PIK3CA-related overgrowth spectrum (PROS) is an umbrella term for rare syndromes characterized by malformations and tissue overgrowth caused by somatic mutations in the PIK3CA gene. In PROS diseases, malformations are seen in several different tissues such as skin, vasculature, bones, fat and brain tissue depending on the specific disease.
The clinical diagnoses in patients with PIK3CA activating mutations have included Fibroadipose hyperplasia or Overgrowth (FAO/FAVA), Hemihyperplasia Multiple Lipomatosis (HHML), Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, Scoliosis/Skeletal and Spinal (CLOVES) syndrome, macrodactyly, Facial Infiltrating Lipomatosis (FIL), and the related megalencephaly syndromes, Megalencephaly‐Capillary Malformation (MCAP or M‐CM) and Dysplastic Megalencephaly (DMEG) - (Keppler-Noreuil et al)
Additionally PIK3CA mutations have been found in Klippel-Trenaunay Syndrome as well as Lymphatic Malformation.
Image above from PIK3CA‐related overgrowth spectrum (PROS): Diagnostic and testing eligibility criteria, differential diagnosis, and evaluation - Kim Keppler - Noreuil et al.
Some people with a PIK3CA mutation fall clearly into one of the diagnoses above, whereas others have symptoms of several different PROS syndromes. Additionally some clinicians diagnose patients with PROS, the umbrella term, instead of one of the syndromes under the PIK3CA umbrella. This can be confusing to providers as well as patients and families. Patient Advocacy Organizations for other PROS Diseases are below:
- Association Syndrome CLOVES - CLOVES France
- Asociación Macrocefalia- Malformación Capilar España - M-CM Madrid
- Associazione Italiana Macrodattilia e PROS AIMP Onlus - Macrodactyly/PROS Italy
- CLOVES Syndrome Foundation - CLOVES
- GoPI3KS - PIK3CA Related Overgrowth/PROS
- Klippel Trenaunay Support - KTS
- M-CM Network - M-CM
- M-CM UK - M-CM United Kingdom
- WonderFIL Smiles - FIL