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.