Importance of the number of metaphases analysed to exclude chromosomal DSD.

CASALI BARBARA; GRINSPON R P; REY RA; DEL REY G

San Pablo

Simposio; 7th International DSD Symposium; 2019

I-DSD

Introduction: Chromosomal disorders of sex differentiation(DSD) may be caused by a chromosomal mosaicism. A low number of metaphases analysedmay hamper the detection of chromosomal mosaicism.Case report: a 7-day-old newborn was referred for genitalambiguity. Phallus length and width were 20 and 10 mm respectively, a non-pigmentedbifid scrotum and a perineal-scrotal hypospadias were observed. Left gonad was in scrotal position (2 ml) andright gonad was not palpable. Karyotype in 30 cells was 46,XY. Hormonalevaluation performed at 7 days of life showed high gonadotrophins (LH 10.04 IU/L,FSH 11.41 IU/L, testosterone (136 ng/dL) in the normal male range and AMH (212pmol/L) below the normal male reference levels. 46,XY dysgenetic DSD wasdiagnosed and male sex was assigned.  Thestudy of SRY and NR5A1 genes was normal. At 2 years of life, a laparoscopy was performed.Right abdominal gonad was macroscopically compatible with a streak, so it wasremoved. The histology report described the presence of a streak associatedwith a hypoplastic epididymis and a Fallopian tube and a rudimentary uterus. Leftorchidopexy and biopsy was performed at 5 years of age, due to acquiredcryptorchidism. The histological study described a thin albuginea and scarceseminiferous tubules with isolated germ cells, compatible with a dysgenetictestis. Altogether, these findings confirmed asymmetric gonadaldifferentiation, with a left dysgenetic gonad and a right streak. A newkaryotype was performed on 100 metaphases: mos 45,X [7]/46,XY [93].Conclusion and discussion: The assessment of an insufficient number ofmetaphases may yield a false negative result when a mosaicism is suspected. Thestudy of a sufficient number of metaphases is necessary to rule out thepresence of a mosaicism. As an example, 100 metaphases allow to exclude amosaicism ¡Ý 3% with95% confidence. The identification of an 45,X lineage avoids expensive andunnecessary molecular studies and drives the attention to comorbidities like growthretardation, cardiac and renal malformations and autoimmune diseases.