Müllerian Duct Aplasia in a Girl With SMARCB1 ‐Related Coffin–Siris Syndrome: A Rare Co‐Occurring Anomaly

ABSTRACT

Genetic etiologies of Müllerian aplasia (Mayer–Rokitansky–Küster–Hauser syndrome) remain poorly understood. Identification of patients with monogenic syndromes presenting with Müllerian aplasia may help improve our knowledge of the underlying biology. We investigated a 15‐year‐old female presenting with primary amenorrhea due to Müllerian aplasia, dysmorphic features, and intellectual disability. Trio whole genome sequencing identified a pathogenic de novo missense variant in NM_003073.5( SMARCB1 ): c.1096C>T, p.(Arg366Cys) confirming the diagnosis of Coffin–Siris syndrome 3 (OMIM #614608). This patient represents the first molecularly confirmed case of Coffin–Siris syndrome presenting with Müllerian aplasia; however, two previous clinical reports support this potential rare association. Research is needed to further investigate this possible association, determine the prevalence of Müllerian aplasia in adolescent/adult female patients with Coffin–Siris syndrome and whether it may be associated with other BAF (BRG1/BRM‐associated factor) complex genes than SMARCB1 . Finally, it is unknown how BAF complex dysfunction may be involved in perturbed Müllerian duct development in females.