46 XX karyotype during male fertility evaluation; case series and literature review

Abstract

Forty-six XX disorder of sex development is an uncommon medical condition observed at times during the evaluation of a man's fertility. The following is a case series and literature review of phenotypically normal men diagnosed with this karyotype. Our goal is to comprehend the patients’ clinical presentation as well as their laboratory results aiming to explore options available for their management. A formal literature review through PubMed and MEDLINE databases was performed using “46 XX man” as a word search. A total of 55 patients, including those conveyed in this article were diagnosed with a 46 XX karyotype during their fertility evaluation. The patients’ mean age ± s.d. was 34 ± 10 years and their mean height ± s.d. was 166 ± 6.5 cm. Overall, they presented with hypergonadotropic hypogonadism. Sexual dysfunction, reduced hair distribution, and gynecomastia were reported in 20% (4/20), 25.8% (8/31), and 42% (13/31) of the patients, respectively. The SRY gene was detected in 36 (83.7%) and was absent in the remaining seven (16.3%) patients. We found that a multidisciplinary approach to management is preferred in 46 XX patients. Screening for remnants of the mullerian ducts and for malignant transformation in dysgenetic gonads is imperative. Hypogonadism should be addressed, while fertility options are in vitro fertilization with donor sperm or adoption.

Research Article Microdeletion of the AZFc locus with high frequency of mosaicism 46,XY/47XYY in cases of non obstructive azoospermia in eastern population of India

“…Azoospermic cases with karyotype 46, XX (46, XX maleness, SRY positive XX male) are rare and they are consistently sterile in nature. Clinically, these cases have mature male genitalia, normal height and unimpaired intelligence (Majzoub et al, 2017).…”

“…A large number of genetic factors including microdeletion of Y-chromosome regions (AZF) are known to play crucial roles during spermatogenesis in male infertility (Vogt et al, 1996;Pandey et al, 2013;Yu et al, 2015;Saxena and Kumar, 2016;Saxena et al, 2018;Saxena et al, 2019). The sex determining region SRY gene plays a crucial role in testis determining factor (TDF) located on euchromatic region of Y-chromosome and approximately 80% cases are SRY-positive with normal phenotype having 46,XY karyotypes (Wu et al, 2014;Majzoub et al, 2017;Mohammadpour et al, 2017). Our objective was to investigate 1) cytogenetic abnormalities and their association with the SRY region in variable karyotypes; and, 2) to evaluate microdeletion of the Y chromosome using STS makers to understand the genetic basis of spermatogenesis in azoospermic cases.…”

Varones 46, XX: a propósito de dos casos genéticamente distintos

“…En una amplia revisión de la literatura de los últimos años sobre la base de una investigación de fertilidad masculina, Majzoub y col., (2017) describe una serie significativa de varones 46, XX en los que se detectó mediante FISH la presencia del gen SRY en el 83,7% de los casos (n ¼ 49). 11 La presencia del gen SRY se reconoce como el principal factor determinante en la virilización. 8 Sin embargo, otros genes de la región AZF juegan también un rol determinante en la espermatogénesis El genotipo observado en el caso 1, sugiere una translocación del gen SRY a otro cromosoma que no fue posible definir con exactitud al no realizar el estudio FISH.…”

“…La edad al diagnóstico coincide con la reportada en la literatura que se estima entre 24 a 34 años 13 y el fenotipo presentado ha sido reportado en otras series publicadas donde el aspecto masculino normal, la talla promedio de 1,66 cm AE 6, la azoospermia y el hipogonadismo hipergonadotropico han sido las características más relevantes. 11 Generalmente, para estos casos con virilización normal, la sospecha diagnóstica se establece en la adultez temprana a consecuencia de infertilidad. Es curioso que, en nuestro paciente, la infertilidad no resultara en el motivo inicial para los estudios sino la constatación de unos testes muy pequeños, en el contexto de un examen médico para ingresar a una Institución Armada.…”

46,XX male disorder of sexual development

“…Furthermore, despite several cases describing phenotypic heterogeneity in this genetic condition, 90% of the affected individuals present a normal male phenotype at birth. Generally, diagnosis occurs after the onset of puberty, upon presentation of hypogonadism and/or gynecomastia, or later due to an assessment of infertility, as a lack of spermatogenesis is observed in all cases (2,3).…”