Shifting syndromes: Sex chromosome variations and intersex classifications.

The 2006 'Consensus statement on management of intersex disorders' recommended moving to a new classification of intersex variations, framed in terms of 'disorders of sex development' or DSD. Part of the rationale for this change was to move away from associations with gender, and to increase clarity by grounding the classification system in genetics. While the medical community has largely accepted the move, some individuals from intersex activist communities have condemned it. In addition, people both inside and outside the medical community have disagreed about what should be covered by the classification system, in particular whether sex chromosome variations and the related diagnoses of Turner and Klinefelter's syndromes should be included. This article explores initial descriptions of Turner and Klinefelter's syndromes and their subsequent inclusion in intersex classifications, which were increasingly grounded in scientific understandings of sex chromosomes that emerged in the 1950s. The article questions the current drive to stabilize and 'sort out' intersex classifications through a grounding in genetics. Alternative social and historical definitions of intersex - such as those proposed by the intersex activists - have the potential to do more justice to the lived experience of those affected by such classifications and their consequences.

Clinical and social characteristics of Korean men with Klinefelter syndrome.

OBJECTIVES: To investigate the characteristics of Klinefelter syndrome in a consecutive series of men consulting for sexual as well as fertility problems in Korea. METHODS: A total of 179 men with non-mosaic 47,XXY Klinefelter syndrome of the 1876 azoospermic males who visited the fertility center of our university hospital between January 2002 and January 2010 were included in this analysis. Their semen characteristics, hormone profiles, size of the prostate gland, and education level were assessed and compared with an age-matched control group of 218 fertile males. Additionally, a histological evaluation was carried out. RESULTS: Prostate size, testicular volume, semen volume and symptom severity showed statistically significant differences in both groups (P < 0.0001). As the severity of signs and symptoms worsened, the education level decreased. Each degree of signs and symptoms was associated with a different level of education, as well as with significant differences in the level of testosterone and testicular volume (P < 0.05). Spearman's correlation coefficient showed the severity of signs and symptoms was associated with testosterone (P < 0.0001). CONCLUSIONS: Testosterone has the strongest negative association with the severity of signs and symptoms in patients with Klinefelter syndrome. It influences the reproductive capacity, as well as the manifested signs and symptoms of hypogonadism. Furthermore, it is also associated with various aspects of life in these patients.

Further evidence of the clinical, hormonal, and genetic heterogeneity of Klinefelter syndrome: a study of 216 infertile Egyptian patients.

This study aims to provide further insight into the phenotypic heterogeneity of Klinefelter syndrome (KS) by presenting clinical, hormonal, and genetic data from a large series of Egyptian infertile patients with KS. A retrospective case series of KS patients was studied over a period from January 2003 to April 2010. All patients underwent a complete history and physical examination; color duplex examination; semen analysis; measurement of total testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and prolactin (PRL); and chromosomal typing. Mosaic KS diagnosis was confirmed by fluorescence in situ hybridization. The series included 216 KS patients (198 nonmosaic, 16 mosaic, and 2 KS variants). Typical clinical signs of hypoandrogenism were observed in 86% of patients. Gynecomastia affected 20.8% of the patients. Eunuchoidal body proportions, with arm span exceeding height and lower segment length exceeding upper segment length, were detected in 43.9% and 64.4% of the patients, respectively. In all patients, a reduction in testicular size and azoospermia were detected. Normal levels of T, FSH, LH, E2, and PRL were detected in 44.5%, 3.7%, 3.3%, 93.5%, and 91.2% of patients, respectively. Differences were not significant between patients with classic KS and those with mosaic KS in terms of the frequency of clinical signs of hypoandrogenism, gynecomastia, low T concentrations, or high concentrations of FSH, LH, E2, and PRL (all P > .05). The results of the current study emphasize the heterogeneous clinical, hormonal, and genetic phenotype of infertile KS patients. Our findings support the usefulness of cytogenetic studies in infertile patients showing small testicular size and azoospermia, regardless of the presence of other clinical or endocrine findings.

Clinical and behavioral features of patients with Borjeson-Forssman-Lehmann syndrome with mutations in PHF6.

OBJECTIVE: To describe clinical and behavioral features of 10 men from 2 families with Borjeson-Forssman-Lehmann syndrome (BFLS) and missense mutations in the PHF6 zinc-finger transcription factor gene. STUDY DESIGN: BFLS behavioral features were compared with other age-matched men with other syndromes and similar intellectual functioning through the use of standardized questionnaires: the Child Behavior Checklist, the Vineland Adaptive Behavior Scales, and the Reiss Personality Profile. Participants included 10 with BFLS, 10 with Prader-Willi syndrome, and 23 with Klinefelter syndrome variants (13 with 48,XXYY, 4 with 48,XXXY, and 6 with 49,XXXXY). RESULTS: Contrary to initial reports, our men with BFLS had no microcephaly, seizures, or short stature. They manifested deep-set eyes with large ears, coarse facial features, small external genitalia, gynecomastia, and obesity. Family A had mild to moderate mental retardation, whereas family B was more severely affected. On Vineland Adaptive Behavior Scales, men with BFLS had higher daily living and social skills than communicative skills. Men with BFLS also had lower internalizing and externalizing symptoms and appeared more social and helpful than men with Prader-Willi syndrome or Klinefelter syndrome variant. CONCLUSIONS: Men with BFLS from 2 families with mutations in the PHF6 gene manifested distinctive clinical features and a low risk for maladaptive behaviors.

Y chromosome microdeletions in idiopathic azoospermia and non-mosaic type of Klinefelter syndrome.

The objective of this study was to elucidate the cause of the spermatogenic defect in idiopathic azoospermia and non-mosaic type of Klinefelter syndrome. Genomic DNAs from 9 cases of Korean idiopathic azoospermia and 6 of Korean non-mosaic type of Klinefelter syndrome were used for the detection of Y chromosome microdeletions by polymerase chain reaction using 60 primers. Microdeletions of the Y chromosome were found in 1 of 9 (11.1%) patients with idiopathic azoospermia, whereas none was deleted in non-mosaic type of Klinefelter syndrome. This result suggests that Y chromosome microdeletions could be one of the etiologic factors in idiopathic azoospermia.

[Genetic aspects of the 46, XX male]. / Aspects génétiques du mâle 46, XX.

The XX males represent a proportion of 1/25 of all patients suffering of the Klinefelter syndrome. From a clinical and endocrinological point of view, they exhibit a hypogonadotropic hypogonadism. Isolated cases are rare and familial forms are exceptional. The XX males may be divided in 3 subgroups: 46, XX males with the SRY gene; 46, XX males without the SRY gene and XX/XY mosaics.