Thirty-Year Survival after Cardiac Surgery for Patients with Turner Syndrome.

OBJECTIVE: To evaluate long-term survival in patients with Turner syndrome after congenital heart surgery with a focus on left heart obstructive lesions (LHOLs). STUDY DESIGN: We queried the Pediatric Cardiac Care Consortium, a US-based registry of congenital heart surgery, for patients with Turner syndrome undergoing congenital heart surgery at <21 years of age between 1982 and 2011. Outcomes were obtained from the Pediatric Cardiac Care Consortium and from national death and transplant registries through 2019. Survival of patients with Turner syndrome and nonsyndromic patients with similar LHOL was compared by Kaplan-Meier survival curves and Cox regression adjusted for age, congenital heart disease, and era. RESULTS: We identified 179 patients with Turner syndrome operated for LHOL: 161 with 2-ventricle lesions (coarctation n = 149, aortic stenosis n = 12) and 18 with hypoplastic left heart (HLH) variants. There were 157 with 2-ventricle LHOL and 6 with HLH survived to discharge. Among survivors to hospital discharge, the 30-year transplant-free survival was 90.4% for Turner syndrome with 2-ventricle lesions and 90.9% for nonsyndromic comparators (adjusted hazard ratio [aHR] 1.15, 95% CI 0.64-2.04). The postdischarge survival for HLH was 33% for Turner syndrome and 51% for nonsyndromic patients, with these numbers being too small for meaningful comparisons. There was a higher risk for cardiovascular disease events in patients with Turner syndrome vs male (aHR 3.72, 95% CI 1.64-8.39) and female comparators (aHR 4.55, 95% CI 1.87-11.06) excluding heart failure deaths. CONCLUSIONS: The 30-year transplant-free survival is similar for patients with Turner syndrome and nonsyndromic comparators with operated 2-ventricle LHOL without excess congenital heart disease risk. However, patients with Turner Syndrome still face increased cardiovascular disease morbidity, stressing the importance of lifelong comorbidity surveillance in this population.

Sex Hormone Replacement Therapy in Turner Syndrome: Impact on Morbidity and Mortality.

CONTEXT: The long-term effects of female hormone replacement therapy (HRT) in Turner syndrome (TS) are unknown. OBJECTIVE: To examine morbidity, mortality and medicinal use in TS and the impact of HRT in 45,X women. DESIGN AND SETTING: National cohort study, following all TS individuals ever diagnosed in Denmark from 1977 to 2014. PATIENTS AND METHODS: In the Danish Cytogenetic Central Registry, we identified 1156 females diagnosed with TS from 1960 to 2014, and, subsequently, Statistics Denmark randomly identified 115 577 age-matched female controls. TS women and their matched controls were linked with person-level data from the National Patient Registry and the Medication Statistics Registry, and they were compared concerning mortality, hospitalizations, and medical prescriptions. Among 329 45,X women, 44 had never been HRT treated, and 285 had been treated at some point. HRT treated women were compared with untreated concerning mortality, hospitalizations, and medical prescriptions. RESULTS: Endocrine and cardiovascular mortality and morbidity were significantly increased in TS compared with the matched controls. Comparing HRT treated with nontreated 45,X women, we found a similar mortality (hazard ratio 0.83, 95% confidence interval 0.38-1.79). Among the HRT-treated 45,X women, we found a significantly lower use of antihypertensives, antidiabetics, and thyroid hormones and significantly reduced hospitalization rates for stroke and osteoporotic fractures. CONCLUSION: Women with TS have an increased overall mortality and morbidity. HRT seems to have a beneficial effect on endocrine conditions, hypertension, and stroke in women with 45,X karyotype, with no clear impact on mortality.

Association between cardiovascular anomalies and karyotypes in Turner syndrome patients in Taiwan: A local cohort study.

