A cystic and bullous lung disease associated with a PIK3CA-related overgrowth syndrome

Multifocal cystic lung diseases can be due to numerous causes and their diagnosis may be challenging necessitating a systematic workup. PIK3CA (phosphatidylinositol 3-kinase catalytic subunit alpha related overgrowth syndrome (PROS)) is a rare hypertrophic syndrome due to somatic mosaic mutations in the gene encoding for the PIK3CA. These mutations occur in post-zygotic stage 1 and lead to a hyperactivation of the PI3K-AKT-mTOR pathways, resulting in an increased proliferation, survival and cellular mobility of the impacted cells. PROS phenotypes are multiple and depend on the mutation location as well as on the time of its post-zygotic occurrence. They share clinical characteristics such as congenital or early childhood onset of abnormal and asymmetric tissue overgrowth (adiposis, muscle nerve, skeletal) 2, vascular and/or lymphatic malformations and epidermal nevus 3. Different types of malignant tumors (colon, breast, brain, liver, stomach and lung) 4 have also been described in this context. To our knowledge, PROS associated pulmonary non-malignant manifestations have never been reported before. We describe here a patient with a bullous and cystic lung disease diagnosed in the context of a clinically and genetically diagnosed PROS. Footnotes This manuscript has recently been accepted for publication in the ERJ Open Research . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article. Conflict of interests: DIB, JP, PH, TM have no conflicts to declare. Conflict of interests: GC declare : a patent application ("BYL719 (alpelisib) for use in the treatment of PIK3CA-related overgrowth spectrum" #WO2017140828A1) has been filed by INSERM (Institut National de la Santé et de la Recherche Médicale), Centre National De La Recherche Scientifique (CNRS), Université Paris Descartes, and Assistance Publique-Hôpitaux De Paris (AP-HP) for the use of BYL719 (alpelisib) in the treatment of PIK3CA -related overgrowth spectrum (PROS/CLOVES syndrome). Dr. Canaud is the inventor. This patent is licensed to Novartis. Dr. Canaud receives or has received consulting fees from Novartis, Fresenius Medical Care, Vaderis, Alkermes, IPSEN and BridgeBio.