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Objectives: This study aimed to investigate the triglyceride-glucose (TyG) index, which is a simple surrogate marker of insulin resistance that is associated with various cardiometabolic diseases, in patients with Klinefelter syndrome (KS). Subjects and methods: A total of 30 patients with KS (mean age: 21.53 ± 1.66 years) and 32 healthy controls (mean age: 22.07 ± 1.01 years) were included in the study.The clinical and laboratory parameters,TyG index, asymmetric dimethylarginine (ADMA) level, homeostatic model assessment of insulin resistance (HOMA-IR) score, and high-sensitivity C-reactive protein level were measured in patients with KS and healthy subjects. Results: Patients with KS had higher HOMA-IR score (p = 0.043), ADMA levels (p < 0.001), and TyG index (p = 0.031) and lower high-density lipoprotein cholesterol levels (p < 0.001) than healthy subjects. TyG index was positively correlated with plasma ADMA (r = 0.48, p < 0.001) and HOMA-IR (r = 0.36, p = 0.011). Multivariate analyses showed that total testosterone level (β = −0.44, p = 0.001) and TyG index (β = 0.29, p = 0.045) were independent determinants of plasma ADMA levels. Conclusion: Patients with KS had higher TyG indices than healthy subjects. Moreover, TyG index was independently associated with endothelial dysfunction in patients. TyG index may be a practical and useful measure to show the increased endothelial dysfunction in patients with KS.

Klinefelter syndrome is a sex chromosomal aneuploidies with at least one extra X chromosome than normal male karyotype. The classic form of the 47 / XXY karyotype, the incidence of this syndrome is one in 500-1000 live male births. The incidence of 48 / XXYY male individuals with many phenotypic features of Klinefelter syndrome is extremely rare and occurs in 1: 18000 -1: 100.000 men. However, they differ from Klinefelter syndrome with serious behavioral problems, mental reterdation and susceptibility to psychiatric diseases [1 ]. A 38-year-old man, referred to our Medical Biology and Genetics laboratory for karyotype analysis with primary infertility. He had undergone varicocele surgery and had high levels of FSH, low levels of testosterone and high levels of LH. Semen analysis demonstrated azoospermia In the psychiatric examination of the patient, whose IQ level was 90, language, learning and behavior disorder were diagnosed. The patient with deep vein thrombosis was recommended angiography because of right heart failure. Karyotype analysis revealed with 48,XXYY. This rare case shows the importance of karyotype analysis in diagnosis. In this study, the clinical and laboratory findings of the case are presented with the literature.

Background Supernumerary sex chromosome aneuploidies (SCA) are common genetic conditions characterized by additional X or Y chromosome, affecting ~1/500 individuals, with the most frequent karyotypes of 47,XXY (Klinefelter syndrome), 47,XXX (Trisomy X), and 47,XYY (Jacob syndrome). Although there is considerable phenotypic variation among these diagnoses, these conditions are characterized by the presence of overlapping physical, medical, developmental, and psychological features. Our interdisciplinary clinic’s experience anecdotally supports previous published findings of atopic conditions, feeding difficulties, and gastroesophageal reflux to be more prevalent in SCAs (Bardsley et al., Journal of Pediatrics, 2013, 163, 1085; Samango‐Sprouse et al., The Application of Clinical Genetics, 2019, 12, 191; Tartaglia et al., Acta Paediatrica, 2008, 100, 851). Furthermore, we observed that many of these patients have also been diagnosed with eosinophilic esophagitis (EoE), an association not currently reported in the literature. Methods We conducted a retrospective chart review of all 667 patients with SCA seen at a large tertiary care center to investigate the prevalence and presenting features of EoE. Results Four percent of children with SCAs had a biopsy‐confirmed diagnosis of EoE, which represents an odds ratio of 32 (95% CI 6–185) when compared to the prevalence rates reported in the general population. Conclusion Routine screening for EoE symptoms may be warranted for individuals with SCA and atopic conditions., Sex chromosome aneuploidies (SCA) are common genetic conditions that may be associated with atopic conditions, including eosinophilic esophagitis (EoE). Confirmed EoE was found in 29/650 (4.5%) of youth with SCA, 32 (95% CI 6–185) greater risk than the general pediatric population. Patients with SCA are at risk and should be screened for EoE with age‐appropriate symptoms on a routine basis, as earlier diagnosis and treatment may minimize the severity of disease.

