Late Diagnosis of Turner Syndrome in Adulthood;a Case Study from the Endocrinology-Diabetology Nutrition Department of the National Hospital of Pikine Senegal

Introduction: Turner syndrome is a rare genetic disorder characterised by the presence of one X chromosome and the absence of part or all of an X or Y chromosome and patients may experience delayed puberty and infertility. Our study aimed to evaluate the diagnostic delay in our practice and analyze the impact of this diagnostic delay on the effectiveness of patient management. Patients and Methods: Turner syndrome patients were identified from the endocrinology-diabetology nutrition department Database We examined the records of patients in whom the karyotype analysis favoured Turner syndrome. Results: We have selected 5 patients’ records of female patients with Turner syndrome. The mean age was 25, ranging from 19 to 29 years. Primary amenorrhea and characteristic dysmorphic features were observed in all patients. One married patient, who sought consultation for infertility, expressed a desire for pregnancy. Short stature was identified in 3 patients. Primary hypothyroidism and hypertension were respectively found in 1 and 2 patients. Gonadal dysgenesis was noted in 100% of cases. Karyotype analysis revealed monosomy X in 2 patients and mosaic patterns in others. All patients received estrogen-progestin treatment. Antihypertensive therapy was initiated for 2 patients. One patient is on L-thyroxine. In the short term, treatment led to the onset of menstruation after the initial months. Evaluation of treatment efficacy on internal genital organs is yet to be performed. Due to uncertain benefits at this age, growth hormone therapy was not considered for our patients. We provided counseling on assisted reproductive options for couples desiring to conceive. In our study, all patients were placed on estrogen-progestin therapy, and the response appeared favorable. Conclusion: In our practice, the diagnosis of Turner syndrome occurs very late in adulthood, at an age when growth hormone treatment is nearly ineffective. Treatment typically revolves around estrogen-progestin therapy, along with managing other comorbidities such as hypertension and primary hypothyroidism.

An Uncommon Variant of Turner Syndrome in an African American Woman

The extra gonadal consequences of Turner’s Syndrome (TS) also pose risks to patients, namely cardiovascular. Clinicians should maintain a level of clinical suspicion for TS in patients with primary amenorrhea even without typical physical characteristics. Interestingly, TS has uncommon variant forms with varying degrees of clinical manifestations. Even so, all TS and TS variants maintain a high risk for cardiovascular events. Therefore, early TS diagnosis is of utmost importance. Here, we present a case of a young, African-American woman with primary amenorrhea with few overt clinical signs of TS. With high clinical suspicion, genetic testing is pursued and demonstrates the TS variant. This is important because variant forms have a similar increased risk of premature hypertension, diabetes, and aortic dissection.

Gonadal dysgenesis in Turner syndrome with Y-chromosome mosaicism:Two case reports

BACKGROUND Turner syndrome(TS)has a variety of different karyotypes,with a wide range of phenotypic features,but the specific karyotype may not always predict the phenotype.TS with Y chromosome mosaicism may have mixed gonadal dysgenesis,and the mosaicism is related to the potential for gonadoblastoma.CASE SUMMARY In this case report,we report two cases of TS with different karyotypes and gonadal dysgenesis.Patient 1 had obvious virilization,and was positive for the SRY gene,but her karyotype in peripheral blood lymphocytes was 45X.Patient 2 had a mosaic karyotype,45X/46X,dic(Y:Y)(p11.3:p11.2),and the proportion of Y-bearing cells was 50%in peripheral blood lymphocytes,but the patient had normal female external genitalia and streaky gonads,with no genital virilism.Different tissues in the same TS individual may exhibit different ratios of mosaicism.The gonadal determination and differentiation of mosaic TS are primarily dependent on the predominant cell line in the gonads.CONCLUSION In TS patients with virilization,it is necessary to test at least two to three tissues to search for cryptic Y material.

A case report of Turner syndrome associated with Rathke cleft cyst

It has not been reported that Turner syndromecould be associated with Rathke cleft cyst yet,nowwe report such a case found in our hospital.Clinical data:The patient,social sex female,15.3ys,was a junior high school student.Chief com-plaints:She had short stature for 10^+ years and no pu-berche.She was a first full term fetus with cephalicpresentation.The delivery was accomplished by episi-otomy and vacuum extracter with a history of

Turner syndrome with positive SRY gene and non-classical congenital adrenal hyperplasia: A case report

