- Recurrent lower respiratory tract infections (HP:0002783): An increased susceptibility to lower respiratory tract infections as manifested by a history of recurrent lower respiratory tract infections. Evidence: PCS. Frequency: 20/56. (PMID:9255191)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 5/5. (PMID:10228294)
- Enlarged tonsils (HP:0030812): Increase in size of the tonsils, small collections of lymphoid tissue facing into the aerodigestive tract on either side of the back part of the throat. Evidence: TAS. (OMIM:308230)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 1/1. (PMID:35572607)
- Hoarse voice (HP:0001609): Hoarseness refers to a change in the pitch or quality of the voice, with the voice sounding weak, very breathy, scratchy, or husky. Evidence: PCS. Frequency: 1/1. (PMID:35572607)
- Sepsis (HP:0100806): Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Evidence: PCS. Frequency: 8/56. (PMID:9255191)
- Muscle weakness (HP:0001324): Reduced strength of muscles. Evidence: PCS. Frequency: 0/1. (PMID:35572607)
- Decreased circulating IgG concentration (HP:0004315): An abnormally decreased level of immunoglobulin G (IgG) in blood. Evidence: PCS. Frequency: 6/6. (PMID:35572607;PMID:10228294)
- Reduced total natural killer cell count (HP:0040218): 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:35572607)
- Decreased class-switched memory B cell proportion (HP:0030388): 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: 1/1. (PMID:35572607)
- Global developmental delay (HP:0001263): A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age. Evidence: PCS. Frequency: 3/4. (PMID:10228294)
- Hypoxemia (HP:0012418): An abnormally low level of blood oxygen. Evidence: PCS. Frequency: 1/5. (PMID:10228294)
- Ankle clonus (HP:0011448): Clonus is an involuntary tendon reflex that causes repeated flexion and extension of the foot. Ankle clonus is tested by rapidly flexing the foot upward. Evidence: PCS. Frequency: 1/5. (PMID:10228294)
- Recurrent oral thrush (HP:0009098): Chronic accumulation and overgrowth of the fungus Candida albicans on the mucous membranes of the mouth, generally manifested as associated with creamy white lesions on the tongue or inner cheeks, occasionally spreading to the gums, tonsils, palate or oropharynx. Evidence: PCS. Frequency: 1/5. (PMID:10228294)
- Stomatitis (HP:0010280): Stomatitis is an inflammation of the mucous membranes of any of the structures in the mouth. Evidence: IEA. (OMIM:308230)
- Dysphonia (HP:0001618): Difficulty in speaking due to a physical disorder of the mouth, tongue, throat, or vocal cords. Associated with a known physical or neurological cause. Evidence: PCS. Frequency: 1/1. (PMID:35572607)
- X-linked recessive inheritance (HP:0001419): A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele. Evidence: PCS. (PMID:9255191)
- Inverted CD4:CD8 ratio (HP:0033222): 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:35572607)
- Recurrent otitis media (HP:0000403): Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media. Evidence: PCS. Frequency: 1/1. (PMID:35572607)
- Decreased T cell activation (HP:0005419): Decreased or impaired activation of T cells in response to a mitogen, cytokine, chemokine, cellular ligand, or an antigen for which it is specific. Evidence: IEA. (OMIM:308230)
- Decreased circulating IgE concentration (HP:0005479): An abnormally decreased level of immunoglobulin E (IgE) in blood. Evidence: TAS. (OMIM:308230)
- Highly elevated creatine kinase (HP:0030234): An increased CPK level between 4X and 50X above the upper normal level. Evidence: PCS. Frequency: 1/1. (PMID:35572607)
- Increased circulating IgM concentration (HP:0003496): An abnormally increased level of immunoglobulin M in blood. Evidence: PCS. Frequency: 1/1. (PMID:35572607)
- Sclerosing cholangitis (HP:0030991): Cholangitis associated with evident ductal fibrosis that develops as a consequence of long-standing bile duct inflammatory, obstruction, or ischemic injury; it can be obliterative or nonobliterative. Evidence: PCS. Frequency: 11/56. (PMID:9255191)
- Cirrhosis (HP:0001394): A chronic disorder of the liver in which liver tissue becomes scarred and is partially replaced by regenerative nodules and fibrotic tissue resulting in loss of liver function. Evidence: PCS. Frequency: 6/56. (PMID:9255191)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: IEA. (OMIM:308230)
- Erythema (HP:0010783): Redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin. Evidence: PCS. Frequency: 1/1. (PMID:35572607)
- Enteroviral encephalitis (HP:0034285): Inflammation of the brain related to infection by an enterovirus. Evidence: PCS. Frequency: 3/5. (PMID:10228294)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 18/56. (PMID:9255191)
