THE GENETICS OF SEXUAL DEVELOPMENT DISORDERS

Malik Ejder Yıldırım

doi:10.7197/cmj.1605185

EN TR

THE GENETICS OF SEXUAL DEVELOPMENT DISORDERS

Abstract

Sexual development is one of the significant stages of the embryogenesis. In this process, the gonadal differentiation taking place on a genetic basis (sex chromosomes) determines the sexual identity of the individual. Initially, the gonads are considered bipotential because the gonadal primordium can turn into a testicle or ovary through the activation of certain genetic elements in the subsequent period. When there is a disruption at any phase of this period, various clinical conditions called disorders of sexual development (DSD) arise. These conditions, often accompanied by various mutations or sex chromosome abnormalities, may include gonadal dysgenesis and result in a male (46, XY) or female (46, XX) sex reversal. DSD with 46,XY usually contains ambiguous condition, or the presence of female external and/or internal genitalia depending on whether Müllerian tissues are present. On the other hand, different enzyme defects, again, on a genetic basis can lead to disorders of sex development in both males (e.g. 5α-reductase) and females (e.g. aromatase). Congenital adrenal hyperplasia is a relatively common, autosomal recessive enzyme defect, especially in 46,XX DSD cases. A number of syndromes lead to a certain degree of inadequate sexual development in males or masculinization in females. Patients also have some characteristic physical symptoms accompanied by mental problems. Gonadal dysgenesis can be caused by various mutations, mainly in the SRY gene (e.g. Swyer syndrome) or sex chromosome disorder (Turner syndrome). In cases of 46,XY DSD, mixed gonadal dysgenesis, and some other conditions, prophylactic gonadectomy may be considered because of the malignancy risk.

Keywords

CİNSEL GELİŞİM BOZUKLUKLARININ GENETİĞİ

Öz

Cinsel gelişim embriyogenezin önemli aşamalarından biridir. Bu süreçte, genetik temelde (seks kromozomları) gerçekleşen gonadal farklılaşma bireyin cinsel kimliğini belirler. Başlangıçta gonadlar bipotansiyel olarak kabul edilir çünkü gonadal primordium sonraki dönemde belirli genetik unsurların aktivasyonu ile testis veya overe dönüşebilir. Bu dönemin herhangi bir aşamasında bir aksama olduğunda, cinsel gelişim bozuklukları (DSD) adı verilen çeşitli klinik durumlar ortaya çıkar. Genellikle çeşitli mutasyonlar veya cinsiyet kromozomu anormalliklerinin eşlik ettiği bu koşullara, gonadal disgenezi dahil olabilir ve erkek (46, XY) veya dişi (46, XX) cinsiyet dönüşümü ile sonuçlanabilir. 46,XY DSD genellikle belirsiz bir durumu veya dişi dış ve/veya Müllerian dokuların mevcut olup olmamasına bağlı olarak iç genital organların varlığını içerir. Öte yanda, yine genetik bazda farklı enzim defektleri, hem erkeklerde (örn. 5α-redüktaz) hem de dişilerde (örn. aromataz) cinsiyet gelişimi bozukluklarına yol açabilmektedir. Konjenital adrenal hiperplazi, özellikle 46,XX DSD olgularında, nispeten sık görülen, otozomal resesif bir enzim defektidir. Bir dizi sendrom, erkeklerde belirli ölçüde yetersiz cinsel gelişime veya dişilerde erkekleşmeye yol açar. Hastalar da, ayrıca mental problemlerin eşliğinde bazı karakteristik fiziksel semptomlar bulunur. Gonadal disgeneziye, başta SRY geni olmak üzere, çeşitli mutasyonlar (örneğin Swyer sendromu) veya cinsiyet kromozom bozuklukluğu (Turner sendromu) neden olabilir. Netice itibarıyla, 46,XY DSD, karma gonadal disgenezi ve diğer bazı durumlarda, malignite riski nedeniyle profilaktik gonadektomi düşünülebilir.

Anahtar Kelimeler

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Details

Primary Language

English

Subjects

Multimorbidity

Journal Section

Review

Authors

Malik Ejder Yıldırım ^*
0000-0003-4386-1583
Türkiye

Early Pub Date

March 29, 2025

Publication Date

March 29, 2025

Submission Date

December 21, 2024

Acceptance Date

March 8, 2025

Published in Issue

Year 2025 Volume: 47 Number: 1

DOI

https://doi.org/10.7197/cmj.1605185

IZ

https://izlik.org/JA86YF54PZ

Cite

RIS / Bibtex

AMA

1.Yıldırım ME. THE GENETICS OF SEXUAL DEVELOPMENT DISORDERS. CMJ. 2025;47(1):2-9. doi:10.7197/cmj.1605185