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Amniotic band syndrome refers to a condition in which bands develop from the inner lining of the amnion. The amnion is the sac that surrounds the baby in the womb. As the baby develops in the womb, the bands may attach to and affect the development of different areas of the body. This may result in constriction of the affected area or even amputation. The signs and symptoms vary greatly depending on the area(s) of the body involved and may include: shortened or absent digits (fingers and/or toes) or limbs (arms and/or legs), an opening in the abdomen through which various abdominal organs can protrude (abdominal wall defects), protrusion of a portion of the brain and its surrounding membranes through a skull defect (encephalocele), and cleft lip and/or palate. In most instances, the cause of amniotic bands remains unknown. Researchers have suggested two main theories to explain the development: the extrinsic theory and the intrinsic theory. The extrinsic theory states that amniotic band syndrome occurs due to factors found outside of the developing baby (externally); the intrinsic theory states that amniotic band syndrome occurs due to factors found within the baby (internally). Treatment differs depending on the severity of the condition and the areas of the body affected and may include surgery, physical therapy, and occupational therapy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Amniotic band syndrome	c1857578	3,800	gard	https://rarediseases.info.nih.gov/diseases/429/amniotic-band-syndrome	2021-01-18T18:02:09	{"mesh": ["C565681"], "omim": ["217100"], "orphanet": ["1034"], "synonyms": ["Amniotic bands sequence", "Familial amniotic bands", "Streeter anomaly", "Congenital constricting bands"]}
A number sign (#) is used with this entry because of evidence that variation in the SLC45A2 gene (606202) influences skin, hair, and eye pigmentation. For a general phenotypic description and a discussion of genetic heterogeneity of variation in skin, hair, and eye pigmentation, see 227220. Mapping Graf et al. (2005) demonstrated a highly significant association of polymorphisms in the MATP gene (SLC45A2; 606202) with normal variation in human pigmentation. Studying Caucasians, Asians, African Americans, and Australian Aborigines, they found associations particularly with 2 polymorphisms, G272K (606202.0007) and F374L (606202.0008). The 2 alleles, leu374 and lys272, were associated with dark hair, skin, and eye color in Caucasians. The odds ratios of the leu/leu genotype for black hair and olive skin were 25.63 and 28.65, respectively, and for the lys/lys genotype were 43.23 and 8.27, respectively. The odds ratio for eye color was lower at 3.48 for leu/leu and 6.57 for lys/lys genotypes. Stokowski et al. (2007) demonstrated an association between the SNP 16891982 (F374L; 606202.0008) and skin pigmentation variation in individuals of South Asian descent. Stacey et al. (2009) confirmed association of the SNP 16891982 (L374F) with fair pigmentation using samples from Iceland, eastern Europe, Spain, and the United States, observing strong association with all traits except red hair and freckles. Stacey et al. (2009) found that this variant was associated with risk of both basal cell carcinoma (BCC; see 605462) and squamous cell carcinoma (odds ratio = 1.97, P = 1.6 x 10(-12) for BCC) in 3,326 basal cell carcinoma cases and 5,493 controls of European ancestry. Molecular Genetics Graf et al. (2007) examined the association between normal skin color variation in several populations and 3 different promoter polymorphisms in the MATP gene: -1721C-G (rs13289), -1169G-A (rs6867641), and a 3-bp duplication, -1174dupAAT. In Caucasian samples, -1721C-G and -1174dupAAT were in complete linkage disequilibrium. In Caucasians only, the -1721G, -1169A, and +dup alleles were significantly associated with olive skin color. Functional analysis in melanoma skin cells showed that this promoter haplotype decreased MATP transcription, suggesting a functional significance. Eyes \- Blue color recessive to green Inheritance \- Autosomal recessive at GEY locus \- Eye color probably polygenic ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	SKIN/HAIR/EYE PIGMENTATION, VARIATION IN, 5	c2673584	3,801	omim	https://www.omim.org/entry/227240	2019-09-22T16:28:03	{"mesh": ["C567119"], "omim": ["227240"], "synonyms": ["Alternative titles", "SKIN/HAIR/EYE PIGMENTATION 5, BLACK/NONBLACK HAIR", "SKIN/HAIR/EYE PIGMENTATION 5, DARK/LIGHT EYES", "SKIN/HAIR/EYE PIGMENTATION 5, DARK/FAIR SKIN"]}
A rare teratogenic disorder due to acitretin or etretinate exposure during the first trimester of pregnancy, carrying a risk of fetal malformations of approximately 20%, including central nervous system, craniofacial, ear, thymic, cardiac and limb anomalies. ## Epidemiology To date, 3 infants/fetuses with anomalies indicative or possibly indicative for the embryopathy whose mothers were treated with acitretin during the first trimester of pregnancy have been reported in the literature. In addition, 23 infants/fetuses with anomalies indicative or possibly indicative for the embryopathy whose mothers were treated with etretinate during the first trimester or before pregnancy have been reported in the literature. ## Clinical description Acitretin/Etretinate embryopathy is characterized by multiple congenital anomalies involving the central nervous system (with neurodevelopmental delay), retinal or optic-nerve, craniofacial (microcephaly, facial dysmorphism displaying epicanthal folds, low nasal bridge, anteverted nostrils, high and cleft palate, micrognathia) and ear abnormalities (microtia/anotia, cup-shaped ears, bilateral sensorineural deafness). Thymic and cardiac defects (atrioventricular canal defect, conotruncal heart malformation, aortic-arch defect) are also observed. Severe anomalies of upper and lower limbs have also been described. ## Etiology Acitretin/etretinate embryopathy is due to acitretin or etretinate exposure during the first trimester of pregnancy. Acitretin is an aromatic retinoid analog of vitamin A used for the treatment of severe forms of psoriasis and disorders of keratinization. Acitretin/etretinate have a teratogenic potential since it affects cellular differentiation and proliferation. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Acitretin/etretinate embryopathy	c4510941	3,802	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=40366	2021-01-23T18:52:52	{"icd-10": ["Q86.8"], "synonyms": ["Fetal acitretin/etretinate syndrome", "Retinoid embryopathy"]}
FACES syndrome, also known as Friedman-Goodman syndrome, is a condition that is characterized by unique Facial features, Anorexia, Cachexia (body wasting) and Eye and Skin lesions. The pattern of inheritance and underlying genetic cause of FACES syndrome has not yet been established. FACES syndrome has only been reported in three members of the same family. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	FACES syndrome	c2931183	3,803	gard	https://rarediseases.info.nih.gov/diseases/2221/faces-syndrome	2021-01-18T18:00:38	{"mesh": ["C536384"], "umls": ["C2931183"], "orphanet": ["1969"], "synonyms": ["Facial features (unique), anorexia, cachexia, eye and skin anomalies", "Friedman-Goodman syndrome"]}
For the Kid Koala album, see Carpal Tunnel Syndrome (album). Carpal tunnel syndrome Untreated carpal tunnel syndrome, showing how the muscles at the base of the thumb have wasted away (atrophied) SpecialtyOrthopedic surgery, plastic surgery SymptomsPain, numbness, tingling in the thumb, index, middle finger, and half of ring finger, weak grip[1][2] CausesCompression of the median nerve at the carpal tunnel[1] Risk factorsGenetics, obesity, repetitive wrist work, pregnancy, rheumatoid arthritis[3][4][5] Diagnostic methodBased on symptoms, specific physical tests, electrodiagnostic tests[2] PreventionPhysical activity[3] TreatmentWrist splint, corticosteroid injections, surgery[3] Frequency5–10%[6][7] Carpal tunnel syndrome (CTS) is a medical condition due to compression of the median nerve as it travels through the wrist at the carpal tunnel.[1] The main symptoms are pain, numbness and tingling in the thumb, index finger, middle finger and the thumb side of the ring finger.[1] Symptoms typically start gradually and during the night.[2] Pain may extend up the arm.[2] Weak grip strength may occur, and after a long period of time the muscles at the base of the thumb may waste away.[2] In most cases, both hands are affected.[1] Risk factors include obesity, repetitive wrist work, pregnancy, genetics, and rheumatoid arthritis.[3][4][5] There is tentative evidence that hypothyroidism increases the risk.[8] Diabetes mellitus is weakly associated with CTS.[3][7] The use of birth control pills does not affect the risk.[3] Types of work that are associated include computer work, work with vibrating tools and work that requires a strong grip.[3] Diagnosis is suspected based on signs, symptoms and specific physical tests and may be confirmed with electrodiagnostic tests.[2] If muscle wasting at the base of the thumb is present, the diagnosis is likely.[3] Being physically active can decrease the risk of developing CTS.[3] Symptoms can be improved by wearing a wrist splint or with corticosteroid injections.[3] Taking NSAIDs or gabapentin does not appear to be useful.[3] Surgery to cut the transverse carpal ligament is effective with better results at a year compared to non-surgical options.[3] Further splinting after surgery is not needed.[3] Evidence does not support magnet therapy.[3] About 5% of people in the United States have carpal tunnel syndrome.[6] It usually begins in adulthood, and women are more commonly affected than men.[2] Up to 33% of people may improve without specific treatment over approximately a year.[1] Carpal tunnel syndrome was first fully described after World War II.[9] ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Genetics * 2.2 Work related * 2.3 Associated conditions * 3 Pathophysiology * 4 Diagnosis * 4.1 Physical exam * 4.2 Imaging * 4.3 Differential diagnosis * 5 Prevention * 6 Treatment * 6.1 Splints * 6.2 Corticosteroids * 6.3 Surgery * 6.4 Physical therapy * 7 Prognosis * 8 Epidemiology * 8.1 Occupational * 9 History * 10 See also * 11 References * 12 External links ## Signs and symptoms[edit] People with CTS experience numbness, tingling, or burning sensations in the thumb and fingers, in particular the index and middle fingers and radial half of the ring finger, because these receive their sensory and motor function (muscle control) from the median nerve. Ache and discomfort can possibly be felt more proximally in the forearm or even the upper arm.[10] Less-specific symptoms may include pain in the wrists or hands, loss of grip strength,[11] and loss of manual dexterity.[12] Some suggest that median nerve symptoms can arise from compression at the level of the thoracic outlet or the area where the median nerve passes between the two heads of the pronator teres in the forearm,[13] although this is debated. Numbness and paresthesias in the median nerve distribution are the hallmark neuropathic symptoms (NS) of carpal tunnel entrapment syndrome.[7] Weakness and atrophy of the thumb muscles may occur if the condition remains untreated, because the muscles are not receiving sufficient nerve stimulation.[7] Discomfort is usually worse at night and in the morning. ## Causes[edit] Anatomy of the carpal tunnel, showing the median nerve passing through the tight space it shares with the finger tendons Most cases of CTS are of unknown cause.[14] Risk factors include obesity, repetitive wrist work, pregnancy, genetics, and rheumatoid arthritis.[3][4][5] There is tentative evidence that hypothyroidism increases the risk.[8] Diabetes mellitus is weakly associated with CTS.[3][7] The use of birth control pills does not affect the risk.[3] Types of work that are associated include computer work, work with vibrating tools and work that requires a strong grip.[3] Trauma may also place a role,[15] as may genetics.[16] Carpal tunnel is a feature of a form of Charcot-Marie-Tooth syndrome type 1 called hereditary neuropathy with susceptibility to pressure palsies. Other causes of this condition include intrinsic factors that exert pressure within the tunnel, and extrinsic factors (pressure exerted from outside the tunnel), which include benign tumors such as lipomas, ganglion, and vascular malformation.[17] Severe carpal tunnel syndrome often is a symptom of transthyretin amyloidosis-associated polyneuropathy and prior carpal tunnel syndrome surgery is very common in individuals who later present with transthyretin amyloid-associated cardiomyopathy, suggesting that transthyretin amyloid deposition may cause carpal tunnel syndrome in these people.[18] The median nerve can usually move up to 9.6 mm to allow the wrist to flex, and to a lesser extent during extension.[19] Long-term compression of the median nerve can inhibit nerve gliding, which may lead to injury and scarring. When scarring occurs, the nerve will adhere to the tissue around it and become locked into a fixed position, so that less movement is apparent.[20] Normal pressure of the carpal tunnel has been defined as a range of 2–10 mm, and wrist flexion increases this pressure 8-fold, while extension increases it 10-fold.[19] Repetitive flexion and extension in the wrist significantly increase the fluid pressure in the tunnel through thickening of the synovial tissue that lines the tendons within the carpal tunnel.[21] ### Genetics[edit] Genetic factors are believed to be the most important determinants of who develops carpal tunnel syndrome.[5] A genome-wide association study (GWAS) of carpal tunnel syndrome identified 16 genomic loci significantly associated with the disease, including several loci previously known to be associated with human height.[22] ### Work related[edit] The international debate regarding the relationship between CTS and repetitive motion in work is ongoing. The Occupational Safety and Health Administration (OSHA) has adopted rules and regulations regarding cumulative trauma disorders. Occupational risk factors of repetitive tasks, force, posture, and vibration have been cited. The relationship between work and CTS is controversial; in many locations, workers diagnosed with carpal tunnel syndrome are entitled to time off and compensation.[23][24] Some speculate that carpal tunnel syndrome is provoked by repetitive movement and manipulating activities and that the exposure can be cumulative. It has also been stated that symptoms are commonly exacerbated by forceful and repetitive use of the hand and wrists in industrial occupations,[25] but it is unclear as to whether this refers to pain (which may not be due to carpal tunnel syndrome) or the more typical numbness symptoms.[26] A review of available scientific data by the National Institute for Occupational Safety and Health (NIOSH) indicated that job tasks that involve highly repetitive manual acts or specific wrist postures were associated with incidents of CTS, but causation was not established, and the distinction from work-related arm pains that are not carpal tunnel syndrome was not clear. It has been proposed that repetitive use of the arm can affect the biomechanics of the upper limb or cause damage to tissues. It has also been proposed that postural and spinal assessment along with ergonomic assessments should be included in the overall determination of the condition. Addressing these factors has been found to improve comfort in some studies.[27] A 2010 survey by NIOSH showed that 2/3 of the 5 million carpal tunnel cases in the US that year were related to work.[28] Women have more work-related carpal tunnel syndrome than men.[29] Speculation that CTS is work-related is based on claims such as CTS being found mostly in the working adult population, though evidence is lacking for this. For instance, in one recent representative series of a consecutive experience, most patients were older and not working.[30] Based on the claimed increased incidence in the workplace, arm use is implicated, but the weight of evidence suggests that this is an inherent, genetic, slowly but inevitably progressive idiopathic peripheral mononeuropathy.[31] ### Associated conditions[edit] A variety of patient factors can lead to CTS, including heredity, size of the carpal tunnel, associated local and systematic diseases, and certain habits.[32] Non-traumatic causes generally happen over a period of time, and are not triggered by one certain event. Many of these factors are manifestations of physiologic aging.[33] Examples include: * Rheumatoid arthritis and other diseases that cause inflammation of the flexor tendons. * With hypothyroidism, generalized myxedema causes deposition of mucopolysaccharides within both the perineurium of the median nerve, as well as the tendons passing through the carpal tunnel. * During pregnancy, women commonly experience CTS due to hormonal changes (high progesterone levels) and water retention, which swells the synovium. * Previous injuries including fractures of the wrist. * Medical disorders that lead to fluid retention or are associated with inflammation such as: inflammatory arthritis, Colles' fracture, amyloidosis, hypothyroidism, diabetes mellitus, acromegaly, and use of corticosteroids and estrogens. * Carpal tunnel syndrome is also associated with repetitive activities of the hand and wrist, in particular with a combination of forceful and repetitive activities.[15] * Acromegaly causes excessive secretion of growth hormones. This causes the soft tissues and bones around the carpel tunnel to grow and compress the median nerve.[34] * Tumors (usually benign), such as a ganglion or a lipoma, can protrude into the carpal tunnel, reducing the amount of space. This is exceedingly rare (less than 1%). * Obesity also increases the risk of CTS: individuals classified as obese (BMI > 29) are 2.5 times more likely than slender individuals (BMI < 20) to be diagnosed with CTS.[35] * Double-crush syndrome is a debated hypothesis that compression or irritation of nerve branches contributing to the median nerve in the neck, or anywhere above the wrist, increases sensitivity of the nerve to compression in the wrist. There is little evidence, however, that this syndrome really exists.[36] * Heterozygous mutations in the gene SH3TC2, associated with Charcot-Marie-Tooth, confer susceptibility to neuropathy, including CTS.[37] ## Pathophysiology[edit] Main article: Carpal tunnel Transverse section at the wrist. The median nerve is colored yellow. The carpal tunnel consists of the bones and transverse carpal ligament. The carpal tunnel is an anatomical compartment located at the base of the palm. Nine flexor tendons and the median nerve pass through the carpal tunnel that is surrounded on three sides by the carpal bones that form an arch. The median nerve provides feeling or sensation to the thumb, index finger, long finger, and half of the ring finger. At the level of the wrist, the median nerve supplies the muscles at the base of the thumb that allow it to abduct, move away from the other four fingers, as well as move out of the plane of the palm. The carpal tunnel is located at the middle third of the base of the palm, bounded by the bony prominence of the scaphoid tubercle and trapezium at the base of the thumb, and the hamate hook that can be palpated along the axis of the ring finger. From the anatomical position, the carpal tunnel is bordered on the anterior surface by the transverse carpal ligament, also known as the flexor retinaculum. The flexor retinaculum is a strong, fibrous band that attaches to the pisiform and the hamulus of the hamate. The proximal boundary is the distal wrist skin crease, and the distal boundary is approximated by a line known as Kaplan's cardinal line.[38] This line uses surface landmarks, and is drawn between the apex of the skin fold between the thumb and index finger to the palpated hamate hook.[39] The median nerve can be compressed by a decrease in the size of the canal, an increase in the size of the contents (such as the swelling of lubrication tissue around the flexor tendons), or both.[40] Since the carpal tunnel is bordered by carpal bones on one side and a ligament on the other, when the pressure builds up inside the tunnel, there is nowhere for it to escape and thus it ends up pressing up against and damaging the median nerve. Simply flexing the wrist to 90 degrees will decrease the size of the canal. Compression of the median nerve as it runs deep to the transverse carpal ligament (TCL) causes atrophy of the thenar eminence, weakness of the flexor pollicis brevis, opponens pollicis, abductor pollicis brevis, as well as sensory loss in the digits supplied by the median nerve. The superficial sensory branch of the median nerve, which provides sensation to the base of the palm, branches proximal to the TCL and travels superficial to it. Thus, this branch spared in carpal tunnel syndrome, and there is no loss of palmar sensation.[41] ## Diagnosis[edit] There is no consensus reference standard for the diagnosis of carpal tunnel syndrome. A combination of described symptoms, clinical findings, and electrophysiological testing may be used. Correct diagnosis involves identifying if symptoms matches the distribution pattern of the median nerve (which does not normally include the 5th digit). CTS work up is the most common referral to the electrodiagnostic lab. Historically, diagnosis has been made with the combination of a thorough history and physical examination in conjunction with the use of electrodiagnostic (EDX) testing for confirmation. Additionally, evolving technology has included the use of ultrasonography in the diagnosis of CTS. However, it is well established that physical exam provocative maneuvers lack both sensitivity and specificity. Furthermore, EDX cannot fully exclude the diagnosis of CTS due to the lack of sensitivity. A joint report published by the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM), the American Academy of Physical Medicine and Rehabilitation (AAPM&R) and the American Academy of Neurology defines practice parameters, standards and guidelines for EDX studies of CTS based on an extensive critical literature review. This joint review concluded median and sensory nerve conduction studies are valid and reproducible in a clinical laboratory setting and a clinical diagnosis of CTS can be made with a sensitivity greater than 85% and specificity greater than 95%. Given the key role of electrodiagnostic testing in the diagnosis of CTS, The AANEM has issued evidence-based practice guidelines, both for the diagnosis of carpal tunnel syndrome. Numbness in the distribution of the median nerve, nocturnal symptoms, thenar muscle weakness/atrophy, positive Tinel's sign at the carpal tunnel, and abnormal sensory testing such as two-point discrimination have been standardized as clinical diagnostic criteria by consensus panels of experts.[42][43] Pain may also be a presenting symptom, although less common than sensory disturbances. Electrodiagnostic testing (electromyography and nerve conduction velocity) can objectively verify the median nerve dysfunction. Normal nerve conduction studies, however, do not exclude the diagnosis of CTS. Clinical assessment by history taking and physical examination can support a diagnosis of CTS. If clinical suspicion of CTS is high, treatment should be initiated despite normal electrodiagnostic testing. ### Physical exam[edit] Although widely used, the presence of a positive Phalen test, Tinel sign, Flick sign, or upper limb nerve test alone is not sufficient for diagnosis.[3] * Phalen's maneuver is performed by flexing the wrist gently as far as possible, then holding this position and awaiting symptoms.[44] A positive test is one that results in numbness in the median nerve distribution when holding the wrist in acute flexion position within sixty seconds. The quicker the numbness starts, the more advanced the condition. Phalen's sign is defined as pain or paresthesias in the median-innervated fingers with one minute of wrist flexion. Only this test has been shown to correlate with CTS severity when studied prospectively.[32] The test characteristics of Phalen's maneuver have varied across studies ranging from 42–85% sensitivity and 54–98% specificity.[7] * Tinel's sign is a classic test to detect median nerve irritation. Tinel's sign is performed by lightly tapping the skin over the flexor retinaculum to elicit a sensation of tingling or "pins and needles" in the median nerve distribution. Tinel's sign (pain or paresthesias of the median-innervated fingers with percussion over the median nerve), depending on the study, has 38–100% sensitivity and 55–100% specificity for the diagnosis of CTS.[7] * Durkan test, carpal compression test, or applying firm pressure to the palm over the nerve for up to 30 seconds to elicit symptoms has also been proposed.[45][46] * Hand elevation test The hand elevation test is performed by lifting both hands above the head, and if symptoms are reproduced in the median nerve distribution within 2 minutes, considered positive. The hand elevation test has higher sensitivity and specificity than Tinel's test, Phalen's test, and carpal compression test. Chi-square statistical analysis has shown the hand elevation test to be as effective, if not better than, Tinel's test, Phalen's test, and carpal compression test.[47] As a note, a person with true carpal tunnel syndrome (entrapment of the median nerve within the carpal tunnel) will not have any sensory loss over the thenar eminence (bulge of muscles in the palm of hand and at the base of the thumb). This is because the palmar branch of the median nerve, which innervates that area of the palm, branches off of the median nerve and passes over the carpal tunnel.[48] This feature of the median nerve can help separate carpal tunnel syndrome from thoracic outlet syndrome, or pronator teres syndrome. Other conditions may also be misdiagnosed as carpal tunnel syndrome. Thus, if history and physical examination suggest CTS, patients will sometimes be tested electrodiagnostically with nerve conduction studies and electromyography. The role of confirmatory nerve conduction studies is controversial.[7] The goal of electrodiagnostic testing is to compare the speed of conduction in the median nerve with conduction in other nerves supplying the hand. When the median nerve is compressed, as in CTS, it will conduct more slowly than normal and more slowly than other nerves. There are many electrodiagnostic tests used to make a diagnosis of CTS, but the most sensitive, specific, and reliable test is the Combined Sensory Index (also known as the Robinson index).[49] Electrodiagnosis rests upon demonstrating impaired median nerve conduction across the carpal tunnel in context of normal conduction elsewhere. Compression results in damage to the myelin sheath and manifests as delayed latencies and slowed conduction velocities [32] However, normal electrodiagnostic studies do not preclude the presence of carpal tunnel syndrome, as a threshold of nerve injury must be reached before study results become abnormal and cut-off values for abnormality are variable.[43] Carpal tunnel syndrome with normal electrodiagnostic tests is very, very mild at worst. ### Imaging[edit] The role of MRI or ultrasound imaging in the diagnosis of carpal tunnel syndrome is unclear.[50][51][52] Their routine use is not recommended.[3] MRI has high sensitivity but low specificity to CTS. High signal intensity would show accumulation of axonal transportation, myelin sheath degeneration or oedema.[53] ### Differential diagnosis[edit] There are few disorders on the differential diagnosis for carpal tunnel syndrome. Cervical radiculopathy can be mistaken for carpal tunnel syndrome since it can also cause abnormal or painful sensations in the hands and wrist.[7] In contrast to carpal tunnel syndrome, the symptoms of cervical radiculopathy usually begins in the neck and travels down the affected arm and may be worsened by neck movement.[7] Electromyography and imaging of the cervical spine can help to differentiate cervical radiculopathy from carpal tunnel syndrome if the diagnosis is unclear.[7] Carpal tunnel syndrome is sometimes applied as a label to anyone with pain, numbness, swelling, or burning in the radial side of the hands or wrists. When pain is the primary symptom, carpal tunnel syndrome is unlikely to be the source of the symptoms.[26] As a whole, the medical community is not currently embracing or accepting trigger point theories due to lack of scientific evidence supporting their effectiveness. ## Prevention[edit] There is little or no data to support the concept that activity adjustment prevents carpal tunnel syndrome.[54] The evidence for wrist rest is debated.[55] There is also little research supporting that ergonomics is related to CTS.[56] Due to risk factors for hand and wrist dysfunction being multifactorial and very complex it is difficult to assess the true physical factors of CTS.[57] Biological factors such as genetic predisposition and anthropometric features had significantly stronger causal association with carpal tunnel syndrome than occupational/environmental factors such as repetitive hand use and stressful manual work.[54] This suggests that carpal tunnel syndrome might not be preventable simply by avoiding certain activities or types of work/activities. ## Treatment[edit] Generally accepted treatments include: physiotherapy, steroids either orally or injected locally, splinting, and surgical release of the transverse carpal ligament.[58] Limited evidence suggests that gabapentin is no more effective than placebo for CTS treatment.[7] There is insufficient evidence for therapeutic ultrasound, yoga, acupuncture, low level laser therapy, vitamin B6, and exercise.[7][58] Change in activity may include avoiding activities that worsen symptoms.[16] The American Academy of Orthopedic Surgeons recommends proceeding conservatively with a course of nonsurgical therapies tried before release surgery is considered.[59] A different treatment should be tried if the current treatment fails to resolve the symptoms within 2 to 7 weeks. Early surgery with carpal tunnel release is indicated where there is evidence of median nerve denervation or a person elects to proceed directly to surgical treatment.[59] Recommendations may differ when carpal tunnel syndrome is found in association with the following conditions: diabetes mellitus, coexistent cervical radiculopathy, hypothyroidism, polyneuropathy, pregnancy, rheumatoid arthritis, and carpal tunnel syndrome in the workplace.[59] ### Splints[edit] A rigid splint can keep the wrist straight A different type of rigid splint used in carpal tunnel syndrome. The importance of wrist braces and splints in the carpal tunnel syndrome therapy is known, but many people are unwilling to use braces. In 1993, The American Academy of Neurology recommend a non-invasive treatment for the CTS at the beginning (except for sensitive or motor deficit or grave report at EMG/ENG): a therapy using splints was indicated for light and moderate pathology.[60] Current recommendations generally don't suggest immobilizing braces, but instead activity modification and non-steroidal anti-inflammatory drugs as initial therapy, followed by more aggressive options or specialist referral if symptoms do not improve.[61][62] Many health professionals suggest that, for the best results, one should wear braces at night. When possible, braces can be worn during the activity primarily causing stress on the wrists.[63][64] The brace should not generally be used during the day as wrist activity is needed to keep the wrist from becoming stiff and to prevent muscles from weakening.[65] ### Corticosteroids[edit] Corticosteroid injections can be effective for temporary relief from symptoms while a person develops a long-term strategy that fits their lifestyle.[66] This form of treatment is thought to reduce discomfort in those with CTS due to its ability to decrease median nerve swelling.[7] The use of ultrasound while performing the injection is more expensive but leads to faster resolution of CTS symptoms.[7] The injections are done under local anesthesia.[67][68] This treatment is not appropriate for extended periods, however. In general, local steroid injections are only used until more definitive treatment options can be used. Corticosteroid injections do not appear to be very effective for slowing disease progression.[7] ### Surgery[edit] Main article: Carpal tunnel surgery Carpal tunnel syndrome operation Release of the transverse carpal ligament is known as "carpal tunnel release" surgery. It is recommended when there is static (constant, not just intermittent) numbness, muscle weakness, or atrophy, and when night-splinting or other conservative interventions no longer control intermittent symptoms.[69] The surgery may be done with local[70][71][72] or regional anesthesia[73] with[74] or without[71] sedation, or under general anesthesia.[72][73] In general, milder cases can be controlled for months to years, but severe cases are unrelenting symptomatically and are likely to result in surgical treatment.[75] Surgery is more beneficial in the short term to alleviate symptoms (up to six months) than wearing an orthosis for a minimum of six weeks. However, surgery and wearing a brace resulted in similar symptom relief in the long term (12–18 month outcomes).[76] ### Physical therapy[edit] Main article: Physical therapy in carpal tunnel syndrome An evidence based guideline produced by the American Academy of Orthopedic Surgeons assigned various grades of recommendation to physical therapy and other nonsurgical treatments.[77] One of the primary issues with physiotherapy is that it attempts to reverse (often) years of pathology inside the carpal tunnel. Practitioners caution that any physiotherapy such as myofascial release may take weeks of persistent application to effectively manage carpal tunnel syndrome.[78] Again, some claim that pro-active ways to reduce stress on the wrists, which alleviates wrist pain and strain, involve adopting a more ergonomic work and life environment. For example, some have claimed that switching from a QWERTY computer keyboard layout to a more optimised ergonomic layout such as Dvorak was commonly cited as beneficial in early CTS studies; however, some meta-analyses of these studies claim that the evidence that they present is limited.[79][80] Tendon and nerve gliding exercises appear to be useful in carpal tunnel syndrome.[81] ## Prognosis[edit] Scars from carpal tunnel release surgery. Two different techniques were used. The left scar is 6 weeks old, the right scar is 2 weeks old. Also note the muscular atrophy of the thenar eminence in the left hand, a common sign of advanced CTS Most people relieved of their carpal tunnel symptoms with conservative or surgical management find minimal residual or "nerve damage".[82] Long-term chronic carpal tunnel syndrome (typically seen in the elderly) can result in permanent "nerve damage", i.e. irreversible numbness, muscle wasting, and weakness. Those that undergo a carpal tunnel release are nearly twice as likely as those not having surgery to develop trigger thumb in the months following the procedure.[83] While outcomes are generally good, certain factors can contribute to poorer results that have little to do with nerves, anatomy, or surgery type. One study showed that mental status parameters or alcohol use yields much poorer overall results of treatment.[84] Recurrence of carpal tunnel syndrome after successful surgery is rare.[85] ## Epidemiology[edit] Rates of carpal tunnel syndrome by ethnicity. CTS is much more common in Caucasians. Carpal tunnel syndrome is estimated to affect one out of ten people during their lifetime and is the most common nerve compression syndrome.[7] It accounts for about 90% of all nerve compression syndromes.[86] In the U.S., 5% of people have the effects of carpal tunnel syndrome. Caucasians have the highest risk of CTS compared with other races such as non-white South Africans.[87] Women suffer more from CTS than men with a ratio of 3:1 between the ages of 45–60 years. Only 10% of reported cases of CTS are younger than 30 years.[87] Increasing age is a risk factor. CTS is also common in pregnancy.[7] ### Occupational[edit] As of 2010[update], 8% of U.S. workers reported ever having carpal tunnel syndrome and 4% reported carpal tunnel syndrome in the past 12 months. Prevalence rates for carpal tunnel syndrome in the past 12 months were higher among females than among males; among workers aged 45–64 than among those aged 18–44. Overall, 67% of current carpal tunnel syndrome cases among current/recent workers were reportedly attributed to work by health professionals, indicating that the prevalence rate of work-related carpal tunnel syndrome among workers was 2%, and that there were approximately 3.1 million cases of work-related carpal tunnel syndrome among U.S. workers in 2010. Among current carpal tunnel syndrome cases attributed to specific jobs, 24% were attributed to jobs in the manufacturing industry, a proportion 2.5 times higher than the proportion of current/recent workers employed in the manufacturing industry, suggesting that jobs in this industry are associated with an increased risk of work-related carpal tunnel syndrome.[88] ## History[edit] The condition known as carpal tunnel syndrome had major appearances throughout the years but it was most commonly heard of in the years following World War II.[9] Individuals who had suffered from this condition have been depicted in surgical literature for the mid-19th century.[9] In 1854, Sir James Paget was the first to report median nerve compression at the wrist in two cases.[89][90] The first to notice the association between the carpal ligament pathology and median nerve compression appear to have been Pierre Marie and Charles Foix in 1913.[91] They described the results of a postmortem of an 80-year-old man with bilateral carpal tunnel syndrome. They suggested that division of the carpal ligament would be curative in such cases. Putman had previously described a series of 37 patients and suggested a vasomotor origin.[92] The association between the thenar muscle atrophy and compression was noted in 1914.[93] The name "carpal tunnel syndrome" appears to have been coined by Moersch in 1938.[94] In the early 20th century there were various cases of median nerve compression underneath the transverse carpal ligament.[90] Physician George S. Phalen of the Cleveland Clinic identified the pathology after working with a group of patients in the 1950s and 1960s.[95][96] Treatment Paget described two cases of carpal tunnel syndrome. The first was due to an injury where a cord had been wrapped around a man's wrist. The second was due to a distal radial fracture. For the first case Paget performed an amputation of the hand. For the second case Paget recommended a wrist splint – a treatment that is still in use today. Surgery for this condition initially involved the removal of cervical ribs despite Marie and Foix's suggested treatment. In 1933 Sir James Learmonth outlined a method of decompression of the nerve at the wrist.[97] This procedure appears to have been pioneered by the Canadian surgeons Herbert Galloway and Andrew MacKinnon in 1924 in Winnipeg but was not published.[98] Endoscopic release was described in 1988.[99] ## See also[edit] * Repetitive strain injury * Tarsal tunnel syndrome * Ulnar nerve entrapment ## References[edit] 1. ^ a b c d e f Burton, C; Chesterton, LS; Davenport, G (May 2014). "Diagnosing and managing carpal tunnel syndrome in primary care". The British Journal of General Practice. 64 (622): 262–3. doi:10.3399/bjgp14x679903. PMC 4001168. PMID 24771836. 2. ^ a b c d e f g "Carpal Tunnel Syndrome Fact Sheet". National Institute of Neurological Disorders and Stroke. January 28, 2016. Archived from the original on 3 March 2016. 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L.; McGowan, R. (4 January 2010). "American Academy of Orthopaedic Surgeons Clinical Practice Guideline on The Treatment of Carpal Tunnel Syndrome". The Journal of Bone and Joint Surgery. 92 (1): 218–219. doi:10.2106/JBJS.I.00642. PMC 6882524. PMID 20048116. S2CID 7604145. 78. ^ Siu, G.; Jaffee, J.D.; Rafique, M.; Weinik, M.M. (1 March 2012). "Osteopathic Manipulative Medicine for Carpal Tunnel Syndrome". The Journal of the American Osteopathic Association. 112 (3): 127–139. PMID 22411967. 79. ^ Lincoln, A; Vernick, JS; Ogaitis, S; Smith, GS; Mitchell, CS; Agnew, J (2000). "Interventions for the primary prevention of work-related carpal tunnel syndrome". American Journal of Preventive Medicine. 18 (4 Suppl): 37–50. doi:10.1016/S0749-3797(00)00140-9. PMID 10793280. 80. ^ Verhagen, Arianne P; Karels, Celinde C; Bierma-Zeinstra, Sita MA; Burdorf, Lex L; Feleus, Anita; Dahaghin, Saede SD; De Vet, Henrica CW; Koes, Bart W; Verhagen, Arianne P (2006). Verhagen, Arianne P (ed.). "Ergonomic and physiotherapeutic interventions for treating work-related complaints of the arm, neck or shoulder in adults". Cochrane Database of Systematic Reviews. 3 (3): CD003471. doi:10.1002/14651858.CD003471.pub3. PMID 16856010. (Retracted, see doi:10.1002/14651858.cd003471.pub4. If this is an intentional citation to a retracted paper, please replace `{{Retracted}}` with `{{Retracted\|intentional=yes}}`.) 81. ^ Kim, SD (August 2015). "Efficacy of tendon and nerve gliding exercises for carpal tunnel syndrome: a systematic review of randomized controlled trials". Journal of Physical Therapy Science. 27 (8): 2645–8. doi:10.1589/jpts.27.2645. PMC 4563334. PMID 26357452. 82. ^ Olsen, K. M.; Knudson, D. V. (2001). "Change in Strength and Dexterity after Open Carpal Tunnel Release". International Journal of Sports Medicine. 22 (4): 301–3. doi:10.1055/s-2001-13815. PMID 11414675. 83. ^ King, Bradley A.; Stern, Peter J.; Kiefhaber, Thomas R. (2013). "The incidence of trigger finger or de Quervain's tendinitis after carpal tunnel release". Journal of Hand Surgery (European Volume). 38 (1): 82–3. doi:10.1177/1753193412453424. PMID 22791612. S2CID 30644466. 84. ^ Katz, Jeffrey N.; Losina, Elena; Amick, Benjamin C.; Fossel, Anne H.; Bessette, Louis; Keller, Robert B. (2001). "Predictors of outcomes of carpal tunnel release". Arthritis & Rheumatism. 44 (5): 1184–93. doi:10.1002/1529-0131(200105)44:5<1184::AID-ANR202>3.0.CO;2-A. PMID 11352253. 85. ^ Ruch, DS; Seal, CN; Bliss, MS; Smith, BP (2002). "Carpal tunnel release: efficacy and recurrence rate after a limited incision release". Journal of the Southern Orthopaedic Association. 11 (3): 144–7. PMID 12539938.[unreliable medical source?] 86. ^ Ibrahim I.; Khan W. S.; Goddard N.; Smitham P. (2012). "Carpal Tunnel Syndrome: A Review of the Recent Literature". The Open Orthopaedics Journal. 6: 69–76. doi:10.2174/1874325001206010069. PMC 3314870. PMID 22470412. 87. ^ a b Ashworth, Nigel L. (December 4, 2008). "Carpal Tunnel Syndrome". eMedicine. Archived from the original on July 28, 2010. Cite journal requires `\|journal=` (help) 88. ^ Luckhaupt SE, Dahlhamer JM, Ward BW, Sweeney MH, Sestito JP, Calvert GM (June 2013). "Prevalence and work-relatedness of carpal tunnel syndrome in the working population, United States, 2010 National Health Interview Survey". American Journal of Industrial Medicine. 56 (6): 615–24. doi:10.1002/ajim.22048. PMC 4557701. PMID 22495886. 89. ^ Paget J (1854) Lectures on surgical pathology. Lindsay & Blakinston, Philadelphia 90. ^ a b Fuller, David A. (September 22, 2010). "Carpal Tunnel Syndrome". eMedicine. Archived from the original on July 27, 2010. Cite journal requires `\|journal=` (help) 91. ^ Marie P, Foix C (1913). "Atrophie isolée de l'éminence thenar d'origine névritique: role du ligament annulaire antérieur du carpe dans la pathogénie de la lésion". Rev Neurol. 26: 647–649. 92. ^ Putnam JJ (1880). "A series of cases of paresthesia, mainly of the hand, or periodic recurrence, and possibly of vaso-motor origin". Arch Med. 4: 147–162. 93. ^ Hunt JR (1914). "The neural atrophy of the muscle of the hand, without sensory disturbances". Rev Neurol Psych. 12: 137–148. 94. ^ Moersch FP (1938). "Median thenar neuritis". Proc Staff Meet Mayo Clin. 13: 220. 95. ^ Phalen GS, Gardner WJ, Lalonde AA (1950). "Neuropathy of the median nerve due to compression beneath the transverse carpal ligament". J Bone Joint Surg Am. 1 (1): 109–112. doi:10.2106/00004623-195032010-00011. PMID 15401727. 96. ^ Gilliatt RW, Wilson TG (1953). "A pneumatic-tourniquet test in the carpal-tunnel syndrome". Lancet. 262 (6786): 595–597. doi:10.1016/s0140-6736(53)90327-4. PMID 13098011. 97. ^ Learmonth JR (1933). "The principle of decompression in the treatment of certain diseases of peripheral nerves". Surg Clin North Am. 13: 905–913. 98. ^ Amadio PC (1995). "The first carpal tunnel release?". J Hand Surg: British & European. 20 (1): 40–41. doi:10.1016/s0266-7681(05)80013-0. PMID 7759932. S2CID 534160. 99. ^ Chow JC (1989). "Endoscopic release of the carpal tunnel ligament: a new technique for carpal tunnel syndrome". Arthroscopy. 6 (4): 288–296. doi:10.1016/0749-8063(90)90058-l. PMID 2264896. ## External links[edit] Classification D * ICD-10: G56.0 * ICD-9-CM: 354.0 * OMIM: 115430 * MeSH: D002349 * DiseasesDB: 2156 External resources * MedlinePlus: 000433 * eMedicine: orthoped/455 pmr/21 emerg/83 radio/135 * Carpal Tunnel Syndrome Fact Sheet (National Institute of Neurological Disorders and Stroke) * NHS website carpal-tunnel.net provides a free to use, validated, online self diagnosis questionnaire for CTS * "Carpal Tunnel Syndrome". MedlinePlus. U.S. National Library of Medicine. * v * t * e Diseases relating to the peripheral nervous system Mononeuropathy Arm median nerve * Carpal tunnel syndrome * Ape hand deformity ulnar nerve * Ulnar nerve entrapment * Froment's sign * Ulnar tunnel syndrome * Ulnar claw radial nerve * Radial neuropathy * Wrist drop * Cheiralgia paresthetica long thoracic nerve * Winged scapula * Backpack palsy Leg lateral cutaneous nerve of thigh * Meralgia paraesthetica tibial nerve * Tarsal tunnel syndrome plantar nerve * Morton's neuroma superior gluteal nerve * Trendelenburg's sign sciatic nerve * Piriformis syndrome Cranial nerves * See Template:Cranial nerve disease Polyneuropathy and Polyradiculoneuropathy HMSN * Charcot–Marie–Tooth disease * Dejerine–Sottas disease * Refsum's disease * Hereditary spastic paraplegia * Hereditary neuropathy with liability to pressure palsy * Familial amyloid neuropathy Autoimmune and demyelinating disease * Guillain–Barré syndrome * Chronic inflammatory demyelinating polyneuropathy Radiculopathy and plexopathy * Brachial plexus injury * Thoracic outlet syndrome * Phantom limb Other * Alcoholic polyneuropathy Other General * Complex regional pain syndrome * Mononeuritis multiplex * Peripheral neuropathy * Neuralgia * Nerve compression syndrome [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Carpal tunnel syndrome	c0007286	3,804	wikipedia	https://en.wikipedia.org/wiki/Carpal_tunnel_syndrome	2021-01-18T19:04:38	{"mesh": ["D002349"], "umls": ["C0007286"], "wikidata": ["Q332293"]}
