Mosaic Turner Syndrome Research Articles

B-213 Including Turner Syndrome Screening in Newborn Sequencing by Using NGS Read Counts to Infer Sex Chromosomes Copy Number: Leveraging Existing Data to Enhance Early Diagnosis

Abstract Background Turner Syndrome (TS) can lead to heart defects, short stature, and premature ovarian failure. Early diagnosis can improve outcomes, but routine screening is not standard, often delaying diagnosis until symptoms prompt karyotype analysis. Newborn NGS sequencing offers potential for early detection of genetic disorders and targets numerous gene regions on autosomes and sex chromosomes. It could be utilized to deduce sexual chromosomal copy number variations, including not only chrX monosomy but also its partial deletions and structural alterations, and chrY, which increases the risk of gonadoblastoma in TS patients. Thus, this study aims to validate a TS screening approach using NGS read count data from newborn sequencing to develop a strategy for early detection. Methods DNA samples with established chromosomal microarray ChrX and ChrY copy-number assessments were used. The cohort included 13 males (46,XY), 10 females (46,XX), 5 TS cases (45,X), 5 mosaic TS cases (2 with chrY, 3 without), 1 TS case with Isochromosome Xq, 8 Klinefelter Syndrome cases (47,XXY), and one case (48,XXYY). For NGS, a focused newborn sequencing panel targeting 388 genes derived from the larger xGEN Inherited Disease Panel (Integrated DNA Technologies) was employed. The larger panel covers 2,968 chrX regions, 53,455 autosomal regions, and 135 chrY regions. Sample processing utilized the xGEN DNA Library Prep and Hybridization Capture (Integrated DNA Technologies) and sequencing on NextSeq-500 (Illumina). The alignment was conducted with Dragen Enrichment v.3.9.5 and read count analysis with Samtools v.1.19.2. ChrX and ChrY copy numbers were assessed by comparing chrX and chrY read count ratios to autosomal read counts. Hierarchical clustering grouped samples based on ratio similarities, aiding result attribution. To identify structural alterations in each arm of chrX, every tested chrX region was analyzed for read count ratio calculation and subjected to circular binary segmentation using the DNAcopy R package. The observed sex chromosome counts were compared to expected results to validate the approach. Results Observed chrX/autosome and chrY/autosome ratio ranges matched the expected sex chromosome counts: 0.99-1.03 and 0.82-1.02 for 46,XY; 1.92-1.97 and 0.00-0.01 for 46,XX; 1.00-1.02 and 0.00-0.00 for 45,X; 1.15-1.46 and 0.00-0.00 for mosaic TS without chrY; 0.98-1.06 and 0.27-0.32 for mosaic TS with chrY; 2.45 and 0.0 for TS with Isochromosome Xq; 1.82-2.01 and 0.87-0.95 for 47,XXY; and 2.02 and 1.96 for 48,XXYY. Hierarchical cluster analysis grouped these values into three branches: one for 48,XXYY, one for 47,XXY, 46,XX, and Isochromosome Xq, and one for all other TS samples and 46,XY. TS and 47,XXY samples were further divided into subbranches from 46,XX and 46,XY. Circular binary segmentation of chrX read counts provided a visual profile of the copy number for each arm of chrX, explaining structural alterations in out-of-pattern chrX dosages, such as 2.45, 1.15, and 1.46. Conclusions There was complete agreement between the NGS read count-based assessment of sex chromosome copy number and the expected results for 46,XY, 46,XX, 45,X, TS with mosaic and structural variants, 47,XXY, and 48,XXYY samples. This suggests that TS can be effectively screened using newborn sequencing NGS data.

A Rare Coexistence of Turner Syndrome and Mycosis Fungoides: A Case Report.

