Including Klinefelter Syndrome Research Articles

Global, regional and national burdens of reproduction-related congenital birth defects, 1990-2019.

Reproduction-related congenital birth defects (RCBDs), including Klinefelter syndrome (KS), Turner syndrome (TS), and urogenital congenital anomalies (UCA), can lead to severe physical and psychosocial disorders. The global impact of RCBDs on children and adults is unknown, which limits high-quality development of populations and increases in life expectancy per capita. Annual incidence rates, prevalence rates (PR), and disability-adjusted life year (DALY) rates were collected for KS, TS, and UCA for 204 countries and territories, including at birth, for children younger than 1 year, and age-standardized (AS) for all ages. Linear regression was used to calculate their estimated annual percentage changes (EAPCs). Finally, the relationships between EAPCs of each indicator and sociodemographic index (SDI) was investigated using Pearson correlation analysis. Globally, the age-standardized prevalence rate (ASPR) trend is decreasing in KS and TS and increasing in UCA. The DALY rates for children younger than 1 year were on a downward trend in KS and UCA, while they were still rising for TS. The AS-DALY rates were all on a downward trend in KS, TS, and UCA. The DALY rates of KS, TS and UCA were found higher in high-income countries in North America. In addition, the burdens of TS and UCA went down with increasing SDI, whereas the burden of KS increased with increasing SDI. The global burdens of RCBDs have decreased since 1990. This finding can help policymakers implement cost-effective interventions to reduce the burdens of RCBDs.

Gender assignment in disorders of sex: An Islamic perspective from Saudi Arabia

Genital ambiguity, is defined as a group of congenital conditions in which development of chromosomal, gonadal, or anatomic sex is atypical. It constitutes a major social emergency and the decision making in relation to sex assignment has been perceived as an extremely disturbing and difficult to both families and health care professionals. It can also be a medical emergency as it may lead to life-threatening adrenal crisis. Each patient should be evaluated individually by a well-coordinated experienced multidisciplinary team of specialists in a higher center capable of managing such disorders. The team should include a geneticist, neonatologist, endocrinologist, pediatric surgeon, urologist, psychiatrist and psychologist, a social worker, and other specialists such as a nurse, and gynecologist to be consulted whenever needed. The estimated incidence was found to be approximately 0.1% to 0.2% worldwide i.e, 1:4500-5000 live birth. The 46XX is the most common cause, while the majority of these patients congenital adrenal hyperplasia (CAH) is the most underlying aetiology. The 46XY DSD is a heterogeneous disorders that often result from a disruption in the production or response to testosterone, dihydrotestosterone, or Mullerian inhibitory substances. Chromosomal DSD includes condition resulting from abnormal meiosis, including Klinefelter syndrome (47XXY) and Turner syndrome. The evaluation of patients with sex disorders requires a through history, physical examination, karyotype, serum electrolytes, and specific hormones, such as 17-OH-progesterone.The pediatric radiologist has a major role in diagnosis. In Saudi Arabia, a general guidelines were suggested by the council of senior ulama to manage patients with DSD in accordance with the islamic laws. This should be the practice in other muslim countries. Health professionals need to be aware of the existence of such recommendation for a better care of patients.

Karyotype analysis of amniotic fluid cells and report of chromosomal abnormalities in 15,401 cases of Iranian women