BACKGROUND: Turner syndrome (TS) is characterized by growth failure, primary ovarian failure, cardiac anomalies, and other anomalies. Cardiovascular abnormalities such as bicuspid aortic valve (BAV), coarctation of the aorta (CoA), aortic stenosis (AS), and aortic dilatation (AD) account for some cases of TS-related early mortality. In this study, we investigated the correlations between cardiovascular phenotypes and karyotypes in TS. METHODS: We conducted a retrospective cohort analysis of 105 local patients with TS aged 6-43 years between January 1994 and December 2018. They were categorized into two groups of complete monosomy X (45,X) and other X chromosome abnormalities. Most of the patients underwent echocardiography (n = 88, 83.8%), cardiac computed tomography (CT) angiography, and/or cardiovascular magnetic resonance imaging (MRI) (n = 58, 55.2%). We used independent the Student's t test, chi-square test or Fisher's exact test, and log-rank test to compare differences in continuous data, proportions, and Kaplan-Meier survival analysis results between the two TS groups. RESULTS: 45,X was the most common karyotype (n = 47, 44.8%). Phenotypically, cardiovascular malformations were found in 29 patients with TS (27.6%). BAV (n = 6), CoA (n = 3), AS (n = 2), ASD (n = 1, 2.5%), and PAPVR (n = 1, 2.5%) were found in only the 45,X group. The mean age at AD onset was 25.55 ± 5.78 years (mean ± SD). Survival analysis of age at onset of AD demonstrated no significant difference between the two groups (p = 0.051). CONCLUSION: Cardiovascular abnormalities, such as BAV, CoA, AS, and AD, are common and potentially progressive in patients with TS, especially those with the 45,X karyotype. They should receive immediate cardiological assessments upon receiving diagnosis, regular assessments, and treatment to carefully control blood pressure, even with no apparent congenital heart disease.

Obstetric complications in pregnancies with life-limiting malformations.

PURPOSE OF REVIEW: The implementation of palliative care at birth has led to a significant rise in the number of couples who choose to continue with pregnancies complicated by life-limiting malformations (LLMs). Prenatal counselling and appropriate antenatal/perinatal management in these cases are poorly studied and may pose significant challenges. The purpose of this review is to outline specific obstetric risks and to suggest management for mothers who choose to continue with pregnancies with the most common LLMs. RECENT FINDINGS: In pregnancies complicated by LLMs where parents opt for expectant management, clinicians should respect parental wishes, whilst openly sharing potential serious maternal medical risks specific for the identified abnormalities. The focus of both antenatal and perinatal care should be maternal wellbeing rather than foetal survival. Follow-up ultrasound examinations and maternal surveillance should be aimed at achieving timely diagnosis and effective management of obstetric complications. A clear perinatal plan, agreed with the couples by a multi-disciplinary team including a foetal medicine specialist, a neonatologist and a geneticist, is crucial to reduce maternal morbidity. SUMMARY: This review provides a useful framework for clinicians who face the challenges of counselling and managing cases complicated by LLMs where parents opt for pregnancy continuation.

Long-Term Outcomes in Patients With Turner Syndrome: A 68-Year Follow-Up.

Background Turner syndrome ( TS ) is the most common sex chromosome abnormality in women and is associated with increased morbidity and mortality. We describe long-term outcomes in a large cohort of patients with TS . Methods and Results Retrospective review of patients with TS followed at Mayo Clinic Rochester from 1950 to 2017 was performed. Clinical, imaging, surgical, and genetic data were analyzed. Survival analysis was performed with the Kaplan-Meier method using age- and sex-matched Olmsted County residents as the reference group. The study cohort comprised 317 patients with TS . Average age at diagnosis was 9 (range, 2-12) years, genetic testing was performed in 202 (64%), and pure monosomy X was present in 75 (37%). Congenital heart disease occurred in 131 (41%), with the most frequent lesions being bicuspid aortic valve (n=102, 32%) and coarctation of the aorta (n=43, 14%). Ascending aortic dilation was common, with mean aortic root size index 2 cm/m2, and aortic dissection occurred in 6 (2%) patients. The average follow-up was 11 (range, 2-26) years, yielding 3898 patient-years, and during this period 46 (14%) patients died; mean age at the time of death was 53±17 years. Patients with TS had reduced survival compared with the control group (82% versus 94% at 30 years; P<0.001), and the leading causes of death were cardiovascular disease, liver disease, and malignancy. Conclusions Patients with TS have reduced survival compared with age-matched controls, and cardiovascular disease is the major cause of death. Further studies are required to determine if targeted cardiovascular risk factor modification will result in improved survival in this population.