BACKGROUND Co-morbidity of SRY gene turner syndrome(TS)with positive SRY gene and nonclassical congenital adrenal hyperplasia(NCAH)is extremely rare and has never been reported to date.CASE SUMMARY In this article,we present a 14-year-old girl who was referred to our hospital with short stature(weight of 43 kg and height of 143 cm,<-2 SD)with no secondary sexual characteristics(labia minora dysplasia).Laboratory tests indicated hypergonadotropic hypogonadism with significantly increased androstenedione and 17-hydroxyprogesterone(17-OHP)levels.This was accompanied by the thickening of the extremity of the left adrenal medial limb.The patient’s karyotype was 45,X/46,X,+mar,and cytogenetic analysis using multiplex ligation-dependent probe amplification and high-throughput sequencing indicated that the SRY gene was positive with compound heterozygous mutations in CYP21A2 as the causative gene for congenital adrenal hyperplasia.The sites of the suspected candidate mutations were amplified and verified using Sanger sequencing.The patient was finally diagnosed as having SRY positive TS with NCAH.The patient and her family initially refused medical treatment.At her most recent follow-up visit(age=15 years old),the patient presented facial hair,height increase to 148 cm,and weight of 52 kg,while androstenedione and 17-OHP levels remained high.The patient was finally willing to take small doses of hydrocortisone(10 mg/d).CONCLUSIONIn conclusion, upon evaluation of the patient mentioned in the report, we feel that17-OHP measurement and cytogenetic analysis are necessary for TS patients evenin the absence of significant virilization signs. This will play a significant role inguiding diagnosis and treatment.

Turner syndrome with primary myelofibrosis,cirrhosis and ovarian cystic mass:A case report

BACKGROUND Turner syndrome(TS)with leukemia is a complicated clinical condition.The clinical course and outcome of these patients are poor,so the treatment and prognosis of TS with hematological malignancies deserve our attention.CASE SUMMARY Here,we report a case of a 20-year-old woman diagnosed with TS,primary myelofibrosis(PMF),cirrhosis,and an ovarian cystic mass.This is the first report on the coexistence of TS and PMF with the MPL and SH2B3 mutations.The patient was diagnosed with cirrhosis of unknown cause,splenomegaly and severe gastroesophageal varices.Additionally,an ovarian cystic mass caused the patient to appear pregnant.The patient was treated with the JAK2 inhibitor-ruxolitinib according to peripheral blood cells,although myelofibrosis was improved,the splenomegaly did not reduce.Moreover,hematemesis and melena occasionally occurred.CONCLUSION Ruxolitinib may clearly reduce splenomegaly.Though myelofibrosis was improved,cirrhosis and splenomegaly in this case continued to worsen.Effective treatment should be discussed.

Prevalence of Bicuspid Aortic Valve in Turner Syndrome Patients Receiving Cardiac MRI and CT: A Meta-Analysis

Turner syndrome(TS)is a rare disorder affecting 25–50 in 100000 female newborns.Bicuspid aortic valve(BAV)is assumed to be the most common congenital heart defect(CHD)in TS.In literature,reported BAV prevalence in TS ranges between 14%and 34%.The specific BAV prevalence in TS is still unknown.The aim of this study was to give a more precise estimation of BAV prevalence in TS by conducting a meta-analysis of TS-studies,which detected BAV by either cardiac magnetic resonance imaging(MRI)or cardiac computed tomography(CT).We searched PubMed,Cochrane Library,and Web of Science databases to collect observational studies including the prevalence of BAV identified by cardiac MRI or cardiac CT in TS patients up to June 4th,2021.After screening for inclusion,data extraction,and quality assessment by two independent reviewers,the meta-analysis was performed with R 4.1.1 software.Results are shown as proportion and weighted mean difference with 95%confidence intervals(95%CI).In total,11 studies involving 1177 patients were included.Pooled data showed that the prevalence of BAV in TS patients was 23.7%(95%CI:21.3%to 26.1%).No high heterogeneity was found between the included studies.The current meta-analysis reveals that BAVcan be detected in 23.7%of TS patients receiving cardiac MRI or cardiac CT.Therefore,BAV can be considered as the most common CHD in TS.Compared to TTE,cardiac MRI and cardiac CT might represent superior imaging modalities in BAV assessment of adult TS patients.

Bicuspid Aortic Valve Disease in Turner Syndrome: A Meta-Analysis of Prevalence

Turner syndrome patients partially or completely lack the X chromosome. 1 - 2500 female live births are affected. Clinical features include webbed neck, short stature, broad chest etc. Bicuspid aortic valve disease (BAV) occurs in more than 30% of Turner syndrome patients causing significant morbidity and mortality. We aimed to establish a more reliable estimate of the prevalence of BAV in Turner syndrome. PubMed, Embase and PsycINFO databases were searched until 2022. Review Manager (RevMan 5.4.1) and the JASP software (0.16.00) were used for meta-analysis. 15 studies with a total of 3189 patients were combined. The pooled prevalence of BAV in Turner syndrome was 22.0% (95% CI: 15.0% - 29.0%). Sub group analysis by 45, X0 karyotype and age had prevalence of 24.0% and 8% respectively. The studies had high heterogeneity and possible publication biases. In summary, the study established that the prevalence of BAV in Turner syndrome patients diagnosed by echocardiogram, CT and MRI scans, is 22.0%, and 24% in patients with true monosomy 45, X0 karyotypes. Routine BAV exam should pay particular attention to monosomy 45, X0 karyotype patients, and where possible, CT and MRI should always accompany echocardiography for BAV screening, especially for pediatrics.

