47,XXY/46,XX chromosomal DSD with mild virilization: challenges in the diagnosis and management

BASTIDA G; GRINSPON R P; AVILA S; DE CARLI C; DIAZ S; VENARA M; BERGADÁ , IGNACIO; REY RA

Florianopolis

Congreso; XXVIII latin american congress of pediatrics endocrinology; 2019

SLEP

Background:Sex-chromosome DSD may result from a single lineage of sex chromosomes, fromchimerism or from post-zygotic mosaicisms. Usually, virilization iscommensurate with the amount of functional testicular tissue and the proportionof cells carrying a Y chromosome. Various degrees of gonadal dysgenesis mayexist, and rarely ovotesticular differentiation occurs. We report a47,XXY/46,XX patient, with a predominant XXY cell line, mild virilization andpredominant ovarian tissue.CaseReport: A 10 months of age female patient was referred for mild clitoromegaly (unfusedlabia, distinct urethral and vaginal orifices). No gonads were palpable.Ultrasonography showed a uterus and a Fallopian tube and a structure compatiblewith gonad only on the right side. Basalsteroid levels were uninformative (17OHP 0.10 ng/ml, testosterone <10 ng/dland estradiol <10 pg/mL).  LH 0.60IU/L (NR 0.10-0.30), FSH 11.51 IU/L (NR 0.57-7.50), AMH (45 pmol/l( NR female 7-55)were midly elevated.  hCG-stimulatedtestosterone was higher for a girl (79 ng/dl), suggesting the presence ofscarce testicular tissue. Karyotype was 47,XXY [34]/46,XX[18], FISH analysisshowed XXY [118] /XX [82]. Ovotesticular DSD was suspected.  Laparoscopy confirmed the presence of uterusand Fallopian tubes. Gonadal biopsies showed the presence of ovarian tissuewith abundant primordial and primary follicles, but no testicular tissue wasobserved. FISH for the centromeric regions of the X (DXZ1) and Y (DYZ23)chromosomes on histological sections showed: XXY[74%]/XX[26%] in the rightgonad; XXY[65%]/XX [35%] in the left gonad.At 5 yearsof age, hormone levels were normal except mild increase of FSH (5.57 IU/L) andAMH (94.1 pmol/L).Conclusion:We report a female phenotype patient   47,XXY/46,XXDSD, with mild signs of androgenization, persistence of Mullerian structuresand gonadal biopsy showing exclusively ovarian tissue in spite of thepredominance of the XXY line. The existence of mild virilization and lowandrogen production in response to hCG suggests the existence of testiculartissue. Whether this has vanished or it is still present and not detected byhistological studies remains unsolved. The potential existence of testiculartissue in patient with a Y-chromosome cell lineage raises concern aboutmalignancy potential of the gonads and represents a challenge in itsmanagement, especially considering the fertility potential of the ovariantissue.