Turner syndrome (TS) is the most common sex chromosome abnormality among females, characterised by short stature, hypergonadotropic hypogonadism, congenital heart anomalies, and an increased risk of autoimmune diseases. Although TS does not typically increase the absolute risk of malignancy, specific cancers, such as those affecting the nervous system and gastrointestinal tract and malignant melanoma, may occur more frequently. Mycosis fungoides (MF) is the most common type of primary cutaneous T-cell lymphoma, typically affecting adults but also seen in children and adolescents. We report an 11.2-year-old girl with TS presenting with substantial weight gain and short stature. Clinical examination revealed characteristic TS features and karyotype analysis confirmed mosaic TS. Following growth hormone (GH) therapy, the patient developed persistent, erythematous, itchy skin lesions diagnosed as CD4+ MF. GH therapy was discontinued, and topical steroids controlled the skin lesions effectively. MF in TS is rare and unexpected, especially in a child. The coexistence of these conditions suggests a potential link between TS and an increased risk of MF, possibly due to T-cell dysregulation or autoimmune processes. While the clinical course of MF is typically indolent, careful monitoring and annual dermatologic evaluations are recommended for TS patients, particularly when skin lesions are present. This is the first reported case of MF in a child with TS. This case emphasises the importance of carefully evaluating skin lesions in patients with TS and suggests considering MF as a differential diagnosis.

Safety and effectiveness of controlled ovarian stimulation and oocyte retrieval during prepubertal and peripubertal period.

Is itsafe and effective to perform controlled ovarian stimulation (COS) and oocyte retrieval (OR) in prepubertal and peripubertal patients? In this retrospective cohort study, data of 20 pre-/peripubertal patients who underwent COS and OR for the purpose of oocyte cryopreservation (OC) between 2008 and 2023 were reviewed.Following COS, all OR procedures were performed transabdominally using a vaginal ultrasound probe. Ovarian reserve was assessed by serum FSH, LH, estradiol, AMH, and antral follicle counts (AFC) in all subjects. All mature oocytes were vitrified. Mean age of the patients was 15.05 ± 1.87, mean AMH was 0.84 ± 0.8ng/ml, mean FSH was 6.39 ± 3.95IU/L, mean estradiol was 61.6 ± 51.9pg/ml, mean LH was 4.69 ± 3.46IU/L, and mean AFC was 5.5 ± 5.82. Among the patients, 12 had regular menstrual cycle, 5 had irregular menstrual cycle, whereas 3 patients still did not have their menarche yet. The indications for OC were as follows: primary ovarian insufficiency (n = 7), ovarian surgery for ovarian tumors (n = 5) or ovarian torsion (n = 1), mosaic Turner syndrome (n = 2), acute lymphoblastic leukemia (n = 1) anaplastic B-cell lymphoma (n = 1), Ewing's sarcoma (n = 1), Noonan syndrome (n = 1), and Thalassemia (n = 1). The mean number of oocytes retrieved, MII oocytes frozen, and maturation rate were 5.11 ± 5.0, 3.92 ± 4.48, and 75.1 ± 25.6%, respectively.Stepwise linear regression analysis demonstrated a positive correlation between AFC and number of total oocytes retrieved and number of MII oocytes. In the case diagnosed with Noonan syndrome, all 7 retrieved oocytes were MI and all frozen at MI phase. No patient had any complication related to COS or OR. Even though number of the enrolled subjects is limited and mean AMH is lower in our cohort, we demonstrated that performing COS and OR is safe in pre-/peripubertal patients. If required, transabdominal route can be performed in this age group for OR. AFC appears as a prognostic factor for stimulation outcome in this age group. Pediatric patients or young adolescents at risk for primary ovarian insufficiency should not bediscouragedfrom utilizing OC.

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.

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.

Cell Cycle Kinetics and Sister Chromatid Exchange in Mosaic Turner Syndrome.

