Phenotypes associated with the disease Omenn syndrome (OMIM:603554):
- Spongiosis (HP:6001166): Spongiosis refers to the increased intercellular edema in the epidermis resulting in the pulling away of the keratinocytes from their surrounding desmosomes. Histologically, the spongiotic tissue reaction pattern involves the accumulation of fluid in the intercellular spaces of the epidermis, making the desmosomes junctions more easy to appreciate. Parakeratosis forms above the areas of spongiosis. The foci of spongiosis can be microscopic to grossly identifiable clinically with vesicles or bullae. Evidence: PCS. Frequency: 2/2. (PMID:25849362;PMID:28414192)
- Absent eyelashes (HP:0000561): Lack of eyelashes. Evidence: PCS. Frequency: 1/1. (PMID:28414192)
- Absent eyebrow (HP:0002223): Absence of the eyebrow. Evidence: PCS. Frequency: 1/1. (PMID:28414192)
- Seizure (HP:0001250): A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Evidence: PCS. Frequency: 1/1. (PMID:28414192)
- Hypoproteinemia (HP:0003075): A decreased concentration of protein in the blood. Evidence: IEA. (OMIM:603554)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 1/1. (PMID:25849362)
- Hypoalbuminemia (HP:0003073): The concentration of albumin in the blood circulation is below the lower limit of normal. Evidence: PCS. Frequency: 1/1. (PMID:25849362)
- CSF pleocytosis (HP:0012229): An increased white blood cell count in the cerebrospinal fluid. Evidence: PCS. Frequency: 1/1. (PMID:37269334)
- Bacteremia (HP:0031864): Presence of viable bacteria in the blood. Evidence: PCS. Frequency: 1/1. (PMID:37269334)
- Psoriasiform acanthosis (HP:0025817): A type of epidermal acanthosis characterized by regular elongated rete ridges. Evidence: PCS. Frequency: 1/1. (PMID:28414192)
- Sepsis (HP:0100806): Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Evidence: PCS. Frequency: 2/2. (PMID:28414192;PMID:37269334)
- Trichorrhexis invaginata (HP:0025811): A type of hair shaft dysmorphology in which the proximal part of the hair shaft overlaps the distal part, showing a bamboo-like appearance. This feature is pathognomic for Netherton syndrome, and can be ascertained by light microscopy. Evidence: PCS. Frequency: 0/1. (PMID:25849362)
- Absent natural killer cells (HP:0040219): Absence of detectable circulating NK cells, commonly characterized as CD3-CD19- and CD16+ or CD56+ lymphocytes, in the blood. Usually, less than 20 cells per microlitre is considered to be an absence. Evidence: PCS. Frequency: 1/1. (PMID:28414192)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 1/1. (PMID:19830075)
- Decreased circulating IgG concentration (HP:0004315): An abnormally decreased level of immunoglobulin G (IgG) in blood. Evidence: PCS. Frequency: 1/1. (PMID:25849362)
- Pulmonary infiltrates (HP:0002113). Evidence: PCS. Frequency: 1/1. (PMID:19011808)
- Recurrent skin infections (HP:0001581): Infections of the skin that happen multiple times. Evidence: PCS. Frequency: 1/1. (PMID:25849362)
- Oligoclonal T cell expansion (HP:0031430): The presence of a population of T cells with a restricted T cell receptor (TCR) repertoire derived from a limited number of TCR clones. Evidence: PCS. Frequency: 1/1. (PMID:25849362)
- 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: 1/1. (PMID:37269334)
- Edema (HP:0000969): An abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body. Evidence: PCS. Frequency: 1/1. (PMID:19011808)
- Scaling skin (HP:0040189): Refers to the loss of the outer layer of the epidermis in large, scale-like flakes. Evidence: PCS. Frequency: 2/2. (PMID:19011808;PMID:37269334)
- Inguinal lymphadenopathy (HP:0034751): Enlarged lymph node located in the inguinal region (groin). Evidence: PCS. Frequency: 2/2. (PMID:19011808;PMID:37269334)
- Increased CD4:CD8 ratio (HP:0033221): An abnormal elevation of the relative proportion of CD4+ to CD8+ T cells. Evidence: PCS. Frequency: 1/1. (PMID:25849362)
