Turner Patients Research Articles

Emotional-psychological concerns of Turner’s patients regarding social discrimination

IntroductionTurner syndrome characterized by total/partial and/or homogeneous/mosaic X chromosome monosomy is associated with various physical health concerns, including facial dysmorphism, short stature, infertility, and other organ defects such as heart, kidney, bone, skin, … as well as variable degrees of cognitive impairments. Besides, social skills, communication and relationships are usually disordered.ObjectivesThe aim of this study was to report social challenges of Turner syndrome particularly related to discrimination regarding physical and cognitive impairments.MethodsA retrospective analysis of clinic data and karyotypes were carried out for the patients diagnosed with Turner syndrome among patients who consulted at our genetic counselling at the medical University of Sfax, during the last two decades.Cytogenetic analysis were carried out using conventional methods and RHG banding with analysis of at least 20 metaphases and 3 karyotypes for each patient. Social challenges were recorded for each patient during pre-cytogenetic consultation and oriented questioning.ResultsWe identified 23 cases referred with a cytogenetic diagnosis of monsomy X. The karyotyping was indicated for dysmorphism, primary or secondary amenorrhea, female infertility and recurrent pregnancy losses. Homogeneous X chromosome monosomy was recorded in 13% of cases, whereas mosaic forms with and without structural X/Y abnormalities were more frequent (82%). The mean age of patients in the study was twenty years. When the 45,X population was the predominant one (56,5%), dysmorphism and primary amenorrhea were constant. In the mosaic forms, clinical traits of Turner syndrome were insignificant. Discrimination based on physical appearance, intellectual disability, and failure to conceive were the three types of social challenges revealed by patients of our study. Parents of Turner patients were also concerned at the psychological level. They in fact revealed their emotional distress face to stressful experiences of their children with Turner syndrome regarding the social discrimination they encountered particularly in schools.ConclusionsSocial challenges related to discrimination based on physical appearance, intellectual disability, and failure to conceive in Turner syndrome lead to depression, low self-esteem and anxiety.Disclosure of InterestNone Declared

Brain-derived neurotrophic factor G196A (rs6265) gene polymorphism increases Turner syndrome susceptibility

ABSTRACT Brain-derived neurotrophic factor (BDNF) is a member of the nerve growth factor family. It plays a significant role in the regulation of brain metabolic activity, modification of synaptic efficacy, and enhances neuronal survival. A common naturally occurring allelic variation, i.e. G196A (Val66 Met, rs6265) of the BDNF gene is implicated in neuroplasticity. This study analyzes its expression levels and determines the frequency of BDNF G196A gene polymorphism in women with Turner syndrome (TS) compared to the controls. This case–control study comprised 14 TS patients and 8 healthy individuals. The expression levels of BDNF gene in TS patients were checked by qPCR. For BDNF gene, a dynamic expression range along with the presence of G196A polymorphism was found across all TS patients. The effects of Val66 Met mutation on BDNF protein structure and function were studied by molecular dynamics simulations of wild and mutant (Val66 Met) forms. The analysis of different trajectories generated by simulation showed that there was a significant change in the protein structure due to Val66 Met polymorphism, which might lead to functional impairment. This is first time we are reporting the association of BDNF G196A gene polymorphism with TS risk. Our study suggests that in turner patients, BDNF G196A polymorphism may be an important genetic factor predisposing to neuroplasticity risk and can be exploited as diagnostic/prognostic marker for TS. Further study on a large number of TS samples will prove this point beyond doubts or otherwise enriching the much desired repertoire of personalized medicine.

Evaluation of cardiovascular disease in the turner syndrome population in Northern Ireland

Abstract Background There is higher frequency of both congenital heart disease and acquired cardiovascular conditions in patients with Turner syndrome. It is associated with increased early morbidity and mortality compared with the general population related mainly to cardiovascular complications. Purpose We sought to ascertain the prevalence and outcomes of cardiac abnormalities in patients with Turner syndrome in Northern Ireland. Methods Patients with Turner Syndrome who attended cardiology or gynaecology clinics in the Belfast Health and Social Care Trust were identified and demographic and clinical data were obtained. Results 165 patients who had undergone cardiovascular assessment and imaging were identified. The mean age was 38±13 years. Hypercholesterolaemia was present in 49.7%, hypertension in 21% and diabetes mellitus in 15.2%. Patients with these cardiovascular risk factors were older compared to those without (Table 1). Ischaemic heart disease was present in 2.4%. Cardiac structural abnormalities were present in 52 patients (31.5%) and bicuspid aortic valve was the most common abnormality (23.6%). 9.1% of patients had a history of cardiothoracic surgery or catheter intervention and 1 patient had a previous Type A aortic dissection surgically repaired. The variety and frequency of cardiac structural abnormalities are listed in Table 2. Conclusion The prevalence of structural cardiac abnormalities and cardiovascular risk factors in Turner patients greatly exceeds that of the general population. This highlights the need for screening with cross sectional cardiac imaging plus early identification and management of cardiovascular risk factors. Funding Acknowledgement Type of funding sources: None.