Turner syndrome (TS) is caused by a complete or partial absence of an X or Y chromosome, including chromosomal mosaicism, affecting 1 in 2500 female live births. Sister chromatid exchange (SCE) is used as a sensitive indicator of spontaneous chromosome instability. Cells from mosaic patients constitute useful material for SCE evaluations as they grow under the influence of the same genetic background and endogenous and exogenous factors. We evaluated the proliferation dynamics and SCE frequencies of 45,X and 46,XN cells of 17 mosaic TS patients. In two participants, the 45,X cells exhibited a proliferative disadvantage in relation to 46,XN cells after 72 h of cultivation. The analysis of the mean proliferation index (PI) showed a trend for a significant difference between the 45,X and 46,X+der(X)/der(Y) cell lineages; however, there were no intra-individual differences. On the other hand, mean SCE frequencies showed that 46,X+der(X) had the highest mean value and 46,XX the lowest, with 45,X occupying an intermediate position among the lineages found in at least three participants; moreover, there were intra-individual differences in five patients. Although 46,X+der(X)/der(Y) cell lineages, found in more than 70% of participants, were the most unstable, they had a slightly higher mean PI than the 45,X cell lineages in younger (≤17 years) mosaic TS participants. This suggests that cells with a karyotype distinct from 45,X may increase with time in mosaic TS children and adolescents.

In vitro fertilization and pregnancy outcomes of women with X chromosome abnormality: A case series.

To describe and conclude the in vitro fertilization (IVF) results of patients with X chromosome abnormality. A retrospective case series was conducted. According to the number of normal X, patients were allocated into two groups: Group A (patients with only a normal X, while other X has any types of abnormalities) and Group B (patients have two or more normal X chromosomes). Clinical data, including basic information, fertility information, and IVF outcomes, were collected. Fourteen patients with X chromosome abnormality were included, among which 13 patients underwent a total of 29 cycles. Patients in Group B had five successful pregnancies and three live births, while no patient in Group A had a clinical pregnancy. Furthermore, the blastocyst formation rate and incidence of pregnancy were significantly lower in Group A (Z = -3.135, p = .002; Z = -2.946, p = .003, respectively). When controlled covariates, the karyotype of one normal X was also a risk factor for both blastocyst formation rate and success pregnancy (β = .820, 95% confidence interval [CI] = 0.458-1.116, β = .333, 95% CI = 0.017-0.494, respectively). Our results revealed that women with only one normal X might suffer from worse IVF outcomes, mainly blastocyst formation rate, compared with those who had two or more normal X, including mosaic Turner syndrome and 47,XXX.

74 Getting to the Heart of the Cause: Epidermodysplasia verruciformis in a Patient Born with Transposition of the Great Arteries and Mosaic Turner Syndrome

74 Getting to the Heart of the Cause: Epidermodysplasia verruciformis in a Patient Born with Transposition of the Great Arteries and Mosaic Turner Syndrome

Mosaic Form of Turner Syndrome

Objective: To report a case of breast growth disorder in a mosaic form of Turner Syndrome. Turner syndrome is a chromosomal condition characterized by small height and primary ovarian insufficiency that affects one in every 2500 female births. Mosaicism is likely to occur when monosomy X develops in only a few cells during development. The clinical presentation of Turner syndrome mosaicism is atypical, with symptom severity varying based on the number of affected cells. This case discusses issues with secondary sex development, including mild hyperandrogenism, and explores how combination hormonal treatment can aid in enhancing secondary sex development.
 Method: Case Report.
 Case: A 21-year-old woman presented with chief complaint of the lack of breast enlargement. She exhibited normal genitalia internally and externally and had a regular menstrual cycle. Karyotyping revealed a mosaic pattern of 45, X/46, XX (1 percent/99%) with normal estradiol levels and elevated testosterone levels (indicating mild hyperandrogenism). The patient underwent two cycles of hormone therapy using Ethinyl Estradiol and Drospirenone, resulting in breast growth progression from Tanner stage 1 to Tanner stage 2.
 Conclusion: Mosaicism in Turner syndrome is plausible, and the severity of clinical symptoms correlates with the number of defective chromosomes. The presentation of Turner syndrome mosaicism varies, and therapy should be tailored to address specific symptoms. While breast development is observed in some girls with Turner Syndrome, instances of breast growth disorder may occur, involving estrogen activity and estrogen receptor sensitivity. Although the exact cause of impaired breast growth remains unknown, administering estrogen in such cases can improve secondary sexual characteristics.
 Keywords: mild hyperandrogenism, mosaicism, turner syndrome

