1/19. A 46,XX fetus with external female and internal male genitalia, facial dysmorphic features and mildly dilated lateral ventricles of the brain: a new syndrome? The clinical features of a 46,XX fetus with dysmorphic facial features, mild dilatation of the lateral ventricles of the brain, and female external and male internal genitalia are described. This combination of abnormalities does not appear to have been reported previously, and may represent a new syndrome. ( info) |
2/19. Laparoscopic surgery for gonadal dysgenesis in children. Three pediatric phenotypic females presented with gonadal dysgenesis. Their gonads were removed laparoscopically. These phenotypically normal females, who do not have any intersex problems or ambiguous genitalia, represent a unique group of patients having a y chromosome or a fragment of it in their genetic constitutions. We performed laparoscopic adnexectomy with Endoloop ligatures or an ultrasonically activated scalpel. No significant complication occurred in any of the cases. Pathologic examination revealed gonadoblastoma in one of the gonads of one patient. We propose that laparoscopic surgery is a safe and minimally invasive procedure for prophylactic gonadectomy to prevent neoplasia, even when performed on pediatric patients. ( info) |
3/19. trisomy of the short stature homeobox-containing gene (SHOX), resulting from a duplication-deletion of the x chromosome. The turner syndrome (TS) is a complex disorder associated with almost invariant short stature and gonadal dysgenesis, as well as a variety of other major organ malformations. Recently, a homeobox-containing gene entitled short-stature homeobox-containing gene (SHOX), was isolated from a minimal short stature gene interval from the pseudoautosomal region of Xp (and Yp). Together with the demonstrable escape of SHOX from X-inactivation, this suggested SHOX to be a strong candidate gene for the short stature component of TS, and as SHOX haploinsufficiency appears to be the molecular basis of a mesomelic short statured skeletal dysplasia (Leri-Weill syndrome), this suggested that SHOX protein expression levels may confer a dosage effect on human stature. However, in this communication we report a normal statured female with gonadal dysgenesis, due to the inheritance of a recombinant duplication-deletion X-chromosome. The karyotype of the proband was 46,X,rec(X)dup(Xp)inv(X)(p11.22q21.2)mat and fluorescent in situ hybridization of her metaphases with a SHOX cosmid confirmed the proband to be trisomic for SHOX. This communication suggests the relationship between levels of SHOX expression and human stature to be more complex than envisaged previously. The presence of normal stature in our patient rather than tall stature is likely to represent the natural variation seen in patients with transcription factor disorders. ( info) |
| OBJECTIVE: To identify y chromosome material in an azoospermic male with an XX karyotype.DESIGN: Case report. SETTING: faculty of medicine and Centro de Patologia Celular (CPC) medical center. PATIENT(S): A 33-year-old man with infertility. INTERVENTION(S): G-banding, fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), and comparative genomic hybridization (CGH). MAIN OUTCOME MEASURE(S): FISH for X and Y chromosomes, PCR for the SRYgene and amelogenin gene in the Xp (AMGX) and (AMGY), and losses or gains with CGH. RESULT(S): FISH analysis using X and y chromosome-specific probes showed an x chromosome containing y chromosome sequences on the top of the short arm; this Y chromosome region was not visible by conventional cytogenetic analysis. PCR amplification of dna showed the presence of the sex-determining region of the y chromosome (SRY) and the amelogenin gene in the pseudoautosomal boundary of the x chromosome (AMGX). CGH confirmed the presence of the chromosome region Yp11.2-pter and detected the presence of the two otherwise normal X chromosomes. CONCLUSION(S): The two Xpter (XPAR1) pseudoautosomal regions present in this XX male suggest the need to reevaluate XX males using CGH and PCR to characterize the clinical variability in XX males due to genes other than those located on the y chromosome. ( info) |
5/19. SRY-positive 46,XX male with cryptorchidism as the only presenting clinical feature. The SRY gene, located on the short arm of the y chromosome, is responsible for differentiation of the testis from the undifferentiated gonad. We report a 4-year-old patient with male phenotype and female karyotype (46,XX) with cryptorchidism as the only presenting clinical abnormality. Fluorescent in situ hybridization analysis, using Y- and X-specific (whole chromosome painting WCP Y WCP X) dna and SRY probes, detected a small y chromosome fragment, including the SRY gene, transferred to the short arm of the x chromosome. ( info) |
