Prenatal diagnosis of 45,X/46,XY mosaicism with postnatal confirmation in a phenotypically normal male infant

Prenatal detection of chromosome mosaicism has always been a diagnostic dilemma. In 21 reported cases of chromosomal mosaicism in cultured amniotic fluid cells, only two cases had cytogenetic confirmation of the mosaicism. All 21 pregnancies resulted in either phenotypically normal liveborns or grossly normal abortuses. We report a case of XO/XY mosaicism detected prenatally and confirmed postnatally in a grossly normal male infant. The indication for prenatal cytogenetic diagnosis was advanced maternal age (38 years). A diagnosis of XO/XY mosaicism was made from two separate culture flasks of amniotic fluid cells, with 45,X cells predominating (86.4%). The Y chromosome was of normal size but carried no fluorescent band. The parents were counseled and were advised that the phenotype of XO/XY mosaicism can range from relative normality to sexual maldevelopment. They decided to continue this pregnancy. The infant was born at term and was a grossly normal male with normal penis and descended, normal-sized testes. Leukocyte culture from the cord blood and a skin fibroblast culture confirmed the mosaicism of XO/XY. The father's Y chromosome was of identical size and carried a small fluorescent band. It appears that an altered Y chromosome may be predisposed to anaphase lag leading to mosaicism.     

Pathogenetics of 45,X/46,XY gonadal mosaicism

Five patients with 45,X/46,XY mosaicism ranging from 8% to 66% of 46, XY lymphocytes in the peripheral blood were studied. Their age when chromosome studies were performed ranged from a few days to 37 yr. The phenotypic presentations were two females with gonadal dysgenesis and Turner syndrome features (cases 1 and 2), two males with ambiguous genitalia and mixed gonadal dysgenesis (cases 3 and 4), and an infertile male with an atrophic testis (case 5). Fluorescence in situ hybridization (FISH) using dual-color X and Y probes on paraffin-embedded sections of the gonads was performed to assess mosaicism. A mosaic cell line with a Y chromosome was present in the streak ovary, dysgenetic gonad, and testis. In the mixed gonadal dysgenesis cases (cases 3 and 4), the testis had a higher percentage (greater than two fold) of XY cells than the ovary had. However, the highest ratio of cells with a Y chromosome was in the atrophic testis of the infertile male (case 5). The distribution of mosaic clones in the different gonadal cell types was examined. Both females (cases 1 and 2) with dysgenetic gonads had scant ovarian stroma and nests of Leydig or hilus cells. In FISH studies, the coelomic epithelial cells were predominantly 46,XY; in comparison, the Leydig and hilus cells had a lower percentage and the ovarian stroma the least number of cells with a Y signal. A mixed gonadal dysgenesis case (case 3) possessed a right testis with an XY complement in approximately 21% of Sertoli cells and approximately 14% of Leydig cells. The infertile male had an atrophic testis with interstitial hyperplasia (case 5). His testis contained Sertoli cells but no evidence of spermatogenesis. FISH detected a Y signal in about 50-60% of the Sertoli and Leydig cells.     

True hermaphroditism with 46, XY/46, XX/47 XXY mosaicism (author's transl)

A case of true hermaphroditism was described. The patient had an uterus, a fallopian tube, a testide on the left in the position of the ovary and an ovary on the right side. The chromosome picture corresponded to a 47, XXY/46, XX/46 XXY mosaic. The phenotype of the patient was male so the decision for male sex seemed to be justified.     

A case of true hermaphroditism with 45X/46XY mosaicism

The authors describe a case of true hermaphroditism of mainly female phenotype, ambiguous genitalia, and ovotestis. The cytogenetic revealed 45X/46XY mosaicism and an absence of Barr bodies.     

Testicular juvenile granulosa cell tumor in an infant with X/XY mosaicism clinically diagnosed as true hermaphroditism

We report a testicular juvenile granulosa cell tumor (T-JGCT) with characteristic clinical and histopathological features. The tumor was present in the left abdominal testis of a 7-month-old infant with a 45,X/46,XY karyotype and ambiguous genitalia. Preoperatively, the infant was diagnosed as having functional testicular and ovarian elements based on elevated levels of serum testosterone and estradiol following human chorionic gonadotropin and human menopausal gonadotropin administration, respectively. Histologically, the left gonad contained a tumorous lesion composed of an admixture of cellular areas and multiple cystic follicles that had some continuity with the adjacent testicular tubules. Some tumor cells showed immunoreactivity for estradiol. The right gonad was a streak gonad containing small irregular nests of sex cord-type cells. No maturing ovarian follicle was present in either gonad. To our knowledge, this is the fifth reported case of T-JGCT with abnormal sex chromosomes, and the first case of T-JGCT confirmed to have not only the morphological but also the functional characteristics of granulosa cells.     

