Phenotypes associated with the disease proteasome-associated autoinflammatory syndrome 1 (OMIM:256040):
- Decreased circulating HDL-C concentration (HP:0003233): The concentration of high-density lipoprotein cholesterol in the blood circulation is below the lower limit of normal. Evidence: PCS. Frequency: 6/9. (PMID:21129723)
- Hypoplastic scapulae (HP:0000882): Underdeveloped scapula. Evidence: PCS. Frequency: 1/12. (PMID:21129723)
- Mild intellectual disability (HP:0001256): Mild intellectual disability (ID) is defined as a type of ID characterized by mildly sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 50-69. Evidence: PCS. Frequency: 3/12. (PMID:20534754)
- Short stature (HP:0004322): 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: 11/12. (PMID:20534754)
- Flexion contracture (HP:0001371): A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints. Evidence: PCS. Frequency: 12/12. (PMID:20534754)
- 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: 2/12. (PMID:20534754)
- Camptodactyly of finger (HP:0100490): The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers cannot be extended to 180 degrees by either active or passive extension. Evidence: TAS. (OMIM:256040)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 1/3. (PMID:21881205)
- Flexion contracture of finger (HP:0012785): Chronic loss of joint motion in a finger due to structural changes in non-bony tissue. Evidence: PCS. Frequency: 3/3. (PMID:21881205)
- Parotitis (HP:0011850): Inflammation of the parotid gland. Evidence: IEA. Frequency: 2/9. (PMID:21953331)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: IEA. Frequency: 2/3. (PMID:21881205)
- Increased circulating interleukin 8 concentration (HP:0033178): An increased concentration of interleukin-8 in the circulation. Evidence: IEA. Frequency: 2/2. (PMID:21129723)
- Hypertrichosis (HP:0000998): Hypertrichosis is increased hair growth that is abnormal in quantity or location. Evidence: PCS. Frequency: 5/9. (PMID:21953331)
- Hyperpigmentation of the skin (HP:0000953): A darkening of the skin related to an increase in melanin production and deposition. Evidence: TAS. (OMIM:256040)
- Long fingers (HP:0100807): The middle finger is more than 2 SD above the mean for newborns 27 to 41 weeks EGA or above the 97th centile for children from birth to 16 years of age AND the five digits retain their normal length proportions relative to each other (i.e., it is not the case that the middle finger is the only lengthened digit), or, Fingers that appear disproportionately long compared to the palm of the hand. Evidence: TAS. (OMIM:256040)
- Acanthosis nigricans (HP:0000956): A dermatosis characterized by thickened, hyperpigmented plaques, typically on the intertriginous surfaces and neck. Evidence: PCS. Frequency: 2/9. (PMID:21953331)
- Macroglossia (HP:0000158): Increased length and width of the tongue. Evidence: PCS. Frequency: 5/15. (PMID:21881205;PMID:20534754)
- Muscle weakness (HP:0001324): Reduced strength of muscles. Evidence: TAS. (OMIM:256040)
- Premature graying of hair (HP:0002216): Development of gray hair at a younger than normal age. Evidence: PCS. Frequency: 1/12. (PMID:21129723)
- Intellectual disability (HP:0001249): The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence. Evidence: PCS. Frequency: 1/3. (PMID:21881205)
- Progeroid facial appearance (HP:0005328): A degree of wrinkling of the facial skin that is more than expected for the age of the individual, leading to a prematurely aged appearance. Evidence: PCS. Frequency: 1/12. (PMID:21129723)
- Sparse axillary hair (HP:0002215): Reduced number or density of axillary hair. Evidence: PCS. Frequency: 2/12. (PMID:21129723)
- Elevated erythrocyte sedimentation rate (HP:0003565): An increased erythrocyte sedimentation rate (ESR). The ESR is a test that measures the distance that erythrocytes have fallen after one hour in a vertical column of anticoagulated blood under the influence of gravity. The ESR is a nonspecific finding. An elevation may indicate inflammation or may be caused by any condition that elevates fibrinogen. Evidence: PCS. Frequency: 16/22. (PMID:21881205;PMID:21953331;PMID:20534754)
- Skeletal muscle atrophy (HP:0003202): The presence of skeletal muscular atrophy (which is also known as amyotrophy). Evidence: PCS. Frequency: 12/24. (PMID:21881205;PMID:21953331;PMID:21129723)
- Finger swelling (HP:0025131): Enlargement of the soft tissues of one or more fingers. Evidence: PCS. Frequency: 17/19. (PMID:21953331;OMIM:256040)
- Hypertriglyceridemia (HP:0002155): An abnormal increase in the level of triglycerides in the blood. Evidence: PCS. Frequency: 6/21. (PMID:21953331;PMID:20534754)
