title: Hydrops, fetal pleural effusions and chylothorax in three patients with CBL mutations.
abstract: Fetal hydrops, fetal pleural effusions, hydrothorax, and chylothorax, may be associated with various genetic disorders, in particular with the Noonan, cardio-facio-cutaneous and Costello syndromes. These syndromes, collectively called RASopathies, are caused by mutations in the RAS/MAPK pathway, which is known to play a major role in lymphangiogenesis. Recently, germline mutations in the Casitas B-cell lymphoma (CBL) gene were reported in 25 patients and of these, 20 had juvenile myelomonocytic leukemia (JMML). The disorder was named "CBL syndrome" or "Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia" (NSLL). To date, prenatal abnormalities have not been reported and it is still debated whether the CBL syndrome falls into the category of a RASopathy, or represents a different entity. Here we report on three unrelated patients with CBL mutations manifesting with hydrops fetalis, fetal pleural effusions and/or congenital hydro-/chylothorax. Our findings further connect the CBL syndrome with the RASopathies.
authors.affiliation: Institute of Human Genetics, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Luzie
authors.initials: L
authors.lastname: Bülow
authors.forename: Christina
authors.initials: C
authors.lastname: Lissewski
authors.forename: Rainer
authors.initials: R
authors.lastname: Bressel
authors.forename: Anita
authors.initials: A
authors.lastname: Rauch
authors.forename: Zornitza
authors.initials: Z
authors.lastname: Stark
authors.forename: Martin
authors.initials: M
authors.lastname: Zenker
authors.forename: Oliver
authors.initials: O
authors.lastname: Bartsch
mesh_terms: D002675:Child, Preschool; D002916:Chylothorax / Q000151:congenital* / Q000235:genetics; D004252:DNA Mutational Analysis; D019066:Facies; D005260:Female; D006579:Heterozygote; D006801:Humans; D015160:Hydrops Fetalis / Q000235:genetics*; D007223:Infant; D008297:Male; D009154:Mutation; D010641:Phenotype; D010996:Pleural Effusion / Q000235:genetics*; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics*; D022821:RNA Splice Sites
chemical_list: D022821:RNA Splice Sites; D050721:Proto-Oncogene Proteins c-cbl; C067419:CBL protein, human
keywords: CBL gene; Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (OMIM #613563); RASopathy; congenital hydrothorax or chylothorax; hydrops