SCALP syndrome is a rare skin disease characterized by the association of sebaceous nevus and aplasia cutis congenita (usually on the scalp and face) in conjunction with limbal dermoid of the eye, a giant congenital melanocytic nevus and variable central nervous system abnormalities, including seizures, hydrocephalus, neurocutaneous melanosis, arachnoid cysts, and diffuse unilateral hemishpere enlargement. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	SCALP syndrome	None	3,805	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=370052	2021-01-23T17:28:04	{"icd-10": ["Q84.8"], "synonyms": ["Sebaceous nevus-CNS malformations-aplasia cutis congenital-limbal dermoid-pigmented nevus syndrome", "Sebaceous nevus-central nervous system malformations-aplasia cutis congenital-limbal dermoid-pigmented nevus syndrome"]}
Kikuchi-Fujimoto disease (KFD) is a benign and self-limited disorder, characterized by regional cervical lymphadenopathy with tenderness, usually accompanied with mild fever and night sweats. Less frequent symptoms include weight loss, nausea, vomiting, sore throat. ## Epidemiology Kikuchi-Fujimoto disease is an extremely rare disease known to have a worldwide distribution with higher prevalence among Japanese and other Asiatic individuals. Prevalence is unknown. Only isolated cases are reported in Europe. ## Etiology The clinical, histopathological and immunohistochemical features appear to point to a viral etiology, a hypothesis that still has not been proven. ## Diagnostic methods KFD is generally diagnosed on the basis of an excisional biopsy of affected lymph nodes. Its recognition is crucial especially because this disease can be mistaken for systemic lupus erythematosus, malignant lymphoma or even, though rarely, for adenocarcinoma. Clinicians' and pathologists' awareness of this disorder may help prevent misdiagnosis and inappropriate treatment. The diagnosis of KFD merits active consideration in any nodal biopsy showing fragmentation, necrosis and karyorrhexis, especially in young individuals presenting with posterior cervical lymphadenopathy. ## Management and treatment Treatment is symptomatic (analgesics-antipyretics, non-steroidal anti-inflammatory drugs and, rarely, corticosteroids). Patients with Kikuchi-Fujimoto disease should be followed-up for several years to survey the possibility of the development of systemic lupus erythematosus. ## Prognosis Spontaneous recovery occurs in 1 to 4 months. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Kikuchi-Fujimoto disease	c0398367	3,806	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=50918	2021-01-23T18:29:31	{"gard": ["6834"], "mesh": ["D020042"], "umls": ["C0398367"], "icd-10": ["I88.1"], "synonyms": ["Histiocytic necrotizing lymphadenitis", "Kikuchi disease"]}
Alcohol (also known formally as ethanol), found in alcoholic beverages, can exacerbate sleep disturbances. During abstinence, sleep disruption is one of the greatest predictors of relapse.[1] ## Contents * 1 Moderate alcohol consumption and sleep disruptions * 2 Alcohol consumption and sleep improvements * 3 Alcohol consumption and fatigue * 4 Alcohol abstinence and sleep disruptions * 5 See also * 6 References ## Moderate alcohol consumption and sleep disruptions[edit] Moderate alcohol consumption 30–60 minutes before bedtime results in disruptions in sleep maintenance and sleep architecture that are mediated by blood alcohol levels.[2] Disruptions in sleep maintenance are most marked once alcohol has been completely metabolized from the body. Under conditions of moderate alcohol consumption where blood alcohol levels average 0.06–0.08% and decrease 0.01–0.02% per hour, an alcohol clearance rate of 4–5 hours would coincide with disruptions in sleep maintenance in the second half of an 8-hour sleep episode.[2] In terms of sleep architecture, moderate doses of alcohol facilitate "rebounds" in rapid eye movement (REM) and stage 1 sleep; following suppression in REM and stage 1 sleep in the first half of an 8-hour sleep episode, REM and stage 1 sleep increase well beyond baseline in the second half. Moderate doses of alcohol also increase slow wave sleep (SWS) in the first half of an 8-hour sleep episode.[2] Enhancements in REM sleep and SWS following moderate alcohol consumption are mediated by reductions in glutamatergic activity by adenosine in the central nervous system.[2] In addition, tolerance to changes in sleep maintenance and sleep architecture develops within 3 days of alcohol consumption before bedtime.[2] ## Alcohol consumption and sleep improvements[edit] Low doses of alcohol (one 360.0 ml (13 imp fl oz; 12 US fl oz) beer) are sleep-promoting by increasing total sleep time and reducing awakenings during the night. The sleep-promoting benefits of alcohol dissipate at moderate and higher doses of alcohol (two 12 oz. beers and three 12 oz. beers, respectively).[3] Previous experience with alcohol also determines whether or not alcohol is a "sleep promoter" or "sleep disrupter." Under free-choice conditions, in which subjects chose between drinking alcohol or water, inexperienced drinkers were sedated while experienced drinkers were stimulated following alcohol consumption.[4] In insomniacs, moderate doses of alcohol improve sleep maintenance.[5] ## Alcohol consumption and fatigue[edit] Sleepiness influences the severity of alcohol consumption. Conditions of sleep deprivation encourage more episodes of alcohol consumption.[2] Increased alcohol consumption during the winter months for Northern climate residents is attributed to escalations in fatigue.[6] ## Alcohol abstinence and sleep disruptions[edit] Sleep and hormonal disruptions following withdrawal from chronic alcohol consumption are the greatest predictors of relapse.[1] During abstinence, recovering alcoholics have attenuated melatonin secretion in the beginning of a sleep episode, resulting in prolonged sleep latencies.[7] Escalations in cortisol and core body temperatures during the sleep period contribute to poor sleep maintenance.[7][8] Abstinent alcoholics tend to have lighter, more fragmented sleep than normal control subjects. Research indicates that it may take as long as one to two years for sleep to return to normal in abstinent alcoholics and that for some it may never return to normal. ## See also[edit] * Nightcap (beverage) * Short-term effects of alcohol consumption#Sleep * Sleep induction#Alcohol ## References[edit] 1. ^ a b Feige, B., Scaal, S., Hornyak, M., Gann, H., Riemann, D. Sleep electroencephalographic spectral power after withdrawal from alcohol in alcohol-dependent patients. ALcoholism: Clinical and Experimental Research. 2007 Jan; 31 (1): 19-27. 2. ^ a b c d e f Roehrs, T., and Roth, T. Sleep, sleepiness, and alcohol use. Alcohol Research & Health. 2001; 25(2):101-109. 3. ^ Stone, B. Sleep and low doses of alcohol. Electroencephalography and Clinical Neurophysiology. 1980; 48: 706-709. 4. ^ Schuckit, M.A. Low level of response to alcohol as a predictor of future alcoholism. Am J Psychiatry. 1994 Feb; 151(2):184-189. 5. ^ Roehrs, T., Papineau, B.A., Rosenthal, L., Roth, T. Ethanol as a hypnotic in insomniacs: self administration and effects on sleep and mood. Neuropsychopharmacology. 1999 Mar; 20(3):279-86, PMID 10063488. 6. ^ Levine, M.E., Duffy, L.K., Bowyer, R.T. Fatigue, sleep, and seasonal hormone levels: implications for drinking behavior in Northern climates. Drugs & Society. 1994; 8(2): 61-70. 7. ^ a b Kühlwein, E., Hauger, R.L., Irwin, M.R. Abnormal nocturnal melatonin secretion and disordered sleep in abstinent alcoholics. Biol Psychiatry. 2003; 54: 1437-1443. 8. ^ Danel, T., Libersa, C., Touitou, Y. The effect of alcohol consumption on the circadian control of human core body temperature is time dependent. Am J Physiol Regulatory Integrative Comp Physiol. 2001; 281: R52-R55. * v * t * e Alcohol and health Alcohol use Alcohol-related crimes * Drunk drivers * Alcohol-related traffic crashes in the United States * Driving under the influence (DUI) * Drunk driving in the United States * Public intoxication * Rum-running * Adulterated moonshine/Denatured alcohol * List of methanol poisoning incidents Alcoholism * Alcohol and Native Americans * Alcoholism in adolescence * Alcoholism in family systems * Collaborative Study on the Genetics of Alcoholism * College student alcoholism * Disease theory of alcoholism * High-functioning alcoholic (HFA) * Seeing pink elephants Chemistry * Beer chemistry * Congener * Alcohol congener analysis * Ethanol * Blood alcohol content * Breathalyzer * Fusel alcohol * Wine chemistry Effects * Short-term effects of alcohol consumption * Long-term effects of alcohol * On memory * Subjective response to alcohol Interactions * Aging * Brain * Cancer * breast cancer * Cortisol * Pregnancy * Sleep * Tolerance/intolerance * Weight * Beverage-specific * Beer: Potomania * Red wine: Red wine headache Social issues * Alcohol advertising * on college campuses * Sex * Alcohol myopia * Alcohol abuse among college students * Binge drinking * Epidemiology * Blackout (alcohol-related amnesia) * Blackout Wednesday * Drinking game * list * pregaming * Drinking in public * Drunk dialing * Drunk walking * Drunkorexia * Dry drunk * French paradox * Hair of the dog * Nightcap * Pantsdrunk * Passive drinking * Binge drinking devices * Beer bong * Yard of ale * Routes of administration * Alcohol enema * Alcohol inhalation * Sconcing * Surrogate alcohol * Related issues * Balconing * Suicide History * Dionysian Mysteries * Dipsomania * Gin Craze * List of deaths through alcohol * Rum ration * Speakeasy General * Beer day * Drinking culture * Apéritif and digestif * Hangover remedies * Health effects of wine * Wine and food matching * Long-distance race involving alcohol * List of countries by alcohol consumption per capita * Alcohol consumption by youth in the United States * Nip joint Alcohol control Alcohol law * Administrative license suspension (ALS) * Alcohol packaging warning messages * Drunk driving law by country * DWI court * Field sobriety testing * Hip flask defence * Ignition interlock device * Legal drinking age * Age controversy in US * Underage drinking in US * List of alcohol laws of US Alcohol prohibition * List of countries with alcohol prohibition * Neo-prohibitionism * Temperance movement Sobriety * Alcohol detoxification * Alcohol-free zone * Dry campus * United States open-container laws * Designated driver * Alcohol rehabilitation * Drunk tank * Managed alcohol program * Non-alcoholic drink * List of cocktails * List of mixed drinks * Spritzer * Malt drinks * Teetotalism * Temperance bar * Twelve-step groups * Al-Anon/Alateen * Alcoholics Anonymous (AA): * Adult Children of Alcoholics (ACA) Alcohol limitation * 0-0-1-3 * Alcohol education * Alcohol server training * FRAMES * Dry January * Foundation for Advancing Alcohol Responsibility * Campaigns * Get Your Sexy Back * Liquor license * Low-alcohol drinks * Fermented tea * Low-alcohol beer * Low-alcoholic malt drinks * Small beer * Measurement * Alcoholic spirits measure * Standard drink * Recommended maximum intake of alcoholic beverages Addiction medicine * Disulfiram-like drugs: disulfiram, calcium carbimide, cyanamide. Sulfonic acids: Acamprosate Religion and alcohol * Christian views on alcohol * alcohol in the Bible * Islam and alcohol History * Bratt System Related * Index of alcohol-related articles * Austrian syndrome * Ban on caffeinated alcoholic beverages * Brief intervention * Gateway drug effect * Last call * Mood disorder * Non-alcoholic fatty liver disease * Self-medication * Spins * Sober companion * Sober living houses * Sobering center * Town drunk * Category * v * t * e Psychoactive substance-related disorder General * SID * Substance intoxication / Drug overdose * Substance-induced psychosis * Withdrawal: * Craving * Neonatal withdrawal * Post-acute-withdrawal syndrome (PAWS) * SUD * Substance abuse / Substance-related disorders * Physical dependence / Psychological dependence / Substance dependence Combined substance use * SUD * Polysubstance dependence * SID * Combined drug intoxication (CDI) Alcohol SID Cardiovascular diseases * Alcoholic cardiomyopathy * Alcohol flush reaction (AFR) Gastrointestinal diseases * Alcoholic liver disease (ALD): * Alcoholic hepatitis * Auto-brewery syndrome (ABS) Endocrine diseases * Alcoholic ketoacidosis (AKA) Nervous system diseases * Alcohol-related dementia (ARD) * Alcohol intoxication * Hangover Neurological disorders * Alcoholic hallucinosis * Alcoholic polyneuropathy * Alcohol-related brain damage * Alcohol withdrawal syndrome (AWS): * Alcoholic hallucinosis * Delirium tremens (DTs) * Fetal alcohol spectrum disorder (FASD) * Fetal alcohol syndrome (FAS) * Korsakoff syndrome * Positional alcohol nystagmus (PAN) * Wernicke–Korsakoff syndrome (WKS, Korsakoff psychosis) * Wernicke encephalopathy (WE) Respiratory tract diseases * Alcohol-induced respiratory reactions * Alcoholic lung disease SUD * Alcoholism (alcohol use disorder (AUD)) * Binge drinking Caffeine * SID * Caffeine-induced anxiety disorder * Caffeine-induced sleep disorder * Caffeinism * SUD * Caffeine dependence Cannabis * SID * Cannabis arteritis * Cannabinoid hyperemesis syndrome (CHS) * SUD * Amotivational syndrome * Cannabis use disorder (CUD) * Synthetic cannabinoid use disorder Cocaine * SID * Cocaine intoxication * Prenatal cocaine exposure (PCE) * SUD * Cocaine dependence Hallucinogen * SID * Acute intoxication from hallucinogens (bad trip) * Hallucinogen persisting perception disorder (HPPD) Nicotine * SID * Nicotine poisoning * Nicotine withdrawal * SUD * Nicotine dependence Opioids * SID * Opioid overdose * SUD * Opioid use disorder (OUD) Sedative / hypnotic * SID * Kindling (sedative–hypnotic withdrawal) * benzodiazepine: SID * Benzodiazepine overdose * Benzodiazepine withdrawal * SUD * Benzodiazepine use disorder (BUD) * Benzodiazepine dependence * barbiturate: SID * Barbiturate overdose * SUD * Barbiturate dependence Stimulants * SID * Stimulant psychosis * amphetamine: SUD * Amphetamine dependence Volatile solvent * SID * Sudden sniffing death syndrome (SSDS) * Toluene toxicity * SUD * Inhalant abuse [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Alcohol use and sleep	None	3,807	wikipedia	https://en.wikipedia.org/wiki/Alcohol_use_and_sleep	2021-01-18T18:36:38	{"icd-9": ["291.82"], "wikidata": ["Q4713313"]}
A number sign (#) is used with this entry because of evidence that polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy-2 (PLOSL2) is caused by homozygous mutation in the TREM2 gene (605086) on chromosome 6p21. Description Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy-2 (PLOSL2), or Nasu-Hakola disease, is a recessively inherited presenile frontal dementia with leukoencephalopathy and basal ganglia calcification. In most cases the disorder first manifests in early adulthood as pain and swelling in ankles and feet, followed by bone fractures. Neurologic symptoms manifest in the fourth decade of life as a frontal lobe syndrome with loss of judgment, euphoria, and disinhibition. Progressive decline in other cognitive domains begins to develop at about the same time. The disorder culminates in a profound dementia and death by age 50 years (summary by Klunemann et al., 2005). For a discussion of genetic heterogeneity of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, see 221770. Clinical Features Bird et al. (1983) reported PLOSL in 4 of 10 sibs in an American family of Czechoslovakian ancestry. All patients had calcification of the basal ganglia. Electron microscopy of fat cells showed peculiar membrane convolutions. Limited neuropathologic material had shown gliosis and demyelination of white matter, senile plaques and neurofibrillary tangles. The authors noted other possible rare features, including leukemia and a disorder of intestinal motility. The prevalence of the disorder is unknown, partly because it may be confused with Alzheimer disease (see 104300) and fibrous dysplasia of bone. Bird et al. (1983) suggested that radiographs of hands and feet should be part of the evaluation of patients with unexplained presenile dementia. Klunemann et al. (2005) reported 6 patients, including 2 sibs, with PLOSL2. Compared to patients with PLOSL1 (221770), caused by mutations in the DAP12 gene (604142) as described by Paloneva et al. (2001), patients with TREM2 mutations had onset of bone pain about 10 years later and bone fractures were diagnosed 4 years later. There was no difference between the 2 groups in age at onset of dementia or in neurologic symptoms or radiographic findings. Molecular Genetics In affected members of 5 families with PLOSL2, including the family reported by Bird et al. (1983), Paloneva et al. (2002) identified homozygous mutations in the TREM2 gene (605086.0001-605086.0005). Klunemann et al. (2005) reported 6 patients, including 2 sibs, with PLOSL2 caused by homozygous mutations in the TREM2 gene (see, e.g., 605086.0006 and 605086.0007). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	POLYCYSTIC LIPOMEMBRANOUS OSTEODYSPLASIA WITH SCLEROSING LEUKOENCEPHALOPATHY 2	c1857316	3,808	omim	https://www.omim.org/entry/618193	2019-09-22T15:43:16	{"mesh": ["C536329"], "omim": ["618193"], "orphanet": ["2770"]}
A number sign (#) is used with this entry because of evidence that polycystic kidney disease-3 with or without polycystic liver disease (PKD3) is caused by heterozygous mutation in the GANAB gene (104160) on chromosome 11q13. Description Polycystic kidney disease-3, a form of autosomal dominant PKD (ADPKD), is characterized by renal cysts, often associated with liver cysts, that may lead to organ dysfunction. Affected individuals usually present in mid to late adulthood with progressive cysts in the kidney and/or liver. The renal disease is relatively mild, and only some patients develop hypertension; renal insufficiency usually does not occur. The liver disease shows a wide spectrum of severity: some patients have no cysts, whereas others have severe liver involvement (summary by Porath et al., 2016). For a discussion of genetic heterogeneity of PKD, see PKD1 (173900). Clinical Features Porath et al. (2016) reported 20 patients from 9 unrelated families with autosomal dominant polycystic kidney and/or liver disease associated with heterozygous mutations in the GANAB gene. Seven of the families presented with a primary diagnosis of PKD, and 2 with a primary diagnosis of polycystic liver disease (PCLD), although there was significant phenotypic overlap between the 2 groups. Most patients presented in mid- to late-adulthood, although 1 boy became symptomatic at age 9 years. Overall, the renal disease was relatively mild without renal insufficiency, and less than half of patients had high blood pressure. Renal imaging showed variable numbers of multiple cysts (from less than 10 to more than 40) in all patients, including those with a primary diagnosis of PCLD. The liver disease was variable and ranged from no cysts to severe disease requiring surgical intervention in 2 unrelated patients in their forties. Liver imaging showed cysts in most patients with a primary diagnosis of PKD, and in all 5 patients with a primary diagnosis of PCLD. A father and daughter (family M263 with PKD) had mild kidney and significant liver cystic disease, but no high blood pressure. Two sisters (family M641) had mild PKD, but only 1 had multiple liver cysts. However, both had intracranial aneurysms, and the deceased father reportedly had a ruptured aneurysm. In another family (family 290100), a father and son had mild PKD, but only the father had multiple liver cysts. Porath et al. (2016) concluded that GANAB-related PKD and PCLD are not necessarily separate diseases, but rather share overlapping features whose variability may be determined by additional genetic factors. ### Clinical Variability Besse et al. (2018) reported a large family (family T90) in which 6 individuals spanning 2 generations had isolated polycystic liver disease associated with a heterozygous mutation in the GANAB gene (104160.0007). Clinical details of the family were not provided, but they apparently did not have kidney cysts. Molecular Genetics In 20 affected members of 9 unrelated families with PKD3, Porath et al. (2016) identified 8 different heterozygous mutations in the GANAB gene (see, e.g., 104160.0001-104160.0006). Five of the mutations were predicted to result in a truncated protein (frameshift, nonsense, or splicing), and 3 were missense mutations. The mutation in the first family was found by whole-exome sequencing of 6 families with ADPKD; subsequent mutations were identified by Sanger sequencing of the GANAB gene in 321 families with ADPKD and/or ADPLD. Complete knockdown of GANAB in human renal cells resulted in absence of the mature N-terminal polycystin-1 (PKD1; 601313), but full-length polycystin-1 and polycystin-2 (PKD2; 173910) were present, indicating that GANAB plays a major role in the maturation of these proteins. Heterozygous-null GANAB renal cells had a 50% depletion of mature N-terminal polycystin-1. Transfection of the 3 missense mutations into GANAB-null renal cells failed to rescue the lack of surface PKD1 expression, indicating that these mutations resulted in a loss of enzyme function. The authors noted that PRKCSH (177060), mutations in which cause polycystic liver disease-1 (PCLD1; 174050) without renal cysts, and GANAB are subunits of the same protein, so it is not clear why GANAB mutations result in more renal disease. The highly variable phenotype was typical of polycystic kidney and liver disease, and allelic effects did not appear to explain this variability. The cystogenesis was most likely driven by defects in maturation of PKD1, mutations in which cause autosomal dominant polycystic kidney disease-1 (173900). INHERITANCE \- Autosomal dominant CARDIOVASCULAR Vascular \- Hypertension (in some patients) \- Intracranial aneurysm (1 family) ABDOMEN Liver \- Liver cysts \- Liver dysfunction (in some patients) GENITOURINARY Kidneys \- Renal cysts \- Renal dysfunction (in some patients) MISCELLANEOUS \- Onset usually in mid- to late-adulthood \- Highly variable severity \- Renal disease is typically mild MOLECULAR BASIS \- Caused by mutation in the glucosidase, alpha, neutral AB gene (GANAB, 104160.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	POLYCYSTIC KIDNEY DISEASE 3 WITH OR WITHOUT POLYCYSTIC LIVER DISEASE	c3887964	3,809	omim	https://www.omim.org/entry/600666	2019-09-22T16:16:00	{"doid": ["0110860"], "omim": ["600666"], "orphanet": ["730"], "synonyms": ["Alternative titles", "POLYCYSTIC KIDNEY DISEASE, ADULT, TYPE III", "ADPKD"], "genereviews": ["NBK1246"]}
Hematuria Other namesHaematuria, erythrocyturia,[1] blood in the urine Visible Hematuria SpecialtyNephrology, Urology SymptomsBlood in the urine CausesUrinary tract infection, kidney stone, bladder cancer, kidney cancer Hematuria or haematuria is defined as the presence of blood or red blood cells in the urine.[2] An anatomical framework is helpful in developing a comprehensive differential diagnosis. Blood or red blood cells can enter and mix with urine at multiple anatomical sites. These include the urinary system, female reproductive system, and integumentary system. Urinary causes occur anywhere between the kidney glomerulus and the urethral meatus.[3] These can be divided into glomerular and non-glomerular causes.[3] Non-glomerular causes can be further subdivided into upper urinary tract and lower urinary tract causes.[3] After conducting a thorough history and physical examination, further medical testing is warranted. Patients can be stratified into high and low risk.[4] High-risk patients include those with visible hematuria or those with non-visible hematuria and risk factors.[4] A complete evaluation of the urinary tract is indicated for hematuria. This includes imaging of the upper urinary tract and cystoscopy of the lower urinary tract.[4] ## Contents * 1 Differential diagnosis * 1.1 Glomerular hematuria * 1.2 Non-glomerular hematuria[4] * 1.2.1 Upper urinary tract * 1.2.2 Lower urinary tract * 1.3 Microscopic hematuria * 1.4 Hemoglobinuria * 1.5 Non-urinary hematuria * 1.6 Children * 2 Diagnosis * 2.1 Associated symptoms * 2.2 Upper urinary tract imaging * 2.3 Younger people * 2.4 Initial negative evaluation * 3 Management * 3.1 Acute clot retention * 4 Epidemiology * 4.1 Children * 4.2 Trauma * 5 References * 6 External links ## Differential diagnosis[edit] Urinary causes occur anywhere between the kidney glomerulus and the urethral meatus.[3] These can be divided into glomerular and non-glomerular causes.[3] Non-glomerular causes can be further subdivided into upper urinary tract and lower urinary tract causes.[3] In general, nephrologists are the experts of glomerular hematuria while urologists manage non-glomerular hematuria.[3] The differential diagnosis can be furthered refined by the temporality of hematuria and associated symptoms. Microscopic hematuria has a prevalence of 2% to 31%, depending upon age, sex, and other factors.[3] ### Glomerular hematuria[edit] Postrenal hematuria - the presence of blood in urine (because of damage to the urethra and prostate). A glomerular etiology is suggested by dysmorphic red blood cells, protein, and cellular casts in the urine.[3] This requires the consultation of a nephrologist.[3] Common causes include: * IgA nephropathy * Thin glomerular basement membrane disease * Hereditary nephritis (Alport's disease) * Benign familial hematuria * Glomerulonephritis Idiopathic hematuria is hematuria with an unknown cause. It is considered a glomerular syndrome.[5] ### Non-glomerular hematuria[4][edit] #### Upper urinary tract[edit] * Urinary stones (i.e. kidney stone) * Pyelonephritis * Kidney cancer * Ureteral cancer #### Lower urinary tract[edit] * Urinary tract infection (UTI) * Benign prostatic hyperplasia (BPH) * Strenuous exercise * Bladder cancer * Urethral cancer ### Microscopic hematuria[edit] Microscopic hematuria requires medical testing for detection. It is not visible to the naked eye. Rather it requires microscopic examination for detection.[4] It is defined as three or more red blood cells per high-powered field.[3] Another method for detection of microscopic hematuria is the dipstick method. This test works by detecting hemoglobin in a urine sample.[3] False positives can occur with dipstick testing if free hemoglobin or myoglobin are present.[3] "Red urine" can result from the drug phenazopyridine[4]. ### Hemoglobinuria[edit] Hemoglobin in the absence of red blood cells can also turn urine red. The inciting event for hemoglobin in the urine is hemolysis in the bloodstream. Hemolysis is a process where red blood cells lyse or burst. This releases hemoglobin into the bloodstream.[6] Hemoglobin then leaves the bloodstream and enters urinary tract at Bowman's capsule. ### Non-urinary hematuria[edit] * Trauma, especially at the genitourinary area * Vaginal bleeding ### Children[edit] Common causes of hematuria in children are:[7] * congenital abnormalities – * Non-vascular – ureteropelvic junction obstruction, posterior urethral valves, urethral prolapse, urethral diverticula, multicystic dysplastic kidney * Vascular – arteriovenous malformations, hereditary hemorrhagic telangiectasias, renal vascular thromboses * Acute nephritis * Coagulopathy * Urinary stones * IgA nephropathy * Post-streptococcal glomerulonephritis * benign familial hematuria * sickle cell trait or disease * Alport syndrome ## Diagnosis[edit] After conducting a thorough history and physical examination, further medical testing is warranted. Patients can be stratified into high and low risk.[4] High-risk patients include those with visible hematuria or those with non-visible hematuria and risk factors.[4] A complete evaluation of the urinary tract is indicated for hematuria. This includes imaging of the upper urinary tract and cystoscopy of the lower urinary tract.[4] ### Associated symptoms[edit] The differential diagnosis can be furthered refined by the temporality of hematuria and associated symptoms. During urination, blood can appear in the urine at the onset, midstream, or later.[6] It can also have associated symptoms. These include nausea, fever, chills, abdominal pain, flank pain, groin pain, urinary frequency, urinary urgency, and pain or discomfort with urination.[3][6] When hematuria becomes visible during urination can suggest where in the urinary tract the bleeding originates.[6] If it appears soon after the onset of urination, a distal site is suggested.[6] A longer delay suggests a more proximal lesion.[6] In other words, shorter times suggest distal sites while longer times suggest proximal sites. Hematuria that occurs throughout urination suggests that bleeding is occurring above the level of the bladder.[6] The presence of hematuria without accompanying symptoms should be considered a tumor of the urinary tract until proven otherwise.[6] Other possible causes include acute glomerulonephritis, staghorn calculus, polycystic kidneys, benign prostatic hyperplasia, solitary renal cyst, sickle cell disease, and hydronephrosis.[6] It can also develop after vigorous exercise.[6][3] Costovertebral angle tenderness suggests upper urinary tract obstruction.[4] A urinary stone is suggested by the presence of renal colic[6]. The presence of a fever suggests pyelonephritis.[4] ### Upper urinary tract imaging[edit] The preferred modality is a multi-phasic computed topography (CT) urography.[4] This is a three-phase study that includes a non-contrast phase, an arterial phase, and an excretory phase.[3] The study should sufficiently evaluate the kidney and the urothelium lining the upper urinary tracts.[3] If there are contraindications to this study then alternative studies can be used.[4] One alternative is a magnetic resonance (MR) urography with and without intravenous contrast.[3] Another alternative is a retrograde pyelogram paired with either magnetic resonance imaging of the upper urinary tracts (MRI) or a renal ultrasound (US).[4][3] This imaging assessment is capable of excluding upper tract malignancies.[4] ### Younger people[edit] For patients younger than 35 years old presenting with asymptomatic microscopic hematuria, a cystoscopy may be warranted if risk factors are present.[4] ### Initial negative evaluation[edit] Evaluations of hematuria that do not reveal pathology require follow up. A urinary cytology may be helpful.[3] A urinalysis should be repeated once a year. Follow up can be discontinued after two consecutive negative urinalyses.[3] Repeat hematuria on follow-up studies warrants repeat upper urinary tract imaging and a cystoscopy.[3] This should be performed within three to five years of the first evaluation.[3] ## Management[edit] ### Acute clot retention[edit] A 60cc/mL Toomey syringe. 1) Fill syringe with saline. 2) Connect syringe to a catheter port 3) Instill 180cc of saline 4) Draw back 180cc of bladder urine 5) Dispose of medical waste 6) Repeat until all clots are removed Acute clot retention is one of three emergencies that can occur with hematuria.[8] The other two are anemia and shock.[8] Blood clots can prevent urine outflow through either ureter or the bladder.[8] This is known as acute urinary retention. Blood clots that remain in the bladder are digested by urinary urokinase producing fibrin fragments.[8] These fibrin fragments are natural anticoagulants and promote ongoing bleeding from the urinary tract.[8] Removing all blood clots prevents the formation of this natural anticoagulant.[8] This in turns facilitates the cessation of bleeding from the urinary tract.[8] The acute management of obstructing clots is the placement of a large (22-24 French) urethral Foley catheter.[8] Clots are evacuated with a Toomey syringe and saline irrigation.[8] If this does not control the bleeding, management should escalate to continuous bladder irrigation (CBI) via a three-port urethral catheter.[8] If both a large urethral Foley catheter and CBI fail, an urgent cystoscopy in the operating room will be necessary.[8] Lastly, a transfusion and/or a correction of a coexisting coagulopathy may be necessary.[8] ## Epidemiology[edit] In the United States of America, microscopic hematuria has a prevalence of somewhere between 2% and 31%.[3] Higher rates exist in individuals older than 60 years of age and those with a current or past history of smoking.[3] Only a fraction of individuals with microhematuria are diagnosed with a urologic cancer.[3] When asymptomatic populations are screened with dipstick and/or microscopy medical testing about 2% to 3% of those with hematuria have a urologic malignancy.[3] Routine screening is not recommended.[3] Individuals with risk factors who undergo repeated testing have higher rates of urologic malignancies.[3] These risks factors include age (>35 years), male gender, previous or current smoking, chemical exposure (e.g., benzenes or aromatic amines), and prior pelvic radiation therapy.[3] ### Children[edit] In pediatric populations, the prevalence is 0.5–2%.[9] Risks factor include older age and female gender.[10] About 5% of individuals with microscopic hematuria receive a cancer diagnosis. 40% of individuals with macroscopic hematuria (blood easily visible in the urine) receive a cancer diagnosis.[11] ### Trauma[edit] For more information, please see the section on genitourinary tract injury. ## References[edit] 1. ^ Dorland's illustrated medical dictionary. Dorland, W. A. Newman (William Alexander Newman), 1864-1956. (32nd ed.). Philadelphia, PA: Saunders/Elsevier. 2012. p. 645. ISBN 978-1-4160-6257-8. OCLC 706780870.CS1 maint: others (link) 2. ^ "Definition of HEMATURIA". www.merriam-webster.com. Retrieved 2019-11-25. 3. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad Coplen, D.E. (January 2013). "Diagnosis, Evaluation and Follow-Up of Asymptomatic Microhematuria (AMH) in Adults: AUA Guideline". Yearbook of Urology. 2013: 1–2. doi:10.1016/j.yuro.2013.07.019. ISSN 0084-4071. 4. ^ a b c d e f g h i j k l m n o p "Medical Student Curriculum: Hematuria - American Urological Association". www.auanet.org. Retrieved 2019-11-28. 5. ^ Izzo, Joseph L.; Sica, Domenic A.; Black, Henry Richard (2008). Hypertension Primer. Lippincott Williams & Wilkins. p. 382. ISBN 978-0-7817-8205-0. 6. ^ a b c d e f g h i j k McAninch, Jack W.; Lue, Tom (2013). Smith & Tanagho's General Urology. McGraw-Hill Education. pp. Chapter 3: Symptoms of Disorders of the Genitourinary Tract. 7. ^ Pade, Kathryn H.; Liu, Deborah R. (September 2014). "An evidence-based approach to the management of hematuria in children in the emergency department". Pediatric Emergency Medicine Practice. 11 (9): 1–13, quiz 14. ISSN 1549-9650. PMID 25296518. 8. ^ a b c d e f g h i j k l Kaplan, Damara, MD, PhD; Kohn, Taylor. "Urologic Emergencies: Gross Hematuria with Clot Retention". American Urological Association. Retrieved 2019-12-11. 9. ^ Shah, Samir (2014). Step-up to pediatrics. Ronan, Jeanine C.; Alverson, Brian (First ed.). Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins. pp. 175–176. ISBN 978-1451145809. OCLC 855779297. 10. ^ Cohen, Robert A.; Brown, Robert S. (2003-06-05). "Clinical practice. Microscopic hematuria". The New England Journal of Medicine. 348 (23): 2330–2338. doi:10.1056/NEJMcp012694. ISSN 1533-4406. PMID 12788998. 11. ^ Sharp, Victoria; Barnes, Kerri D.; Erickson, Bradley D. (December 1, 2013). "Assessment of Asymptomatic Microscopic Hematuria in Adults". American Family Physician. 88 (11): 747–54. PMID 24364522. ## External links[edit] Classification D * ICD-10: N02, R31 * ICD-9-CM: 599.7, 791.2 * MeSH: D006417 * DiseasesDB: 19635 External resources * MedlinePlus: 003138 * eMedicine: ped/951 * Patient UK: Hematuria Media related to Hematuria at Wikimedia Commons * v * t * e Kidney disease Glomerular disease * See Template:Glomerular disease Tubules * Renal tubular acidosis * proximal * distal * Acute tubular necrosis * Genetic * Fanconi syndrome * Bartter syndrome * Gitelman syndrome * Liddle's syndrome Interstitium * Interstitial nephritis * Pyelonephritis * Balkan endemic nephropathy Vascular * Renal artery stenosis * Renal ischemia * Hypertensive nephropathy * Renovascular hypertension * Renal cortical necrosis General syndromes * Nephritis * Nephrosis * Renal failure * Acute renal failure * Chronic kidney disease * Uremia Other * Analgesic nephropathy * Renal osteodystrophy * Nephroptosis * Abderhalden–Kaufmann–Lignac syndrome * Diabetes insipidus * Nephrogenic * Renal papilla * Renal papillary necrosis * Major calyx/pelvis * Hydronephrosis * Pyonephrosis * Reflux nephropathy * v * t * e Components and results of urine tests Components * Albumin * Myoglobin * hCG * Leukocyte esterase * Urine pregnancy test * Ketone bodies * Glucose * Urobilinogen * Bilirubin * Creatinine * RBC * WBC * Urinary casts Chemical properties * Urine specific gravity * Isosthenuria * Urine osmolality * Hypersthenuria * Urine pH * Urine anion gap Abnormal findings Red blood cells * Hematuria (Microscopic hematuria) White blood cells * Eosinophiluria Proteinuria * Albuminuria/Microalbuminuria * Albumin/creatinine ratio * Urine protein/creatinine ratio * Myoglobinuria * Hemoglobinuria * Bence Jones protein Small molecules * Glycosuria * Ketonuria * Bilirubinuria * Hyperuricosuria * Aminoaciduria Other * Bacteriuria * Chyluria * Crystalluria Authority control * NDL: 00565683 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Hematuria	c0018965	3,810	wikipedia	https://en.wikipedia.org/wiki/Hematuria	2021-01-18T19:06:18	{"mesh": ["D006417"], "umls": ["C0018965"], "icd-9": ["599.7", "791.2"], "icd-10": ["R31", "N02"], "wikidata": ["Q373597"]}