Why Turner patients with 45, X monosomy should not be excluded from fertility preservation services

In this case report, we highlight the practical dilemma, i.e. to perform ovarian tissue cryopreservation surgery in a 45, X Turner Syndrome patient or not, by reporting on the presence of follicles in a 13-year-old female diagnosed with 45, X monosomy and an unmeasurable anti-müllerian hormone serum level. We compare our results with previous research, highlight the challenges we faced in this case and provide recommendations for daily practice. Hereby, we demonstrate that excluding certain subgroups of Turner Syndrome patients (e.g. monosomy patients, and/or girls with an anti-müllerian hormone level below 2.0 ng/l) may be premature, especially based on the current state of published research data. This practical example of a challenging dilemma in the counselling of Turner Syndrome patients for fertility preservation is of interest for clinicians involved in fertility counselling and Turner Syndrome care.

Wall shear stress angle determines aortic growth in patients with bicuspid aortic valves

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The Dutch Heart Foundation Background Patients with bicuspid aortic valve (BAV) have altered flow velocity patterns with different wall shear stress (WSS) distributions in the ascending aorta compared to patients with tricuspid aortic valves. These WSS distributions are associated with aortic dilatation in cross sectional studies, however, longitudinal data demonstrating a potential causative role is missing. Purpose The aim of this study was to assess the differences in WSS distributions between BAV patients and healthy subjects and to determine the predictive value of WSS for aortic growth in patients with a BAV. Methods Forty patients with a BAV and 32 healthy matched subjects were prospectively studied by 4D-flow cardiovascular magnetic resonance (CMR). Peak velocity, pulse wave velocity, aortic distensibility, peak systolic WSS (magnitude), the different WSS components (axial and circumferential), and WSS angle were assessed in the proximal ascending aorta. WSS angle was defined as the angle between the WSSmagnitude and WSSaxial component. In the BAV patients, aortic volumetric growth over three years was determined in the proximal ascending aorta (first 5cm) based on CT angiography. Multivariate linear regression analysis was used to identify independent predictors of aortic volumetric growth. Results Of the BAV patients, 21 (53%) had a left-right fusion pattern and eight patients had Turner syndrome. WSSaxial was significantly lower in BAV patients compared to healthy subjects (p = 0.008) and WSScircumferential and WSS angle were significantly higher (both p < 0.001, see Figure). WSSmagnitude, pulse wave velocity, and aorta distensibility were not statistically significant different. WSSmagnitude (0.69 N/m² [0.51-0.81] vs 1.08 N/m² [0.89-1.24], p = 0.005), WSSaxial (0.50 N/m² [0.39-0.61] vs 0.72 N/m² [0.54-0.94], p = 0.015) and WSScircumferential (0.34 N/m² [0.32-0.46] vs 0.64 N/m² [0.47-0.81], p = 0.008) were significantly lower in BAV Turner patients compared to BAV non-Turner patients, while WSS angle (40° [34-41] vs 40° [32-48], p = 0.607) was not statistically significant different. During a follow-up of three years, there was a significant growth of the proximal ascending aorta in the BAV patients (1.2 cm3 [-0.2-2.5], p = 0.001). In multivariate analysis corrected for baseline aortic volume and diastolic blood pressure, WSS angle was the only independent predictor for proximal aortic volume growth (β=0.108, p = 0.030). Conclusions Increased WSScircumferential and especially WSS angle are present in patients with BAV. WSS angle was the only independent predictor of aortic growth. These findings highlight the potential role of WSS measurements in patients with BAV to stratify patients at risk for aortic dilation.

Hearing abnormalities in Turner patients

Hearing abnormalities in Turner patients

Prevalence of Otological Disease in Turner Syndrome: A Systematic Review.

