PIK3CA-Related Overgrowth Spectrum With Progressive Neurological Manifestations: A Rare Case Report

Abstract

PIK3CA-related overgrowth spectrum (PROS) disorders present complex management challenges due to their multisystem involvement. We describe a teenage male with a genetically confirmed PROS disorder (PIK3CA c.353G>A mutation), specifically megalencephaly-capillary malformation-polymicrogyria (MCAP) syndrome, who developed a unique constellation of neurological symptoms. Initially presenting with fetal macrocephaly, seizures, and developmental delay, he underwent surgical interventions including Chiari decompression and ventriculoperitoneal shunt placement. Concurrent progression of scoliosis and gait instability suggested syrinx progression, though obtaining follow-up imaging proved challenging due to insurance barriers. This case uniquely demonstrates the diagnostic complexity of differentiating between primary neurological symptoms, mechanical complications from structural abnormalities, and vascular phenomena in PROS disorders. Management required coordinated care across multiple subspecialties including neurology, neurosurgery, ophthalmology, and orthopedics. The case highlights multiple learning points: 1) the importance of serial monitoring in PROS/MCAP due to the progressive nature of complications, and 2) the challenge of characterizing episodic symptoms in the context of multiple potential underlying mechanisms.