Síndrome de Klinefelter, testosterona y sueño: a propósito de un caso clínico / Klinefelter's syndrome, testosterone and sleep: a clinical case

Se presenta un caso clínico de Síndrome de Klinefelter y se revisan que los aspectos en relación al sueño en estos pacientes, siendo relevante a ser abordado y estudiado debido a la relación causal entre el metabolismo de esteroides sexuales afectados. En especial la testosterona y cómo esto influye en la microarquitectura del sueño y la probabilidad de presentar síndrome de apnea obstructiva del sueño, con las repercusiones cognitivas que pueden sumarse a las ya descritas por el síndrome en si. De allí la importancia de un seguimiento y abordaje dirigido en este aspecto, al momento del diagnóstico y en el seguimiento a largo plazo.

A clinical case of Klinefelter's Syndrome is presented and the aspects related to sleep in these patients are reviewed, being relevant to be addressed and studied due to the causal relationship between the metabolism of affected sex steroids, especially testosterone and how this influences the microarchitecture of sleep and the probability of presenting obstructive sleep apnea syndrome with the cognitive repercussions that can be added to those already described by the syndrome itself. Hence the importance of a targeted follow-up and approach in this aspect, at the time of diagnosis and in long-term follow-up.

Pulmonary Thromboendarterectomy in Klinefelter Syndrome. Literature Review.

Klinefelter syndrome  is a form of male hypogonadism due to testicular sclerohyalinosis with atrophy and azoospermia, which is the most common cause of male infertility. The syndrome is usually accompanied by metabolic, morphological, and neurobehavioral manifestations; Venous thromboembolic diseases such as deep vein thrombosis and pulmonary embolism. The existence of chronic thromboembolic pulmonary hypertension in patients with Klinefelter syndrome   is scarce in the literature. We present the imaging and genetic analysis of a 37 -year-old male with a history of deep vein thrombosis who was admitted for exertional dyspnea.

Genital malformation: Trigger of the diagnosis of severe variants of Klinefelter syndrome. / Malformación genital: Disparador del diagnóstico de variantes severas de síndrome de Klinefelter.

INTRODUCTION: Among the disorders of sexual development, Klinefelter syndrome and its variants are classified as an alteration in the number of sex chromosomes. These patients show signs of hypergonadotropic hypogonadism at puberty, however cases of severe variants also present neurocognitive and language problems from an early age. OBJECTIVE: To describe two patients with genital malformation with genetic diagnosis of severe variants of Klinefelter syndrome, and to review clinical and therapeutic aspects. CLINICAL CASES: Case 1: Diagnosis of atypical genitalia at birth: Small and curved phallus with the urethral meatus at scrotal level, and bifid scrotum. No other somatic abnormality was observed, except for subtle clinodactyly of the fifth finger. Karyotype: 49, XXXXY. At one year of life, genitalia were reconstructed. The patient presented a global developmental delay, mainly in language, which was managed with early stimulation and speech and language therapy since he was two months old. Finally, he was able to attend kindergarten. Case 2: At one month of life, a small and severe curved phallus (more than 70°) was observed, and testicles were in the scrotum. Karyotype: 48, XXYY. At one year of life, the penile malformation was corrected. The patient presented global developmental delay, mainly in expressive language which was managed with early stimulation since the age of four months, achieving kindergarten attendance. CONCLUSION: Genital malformations led to the diagno sis of severe variants of Klinefelter syndrome, and were corrected around the year of life. The early identification of these variants allowed the intervention of the neurostimulation team, favoring the neurocognitive development and social integration of these children.

Gene Copy Number Quantification of SHOX, VAMP7, and SRY for the Detection of Sex Chromosome Aneuploidies in Neonates.

