1/177. Defective sexual development in an infant with 46, XY, der(9)t(8;9)(q23.1;p23)mat. We report on a male infant with ambiguous genitalia (scrotal hypospadias, sinus urogenitalis) trisomic for 8q23-ter and monosomic for 9p23-ter, who shared craniofacial and other abnormalities with either phenotype. Gonadal histology was nearly normal for age. Normal endocrinological findings and exclusion of mutations in SRY, androgen receptor and alpha-reductase genes point to supplementary gene(s) located in 9p2305-ter, haplo-insufficiency (by deletion) of which is expected to cause defective male morphogenesis. CONCLUSION: This observation lends further support to the hypothesis that genetic factors are located at 9p23-ter which are involved in normal sex determination. ( info) |
2/177. Long arm deletion of chromosome 10 in a boy with monorchidism. We report on a boy with long-arm deletion of chromosome 10 and compare this case to 10 previously reported patients. He had right cryptorchidism and absence of the left testis, but the size of his penis was normal. cytogenetic analysis of the case showed the deficiency of 10q26.1-26.3 and the presence of 10qter. Four of 10 previously reported patients had an intersex phenotype, and all others had combinations of cryptorchidism, micropenis and hypospadias. These facts indicate that the terminal of chromosome 10q is strongly associated with abnormal male development. ( info) |
3/177. Gonadal histology with testicular carcinoma in situ in a 15-year-old 46,XY female patient with a premature termination in the steroidogenic acute regulatory protein causing congenital lipoid adrenal hyperplasia. Mutations in the steroidogenic acute regulatory protein (StAR) gene cause congenital lipoid adrenal hyperplasia, characterized by diminished or absence of adrenal and gonadal steroids, resulting in severe adrenal insufficiency and ambiguous or complete female external genitalia in genetic males. We report on a 15-yr-old 46,XY phenotypic female, referred because of lack of pubertal development. ACTH and gonadotropin concentrations were elevated; and aldosterone, cortisol and its precursors, and sex steroids before and after stimulation were below the lower limit of detection. In the StAR gene, a homozygous nonsense mutation (TGG --> TAG) in exon 7 (W250X) was identified. Histologic examination after gonadectomy showed seminiferous tubules containing immature sertoli cells and a few single germ cells with positive placental-like alkaline phosphatase immunoreactivity, indicating carcinoma in situ. This is the first report on testicular morphology, at a pubertal age, in a female patient with 46,XY karyotype and a mutation in the StAR gene, in whom gonadal neoplasia had developed. ( info) |
| We report three patients with XY pure gonadal dysgenesis. Two of these patients developed gonadoblastoma and associated dysgerminoma. Molecular analyses were undertaken to investigate the relationship between the formation of these tumors and Y chromosome aberrations. Deletion analyses were performed by polymerase chain reaction (PCR) amplification of y chromosome-specific dna sequences (PABY, SRY, DYS250, DYS254, and DYZ1). A cryptic deletion of the short arm of the y chromosome that included the PABY, SRY, DYS250, and DYS254 loci was observed in one of the patients (22-years-old) with an associated tumor. In the other two patients who did not demonstrate such a deletion, the sequence of the SRY open reading frame was determined by the dideoxynucleotide method. Two nucleotide substitutions followed by a seven nucleotide deletion were observed in the 3' end of HMG (high mobility group)-box in the other patient (15-years-old) with an associated tumor. The patient (22-years-old) without an associated tumor did not have the cryptic deletion or mutation of SRY. A y chromosome specific sequence (DYZ1) was demonstrated by PCR amplification of microdissected tumor tissues from these two patients. These results suggest that SRY may play a role in the formation of gonadal tumors, especially dysgerminoma. ( info) |
