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Autoinflammatory syndrome, familial, Behcet-like 1(AIFBL1)

MedGen UID:
898541
Concept ID:
C4225218
Disease or Syndrome
Synonym: AIFBL1
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): TNFAIP3 (6q23.3)
 
Monarch Initiative: MONDO:0800045
OMIM®: 616744
Orphanet: ORPHA476102

Definition

Familial Behcet-like autoinflammatory syndrome-1 (AIFBL1) is an autosomal dominant monogenic autoinflammatory disease characterized predominantly by painful and recurrent mucosal ulceration affecting the oral mucosa, gastrointestinal tract, and genital areas. The onset of symptoms is usually in the first decade, although later onset has been reported. Additional more variable features include skin rash, uveitis, and polyarthritis, consistent with a systemic hyperinflammatory state. Many patients have evidence of autoimmune disease. Rare patients may also have concurrent features of immunodeficiency, including recurrent infections with low numbers of certain white blood cells or impaired function of immune cells. The disorder results from a failure of mutant TNFAIP3 to suppress the activation of inflammatory cytokines in the NFKB (see 164011) signaling pathway; treatment with tumor necrosis factor (TNFA; 191160) inhibitors may be beneficial. Although some of the clinical features of AIFBL1 resemble those of Behcet disease (109650), the more common form of Behcet disease is believed to be polygenic, typically shows later onset in early adulthood, and has symptoms usually restricted to the mucosa (summary by Zhou et al., 2016; Aeschlimann et al., 2018, and Kadowaki et al., 2018). Genetic Heterogeneity of AIFBL See also AIFBL2 (301074), caused by mutation in the ELF4 gene (300775) on chromosome Xq26, and AIFBL3 (618287), caused by mutation in the RELA gene (164014) on chromosome 11q13. [from OMIM]