Aims: To explore the feasibility of detecting sex chromosome aneuploidies (SCAs) by means of gene copy number quantification of short stature homeobox (SHOX), vesicle-associated membrane protein 7 (VAMP7), and SRY in newborns. Materials and Methods: Gene doses of SHOX, VAMP7, and SRY were determined by quantitative polymerase chain reaction (qPCR) using DNA obtained from dried blood samples from newborns. Relative quantification values were obtained. An aneuploidy profile was established according to cutoff values. Samples with ≥2 gene doses (out of range) were reanalyzed, and those with aneuploidy profiles were confirmed by karyotyping. Sensitivity, specificity, and positive and negative predictive values were obtained. Results: A total of 10,033 samples were collected (4945 females and 5088 males). Of 244 (2.43%) samples with ≥2 gene doses that were retested, 20 cases were confirmed. The overall incidence of SCAs was 1 in 500 live newborns. There were six cases of Turner syndrome (1/824), 3 cases of XXX (1/1648), 7 cases of Klinefelter syndrome (1/726), and 4 cases of of XYY (1/1272). The sensitivity was 0.952 (95.42%); the specificity was 0.975 (97.56%); the positive predictive value was 0.909 (90.91%) and the negative predictive value was 0.987 (98.77%). Conclusions: Gene copy number analyses of the VAMP7, SHOX, and SRY genes by qPCR from blood samples spotted onto filter paper is a highly reliable method for the early detection of male and female SCAs.

Cytogenetic assessment of Iranian infertile men with undescended testis: A retrospective study.

OBJECTIVE: Undescended testis (UDT) is a urogenital disease that affects fertility. This study looked into the cytogenetic abnormalities of Iranian infertile patients with UDT. METHODS: Our study included 522 infertile patients with UDT (case group) and two control groups, one with 300 infertile men without UDT and another with 268 fertile men. RESULTS: Chromosomal abnormalities were found in 45 patients with UDT (8.62%). Seven of the alterations were considered as normal features. Klinefelter syndrome and mosaicism were the most common anomalies. Chromosomal abnormalities were found in 31 infertile men in the control group (10.33%), 13 of which deemed normal and 18 (6%) anomalous. Nine chromosomal abnormalities were found in the second control group with fertile men (3.35%), six deemed normal and three (1.11%) anomalous. CONCLUSION: Despite the high rate of abnormalities in infertile controls (6%) and the higher rate seen in infertile individuals with UDT indicate a significant prevalence of chromosomal abnormalities in the Iranian population, particularly when the literature suggests that the normal rate of abnormal karyotypes should be within the 0.7-1% range in the general population. The incidence of abnormal karyotypes increased when infertile patients had additional conditions such as UDT.

Malformación genital: disparador del diagnóstico de variantes severas de síndrome de Klinefelter / Genital malformation: trigger of the diagnosis of severe variants of Klinefelter syndrome

Resumen: Introducción: El síndrome de Klinefelter y sus variantes, como alteración en el número de cromosomas sexuales, se encuentra entre los trastornos del desarrollo sexual. Sus portadores manifiestan hipogonadismo hipergonadotrófico en la pubertad; las variantes severas presentan además problemas neurocognitivos y del lenguaje desde edades tempranas. Objetivo: Describir dos pacientes portadores de mal formación genital con diagnóstico genético de variantes severas de síndrome de Klinefelter; y revisar aspectos clínicos y terapéuticos. Casos Clínicos: Caso 1: Diagnóstico de genitales atípicos al nacer: Falo pequeño y corvo con meato uretral a nivel escrotal y escroto bífido. Sin otra anomalía somática, excepto sutil clinodactilia del 5 dedo. Cariotipo: 49,XXXXY. Al año de vida se reconstruyeron los genitales. Evolucionó con retraso global del desarrollo, principalmente del lenguaje, manejado con estimulación temprana kinésica y fonoaudiológica desde los 2 meses, logró integrarse en un jardín de infantes. Caso 2: Al mes de vida se constató falo pequeño y corvo severo (más de 70°), testículos en bolsa. Cariotipo: 48,XXYY. Al año de vida se corrigió malformación del pene. Evolucionó con retraso global del desarrollo, fundamentalmente en el lenguaje expresivo, y fue manejado con el equipo de estimulación temprana desde los 4 meses, logrando adaptación en un jardín de infantes. Conclusión: Las malformaciones genitales condujeron al diagnóstico de variantes severas de síndrome de Klin efelter, y fueron corregidas alrededor del año de vida. La identificación temprana de estas variantes permitió la intervención del equipo de neuroestimulación, favoreciendo el desarrollo neurocognitivo y la integración social de estos niños.