Periorbital hyperpigmentation SpecialtyDermatology Periorbital hyperpigmentation is characterized by dark circles around the eyes, which are common, often familial, and frequently found in individuals with dark pigmentation or Mediterranean ancestry.[1]:858 Atopic dermatitis patients may also exhibit periorbital pigmentation (allergic shiners) due to lower eyelid venous stasis, and treatment is ineffective.[1]:858 ## See also[edit] * Black eye * Skin lesion ## References[edit] 1. ^ a b James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0. ## External links[edit] Classification D * ICD-10: L81.4 (ILDS L81.408) * v * t * e Pigmentation disorders/Dyschromia Hypo-/ leucism Loss of melanocytes Vitiligo * Quadrichrome vitiligo * Vitiligo ponctué Syndromic * Alezzandrini syndrome * Vogt–Koyanagi–Harada syndrome Melanocyte development * Piebaldism * Waardenburg syndrome * Tietz syndrome Loss of melanin/ amelanism Albinism * Oculocutaneous albinism * Ocular albinism Melanosome transfer * Hermansky–Pudlak syndrome * Chédiak–Higashi syndrome * Griscelli syndrome * Elejalde syndrome * Griscelli syndrome type 2 * Griscelli syndrome type 3 Other * Cross syndrome * ABCD syndrome * Albinism–deafness syndrome * Idiopathic guttate hypomelanosis * Phylloid hypomelanosis * Progressive macular hypomelanosis Leukoderma w/o hypomelanosis * Vasospastic macule * Woronoff's ring * Nevus anemicus Ungrouped * Nevus depigmentosus * Postinflammatory hypopigmentation * Pityriasis alba * Vagabond's leukomelanoderma * Yemenite deaf-blind hypopigmentation syndrome * Wende–Bauckus syndrome Hyper- Melanin/ Melanosis/ Melanism Reticulated * Dermatopathia pigmentosa reticularis * Pigmentatio reticularis faciei et colli * Reticulate acropigmentation of Kitamura * Reticular pigmented anomaly of the flexures * Naegeli–Franceschetti–Jadassohn syndrome * Dyskeratosis congenita * X-linked reticulate pigmentary disorder * Galli–Galli disease * Revesz syndrome Diffuse/ circumscribed * Lentigo/Lentiginosis: Lentigo simplex * Liver spot * Centrofacial lentiginosis * Generalized lentiginosis * Inherited patterned lentiginosis in black persons * Ink spot lentigo * Lentigo maligna * Mucosal lentigines * Partial unilateral lentiginosis * PUVA lentigines * Melasma * Erythema dyschromicum perstans * Lichen planus pigmentosus * Café au lait spot * Poikiloderma (Poikiloderma of Civatte * Poikiloderma vasculare atrophicans) * Riehl melanosis Linear * Incontinentia pigmenti * Scratch dermatitis * Shiitake mushroom dermatitis Other/ ungrouped * Acanthosis nigricans * Freckle * Familial progressive hyperpigmentation * Pallister–Killian syndrome * Periorbital hyperpigmentation * Photoleukomelanodermatitis of Kobori * Postinflammatory hyperpigmentation * Transient neonatal pustular melanosis Other pigments Iron * Hemochromatosis * Iron metallic discoloration * Pigmented purpuric dermatosis * Schamberg disease * Majocchi's disease * Gougerot–Blum syndrome * Doucas and Kapetanakis pigmented purpura/Eczematid-like purpura of Doucas and Kapetanakis * Lichen aureus * Angioma serpiginosum * Hemosiderin hyperpigmentation Other metals * Argyria * Chrysiasis * Arsenic poisoning * Lead poisoning * Titanium metallic discoloration Other * Carotenosis * Tar melanosis Dyschromia * Dyschromatosis symmetrica hereditaria * Dyschromatosis universalis hereditaria See also * Skin color * Skin whitening * Tanning * Sunless * Tattoo * removal * Depigmentation This cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Periorbital hyperpigmentation	c1844606	3,811	wikipedia	https://en.wikipedia.org/wiki/Periorbital_hyperpigmentation	2021-01-18T18:39:23	{"wikidata": ["Q16964509"]}
Bleeding into the subarachnoid space Subarachnoid hemorrhage Other namesSubarachnoid haemorrhage CT scan of the brain showing subarachnoid hemorrhage as a white area in the center and stretching into the sulci to either side (marked by the arrow) Pronunciation * /ˌsʌbəˈræknɔɪd ˈhɛmərɪdʒ/ SpecialtyNeurosurgery SymptomsSevere headache of rapid onset, vomiting, decreased level of consciousness[1] ComplicationsDelayed cerebral ischemia, cerebral vasospasm, seizures[1] TypesTraumatic, spontaneous (aneurysmal, nonaneurysmal, perimesencephalic)[1] CausesHead injury, cerebral aneurysm[1] Risk factorsHigh blood pressure, smoking, alcoholism, cocaine[1] Diagnostic methodCT scan, lumbar puncture[2] Differential diagnosisMeningitis, migraine, cerebral venous sinus thrombosis[3] TreatmentNeurosurgery or radiologically guided interventions[1] MedicationLabetalol, nimodipine[1] Prognosis45% risk of death at 30 days (aneurysmal)[1] Frequency1 per 10,000 per year[1] Subarachnoid hemorrhage (SAH) is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain.[1] Symptoms may include a severe headache of rapid onset, vomiting, decreased level of consciousness, fever, and sometimes seizures.[1] Neck stiffness or neck pain are also relatively common.[2] In about a quarter of people a small bleed with resolving symptoms occurs within a month of a larger bleed.[1] SAH may occur as a result of a head injury or spontaneously, usually from a ruptured cerebral aneurysm.[1] Risk factors for spontaneous cases included high blood pressure, smoking, family history, alcoholism, and cocaine use.[1] Generally, the diagnosis can be determined by a CT scan of the head if done within six hours of symptom onset.[2] Occasionally a lumbar puncture is also required.[2] After confirmation further tests are usually performed to determine the underlying cause.[2] Treatment is by prompt neurosurgery or radiologically guided interventions.[1] Medications such as labetalol may be required to lower the blood pressure until repair can occur.[1] Efforts to treat fevers are also recommended.[1] Nimodipine, a calcium channel blocker, is frequently used to prevent vasospasm.[1] The routine use of medications to prevent further seizures is of unclear benefit.[1] Nearly half of people with a SAH due to an underlying aneurysm die within 30 days and about a third who survive have ongoing problems.[1] Between ten and fifteen percent die before reaching a hospital.[4] Spontaneous SAH occurs in about one per 10,000 people per year.[1] Females are more commonly affected than males.[1] While it becomes more common with age, about 50% of people present under 55 years old.[4] It is a form of stroke and comprises about 5 percent of all strokes.[4] Surgery for aneurysms was introduced in the 1930s.[5] Since the 1990s many aneurysms are treated by a less invasive procedure called endovascular coiling, which is carried out through a large blood vessel.[6] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Pathophysiology * 4 Diagnosis * 4.1 Imaging * 4.2 Lumbar puncture * 4.3 Angiography * 4.4 ECG * 4.5 Classification * 5 Screening and prevention * 6 Treatment * 6.1 Preventing rebleeding * 6.2 Vasospasm * 6.3 Other complications * 7 Prognosis * 7.1 Short-term outcomes * 7.2 Long-term outcomes * 8 Epidemiology * 9 History * 10 References * 11 External links ## Signs and symptoms[edit] The classic symptom of subarachnoid hemorrhage is thunderclap headache (a headache described as "like being kicked in the head",[3] or the "worst ever", developing over seconds to minutes). This headache often pulsates towards the occiput (the back of the head).[7] About one-third of people have no symptoms apart from the characteristic headache, and about one in ten people who seek medical care with this symptom are later diagnosed with a subarachnoid hemorrhage.[4] Vomiting may be present, and 1 in 14 have seizures.[4] Confusion, decreased level of consciousness or coma may be present, as may neck stiffness and other signs of meningism.[4] Neck stiffness usually presents six hours after initial onset of SAH.[8] Isolated dilation of a pupil and loss of the pupillary light reflex may reflect brain herniation as a result of rising intracranial pressure (pressure inside the skull).[4] Intraocular hemorrhage (bleeding into the eyeball) may occur in response to the raised pressure: subhyaloid hemorrhage (bleeding under the hyaloid membrane, which envelops the vitreous body of the eye) and vitreous hemorrhage may be visible on fundoscopy. This is known as Terson syndrome (occurring in 3–13 percent of cases) and is more common in more severe SAH.[9] Oculomotor nerve abnormalities (affected eye looking downward and outward and inability to lift the eyelid on the same side) or palsy (loss of movement) may indicate bleeding from the posterior communicating artery.[4][7] Seizures are more common if the hemorrhage is from an aneurysm; it is otherwise difficult to predict the site and origin of the hemorrhage from the symptoms.[4] SAH in a person known to have seizures is often diagnostic of a cerebral arteriovenous malformation.[7] The combination of intracerebral hemorrhage and raised intracranial pressure (if present) leads to a "sympathetic surge", i.e. over-activation of the sympathetic system. This is thought to occur through two mechanisms, a direct effect on the medulla that leads to activation of the descending sympathetic nervous system and a local release of inflammatory mediators that circulate to the peripheral circulation where they activate the sympathetic system. As a consequence of the sympathetic surge there is a sudden increase in blood pressure; mediated by increased contractility of the ventricle and increased vasoconstriction leading to increased systemic vascular resistance. The consequences of this sympathetic surge can be sudden, severe, and are frequently life-threatening. The high plasma concentrations of adrenaline also may cause cardiac arrhythmias (irregularities in the heart rate and rhythm), electrocardiographic changes (in 27 percent of cases)[10] and cardiac arrest (in 3 percent of cases) may occur rapidly after the onset of hemorrhage.[4][11] A further consequence of this process is neurogenic pulmonary edema[12] where a process of increased pressure within the pulmonary circulation causes leaking of fluid from the pulmonary capillaries into the air spaces, the alveoli, of the lung. Subarachnoid hemorrhage may also occur in people who have had a head injury. Symptoms may include headache, decreased level of consciousness and hemiparesis (weakness of one side of the body). SAH is a frequent occurrence in traumatic brain injury, and carries a poor prognosis if it is associated with deterioration in the level of consciousness.[13] While thunderclap headache is the characteristic symptom of subarachnoid hemorrhage, less than 10% of those with concerning symptoms have SAH on investigations.[2] A number of other causes may need to be considered.[14] ## Causes[edit] Circle of Willis with the most common locations of ruptured aneurysms marked Most cases of SAH are due to trauma such as a blow to the head.[1][15] Traumatic SAH usually occurs near the site of a skull fracture or intracerebral contusion.[16] It often happens in the setting of other forms of traumatic brain injury. In these cases prognosis is poorer; however, it is unclear if this is a direct result of the SAH or whether the presence of subarachnoid blood is simply an indicator of a more severe head injury.[17] In 85 percent of spontaneous cases the cause is a cerebral aneurysm—a weakness in the wall of one of the arteries in the brain that becomes enlarged. They tend to be located in the circle of Willis and its branches. While most cases are due to bleeding from small aneurysms, larger aneurysms (which are less common) are more likely to rupture.[4] Aspirin also appears to increase the risk.[18] In 15–20 percent of cases of spontaneous SAH, no aneurysm is detected on the first angiogram.[16] About half of these are attributed to non-aneurysmal perimesencephalic hemorrhage, in which the blood is limited to the subarachnoid spaces around the midbrain (i.e. mesencephalon). In these, the origin of the blood is uncertain.[4] The remainder are due to other disorders affecting the blood vessels (such as cerebral arteriovenous malformations), disorders of the blood vessels in the spinal cord, and bleeding into various tumors.[4] Cocaine abuse and sickle cell anemia (usually in children) and, rarely, anticoagulant therapy, problems with blood clotting and pituitary apoplexy can also result in SAH.[8][16] Dissection of the vertebral artery, usually caused by trauma, can lead to subarachnoid hemorrhage if the dissection involves the part of the vessel inside the skull.[19] ## Pathophysiology[edit] Cerebral vasospasm is one of the complications caused by subarachnoid haemorrhage. It usually happens from the third day after the aneurysm event, and reaches its peak on 5th to 7th day.[20] There are several mechanisms proposed for this complication. Blood products released from subarachnoid haemorrhage stimulates the tyrosine kinase pathway causing the release of calcium ions from intracellular storage, resulting in smooth muscle contraction of cerebral arteries. Oxyhaemoglobin in cerebrospinal fluid (CSF) causes vasoconstriction by increasing free radicals, endothelin-1, prostaglandin and reducing the level of nitric oxide and prostacyclin. Besides, the disturbances of autonomic nervous system innervating cerebral arteries is also thought to cause vasospasm.[21] ## Diagnosis[edit] A lumbar puncture in progress. A large area on the back has been washed with an iodine-based disinfectant leaving brown coloration As only 10 percent of people admitted to the emergency department with a thunderclap headache are having an SAH, other possible causes are usually considered simultaneously, such as meningitis, migraine, and cerebral venous sinus thrombosis.[3] Intracerebral hemorrhage, in which bleeding occurs within the brain itself, is twice as common as SAH and is often misdiagnosed as the latter.[22] It is not unusual for SAH to be initially misdiagnosed as a migraine or tension headache, which can lead to a delay in obtaining a CT scan. In a 2004 study, this occurred in 12 percent of all cases and was more likely in people who had smaller hemorrhages and no impairment in their mental status. The delay in diagnosis led to a worse outcome.[23] In some people, the headache resolves by itself, and no other symptoms are present. This type of headache is referred to as "sentinel headache", because it is presumed to result from a small leak (a "warning leak") from an aneurysm. A sentinel headache still warrants investigations with CT scan and lumbar puncture, as further bleeding may occur in the subsequent three weeks.[24] The initial steps for evaluating a person with a suspected subarachnoid hemorrhage are obtaining a medical history and performing a physical examination. The diagnosis cannot be made on clinical grounds alone and in general medical imaging and possibly a lumbar puncture is required to confirm or exclude bleeding.[25] ### Imaging[edit] The modality of choice is computed tomography (CT scan), without contrast, of the brain. This has a high sensitivity and will correctly identify 98.7% of cases within six hours of the onset of symptoms.[26] A CT scan can rule out the diagnosis in someone with a normal neurological exam if done within six hours.[27] Its efficacy declines thereafter,[1] and magnetic resonance imaging (MRI) is more sensitive than CT after several days.[4] ### Lumbar puncture[edit] Lumbar puncture, in which cerebrospinal fluid (CSF) is removed from the subarachnoid space of the spinal canal using a hypodermic needle, shows evidence of bleeding in three percent of people in whom a non-contrast CT was found normal.[4] A lumbar puncture or CT scan with contrast is therefore regarded as mandatory in people with suspected SAH when imaging is delayed to after six hours from the onset of symptoms and is negative.[4][27] At least three tubes of CSF are collected.[8] If an elevated number of red blood cells is present equally in all bottles, this indicates a subarachnoid hemorrhage. If the number of cells decreases per bottle, it is more likely that it is due to damage to a small blood vessel during the procedure (known as a "traumatic tap").[24] While there is no official cutoff for red blood cells in the CSF no documented cases have occurred at less than "a few hundred cells" per high-powered field.[28] The CSF sample is also examined for xanthochromia—the yellow appearance of centrifugated fluid. This can be determined by spectrophotometry (measuring the absorption of particular wavelengths of light) or visual examination. It is unclear which method is superior.[29] Xanthochromia remains a reliable ways to detect SAH several days after the onset of headache.[30] An interval of at least 12 hours between the onset of the headache and lumbar puncture is required, as it takes several hours for the hemoglobin from the red blood cells to be metabolized into bilirubin.[4][30] ### Angiography[edit] After a subarachnoid hemorrhage is confirmed, its origin needs to be determined. If the bleeding is likely to have originated from an aneurysm (as determined by the CT scan appearance), the choice is between cerebral angiography (injecting radiocontrast through a catheter to the brain arteries) and CT angiography (visualizing blood vessels with radiocontrast on a CT scan) to identify aneurysms. Catheter angiography also offers the possibility of coiling an aneurysm (see below).[4][24] ### ECG[edit] ECG changes resembling those of an STEMI in a woman who had an acute CNS injury from a subarachnoid hemorrhage. Electrocardiographic changes are relatively common in subarachnoid hemorrhage, occurring in 40–70 percent of cases. They may include QT prolongation, Q waves, cardiac dysrhythmias, and ST elevation that mimics a heart attack.[31] ### Classification[edit] There are several grading scales available for SAH. The Glasgow Coma Scale (GCS) is ubiquitously used for assessing consciousness. Three specialized scores are used to evaluate SAH; in each, a higher number is associated with a worse outcome.[32] These scales have been derived by retrospectively matching characteristics of people with their outcomes. The first scale of severity was described by Hunt and Hess in 1968:[33] Grade Signs and symptoms Survival 1 Asymptomatic or minimal headache and slight neck stiffness 70% 2 Moderate to severe headache; neck stiffness; no neurologic deficit except cranial nerve palsy 60% 3 Drowsy; minimal neurologic deficit 50% 4 Stuporous; moderate to severe hemiparesis; possibly early decerebrate rigidity and vegetative disturbances 20% 5 Deep coma; decerebrate rigidity; moribund 10% The Fisher Grade classifies the appearance of subarachnoid hemorrhage on CT scan.[34] Grade Appearance of hemorrhage 1 None evident 2 Less than 1 mm thick 3 More than 1 mm thick 4 Diffuse or none with intraventricular hemorrhage or parenchymal extension This scale has been modified by Claassen and coworkers, reflecting the additive risk from SAH size and accompanying intraventricular hemorrhage (0 – none; 1 – minimal SAH w/o IVH; 2 – minimal SAH with IVH; 3 – thick SAH w/o IVH; 4 – thick SAH with IVH);.[35] The World Federation of Neurosurgeons (WFNS) classification uses Glasgow coma score and focal neurological deficit to gauge severity of symptoms.[36] Grade GCS Focal neurological deficit 1 15 Absent 2 13–14 Absent 3 13–14 Present 4 7–12 Present or absent 5 <7 Present or absent A comprehensive classification scheme has been suggested by Ogilvy and Carter to predict outcome and gauge therapy.[37] The system consists of five grades and it assigns one point for the presence or absence of each of five factors: age greater than 50; Hunt and Hess grade 4 or 5; Fisher scale 3 or 4; aneurysm size greater than 10 mm; and posterior circulation aneurysm 25 mm or more.[37] ## Screening and prevention[edit] Screening for aneurysms is not performed on a population level; because they are relatively rare, it would not be cost-effective. If someone has two or more first-degree relatives who have had an aneurysmal subarachnoid hemorrhage, screening may be worthwhile.[4][38] Autosomal dominant polycystic kidney disease (ADPKD), a hereditary kidney condition, is known to be associated with cerebral aneurysms in 8 percent of cases, but most such aneurysms are small and therefore unlikely to rupture. As a result, screening is only recommended in families with ADPKD where one family member has had a ruptured aneurysm.[39] An aneurysm may be detected incidentally on brain imaging; this presents a conundrum, as all treatments for cerebral aneurysms are associated with potential complications. The International Study of Unruptured Intracranial Aneurysms (ISUIA) provided prognostic data both in people having previously had a subarachnoid hemorrhage and people who had aneurysms detected by other means. Those having previously had a SAH were more likely to bleed from other aneurysms. In contrast, those having never bled and had small aneurysms (smaller than 10 mm) were very unlikely to have a SAH and were likely to sustain harm from attempts to repair these aneurysms.[40] On the basis of the ISUIA and other studies, it is now recommended that people are considered for preventive treatment only if they have a reasonable life expectancy and have aneurysms that are highly likely to rupture.[38] At the same time, there is only limited evidence that endovascular treatment of unruptured aneurysms is actually beneficial.[41] ## Treatment[edit] Management involves general measures to stabilize the person while also using specific investigations and treatments. These include the prevention of rebleeding by obliterating the bleeding source, prevention of a phenomenon known as vasospasm, and prevention and treatment of complications.[4] Stabilizing the person is the first priority. Those with a depressed level of consciousness may need to be intubated and mechanically ventilated. Blood pressure, pulse, respiratory rate, and Glasgow Coma Scale are monitored frequently. Once the diagnosis is confirmed, admission to an intensive care unit may be preferable, especially since 15 percent may have further bleeding soon after admission. Nutrition is an early priority, mouth or nasogastric tube feeding being preferable over parenteral routes. In general, pain control is restricted to less-sedating agents such as codeine, as sedation may impact on the mental status and thus interfere with the ability to monitor the level of consciousness. Deep vein thrombosis is prevented with compression stockings, intermittent pneumatic compression of the calves, or both.[4] A bladder catheter is usually inserted to monitor fluid balance. Benzodiazepines may be administered to help relieve distress.[8] Antiemetic drugs should be given to awake persons.[7] People with poor clinical grade on admission, acute neurologic deterioration, or progressive enlargement of ventricles on CT scan are, in general, indications for the placement of an external ventricular drain by a neurosurgeon. The external ventricular drain may be inserted at the bedside or in the operating room. In either case, strict aseptic technique must be maintained during insertion. In people with aneurysmal subarachnoid hemorrhage the EVD is used to remove cerebrospinal fluid, blood, and blood byproducts that increase intracranial pressure and may increase the risk for cerebral vasospasm.[42] ### Preventing rebleeding[edit] Arteriogram showing a partially coiled aneurysm (indicated by yellow arrows) of the posterior cerebral artery with a residual aneurysmal sac. The person was a 34-year-old woman initially treated for a subarachnoid hemorrhage. Efforts to keep a person's systolic blood pressure below somewhere between 140 and 160 mmHg is generally recommended.[1] Medications to achieve this may include labetalol or nicardipine.[1] People whose CT scan shows a large hematoma, depressed level of consciousness, or focal neurologic signs may benefit from urgent surgical removal of the blood or occlusion of the bleeding site. The remainder are stabilized more extensively and undergo a transfemoral angiogram or CT angiogram later. It is hard to predict who will have a rebleed, yet it may happen at any time and carries a dismal prognosis. After the first 24 hours have passed, rebleeding risk remains around 40 percent over the subsequent four weeks, suggesting that interventions should be aimed at reducing this risk as soon as possible.[4] Some predictors of early rebleeding are high systolic blood pressure, the presence of a hematoma in the brain or ventricles, poor Hunt-Hess grade (III-IV), aneurysms in the posterior circulation, and an aneurysm >10 mm in size.[43] If a cerebral aneurysm is identified on angiography, two measures are available to reduce the risk of further bleeding from the same aneurysm: clipping[44] and coiling.[45] Clipping requires a craniotomy (opening of the skull) to locate the aneurysm, followed by the placement of clips around the neck of the aneurysm. Coiling is performed through the large blood vessels (endovascularly): a catheter is inserted into the femoral artery in the groin and advanced through the aorta to the arteries (both carotid arteries and both vertebral arteries) that supply the brain. When the aneurysm has been located, platinum coils are deployed that cause a blood clot to form in the aneurysm, obliterating it. The decision as to which treatment is undertaken is typically made by a multidisciplinary team consisting of a neurosurgeon, neuroradiologist, and often other health professionals.[4] In general, the decision between clipping and coiling is made on the basis of the location of the aneurysm, its size and the condition of the person. Aneurysms of the middle cerebral artery and its related vessels are hard to reach with angiography and tend to be amenable to clipping. Those of the basilar artery and posterior cerebral artery are hard to reach surgically and are more accessible for endovascular management.[46] These approaches are based on general experience, and the only randomized controlled trial directly comparing the different modalities was performed in relatively well people with small (less than 10 mm) aneurysms of the anterior cerebral artery and anterior communicating artery (together the "anterior circulation"), who constitute about 20 percent of all people with aneurysmal SAH.[46][47] This trial, the International Subarachnoid Aneurysm Trial (ISAT), showed that in this group the likelihood of death or being dependent on others for activities of daily living was reduced (7.4 percent absolute risk reduction, 23.5 percent relative risk reduction) if endovascular coiling was used as opposed to surgery.[46] The main drawback of coiling is the possibility that the aneurysm will recur; this risk is extremely small in the surgical approach. In ISAT, 8.3 percent needed further treatment in the longer term. Hence, people who have undergone coiling are typically followed up for many years afterwards with angiography or other measures to ensure recurrence of aneurysms is identified early.[48] Other trials have also found a higher rate of recurrence necessitating further treatments.[49][50] ### Vasospasm[edit] Vasospasm, in which the blood vessels constrict and thus restrict blood flow, is a serious complication of SAH. It can cause ischemic brain injury (referred to as "delayed ischemia") and permanent brain damage due to lack of oxygen in parts of the brain.[51] It can be fatal if severe. Delayed ischemia is characterized by new neurological symptoms, and can be confirmed by transcranial doppler or cerebral angiography. About one third of people admitted with subarachnoid hemorrhage will have delayed ischemia, and half of those have permanent damage as a result.[51] It is possible to screen for the development of vasospasm with transcranial Doppler every 24–48 hours. A blood flow velocity of more than 120 centimeters per second is suggestive of vasospasm.[24] The use of calcium channel blockers, thought to be able to prevent the spasm of blood vessels by preventing calcium from entering smooth muscle cells, has been proposed for prevention.[17] The calcium channel blocker nimodipine when taken by mouth improves outcome if given between the fourth and twenty-first day after the bleeding, even if it does not reduce the amount of vasospasm detected on angiography.[52] It is the only Food and Drug Administration (FDA) approved drug for treating cerebral vasospasm.[20] In traumatic subarachnoid hemorrhage, nimodipine does not affect long-term outcome, and is not recommended.[53] Other calcium channel blockers and magnesium sulfate have been studied, but are not presently recommended; neither is there any evidence that shows benefit if nimodipine is given intravenously.[51] Some older studies have suggested that statin therapy might reduce vasospasm, but a subsequent meta-analysis including further trials did not demonstrate benefit on either vasospasm or outcomes.[54] While corticosteroids with mineralocorticoid activity may help prevent vasospasm their use does not appear to change outcomes.[55] A protocol referred to as "triple H" is often used as a measure to treat vasospasm when it causes symptoms; this is the use of intravenous fluids to achieve a state of hypertension (high blood pressure), hypervolemia (excess fluid in the circulation), and hemodilution (mild dilution of the blood).[56] Evidence for this approach is inconclusive; no randomized controlled trials have been undertaken to demonstrate its effect.[57] If the symptoms of delayed ischemia do not improve with medical treatment, angiography may be attempted to identify the sites of vasospasms and administer vasodilator medication (drugs that relax the blood vessel wall) directly into the artery. Angioplasty (opening the constricted area with a balloon) may also be performed.[24] ### Other complications[edit] Hydrocephalus (obstruction of the flow of cerebrospinal fluid) may complicate SAH in both the short and long term. It is detected on CT scanning, on which there is enlargement of the lateral ventricles. If the level of consciousness is decreased, drainage of the excess fluid is performed by therapeutic lumbar puncture, extraventricular drain (a temporary device inserted into one of the ventricles), or occasionally a permanent shunt.[4][24] Relief of hydrocephalus can lead to an enormous improvement in a person's condition.[7] Fluctuations in blood pressure and electrolyte imbalance, as well as pneumonia and cardiac decompensation occur in about half the hospitalized persons with SAH and may worsen prognosis.[4] Seizures occur during the hospital stay in about a third of cases.[24] People have often been treated with preventative antiepileptic medications.[24][58] This is controversial and not based on good evidence.[59][60] In some studies, use of these medications was associated with a worse prognosis; although it is unclear whether this might be because the drugs themselves actually cause harm, or because they are used more often in persons with a poorer prognosis.[61][62] There is a possibility of a gastric hemorrhage due to stress ulcers.[63] ## Prognosis[edit] ### Short-term outcomes[edit] SAH is often associated with a poor outcome.[64] The death rate (mortality) for SAH is between 40 and 50 percent,[22] but trends for survival are improving.[4] Of those that survive hospitalization, more than a quarter have significant restrictions in their lifestyle, and less than a fifth have no residual symptoms whatsoever.[46] Delay in diagnosis of minor SAH (mistaking the sudden headache for migraine) contributes to poor outcome.[23] Factors found on admission that are associated with poorer outcome include poorer neurological grade; systolic hypertension; a previous diagnosis of heart attack or SAH; liver disease; more blood and larger aneurysm on the initial CT scan; location of an aneurysm in the posterior circulation; and higher age.[61] Factors that carry a worse prognosis during the hospital stay include occurrence of delayed ischemia resulting from vasospasm, development of intracerebral hematoma, or intraventricular hemorrhage (bleeding into the ventricles of the brain) and presence of fever on the eighth day of admission.[61] So-called "angiogram-negative subarachnoid hemorrhage", SAH that does not show an aneurysm with four-vessel angiography, carries a better prognosis than SAH with aneurysm, but it is still associated with a risk of ischemia, rebleeding, and hydrocephalus.[16] Perimesencephalic SAH (bleeding around the mesencephalon in the brain), however, has a very low rate of rebleeding or delayed ischemia, and the prognosis of this subtype is excellent.[65] The prognosis of head trauma is thought to be influenced in part by the location and amount of subarachnoid bleeding.[17] It is difficult to isolate the effects of SAH from those of other aspects of traumatic brain injury; it is unknown whether the presence of subarachnoid blood actually worsens the prognosis or whether it is merely a sign that a significant trauma has occurred.[17] People with moderate and severe traumatic brain injury who have SAH when admitted to a hospital have as much as twice the risk of dying as those who do not.[17] They also have a higher risk of severe disability and persistent vegetative state, and traumatic SAH has been correlated with other markers of poor outcome such as post traumatic epilepsy, hydrocephalus, and longer stays in the intensive care unit.[17] More than 90 percent of people with traumatic subarachnoid bleeding and a Glasgow Coma Score over 12 have a good outcome.[17] There is also modest evidence that genetic factors influence the prognosis in SAH. For example, having two copies of ApoE4 (a variant of the gene encoding apolipoprotein E that also plays a role in Alzheimer's disease) seems to increase risk for delayed ischemia and a worse outcome.[66] The occurrence of hyperglycemia (high blood sugars) after an episode of SAH confers a higher risk of poor outcome.[67] ### Long-term outcomes[edit] Autopsy of a case with subarachnoid hemorrhage. The arachnoid mater is left in place on the exterior surface, containing extensive hemorrhage that also fills the sulci, as detailed in magnified image. Neurocognitive symptoms, such as fatigue, mood disturbances, and other related symptoms are common sequelae. Even in those who have made good neurological recovery, anxiety, depression, posttraumatic stress disorder, and cognitive impairment are common; 46 percent of people who have had a subarachnoid hemorrhage have cognitive impairment that affects their quality of life.[24] Over 60 percent report frequent headaches.[68] Aneurysmal subarachnoid hemorrhage may lead to damage of the hypothalamus and the pituitary gland, two areas of the brain that play a central role in hormonal regulation and production. More than a quarter of people with a previous SAH may develop hypopituitarism (deficiencies in one or more of the hypothalamic-pituitary hormones such as growth hormone, luteinizing hormone, or follicle-stimulating hormone).[69] ## Epidemiology[edit] Average number of people with SAH per 100,000 person-years, broken down by age.[70] According to a review of 51 studies from 21 countries, the average incidence of subarachnoid hemorrhage is 9.1 per 100,000 annually. Studies from Japan and Finland show higher rates in those countries (22.7 and 19.7, respectively), for reasons that are not entirely understood. South and Central America, in contrast, have a rate of 4.2 per 100,000 on average.[70] Although the group of people at risk for SAH is younger than the population usually affected by stroke,[64] the risk still increases with age. Young people are much less likely than middle-age people (risk ratio 0.1, or 10 percent) to have a subarachnoid hemorrhage.[70] The risk continues to rise with age and is 60 percent higher in the very elderly (over 85) than in those between 45 and 55.[70] Risk of SAH is about 25 percent higher in women over 55 compared to men the same age, probably reflecting the hormonal changes that result from the menopause, such as a decrease in estrogen levels.[70] Genetics may play a role in a person's disposition to SAH; risk is increased three- to fivefold in first-degree relatives of people having had a subarachnoid hemorrhage.[3] But lifestyle factors are more important in determining overall risk.[64] These risk factors are smoking, hypertension (high blood pressure), and excessive alcohol consumption.[22] Having smoked in the past confers a doubled risk of SAH compared to those who have never smoked.[64] Some protection of uncertain significance is conferred by caucasian ethnicity, hormone replacement therapy, and diabetes mellitus.[64] There is likely an inverse relationship between total serum cholesterol and the risk of non-traumatic SAH, though confirmation of this association is hindered by a lack of studies.[71] Approximately 4 percent of aneurysmal bleeds occur after sexual intercourse and 10 percent of people with SAH are bending over or lifting heavy objects at the onset of their symptoms.[7] Overall, about 1 percent of all people have one or more cerebral aneurysms. Most of these are small and unlikely to rupture.[40] ## History[edit] While the clinical picture of subarachnoid hemorrhage may have been recognized by Hippocrates, the existence of cerebral aneurysms and the fact that they could rupture was not established until the 18th century.[72] The associated symptoms were described in more detail in 1886 by Edinburgh physician Dr Byrom Bramwell.[73] In 1924, London neurologist Sir Charles P. Symonds (1890–1978) gave a complete account of all major symptoms of subarachnoid hemorrhage, and he coined the term "spontaneous subarachnoid hemorrhage".[5][72][74] Symonds also described the use of lumbar puncture and xanthochromia in diagnosis.[75] The first surgical intervention was performed by Norman Dott, who was a pupil of Harvey Cushing then working in Edinburgh. He introduced the wrapping of aneurysms in the 1930s, and was an early pioneer in the use of angiograms.[5] American neurosurgeon Dr Walter Dandy, working in Baltimore, was the first to introduce clips in 1938.[44] Microsurgery was applied to aneurysm treatment in 1972 in order to further improve outcomes.[76] The 1980s saw the introduction of triple H therapy[56] as a treatment for delayed ischemia due to vasospasm, and trials with nimodipine[52][77] in an attempt to prevent this complication. In 1983, the Russian neurosurgeon Zubkov and colleagues reported the first use of transluminal balloon angioplasty for vasospasm after aneurysmal SAH.[78][79] The Italian neurosurgeon Dr. Guido Guglielmi introduced his endovascular coil treatment in 1991.[6][45] ## References[edit] 1. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z Abraham MK, Chang WW (November 2016). "Subarachnoid Hemorrhage". Emergency Medicine Clinics of North America. 