Girls and women with Turner syndrome (TS) present with multiple ear and hearing problems, ranging from external morphologic abnormalities to sensorineural or conductive hearing loss. The exact pathophysiology behind these otological diseases is not yet completely understood. The aim of this study is to provide a systematic review on the prevalence of otological disease in TS. We conducted a systematic review according to the PRISMA guidelines. A database search was performed in PubMed, Embase, Web of Science, and Cochrane library. The prevalence of otological disease as external ear deformities (20-62%), recurrent otitis media (24-48%), and hearing loss (36-84%) is high in TS. The auditory phenotype in TS is complex and seems to be dynamic with CHL due to middle ear disease at young age and sensorineural hearing loss later in life. This systematic review of the literature confirms that otological disease is definitely part of the widely variable phenotype in Turner patients. Strong evidence is lacking on the exact prevalence numbers, emphasizing the need for more prospective data gathering. Growing insights in its pathophysiology will help in the understanding and management of hearing problems in TS across lifespan.

Turner Syndrome with Ring X Chromosome: Do They Have a Distinct Phenotype?

In contrast to classic Turner syndrome, Turner patients with ring X chromosome are associated with distinct dysmorphism and are likely to be mentally impaired. Four Turner patients with ring X chromosome were examined for phenotypic features of Turner syndrome and additional dysmorphism. Both patients 1 and 2 are twins with normal intelligence whereas patients 3 and 4 have mental impairment. With the exception of patient 4, the other three patients only have few Turner characteristics. None of the patients have the distinctive dysmorphism previously reported in Turner syndrome with ring X chromosome. Both twins developed spontaneous puberty. Patients 3 and 4 however had no spontaneous puberty. We postulate that this variation may be related to the ring size, the proportion of 45,X and ring X chromosome in cell lines of various body tissues as well as the ability of these rings to be inactivated as a result of lyonisation.

Clinical Features of Girls with Turner Syndrome in a Single Centre in Malaysia.

ObjectivesDiagnosis of Turner syndrome in Malaysia is often late. This may be due to a lack of awareness of the wide clinical variability in this condition. In our study, we aim to examine the clinical features of all our Turner patients during the study period and at presentation.MethodologyThis was a cross-sectional study. Thirty-four (34) Turner patients were examined for Turner-specific clinical features. The karyotype, clinical features at presentation, age at diagnosis and physiologic features were retrieved from their medical records.ResultsPatients with 45,X presented at a median age of 1 month old with predominantly lymphoedema and webbed neck. Patients with chromosome mosaicism or structural X abnormalities presented at a median age of 11 years old with a broader clinical spectrum, short stature being the most common presenting clinical feature. Cubitus valgus deformity, nail dysplasia and short 4th/5th metacarpals or metatarsals were common clinical features occurring in 85.3%-94.1% of all Turner patients. Almost all patients aged ≥2 years were short irrespective of karyotype.ConclusionAlthough short stature is a universal finding in Turner patients, it is usually unrecognised till late. Unlike the 45,X karyotype, non-classic Turner syndrome has clinical features which may be subtle and difficult to discern. Our findings underscore the importance of proper serial anthropometric measurements in children. Awareness for the wide spectrum of presenting features and careful examination for Turner specific clinical features is crucial in all short girls to prevent a delay in diagnosis.

Intermodality variation of aortic dimensions: How, where and when to measure the ascending aorta

BackgroundNo established reference-standard technique is available for ascending aortic diameter measurements. The aim of this study was to determine agreement between modalities and techniques. MethodsIn patients with aortic pathology transthoracic echocardiography, computed tomography angiography (CTA) and magnetic resonance angiography (MRA) were performed. Aortic diameters were measured at the sinus of Valsalva (SoV), sinotubular junction (STJ) and tubular ascending aorta (TAA) during mid-systole and end-diastole. In echocardiography both the inner edge-to-inner edge (I-I edge) and leading edge-to‑leading edge (L-L edge) methods were applied, and the length of the aortic annulus to the most cranial visible part of the ascending aorta was measured. In CTA and MRA the I-I method was used. ResultsFifty patients with bicuspid aortic valve (36 ± 13 years, 26% female) and 50 Turner patients (35 ± 13 years) were included. Comparison of all aortic measurements showed a mean difference of 5.4 ± 2.7 mm for the SoV, 5.1 ± 2.0 mm for the STJ and 4.8 ± 2.1 mm for the TAA. The maximum difference was 18 mm. The best agreement was found between echocardiography L-L edge and CTA during mid-systole. CTA and MRA showed good agreement. A mean difference of 1.5 ± 1.3 mm and 1.8 ± 1.5 mm was demonstrated at the level of the STJ and TAA comparing mid-systolic with end-diastolic diameters. The visible length of the aorta increased on average 5.3 ± 5.1 mmW during mid-systole. ConclusionsMRA and CTA showed best agreement with L-L edge method by echocardiography. In individual patients large differences in ascending aortic diameter were demonstrated, warranting measurement standardization. The use of CTA or MRA is advised at least once.