Klinefelter syndrome (KS), also known as 47, XXY, shows increased mortality when compared with mortality rates among the general population. Cardiovascular, hemostatic, metabolic diseases are implicated. Moreover, cardiac congenital anomalies in KS can contribute to the increase in mortality.In this study, we have systematically reviewed the relationships between KS and the cardiovascular system and the management of cardiovascular complication. In summary, patients with KS display increased cardiovascular risk profile, characterized by increased prevalence of metabolic alterations including dyslipidemia, diabetes mellitus (DM), and abnormalities in biomarkers of cardiovascular disease. KS subjects are characterized by subclinical abnormalities in endothelial function and in left ventricular (LV) systolic and diastolic function, which - when associated with chronotropic incompetence - may negatively influence cardiopulmonary performance. Moreover, KS patients appear to be at a higher risk for cardiovascular disease, due to thromboembolic events with high prevalence of recurrent venous ulcers, venous insufficiency, recurrent venous and arterial thromboembolism leading to deep venous thrombosis or pulmonary embolism.Considering the unequivocal finding of increased mortality of KS patients, we suggest a periodic cardiovascular follow up in specialized centers with multidisciplinary care teams that comprise endocrinologists and cardiologists dedicated to KS syndrome.

Background Idiopathic central precocious puberty (ICPP) is supposed to be non-existent in a context of testicular destruction that is typically present in Klinefelter syndrome (KS). Herein, we describe a rare case of ICPP in a Klinefelter patient (47,XXY) with 2 maternal X chromosomes. Moreover, we highlight the differences in gonadotropin levels in comparison to males with ICPP and a normal karyotype. Case presentation An 8 years old boy with a history of cryptorchidism was evaluated for precocious puberty (Tanner staging: P2/G3). Both testes measured 25x35mm. His hormonal profile confirmed a central origin of precocious puberty with high serum testosterone (4.3 ng/ml), luteinizing hormone [LH (3.5 UI/l)] and follicle stimulating hormone [FSH (7.7 UI/l)] levels. Luteinizing hormone-releasing hormone (LHRH) test amplified LH and FSH secretion to 24 and 14 UI/l respectively. Brain magnetic resonance imaging (MRI) was normal. No MKRN3 mutation was detected. He was treated for ICPP for two years. During puberty, he suffered from hypergonadotropic hypogonadism leading to the diagnosis of KS (47,XXY karyotype). Chromosomal analysis by fluorescent multiplex polymerase chain reaction (PCR) using X chromosome microsatellite markers identified 2 maternal X chromosomes. Analysing 8 cases of KS developing ICPP (our reported case and 7 other published cases) revealed that these KS patients with ICPP have higher LH and FSH levels during ICPP episode than in ICPP patients with a normal karyotype (ICPP with KS vs ICPP with a normal karyotype: LH levels 9.4 ± 12 vs 1.1 ± 0.6 UI/l; FSH levels 23.1 ± 38.5 vs 2.7 ± 1.5 UI/l). Furthermore, their response to gonadotropin-releasing hormone (GnRH) stimulation is characterized by excessive LH and FSH secretion (LH levels post-GnRH: 58 ± 48 vs 15.5 ± 0.8 UI/l; FSH levels post-GnRH: 49.1 ± 62.1 vs 5.7 ± 3.9 UI/l). Conclusions ICPP in boys is extremely rare. The pathophysiology of ICPP in KS is unknown. However, maternal X supplementary chromosome and early testicular destruction may play a significant role in the initiation of ICPP, in part explaining the relative “overrepresentation of ICPP in KS. Thus, karyotype analysis could be considered for boys suffering from ICPP, especially if testicular size is smaller or gonadotropins are significantly elevated.