The aim of present study was to assess the karyotypes of amniotic fluid cells and find the frequency of chromosomal abnormalities and their significance in clinical setting. A total of 15,401 pregnant women were assessed from March 2016 to May 2019, and 14,968 amniotic fluid samples were successfully cultured. These fetuses were grouped according to different indications including advanced maternal age, abnormal nuchal translucency (NT) values, positive first/second trimester screening results, high risk NIPT results, very low PAPP-A and free β-hCG multiples of the normal median (MoM) results, abnormal ultrasound findings or previous history of chromosomal abnormalities. Results indicated the presence of normal karyotype in 90.2% (13,497/14,968) of fetuses. Totally, 46.4% (6945/14,968) of fetuses were 46,XX and 43.8% (6552/14,968) had 46,XY chromosome pattern. A total of 1077 abnormal karyotypes were found among 14,968 fetuses, thus the rate of abnormal fetuses was calculated to be 7.2% (1072/14,968). Meanwhile, a total of 394 cases (2.8%) had a normal polymorphism in their karyotype. In other words, abnormal karyotypes were detected in one of 13.9 cases of patients underwent amniocentesis. Down syndrome, Edward’s syndrome, abnormal mosaicisms and Patau’s syndrome were detected in 4.4% (659/14,968), 0.57% (85/14,968), 0.49% (74/14,968) and 0.24% (36/14,968) of cases, respectively. Sex chromosomal abnormalities including Klinefelter syndrome, Turner syndrome and 47,XXX karyotype were detected in 64 cases (0.43%). In this article, the rates of chromosomal abnormalities are compared between different groups of patients based on the advanced maternal age, abnormal NT values, very low PAPP-A and free β-hCG MoMs results, and positive FTS results. The current investigation provides insight into the most appropriate indications for amniocentesis in Iran.

CLINICAL CONSEQUENCES OF MICRODISSECTION TESTICULAR EXTRACTION AND INTRACYTOPLASMIC SPER INJECTION (ICSI) IN COUPLES WITH KLINEFELTER SYNDROME (KS)

Microdissection (Micro) TESE, in combination with intracytoplasmic sperm injection (ICSI), is presently used to treat infertility in cases of NOA including Klinefelter syndrome (KS), which is the most common sex-chromosome disorder among infertile males, with a prevalence of 1 in 660 men and is a frequent cause of male infertility. The aim of this study is to assess the prevalence and the significance including sperm retrieval rate (SRR) by micro TESE and ICSI outcomes with embryonic development in KS couples.

Stereological properties of seminiferous tubules in infertile men with chromosomal and genetic abnormalities.

Male infertility is caused by genetic anomalies in 15-30% of cases. This study aimed to determine stereological properties of seminiferous tubules in infertile men with genetic anomalies, including Klinefelter Syndrome (KS), Y chromosome microdeletions (MYC) and CFTR gene mutations (CFTR); and to compare them to seminiferous tubules of men with obstructive azoospermia of non-genetic origin (control group). The study was conducted on 28 human testis biopsy specimens obtained from 14 patients with MYC, 18 samples from 9 patients with KS, and 6 samples from 3 patients with CFTR. Whenever possible, a bilateral biopsy was included in the study. The control group had 33 samples from 18 patients (3 of them with a solitary testis). Qualitative and quantitative (stereological) analysis of seminiferous tubules (including the status of spermatogenesis, volume, surface area, length and number of tubules) were performed in all groups. Qualitative histological analysis revealed significant impairment of spermatogenesis in KS and MYC, whereas testicular parenchyma was fully maintained in CFTR and control groups. Spermatogenesis was most seriously impaired in KS. All stereological parameters were significantly lower in KS and MYC, compared to the CFTR and control groups. The total volume, surface and length of seminiferous tubules were significantly lower in KS compared with MYC. Stereological analysis is valuable in evaluating male infertility, whereas qualitative histological analysis can be helpful in assessing sperm presence in testicular tissue of patients with KS or MYK undergoing TESE.

Genetic disorders and male infertility.

BackgroundAt present, one out of six couples is infertile, and in 50% of cases, infertility is attributed to male infertility factors. Genetic abnormalities are found in 10%‐20% of patients showing severe spermatogenesis disorders, including non‐obstructive azoospermia.MethodsLiteratures covering the relationship between male infertility and genetic disorders or chromosomal abnormalities were studied and summarized.Main findings (Results)Genetic disorders, including Klinefelter syndrome, balanced reciprocal translocation, Robertsonian translocation, structural abnormalities in Y chromosome, XX male, azoospermic factor (AZF) deletions, and congenital bilateral absence of vas deferens were summarized and discussed from a practical point of view. Among them, understanding on AZF deletions significantly changed owing to advanced elucidation of their pathogenesis. Due to its technical progress, AZF deletion test can reveal their delicate variations and predict the condition of spermatogenesis. Thirty‐nine candidate genes possibly responsible for azoospermia have been identified in the last 10 years owing to the advances in genome sequencing technologies.ConclusionGenetic testing for chromosomes and AZF deletions should be examined in cases of severe oligozoospermia and azoospermia. Genetic counseling should be offered before and after genetic testing.

