The SMARCA4 gene is associated with SMARCA4-related tumor predisposition syndrome, most notably increasing the risk for small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), a highly aggressive ovarian cancer that often occurs at young ages, as well as certain rhabdoid tumors (childhood cancers) and other rare cancers. Management focuses on early awareness of symptoms, discussion of risk-reducing surgical options, and coordination with oncology and genetics specialists to guide individualized surveillance or preventive strategies. SMARCA4-related cancer risk is not known to be more common in the Ashkenazi Jewish population.
In addition, some people with SMARCA4 pathogenic variants develop Coffin-Siris syndrome. Coffin-Siris syndrome is a condition that affects several body systems and can include developmental disability, abnormalities of the fifth (pinky) fingers or toes, and characteristic facial features.
Pathogenic variants in SMARCA4 exhibit autosomal dominant inheritance. This means there is a 50% chance the condition can be passed from generation-to-generation. First degree relatives (parents, siblings, children) have a 50% chance to have the same pathogenic variant whereas second degree relatives (grandparents, aunts/uncles, nieces/nephews, half-siblings) have a 25% chance. More distant relatives have lower chances of having the same pathogenic variant when one is identified in the family.
Resources:
Coffin-Siris Syndrome Foundation
Small Cell Ovarian Cancer Foundation
Written December 2025
