/CBL-related disorder

CBL-related disorder

Rare Disease

MONDO:0013308

Also Known As

CBL-related disorderCbl syndromeNoonan syndrome-like disorder with JMMLNoonan syndrome-like disorder with juvenile myelomonocytic leukaemiaNoonan syndrome-like disorder with juvenile myelomonocytic leukemiaNoonan-like syndromeCbl mutation-associated syndromeNSLLNoonan syndrome-like disorder with or without juvenile myelomonocytic leukaemiaNoonan syndrome-like disorder with or without juvenile myelomonocytic leukemia

Definition

CBL-related disorder is a genetic condition caused by pathogenic variants in the Cbl ubiquitin ligase gene, (CBL; HGNC:1541). Due to the proposed mechanism indicating the CBL gene's relationship to the RAS-MAPK pathway and the phenotypic presentation similar to that of the RASopathies, CBL-related disorder should be considered a RASopathy disorder. Though there is a wide spectrum of phenotypic variability, broadly, patients with CBL-related disorder have presented with developmental delay, intellectual disability, neurodevelopmental alterations, prenatal lymphatic anomalies, cardiac malformations as well as vascular anomalies particularly affecting the brain (e.g. Moya-moya arteriopathies), craniofacial features indicative of a RASopathy, hypotonia, feeding difficulties, edema of the legs, musculoskeletal and respiratory thorax abnormalities, ectodermal features including cafe-au-lait spots, immunological and hematological disorders and susceptibility to tumors diagnosed as juvenile myelomonocytic leukemia (JMML) that is usually self-remitting. Note tumor risk beyond JMML has not yet been thoroughly assessed. Due to the clinical presentation of a broad spectrum of these and other phenotypes in patients with variants in CBL, these conditions are currently defined by experts in reference to the causal gene, CBL.