- Erythroderma (HP:0001019): An inflammatory exfoliative dermatosis involving nearly all of the surface of the skin. Erythroderma develops suddenly. A patchy erythema may generalize and spread to affect most of the skin. Scaling may appear in 2-6 days and be accompanied by hot, red, dry skin, malaise, and fever. Evidence: IEA. (OMIM:603554)
- Eczematoid dermatitis (HP:0000964): Eczema is a form of dermatitis that is characterized by scaly, pruritic, erythematous lesions located on flexural surfaces. Evidence: PCS. Frequency: 3/3. (PMID:25849362;PMID:28414192;PMID:37269334)
- Autosomal recessive inheritance (HP:0000007): 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:19011808)
- Subcutaneous abscess (HP:0020116): A circumscribed area of pus or necrotic debris located in the subcutaneous tissue (subcutaneous fat layer), below the dermis. Evidence: PCS. Frequency: 1/1. (PMID:28414192)
- Absent circulating T cells (HP:0025805): Absence of detectable circulating T cells, commonly characterized as CD3+ lymphocytes, in the blood. These may include both TCR alpha/beta and gamma/delta T cells. Usually, less than 50 T cells per microlitre is considered to be an absence. Evidence: PCS. Frequency: 1/1. (PMID:28414192)
- Increased total leukocyte count (HP:0001974): An abnormal increase in the number of leukocytes in the blood. Evidence: PCS. Frequency: 2/2. (PMID:37269334;PMID:19830075)
- Hyperkeratosis (HP:0000962): Hyperkeratosis is a histopathological term defining a thickened stratum corneum and may be present in many different skin conditions, with many possible overlaps. Hyperkeratosis refers to the increased thickness of the stratum corneum, the outer layer of the skin. Hyperkeratosis is subclassified as orthokeratotic or parakeratotic. Orthokeratotic hyperkeratosis refers to the thickening of the keratin layer with preserved keratinocyte maturation, while parakeratotic hyperkeratosis shows retained nuclei as a sign of delayed maturation of keratinocytes. Evidence: PCS. Frequency: 1/1. (PMID:19011808)
- Decreased total CD8+ T cell proportion (HP:0005415): Abnormal decrease of cytotoxic CD3+CD8+ T cells, measured as percentage of total CD3+ T cells in the blood, compared to a reference range for a given sex and age-group. These are usually measured within the TCR alpha/beta positive population. Evidence: PCS. Frequency: 1/1. (PMID:25849362)
- Decreased naive CD4+ T cell proportion (HP:0410378): 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: 1/1. (PMID:37269334)
- Aplasia of the thymus (HP:0005359): Absence of the thymus. This feature may be appreciated by the lack of a thymic shadow upon radiographic examination. Evidence: PCS. Frequency: 1/1. (PMID:19011808)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 2/2. (PMID:28414192;PMID:19011808)
- Parakeratosis (HP:0001036): Abnormal formation of the keratinocytes of the epidermis characterized by persistence of nuclei, incomplete formation of keratin, and moistness and swelling of the keratinocytes. Evidence: PCS. Frequency: 2/2. (PMID:28414192;PMID:19011808)
- Increased circulating IgE concentration (HP:0003212): An abnormally increased overall level of immunoglobulin E in blood. Evidence: PCS. Frequency: 3/3. (PMID:25849362;PMID:28414192;PMID:19830075)
- Alopecia (HP:0001596): A noncongenital process of hair loss, which may progress to partial or complete baldness. Evidence: PCS. Frequency: 2/2. (PMID:19011808;PMID:19830075)
- Pustule (HP:0200039): A small elevation of the skin containing cloudy or purulent material usually consisting of necrotic inflammatory cells. Evidence: PCS. Frequency: 1/1. (PMID:28414192)
- Protracted diarrhea (HP:0004385). Evidence: PCS. Frequency: 1/1. (PMID:19830075)
- Intractable diarrhea (HP:0002041). Evidence: PCS. Frequency: 1/1. (PMID:19011808)
- Complete or near-complete absence of specific antibody response to tetanus vaccine (HP:0410295): The inability to synthesize postvaccination antibodies against a tetanus antigen, as measured by antibody titer determination following vaccination. Evidence: PCS. Frequency: 1/1. (PMID:25849362)