34 (4): 901–916. doi:10.1016/j.emc.2016.06.011. 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Stroke. 36 (12): 2773–80. doi:10.1161/01.STR.0000190838.02954.e8. PMID 16282541. 65. ^ Greebe P, Rinkel GJ (April 2007). "Life expectancy after perimesencephalic subarachnoid hemorrhage". Stroke. 38 (4): 1222–4. doi:10.1161/01.STR.0000260093.49693.7a. PMID 17332451. 66. ^ Lanterna LA, Ruigrok Y, Alexander S, Tang J, Biroli F, Dunn LT, Poon WS (August 2007). "Meta-analysis of APOE genotype and subarachnoid hemorrhage: clinical outcome and delayed ischemia". Neurology. 69 (8): 766–75. doi:10.1212/01.wnl.0000267640.03300.6b. PMID 17709709. S2CID 8596810. 67. ^ Kruyt ND, Biessels GJ, de Haan RJ, Vermeulen M, Rinkel GJ, Coert B, Roos YB (June 2009). "Hyperglycemia and clinical outcome in aneurysmal subarachnoid hemorrhage: a meta-analysis". Stroke. 40 (6): e424-30. doi:10.1161/STROKEAHA.108.529974. PMID 19390078. S2CID 7684816. 68. ^ Powell J, Kitchen N, Heslin J, Greenwood R (June 2002). "Psychosocial outcomes at three and nine months after good neurological recovery from aneurysmal subarachnoid haemorrhage: predictors and prognosis". Journal of Neurology, Neurosurgery, and Psychiatry. 72 (6): 772–81. doi:10.1136/jnnp.72.6.772. PMC 1737916. PMID 12023423. 69. ^ Schneider HJ, Kreitschmann-Andermahr I, Ghigo E, Stalla GK, Agha A (September 2007). "Hypothalamopituitary dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a systematic review". JAMA. 298 (12): 1429–38. doi:10.1001/jama.298.12.1429. PMID 17895459. 70. ^ a b c d e de Rooij NK, Linn FH, van der Plas JA, Algra A, Rinkel GJ (December 2007). "Incidence of subarachnoid haemorrhage: a systematic review with emphasis on region, age, gender and time trends". Journal of Neurology, Neurosurgery, and Psychiatry. 78 (12): 1365–72. doi:10.1136/jnnp.2007.117655. PMC 2095631. PMID 17470467. 71. ^ Wang X, Dong Y, Qi X, Huang C, Hou L (July 2013). "Cholesterol levels and risk of hemorrhagic stroke: a systematic review and meta-analysis". Stroke. 44 (7): 1833–9. doi:10.1161/STROKEAHA.113.001326. PMID 23704101. 72. ^ a b Longstreth WT, Koepsell TD, Yerby MS, van Belle G (1985). "Risk factors for subarachnoid hemorrhage". Stroke. 16 (3): 377–85. doi:10.1161/01.STR.16.3.377. PMID 3890278. 73. ^ Bramwell B (1886). "Spontaneous meningeal haemorrhage". Edinburgh Medical Journal. 32: 101. 74. ^ Symonds CP (1924). "Spontaneous subarachnoid hemorrhage". Quarterly Journal of Medicine. 18 (69): 93–122. doi:10.1093/qjmed/os-118.69.93. 75. ^ Symonds CP (1924). "Spontaneous Sub-arachnoid Haemorrhage". Proceedings of the Royal Society of Medicine. 17 (Neurol Sect): 39–52. doi:10.1177/003591572401700918. PMC 2201441. PMID 19983808. 76. ^ Krayenbühl HA, Yaşargil MG, Flamm ES, Tew JM (December 1972). "Microsurgical treatment of intracranial saccular aneurysms". Journal of Neurosurgery. 37 (6): 678–86. doi:10.3171/jns.1972.37.6.0678. PMID 4654697. 77. ^ Pickard JD, Murray GD, Illingworth R, et al. (March 1989). "Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial". BMJ. 298 (6674): 636–42. doi:10.1136/bmj.298.6674.636. PMC 1835889. PMID 2496789. 78. ^ Zubkov I, Nikiforov BM, Shustin VA (September–October 1983). "[1st attempt at dilating spastic cerebral arteries in the acute stage of rupture of arterial aneurysms]". Zhurnal Voprosy Neirokhirurgii Imeni N. N. Burdenko. 5 (5): 17–23. PMID 6228084. 79. ^ Zubkov YN, Nikiforov BM, Shustin VA (September–October 1984). "Balloon catheter technique for dilatation of constricted cerebral arteries after aneurysmal SAH". Acta Neurochirurgica. 70 (1–2): 65–79. doi:10.1007/BF01406044. PMID 6234754. S2CID 1628687. ## External links[edit] Wikimedia Commons has media related to Subarachnoid hemorrhage. Classification D * ICD-10: I60, P10.3, S06.6 * ICD-9-CM: 430, 852.0-852.1 * OMIM: 105800 * MeSH: D013345 * DiseasesDB: 12602 External resources * MedlinePlus: 000701 * eMedicine: med/2883 neuro/357 emerg/559 Listen to this article (12.3 megabytes) This audio file was created from a revision of this article dated 9 August 2008 (2008-08-09), and does not reflect subsequent edits. (Audio help · More spoken articles) * v * t * e Cerebrovascular diseases including stroke Ischaemic stroke Brain * Anterior cerebral artery syndrome * Middle cerebral artery syndrome * Posterior cerebral artery syndrome * Amaurosis fugax * Moyamoya disease * Dejerine–Roussy syndrome * Watershed stroke * Lacunar stroke Brain stem * Brainstem stroke syndrome * Medulla * Medial medullary syndrome * Lateral medullary syndrome * Pons * Medial pontine syndrome / Foville's * Lateral pontine syndrome / Millard-Gubler * Midbrain * Weber's syndrome * Benedikt syndrome * Claude's syndrome Cerebellum * Cerebellar stroke syndrome Extracranial arteries * Carotid artery stenosis * precerebral * Anterior spinal artery syndrome * Vertebrobasilar insufficiency * Subclavian steal syndrome Classification * Brain ischemia * Cerebral infarction * Classification * Transient ischemic attack * Total anterior circulation infarct * Partial anterior circulation infarct Other * CADASIL * Binswanger's disease * Transient global amnesia Haemorrhagic stroke Extra-axial * Epidural * Subdural * Subarachnoid Cerebral/Intra-axial * Intraventricular Brainstem * Duret haemorrhages General * Intracranial hemorrhage Aneurysm * Intracranial aneurysm * Charcot–Bouchard aneurysm Other * Cerebral vasculitis * Cerebral venous sinus thrombosis * v * t * e Neurotrauma Traumatic brain injury * Intracranial hemorrhage * Intra-axial * Intraparenchymal hemorrhage * Intraventricular hemorrhage * Extra-axial * Subdural hematoma * Epidural hematoma * Subarachnoid hemorrhage * Brain herniation * Cerebral contusion * Cerebral laceration * Concussion * Post-concussion syndrome * Second-impact syndrome * Dementia pugilistica * Chronic traumatic encephalopathy * Diffuse axonal injury * Abusive head trauma * Penetrating head injury Spinal cord injury * Anterior spinal artery syndrome * Brown-Séquard syndrome * Cauda equina syndrome * Central cord syndrome * Paraplegia * Posterior cord syndrome * Spinal cord injury without radiographic abnormality * Tetraplegia (Quadriplegia) Peripheral nerves * Nerve injury * Peripheral nerve injury * classification * Wallerian degeneration * Injury of accessory nerve * Brachial plexus injury * Traumatic neuroma [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Subarachnoid hemorrhage	c0038525	3,812	wikipedia	https://en.wikipedia.org/wiki/Subarachnoid_hemorrhage	2021-01-18T18:30:20	{"mesh": ["D013345"], "umls": ["C0038525"], "icd-9": ["430", "852.1", "852.0"], "icd-10": ["I60", "S06.6", "P10.3"], "wikidata": ["Q693442"]}
Blake pouch cyst is a non-syndromic, usually benign, cystic malformation of the posterior fossa characterized by a midline outpouching of the superior medullary velum into the cisterna magna that results from failure of the rudimental fourth ventricular tela choroidea to regress during embryogenesis. Patients can be asymptomatic or present in childhood or adulthood with clinical manifestations of hydrocephalus, such as headache, hypotonia, vertigo, syncope, vomiting, blurred or double vision, nystagmus, papilledema, and delayed gait development. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Blake pouch cyst	None	3,813	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98922	2021-01-23T18:50:31	{"icd-10": ["Q03.1"]}
For other uses, see MAT (disambiguation). Multifocal atrial tachycardia Other namesChaotic atrial tachycardia[1] Multifocal atrial tachycardia Multifocal (or multiform) atrial tachycardia (MAT) is an abnormal heart rhythm,[2] specifically a type of supraventricular tachycardia, that is particularly common in older people and is associated with exacerbations of chronic obstructive pulmonary disease (COPD). Normally, the heart rate is controlled by a cluster of cells called the sinoatrial node (SA node). When a number of different clusters of cells outside the SA node take over control of the heart rate, and the rate exceeds 100 beats per minute, this is called multifocal atrial tachycardia (if the heart rate is ≤100, this is technically not a tachycardia and it is then termed multifocal atrial rhythm).[3] 'Multiform' simply describes the variable P wave shapes and is an observation, 'multifocal' is an inference about the underlying cause. Although these are interchangeable terms, some purists prefer the former nomenclature since it does not presume any underlying mechanism. ## Contents * 1 Diagnosis * 1.1 Additional workup * 2 Causes * 3 Pathophysiology * 4 Treatment * 5 References * 6 External links ## Diagnosis[edit] Multifocal atrial tachycardia is characterized by an electrocardiogram (ECG) strip with three or more discrete P wave morphologies in the same lead, not including that originating from the sinoatrial node , plus tachycardia, which is a heart rate exceeding 100 beats per minute (although some suggest using a threshold of 90 beats per minute). Furthermore, there should be irregular PP intervals, and the baseline should be isoelectric between P waves. Other findings that are commonly seen, but are not diagnostic include irregular PR and RR intervals. Variation in PR intervals has not been included in the diagnostic criteria because the PR interval varies with the length of the preceding RP interval.[4] Other diagnoses that may present with similar findings on electrocardiogram that should be included in the differential diagnosis include sinus tachycardia with frequent premature atrial contractions (this would have regular PP intervals), atrial flutter with variable AV node conduction (this would have regular PP intervals and flutter waves), atrial fibrillation (this would not have discrete P-wave morphologies), and wandering atrial pacemaker which would have a heart rate less than 100 beats per minute).[4] ### Additional workup[edit] If arrhythmia persists despite the treatment of underlying medical conditions it may be worth checking a complete blood count and serum chemistry for signs of infection, anemia, or electrolyte abnormalities such as hypokalemia and hypomagnesemia.[4] ## Causes[edit] MAT usually arises because of an underlying medical condition. Its prevalence has been estimated at about 3 per 1000 in adult hospital inpatients and is much rarer in paediatric practice; it is more common in the elderly, and its management and prognosis are both those of the underlying diagnosis.[5] It is mostly common in patients with lung disorders, but it can occur after acute myocardial infarction and can also occur in the setting of low blood potassium or low blood magnesium.[6] It is sometimes associated with digitalis toxicity in patients with heart disease. It is most commonly associated with hypoxia and COPD. Additionally, it can be caused by theophylline toxicity, a drug with a narrow therapeutic index commonly used to treat COPD. Theophylline can cause a number of different abnormal heart rhythms when in excess, and thus further predisposes COPD patients to MAT. Theophylline toxicity often occurs following acute or chronic overtreatment or factors lowering its clearance from the body.[7] ## Pathophysiology[edit] The P-waves and P–R intervals are variable due to a phenomenon called wandering atrial pacemaker (WAP). The electrical impulse is generated at a different focus within the atria of the heart each time. WAP is positive once the heart generates at least three different P-wave formations from the same ECG lead. Then, if the heart rate exceeds 100 beats per minute, the phenomenon is called multifocal atrial tachycardia. ## Treatment[edit] Management of multifocal atrial tachycardia consists mainly of the treatment of the underlying cause.[5][4] If treatment is indicated, therapy should begin with first correcting underlying electrolyte abnormalities with the repletion of potassium to maintain greater than 4 mEq/L and magnesium greater than 2 mEq/L. Studies have shown magnesium suppresses ectopic atrial activity and can be beneficial even if magnesium levels are within the normal range. Once electrolyte abnormalities have been corrected, possible treatment options include non-dihydropyridine calcium channel blockers, beta-blockers, and atrioventricular (AV) node ablation. Studies have found no role for antiarrhythmic agents, cardioversion, or anticoagulation. In the absence of underlying pulmonary disease, the first-line agent is beta-blockers. A beta-blockers act to suppress ectopic foci by reducing sympathetic stimulation and decreasing conduction through the atrioventricular node, thereby slowing the ventricular response. Studies have found an average decrease in heart rate of 51 beats per minute and 79% of patients reverted to sinus rhythm. Most patients did not need beta-blocker therapy long term as studies found long-term therapy was needed in only 25% of patients. Caution should be used in patients with an underlying pulmonary disease such as COPD and patients with decompensated heart failure due to the increased risk for bronchospasms and decreased cardiac output. Furthermore, beta-blockers should be avoided in patients with atrioventricular blocks unless a pacemaker has been implanted.[4] In the presence of underlying pulmonary disease, the first-line agent is a non-dihydropyridine calcium channel blocker such as verapamil or diltiazem. These agents act to suppress atrial rate and decrease conduction through the atrioventricular node, thereby slowing the ventricular rate. Studies have found an average reduction in the ventricular rate of 31 beats per minute and 43% of patients reverted to sinus rhythm. Caution should be used in patients with preexisting heart failure or hypotension due to negative inotropic effects and peripheral vasodilation. Similarly, calcium channel blockers should also be avoided in patients with atrioventricular blocks unless a pacemaker has been implanted.[4] In select cases of refractory multifocal atrial tachycardia, AV node ablation has been performed. Studies have found an average reduction in the ventricular rate of 56 beats per minute with adequate control of ventricular response in 84% of patients. However, AV node ablation creates a complete heart block and requires the placement of a permanent pacemaker.[4] Administration of oxygen may play a role in the treatment of some patients.[8] ## References[edit] 1. ^ "Multifocal atrial tachycardia: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 28 May 2019. 2. ^ Bradley DJ, Fischbach PS, Law IH, Serwer GA, Dick M (August 2001). "The clinical course of multifocal atrial tachycardia in infants and children". J. Am. Coll. Cardiol. 38 (2): 401–08. doi:10.1016/S0735-1097(01)01390-0. PMID 11499730. 3. ^ "ECG Learning Center – An introduction to clinical electrocardiography". Library.med.utah.edu. Retrieved 2013-04-24. 4. ^ a b c d e f g Custer, Adam M.; Yelamanchili, Varun S.; Lappin, Sarah L. (2020). "Multifocal Atrial Tachycardia (MAT)". StatPearls. StatPearls Publishing. PMID 29083603. Retrieved 18 August 2020. Text was copied from this source, which is available under a Creative Commons Attribution 4.0 International License. 5. ^ a b McCord J, Borzak S (January 1998). "Multifocal atrial tachycardia". Chest. 113 (1): 203–09. doi:10.1378/chest.113.1.203. PMID 9440591.[permanent dead link] 6. ^ Kastor JA (1990). "Multifocal Atrial Tachycardia". N Engl J Med. 322 (24): 1713–17. doi:10.1056/NEJM199006143222405. PMID 2188131. 7. ^ Sessler CN (1990). "Theophylline toxicity: Clinical features of 116 consecutive cases". Am J Med. 88 (6): 567–76. doi:10.1016/0002-9343(90)90519-J. PMID 2189301. 8. ^ American College of Physicians; Acp (15 June 2008). MKSAP for students four. ACP Press. pp. 37–. ISBN 978-1-934465-03-5. Retrieved 11 November 2010. ## External links[edit] Classification D * ICD-9-CM: 427.89 * DiseasesDB: 31111 External resources * MedlinePlus: 000186 * eMedicine: article/759135 * v * t * e Cardiovascular disease (heart) Ischaemic Coronary disease * Coronary artery disease (CAD) * Coronary artery aneurysm * Spontaneous coronary artery dissection (SCAD) * Coronary thrombosis * Coronary vasospasm * Myocardial bridge Active ischemia * Angina pectoris * Prinzmetal's angina * Stable angina * Acute coronary syndrome * Myocardial infarction * Unstable angina Sequelae * hours * Hibernating myocardium * Myocardial stunning * days * Myocardial rupture * weeks * Aneurysm of heart / Ventricular aneurysm * Dressler syndrome Layers Pericardium * Pericarditis * Acute * Chronic / Constrictive * Pericardial effusion * Cardiac tamponade * Hemopericardium Myocardium * Myocarditis * Chagas disease * Cardiomyopathy * Dilated * Alcoholic * Hypertrophic * Tachycardia-induced * Restrictive * Loeffler endocarditis * Cardiac amyloidosis * Endocardial fibroelastosis * Arrhythmogenic right ventricular dysplasia Endocardium / valves Endocarditis * infective endocarditis * Subacute bacterial endocarditis * non-infective endocarditis * Libman–Sacks endocarditis * Nonbacterial thrombotic endocarditis Valves * mitral * regurgitation * prolapse * stenosis * aortic * stenosis * insufficiency * tricuspid * stenosis * insufficiency * pulmonary * stenosis * insufficiency Conduction / arrhythmia Bradycardia * Sinus bradycardia * Sick sinus syndrome * Heart block: Sinoatrial * AV * 1° * 2° * 3° * Intraventricular * Bundle branch block * Right * Left * Left anterior fascicle * Left posterior fascicle * Bifascicular * Trifascicular * Adams–Stokes syndrome Tachycardia (paroxysmal and sinus) Supraventricular * Atrial * Multifocal * Junctional * AV nodal reentrant * Junctional ectopic Ventricular * Accelerated idioventricular rhythm * Catecholaminergic polymorphic * Torsades de pointes Premature contraction * Atrial * Junctional * Ventricular Pre-excitation syndrome * Lown–Ganong–Levine * Wolff–Parkinson–White Flutter / fibrillation * Atrial flutter * Ventricular flutter * Atrial fibrillation * Familial * Ventricular fibrillation Pacemaker * Ectopic pacemaker / Ectopic beat * Multifocal atrial tachycardia * Pacemaker syndrome * Parasystole * Wandering atrial pacemaker Long QT syndrome * Andersen–Tawil * Jervell and Lange-Nielsen * Romano–Ward Cardiac arrest * Sudden cardiac death * Asystole * Pulseless electrical activity * Sinoatrial arrest Other / ungrouped * hexaxial reference system * Right axis deviation * Left axis deviation * QT * Short QT syndrome * T * T wave alternans * ST * Osborn wave * ST elevation * ST depression * Strain pattern Cardiomegaly * Ventricular hypertrophy * Left * Right / Cor pulmonale * Atrial enlargement * Left * Right * Athletic heart syndrome Other * Cardiac fibrosis * Heart failure * Diastolic heart failure * Cardiac asthma * Rheumatic fever [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Multifocal atrial tachycardia	c0221158	3,814	wikipedia	https://en.wikipedia.org/wiki/Multifocal_atrial_tachycardia	2021-01-18T18:40:17	{"gard": ["1235"], "umls": ["C0221158"], "icd-9": ["427.89"], "orphanet": ["3282"], "wikidata": ["Q1165996"]}
## Clinical Features Sallis and Beighton (1972) described a new syndrome consisting of flexion deformity of the fingers and 'rocker-bottom' feet due to vertical talus. Fourteen persons in 5 generations were affected but no instance of male-to-male transmission was observed. Stevenson et al. (1975) described the same trait in a large American Black family. They emphasized the ulnar deviation of the fingers. Their patients lacked vertical talus and short stature. Male-to-male transmission was noted. They also noted adduction contraction of the thumb in a newborn in their family. Dhaliwal and Myers (1985) reported what they believed to be the first affected American Caucasian kindred. Father and son were affected; both showed ulnar deviation of the fingers, adduction and flexion deformity of the thumbs, bilateral vertical talus with 'rocker-bottom' feet, and moderate short stature. See arthrogryposis multiplex congenita, distal, type I (108120). Inheritance Male-to-male transmission in some reported families is consistent with autosomal dominant transmission (Stevenson et al., 1975; Dhaliwal and Myers, 1985). Radiology \- Vertical talus Limbs \- Flexion deformity of fingers \- Rocker-bottom feet \- Ulnar deviation of fingers \- Thumb adduction contraction Growth \- Variable moderate short stature Inheritance \- Autosomal dominant ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	DIGITOTALAR DYSMORPHISM	c1852085	3,815	omim	https://www.omim.org/entry/126050	2019-09-22T16:42:15	{"mesh": ["C565097"], "omim": ["126050"], "orphanet": ["1146"], "synonyms": ["Alternative titles", "ULNAR DRIFT, HEREDITARY"]}
A number sign (#) is used with this entry because of evidence that nonsyndromic microphthalmia with coloboma-9 (MCOPCB9) and microphthalmia and/or coloboma with developmental delay (MCOPS15) are caused by homozygous mutation in the ODZ3 gene (TENM3; 610083) on chromosome 4q35. One family with MCOPCB9 has been reported. For a discussion of genetic heterogeneity of isolated colobomatous microphthalmia, see MCOPCB1 (300345). Description MCOPCB9 is characterized by isolated microphthalmia and coloboma (Aldahmesh et al., 2012). MCOPS15 is characterized by microphthalmia and/or coloboma, with developmental delay in which speech appears to be more severely affected than motor abilities. Additional ocular anomalies that have been observed include ptosis, keyhole-shaped pupils, microcornea, sclerocornea, and anterior segment dysgenesis (Chassaing et al., 2016; Stephen et al., 2018; Singh et al., 2019). Clinical Features ### Isolated Microphthalmia and Coloboma 9 Aldahmesh et al. (2012) reported a Saudi Arabian brother and sister, born of third-cousin parents, who had nonsyndromic bilateral colobomatous microphthalmia. The 11-year-old brother had no medical history other than congenitally small eyes and accompanying poor vision, with 20/50 visual acuity on the right and hand motion on the left; similarly, his 9-year-old sister had visual acuities of 20/200 and 20/300 on the right and left, respectively. Anterior segment examination of both sibs revealed microcornea, microphthalmos, and iris coloboma, and funduscopic examination showed grossly anomalous discs and total coloboma involving the macula. Both sibs had normal cognitive and motor development. Their parents had normal eyes upon examination, and there were 2 other unaffected sisters. ### Syndromic Microphthalmia 15 Chassaing et al. (2016) reported a 9-year-old boy, born of first-cousin parents, who had bilateral colobomatous microphthalmia noted at birth and developed pendular nystagmus and esotropia. Examination revealed bilateral microcornea and iris coloboma with clear lenses, as well as bilateral optic disc and chorioretinal colobomas involving the macula. Both eyes were myopic. At age 2 years, he developed a retinal detachment in the left eye, and at age 8, a retinal detachment in the right eye. Visual acuity was estimated at hand movements bilaterally at age 9, and he also exhibited developmental delay with intellectual disability. Stephen et al. (2018) studied 2 sisters with vertically oval microcornea, inferonasal iris coloboma, keyhole-shaped pupils, and inferomedial retinal coloboma, which involved the optic discs and fovea in one sister and spared those in the other. The older sister had unilateral ptosis, whereas the younger sister had bilateral partial ptosis and left convergent squint. Axial lengths were not reported. Dysmorphic features included broad eyebrows, hypertelorism, narrow palpebral fissures, long philtrum, and low-set flared pinnae. Both sisters exhibited developmental delay, with the younger sister showing mild motor delay and more significant speech delay, with only a few words at age 4 years. A maternal uncle had severe vision loss and was reported to have had small eyes. Singh et al. (2019) reported a 9-year-old Indian boy who presented at age 6 years with severe global developmental delay and ocular malformations that had been noted at birth. Examination revealed dysmorphic features including plagiocephaly, low anterior hairline, supraorbital flattening, and large ears. He had right microphthalmia, bilateral sclerocornea, and anterior segment dysgenesis. He walked at 3 years of age and was toilet trained by age 7; speech delay was more severe, with only 10 words and inability to make sentences at age 9. Brain MRI did not show any intracranial abnormality. Molecular Genetics ### Isolated Microphthalmia and Coloboma 9 In a Saudi Arabian brother and sister with nonsyndromic bilateral colobomatous microphthalmia, who were negative for mutation in known microphthalmia genes, Aldahmesh et al. (2012) performed combined autozygome and exome analysis, which revealed homozygosity for a frameshift mutation in the ODZ3 gene (610083.0001). Their unaffected parents were heterozygous for the mutation, which was not found in ethnically matched controls or in the Exome Variant Server. ### Syndromic Microphthalmia 15 In 96 patients with microphthalmia, Chassaing et al. (2016) analyzed 187 genes associated with ocular development and identified homozygosity for a splice site mutation in the TENM3 gene (610083.0002) in a 9-year-old boy with bilateral colobomatous microphthalmia. His unaffected first-cousin parents and an unaffected sister were heterozygous for the mutation. The patient also exhibited intellectual disability, which the authors noted might be an inconstant feature associated with TENM3 mutation, or the result of other genetic variants in this consanguineous family. In 2 sisters with ocular coloboma and microcornea as well as developmental delay, Stephen et al. (2018) performed whole-exome sequencing and identified homozygosity for a nonsense mutation in the TENM3 gene (C619X; 610083.0003) that segregated with disease in the family. By exome sequencing in a 9-year-old Indian boy with unilateral microphthalmia, bilateral sclerocornea, anterior segment dysgenesis, and severe developmental delay, Singh et al. (2019) identified compound heterozygosity for 2 missense mutations in the TENM3 gene (A1349G, 610083.0004 and R2563W, 610083.0005). His unaffected father and brother were heterozygous for the A1349G mutation, whereas his unaffected mother did not carry either mutation, suggesting mosaicism in the mother or occurrence of a de novo variant in the proband. INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Long philtrum Ears \- Large ears \- Low-set ears \- Flared pinnae Eyes \- Microphthalmia \- Microcornea \- Vertically oval cornea \- Iris coloboma \- Ptosis, unilateral or bilateral \- Narrow palpebral fissures \- Keyhole-shaped pupils \- Sclerocornea \- Anterior segment dysgenesis \- Hypertelorism \- Decreased visual acuity \- Anomalous discs \- Total coloboma, involving the macula \- Retinal detachment, bilateral (in 1 patient) \- Pendular nystagmus \- Esotropia NEUROLOGIC Central Nervous System \- Global developmental delay \- Intellectual disability \- Speech delay MISCELLANEOUS \- Inter- and intrafamilial phenotypic variability MOLECULAR BASIS \- Caused by mutation in the homolog of Drosophila ODZ-3 gene (ODZ3, 610083.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	MICROPHTHALMIA, ISOLATED, WITH COLOBOMA 9	c2931501	3,816	omim	https://www.omim.org/entry/615145	2019-09-22T15:53:03	{"mesh": ["C537463"], "omim": ["615145"], "orphanet": ["98938"]}
A number sign (#) is used with this entry because autoinflammation with infantile enterocolitis (AIFEC) is caused by heterozygous mutation in the NLRC4 gene (606831) on chromosome 2p22. Description Autoinflammation with infantile enterocolitis is an autosomal dominant disorder characterized by onset of recurrent flares of autoinflammation in early infancy. Affected individuals tend to have poor overall growth and gastrointestinal symptoms in infancy associated with laboratory evidence of activated inflammation. This initial presentation is followed by recurrent febrile episodes with splenomegaly and sometimes hematologic disturbances, arthralgias, or myalgias. The disorder results from overactivation of an arm of the immune response system (Romberg et al., 2014; Canna et al., 2014). Clinical Features Romberg et al. (2014) reported a father and his 2 sons with an autoinflammatory syndrome characterized by neonatal-onset enterocolitis, periodic fever, and fatal or near-fatal episodes of autoinflammation. The proband presented at 1 week of age with secretory diarrhea, fever, and laboratory evidence of systemic inflammation, including increased ferritin and increased C-reactive protein. He developed a coagulopathy with pancytopenia and died at age 23 days from diffuse alveolar hemorrhage. Postmortem examination showed splenomegaly, bowel autolysis, villous blunting with inflammatory cells, and activated macrophages in the central nervous system. The patient's father had colitis as an infant that resolved by 1 year of age, as well as recurrent periodic fevers, erythematous plaques, and seronegative psoriatic arthritis. At age 43 years, he had an acute inflammatory episode complicated by disseminated intravascular coagulation with increased IL18 (600953), ferritin, and C-reactive protein. Bone marrow biopsy showed erythro- and myelophagocytosis. Both patients also had NK cell lymphopenia. The proband's 5-year-old paternal half brother had similar symptoms. Canna et al. (2014) reported a 7-year-old girl of European descent with a recurrent autoinflammatory syndrome. She presented at age 2 months with failure to thrive associated with anemia and increased serum ferritin. Around age 6 months, she developed vomiting and loose stools; upper endoscopy showed a nonspecific inflammatory infiltrate in the lamina propria and mild villous blunting. At 2 years of age, she developed recurrent episodic flares manifest as fever, malaise, and splenomegaly, and precipitated by viral infections, stress, or fatigue. Clinical Management Canna et al. (2014) found that treatment of an AIFEC patient with an IL1R (147810) antagonist reduced flare frequency, C-reactive protein levels, splenomegaly, and prednisone dose. Inheritance The transmission pattern of AIFEC in the family reported by Romberg et al. (2014) was consistent with autosomal dominant inheritance. Molecular Genetics In a father and his 2 sons with autoinflammation with infantile enterocolitis, Romberg et al. (2014) identified a heterozygous missense mutation in the NLRC4 gene (V341A; 606831.0001). The mutation, which was identified by exome sequencing, occurred de novo in the father. Simultaneously and independently, Canna et al. (2014) identified a de novo heterozygous missense mutation in the NLRC4 gene (T337S; 606831.0002) in a girl with AIFEC. Both Romberg et al. (2014) and Canna et al. (2014) demonstrated that patient-derived monocytes and macrophages had increased and constitutive inflammasome activation and increased secretion of IL1B (147720) and IL18 (600953), as well as increased cell death (pyroptosis), compared to controls. Cellular transfection of the mutations also resulted in increased secretion of IL1B and IL18, indicating that both mutations caused a gain of function with constitutive activation of CASP1 (147678). INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature Other \- Failure to thrive ABDOMEN Spleen \- Splenomegaly Gastrointestinal \- Enterocolitis, infantile \- Secretory diarrhea, infantile \- Vomiting, infantile \- Villous blunting SKELETAL \- Arthralgias SKIN, NAILS, & HAIR Skin \- Rash MUSCLE, SOFT TISSUES \- Myalgias METABOLIC FEATURES \- Fever, episodic HEMATOLOGY \- Disseminated intravascular coagulation, episodic \- Pancytopenia, episodic IMMUNOLOGY \- Autoinflammation, systemic \- Activated macrophages \- Low NK cells \- Dysfunctional NK cells LABORATORY ABNORMALITIES \- Increased C-reactive protein \- Increased serum ferritin \- Increased IL18 \- Increased IL1B Increased soluble IL2R MISCELLANEOUS \- Onset in neonatal period or early infancy \- Enterocolitis tends to remit with age \- Flares triggered by viral infection, overexertion, stress \- Two unrelated families have been reported (last curated October 2014) MOLECULAR BASIS \- Caused by mutation in the NLR family, caspase recruitment domain-containing 4 gene (NLRC4, 606831.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	AUTOINFLAMMATION WITH INFANTILE ENTEROCOLITIS	c4015067	3,817	omim	https://www.omim.org/entry/616050	2019-09-22T15:50:02	{"omim": ["616050"], "orphanet": ["436166"], "synonyms": ["NLRC4-related MAS", "NLRC4-related autoinflammatory syndrome with MAS", "NLRC4-related autoinflammatory syndrome with macrophage activation syndrome", "NLRC4-related infantile enterocolitis-autoinflammatory syndrome", "NLRC4-related macrophage activation syndrome"]}
Limbic encephalitis with DPP6 antibodies is a rare brain inflammatory disease characterized by subacute or insidious onset of variable neurological features including cognitive dysfunction (memory impairment, hallucinations, confusion, amnesia), central hyperexcitability (agitation, tremor, myoclonus, exaggerated startle), brain stem involvement (dysphagia, dysarthia, ataxia) and disturbed sleep. Symptoms of dysautonomia include diarrhea, gastroparesis, and constipation. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Limbic encephalitis with DPP6 antibodies	None	3,818	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=329341	2021-01-23T17:45:16	{"icd-10": ["G04.8"], "synonyms": ["Limbic encephalitis with DPPX antibodies", "Limbic encephalitis with dipeptidyl-peptidase 6 antibodies"]}
A number sign (#) is used with this entry because the phenotype can be caused by mutation in the keratin 1 gene (KRT1; 139350) or the keratin 10 gene (KRT10; 148080). Clinical Features Sybert et al. (1999) described 4 individuals from 2 families with a unique clinical disorder with histologic findings of epidermolytic hyperkeratosis, a hallmark feature of bullous congenital ichthyosiform erythroderma (113800) on light and electron microscopy. Affected individuals manifested erythema and superficial erosions at birth, which improved during the first few months of life; later, palmoplantar hyperkeratosis with patchy erythema and scale developed elsewhere on the body. Three affected individuals exhibited dramatic episodic flares of annular, polycyclic erythematous plaques with scale, which coalesced to involve most of the body surface. The flares lasted weeks to months. In the interim periods the skin was normal except for palmoplantar hyperkeratosis. Abnormal keratin-filament aggregates were observed in suprabasal keratinocytes from both probands. Joh et al. (1997) reported a family with a similar phenotype, characterized by blistering in childhood accompanying and followed by polycyclic erythematous hyperkeratosis but without palmoplantar involvement. The proband suffered from bullous ichthyosis and had bouts of disease activity associated with the development of numerous annular and polycyclic erythematous, hyperkeratotic plaques on the trunk and the proximal extremities. Molecular Genetics In the proband of one family affected with cyclic ichthyosis with epidermolytic hyperkeratosis, Sybert et al. (1999) found a 1436T-C transition mutation in the keratin 1 gene that predicted an amino acid change from isoleucine to threonine at codon 479 (I479T; 139350.0005). This alteration in the highly conserved portion of helix 2B, known as the helix termination motif, created a new BsmAI restriction site. In the second family, Sybert et al. (1999) detected a 1435A-T translation that predicted a substitution of isoleucine-479 by phenylalanine (I479F; 139350.0006). This mutation was carried by the proband, his mother, and his maternal aunt. Both mutations were found in heterozygosity. A mutation in the 2B helical segment of the KRT10 protein, arg83 to glu (R83E; 148080.0014), caused the phenotype in the family of Joh et al. (1997). KRT10 encodes the partner keratin of KRT1; both are present in suprabasal cells. INHERITANCE \- Autosomal dominant SKIN, NAILS, & HAIR Skin \- Neonatal blisters and erosions \- Hyperkeratosis of the palms and soles \- Erythema, blisters, pustules (cyclical, explosive episodes) \- Ichthyosis of scalp and flexural areas \- Migratory plaques of thickened, sharply demarcated erythema and hyperkeratosis Skin Histology \- Intraepidermal vesicles \- Epidermal spongiosis \- Eosinophils and neutrophils in the epidermis \- Superficial and deep perivascular infiltrates in the dermis Electron Microscopy \- Cytolysis \- Circumscribed clumps of keratin filaments (some associated with desmosomes) \- Dense whorls of keratin filaments in the lower and middle spinous layers Nails \- Normal Hair \- Normal MOLECULAR BASIS \- Caused by mutation in the keratin 1 gene (KRT1, 139350.0005 ) \- Caused by mutation in the keratin 10 gene (KRT10, 148080.0014 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	ICHTHYOSIS, CYCLIC, WITH EPIDERMOLYTIC HYPERKERATOSIS	c0079153	3,819	omim	https://www.omim.org/entry/607602	2019-09-22T16:08:59	{"mesh": ["D017488"], "omim": ["607602"], "orphanet": ["312", "281139"], "synonyms": ["Alternative titles", "CIEHK", "EPIDERMOLYTIC ICHTHYOSIS, ANNULAR"]}
Acute Retinal Necrosis SpecialtyOphthalmology, optometry Acute retinal necrosis (ARN)[1] is a medical inflammatory condition of the eye.[2] The condition presents itself as a necrotizing retinitis.[3] The inflammation onset is due to certain herpes viruses, varicella zoster virus (VZV), herpes simplex virus (HSV-1 and HSV-2) and Epstein–Barr virus (EBV).[2][3] People with the condition usually display redness of the eye, white or off-white colored patches that are patches of retinal necrosis.[3] ARN can progress into other conditions such as uveitis, detachment of the retina, and ultimately can lead to blindness.[4] The disease was first characterized in 1971, in Japan. Akira Urayama and his colleagues had six patients whose cases showed signs of acute necrotizing retinitis, retinal arteritis, choroiditis, and late-onset retinal detachment.[5] The combination of the conditions was given the name acute retinal necrosis.[2] The first reports of ARN came about in 1971. It is unclear whether it was previously just reported as something else. Urayama and his colleagues reported the disease that they saw in six Japanese patients. Since then the disease has been seen in patient's with AIDS, children, and people who are immunocompromised.[2][6] In 1978, Young and Bird named the disease when presented in both eyes, Bilateral Acute Retinal Necrosis, otherwise known as BARN.[6] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Pathophysiology * 3.1 Acute Herpetic Phase * 3.2 Late Cicatricial Phase * 4 Diagnosis * 5 Prevention * 6 Treatment * 6.1 Medication * 7 Research * 8 See also * 9 References * 10 External links ## Signs and symptoms[edit] Patients with ARN typically present * floaters * redness of the eye * flashes * decreased sharpness of vision * photophobia.[2][6] Though uncommon, some patients may experience pain.[6] Most patients will only experience this in one eye (unilateral), though possible for the condition to be seen in both (bilateral, BARN).[2] If the first eye is left without treatment, some cases have shown the disease progressing to the other eye in a month's time.[6] Further progressed stages of the disease can cause blindness in the eye experiencing ARN.[2] Though the disease may be present itself, the inflammation of the retina may not been visualized for decades after the initial signs.[6] ## Causes[edit] ARN is associated with people who have latent herpes viruses that have been reactivated. The most common causes of the disease have been linked to VZV, HSV-1, HSV-2, and CMV respectively.[6] ARN cases have been reported in patients who have AIDS, are immunocompromised and in children. The disease is not limited to a specific gender. Most cases have been reported in young adults though children and the elderly can be affected.[6] Specific genetic markers in Caucasians in the United States have shown elevated risk for disease development (HLA-DQw7 and Bw62, DR4) as well as HLA-Aw33, B44, and DRw6 in the Japanese population.[6] ## Pathophysiology[edit] ARN presentation in individuals can be characterized by two separate phases as listed below. ### Acute Herpetic Phase[edit] The acute herpetic phase is characterized by when viral particles infiltrate the retina and vitreous causing an inflammatory reaction. Together, the viral particles and mononuclear cells in the vitreous cause the retina to become opaque. In response to all this, lymphocytes and plasma cells diffuse into the vitreous as well.[2] ### Late Cicatricial Phase[edit] The late cicatricial phase of ARN includes changes in the way the vitreous is organized due to the cellular infiltration seen in the previous phase.[2] In the vitreous and on top of the thinned necrotic retina, contractile membranes may form. Majority of patients with ARN will experience detachment of their retina in the affected eye.[2] ## Diagnosis[edit] Diagnosis of ARN is outlined by the American Uveitis Society. Though most diagnoses of ARN are made by clinical features, a physician may take a vitreous sample and have it tested for herpes markers. Common lab tests that are run on the sample include a viral culture, viral PCR, direct/indirect immunofluorescence, viral antibody measurement.[2] The American Uveitis Society has established the following guidelines for ARN diagnosis: 1. Retinal necrosis with one or more focus points borders in the peripheral retina 2. In the absence of antiviral treatment, the condition progresses rapidly 3. Spreading to the surroundings 4. Buildup of blood vessels 5. Inflammation of the vitreous.[5] ## Prevention[edit] While there is no prevention for ARN, exposing a patient to antiviral agents in the earlier phases of the outbreak tend to decrease the duration of the active phase of the disease. Taking antiviral agents after the issue is resolved seems to lessen the chance of it spreading to the other eye.[2] ## Treatment[edit] ### Medication[edit] Currently treatment of ARN consists of antiviral therapy administered orally. Typical antiviral agents used include famciclovir, valganciclovir, and valacyclovir. While on these medications, a patient's kidney function should be watched. Some physician's also may administer the antiviral agents via intravitreal delivery. Though controversial, some physicians administer steroids (prednisone) and antithrombotic therapy (aspirin). Some commonly administered antiviral agents are as follows: * Acyclovir * Famciclovir * Valacyclovir * Gancicilovir * Valganciclovir[2] ## Research[edit] In a study done published by the British Journal of Ophthalmology, the cases of ARN/BARN reported in 2001-2002 in the UK, Varicella Zoster Virus was the most common culprit for the disease and presented mostly in men than in women.[7] Researchers have also looked at two cases of ARN in patients who have been diagnosed with an immunodeficiency virus. The disease presented itself more so in the outer retina until it progressed far enough to then affect the inner retina. The patients were not so responsive to the antiviral agents given to them through an IV, acyclovir specifically. The cases progressed to retinal detachment. The patients tested positive for the herpes virus. Researchers are now wondering if this type of ARN is specific to those who have the immunodeficiency virus.[1] ## See also[edit] * Cytomegalovirus retinitis * Progressive outer retinal necrosis ## References[edit] 1. ^ a b Forster, David (1990). "Rapidly Progressive Outer Retinal Necrosis in the Acquired Immunodeficiency Syndrome". American Journal of Ophthalmology. 110 (4): 341–348. doi:10.1016/S0002-9394(14)77012-6. PMID 2220967. 2. ^ a b c d e f g h i j k l m "Acute retinal necrosis - EyeWiki". eyewiki.aao.org. Retrieved 2015-10-27. 3. ^ a b c "Acute Retinal Necrosis - Ophthalmology". www.aaojournal.org. Retrieved 2015-10-27. 4. ^ "Acute Retinal Necrosis: Background, Pathophysiology, Epidemiology". 2018-08-22. Cite journal requires `\|journal=` (help) 5. ^ a b "Diagnosing and Managing Acute Retinal Necrosis". www.retinalphysician.com. Retrieved 2015-12-10. 6. ^ a b c d e f g h i "Necrotizing Herpetic Retinopathies: Acute Retinal Necrosis". www.aao.org. Retrieved 2015-11-04. 7. ^ Muthiah, M. N.; Michaelides, M.; Child, C. S.; Mitchell, S. M. (2007-11-01). "Acute retinal necrosis: a national population-based study to assess the incidence, methods of diagnosis, treatment strategies and outcomes in the UK". British Journal of Ophthalmology. 91 (11): 1452–1455. doi:10.1136/bjo.2007.114884. ISSN 1468-2079. PMC 2095441. PMID 17504853. ## External links[edit] Classification D * ICD-10: H35.89 * ICD-9-CM: 362.89 * MeSH: D015882 * DiseasesDB: 4973 External resources * eMedicine: oph/377 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Acute retinal necrosis	c0035319	3,820	wikipedia	https://en.wikipedia.org/wiki/Acute_retinal_necrosis	2021-01-18T18:33:45	{"mesh": ["D015882"], "umls": ["C0035319"], "wikidata": ["Q4677951"]}