A New Case of Turner Syndrome with Early Pubertal Development

Turner syndrome (TS) is a relatively common chromosomal disorder caused by complete or partial X monosomy. The most frequently observed karyotype, 45, X, arises more often by loss of the paternal X or Y chromosome in meiosis or in early embryogenesis than by loss of the maternal X chromosome. The main clinical features of TS are short stature, gonadal dysgenesis, and not to undergo pubertal development (e.g. primary amenorrhea). However, a few rare cases of TS have shown precocious puberty. Our case of a 9-year-old girl did not have any TS-specific clinical hallmarks, with the exception of short stature. She visited our clinic because of her pubertal development and short stature. In this report, we highlight the variability that can occur in patients with TS and emphasizes the need to carefully assess unusual growth patterns in any child, regardless of other underlying conditions.

Ensemble of Two-Path Capsule Networks for Diagnosis of Turner Syndrome Using Global-Local Facial Images

Turner syndrome(TS)is a chromosomal disorder disease that only affects the growth of female patients.Prompt diagnosis is of high significance for the patients.However,clinical screening methods are time-consuming and cost-expensive.Some researchers used machine learning-based methods to detect TS,the performance of which needed to be improved.Therefore,we propose an ensemble method of two-path capsule networks(CapsNets)for detecting TS based on global-local facial images.Specifically,the TS facial images are preprocessed and segmented into eight local parts under the direction of physicians;then,nine two-path CapsNets are respectively trained using the complete TS facial images and eight local images,in which the few-shot learning is utilized to solve the problem of limited data;finally,a probability-based ensemble method is exploited to combine nine classifiers for the classification of TS.By studying base classifiers,we find two meaningful facial areas are more related to TS patients,i.e.,the parts of eyes and nose.The results demonstrate that the proposed model is effective for the TS classification task,which achieves the highest accuracy of 0.9241.

Growth-Promoting Effect of Recombinant Human Growth Hormone and Stanozolol in Girls with Turner Syndrome

Summary: Ten girls with Turner syndrome were treated with a combination therapy of recombinant human growth hormone (R hGH) and low dose stanozolol for a period of 8 to 36 months. The results showed that when compared with the growth rate before the treatment, the growth rates after treatment with R hGH and stanozolol showed a sustained increase, reaching 9.0±1.9 cm/year during the first year of treatment; the height age increase by 2.5±0.8 years while the bone age increase were 1.0±0.7 years; and the predicted final adult height at the end of the first year of the treatment increased to 149.4±6.1 cm compared to their original mean of 142.8±4.2 cm. We are led to conclude that therapy with R hGH in combination with stanozolol can increase the growth velocity and significantly increase the predicted adult height of children with Turner syndrome.

Cytogenetic and Clinical Analysis of 340 Chinese Patients with Primary Amenorrhea

Objective To analyze the relationship between karyotypes and clinic features of patients with primary amenorrhea.Methods G banding was done for 340 patients with primary amenorrhea to facilitate individual chromosome identification,and if specific staining for certain portions of the chromosome was necessary,C banding was used.The clinical data were recorded by physical examination and ultrasound scanning.Results Karyotype analysis of the 340 patients revealed that 180(52.94%) patients had normal female karyotypes and 160(47.06%) patients had abnormal karyotypes.The abnormal karyotypes included abnormal X chromosome(150 patients),mosaic X-Y chromosome(4 patients),abnormal autosome(5 patients),and X-autosome translocation(1 patient).The main clinical manifestations in patients with primary amenorrhea were primordial or absent uterus(95.9%),invisible secondary sex features(68.8%),little or absent ovary(62.6%),and short stature(30.0%).The incidence of short stature in patients with X chromosome aberration(46%,69/150) was significangly higher that in patients with 46,XX(9.44%,17/180) as well as 46,XY(6.67%,3/45;χ2=146.25,P=0.000).All primary amenorrhea patients with deletion or break-point at Xp11.1-11.4 were short statures.Conclusions One of the main reasons of primary amenorrhea is choromosome abnormality,especially heterosome abnormality.It implies the need to routinely screen chromosomal anomalies for such patients.There might be relationship between Xp11.1-11.4 integrity and height improvement.