- Cervical lymphadenopathy (HP:0025289): Enlarged lymph nodes in the neck. Evidence: PCS. Frequency: 2/2. (PMID:19011808;PMID:37269334)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: IEA. (OMIM:603554)
- Abnormal total T cell number (HP:0011839): Abnormal increase or decrease of absolute number (either count per volume or proportion of total lymphocytes) of T cells or of a subset of T cells, commonly characterized as CD3+ lymphocytes, in the blood, compared to a reference range for a given sex and age-group. These may include both TCR alpha/beta and gamma/delta T cells. Evidence: PCS. Frequency: 0/1. (PMID:37269334)
- Axillary lymphadenopathy (HP:0034752): Enlarged lymph node located in the axillary region (armpit). Evidence: PCS. Frequency: 3/3. (PMID:28414192;PMID:19011808;PMID:37269334)
- Thickened skin (HP:0001072): Laminar thickening of skin. Evidence: TAS. (OMIM:603554)
- 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:37269334)
- Decreased circulating isohemagglutinin concentration (HP:0032139): Level of isohemagglutinin reduced below expected concentration. An isohemagglutinin refers to the naturally occurring antibodies in the ABO blood group system (i.e., anti-A in a group B person, anti-B in a group A person, and anti-A, anti-B, and anti-A,B in a group O person). Evidence: PCS. Frequency: 1/1. (PMID:25849362)
- Sparse hair (HP:0008070): Reduced density of hairs. Evidence: PCS. Frequency: 1/1. (PMID:25849362)
- Congenital exfoliative erythroderma (HP:0007381). Evidence: PCS. Frequency: 5/5. (PMID:25849362;PMID:28414192;PMID:19011808;PMID:37269334;PMID:19830075)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 3/3. (PMID:28414192;PMID:19011808;PMID:19830075)
- Anemia (HP:0001903): A reduction in erythrocytes volume or hemoglobin concentration. Evidence: PCS. Frequency: 1/1. (PMID:19011808)
- Eosinophilic dermal infiltration (HP:0032022): Presence of abnormally increased amounts of intraepidermal inflammatory cells with a predominance of eosinophils. Evidence: PCS. Frequency: 2/2. (PMID:25849362;PMID:19011808)
- Recurrent bacterial infections (HP:0002718): Increased susceptibility to bacterial infections as manifested by recurrent episodes of bacterial infection. Evidence: PCS. Frequency: 1/1. (PMID:37269334)
- Impaired phytohemagglutinin-induced T lymphocyte transformation (HP:0025834): Def: A reduced rate of T lymphocyte transformation in response to in vitro stimulation to the mitogen phytohemagglutinin (PHA). Following PHA stimulation, T cells normally undergo morphological and biochemical alterations that reflect the transformation into lymphoblasts. There are several methods for quantifying this effect including measuring the uptake of the radioactive marker 3H-TdR, methyl thiazolyl tetrazolium colorimetric analysis (MTT assay), and morphological examination under the microscope or using a hematology analyzer. Various types of stimulation index compare the amount of proliferation between treated and control cells. An impaired test refers to a result in which the amount of stimulation is subnormal. Evidence: PCS. Frequency: 3/3. (PMID:25849362;PMID:19011808;PMID:19830075)
- Hypoplasia of the thymus (HP:0000778): Underdevelopment of the thymus. Evidence: TAS. (OMIM:603554)
- Lymphadenopathy (HP:0002716): Enlargement (swelling) of a lymph node. Evidence: PCS. Frequency: 10/11. (OMIM:603554;PMID:19830075)
- Increased total lymphocyte count (HP:0100827): Increase in the number or proportion of lymphocytes in the blood. Evidence: PCS. Frequency: 1/2. (PMID:28414192;PMID:19830075)
- Splenomegaly (HP:0001744): Abnormal increased size of the spleen. Evidence: IEA. (OMIM:603554)
- Meningitis (HP:0001287): Inflammation of the meninges. Evidence: PCS. Frequency: 2/2. (PMID:28414192;PMID:37269334)