Background The purpose of this study is to evaluate the prognostic factors for sperm retrieval and determine if Y chromosome deletion is associated with deleterious effects on spermatogenesis in non-mosaic Klinefelter patients. Whether Y chromosome deletion determines the sperm retrieval rate in non-mosaic Klinefelter patients has not yet been addressed. Methods We retrospectively collected medical records of azoospermic patients from Sep 2009 to Dec 2018, and enrolled 66 non-mosaic 47, XXY patients who were receiving mTESE. The predictive values of patients age, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, prolactin, estradiol and Y chromosome deletion were assessed for successful sperm recovery. Results Testicular sperm recovery was successful in 24 (36.4%) of 66 men. The mean age (36.0 vs. 36.6 years), and levels of FSH (30.0 vs 36.9 IU/L), LH (17.7 vs 21.9 IU/L), testosterone (2.4 vs. 2.1 ng/ml), prolactin (9.1 vs. 8.8 ng/ml), and estradiol (19.4 vs. 22.3 pg/ml) did not show any significant difference when comparing patients with and without successful sperm retrieval. Partial deletion of azoospermic factor c (AZFc) was noted in 5 (20.8%) of 24 patients with successful sperm retrieval, including three b2/b3 and two gr/gr deletion cases, whereas 4 (9.5%) of 42 patients with unsuccessful sperm retrieval were noted to have AZFc partial deletion (one b2/b3, one sY1206 and two gr/gr deletion), though the difference was not statistically significant (p = 0.27). Conclusion According to present results, age and AZFc partial deletion status should not be a deterrent for azoospermic males with non-mosaic Klinefelter syndrome to undergo mTESE.

In about one-half of adult Klinefelter syndrome (KS) patients, spermatozoa can be retrieved by means of testicular biopsy (TESE). Given the expected increase in the number of diagnosed KS patients owing to the use of noninvasive prenatal testing, the probable questions of young KS patients and their parents regarding future fertility, and the fact that widespread apoptosis of spermatogonia occurs at onset of puberty, an attempt to increase the retrieval rates at TESE above those found in adult KS men by undertaking preservation techniques peripubertally has been initiated. To date, however, only a limited number of KS adolescents have been examined, demonstrating no increases in the chances of finding sperm. Furthermore, spermatogonial stem cell and testicular tissue freezing techniques, as well as in vitro maturation strategies, require further validation. Given these controversies, banking testicular tissue from prepubertal KS boys should be performed only in a research framework.

Historically, it was thought that the number of X chromosomes plays little role in causing sex differences in traits. Recently, selected mouse models have been used increasingly to compare mice with the same type of gonad but with one versus two copies of the X chromosome. Study of these models demonstrates that mice with one X chromosome can be strikingly different from those with two X chromosomes, when the differences are not attributable to confounding group differences in gonadal hormones. The number of X chromosomes affects adiposity and metabolic disease, cardiovascular ischaemia/reperfusion injury and behaviour. The effects of X chromosome number are likely the result of inherent differences in expression of X genes that escape inactivation, and are therefore expressed from both X chromosomes in XX mice, resulting in a higher level of expression when two X chromosomes are present. The effects of X chromosome number contribute to sex differences in disease phenotypes, and may explain some features of X chromosome aneuploidies such as in Turner and Klinefelter syndromes.

La préservation de la fertilité chez l'homme reçoit une attention croissante dans le domaine de la médecine de la reproduction. Les premiers programmes cliniques ont été créés pour préserver le potentiel de reproduction chez les hommes ayant besoin d'un traitement gonadotoxique. La cryoconservation du sperme est maintenant une procédure standard. Depuis quelques années, plusieurs centres offrent la cryoconservation de tissu testiculaire pour les garçons prépubères. Cette méthode est encore au stade expérimental et d'autres recherches sont nécessaires pour mettre en oeuvre les techniques de transplantation en clinique. Dans le but de préserver ou de restaurer la fertilité chez les patients atteints par d'autres maladies (syndrome de Klinefelter, Sertoli cell only syndrome) des techniques de spermatogénèse in vitro sont en cours d'élaboration., Male fertility preservation receives growing attention in the field of reproductive medicine. The first clinical programs were established to preserve reproductive potential in men needing gonadotoxic treatment. Sperm cryopreservation is now a standard procedure. Since a few years, several centers offer testicular tissue cryopreservation to prepubertal boys. This method is still experimental and further research is needed to implement the transplantation techniques in the clinic. With the aim to preserve or restore fertility in patients affected by other diseases (Klinefelter syndrome, Sertoli cell only syndrome) techniques for in-vitro spermatogenesis are being developed.