Detection of chromosomal aneuploidy in ancient genomes

Ancient DNA is a valuable tool for investigating genetic and evolutionary history that can also provide detailed profiles of the lives of ancient individuals. In this study, we develop a generalised computational approach to detect aneuploidies (atypical autosomal and sex chromosome karyotypes) in the ancient genetic record and distinguish such karyotypes from contamination. We confirm that aneuploidies can be detected even in low-coverage genomes ( ~ 0.0001-fold), common in ancient DNA. We apply this method to ancient skeletal remains from Britain to document the first instance of mosaic Turner syndrome (45,X0/46,XX) in the ancient genetic record in an Iron Age individual sequenced to average 9-fold coverage, the earliest known incidence of an individual with a 47,XYY karyotype from the Early Medieval period, as well as individuals with Klinefelter (47,XXY) and Down syndrome (47,XY, + 21). Overall, our approach provides an accessible and automated framework allowing for the detection of individuals with aneuploidies, which extends previous binary approaches. This tool can facilitate the interpretation of burial context and living conditions, as well as elucidate past perceptions of biological sex and people with diverse biological traits.

Progressive Oestrogen Deficiency in a Young Woman with 45X/46XX Mosaicism: A Case Report

Oestrogen is a vital hormone for woman’s health. Naturally, oestrogen hormone level begins to gradually decline leading to related symptoms after the age of 40 years in most women. This case report illustrates a progressive oestrogen deficiency in young woman since she was 19 years old. She was having hypomenorrhea for a year followed with amenorrhoea and was managed conservatively including progestogen challenge for about a year. She responded to the treatment once and remained amenorrhoeic thereafter. She was referred to our centre at 22 years old for further evaluation of premature ovarian insufficiency primarily concerning her fertility. Clinical examination showed a thin young woman with breasts, axillary and pubic hair of Tanner Stage 3. Blood investigation showed low oestrogen level with persistently high gonadotrophins suggestive of primary ovarian insufficiency. The urogenital pelvic ultrasound showed a small thin uterus with normal ovaries. She was diagnosed with Turner Syndrome of 45X/46XX mosaicism based on a blood karyotype test. The lack of typical feature of Turner Syndrome in this case had delayed the initial investigations and management. This case report aimed to highlight on the importance of a comprehensive evaluation in young women presenting with chronic oestrogen deficiency state. This will allow an early diagnosis and treatment of rare condition like mosaic Turner Syndrome and thus, preventing complications.

Cytogenetic analysis of 3488 patients with recurrent pregnancy loss: An experience of two decades from a tertiary care center in South India

BackgroundRecurrent pregnancy loss (RPL) affects approximately 15–20% of couples. Constitutional chromosomal abnormalities (CA) are an important cause of RPL because the gametes of carriers may have chromosomal imbalance which is lethal to the fetus. Therefore, the identification of CA helps to provide information about likely outcome of pregnancy in carriers. The objective of this study was to determine the frequency and types of CA in RPL. MethodsThe study group consisted of individuals with RPL seen at a tertiary care center in South India from 2001 to 2019, whose karyotypes were reviewed retrospectively. Cytogenetic analysis was performed on peripheral blood using standard protocols. The number of metaphases analyzed per patient was 20 and extended up to 50 for confirmation of low-level mosaicism. ResultsThere were 3488 individuals (1663 couples and 162 where only partner was tested of whom 104 were females). The frequency of CA was 3.6% (127/3488) (M:F ratio of 1:2.6). Structural aberrations were seen in 2.5% (90/3488) and numerical aberrations of sex chromosomes in 1.1% (37/3488) of patients. Structural aberrations included 68 balanced translocations including one three-way translocation, seven inversions, one insertion and duplication each, and 14 Robertsonian translocations. There was one patient each with Turner syndrome (TS) and 47,XYY syndrome. We had 37 mosaics, comprising 29 with mosaic TS and 6 with triple X mosaicism and 2 with mosaicism for balanced translocation. ConclusionThe frequency of CA is comparable to the literature. We have described a few less commonly seen aberrations as well as sex chromosomal aneuploidies, almost all of which were due to low-level mosaicism.