Partial anomalous pulmonary venous return in Turner syndrome

PurposeThe aim of this study is to describe the prevalence, anatomy, associations and clinical impact of partial anomalous pulmonary venous return in patients with Turner syndrome. Methods and resultsAll Turner patients who presented at our Turner clinic, between January 2007 and October 2015 were included in this study and underwent ECG, echocardiography and advanced imaging such as cardiac magnetic resonance or computed tomography as part of their regular clinical workup. All imaging was re-evaluated and detailed anatomy was described. Partial anomalous pulmonary venous return was diagnosed in 24 (25%) out of 96 Turner patients included and 14 (58%) of these 24 partial anomalous pulmonary venous return had not been reported previously. Right atrial or ventricular dilatation was present in 11 (46%) of 24 partial anomalous pulmonary venous return patients. ConclusionWhen studied with advanced imaging modalities and looked for with specific attention, PAPVR is found in 1 out of 4 Turner patients. Half of these patients had right atrial and/or ventricular dilatation. Evaluation of pulmonary venous return should be included in the standard protocol in all Turner patients.

P6315Outcome in Turner patients with aortic dilation

P6315Outcome in Turner patients with aortic dilation

Magnetic resonance imaging 4-D flow-based analysis of aortic hemodynamics in Turner syndrome.

Cardiovascular surveillance is important in Turner syndrome because of the increased risk of aortic dilation and dissection with consecutively increased mortality. To compare 4-D flow MRI for the characterization of aortic 3-D flow patterns, dimensions and vessel wall parameters in pediatric patients with Turner syndrome and age-matched controls. We performed 4-D flow MRI measuring in vivo 3-D blood flow with coverage of the thoracic aorta in 25 patients with Turner syndrome and in 16 female healthy controls (age mean ± standard deviation were 16 ± 5years and 17 ± 4years, respectively). Blood flow was visualized by time-resolved 3-D path lines. Visual grading of aortic flow in terms of helices and vortices was performed by two independent observers. Quantitative analysis included measurement of aortic diameters, quantification of peak systolic wall shear stress, pulsatility index and oscillatory shear index at eight defined sites. Patients with Turner syndrome had significantly larger aortic diameters normalized to BSA, increased vortices in the ascending aorta and elevated helix flow in the ascending and descending aorta compared to controls (all P<0.03). Patients with abnormal helical or vortical flow in the ascending aorta had significantly larger diameters of the ascending aorta (P<0.03). Peak systolic wall shear stress, pulsatility index and oscillatory shear index were significantly lower in Turner patients compared to controls (p=0.02, p=0.002 and p=0.01 respectively). Four-dimensional flow MRI provides new insights into the altered aortic hemodynamics and wall shear stress that could have an impact on the development of aortic dissections.

Proximal aortic stiffening in Turner patients may be present before dilation can be detected: a segmental functional MRI study

BackgroundTo study segmental structural and functional aortic properties in Turner syndrome (TS) patients. Aortic abnormalities contribute to increased morbidity and mortality of women with Turner syndrome. Cardiovascular magnetic resonance (CMR) allows segmental study of aortic elastic properties.MethodWe performed Pulse Wave Velocity (PWV) and distensibility measurements using CMR of the thoracic and abdominal aorta in 55 TS-patients, aged 13-59y, and in a control population (n = 38;12-58y). We investigated the contribution of TS on aortic stiffness in our entire cohort, in bicuspid (BAV) versus tricuspid (TAV) aortic valve-morphology subgroups, and in the younger and older subgroups.ResultsDifferences in aortic properties were only seen at the most proximal aortic level. BAV Turner patients had significantly higher PWV, compared to TAV Turner (p = 0.014), who in turn had significantly higher PWV compared to controls (p = 0.010). BAV Turner patients had significantly larger ascending aortic (AA) luminal area and lower AA distensibility compared to both controls (all p < 0.01) and TAV Turner patients. TAV Turner had similar AA luminal areas and AA distensibility compared to Controls. Functional changes are present in younger and older Turner subjects, whereas ascending aortic dilation is prominent in older Turner patients. Clinically relevant dilatation (TAV and BAV) was associated with reduced distensibility.ConclusionAortic stiffening and dilation in TS affects the proximal aorta, and is more pronounced, although not exclusively, in BAV TS patients.Functional abnormalities are present at an early age, suggesting an aortic wall disease inherent to the TS. Whether this increased stiffness at young age can predict later dilatation needs to be studied longitudinally.