Clinical features

From HPO
Genital ulcers
MedGen UID:
57716
Concept ID:
C0151281
Disease or Syndrome
Colitis
MedGen UID:
40385
Concept ID:
C0009319
Disease or Syndrome
Ulcerative colitis is a chronic disorder that affects the digestive system. This condition is characterized by abnormal inflammation of the inner surface (epithelium) of the rectum and colon. The rectum and colon make up most of the length of the large intestine. The inflammation usually causes open sores (ulcers) to develop in the large intestine. Ulcerative colitis usually appears between the age of 15 and 30, although it can develop at any age. The inflammation tends to flare up multiple times throughout a person's life, which causes recurring signs and symptoms.\n\nThe most common symptoms of ulcerative colitis are cramping abdominal pain and frequent diarrhea, often with blood, pus, or mucus in the stool. Other signs and symptoms include nausea, loss of appetite, bowel urgency, fatigue, and fevers. Chronic bleeding from the inflamed and ulcerated intestinal tissue can cause a shortage of red blood cells (anemia) in some affected individuals. People with this disorder have difficulty absorbing enough fluids and nutrients from their diet and often experience weight loss. Affected children usually grow more slowly than normal. Less commonly, ulcerative colitis causes problems with the skin, joints, eyes, kidneys, or liver, which are most likely due to abnormal inflammation.\n\nToxic megacolon is a rare complication of ulcerative colitis that can be life-threatening. Toxic megacolon involves a widening (dilation) of the colon and an overwhelming inflammatory response. Ulcerative colitis also increases the risk of developing colon cancer, especially in people whose entire colon is inflamed and in those who have had ulcerative colitis for 8 years or more.\n\nUlcerative colitis is one common form of inflammatory bowel disease (IBD). Another type of IBD, Crohn's disease, also causes chronic inflammation of the intestines. Unlike ulcerative colitis, which affects only the inner surface of the large intestine, Crohn's disease can cause inflammation in any part of the digestive system, and the inflammation extends deeper into the intestinal tissue.
Ileal ulcer
MedGen UID:
99248
Concept ID:
C0520564
Disease or Syndrome
An erosion of the mucous membrane in a portion of the ileum.
Chorea
MedGen UID:
3420
Concept ID:
C0008489
Disease or Syndrome
Chorea (Greek for 'dance') refers to widespread arrhythmic involuntary movements of a forcible, jerky and restless fashion. It is a random-appearing sequence of one or more discrete involuntary movements or movement fragments. Movements appear random because of variability in timing, duration or location. Each movement may have a distinct start and end. However, movements may be strung together and thus may appear to flow randomly from one muscle group to another. Chorea can involve the trunk, neck, face, tongue, and extremities.
Hemolytic anemia
MedGen UID:
1916
Concept ID:
C0002878
Disease or Syndrome
A type of anemia caused by premature destruction of red blood cells (hemolysis).
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Polyarticular arthritis
MedGen UID:
56408
Concept ID:
C0162323
Disease or Syndrome
An arthritis affecting five or more separate joints.
Lymphopenia
MedGen UID:
7418
Concept ID:
C0024312
Disease or Syndrome
A reduced number of lymphocytes in the blood.
Anterior uveitis
MedGen UID:
22595
Concept ID:
C0042165
Disease or Syndrome
Inflammation of the uveal tract in which the primary site of inflammation is the anterior chamber.
Antinuclear antibody positivity
MedGen UID:
101792
Concept ID:
C0151480
Laboratory or Test Result
The presence of autoantibodies in the serum that react against nuclei or nuclear components.
Lupus anticoagulant
MedGen UID:
1370558
Concept ID:
C4321325
Finding
Presence of lupus anticoagulant (LA) autoantibodies. LA represent a heterogeneous group of autoantibodies, IgG, IgM, or a mixture of both classes, that interfere with standard phospholipid-based coagulant tests (this is only an in vitro phenomenon, LA do not cause reduction of coagulation in vivo). The antibodies are directed against plasma proteins which also bind to phospholipid surfaces.
Skin rash
MedGen UID:
1830322
Concept ID:
C5779628
Sign or Symptom
A red eruption of the skin.
Recurrent fever
MedGen UID:
811468
Concept ID:
C3714772
Sign or Symptom
Periodic (episodic or recurrent) bouts of fever.
Oral ulcer
MedGen UID:
57699
Concept ID:
C0149745
Disease or Syndrome
Erosion of the mucous mebrane of the mouth with local excavation of the surface, resulting from the sloughing of inflammatory necrotic tissue.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Recent clinical studies

Etiology

Jiang W, Deng M, Gan C, Wang L, Mao H, Li Q
Cell Immunol 2022 Jan;371:104453. Epub 2021 Nov 10 doi: 10.1016/j.cellimm.2021.104453. PMID: 34808442

Diagnosis

Jiang W, Deng M, Gan C, Wang L, Mao H, Li Q
Cell Immunol 2022 Jan;371:104453. Epub 2021 Nov 10 doi: 10.1016/j.cellimm.2021.104453. PMID: 34808442
Yan M, Li D, Aknai S, Zhu H, Abudureyim M
Medicine (Baltimore) 2021 May 21;100(20):e25954. doi: 10.1097/MD.0000000000025954. PMID: 34011076Free PMC Article

Therapy

Yan M, Li D, Aknai S, Zhu H, Abudureyim M
Medicine (Baltimore) 2021 May 21;100(20):e25954. doi: 10.1097/MD.0000000000025954. PMID: 34011076Free PMC Article

Clinical prediction guides

Jiang W, Deng M, Gan C, Wang L, Mao H, Li Q
Cell Immunol 2022 Jan;371:104453. Epub 2021 Nov 10 doi: 10.1016/j.cellimm.2021.104453. PMID: 34808442
Yan M, Li D, Aknai S, Zhu H, Abudureyim M
Medicine (Baltimore) 2021 May 21;100(20):e25954. doi: 10.1097/MD.0000000000025954. PMID: 34011076Free PMC Article

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