Genetic diagnosis of macrotia in PIK3CA-Related Overgrowth Spectrum (PROS) and long-term outcome of otoplasty: a case report and literature review.

[OBJECTIVES] PIK3CA-Related Overgrowth Spectrum (PROS) is a highly heterogeneous disease. Facial Infiltrating Lipomatosis (FIL) is a rare PROS subset, and its atypical phenotypes, such as macrotia, present diagnostic and therapeutic challenges due to limited data. This study aims to detail the diagnostic and long-term management procedures for an extremely rare case of Macrotia associated with PROS/FIL.

[METHODS] To confirm the underlying etiology, Whole Exome Sequencing (WES) was performed, complementing routine clinical and pathological examinations. Otoplasty was used as the intervention to reduce ear size. Long-term follow-up was conducted to monitor surgical outcome, stability, and potential recurrence.

[RESULTS] WES identified a PIK3CA pathogenic variant (p.H1047R). Combined with pathological findings, the patient was definitively diagnosed with PROS manifesting as the FIL phenotype. The reductive otoplasty surgery achieved significant improvement in the affected ear's morphology, reducing the deformity to a minimal, aesthetically pleasing level. Crucially, the 1-year follow-up showed remarkable stability in the near-normal ear contour, without any signs of recurrence or overgrowth. The successful aesthetic restoration significantly alleviated the patient's psychological distress.

[CONCLUSIONS] This case demonstrates that WES is essential for accurate molecular diagnosis of PROS/FIL in patients presenting with atypical phenotypes like Macrotia. Furthermore, otoplasty is an effective and reliable reconstructive strategy for restoring ear aesthetics in these patients, providing excellent and stable long-term results and improving patient quality of life.

[LEVEL OF EVIDENCE] Level 4.