X/46,XX.

Prevalence of hepatic steatosis and fibrosis in Turner syndrome: A prospective case-control study.

BACKGROUND AND AIMS: Abnormal liver chemistries are common in Turner syndrome (TS). Guidelines suggest that TS patients undergo annual screening of liver enzymes, but the role of non-invasive screening for steatosis and fibrosis is not clearly defined. We compared the prevalence of hepatic steatosis and fibrosis among TS patients to healthy controls using ultrasound with shear-wave elastography (SWE) and assessed for risk factors associated with steatosis and fibrosis in TS. METHODS: Prospective case-control study of TS versus control patients from 2019 to 2021. All patients underwent abdominal ultrasound with doppler and SWE to assess hepatic fibrosis and steatosis. Risk factors were compared between TS and controls, as well as within the TS group. RESULTS: A total of 55 TS and 50 control patients were included. Mean age was 23.6 years vs. 24.6 years in the control group (p = .75). TS patients had significantly more steatosis (65% vs. 12%, stage 1 vs. 0, p < .0001) and fibrosis (39% vs. 2%, average Metavir F2 vs. F0, p < .00001) than controls. These findings remained significant after adjusting for body mass index (BMI) (p < .01). GGT is more sensitive than AST or ALT in identifying these changes. CONCLUSION: TS is associated with an increased prevalence of hepatic steatosis and fibrosis compared to healthy controls. Our findings suggest that serum GGT and ultrasound with SWE may help identify TS patients with liver disease. Early risk factor mitigation including timely oestrogen replacement, weight control, normalization of lipids and promoting multidisciplinary collaboration should be encouraged.

Neuropathies related to hepatitis E virus infection: A prospective, matched case-control study.

BACKGROUND: Acute hepatitis E virus (HEV) infection has recently emerged as a potential trigger for acute dysimmune neuropathies, but prospective controlled studies are lacking. AIMS: To compare the frequency of concomitant acute HEV infection in patients with neuralgic amyotrophy (NA), Guillain-Barré syndrome (GBS), and Bell's palsy with a matched control population. METHODS: Swiss multicenter, prospective, observational, matched case-control study over 3 years (September 2019-October 2022). Neurological cases with NA, GBS, or Bell's palsy were recruited within 1 month of disease onset. Healthy controls were matched for age, sex, geographical location, and timing of blood collection. Diagnostic criteria for acute hepatitis E were reactive serum anti-HEV IgM and IgG assays (ELISA test) and/or HEV RNA detection in serum by real-time polymerase chain reaction (RT-PCR). RT-PCR was performed on sera to confirm IgM positivity. RESULTS: We included 180 patients (59 GBS, 51 NA, 70 Bell's palsy cases) and corresponding matched controls (blood donors) with median age 51 years for both groups and equal gender distribution. Six IgM+ cases were detected in the NA, two in the GBS, and none in the Bell's palsy group. Two controls were anti-HEV IgM-positive. At disease onset, most cases with acute HEV infection had increased liver enzymes. A moderate association (p = 0.027, Fisher's exact test; Cramér's V = -0.25) was observed only between acute HEV infection and NA. CONCLUSION: This prospective observational study suggests an association between concomitant acute HEV infection and NA, but not with GBS or Bell's palsy.

Parsonage-Turner syndrome, affecting suprascapular nerve and especially to infraspinatus muscles after COVID-19 vaccination in a professional wrestler, a case report and literature review of causes and treatments.

BACKGROUND: Acute peripheral neuropathy, also known as Parsonage-Turner syndrome or neuralgic amyotrophy, mostly affects the upper brachial plexus trunks, which include the shoulder girdle. It is typically accompanied by abrupt, intense pain, weakness, and sensory disruption. The etiology and causes of this disease are still unknown because of its low prevalence, however viral reactions-induced inflammation is one of its frequent causes. CASE PRESENTATION: Here, we introduce a professional wrestler patient who was diagnosed with PTS after vaccination and was treated, and we review some articles in this field. CONCLUSION: When it comes to shoulder-girdle complaints and pain, Parsonage-Turner syndrome can be a differential diagnosis. Corticosteroids during the acute period, followed by physical therapy, appear to be an efficient way to manage pain, inflammation, muscular atrophy, and the process of recovering to full nerve regeneration.

