분절 과증식 증후군 환자의 임상적 유전학적 특성과 치료 경과에 대한 고찰

Abstract

Purpose: Segmental overgrowth syndrome refers to a group of proliferative disorders with diverse and overlapping symptoms. It is difficult to differentiate these diseases because their clinical aspects overlap with each other and the phenotype is very diverse within the same disease. Furthermore, effective treatments for these diseases have not yet been developed. This study investigated the clinical and genetic diagnosis and treatment outcomes of segmental overgrowth syndrome. Methods: Fifteen patients with segmental overgrowth syndrome were enrolled. Clinical diagnosis with clinical characteristics and whole body magnetic resonance imaging (WB-MRI) findings were evaluated. Genetic diagnosis was made through targeted customized gene panel testing with affected tissues and peripheral white blood cells. Propranolol was administered and plasma cytokines and WB-MRI findings were examined. Clinical trial with the PIK3CA inhibitor or alpelisib was performed in two patients by managed access program. Results: Clinically, 14 patients were suggested as having PIK3CA-related overgrowth spectrum (PROS) disorder; 12 patients as Klippel-Trenaunay syndrome and two patients as undetermined type of PROS. One patient was suspected to have Parkes-Weber syndrome. Seven patients (46.7%) were identified to have PIK3CA mutation. Two patients (13.3%) had KRAS mutation. Other identified mutations included 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%). Propranolol was administered in 12 patients and seven patients experienced improvement of symptoms. Alpelisib was administered in two patients and the WB-MRI after one year of treatment showed reduction of proliferated masses. Conclusion: Targeted panel sequencing is useful in identifying the causative gene of segmental overgrowth syndrome. Propranolol could be used as an adjuvant therapy for reducing vascular symptoms of overgrowth syndrome. Targeted therapy considering genetic causes such as PIK3CA inhibitor would be the leading therapeutic strategy of overgrowth syndrome in the future.