European academy of andrology guidelines on Klinefelter Syndrome Endorsing Organization: European Society of Endocrinology

Michael Zitzmann; Lise Aksglaede; Giovanni Corona; Andrea M Isidori; Anders Juul; Guy T'Sjoen; Sabine Kliesch; Kathleen D'Hauwers; Jorma Toppari; Jolanta Słowikowska-Hilczer; Frank Tüttelmann; Alberto Ferlin

doi:10.1111/andr.12909

Clinical Guidelines and Standards Guidelines by Clinical Area

European academy of andrology guidelines on Klinefelter Syndrome Endorsing Organization: European Society of Endocrinology

Zitzmann M, Aksglaede L, Corona G, Isidori AM, Juul A, T'Sjoen G, Kliesch S, D'Hauwers K, Toppari J, Słowikowska-Hilczer J, Tüttelmann F, Ferlin A

Published January 2021 Andrology

DOI 10.1111/andr.12909 PMID 32959490

RRM Academy Synopsis

Klinefelter syndrome guidelines set care from childhood to adulthood

The first European Academy of Andrology guidelines on Klinefelter syndrome lay out care for boys and men from childhood to adulthood. An appointed expert panel wrote them. Most patients are diagnosed in adulthood, although symptoms can appear in infancy, childhood or adolescence.

Key Findings

The European Academy of Andrology appointed academic experts, who wrote a consensus guideline for Klinefelter syndrome with GRADE (Grading of Recommendations, Assessment, Development and Evaluation).
Men with Klinefelter syndrome commonly have very little sperm production and weak testosterone-making cells. The result is azoospermia (no sperm in the semen) and hypergonadotropic hypogonadism.
Patients show a higher prevalence of heart, metabolic and bone conditions, which might explain higher illness and death rates. Dental, clotting and autoimmune disorders are likely more common than in other men.
Genetic and epigenetic effects of the extra X chromosome, along with testosterone deficiency, contribute to these health patterns.
Most patients are diagnosed as adults, yet symptoms can already appear in infancy, childhood or adolescence. The authors say younger patients need specific attention to development and fertility.

Interpretation

This synopsis draws on the published abstract only. The guidelines are a consensus document from experts the academy appointed, covering patients from childhood to adulthood. They rest on recent research and expert checks. The authors say features vary widely between patients, and too few cases are found for how common the condition is.

RRM Context

Klinefelter syndrome commonly lowers sperm production and testosterone, so it is a male factor in infertility. Restorative reproductive medicine looks for causes in both partners from the start. The guideline also addresses heart, metabolic and bone conditions, plus effects on thinking and social life. Early diagnosis gives families more time to plan for growth and fertility.

Our editorial summary of this paper, not the article's abstract.

Abstract

Background

Knowledge about Klinefelter syndrome (KS) has increased substantially since its first description almost 80 years ago. A variety of treatment options concerning the spectrum of symptoms associated with KS exists, also regarding aspects beyond testicular dysfunction. Nevertheless, the diagnostic rate is still low in relation to prevalence and no international guidelines are available for KS.

Objective

To create the first European Academy of Andrology (EAA) guidelines on KS.

Methods

An expert group of academicians appointed by the EAA generated a consensus guideline according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system.

Results

Clinical features are highly variable among patients with KS, although common characteristics are severely attenuated spermatogenesis and Leydig cell impairment, resulting in azoospermia and hypergonadotropic hypogonadism. In addition, various manifestations of neurocognitive and psychosocial phenotypes have been described as well as an increased prevalence of adverse cardiovascular, metabolic and bone-related conditions which might explain the increased morbidity/mortality in KS. Moreover, compared to the general male population, a higher prevalence of dental, coagulation and autoimmune disorders is likely to exist in patients with KS. Both genetic and epigenetic effects due to the supernumerary X chromosome as well as testosterone deficiency contribute to this pathological pattern. The majority of patients with KS is diagnosed during adulthood, but symptoms can already become obvious during infancy, childhood or adolescence. The paediatric and juvenile patients with KS require specific attention regarding their development and fertility.

Conclusion

These guidelines provide recommendations and suggestions to care for patients with KS in various developmental stages ranging from childhood and adolescence to adulthood. This advice is based on recent research data and respective evaluations as well as validations performed by a group of experts.

Topics

Clinical Guidelines and Standards › Guidelines by Clinical Area › Fertility and Infertility Guidelines · Male Fertility › Male Endocrine and Genetic Factors › Genetic Causes of Male Infertility · Genetics and Immunology › Reproductive Genetics › Chromosomal Abnormalities

Michael Zitzmann, Lise Aksglaede, Giovanni Corona, Andrea M Isidori, Anders Juul, Guy T'Sjoen, Sabine Kliesch, Kathleen D'Hauwers, Jorma Toppari, Jolanta Słowikowska-Hilczer, Frank Tüttelmann, Alberto Ferlin

Mike Zitzmann, M Zitzmann, L Aksglaede, G Corona, A Isidori, A Juul, G T'Sjoen, S Kliesch, K D'Hauwers, J Toppari, J Słowikowska-Hilczer, F Tüttelmann, A Ferlin

PMID 32959490 32959490 DOI 10.1111/andr.12909 10.1111/andr.12909 Zitzmann et al. 2021, Zitzmann 2021

European academy of andrology guidelines on Klinefelter Syndrome Endorsing Organization: European Society of Endocrinology

Klinefelter syndrome guidelines set care from childhood to adulthood

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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