FaCD Online Syndrome Fact Sheet

Last updated: 02 Jul 2008

Name: Mast Cell disease, Familial Clustering of

Synonym: incl.: Familial Cutaneous Mastocytosis (Urticaria Pigmentosum)

Mode of Inheritance: AD?/ multifact?

Genes

KIT, mapped to 4q12

Tumor features (possible)

leukemia, acute lymphoblastic (ALL)
leukemia, acute myeloid (AML, incl. ANLL)
ovarian fibroma
ovarian germ cell tumor

Non-tumor features

mastocytosis, systemic
urticaria pigmentosum (cutaneous mastocytosis)

Comment

The familial occurrence of cutaneous mastocytosis, often referred to as urticaria pigmentosum, UP has been reported[1-3]. In addition to UP, cutaneous mastocytosis may also present with solitary cutaneous mastocytoma, telangiectasia macularis eruptiva perstans, diffuse cutaneous mastocytosis and bullous mastocytosis (which has been rarely reported to cluster in families[4]) and sometimes mast cell infiltration of the skin is not associated with skin lesions at all[2]. Sometimes mastocytosis is more generalized (systemic indolent/benign mastocytosis) and may be fatal (aggressive/malignant mastocytosis), but this appears to be rare or absent in familial cases.[5,6,14,15]. In general, UP can be found with and without involvement of other organs.

Various malignant and pre-malignant hematological disorders have been reported in patients with systemic mast cell disease[7]. These include primary mast cell leukemia, but to our knowledge no such cases have been reported in familial mast cell disease. UP without systemic mastocytosis has been reported in association with hematological malignancies, mainly AML and ALL[8,9] and occasionally with malignant ovarian germ cell tumors[10].

In a subset of patients cKIT mutations have been detected[11-13], a gene also involved in familial gastrointestinal stromal tumors.

References

[1] Fowler JF, Parsley WM, Cotter PG. Familial urticaria pigmentosa. Arch Dermatol 1986; 122:80-81.
[2] Clark DP, Buescher L, Havey A. Familial urticaria pigmentosa. Arch Intern Med 1990; 150:1742-1744.
[3] Anstey A, Lowe DG, Kirby JD, Horton MA. Familial mastocytosis: a clinical, immunophenotypic, light and electron microscopic study. Br J Dermatol 1991; 125:583-587.
[4] Oku T, Hashizume H, Yokote R, Sano T, Yamada M. The familial occurrence of bullous mastocytosis (diffuse cutaneous mastocytosis). Arch Dermatol 1990; 126:1478-1484.
[5] Valent P. Biology,classification and treatment of human mastocytosis. Wien Klin Wochenschr 1996; 108(13):385-397.
[6] Födinger M, Mannhalter C. molecular genetics and development of mast cells: implications for molecular medicine. Mol Med Today 1997; march:131-137.
[7] Parker RI. Hematologic aspects of mastocytosis:II: management of hematologic disorders in association with systemic mast cell disease. J Invest Dermatol 1991; 96(3 suppl):52S-54S.
[8] Lewis HM, Winter E, Darbyshire P, Yoong A, Marsden JR, Moss C. Urticaria pigmentosa nad acute lymphoblastic leukaemia. J R Soc Med 1995; 88:530P-531P.
[9] Ogg GS, Rosbotham JL, MacDonald DM. Urticaria pigmentosa coexisting with multiple myeloma. Clin Exp Dermatol 1996; 21:365-366.
[10] Drut R. Case 2 malignant germ cell tumor and urticaria pigmentosa. Pediatr Pathol Lab Med 1995; 15:163-168.
[11] Longley BJJr, Metcalfe DD, Tharp M, Wang XM, Tyrrell L, Lu SZ, Heitjan D, Ma YS. Activating and dominant inactivating c-KIT catalytic domain mutations in distinct clinical forms of human mastocytosis. Proc Natl Acad Sci U S A 96, 1609-1614. 1999.
[12] Zhang LY, Smith ML, Schultheis B, Fitzgibbon J, Lister TA, Melo JV, Cross NC, Cavenagh JD. A novel K509I mutation of KIT identified in familial mastocytosis-in vitro and in vivo responsiveness to imatinib therapy. Leukemia research 2006; 30(4):373-8.
[13] Tang X, Boxer M, Drummond A, Ogston P, Hodgins M, Burden AD. A germline mutation in KIT in familial diffuse cutaneous mastocytosis. Journal of medical genetics 2004; 41(6):e88.
[14] Valent P, Horny HP, Escribano L, Longley BJ, Li CY, Schwartz LB, Marone G, Nuñez R, Akin C, Sotlar K, Sperr WR, Wolff K, Brunning RD, Parwaresch RM, Austen KF, Lennert K, Metcalfe DD, Vardiman JW, Bennett JM. Diagnostic criteria and classification of mastocytosis: a consensus proposal. Leukemia research 2001; 25(7):603-25.
[15] Horny HP, Sotlar K, Valent P. Mastocytosis: state of the art. Pathobiology : journal of immunopathology, molecular and cellular biology 2007; 74(2):121-32.