Genetic and Clinical Aspects of Müllerian Duct Anomalies

Müllerian duct anomalies (MDAs) represent a diverse group of congenital disorders arising from aberrant development of the embryonic structures that form the female reproductive tract. These anomalies range from complete absence of the uterus and upper vagina, as seen in Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome, to malformations such as septate or unicornuate uteri. The estimated prevalence of MDAs is approximately 1–5 per 1 000 women, with MRKH syndrome occurring in about 1 in 4 500–5 000 live female births. Genetically, MDAs display a complex, often oligogenic architecture: recurrent copy number variations at 16p11.2 and 17q12, sequence variants in transcription factors (for example LHX1, TBX6, WNT4, PAX8, GREB1L) and recently identified CHD1L mutations all contribute to phenotypic heterogeneity. Epigenetic influences and mosaicism further complicate the landscape. Clinically, patients frequently present in adolescence with primary amenorrhoea, cyclical pain or associated renal and skeletal defects. Diagnostic pathways combine imaging modalities—magnetic resonance imaging and ultrasound—with genetic testing to inform classification, prognostication and personalised counselling. Management encompasses non-invasive vaginal dilation or surgical neovaginoplasty, psychosocial support and, in cases of absolute uterine factor infertility, assisted reproductive technologies including gestational surrogacy and, more recently, uterus transplantation. Understanding the interplay between genetic drivers and clinical phenotype is essential for optimising outcomes and advancing translational research in MDAs.

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Genetic and Clinical Aspects of Müllerian Duct Anomalies publication trend

The graph below shows the total number of articles in genetic and clinical aspects of müllerian duct anomalies across all publications each year (not limited to Nature Index journals).

Technical terms

Müllerian duct anomalies (MDAs): Congenital malformations of the paramesonephric (Müllerian) ducts, affecting uterine and vaginal formation.

Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome: A form of MDA characterised by uterovaginal aplasia in 46,XX females with normal ovarian function and secondary sexual characteristics.

Copy number variation (CNV): A structural genomic alteration involving duplication or deletion of DNA segments, which can disrupt gene dosage.

Whole-exome sequencing (WES): A high-throughput technique that sequences all protein-coding regions of the genome to identify sequence variants.

Chromosomal microarray analysis: A genomic method to detect CNVs across the genome by comparing patient DNA to a reference sample.

References

1. Molecular Basis of Müllerian Agenesis Causing Congenital Uterine Factor Infertility—A Systematic Review. International Journal of Molecular Sciences (2023).
2. Genetics of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome: advancements and implications. Frontiers in Endocrinology (2024).
3. Identification and functional characteristics of CHD1L gene variants implicated in human Müllerian duct anomalies. Biological Research (2024).
4. Magnetic resonance imaging and clinical features of Mayer–Rokitansky–Küster–Hauser syndrome: A 10‐year review from a dedicated specialist centre. BJOG An International Journal of Obstetrics & Gynaecology (2024).
5. Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome: a comprehensive update. Orphanet Journal of Rare Diseases (2020).