Clinical practice guidelines for the care of girls and women with Turner syndrome

Abstract

Turner syndrome (TS) affects 50 per 100 000 females. TS affects multiple organs through all stages of life, necessitating multidisciplinary care. This guideline extends previous ones and includes important new advances, within diagnostics and genetics, estrogen treatment, fertility, co-morbidities, and neurocognition and neuropsychology. Exploratory meetings were held in 2021 in Europe and United States culminating with a consensus meeting in Aarhus, Denmark in June 2023. Prior to this, eight groups addressed important areas in TS care: (1) diagnosis and genetics, (2) growth, (3) puberty and estrogen treatment, (4) cardiovascular health, (5) transition, (6) fertility assessment, monitoring, and counselling, (7) health surveillance for comorbidities throughout the lifespan, and (8) neurocognition and its implications for mental health and well-being. Each group produced proposals for the present guidelines, which were meticulously discussed by the entire group. Four pertinent questions were submitted for formal GRADE (Grading of Recommendations, Assessment, Development and Evaluation) evaluation with systematic review of the literature. The guidelines project was initiated by the European Society for Endocrinology and the Pediatric Endocrine Society, in collaboration with members from the European Society for Pediatric Endocrinology, the European Society of Human Reproduction and Embryology, the European Reference Network on Rare Endocrine Conditions, the Society for Endocrinology, and the European Society of Cardiology, Japanese Society for Pediatric Endocrinology, Australia and New Zealand Society for Pediatric Endocrinology and Diabetes, Latin American Society for Pediatric Endocrinology, Arab Society for Pediatric Endocrinology and Diabetes, and the Asia Pacific Pediatric Endocrine Society. Advocacy groups appointed representatives for pre-meeting discussions and the consensus meeting.

Keywords: Turner syndrome; cardiovascular health; co-morbidity; hypogonadism; infertility; neurocognition; transition.

Figure 1.

Summary of the issues discussed and questions raised in relation to puberty and HRT.

Figure 2.

Suggested workflow for cardiovascular follow-up from gestation to transition. TTE, transthoracic echocardiogram; BAV, bicuspid aortic valve; CoA, aortic coarctation; PAPVR, partial anomalous pulmonary venous return; HLHS, hypoplastic left heart syndrome; ECG, electrocardiogram; BP, blood pressure; CMR, cardiovascular magnetic resonance; CT, computed tomography. (A) Consider earlier visit if clinical concern for symptoms, murmur, or other abnormal cardiovascular exam finding. If neonatal images were reviewed by a cardiologist, clinically significant congenital lesions were ruled out, and there are no signs or symptoms concerning CHD, it is reasonable to defer cardiovascular follow up until age 9-11. (B) Cardiologist may order additional imaging before or with visit if neonatal TTE inconclusive for valve morphology, coronary anatomy, or pulmonary venous anomaly. (C) Consider 24-h ambulatory blood pressure measurement (ABPM) if available.

Figure 3.

Indications to consider cardiology consultation. CV, cardiovascular; TTE, transthoracic echocardiogram; CMR, cardiovascular magnetic resonance; CT, computed tomography; CHD, congenital heart disease; QTc, corrected QT interval; ms, milliseconds. (A) If neonatal images were reviewed by a cardiologist, clinically significant congenital lesions were ruled out, and there are no signs or symptoms concerning CHD, it is reasonable to defer cardiovascular follow up until age 9-11. (B) In these situations, recommendations for cardiology surveillance and follow up may be more frequent and will depend on the type and severity of the lesion. (C) Before pregnancy or fertility treatments, the most recent cardiovascular imaging should not be older than 2 years and should not be overdue based on the cardiologist's last set of recommendations. CT or MRI is advised for the most thorough assessment.

Figure 4.

Suggested algorithm for the frequency of aortic surveillance of children and adolescents with TS, based on the perceived severity of aortic dilation and additional risk factors for aortic dissection. BAV, bicuspid aortic valve; HTN, hypertension; CoA, aortic coarctation; Z, Z-score. Frequency of surveillance may be affected by additional risk factors such as rapid aortic dilation. Aortic surveillance refers to measurement of aorta using TTE, cardiovascular magnetic resonance, or CT by a cardiovascular specialist.

Figure 5.

Suggested algorithm for the frequency of aortic surveillance of adults with TS based on the perceived severity of aortic dilation and additional risk factors for aortic dissection. BAV, bicuspid aortic valve; HTN, hypertension; CoA, aortic coarctation; ASI, aortic size index; AHI, aortic height index; Z, Z-score. Frequency of surveillance may be affected by additional risk factors such as rapid aortic dilation. If ASI >2.5 cm m⁻² (corresponding to AHI >25 mm m⁻¹ or Z > 4) or ASI >2.3 cm m⁻² (corresponding to AHI >23 mm m⁻¹ or Z > 3.5) with additional risk factors (see text), consider evaluation for elective aortic repair. Aortic surveillance refers to measurement of aorta using TTE, cardiovascular magnetic resonance, or CT by a cardiovascular specialist.

Figure 6.

Algorithm for management of hypertension in TS. BP, blood pressure; LVH, evidence of left ventricular hypertrophy on ECG or echocardiogram; ABPM, ambulatory blood pressure monitoring; HBPM, home blood pressure monitoring; SBP, systolic blood pressure; DBP, diastolic blood pressure; BAV, bicuspid aortic valve; TAV, tricuspid aortic valve; AHI, aortic height index (mm m⁻¹); ASI, aortic size index (cm m⁻²); ARB, angiotensin receptor blocker; ACEi, angiotensin converting enzyme inhibitor; CCB, dihydropyridine calcium channel blocker; Aortic disease, aortic dilation or dissection. *For children, diagnosis of hypertension is dependent on normative values based on age, sex, and height that may vary between regional guidelines.^,

Figure 7.

Proposed TS transition timeline (adapted from White 2018).

Figure 8.

Comprehensive neuropsychological evaluation (see also Table 18).