<unk>  is a form of<unk>  disorder.  It affects lymphocyte apoptosis.<unk>  <unk>  is a rare disorder of abnormal lymphocyte survival caused defective Fas mediated apoptosis.<unk>  was first reported in 1967 by Canale and Smith; thus it was named initially as Canale and Smith<unk> . According to the 2010 revised guidelines, now<unk>  is defined by the presence of chronic, non-malignant, and non-infectious lymphadenopathy along with<unk>  cytopenias.<unk>  was first explained in 1990 in a cohort of patients with chronic lymphoproliferation and increased numbers of double-negative T cells (DNTs).  Also<unk>  is associated with increased level of IL-10,IL-12,vitamin B 12, soluble FAS ligand and IgG in serum. In vitro evidence of defective FAS mediated apoptosis is also found in<unk> . For proper development of immune system and regulation of apoptosis FAS receptor pathway is very important. Heterozygous mutation in genes in the FAS pathway cause<unk> . Other different kinds of mutations also identified and gene based nomenclature is recommended nowadays to describe new cases. The true incidence and prevalence of<unk>  are still not known due to the high rate of misdiagnosis or remain undiagnosed. FAS plays an important role in controlling the malignant transformation of lymphocytes. Hence,<unk>  patients are at high risk of developing lymphoma. Germline FAS mutation is the most common while somatic mutation is the second most common cause. Many of the patients with<unk>  have unidentified genetic defects.<unk>  mostly occur in early childhood with a median age of 18 months. Common clinical features are chronic lymphadenopathy(95% of patients), splenomegaly(90% of patients), or hepatomegaly(40-50% of patients). Lymphoproliferation is the earliest symptom with a median age of onset is 11.5 months. Lymphoproliferation can get worsen in adolescence and eventually get resolved in early 20s.Most of the<unk>  patients have non tender, enlarged lymph nodes for a prolonged duration. In<unk> , second most common clinical manifestations are related to<unk> ty as hemolytic anemia, thrombocytopenia and neutropenia. Cytopenias are accompanied with elevated or reduced serum IgG.<unk>  cytopenias might be absent in the intital periods of<unk>  but Coombs positive<unk>  hemolytic anemia and thrombocytopenia with or without autoantibodies might get detected even before any clinical manifestations.<unk>  cytopenias can be asymptomatic to life threatening illiness. Treatment of cytopenias in<unk>  may range from periodic treatment to chronic. Similar to lymphoproliferation,<unk>  cytopenias may improve with age but less chance of complete resolution by adulthood.10-20% of patients with<unk>  can have<unk>  manifestations involving other organ systems such as skin rashes, pulmonary fibrosis, hepatitis, uveitis,colitis,pancreatitis,Systemic lupus erythematosus,Guillain-Barre<unk> , transverse myelitis, cerebellar ataxia and arthritis. Anticardiolipin antibodies are also commonly found but thromboembolic events are rare. The symptoms of lymphadenopathy, splenomegaly and<unk>  cytopenias in<unk>  create a challenge to reach proper diagnosis as these symptoms overlap with other childhood hematologic disorders as histiocytosis,lymphoma,heredietary spherocytosis, Evans<unk>  and Rosai-Dorfman<unk> . Immune disorders with<unk>  componenet as common variable immunodeficiency and Wiskott-Aldrich<unk>  also should be excluded. According to the revised guideline in 2010, to diagnose<unk>  there should be 2 required and 6 additional criterias.Required criterias are chronic Lymphadenopathy with or without splenomegaly and increased TCRαβ+ DNT cells in circulation. Primary additional criterias are abnormal lymphocyte apoptosis assay and the presence of pathogenic mutations in FAS gene.Definitive diagnosis of<unk>  requires 2 required criteria and one of the two primary additional criteria. There is no single laboratory test to diagnose<unk> . Patients with suspected<unk>  should get investigated for<unk>  related mutations.Treatment of<unk>  is focused mainly on immunosuppression to treat<unk>  symptoms as  cytopenias and to avoid splenectomy. In severe cases of<unk>  which are refractory to immunosuppressors, hematopoietic stem cell transplant is the final treatment of choice.
Autoimmune lymphoproliferative syndrome
Bare lymphocyte syndrome
X-linked lymphoproliferative disease
Nodal marginal zone lymphoma
Post transplant lymphoproliferative disorder
Peripheral T cell lymphoma
Posttransplantation lymphoproliferative disorder
AIDS-related lymphoma