Title：Testicular yolk sac tumor in Coffin-Siris syndrome with a missense mutation in SMARCA4

Abstract

Background：Coffin-Siris syndrome（CSS,MIM 135900），is a multiple congenital anomaly syndrome characterized by developmental disability，coarse facial features，microcephaly and hypoplastic nails of the fifth fingers or toes. CSS is caused by mutations in several genes of the BRG1-associated factor（BAF） pathway including SMARCA4. Individuals with SMARCA4 variants have been previously reported and appear to display a variable phenotype. Pathogenic variants in SMARCA4 genes have been associated with an increasing risk of Coffin-Siris syndrome 4（MIM 614609）and Rhabdoid Tumor Predisposition Syndrome2（RTPS2）. Methods：Whole-exome sequencing（WES） was performed on an infant who presented with developmental delay，feeding difficulties，and laryngomalacia. He was also found to have testicular yolk sac tumor that has not been previously reported in CSS. Results: Germline testing identified a pathogenic variant in SMARCA4 c.2932C＞G. Conclusions: To our knowledge，this is the first report of testicular yolk sac tumor in an infant with a diagnosis of CSS with a potential predisposition to RTPS2.