Síndrome de Turner: nuestra experiencia en la creación del Registro Institucional y de la Unidad Interdisciplinaria en el Hospital Italiano de Buenos Aires: un primer paso para el mejor seguimiento / Turner syndrome: our experience in the creation of the Registry Institutional and Interdisciplinary Unit at the Italian Hospital of Buenos Aires: a first step to the best follow-up

El síndrome de Turner (ST) resulta de la ausencia completa o parcial del segundo cromosoma sexual en fenotipos femeninos. Tiene una incidencia de 1:2000- 2500 nacidas vivas. Recién en la última década se ha puesto atención a la salud de las adultas con ST. La mortalidad es 3 veces superior respecto de la población general debido al riesgo de disección aórtica por anomalías cardiovasculares estructurales y aterosclerosis vinculada a hipertensión arterial, diabetes, dislipidemia y obesidad. También presentan elevada prevalencia de enfermedades autoinmunitarias. Objetivo: evaluar la calidad del seguimiento clínico de pacientes adultas con ST, comparando los controles de salud preconformación y posconformación del Registro y de la Unidad Interdisciplinaria. En el año 2017 fuimos convocados para integrar el Programa de Enfermedades Raras del Hospital Italiano de Buenos Aires. A partir de la creación del Registro Institucional y del equipo multidisciplinario obtuvimos mejoría significativa en los controles por las especialidades de cardiología, endocrinología y otorrinolaringología, en los controles bioquímicos del metabolismo lipídico, hidrocarbonado, hepatograma, TSH y anticuerpos para celiaquía e imágenes cardiovasculares y densitometría ósea. En conclusión, el seguimiento sistematizado e institucional, mediante el Registro y la creación de la Unidad Interdisciplinaria de Síndrome de Turner, permitió encontrar las falencias del sistema de atención y optimizar el seguimiento de esta población. (AU)

Turner syndrome (TS) results from the complete or partial absence of the second sex chromosome in female phenotypes. It has an incidence of 1: 2000-2500 girls born alive. Only in the last decade has been paid attention to the health of adults women with TS. Mortality is 3 times higher than in the general population due to the risk of aortic dissection cause to structural cardiovascular anomalies and atherosclerosis related to hypertension, diabetes, dyslipidemia and obesity. They also have a high prevalence of autoimmune diseases. Until nowadays in Argentina do not exist a national registry of this disease that complies with the international follow-up recommendations for these patients. We proposed to develop the institutional register at 2014 and a multidisciplinary team was created to care and follow up girls and women with TS during 2015. It was indexed to Italian Hospital of Buenos Aires' Rare Diseases Program since 2017. After the creation of the institutional registry and the multidisciplinary team we obtained a significant improvement in cardiology, endocrinology and otorhinolaryngology schedule visits, in lipids and hydrocarbon metabolism, liver, thyroid and celiac diseases biochemical controls and in the performance of cardiovascular MNR and bone densitometry. In conclusion, the systematized and institutional follow-up, through the registry and the creation of the Interdisciplinary Unit of Turner Syndrome, allowed us to find the flaws of the care system and to optimize the follow up of this population. (AU)

Cardiovascular imaging in Turner syndrome: state-of-the-art practice across the lifespan.

Cardiovascular imaging is essential to providing excellent clinical care for girls and women with Turner syndrome (TS). Congenital and acquired cardiovascular diseases are leading causes of the lifelong increased risk of premature death in TS. Non-invasive cardiovascular imaging is crucial for timely diagnosis and treatment planning, and a systematic and targeted imaging approach should combine echocardiography, cardiovascular magnetic resonance and, in select cases, cardiac CT. In recent decades, evidence has mounted for the need to perform cardiovascular imaging in all females with TS irrespective of karyotype and phenotype. This is due to the high incidence of outcome-determining lesions that often remain subclinical and occur in patterns specific to TS. This review provides an overview of state-of-the-art cardiovascular imaging practice in TS, by means of a review of the most recent literature, in the context of a recent consensus statement that has highlighted the role of cardiovascular diseases in these females.

Cardiac transplantation in children with Down syndrome, Turner syndrome, and other chromosomal anomalies: A multi-institutional outcomes analysis.

