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

TL;DR

A rare case of macrotia caused by PIK3CA-Related Overgrowth Spectrum (PROS) was diagnosed using genetic testing and successfully treated with surgery, showing long-term improvement.

Contribution

Demonstrates the effectiveness of WES for diagnosing atypical PROS/FIL cases and confirms the long-term success of reductive otoplasty in adulthood.

Findings

Whole exome sequencing identified a PIK3CA pathogenic variant in a patient with FIL-associated macrotia.

Reductive otoplasty in adulthood resulted in stable and durable aesthetic outcomes with no recurrence after one year.

Successful surgical intervention significantly reduced patient anxiety and improved quality of life.

Abstract

•WES provides essential molecular confirmation for atypical PROS/FIL phenotypes such as macrotia.•Delayed reductive otoplasty in adulthood yields durable and stable aesthetic outcomes in FIL-associated macrotia.•Successful surgical management relieves patient anxiety and highlights the value of personalized treatment.

WES provides essential molecular confirmation for atypical PROS/FIL phenotypes such as macrotia.

Delayed reductive otoplasty in adulthood yields durable and stable aesthetic outcomes in FIL-associated macrotia.

Successful surgical management relieves patient anxiety and highlights the value of personalized treatment.

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.

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.

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.

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 4.

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