Phenotypes associated with the disease immunodysregulation with variable immunodeficiency and autoimmunity (OMIM:621233, an entry in Online Mendelian Inheritance in Man):
- Decreased body weight (HP:0004325, a Human Phenotype Ontology term): Abnormally low body weight. Evidence: PCS. Frequency: 1/1. (PMID:34826259)
- Short stature (HP:0004322, a Human Phenotype Ontology term): A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms). Evidence: PCS. Frequency: 1/1. (PMID:34826259)
- Increased central memory CD8+ T cell proportion (HP:0410396, a Human Phenotype Ontology term): An increased proportion of central memory CD8-positive, alpha-beta T cells compared to the total number of T cells in the blood. These cells have the phenotype CCR7-positive, CD127-positive, CD45RA-negative, CD45RO-positive, and CD25-negative. Evidence: PCS. Frequency: 2/2. (PMID:34826260)
- Childhood onset (HP:0011463, a Human Phenotype Ontology term): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 1/1. (PMID:34826259)
- Young adult onset (HP:0011462, a Human Phenotype Ontology term): Onset of disease at the age of between 16 and 40 years. Evidence: PCS. Frequency: 3/4. (PMID:34826260;PMID:34920454)
- Increased transitional B cell proportion (HP:0030381, a Human Phenotype Ontology term): Abnormal increase of the transitional B cell subpopulation, commonly characterized as CD27-CD24hiCD38hi or CD27-IgMhiCD38hi, measured as percentage of total B cells in the blood, compared to a reference range for a given sex and age-group. Evidence: PCS. Frequency: 2/2. (PMID:34826260)
- Arthritis (HP:0001369, a Human Phenotype Ontology term): Inflammation of a joint. Evidence: PCS. Frequency: 2/2. (PMID:34920454)
- Reduced total natural killer cell count (HP:0040218, a Human Phenotype Ontology term): The absolute count of natural killer cells in the blood, per microlitre, is below the lower limit of normal. Evidence: PCS. Frequency: 1/1. (PMID:34826259)
- Decreased class-switched memory B cell proportion (HP:0030388, a Human Phenotype Ontology term): A reduction in the normal proportion of class-switched memory B cells (CD19+/CD27+/IgM+/IgD+) relative to the total number of B cells. Marginal zone B cells undergo limited somatic hypermutation and produce high-affinity IgM and some IgG, whereas class-switched memory B cells synthetize IgG, IgM, and IgA. Evidence: PCS. Frequency: 1/2. (PMID:34826260)
- Bronchiectasis (HP:0002110, a Human Phenotype Ontology term): Persistent abnormal dilatation of the bronchi owing to localized and irreversible destruction and widening of the large airways. Evidence: PCS. Frequency: 1/1. (PMID:34826259)
- Abnormal effector memory CD8+ T cell proportion (HP:0410383, a Human Phenotype Ontology term): An abnormal proportion of effector memory CD8-positive, alpha-beta memory T cells compared to the total number of T cells in the blood. These cells have the phenotype of CCR7-negative, CD127-positive, CD45RA-negative, CD45RO-positive, and CD25-negative. Evidence: PCS. Frequency: 0/2. (PMID:34826260)
- Increased circulating ferritin concentration (HP:0003281, a Human Phenotype Ontology term): Increased concentration of ferritin in the blood circulation. Evidence: PCS. Frequency: 0/1. (PMID:34920454)
- Decreased unswitched memory B cell proportion (HP:0032126, a Human Phenotype Ontology term): Abnormal reduction of the unswitched memory B cell subpopulation, commonly characterized as CD27+IgM+, measured as percentage of total B cells in the blood, compared to a reference range for a given sex and age-group. Evidence: PCS. Frequency: 1/2. (PMID:34826260)
- Decreased plasmablast proportion (HP:0032129, a Human Phenotype Ontology term): Abnormal decrease of plasmablasts, commonly characterized as CD27+CD38hi and sometimes additionally as IgMlowCD24-, measured as percentage of total B cells in the blood, compared to a reference range for a given sex and age-group. Evidence: PCS. Frequency: 1/2. (PMID:34826260)
