FaCD Online Syndrome Fact Sheet

Last updated: 16 Sep 2008

Name: X-linked Lymphoproliferative syndrome

Synonym: XLP, Duncan syndrome, Familial Fatal Epstein-Barr Infection, incl. XLP2

Mode of Inheritance: XLR

Genes

SH2D1A/SAP, mapped to Xq25
XIAP, mapped to Xq25

Tumor features

Burkitt lymphoma
non-Hodgkin lymphoma

Non-tumor features

agammaglobulinemia
anemia, aplastic
hypogammaglobulinemia
immunodeficiency

Comment

This type of combined variable immunodeficiency, XLP, is characterized by a selective susceptibility to Epstein-Barr virus (EBV) infection. Men with the germline defect have a high risk of developing (B-cell) non-Hodgkin lymphoma (especially Burkitt lymphoma[1])[5]. The NHL's are often located in the terminal ileum, other reported locations are liver, kidney, thymus, colon, tonsils and psoas muscle[2;3]. As a rule aplastic anemia in these patients is not associated with NHL[2]. Hypogammaglobulinemia [6,7], growth hormone deficiency[7] and vasulitis/vasculopathy have been reported[8,9] in a few cases. Approximately 80 % of the XLP patients die during childhood and all will have died by the age of 40. In rare cases female carriers are affected[10].
Strahm et al.[4] reported 2 brothers with a germline mutation in SH2D1A who both developed recurrent B-cell non-Hodgkin lymphoma in the absence of evidence of EBV infection. The authors therefore postulated that EBV infection is not a obligate prerequisite for the development of B-cell NHL in XLP and others have reported this as well[10].

Links

International Patient Organisation for Primary Immunodeficiencies (IPOPI) 18 1 08
SH2D1Abase: Mutation registry for X-linked lymphoproliferative syndrome 24 1 08

References

[1] Egeler RM, de Kraker J, Slater R, Purtilo DT. Documentation of Burkitt lymphoma with t(8;14) (q24;q32) in X- linked lymphoproliferative disease. Cancer 1992; 70(3):683-687.
[2] Purtilo DT, Sakamoto K, Barnabei V, Seeley J, Bechtold T, Rogers G, Yetz J, Harada S. Epstein-Barr virus-induced diseases in boys with the X-linked lymphoproliferative syndrome (XLP): update on studies of the registry. Am J Med 1982; 73:49-56.
[3] Harrington DS, Weisenburger DD, Purtilo DT. Malignant lymphoma in the X-linked lymphoproliferative syndrome. Cancer 1987; 59:1419-1429.
[4] Strahm B, Rittweiler K, Duffner U, Brandau O, Orlowska-Volk M, Karajannis MA, zur Stadt U, Tiemann M, Reiter A, Brandis M, Meindl A, Niemeyer CM. Recurrent B-cell non-Hodgkin's lymphoma in two brothers with X- linked lymphoproliferative disease without evidence for Epstein- Barr virus infection. Br J Hematol 2000; 108(2):377-382.
[5] Carbone A, Gloghini A, Dotti G. EBV-Associated Lymphoproliferative Disorders: Classification and Treatment. The oncologist 2008; 13(5):577-85.
[6] Hoshino T, Kanegane H, Doki N, Irisawa H, Sakura T, Nojima Y, Miyawaki S, Miyawaki T. X-linked lymphoproliferative disease in an adult. International journal of hematology 2005; 82(1):55-8.
[7] Alangari A, Abobaker A, Kanegane H, Miyawaki T. X-linked lymphoproliferative disease associated with hypogammaglobulinemia and growth-hormone deficiency. European journal of pediatrics 2006; 165(3):165-7.
[8] Weeks JK, Helton KJ, Conley ME, Onciu M, Khan RB. Diffuse CNS vasculopathy with chronic Epstein-Barr virus infection in X-linked lymphoproliferative disease. AJNR. American journal of neuroradiology 2006; 27(4):884-6.
[9] Kanegane H, Ito Y, Ohshima K, Shichijo T, Tomimasu K, Nomura K, Futatani T, Sumazaki R, Miyawaki T. X-linked lymphoproliferative syndrome presenting with systemic lymphocytic vasculitis. American journal of hematology 2005; 78(2):130-3.
[10] Woon ST, Ameratunga R, Croxson M, Taylor G, Neas K, Edkins E, Browett P, Gane E, Munn S. Follicular lymphoma in a X-linked lymphoproliferative syndrome carrier female. Scandinavian journal of immunology 2008; 68(2):153-8.