Cytogenetic Spectrum of Ovotesticular Difference of Sex Development (OT DSD) among a Large Cohort of DSD Patients and Literature Review

Abstract

Ovotesticular difference of sex development (OT DSD) is a rare genetic disorder with an incidence of about 1/100,000 live births. The majority of OT DSD patients show a 46,XX karyotype, others may have 46,XX/46,XY chimerism or exhibit various mosaic sex chromosome combinations, and less commonly they may have a 46,XY karyotype. The aim of this work is to report the clinical, pathological, and karyotypic variations in OT DSD patients diagnosed among a large cohort of DSD patients. The study included 10 patients thoroughly evaluated for clinical, genital, and hormonal abnormalities and subjected to imaging studies, laparoscopy with gonadal biopsy, karyotype, and FISH analysis. The current study revealed a greater percentage of mosaic cell line combinations than previously reported and showed variable cytogenetic abnormalities, including the rare isodicentric (Y)(p11.32) abnormality and X;Y translocation. The study also revealed a unique pattern of gonadal type and combination frequencies. To our knowledge, this is the first study on OT DSD patients among a large cohort of DSD patients in Egypt and the Middle East.

Advances in genomic diagnosis of a large cohort of Egyptian patients with disorders of sex development

“…Most of our 46,XX males presenting with infertility were positive for SRY gene (five out of seven), while the remainders were all SRY ‐negative. The SRY gene is present in about 80% of classic XX testicular DSD as a result of abnormal X/Y interchange during paternal meiosis and could be detected by FISH analysis on the X short arm, while most patients with atypical genitalia and OT DSD patients are SRY ‐negative (McElreavey & Cortes, 2001; Mekkawy et al, 2020). In patients with no SRY gene, the presence of gonadal 46,XY cell line may explain testicular development, as evidenced in one of our 46,XX OT DSD patients.…”

Cytogenomic description of a Mexican cohort with differences in sex development

“…The estimated incidence of chromosomal DSDs is 1:2,500 live infant girls for patients with Turner syndrome and 1:500 live boy births for patients with Klinefelter syndrome [ 2 , 14 ]. Regarding patients with DSD and karyotype 46, XY, the overall incidence is 1:20,000 births; for patients with ovotesticular DSD, a frequency of 1:100,000 has been estimated [ 15 , 16 ]. Finally, in patients with DSD 46, XX, it has been described that congenital adrenal hyperplasia (CAH) is the major cause of alterations in female genitalia, showing an overall incidence of 1:14,000–15,000 [ 17 ].…”

Análise por sequenciamento paralelo de larga escala de uma coorte de pacientes com distúrbios/diferenças do desenvolvimento do sexo 46,XX testicular e ovotesticular SRYnegativo

“…Se ovotestis presente nos dois lados é classificado como tipo bilateral, se os tecidos ovariano e testicular se apresentarem separadamente, um em cada gônada, é classificado em tipo lateral ou, ainda, comumente, como tipo unilateral, ovotestis unilateral e um testículo ou ovário contralateral 27 .…”