Cases reported • Gonadal Dysgenesis, Mixed; Mixed Gonadal Dysgenesis

11/19. Partial androgen receptor deficiency and mixed gonadal dysgenesis in Drash syndrome.

Drash syndrome associates a nephropathy characterized by a diffuse mesangial sclerosis of early onset, wilms tumor, and male pseudohermaphroditism (MPH). A patient with Drash syndrome is reported with the following: karyotype 46,XY, external genitalia near normal female, mixed gonadal dysgenesis, severe androgen receptor deficiency demonstrated for the first time in this syndrome. The possibility of a common genetic denominator with the del 11p13 WAGR complex is suggested. MPH/nephroblastoma association is common. Androgen receptor deficiency has been observed in one case of each syndrome, respectively.

- - - - - - - - - -

ranking = 1
keywords = karyotype
(Clic here for more details about this article)

12/19. Dysgenetic male pseudohermaphroditism in a 45,X/46,X,del(Y)(q11.1) mosaic infant.

We describe an infant with dysgenetic male pseudohermaphroditism and the karyotype 45,X/46,X,del(Y)(q11.1). Histologic examination of the resected gonads showed cortical dysplasia indicative of incipient gonadoblastoma.

- - - - - - - - - -

ranking = 1
keywords = karyotype
(Clic here for more details about this article)

13/19. Juvenile granulosa cell tumor--another neoplasm associated with abnormal chromosomes and ambiguous genitalia. A report of three cases.

Three infants, 3 months of age or younger with abnormal karyotypes and ambiguous genitalia, had gonadal juvenile granulosa cell tumors. Two of the patients had mixed gonadal dysgenesis and the third had an intersexual disorder of undetermined type. Two tumors arose in undescended testes, and the third in an undescended gonad of uncertain nature. The occurrence of this uncommon neoplasm in these infants indicates that it is another type of neoplasm that may develop in the gonad of a patient with an abnormal karyotype and ambiguous genitalia.

- - - - - - - - - -

ranking = 2
keywords = karyotype
(Clic here for more details about this article)

14/19. h-y antigen expression in a case of mixed gonadal dysgenesis.

h-y antigen expression was studied on leukocytes and gonad-derived fibroblasts from a patient affected by mixed gonadal dysgenesis. Blood leukocytes and fibroblasts derived from the testis were typed H-Y positive, but the fibroblasts derived from the streak gonad were H-Y negative. Although the patient's karyotype was a mosaic, 45,XO/46,X+mar, as detected in-peripheral blood cells and testis-derived fibroblasts, all the fibroblasts derived from the streak gonad were 45,XO. These data suggests that the marker chromosome was in fact a Y-derived chromosome. Moreover, they showed that, at the gonadal level, a minority of H-Y positive 46,X+mar cells were able to organize a testis. Nevertheless, a large number of XO cells probably did not receive the testicular forming influence of the h-y antigen and of the other masculinizing factors.

- - - - - - - - - -

ranking = 1
keywords = karyotype
(Clic here for more details about this article)

15/19. Structural abnormalities of the y chromosome and abnormal external genitals.

Three infants with different types of Y-chromosome anomalies, including short- and/or long-arm deletion and mosaicism, are reported. The karyotypes of these patients were: 45,X/46, X,del(Y)/47,X,del(Y), del(Y) on peripheral lymphocytes and 45,X/46,2, del(Y) on gonadal tissue (case 1), 45,X/46X,del(Y) (case 2), and 45,X/46X,r(Y) (case 3). In case 1 the euchromatic segment on the deleted Y was distinctly larger than that of the father's Y. The three infants had no gross phenotypic anomalies except ambiguous genitals and low birth weight, and they were small for date. The histologic diagnosis in two of them was mixed gonodal dysgenesis (cases 1 and 2). The relationship between structural abnormalities of the y chromosome and ambiguous genitals as well as male-determining factors is discussed.

- - - - - - - - - -

ranking = 1
keywords = karyotype
(Clic here for more details about this article)

16/19. Ambiguous genitalia in an elderly woman with a mosaic 45,X/46,X,dic(Y)(Q11.2) karyotype.