Gender identity and coping in female 46, XY adults with androgen biosynthesis deficiency (intersexuality/DSD).

Individuals living with an intersex condition have not received much attention in counseling psychology, although a high need for psychosocial care is obvious. Using a mixed-methods multiple case study with qualitative and quantitative data, the authors explore coping and gender experiences in seven 46, XY intersexual persons with deficiencies of androgen biosynthesis. These were assigned female at birth. At puberty, the participants experienced unexpected physical virilization due to 5alpha-reductase-2 (n = 3) and 17beta-hydroxysteroid dehydrogenase-3 deficiency (n = 4). All 7 received medical treatment (e.g., gonadal removal, genital surgery) to stop virilization and maintain the primarily assigned female sex and gender. The cases illustrate high adjustment challenges caused by the condition itself and the medical treatment experienced. None changed to male during adolescence as reported in previous studies. Highly variable patterns of gender identification become visible with subjectivities that do not only represent a binary gender model. Adult gender identity outcome of the participants is characterized by an increased uncertainty of gender identity, high male and low female gender identity. Implications for clinical management, particularly psychological counseling, are drawn. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Duchenne's muscular dystrophy in a girl with 45,X/46,XX chromosomal mosaicism

The paper is concerned with a case history of a girl with a rare combination of 2 rare anomalies (only 4 cases in the world literature); monosomia by X chromosome and Duchenne's muscular dystrophy. Mosaicism 45,X/46,XX in a 5 year old girl with a mild picture of Duchenne's muscular dystrophy was confirmed by a study of the kariotype in lymphocytes of the peripheral blood and skin fibroblasts. The authors indicate to a necessity of a thorough cytogenetical study in girls, if there is a clinical picture of Duchennes muscular dystrophy.     

Congenital diabetes in an infant with trisomy 21

A newborn infant with trisomy 21 was found to have congenital diabetes which appears to be permanent. Congenital diabetes is extremely rare and differs from type I or type II diabetes. It has never been reported previously in Down's syndrome and it seems to be due to a selective beta cell defect with undetectable C-peptide but normal alpha-cell function.     

Polymorphic detection of a parthenogenetic maternal and double paternal contribution to a 46,XX/46,XY hermaphrodite

OBJECTIVE AND IMPORTANCE: Epidural invasion and the resulting cord compression are clinical entities not usually associated with actinomycosis, and we found only 11 reported cases of cord compression caused by Actinomyces infection in the literature. Only one reported case was described as actinomycosis with epidural granuloma (14, 16), whereas in the other cases, epidural macroabscess (phlegm) formation caused the symptoms. Histopathological demonstration of the inflammatory granulation tissue and gram-positive sulfur-containing filamentous bacteria are important for the diagnosis of actinomycosis, because the clinical and microbiological studies cannot always demonstrate the causative microorganism and primary infection source. CLINICAL PRESENTATION: In this article, a case of Actinomyces infection causing cervical cord compression is presented. Precise diagnosis was accomplished using specific histopathological studies of the surgical specimens; such a precise diagnosis cannot always be achieved using preoperative investigations and microbiological studies. The treatment modalities and the patient's outcome are also discussed. CONCLUSION: As shown by hematoxylin and eosin stain, in contrast to the Nocardia species, Actinomyces filaments histopathologically are basophilic in nature and terminate in eosinophilic clubs as a predictive feature. The clinical and radiological findings closely resemble metastatic tumors and other infectious processes. A differential diagnosis is also emphasized in this article, along with a review of the literature.     