Possible link between FSH and RANKL release from adipocytes in men with impaired gonadal function including Klinefelter syndrome.

The FSH receptor (FSHR) has been found to be expressed in human bone cells and bone marrow-adipocytes, and highly-debated mouse studies have suggested extra-gonadal effects of gonadotropins on glucose, adipocyte and bone homeostasis. These putative effects could be direct or indirectly mediated by endocrine factors released from bone-cells or adipocytes. Here, we investigated whether gonadotropins are linked with glucose- and lipid-metabolism in hypergonadotropic men. Single centre, cross-sectional study of 307 men with idiopathic infertility and 28 men with Klinefelter syndrome (KS). associations between serum LH and FSH with soluble-RANKL (sRANKL), osteoprotegerin (OPG), osteocalcin, fasting glucose and insulin, sex steroids, and body composition. Expression of FSHR was studied in human-derived adipocyte-cell-models (hMADS, TERT-hWA) and FSH stimulation of RANKL expression and secretion in hMADS in vitro. Serum FSH was not directly linked with glucose- and lipid-metabolism. However, FSH was inversely associated with sRANKL in both infertile men and KS men (p = .023 and p = .012). Infertile men with elevated FSH (>11 U/L) had significantly lower sRANKL (p = .015). sRANKL was positively associated with fat percentage, fasting insulin, and glucose (all p < .05). Men with prediabetes had higher sRANKL (p = .021), but lower testosterone (p < .0001) and Inhibin B (p = .005). The FSHR was expressed in the investigated human derived adipocytes, and 3-6 h treatment with FSH markedly increased RANKL release (p < .05). KS and infertile men with prediabetes have low Inhibin B, and testosterone but elevated RANKL compared with non-prediabetic men despite comparable levels of serum gonadotropins. Serum FSH and sRANKL was inversely associated in both infertile and KS men, but the increased release of RANKL from FSH treated adipocytes suggest a direct effect of FSH on RANKL production in some tissues. Further studies are required to clarify whether FSH targets RANKL in the skeleton. ClinicalTrial_ID:NCT01304927.

A Search for Disorders of Sex Development among Infertile Men

A retrospective cross-sectional study was performed in a DSD clinic at a tertiary service (University Hospital) to estimate the frequency of disorders of sex development (DSD) among men who seek medical care because of infertility. The sample included 84 men >20 years of age referred from 2010-2017 due to oligozoospermia or nonobstructive azoospermia of unknown etiology. Twelve cases (14%) were diagnosed as DSD, including Klinefelter Syndrome, 46,XX testicular DSD, and mild androgen insensitivity syndrome. Y chromosome microdeletions were detected in 2 patients. Among the remaining 70 cases there were patients with chromosome abnormalities which are not included in the DSD classification as well as rare NR5A1 variants of uncertain significance and hypergonadotropic hypogonadism and microorchidism in 46,XY subjects. In conclusion, the frequency of DSD in this study was 14%, consisting mainly of sex chromosome abnormalities but also 46,XX and 46,XY DSD. However, this figure may increase as further investigations are conducted in idiopathic cases with signs of primary testicular failure, which may present partial gonadal dysgenesis.

Neuroanatomical and molecular correlates of cognitive and behavioural outcomes in hypogonadal males.

