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.

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.

Clinical Significance of Multiple Hypothalamic－Pituitary Functions Assessment in Patients with Turner＇s Syndrome

Hypothalamic-pituitary functions in 26 cases of Turner syndrome were assessed with a combined stimulation test.The results showed that the peak GH levels of 12 cases were less than 10 μg/L; 3 patients were demonstrated as having an even TSH response, while another one with a delayed TSH peak, and other 4 had high basal values and consistent exaggerated TSH responses to TRH; all patients showed increased basal and peak LH and FSH levels but 5, whose LH and FSH secretion patterns were similar to normal. 12 cases have been treated with individualized protocols and followed up for 12 months or more, of them the growth velocity all increased, especially those with hypothyroidism or with a BA less than 13. It is suggested that multiple functions of hypothalamic-pituitary axis in Turner patients be evaluated as early as possible, in order that proper treatment could be adopted and their growth and development improved.

Unreliability of aortic size index to predict risk of aortic dissection in a patient with Turner syndrome

Aortic size index(ASI) has been proposed as a reliable criterion to predict risk for aortic dissection in Turner syndrome with significant thresholds of 20-25 mm/m2. We report a case of aortic arch dissection in a patient with Turner syndrome who, from the ASI thresholds proposed, was deemed to be at low risk of aortic dis-section or rupture and was not eligible for prophylactic surgery. This case report strongly supports careful monitoring and surgical evaluation even when the ASI is < 20 mm/m2 if other significant risk factors are present.

Luteolin induces hippocampal neurogenesis in the Ts65Dn mouse model of Down syndrome

Studies have shown that the natural flavonoid luteolin has neurotrophic activity. In this study, we investigated the effect of luteolin in a mouse model of Down syndrome. Ts65 Dn mice, which are frequently used as a model of Down syndrome, were intraperitoneally injected with 10 mg/kg luteolin for 4 consecutive weeks starting at 12 weeks of age. The Morris water maze test was used to evaluate learning and memory abilities, and the novel object recognition test was used to assess recognition memory. Immunohistochemistry was performed for the neural stem cell marker nestin, the astrocyte marker glial fibrillary acidic protein, the immature neuron marker DCX, the mature neuron marker NeuN, and the cell proliferation marker Ki67 in the hippocampal dentate gyrus. Nissl staining was used to observe changes in morphology and to quantify cells in the dentate gyrus. Western blot assay was used to analyze the protein levels of brain-derived neurotrophic factor(BDNF) and phospho-extracellular signal-regulated kinase 1/2(p-ERK1/2) in the hippocampus. Luteolin improved learning and memory abilities as well as novel object recognition ability, and enhanced the proliferation of neurons in the hippocampal dentate gyrus. Furthermore, luteolin increased expression of nestin and glial fibrillary acidic protein, increased the number of DCX^+ neurons in the granular layer and NeuN^+ neurons in the subgranular region of the dentate gyrus, and increased the protein levels of BDNF and p-ERK1/2 in the hippocampus. Our findings show that luteolin improves behavioral performance and promotes hippocampal neurogenesis in Ts65 Dn mice. Moreover, these effects might be associated with the activation of the BDNF/ERK1/2 pathway.

Turner’s Syndrome产前诊断和治疗进展

脱纳氏综合征 (turner s syndrome,TS)是比较常见的染色体疾病 ,性染色体 X的部分或完全缺失或镶嵌型是本病的基本病因。身材矮小和性腺发育不全是其主要临床特征。如从儿童时代起及时应用生长激素 (GH)有效改善身长高度 ,适时采用雌激素诱导青春期发育 ,TS的成年妇女用 HRT等综合治疗对 TS的女孩和妇女改善生活质量是非常重要的 。

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

Small intestinal tubular adenoma in a pediatric patient with Turner syndrome

Turner syndrome (TS) is a female chromosomal disorder caused by the lack of an X chromosome. The loss of this chromosome may result in the deficiency of tumorsuppressive or DNA repair genes, leading to tumorigenesis. Recombinant human growth hormone (GH) has been popularly used for treatment in TS patients for growth promotion. Although treatment with GH has been correlated with precancerous and cancerous lesions in TS children, its associations with gastric or colonic tumors, especially ileal tubular adenomas, have not been reported frequently. We here report a case of a 16-year-old patient with TS and tubular adenoma of the small intestine. Whether the ileal adenoma was caused by TS itself or GH therapy was discussed.

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.

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.

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.

