Ovarian Gonadoblastoma with the Karyotype of 46, XX: A Case Report

Gonadoblastoma is a rare tumor comprised of sex cord derivatives and germ cells. The risk for developing gonadoblastoma increases significantly in patients who possess a Y chromosome or Y chromosome material. A 49-year-old Chinese woman found a pelvic mass during a routine physical examination. Pathological analysis after surgery indicated that the tumor was unilateral ovarian gonadoblastoma with dysgerminoma. Compared with other cases in the literature, our patient was the oldest, and the tumor mass was smaller. Karyotype analysis of peripheral blood lymphocytes revealed that the woman had a 46, XX female karyotype. Whole-exon sequencing revealed that some mutations, such as altered somatic genes in the Forkhead box protein O (FoxO) signaling pathway and KIT, might cause the disease. In conclusion, we described a rare case of gonadoblastoma in a woman who had normal routine menstruation, sexual development, and successful pregnancies and possessed a normal female 46, XX karyotype.

Can Boys Have Turner Syndrome? More than a Question of Semantics

Individuals with 45,X mosaicism with Y chromosome material raised as boys are not diagnosed with Turner syndrome, a label restricted to phenotypic females. We sought to determine if boys with 45,X mosaicism had features consistent with Turner syndrome. Twenty-two patients (14 girls, 8 boys) seen in our Differences of Sex Development (DSD) clinic were identified for review. Standardized height (z-scores) by sex of rearing and results of cardiology, renal, audiology, thyroid, and celiac screenings were recorded. All subjects had heights below the mean for sex. Z-scores were not significantly different between boys and girls (<i>p</i> = 0.185). There were no significant differences in the incidence of cardiac anomalies between boys and girls (<i>p</i> = 0.08). Girls were more likely to have additional screenings (<i>p</i> = 0.042), but there were no significant differences in the number of positive screenings between boys and girls (<i>p</i> = 0.332). Patients with 45,X mosaicism raised as boys appear to have features similar to patients with the same karyotype raised as girls. Routine screening of boys following the Turner Syndrome Clinical Practice Guidelines may allow early recognition of comorbidities. Additionally, obtaining karyotypes on boys with short stature or other features of Turner syndrome may identify unrecognized cases of 45,X mosaicism.

Karyotype is associated with timing of ovarian failure in women with Turner syndrome

Objective To characterize the age of ovarian failure in Turner Syndrome (TS) patients by karyotype. Methods Retrospective cohort study of individuals with TS at an academic university hospital. Subjects were seen in TS Clinic at UNC Hospital between 2014 and 2018. Individuals were analyzed by karyotype category (45X, 45X/46XX mosaicism, miscellaneous) and percentage of 45X cells. Age at follicle-stimulating hormone> 30 was defined as the age at loss of ovarian function. Results A total of 79 patients were identified after excluding individuals with unknown ovarian function and those with Y chromosome material. Thirty-eight percent were 45X monosomic, 62% were 45X/46XX mosaic or miscellaneous karyotypes. Fifty-five of 79 (70%) patients had evidence of ovarian failure, median age of failure 11 years (IQR: 4,12). Ovarian failure was more prevalent among individuals with 45X karyotype (100%). The median age of ovarian failure for 45X patients (n=30) was 10 years old, which is significantly younger than other karyotypes (n=49), with a median of 15 years, p<0.01. Linear regression analysis found that 1 percentage point increase in 45X cells in the peripheral karyotype is associated with a 0.09 year decrease in age of ovarian failure (p value=0.01). Only 9% of individuals were referred for fertility counseling. Conclusions There is a lower prevalence of ovarian failure among individuals with mosaic TS karyotypes, and referral rate for fertility counseling of patients with TS is low. These findings are in line with published literature. The finding that percentage of 45X cells in peripheral karyotype is associated with earlier age of ovarian failure is novel and warrants further investigation in a larger prospective cohort.

Elements of Medical Cytogenetics

Chromosome is a combination of Greek words meaning colored (chrom) body (soma). Albeit that molecular methodologies have substantially taken over from classical cytogenetics, and providing a different view of the genetic material, the word chromosome will surely last forever. This chapter provides a very brief historical introduction, and a basic introduction to what chromosomes are, and the ways in which they can be abnormal. The distinction is made between disorders in which there is an excess (trisomy, duplication) of chromosome material, and those in which there is a deficiency (monosomy, deletion). Ethical questions are rehearsed that may arise in the context of the clinical management of chromosome abnormalities.

Prevalence and Physical Distribution of SRY in the Gonads of a Woman with Turner Syndrome: Phenotypic Presentation, Tubal Formation, and Malignancy Risk

Although monosomy X is the most common karyotype in patients with Turner syndrome, the presence of Y chromosome material has been observed in about 10% of patients. Y chromosome material in patients with Turner syndrome poses an increased risk of gonadoblastoma and malignant transformation. We report a woman with a diagnosis of Turner syndrome at 12 years of age, without signs of virilization, and karyotype reported as 46,X,del(X)(q13). At 26 years, cytogenetic studies indicated the patient to be mosaic for monosomy X and a cell line that contained a du­plicated Yq chromosome. Bilateral gonadectomy was performed and revealed streak gonads, without evidence of gonadoblastoma. Histological analysis showed ovarian stromal cells with few primordial tubal structures. FISH performed on streak gonadal tissue showed a heterogeneous distribution of SRY, with exclusive localization to the primordial tubal structures. DNA extraction from the gonadal tissue showed a 6.5% prevalence of SRY by microarray analysis, contrasting the 86% prevalence in the peripheral blood sample. This indicates that the overall gonadal sex appears to be determined by the majority gonosome complement in gonadal tissue in cases of sex chromosome mosaicism. This case also raises questions regarding malignancy risk associated with Y prevalence and tubal structures in gonadal tissue.