Familial Mediterranean fever- MedGen UID:
- 45811
- •Concept ID:
- C0031069
- •
- Disease or Syndrome
Familial Mediterranean fever (FMF) is divided into two phenotypes: type 1 and type 2. FMF type 1 is characterized by recurrent short episodes of inflammation and serositis including fever, peritonitis, synovitis, pleuritis, and, rarely, pericarditis and meningitis. The symptoms and severity vary among affected individuals, sometimes even among members of the same family. Amyloidosis, which can lead to renal failure, is the most severe complication, if untreated. FMF type 2 is characterized by amyloidosis as the first clinical manifestation of FMF in an otherwise asymptomatic individual.
Crohn disease-associated growth failure, susceptibility to- MedGen UID:
- 436348
- •Concept ID:
- C2675113
- •
- Finding
Vasculitis due to ADA2 deficiency- MedGen UID:
- 854497
- •Concept ID:
- C3887654
- •
- Disease or Syndrome
Adenosine deaminase 2 deficiency (DADA2) is a complex systemic autoinflammatory disorder in which vasculopathy/vasculitis, dysregulated immune function, and/or hematologic abnormalities may predominate. Inflammatory features include intermittent fevers, rash (often livedo racemosa/reticularis), and musculoskeletal involvement (myalgia/arthralgia, arthritis, myositis). Vasculitis, which usually begins before age ten years, may manifest as early-onset ischemic (lacunar) and/or hemorrhagic strokes, or as cutaneous or systemic polyarteritis nodosa. Hypertension and hepatosplenomegaly are often found. More severe involvement may lead to progressive central neurologic deficits (dysarthria, ataxia, cranial nerve palsies, cognitive impairment) or to ischemic injury to the kidney, intestine, and/or digits. Dysregulation of immune function can lead to immunodeficiency or autoimmunity of varying severity; lymphadenopathy may be present and some affected individuals have had lymphoproliferative disease. Hematologic disorders may begin early in life or in late adulthood, and can include lymphopenia, neutropenia, pure red cell aplasia, thrombocytopenia, or pancytopenia. Of note, both interfamilial and intrafamilial phenotypic variability (e.g., in age of onset, frequency and severity of manifestations) can be observed; also, individuals with biallelic ADA2 pathogenic variants may remain asymptomatic until adulthood or may never develop clinical manifestations of DADA2.
Familial cold autoinflammatory syndrome 1- MedGen UID:
- 1647324
- •Concept ID:
- C4551895
- •
- Disease or Syndrome
Cryopyrin-associated periodic syndromes (CAPS) are a group of conditions that have overlapping signs and symptoms and the same genetic cause. The group includes three conditions known as familial cold autoinflammatory syndrome type 1 (FCAS1), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disorder (NOMID). These conditions were once thought to be distinct disorders but are now considered to be part of the same condition spectrum. FCAS1 is the least severe form of CAPS, MWS is intermediate in severity, and NOMID is the most severe form.\n\nThe signs and symptoms of CAPS affect multiple body systems. Generally, CAPS are characterized by periodic episodes of skin rash, fever, and joint pain. These episodes can be triggered by exposure to cold temperatures, fatigue, other stressors, or they may arise spontaneously. Episodes can last from a few hours to several days. These episodes typically begin in infancy or early childhood and persist throughout life.\n\nWhile the CAPS spectrum shares similar signs and symptoms, the individual conditions tend to have distinct patterns of features. People with FCAS1 are particularly sensitive to the cold, and exposure to cold temperatures can trigger a painful or burning rash. The rash usually affects the torso and limbs but may spread to the rest of the body. In addition to fever and joint pain, other possible symptoms include muscle aches, chills, drowsiness, eye redness, headache, and nausea.\n\nIn people with NOMID, the signs and symptoms of the condition are usually present from birth and persists throughout life. In addition to skin rash and fever, affected individuals may have joint inflammation, swelling, and joint deformities called contractures that may restrict movement. People with NOMID typically have headaches, seizures, and cognitive impairment resulting from chronic meningitis, which is inflammation of the tissue that covers and protects the brain and spinal cord (meninges). Other features of NOMID include eye problems, short stature, distinctive facial features, and kidney damage caused by amyloidosis.\n\nIndividuals with MWS develop the typical periodic episodes of skin rash, fever, and joint pain after cold exposure, although episodes may occur spontaneously or all the time. Additionally, they can develop progressive hearing loss in their teenage years. Other features of MWS include skin lesions or kidney damage from abnormal deposits of a protein called amyloid (amyloidosis).
IL21-related infantile inflammatory bowel disease- MedGen UID:
- 1799211
- •Concept ID:
- C5567788
- •
- Disease or Syndrome
A rare autosomal recessive primary immunodeficiency characterized by infancy onset of severe inflammatory bowel disease with life-threatening diarrhea and failure to thrive, oral aphthous ulcers, and recurrent severe upper and lower respiratory tract infections with finger clubbing. Laboratory examination reveals increased IgE and decreased IgG levels, as well as reduced numbers of circulating CD19+ B-cells including IgM+ naive and class-switched IgG memory B-cells, with a concomitant increase in transitional B-cells, while T-cell numbers and function are normal.
Immunodeficiency 102- MedGen UID:
- 1812534
- •Concept ID:
- C5676886
- •
- Disease or Syndrome
Immunodeficiency-102 (IMD102) is an X-linked recessive immunologic disorder characterized by the onset of recurrent sinopulmonary, mucosal, and other infections in early childhood, usually accompanied by refractory autoimmune cytopenias. Affected individuals have bacterial, viral, and fungal infections, as well as hemolytic anemia, thrombocytopenia, lymphopenia, and decreased NK cells. Laboratory studies show defective T-cell proliferation and function, likely due to signaling abnormalities. The disorder may also manifest as a hyperinflammatory state with immune dysregulation (Delmonte et al., 2021).
Immunodeficiency 114, folate-responsive- MedGen UID:
- 1848890
- •Concept ID:
- C5882719
- •
- Disease or Syndrome
Folate-responsive immunodeficiency-114 (IMD114) is an autosomal recessive immunologic disorder characterized by the onset of oral ulcers and recurrent skin and respiratory infections in early infancy. Affected individuals have lip fissures, skin sores and abscesses, genital dermatitis, chronic diarrhea, and poor overall growth. Laboratory studies show megaloblastic anemia, thrombocytopenia, and lymphopenia with decreased Ig levels. Some individuals have global developmental delay, often with brain imaging abnormalities. Treatment with folic acid supplementation results in significant clinical improvement of the hematologic and immunologic abnormalities, although neurologic abnormalities, if already present, do not respond to treatment. Early intervention and treatment with folic acid supplementation may prevent or delay neurologic deficits in affected infants (Gok et al., 2023; Shiraishi et al., 2023).
Neutropenia, severe congenital, 11, autosomal dominant- MedGen UID:
- 1846394
- •Concept ID:
- C5882742
- •
- Disease or Syndrome
Autosomal dominant severe congenital neutropenia-11 (SCN11) is characterized by the onset of recurrent infections, mainly bacterial, in early childhood. Laboratory studies show severe neutropenia due to maturation arrest and impaired development of myeloid cells. Other leukocyte subsets, including B cells and NK cells, may also be subtly affected. Patients should be followed for possible renal dysfunction (Van Nieuwenhove et al., 2020).
For discussion of genetic heterogeneity of severe congenital neutropenia, see SCN1 (202700).