FaCD Online Syndrome Fact Sheet

Last updated: 24 Jun 2008

Name: Platelet disorder associated with Myeloid Malignancies

Synonym: Familial Platelet Disorder with Predisposition to Acute Myelogenous Leukemia, FPD/AML, Familial Thrombocytopenia with Propensity to Acute Myelogenous Leukemia

Mode of Inheritance: AD

Genes

CBFA2/RUNX1/AML1, mapped to 21q22.1-q22.2

Tumor features

leukemia, acute myeloid (AML, incl. ANLL)

Tumor features (possible)

mixed tumor of lacrimal gland
neuroblastoma, adrenal

Non-tumor features

platelet deficiency/ abnormal function
thrombocytopenia

Comment

Ho et al.[1] performed linkage analysis in a large family with a platelet dysfunction, thrombopenia and platelet dense granule storage pool deficiency, and a propensity to develop hematological malignancies, especially AML. Two cases of neuroblastoma, a mixed tumor of a lacrimal gland in a 20 year old and a range of late-onset neoplasms had been reported earlier in this family by Dowton et al.[2]. Gerrard et al.[3] also reported on a family with a platelet defect associated with a high incidence of AML. Arepally et al.[4] reported an additional family, in which they mapped the disorder to a 21q region, overlapping the 21q22 region found by Ho et al.[1]. Subsequently, the gene in question, RUNX1, was identified by Song et al.[5]. Constitutional microdeletions of the RUNX1 gene region lead, in addition to developmental delay and dysmorphic features to thrombocytopenia and predisposition to acute myelogenous leukemia[6,7].

References

[1] Ho CY, Otterud B, Legare RD, Varvil T, Saxena R, DeHart DB, Kohler SE, Aster JC, Dowton SB, Li FP, Leppert M, Gilliland DG. Linkage of a familial platelet disorder with a propensity to develop myeloid malignancies to human chromosome 21q22.1-22.2. Blood 87[12], 5218-5224. 1996.
[2] Dowton SB, Beardsley D, Jamison D, Blattner S, Li FP. Studies of a familial platelet disorder. Blood 1985; 65(3):557-563.
[3] Gerrard JM, Israels ED, Bishop AJ, Schroeder ML, Beattie LL, McNicol A, Israels SJ, Walz D, Greenberg AH, Ray M, Israels LG. Inherited platelet-storage pool deficiency associated with a high incidence of acute myeloid leukaemia. Br J Hematol 1991; 79:246-255.
[4] Arepally G, Rebbeck TR, Song W, Gilliland G, Maris JM, Poncz M. Evidence for genetic homogeneity in a familial platelet disorder with predisposition to acute myelogenous leukemia (FPD/AML). Blood 92[7], 2600-2602. 1998.
[5] Song WJ, Sullivan MG, Legare RD, Hutchings S, Tan X, Kufrin D, Ratajczak J, Resende IC, Haworth C, Hock R, Loh M, Felix C, Roy DC, Busque L, Kurnit D, Willman C, Gewirtz AM, Speck NA, Bushweller JH, Li FP, Gardiner K, Poncz M, Maris JM, Gilliland DG. Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia [see comments]. Nat Genet 1999; 23(2):166-175.
[6] Shinawi M, Erez A, Shardy DL, Lee B, Naeem R, Weissenberger G, Chinault AC, Cheung SW, Plon SE. Syndromic thrombocytopenia and predisposition to acute myelogenous leukemia caused by constitutional microdeletions on chromosome 21q. Blood 2008; epub ahead of print.
[7] Béri-Dexheimer M, Latger-Cannard V, Philippe C, Bonnet C, Chambon P, Roth V, Grégoire MJ, Bordigoni P, Lecompte T, Leheup B, Jonveaux P. Clinical phenotype of germline RUNX1 haploinsufficiency: from point mutations to large genomic deletions. European journal of human genetics 2008; epub ahead of print .