- Diarrhea (HP:0002014): Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day. Evidence: IEA. (OMIM:603554)
- Increased total eosinophil count (HP:0001880): Increased count of eosinophils in the blood. Evidence: PCS. Frequency: 3/3. (PMID:25849362;PMID:19011808;PMID:37269334)
- Brittle hair (HP:0002299): Fragile, easily breakable hair, i.e., with reduced tensile strength. Evidence: PCS. Frequency: 1/1. (PMID:25849362)
- Agammaglobulinemia (HP:0004432): A lasting absence of total IgG and total IgA and total IgM in the blood circulation, whereby at most trace quantities can be measured. Evidence: PCS. Frequency: 1/1. (PMID:19011808)
- Persistent fever (HP:0033399): Fever that persists longer than expected for an acute infectious disease. No precise threshold exists, and the clinical interpretation of fever is context-dependent, but as a rule of thumb, this term refers to fever that persists longer than 2-3 weeks. Evidence: PCS. Frequency: 1/1. (PMID:19830075)
- Alopecia of scalp (HP:0002293). Evidence: PCS. Frequency: 1/1. (PMID:28414192)
- Pneumonia (HP:0002090): Inflammation of any part of the lung parenchyma. Evidence: PCS. Frequency: 1/1. (PMID:19830075)
- 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: 2/2. (PMID:19011808;PMID:37269334)
- Elevated circulating C-reactive protein concentration (HP:0011227): The concentration of C-reactive protein in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 2/2. (PMID:28414192;PMID:37269334)
- Decreased anti-CD3/28-induced T-cell proliferation (HP:0031382): Abnormal decrease of T cell proliferation in response to anti-CD3/28 stimulation. This is commonly measured through intracellular expression of Ki67, decreasing surface expression of carboxyfluorescein diacetate (CFSE), or 3H-thymidine incorporation. Length of incubation and strength of stimulation may vary between laboratories. Evidence: PCS. Frequency: 1/1. (PMID:37269334)
- Abnormal total natural killer cell count (HP:0040089): Abnormal increase or decrease of total natural killer (NK) cells, commonly characterized as CD3-CD19- and CD16+ or CD56+ lymphocytes, in the blood, per microlitre, or altered NK cell phenotype, compared to a reference range for a given sex and age-group, measured ex vivo. Evidence: PCS. Frequency: 0/3. (PMID:19011808;PMID:37269334;PMID:19830075)
- Absent circulating B cells (HP:0030252): Absence of detectable circulating B cells, commonly characterized as CD19+ or CD20+ lymphocytes, in the blood. Usually, less than 20 cells per microlitre is considered to be an absence. Evidence: PCS. Frequency: 3/3. (PMID:25849362;PMID:28414192;PMID:19830075)
- Recurrent fever (HP:0001954): Periodic (episodic or recurrent) bouts of fever. Evidence: PCS. Frequency: 1/1. (PMID:19011808)
- Skin rash (HP:0000988): A red eruption of the skin. Evidence: PCS. Frequency: 1/1. (PMID:25849362)
- Recurrent viral infections (HP:0004429): Increased susceptibility to viral infections as manifested by recurrent episodes of viral infection. Evidence: PCS. Frequency: 1/1. (PMID:19011808)
- Generalized lymphadenopathy (HP:0008940): A generalized form of lymphadenopathy. Evidence: PCS. Frequency: 1/1. (PMID:25849362)
- Thrombocytopenia (HP:0001873): A reduction in the number of circulating thrombocytes. Evidence: IEA. (OMIM:603554)
- Hepatosplenomegaly (HP:0001433): Simultaneous enlargement of the liver and spleen. Evidence: PCS. Frequency: 3/5. (PMID:25849362;PMID:28414192;PMID:19011808;PMID:37269334;PMID:19830075)
- Recurrent fungal infections (HP:0002841): Increased susceptibility to fungal infections as manifested by multiple episodes of fungal infection. Evidence: TAS. (OMIM:603554)
- Decreased circulating IgA concentration (HP:0002720): Decreased levels of immunoglobulin A (IgA). Evidence: PCS. Frequency: 1/1. (PMID:25849362)
- 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: PCS. Frequency: 1/1. (PMID:28414192)
- 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: 1/1. (PMID:19011808)