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