Because of the risk for development of psychopathology such as psychotic symptoms, it has been suggested that studying men with the XXY karyotype may help in the search for underlying cognitive, neural and genetic mechanisms. The aim of this study was to identify cognitive mechanisms that may contribute to disorganization of thought in XXY men.A group of 24 XXY men and two non-clinical control groups (N = 20, N 18) participated in the study. The level of disorganization of thought was measured using the Schizotypal Personality Questionnaire. We assessed IQ lateralization of verbal information processing and executive functions including inhibition and mental flexibility.XXY men with high levels of disorganization showed More severe impairments in mental flexibility and inhibition as compared to non-clinical controls and other XXY men. This subgroup also showed a stronger reduction in lateralization of verbal information processing. IQ measures did not differentiate XXY men with high versus low levels of disorganization.These findings indicate that executive impairments in the domains of inhibition and mental flexibility might play a role in the increased vulnerability for disorganized thought in the XXY group. Reduced lateralization of verbal information processing points to non-optimal cerebral specialization in the XXY group, especially in XXY men with high levels of disorganization. This fits with deficits in brain functions most vulnerable to such Maturational disruptions, i.e. executive dysfunctions. Our findings are in line with those reported for schizophrenia patients with thought disorder. We speculate that the underlying mechanisms of thought disorder probably are deficit specific rather than disorder specific. (C) 2009 Elsevier B.V. All rights reserved.

Background Abnormal sex chromosome numbers in humans are observed in Turner (45,X) and Klinefelter (47,XXY) syndromes. Both syndromes are associated with several clinical phenotypes, whose molecular mechanisms are obscure, and show a range of inter-individual penetrance. In order to understand the effect of abnormal numbers of X chromosome on the methylome and its correlation to the variable clinical phenotype, we performed a genome-wide methylation analysis using MeDIP and Illumina’s Infinium assay on individuals with four karyotypes: 45,X, 46,XY, 46,XX, and 47,XXY. Results DNA methylation changes were widespread on all autosomal chromosomes in 45,X and in 47,XXY individuals, with Turner individuals presenting five times more affected loci. Differentially methylated CpGs, in most cases, have intermediate methylation levels and tend to occur outside CpG islands, especially in individuals with Turner syndrome. The X inactivation process appears to be less effective in Klinefelter syndrome as methylation on the X was decreased compared to normal female samples. In a large number of individuals, we verified several loci by pyrosequencing and observed only weak inter-loci correlations between the verified regions. This suggests a certain stochastic/random contribution to the methylation changes at each locus. Interestingly, methylation patterns on some PAR2 loci differ between male and Turner syndrome individuals and between female and Klinefelter syndrome individuals, which possibly contributed to this distinguished and unique autosomal methylation patterns in Turner and Klinefelter syndrome individuals. Conclusions The presented data clearly show that gain or loss of an X chromosome results in different epigenetic effects, which are not necessary opposite. Electronic supplementary material The online version of this article (doi:10.1186/s13148-015-0112-2) contains supplementary material, which is available to authorized users.

Boys and men with an extra X chromosome (47,XXY, Klinefelter syndrome) are at risk for problems in social functioning and have an increased vulnerability for autism spectrum disorders (ASD). In the search for underlying mechanisms driving this increased risk, this study focused on social attention, that is, spontaneous orientation toward facial expressions. Seventeen adults with 47,XXY and 20 non-clinical controls participated in this study. Social attention was measured using an eyetracking method that quantifies the visual scanning patterns of faces expressing different types of emotions (happy, fearful, angry, neutral) and their varying intensity levels (25%, 50%, 75%, 100%). Overall, the group with Klinefelter syndrome fixated less on the eye region of faces when compared to controls (Cohen’s d 1.4), and did not show the typical tendency, as was found in the control group, to first fixate on the eyes when presented with a face (Cohen’s d 1.0). There was no significant effect of type or intensity of emotion. Shorter looking times toward eyes showed a borderline significant correlation with self-reports of poorer social functioning, with 29% explained variance. These findings suggest a reduced tendency to rapidly and automatically attend to the eyes of others in individuals with 47,XXY. This may have impact on more complex social-cognitive abilities that build upon this. In addition to studies of behaviorally defined disorders such as ASD, studying individuals with Klinefelter syndrome provide insight into mechanisms underlying various “at risk” pathways of social dysfunction and the factors that mediate this risk. (JINS, 2015, 21, 364–372)

Youth with an extra X chromosome (47, XXY & 47, XXX) display higher levels of schizotypal symptoms and social anxiety as compared to typically developing youth. It is likely that the extra X chromosome group is at-risk for clinical levels of schizotypy and social anxiety. Hence, this study investigated how schizotypal and social anxiety symptoms are related and mechanisms that may explain their association in a group of 38 children and adolescents with an extra X chromosome and a comparison group of 109 typically developing peers (8–19 years). Three cognitive coping strategies were investigated as potential mediators, rumination, catastrophizing, and other-blame. Moderated mediation analyses revealed that the relationship between schizotypal symptoms and social anxiety was mediated by catastrophizing coping in the extra X chromosome group but not in the comparison group. The results suggest that youth with an extra X chromosome with schizotypal symptoms could benefit from an intervention to weaken the tendency to catastrophize life events as a way of reducing the likelihood of social anxiety symptoms.

