P2.L238: Navigating the Labyrinth: Unveiling Rare Paths in Neonatal Overgrowth and the Odyssey of Novel Interventions

Introduction: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-related overgrowth spectrum (PROS) includes disorders driven by somatic mutations, manifesting as diverse and complex overgrowth and vascular anomalies. This case report delineates a rare and challenging presentation of PROS in a premature neonate marked by a significant and enlarging scalp hemangioma, highlighting diagnostic challenges and the innovative application of sirolimus, a treatment seldom used in neonates due to concerns over potential side effects

Case Description: A female neonate delivered at 32 weeks and 6 days via cesarean section due to maternal gestational diabetes and hypertension, displayed immediate respiratory distress, necessitating intubation and surfactant therapy. A prominent, enlarging purple scalp lesion measuring 14 x 14 cm, coupled with multiple smaller hemangiomas, prompted urgent diagnostic evaluations (Figure 1). MRI of the head confirmed the lesion was confined to the scalp without intracranial involvement. Initial management addressed severe thrombocytopenia and coagulopathy with necessary transfusions. The rapid growth of the lesion and its potential complications led to an off-label use of sirolimus, a choice influenced by its efficacy but tempered by its limited testing in neonatal populations.

Discussion: The newborn's complex presentation required an integrated approach from neonatology, dermatology, and genetics, facilitating early and aggressive investigations including skin biopsy and genetic analysis. Confirmation of a PIK3CA gene mutation solidified the diagnosis of PROS. Sirolimus was selected for its capacity to target the mTOR signaling pathway, crucial in regulating cellular growth and vascular development. This case's response to sirolimus was noteworthy , with significant reduction in lesion size (Figure 2) and improvement in coagulopathy, demonstrating its potential despite typical reservations about its use in neonates due to side effects and long-term impact concerns.

Conclusion: This case highlights the complexities of diagnosing and managing rare genetic disorders like PROS in neonates, especially those with unusual and severe manifestations. The successful application of sirolimus, though unconventional, offers a promising avenue for similar cases, suggesting a possible shift towards more targeted therapies in neonatal care. It also emphasizes the necessity for ongoing research and clinical trials to better understand the safety and efficacy of such treatments in newborns, ensuring that future therapeutic decisions can be made with greater confidence and precision.