New Clinical Guidelines for Turner Syndrome

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An international, multidisciplinary panel of experts met in April 2006 for 3 days to discuss key issues in the evaluation and treatment of patients with Turner syndrome (TS). The conference, supported by the National Institute of Child Health and Human Development (NICHD) and unrestricted educational grants from multiple pharmaceutical companies, culminated in consensus guidelines that drew upon peer-reviewed published information and expert judgment. These guidelines reflect new developments since the last set of guidelines¹ which were published in 2001. I strongly encourage readers to review the paper itself, as what follows here only covers highlights due to space limitations.

The guidelines were divided thematically, as follows.
1. Diagnostic issues
Increased genetic testing, in terms of both populations and finer methodologies, have led to the recognition of greater variability, both phenotypically and genotypically. This has impacted several arenas. First, the diagnosis of TS has been sharpened to require fulfillment of 3 criteria: (1) female phenotype, (2) characteristic physical features, and (3) complete or partial absence of the second sex chromosome, ± mosaicism. Thus, the diagnosis excludes: (1) phenotypic males regardless of karyotype, (2) women with 45,X cell lines but no clinical features, and (3) women with small Xp deletions that do not include band Xp22.3 (SHOX-related skeletal abnormalities without ovarian failure) and Xq deletions distal to Xq24 (isolated premature ovarian failure). Second, the broader clinical spectrum of patients diagnosed incidentally through prenatal chromosome analyses versus those diagnosed clinically has changed the prognostic counseling that should be offered to families. Third, although a standard 30-cell karyotype is still the gold-standard diagnostic test (it identifies at least 10% mosaicism with 95% confidence), newer more sensitive assays raise the question of how hard should we seek Y chromosome material, vis-à-vis gonadoblastoma risk? Finally, pros and cons for potential newborn screening programs are discussed.

2. Cardiovascular system
Magnetic resonance angiographic screening studies have similarly increased the visibility of cardiovascular anomalies. Magnetic resonance imaging (MRI) can detect cases of aortic coarctation that have been missed by echocardiography; this has led to the appreciation of the high frequency of vascular anomalies in asymptomatic patients with TS. Likewise, electrocardiography in adult patients has revealed a high prevalence of conduction and repolarization abnormalities. Thus, the new guidelines stress an augmented cardiovascular surveillance program with more comprehensive monitoring throughout the lifespan and more aggressive treatment of hypertension, with the aim of better preventing aortic dilation, dissection, or rupture. Aortic dilation/dissection risks are further increased by pregnancy and very strenuous or isometric exercises that increase pulse and blood pressure.

3. General medical care
A multidisciplinary treatment approach is encouraged for both the pediatric and adult patient populations, with careful transitioning. Highlights from the management of pediatric patients include: (1) shifts in the treatment of lymphedema, (2) more aggressive surveillance and treatment of ear and hearing problems, (3) younger initiation of treatment with growth hormone, as soon as height percentiles decrease from the normal curve and (4) enhanced estrogen replacement, with estrogen no longer withheld in order to prolong time for statural growth since a fuller spectrum of pharmacologic options are available. Regarding adult patients, more comprehensive surveillance is outlined, with particular attention to the cardiovascular system, hearing, bone mineralization, obesity, insulin resistance, and hyperlipidemia. Reproductive and gynecologic issues were also highlighted. While past reviews of TS asked, “Can these women ever have children?,” the current guidelines start from the observation that assisted reproductive techniques may allow women with TS to become pregnant as easily as women with other causes of infertility. Thus, the focus shifts to the various reproductive options as well as the maternal complications of pregnancy and delivery.

4. Psychological and educational issues
Most patients with TS generally have normal intelligence, behavioral function, and self-perceived physical/mental health. However, more subtle difficulties have been recognized. These include selective impairments in nonverbal skills, slowed response times, increased rates of attention deficit disorder, increased risk for social isolation, immaturity, depression, and anxiety. Shyness, social anxiety, and reduced self-esteem generally relate to the premature ovarian failure and fertility issues. The new guidelines recommend timely, comprehensive psycho-educational evaluations and re-evaluations as needed, age-appropriate pubertal induction and social interactions, and career and vocational planning.

Bondy CA, Turner Syndrme Study Group. Care of girls and women with Turner syndrome: A guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab. 2007;92:10-25.

Editor’s Comment

Enhanced sensitivity to the broader clinical spectra and increased surveillance for the problems associated with TS will allow better clinical care of these patients. Several hurdles persist: rigorous, outcome-based studies of various management issues are still needed to support recommendations; providing cohesive, multidisciplinary care remains far more challenging in reality than in theory; because growth failure is the key to diagnosis of TS in childhood,² as a group, these girls are particularly vulnerable to the gender-related biases in seeking endocrine care.³ Thus, delayed diagnosis remains a problem.²

Adda Grimberg , MD

References - (linked to )

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Last Updated: 04/30/2008