CBL-related disorder

For new term requests, please provide the following information:

The ClinGen RASopathy Expert Panel would like this term to replace the term: Noonan syndrome-like disorder with juvenile myelomonocytic leukemia MONDO:0013308. We understand that "gene-related disorder" terms are of last resort, but the phenotypic spectrum associated with this gene is variable and experts have described this RASopathy only in context of the gene, CBL.

Synonyms

Noonan-like syndrome, NSLL, Cbl mutation-associated syndrome

Textual 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 (PMID's: 20619386, 25283271, 25358541, 28589114, 28414188, 28343148, 24458550, 29259247, 26911351, 21901340, 25952305)"

Suggested parent term

"Noonan syndrome and Noonan-related syndrome", to be replaced by "RASopathy"

http://purl.obolibrary.org/obo/MONDO_0020297

Please look in the hierarchy in a browser such as OLS

Attribution

monarch-initiative / mondo