Somatomammotropinoma is a rare, mixed, functioning pituitary adenoma characterized by the cosecretion of growth hormone and prolactin, which manifests with signs and symptoms of both acromegaly and hyperprolactinemia. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Somatomammotropinoma	None	3,821	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=314769	2021-01-23T18:41:37	{"icd-10": ["D35.2"], "synonyms": ["GH and PRL cosecreting pituitary adenoma", "Growth hormone and prolactin cosecreting pituitary adenoma", "Somatolactotropinoma", "Somatoprolactinoma"]}
Darwin's tubercle Left: Darwin's tubercle. Right: the homologous point in a macaque. Details Identifiers Latintuberculum auriculare TA98A15.3.01.020 TA2194 FMA61151 Anatomical terminology [edit on Wikidata] Darwin's tubercle (helix) Darwin's tubercle (or auricular tubercle) is a congenital ear condition which often presents as a thickening on the helix at the junction of the upper and middle thirds. ## Contents * 1 History * 2 Prevalence * 3 Inheritance * 4 See also * 5 References * 6 External links ## History[edit] Scan of Figure 2, from Darwin's Descent of Man, second edition, illustrating Darwin's tubercle This atavistic feature is so called because its description was first published by Charles Darwin in the opening pages of The Descent of Man, and Selection in Relation to Sex, as evidence of a vestigial feature indicating common ancestry among primates which have pointy ears. However, Darwin himself named it the Woolnerian tip, after Thomas Woolner, a British sculptor who had depicted it in one of his sculptures and had first theorised that it was an atavistic feature.[1] ## Prevalence[edit] The feature is present in approximately 10.4% of the Spanish adult population, 40% of adults in India, and 58% of Swedish school children.[2][3][4][5] This acuminate nodule represents the point of the mammalian ear. The trait can potentially be bilateral, meaning present on both ears, or unilateral, where it is present on only one ear. There is mixed evidence in regard to whether the bilateral or unilateral expression is related to population, or other factors. Some populations express full bilateral, while others may express either unilateral or bilateral. However, bilateral appears to be more common than unilateral as it pertains to the expression of the trait.[3][6][7][8][9] ## Inheritance[edit] The gene for Darwin's tubercle was once thought to be inherited in an autosomal dominant pattern with incomplete penetrance, meaning that those who possess the allele (version of a gene) will not necessarily present with the phenotype.[10] However, genetic and family studies have demonstrated that the presence of Darwin's tubercle may be more likely to be influenced by one's environment or developmental accidents than it is by genetics alone.[11][12][5] There is no clear argument for whether the trait has significance in sexual dimorphism studies or age related studies. In some studies, there is clear data that Darwin's tubercle is not associated with sex.[7][6] In contrast, others indicate that there is a correlation with sexual dimorphism between men and women, where men tend to have the tubercle more than women in some populations.[3] Two studies indicate that older men tend to have greater expression of Darwin's tubercle than do older women.[13] ## See also[edit] * Human vestigiality ## References[edit] 1. ^ Millard, D. Ralph; Pickard, Robert E. (1970-04-01). "Darwin's Tubercle Belongs to Woolner". Archives of Otolaryngology. 91 (4): 334–335. doi:10.1001/archotol.1970.00770040492005. ISSN 0003-9977. PMID 4909009. 2. ^ Ruiz, A. (1986). "An anthropometric study of the ear in an adult population". International Journal of Anthropology. 1 (2): 135–43. doi:10.1007/BF02447350. S2CID 85200552. 3. ^ a b c Singh, P.; Purkait, R. (2009). "Observations of external ear—an Indian study". HOMO: Journal of Comparative Human Biology. 60 (5): 461–472. doi:10.1016/j.jchb.2009.08.002. PMID 19748090. 4. ^ Hildén, K. (1929). "Studien über das Vorkommen der darwinschen Ohrspitze in der Bevölkerung Finnlands". Fennia (52): 3–39. 5. ^ a b "Myths of Human Genetics: Darwin's tubercle". udel.edu. Retrieved 2015-11-02. 6. ^ a b Gurbuz, H.; Karaman, F.; Mesut, R. (2005). "The variations of auricular tubercle in Turkish people. Institute of Experimental Morphology and Anthropology". Acta Morphol. Anthropol. 10: 150–156. 7. ^ a b Rubio, O.; Galera, V.; Alonso, M.C. (August 2015). "Anthropological study of ear tubercles in a Spanish sample". HOMO: Journal of Comparative Human Biology. 66 (4): 343–356. doi:10.1016/j.jchb.2015.02.005. PMID 25916201. 8. ^ Bean, R.B. (1915). "Some characteristics of the external ear of American Whites, American Indians, American Negroes, Alaskan Eskimos, and Filipinos". American Journal of Anatomy. 18 (1915): 201–225. doi:10.1002/aja.1000180204. 9. ^ Singh, L. (1977). "Hypertrichosis pinnae auris, Darwin's tubercle and palmaris longus among Khatris and Baniyas of Patiala, India". Acta Genet. Med. Gemellol. (Rome). 26 (1977): 183–184. doi:10.1017/S0001566000010011. PMID 596117. 10. ^ Spinney, Laura (2008). "Vestigial organs: Remnants of evolution". New Scientist. 198 (2656): 42. doi:10.1016/S0262-4079(08)61231-2. 11. ^ Quelprud, T. (1936). "Zur erblichkeit des darwinschen höckerchens". Zeitschrift für Morphologie und Anthropologie. 34: 343–363. 12. ^ Beckman, L (1960). "An evaluation of some anthropological traits used in paternity tests". Hereditas (46): 543–569. 13. ^ Vollmer, H. (1937). "The shape of the ear in relation to body constitution". Arch. Pediatr. 54 (1937): 574–590. ## External links[edit] Wikimedia Commons has media related to Darwin's tubercle. Authority control * TA98: A15.3.01.020 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Darwin's tubercle	c1852294	3,822	wikipedia	https://en.wikipedia.org/wiki/Darwin%27s_tubercle	2021-01-18T19:03:53	{"umls": ["C1852294", "C2751189"], "wikidata": ["Q1166866"]}
Pudendal nerve entrapment Other namesAlcock canal syndrome SpecialtyNeurology Pudendal nerve entrapment (PNE), also known as Alcock canal syndrome,[1][2] is an uncommon[1][3][4][5] source of chronic pain, in which the pudendal nerve (located in the pelvis) is entrapped or compressed.[6] Pain is positional and is worsened by sitting. Other symptoms include genital numbness, fecal incontinence and urinary incontinence. The term pudendal neuralgia (PN) is used interchangeably with "pudendal nerve entrapment", but a 2009 review study found both that "prevalence of PN is unknown and it seems to be a rare event" and that "there is no evidence to support equating the presence of this syndrome with a diagnosis of pudendal nerve entrapment," meaning that it is possible to have all the symptoms of pudendal nerve entrapment (otherwise known as pudendal neuralgia) based on the criteria specified at Nantes in 2006, without having an entrapped pudendal nerve.[7] A 2015 study of 13 normal female cadavers found that the pudendal nerve was attached or fixed to the sacrospinous ligament in all cadavers studied, suggesting that the diagnosis of pudendal nerve entrapment may be overestimated.[8] ## Contents * 1 Symptoms * 2 Causes * 3 Diagnosis * 4 Treatment * 4.1 Physical therapy * 4.2 Medications * 4.3 Injections * 4.4 Pulsed radiofrequency * 4.5 Ergonomics * 4.6 Surgical * 5 References * 6 External links ## Symptoms There are no specific clinical signs or complementary test results for this condition.[9] The typical symptoms of PNE or PN are seen, for example, in male competitive cyclists (it is often called "cyclist syndrome"[5]), who can rarely develop recurrent numbness of the penis and scrotum after prolonged cycling, or an altered sensation of ejaculation, with disturbance of micturition (urination) and reduced awareness of defecation.[10][11] Nerve entrapment syndromes, presenting as genitalia numbness, are amongst the most common bicycling associated urogenital problems.[12] The pain is typically caused by sitting, relieved by standing, and is absent when recumbent (lying down) or sitting on a toilet seat.[13] If the perineal pain is positional (changes with the patient's position, for example sitting or standing), this suggests a tunnel syndrome.[14] Anesthesiologist John S. McDonald of UCLA reports that sitting pain relieved by standing or sitting on a toilet seat is the most reliable diagnostic parameter.[15] Other than positional pain and numbness, the main symptoms are fecal incontinence and urinary incontinence.[16][17] Differential diagnosis should consider the far commoner conditions chronic prostatitis/chronic pelvic pain syndrome and interstitial cystitis.[13] ## Causes PNE can be caused by pregnancy, scarring due to surgery, accidents and surgical mishaps.[18] Anatomic abnormalities can result in PNE due to the pudendal nerve being fused to different parts of the anatomy, or trapped between the sacrotuberous and sacrospinalis ligaments. Heavy and prolonged bicycling, especially if an inappropriately shaped or incorrectly positioned bicycle seat is used, may eventually thicken the sacrotuberous and/or sacrospinous ligaments and trap the nerve between them, resulting in PNE. ## Diagnosis Similar to a tinel sign digital palpitation of the ischial spine may produce pain. In contrast, patients may report temporary relief with a diagnostic pudendal nerve block (see Injections), typically infiltrated near the ischial spine.[4][9] Electromyography can be used to measure motor latency along the pudendal nerve. A greater than normal conduction delay can indicate entrapment of the nerve.[4] Imaging studies using MR neurography may be useful. In patients with unilateral pudendal entrapment in the Alcock's canal, it is typical to see asymmetric swelling and hyperintensity affecting the pudendal neurovascular bundle.[19] ## Treatment Treatments include behavioral modifications, physical therapy, analgesics and other medications, pudendal nerve block, and surgical nerve decompression.[7] A newer form of treatment is pulsed radiofrequency.[20] This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Pudendal nerve entrapment" – news · newspapers · books · scholar · JSTOR (September 2014) (Learn how and when to remove this template message) ### Physical therapy There are stretches and exercises which have provided reduced levels of pain for some people. There are different sources of pain for people since there are so many ligament, muscles and nerves in the area. Sometimes women do pelvic floor exercises for compression after childbirth. However, there have been cases where the wrong stretches make the constant pain worse. Some people need to strengthen the muscles, others should stretch, while for some people it is purely neurological. There have been cases where doing stretches have helped bicyclists. ### Medications There are numerous pharmaceutical treatments for neuropathic pain associated with pudendal neuralgia. Drugs used include anti-epileptics (like gabapentin[20]), antidepressants (like amitriptyline[13]), and palmitoylethanolamide.[21] ### Injections Alcock canal infiltration with corticosteroids is a minimally invasive technique which allows for pain relief and could be tried when physical therapy has failed and before surgery. A long-acting local anesthetic (bupivacaine hydrochloride) and a corticosteroid (e.g. methylprednisolone) are injected to provide immediate pudendal anesthesia.[13] The injections may also bring a long-term response because the anti-inflammatory effects of the steroid and steroid-induced fat necrosis can reduce inflammation in the region around the nerve and decrease pressure on the nerve itself. This treatment may be effective in 65–73% of patients.[13] ### Pulsed radiofrequency Pulsed radiofrequency has been successful in treating a refractory case of PNE.[20] ### Ergonomics Various ergonomic devices can be used to allow an individual to sit while helping to take pressure off of the nerve. With bicycles the seat height and tilt can be adjusted to help alleviate compression. There are also bicycle seats designed to prevent pudendal nerve compression, these seats usually have a narrow channel in the middle of them. For sitting on hard surfaces, a cushion or coccyx cushion can be used to take pressure off the nerves. ### Surgical Decompression surgery is a "last resort", according to surgeons who perform the operation.[14] The surgery is performed by a small number of surgeons in a limited number of countries. The validity of decompression surgery as a treatment and the existence of entrapment as a cause of pelvic pain are highly controversial.[22][23] While a few doctors will prescribe decompression surgery, most will not. Notably, in February 2003 the European Association of Urology in its Guidelines on Pelvic Pain said[24] that expert centers in Europe have found no cases of PNE and that surgical success is rare: > Pudendal nerve neuropathy is likely to be a probable diagnosis if the pain is unilateral, has a burning quality and is exacerbated by unilateral rectal palpation of the ischial spine, with delayed pudendal motor latency on that side only. However, such cases account for only a small proportion of all those presenting with perineal pain. Proof of diagnosis rests on pain relief following decompression of the nerve in Alcock’s canal and is rarely achieved. The value of the clinical neurophysiological investigations is debatable; some centres in Europe claim that the investigations have great sensitivity, while other centres, which also have a specialized interest in pelvic floor neurophysiology, have not identified any cases. > > — European Association of Urology, Guidelines on Chronic Pelvic Pain Three types of surgery have been done to decompress the pudendal nerve: transperineal, transgluteal, and transichiorectal. A follow-up of patients of this surgery after 4 years found that 50% felt their pain had improved to various extents, although control patients were not followed up for comparison.[25] If surgery does bring relief of symptoms, patients will mostly experience it within 4 weeks of surgery.[26] However, the studies and surgical methods cited above generally focused on the Alcock’s canal and the area between the sacrotuberous and sacrospinous ligaments as likely sites for entrapment. More recent studies have identified possible entrapment sites anterior to Alcock’s canal.[27] ## References 1. ^ a b Insola, A.; Granata, G.; Padua, L. (Sep 2010). "Alcock canal syndrome due to obturator internus muscle fibrosis". Muscle Nerve. 42 (3): 431–2. doi:10.1002/mus.21735. PMID 20665515. 2. ^ Possover, M. (Apr 2009). "Laparoscopic management of endopelvic etiologies of pudendal pain in 134 consecutive patients". J Urol. 181 (4): 1732–6. doi:10.1016/j.juro.2008.11.096. PMID 19233408. 3. ^ Itza Santos, F.; Salinas, J.; Zarza, D.; Gómez Sancha, F.; Allona Almagro, A. (Jun 2010). "[Update in pudendal nerve entrapment syndrome: an approach anatomic-surgical, diagnostic and therapeutic]". Actas Urol Esp. 34 (6): 500–9. doi:10.1016/s2173-5786(10)70121-9. PMID 20510112. 4. ^ a b c Ramsden, CE.; McDaniel, MC.; Harmon, RL.; Renney, KM.; Faure, A. (Jun 2003). "Pudendal nerve entrapment as source of intractable perineal pain". Am J Phys Med Rehabil. 82 (6): 479–84. doi:10.1097/00002060-200306000-00013. PMID 12820792. 5. ^ a b Durante, JA.; Macintyre, IG. (Dec 2010). "Pudendal nerve entrapment in an Ironman athlete: a case report". J Can Chiropr Assoc. 54 (4): 276–81. PMC 2989401. PMID 21120020. 6. ^ Filler, Aaron G. (2009). "Diagnosis and treatment of pudendal nerve entrapment syndrome subtypes: Imaging, injections, and minimal access surgery". Neurosurgical Focus. 26 (2): E9. doi:10.3171/FOC.2009.26.2.E9. PMID 19323602. 7. ^ a b Stav, K.; Dwyer, PL.; Roberts, L. (Mar 2009). "Pudendal neuralgia. Fact or fiction?". Obstet Gynecol Surv. 64 (3): 190–9. doi:10.1097/ogx.0b013e318193324e. PMID 19238769. 8. ^ Maldonado PA, Chin K, Garcia AA, Corton MM (2015). "Anatomic variations of pudendal nerve within pelvis and pudendal canal: clinical applications". Am. J. Obstet. Gynecol. 213 (5): 727.e1–6. doi:10.1016/j.ajog.2015.06.009. PMID 26070708. 9. ^ a b Labat, JJ.; Riant, T.; Robert, R.; Amarenco, G.; Lefaucheur, JP.; Rigaud, J. (2008). "Diagnostic criteria for pudendal neuralgia by pudendal nerve entrapment (Nantes criteria)". Neurourol Urodyn. 27 (4): 306–10. doi:10.1002/nau.20505. PMID 17828787. 10. ^ Silbert, PL.; Dunne, JW.; Edis, RH.; Stewart-Wynne, EG. (1991). "Bicycling induced pudendal nerve pressure neuropathy". Clin Exp Neurol. 28: 191–6. PMID 1821826. 11. ^ Oberpenning, F.; Roth, S.; Leusmann, DB.; van Ahlen, H.; Hertle, L. (Feb 1994). "The Alcock syndrome: temporary penile insensitivity due to compression of the pudendal nerve within the Alcock canal". J Urol. 151 (2): 423–5. doi:10.1016/s0022-5347(17)34970-4. PMID 8283544. 12. ^ Leibovitch, I.; Mor, Y. (Mar 2005). "The vicious cycling: bicycling related urogenital disorders". Eur Urol. 47 (3): 277–86, discussion 286–7. doi:10.1016/j.eururo.2004.10.024. PMID 15716187. 13. ^ a b c d e "Chronic Perineal Pain Caused by Pudendal Nerve Entrapment: Anatomy and CT-Guided Perineural Injection Technique -- Hough et al. 181 (2): 561 -- American Journal of Roentgenology". www.ajronline.org. Retrieved 2011-01-09. 14. ^ a b Robert, R.; Labat, JJ.; Riant, T.; Louppe, JM.; Hamel, O. (Oct 2009). "[The pudendal nerve: clinical and therapeutic morphogenesis, anatomy, and physiopathology]". Neurochirurgie. 55 (4–5): 463–9. doi:10.1016/j.neuchi.2009.07.004. PMID 19748642. 15. ^ Nickel JC, Berger R, Pontari M (2006). "Changing Paradigms for Chronic Pelvic Pain". Rev Urol. 8 (1): 28–35. PMC 1471766. PMID 16985558. 16. ^ Beco, J.; Climov, D.; Bex, M. (2004). "Pudendal nerve decompression in perineology: a case series". BMC Surg. 4: 15. doi:10.1186/1471-2482-4-15. PMC 529451. PMID 15516268. 17. ^ Shafik, A. (1997). "Role of pudendal canal syndrome in the etiology of fecal incontinence in rectal prolapse". Digestion. 58 (5): 489–93. doi:10.1159/000201488. PMID 9383642. 18. ^ Alevizon, SJ.; Finan, MA. (Oct 1996). "Sacrospinous colpopexy: management of postoperative pudendal nerve entrapment". Obstet Gynecol. 88 (4 Pt 2): 713–5. doi:10.1016/0029-7844(96)00127-5. PMID 8841264. 19. ^ Filler A (October 2009). "MR Neurography and Diffusion Tensor Imaging: Origins, History & Clinical Impact of the first 50,000 cases with an Assessment of Efficacy and Utility in a Prospective 5,000 Patient Study Group". Neurosurgery. 65 (4 Suppl): A29–43. doi:10.1227/01.NEU.0000351279.78110.00. PMC 2924821. PMID 19927075. 20. ^ a b c Rhame, EE.; Levey, KA.; Gharibo, CG. (2009). "Successful treatment of refractory pudendal neuralgia with pulsed radiofrequency". Pain Physician. 12 (3): 633–8. PMID 19461829. 21. ^ Calabrò, RS.; Gervasi, G.; Marino, S.; Mondo, PN.; Bramanti, P. (May 2010). "Misdiagnosed chronic pelvic pain: pudendal neuralgia responding to a novel use of palmitoylethanolamide". Pain Med. 11 (5): 781–4. doi:10.1111/j.1526-4637.2010.00823.x. PMID 20345619. 22. ^ "Pudendal Nerve Entrapment – Department of Neurosurgery – NYU Medical Center, New York, NY". www.med.nyu.edu. Retrieved 2010-12-14. 23. ^ Spinner, RJ. (2006). "Outcomes for peripheral nerve entrapment syndromes" (PDF). Clin Neurosurg. 53: 285–94. PMID 17380764. 24. ^ "European Association of Urology (EAU) - Guidelines". www.uroweb.org. Retrieved 2010-06-16. 25. ^ Robert, R.; Labat, JJ.; Bensignor, M.; Glemain, P.; Deschamps, C.; Raoul, S.; Hamel, O. (Mar 2005). "Decompression and transposition of the pudendal nerve in pudendal neuralgia: a randomized controlled trial and long-term evaluation". Eur Urol. 47 (3): 403–8. doi:10.1016/j.eururo.2004.09.003. PMID 15716208. 26. ^ Filler, AG. (Feb 2009). "Diagnosis and treatment of pudendal nerve entrapment syndrome subtypes: imaging, injections, and minimal access surgery". Neurosurg Focus. 26 (2): E9. doi:10.3171/FOC.2009.26.2.E9. PMID 19323602. 27. ^ Hruby, S. (May 2005). "Anatomy of Pudendal Nerve at Urogenital Diaphragm—New Critical Site for Nerve Entrapment". Urology. 66 (5): 949–952. doi:10.1016/j.urology.2005.05.032. PMID 16286101. ## External links * Pudendal nerve decompression in perineology : a case series * v * t * e Diseases relating to the peripheral nervous system Mononeuropathy Arm median nerve * Carpal tunnel syndrome * Ape hand deformity ulnar nerve * Ulnar nerve entrapment * Froment's sign * Ulnar tunnel syndrome * Ulnar claw radial nerve * Radial neuropathy * Wrist drop * Cheiralgia paresthetica long thoracic nerve * Winged scapula * Backpack palsy Leg lateral cutaneous nerve of thigh * Meralgia paraesthetica tibial nerve * Tarsal tunnel syndrome plantar nerve * Morton's neuroma superior gluteal nerve * Trendelenburg's sign sciatic nerve * Piriformis syndrome Cranial nerves * See Template:Cranial nerve disease Polyneuropathy and Polyradiculoneuropathy HMSN * Charcot–Marie–Tooth disease * Dejerine–Sottas disease * Refsum's disease * Hereditary spastic paraplegia * Hereditary neuropathy with liability to pressure palsy * Familial amyloid neuropathy Autoimmune and demyelinating disease * Guillain–Barré syndrome * Chronic inflammatory demyelinating polyneuropathy Radiculopathy and plexopathy * Brachial plexus injury * Thoracic outlet syndrome * Phantom limb Other * Alcoholic polyneuropathy Other General * Complex regional pain syndrome * Mononeuritis multiplex * Peripheral neuropathy * Neuralgia * Nerve compression syndrome [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Pudendal nerve entrapment	c1997249	3,823	wikipedia	https://en.wikipedia.org/wiki/Pudendal_nerve_entrapment	2021-01-18T18:41:14	{"gard": ["10713"], "mesh": ["D060545"], "umls": ["C1997249"], "orphanet": ["60039"], "wikidata": ["Q1987592"]}
Godel et al. (1978) and Godel and Goodman (1981) described an Iraqi-Jewish family in which a son of each of 5 sisters had retinal dysplasia. It is not clear that this is distinct from retinoschisis (312700) of which congenital falciform fold of the retina may be an expression. In Godel's cases the characteristic ophthalmoscopic finding was an elevated retinal fold emanating from the optic disc, covering the macular area and widening toward the temporal fundus. Partial affection was found in 2 of 5 obligatory heterozygotes: 'paramacular small retinal foldlike structure' in one and 'retinal dysplastic tissue in the upper temporal periphery of the left eye' in the other. Weve (1938) commented on the preponderance of boys with falciform folds of the retina (ablatio falciformis congenita) and suggested that there is an X-linked form. Godel and Goodman (1981) postulated that the disorder in this family was distinct from Norrie disease (310600), since in affected males no clinical findings other than those associated with the eyes could be demonstrated. Moreover, 2 out of the 5 obligatory carrier females showed minimal eye changes, including retinal folds and changes in the stroma of the irides, which are atypical findings for carriers of Norrie disease. However, Ravia et al. (1993) found that the gene for X-linked recessive primary retinal dysplasia showed the same linkage relationships to markers on Xp as does Norrie disease. Thus, it may be allelic. Identification of mutations in the Norrie disease gene will settle the matter. Eyes \- Retinal dysplasia \- Elevated retinal fold from optic disc over macula \- Falciform retinal fold Inheritance \- X-linked \- ? same as retinoschisis \- ? allelic to Norrie disease ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	RETINAL DYSPLASIA, PRIMARY	c3887971	3,824	omim	https://www.omim.org/entry/312550	2019-09-22T16:17:18	{"omim": ["312550"], "orphanet": ["1852"], "synonyms": []}
Hypohidrotic ectodermal dysplasia with immunodeficiency (HED-ID) is a type of HED (see this term) characterized by the malformation of ectodermal structures such as skin, hair, teeth and sweat glands, and associated with immunodeficiency. ## Epidemiology Prevalence is not known. The incidence is approximately 1/250,000 live male births for the X-linked form. Fewer than 10 patients with the autosomal-dominant form have been reported. ## Clinical description The clinical picture is variable. Typical signs of HED may be observed, such as sparse hair (atrichosis/ hypotrichosis), abnormal (e.g. conical) or missing teeth (anodontia/ hypodontia), decreased or absent sudation due to a lack of sweat glands (anhidrosis/ hypohidrosis), and typical facial features (protruding forehead, wrinkles under the eyes, characteristic periorbital hyperpigmentation) which are associated with immunologic defects such as susceptibility to opportunistic infections, hypogammaglobulinemia, impaired antibody response to polysaccharides or impaired NK-cell activity. Many patients fail to thrive. Ectodermal dysplasia-related symptoms of HED-ID, however, tend to be milder than in patients with other forms of HED. The disease can also be associated with osteopetrosis and lymphedema (hypohidrotic ectodermal dysplasia with immunodeficiency, osteopetrosis, lymphedema; see this term). ## Etiology HED-ID is caused by hypomorphic mutations in the coding region of the IKBKG (or NEMO) gene (Xq28) or, less often, mutations in the NFKBIA gene (14q13), both involved in NF-κB activation. ## Genetic counseling Transmission is X-linked recessive in case of IKBKG mutations and autosomal-dominant in case of NFKBIA mutations. Somatic mosaicism seems to occur frequently in HED-ID patients. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Hypohidrotic ectodermal dysplasia with immunodeficiency	c1846006	3,825	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98813	2021-01-23T18:57:34	{"gard": ["9936"], "mesh": ["C536181"], "omim": ["300291", "612132"], "umls": ["C1846006"], "icd-10": ["D82.8"], "synonyms": ["Anhidrotic ectodermal dysplasia with immunodeficiency", "EDA-ID", "HED-ID"]}
A number sign (#) is used with this entry because of evidence that Joubert syndrome-3 (JBTS3) is caused by homozygous mutation in the AHI1 gene (608894) on chromosome 6q23. For a phenotypic description and a discussion of genetic heterogeneity of Joubert syndrome, see JBTS1 (213300). Clinical Features Lagier-Tourenne et al. (2004) described 2 consanguineous families with Joubert syndrome, one Turkish and the other of Swiss origin; the latter was originally described by Boltshauser and Isler (1977). There were 5 affected members in the Turkish family and 2 in the Swiss family. All patients had early hypotonia, molar tooth sign, and cerebellar vermis hypoplasia. Other clinical features included cognitive impairment, neonatal breathing problems, cerebellar ataxia, nystagmus, retinal dystrophy, reduced vision, kyphoscoliosis, and retarded skeletal growth. In a review of patients with JBTS3, Valente et al. (2005) found that multiple central nervous system anomalies often occurred, including polymicrogyria, malformations of the corpus callosum, seizures, and spasticity. In contrast to patients with JBTS1, renal disease, liver disease, and polydactyly had not been reported. Utsch et al. (2006) reported 2 Pakistani brothers, born of consanguineous parents, with JBTS3. Both boys had cerebellar ataxia, developmental delay, nystagmus, oculomotor apraxia. One developed end-stage renal failure by age 16 years due to nephronophthisis. Molecular analysis identified a homozygous mutation in the AHI1 gene (608894.0007). The findings indicated that renal involvement can occur in patients with JBTS3. Mapping By linkage analysis, Lagier-Tourenne et al. (2004) identified a 13.1-cM interval spanning 8.2 Mb between markers D6S1620 and D6S1699 on chromosome 6q23 associated with Joubert syndrome. In the Turkish and Swiss families studied, the lod scores in favor of linkage at zero recombination were 4.1 and 2.3, respectively. Genotype-phenotype studies indicated that, unlike CORS2 (608091), JBTS3 appeared not to be associated with renal dysfunction. Molecular Genetics Ferland et al. (2004) identified a locus associated with Joubert syndrome on 6q23.2-q23.3 and found 3 deleterious mutations in the gene encoding Abelson helper integration site-1 (AHI1; 608894.0001-608894.0003). AHI1 was found to be most highly expressed in brain, particularly in neurons that give rise to the crossing axons of the corticospinal tract and superior cerebellar peduncles. Comparative genetic analysis of AHI1 indicated that it has undergone positive evolutionary selection along the human lineage. Therefore, changes in AHI1 may have been important in the evolution of human-specific motor behaviors. In affected members of 3 consanguineous families with Joubert syndrome, some with cortical polymicrogyria, Dixon-Salazar et al. (2004) identified 1 missense and 2 frameshift mutations in the AHI1 gene. Using a combination of haplotype analysis and gene sequencing, Parisi et al. (2006) screened 117 probands with Joubert syndrome for mutations in the AHI1 gene and identified a total of 15 novel and 5 previously identified mutations in 19 families, including nonsense, missense, splice site, and insertion mutations. Fourteen of the mutation-positive families were consanguineous, but no single founder mutation was apparent. In addition to the molar tooth sign, retinal dystrophy was present in 12 families; however, no individuals exhibited variable signs of Joubert syndrome such as polydactyly, encephalocele, colobomas, or liver fibrosis. Valente et al. (2006) identified 15 different mutations (see, e.g., 608894.0004-608894.0006) in the AHI1 gene in 11 patients from 10 families with Joubert syndrome. These patients accounted for 7.3% of 137 probands with the molar tooth sign and Joubert-related disorders. A phenotype-specific group of Joubert syndrome plus retinopathy had an AHI1 mutation frequency was 21.7% (5 of 23 probands). Clinical analysis indicated that AHI1 mutations were not associated with kidney or liver changes. Retinal abnormalities ranged from retinitis pigmentosa to blindness. In 2 Egyptian patients with JBTS3 originally reported by Valente et al. (2006), Elsayed et al. (2015) found that the causative AHI1 mutation was a homozygous missense change (S761L; 608894.0011) rather than a C-terminal deletion (c.3263delGG; 608894.0004). The missense mutation was found by homozygosity mapping and whole-exome sequencing. Functional studies of the S761L variant were not performed, but structural modeling predicted that it would cause detrimental structural changes. Expression of the c.3263delGG mutation in zebrafish did not cause any abnormalities, suggesting that the C-terminal SH3 domain of AHI1 is not required for normal development. By homozygosity mapping followed by exon enrichment and next-generation sequencing in 136 consanguineous families (over 90% Iranian and less than 10% Turkish or Arabic) segregating syndromic or nonsyndromic forms of autosomal recessive intellectual disability, Najmabadi et al. (2011) identified homozygosity for a nonsense and a missense mutation in the AHI1 gene in affected members of 2 families with Joubert syndrome-3 (608894.0008 and 608894.0009, respectively). Genotype/Phenotype Correlations Elsayed et al. (2015) determined that 2 variants in the AHI1 gene resulting in truncated proteins at the C terminus and lacking the SH3 domain (c.3263delGG, 608894.0004 and c.3196C-T) did not cause any abnormalities when expressed in zebrafish. In contrast, morpholinos against the N-terminal domain produced a ciliopathy phenotype in zebrafish. In addition, Elsayed et al. (2015) reported an unaffected member of a family segregating nonsyndromic hearing loss who carried the c.3196C-T variant in homozygosity. The findings indicated that the C-terminal SH3 domain of AHI1 is not required for normal development. Elsayed et al. (2015) noted the implications for assessing variants in AHI1 that are part of preconception screening panels, and emphasized that even truncating variants identified in known disease genes must undergo stringent functional and segregation analysis before being classified as pathogenic. INHERITANCE \- Autosomal recessive HEAD & NECK Face \- High-rounded eyebrows Ears \- Low-set ears Eyes \- Abnormal eye movements \- Oculomotor apraxia \- Nystagmus \- Retinal dystrophy \- Pigmentary retinopathy \- Impaired vision \- Abnormal electroretinogram (ERG) \- Ptosis \- Epicanthal folds, mild Nose \- Broad nasal bridge \- Anteverted nostrils Mouth \- Triangular-shaped, open mouth RESPIRATORY \- Neonatal breathing dysregulation \- Hyperpnea, episodic \- Tachypnea, episodic \- Central apnea GENITOURINARY Kidneys \- Nephronophthisis (less common) \- End-stage renal disease NEUROLOGIC Central Nervous System \- Hypotonia \- Ataxia \- Delayed walking \- Delayed motor development \- Mental retardation \- Impaired expressive speech \- Lack of verbal communication \- Cerebellar vermis hypoplasia \- 'Molar tooth sign' on MRI \- Deep posterior interpeduncular fossa \- Thick and elongated superior cerebellar peduncles MISCELLANEOUS \- Genetic heterogeneity MOLECULAR BASIS \- Caused by mutation in the abelson helper integration site 1 gene (AHI1, 608894.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	JOUBERT SYNDROME 3	c1837713	3,826	omim	https://www.omim.org/entry/608629	2019-09-22T16:07:36	{"doid": ["0110998"], "mesh": ["C536295"], "omim": ["608629"], "orphanet": ["220493"], "synonyms": ["JS-O", "Joubert syndrome with retinopathy"], "genereviews": ["NBK1325"]}
