FaCD Online Syndrome Fact Sheet

Last updated: 30 Aug 2010

Name: CBL gene-associated Juvenile Myelomonocytic Leukemia and Developmental Anomalies

Synonym: CBL-associated JMML

Mode of Inheritance: AD

Genes

CBL, mapped to 11q23.3

Tumor features

germinoma, intracranial
juvenile myeloid / myelomonocytic leukemia (JMML)
juvenile xanthogranuloma

Tumor features (possible)

Hodgkin disease (Hodgkin's lymphoma)

Non-tumor features

café au lait spots
cardiomyopathy
craniofacial dysmorphisms
cryptorchism
developmental delay/mental deficiency/mental retardation
frontal bossing / prominent forehead
growth deficieny
hearing loss
nasal bridge, depressed
optic atrophy
palpebral fissures, downward slanting
ptosis
vasculitis

Comment

Somatic CBL mutations have been detected in myeloproliferative syndromes. Niemeyer et al[1] observed mono-allelic germline CBL mutations in patients with juvenilie myelomonocytic leukemia (JMML). Some mutation carriers showed spontaneous regression of their JMML and developed vascular pathology and other autoimmune disease associated features later in life. An intracranial germinoma with homozygous CBL mutations was observed in one patient. Hodgkin lymphoma was reported in the father of one of the patients.
Congenital anomalies in the studied patients overlapped with NF1, Noonan syndrome and Legius syndrome. In another study, germline CBL mutations have been detected in patients with Noonan-like features as well[2]. See also Noonan syndrome.

References

[1] Niemeyer CM, Kang MW, Shin DH, Furlan I, Erlacher M, Bunin NJ, Bunda S, Finklestein JZ, Sakamoto KM, Gorr TA, Mehta P, Schmid I, Kropshofer G, Corbacioglu S, Lang PJ, Klein C, Schlegel PG, Heinzmann A, Schneider M, Starý J, van den Heuvel-Eibrink MM, Hasle H, Locatelli F, Sakai D, Archambeault S, Chen L, Russell RC, Sybingco SS, Ohh M, Braun BS, Flotho C, Loh ML. Germline CBL mutations cause developmental abnormalities and predispose to juvenile myelomonocytic leukemia. Nat Genet. 2010 Aug 8. [Epub ahead of print]
[2] Martinelli S, De Luca A, Stellacci E, Rossi C, Checquolo S, Lepri F, Caputo V, Silvano M, Buscherini F, Consoli F, Ferrara G, Digilio MC, Cavaliere ML, van Hagen JM, Zampino G, van der Burgt I, Ferrero GB, Mazzanti L, Screpanti I, Yntema HG, Nillesen WM, Savarirayan R, Zenker M, Dallapiccola B, Gelb BD, Tartaglia M. Heterozygous germline mutations in the CBL tumor-suppressor gene cause a Noonan syndrome-like phenotype. Am J Hum Genet. 2010 Aug 13;87(2):250-7.