6/19. Cytogenetic and molecular study of a premature male infant with 46,XX derived from ICSI: case report. We investigated the aetiology of the male phenotype in a premature infant derived from ICSI with a 46,XX karyotype. A karyotypically normal couple underwent ICSI because of obstructive azoospermia in the male partner. Sperm were retrieved by testicular sperm extraction (TESE), cryopreserved, and later used for ICSI. The pregnancy after ICSI ended at 20 weeks. A normal-appearing male was delivered but he did not survive. umbilical cord blood and placenta were sampled and used for molecular and cytogenetic investigation. The 46,XX karyotype from G-banding in this male infant correlated to a balanced female comparative genomic hybridization (CGH) profile in placental tissue. No PCR amplification of SRY on the p arm of the y chromosome was observed while fluorescence in-situ hybridization (FISH) with the SRY probe also could not detect the gene in cord blood or placental tissues. CGH and FISH, with X and Y centromeric probes, failed to detect mosaicism in the trophoblast, stroma and amnion. Skewed X-chromosome inactivation (81%) was found in the chorionic villi. The molecular and cytogenetic studies indicated a 46,XX male infant without the SRY gene or 46,XX/XY mosaicism. The possible mechanism in this SRY-negative XX male by ICSI is discussed. ( info) |
7/19. XX-agonadism in a fetus with multiple congenital anomalies. We report on an 18-week gestation fetus with 46,XX karyotype, gonadal agenesis, meningo-encephalocele, spina bifida, omphalocele, webbing of right upper limb, deformed right clavicle and right sided ribs, absent interventricular septum, hypoplastic aorta, hypoplastic spleen, and single umbilical artery. This case is similar to the one previously described by Kennerknecht et al. in 1997 and may represent a unique syndrome. ( info) |
| Although testicular development has been shown to be variably impaired in XY patients with distal 9p monosomy, ovarian and other genitourinary phenotype has poorly been studied in XX patients monosomic for the distal 9p region. Thus, we studied a 13-month-old infant with 46,XX,der(9)t(9;10)(p23;p13) (case 1) and an 11-year-old girl with 46,XX,der(9)t(9;16)(p23;q22) (case 2). Case 1 had primary hypogonadism (basal serum follicle stimulating hormone [FSH], 40.0 mIU/mL; leteinizing hormone [LH], 1.2 mIU/mL; estradiol [E2], <10 pg/mL), whereas case 2 had age-appropriate pubertal development (breast, Tanner stage 4; pubic hair, Tanner stage 3; menarche 11.7 years of age) and hormone values (FSH, 7.3 mIU/mL; LH, 6.7 mIU/mL; E2, 47 pg/mL). In addition, case 1 had hypoplastic labia majora, short distance between the vaginal orifice and the anus, and five renal cysts, and case 2 had anal atresia, short distance between the vaginal orifice and the anus, bilateral hydronephrosis of grade 3 with probable ureteropelvic junction stenosis, and renal dysfunction (serum creatinine, 1.52 mg/dL; urea nitrogen, 34.5mg/dL). fluorescence in situ hybridization analysis for five regions and microsatellite analysis for 10 loci on 9p confirmed hemizygosity for the distal 9p region with the breakpoints between IFNA and D9S285 in case 1 and between D9S168 and D9S286 in case 2. The results, in conjunction with the previous data in XX patients with molecularly defined distal 9p monosomy, are consistent with the presence of a gene(s) involved in the development of indifferent gonad or subsequent ovarian differentiation in a approximately 11 Mb region distal to D9S168. In addition, it is possible that a gene(s) for anoperineal and renal development also maps distal to D9S168 and that for external genital development maps distal to D9S285 at the position approximately 16 Mb from the 9p telomere. ( info) |
9/19. An unusal case of hermaphroditism--a 46,XX/69,XXY chimera. A diploid/triploid karyotype is an uncommon but important cause of true hermaphroditism and ambiguous genitalia. Individuals have a recognisable phenotype and characteristic hydatidiform placental changes. We report a 46,XX/69,XXY chimeric hermaphrodite. This case highlights the typical features (large placenta, intrauterine growth retardation, asymmetric growth, cranio-facial anomalies, syndactyly and pigmentary dysplasia). It illustrates the importance of obtaining skin and gonadal karyotypes in the case of genital ambiguity, as the venous lymphocytic karyotype is usually diploid. ( info) |
| Non-random de novo autosomal chromosomal rearrangements have not been shown to cause exocrine or gonadal dysfunction. We report on two siblings, a brother and a sister, both with de novo chromosomal rearrangements and gonadal deficiency including premature ovarian failure. They had normal phenotypes without additional manifestations of known chromosomal breakage syndromes (except for the gonadal dysfunction) and normal alpha-fetoprotein dosage level. The association of sperm abnormalities in the brother and ovarian dysfunction in the sister suggested an increased spontaneous chromosomal instability. Since the co-occurrence of chromosomal anomalies and reproductive failures may not be coincidental, we performed repeated chromosomal analysis of peripheral blood lymphocytes prior to proposing ICSI for IVF (for the brother). In both sibs, infertility was associated with random and non-random de novo autosomal chromosomal abnormalities. We discuss the possible relationship between these unusual clinical and cytogenetic features and their potential links to ataxia-telangiectasia. ( info) |