BACKGROUND: The purpose of this study was to describe the prevalence, characteristics, and outcomes in pediatric patients with chromosomal anomalies (CA) undergoing orthotopic heart transplantation (OHT). METHODS: A query of the database of the Pediatric Health Information System, a large administrative and billing database of 43 tertiary children's hospitals, was performed for the Years 2004 to 2016. Pediatric patients who received OHT were analyzed based on presence and type of CA. CA analyzed included: Down syndrome (DS); Turner syndrome (TS)/gonadal dysgenesis; conditions due to anomaly of unspecified chromosome; autosomal deletion; microdeletion; and autosomal anomaly. Healthcare-associated charge analysis during hospitalization for OHT and survival after OHT were assessed. RESULTS: A total of 3,080 hospitalizations were identified in which OHTs were performed. Of these OHTs, 64 (2.1%) were performed in patients with a concomitant diagnosis of CA. The presence of CA did not confer a higher risk of in-hospital mortality after OHT (odds ratio 1.2 [0.5 to 3.2], p = 0.651). Differences in in-hospital mortality between different types of CA, including DS and TS, did not reach statistical significance. Survival at 1-year post-OHT was similar in patients with CA compared to those without CA (p = 0.248). Length of stay after OHT was longer in patients with CA: 76 (interquartile range [IQR] 76 to 142 days vs 49 [IQR 21 to 98] days) (p < 0.001), respectively. Overall adjusted hospital charges were significantly higher in the CA group: $1.2 million (IQR $740,000 to $2.2 million) vs $792,000 (IQR $425,000 to $1.5 million] (p < 0.001), respectively. CONCLUSIONS: CA is present in ~2% of pediatric patients undergoing OHT. The presence of CA was not associated with increased mortality in pediatric patients undergoing OHT. Limitations of this study include the small number of patients available for analysis and a likely highly selective cohort of patients with CA.

Hypoplastic left heart in Turner's syndrome: a primary indication for transplant?

Survival for hypoplastic left heart syndrome patients following the Norwood procedure is 71-90%. Mortality in patients with Turner's syndrome and hypoplastic left heart syndrome after conventional palliation (Norwood operation) has been reported as high as 80%. This questions the approach of traditional staged palliation. Here, we report a patient with hypoplastic left heart syndrome and Turner's syndrome bridged to orthotopic heart transplantation following a hybrid procedure.

Increased aortic stiffness in prepubertal girls with Turner syndrome.

BACKGROUND: Aortic dilation and dissection contribute highly to the increased mortality of Turner syndrome (TS) but the exact pathophysiology is not completely understood. DESIGN: Prospective case - control study. METHODS: 15 prepubertal TS girls (median age 10.64, IQ 8.31-11.04) with a tricuspid (TAV, n=9) or a bicuspid (BAV, n=6) aortic valve, and 31 sex-, age-, and height-matched healthy controls underwent a cardiac and vascular ultrasound to evaluate aortic dimensions and elastic properties of the aortic wall. RESULTS: TS BAV had significantly larger ascending aortic diameters than controls for absolute diameter, 22.2±5.1mm vs. 18.6±1.9mm (p=0.014) and z-score 1.7±2.1 vs. 0.1±0.7 (p=0.008). Distensibility of the ascending aorta was lower in the TS than in controls (40.2×10-3kPa-1, IQ 31.3-56.2 vs. 62.9×10-3kPa-1, IQ 55.5-76.5, p=0.003), both for TS TAV (p=0.014) and BAV (p=0.005). Stiffness index was higher in TS than in controls (5.26, IQ 3.34-5.26 vs. 3.23, IQ 2.55-3.24, p=0.005), both for TS TAV (p=0.028) and TS BAV (p=0.006). Pulse wave velocity was not different between groups. There was no correlation between stiffness and z-score of the ascending aortic diameter. CONCLUSIONS: In prepubertal TS girls, stiffness of the ascending aorta is increased in patients with a BAV and TAV while dilation of the ascending aorta is more frequent in BAV. This suggests an intrinsic aortic wall abnormality making all TS patients at increased risk for severe aortic complications although the risk is the highest for TS with BAV.

Adverse outcome of coarctation stenting in patients with Turner syndrome.