Clinical Characteristics, Cytogenetic and Molecular Findings in Patients with Disorders of Sex Development

The clinical characteristics of patients with disorders of sex development（DSD）, and the diagnostic values of classic cytogenetic and molecular genetic assays for DSD were investigated. In the enrolled 56 cases, there were 9 cases of 46,XY DSD, 6 cases of Turner syndrome（TS）, one case of Super female syndrome, 25 cases of Klinefelter syndrome, 14 cases of 46,XX DSD, and one case of autosomal balanced rearrangements with hypospadias. The diagnosis of sex was made through physical examination, cytogenetic assay, ultrasonography, gonadal biopsy and hormonal analysis. PCR was used to detect SRY, ZFX, ZFY, DYZ3 and DYZ1 loci on Y and X chromosomes respectively. The DSD patients with the same category had similar clinical characteristics. The karyotypes in peripheral blood lymphocytes of all patients were identified. PCR-based analysis showed presence or absence of the X/Y-linked loci in several cases. Of the 9 cases of 46,XY DSD, 6 were positive for SRY, 9 for ZFX/ZFY, 9 for DYZ3 and 8 for DYZ1 loci. Of the 6 cases of TS, only 1 case with the karyotype of 45,X,/46,XX/46,XY was positive for all 5 loci. Of the 25 cases of Klinefelter syndrome, all were positive for all 5 loci. In one case of rare Klinefelter syndrome variants azoospermia factor（AZF） gene detection revealed the loss of the AZFa＋AZFb region. In 14 cases of 46,XX DSD, 7 cases were positive for SRY, 14 for ZFX, 7 for ZFY, 7 for ZYZ3, and 5 for DYZ1. PCR can complement and also confirm cytogenetic studies in the diagnosis of sex in cases of DSD.

Pathological conditions predisposing to infertility and gynaecological neoplasia

Some of the conditions long blamed for female factor infertility are now acknowledged as well established risk factors of gynecological neoplasia. This realization has lead to the proposition that infertility might be a risk factor for the development of several types of gynecological neoplasms. This review addresses different conditions that play a role in both infertility and gynaecological neoplasia. An intricate interplay between growth factors and hormonal factors(estrogens and progestins, androgens and gonadotropins) is said to link the state of infertility to some gynecological tumors. The relation between endometriosis-as one of the well established causes of female infertility- and ovarian cancer is well known. Endometriosis has been particularly related to endometrioid and clear-cell ovarian carcinomas. Another evidence for this association is embodied in finding endometriotic lesions adjacent to ovarian cancers. The polycystic ovary syndrome(PCOS), one of the most prevalent endocrine disorders and a long studied cause of female infertility increases the risk of endometrial carcinoma. The link between PCOS and endometrial carcinoma seems to be endometrial hyperplasia. PCOS-associated endometrial carcinoma tends to present at a younger age and early stage, with lower grade and lower risk of metastasis. Turner's syndrome and other types of ovarian dysgenesis constitutea rare cause of infertility and are known to confer a definite risk of germ cell tumors. There seems to be a link between infertility and an increased risk of gynecological neoplasia. Hence, it is important to assess the risk of malignancy in each category of infertile patients so as to provide optimal and timely intervention.

Dissecting Human Gonadal Cell Lineage Specification and Sex Determination Using A Single-cell RNA-seq Approach

Gonadal somatic cells are the main players in gonad development and are important for sex determination and germ cell development.Here,using a time-series single-cell RNA sequencing(scRNA-seq)strategy,we analyzed fetal germ cells(FGCs)and gonadal somatic cells in human embryos and fetuses.Clustering analysis of testes and ovaries revealed several novel cell subsets,including POU5F1^(+)SPARC^(+)FGCs and KRT19^(+) somatic cells.Furthermore,our data indicated that the bone morphogenetic protein(BMP)signaling pathway plays cell type-specific and developmental stage-specific roles in testis development and promotes the gonocyte-to-spermatogonium transition(GST)in late-stage testicular mitotic arrest FGCs.Intriguingly,testosterone synthesis function transitioned from fetal Sertoli cells to adult Leydig cells in a stepwise manner.In our study,potential interactions between gonadal somatic cells were systematically explored and we identified cell type-specific developmental defects in both FGCs and gonadal somatic cells in a Turner syndrome embryo(45,XO).Our work provides a blueprint of the complex yet highly ordered development of and the interactions among human FGCs and gonadal somatic cells.

Central precocious puberty as a prelude of gonad dysplasia

There is increasing evidence that patients with gonad dysplasia,as characterized by absent or incomplete puberty,can also exhibit central precocious puberty(CPP).Herein,we review the reported cases that manifest with both gonad dysplasia and CPP.Further,we examine the hypothesis that these patients exhibit a normal hypothalamic-pituitarygonadal axis,hypogonadism,and the presence of residual gonadal function,and that the onset of disease is related to early initiation of the hypothalamic-pituitary-gonadal axis.Thus,we suggest that CPP is a prelude of some partial hypogonadism.