Hemifacial myohyperplasia is due to somatic muscular PIK3CA gain-of-function mutations and responds to pharmacological inhibition

• DOI: 10.1084/jem.20230926
• Publication Date: 2023-09-15T13:38:29Z
• Authors: Charles Bayard; Eleonora Segna; Maxime Taverne; Antoine Fraissenon; Quentin Hennocq; Baptiste Periou; Lola Zerbib; Sophia Ladraa; Célia Chapelle; Clément Hoguin; Sophie Kaltenbach; Patrick Villarese; Vahid Asnafi; Christine Broissand; Ivan Nemazanyy; Gwennhael Autret; Nicolas Goudin; Christophe Legendre; François-Jérôme A...; Thomas Viel; Bertrand Tavitian; Cyril Gitiaux; Sylvie Fraitag; Jean-Paul Duong; Clarisse Delcros; Bernard Sergent; Arnaud Picard; Michael Dussiot; Laurent Guibaud; Roman Khonsari; Guillaume Canaud
• Keywords: Mice; Disease Models, Animal; Facial Asymmetry; Class I Phosphatidylinositol 3-Kinases; Gain of Function Mutation; Animals; Humans; Hypertrophy; Child; Article

Hemifacial myohyperplasia (HFMH) is a rare cause of facial asymmetry exclusively involving muscles. The underlying and the mechanism disease progression are unknown. Here, we identified somatic gain-of-function mutation PIK3CA in five pediatric patients with HFMH. To understand physiopathology muscle hypertrophy this context, created mouse model carrying specifically skeletal led to striated cell hypertrophy, mitochondria dysfunction, hypoglycemia low circulating insulin levels. Alpelisib treatment, an approved inhibitor, was able prevent reduce correction endocrine anomalies. Based on these findings, treated HFMH patients. All demonstrated clinical, esthetical, radiological improvement proof target engagement. In conclusion, show that due alteration accessible pharmacological intervention.