B - 106 Case Illustration of an Adolescent with Nonverbal Learning Disability and Mosiac Turner Syndrome: Neuropsychological and Personality Assessment.

Nonverbal Learning Disability (NLD) is a controversial diagnosis which continues to lack an agreed upon diagnostic taxonomy despite its long existence and overlap with other disorders. NLD is considered a dysfunction of the right hemisphere with neuropsychological, academic, and social-emotional/adaptation deficits along with poor motor coordination. This case study reviews an adolescent diagnosed with NLD and Mosaic Turner Syndrome (MTS) and discusses challenges encountered to emphasize importance of an early diagnostic accuracy and the effect of developmental conditions. A 17-year-old female presented for neuropsychological evaluation for a mental health diagnosis and possible academic accommodations. Chief complaints included lifelong functionally interfering difficulties with attention, organization, and emotional and social functioning. Medical history was significant for MTS. The patient's VCI was in the high-average range (VCI = 114), while her PSI was in the low-average range (PSI = 81). She demonstrated high-average to average visual-spatial, construction abilities, and language skills, while performance ranged low-average for perceptual-motor processing and processing speed. Performance on delayed visual-graphic figures was significantly weaker compared to her superior performance on verbal memory for meaningful information. Finally, her delayed visual-graphic was significantly impaired compared to her general performance visual-spatial and construction abilities. The constellation of symptoms reported by the patient, combined with the results of neuropsychological assessment, was highly congruent with prototypical nonverbal learning disability, except for difficulties in mathematical skills. This case demonstrates the importance of proper diagnosis during childhood, the role of neuropsychological evaluation in specific learning disability (SLD) assessment, and lasting effects of a developmental condition on adult functioning.

Oocyte cryopreservation in mosaic Turner syndrome with polycystic ovaries

To report a case of a patient with Turner syndrome (TS) mosaicism and polycystic ovarian syndrome (PCOS), who underwent successful ovarian stimulation, oocyte retrieval, and cryopreservation. Case report. A female patient with mosaic TS (45,X [24%]/46,XX [76%]) and a paternally inherited balanced reciprocal translocation t(2:6) diagnosed with PCOS. Controlled ovarian stimulation, oocyte retrieval, and cryopreservation. Successful oocyte retrieval and cryopreservation. We report an interesting case of a patient with TS mosaicism 45,X [24%]/46,XX [76%] and a paternally inherited t(2:6) balanced reciprocal translocation, who was diagnosed with PCOS on the basis of oligomenorrhea and ultrasound polycystic ovary morphology (antral follicle count of 17 and >20, left and right ovaries, respectively), underwent 2 cycles of ovarian stimulation, oocyte retrieval, and cryopreservation, resulting in 19 cryopreserved oocytes. Our case highlights the importance of early counseling regarding fertility options in patients with mosaic TS and the need for careful monitoring of ovarian reserve during this process, which could be done by measuring the anti-müllerian hormone or antral follicle count. It also underscores the possibility of women with mosaic TS being affected by PCOS.

Live birth after single euploid frozen embryo transfer in a 39-year-old woman with high-grade mosaic Turner syndrome

Objective To describe the reproductive and obstetric outcomes of an intracytoplasmic sperm injection cycle with preimplantation genetic testing for aneuploidy in an advanced reproductive-age woman with high-grade mosaic Turner syndrome. Methods Case report of a 39-year-old woman diagnosed with mosaic Turner Syndrome 45,X[90]/46,XX[10] karyotype who underwent in vitro fertilization treatment with blastocyst trophectoderm biopsy for preimplantation genetic testing using next-generation sequencing. Result(s) Two of the four blastocysts biopsied were euploid. The patient achieved ongoing pregnancy after the first single euploid frozen embryo transfer, followed by the birth of a healthy child. Conclusion Autologous intracytoplasmic sperm injection cycles can be considered in a select group of advanced reproductive-age women diagnosed with high-grade mosaic Turner syndrome.