OBJECTIVES: This study examines the outcome and procedural outcomes of percutaneous stent angioplasty for aortic coarctation in patients with Turner syndrome (TS). BACKGROUND: TS occurs in 1 in 2,500 live-born females and is associated with aortic coarctation. METHODS: In this multicenter, retrospective cohort study, all patients with TS and a coarctation of the aorta, treated with percutaneous stent implantation were included. The procedural strategies were dictated by local protocols. Adverse events at short- and long-term follow-up and qualitative parameters concerning the stent implantation were assessed. RESULTS: In the largest study to date of TS patients receiving aortic stents, a total of 19 patients from 10 centers were included. Twelve patients were treated for native and 7 for recurrent coarctation. Age at intervention was 16.9 (7-60) years (median; min-max). The coarctation diameter increased significantly from 8.0 mm (2-12) pre-intervention to 15.0 mm (10-19) post-intervention (P < 0.001). Three (15.8%) adverse events occurred within 30 days of the procedure, including two dissections despite the use of covered stents, one resulting in death. At long-term follow-up (6.5 years, min-max: 1-16), two additional deaths occurred not known to be stent-related. CONCLUSIONS: Though percutaneous treatment of aortic coarctation in TS patients is effective, it is associated with serious morbidity and mortality. These risks suggest that alternative treatment options should be carefully weighed against percutaneous stenting strategies. © 2016 Wiley Periodicals, Inc.

A population-based analysis of mortality in patients with Turner syndrome and hypoplastic left heart syndrome using the Texas Birth Defects Registry.

BACKGROUND: Hypoplastic left heart syndrome (HLHS) is strongly associated with Turner syndrome (TS); outcome data when these conditions coexist is sparse. We aimed to investigate long-term survival and causes of death in this population. METHODS: The Texas Birth Defects Registry was queried for all live born infants with HLHS during 1999-2007. We used Kaplan-Meier and Cox regression analyses to compare survival among patients with HLHS with TS (HLHS/TS+) to patients who had HLHS without genetic disorders or extracardiac birth defects (HLHS/TS-). RESULTS: Of the 542 patients with HLHS, 11 had TS (2.0%), 71 had other extracardiac birth defects or genetic disorders, and 463 had neither. The median follow-up time was 4.2 y (interquartile range [IQR] 2.1-6.5). Comparing those with HLHS/TS+ to HLHS/TS-, 100% versus 35% were female (P < .001), and median birth weight was 2140 g (IQR 1809-2650) versus 3196 g (IQR 2807-3540, P < .001). Neonatal mortality was 36% in HLHS/TS+ versus 27% in HLHS/TS- (log rank = 0.431). Ten of the 11 TS+ patients died during the study period for cumulative mortality of 91% versus 50% (hazard ratio (HR) for TS+: 2.90, 95% CI 1.53-5.48). Six patients died prior to surgery, 5 underwent Stage 1 palliation (S1P), 3 died after S1P, 2 survived past S2P, and one of these died at age 19 mo. The underlying cause of death was listed as congenital heart disease on all the death certificates of HLHS/TS+ patients. In multivariable analysis controlling for low birth weight (<2500 g), TS remained associated with significantly increased cumulative mortality, although females without TS had higher mortality than males (HR for TS+ versus males: 2.42, 95% CI 1.24-4.73; HR for TS- females versus males: 1.41, 95% CI 1.08-1.83). CONCLUSION: TS with HLHS is associated with significant mortality. The increased mortality in females without documented TS calls to question if TS is undetected in a portion of females with HLHS.

Intrauterine death in singleton pregnancies with trisomy 21, 18, 13 and monosomy X.

A retrospective study from November 2004 to May 2012, conducted at the Obstetric Clinic of Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HC-FMUSP), which included 92 singleton pregnancies with prenatal diagnosis of trisomy of chromosome 21 (T21), 18, 13 (T13/18) and monosomy X (45X), with diagnosis performed until the 26th week of pregnancy. The aim of the study was to describe the frequency and to investigate predictors of spontaneous fetal death (FD). Diagnosis (T21, n=36; T13/18, n=25; 45X, n=31) was made at a mean gestational age of 18.3±3.7 weeks, through chorionic villus biopsy (n=22,24%), amniocentesis (n=66, 72%) and cordocentesis (n=4, 4%). Major malformations were present in 45 (49%); with hydrops in 32 (35%) fetuses, more frequently in 45X [n=24/31, 77% vs. T21 (n=6/36, 17%) and T13/18 (n=2/25, 8%), p<0.001]. Specialized fetal echocardiography was performed in 60% (55/92). Of these, 60% (33/55) showed changes in heart morphology and/or function. Fetuses with T13/18 had a higher incidence of cardiac anomalies [60 vs. 25% (T21) and 29% (45X), p= 0.01]. FD occurred in 55 (60%) gestations, being more frequent in 45X [n=26/31, 84% vs. T21 (n=13/36, 36%) and T13/18 (n=16/25, 64%), p<0.01]. Stepwise analysis showed a correlation between hydrops and death in fetuses with T21 (LR= 4.29; 95CI=1.9-8.0, p<0.0001). In fetuses with 45X, the presence of echocardiographic abnormalities was associated with lower risk of FD (LR= 0.56; 95CI=0.27- 0.85, p=0.005). No predictive factors were identified in the T13/18 group. Intra- uterine lethality of aneuploid fetuses is high. Occurrence of hydrops increases risk of FD in pregnancies with T21. In pregnancies with 45X, the occurrence of echocardiographic changes reduces this risk.

