A Case of 45,X/46,XY Mosaicism Presenting as Swyer Syndrome

Chand, Momal; Turner, Stefanie; Solomon, Liza; Jay, Allison; Rabah, Raja; Misra, Vinod K.

doi:10.1016/j.jpag.2020.06.008

Cited by 12 publications

(22 citation statements)

References 8 publications

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“…46,XY DSD is a highly heterogeneous group , which includes many different clinical and genetic variants. The cases of cryptic tissue gonosomal mosaicism with the 45,X cell line in 46,XY DSD patients with testicular gonadal dysgenesis (including Swyer syndrome patients), ovotesticular DSD, and testicular regression are described in literature [15][16][17][18][19]. The 45,X cell line presence in the bipotential gonad may negatively affect its further differentiation [20].…”

Section: Discussionmentioning

confidence: 99%

Inter-Tissue Gonosomal Mosaicism in Patients with Disorders of Sex Development, Associated with Abnormalities of Gonadal Differentiation

et al. 2021

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We present results of the study to identify gonosomal mosaicism and examine its inter-tissue variability in peripheral blood lymphocytes, buccal epithelium, and gonadal tissue in patients with disorders of sex development (DSD) associated with sex chromosome abnormalities (gonosomal DSD, n = 8) and gonad differentiation anomalies (46,XY DSD, n = 10). The study used a set of methods for analyzing individual cells: karyotyping and interphase FISH. According to the study results, gonosomal mosaicism was detected in 12 (67%) of the 18 examined patients. Cryptic, isolated by gonadal tissue, somatic mosaicism with 45,X cell line was detected in 4/10 46,XY DSD group patients. True inter-tissue mosaicism with two cell lines, one of which 45,X, was detected in 8/8 gonosomal DSD group patients. We propose using a new approach for mosaicism examination and quantifying mosaic cell lines variability. For this purpose, the coefficient of variation (CV) was used, the range of detected values was from 2.3 to 49%. In accordance with the obtained CV values, the inter-tissue variability was estimated as low, moderate or high. The correlation analysis revealed a statistically significant (p < 0.1) inverse correlation between Prader's stage and 45,X cell line percentage in lymphocytes, buccal epithelium, and gonadal tissue, as well as a direct correlation between the 45,X cell line presence in one of the tissues and its presence in other tissues. The search for mosaicism in tissues of different histogenesis origin using a set of methods for analyzing individual cells allows us to get a more complete picture of the gonosomal constitution and reveal a hidden imbalance, which is very important in examining patients with DSD. We proposed and used in this study the coefficient of variation (CV), which is a convenient statistical metric for quantifying the variability of cell lines in different tissues of a single patient and a step towards standardizing the results of genetic studies.

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Section: Discussionmentioning

confidence: 99%

Inter-Tissue Gonosomal Mosaicism in Patients with Disorders of Sex Development, Associated with Abnormalities of Gonadal Differentiation

et al. 2021

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“…46,XY gonadal dysgenesis is heterogeneous and can result from defects of any gene involved in the process of gonadal formation [2]. Complete gonadal dysgenesis is a difference in sex development typically associated with mutations in genes responsible for testicular development [11]. In the second month of pregnancy, the initial stage of testicular formation requires the function of several genes, the most important of which is SRY (Sex-determining region Y chromosome) [21].…”

Section: Genetic Characteristicsmentioning

confidence: 99%

“…The uterus is small or rudimentary. The gonads are dysgenetic strips consisting of fibrous tissue [1,11,12].…”

Section: Clinical Characteristicsmentioning

confidence: 99%

“…Malignancy 46,XY gonadal dysgenesis has a significant risk factor for type II germ cell tumors [2]. The presence of Y chromosome is associated with a high incidence of gonadoblastoma and dysgerminoma [11]. The risk of tumors in complete gonadal dysgenesis patients is approximately 20-30% [28].…”

Section: Clinical Characteristicsmentioning

confidence: 99%

“…According to the literature, complete gonadal dysgenesis has a high tumor development incidence in 20-30% of the cases. The presence of the Y chromosome increases the risk of germ cell neoplasms [11]. In most cases bilateral gonadoblastoma, dysgerminoma in 5% and less frequently embryonal carcinoma were found [10,12,13].…”

Section: Introductionmentioning

confidence: 99%

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Complete gonadal dysgenesis analysis in the population of Latvia: malignant outcomes and a review of literature

Jakovleva

Kovalova

2021

Medicine and Pharmacy Reports

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Background and aim. Complete gonadal dysgenesis or Swyer syndrome is a rare genetic disorder characterized by 46,XY karyotype and female phenotype with undeveloped streak gonads and high malignancy risk. The condition usually manifests in teenage and young adults with delayed puberty and primary amenorrhea. The purpose of this study was to investigate the incidence and potential malignant outcomes of complete gonadal dysgenesis in Latvia. Methods. 37 patients were included in a retrospective study from 1996 to 2016. In fifteen cases, additional patient information was available. Information from medical records was collected on age at the time of diagnosis: anamnesis data, laboratory results, histology of gonads, and treatment. Results. Complete gonadal dysgenesis with karyotype 46,XY was proven in 36 (97.3%) cases and one (2.7%) case with karyotype 47,XY,+21. The average age of patients at the time of diagnosis was 15.4 ± 8.0 years. The study included 15 cases: eight patients (53.3%) were investigated for primary amenorrhea, and incomplete development of secondary sexual characteristics, 5 patients (33.3%) with abdominal pain and lower abdominal mass, 2 patients (13.3%) were diagnosed at birth. Gonadectomy was performed in 12 cases (80%). The median time between diagnosis and gonadectomy was 0.4 ± 4.3 years. The histopathology results from the gonadal biopsy showed malignancy in 7 cases (58.3%). The most commonly diagnosed tumors were dysgerminoma and gonadoblastoma. Conclusion. Early diagnosis of Swyer syndrome is necessary in view of the risk of malignancy that can develop at a young age. In several cases, the diagnosis of the syndrome was made only after the malignant process development. The study showed the median time between diagnosis and gonadectomy was suboptimal. Therefore, women with amenorrhea and lack of secondary sexual characteristics require careful investigation.

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