The 47,XXY syndrome, or Klinefelter syndrome, though it is a rare occurrence, it is the most common sex choromosome disorder affecting male subjects. This syndrome is underdiagnosed and seldomly before puberty. In this case, diagnosis was made before birth, through chorion villus sampling. CASE REPORT: A 16 month-old Italian male with 47 XXY syndrome showed the absence of primary teeth, with a delay of about 8-10 months, whereas during the first 15 months of life the auxological development has been normal both in weight and height (about 50th percentile). We assumed that this delay may be linked with Klinefelter syndrome, as sexual chromosomes play an important role in the dental development.

Klinefelter's syndrome (KS) is due to the presence of one or more supernumerary X chromosomes. Aneuploidy 47,XXY is the most common abnormality of sex chromosomes in humans, with an incidence of 1/500 male live births. Only one-third of subjects with KS is, however, diagnosed. The aim of this work is to present a review of current literature about neurogenetic functions in KS, referring to both clinical and therapeutics aspects. If it is well known that the majority of subjects with 47,XXY karyotype have a normal intellectual level, the identification of strengths and weaknesses of their intellectual functioning is important for the purpose of planning early psycho-edu- cational interventions. Language difficulties are one of the more distinctive traits in cognitive functioning of people with KS. It has also been suggested that the limitations in communication markedly affect social adaptation and behavioral aspects, as well as the development of personality. Moreover, difficulties in learning language appear to be related to an altered functional lateralization; therefore, KS subjects are a suitable model for studying genetic abnormalities of lateralization. In this, perspective psychopathological risk is analyzed. Early recognition of this aspect is needed to address the educational and therapeutic perspectives for KS subjects.

Encara no està clar el risc de recurrència en individus amb descendència aneuploide d'origen patern. S'han estudiat les freqüències de disomia en caps d'espermatozoides en pares amb descendència o avortaments amb la síndrome de Klinefelter (SK). També s'ha analitzat l'efecte de l'edat paterna en els percentatges de disomia en espermatozoides d'aquest individus. Mitjançant l'amplificació de polimorfismes del cromosoma X s'ha pogut determinat l'origen patern del cromosoma X addicional en 18 individus o avortaments amb la síndrome de Klinefelter. S'han estudiat les freqüències de diploïdia i disomia per als cromosomes 6, 13, 18, 21, 22, X i Y mitjançant hibridació in situ fluorescent (FISH) en els espermatozoides dels seus pares. En el 56% dels casos estudiats el cromosoma X addicional era d'origen patern. El grup de pares amb descendència SK d'origen patern presentava un increment estadísticament significatiu de disomia XY comparat amb els pares del grup d'origen matern. Només en els pares del grup d'origen patern s'ha observat una correlació entre edat paterna i freqüència de disomia XY. En canvi, les freqüències de diploïdia i disomia per als autosomes analitzats no eren diferents en el grup d'origen patern respecte als pares del grup d'origen matern. Es pot concloure que la freqüència de disomia XY incrementa amb l'edat paterna avançada només en els pares amb descendència Klinefelter d'origen patern. En una família, es va observar un cromosoma Y en anell al cariotip del nen amb la SK i al seu pare. Aquest és el primer cas descrit de transmissió natural d'un cromosoma Y en anell a la descendència. Per aquest motiu, es va fer un estudi més exhaustiu en aquesta família. Les tècniques de bandes G i FISH ens van indicar un percentatge similar de mosaicisme en pare i fill producte de la pèrdua del cromosoma en anell en mitosi. L'amplificació per PCR del gen SRY i de dos marcadors del cromosoma Y, la FISH amb sondes subtelomèriques per Xp/Yp i Xq/Yq, i la tècnica d'hibridació genòmica comparada (CGH) van indicar la presència de la zona del cromosoma Y compresa entre SRY i el subtelòmer Yq. El resultat de la FISH en espermatozoides de l'individu portador d'un cromosoma Y en anell, van indicar un increment de les freqüències de diploïdia i disomia per als cromosomes 6, 13, 18, 21, 22, XX, XY respecte al grup control. Per tant, un r(Y) amb una petita pèrdua de material genètic pot ser transmès de manera natural de pare a fill amb un comportament mitòtic similar. La presència d'un cromosoma Y en anell a les cèl.lules germinals incrementa el risc de descendència aneuploide, fins i tot per als cromosomes no implicats en la reorganització cromosòmica., It is still unclear if a recurrence risk would exist in fathers of an aneuploid offspring of paternal origin. We have studied disomy frequencies in spermatozoa from fathers having Klinefelter syndrome (KS) offspring or miscarriages. The effect of paternal age on sperm disomy percentages is also analysed. Parental origin of 18 Klinefelter patients were carried out by amplification of X chromosome polymorphisms. Spermatozoa from their fathers were studied by multicolour fluorescent in situ hybridization (FISH) using probes for chromosomes 6, 13, 18, 21, 22, X and Y. In 56% of KS cases studied the additional X chromosome was of paternal origin. The paternally transmitted KS group of fathers showed significantly higher frequencies for XY disomy sperm as compared to fathers of the maternal origin group. A correlation between paternal age and XY disomy frequencies was only found in the paternally derived cases. In contrast, similar disomy frequencies for all autosomes analysed were found in both groups of fathers. XY disomy frequencies increase with advancing paternal age only in fathers with paternally inherited KS offspring. In one case, a ring Y chromosome was found in the KS son and his father. This is the first reported case of natural transmission of an r(Y). For this reason we amplified the study in this family. G-banding and FISH studies revealed a similar percentage of mosaicism in father and son by mitotic loss of r(Y). SRY gene and Y marker amplification by PCR, FISH with subtelomeric probes for Xp/Yp and Xq/Yq, and comparative genomic hybridization analyses indicated the intactness of the Y chromosome from SRY to subtelomere Yq. FISH analysis of sperm from the father showed significantly higher frequencies for diploidy and for 6, 13, 18, 21, 22, XX, XY disomies than those observed in control donors. An r(Y) with low material loss can be naturally transmitted, showing similar mitotic behaviour in the offspring. The presence of an r(Y) chromosome in germinal cells increased the risk of fathering offspring with numerical abnormalities, even for chromosomes not involved in the arrangement.