- Hodgkin lymphoma (HP:0012189, a Human Phenotype Ontology term): A type of lymphoma characterized microscopically by multinucleated Reed-Sternberg cells. Evidence: PCS. Frequency: 1/2. (PMID:34826260)
- Arthralgia (HP:0002829, a Human Phenotype Ontology term): Joint pain. Evidence: PCS. Frequency: 1/1. (PMID:34826259)
- Decreased circulating total IgG concentration (HP:0032132, a Human Phenotype Ontology term): A reduction beneath the normal level of total immunoglobulin G (IgG) in the blood. Evidence: PCS. Frequency: 2/3. (PMID:34826260;PMID:34826259)
- Inverted CD4:CD8 ratio (HP:0033222, a Human Phenotype Ontology term): CD4:CD8 ratio less than 1, measured either as proportion of total CD3+ T cells, or in absolute numbers per microliter. These are usually measured within the TCR alpha/beta positive population. Normally there are relatively more CD4+ than CD8+ T cells. Evidence: PCS. Frequency: 1/1. (PMID:34826259)
- Recurrent otitis media (HP:0000403, a Human Phenotype Ontology term): Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media. Evidence: PCS. Frequency: 1/1. (PMID:34826259)
- Autosomal recessive inheritance (HP:0000007, a Human Phenotype Ontology term): 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 individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Evidence: PCS. (PMID:34826259)
- Autoimmune thrombocytopenia (HP:0001973, a Human Phenotype Ontology term): The presence of thrombocytopenia in combination with detection of antiplatelet antibodies. Evidence: PCS. Frequency: 1/1. (PMID:34920454)
- Autosomal dominant inheritance (HP:0000006, a Human Phenotype Ontology term): 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. Evidence: PCS. (PMID:34826260)
- Increased total leukocyte count (HP:0001974, a Human Phenotype Ontology term): An abnormal increase in the number of leukocytes in the blood. Evidence: PCS. Frequency: 1/1. (PMID:34920454)
- Chronic diarrhea (HP:0002028, a Human Phenotype Ontology term): The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks. Evidence: PCS. Frequency: 1/1. (PMID:34826260)
- Decreased naive CD4+ T cell proportion (HP:0410378, a Human Phenotype Ontology term): The proportion of naive CD4 T cells relative to the total number of T cells is below the lower limit of normal. Evidence: PCS. Frequency: 1/2. (PMID:34826260)
- Decreased naive CD8+ T cell proportion (HP:0410377, a Human Phenotype Ontology term): Abnormal decrease of the naive CD8+ T cell subpopulation, commonly characterized as CD45RA+, CD45RO-, or CD27+, measured as percentage of total CD8+ T cells in the blood, compared to a reference range for a given sex and age-group. These cells are sometimes also characterized as CD62L+ and CCR7+. Evidence: PCS. Frequency: 2/2. (PMID:34826260)
- Partial absence of specific antibody response to tetanus vaccine (HP:0410297, a Human Phenotype Ontology term): A reduced ability to synthesize postvaccination antibodies against a tetanus antigen, as measured by antibody titer determination following vaccination. Evidence: PCS. Frequency: 1/1. (PMID:34826259)
- Anti-dsDNA antibody positivity (HP:0020151, a Human Phenotype Ontology term): The presence of autoantibodies (immunoglobulins) in the serum that react against double-stranded DNA. Evidence: PCS. Frequency: 1/1. (PMID:34920454)
- Protracted diarrhea (HP:0004385, a Human Phenotype Ontology term). Evidence: PCS. Frequency: 1/1. (PMID:34826260)
- Decreased circulating IgG1 concentration (HP:0032136, a Human Phenotype Ontology term): A reduction in immunoglobulin levels of the IgG1 subclass in the blood circulation. Evidence: PCS. Frequency: 1/2. (PMID:34826260)
- Decreased circulating IgG3 concentration (HP:0032137, a Human Phenotype Ontology term): A reduction in immunoglobulin levels of the IgG3 subclass in the blood circulation. Evidence: PCS. Frequency: 0/2. (PMID:34826260)