Robust epidemiological, clinical and laboratory evidence supports emerging roles for the sex steroids in such domains as neurodevelopment, behaviour, learning and cognition. Regions of the mammalian brain that are involved in cognitive development and memory do not only express the classical nuclear androgen receptor, but also the non-genomic membrane receptor, which is a G protein-coupled receptor that mediates some rapid effects of the androgens on neurogenesis and synaptic plasticity. Under physiological conditions, hippocampal neurons do express the enzyme aromatase, and therefore actively aromatize testosterone to oestradiol. Although glial expression of the aromatase enzyme is minimal, increased expression following injury suggests a role for sex steroids in neuroprotection. It is therefore plausible to deduce that low levels of circulating androgens in males would perturb neuronal functions in relation to cognition and memory, as well as neural repair following injury. The present review is an overview of some roles of the sex steroids on cognitive function in males, and the neuroanatomical and molecular underpinnings of some behavioural and cognitive deficits characteristic of such genetic disorders noted for low androgen levels, including Klinefelter syndrome, Bardet-Biedl syndrome, Kallman syndrome and Prader-Willi syndrome. Recent literature in relation to some behavioural and cognitive changes secondary to surgical and pharmacological castration are also appraised.

Clinical outcomes of microdissection testicular sperm extraction (micro TESE) and intracytoplasmic sperm injection (ICSI) in patients with Klinefelter syndrome

Microdissection (Micro) TESE, in combination with intracytoplasmic sperm injection (ICSI), is presently used to treat infertility in cases of NOA including Klinefelter syndrome (KS). KS is the most common sex-chromosome disorder among infertile males, with a prevalence of 1 in 660 men and is a frequent cause of hypogonadism and infertility. The aim of this study is to assess the prevalence and the significance including sperm retrieval rate (SRR) by micro-TESE and ICSI outcomes with embryonic development in KS couples.

Pre-pregnancy cytogenetic analysis of general couples in eastern China.

The aim of this study was to investigate the contribution of chromosomal anomalies and the frequency of particular types of aberrations in general couples preparing for pregnancy and make recommendations for pregnancy on the basis of the medical literature. A total of 6,198 general couples were included in the present study. The karyotypes were generated from the peripheral blood lymphocyte cultures and the cytogenetic analysis was performed using G-banding. In 12,396 cases, chromosomal anomalies were detected in 59 cases (0.48%, 59/12,396). Among of them, the frequency of translocation was 0.35% (n = 43). Sex chromosomal anomalies accounted for 0.07% (n = 9), including Klinefelter syndrome (KS) (n = 4), Turner syndrome (TS) (n = 4), and XYY syndrome (n = 1). The others, including inversions (n = 6) and deletion (n = 1), accounted for 0.06%. Our study indicates that clinically important chromosomal defects are present at a remarkable frequency in the general couples in eastern China, suggesting pre-pregnancy cytogenetic analysis should be routinely performed among general couples in this area so that informed decision can be made, which will help to improve the quality of the pregnancy.

Microdissection testicular sperm extraction for non-mosaic klinefelter syndrome patients

OBJECTIVE: Fertilization and pregnancies can be obtained with spermatozoa recovered not only from the ejaculate, but seminiferous tubules (testicular sperm extraction, TESE). Microdissection (Micro)TESE, in combination with intracytoplasmic sperm injection (ICSI), presently is used to treat infertility in cases of NOA including Klinefelter syndrome (KS). KS is the most common sex-chromosome disorder among infertile males, with a prevalence of 1 in 660 men and is a frequent cause of hypogonadism and infertility. The aim of this study is to assess the prevalence and the significance including sperm retrieval rate (SRR) by micro-TESE in non-obstructive azoospermic patients including KS. DESIGN: Retrospective clinical analysis. MATERIALSANDMETHODS: The records were retrospectively evaluated for 1028 NOA patients (including 123 non-mosaic KS patients) who were underwent micro-TESE. Chromosomal analysis was performed on all patients on cultured lymphocytes from peripheral blood. Micro-TESE was used in which seminiferous tubule are directly examined throughout the testicle using an operating microscope and selectively biopsied for all of the NOA patients in modified Schlegel’s method. We did not undergo preoperative hormonal therapy for KS patients. In our study, KS patients did not have microdeletion of Y chromosomes. RESULTS: Testicular sperm were successfully retrieved by microTESE in 69 of 123 (56.1%) non-mosaic KS and 380 of 905 (42.0%) not KS NOA patients. Of these, 48 (69.6%) KS and 344 (90.5%) not KS NOA patinets had sperm identified through the initial wide incision alone. For patients with KS, the chance of sperm retrieval on the contralateral side after a negative unilateral microdissection was 28.0% (21/75) and significant higher than not KS NOA patients (36/5611⁄46.4%) (p <0.001). In almost all patients in whom micro-TESE was successful we could identify focal spermatogenesis in dilated and opaque seminiferous tubules surrounded by shrunken tubules or fibrous tissue. No correlation was found between serum FSH, LH, and T level with the success of sperm retrieval. Testicular volume also did not affect the SRR for micro-TESE. Patient age in successful micro-TESE for cases of KS is significantly younger (33.5 4.2 years) than that in failed cases (37.4 3.9 years) (p <0.05). CONCLUSION: Micro-TESE is particularly helpful for successful sperm retrieval in KS cases. In NOA, the absence of uniformity in testicular tissue is a critical key to succeed and rationale in microTESE.

