FaCD Online Syndrome Fact Sheet

Last updated: 21 Nov 2011

Name: Legius syndrome

Synonym: Neurofibromatosis type 1 - like syndrome, SPRED1 disorder

Mode of Inheritance: AD

Genes

SPRED1, mapped to 15q13.2

Tumor features (possible)

leukemia, acute myeloblastic (AML, M2)

Non-tumor features

axillary freckling
café au lait spots
macrocephaly

Comment

Germline mutations in SRED1 cause a phenotype resembling that of neurofibromatosis type 1 and consists of multiple café-au-lait spots, axillary freckling and macrocephaly[1-4].
Acute monoblastic/myeloblastic leukemia[4,5] has been reported in two patients; whether there is a causal link is unsure[6].

References

[1] Brems H, Chmara M, Sahbatou M, Denayer E, Taniguchi K, Kato R, Somers R, Messiaen L, De Schepper S, Fryns JP, Cools J, Marynen P, Thomas G, Yoshimura A, Legius E. Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype. Nat Genet. 2007 Sep;39(9):1120-6.
[2] Messiaen L, Yao S, Brems H, Callens T, Sathienkijkanchai A, Denayer E, Spencer E, Arn P, Babovic-Vuksanovic D, Bay C, Bobele G, Cohen BH, Escobar L, Eunpu D, Grebe T, Greenstein R, Hachen R, Irons M, Kronn D, Lemire E, Leppig K, Lim C, McDonald M, Narayanan V, Pearn A, Pedersen R, Powell B, Shapiro LR, Skidmore D, Tegay D, Thiese H, Zackai EH, Vijzelaar R, Taniguchi K, Ayada T, Okamoto F, Yoshimura A, Parret A, Korf B, Legius E. Clinical and mutational spectrum of neurofibromatosis type 1-like syndrome. JAMA. 2009 Nov 18;302(19):2111-8.
[3] Denayer E, Chmara M, Brems H, Kievit AM, van Bever Y, Van den Ouweland AM, Van Minkelen R, de Goede-Bolder A, Oostenbrink R, Lakeman P, Beert E, Ishizaki T, Mori T, Keymolen K, Van den Ende J, Mangold E, Peltonen S, Brice G, Rankin J, Van Spaendonck-Zwarts KY, Yoshimura A, Legius E. Legius syndrome in fourteen families. Hum Mutat. 2011 Jan;32(1):E1985-98.
[4] Pasmant E, Sabbagh A, Hanna N, Masliah-Planchon J, Jolly E, Goussard P, Ballerini P, Cartault F, Barbarot S, Landman-Parker J, Soufir N, Parfait B, Vidaud M, Wolkenstein P, Vidaud D, France RN. SPRED1 germline mutations caused a neurofibromatosis type 1 overlapping phenotype. J Med Genet. 2009 Jul;46(7):425-30.
[5] SPRED1 disorder and predisposition to leukemia in children. Pasmant E, Ballerini P, Lapillonne H, Perot C, Vidaud D, Leverger G, Landman-Parker J. Blood. 2009 Jul 30;114(5):1131.
[6] Batz Christiane et al. Does SPRED1 contribute to leukemogenesis in juvenile myelomonocytic leukemia (JMML)?. Blood 2010; 115:2557-8.