Brain Abnormalities in PIK3CA-Related Overgrowth Spectrum: Physician, Patient, and Caregiver Experiences

Abstract

PIK3CA-related overgrowth spectrum (PROS) disorders are caused by somatic, gain-of-function mutations in PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) that result in hyperactivation of the phosphatidylinositol-3-kinase (PI3K) signaling pathway. PROS encompasses a broad spectrum of overlapping phenotypes that vary considerably in their severity and tissue distribution, leading to different and complex experiences for affected children and their families. The parent of a child with the PROS disorder megalencephaly-capillary malformation (MCAP) coauthored this article. MCAP is char-acterized by significant neurological involvement, and she describes personal experiences with this condition, including delays associated with obtaining a correct diagnosis, finding an experienced care team, challenges with schooling, medical complications, and the ongoing emotional and financial impacts on their lives. A physician perspective, which reinforces the challenges faced by the young child and his family, is provided by a clinician and researcher specializing in PROS disorders with central nervous system involvement. The physician reviews the mechanism of disease, some of the challenges in accurately diagnosing PROS conditions, disease-related complications, current treatment options and their limitations, and emerging therapeutic options including ongoing clinical trials. Our objective is to share these experiences and insights to benefit patients with PROS disorders, their families, and health care professionals involved with caring for patients with PROS.

Work-Up and Treatment Strategies for Individuals with PIK3CA-Related Disorders: A Consensus of Experts from the Scientific Committee of the Italian Macrodactyly and PROS Association

“…The early initiation of appropriate, meaningful, and effective teaching and learning activities, the development of an individualized education plan in collaboration with special needs teachers and pediatric neurologists, are important support tools for patients' development. Psychologists/psychotherapists also represent an important aid for families to guide habilitative and therapeutic decisions [61].…”

“…Despite the available resources, patients with PROS often encounter many challenges in everyday life besides disease-related issues. The risk of receiving a delayed diagnosis and the difficult task of finding the right care team are only some of the first issues to arise, followed by the difficult management of symptoms and the lack of effective therapeutic options [61]. Furthermore, sporadic case reports of patients with germline variants in PIK3CA are not sufficient to obtain enough evidence to justify surveillance protocols [62,63].…”