Pleuropulmonary blastoma Other namesPulmonary blastoma SpecialtyOncology Pleuropulmonary blastoma (PPB) is a rare cancer originating in the lung or pleural cavity. It occurs most often in infants and young children[1] but also has been reported in adults.[2] In a retrospective review of 204 children with lung tumors, pleuropulmonary blastoma and carcinoid tumor were the most common primary tumors (83% of the 204 children had secondary tumors spread from cancers elsewhere in the body).[1] Pleuropulmonary blastoma is regarded as malignant. The male:female ratio is approximately one. ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Diagnosis * 3.1 Types * 4 Treatment * 5 History * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] Symptoms may include coughing, an upper respiratory tract infection, shortness of breath, and chest pain. These symptoms are very non-specific, and can be caused by other types of tumor in the lung or mediastinum more generally, and by other conditions. Imaging (X-ray, CT, MRI) may be used to determine the presence and precise location of a tumor, but not a specific diagnosis of PPB or other tumor.[3] Doctors are unable to tell if a child has PPB right away, and not upper respiratory tract infection, until more test are taken and they show that there is no infection. Another symptom is pneumothorax.[citation needed] ## Genetics[edit] A number of PPBs have shown trisomy 8 (17 out of 23 cases studied per the PPB registry). Trisomy 2 and p53 mutations/deletions have also been described.[citation needed] An association with mutations in the DICER1 gene has been reported.[4] Mutations in this gene are found in 2/3 cases. ## Diagnosis[edit] The most common way to test someone for PPB is to take a biopsy. Other tests like x-rays, CAT scans, and MRI's can suggest that cancer is present, but only an examination of a piece of the tumor can make a definite diagnosis.[citation needed] ### Types[edit] Pleuropulmonary blastoma is classified into 3 types: * Type I is multicystic * Type II shows thickening areas (nodules) within this cystic lesion * Type III shows solid masses. Type I PPB is made up of mostly cysts, and may be hard to distinguish from benign lung cysts, and there is some evidence that not all type I PPB will progress to types II and III.[5] Types II and III are aggressive, and cerebral metastasis is more frequent in PPB than in other childhood sarcomas.[6] ## Treatment[edit] Treating PPB depends on the size and location of the tumor, whether the cancer has spread, and the child's overall health. Surgery is the main treatment for PPB. The main goal of surgery is to remove the tumor. If the tumor is too large to be completely removed, or if it's not possible to completely remove the tumor, surgery may be performed after chemotherapy. Because PPB can return after treatment, regular screening for possible recurrence should continue for 48 to 60 months, after diagnosis.[citation needed] ## History[edit] Pleuropulmonary blastoma was first described in 1988.[7] An international registry has been established.[5] ## See also[edit] * Lung cancer ## References[edit] 1. ^ a b Dishop MK, Kuruvilla S (July 2008). "Primary and metastatic lung tumors in the pediatric population: a review and 25-year experience at a large children's hospital". Arch. Pathol. Lab. Med. 132 (7): 1079–103. doi:10.1043/1543-2165(2008)132[1079:PAMLTI]2.0.CO;2 (inactive 2021-01-16). PMID 18605764.CS1 maint: DOI inactive as of January 2021 (link) 2. ^ Indolfi P, Casale F, Carli M, et al. (September 2000). "Pleuropulmonary blastoma: management and prognosis of 11 cases". Cancer. 89 (6): 1396–401. doi:10.1002/1097-0142(20000915)89:6<1396::AID-CNCR25>3.0.CO;2-2. PMID 11002236. 3. ^ Cakir O, Topal U, Bayram AS, Tolunay S (March 2005). "Sarcomas: rare primary malignant tumors of the thorax". Diagn Interv Radiol. 11 (1): 23–7. PMID 15795839. 4. ^ Cai S, Wang X, Zhao W, Fu L, Ma X, Peng X (2017) DICER1 mutations in twelve Chinese patients with pleuropulmonary blastoma. Sci China Life Sci doi: 10.1007/s11427-017-9081-x 5. ^ a b Hill DA, Jarzembowski JA, Priest JR, Williams G, Schoettler P, Dehner LP (February 2008). "Type I pleuropulmonary blastoma: pathology and biology study of 51 cases from the international pleuropulmonary blastoma registry". Am. J. Surg. Pathol. 32 (2): 282–95. doi:10.1097/PAS.0b013e3181484165. PMID 18223332. S2CID 3193037. 6. ^ Priest JR, Magnuson J, Williams GM, Abromowitch M, Byrd R, Sprinz P, Finkelstein M, Moertel CL, Hill DA (September 2007). "Cerebral metastasis and other central nervous system complications of pleuropulmonary blastoma". Pediatr Blood Cancer. 49 (3): 266–73. doi:10.1002/pbc.20937. PMID 16807914. S2CID 20486633. 7. ^ Manivel JC, Priest JR, Watterson J, et al. (October 1988). "Pleuropulmonary blastoma. The so-called pulmonary blastoma of childhood". Cancer. 62 (8): 1516–26. doi:10.1002/1097-0142(19881015)62:8<1516::AID-CNCR2820620812>3.0.CO;2-3. PMID 3048630. ## External links[edit] Classification D * ICD-10: C34.1 C34.2 C34.3 C34.9 * ICD-O: M8973/3 * OMIM: 601200 * MeSH: C537516 External resources * Orphanet: 64742 * v * t * e Connective/soft tissue tumors and sarcomas Not otherwise specified * Soft-tissue sarcoma * Desmoplastic small-round-cell tumor Connective tissue neoplasm Fibromatous Fibroma/fibrosarcoma: * Dermatofibrosarcoma protuberans * Desmoplastic fibroma Fibroma/fibromatosis: * Aggressive infantile fibromatosis * Aponeurotic fibroma * Collagenous fibroma * Diffuse infantile fibromatosis * Familial myxovascular fibromas * Fibroma of tendon sheath * Fibromatosis colli * Infantile digital fibromatosis * Juvenile hyaline fibromatosis * Plantar fibromatosis * Pleomorphic fibroma * Oral submucous fibrosis Histiocytoma/histiocytic sarcoma: * Benign fibrous histiocytoma * Malignant fibrous histiocytoma * Atypical fibroxanthoma * Solitary fibrous tumor Myxomatous * Myxoma/myxosarcoma * Cutaneous myxoma * Superficial acral fibromyxoma * Angiomyxoma * Ossifying fibromyxoid tumour Fibroepithelial * Brenner tumour * Fibroadenoma * Phyllodes tumor Synovial-like * Synovial sarcoma * Clear-cell sarcoma Lipomatous * Lipoma/liposarcoma * Myelolipoma * Myxoid liposarcoma * PEComa * Angiomyolipoma * Chondroid lipoma * Intradermal spindle cell lipoma * Pleomorphic lipoma * Lipoblastomatosis * Spindle cell lipoma * Hibernoma Myomatous general: * Myoma/myosarcoma smooth muscle: * Leiomyoma/leiomyosarcoma skeletal muscle: * Rhabdomyoma/rhabdomyosarcoma: Embryonal rhabdomyosarcoma * Sarcoma botryoides * Alveolar rhabdomyosarcoma * Leiomyoma * Angioleiomyoma * Angiolipoleiomyoma * Genital leiomyoma * Leiomyosarcoma * Multiple cutaneous and uterine leiomyomatosis syndrome * Multiple cutaneous leiomyoma * Neural fibrolipoma * Solitary cutaneous leiomyoma * STUMP Complex mixed and stromal * Adenomyoma * Pleomorphic adenoma * Mixed Müllerian tumor * Mesoblastic nephroma * Wilms' tumor * Malignant rhabdoid tumour * Clear-cell sarcoma of the kidney * Hepatoblastoma * Pancreatoblastoma * Carcinosarcoma Mesothelial * Mesothelioma * Adenomatoid tumor * v * t * e Cancer involving the respiratory tract Upper RT Nasal cavity Esthesioneuroblastoma Nasopharynx Nasopharyngeal carcinoma Nasopharyngeal angiofibroma Larynx Laryngeal cancer Laryngeal papillomatosis Lower RT Trachea * Tracheal tumor Lung Non-small-cell lung carcinoma * Squamous-cell carcinoma * Adenocarcinoma (Mucinous cystadenocarcinoma) * Large-cell lung carcinoma * Rhabdoid carcinoma * Sarcomatoid carcinoma * Carcinoid * Salivary gland–like carcinoma * Adenosquamous carcinoma * Papillary adenocarcinoma * Giant-cell carcinoma Small-cell carcinoma * Combined small-cell carcinoma Non-carcinoma * Sarcoma * Lymphoma * Immature teratoma * Melanoma By location * Pancoast tumor * Solitary pulmonary nodule * Central lung * Peripheral lung * Bronchial leiomyoma Pleura * Mesothelioma * Malignant solitary fibrous tumor [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Pleuropulmonary blastoma	c1266144	3,827	wikipedia	https://en.wikipedia.org/wiki/Pleuropulmonary_blastoma	2021-01-18T18:30:05	{"gard": ["8757"], "mesh": ["C537516"], "umls": ["CN072455"], "orphanet": ["284343", "64742"], "synonyms": ["DICER1 syndrome", "PPB familial tumor susceptibility syndrome", "PPBFTDS", "Pleuro-pulmonary blastoma familial tumor susceptibility syndrome"], "wikidata": ["Q7204815"]}
Psychiatric factitious disorder For cases of feigned illness not driven by a psychiatric disorder, see Malingering. Factitious disorder imposed on self Other namesMunchausen syndrome[1] SpecialtyPsychology, Psychiatry Factitious disorder imposed on self, also known as Munchausen syndrome, is a factitious disorder wherein those affected feign disease, illness, or psychological trauma to draw attention, sympathy, or reassurance to themselves. Munchausen syndrome fits within the subclass of factitious disorder with predominantly physical signs and symptoms, but patients also have a history of recurrent hospitalization, travelling, and dramatic, extremely improbable tales of their past experiences.[2] The condition derives its name from the fictional character Baron Munchausen. Factitious disorder imposed on self is related to factitious disorder imposed on another, which refers to the abuse of another person, typically a child, in order to seek attention or sympathy for the abuser. This drive to create symptoms for the victim can result in unnecessary and costly diagnostic or corrective procedures.[3] ## Contents * 1 Signs and symptoms * 2 Diagnosis * 3 Treatment * 4 History * 5 Munchausen by Internet * 6 See also * 7 References * 8 Bibliography * 9 External links ## Signs and symptoms[edit] In factitious disorder imposed on self, the affected person exaggerates or creates symptoms of illnesses in themselves to gain examination, treatment, attention, sympathy or comfort from medical personnel. It often involves elements of victim playing and attention seeking. In some extreme cases, people suffering from Munchausen syndrome are highly knowledgeable about the practice of medicine and are able to produce symptoms that result in lengthy and costly medical analysis, prolonged hospital stays, and unnecessary operations. The role of patient is a familiar and comforting one, and it fills a psychological need in people with this syndrome. This disorder is distinct from hypochondriasis and other somatoform disorders in that those with the latter do not intentionally produce their somatic symptoms.[4] Factitious disorder is distinct from malingering in that people with factitious disorder imposed on self don't fabricate symptoms for material gain such as financial compensation, absence from work, or access to drugs. The exact cause of factitious disorder is not known, but researchers believe both biological and psychological factors play a role in the development of this disorder. Risk factors for developing factitious disorder may include childhood traumas, growing up with parents/caretakers who were emotionally unavailable due to illness or emotional problems, a serious illness as a child, failed aspirations to work in the medical field, personality disorders, and low self-esteem. While there are no reliable statistics regarding the number of people in the United States who suffer from factitious disorder, FD is believed to be most common in mothers having the above risk factors. Those with a history of working in healthcare are also at greater risk of developing it.[5] Arrhythmogenic Munchausen syndrome describes individuals who simulate or stimulate cardiac arrhythmias to gain medical attention.[6] A similar behavior called factitious disorder imposed on another has been documented in the parent or guardian of a child. The adult ensures that his or her child will experience some medical affliction, therefore compelling the child to suffer through treatments and spend a significant portion during youth in hospitals. Furthermore, a disease may actually be initiated in the child by the parent or guardian. This condition is considered distinct from Munchausen syndrome. There is growing consensus in the pediatric community that this disorder should be renamed "medical abuse" to highlight the harm caused by the deception and to make it less likely that a perpetrator can use a psychiatric defense when harm is done.[7] ## Diagnosis[edit] Due to the behaviors involved, diagnosing factitious disorder is very difficult. If the healthcare provider finds no physical reason for the symptoms, he or she may refer the person to a psychiatrist or psychologist (mental health professionals who are specially trained to diagnose and treat mental illnesses). Psychiatrists and psychologists use thorough history, physical examinations, laboratory tests, imagery, and psychological testing to evaluate a person for physical and mental conditions. Once the person's history has been thoroughly evaluated, diagnosing factitious disorder imposed on self requires a clinical assessment.[8] Clinicians should be aware that those presenting with symptoms (or persons reporting for that person) may exaggerate, and caution should be taken to ensure there is evidence for a diagnosis.[8] Lab tests may be required, including complete blood count (CBC), urine toxicology, drug levels from blood, cultures, coagulation tests, assays for thyroid function, or DNA typing. In some cases CT scan, magnetic resonance imaging, psychological testing, electroencephalography, or electrocardiography may also be employed.[8] A summary of more common and reported cases of factitious disorder (Munchausen syndrome), and the laboratory tests used to differentiate these from physical disease is provided below:[9] Disease Mimicked Method of Imitation Laboratory/Diagnostic Confirmation Bartter syndrome * Surreptitious intake of diuretics * Self-induced vomiting * High performance liquid chromatography (HPLC) analysis of urine * Urine chloride analysis Catecholamine-secreting tumor Injection of epinephrine into urine or blood stream Adjunct analysis of increased Chromogranin A Cushing’s syndrome Surreptitious steroid administration HPLC to differentiate endogenous and exogenous steroids Hyperthyroid Surreptitious thyroxine administration Blood tests for free T4 and thyroid stimulating hormone Hypoglycaemia Exogenous insulin or insulin secretagogues Simultaneous blood analysis of insulin, C-peptide, proinsulin, and insulin secretagogues Sodium imbalance Intake large quantities of salt Measure fractional sodium excretion to differentiate intentional salt overload from dehydration. Chronic diarrhea * Watered down stool samples * Laxative abuse * Measure fecal osmolarity * Urine analysis to screen for laxatives using gas chromatography or mass spectrometry Induced vomiting Although many alternatives possible, ipecacuanha ingestion HPLC measurement of serum or urine for elevated creatine kinase, transaminases and ipecacuanha Proteinuria Egg protein injection into bladder, albumin (protein) addition to urine samples Urine protein electrophoresis analysis Haematuria Blood introduction to urine samples, deliberate trauma to the urethra Imaging to rule out insertion of a foreign body, monitor sample collection, analysis of red blood cell shape in samples There are several criteria that together may point to factitious disorder, including frequent hospitalizations, knowledge of several illnesses, frequently requesting medication such as pain killers, openness to extensive surgery, few or no visitors during hospitalizations, and exaggerated or fabricated stories about several medical problems. Factitious disorder should not be confused with hypochondria, as people with factitious disorder syndrome do not really believe they are sick; they only want to be sick, and thus fabricate the symptoms of an illness. It is also not the same as pretending to be sick for personal benefit such as being excused from work or school.[10] People may fake their symptoms in multiple ways. Other than making up past medical histories and faking illnesses, people might inflict harm on themselves by consuming laxatives or other substances, self-inflicting injury to induce bleeding, and altering laboratory samples".[11] Many of these conditions do not have clearly observable or diagnostic symptoms and sometimes the syndrome will go undetected because patients will fabricate identities when visiting the hospital several times. Factitious disorder has several complications, as these people will go to great lengths to fake their illness. Severe health problems, serious injuries, loss of limbs or organs, and even death are possible complications.[medical citation needed] ## Treatment[edit] Because there is uncertainty in treating suspected factitious disorder imposed on self, some advocate that health care providers first explicitly rule out the possibility that the person has another early-stage disease.[12] Then they may take a careful history and seek medical records to look for early deprivation, childhood abuse, or mental illness.[citation needed][8] If a person is at risk to themself, psychiatric hospitalization may be initiated.[13] Healthcare providers may consider working with mental health specialists to help treat the underlying mood or disorder as well as to avoid countertransference.[14] Therapeutic and medical treatment may center on the underlying psychiatric disorder: a mood disorder, an anxiety disorder, or borderline personality disorder. The patient's prognosis depends upon the category under which the underlying disorder falls; depression and anxiety, for example, generally respond well to medication or cognitive behavioral therapy, whereas borderline personality disorder, like all personality disorders, is presumed to be pervasive and more stable over time,[15] and thus offers a worse prognosis. People affected may have multiple scars on their abdomen due to repeated "emergency" operations.[16] ## History[edit] The name "Munchausen syndrome" derives from Baron Munchausen, a literary character loosely based on the German nobleman Hieronymus Karl Friedrich, Freiherr von Münchhausen (1720–1797). The historical baron became a well-known storyteller in the late 18th century for entertaining dinner guests with tales about his adventures during the Russo-Turkish War. In 1785 German-born writer and con artist Rudolf Erich Raspe anonymously published a book in which a heavily fictionalized version of "Baron Munchausen" tells many fantastic and impossible stories about himself. Raspe's Munchausen became a sensation, establishing a literary exemplar of a bombastic liar or exaggerator.[17][18] In 1951, Richard Asher was the first to describe a pattern of self-harm, wherein individuals fabricated histories, signs, and symptoms of illness. Remembering Baron Munchausen, Asher named this condition Munchausen's Syndrome in his article in The Lancet in February 1951,[19] quoted in his obituary in the British Medical Journal: > "Here is described a common syndrome which most doctors have seen, but about which little has been written. Like the famous Baron von Munchausen, the persons affected have always travelled widely; and their stories, like those attributed to him, are both dramatic and untruthful. Accordingly the syndrome is respectfully dedicated to the Baron, and named after him." > > — British Medical Journal, R.A.J. Asher, M.D., F.R.C.P.[20] Asher's nomenclature sparked some controversy, with medical authorities debating the appropriateness of the name for about fifty years. While Asher was praised for bringing cases of factitious disorder to light, participants in the debate objected variously that a literary allusion was inappropriate given the seriousness of the disease; that its use of the anglicized spelling "Munchausen" showed poor form; that the name linked the disease with the real-life Münchhausen, who did not have it; and that the name's connection to works of humor and fantasy, and to the essentially ridiculous character of the fictional Baron Munchausen, was disrespectful to patients suffering from the disorder.[21] Originally, this term was used for all factitious disorders. Now, however, in the DSM-5, "Munchausen syndrome" and "Munchausen by proxy" have been replaced with "factitious disorder" and "factitious disorder by proxy" respectively. ## Munchausen by Internet[edit] Munchausen by Internet is a term describing the pattern of behavior in factitious disorder imposed on self, wherein those affected feign illnesses in online venues. It has been described in medical literature as a manifestation of factitious disorder imposed on self.[22] Reports of users who deceive Internet forum participants by portraying themselves as gravely ill or as victims of violence first appeared in the 1990s due to the relative newness of Internet communications. The specific internet pattern was named "Münchausen by Internet" in 1998 by psychiatrist Marc Feldman. [22] People may attempt to gain sympathy from a group whose sole reason for existence is to support others. Some have speculated that Health care professionals, with their limited time, greater medical knowledge, and tendency to be more skeptical in their diagnoses, may be less likely to provide that support.[22][23][24] In an article published in The Guardian, Steve Jones, speculated that the anonymity of the Internet impedes people's abilities to realize when someone is lying.[25] Online interaction has only been possible since the 1980s, steadily growing over the years.[26][27][28] When discovered, forum members are frequently banned from some online forums. Because no money is exchanged and laws are rarely broken, there is little legal recourse to take upon discovery of someone faking illness.[29] Such dramatic situations can polarize online communities. Members may feel ashamed for believing elaborate lies, while others remain staunch supporters. [22][30] Feldman admits that an element of sadism may be evident in some of the more egregious abuses of trust.[31][23][32][26] Other perpetrators react by issuing general accusations of dishonesty to everyone, following the exposure of such fabrications. The support groups themselves often bar discussion about the fraudulent perpetrator, in order to avoid further argument and negativity. Many forums do not recover, often splintering or shutting down.[23][32] In 2004, members of the blog hosting service LiveJournal established a forum dedicated to investigating cases of members of online communities dying—sometimes while online. New Zealand PC World Magazine called Munchausen by Internet "cybermunch", and those who posed online "cybermunchers".[33] In 2007 The LiveJournal forum reported that, of the deaths reported to them, about 10% were real.[34] ## See also[edit] * Psychiatry portal * Hypochondriasis * Psychosomatic illness * Sickened, an autobiography by Julie Gregory ## References[edit] 1. ^ Ray, William J. (2016). Abnormal Psychology. SAGE Publications. p. PT794. ISBN 9781506333373. 2. ^ Kay, Jerald; Tasman, Allan (2006). Essentials of psychiatry. Hoboken, New Jersey: John Wiley & Sons, Ltd. p. 680. ISBN 978-0-470-01854-5. 3. ^ Huffman, Jeffrey C.; Stern, Theodore A. (2003). "The diagnosis and treatment of Munchausen's syndrome". General Hospital Psychiatry. Amsterdam, Netherlands: Elsevier. 25 (5): 358–63. doi:10.1016/S0163-8343(03)00061-6. PMID 12972228. 4. ^ Sadock, Benjamin J.; Sadock, Virginia A., eds. (15 January 2000). Kaplan & Sadock's Comprehensive Textbook of Psychiatry (2 Volume Set) (7th ed.). Philadelphia, Pennsylvania: Lippincott Williams & Wilkins. p. 3172. ISBN 978-0683301281. 5. ^ Repper, John (February 1995). "Münchausen syndrome by proxy in health care workers". Journal of Advanced Nursing. Hoboken, New Jersey: John Wiley and Sons. 21 (2): 299–304. doi:10.1111/j.1365-2648.1995.tb02526.x. ISSN 0309-2402. PMID 7714287. 6. ^ Vaglio, Jeffrey C.; Schoenhard, JA; Saavedra, PJ; Williams, SR; Raj, SR (2010). "Arrhythmogenic Munchausen syndrome culminating in caffeine-induced ventricular tachycardia". Journal of Electrocardiology. London, England: Churchill Livingstone. 44 (2): 229–31. doi:10.1016/j.jelectrocard.2010.08.006. PMID 20888004. 7. ^ Stirling J (2007). "Beyond Munchausen syndrome by proxy: identification and treatment of child abuse in a medical setting". Pediatrics. 119 (5): 1026–30. doi:10.1542/peds.2007-0563. PMID 17473106. 8. ^ a b c d Brannon, Guy E. (11 November 2015). "Factitious Disorder Imposed on Another: Practice Essentials, Background, Pathophysiology". Medscape. 9. ^ Kinns, H; Housley, D; Freedman, DB (May 2013). "Munchausen syndrome and factitious disorder: the role of the laboratory in its detection and diagnosis". Annals of Clinical Biochemistry. 50 (Pt 3): 194–203. doi:10.1177/0004563212473280. PMID 23592802. 10. ^ Worley, Courtney B.; Feldman, Marc D.; Hamilton, James C. (30 October 2009). "The Case of Factitious Disorder Versus Malingering". Psychiatric Times. Cranbury, New Jersey: MJH Associates. 11. ^ Kinns, H; Housley, D; Freedman, DB (May 2013). "Munchausen syndrome and factitious disorder: the role of the laboratory in its detection and diagnosis". Annals of Clinical Biochemistry. 50 (Pt 3): 194–203. doi:10.1177/0004563212473280. PMID 23592802. 12. ^ Bursztajn, H; Feinbloom, RI; Hamm, RM; Brodsky, A (1981). Medical Choices, medical chances: How patients, families and physicians can cope with uncertainty. New York: Delacourte/Lawrence.[page needed] 13. ^ Johnson, BR; Harrison, JA (2000). "Suspected Munchausen's syndrome and civil commitment". The Journal of the American Academy of Psychiatry and the Law. 28 (1): 74–6. PMID 10774844. 14. ^ Elder W, Coletsos IC, Bursztajn HJ. Factitious Disorder/Munchhausen Syndrome. The 5-Minute Clinical Consult. 18th Edition. 2010. Editor. Domino, F.J. Wolters Kluwer/Lippincott. Philadelphia.[page needed] 15. ^ Davison, Gerald C.; Blankstein, Kirk R.; Flett, Gordon L.; Neale, John M. (2008). Abnormal Psychology (3rd Canadian ed.). Mississauga: John Wiley & Sons Canada. p. 412. ISBN 978-0-470-84072-6. 16. ^ Giannini, A. James; Black, Henry Richard; Goettsche, Roger L. (1978). Psychiatric, Psychogenic and Somatopsychic Disorders Handbook. New Hyde Park, NY: Medical Examination Publishing. pp. 194–5. ISBN 978-0-87488-596-5. 17. ^ McCoy, Monica L.; Keen, Stefanie M. (2013). Child Abuse and Neglect: Second Edition. Psychology Press. p. 210. ISBN 978-1136322877. 18. ^ Olry, Regis (June 2002). "Baron Munchhausen and the Syndrome Which Bears His Name: History of an Endearing Personage and of a Strange Mental Disorder" (PDF). Vesalius. 8 (1): 53–7. PMID 12422889. 19. ^ Asher, Richard (1951). "Munchausen's Syndrome". The Lancet. 257 (6650): 339–41. doi:10.1016/S0140-6736(51)92313-6. PMID 14805062. 20. ^ Atthili, Lombe (1873). "Reports of Societies". BMJ. 2 (665): 388. doi:10.1136/bmj.2.665.388. JSTOR 25235514. S2CID 220136795. 21. ^ Fisher, Jill A. (2006). "Investigating the Barons: Narrative and nomenclature in Munchausen syndrome". Perspectives in Biology and Medicine. 49 (2): 250–62. doi:10.1353/pbm.2006.0024. PMID 16702708. S2CID 12418075. 22. ^ a b c d Feldman MD (July 2000). "Munchausen by Internet: detecting factitious illness and crisis on the Internet". South. Med. J. 93 (7): 669–72. doi:10.1097/00007611-200093070-00006. PMID 10923952. 23. ^ a b c Shreve, Jenn (June 6, 2001). "They Think They Feel Your Pain", Wired.com. Retrieved on July 28, 2009. 24. ^ Stephenson, Joan (21 October 1998). "Patient Pretenders Weave Tangled "Web" of Deceit". Journal of the American Medical Association. 280 (15): 1297. PMID 9794296. Archived from the original on 15 December 2004. Retrieved 28 July 2009. 25. ^ Jones, Steve Computer-Mediated Communication and Community: Introduction Archived 1999-08-24 at Archive.today: Introductory chapter to CyberSociety (1995), Sage Publications. Retrieved on August 16, 2009. 26. ^ a b Joinson Adam, Dietz-Uhler Beth (2002). "Explanations for the Perpetration of and Reactions to Deception in a Virtual Community". Social Science Computer Review. 20 (3): 275–289. doi:10.1177/08939302020003005. 27. ^ See also Danet, B., Ruedenberg, L., & Rosenbaum-Tamari, Y. (1998). " 'Hmmm ... Where’s that smoke coming from?' Writing, Play and Performance on Internet Relay Chat. In F. Sudweeks, M. McLaughlin, & S. Rafaeli (Eds.), Network and Netplay: Virtual Groups on the Internet (pp. 41-76). Cambridge, MA: MIT Press. 28. ^ Caspi Avner, Gorsky Paul (2006). "Online Deception: Prevalence, Motivation, and Emotion". CyberPsychology & Behavior. 9 (1): 54–59. doi:10.1089/cpb.2006.9.54. PMID 16497118. 29. ^ Feldman Marc, Peychers M.E. (2007). "Legal Issues Surrounding the Exposure of 'Munchausen by Internet'". Psychosomatics. 48 (5): 451–452. doi:10.1176/appi.psy.48.5.451-a. PMID 17878508. 30. ^ Kruse, Michael (February 28, 2010). "Death and Betrayal in Chat Room", The St. Petersburg Times (Florida), p. 1A. 31. ^ Swains, Howard (March 25, 2009). "Q&A: Munchausen by Internet" Archived 2010-01-10 at the Wayback Machine, Wired.com. Retrieved on July 28, 2009. 32. ^ a b Russo, Francine (26 June 2001). "Cybersickness: Munchausen by Internet Breeds a Generation of Fakers". The Village Voice. Archived from the original on 1 December 2008. 33. ^ Todd, Belinda (October 21, 2002)."Faking It" Archived 2011-07-17 at the Wayback Machine, New Zealand PC World Magazine. Retrieved on July 29, 2009. 34. ^ Swains, Howard (March 5, 2007). "Fake deaths thriving: Online tragedy can be greatly exaggerated", The Gazette (Montreal), p. D1. ## Bibliography[edit] * Feldman, Marc (2004). Playing sick?: untangling the web of Munchausen syndrome, Munchausen by proxy, malingering & factitious disorder. Philadelphia: Brunner-Routledge. ISBN 978-0-415-94934-7. * Fisher JA (2006). "Playing patient, playing doctor: Munchausen syndrome, clinical S/M, and ruptures of medical power". The Journal of Medical Humanities. 27 (3): 135–49. doi:10.1007/s10912-006-9014-9. PMID 16817003. S2CID 40739963. * Fisher JA (2006). "Investigating the Barons: narrative and nomenclature in Munchausen syndrome". Perspect. Biol. Med. 49 (2): 250–62. doi:10.1353/pbm.2006.0024. PMID 16702708. S2CID 12418075. * Friedel, Robert O., MD (4 August 2004). Borderline Personality Disorder Demystified. pp. 9–10. ISBN 978-1-56924-456-2.CS1 maint: multiple names: authors list (link) * Davidson, G.; et al. (2008). Abnormal Psychology - 3rd Canadian Edition. Mississauga: John Wiley & Sons Canada, Ltd. p. 412. ISBN 978-0-470-84072-6. * Prasad, A.; Oswald, A. G. (1985). "Munchausen's syndrome: an annotation". Acta Psychiatrica Scandinavica. 72 (4): 319–22. doi:10.1111/j.1600-0447.1985.tb02615.x. PMID 4072733. * Leila Schneps and Coralie Colmez (2013). "[Chapter 1:] Math error number 1: multiplying non-independent probabilities. The case of Sally Clark: motherhood under attack". Math on trial. How numbers get used and abused in the courtroom. Basic Books. ISBN 978-0-465-03292-1. * Staff, Mayo Clinic (13 May 2011). "Munchausen syndrome". Mayo Foundation for Medical Education and Research. Retrieved 11 April 2013. ## External links[edit] Look up factitious disorder imposed on self in Wiktionary, the free dictionary. * Article in Discover magazine, July 1993, by Abigail Zuger Classification D * ICD-10: F68.1 * ICD-9-CM: 301.51 * MeSH: D009110 * DiseasesDB: 8459 External resources * eMedicine: med/3543 emerg/322 emerg/830 * v * t * e Mental and behavioral disorders Adult personality and behavior Gender dysphoria * Ego-dystonic sexual orientation * Paraphilia * Fetishism * Voyeurism * Sexual maturation disorder * Sexual relationship disorder Other * Factitious disorder * Munchausen syndrome * Intermittent explosive disorder * Dermatillomania * Kleptomania * Pyromania * Trichotillomania * Personality disorder Childhood and learning Emotional and behavioral * ADHD * Conduct disorder * ODD * Emotional and behavioral disorders * Separation anxiety disorder * Movement disorders * Stereotypic * Social functioning * DAD * RAD * Selective mutism * Speech * Stuttering * Cluttering * Tic disorder * Tourette syndrome Intellectual disability * X-linked intellectual disability * Lujan–Fryns syndrome Psychological development (developmental disabilities) * Pervasive * Specific Mood (affective) * Bipolar * Bipolar I * Bipolar II * Bipolar NOS * Cyclothymia * Depression * Atypical depression * Dysthymia * Major depressive disorder * Melancholic depression * Seasonal affective disorder * Mania Neurological and symptomatic Autism spectrum * Autism * Asperger syndrome * High-functioning autism * PDD-NOS * Savant syndrome Dementia * AIDS dementia complex * Alzheimer's disease * Creutzfeldt–Jakob disease * Frontotemporal dementia * Huntington's disease * Mild cognitive impairment * Parkinson's disease * Pick's disease * Sundowning * Vascular dementia * Wandering Other * Delirium * Organic brain syndrome * Post-concussion syndrome Neurotic, stress-related and somatoform Adjustment * Adjustment disorder with depressed mood Anxiety Phobia * Agoraphobia * Social anxiety * Social phobia * Anthropophobia * Specific social phobia * Specific phobia * Claustrophobia Other * Generalized anxiety disorder * OCD * Panic attack * Panic disorder * Stress * Acute stress reaction * PTSD Dissociative * Depersonalization disorder * Dissociative identity disorder * Fugue state * Psychogenic amnesia Somatic symptom * Body dysmorphic disorder * Conversion disorder * Ganser syndrome * Globus pharyngis * Psychogenic non-epileptic seizures * False pregnancy * Hypochondriasis * Mass psychogenic illness * Nosophobia * Psychogenic pain * Somatization disorder Physiological and physical behavior Eating * Anorexia nervosa * Bulimia nervosa * Rumination syndrome * Other specified feeding or eating disorder Nonorganic sleep * Hypersomnia * Insomnia * Parasomnia * Night terror * Nightmare * REM sleep behavior disorder Postnatal * Postpartum depression * Postpartum psychosis Sexual dysfunction Arousal * Erectile dysfunction * Female sexual arousal disorder Desire * Hypersexuality * Hypoactive sexual desire disorder Orgasm * Anorgasmia * Delayed ejaculation * Premature ejaculation * Sexual anhedonia Pain * Nonorganic dyspareunia * Nonorganic vaginismus Psychoactive substances, substance abuse and substance-related * Drug overdose * Intoxication * Physical dependence * Rebound effect * Stimulant psychosis * Substance dependence * Withdrawal Schizophrenia, schizotypal and delusional Delusional * Delusional disorder * Folie à deux Psychosis and schizophrenia-like * Brief reactive psychosis * Schizoaffective disorder * Schizophreniform disorder Schizophrenia * Childhood schizophrenia * Disorganized (hebephrenic) schizophrenia * Paranoid schizophrenia * Pseudoneurotic schizophrenia * Simple-type schizophrenia Other * Catatonia Symptoms and uncategorized * Impulse control disorder * Klüver–Bucy syndrome * Psychomotor agitation * Stereotypy * v * t * e Baron Munchausen Authors * Rudolf Erich Raspe * Gottfried August Bürger Films * Baron Munchausen's Dream (1911) * Meet the Baron (1933) * Baron Prášil (1940) * Münchhausen (1943) * The Fabulous Baron Munchausen (1961) * The Very Same Munchhausen (1979) * The Secret of the Selenites (1984) * The Adventures of Baron Munchausen (1988) Related * The Extraordinary Adventures of Baron Munchausen (game) * Munchausen syndrome * Munchausen syndrome by proxy * Munchausen by Internet * Münchhausen trilemma * Munchausen number * 14014 Münchhausen [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Factitious disorder imposed on self	c0026785	3,828	wikipedia	https://en.wikipedia.org/wiki/Factitious_disorder_imposed_on_self	2021-01-18T19:10:15	{"mesh": ["D009110"], "icd-9": ["301.51"], "icd-10": ["F68.1"], "wikidata": ["Q642598"]}
De Barsy syndrome is a rare genetic disorder originally described in 1968 and classified as a form of cutis laxa. Cutis laxa is characterized by skin that is loose (lax), wrinkled, sagging, and lacking elasticity. The specific symptoms and the severity of De Barsy syndrome can vary greatly. Features that may be seen include eye abnormalities, growth abnormalities, and a prematurely-aged appearance. Distinctive facial features, skeletal malformations, and neurological abnormalities may also occur. Some cases of De Barsy syndrome have been linked to mutations in either the PYCR1 or ALDH18A1 genes. De Barsy syndrome is inherited in an autosomal recessive manner. There are no standardized treatment protocols; treatment generally focuses on the signs and symptoms present in each individual. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	De Barsy syndrome	c0268354	3,829	gard	https://rarediseases.info.nih.gov/diseases/49/de-barsy-syndrome	2021-01-18T18:00:57	{"mesh": ["C535990"], "omim": ["219150"], "umls": ["C0268354"], "orphanet": ["2962"], "synonyms": ["Corneal clouding, cutis laxa and intellectual disability", "Progeroid syndrome of De Barsy", "Cutis laxa growth deficiency syndrome", "Progeroid syndrome, De Barsy type", "Cutis laxa-corneal clouding-intellectual disability syndrome"]}
ZAP70-related severe combined immunodeficiency (SCID) is an inherited disorder that damages the immune system. ZAP70-related SCID is one of several forms of severe combined immunodeficiency, a group of disorders with several genetic causes. Children with SCID lack virtually all immune protection from bacteria, viruses, and fungi. They are prone to repeated and persistent infections that can be very serious or life-threatening. Often the organisms that cause infection in people with this disorder are described as opportunistic because they ordinarily do not cause illness in healthy people. Infants with SCID typically experience pneumonia, chronic diarrhea, and widespread skin rashes. They also grow much more slowly than healthy children. If not treated in a way that restores immune function, children with SCID usually live only a year or two. Most individuals with ZAP70-related SCID are diagnosed in the first 6 months of life. At least one individual first showed signs of the condition later in childhood and had less severe symptoms, primarily recurrent respiratory and skin infections. ## Frequency ZAP70-related SCID is a rare disorder. Only about 20 affected individuals have been identified. The prevalence of SCID from all genetic causes combined is approximately 1 in 50,000. ## Causes As the name indicates, this condition is caused by mutations in the ZAP70 gene. The ZAP70 gene provides instructions for making a protein called zeta-chain-associated protein kinase. This protein is part of a signaling pathway that directs the development of and turns on (activates) immune system cells called T cells. T cells identify foreign substances and defend the body against infection. The ZAP70 gene is important for the development and function of several types of T cells. These include cytotoxic T cells (CD8+ T cells), whose functions include destroying cells infected by viruses. The ZAP70 gene is also involved in the activation of helper T cells (CD4+ T cells). These cells direct and assist the functions of the immune system by influencing the activities of other immune system cells. Mutations in the ZAP70 gene prevent the production of zeta-chain-associated protein kinase or result in a protein that is unstable and cannot perform its function. A loss of functional zeta-chain-associated protein kinase leads to the absence of CD8+ T cells and an excess of inactive CD4+ T cells. The resulting shortage of active T cells causes people with ZAP70-related SCID to be more susceptible to infection. ### Learn more about the gene associated with ZAP70-related severe combined immunodeficiency * ZAP70 ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	ZAP70-related severe combined immunodeficiency	c2931299	3,830	medlineplus	https://medlineplus.gov/genetics/condition/zap70-related-severe-combined-immunodeficiency/	2021-01-27T08:24:36	{"gard": ["387"], "mesh": ["C536722"], "omim": ["176947"], "synonyms": []}
A number sign (#) is used with this entry because of evidence that primary microcephaly-11 (MCPH11) is caused by homozygous mutation in the PHC1 gene (602978) on chromosome 12p13. One such family has been reported. For a phenotypic description and discussion of genetic heterogeneity of primary microcephaly, see MCPH1 (251200). Clinical Features Awad et al. (2013) reported a 12-year-old girl and her 6-year old brother, born of related Saudi parents, with primary microcephaly (-5.8 and -4.3 SD, respectively) and low-normal cognitive function. Brain MRI was normal except for small brain size. The sister and brother also had short stature (-3.6 SD and -2.3 SD, respectively). Inheritance The transmission pattern of MCPH11 in the family reported by Awad et al. (2013) was consistent with autosomal recessive inheritance. Molecular Genetics In 2 sibs with MCPH11, Awad et al. (2013) identified a homozygous mutation in the PHC1 gene (L992F; 602978.0001). The mutation, which was found by homozygosity mapping combined with exome sequencing, segregated with the disorder and was not found in the dbSNP, Exome Variant Server, or 1000 Genomes database or in 199 Saudi exomes or 554 Saudi control individuals. Patient cells showed normal amounts of mutant PHC1 mRNA, but a significant reduction (about 72%) in mutant protein levels, which was shown to result from proteosome-mediated degradation. Patient cells showed increased expression of geminin (GMNN; 602842) and decreased interaction between PHC1 and ubiquitinated H2A (613499) compared to control cells. These changes were replicated by siRNA against PHC1. Patient cells also showed an increase in DNA damage and defective DNA repair in response to irradiation, as well as abnormal cell cycle activity consistent with reduced proliferative activity, compared to controls. These defects were associated with abnormalities in chromatin regulation, and could be rescued in patient cells by overexpression of wildtype PHC1. Gene microarray analysis of patient cells showed dysregulation of a large number of genes involved in cell cycle regulation. The findings highlighted a role for chromatin remodeling in the pathogenesis of primary microcephaly. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature HEAD & NECK Head \- Microcephaly (-4 to -5 SD) NEUROLOGIC Central Nervous System \- Low-normal intelligence \- Normal brain MRI MISCELLANEOUS \- One family has been reported (last curated September 2013) MOLECULAR BASIS \- Caused by mutation in the polyhomeotic-like 1 gene (PHC1, 602978.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	MICROCEPHALY 11, PRIMARY, AUTOSOMAL RECESSIVE	c3711387	3,831	omim	https://www.omim.org/entry/615414	2019-09-22T15:52:13	{"doid": ["0070287"], "mesh": ["C579935"], "omim": ["615414"], "orphanet": ["2512"]}