Abstract: Introduction: Among the disorders of sexual development, Klinefelter syndrome and its variants are classified as an alteration in the number of sex chromosomes. These patients show signs of hypergonadotropic hypogonadism at puberty, however cases of severe variants also present neurocognitive and language problems from an early age. Objective: To describe two patients with genital malformation with genetic diagnosis of severe variants of Klinefelter syndrome, and to review clinical and therapeutic aspects. Clinical Cases: Case 1: Diagnosis of atypical genitalia at birth: Small and curved phallus with the urethral meatus at scrotal level, and bifid scrotum. No other somatic abnormality was observed, except for subtle clinodactyly of the fifth finger. Karyotype: 49, XXXXY. At one year of life, genitalia were reconstructed. The patient presented a global developmental delay, mainly in language, which was managed with early stimulation and speech and language therapy since he was two months old. Finally, he was able to attend kindergarten. Case 2: At one month of life, a small and severe curved phallus (more than 70°) was observed, and testicles were in the scrotum. Karyotype: 48, XXYY. At one year of life, the penile malformation was corrected. The patient presented global developmental delay, mainly in expressive language which was managed with early stimulation since the age of four months, achieving kindergarten attendance. Conclusion: Genital malformations led to the diagno sis of severe variants of Klinefelter syndrome, and were corrected around the year of life. The early identification of these variants allowed the intervention of the neurostimulation team, favoring the neurocognitive development and social integration of these children.

[Thymoma in a patient with klinefelter syndrome. Case report]. / Síndrome de Klinefelter diagnosticado en un adulto a raíz del estudio de infección respiratoria recurrente y masa mediastínica. Caso clínico.

Klinefelter syndrome (47, XXY in most cases) is a frequently underdiagnosed chromosomal anomaly associated with multiple comorbidities in adult life. Patients with Klinefelter syndrome have a higher risk of cancer. Specifically, these patients have a higher risk for mediastinal germ cell tumors. It is estimated that 8% of male patients with mediastinal tumors have Klinefelter. We report a 42-years-old male who suffered recurrent respiratory infections. During the study, a mediastinal mass was found, whose pathological study disclosed a type B thymoma. The patient had a history of infertility, high stature, gynecomastia, obesity with gynecoid distribution of body fat and testicular atrophy. A karyotype was requested (47, XXY), confirming the diagnosis of Klinefelter syndrome.

Síndrome de Klinefelter diagnosticado en un adulto a raíz del estudio de infección respiratoria recurrente y masa mediastínica: caso clínico / Thymoma in a patient with klinefelter syndrome: case report

Klinefelter syndrome (47, XXY in most cases) is a frequently underdiagnosed chromosomal anomaly associated with multiple comorbidities in adult life. Patients with Klinefelter syndrome have a higher risk of cancer. Specifically, these patients have a higher risk for mediastinal germ cell tumors. It is estimated that 8% of male patients with mediastinal tumors have Klinefelter. We report a 42-years-old male who suffered recurrent respiratory infections. During the study, a mediastinal mass was found, whose pathological study disclosed a type B thymoma. The patient had a history of infertility, high stature, gynecomastia, obesity with gynecoid distribution of body fat and testicular atrophy. A karyotype was requested (47, XXY), confirming the diagnosis of Klinefelter syndrome.

Down-Klinefelter syndrome (48,XXY,+21) in a neonate associated with congenital heart disease.

