Klinefelter syndrome with hypogonadotropic hypogonadism and absence of Leydig cells

Klinefelter's syndrome is characterized by hypergonadotropic hypogonadism, 47,XXY karyotype, gynecomastia, azoospermia and testicular atrophy with hyalinization of seminiferous tubules and hyperplasia of Leydig cells. Some cases of Klinefelter's syndrome with unexplainably low levels of gonadotropins have been reported in the literature. Two additional cases of Klinefelter's syndrome with hypogonadotropic hypogonadism and absence of Leydig cells are described.     

Effects of gonadotropin and testosterone treatments on plasma leptin levels in male patients with idiopathic hypogonadotropic hypogonadism and Klinefelter's syndrome

Since little is known about the effects of gonadotropin and testosterone treatment on leptin levels in male hypogonadism, we determined fasting plasma leptin levels before and 3 months after treatment in 21 patients with idiopathic hypogonadotropic hypogonadism (IHH), 16 patients with Klinefelter's syndrome and 20 male controls. Patients with IHH were treated with hCG/human menopausal gonadotropin, whereas patients with Klinefelter's syndrome received T treatment. Plasma leptin levels were measured by an RIA with a sensitivity of 0.5 microg/L. Mean leptin levels in patients with IHH before treatment (9.23+/-4.09 microg/L) were not significantly different from those in patients with Klinefelter's syndrome (7.29+/-5.05 microg/L; z=-1.41; P=0.15). Leptin levels in both IHH and Klinefelter's syndrome groups were, however, significantly higher than in the normal men (3.91+/-1.67 microg/L) (P<0.001 and P<0.01, respectively). Mean leptin levels did not change significantly 3 months after the initiation of gonadotropin (11.6+/-6.44 microg/L) or T (8.32+/-5.17 microg/L) treatment in either IHH or Klinefelter's syndrome. Our study demonstrated that mean plasma leptin levels are not influenced by short-term gonadotropin or T treatment in male hypogonadism.     

Testicular sperm recovery in nine 47,XXY Klinefelter patients

Klinefelter's syndrome is generally characterized by hypergonadotrophic hypogonadism and azoospermia. The clinical features, however, are variable, and occasionally severe oligozoospermia may be present. Usually in these cases a 46,XY/47,XXY mosaic karyotype is involved. However, focal spermatogenesis and severe oligozoospermia have been reported in 47,XXY individuals too. In the present study we investigated whether testicular spermatozoa can be recovered in 47,XXY patients with a view to intracytoplasmic sperm injection (ICSI). In four out of nine apparently non-mosaic 47,XXY patients, spermatozoa were recovered from the wet preparations of testicular tissue and ICSI was performed in three couples. In one patient in whom spermatozoa were successfully recovered and used for ICSI, no spermatozoa were retrieved at a second trial. Although these results show that in some 47,XXY individuals testicular spermatozoa can be successfully recovered and even used for ICSI, at present this approach should be considered experimental. There may indeed be some concern about the chromosomal normality of the embryos generated through this infertility treatment. Patients with Klinefelter's syndrome should therefore be counselled about the complexity of this treatment, which involves multiple testicular biopsies from hypogonadal testes, ICSI and preimplantation diagnosis by fluorescence-in-situ hybridization.     

Diagnosis of genetic defects by chromosomal analysis

Of 901 karyotypes performed over a period of 4 years, genetic anomalies were detected in 162 cases. Down's syndrome (trisomy 21) was the most common (168.8%) genetic disorder followed by Turner's syndrome, Philadelphia chromosome, Klinefelter's syndrome, Edward's syndrome (trisomy 18) and Patau's syndrome (trisomy 13). All the three trisomies were detected very early in life. Mean age at the time of diagnosis for Turner's syndrome was 13.3 years, allowing a timely hormone replacement therapy to improve secondary sexual characters. Patients with Klinefelter's syndrome were diagnosed late (mean age 23.6 years), which greatly reduced their chances of an effective therapy to improve the clinical and social outcome.     