- Increased circulating immunoglobulin concentration (HP:0010702, a Human Phenotype Ontology term): An increased level of gamma globulin (immunoglobulin) in the blood. Evidence: PCS. Frequency: 1/1. (PMID:34920454)
- Decreased circulating IgG4 concentration (HP:0032138, a Human Phenotype Ontology term): A reduction in immunoglobulin levels of the IgG4 subclass in the blood circulation. Evidence: PCS. Frequency: 2/2. (PMID:34826260)
- Recurrent vulvovaginal candidiasis (HP:0012204, a Human Phenotype Ontology term): Recurrent infection involving the vulva, vagina, and adjacent crural areas, whereby the causative agent belongs to the genus Candida. Evidence: PCS. Frequency: 1/2. (PMID:34826260)
- Polyclonal elevated circulating IgE concentration (HP:0032339, a Human Phenotype Ontology term): A heterogeneous increase in IgE mmunoglobulins characterized by a diffuse band on serum electrophoresis. Evidence: PCS. Frequency: 1/2. (PMID:34826260)
- Decreased specific antibody response to vaccination (HP:0032140, a Human Phenotype Ontology term): A reduced ability to synthesize postvaccination antibodies against toxoids and polysaccharides in vaccines, as measured by antibody titer determination following vaccination. Evidence: PCS. Frequency: 1/2. (PMID:34826260)
- Osteopenia (HP:0000938, a Human Phenotype Ontology term): Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5. Evidence: PCS. Frequency: 1/1. (PMID:34826259)
- Severe Epstein Barr virus infection (HP:0031693, a Human Phenotype Ontology term): An unusually severe Epstein Barr virus (EBV) infection. Evidence: PCS. Frequency: 1/1. (PMID:34920454)
- Lymphadenopathy (HP:0002716, a Human Phenotype Ontology term): Enlargement (swelling) of a lymph node. Evidence: PCS. Frequency: 1/1. (PMID:34826260)
- Positive Coombs test (HP:0020026, a Human Phenotype Ontology term): A positive (abnormal) result of the direct antiglobulin test (DAT; sometimes referred to as the Coombs test). The test is a method of demonstrating the presence of antibody or complement bound to red blood cell (RBC) membranes by the use of anti-human globulin to form a visible agglutination reaction. The DAT tests for antibodies or complement bound directly to erythrocytes, indicating in vivo sensitization. Evidence: PCS. Frequency: 0/1. (PMID:34826259)
- Fever (HP:0001945, a Human Phenotype Ontology term): Body temperature elevated above the normal range. Evidence: PCS. Frequency: 0/1. (PMID:34920454)
- Recurrent pneumonia (HP:0006532, a Human Phenotype Ontology term): An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia. Evidence: PCS. Frequency: 2/3. (PMID:34826260;PMID:34826259)
- Splenomegaly (HP:0001744, a Human Phenotype Ontology term): Abnormal increased size of the spleen. Evidence: PCS. Frequency: 0/1. (PMID:34920454)
- Myalgia (HP:0003326, a Human Phenotype Ontology term): Pain in muscle. Evidence: PCS. Frequency: 0/1. (PMID:34920454)
- Decreased circulating IgM concentration (HP:0002850, a Human Phenotype Ontology term): An abnormally decreased level of immunoglobulin M (IgM) in blood. Evidence: PCS. Frequency: 2/3. (PMID:34826260;PMID:34826259)
- Vitiligo (HP:0001045, a Human Phenotype Ontology term). Evidence: PCS. Frequency: 1/2. (PMID:34826260)
- Juvenile onset (HP:0003621, a Human Phenotype Ontology term): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. Frequency: 1/2. (PMID:34920454)
- Cutaneous photosensitivity (HP:0000992, a Human Phenotype Ontology term): An increased sensitivity of the skin to light. Photosensitivity may result in a rash upon exposure to the sun (which is known as photodermatosis). Photosensitivity can be diagnosed by phototests in which light is shone on small areas of skin. Evidence: PCS. Frequency: 1/1. (PMID:34920454)
- Decreased total leukocyte count (HP:0001882, a Human Phenotype Ontology term): An abnormal decreased number of leukocytes in the blood. Evidence: PCS. Frequency: 1/1. (PMID:34826259)