A 66-year-old woman presented with clitoromegaly since childhood, primary amenorrhea, no breast development, and a large right inguinal hernia. A mosaic karyotype was identified containing a predominant 45,X cell line and a cell line with 46 chromosomes, one x chromosome, and a small dicentric y chromosome with a breakpoint in band qII.2. The patient underwent hysterectomy, bilateral gonadectomy, inguinal hernia repair, clitoral recession, and formation of a neointroitus. A dysgerminoma was identified in the right dysgenetic gonad. This report demonstrates the natural history of untreated mixed gonadal dysgenesis and the importance of early evaluation and treatment, as well as the molecular characterization of a dicentric y chromosome.

- - - - - - - - - -

ranking = 5
keywords = karyotype
(Clic here for more details about this article)

17/19. Mixed gonadal dysgenesis: histological and ultrastructural findings in two cases.

Mixed gonadal dysgenesis (MGD) is an intersex genetic abnormality characterized by a streak gonad and a contralateral testis (that is typically cryptorchid) or bilateral streak testes. A uterus and one or both fallopian tubes also may be present. The external genitalia are frequently ambiguous. We studied two phenotypic "females" with MGD. One had a mosaic 45X (40%) and 46XYq (60%) karyotype, a left streak gonad, and a small testis in a right inguinal hernia, whereas the other had a 46XY karyotype, a left streak gonad, and, on the right, a testis with gonadoblastoma. On histological and ultrastructural examination the testis in the first case showed prepubertal tubules lined by a few spermatogonia and immature sertoli cells with asynchronism in nuclear-cytoplasmic maturation. Ultrastructural examination of the gonadoblastoma in the second case showed neoplastic sertoli cells. Irregular maturation of sertoli cells appears to be a feature of MGD. Gonadal extirpation and pathological examination in these cases are important in order to make the correct diagnosis and prevent neoplastic changes.

- - - - - - - - - -

ranking = 2
keywords = karyotype
(Clic here for more details about this article)

18/19. Characterization of an isodicentric Y-chromosome for the long arm in a newborn with mixed gonadal dysgenesis.

A newborn infant was referred for evaluation because of ambiguous genitalia. Examination of the genitalia revealed a hypospadiac phallus measuring 1.5 cm in length with chordee. Subtle phenotypic features consistent with turner syndrome were present including hypertelorism, anti-mongoloid slant to the eyes, mild widening of the neck, but no definitive webbing, shield like chest and positive cubitus valgus. A pelvic and renal sonogram confirmed the presence of a uterus and normal-appearing kidneys. There was incomplete fusion of the scrotum. No gonads were palpable within the scrotal sac. The patient was assigned a female gender on the basis of the presence of a uterus, the phenotypic appearance of the genitalia and the malignant potential of the gonads. The cytogenetic findings with QFQ-banding revealed an abnormal karyotype, i.e., mos 46,X,idic(Y) (p11.2)[77]/45,X[29]/46,X,idic(Y) (p11?) [2]/ 47,XY,idic(Y)(p11.2)[2]/47,X,idic(Y)(p11.2), + idic(Y)(p11.2)[1]/46,XY[1]. The presence of an abnormal isodicentric Y-chromosome was evaluated by FISH-technique to ensure a finer characterization than routine methods. The genotype-phenotype correlation could not be established since mosaicisms of highly variable nature can exhibit an unpredictable outcome.

- - - - - - - - - -

ranking = 1
keywords = karyotype
(Clic here for more details about this article)

19/19. Discordant phenotypes and 45,X/46,X,idic(Y).

mosaicism introduces wide variability into the clinical expression of numerical and unbalanced structural chromosomal abnormalities. The phenotypic range of variability of 45,X/46,XY mosaicism extends from turner syndrome to mixed gonadal dysgenesis to normal males. The specific phenotype is primarily dependent on the chromosomal constitution of the developing gonad. Similar phenotypic variability is observed with mosaicism for 45,X and a second cell line with an abnormal sex chromosome. This report describes a patient with turner syndrome and a patient with mixed gonadal dysgenesis who have identical karyotypes, namely 45,X/46,X,idic(Y)(p11.2). While mosaicism alone might have accounted for the phenotypic differences, by PCR analysis the turner syndrome patient was SRY and ZFY negative and the mixed gonadal dysgenesis patient was SRY and ZFY positive.

- - - - - - - - - -

ranking = 1
keywords = karyotype
(Clic here for more details about this article)