Intrauterine death in singleton pregnancies with trisomy 21, 18, 13 and monosomy X / Óbito fetal em gestações únicas com diagnóstico de trissomias dos cromossomos 21, 18, 13 e monossomia do X

Summary A retrospective study from November 2004 to May 2012, conducted at the Obstetric Clinic of Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HC-FMUSP), which included 92 singleton pregnancies with prenatal diagnosis of trisomy of chromosome 21 (T21), 18, 13 (T13/18) and monosomy X (45X), with diagnosis performed until the 26th week of pregnancy. The aim of the study was to describe the frequency and to investigate predictors of spontaneous fetal death (FD). Diagnosis (T21, n=36; T13/18, n=25; 45X, n=31) was made at a mean gestational age of 18.3±3.7 weeks, through chorionic villus biopsy (n=22,24%), amniocentesis (n=66, 72%) and cordocentesis (n=4, 4%). Major malformations were present in 45 (49%); with hydrops in 32 (35%) fetuses, more frequently in 45X [n=24/31, 77% vs. T21 (n=6/36, 17%) and T13/18 (n=2/25, 8%), p<0.001]. Specialized fetal echocardiography was performed in 60% (55/92). Of these, 60% (33/55) showed changes in heart morphology and/or function. Fetuses with T13/18 had a higher incidence of cardiac anomalies [60 vs. 25% (T21) and 29% (45X), p= 0.01]. FD occurred in 55 (60%) gestations, being more frequent in 45X [n=26/31, 84% vs. T21 (n=13/36, 36%) and T13/18 (n=16/25, 64%), p<0.01]. Stepwise analysis showed a correlation between hydrops and death in fetuses with T21 (LR= 4.29; 95CI=1.9-8.0, p<0.0001). In fetuses with 45X, the presence of echocardiographic abnormalities was associated with lower risk of FD (LR= 0.56; 95CI=0.27- 0.85, p=0.005). No predictive factors were identified in the T13/18 group. Intra- uterine lethality of aneuploid fetuses is high. Occurrence of hydrops increases risk of FD in pregnancies with T21. In pregnancies with 45X, the occurrence of echocardiographic changes reduces this risk.

Resumo Estudo retrospectivo, de novembro de 2004 a maio de 2012, na Clínica Obstétrica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, incluindo 92 gestações únicas com diagnóstico pré-natal de trissomia dos cromossomos 21 (T21), 18, 13 (T13/18) e monossomia do X (45X), realizado até a 26a semana, com o objetivo de descrever a frequência e investigar preditores do óbito fetal espontâneo (OF). O diagnóstico (T21: n=36; T13/T18: n=25; 45X: n=31) foi realizado em idade gestacional média de 18,3±3,7 semanas, por biópsia de vilo corial (n=22; 24%), amniocentese (n=66; 72%) e cordocentese (n=4; 4%). Malformação major presente em 45 (49%) fetos e hidropisia em 32 (35%), mais frequente no grupo 45X [n=24/31, 77% vs. T21 (n=6/36, 17%) e T13/18 (n=2/25, 8%); p<0,001]. Ecocardiografia fetal especializada foi realizada em 60% (55/92). Destes, 60% (33/55) tinham alterações na morfologia e/ou na função cardíaca. Fetos com T13/18 apresentaram incidência maior de anomalias cardíacas [60 vs. 25% (T21) e 29% (45X); p=0,01]. Ocorrência de OF em 55 (60%) gestações e mais frequente no grupo 45X [n=26/31, 84% vs. T21 (n=13/36, 36%) e T13/18 (n=16/25, 64%); p<0,01]. Análise stepwise demonstrou associação entre hidropisia e óbito em fetos com T21 (LR=4,29; IC95%=1,9-8,0; p<0,0001). Em fetos com 45X, a presença de alterações ecocardiográficas esteve associada com menor risco de OF (LR=0,56; IC95%=0,27-0,85; p=0,005). Não foram identificados fatores preditores no grupo T13/18. A letalidade intrauterina de fetos aneuploides é elevada. A presença de hidropisia aumenta o risco de OF em gestações com T21. Em gestações com 45X, a ocorrência de alterações ecocardiográficas reduz esse risco.