Gonadoblastoma and selected other aspects of gonadal pathology in young patients with disorders of sex development.

Some patients with disorders of sex development (DSDs), previously known as intersex disorders, have abnormal gonadal development and an increased risk of germ cell tumors. Because of their relative rarity, however, many pathologists are unfamiliar with the morphological findings in the gonads of DSD patients and their clinical significance. This review concentrates on some of the most common DSDs where gonadal specimens may come to the attention of pathologists. It highlights the findings in gonadal dysgenesis, a DSD with a spectrum of clinical, pathologic, and molecular features but with the shared attributes of having both Y chromosomal material (even if in very limited amounts) in the gonad and also having mutations or deletions in genes necessary for normal gonadal development, mostly in those upstream of the SOX9 gene. This situation results in testicular tissue lacking normal Sertoli cells, which are now considered an essential element for the normal maturation of the primordial germ cells that migrate to the gonad from the embryonic yolk sac. Germ cells with delayed maturation mimic neoplastic germ cells, but there are both morphological and immunohistochemical differences. If the gonad having germ cells with delayed maturation also harbors the TSPY gene on the GBY locus of the Y chromosome, the cells may undergo neoplastic transformation and result in the distinctive gonadoblastoma, whose pathologic features are explored at length herein, including its potential for variant morphologies, such as a "dissecting" pattern. Another important DSD, the androgen insensitivity syndrome (AIS), is discussed at length, including the varied appearances of the testis and its distinctive lesions-hamartomas and Sertoli cell adenomas. The potential for germ cell neoplasia in the partial AIS is also discussed and contrasted with that of the complete AIS. A third major topic is ovotesticular DSD (true hermaphroditism). The clinical features and morphology of this condition are reviewed, including the arrangements of the tissue components in an ovotestis. Several other DSDs with distinctive gonadal findings are also considered, including Klinefelter syndrome, 5α-reductase deficiency, 17β-hydroxysteroid dehydrogenase deficiency, and female adrenogenital syndrome.

Chromosomal evaluation in a group of Tunisian patients with non-obstructive azoospermia and severe oligozoospermia attending a Tunisian cytogenetic department

Male infertility is the cause in half of all childless partnerships. Numerous factors contribute to male infertility, including chromosomal aberrations and gene defects. Few data exist regarding the association of these chromosomal aberrations with male infertility in Arab and North African populations. We therefore aimed to evaluate the frequency of chromosomal aberrations in a sample of 476 infertile men with non-obstructive azoospermia (n=328) or severe oligozoospermia (n=148) referred for routine cytogenetic analysis to the department of cytogenetics of the Pasteur Institute of Tunis. The overall incidence of chromosomal abnormalities was about 10.9%. Out of the 52 patients with abnormal cytogenetic findings, sex chromosome abnormalities were observed in 42 (80.7%) including Klinefelter syndrome in 37 (71%). Structural chromosome abnormalities involving autosomes (19.2%) and sex chromosomes were detected in 11 infertile men. Abnormal findings were more prevalent in the azoospermia group (14.02%) than in the severe oligozoospermia group (4.05%). The high frequency of chromosomal alterations in our series highlights the need for efficient genetic testing in infertile men, as results may help to determine the prognosis, as well as the choice of an assisted reproduction technique. Moreover, a genetic investigation could minimize the risk of transmitting genetic abnormalities to future generations.

