Familial hemophagocytic lymphohistiocytosis is a rare disease that commonly appears in infancy, and is characterized by proliferation and infiltration of hyperactivated T cells, natural killer cells, B cells, and macrophages (histiocytes) manifesting as acute illness with prolonged fever, hepatosplenomegaly, and cytopenias.  Neurological features, including cranial nerve palsies, irritability, hypotonia, hypertonia, convulsions, ataxia, hemiplegia, neck stiffness, blindness, paralysis, seizures, and coma may also be present,.  In addition, patients with FHL have an increased risk of developing leukemia and lymphoma.  There are five disease subtypes: FHL1, FHL2, FHL3, FHL4, and FHL5, with each type having a different causative gene. 

Almost all patients reported with FHL4 are of Middle Eastern descent. The diagnosis of FHL is based on clinical features and is confirmed by genetic testing.  Without treatment, the median survival of children with familial hemophagocytic lymphohistiocytosis is only a few months.  Patients with FHL4 typically present with symptoms at a later age than those with FHL2.  Treatments include antibiotics or antiviral agents to prevent infections.  Individuals with FHL are treated with chemotherapy and immunotherapy prior to allogeneic hematopoietic cell transplantation (HCT).

Mutations in the STX11 gene have been reported in patients with FHLH type 4.  These mutations include a large 19.2 kb genomic deletion spanning the entire coding region of exon 2, and a nonsense mutation resulting in a premature stop codon in the C-terminal end of the protein.  The encoded protein, t-SNARE syntaxin 11, plays a role in targeting and fusion of intracellular transport vesicles and regulates protein transport between late endosomes and the trans-Golgi network.  

Patients with a nonsense mutation in the gene generally present during infancy, whereas those with biallelic missense mutations may show symptoms at older ages.