- Gynecomastia (HP:0000771): Abnormal development of large mammary glands in males resulting in breast enlargement. Evidence: PCS. Frequency: 1/6. (PMID:21129723)
- Increased circulating interleukin 6 concentration (HP:0030783): The concentration of interleukin-6 in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 2/2. (PMID:21129723)
- Loss of facial adipose tissue (HP:0000292): Loss of normal subcutaneous fat tissue in the face. Evidence: PCS. (PMID:21129723)
- Impaired glucose tolerance (HP:0040270): An abnormal resistance to glucose, i.e., a reduction in the ability to maintain glucose levels in the blood stream within normal limits following oral or intravenous administration of glucose. Evidence: PCS. (PMID:21129723)
- Erythema nodosum (HP:0012219): An erythematous eruption commonly associated with drug reactions or infection and characterized by inflammatory nodules that are usually tender, multiple, and bilateral. Evidence: PCS. Frequency: 3/3. (PMID:21881205)
- Episcleritis (HP:0100534): Inflammation of the episclera, a thin layer of tissue covering the white part (sclera) of the eye. Evidence: PCS. Frequency: 4/9. (PMID:21953331)
- Arthralgia (HP:0002829): Joint pain. Evidence: PCS. Frequency: 9/9. (PMID:21953331)
- Prominent nose (HP:0000448): Distance between subnasale and pronasale more than two standard deviations above the mean, or alternatively, an apparently increased anterior protrusion of the nasal tip. Evidence: IEA. (OMIM:256040)
- 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:21129723)
- Recurrent otitis media (HP:0000403): Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media. Evidence: PCS. Frequency: 4/9. (PMID:21953331)
- Microcytic anemia (HP:0001935): A kind of anemia in which the volume of the red blood cells is reduced. Evidence: PCS. Frequency: 3/12. (PMID:20534754)
- Skin plaque (HP:0200035): A plaque is a solid, raised, plateau-like (flat-topped) lesion greater than 1 cm in diameter. Evidence: PCS. Frequency: 9/9. (PMID:21953331)
- Protuberant abdomen (HP:0001538): A thrusting or bulging out of the abdomen. Evidence: PCS. Frequency: 7/9. (PMID:21953331)
- Macrotia (HP:0000400): Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective). Evidence: IEA. (OMIM:256040)
- Recurrent upper respiratory tract infections (HP:0002788): An increased susceptibility to upper respiratory tract infections as manifested by a history of recurrent upper respiratory tract infections (running ears - otitis, sinusitis, pharyngitis, tonsillitis). Evidence: PCS. Frequency: 1/9. (PMID:21953331)
- Adipose tissue loss (HP:0008887): A reduction in the amount of adipose tissue (fat) compared with the amount previously present in an individual. Evidence: IEA. (OMIM:256040)
- Elbow flexion contracture (HP:0002987): An elbow contracture that limits the ability of the elbow joint to be extended (straightened), meaning that the elbow is fixed in an flexed (bent) position. Evidence: TAS. (OMIM:256040)
- Proptosis (HP:0000520): An eye that is protruding anterior to the plane of the face to a greater extent than is typical. Evidence: PCS. Frequency: 1/12. (PMID:21129723)
- Increased circulating IgG concentration (HP:0003237): An abnormally increased level of immunoglobulin G in blood. Evidence: PCS. Frequency: 3/3. (PMID:21881205)
- Flexion contracture of toe (HP:0005830): One or more bent (flexed) toe joints that cannot be straightened actively or passively. Evidence: TAS. (OMIM:256040)
- Increased circulating interferon-gamma concentration (HP:0030356): An elevation in the concentration of interferon gamma measured in the blood circulation. Evidence: PCS. Frequency: 2/2. (PMID:21129723)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: PCS. Frequency: 19/24. (PMID:21881205;PMID:21953331;PMID:20534754)
- Arrhythmia (HP:0011675): Any cardiac rhythm other than the normal sinus rhythm. Such a rhythm may be either of sinus or ectopic origin and either regular or irregular. An arrhythmia may be due to a disturbance in impulse formation or conduction or both. Evidence: PCS. Frequency: 2/3. (PMID:21881205)
- Erythema (HP:0010783): Redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin. Evidence: IEA. (OMIM:256040)
- Increased circulating immunoglobulin concentration (HP:0010702): An increased level of gamma globulin (immunoglobulin) in the blood. Evidence: PCS. Frequency: 6/12. (PMID:20534754)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 15/19. (PMID:21953331;OMIM:256040)
- Growth abnormality (HP:0001507). Evidence: IEA. (OMIM:256040)
- Irregular menstruation (HP:0000858): Abnormally high variation in the amount of time between periods. Evidence: PCS. Frequency: 1/6. (PMID:21129723)