[Cardiometabolic risk factors in Turner syndrome]. / Czynniki ryzyka sercowo-metabolicznego w zespole Turnera.

Congenital cardiovascular structural abnormalities, hypertension, low birth weight, increased prevalence of obesity, frequent glucose intolerance and dyslipidemia are risk factors of premature mortality for cardiovascular events in Turner syndrome (TS). The life expectancy in TS is reduced by at least 10 years and the risk of premature death is increased 3-fold compared to general female population. Hormonal therapy in TS, both estrogens in different algorithms and growth hormone in supraphysiological dose, may additionally modify these factors. In this review we summarize cardiometabolic markers potentially present in girls and women with TS.

Aortic dilatation and dissection in Turner syndrome: what we know, what we are unclear about and what we should do in clinical practice?

Aortic dilatation and aortic dissection are increasingly recognised in patients with Turner syndrome (TS). Risk factors for aortic dissection include aortic dilatation, bicuspid aortic valves, coarctation of aorta and pregnancy. The risk of death due to aortic dissection in pregnancy in TS is 2%, which is approximately 100 times higher than the general population, as maternal mortality is extremely low. Ongoing cardiovascular monitoring is recommended, although there remain several unanswered questions in relation to cardiovascular imaging especially the choice of modality for detection of vascular, valvular abnormalities and measurements of aortic dimensions. Due to the relative short stature of patients with TS, aortic dimensions need to be defined by aortic measurements adjusted for body surface area, known as aortic sized index (ASI). The relationship of ASI and other risk factors with aortic dissection is only beginning to be clarified. Clinical management and monitoring of such patients should be delivered by a group of clinicians familiar with the issues unique to TS patients in a multidisciplinary fashion. All clinicians including the non-specialists need to have a low threshold of suspecting aortic dissection in these adolescents and young adults. This up to date review, including a summary of all 122 published cases of TS patients with aortic dissection, aims to provide a summary of recent publications on characteristics of aortic dissection and aortic dilatation in TS to highlight gaps in knowledge and propose possible clinical monitoring pathway of cardiovascular health in children and adults with TS. Cardiovascular assessment and risk counselling is especially crucial during the period of transition of adolescents with TS, although life long monitoring by expert cognizant to the issues specific in TS is essential.

Long QT interval in Turner syndrome--a high prevalence of LQTS gene mutations.

OBJECTIVES: QT-interval prolongation of unknown aetiology is common in Turner syndrome. This study set out to explore the presence of known long QT mutations in Turner syndrome and to examine the corrected QT-interval (QTc) over time and relate the findings to the Turner syndrome phenotype. METHODS: Adult women with Turner syndrome (n = 88) were examined thrice and 68 age-matched healthy controls were examined once. QTc was measured by one blinded reader (intra-reader variability: 0.7%), and adjusted for influence of heart rate by Bazett's (bQTc) and Hodges's formula (hQTc). The prevalence of mutations in genes related to Long QT syndrome was determined in women with Turner syndrome and a QTc >432.0 milliseconds (ms). Echocardiographic assessment of aortic valve morphology, 24-hour blood pressures and blood samples were done. RESULTS: The mean hQTc in women with Turner syndrome (414.0 ± 25.5 ms) compared to controls (390.4 ± 17.8 ms) was prolonged (p<0.001) and did not change over time (416.9 ± 22.6 vs. 415.6 ± 25.5 ms; p =0.4). 45,X karyotype was associated with increased hQTc prolongation compared to other Turner syndrome karyotypes (418.2 ± 24.8 vs. 407.6 ± 25.5 ms; p = 0.055). In women with Turner syndrome and a bQTc >432 ms, 7 had mutations in major Long QT syndrome genes (SCN5A and KCNH2) and one in a minor Long QT syndrome gene (KCNE2). CONCLUSION: There is a high prevalence of mutations in the major LQTS genes in women with TS and prolonged QTc. It remains to be settled, whether these findings are related to the unexplained excess mortality in Turner women. CLINICAL TRIAL REGISTRATION: NCT00624949. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol/sid/S0001FLI/selectaction/View/ts/3/uid/U000099E.