Turner综合征孕妇的产前指征与染色体核型及妊娠结局分析

目的分析介入性产前诊断Turner综合征(TS)孕妇的产前指征、染色体核型及妊娠结局,总结特征,为TS诊疗提供参考。方法收集2014年1月至2023年1月期间在我院围产保健并实施介入性产前诊断的孕妇资料进行回顾性分析,统计介入性产前诊断的诊断指征、染色体核型异常检出情况及TS检出情况,随访至分娩,统计TS病例妊娠结局。结果纳入实施介入性产前诊断孕妇1876例,染色体核型异常检出率为5.81%,TS检出率为1.33%(25例),TS病例表型以X单体最为典型,其他染色体核型异常主要为21三体综合征、18三体综合征、13三体综合征。染色体核型异常的介入性产前诊断指征以超声异常最为常见,其次分别为血清学筛查高风险、NIPT性染色体异常高风险、高龄孕妇和其他。TS病例中与非TS病例的各介入性产前诊断指征分布比较,差异无统计学意义(P>0.05)。TS病例超声异常指征中,X单体的NT增厚、淋巴水囊瘤占比高于非X单体,差异有统计学意义(P<0.05)。23例TS病例产妇随访至分娩,活产率为8.70%(2/23),X单体活产率与非X单体比较差异无统计学意义(P>0.05)。结论超声异常是染色核型异常最常见的介入性产前诊断指征。TS病例中X单体是最常见的染色体核型异常,其超声异常类型以NT增厚、淋巴水囊瘤最为常见,活产率较低。

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.

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.

Study on the Relationship between Cytogenetics and Phenotypic Effect in Turner＇s Syndrome

The cytogenetics and clinical stigmata in 5 cases of Turner's syndrome were studied. Three of them were non-mosaic i(Xq) and two with partial monosome of a X chromosome short are (Xp21), whose DNA replication patterns of inactive X chromosome were analyzed by RBG technique. Results showed that differences between the replication patterns in cases of X chromosome deletion (Xp21) and normal females existed; that the behavior of abnormal X expressed nonrandom inactivation. It was suggested that the phenotype may be closely related with both X chromosome replication pattern and its inactivation behavior,which might be useful in genetic counselling.

Cardiovascular surgery in Turner syndrome-early outcome and long-term follow-up

BACKGROUND Cardiovascular disease is the leading cause of death in patients with Turner syndrome(TS),and cardiovascular surgery is frequently required for management of these patients.TS is associated with medical comorbidities than can complicate the care of this patient population.AIM To describe the cardiovascular surgical outcomes of patients with TS.METHODS A retrospective case series was compiled of 51 consecutive TS patients who had at least one cardiovascular surgery at Mayo Clinic Rochester from 1977-2017.The baseline clinical data of these patients were reviewed including demographics,medical comorbidities,congenital heart disease history,and medications.Echocardiographic reports were analyzed in detail.Operative reports and surgical hospital courses were reviewed.Long-term mortality was determined using medical records and the Social Security Death Index.Survival analysis was performed with the Kaplan Meier method.RESULTS The cohort comprised 51 TS patients,average age at the time of surgery at Mayo Clinic was 28(8-41)years,and 23(45%)patients were under the age of 18.At the time of first Mayo Clinic surgery,18(35%)patients had previously undergone cardiac surgery at another institution.The most common procedures were repair of aortic coarctation in 14(28%)patients,aortic valve replacement in 6(12%)patients,and composite aortic root/ascending aorta replacement in 7(14%)patients,with 7 patients undergoing repair of more than one lesion.Aortic dissection required operative intervention in 5 patients.After initial Mayo Clinic surgery,subsequent operations were required in 6(13%)patients.Average hospital length of stay was 6±2 d.There were 4(8%)early surgical deaths.Freedom from death was 97%and 89%at 10 and 20 years,and the freedom from reoperation was 93%and 81%at 10 and 20 years.CONCLUSION Cardiovascular surgery is associated with 8%early mortality given the medical complexity of TS patients.Those who survive to dismissal have good survival.Later cardiovascular reoperations are not rare.

Clinical Syndromes Associated with Cardiovascular Diseases:A Review

In clinical practice,a variety of syndromes are associated with cardiovascular disease and have characteristic findings.Most of them are an autosomal dominant genetic disorder and have different types of cardiovascular abnormalities,including electrocardiographic conduction defects,arrhythmias,cardiomyopathy,vascular and valvular diseases,cardiac septal defects,and pulmonary problems.There is a growing need for physicians to pay more attention to these syndromes.