Anesthetic drug interactions

A patient with bipolar disorder and previously undiagnosed Klinefelter's syndrome presented with acute mania refractory to pharmacotherapy and was successfully treated with electroconvulsive therapy. This case constitutes the 31st case report documenting the coexistence of bipolar disorder with chromosomal anomalies and the 14th such patient with Klinefelter's syndrome. The relevance of this case to understanding the genetics of bipolar disorder is explored through a review of previously published reports of bipolar patients with chromosomal abnormalities. The relatively high incidence of Klinefelter's syndrome among this group of patients is discussed in the context of evidence for linkage of bipolar illness to the X chromosome.     

Benign testicular tumor associated with Klinefelter's syndrome

Testicular tumors associated with Klinefelter's syndrome are rare. We report a benign testicular epidermal cyst that was diagnosed in a patient with Klinefelter's syndrome. The association between testicular tumors and Klinefelter's syndrome, and management of a testicular epidermal cyst are discussed.     

The initiation and sequence of digital joint motion. A three-dimensional motion analysis

We report the first case of a child with mild dystrophinopathy associated with Klinefelter's syndrome (karyotype 47, XXY). This 3.5-year-old boy was affected by some symptoms suggestive of Becker's muscular dystrophy. Dystrophin immunostaining and immunoblotting procedures confirmed the diagnosis, but polymerase chain reaction-directed gene analysis failed to reveal any macrodeletion. Methylation-based assay did not show preferential X-inactivation. This confirmed the coexistence of the two active X-chromosomes (one of which was of paternal origin), thus accounting for the mild form of dystrophinopathy in this child affected by Klinefelter's syndrome.     

The role of the clinical rheumatologist in the establishment of a large sibling pair resource for systemic lupus erythematosus

OBJECTIVE: To report the sex chromosome aberrations in the sperm of a patient with mosaic Klinefelter's syndrome before ICSI. DESIGN: Case report. SETTING: Institute of Human Genetics, University Hospital PATIENT(S): A patient with an XXY/XXXY/XY mosaic Klinefelter's syndrome and extreme oligozoospermia. INTERVENTION(S): Skin biopsy, buccal smear, hair root sampling, and semen sampling. MAIN OUTCOME MEASURE(S): The karyotypes of three additional somatic cell systems and the ratio of sex chromosome aberrations in sperm. RESULT(S): After two-color fluorescence in situ hybridization of 202 interphase sperm nuclei, both the proportion of hyperhaploid 24, XY and 25, XXY sperm (5.0% and 0.5%, respectively) and of hyperhaploid 24, XX sperm (2.0%) were elevated. In contrast with peripheral lymphocytes, 93.9% of which showed sex chromosome aberrations, in the present patient only 7.5% of sperm proved to be hyperhaploid with an extra sex chromosome. CONCLUSION(S): The determination of sex chromosome aberrations in the sperm of a patient with mosaic Klinefelter's syndrome may provide additional information to estimate the transmission risk to his offspring.     

What journals for the physicians

An extragenital metastatic seminoma in a patient with Klinefelter's syndrome is described. The increased incidence of many types of malignancies in patients with this chromosomal abnormality and the increased susceptibility of XXY cells to transformation by oncogenic SV-40 virus are discussed. A relationship is suggested circumstantially by these observations.     

Hypospermiogenesis and chromosomal aberrations. A clinical study of azoospermic and oligozoospermic men with normal and abnormal karyotype

Clinical examinations including cytogenetical analyses were performed in 356 male partners of barren couples, 176 with azoospermia and 180 men with sperm counts below 10 million/ml. The chromosomal aberrations observed were: Klinefelter's syndrome (15 cases), 46 XX (3), 47 XYY (1), Y-chromosome anomalies (5), robertsonian (8) and reciprocal autosomal translocations (1), and 46 XY 16 h + (1). If minor variants were excluded this gave an incidence of constitutional chromosomal abnormalities of 11.9% in the azoospermia group and 4.4% in the oligozoospermia group. The phenotypes expressed by the specific anomalies showed great variations and appeared to be practically indistinguishable from those individuals having a normal karyotype.     