Oocyte cryopreservation with in vitro maturation for fertility preservation in girls at risk for ovarian insufficiency.

To assess the feasibility and outcomes of oocyte cryopreservation with in vitro maturation (IVM) in post-pubertal girls undergoing fertility preservation (FP) for primary ovarian insufficiency (POI) risk. Ovarian stimulation was performed with an antagonist protocol or progesterone priming. Ultrasound monitoring was performed transabdominally. Oocytes were retrieved transvaginally under IV sedation. Immature oocytes were subjected to IVM for up to 36h. All MII oocytes were vitrified. The main outcome measure was the total number of mature oocytes cryopreserved. The secondary outcome was the increase in the mature oocyte yield after IVM. Indications for FP included mosaic Turner syndrome (mTS; n = 10), malignancy (n = 3), and POI risk (n = 2). The mean ± SD age, antral follicle count (AFC), and AMH levels were 14.2 ± 1.4years, 8 ± 5.2 and 1.3 ± 1.3ng/mL. In girls with mTS, the ovarian reserve was low for age (AFC 7.4 ± 4.7 and AMH 1.4 ± 1.6ng/mL). Oocyte cryopreservation was possible in all girls with a range of 1-27 mature oocytes obtained, even in those who were previously exposed to chemotherapy or with low ovarian reserve, and no surgical complications were encountered. After IVM, the median mature oocyte yield increased significantly from 7.5 to 10.5 (p = 0.001). Oocyte cryopreservation appears to be feasible and safe in girls as young as 12years of age at risk for POI The utility of IVM increases the yield of cryopreserved mature oocytes. Prior exposure to chemotherapy or low ovarian reserve should not be an automatic reason to exclude these girls from FP consideration.

Isochromosome Mosaic Turner Syndrome with Delayed Growth and Puberty: A Case Report

Isochromosome Mosaic Turner Syndrome, a variant of Turner syndrome which has a milder presentation, can present without the typical features of Turner syndrome. Evaluation of Turner syndrome with karyotyping has to be performed in females presenting with short stature. We present a case of 15 years girl who presented with delayed growth and puberty with primary amenorrhea and hyperthyroidism. Cytogenetic study of peripheral blood revealed 45,X [31]; 46, X,i(X)(q10) [19] suggestive of Isochromosome Mosaic Turner Syndrome.

Sex chromosome aneuploidies and fertility: 47,XXY, 47,XYY, 47,XXX, and 45,X/47,XXX.

The overall incidence of sex chromosome aneuploidies is approximately 1 per 500 live-born infants, but far more common at conception. I shall review the fertility aspects of the sex chromosome trisomies, XXY, XYY, XXX, with special reference to the karyotype 45,X/47,XXX. Each has a "specific" (but variable) phenotype, but may be modified by mosaicism. Although the alterations in the hypothalamic-pituitary-gonadal axis are important (and discussed), the emphasis is on potential fertility. The reproductive axis is often affected in females with the 47,XXX karyotype with diminished ovarian reserve and accelerated loss of ovarian function. Fewer than 5 % of females with the Turner syndrome have the 45,X/47,XXX karyotype. They have taller stature and less severe fertility issues compared to females with the 45,X or other forms of Turner syndrome mosaicism. For the 47,XXY karyotype non-obstructive azoospermia is almost universal with sperm retrieval by micro-testicular sperm extraction possible in slightly fewer than half of the men. Men with the 47,XYY karyotype have normal to large testes and much less testicular dysfunction than those with the 47,XXY karyotype. They do have a slight increase in infertility compared to the reference population, but not nearly so severe as those with 47,XXY karyotype. Assisted reproductive technology, especially micro-TESE has an important role, especially for those with 47,XXY; however, more recent data show promising techniques for the in vitro maturation of spermatogonial stem cells and 3-D organoids in culture. Assisted reproductive technology is more complex for the female, but vitrification of oocytes has shown promising advances.