Double aneuploidy is considered a rare phenomenon. Herein, we describe a case of double aneuploidy 48,XXY,+21 in a neonate with congenital heart defects. The 28-day-old neonate male (23-year-old mother and 24-year-old father) was admitted to a neonatal intensive care unit owing to congenital heart disease. Echocardiography showed a complete atrioventricular septal defect with Rastelli type B and significant left ventricular failure, moderate atrioventricular valve regurgitation, right-sided heart failure, and preserved systolic function. Cytogenetic analysis of the newborn showed double aneuploidy 48,XXY,+21. The maternal karyotype was 46,XX,inv(9)(p11q13) and the paternal was 46,XY. Characteristics associated with Down syndrome are observed in newborns; on the other hand, children under 10 months of age and neonates may show little or no signs of the Klinefelter syndrome. According to this study, there seem to be differences between the frequency of congenital heart disease among patients with Down-Klinefelter and Down syndrome. At about 11 months of age, the child died after undergoing heart surgeries. The early cytogenetic study is important for better diagnosis and management of the disease.

Asociación de craneofaringioma y síndrome de Klinefelter en la transición puberal: un desafío diagnóstico / Craniopharyngioma and Klinefelter syndrome during the pubertal transition: A diagnostic challenge

Los craneofaringiomas son de los tumores hipofisarios más frecuentes en la niñez y, sea por su evolución o por el tratamiento que requieren, pueden comprometer el desarrollo puberal. El síndrome de Klinefelter es la causa más frecuente de hipogonadismo hipergonadotrópico en el varón. La presentación concomitante de ambas entidades es extremadamente baja (1/10(9)) y plantea un interrogante acerca de una probable asociación fisiopatológica. Se presenta el caso de un paciente belga de 18 años, con diagnóstico de craneofaringioma en la niñez y panhipopituitarismo luego del tratamiento quirúrgico y radioterápico. Al llegar a los 14 años, se inició la inducción puberal con gonadotropinas. Ante la falta de respuesta clínica, se completó una evaluación genética, que evidenció, de manera homogénea, una trisomía XXY. La falta de respuesta al tratamiento de inducción con gonadotropina exógena reveló la asociación de hipogonadismo primario y secundario, que demostró la importancia del seguimiento multidisciplinario que estos pacientes requieren.

Craniopharyngioma is the most common pituitary tumor in childhood. It can compromise the pubertal development because of its evolution or treatment. Syndrome of Klinefelter is the most common cause of hipergonadotrophic hypogonadism in males. The concomitant presentation of both entities is extremely low (1/10(9)) and the pathophysiological association is questionned. We present the case of a 18-year-old Belgian patient. He had a diagnosis of craniopharyngioma in childhood and he presented with panhypopituitarism after radiotherapy and surgical treatment. At the age of 14, he started pubertal induction with gonadotropin therapy without clinical response. A genetic evaluation confirmed a homogeneous 47, XXY karyotype. Failure of exogenous gonadotropin therapy revealed the hidden association of primary and secondary hypogonadism, demonstrating the importance of the followup and a multidisciplinary approach in these patients.

MANAGEMENT OF ENDOCRINE DISEASE: Diagnostic and therapeutic approach of tall stature.

Tall stature is defined as a height of more than 2 standard deviations (s.d.) above average for same sex and age. Tall individuals are usually referred to endocrinologists so that hormonal disorders leading to abnormal growth are excluded. However, the majority of these patients have familial tall stature or constitutional advance of growth (generally associated with obesity), both of which are diagnoses of exclusion. It is necessary to have familiarity with a large number of rarer overgrowth syndromes, especially because some of them may have severe complications such as aortic aneurysm, thromboembolism and tumor predisposition and demand-specific follow-up approaches. Additionally, endocrine disorders associated with tall stature have specific treatments and for this reason their recognition is mandatory. With this review, we intend to provide an up-to-date summary of the genetic conditions associated with overgrowth to emphasize a practical diagnostic approach of patients with tall stature and to discuss the limitations of current growth interruption treatment options.

[Craniopharyngioma and Klinefelter syndrome during the pubertal transition: A diagnostic challenge]. / Asociación de craneofaringioma y síndrome de Klinefelter en la transición puberal: un desafío diagnóstico.

