Scientists have recently identified the first case of a child presenting with both DeSanto-Shinawi syndrome and a rare brain tumor. DeSanto-Shinawi syndrome (DESSH) typically results from loss-of-function variants in the WAC gene. This autosomal dominant disorder causes global developmental delay, intellectual disability, and distinctive facial features. However, its potential link to oncogenesis remains an area of active investigation. Consequently, this specific case involving a 15-year-old boy provides new insights into the syndrome's clinical spectrum. Moreover, the report emphasizes the complexity of managing rare genetic conditions.

Understanding DeSanto-Shinawi Syndrome and Tumor Risks

The patient in this report received a diagnosis of DESSH along with a polymorphous low-grade neuroepithelial tumor of the young (PLNTY). Genetic analysis revealed a unique FGFR2:INA fusion within the tumor. Additionally, researchers identified germline variants in the NF1 and SDHA genes. These findings are significant because the WAC protein plays a vital role in regulating gene transcription and cell cycle checkpoints. Therefore, any disruption in WAC function might predispose individuals to early tumor development. Furthermore, the presence of multiple germline variants suggests a multi-hit mechanism in cancer progression.

Notably, the WAC gene complex interacts directly with the p53 tumor suppressor protein. It regulates gene transcription and the monoubiquitination of histone H2B. Consequently, WAC variants may impair the body's response to DNA damage and disrupt cell cycle activation. Although DESSH primarily manifests as a neurodevelopmental condition, this case underscores the importance of oncogenetic monitoring. Thus, physicians should consider comprehensive genetic testing for patients with rare syndromes who develop unusual neoplasms. Furthermore, early detection of these fusions can guide personalized treatment strategies for pediatric patients. In addition, the case highlights the evolving nature of neuro-oncology.

Frequently Asked Questions

What is the primary cause of DeSanto-Shinawi syndrome?

DeSanto-Shinawi syndrome is caused by mutations or deletions in the WAC gene, which is located on chromosome 10. This gene is responsible for producing a protein that regulates gene expression and helps the cell respond to DNA damage.

Does DeSanto-Shinawi syndrome increase the risk of cancer?

While primarily known as a neurodevelopmental disorder, recent evidence suggests that WAC variants may have a role in tumor development due to their interaction with p53. This case report is the first to link the syndrome with a specific brain tumor like PLNTY.

Disclaimer: This content is for informational and educational purposes only. It does not constitute medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Refer to the latest local and national guidelines for clinical practice.

References

Cipri S et al. First Report of a Child With a DeSanto-Shinawi Syndrome and a Polymorphous Low-Grade Neuroepithelial Tumor of the Young. Am J Med Genet A. 2026 Feb 17. doi: 10.1002/ajmg.a.70085. PMID: 41700448.
Gupta R et al. Low-grade glioneuronal tumors with FGFR2 fusion resolve into a single epigenetic group corresponding to 'Polymorphous low-grade neuroepithelial tumor of the young'. Acta Neuropathol. 2021;142(3):595-607.
Wang Y et al. Ring finger 20/ring finger 40/WW domain-containing adaptor with coiled-coil complex interacts with p53 to regulate gene transcription in DNA damage response. Oncol Lett. 2021;21(6):436.