FaCD Online Syndrome Fact Sheet

Last updated: 18 Apr 2008

Name: Familial Hemophagocytic Lymphohistiocytosis

Synonym: FHLH, FHL, Familial Hemophagocytic Reticulosis, FHR

Mode of Inheritance: AR

Genes

HPLH1#, mapped to 9q21.3-q22
PRF1, mapped to 10q22
RAG1, mapped to 11p13
RAG2, mapped to 11p13
STX11, mapped to 6q24
UNC13D, mapped to 17q25.1

Tumor features (possible)

leukemia, acute myeloid (AML, incl. ANLL)
myelodysplastic syndrome (MDS)
non-Hodgkin lymphoma

Non-tumor features

histiocytosis

Comment

Many types of histiocytosis, including several hereditary types[1], exist and although many of them can be fatal, only Class III histiocytosis is regarded as neoplastic[2]. FHL is a group of histiocytosis including familial lymphohistiocytosis, familial erythrophagocytic lymphohistiocytosis, familial hemophagocytic reticulosis, familial histiocytic reticulosis (a subset which includes Omenn syndrome), Nelson syndrome, familial Letterer-Siwe disease, acute infantile non-lipoid reticuloendotheliosis and acute disseminated histiocytosis X[1]. It is characterized by infiltration of histiocytes in internal organs, bone marrow, lymph nodes, central nervous system and other tissues. Onset of the disease is usually in early infancy. Outcome is generally fatal, although new treatment modalities may improve the course of the disease.[1;3].

Mache et al.[4] reported 2 siblings with FHL both of whom developed a disseminated T-cell lymphoma.
Myelodysplastic syndrome and AML have been observed in patients with syntaxin 11 gene mutations[5].

References

[1] Spritz RA. The familial histiocytoses. Pediatr Pathol 1985; 3(1):43-57.
[2] Stephan JL. Histiocytoses. Eur J Pediatr 1995; 154(8):600-609.
[3] Caballes RL, Caballes-Ponce MG, Kim DU. Familial hemophagocytic lymphohistiocytosis (FHLH). Pathology 1997; 29(1):92-95.
[4] Mache CJ, Slavc I, Schmid C, Hoefler G, Urban CE, Schwinger W, Winter E, Hulla W, Zenz W, Holter W. Familial hemophagocytic lymphohistiocytosis associated with disseminated T-cell lymphoma: a report of two siblings. Ann Hematol 1994; 69(2):85-91.
[5] Rudd E, Göransdotter Ericson K, Zheng C, Uysal Z, Ozkan A, Gürgey A, Fadeel B, Nordenskjöld M, Henter JI. Spectrum and clinical implications of syntaxin 11 gene mutations in familial haemophagocytic lymphohistiocytosis: association with disease-free remissions and haematopoietic malignancies. Journal of medical genetics 2006; 43(4):e14.