Primary mediastinal non-seminomatous germ-cell tumors: from clinics to biology

Primary mediastinal non-seminomatous germ-cell tumors (PMNSGCTs) are rare neoplasms that occur in young male adults. Incidence is evaluated about half that of extra-gonadal GCT. Their treatment is generally based on protocols used for testicular cancer, but with poorer results. Based on our experience of 40 patients with PMNSGCTs and data from the literature, we review here the clinical and biological data of these neoplasms. PMNSGCTs seem to constitute a specific entity, distinct from other GCT by the following criteria: true extra-gonadal origin, high incidence in patients with the Klinefelter's syndrome, over-representation of the yolk-sac component, poorer chemosensitivity and survival compared to other GCT, frequent occurrence of non-treatment related hematological neoplasia. The finding of an isochromosome of the short arm of the chromosome 12 in the leukemic karyotype is one of the strongest argument for a common origin in the yolk-sac component of the PMNSGCTs and their associated leukemia. Treatment of PMNSGCTs is still a challenge and should be conducted by a well-trained medical team.     

Rupture of silicone gel filled testicular prosthesis: causes, diagnostic modalities and treatment of a rare event

PURPOSE: Rupture of the envelope of silicone gel filled testicular prostheses is rare and alleged to be unlikely without intraoperative needle puncture. We observed that it may be caused by chronic intermittent trauma or a single acute increase of pressure, and report diagnostic and therapeutic modalities. MATERIALS AND METHODS: Four cases treated by us during the last 10 years are presented. One patient had testicular implants for Klinefelter's syndrome, whereas the other 3 had been treated for female-to-male transsexualism. Diagnosis was confirmed by ultrasonography and magnetic resonance imaging. The fibrous capsule surrounding the ruptured prosthesis was left intact to allow en bloc surgical extirpation. Histological evaluation of the resected specimen was performed. RESULTS: Rupture of silicone gel filled testicular implants may be caused by acute or chronic pressure without intraoperative needle puncture. CONCLUSIONS: Magnetic resonance imaging offers superior diagnostic accuracy and should be regarded the gold standard in the evaluation of implant rupture. Ultrasonography is an acceptable alternative. In cases when gross symptoms of scrotal inflammation are lacking replacement of implants is facilitated by the fibrous capsule that forms around any prosthesis. Transcapsular migration of silicone particles was observed even when the fibrous capsule was intact.     

Klinefelter's syndrome as a model for skin changes in venous insufficiency

Chronic venous insufficiency is a common disease with skin changes, varicosity and leg ulceration. Several theories have been proposed to explain all the changes that occur. We recently saw several patients with Klinefelter's syndrome complicated by leg ulceration and all the typical skin changes of venous insufficiency. The underlying disease was however lacking. They all showed disturbances in their fibrinolytic parameters. In this article we discuss (local) fibrinolytic disturbances as a possible factor in the pathogenesis of the skin changes in chronic venous insufficiency.     

Lipids in human testis

The lipid composition of human testis intesticular and post-testicular causes of infertility was studied. The testicular causes of infertility was represented by patients with adult seminiferous tubule failure and Klinefelter's syndrome. The post-testicular causes of infertility were represented by patients with obstruction of efferent ducts of testes. A significant accumulation of total testicular lipids was observed in both causes of infertility. A marked increase in free and esterified cholesterol, monoglycerides and triglycerides caused the accumulation of total testicular lipids in testicular causes of infertility. The accumulation of these lipids was more pronounced in Klinefelter's syndrome compared to adult seminiferous tubule failure. In post-testicular causes of infertility, a vary marked increase in phospholipids along with cholesterol fractions and glycerides led to the accumulation of total testicular lipids. The significant increase in total phospholipids caused by the increases in phosphatidylcholine and phosphatidylethanolamine differentiates post-testicular causes of infertility from testicular causes in which phospholipid classes remained unaffected. Thus, changes in hormonal mileu due to pathological conditions also lead to marked alterations in testicular lipids.     