Neoplasia in Turner syndrome. The importance of clinical and screening practices during follow-up

Aim of the studyTurmer syndrome (TS) patients show increased morbidity due to metabolic, autoimmune and cardiovascular disorders. A risk of neoplasia is also reported. Here, we review the prevalence of neoplasia in a cohort of Turner patients. MethodsWe retrospectively evaluated 87 TS women. Follow-up included periodic ultrasound of the neck, abdominal and pelvic organs, dermatologic evaluation and fecal occult blood test. Karyotype was 45,X in 46 patients. During follow-up, 63 girls were treated with growth hormone, 65 with estro-progestin replacement therapy and 20 with L-thyroxine. Autoimmune diseases were present in 29 TS. ResultsA total of 17 neoplasms in 14 out of 87 patients were found. Six skin neoplasia, 3 central nervous system tumors, 3 gonadal neoplasia, 2 breast tumors, 1 hepatocarcinoma, 1 carcinoma of the pancreas and 1 follicular thyroid cancer were detected. Age at tumor diagnosis was higher in 45,X pts than in those with other karyotypes (p = 0.003). Adenomioma gallbladdder (AG) was detected in 15.3% of the patients, with a lower age in girls at diagnosis with an associated neoplasia in comparison with TS without tumors (p = 0.017). No correlation between genetic make up, treatment, associated autoimmune diseases and neoplastia was found. ConclusionIn our TS population an increased neoplasia prevalence was reported. A high prevalence of AG was also noted and it might be indicative of a predisposition to neoplasia. Further studies are needed to define the overall risk for neoplasia, and to determine the role of the loss of the X-chromosome and hormonal therapies.

Impaired Elasticity and Ascending Aortic Size in Young Turner Patients

Impaired Elasticity and Ascending Aortic Size in Young Turner Patients

Final size of turner patients: about 40 patients

Final size of turner patients: about 40 patients

A case series of intracranial hypertension in patients with Turner syndrome, with and without growth hormone therapy

Intracranial Hypertension (IH) is a known side effect of GH therapy [1], but has many other aetiologies. Turner syndrome patients have growth failure related to loss of the SHOX transcription factor and so respond to high dose GH therapy. Turner patients also have a high incidence of middle ear disease that can cause intracranial hypertension via mastoiditis and venous sinus thrombosis. IH has been reported in Turner syndrome with no predisposing cause.

Spontaneous uterine rupture at 14 weeks gestation during a pregnancy consecutive to an oocyte donation in a woman with Turner's syndrome

We describe a spontaneous uterine rupture at 14 weeks gestation in a Turner patient. A 39 year-old patient was admitted for abdominal pain and hypotension at 14 weeks of pregnancy. The pregnancy had been obtained by oocyte donation and in vitro fertilization (IVF) because of Turner's syndrome. The abdominal ultrasound scan showed a normal pregnancy and a conserved foetal cardiac activity. It also showed a large amount of free fluid in the perihepatic space. Haemoglobin was 11.2g/dL. After hemodynamic degradation, urgent laparoscopy showed an unrepairable uterine rupture with partial exteriorisation of the pregnancy, and placenta percreta. Urgent conversion to laparotomy allowed haemostatic hysterectomy. Uterine rupture during pregnancy obtained by oocyte donation in Turner's syndrome may be life threatening. The possibility of such a complication should be considered before oocyte donation for IVF in Turner's patients. Early spontaneous uterine rupture (second trimester) is a challenging diagnostic that should be evoked in case of non-specific abdominal pain in the presence of risk factors.

Pregnancy and cardiovascular risk for women with Turner syndrome.

Most women with Turner syndrome (TS) are infertile due to primary ovarian failure. However, approximately 5% experience spontaneous pregnancy, and recently, more women with TS have used assisted reproductive technology with donated oocytes (ART-OD) to become pregnant. The firstgeneration of Turner patients undergoing ART-OD demonstrated a high rate of fatal aortic dissection in late pregnancy or postpartum. More recent observations, particularly from Nordic countries, suggest a lesser risk of dissection, but confirm a high rate of pre-eclampsia in ART-OD pregnancies. This article reviews publications since 2000 concerning maternal outcomes for pregnancies in women with TS to determine if specific risk factors such as type of pregnancy, age, or presence of underlying congenital cardiovascular disease may identify women at special risk.