Cardiovascular Manifestations of Turner Syndrome: Phenotypic Differences Between Karyotype Subtypes.

Turner syndrome (TS) is a genetic disorder presenting in phenotypic females with total or partial monosomy of the X chromosome. Cardiovascular abnormalities are common, including congenital heart defects (CHD) and aortic dilation. Although mosaic TS is suspected to have less severe phenotype as compared to non-mosaic TS, differences in cardiovascular manifestations between karyotypes are not well studied. This is a single-center retrospective cohort study including patients with TS seen from 2000 to 2022. Demographic data, chromosomal analysis, and imaging were reviewed. Karyotypes were categorized as monosomy X (45X), 45X mosaicism, isochromosome Xq, partial X deletions, ring X(r(X)), TS with Y material, and others. Prevalence of CHD and aortic dilation were compared between monosomy X and other subtypes using Pearson's chi-square test and Welch two-sample t-test. We included 182 TS patients with median age 18 (range 4-33) years. CHD was more common in monosomy X as compared with others (61.4%vs.26.8%, p < 0.001), including bicuspid aortic valve (44.3%vs.16.1%, p < 0.001), partial anomalous pulmonary venous return (12.9%vs.2.7%, p = 0.023), persistent left superior vena cava (12.9%vs.1.8%, p = 0.008), and coarctation of the aorta (20.0%vs.4.5%, p = 0.003). Cardiac surgery (24.3%vs.8.9%, p = 0.017) was more prevalent in the monosomy X group. There was no statistically significant difference for presence of aortic dilation (7.1% vs 1.8%, p = 0.187). Although CHD and need for cardiac surgery are more common in TS with monosomy X as compared to others, all TS subtypes may have similar risk of developing aortic dilation. All TS patients should have similar cardiovascular surveillance testing to monitor for aortic dilation.

Spontaneous Menarche in 45, X/47, XXX Mosaicism

Backgrounds: Turner syndrome (TS) also called monosomy X or Ulrich, is a congenital disorder caused by one intact X chromosome and the absence of second sex chromosomes. Only females are affected by Turner syndrome, characterized by abnormalities affecting the X chromosomes. Its incidence about 2.5-5.5 per 10,000 live births of girls. Mosaic 47, XXX karyotype is found in 3%-4% of TS patients. Objective: To describe clinical manifestation and examination aspects of mosaicism turner syndrome. Case presentation: An 18-years-old girl came with complaint short stature. This complaint has been noticed since the patient was in elementary school. The patient's parents initiated to have their child checked by pediatric endocrinologist when the patient was 6 years old. The patient was diagnosed with Turner syndrome from the result of chromosomal examination. The patient was given growth hormone by pediatrician with unknown dosage for approximately 1.5 years but the patient has never returned to control. During that period of time, her breast developed when she was 11 years old and the patient had menstruation at the age of 14 but the menstrual cycle was irregular. Physical examination showed the patient with short stature, low hairline, shield-shaped chest and right elbow deformity. The Sexual Maturity Rating score was M4P4. Her anthropometric status was overweight and short stature with height for age &lt; P3rd. The patient's bone age was equivalent with child age 17-years-old. Karyotype examination with G-banding technique, the chromosomes from 40 cells have been studied and the number of chromosomes in each cell studied is mos 47, XXX[30]/45, X[10]. Ultrasonography examination showed the uterus anteflexed below normal size, the right ovary appears below normal size, and the left ovary is not visible. Conclusion: An 18-year-old girl with mosaic Turner syndrome. The diagnosis is established by history taking, physical examination, hormone examination, imaging and karyotyping. Patient was treated with growth hormone.