Endocrine Abstracts

Background: Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is a congenital disorder characterized by uterovaginal aplasia in women with a normal female karyotype and secondary sex characteristics. The condition is typically diagnosed during late adolescence and has profound psychosocial and reproductive consequences. MRKHS is classified into two groups, i.e. type I (isolated) and type II (with extragenital malformations typically involving the kidneys, skeleton, heart, and auditory system). Although the aetiology remains largely unknown, increasing evidence suggests a heterogeneous genetic background. This nationwide study aims to comprehensively characterize the phenotypic and genetic spectrum of MRKHS patients in Denmark.

Methods: Supported by nationwide population-based registry data, we aim to recruit approximately 150 women nationwide with MRKHS for detailed clinical, biochemical, and genetic evaluation. Parents and affected relatives are also recruited for genetic analysis when possible. Phenotypic evaluations include gynaecological and anthropometric assessments, as well as imaging (pelvic and kidney MRI, spine X-ray, and echocardiography) to detect associated extragenital anomalies. Biological samples (blood, urine, cheek, and vaginal swabs) are collected to establish a biobank for molecular analyses. High-fidelity long-read genome sequencing (PacBio) of family trios is performed to identify and characterize single nucleotide variants, copy number variants, and structural genomic rearrangements associated with MRKHS.

Results: To date, 35 patients have been included in the project. In addition, 12 patients are awaiting clinical evaluation, and 14 additional individuals have registered for participation.

Discussion/conclusions: We anticipate that this study will provide unprecedented insight into the clinical heterogeneity and molecular basis of MRKHS. Establishing the genetic architecture of MRKHS will advance understanding of Müllerian duct development and its malformations. Furthermore, emerging reproductive options such as uterus transplantation and gestational surrogacy are likely to increase the number of affected individuals seeking reproductive counselling, highlighting the growing need for accurate genetic diagnostics and informed genetic counselling on recurrence risk.