Mixed Gonadal Dysgenesis in a 45,X Neonate with Chromosome Y Material in the Dysgenetic Gonad

Abstract

We report on a neonate with a disorder of sex development, Prader 3-4 external genitalia and a palpable structure in the right inguinal canal suggestive of gonadal tissue. Chromosome studies on blood lymphocytes showed monosomy of chromosome X. Laparoscopy identified a streak-like gonad on the left side, unicorn uterus and a dysgenetic testis on the right, attached to a Fallopian tube. Because of the unilateral palpable gonad and the presence of ambiguous genitalia we investigated further for the presence of Y material. Quantitative fluorescent PCR analysis of material from the dysgenetic gonad and skin fibroblasts revealed the presence of chromosome Y-derived sequences, suggesting sex chromosome mosaicism. In 45,X/46,XY mosaicism, chromosome studies carried out on peripheral lymphocytes do not always reflect the proportion of cell lines in the gonads. The detection of Y chromosome material in a dysgenetic gonad is extremely significant, due to the high risk of malignant transformation.

Combination of Gonadal Dysgenesis and Monosomy X with a Novo Translocation (13,14)

“…Hence there is the need to use the fluorescence in situ hybridization (FISH) and the polymerase chain reaction (PCR) which can improve greatly the detection of low-frequency cell line and possible structural abnormalities. Peripheral blood lymphocytes are the material of choice for cytogenetic analysis on patients with monosomy X [3, 6–8]. In our case, the detection of Y material by PCR and FISH was negative.…”

“…The chromosome studies carried out on peripheral lymphocytes do not always reflect the proportion of cell lines in the gonads. The detection of Y chromosome material in a gonadal tissue could be necessary given the risk of malignant transformation [3, 6]. This complementary research in the gonadal tissue or another tissue (buccal mucosa) could not be performed in our case.…”

Sex Chromosome Mosaicism in the Gonads of DSD Patients: A Karyotype/Phenotype Correlation

“…It was suggested that the presence of a double dose of the SRY gene initiated male sexual development, but the existence of a 45,X cell line affected the threshold of SRY expression needed to establish adequate testicular differentiation. On the other hand, Karatza et al [2009] reported a neonate with MGD presenting with ambiguous genitalia and a palpable gonad in the right inguinal canal with blood karyotypes showing a non-mosaic X monosomy, while the chromosome Y-derived sequence was detected in the dysgenetic gonad and skin fibroblasts by molecular analysis. They concluded that chromosome studies carried out on peripheral lymphocytes do not always reflect the proportion of cell lines in the gonads.…”