Frequency and outcomes of cardiac operations and catheter interventions in Turner syndrome.

Cardiac malformations occur commonly in Turner syndrome (TS), but the outcomes of cardiac operations and catheter-based procedures are unknown. The Pediatric Cardiac Care Consortium database was queried for individuals with TS and other female subjects without genetic abnormalities or syndromes (non-TS [NTS]). Procedures for left-sided heart lesions represented most TS procedures (95.2%). Three hundred ninety-eight patients with TS who underwent 637 of these procedures of interest were compared with 25,913 female NTS subjects who underwent 56,625 procedures. The numbers of procedures per admission (1.47 vs 1.61, p = 0.01) and per patient (1.85 vs 2.16, p <0.0001) were significantly lower in patients with TS. Procedures for cyanotic heart disease other than hypoplastic left heart (HLH) were performed 4.5-fold less frequently in patients with TS. Patients with TS and NTS subjects had equivalent hospital lengths of stay, except for patients with TS who underwent hypoplastic aortic arch operations, patent ductus arteriosus ligation, pulmonary artery balloon dilation, balloon atrial septostomy, and catheter closure of atrial septal defects. There were 34 deaths among patients with TS and 1,795 among NTS subjects (8.6% vs 7.2%, p = 0.30). When HLH was excluded, mortality was lower in the TS group (3.9% vs 6.5%, p = 0.05). Operations for partial anomalous pulmonary venous connection (14.3% vs 1.9%, p = 0.03) and HLH (90.4% vs 70.5%, p = 0.08) were more likely to result in death in patients with TS. In conclusion, given generally comparable lengths of stay and numbers of procedures as well as uniformly excellent results, these data suggest that the diagnosis of TS does not increase the utilization of limited health care resources. Operations for HLH and partial anomalous pulmonary vein connection carry additional risk for those with TS. These results will permit risk stratification, prognostication, and counseling of individuals with TS and their families.

Socioeconomic parameters and mortality in Turner syndrome.

BACKGROUND: Turner syndrome (TS) is characterized by hypogonadism, short adult height, increased morbidity and mortality, contrasted by self-reported normal quality of life and perception of health. Small studies have indicated a similar level of education compared with the background population. AIM: To study the socioeconomic profile in TS and the impact of these factors on mortality. MATERIALS AND METHODS: Register study using Danish nationwide registries. Nine hundred and seventy-nine TS females and 94,850 controls were included. Information concerning cohabitation, motherhoods, level of education (bachelor degree), income, retirement, and death were obtained. One hundred and three TS and 5989 controls died during the study period. For the socioeconomic parameters, median age at first relevant episode was calculated. Income was analyzed using conditional logistic regression and the other parameters using Cox regression. RESULTS: In comparison with controls, TS had significantly fewer partnerships (hazard ratio (HR): 0.45), fewer motherhoods (HR: 0.18), and retired earlier (HR: 1.8). After the diagnosis of TS, the risk of retiring was increased. Educational attainment (HR: 1.0) as well as risk of unemployment was similar. Before the age of 30, low income was significantly more frequent; hereafter, it was similar to controls. Mortality was significantly increased (HR: 2.9) and slightly lower after adjustment for cohabitation and education (HR: 2.7). CONCLUSIONS: A divergent socioeconomic profile is apparent, with a reduced proportion of TS persons finding a partner and becoming mothers. The educational level was similar to controls. The increased mortality in TS was not materially affected after adjustment for cohabitation and education.

Increased maternal cardiovascular mortality associated with pregnancy in women with Turner syndrome.

In women with Turner syndrome, the risk of death from aortic dissection or rupture during pregnancy may be 2%, and this risk persists during the postpartum period owing to pregnancy-related aortic changes. Turner syndrome is a relative contraindication for pregnancy; however, it is an absolute contraindication for pregnancy in a patient with a documented cardiac anomaly. This document replaces the 2008 document of the same name.