Index of Suspicion in the Nursery

A term male infant is transferred to the NICU for persistent hypoglycemia at age 3.5 hours. The infant had a blood sugar level of 21 mg/dL at age 3 hours and despite refeeding 20 mL of 20 calories per ounce of formula, his blood glucose level remained at 20 mg/dL at 3.5 hours. The infant was born via cesarean delivery for a nonreassuring heart rate tracing to a 19-year-old G1P 0 African-American mother. All prenatal laboratory results were negative, including an oral glucose tolerance test. Prenatal ultrasonography was performed during the second trimester and showed no gross fetal anomalies other than the presence of a two-vessel cord. The infant cried spontaneously at birth and had some transient respiratory distress. The infant weighs 2,960 g (50th percentile) with a length of 48 cm (50th percentile) and a head circumference of 32.5 cm (25th–50th percentile). Results of the physical examination are normal except for a small penis (stretched penile length of 1.5 cm, width of 0.6 cm) and an undescended left testicle. Blood glucose levels below 40 mg/dL persist despite two boluses of 10% dextrose and administration of continuous dextrose infusion with a glucose infusion rate of ∼5 mg/kg per minute. Glucose levels above 40 mg/dL are eventually achieved with a glucose infusion rate of 8 mg/kg per minute. The pediatric endocrinology service was consulted on the second day for persistent hypoglycemia. A 3,490-g term male infant is born to a 20-year-old primigravida mother. She received good prenatal care, and her pregnancy was uncomplicated. Antenatal screening for human immunodeficiency virus, hepatitis B, and syphilis were negative, and she had immunity against rubella. Results of the patient’s cervical culture were positive for group B streptococcus, but she received adequate intrapartum penicillin prophylaxis before delivery. There was no abnormality noted on the fetal cardiotocography. …

Surgical recovery of sperm in non-obstructive azoospermia

The development of intracytoplasmic sperm injection (ICSI) opened a new era in the field of assisted reproduction and revolutionized the assisted reproductive technology protocols for couples with male factor infertility. Fertilisation and pregnancies can be achieved with spermatozoa recovered not only from the ejaculate but also from the seminiferous tubules. The most common methods for retrieving testicular sperm in non-obstructive azoospermia (NOA) are testicular sperm aspiration (TESA: needle/fine needle aspiration) and open testicular biopsy (testicular sperm extraction: TESE). The optimal technique for sperm extraction should be minimally invasive and avoid destruction of testicular function, without compromising the chance to retrieve adequate numbers of spermatozoa to perform ICSI. Microdissection TESE (micro-TESE), performed with an operative microscope, is widely considered to be the best method for sperm retrieval in NOA, as larger and opaque tubules, presumably with active spermatogenesis, can be directly identified, resulting in higher spermatozoa retrieval rates with minimal tissue loss and low postoperative complications. Micro-TESE, in combination with ICSI, is applicable in all cases of NOA, including Klinefelter syndrome (KS). The outcomes of surgical sperm retrieval, primarily in NOA patients with elevated serum follicle-stimulating hormone (FSH) (NOA including KS patients), are reviewed along with the phenotypic features. The predictive factors for surgical sperm retrieval and outcomes of treatment were analysed. Finally, the short- and long-term complications in micro-TESE in both 46XY males with NOA and KS patients are considered.

