Clinical and Genetic Analyses and Treatment Experiences of Patients with Lateralized Overgrowth

Abstract Background The genetic features and management of lateralized overgrowth have been elusive. This study was performed to investigate the causative genes and outcomes of alpelisib-treated patients with lateralized overgrowth. Methods Fourteen patients with lateralized overgrowth were enrolled. Clinical features and whole-body magnetic resonance imaging (WB-MRI) findings were evaluated. Deep sequencing with a customized 143 gene panel of affected tissue and peripheral white blood cells was performed. Propranolol was administered and clinical outcomes were examined. The PIK3CA inhibitor alpelisib was administered via a managed access program. Results Genetic testing identified PIK3CA (n = 7, 50%), KRAS (n = 2, 14.3%), PTEN (n = 1, 7.1%), MAP2K3 (n = 1, 7.1%), GNAQ (n = 1, 7.1%), TBC1D4 (n = 1, 7.1%), and TEK (n = 1, 7.1%) mutations. Propranolol was administered in 12 patients, and 7 experienced relief of symptoms. Alpelisib was administered in two volunteers with a PIK3CA mutation, and the WB-MRI after 1 year of treatment showed a reduction in proliferated masses. Conclusions Deep sequencing identified diverse genetic features of lateralized overgrowth. Targeted therapy with a PIK3CA inhibitor would be the primary therapeutic strategy for PIK3CA-related overgrowth syndrome.