A number sign (#) is used with this entry because of evidence that hyperphosphatasia with mental retardation syndrome-6 (HPMRS6) is caused by homozygous mutation in the PIGY gene (610662) on chromosome 4q22. Description Hyperphosphatasia with mental retardation syndrome-6 (HPMRS6) is an autosomal recessive multisystem disorder characterized by global developmental delay, dysmorphic features, seizures, and congenital cataracts. Severity is variable, and the disorder may show a range of phenotypic and biochemical abnormalities, including increased serum alkaline phosphatase levels (summary by Ilkovski et al., 2015). The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis. For a discussion of genetic heterogeneity of HPMRS, see HPMRS1 (239300). For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293). Clinical Features Ilkovski et al. (2015) reported 2 sisters, born of possibly remotely related Australian parents, with a severe multisystem disorder resulting in early death. One patient was born at 32 weeks' gestation and had a complicated course with necrotizing enterocolitis and chronic lung disease. She developed intractable seizures at age 5 months, followed by developmental regression and death from respiratory infection at age 2 years. Her sister was born at 28 weeks' gestation due to polyhydramnios. There was dilatation of the renal collecting systems and increased echogenicity of the renal parenchyma. She developed intractable seizures at age 6 weeks followed by developmental regression and death at age 7 months secondary to aspiration. Both patients had dysmorphic features, including bitemporal narrowing, depressed nasal bridge with upturned nares, deep-set eyes, congenital cataracts, short neck, fleshy earlobes, brachytelephalangy, proximal limb shortening, flexion contractures, hip dysplasia, and osteopenia. The patients also had poor feeding and abdominal discomfort resulting in poor growth and hypotonia. Creatine kinase was increased, and muscle biopsy showed variation in fiber size with small rounded atrophic fibers and increased fibrosis. Serum alkaline phosphatase was also increased. ### Clinical Variability Ilkovski et al. (2015) reported 2 Pakistani sibs, born of consanguineous parents, with global developmental delay, poor speech, and microcephaly (-3 to -5 SD). They had mild dysmorphic features with long palpebral fissures, bulbous nasal tip, and wide mouth; 1 had strabismus. Neither patient had brachytelephalangy or seizures, and both had normal alkaline phosphatase levels. The phenotype was much less severe than that found by Ilkovski et al. (2015) in the Australian sisters. Inheritance The transmission pattern of HPMRS6 in the family reported by Ilkovski et al. (2015) was consistent with autosomal recessive inheritance. Molecular Genetics In 2 sisters, born of Australian parents, with HPMRS6, Ilkovski et al. (2015) identified a homozygous missense mutation in the PIGY gene (L46P; 610662.0001). The mutation was identified by whole-exome sequencing and segregated with the disorder in the family. Patient fibroblasts showed a 20 to 50% reduction in surface expression of GPI-anchored proteins CD55 (125240) and CD59 (107271). Transfection of the mutation into PIGY-null cells could only partially restore CD55 and CD59 expression under a strong promoter. Western blot analysis showed decreased expression of the mutant protein, consistent with reduced stability resulting in impaired PIGY function. The findings suggested that this mutation disrupts GPI biosynthesis or interferes with GPI anchoring capacity. Two sibs, born of consanguineous Pakistani parents, with a mild form of HPMRS6 had a homozygous mutation in the promoter region of the PIGY gene (610662.0002). Patient blood cells showed significantly decreased PIGY expression (6-10% of controls). Patient fibroblasts were not available for study of GPI-anchored proteins, but granulocytes showed normal CD16 surface expression (see 146740), indicating that PIGY levels in some tissues are sufficient for normal GPI synthesis. These findings were consistent with the less severe phenotype in these patients. INHERITANCE \- Autosomal recessive GROWTH Other \- Poor growth (family A) HEAD & NECK Head \- Microcephaly (-3 to -5 SD) (family B) Face \- Bitemporal narrowing (family A) Ears \- Thickened helices (family A) \- Fleshy earlobes (family A) Eyes \- Congenital cataracts (family A) \- Cerebral visual impairment (family A) \- Deep-set eyes (family A) \- Long palpebral fissures (family B) \- Strabismus (family B) Nose \- Depressed nasal bridge (family A) \- Upturned nares (family A) \- Bulbous nasal tip (family B) Mouth \- High-arched palate (family A) \- Wide mouth (family B) Neck \- Short neck (family A) ABDOMEN Gastrointestinal \- Poor feeding (family A) \- Abdominal distress (family A) GENITOURINARY Kidneys \- Renal dilatation (1 patient in family A) \- Increased echogenicity of the renal parenchyma (1 patient in family A) SKELETAL \- Joint contractures (family A) \- Osteopenia (family A) Pelvis \- Hip dysplasia Limbs \- Proximal limb shortening (family A) Hands \- Brachyphalangy (family A) \- Clinodactyly (family A) MUSCLE, SOFT TISSUES \- Truncal hypotonia (family A) \- Muscle biopsy shows variation in fiber size (family A) \- Rounded, atrophic fibers (family A) \- Increased fibrosis (family A) NEUROLOGIC Central Nervous System \- Delayed psychomotor development (family B) \- Delayed speech (family B) \- Developmental regression (family A) \- Seizures, intractable (family A) \- Truncal hypotonia (family A) Behavioral Psychiatric Manifestations \- Poor attention (family B) \- Hyperactivity (family B) \- Aggressive outbursts (family B) PRENATAL MANIFESTATIONS Amniotic Fluid \- Polyhydramnios (1 patient in family A) LABORATORY ABNORMALITIES \- Increased serum creatine kinase (family A) \- Increased alkaline phosphatase (family A) \- Decreased expression of GPI-anchored proteins on fibroblasts (family A) MISCELLANEOUS \- Two unrelated families have been reported (last curated February 2016) \- Family A had a severe multisystem disorder resulting in death before age 2 years \- Family B had a milder phenotype MOLECULAR BASIS \- Caused by mutation in the phosphatidylinositol glycan, class Y gene (PIGY, 610662.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	HYPERPHOSPHATASIA WITH MENTAL RETARDATION SYNDROME 6	c1855923	3,832	omim	https://www.omim.org/entry/616809	2019-09-22T15:47:51	{"mesh": ["C565495"], "omim": ["616809"], "orphanet": ["247262"], "synonyms": ["Alternative titles", "GLYCOSYLPHOSPHATIDYLINOSITOL BIOSYNTHESIS DEFECT 12"]}
A number sign (#) is used with this entry because of evidence that mitochondrial complex I deficiency nuclear type 30 (MC1DN30) is caused by hemizygous mutation in the NDUFB11 gene (300403) on chromosome Xp11. One such patient has been reported. For a discussion of genetic heterogeneity of mitochondrial complex I deficiency, see 252010. Clinical Features Kohda et al. (2016) reported a male infant (patient 067) with lethal mitochondrial complex I deficiency. The patient had intrauterine growth restriction, premature birth, heart failure, respiratory failure, and metabolic acidosis; he died at 55 hours of age. He had redundant skin but no linear skin defects. Molecular Genetics In a male infant (patient 067) with lethal mitochondrial complex I deficiency nuclear type 30, Kohda et al. (2016) identified a de novo hemizygous missense mutation in the NDUFB11 gene (E121K; 300403.0003). The mutation, which was found by high-throughput exome sequencing of 142 patients with childhood-onset mitochondrial respiratory chain disorders, was confirmed by Sanger sequencing. INHERITANCE \- X-linked GROWTH Other \- Intrauterine growth restriction (IUGR) CARDIOVASCULAR Heart \- Cardiac failure RESPIRATORY \- Respiratory failure SKIN, NAILS, & HAIR Skin \- Redundant skin METABOLIC FEATURES \- Metabolic acidosis PRENATAL MANIFESTATIONS Delivery \- Premature birth LABORATORY ABNORMALITIES \- Mitochondrial complex I deficiency in various tissues MISCELLANEOUS \- Onset at birth \- Neonatal death \- One patient has been reported (last curated January 2018) MOLECULAR BASIS \- Caused by mutation in the NADH-ubiquinone oxidoreductase subunit B11 gene (NDUFB11, 300403.0003 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 30	c2936907	3,833	omim	https://www.omim.org/entry/301021	2019-09-22T16:18:56	{"mesh": ["C537475"], "omim": ["301021"], "orphanet": ["2609"]}
Escherichia coli O104:H4 is an enteroaggregative Escherichia coli strain of the bacterium Escherichia coli, and the cause of the 2011 Escherichia coli O104:H4 outbreak.[1] The "O" in the serological classification identifies the cell wall lipopolysaccharide antigen, and the "H" identifies the flagella antigen. Analysis of genomic sequences obtained by BGI Shenzhen shows that the O104:H4 outbreak strain is an enteroaggregative E. coli (EAEC or EAggEC) type that has acquired Shiga toxin genes, presumably by horizontal gene transfer.[2][3][4] Genome assembly and copy-number analysis both confirmed that two copies of the Shiga toxin stx2 prophage gene cluster are a distinctive characteristic of the genome of the O104:H4 outbreak strain.[5][6] The O104:H4 strain is characterized by these genetic markers:[6][7] * Shiga toxin stx2 positive * tellurite resistance gene cluster positive * intimin adherence gene negative * β-lactamases ampC, ampD, ampE, ampG, ampH are present. The European Commission (EC) integrated approach to food safety[8] defines a case of Shiga-like toxin-producing E. coli (STEC) diarrhea caused by O104:H4 by an acute onset of diarrhea or bloody diarrhea together with the detection of the Shiga toxin 2 (Stx2) or the Shiga gene stx2.[9] Prior to the 2011 outbreak, only one case identified as O104:H4 had been observed, in a woman in South Korea in 2005.[10] ## Contents * 1 Pathophysiology * 2 Infection * 3 Diagnosis * 4 Treatment * 5 Prevention * 6 References ## Pathophysiology[edit] E. coli O104 is a Shiga toxin–producing E. coli (STEC). The toxins cause illness and the associated symptoms by sticking to the intestinal cells and aggravating the cells along the intestinal wall.[11][12] This, in turn, can cause bloody stools to occur. Another effect from this bacterial infection is hemolytic uremic syndrome (HUS), which is a condition characterized by destruction of red blood cells, that over a long period of time can cause kidney failure.[13]Some common symptoms of HUS are vomiting, bloody diarrhea, and blood in the urine.[12] ## Infection[edit] A common mode of E. coli O104:H4 infection involves ingestion of fecally contaminated food; the disease can thus be considered a foodborne illness. Most recently in 2011, an outbreak of the O104:H4 strain in Germany caused the death of several people, and landed hundreds of citizens in hospital.[14][15][12] German authorities traced the infection back to fenugreek sprouts grown from contaminated seeds imported from Egypt, but these results are debated.[citation needed] ## Diagnosis[edit] To diagnose infection with STEC, a patient's stool (feces) can be tested in a laboratory for the presence of Shiga toxin. Testing methods used include direct detection of the toxin by immunoassay, or detection of the stx2 gene or other virulence-factor genes by PCR. If infection with STEC is confirmed, the E. coli strain may be serotyped to determine whether O104:H4 is present.[11] ## Treatment[edit] E. coli O104:H4 is difficult to treat as it is resistant to many antibiotics, although it is susceptible to carbapenems.[14] ## Prevention[edit] Spread of E. coli is prevented simply by thorough hand-washing with soap, washing and hygienically preparing food, and properly heating/cooking food, so the bacteria are destroyed.[16] ## References[edit] 1. ^ Mellman, Alexander; Harmsen, D; Cummings, CA; et al. (July 20, 2011). "Prospective genomic characterization of the German enterohemorrhagic Escherichia coli O104:H4 outbreak by rapid next generation sequencing technology". PLoS One. 6 (7): e22751. doi:10.1371/journal.pone.0022751. PMC 3140518. PMID 21799941. 2. ^ "BGI Sequences Genome of the Deadly E. coli in Germany and Reveals New Super-Toxic Strain". BGI. 2011-06-02. Archived from the original on 2011-06-06. Retrieved 2011-06-02. 3. ^ David Tribe (2011-06-02). "BGI Sequencing news: German EHEC strain is a chimera created by horizontal gene transfer". Biology Fortified. Archived from the original on 2012-05-27. Retrieved 2011-06-02. 4. ^ Maev Kennedy and agencies (2011-06-02). "E. coli outbreak: WHO says bacterium is a new strain". London: guardian.co.uk. Retrieved 2011-06-04. 5. ^ "BGI releases the complete map of the Germany E. coli O104 genome and attributed the strain as a category of Shiga toxin-producing enteroaggregative Escherichia coli (STpEAEC)". BGI. 2011-06-16. Retrieved 2011-06-20. 6. ^ a b "Copy number analysis of German outbreak strain E. coli EHEC O104:H4". Johannes Kepler University of Linz. 2011-06-11. Retrieved 2011-06-15. 7. ^ "Characterization of EHEC O104:H4" (PDF). Robert Koch Institute. 2011-06-03. Retrieved 2011-06-15. 8. ^ "The EU integrated approach to food safety". 9. ^ "Case Definition for diarrhoea and haemolytic uremic syndrome caused by O104:H4" (PDF). European Commission. 2011-06-03. Retrieved 2011-06-16. 10. ^ Bae, WK; Lee, YK; Cho, MS; et al. (June 30, 2006). "A case of haemolytic uremic syndrome caused by Escherichia coli O104:H4". Yonsei Medical Journal. 47 (3): 473–479. doi:10.3349/ymj.2006.47.3.437. PMC 2688167. PMID 16807997. 11. ^ a b Frank, C; Werber, D; Cramer, JP; et al. (October 26, 2011). "Epidemic profile of Shiga-toxin–producing Escherichia coli O104:H4 outbreak in Germany". New England Journal of Medicine. 365 (19): 1771–1780. doi:10.1056/NEJMoa1106483. PMID 21696328.<http://www.nejm.org/doi/full/10.1056/NEJMoa1106483> 12. ^ a b c Reinberg, Steven. "German E. Coli Strain Especially Lethal - Infectious Diseases: Causes, Types, Prevention, Treatment and Facts on MedicineNet.com." Medicinenet.com. MedicineNet Inc, 22 June 2011. Web. 08 Nov. 2011. <http://www.medicinenet.com/script/main/art.asp?articlekey=146119 Archived 2012-01-18 at the Wayback Machine>. 13. ^ European Food Safety Authority. "Shiga Toxin-producing E. Coli (STEC) O104:H4 2011 Outbreaks in Europe:." EFSA Journal. European Food Safety Authority, 3 Nov. 2011. Web. 08 Nov. 2011. <http://www.efsa.europa.eu/en/efsajournal/pub/2390>. 14. ^ a b Gorman, Christine. "E. Coli on the March: Scientific American." Science News, Articles and Information \| Scientific American. Scientific American, 7 Aug. 2011. Web. 08 Nov. 2011. <http://www.scientificamerican.com/article.cfm?id=e-coli-on-the-march>. 15. ^ "July 8, 2011: Outbreak of Shiga Toxin-producing E. Coli O104 (STEC O104:H4) Infections Associated with Travel to Germany \| E. Coli." Centers for Disease Control and Prevention. Center for Disease Control and Prevention, 8 July 2011. Web. 08 Nov. 2011. <https://www.cdc.gov/ecoli/2011/ecolio104/>. 16. ^ "CDC - Escherichia coli O157:H7, General Information - NCZVED." Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 8 July 201. Web. 08 Nov. 2011. * v * t * e Escherichia coli Outbreaks * 1993 Jack in the Box * 1996 Odwalla * 2000 Walkerton * 2005 South Wales (O157) * 2006 North American (spinach; O157:H7) * 2006 North American (multiple; O157:H7) * 2009 United Kingdom * 2011 Germany (O104:H4) * 2015 United States Genes * CPS operon * DnaG * Fis * FNR regulon * OmpT * RecBCD * RpoE * RpoF * RpoN * RpoS Strains * Enterohemorrhagic * Enteroinvasive * Enterotoxigenic * O104:H21 * O104:H4 * O121 * O157:H7 * Verotoxin-producing Related * Aerobactin * Coliform index * Long-term evolution experiment * EcoCyc * Enteroaggregative * Molecular biology * Hok/sok system * LacUV5 * Min System * Pathogenic * EnvZ/OmpR * Rho factor * T4 rII system * Theodor Escherich * v * t * e Proteobacteria-associated Gram-negative bacterial infections α Rickettsiales Rickettsiaceae/ (Rickettsioses) Typhus * Rickettsia typhi * Murine typhus * Rickettsia prowazekii * Epidemic typhus, Brill–Zinsser disease, Flying squirrel typhus Spotted fever Tick-borne * Rickettsia rickettsii * Rocky Mountain spotted fever * Rickettsia conorii * Boutonneuse fever * Rickettsia japonica * Japanese spotted fever * Rickettsia sibirica * North Asian tick typhus * Rickettsia australis * Queensland tick typhus * Rickettsia honei * Flinders Island spotted fever * Rickettsia africae * African tick bite fever * Rickettsia parkeri * American tick bite fever * Rickettsia aeschlimannii * Rickettsia aeschlimannii infection Mite-borne * Rickettsia akari * Rickettsialpox * Orientia tsutsugamushi * Scrub typhus Flea-borne * Rickettsia felis * Flea-borne spotted fever Anaplasmataceae * Ehrlichiosis: Anaplasma phagocytophilum * Human granulocytic anaplasmosis, Anaplasmosis * Ehrlichia chaffeensis * Human monocytotropic ehrlichiosis * Ehrlichia ewingii * Ehrlichiosis ewingii infection Rhizobiales Brucellaceae * Brucella abortus * Brucellosis Bartonellaceae * Bartonellosis: Bartonella henselae * Cat-scratch disease * Bartonella quintana * Trench fever * Either B. henselae or B. quintana * Bacillary angiomatosis * Bartonella bacilliformis * Carrion's disease, Verruga peruana β Neisseriales M+ * Neisseria meningitidis/meningococcus * Meningococcal disease, Waterhouse–Friderichsen syndrome, Meningococcal septicaemia M− * Neisseria gonorrhoeae/gonococcus * Gonorrhea ungrouped: * Eikenella corrodens/Kingella kingae * HACEK * Chromobacterium violaceum * Chromobacteriosis infection Burkholderiales * Burkholderia pseudomallei * Melioidosis * Burkholderia mallei * Glanders * Burkholderia cepacia complex * Bordetella pertussis/Bordetella parapertussis * Pertussis γ Enterobacteriales (OX−) Lac+ * Klebsiella pneumoniae * Rhinoscleroma, Pneumonia * Klebsiella granulomatis * Granuloma inguinale * Klebsiella oxytoca * Escherichia coli: Enterotoxigenic * Enteroinvasive * Enterohemorrhagic * O157:H7 * O104:H4 * Hemolytic-uremic syndrome * Enterobacter aerogenes/Enterobacter cloacae Slow/weak * Serratia marcescens * Serratia infection * Citrobacter koseri/Citrobacter freundii Lac− H2S+ * Salmonella enterica * Typhoid fever, Paratyphoid fever, Salmonellosis H2S− * Shigella dysenteriae/sonnei/flexneri/boydii * Shigellosis, Bacillary dysentery * Proteus mirabilis/Proteus vulgaris * Yersinia pestis * Plague/Bubonic plague * Yersinia enterocolitica * Yersiniosis * Yersinia pseudotuberculosis * Far East scarlet-like fever Pasteurellales Haemophilus: * H. influenzae * Haemophilus meningitis * Brazilian purpuric fever * H. ducreyi * Chancroid * H. parainfluenzae * HACEK Pasteurella multocida * Pasteurellosis * Actinobacillus * Actinobacillosis Aggregatibacter actinomycetemcomitans * HACEK Legionellales * Legionella pneumophila/Legionella longbeachae * Legionnaires' disease * Coxiella burnetii * Q fever Thiotrichales * Francisella tularensis * Tularemia Vibrionaceae * Vibrio cholerae * Cholera * Vibrio vulnificus * Vibrio parahaemolyticus * Vibrio alginolyticus * Plesiomonas shigelloides Pseudomonadales * Pseudomonas aeruginosa * Pseudomonas infection * Moraxella catarrhalis * Acinetobacter baumannii Xanthomonadaceae * Stenotrophomonas maltophilia Cardiobacteriaceae * Cardiobacterium hominis * HACEK Aeromonadales * Aeromonas hydrophila/Aeromonas veronii * Aeromonas infection ε Campylobacterales * Campylobacter jejuni * Campylobacteriosis, Guillain–Barré syndrome * Helicobacter pylori * Peptic ulcer, MALT lymphoma, Gastric cancer * Helicobacter cinaedi * Helicobacter cellulitis * v * t * e Consumer food safety Adulterants, food contaminants * 3-MCPD * Aldicarb * Antibiotic use in livestock * Cyanide * Formaldehyde * HGH controversies * Lead poisoning * Melamine * Mercury in fish * Sudan I Flavorings * Monosodium glutamate (MSG) * Salt * Sugar * High-fructose corn syrup Intestinal parasites and parasitic disease * Amoebiasis * Anisakiasis * Cryptosporidiosis * Cyclosporiasis * Diphyllobothriasis * Enterobiasis * Fasciolopsiasis * Fasciolosis * Giardiasis * Gnathostomiasis * Paragonimiasis * Toxoplasmosis * Trichinosis * Trichuriasis Microorganisms * Botulism * Campylobacter jejuni * Clostridium perfringens * Cronobacter * Enterovirus * Escherichia coli O104:H4 * Escherichia coli O157:H7 * Hepatitis A * Hepatitis E * Listeria * Norovirus * Rotavirus * Salmonella * Vibrio cholerae Pesticides * Chlorpyrifos * DDT * Lindane * Malathion * Methamidophos Preservatives * Benzoic acid * Ethylenediaminetetraacetic acid (EDTA) * Sodium benzoate Sugar substitutes * Acesulfame potassium * Aspartame * Saccharin * Sodium cyclamate * Sorbitol * Sucralose Toxins, poisons, environment pollution * Aflatoxin * Arsenic contamination of groundwater * Benzene in soft drinks * Bisphenol A * Dieldrin * Diethylstilbestrol * Dioxin * Mycotoxins * Nonylphenol * Shellfish poisoning Food contamination incidents * Devon colic * Swill milk scandal * Esing Bakery incident * 1858 Bradford sweets poisoning * 1900 English beer poisoning * Morinaga Milk arsenic poisoning incident * Minamata disease * 1971 Iraq poison grain disaster * Toxic oil syndrome * 1985 diethylene glycol wine scandal * UK mad cow disease outbreak * 1993 Jack in the Box E. coli outbreak * 1996 Odwalla E. coli outbreak * 2006 North American E. coli outbreaks * ICA meat repackaging controversy * 2008 Canada listeriosis outbreak * 2008 Chinese milk scandal * 2008 Irish pork crisis * 2008 United States salmonellosis outbreak * 2011 Germany E. coli outbreak * 2011 United States listeriosis outbreak * 2013 Bihar school meal poisoning * 2013 horse meat scandal * 2015 Mozambique beer poisoning * 2017 Brazil weak meat scandal * 2017–18 South African listeriosis outbreak * 2018 Australian rockmelon listeriosis outbreak * 2018 Australian strawberry contamination * Food safety incidents in China * Food safety incidents in Taiwan * Food safety in Australia * Foodborne illness * outbreaks * death toll * United States Regulation, standards, watchdogs * Acceptable daily intake * E number * Food labeling regulations * Food libel laws * International Food Safety Network * ISO 22000 * Nutrition facts label * Organic certification * The Non-GMO Project * Quality Assurance International * Food Standards Agency Institutions * Institute for Food Safety and Health * European Food Safety Authority * International Food Safety Network * Spanish Agency for Food Safety and Nutrition * Food Information and Control Agency (Spain) * Centre for Food Safety (Hong Kong) * Ministry of Food and Drug Safety (South Korea) [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Escherichia coli O104:H4	None	3,834	wikipedia	https://en.wikipedia.org/wiki/Escherichia_coli_O104:H4	2021-01-18T18:30:56	{"wikidata": ["Q310454"]}
A very severe type of RAEB characterized by cytopenias and the following hematological parameters: uni- or multilineage dysplasia, 10% to 19% blasts in bone marrow or 5% to 19% in peripheral blood, variable presence of Auer rods (abnormal, needle-shaped or round inclusions in the cytoplasm of myeloblasts and promyelocytes). Median survival has been reported to be 18 months. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Refractory anemia with excess blasts type 2	c1318551	3,835	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=100020	2021-01-23T18:00:10	{"umls": ["C1318551"], "icd-10": ["D46.2"], "synonyms": ["RAEB-2"]}
Microvascular angina SpecialtyCardiology Cardiac syndrome X is a historic term for microvascular angina, angina (chest pain) with signs associated with decreased blood flow to heart tissue but with normal coronary arteries. The use of the term CSX can lead to the lack of appreciation of how microvascular angina is a debilitating heart related pain condition with the increased risk of heart attack and other heart problems. Many mainly women can have difficulty accessing the specialist care of a cardiologist for this reason. Some studies have found increased risk of other vasospastic disorders in cardiac microvascular angina parients, such as migraine and Raynaud's phenomenon. It is treated with beta-blockers, such as metoprolol however beta blockers can make coronary spasms worse. This is a distinct diagnosis from Prinzmetal's angina. ## Contents * 1 Signs and symptoms * 2 Causes * 3 Pathophysiology * 4 Diagnosis * 4.1 Differential diagnosis * 5 Treatment * 6 Incidence * 7 See also * 8 References * 9 Further reading * 10 External links ## Signs and symptoms[edit] While there is no formal definition of microvascular angina, the general consensus is that it entails all of the following: * Angina: This usually does not cause dysfunction on echocardiogram and can last longer than that of heart disease. * Abnormal cardiac stress test: ST changes are typically similar to those of coronary artery disease, and the opposite of those of Prinzmetal's angina. Myocardial perfusion imaging can be abnormal in 30% of patients. * Coronary angiogram: Normal * Other causes of chest pain must be ruled out, including: * Prinzmetal's angina aka vasospastic or variant angina / Coronary artery spasm. * Esophageal spasm ## Causes[edit] Narrowing of the artery due to plaque formation. There is no specific known cause for microvascular angina but rather a multitude of risk factors that act together. It is believed that the lack of blood flow caused by a microvascular disease and enhanced pain perception are two of the factors that may cause it.[1] The microvascular dysfunctions refer to the abnormalities in the very small blood vessels of the heart. The narrowing of these vessels may lead to lack of oxygen in specific areas of the cardiac muscle causing chest pain. Several studies have shown that patients living with microvascular angina may have an enhanced pain perception, and usually feel more intense chest pain than individuals without microvascular angina. The risk factors include abdominal obesity, meaning excessive fat tissue in and around the abdomen, atherogenic dyslipidemia which is a blood fat disorder, and elevated blood pressure.[2] Other risk factors are insulin resistance or intolerance to glucose, prothrombotic state or proinflammatory state. Older people are more at risk to develop this condition, and there is some evidence that suggests that there are genetic mutations that predispose to the syndrome.[3] Women are more prone to this condition than men, as well as those who have a history of heart disease in the family.[4] ## Pathophysiology[edit] This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (March 2019) (Learn how and when to remove this template message) In a large percentage of patients, there is a finding of systemic microvascular abnormalities, causing reduced blood flow in the microvasculature of the cardiac muscles. When the blood vessels constrict and fail to dilate there is decreased oxygen levels to the cardiac muscles resulting in hypoxia which lead to chest pain.[5] While numerous physiological mechanisms have been proposed, none have been proven. ## Diagnosis[edit] Microvascular angina is a diagnosis of exclusion. Typically this will necessitate both a clinical diagnosis, appropriate stress testing, and a coronary angiogram that meet the above criteria. Cardiac MRI can be used to diagnose microvascular angina. Studies are ongoing to validate this approach. There is growing evidence that microvascular angina is caused by a functional disorder of the microvessels, coronary microvascular dysfunction. Blood vessels either fail to dilate or constrict in response to various stressors such as exercise, the cold or emotional stress. An angiogram with acetylcholine can demonstrate microvascular dysfunction which can affect the microvessels and larger coronary arteries leading to either microvascular angina or coronary artery spasms (Prinzmetal's angina). These are considered discrete conditions though some individuals can be effected by both. Microvascular angina can be diagnosed using different tests and exams, but it is mainly a diagnosis of exclusion. However, sedentary and overweight individuals with a family history of type 2 diabetes should be tested regularly to determine whether they have irregular levels of glucose or lipids, or blood pressure abnormalities,[6] factors which are usually associated with microvascular angina. A first test to be taken is an exercise stress test which shows if the heart is not getting blood during exertion. Angiograms may be useful and conclusive when microvascular angina they offer a detailed image of the heart. However, they cannot detect potential abnormalities in the small arteries, and the doctor may ask for more tests in order to rule out other heart conditions, such as Prinzmetal's angina (variant/vasospastic angina, coronary artery spasm) which has similar symptoms. ### Differential diagnosis[edit] Chest pain caused by microvascular angina is most of the time unpredictable and it can occur when at rest and/or during exercise. The pain associated with microvascular angina is normally more intense and it lasts for longer periods of time compared to pain caused by other conditions. For example, a stable angina causes chest pain that goes away when at rest. Another difference is that while chest pain caused by any type of stable angina is relieved with nitroglycerin, this drug is not effective in most patients with microvascular angina. ## Treatment[edit] This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (August 2014) (Learn how and when to remove this template message) * * calcium channel blockers \- specifically nifedipine and diltiazem can be effective. * beta blockers \- also work. Can make coronary spasms worse * aminophylline \- may work by inhibiting adenosine receptors. * estrogen \- may work in women. * L-Arginine \- increases release of NO at vascular level, thus leading to vasodilatory effect * Ranolazine \- shown to improve angina and myocardial ischemia * Statins * Aspirin * Clopidogrel * ACE inhibitors and ARBs * Lifestyle changes such as diet and exercise. * Pain Management through CBT, Mindfulness meditation, yoga and Tai Chi. Microvascular angina is an chronic long term condition which increases the risk of heart attack and other cardiac events such as heart failure and frequent hospital admissions. The treatment consists of drugs, mainly to relieve chest pain, but a very important part of the treatment is regularly visiting the doctor and repeating the tests to make sure the condition was taken care of in full. The first step in managing Microvascular angina is the administration of nitrates which may relieve the chest pain. They are used because of their ability to relax the muscles of the heart and blood vessels. However, they prove to be inefficient in as many as half of patients. Alternative treatments may consist of calcium channel blockers or beta blockers which reduce chest pain by relaxing the muscle cells lining the artery and improving blood flow to the heart while lowering blood pressure. Aminophylline may also work, while estrogen can be effective in women. There is at present no known cure however a change in lifestyle is important. Patients should start following healthier diets which are low in saturated fats, and should participate in regular physical activities. However, any patient with a heart disease condition should first seek for a medical opinion before starting exercising. Quitting smoking is also highly recommended. ## Incidence[edit] The reasons why women are more prone than men to develop a Microvascular angina are still not clear. However, it is believed[by whom?] that hormones along with other risk factors unique to women play a very important role.[vague] The constant changing of the estrogen levels may be one of the reasons along with the changes brought by birth. ## See also[edit] * Takotsubo cardiomyopathy ## References[edit] 1. ^ Healthy Heart Information Archived September 21, 2009, at the Wayback Machine Heart healthy women Portal. Retrieved on 2010-01-31 2. ^ Heart Disease Information American Heart Association. Retrieved on 2010-02-02 3. ^ Alroy S, Preis M, Barzilai M, Cassel A, Lavie L, Halon DA, Amir O, Lewis BS, Flugelman MY (2007). "Endothelial cell dysfunction in women with cardiac syndrome X and MTHFR C677T mutation". Isr. Med. Assoc. J. 9 (4): 321–5. PMID 17491230. 4. ^ Cardiac Syndrome Details Archived January 9, 2010, at the Wayback Machine Retrieved on 2010-02-02 5. ^ Kaski, Juan Carlos; Aldama, Guillermo; Cosín-Sales, Juan (2004). "Cardiac syndrome X. Diagnosis, pathogenesis and management". American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions. 4 (3): 179–194. doi:10.2165/00129784-200404030-00005. ISSN 1175-3277. PMID 15134470. 6. ^ Heart Disease Conditions Diagnose Me Online Portal. Retrieved on 2010-02-02 ## Further reading[edit] * Botker HE, Sonne HS, Sorensen KE (1996). "Frequency of systemic microvascular dysfunction in syndrome X and in variant angina". Am J Cardiol. 78 (2): 182–6. doi:10.1016/S0002-9149(96)90393-8. PMID 8712140. * Kaski JC, Russo G (2000). "Cardiac syndrome X: an overview". Hosp Pract. 35 (2): 75–6, 79–82, 85–8 passim. doi:10.3810/hp.2000.02.183. PMID 10689391. ## External links[edit] Classification D External resources * eMedicine: article/1967073 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Microvascular angina	c0206064	3,836	wikipedia	https://en.wikipedia.org/wiki/Microvascular_angina	2021-01-18T18:43:21	{"mesh": ["D017566"], "icd-9": ["413.9"], "icd-10": ["I20.8"], "wikidata": ["Q1540658"]}
A number sign (#) is used with this entry because of evidence that variation in glycerol release during exercise can be caused by mutation in the AQP7 gene (602974) on chromosome 9p13.3. In addition, there is evidence that variation in body mass index (BMIQ17) is associated with variation in the AQP7 gene. Molecular Genetics Kondo et al. (2002) identified homozygosity for a missense mutation in the AQP7 gene (G264V; 602974.0001) in a 48-year-old Japanese man who exhibited greatly diminished glycerol release during exercise, despite a normal increase in plasma noradrenaline. The man had a normal body mass index (BMI), as well as normal plasma concentrations of glycerol, glucose, total cholesterol, HDL cholesterol, and triglyceride. In addition, his fertility appeared to be intact, as he had 3 children. Kondo et al. (2002) noted that the normal adiposity and normal plasma glycerol level at rest in this individual suggested the existence of another pathway to maintain plasma glycerol in the resting state. Ceperuelo-Mallafre et al. (2007) screened 178 Spanish individuals, including 37 lean and 90 obese (see 606641) nondiabetics and 14 lean and 37 obese patients with type 2 diabetes (see 125853), for the G264V mutation in the AQP7 gene. Fourteen (8%) of the 178 individuals carried the mutation, and there was no significant difference in its distribution between lean and obese individuals or between diabetics and nondiabetics. The only individual homozygous for G264V was an obese patient with type 2 diabetes who also had glycerol levels below the 10th percentile. Ceperuelo-Mallafre et al. (2007) stated that the low-normal plasma glycerol levels in this patient supported the hypothesis of an alternative glycerol channel in adipocytes. ### Body Mass Index Quantitative Trait Locus 17 Prudente et al. (2007) analyzed SNPs in the AQP7 gene in 977 Italian individuals (530 women and 447 men) and initially found an association between a -953A-G promoter SNP and type 2 diabetes (125853) in women; however, that association was no longer significant after adjustment for BMI. The authors observed that women with a GA or GG genotype had a higher BMI than AA women (p = 0.002), and confirmed the association in an independent case-control study of morbid obesity involving 299 women (odds ratio, 1.66; p = 0.04). Functional studies showed that the -953G promoter had reduced transcriptional activity and impaired ability to bind CCAAT/enhancer binding protein-beta (CEBPB; 189965) transcription factor. In addition, AQP7 expression in adipose tissue decreased from AA to AG to GG individuals (p = 0.038). INHERITANCE \- Autosomal recessive METABOLIC FEATURES \- Defective glycerol release during exercise \- Normal plasma glycerol level at rest MOLECULAR BASIS \- Caused by mutation in the aquaporin 7 gene (AQP7, 602974.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	GLYCEROL QUANTITATIVE TRAIT LOCUS	c3280715	3,837	omim	https://www.omim.org/entry/614411	2019-09-22T15:55:22	{"omim": ["614411"], "synonyms": ["Alternative titles", "GLYCEROL RELEASE DURING EXERCISE, DEFECTIVE"]}
A number sign (#) is used with this entry because this form of limb-girdle muscular dystrophy-dystroglycanopathy (type C1; MDDGC1), also known as LGMDR11 and LGMD2K, is caused by homozygous or compound heterozygous mutation in the gene encoding protein O-mannosyltransferase (POMT1; 607423). Mutation in the POMT1 gene can also cause a more severe congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A1; MDDGA1; 236670) and a congenital muscular dystrophy-dystroglycanopathy with mental retardation (type B1; MDDGB1; 613155). Description Limb-girdle muscular dystrophies resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239) represent the mildest end of the phenotypic spectrum of muscular dystrophies collectively known as dystroglycanopathies. The limb-girdle phenotype is characterized by onset of muscular weakness apparent after ambulation is achieved; mental retardation and mild brain anomalies are variable (Balci et al., 2005; review by Godfrey et al., 2007). The most severe end of the phenotypic spectrum of dystroglycanopathies is represented by congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A; see MDDGA1, 236670), previously designated Walker-Warburg syndrome (WWS) or muscle-eye-brain disease (MEB), and the intermediate range of the spectrum is represented by congenital muscular dystrophy-dystroglycanopathy with or without mental retardation (type B; see MDDGB1, 613155). ### Genetic Heterogeneity of Limb-Girdle Muscular Dystrophy-Dystroglycanopathy (Type C) Limb-girdle muscular dystrophy due to defective glycosylation of DAG1 is genetically heterogeneous. See also MDDGC2 (613158), caused by mutation in the POMT2 gene (607439); MDDGC3 (613157), caused by mutation in the POMGNT1 gene (606822); MDDGC4 (611588), caused by mutation in the FKTN gene (607440); MDDGC5 (607155), caused by mutation in the FKRP gene (606596); MDDGC7 (616052), caused by mutation in the ISPD gene (614631); MDDGC8 (618135), caused by mutation in the POMGNT2 gene (614828); MDDGC9 (613818) caused by mutation in the DAG1 gene (128239); MDDGC12 (616094), caused by mutation in the POMK gene (615247); MDDGC14 (615352) caused by mutation in the GMPPB gene (615320); and MDDGC15 (612937), caused by mutation in the DPM3 gene (605951). Clinical Features Dincer et al. (2003) reported 7 patients from 6 consanguineous Turkish families with autosomal recessive mental retardation and limb-girdle muscular dystrophy. An eighth British patient, who was not from a consanguineous family, had a similar phenotype. All patients acquired early motor milestones, excluding a congenital muscular dystrophy. Age at onset ranged from 1 to 6 years, with difficulty in walking and climbing stairs. Other features included slow progression, proximal muscle weakness, mild muscle hypertrophy, increased serum creatine kinase, microcephaly, and mental retardation (IQ range 50 to 76). Brain imaging was normal in all cases, with no structural abnormalities or white matter changes. Skeletal muscle biopsy showed dystrophic changes, including mild fibrosis with many regenerating and few necrotic fibers, increased fiber size variability, and multiple central nuclei. Immunohistochemical staining showed severe hypoglycosylation of alpha-dystroglycan. Lommel et al. (2010) reported a 10-year-old boy with LGMD2K resulting from compound heterozygous mutations in the POMT1 gene. He had delayed motor milestones and achieved walking at age 22 months. He also had secondary microcephaly and mental retardation with an IQ of 68. Brain MRI did not show structural changes. Other features included hypertrophy of the calf muscle, positive Gowers sign, limb-girdle weakness, and increased serum creatine kinase. Dermal fibroblasts from the patient showed decreased, but not absent, levels of POMT1 protein and 40% residual protein activity. This was increased compared to 6% residual protein activity and lack of protein detection in dermal fibroblasts from a patient with severe POMT1-related muscular dystrophy with brain and eye anomalies. Thus, the phenotypic severity was inversely correlated with residual O-mannosyltransferase activity of the POMT1 gene. Bello et al. (2012) reported 2 unrelated patients with LGMD2K who developed cardiomyopathy. One presented at age 3 years with increased serum creatine kinase. Muscle biopsy at age 5 years showed mild myopathic changes. His psychomotor development was normal. At age 12 years, routine echocardiography showed diffuse left ventricular wall hypokinesia. He presented at the age of 17 years with shortness of breath and easy fatigability, and cardiac work-up showed left ventricular hypertrophy, left ventricular dilation, systolic dysfunction, and right ventricular dilation. Neurologic examination showed calf and thigh hypertrophy, relative wasting of the scapulohumeral girdle, and mild symmetrical weakness of the proximal muscles. Brain MRI was normal, but the patient showed some executive dysfunction; his IQ was 82. The second patient was a 34-year-old man who presented at age 33 with muscle weakness of the lower limbs and myalgias in the shoulder girdle. Serum creatine kinase was increased, and muscle biopsy showed a severe myopathy with type I fiber predominance, central nuclei, and cores. Neurologic examination showed calf hypertrophy and normal cognition. Echocardiography showed biventricular dilatation, consistent with cardiomyopathy. Muscle biopsy in both patients showed reduced DAG glycosylation. Bello et al. (2012) reported another patient with congenital muscular dystrophy (MDDGB1; 613155) due to POMT1 mutations who also developed cardiomyopathy, suggesting that cardiac involvement can be added to the phenotypic spectrum of POMT1 mutations. Molecular Genetics In 5 Turkish patients, born of consanguineous parents, with limb-girdle muscular dystrophy and mental retardation, some of whom were described by Dincer et al. (2003), Balci et al. (2005) identified a homozygous mutation in the POMT1 gene (A200P; 607423.0005). Haplotype analysis indicated that it was a common founder mutation. Balci et al. (2005) noted that the phenotype associated with the A200P mutation was significantly milder than that found in other patients with POMT1 mutations. In 2 unrelated patients with LGMD2K who also developed cardiomyopathy, Bello et al. (2012) identified compound heterozygous mutations in the POMT1 gene (see, e.g., 607423.0019 and 607423.0020). INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Microcephaly CARDIOVASCULAR Heart \- Cardiomyopathy (reported in 2 patients) SKELETAL \- Joint contractures, mild Spine \- Rigid spine \- Lumbar lordosis MUSCLE, SOFT TISSUES \- Muscular weakness, limb-girdle \- Difficulty walking, running, climbing stairs \- Easy fatigability \- Muscle pseudohypertrophy \- Muscle biopsy shows dystrophic changes \- Decreased glycosylation of alpha-dystroglycan (DAG1, 128239 ) NEUROLOGIC Central Nervous System \- Mental retardation, mild to moderate (in some patients) \- Delayed motor development \- No structural brain abnormalities seen on MRI LABORATORY ABNORMALITIES \- Increased serum creatine kinase MISCELLANEOUS \- Onset in infancy or early childhood (birth to 6 years) \- Variable severity \- Slowly progressive MOLECULAR BASIS \- Caused by mutation in the protein O-mannosyltransferase-1 gene (POMT1, 607423.0005 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 1	c1836373	3,838	omim	https://www.omim.org/entry/609308	2019-09-22T16:06:17	{"doid": ["0110297"], "mesh": ["D058494"], "omim": ["609308"], "orphanet": ["86812"], "synonyms": ["Alternative titles", "MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 11", "MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 2K"]}