- Recurrent bacterial vaginosis (HP:0030683, a Human Phenotype Ontology term): Repeated symptomatic episodes of inflammation of the vagina that can result from a spectrum of conditions that cause vaginal and sometimes vulvar symptoms, such as itching, burning, irritation, odor, and vaginal discharge. Evidence: PCS. Frequency: 1/1. (PMID:34826260)
- Abnormal circulating IgA concentration (HP:0410240, a Human Phenotype Ontology term): An abnormal deviation from normal levels of IgA immunoglobulin in blood. Evidence: PCS. Frequency: 0/2. (PMID:34826260)
- Abnormal circulating IgE concentration (HP:0410241, a Human Phenotype Ontology term): An abnormal deviation from normal levels of IgE immunoglobulin in blood. Evidence: PCS. Frequency: 0/1. (PMID:34826259)
- Lichenoid skin lesion (HP:0031452, a Human Phenotype Ontology term): Multiple skin lesions resembling those characteristic of the disease lichen planus. These lesions are violaceous (reddish-purple), shiny, isolated, flat-topped papules and plaques. Evidence: PCS. Frequency: 0/1. (PMID:34826260)
- Recurrent sinusitis (HP:0011108, a Human Phenotype Ontology term): A recurrent form of sinusitis. Evidence: PCS. Frequency: 3/3. (PMID:34826260;PMID:34920454;PMID:34826259)
- Recurrent aphthous stomatitis (HP:0011107, a Human Phenotype Ontology term): Recurrent episodes of ulceration of the oral mucosa, typically presenting as painful, sharply circumscribed fibrin-covered mucosal defects with a hyperemic border. Evidence: PCS. Frequency: 2/2. (PMID:34826260)
- Recurrent mucocutaneous candidiasis (HP:0002728, a Human Phenotype Ontology term): Recurrent or persistent superficial Candida infections of the skin, mucous membranes, and nails. Evidence: PCS. Frequency: 1/1. (PMID:34826260)
- Follicular hyperplasia (HP:0002729, a Human Phenotype Ontology term): Lymphadenopathy (enlargement of lymph nodes) owing to hyperplasia of follicular (germinal) centers. Evidence: PCS. Frequency: 1/1. (PMID:34826260)
- Increased effector memory CD4+ T cell proportion (HP:0025625, a Human Phenotype Ontology term): An abnormally increased proportion of effector memory CD4+ T cells compared to the total number of T cells in the blood. These are memory cells that are short-lived cells that migrate to the site of an infection and attempt to eliminate the pathogen. These cells may have a CD3/CD4/CD62L-/CD45RA phenotype. Evidence: PCS. Frequency: 1/2. (PMID:34826260)
- Hypothyroidism (HP:0000821, a Human Phenotype Ontology term): Deficiency of thyroid hormone. Evidence: PCS. Frequency: 3/3. (PMID:34826260;PMID:34826259)
- Increased naive B cell proportion (HP:0030371, a Human Phenotype Ontology term): The proportion of naive B cellsin the blood circulation is above the upper limit of normal with respect to the reference range for a given sex and age-group. Evidence: PCS. Frequency: 1/2. (PMID:34826260)
- Systemic lupus erythematosus (HP:0002725, a Human Phenotype Ontology term): A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. Evidence: PCS. Frequency: 1/1. (PMID:34920454)
- Skin rash (HP:0000988, a Human Phenotype Ontology term): A red eruption of the skin. Evidence: PCS. Frequency: 2/2. (PMID:34920454)
- Decreased circulating IgG2 concentration (HP:0008348, a Human Phenotype Ontology term): A reduction in immunoglobulin levels of the IgG2 subclass in the blood circulation. Evidence: PCS. Frequency: 1/2. (PMID:34826260)
- Decreased circulating IgA concentration (HP:0002720, a Human Phenotype Ontology term): Decreased levels of immunoglobulin A (IgA). Evidence: PCS. Frequency: 1/1. (PMID:34826259)
- Immunodeficiency (HP:0002721, a Human Phenotype Ontology term): Failure of the immune system to protect the body adequately from infection, due to the absence or insufficiency of some component process or substance. Evidence: PCS. Frequency: 2/2. (PMID:34826260)