Journal Article

Genetics and clinical phenotype of Erdheim–Chester disease: A case report of constrictive pericarditis and a systematic review of the literature

Angeli, Francesco, Zinzani, Pier Luigi, Rucci, Paola, Stefanizzi, Andrea, Fabrizio, Michele, Broccoli, Alessandro, Pizzi, Carmine, Foà, Alberto, Bartoli, Lorenzo, Bergamaschi, Luca, Galiè, Nazzareno, Paolisso, Pasquale

2022

Overview

BackgroundErdheim–Chester disease (ECD) is a rare form of histiocytosis. An increasing number of genetic mutations have been associated with this syndrome, confirming its possible neoplastic origin. Recently, a connection between the BRAF mutational status and a specific phenotype was described; however, no studies have yet evaluated the correlations between other mutations and the clinical features of the disease.ObjectivesThis study aims to clarify the association between the clinical phenotype and genetic mutations identified in the neoplastic cell lines of ECD.MethodsWe describe a case of ECD characterized by pericardial involvement and a KRAS mutation shared with chronic myelomonocytic leukemia. Hence, through a meta-analysis of individual participant data of all genetically and clinically described cases of ECD in the literature, we aimed to elucidate the association between its clinical phenotype and baseline genetic mutations.ResultsOf the 760 studies screened, our review included 133 articles published from 2012 to April 2021. We identified 311 ECD patients whose genotype and phenotype were described. We found five main genes (BRAF, KRAS, NRAS, PIK3CA, and MAP2K1) whose mutation was reported at least three times. Mutation of BRAF led to a neurological disease (183 of 273 patients, 67%; p < 0.001); KRAS- and NRAS-mutated patients mainly showed cutaneous (five of six patients, 83.3%, p < 0.004) and pleural (four of nine patients, 44%, p = 0.002) involvement, respectively; PIK3CA was not associated with specific organ involvement; and MAP2K1 mutations caused the disease to primarily involve the peritoneum and retroperitoneum (4 of 11, 36.4%, p = 0.01).ConclusionThis work implies a possible influence of baseline mutation over the natural history of ECD, underscoring the importance of a thorough genetic analysis in all cases with the ultimate goal of identifying a possible targeted therapy for each patient.

• Publisher: Frontiers Media SA
• Subject: Abdomen / Asymptomatic / Biopsy / Blood tests / Bone marrow / Case reports / Edema / Genes / Genotype & phenotype / Kinases / Leukemia / Literature reviews / Medical imaging / Meta-analysis / Mutation / Patients / Pericarditis / Pleural effusion / Scintigraphy / Skin / Tomography