- Severe Leishmania infection (HP:5210131): Increased susceptibility to Leishmania infections as manifested by a severe or invasive infection with Leishmania. Evidence: PCS. Frequency: 1/1. (PMID:35572607)
- Impaired Ig class switch recombination (HP:0002959): An impairment of the class-switch recombination process that normally leads B lymphocytes to produce IgG, IgA, or IgE. Evidence: TAS. (OMIM:308230)
- Recurrent bacterial infections (HP:0002718): Increased susceptibility to bacterial infections as manifested by recurrent episodes of bacterial infection. Evidence: TAS. (OMIM:308230)
- Chronic hepatitis (HP:0200123): Hepatitis that lasts for more than six months. Evidence: TAS. (OMIM:308230)
- Pneumocystis jirovecii pneumonia (HP:0020102): An opportunistic disease caused by invasion of unicellular fungus Pneumocystis jirovecii. Transmission of P. jirovecii cysts takes place through the airborne route, and usually, its presence in lungs is asymptomatic. However, people with impaired immunity, especially those with CD4+ T cell count below 200/microliter, are still at risk of the development of Pneumocystis pneumonia due to P. jirovecii invasion. Symptoms induced by this disease are not specific: progressive dyspnea, non-productive cough, low-grade fever, arterial partial pressure of oxygen below 65 mmHg, and chest radiographs demonstrating bilateral, interstitial shadowing. Evidence: PCS. Frequency: 4/5. (PMID:10228294)
- Splenomegaly (HP:0001744): Abnormal increased size of the spleen. Evidence: IEA. (OMIM:308230)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: PCS. Frequency: 1/5. (PMID:10228294)
- Myalgia (HP:0003326): Pain in muscle. Evidence: PCS. Frequency: 0/1. (PMID:35572607)
- Diarrhea (HP:0002014): Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day. Evidence: PCS. Frequency: 31/56. (PMID:9255191)
- Meningitis (HP:0001287): Inflammation of the meninges. Evidence: PCS. Frequency: 5/56. (PMID:9255191)
- Gingivitis (HP:0000230): Inflammation of the gingiva. Evidence: IEA. (OMIM:308230)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 1/5. (PMID:10228294)
- Oral ulcer (HP:0000155): Erosion of the mucous mebrane of the mouth with local excavation of the surface, resulting from the sloughing of inflammatory necrotic tissue. Evidence: PCS. Frequency: 25/56. (PMID:9255191)
- Abnormal circulating IgM concentration (HP:0410243): An abnormal deviation from normal levels of IgM immunoglobulin in blood. Evidence: PCS. Frequency: 0/5. (PMID:10228294)
- Biliary tract abnormality (HP:0001080): An abnormality of the biliary tree. Evidence: PCS. Frequency: 0/1. (PMID:35572607)
- Increased circulating IgA concentration (HP:0003261): An abnormally increased level of immunoglobulin A in blood. Evidence: PCS. Frequency: 1/5. (PMID:10228294)
- Decreased total B cell count (HP:0010976): The absolute number of B cells in the blood, per microlitre is below the lower limit of normal of the reference range for the appropriate sex and age-group. Evidence: PCS. Frequency: 1/1. (PMID:35572607)
- Hepatitis (HP:0012115): Inflammation of the liver. Evidence: PCS. Frequency: 9/56. (PMID:9255191)
- Inflammatory myopathy (HP:0009071): Chronic muscle inflammation accompanied by muscle weakness. Evidence: PCS. Frequency: 1/1. (PMID:35572607)
- Absence of lymph node germinal center (HP:0002849): Absence of germinal centers in lymph nodes. Germinal centers are the parts of lymph nodes in which B lymphocytes proliferate, differentiate, mutate through somatic hypermutation and class switch during antibody responses. Evidence: IEA. (OMIM:308230)
- Periorbital fullness (HP:0000629): Increase in periorbital soft tissue. Evidence: PCS. Frequency: 1/1. (PMID:35572607)
- Hemolytic anemia (HP:0001878): A type of anemia caused by premature destruction of red blood cells (hemolysis). Evidence: IEA. (OMIM:308230)
- Impaired memory B cell generation (HP:0002847): Impaired production of memory cells, the B cells that persist for years or an entire lifetime and which confer rapid and enhanced response to secondary challenge. Evidence: IEA. (OMIM:308230)
- Thrombocytopenia (HP:0001873): A reduction in the number of circulating thrombocytes. Evidence: IEA. (OMIM:308230)
- Decreased circulating IgA concentration (HP:0002720): Decreased levels of immunoglobulin A (IgA). Evidence: TAS. (OMIM:308230)
- Decreased total neutrophil count (HP:0001875): Abnormal decrease of absolute number of neutrophils in the blood, per microlitre, compared to a reference range for a given sex and age-group. Evidence: PCS. Frequency: 39/62. (PMID:35572607;PMID:9255191;PMID:10228294)
- Immunodeficiency (HP:0002721): 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: IEA. (OMIM:308230)
These phenotypes are associated with the disease hyper-IgM syndrome type 1 (OMIM:308230).