A chronic granulomatous inflammatory disease of the intestines that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms. It primarily causes abdominal pain, diarrhea which may be bloody, vomiting, or weight loss, but may also cause complications outside of the gastrointestinal tract such as skin rashes, arthritis, inflammation of the eye, tiredness, and lack of concentration. Crohn's disease is thought to be an autoimmune disease, in which the body's immune system attacks the gastrointestinal tract, causing inflammation.

The WAS-related disorders, which include Wiskott-Aldrich syndrome, X-linked thrombocytopenia (XLT), and X-linked congenital neutropenia (XLN), are a spectrum of disorders of hematopoietic cells, with predominant defects of platelets and lymphocytes caused by pathogenic variants in WAS. WAS-related disorders usually present in infancy. Affected males have thrombocytopenia with intermittent mucosal bleeding, bloody diarrhea, and intermittent or chronic petechiae and purpura; eczema; and recurrent bacterial and viral infections, particularly of the ear. At least 40% of those who survive the early complications develop one or more autoimmune conditions including hemolytic anemia, immune thrombocytopenic purpura, immune-mediated neutropenia, rheumatoid arthritis, vasculitis, and immune-mediated damage to the kidneys and liver. Individuals with a WAS-related disorder, particularly those who have been exposed to Epstein-Barr virus (EBV), are at increased risk of developing lymphomas, which often occur in unusual, extranodal locations including the brain, lung, or gastrointestinal tract. Males with XLT have thrombocytopenia with small platelets; other complications of Wiskott-Aldrich syndrome, including eczema and immune dysfunction, are usually mild or absent. Males with XLN have congenital neutropenia, myeloid dysplasia, and lymphoid cell abnormalities.

An inflammatory bowel disease that has material basis in variation in the chromosome region 6p21.3.

An inflammatory bowel disease that has material basis in variation in the chromosome region 18p11.

MASP2 deficiency, classically defined as MASP2 protein level of less than 100 ng/ml, occurs in about 4% of Caucasians and up to 18% of some African populations. Some MASP2-deficient individuals have increased risk of infection or autoimmune disease, but most are asymptomatic. MASP2 plays a role in activation of the lectin pathway of the complement system; deficiency may thus lead to defects in the complement system (summary by Thiel et al., 2007 and Sokolowska et al., 2015). For a discussion of genetic heterogeneity of lectin complement activation pathway defects, see LCAPD1 (614372).

Autoinflammation, antibody deficiency, and immune dysregulation (APLAID) is an autosomal dominant systemic disorder characterized by recurrent blistering skin lesions with a dense inflammatory infiltrate and variable involvement of other tissues, including joints, the eye, and the gastrointestinal tract. Affected individuals have a mild humoral immune deficiency associated with recurrent sinopulmonary infections, but no evidence of circulating autoantibodies (summary by Zhou et al., 2012).

Frontometaphyseal dysplasia (FMD) is a progressive sclerosing skeletal dysplasia characterized by supraorbital hyperostosis, undermodeling of the small bones, and small and large joint contractures, as well as extraskeletal developmental abnormalities, primarily of the cardiorespiratory system and genitourinary tract. Patients with FMD2 appear to have a propensity for keloid formation (summary by Wade et al., 2016). For a discussion of genetic heterogeneity of frontometaphyseal dysplasia, see FMD1 (305620).

IMD11B is an autosomal dominant disorder of immune dysfunction characterized by onset of moderate to severe atopic dermatitis in early childhood. Some patients may have recurrent infections and other variable immune abnormalities. Laboratory studies show defects in T-cell activation, increased IgE, and eosinophilia (summary by Ma et al., 2017).

Inflammatory bowel disease is a chronic inflammatory condition of the gastrointestinal tract (summary by Mohanan et al., 2018). For a general description and a discussion of genetic heterogeneity of inflammatory bowel disease, including Crohn disease (CD) and ulcerative colitis (UC), see IBD1 (266600).

Immunodeficiency-60 and autoimmunity (IMD60) is an autosomal dominant primary immunologic disorder characterized by inflammatory bowel disease and recurrent sinopulmonary infections. The age at symptom onset is highly variable, ranging from infancy to mid-adulthood. Laboratory studies show dysregulation of both B and T cells, with variably decreased immunoglobulin production, decreased T-regulatory cells, and overall impaired lymphocyte maturation (summary by Afzali et al., 2017).

Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder of phagocytes (neutrophils, monocytes, macrophages, and eosinophils) resulting from impaired killing of bacteria and fungi. CGD is characterized by severe recurrent bacterial and fungal infections and dysregulated inflammatory responses resulting in granuloma formation and other inflammatory disorders such as colitis. Infections typically involve the lung (pneumonia), lymph nodes (lymphadenitis), liver (abscess), bone (osteomyelitis), and skin (abscesses or cellulitis). Granulomas typically involve the genitourinary system (bladder) and gastrointestinal tract (often the pylorus initially, and later the esophagus, jejunum, ileum, cecum, rectum, and perirectal area). Some males with X-linked CGD have McLeod neuroacanthocytosis syndrome as the result of a contiguous gene deletion. While CGD may present anytime from infancy to late adulthood, the vast majority of affected individuals are diagnosed before age five years. Use of antimicrobial prophylaxis and therapy has greatly improved overall survival.

Infantile ulcerative colitis (IBD31) is characterized by the presence of ulcers throughout the colon and rectum with normal-appearing ileum. Affected infants present with recurrent bloody diarrhea with anemia and leukocytosis, with extensive lymphoplasmocytic infiltration, cryptitis, and apoptotic crypt abcesses throughout the colon and rectum (Zhang et al., 2021). Infantile bowel disease has also been referred to as very-early-onset IBD (VEOIBD). For a general description and discussion of genetic heterogeneity of inflammatory bowel disease, including Crohn disease (CD) and ulcerative colitis, see IBD1 (266600).

X-linked multisystem autoinflammatory disease with immune dysregulation (ADMIDX) is an X-linked recessive disorder with onset of symptoms in infancy or early childhood. Affected individuals may present with variable cytopenias, including anemia, thrombocytopenia, neutropenia, lymphopenia, or hypogammaglobulinemia, and systemic or organ-specific autoinflammatory manifestations. These include skin lesions, panniculitis, inflammatory bowel disease, pulmonary disease, or arthritis associated with recurrent fever, leukocytosis, lymphoproliferation, and hepatosplenomegaly in the absence of an infectious agent. Some patients have circulating autoantibodies that underlie the cytopenias or systemic features, whereas others do not have circulating autoantibodies. In addition, some patients have recurrent infections, whereas others do not show signs of an immunodeficiency. Laboratory studies are consistent with immune dysregulation, including altered B-cell subsets and variably elevated proinflammatory cytokines. Detailed functional studies of platelets, red cells, and T lymphocytes suggest that abnormal actin cytoskeleton remodeling is a basic defect, indicating that this disorder can be classified as an immune-related actinopathy. Severe complications of the disease may result in death in childhood (Boussard et al., 2023; Block et al., 2023).