True hermaphroditism with XX/XY sex chromosome mosaicism: report of a case

A case of true hermaphroditism with 46, XX/46, XY karyotype is reported. The propositus, reared as a male, showed ambiguous external genitalia with perineoscrotal hypospadias, and internal genitalia represented by bilateral ovotestes, normal uterus and tubes. Periodic menstrual bleedings appeared at puberty. The endocrinologic data demonstrated the secretory activity of both the ovarian and the testicular tissue. The analysis of red cell, lymphocyte and serum markers, done on the propositus and on his parents, failed to show any evidence of double fertilization. On this basis, the origin of the XX/XY condition (mosaicism versus chimerism) and its developmental consequences are discussed.     

Infertility and multiple urogenital abnormalities in a male with mosaic 46,XY/45,XO/47,XXY karyotype and mixed phenotype

The effect of infusing the neuroactive steroids pregnanolone and iso-pregnanolone on somatosensory evoked potentials (SEP) and electrocortical (ECoG) activity was studied in unanaesthetised fetal sheep, 130-135 days gestation. Intravenous infusion of pregnanolone (6 mg/kg per h) significantly increased the proportion of high voltage ECoG (56.1+/-4.8% vs. control 43.5+/-3.2%, P < 0.05), and decreased low voltage ECoG (43.9+/-4.8% vs. control 56.6+/-3.2%, P < 0.05). Pregnanolone treatment decreased the amplitude of the N25 peak of the SEP (89.9+/-2.8% of control, P < 0.05) evoked following stimulation of the skin of the upper lip. In contrast, iso-pregnanolone treatment had no effect on ECoG activities, or on the amplitude and latency of peaks in the SEP. We conclude that 3alpha-hydroxy pregnane steroids are active at GABA(A) receptors in fetal sheep and can modulate sleep/wake activity before birth.     

Diploid/tetraploid mosaicism in the offspring of a 46XX/47XXX mosaic mother

A 10?-year-old boy with an IQ of 71, short stature, and isolated growth hormone deficiency was found to have diploid/tetraploid mosaicism. He was born to a 46xx/47xxx mosaic mother. The mother was found to be moderately mentally retarded but showed no other abnormalities. A review of literature pertinent to this case is presented.     

Elevation of serum luteinizing hormone levels during hydrocortisone treatment in infant girls with 21-hydroxylase deficiency

This preliminary study in 20 patients demonstrated that ultrasonic coronary angioplasty in the setting of bypass grafting is feasible, safe, and able to recanalize atherosclerotic vessels. Shorter monorail probes were superior to longer probes without guidewires in terms of success of vessel recanalization; >95% of particle debris was <25 microm in size.     

A child with presumptive monosomy 21 (45,XY,-21) in a family in which some members are Gq-

Presumptive monosomy for chromosome 21 was found in a male child with multiple malformations and severe psychomotor retardation. Chromosome analyses of cells from blood and skin samples were performed at intervals during the first few years of his life. In preparations stained with nonbanding was well as quinacrine, Giemsa, and reverse acridine orange banding techniques, only one No. 21 chromosome could be detected with no apparent abnormalities of the other chromosomes. The proband's phenotypically normal father, paternal grandfather, brother, and paternal aunt have a deletion for a short segment of the long arm of a G-group chromosome. Genetic-marker studies allow the exclusion of a number of blood groups as being associated with No 21. There is inconclusive evidence suggesting that expression of the Duffy blood group, which has been mapped to chromosome 1, may be influenced by genetic information on chromosome 21. This family is of potential value for further gene-mapping studies.     

Anemia and neutropenia due to copper deficiency in enteral nutrition

Although thrombomodulin (TM) in circulating blood is regarded as an indicator of vascular endothelial disorders, blood TM levels are also known to be affected by renal dysfunction. We measured plasma TM levels in primary glomerular disease (PGD) and lupus glomerulonephritis (GN) with the EIA method, and assessed the extent to which renal dysfunction and endothelial disorders contribute to plasma TM levels in these diseases. The plasma TM/serum creatinine (TM/Cr) ratio was significantly higher in lupus GN patients than in PGD patients or normal controls. A significant positive correlation was found between plasma TM and serum Cr levels in both PGD and lupus GN patients, but the slope (A) of the regression line (TM = A.Cr+B) in lupus GN patients was significantly steeper than in PGD patients. We conclude that plasma TM levels are greatly influenced by renal dysfunction, but that not only renal dysfunction but endothelial disorders may be an important determinant of increased plasma TM levels in diseases such as lupus GN.