Craniopharyngioma is the most common pituitary tumor in childhood. It can compromise the pubertal development because of its evolution or treatment. Syndrome of Klinefelter is the most common cause of hipergonadotrophic hypogonadism in males. The concomitant presentation of both entities is extremely low (1/109) and the pathophysiological association is questionned. We present the case of a 18-year-old Belgian patient. He had a diagnosis of craniopharyngioma in childhood and he presented with panhypopituitarism after radiotherapy and surgical treatment. At the age of 14, he started pubertal induction with gonadotropin therapy without clinical response. Asociación de craneofaringioma y síndrome de Klinefelter en la transición puberal: un desafío diagnóstico Craniopharyngioma and Klinefelter syndrome during the pubertal transition: A diagnostic challenge A genetic evaluation confirmed a homogeneous 47, XXY karyotype. Failure of exogenous gonadotropin therapy revealed the hidden association of primary and secondary hypogonadism, demonstrating the importance of the followup and a multidisciplinary approach in these patients.

Los craneofaringiomas son de los tumores hipofisarios más frecuentes en la niñez y, sea por su evolución o por el tratamiento que requieren, pueden comprometer el desarrollo puberal. El síndrome de Klinefelter es la causa más frecuente de hipogonadismo hipergonadotrópico en el varón. La presentación concomitante de ambas entidades es extremadamente baja (1/109) y plantea un interrogante acerca de una probable asociación fisiopatológica. Se presenta el caso de un paciente belga de 18 años, con diagnóstico de craneofaringioma en la niñez y panhipopituitarismo luego del tratamiento quirúrgico y radioterápico. Al llegar a los 14 años, se inició la inducción puberal con gonadotropinas. Ante la falta de respuesta clínica, se completó una evaluación genética, que evidenció, de manera homogénea, una trisomía XXY. La falta de respuesta al tratamiento de inducción con gonadotropina exógena reveló la asociación de hipogonadismo primario y secundario, que demostró la importancia del seguimiento multidisciplinario que estos pacientes requieren.

Aneuplodia de cromossomos sexuais em gato de pelagem tortoiseshell - relato de caso / Aneuploidy of sex chromosomes in a tortoiseshell cat - case report / Aneuploidía de cromosomas sexuales en un gato de pelaje tortoiseshell - reporte de un caso

A análise citogenética é uma importante etapa no diagnóstico de animais com histórico de esterilidade ou infertilidade. Durante anos, os estudos cromossômicos foram indicados para as espécies de produção. Atualmente, a procura por tais análises em animais de companhia tem aumentado. Em gatos, a coloração da pelagem tortoiseshell apresenta predominância de pêlos pretos mesclados com pêlos brancos e laranja pelo corpo todo, e, na coloração denominada calico, essas três cores se apresentam como manchas independentes, com predominância da cor branca. Porém, todos esses padrões são restritos a fêmeas. É raro observar gatos machos tortoiseshell ou calico, fruto da ocorrência de aberrações cromossômicas. Relata-se, neste caso, a análise cromossômica de um gato tortoiseshell com conjunto cromossômico diploide de 2n = 39,XXY, ou seja, um cromossomo X extra, semelhante ao que ocorre na síndrome de Klinefelter, em humanos.(AU)

Cytogenetic analysis is an important step in the diagnosis of animals with a history of infertility or sterility. While chromosomal studies have been indicated for livestock species for years, the demand for such analyzes in companion animals has recently increased. The coat color in cats known as tortoiseshell presents predominance of black hair mixed with white and orange hair all over the body and, in the color pattern known as calico, these three colors are presented as independent spots with predominance of white hair. However, all of these patterns are limited to females due to sex-linked inheritance. Male tortoiseshell or calico cats occur rarely, due to the occurrence of chromosomal aberrations. This article reports the chromosomal analysis of a male cat with tortoiseshell pelage that presented an extra X chromosome (diploid chromosome set of 2n = 39,XXY), a condition which is similar to Klinefelter syndrome in humans.(AU)