Working towards risk stratification for ascending aortic dilatation in pediatric Turner syndrome patients: results of a longitudinal echocardiographical observation.

This study aimed to longitudinally evaluate aortic root dimensions and elasticity in pediatric Turner syndrome (TS) in relation to known cardiac implications such as coarctation of the aorta (CoA) and bicuspid aortic valves (BAV) in order to create an improved risk profile for the presumed underlying vessel pathology in childhood. We report on the longitudinal findings of our pediatric TS outpatient clinic over a period of up to 7.6 years. Forty-nine TS patients (median age at baseline 9.7 ± 5.9 years, range 0-19.8) were followed-up for on average 2.9 ± 1.1 examinations and a median time of 3.4 ± 1.6 years. Aortic root (AoR) diameters and corresponding Z-scores were determined echocardiographically, and elasticity parameters as well as annual progression rates were calculated. At baseline, 16.3% of patients showed Z-scores > 2 at one or more levels of the AoR (35.7% of patients with BAV, odds ratio of 4.2). There was net progression to be noted at all measuring levels, leading to 28.6% of patients (50% of patients with BAV) exhibiting aortic dilatation at the end of follow-up. Progression correlated with the presence of BAV, non-mosaic monosomy, and age. A levelling-off of progression was seen with the onset of adolescence. CONCLUSIONS: Marked progression of aortic diameters leading to the development of dilatation can be observed in TS patients during childhood and stresses the importance of close surveillance during childhood. Main risk factors are BAV and complete monosomy 45X0. A beneficial influence of estrogen substitution can be suspected but needs further investigation. WHAT IS KNOWN: • Patients with Turner syndrome are at an increased risk for aortic dilatation and dissection. • The presence of BAV and complete monosomy 45X are additional risk factors. WHAT IS NEW: • Aortic dilatation can be detected in pediatric patients with Turner syndrome. • Relevant progression in childhood is possible in at-risk individuals and warrants close surveillance.

Abnormal Body Composition Increases the Cardiometabolic Risk in Adolescents and Young Adults With Turner Syndrome.

OBJECTIVE: To determine the cardiometabolic risk of adolescents and adults with Turner syndrome (TS) and whether and how anthropometry and body composition predict this risk. METHODS: We compared the anthropometric, biochemical, and dual-energy x-ray absorptiometry-derived body composition parameters of 103 girls and women with TS aged 12 to 30 years and 103 controls of the same age and body mass index: (1) between TS with and without metabolic syndrome (MetS), (2) between the different karyotypes of TS, and (3) between growth hormone recipients and nonrecipients. RESULTS: Individuals with TS had higher prevalence rates of truncal obesity (57.2%), MetS (37.9%), prediabetes (20.4%), dyslipidemia (73.8%), hypertension (9.7%), and hepatic steatosis (15.5%) and a greater total body fat percentage (38.43% vs 34.26%) and fat mass index (9.15 vs 6.71 kg/m2) but a lower lean mass index (11.05 vs 12.49 kg/m2) than controls (P <.001). Individuals with TS and MetS (n = 39) had a higher total body fat percentage (41.74% vs 36.42%, P <.0001), truncal fat percentage (44.66% vs 36.09%, P <.0001), and visceral adipose tissue mass (495.57 vs 276 g, P <.0001) than those with TS but without MetS. Those with classic TS (45,X) had a higher prevalence of prediabetes (32.6% vs 10.5%, P =.01). Growth hormone recipients had a lower prevalence of MetS and lesser truncal obesity. Altered body composition was significantly correlated with metabolic risk. The truncal fat percentage independently predicted MetS (odds ratio, 1.12; 95% confidence interval, 1.003-1.24; P =.04). Waist circumference and waist-hip ratio predicted metabolic risk with good sensitivity and specificity. CONCLUSION: Adverse cardiometabolic risk and altered body composition start early in life in TS. Postpubertal women with TS should be routinely assessed for truncal obesity, dysglycemia, dyslipidemia, and liver steatosis, irrespective of body mass index and karyotype.

Transition from pediatric to adult care in patients with Turner syndrome in Italy: a consensus statement by the TRAMITI project.

