Details of Disease | DrugMAP

General Information of Disease (ID: DISY9Q92)

Disease Name	CBL-related disorder
Synonyms	Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia; NSLL; Cbl mutation-associated syndrome; Noonan syndrome-like disorder with or without juvenile myelomonocytic leukaemia; Noonan syndrome-like disorder with juvenile myelomonocytic leukemia; Cbl syndrome; Noonan-like syndrome; Noonan syndrome-like disorder with JMML; Noonan syndrome-like disorder with juvenile myelomonocytic leukaemia; CBL-related disorder
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.
Disease Hierarchy	DISPAV44: RASopathy DISY9Q92: CBL-related disorder
Disease Identifiers	MONDO ID MONDO_0013308 UMLS CUI C3150803 OMIM ID 613563 MedGen ID 462153 Orphanet ID 363972

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 2 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CBL	TT7QT13	Limited	Genetic Variation	[1]
CBL	TT7QT13	Definitive	Autosomal dominant	[2]
------------------------------------------------------------------------------------

This Disease Is Related to 1 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CBL	OTTKELCU	Definitive	Autosomal dominant	[2]
------------------------------------------------------------------------------------

References

1	A case of splenomegaly in CBL syndrome.Eur J Med Genet. 2017 Jul;60(7):374-379. doi: 10.1016/j.ejmg.2017.04.009. Epub 2017 Apr 13.
2	Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.