Background: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a rare congenital disorder characterized by agenesis or hypoplasia of the uterus and upper vagina due to Müllerian duct anomalies. Fragile X syndrome (FXS), a leading cause of inherited intellectual disability, is caused by CGG repeat expansions in the FMR1 gene and has been associated with premature ovarian insufficiency (FXPOI). Objective: We report a unique case of co-occurrence of MRKH syndrome and a premutation in the FMR1 gene, raising the question of a possible link between FMR1-related genomic instability and Müllerian developmental anomalies. Case Presentation: A 25-year-old woman with a history of delayed psychomotor development and familial intellectual disability presented with primary amenorrhea. Clinical evaluation revealed hypergonadotropic hypogonadism, absent pubertal development, neuropsychiatric symptoms, and bilateral sensorineural hearing loss. Pelvic MRI confirmed the diagnosis of MRKH syndrome. Molecular testing revealed a premutation in the FMR1 gene. Conclusion: This rare association between MRKH syndrome and FMR1 premutation highlights the potential role of FMR1 or related loci in embryonic morphogenesis beyond its known neurological and ovarian functions. Further studies are needed to explore the possible pathogenic link between genomic instability and Müllerian tract development.
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