Malignant cutaneous melanoma associated with neurofibromatosis in two sisters from a family with familial atypical multiple mole melanoma syndrome. Case reports and review of the literature

Two cases of malignant melanoma associated with neurofibromatosis in two first-degree female relatives from a family with familial atypical multiple mole melanoma (FAMMM) syndrome are presented. The types of neurofibromatosis and the FAMMM syndrome are discussed in relation to these cases and the family genealogic tree. Although the FAMMM syndrome could probably be seen as the underlying disease in the current cases, review of literature has failed to establish a clear relation. Research into pigmentary disturbance in neurofibromatosis is necessary to give a final explanation. To our knowledge, this is the first report in literature describing the familial occurrence of both diseases and it might present an addition to the tumor spectrum in the FAMMM syndrome.     

47,XYY syndrome. Is diagnosis of significance?

Over a 10-year period, from 1984-1995, in the Norwegian county of Vest-Agder, five patients in a paediatric clinic were diagnosed as having chromosome constitution 47,XYY. There are 1,250 males born a year in Vest-Agder. The patients were identified with bias, and not in a routine or prospective screening programme. All patients except one, a child who was diagnosed by chance at the age of one week; were admitted because of moderate conduct disorders or problems at school and striking tallness of stature. The half-brother of one of the 47,XYY boys had Klinefelter's syndrome 47,XYY. We conclude that identification of 47,XYY syndrome and information about it were of significance and help in counselling the patients and their families.     

The azoospermic factor on the Y chromosome

Azoospermia is the most frequent cause of male infertility. After excluding the obvious urological reasons and the effect of Klinefelter's syndrome, azoospermia may be caused by an abnormality in the crucial gene(s) expressed during male germ cell differentiation. Recently, two candidate genes for azoospermia have been cloned from the azoospermic factor (AZF) locus on the Y chromosome long arm (Yq). One is YRRM (Y chromosome RNA recognition motif) gene, and the other is DAZ (deletion in azoospermia) gene. Both genes encode RNA binding protein and their expression is restricted to the testis. Therefore they are good candidates for AZF, although their function remains unclear. Here, the genes on the Y chromosome possibly involved in spermatogenesis and the role of the Y chromosome in evolution are discussed.     

Management of collagen vascular diseases in childhood

Collagen vascular diseases seen in children include systemic, discoid and neonatal lupus, dermatomyositis, scleroderma, juvenile rheumatoid arthritis, and, in rare cases, Sjogren's syndrome. Although these diseases are uncommon in children, when seen, they are associated with significant morbidity. This review describes the clinical features of each condition and provides an overview of treatment options now available. These include numerous systemic treatments which can be used as steroid-sparing agents.     

Disseminated histoplasmosis in AIDS patients. A study of 2 cases and review of the Spanish literature

The characteristics of two cases of histoplasmosis in AIDS patients in our institution are presented together with a review of the 11 cases published in Spain since 1988 in addition to the current knowledge on histoplasmosis in patients with human immunodeficiency virus infection (HIV). In all except 2 of the 13 patients there was epidemiologic history of a stay in a country in which histoplasmosis is endemic. The 12 cases described in which this information is available had CD4 counts under 100/microL. The clinical manifestations of presentation were fever (92.3%) associated or not with other unspecific symptoms (asthenia, anorexia, cough, diarrhea) with a subacute course of two or three months. Physical examination demonstrated hepatosplenomegaly in 76.9% of the cases and 61.5% of the patients presented cutaneous lesions. Thoracic radiography was abnormal in 55% (61.5% had respiratory symptoms). Diagnosis was achieved by isolation of the fungus in the cutaneous biopsies in all the patients with dermatologic involvement and in 7 cases identification was performed in the bone marrow. In all the cases induction treatment was with anphotericin B and in those who reached the maintenance phase itraconazol was used in 7 cases and ketoconazol in one case. None of the patients treated with itraconazol, including the two in our center, presented recurrence at the time of completion of follow up. In conclusion, histoplasmosis is frequently presented as a prolonged febrile syndrome with unspecific characteristics, thus emphasizing the importance of including travel history to other countries in the anamnesis. The increase in journeys to endemic countries and immigration from these areas had led to an increase in the number of cases of histoplasmosis in patients with HIV infection in Spain.