PURPOSE: Transition from pediatric to adult care is associated with significant challenges in patients with Turner syndrome (TS). The objective of the TRansition Age Management In Turner syndrome in Italy (TRAMITI) project was to improve the care provided to patients with TS by harnessing the knowledge and expertise of various Italian centers through a Delphi-like consensus process. METHODS: A panel of 15 physicians and 1 psychologist discussed 4 key domains: transition and referral, sexual and bone health and oncological risks, social and psychological aspects and systemic and metabolic disorders. RESULTS: A total of 41 consensus statements were drafted. The transition from pediatric to adult care is a critical period for patients with TS, necessitating tailored approaches and early disclosure of the diagnosis to promote self-reliance and healthcare autonomy. Fertility preservation and bone health strategies are recommended to mitigate long-term complications, and psychiatric evaluations are recommended to address the increased prevalence of anxiety and depression. The consensus also addresses the heightened risk of metabolic, cardiovascular and autoimmune disorders in patients with TS; regular screenings and interventions are advised to manage these conditions effectively. In addition, cardiac abnormalities, including aortic dissections, require regular monitoring and early surgical intervention if certain criteria are met. CONCLUSIONS: The TRAMITI consensus statement provides valuable insights and evidence-based recommendations to guide healthcare practitioners in delivering comprehensive and patient-centered care for patients with TS. By addressing the complex medical and psychosocial aspects of the condition, this consensus aims to enhance TS management and improve the overall well-being and long-term outcomes of these individuals.

The TRansition Age Management in Turner syndrome in Italy (TRAMITI) project aims to improve care for individuals with Turner Syndrome (TS) during their transition from pediatric to adult care. A team of 15 physicians and 1 psychologist collaborated to create a comprehensive set of 41 consensus statements, covering four key areas: transition and referral, sexual and bone health and oncological risks, social and psychological aspects and systemic and metabolic disorders. The consensus statements highlight the importance of patient-centered care, early intervention and long-term monitoring. They emphasize a multidisciplinary approach to address the complex medical and psychosocial aspects of TS. During the critical transition period, tailored approaches and early disclosure of the diagnosis are recommended to promote self-reliance and healthcare autonomy. To mitigate long-term complications, the consensus addresses fertility preservation and bone health strategies. It also recommends psychological or psychiatric evaluations to tackle the increased prevalence of anxiety and depression in patients with TS. In addition, strategies for addressing the heightened risk of metabolic, cardiovascular and autoimmune disorders in patients with TS are proposed. Regular screenings and interventions are advised to effectively manage these conditions. Furthermore, cardiac abnormalities, including aortic dissections, require close monitoring and early surgical intervention if specific criteria are met. Overall, the TRAMITI consensus statement provides valuable insights and evidence-based recommendations. It offers guidance for healthcare practitioners in delivering comprehensive and patient-centered care for individuals with TS. By addressing both medical and psychosocial aspects, the consensus aims to enhance TS management and improve the well-being and long-term outcomes of those affected by this genetic disorder.

Lifelong cardiovascular care in Turner syndrome: two cases with review of literature.

Cardiovascular disease is one of the most important complications in girls and women with Turner syndrome (TS). Although the latest international guideline provides useful suggestions for the management of cardiovascular diseases in TS, some unknown cardiac conditions warrant physicians' attention and awareness. Here, we have reported two adult cases wherein significant cardiovascular diseases were detected during the transition period. The first case patient was diagnosed with aortic crank deformity and left subclavian artery aneurysm at 14 years based on the report of cardiac catheterization, computed tomography angiography, and cardiac magnetic resonance imaging, which had remained undetected by annual evaluations using transthoracic echocardiography (TTE). This case emphasizes the importance of cardiac reevaluation during the transition period. The second case patient was diagnosed with moderate mitral valve regurgitation (MR) due to mitral valve prolapse at 18 years through TTE, although the first evaluation at 7 years by TTE detected slight MR without any clinical concerns. The condition however progressed to severe MR at 28 years, requiring mitral valvuloplasty. MR is the most common valve disease worldwide, which makes it challenging to comprehend whether the condition is a complication. However, the condition requiring surgery at this age is extremely rare, which implies the possibility of early progression. Because almost all literature on cardiovascular complications in TS is cross-sectional, further information about longitudinal cardiovascular conditions is vital for optimal care for girls and women with TS. The two cases reported in this article provide significant information for improving lifelong cardiovascular health issues in TS.