Clinical and Genetic Analyses and Treatment Outcomes 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 genetic profiles and outcomes of propranolol- or alpelisib-treated patients with lateralized overgrowth. Methods: Fifteen patients with lateralized overgrowth were enrolled. Clinical features and whole-body magnetic resonance imaging (WB-MRI) findings were evaluated. Deep sequencing with a customized 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, 46.7%), KRAS (n=2, 13.3%), PTEN (n=1, 6.7%), MAP2K3 (n=1, 6.7%), GNAQ (n=1, 6.7%), TBC1D4 (n=1, 6.7%), and TEK (n=1, 6.7%) mutations. Propranolol was administered in 12 patients, and 7 experienced limited improvement of symptoms. Alpelisib was administered in two patients 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. Propranolol could be used as an adjuvant therapy for reducing vascular symptoms, but targeted therapy with a PIK3CA inhibitor would be the primary therapeutic strategy for PIK3CA-related overgrowth syndrome.