5/177. semen analysis and seminal plasma biochemistry in two brothers with familial reciprocal translocation 46,XY,t(8;9)(p10;p10) transmitted by the father. Here we report familial balanced translocation (46,XY,t(8;9)(p10;p10) inherited by two brothers from the father. The first subject, 33 years old, was examined after 3 years of childless marriage. semen analysis showed severe oligozoospermia, hypomotility and teratozoospermia. His brother, 29 years old, volunteered to join this study. He had not yet tried to start a family. semen analysis showed dyspermia, but the condition was much less serious than his brother's. In both subjects, the secretory function of the epididymis and the genital tract accessory glands did not seem to be affected by this particular translocation. This case report highlights the importance of cytogenetic analysis in dealing with infertile patients suffering from severe dyspermia apparently sine causa. This is particularly the case when certain Assisted Reproductive technology (art) programs are recommended, where natural selection of the sperm no longer takes place (e.g. ICSI). The possible risk of an increase in fetal chromosomal abnormalities would suggest genetic counselling in all such situations. ( info) |
| The occurrence of nephrosis in the first 3 months of life is rare and is termed 'congenital nephrotic syndrome.' The congenital nephrotic syndrome is a group of heterogeneous diseases with a clinical course that differs markedly from the childhood nephrotic syndrome. The coexistence of a congenital nephrotic syndrome and gonadal dysgenesis in a 46,XY karyotype with normal female external genitalia is extremely rare. Frequent severe infections are often seen in the Finnish type, but sepsis leading to death is rare in the neonatal onset of gonadal dysgenesis. This report describes an unusual case of complete XY gonadal dysgenesis in a 46,XY female neonate with the congenital nephrotic syndrome and overwhelming sepsis. ( info) |
7/177. Subsequent successful pregnancy and delivery after intracytoplasmic sperm injection in a patient with XY gonadal dysgenesisms. Report of a rare case of subsequent twin delivery after intracytoplasmic sperm injection (ICSI) into donated oocytes in a 30-year-old woman with a diagnosis of XY dysgenesis, who underwent a gonadectomy at the age of 13 years. Her husband suffers from severe oligo-astheno-terato-spermia. ( info) |
8/177. Syndromal (and nonsyndromal) forms of male pseudohermaphroditism. The term sex determination refers to the genetic events that bring about male or female gonadal development; sex differentiation to all subsequent morphogenetic and physiological events that establish functional sexuality, sexual dimorphism and the secondary sexual characteristics. Virtually all of the steps of sex differentiation are under genetic control; consequently each one of them can fail as result of mutation of the corresponding genes. We shall be concerned with those genes and their mutations that cause pseudohermaphroditism in males and more rarely in females (with the exception of congenital adrenal hyperplasia). Special emphasis will be placed on Swyer, Denys-Drash, RSH, GBBB, campomelic and ATR-X syndromes, whose genes were recently identified. ( info) |
| Gonadoblastomas are known to be hormonally active tumors that occur in streak or dysgenetic gonads of patients with intersex abnormalities. Several reports document their ability to produce beta-human chorionic gonadotropin (HCG), but none have documented an elevated peripheral serum beta-HCG. We report on the case of a patient with pure gonadal dysgenesis with XY karyotype who was found to have an elevated peripheral serum beta-HCG after a positive pregnancy test. knowledge of gonadoblastoma's potential to elevate serum beta-HCG levels may prevent unnecessary searches for other causes. ( info) |
10/177. Prenatal karyotype and ultrasound discordance in intersex conditions. An infant born at 38 weeks' gestation with ambiguous genitalia had a prenatal 45X karyotype but an enlarged phallus on an ultrasound scan at 31 weeks' gestation. The newborn examination demonstrated penoscrotal hypospadias with chordee and two gonads palpable in the scrotum with a right hydrocele. Ultrasound showed a saccular structure containing debris behind the bladder. The postnatal karyotype was revealed to be 45X/46XY, with a pseudodicentric y chromosome. cystoscopy/genitography identified a uterus and a right fallopian tube, which were removed along with a dysgenetic right gonad. biopsy of the descended left gonad revealed rare germ cells. The final diagnosis was 45X/46XY male pseudohermaphroditism with testicular dysgenesis. One should be aware of possible chromosomal mosaicism and combine the prenatal karyotype with the ultrasound genital findings to formulate an intersex differential diagnosis. ( info) |