El examen citogenético representa una importante etapa en el diagnóstico de animales con antecedentes de esterilidad o infertilidad. Durante muchos años, los estudios cromosómicos sólo eran indicados para las especies utilizadas en producción animal. Actualmente, la búsqueda de dichos análisis en perros y gatos se ha incrementado. En los gatos, la coloración del pelaje tortoiseshell puede tener una predominancia de pelos negros mezclados con pelos blancos y anaranjados distribuidos en todo el cuerpo, o bien presentarse una coloración denominada calicó, en la que esos tres colores se muestran como manchas independientes, con predominancia del color blanco. Este tipo de pelaje ocurre en hembras, y en raras ocasiones puede ser observado en gatos machos, debido a la presencia de aberraciones cromosómicas. En este trabajo se relata un caso donde se realizó el análisis cromosómico de un gato tortoiseshell, que tenía un conjunto cromosómico diploide de 2n = 39,XXY, es decir un cromosoma X de más, similar a lo que ocurre en el síndrome de Klinefelter en seres humanos.(AU)

Aneuplodia de cromossomos sexuais em gato de pelagem tortoiseshell - relato de caso / Aneuploidy of sex chromosomes in a tortoiseshell cat - case report / Aneuploidía de cromosomas sexuales en un gato de pelaje tortoiseshell - reporte de un caso

A análise citogenética é uma importante etapa no diagnóstico de animais com histórico de esterilidade ou infertilidade. Durante anos, os estudos cromossômicos foram indicados para as espécies de produção. Atualmente, a procura por tais análises em animais de companhia tem aumentado. Em gatos, a coloração da pelagem tortoiseshell apresenta predominância de pêlos pretos mesclados com pêlos brancos e laranja pelo corpo todo, e, na coloração denominada calico, essas três cores se apresentam como manchas independentes, com predominância da cor branca. Porém, todos esses padrões são restritos a fêmeas. É raro observar gatos machos tortoiseshell ou calico, fruto da ocorrência de aberrações cromossômicas. Relata-se, neste caso, a análise cromossômica de um gato tortoiseshell com conjunto cromossômico diploide de 2n = 39,XXY, ou seja, um cromossomo X extra, semelhante ao que ocorre na síndrome de Klinefelter, em humanos.

Cytogenetic analysis is an important step in the diagnosis of animals with a history of infertility or sterility. While chromosomal studies have been indicated for livestock species for years, the demand for such analyzes in companion animals has recently increased. The coat color in cats known as tortoiseshell presents predominance of black hair mixed with white and orange hair all over the body and, in the color pattern known as calico, these three colors are presented as independent spots with predominance of white hair. However, all of these patterns are limited to females due to sex-linked inheritance. Male tortoiseshell or calico cats occur rarely, due to the occurrence of chromosomal aberrations. This article reports the chromosomal analysis of a male cat with tortoiseshell pelage that presented an extra X chromosome (diploid chromosome set of 2n = 39,XXY), a condition which is similar to Klinefelter syndrome in humans.

El examen citogenético representa una importante etapa en el diagnóstico de animales con antecedentes de esterilidad o infertilidad. Durante muchos años, los estudios cromosómicos sólo eran indicados para las especies utilizadas en producción animal. Actualmente, la búsqueda de dichos análisis en perros y gatos se ha incrementado. En los gatos, la coloración del pelaje tortoiseshell puede tener una predominancia de pelos negros mezclados con pelos blancos y anaranjados distribuidos en todo el cuerpo, o bien presentarse una coloración denominada calicó, en la que esos tres colores se muestran como manchas independientes, con predominancia del color blanco. Este tipo de pelaje ocurre en hembras, y en raras ocasiones puede ser observado en gatos machos, debido a la presencia de aberraciones cromosómicas. En este trabajo se relata un caso donde se realizó el análisis cromosómico de un gato tortoiseshell, que tenía un conjunto cromosómico diploide de 2n = 39,XXY, es decir un cromosoma X de más, similar a lo que ocurre en el síndrome de Klinefelter en seres humanos.

Sperm Retrieval in Adolescents and Young Adults with Klinefelter Syndrome: A Prospective, Pilot Study.