Comprehensive 5-Year Study of Cytogenetic Aberrations in 668 Infertile Men

The causes of male infertility are heterogeneous but more than 50% of cases have a genetic basis. Specific genetic defects have been identified in less than 20% of infertile males and, thus, most causes remain to be elucidated. The most common cytogenetic defects associated with nonobstructive azoospermia are numerical and structural chromosome abnormalities, including Klinefelter syndrome (47,XXY) and Y chromosome microdeletions. To refine the incidence and nature of chromosomal aberrations in males with infertility we reviewed cytogenetic results in 668 infertile men with oligozoospermia and azoospermia. High resolution Giemsa banding chromosome analysis and/or fluorescence in situ hybridization were done in 668 infertile males referred for routine cytogenetic analysis between January 2004 and March 2009. The overall incidence of chromosomal abnormalities was about 8.2%. Of the 55 patients with abnormal cytogenetic findings sex chromosome aneuploidies were observed in 29 (53%), including Klinefelter syndrome in 27 (49%). Structural chromosome abnormalities involving autosomes (29%) and sex chromosomes (18%) were detected in 26 infertile men. Abnormal cytogenetic findings were observed in 35 of 264 patients (13.3%) with azoospermia and 19 of 365 (5.2%) with oligozoospermia. Structural chromosomal defects and low level sex chromosome mosaicism are common in oligozoospermia cases. Extensive cytogenetic assessment and fluorescence in situ hybridization may improve the detection rate in males with oligozoospermia. These findings highlight the need for efficient genetic testing in infertile men so that couples may make informed decisions on assisted reproductive technologies to achieve parenthood.

Genetic Alterations Associated With Cryptorchidism

Cryptorchidism is the most frequent congenital birth defect in male children and represents an important risk factor for infertility and testicular cancer. Major regulators of testicular descent are the hormones insulin-like factor 3 (INSL3) and testosterone, and disruption of these pathways might cause cryptorchidism. To determine the frequency of genetic alterations in cryptorchidism. Case-control study in 2 departments of pediatric surgery in Italy between January 2003 and March 2005. Six hundred male infants with cryptorchidism. Boys were followed up for 2 to 3 years (through January 2008) and orchidopexy was performed in those who were persistently cryptorchid. We analyzed 300 noncryptorchid male children aged 1 to 4 years as controls. Karyotype anomalies and INSL3, INSL3 receptor, and androgen receptor gene mutations. The frequency of genetic alterations in boys with cryptorchidism was low (17/600 [2.8%; 95% confidence interval {CI}, 1.7%-4.5%]) and was significantly higher in participants with persistent cryptorchidism (16/303 [5.3%; 95% CI, 3.0%-8.4%]; P = .001) and those with bilateral cryptorchidism (10/120 [8.3%; 95% CI, 4.1%-14.8%]; P = .001) than in controls (1/300 [0.3%; 95% CI, 0.1%-0.8%]). Boys with persistent cryptorchidism had a 17-fold greater odds of having a genetic alteration (odds ratio, 16.7; 95% CI, 2.2-126.5). The most common genetic findings in those with cryptorchidism were 8 cases of Klinefelter syndrome and 5 cases of mutations in the INSL3 receptor gene. Genetic alterations were not found in boys with low birth weight or low gestational age, who had frequent spontaneous descent of the testes. In a small percentage of the study population, there was a statistically significant association between bilateral and persistent cryptorchidism and genetic alterations, including Klinefelter syndrome and INSL3 receptor gene mutations.

Genetik der männlichen Infertilität

Genetic causes of male infertility increase in frequency with decreasing sperm concentration (oligo-/azoospermia). The decision about genetic tests should be made after a complete andrological work-up. Common causes comprise chromosomal aberrations (including Klinefelter syndrome), microdeletions of the AZF loci of the Y chromosome, mutations in the gene responsible for cystic fibrosis (CFTR) causing CBAVD and in genes involved in hypogonadotropic hypogonadism (including Kallmann syndrome). Every genetic investigation should be accompanied by comprehensive genetic counselling to help with the interpretation of results and support the patient/the couple concerning consequences for their family planning and treatment options.

Molecular diagnosis of chromosomal aneuploidy including Klinefelter syndrome

Molecular diagnosis of chromosomal aneuploidy including Klinefelter syndrome