Beyond the Spectrum: A Case Report of Phelan-McDermid Syndrome and the Atypical Teratoid/Rhabdoid Tumor Co-Occurrence.

INTRODUCTION: Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder most often caused by terminal 22q13.3 deletions involving SHANK3. Although primarily associated with developmental delay, hypotonia, and autism spectrum disorder-like features, rare reports have described atypical teratoid/rhabdoid tumor (AT/RT) in PMS, suggesting a potential oncogenic link.

CASE PRESENTATION: We report the clinical, molecular, and treatment features of a child with PMS and AT/RT and review previously published cases. The proband presented with global developmental delay, absent speech, hypotonia, joint laxity, and characteristic dysmorphic features. Chromosomal microarray revealed a ∼2.26 Mb terminal deletion at 22q13.32q13.33, encompassing 31 OMIM-listed genes including SHANK3. At 6 months of age, he was diagnosed with AT/RT and treated with multimodal chemotherapy and craniospinal radiotherapy, achieving remission. Literature review identified additional PMS patients with AT/RT, supporting a role for 22q instability in tumorigenesis.

CONCLUSION: This case highlights a rare but clinically significant association between PMS and AT/RT. Awareness of this potential link and careful radiotherapy planning are warranted to optimize outcomes in affected individuals.