OBJECTIVE: To assess sperm retrieval rates in adolescents and young adults with Klinefelter syndrome, with the ultimate goal of improving fertility in this population. Secondary aims were to evaluate other clinical characteristics of the cohort and identify predictors of sperm retrieval. STUDY DESIGN: Patients 12-25 years of age with Klinefelter syndrome (47,XXY) were recruited at the Boston Children's Hospital. Physical examination, biochemical evaluation, scrotal ultrasonography, and semen analysis were performed. Neurocognitive data were collected. Microdissection sperm extraction (unilateral micro-testicular sperm extraction) was offered to individuals with no sperm in their ejaculates. Given the small sample size, analysis was primarily descriptive. RESULTS: Fifteen patients were enrolled. None had sperm in their ejaculates. Ten patients underwent unilateral micro-testicular sperm extraction. Sperm retrieval rate was 50%. From a neurocognitive standpoint, subjects reported problems with peers, conduct, and overall difficulties. Incidentally, one-third of the patients were found to have testicular microlithiasis and 17% of subjects with renal ultrasound imaging had bilateral renal medullary nephrocalcinosis. CONCLUSIONS: This pilot study suggests that sperm retrieval rates in adolescents and young adults with Klinefelter syndrome are comparable with those reported in older men. However, larger studies are needed to confirm our findings. The clinical significance of the scrotal and renal ultrasound findings merits further investigation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01817296.

Clinical characteristics of men with non-mosaic Klinefelter syndrome in northeastern China: implications for genetic counseling.

Klinefelter syndrome (KS) is the most common genetic cause of male infertility. Widespread development in assisted reproductive technology has provided non-mosaic KS patients with the opportunity of having biological children. Testosterone replacement therapy and micro-dissection testicular sperm extraction are effective sperm retrieval techniques for KS patients. Despite the success of sperm retrieval and intracytoplasmic sperm injection (ICSI), some areas of early aggressive hormonal spermatogenesis and appropriate management of KS remain controversial. Androgenotherapy, a common treatment for KS, carries a risk of decreasing focal spermatogenesis by lowering the gonadotropin content. Inadequately treated hypogonadism increases psychosocial morbidity in KS patients. Preventive care must be provided from the time of diagnosis, preferentially through a multidisciplinary approach. This indicates the need for improved genetic counseling of KS patients. The aim of this study was to report the prevalence of non-mosaic KS in a Chinese infertile male population. The rate of early diagnosis was lower in KS patients; most of these were diagnosed after rising concerns of reproductive capacity. The mean age of patients with sperm or germ cells was significantly lower, while the semen volume of these patients was significantly higher. However, the semen volume was negatively correlated with the age and ratio of luteinizing hormone/testosterone content in KS patients. Therefore, genetic counseling of KS patients should focus on early diagnosis and timely treatment, in addition to improving the quality of life of all KS patients. The use of testosterone replacement therapy and/ or micro-dissection testicular sperm extraction should be preferentially considered for fertility preservation.

Klinefelter syndrome: an unusual diagnosis in pediatric patients.

OBJECTIVE: To identify clinical and laboratory data which differentiate Klinefelter syndrome (KS) patients according to age group. METHODS: The study included all cases of hypogonadism, gynecomastia and/or infertility whose karyotype was performed at a university hospital from January 1989 to December 2011, in a total of 105 subjects. The following data were retrospectively analyzed: age at first visit, ratio of arm span to height, pubic hair, gynecomastia, testicular volume, luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone (T), and spermiogram. RESULTS: During the study period, 33 patients were diagnosed with Klinefelter syndrome (KS+) and 72 were not (KS-). Out of all KS cases, only seven (21.2%) were diagnosed before 20 years old and two (6.1%) before 10 years old. Age at first consultation (in years) was similar in both groups (KS+ = 31.3±12.9 and KS- = 27.6±12.1), as were ratio of arm span to height and frequency of gynecomastia. However, in KS+ patients, pubic hair was less developed, testicular volume was smaller and testosterone levels were lower, while LH and FSH levels and frequency of azoospermia were higher. CONCLUSIONS: Klinefelter syndrome is both an under and late diagnosed condition. The most important data for diagnosis are testicular volume, hormone levels and presence of azoospermia in spermiogram, especially in puberty and adult life.