Clinical Significance of the Parental Origin of the X Chromosome in Turner Syndrome

825

1,259

Turner syndrome affects 25-50 per 100,000 females and can involve multiple organs through all stages of life, necessitating multidisciplinary approach to care. Previous guidelines have highlighted this, but numerous important advances have been noted recently. These advances cover all specialty fields involved in the care of girls and women with TS. This paper is based on an international effort that started with exploratory meetings in 2014 in both Europe and the USA, and culminated with a Consensus Meeting held in Cincinnati, Ohio, USA in July 2016. Prior to this meeting, five groups each addressed important areas in TS care: 1) diagnostic and genetic issues, 2) growth and development during childhood and adolescence, 3) congenital and acquired cardiovascular disease, 4) transition and adult care, and 5) other comorbidities and neurocognitive issues. These groups produced proposals for the present guidelines. Additionally, four pertinent questions were submitted for formal GRADE (Grading of Recommendations, Assessment, Development and Evaluation) evaluation with a separate systematic review of the literature. These four questions related to the efficacy and most optimal treatment of short stature, infertility, hypertension, and hormonal replacement therapy. The guidelines project was initiated by the European Society of Endocrinology and the Pediatric Endocrine Society, in collaboration with the European Society for Paediatric Endocrinology, the Endocrine Society, the European Society of Human Reproduction and Embryology, the American Heart Association, the Society for Endocrinology, and the European Society of Cardiology. The guideline has been formally endorsed by the European Society of Endocrinology, the Pediatric Endocrine Society, the European Society for Paediatric Endocrinology, the European Society of Human Reproduction and Embryology and Summary of recommendationsThe recommendations (R) are worded as recommend (strong recommendation) and suggest (weak recommendation). We formally graded only the evidence underlying recommendations for therapeutic choices. The quality of evidence behind the recommendations is classified as very low (⨁◯◯◯), low (⨁⨁◯◯), moderate (⨁⨁⨁◯) and strong (⨁⨁⨁⨁). See further section 'Summary of methods used for guideline development'. Diagnosis and geneticsR 1.1. We recommend considering a diagnosis of TS in phenotypic females with a karyotype containing one X chromosome and complete or partial absence of the second sex chromosome, associated with one or more typical clinical manifestations of TS (⨁⨁⨁⨁). R 1.2. We recommend against considering a diagnosis of TS in females with one X chromosome and a deletion distal to Xq24 on the other X chromosome, and in women over the age of 50 years with less than 5% 45,X mosaicism (⨁⨁◯◯). R 1.3. We suggest that the new general surveillance management guideline applies to TS patients with any karyotype (⨁⨁◯◯). R 1.4. We recommend to consider testing for Turner syndrome (TS) in a female with typical signs (Table 2) (⨁⨁⨁⨁). R 1.5. We ...

Section: 112mentioning

confidence: 99%

Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting

Gravholt¹,

Andersen

Conway

et al. 2017

825

1,259

“…During the last decade many studies showed growth hormone (GH) treatment as safe and effective for growth promotion in TS. Table 2 presents the results of growth therapy and indicates positive, negative and neutral determinants of therapy effectiveness as well as consequences and side effects of hormonal therapy in the analysed articles (4,5,7,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50).…”

Section: Growth and Growth Therapy And Consequencesmentioning

confidence: 99%

“…The complete or partial absence of one of the two X chromosomes in a phenotypic female is usually accompanied by short stature, gonadal dysgenesis, lymphedema, and characteristic dysmorphic appearance in the severe phenotype, though it has a minimal impact on stature or secondary amenorrhea in the mild phenotype (2). Monosomy 45,X is prevalent, and the X-chromosome is of maternal origin in w70% of TS patients (3,4,5). Structural abnormalities of the sex chromosome can include deletions of the short arm and duplication of the long arm to form isochromosome (isoXq) and undergo ring formation (rX) and deletion in the short or long arm (Xp-, Xq-respectively).…”

Section: Introductionmentioning

confidence: 99%

“…However, patients with monosomy X tend to have the most severe phenotype. The results of studies assessing the impact of X origin (maternal/paternal) on TS phenotype are inconclusive (4,6,7,8). The isoX anomaly is often associated with autoimmunity, whilst the ring X karyotype is also associated with psychological and learning difficulties (9,10,11).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

TRANSITION IN ENDOCRINOLOGY: Treatment of Turner's syndrome during transition

Gawlik

Małecka-Tendera

2014

Self Cite

Transition in health care for young patients with Turner's syndrome (TS) should be perceived as a staged but uninterrupted process starting in adolescence and moving into adulthood. As a condition associated with high risk of short stature, cardiovascular diseases, ovarian failure, hearing loss and hypothyroidism, TS requires the attention of a multidisciplinary team. In this review paper, we systematically searched the relevant literature from the last decade to discuss the array of problems faced by TS patients and to outline their optimal management during the time of transfer to adult service. The literature search identified 233 potentially relevant articles of which 114 were analysed. The analysis confirmed that all medical problems present during childhood should also be followed in adult life. Additionally, screening for hypertension, diabetes mellitus, dyslipidaemia, and osteoporosis is needed. After discharge from the paediatric clinic, there is still a long way to go.

“…It is characterized by growth retardation, with short adult stature and gonadal dysgenesis. It may be associated with a large number of diseases and conditions: physical abnormalities, congenital cardiac/renal malformations, and acquired conditions that may occur at any time in the patient's life (1,2,3,4,5,6,7,8). Its genetic basis is highly variable, with diverse causal gene defects.…”

Section: Introductionmentioning

confidence: 99%

X-chromosome gene dosage as a determinant of impaired pre and postnatal growth and adult height in Turner syndrome

Fiot

Zénaty

Boizeau

et al. 2016

Objective: Short stature is a key aspect of the phenotype of patients with Turner syndrome (TS). SHOX haploinsufficiency is responsible for about two-thirds of the height deficit. The aim was to investigate the effect of X-chromosome gene dosage on anthropometric parameters at birth, spontaneous height, and adult height (AH) after growth hormone (GH) treatment. Design: We conducted a national observational multicenter study. Methods: Birth parameter SDS for gestational age, height, and AH before and after GH treatment respectively, and height deficit with respect to target height (SDS) were classified by karyotype subgroup in a cohort of 1501 patients with TS: 45,X (36%), isoXq (19%), 45,X/46,XX (15%), XrX (7%), presence of Y (6%), or other karyotypes (17%). Results: Birth weight, length (P!0.0001), and head circumference (P!0.001), height and height deficit with respect to target height (SDS) before GH treatment, at a median age of 8.8 (5.3-11.8) years and after adjustment for age and correction for multiple testing (P!0.0001), and AH deficit with respect to target height at a median age of 19.3 (18.0-21.8) years and with additional adjustment for dose and duration of GH treatment (PZ0.006), were significantly associated with karyotype subgroup. Growth retardation tended to be more severe in patients with XrX, isoXq, and, to a lesser extent, 45,X karyotypes than in patients with 45,X/46,XX karyotypes or a Y chromosome. Conclusion: These data suggest that haploinsufficiency for an unknown Xp gene increases the risk of fetal and postnatal growth deficit and short AH with respect to target height after GH therapy.