- Chronic constipation (HP:0012450): Constipation for longer than three months with fewer than 3 bowel movements per week, straining, lumpy or hard stools, and a sensation of anorectal obstruction or incomplete defecation. Evidence: PCS. Frequency: 2/12. (PMID:21129723)
- Hallux valgus (HP:0001822): Lateral deviation of the great toe (i.e., in the direction of the little toe). Evidence: PCS. Frequency: 2/12. (PMID:21129723)
- Lipodystrophy (HP:0009125): Degenerative changes of the fat tissue. Evidence: PCS. Frequency: 12/12. Onset: Childhood onset (HP:0011463). (PMID:20534754)
- Lipodystrophy (HP:0009125): Degenerative changes of the fat tissue. Evidence: PCS. Frequency: 3/3. (PMID:21881205)
- Lipodystrophy (HP:0009125): Degenerative changes of the fat tissue. Evidence: PCS. Frequency: 9/9. (PMID:21953331)
- Lymphadenopathy (HP:0002716): Enlargement (swelling) of a lymph node. Evidence: PCS. Frequency: 7/9. (PMID:21953331)
- Panniculitis (HP:0012490): Inflammation of subcutaneous adipose tissue. Evidence: PCS. (PMID:20534754)
- Elevated circulating hepatic transaminase concentration (HP:0002910): Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage. Evidence: PCS. Frequency: 8/9. (PMID:21953331)
- Thick lower lip vermilion (HP:0000179): Increased thickness of the lower lip, leading to a prominent appearance of the lower lip. The height of the vermilion of the lower lip in the midline is more than 2 SD above the mean. Alternatively, an apparently increased height of the vermilion of the lower lip in the frontal view (subjective). Evidence: TAS. (OMIM:256040)
- Splenomegaly (HP:0001744): Abnormal increased size of the spleen. Evidence: PCS. Frequency: 10/24. (PMID:21881205;PMID:21953331;PMID:20534754)
- Basal ganglia calcification (HP:0002135): The presence of calcium deposition affecting one or more structures of the basal ganglia. Evidence: PCS. Frequency: 7/19. (PMID:21881205;PMID:21953331;PMID:20534754)
- Bone pain (HP:0002653): An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to bone. Evidence: PCS. Frequency: 2/12. (PMID:21129723)
- Cardiomegaly (HP:0001640): Increased size of the heart, clinically defined as an increased transverse diameter of the cardiac silhouette that is greater than or equal to 50% of the transverse diameter of the chest (increased cardiothoracic ratio) on a posterior-anterior projection of a chest radiograph or a computed tomography. Evidence: IEA. (OMIM:256040)
- Epididymitis (HP:0000031): The presence of inflammation of the epididymis. Evidence: PCS. Frequency: 2/5. (PMID:21953331)
- Increased circulating IgA concentration (HP:0003261): An abnormally increased level of immunoglobulin A in blood. Evidence: PCS. Frequency: 3/3. (PMID:21881205)
- Death in adolescence (HP:0011421): Death during adolescence, the period between childhood and adulthood (roughly between the ages of 10 and 16 years). Evidence: PCS. Frequency: 1/9. (PMID:21953331)
- Recurrent sinusitis (HP:0011108): A recurrent form of sinusitis. Evidence: PCS. Frequency: 2/9. (PMID:21953331)
- 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: 12/12. (PMID:21881205;PMID:21953331)
- Clubbing of fingers (HP:0100759): Terminal broadening of the fingers (distal phalanges of the fingers). Evidence: TAS. (OMIM:256040)
- Conjunctivitis (HP:0000509): Inflammation of the conjunctiva. Evidence: PCS. Frequency: 4/9. (PMID:21953331)
- Congestive heart failure (HP:0001635): The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction. Evidence: IEA. (OMIM:256040)
- Recurrent fever (HP:0001954): Periodic (episodic or recurrent) bouts of fever. Evidence: PCS. Frequency: 12/12. (PMID:21881205;PMID:21953331)
- Stiff skin (HP:0030053): An induration (hardening) of the skin. Evidence: PCS. (PMID:20534754)
- Elevated circulating thyroid-stimulating hormone concentration (HP:0002925): Increased concentration of thyroid-stimulating hormone (TSH) in the blood circulation. Evidence: PCS. Frequency: 2/9. (PMID:21953331)
- Growth delay (HP:0001510): A deficiency or slowing down of growth pre- and postnatally. Evidence: PCS. (PMID:21953331)
- Thrombocytopenia (HP:0001873): A reduction in the number of circulating thrombocytes. Evidence: PCS. Frequency: 1/9. (PMID:21953331)
- Diminished deep tendon reflex (HP:0001315): A reduction (hyporeflexia) or complete absence (areflexia) of the involuntary muscle contraction normally elicited by a reflex stimulus, such as tapping a deep tendon. Evidence: PCS. Frequency: 1/12. (PMID:21129723)
- Punctate opacification of the cornea (HP:0007856): Punctate opacification (reduced transparency) of the corneal stroma. Evidence: PCS. Frequency: 1/12. (PMID:21129723)