Focal nodular hyperplasia is a benign lesion of the liver, predominantly affecting women. Its etiology is unknown. Elevated levels of estrogens have been invoked to play a role in the disease. Klinefelter syndrome is the most common sex chromosome disorder, characterized by 47, XXY karyotype, resulting in male hypogonadism and sex hormone imbalance. We present a case of a 25-year-old man affected by Klinefelter syndrome, admitted to our hospital for aspecific dyspeptic symptoms. During admission he underwent: blood test for the liver function and sexual hormonal status, ultrasonography, echo color power Doppler and computerized tomography scan of the liver, and liver biopsy. A hypergonadotropic hypogonadism was present. Imaging of the liver showed an hepatic lesion that liver biopsy confirmed to be a focal nodular hyperplasia. Although the association could be casual, the sex hormone imbalance present in Klinefelter syndrome may suggest a role in the development of this benign liver lesion.

Although early development of testis appears normal in boys with Klinefelter syndrome (KS), spermatogonial stem cell (SSC) depletion occurs in mid puberty, leading to infertility. Therefore, freezing of semen samples or testicular tissue sampling could be offered to KS boys at onset of puberty. However, only in about half of KS patients, adult or prepubertal, spermatozoa or SSCs can be observed, and to date, no clinical parameters are available to detect patients who might benefit from these techniques. Furthermore, strategies for the further use of the cryopreserved material are still under investigation. Retrieval of spermatogonial cells in prepubertal KS boys should therefore still be viewed as experimental and patients and their parents must be counseled accordingly.

Given the better survival rates for many cancers, even cancers occurring in childhood, quality of life has become an important issue in cancer treatment [8]. While sperm banking is the golden standard to preserve male fertility in adult men undergoing potential sterilizing treatment [9], not all adult men present spermatozoa in their ejaculates when cancer is being diagnosed [10]. When cancer is diagnosed in childhood, active spermatogenesis is not present, ; hence cryobanking of spermatozoa is not an option. When ejaculated spermatozoa cannot be cryopreserved, cryopreservation of testicular tissue either containing spermatozoa or spermatogonial stem cells may be considered.