Dissecting cellulitis of the scalp Boggy, suppurative nodule with patchy hair loss typical of dissecting cellulitis of the scalp. SpecialtyDermatology MedicationIsotretinoin Dissecting cellulitis of the scalp, also known as dissecting folliculitis of the scalp, perifolliculitis capitis abscedens et suffodiens of Hoffman, perifolliculitis abscedens et suffodiens, or folliculitis abscedens et suffodiens, is an inflammatory condition of the scalp that can lead to scarring alopecia, which begins with deep inflammatory nodules, primarily over occiput, that progresses to coalescing regions of boggy scalp. Boggy tissue has a high fluid level that results in a spongy feeling. Isotretinoin proves to be the medicine of choice for the treatment of the disease.[1][2][3][4]:649[5]:761[6] ## See also[edit] * List of cutaneous conditions ## References[edit] 1. ^ Alexis, Andew F. "Dissecting cellulitis of the scalp". uptodate.com. Archived from the original on 2020-11-12. Retrieved 2021-01-06. 2. ^ Dunwoodie, Hamish (2009-02-11). "Virtual Grand Rounds in Dermatology". vgrd.org. Archived from the original on 2018-12-13. Retrieved 2021-01-06. 3. ^ Jones, Leah. "Perifolliculitis capitis abscedens et suffodiens \| DermNet NZ". dermnetnz.org. Archived from the original on 2020-10-31. Retrieved 2021-01-06. 4. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0. 5. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0. 6. ^ Scheinfeld NS (February 2003). "A case of dissecting cellulitis and a review of the literature". Dermatol. Online J. 9 (1): 8. PMID 12639466. ## External links[edit] Classification D * ICD-10: L08.8 * OMIM: 260910 * MeSH: C562486 External resources * eMedicine: article/1072603 * Orphanet: 345 This cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Dissecting cellulitis of the scalp	c0263506	3,839	wikipedia	https://en.wikipedia.org/wiki/Dissecting_cellulitis_of_the_scalp	2021-01-18T18:59:40	{"gard": ["1883"], "mesh": ["C562486"], "umls": ["C0263506"], "orphanet": ["345"], "wikidata": ["Q7168463"]}
Alveolar osteitis Other namesDry socket, fibrinolytic alveolitis Alveolar osteitis of a socket after tooth extraction of all maxillary teeth; note lack of blood clot in socket and exposed alveolar bone SpecialtyDentistry Alveolar osteitis, also known as dry socket, is inflammation of the alveolar bone (i.e., the alveolar process of the maxilla or mandible). Classically, this occurs as a postoperative complication of tooth extraction. Alveolar osteitis usually occurs where the blood clot fails to form or is lost from the socket (i.e., the defect left in the gum when a tooth is taken out). This leaves an empty socket where bone is exposed to the oral cavity, causing a localized alveolar osteitis limited to the lamina dura (i.e., the bone which lines the socket). This specific type is known as dry socket and is associated with increased pain and delayed healing time.[1] Dry socket occurs in about 0.5–5% of routine dental extractions,[2][3][4] and in about 25–30% of extractions of impacted mandibular third molars (wisdom teeth which are buried in the bone of the lower jaw and which erupt during adulthood).[1] If it is going to occur, the pain of dry socket may appear as early as three days following surgery; however, a patient who has gone a full week without experiencing this kind of pain is highly unlikely to develop it.[5] ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Extraction site * 2.2 Infection * 2.3 Smoking * 2.4 Surgical trauma * 2.5 Vasoconstrictors * 2.6 Radiotherapy * 2.7 Menstrual cycle * 3 Diagnosis * 4 Prevention * 5 Treatment * 6 Prognosis * 7 Epidemiology * 8 Etymology * 9 References * 10 External links ## Signs and symptoms[edit] The most common location of dry socket: in the socket of an extracted mandibular third molar (wisdom tooth). Since alveolar osteitis is not primarily an infection, there is not usually any pyrexia (fever) or cervical lymphadenitis (swollen glands in the neck), and only minimal edema (swelling) and erythema (redness) is present in the soft tissues surrounding the socket. Signs may include: * An empty socket, which is partially or totally devoid of blood clot.[4] Exposed bone may be visible or the socket may be filled with food debris which reveals the exposed bone once it is removed.[2] The exposed bone is extremely painful and sensitive to touch.[6] Surrounding inflamed soft tissues may overlie the socket and hide the dry socket from casual examination.[1] * Denuded (bare) bone walls.[7] Symptoms may include: * Dull, aching, throbbing pain in the area of the socket, which is moderate to severe and may radiate to other parts of the head such as the ear, eye, temple and neck.[2][4][7][8] The pain normally starts on the second to fourth day after the extraction,[4][8] and may last 10–40 days.[1] The pain may be so strong that even strong analgesics do not relieve it.[4] * Intraoral halitosis (oral malodor).[7] * Bad taste in the mouth.[7] ## Causes[edit] The cause(s) of dry socket are not completely understood.[2] Normally, following extraction of a tooth, blood is extravasated into the socket, and a blood clot (thrombus) forms.[3] This blood clot is replaced with granulation tissue which consists of proliferating fibroblasts and endothelial cells derived from remnants of the periodontal membrane, surrounding alveolar bone and gingival mucosa.[3] In time this in turn is replaced by coarse, fibrillar bone and finally by mature, woven bone.[1] The clot may fail to form because of poor blood supply (e.g., secondary to local factors such as smoking, anatomical site, bone density and conditions which cause sclerotic bone to form).[7] The clot may be lost because of excessive mouth rinsing, or disintegrate prematurely due to fibrinolysis.[3] Fibrinolysis is the degeneration of the clot and may be caused by the conversion of plasminogen to plasmin and formation of kinins.[1] Factors which promote fibrinolysis include local trauma, estrogens, and pyrogens from bacteria.[1] Bacteria may secondarily colonize the socket, and lead to further dissolution of the clot.[4] Bacterial breakdown and fibrinolysis are widely accepted as a major contributing factors to the loss of the clot.[4] Bone tissue is exposed to the oral environment, and a localized inflammatory reaction takes place in the adjacent marrow spaces.[3] This localizes the inflammation to the walls of the socket, which become necrotic.[7] The necrotic bone in the socket walls is slowly separated by osteoclasts and fragmentary sequestra may form.[3] The bones of the jaws seem to have some evolutionary resistance to this process. When bone is exposed at other sites in the human body, this is a much more serious condition. In a dry socket, healing is delayed because tissue must grow from the surrounding gingival mucosa, which takes longer than the normal organisation of a blood clot. Some patients may develop short term halitosis,[4] which is the result of food debris stagnating in the socket and the subsequent action of halitogenic bacteria.[9] The main factors involved in the development of dry socket are discussed below. ### Extraction site[edit] Dry sockets more commonly occur in the mandible than the maxilla, due to the relatively poor blood supply of the mandible and also because food debris tends to gather in lower sockets more readily than upper ones.[2] It more commonly occurs in posterior sockets (molar teeth) than anterior sockets (premolars and incisors),[3] possibly because the size of the created surgical defect is relatively larger, and because the blood supply is relatively poorer at these sites. Dry socket is especially associated with extraction of lower wisdom teeth.[3] Inadequate irrigation (washing) of the socket has been associated with increased likelihood of dry socket.[1] ### Infection[edit] Dry socket is more likely to occur where there is a pre-existing infection in the mouth,[1] such as necrotizing ulcerative gingivitis or chronic periodontitis. Wisdom teeth not associated with pericoronitis are less likely to cause a dry socket when extracted.[1] The oral microbiota has been demonstrated to have fibrinolytic action in some individuals, and these persons may be predisposed to developing dry sockets after tooth extraction.[2] Infection of the socket following tooth extraction is different from dry socket, although in dry socket secondary infection may occur in addition. ### Smoking[edit] Smoking and tobacco use of any kind are associated with increased risk of dry socket.[2] This may be partially due to the vasoconstrictive action of nicotine on small blood vessels.[2] Abstaining from smoking in the days immediately following a dental extraction reduces the risk of a dry socket occurring. ### Surgical trauma[edit] Dry socket is more likely to occur following a difficult tooth extraction.[2] It is thought that excessive force applied to the tooth, or excessive movement of the tooth burnishes the bony walls of the socket and crushes blood vessels, impairing the repair process.[2] ### Vasoconstrictors[edit] Vasoconstrictors are present in most local anesthetics, and are intended to increase the length of analgesia by reducing blood supply to the region which reduces the amount of local anesthetic solution that is absorbed into the circulation and carried from the local tissues. Hence, use of local anesthetics with vasoconstrictors is associated with an increased risk of dry socket occurring.[2] However, on occasion, use of local anesthetic without vasoconstrictors would not provide sufficient analgesia, especially in the presence of acute pain and infection on maxillary teeth, meaning that the total dose of local anesthetic may need to be increased. Adequate pain control during the extraction is balanced against an increased risk of dry socket. However, the use of 3% mepivacaine without epinephrine in inferior alveolar nerve blocks has been found to have a similar anesthetic effect to that of lidocaine with 1:100,000 epinephrine, save for a shorter duration of action, and, as such, this may be considered as an alternative in simple mandibular extractions. ### Radiotherapy[edit] Radiotherapy directed at the bones of the jaws causes several changes to the tissue, resulting in decreased blood supply.[3] ### Menstrual cycle[edit] The menstrual cycle could be a determinant risk factor in the frequency of alveolar osteitis. Studies have shown that because of hormonal changes, women in the middle of menstrual cycle and the ones taking oral contraceptives (birth control pills) have a higher tendency of having alveolar osteitis after their tooth extraction surgery. It is recommended that elective surgeries be performed during the menstrual period in both oral contraceptives users and non users to eliminate the effect of cycle-related hormonal changes on the development of alveolar osteitis.[10] ## Diagnosis[edit] Dry socket typically causes pain on the second to fourth day following a dental extraction. Other causes of post extraction pain usually occur immediately after the anesthesia/analgesia has worn off, (e.g., normal pain from surgical trauma or mandibular fracture) or has a more delayed onset (e.g., osteomyelitis, which typically causes pain several weeks following an extraction).[9] Examination typically involves gentle irrigation with warm saline and probing of the socket to establish the diagnosis.[1] Sometimes part of the root of the tooth or a piece of bone fractures off and is retained in the socket. This can be another cause of pain in a socket, and causes delayed healing. A dental radiograph (X-ray) may be indicated to demonstrate such a suspected fragment.[9] ## Prevention[edit] Some evidence suggests that rinsing with chlorhexidine (0.12% or 0.2%) or placing chlorhexidine gel (0.2%) in the sockets of extracted teeth reduces the frequency of dry socket.[4] Another review concluded that preventative antibiotics reduce the risk of dry socket (and infection and pain) following third molar extractions of wisdom teeth, however their use is associated with an increase in mild and transient adverse effects.[11] The authors questioned whether treating 12 people with antibiotics to prevent one infection would do more harm overall than good,[11] in view of the potential side effects and also of antibiotic resistance. Nevertheless, there is evidence that individuals who are at clear risk may benefit from antibiotics.[11] There is also evidence that antifibrinolytic agents applied to the socket after the extraction may reduce the risk of dry socket.[4] Some dentists and oral surgeons routinely debride the bony walls of the socket to encourage hemorrhage (bleeding) in the belief that this reduces the incidence of dry socket, but there is no evidence to support this practice. It has been suggested that dental extractions in females taking oral contraceptives be scheduled on days without estrogen supplementation (typically days 23–28 of the menstrual cycle).[1] It has also been suggested that teeth to be extracted be scaled prior to the procedure.[2] Prevention of alveolar osteitis can be exacted by following post-operative instructions, including: 1. Taking any recommended medications 2. Avoiding intake of hot fluids for one to two days. Hot fluids raise the local blood flow and thus interfere with organization of the clot. Therefore, cold fluids and foods are encouraged, which facilitate clot formation and prevent its disintegration. 3. Avoiding smoking. It reduces the blood supply, leading to tissue ischemia, reduced tissue perfusion and eventually higher incidence of painful socket. 4. Avoiding drinking through a straw or spitting forcefully as this creates a negative pressure within the oral cavity leading to an increased chance of blood clot instability.[8] ## Treatment[edit] Treatment is usually symptomatic,[4] (i.e., pain medications) and also the removal of debris from the socket by irrigation with saline or local anesthetic.[4] Medicated dressings are also commonly placed in the socket;[4] although these will act as a foreign body and prolong healing, they are usually needed due to the pain. The dressings are usually stopped once the pain is lessened. Examples of medicated dressings include antibacterials, topical anesthetics and obtundants, or combinations of all three, e.g., zinc oxide and eugenol impregnated cotton pellets, alvogyl (eugenol, iodoform and butamen), dentalone, bismuth subnitrate and iodoform paste (BIPP) on ribbon gauze and metronidazole and lidocaine ointment.[4][12] A 2012 review of treatments for dry socket concluded that there was not enough evidence to determine the effectiveness of any treatments.[4] People who develop a dry socket typically seek healthcare advice several times after the dental extraction, where the old dressing is removed, the socket irrigated and a new dressing placed. Curettage of the socket increases the pain and whether it is of overall benefit is debated.[1][13] ## Prognosis[edit] If a dry socket occurs, the total healing time is increased. Postoperative pain is also worse than the normal discomfort which accompanies healing following any minor surgical procedure. The pain may last for seven to forty days.[1][2] ## Epidemiology[edit] Overall, the rate of dry socket is about 0.5–5% for routine dental extractions,[2][3][4] and about 25–30% for impacted mandibular third molars (wisdom teeth which are buried in the bone).[1] Females are more frequently affected than males, but this appears to be related to oral contraceptive use rather than any underlying gender predilection.[1][2] The majority of dry sockets occur in individuals aged between 20 and 40 which is when most dental extractions occur, although for any given individual it is more likely to occur with increasing age.[1] Other possible risk factors include periodontal disease, acute necrotizing ulcerative gingivitis, local bone disease, Paget's disease of bone, osteopetrosis, cemento-osseous dysplasia, a history of previously developing a dry socket with past extractions and inadequate oral hygiene.[3][4][9] Other factors in the postoperative period that may lead to loss of the blood clot include forceful spitting, sucking through a straw, and coughing or sneezing.[4] ## Etymology[edit] Alveolar refers to the alveolus, the alveolar processes of the mandible or maxilla; osteitis is derived from oste-, from Greek, osteon meaning "bone"; and -itis means a disease characterized by inflammation. Osteitis generally refers to localized inflammation of bone with no progression through marrow spaces (compare with osteomyelitis).[3] Often, the term alveolar osteitis is considered synonymous with "dry socket", but some specify that dry socket is a focal or localized alveolar osteitis.[2] An example of another type of osteitis is focal sclerosing/condensing osteitis.[3] The name dry socket is used because the socket has a dry appearance once the blood clot is lost and debris is washed away. ## References[edit] 1. ^ a b c d e f g h i j k l m n o p q Neville, BW; Damm, DD; Allen, CM; Bouquot, JE (2002). Oral & Maxillofacial Pathology (2nd ed.). Philadelphia: W.B. Saunders. p. 133. ISBN 0721690033. 2. ^ a b c d e f g h i j k l m n o p Wray, D; Stenhouse D; Lee D; Clark AJE (2003). Textbook of general and oral surgery. Edinburgh [etc.]: Churchill Livingstone. pp. 216–217. ISBN 0443070830. 3. ^ a b c d e f g h i j k l m Soames JV; Southam JC (1999). Oral pathology (3. ed., [Nachdr.] ed.). Oxford [u.a.]: Oxford Univ. Press. pp. 296–298. ISBN 0192628941. 4. ^ a b c d e f g h i j k l m n o p q r Daly, B; Sharif, MO; Newton, T; Jones, K; Worthington, HV (Dec 12, 2012). "Local interventions for the management of alveolar osteitis (dry socket)". Cochrane Database of Systematic Reviews. 12: CD006968. doi:10.1002/14651858.CD006968.pub2. PMID 23235637. 5. ^ Taylor Norris (30 October 2019). "How Long Does It Take to Recover from Dry Socket, and How Long Are You at Risk?". Healthline. 6. ^ Coulthard, P; Horner K; Sloan P; Theaker E (2008). Master dentistry. volume 1: Oral and maxillofacial surgery, radiology, pathology and oral medicine (2nd ed.). Edinburgh: Churchill Livingstone/Elsevier. p. 90. ISBN 9780443068966. 7. ^ a b c d e f Fragiskos, FD (2007). Oral surgery. Berlin: Springer. p. 199. ISBN 3-540-25184-7. 8. ^ a b c Tucker, MR; Hupp JR; Ellis E (2008). Contemporary oral and maxillofacial surgery (5th ed.). St. Louis, Mo.: Mosby Elsevier. p. 198. ISBN 9780323049030. 9. ^ a b c d Odell, Edward W., ed. (2010). Clinical problem solving in dentistry (3rd ed.). Edinburgh: Churchill Livingstone. pp. 67–69. ISBN 9780443067846. 10. ^ Eshghpour, Majid; Rezaei, Naser Mohammadzadeh; Nejat, AmirHossein (2013-09-01). "Effect of menstrual cycle on frequency of alveolar osteitis in women undergoing surgical removal of mandibular third molar: a single-blind randomized clinical trial". Journal of Oral and Maxillofacial Surgery. 71 (9): 1484–1489. doi:10.1016/j.joms.2013.05.004. ISSN 1531-5053. PMID 23866782. 11. ^ a b c Lodi, G; Figini, L; Sardella, A; Carrassi, A; Del Fabbro, M; Furness, S (Nov 14, 2012). "Antibiotics to prevent complications following tooth extractions". Cochrane Database of Systematic Reviews. 11: CD003811. doi:10.1002/14651858.CD003811.pub2. PMID 23152221. 12. ^ Tarakji B, Saleh LA, Umair A, Azzeghaiby SN, Hanouneh S (April 2015). "Systemic review of dry socket: aetiology, treatment, and prevention". J Clin Diagn Res. 9 (4): ZE10–3. doi:10.7860/JCDR/2015/12422.5840. PMC 4437177. PMID 26023661. 13. ^ Taberner-Vallverdu, M; Nazir, M; Sánchez-Garcés, MA; Gay-Escoda, C (Sep 1, 2015). "Efficacy of different methods used for dry socket management: A systematic review". Med Oral Patol Oral Cir Bucal. 20: 633. doi:10.4317/medoral.20589.> ## External links[edit] Classification D * ICD-10: K10.3 * MeSH: D004368 * v * t * e Oral and maxillofacial pathology Lips * Cheilitis * Actinic * Angular * Plasma cell * Cleft lip * Congenital lip pit * Eclabium * Herpes labialis * Macrocheilia * Microcheilia * Nasolabial cyst * Sun poisoning * Trumpeter's wart Tongue * Ankyloglossia * Black hairy tongue * Caviar tongue * Crenated tongue * Cunnilingus tongue * Fissured tongue * Foliate papillitis * Glossitis * Geographic tongue * Median rhomboid glossitis * Transient lingual papillitis * Glossoptosis * Hypoglossia * Lingual thyroid * Macroglossia * Microglossia * Rhabdomyoma Palate * Bednar's aphthae * Cleft palate * High-arched palate * Palatal cysts of the newborn * Inflammatory papillary hyperplasia * Stomatitis nicotina * Torus palatinus Oral mucosa – Lining of mouth * Amalgam tattoo * Angina bullosa haemorrhagica * Behçet's disease * Bohn's nodules * Burning mouth syndrome * Candidiasis * Condyloma acuminatum * Darier's disease * Epulis fissuratum * Erythema multiforme * Erythroplakia * Fibroma * Giant-cell * Focal epithelial hyperplasia * Fordyce spots * Hairy leukoplakia * Hand, foot and mouth disease * Hereditary benign intraepithelial dyskeratosis * Herpangina * Herpes zoster * Intraoral dental sinus * Leukoedema * Leukoplakia * Lichen planus * Linea alba * Lupus erythematosus * Melanocytic nevus * Melanocytic oral lesion * Molluscum contagiosum * Morsicatio buccarum * Oral cancer * Benign: Squamous cell papilloma * Keratoacanthoma * Malignant: Adenosquamous carcinoma * Basaloid squamous carcinoma * Mucosal melanoma * Spindle cell carcinoma * Squamous cell carcinoma * Verrucous carcinoma * Oral florid papillomatosis * Oral melanosis * Smoker's melanosis * Pemphigoid * Benign mucous membrane * Pemphigus * Plasmoacanthoma * Stomatitis * Aphthous * Denture-related * Herpetic * Smokeless tobacco keratosis * Submucous fibrosis * Ulceration * Riga–Fede disease * Verruca vulgaris * Verruciform xanthoma * White sponge nevus Teeth (pulp, dentin, enamel) * Amelogenesis imperfecta * Ankylosis * Anodontia * Caries * Early childhood caries * Concrescence * Failure of eruption of teeth * Dens evaginatus * Talon cusp * Dentin dysplasia * Dentin hypersensitivity * Dentinogenesis imperfecta * Dilaceration * Discoloration * Ectopic enamel * Enamel hypocalcification * Enamel hypoplasia * Turner's hypoplasia * Enamel pearl * Fluorosis * Fusion * Gemination * Hyperdontia * Hypodontia * Maxillary lateral incisor agenesis * Impaction * Wisdom tooth impaction * Macrodontia * Meth mouth * Microdontia * Odontogenic tumors * Keratocystic odontogenic tumour * Odontoma * Dens in dente * Open contact * Premature eruption * Neonatal teeth * Pulp calcification * Pulp stone * Pulp canal obliteration * Pulp necrosis * Pulp polyp * Pulpitis * Regional odontodysplasia * Resorption * Shovel-shaped incisors * Supernumerary root * Taurodontism * Trauma * Avulsion * Cracked tooth syndrome * Vertical root fracture * Occlusal * Tooth loss * Edentulism * Tooth wear * Abrasion * Abfraction * Acid erosion * Attrition Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures * Cementicle * Cementoblastoma * Gigantiform * Cementoma * Eruption cyst * Epulis * Pyogenic granuloma * Congenital epulis * Gingival enlargement * Gingival cyst of the adult * Gingival cyst of the newborn * Gingivitis * Desquamative * Granulomatous * Plasma cell * Hereditary gingival fibromatosis * Hypercementosis * Hypocementosis * Linear gingival erythema * Necrotizing periodontal diseases * Acute necrotizing ulcerative gingivitis * Pericoronitis * Peri-implantitis * Periodontal abscess * Periodontal trauma * Periodontitis * Aggressive * As a manifestation of systemic disease * Chronic * Perio-endo lesion * Teething Periapical, mandibular and maxillary hard tissues – Bones of jaws * Agnathia * Alveolar osteitis * Buccal exostosis * Cherubism * Idiopathic osteosclerosis * Mandibular fracture * Microgenia * Micrognathia * Intraosseous cysts * Odontogenic: periapical * Dentigerous * Buccal bifurcation * Lateral periodontal * Globulomaxillary * Calcifying odontogenic * Glandular odontogenic * Non-odontogenic: Nasopalatine duct * Median mandibular * Median palatal * Traumatic bone * Osteoma * Osteomyelitis * Osteonecrosis * Bisphosphonate-associated * Neuralgia-inducing cavitational osteonecrosis * Osteoradionecrosis * Osteoporotic bone marrow defect * Paget's disease of bone * Periapical abscess * Phoenix abscess * Periapical periodontitis * Stafne defect * Torus mandibularis Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities * Bruxism * Condylar resorption * Mandibular dislocation * Malocclusion * Crossbite * Open bite * Overbite * Overeruption * Overjet * Prognathia * Retrognathia * Scissor bite * Maxillary hypoplasia * Temporomandibular joint dysfunction Salivary glands * Benign lymphoepithelial lesion * Ectopic salivary gland tissue * Frey's syndrome * HIV salivary gland disease * Necrotizing sialometaplasia * Mucocele * Ranula * Pneumoparotitis * Salivary duct stricture * Salivary gland aplasia * Salivary gland atresia * Salivary gland diverticulum * Salivary gland fistula * Salivary gland hyperplasia * Salivary gland hypoplasia * Salivary gland neoplasms * Benign: Basal cell adenoma * Canalicular adenoma * Ductal papilloma * Monomorphic adenoma * Myoepithelioma * Oncocytoma * Papillary cystadenoma lymphomatosum * Pleomorphic adenoma * Sebaceous adenoma * Malignant: Acinic cell carcinoma * Adenocarcinoma * Adenoid cystic carcinoma * Carcinoma ex pleomorphic adenoma * Lymphoma * Mucoepidermoid carcinoma * Sclerosing polycystic adenosis * Sialadenitis * Parotitis * Chronic sclerosing sialadenitis * Sialectasis * Sialocele * Sialodochitis * Sialosis * Sialolithiasis * Sjögren's syndrome Orofacial soft tissues – Soft tissues around the mouth * Actinomycosis * Angioedema * Basal cell carcinoma * Cutaneous sinus of dental origin * Cystic hygroma * Gnathophyma * Ludwig's angina * Macrostomia * Melkersson–Rosenthal syndrome * Microstomia * Noma * Oral Crohn's disease * Orofacial granulomatosis * Perioral dermatitis * Pyostomatitis vegetans Other * Eagle syndrome * Hemifacial hypertrophy * Facial hemiatrophy * Oral manifestations of systemic disease * Medicine portal [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Alveolar osteitis	c0013240	3,840	wikipedia	https://en.wikipedia.org/wiki/Alveolar_osteitis	2021-01-18T18:51:01	{"mesh": ["D004368"], "umls": ["C0013240"], "wikidata": ["Q448753"]}
Not to be confused with Aboulia. This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (August 2015) Motivational deficiency disorder is the name of a fake disease imagined for a health campaign to raise awareness of disease mongering. ## Campaign[edit] the original campaign included a notice to read this issue of PLOS The disease was first described in an effort coordinated by Ray Moynihan when BMJ published a description of it for April Fool's Day in 2006.[1] Fake neurologist "Leth Argos" is said to have described the disorder, finding that "extreme laziness may have a medical basis" and that "motivational deficiency disorder can be fatal, because the condition reduces the motivation to breathe."[1] Despite the condition being poorly understood, it is also "underdiagnosed and undertreated."[1] A person living with the condition complained that he would spend all day at the beach.[2] In the original campaign medical marketers recommended treating the disease with a drug called "Indolebant". They presented a case study in which a lazy man who took the drug then got off his sofa to begin a job as an investment adviser.[1] The original campaign also contained an advertisement for an issue of PLOS on disease mongering.[1] In 2008 Consumers International revived the campaign to draw further attention to the issue of disease mongering.[3] Although a spoof, some news outlets have reported the disease as if this were a real disorder.[4][5] The disease was invented and presented to the public as a demonstration that some media outlets are willing to publish sensational health stories and that people respond with worry when they do.[6] ## References[edit] 1. ^ a b c d e Moynihan, R. (2006). "Scientists find new disease: Motivational deficiency disorder". BMJ. 332 (7544): 745. doi:10.1136/bmj.332.7544.745-a. PMC 1420696. 2. ^ "A New Epidemic". youtube.com. 23 November 2006. Retrieved 13 September 2013. 3. ^ Whalen, Jeanne (5 February 2008). "Striving for an Antidote to Drug Marketing - Health Blog - WSJ". blogs.wsj.com. Retrieved 13 September 2013. 4. ^ Mirsky, Steve (22 May 2006). "Up the Lazy Creek: Scientific American". scientificamerican.com. Retrieved 13 September 2013. 5. ^ Cassels, Alan (4 March 2008). "Spreading disease by word of mouth". Toronto Star. Retrieved 13 September 2013. 6. ^ Barber, Charles (2009). Comfortably numb : how psychiatry is medicating a nation (1st Vintage Books ed.). New York: Vintage Books. pp. 123–124. ISBN 978-0307274953. ## External links[edit] * 4-minute report about motivational deficiency disorder * 1-minute video advertising a drug to treat motivational deficiency disorder * issue of PLOS advertised in original article * transcript of radio report on the condition [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Motivational deficiency disorder	None	3,841	wikipedia	https://en.wikipedia.org/wiki/Motivational_deficiency_disorder	2021-01-18T18:59:20	{"wikidata": ["Q22907063"]}
Primary orthostatic hypotension is a rare type of orthostatic hypotension. It is not a disease per se, but a condition caused by several disorders that affect a specific part of the autonomic nervous system, such as multiple system atrophy, young-onset Parkinson’s disease, pure autonomic failure, dopamine beta-hydroxylase deficiency, familial dysautonomia, and pure autonomic failure among others. The autonomic nervous system is the part of the nervous system that regulates certain involuntary body functions such as heart rate, blood pressure, sweating, and bowel and bladder control. Orthostatic hypotension is a form of low blood pressure that happens when standing-up from sitting or lying down. Common symptoms may include dizziness, lightheadedness, generalized weakness, leg buckling, nausea, blurry vision, fatigue, and headaches. Additional symptoms can include chest pain (angina), head and neck pain (often affecting neck and shoulders with a coat hanger distribution), decline in cognitive functioning such as difficulty concentrating, temporary loss of consciousness or “blackout”. Some people with primary orthostatic hypotension may also have high blood pressure when lying down. The treatment depends upon several factors including the specific underlying cause including The treatment depends upon several factors including the specific underlying cause and may include physical counter-maneuvers like lying down, sitting down, squatting clenching buttocks, leg crossing, and support garment and medication. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Primary orthostatic hypotension	None	3,842	gard	https://rarediseases.info.nih.gov/diseases/12959/primary-orthostatic-hypotension	2021-01-18T17:58:10	{"orphanet": ["182058"], "synonyms": ["Neurogenic Orthostatic Hypotension"]}
Epithelioid sarcoma Micrograph of an epithelioid sarcoma. H&E stain. SpecialtyOncology Epithelioid sarcoma is a rare soft tissue sarcoma arising from mesenchymal tissue and characterized by epithelioid-like features. It accounts for less than 1% of all soft tissue sarcomas. It was first clearly characterized by F.M. Enzinger in 1970.[1] It commonly presents itself in the distal limbs (fingers, hands, forearms, or feet) of young adults as a small, soft mass or a series of bumps. A proximal version has also been described, frequently occurring in the upper extremities.[2] Rare cases have been reported in the pelvis, vulva, penis, and spine. Histologically, epithelioid sarcoma forms nodules with central necrosis surrounded by bland, polygonal cells with eosinophilic cytoplasm and peripheral spindling.[3] Epithelioid sarcomas typically express vimentin, cytokeratins, epithelial membrane antigen, and CD34, whereas they are usually negative for S100, desmin, and FLI1 (FLI-1).[3] They typically stain positive for CA125.[4] Epithelioid sarcoma most commonly strikes young adults, yet no age group is immune. The disease has a tendency to develop local recurrences and metastasis thereafter to regional lymph nodes, lung, bone, brain, and other locations, including the scalp.[3] Generally speaking, epithelioid sarcoma has a high rate of relapse after initial treatment and tends to recur locally (at or near the original tumor site). Epithelioid sarcoma also demonstrates lymphatic spread (in 22-48% of cases), and metastasis (in 21-63% of cases).[5] These events, as well as advanced stage (progression) and grade (aggressiveness), are predictive of an overall worse outcome. The overall five-year survival rate for epithelioid sarcoma is anywhere from 25 to 78%.[5] Importantly, the 10-year and 15-year survival rate drops off significantly.[6][7] Associated with a more positive outcome are younger age, female vs. male sex, distal vs. proximal location, smaller tumor size, and negative margins upon tumor resection.[1][7][8] ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Molecular biology * 3.1 VEGF * 3.2 MET * 3.3 Sonic hedgehog and Notch * 3.4 mTOR * 3.5 EGFR * 3.6 CD109 * 3.7 Cyclin D1 * 4 Diagnosis * 4.1 Staging * 5 Treatment * 6 Prognosis * 7 Research * 7.1 Chemotherapy * 7.2 Immunotherapies * 7.3 Anti-angiogenic therapies * 7.4 Targeted therapies * 7.4.1 Tyrosine kinase inhibitors * 7.4.2 SINE * 7.4.3 HDAC inhibitors * 7.4.4 CDK inhibitors * 7.5 Targeting the cancer stem cell * 7.6 Oncolytic viral therapy * 7.6.1 CGTG-102 * 8 Additional images * 9 See also * 10 References * 11 Further reading * 12 External links ## Signs and symptoms[edit] Epithelioid sarcoma is a slow-growing and relatively painless tumor, often resulting in a lengthy period of time between presentation and diagnosis.[6] Due to its ambiguity, it is often misdiagnosed, mistaken as a persistent wart or cyst. It most commonly presents itself in the distal limbs (fingers, hands, forearms, or feet) as a small, soft mass or a series of bumps. It is most often described as a firm-to-hard palpable mass, either in the deep soft tissue or in the dermis. Often, ulcerate causing a mistaken diagnosis of a poorly healing traumatic wound or wart. About 13% of patients will present with multifocal tumors, and about 13% of patients will present with metastatic disease.[9] ## Genetics[edit] The most common genetic mutation (found in 80-90% of epithelioid sarcomas) is the inactivation of the SMARCB1 gene, or the loss of INI-1 function,[10][11] which is thought to be a major contributor to disease progression. Epithelioid sarcoma typically contains chromosome 22q11.2 mutations or deletions and 8q gains, particularly i(8) (>q10). Aberrations of 18q and 8q, as well as recurrent gains at 11q13, have also been observed.[12][13][14] The SMARCB1 gene (also termed BAF47, INI1, or hSNF5) is located on chromosome 22q11.2[10] and codes for a member of the SWI/SNF chromatin remodeling complex. Loss of SMARCB1 function is the most common genetic mutation observed in epithelioid sarcoma, and this dysfunction is likely a major driver of disease progression. SMARCB1 is a core protein subunit of the 15 subunit SWI/SNF (or BAF) complex involved in regulating the nucleosome architecture of our genome[10] and has been shown to be a potent tumor suppressor gene,[11][15] meaning that its primary role is to control cell division and to even halt division under appropriate circumstances (i.e. signals to over-replicate). As this tumor suppressor is commonly inactivated in epithelioid sarcoma, cell division can fail to appropriately halt, resulting in unregulated cellular growth and the formation of cancer tumors. Several research teams are currently developing techniques to reverse this loss of genetic function characteristic of epithelioid sarcoma.[6] ## Molecular biology[edit] ### VEGF[edit] VEGF (vascular endothelial growth factor) is often over-expressed in epithelioid sarcoma.[16] This is a critical pathway in angiogenesis, a process that cancer cells use to form new blood vessels, which provide necessary elements to the tumor for tumor survival. Anti-VEGF agents such as pazopanib have shown promise across several different carcinomas and in soft tissue sarcomas.[17] In one case study, a patient with advanced metastatic vulvar epithelioid sarcoma showed a partial resolution of both lung and pleural metastases when pazopanib was administered, whereas all other therapies had failed[18] ### MET[edit] MET (mesenchymal to epithelial transition) is another biological pathway that is likely involved in the development and progression of epithelioid sarcoma.[19][20] c-MET is a tyrosine kinase oncogene, and its signaling pathway has been implicated in a variety of malignancies, including many cancers.[citation needed] ### Sonic hedgehog and Notch[edit] The Sonic hedgehog and Notch signaling pathways are also suspected to be up-regulated in epithelioid sarcoma. These cell signaling pathways control cellular proliferation and differentiation. They are also involved in cancer stem cell coordination and disease invasiveness and metastasis. Hhat inhibitors (such as RU-SKI 43) block the Sonic hedgehog signaling pathway by inhibiting hedgehog palmitoyl acytl-transferase. Current trials are investigating Notch inhibitors against epithelioid sarcoma.[21] ### mTOR[edit] The frequent hyperactivation of mTOR (mammalian target of rapamycin) signaling has also been observed in epithelioid sarcoma.[20][22] The mTOR pathway has been described as a “master switch” for cellular catabolism and anabolism, and it can enhance cell cycle progression, cell survival, and block normal cell death (apoptosis).[17] It has been demonstrated that simply blocking mTOR signaling can result in the reactivation of the AKT pathway, negating much of the anti-mTOR's efficacy.[20] This reactivation of AKT has been shown to be c-MET-dependent,[20] resulting in the rationale that blocking both mTOR and c-MET concurrently would show increased efficacy. ### EGFR[edit] The over-expression of epidermal growth factor receptor (EGFR) has been reported in a majority of epithelioid sarcomas.[22][23] EGFR is a member of the HER receptor family. Upon ligand binding, EGFR phosphorylation triggers the activation of downstream signaling pathways involved in critical cellular functions such as proliferation, survival, and angiogenesis.[24] In-vitro and in-vivo laboratory experiments have demonstrated that the blockade of EGFR in epithelioid sarcoma results in decreased cell proliferation, increased apoptosis, and abrogated invasion and migration capacities.[22] While the simple blockade of EGFR with a single agent has shown limited results in the clinical setting, when used as part of a combination regime (where an EGFR inhibitor is combined with an mTOR inhibitor), a synergism has been observed, and superior tumor growth inhibition has been demonstrated.[22] ### CD109[edit] CD109 is often expressed in advanced epithelioid sarcoma and is thought to mark the cancer stem cell (or cancer initiating cell) of the disease.[25] Its level of expression has also been shown to be predictive of outcome. Cancer stem cells are a small population of tumor cells characterized by general chemo-resistance, the ability to self-renew, multi-differentiation potential, dormancy capabilities, and tumorigenesis. Therefore, cancer stem cells are thought to play key roles in the progression and relapse of cancer. ### Cyclin D1[edit] Cyclin D1 is a protein requisite for cell cycle progression and has been shown to be up-regulated in epithelioid sarcoma.[14] Cyclin D-1 is a regulator of cyclin-dependent kinases (CDK4 and CDK6). It has been shown to interact with the retinoblastoma protein (a tumor suppressor gene), CDK4 and CDK6, thyroid hormone receptor beta, and nuclear receptor coactivator 1, among others.[14] Cyclin D and CDKs promote cell cycle progression by releasing transcription factors that are important for the initiation of DNA replication. Abnormal levels of cyclin D-1 may promote rapid cell division in epithelioid sarcoma. ## Diagnosis[edit] Tissue biopsy is the diagnostic modality of choice. Due to a high incidence of lymph node involvement, a sentinel lymph node biopsy is often performed. A common characteristic of epithelioid sarcoma (observed in 80% of all cases) is the loss of function of the SMARCB1 gene (also termed BAF47, INI1, or hSNF5). Immunohistochemical staining of INI1 is available and can be used for the diagnosis of epithelioid sarcoma. MRI is the diagnostic modality of choice for imaging prior to biopsy and pathologic diagnosis, with the primary role being the determination of anatomic boundaries.[citation needed] ### Staging[edit] The staging for epithelioid sarcoma takes into account size and location of the primary tumor, lymph node involvement, presence and location of metastasis, and histologic grade (a measure of disease aggressiveness)[26] ## Treatment[edit] Surgical resection of the tumor with wide margins remains the preferred method of treatment,[27] and has shown the most success against the disease.[27][28][29] Recently, limb-sparing surgery has been explored with moderate success.[30] In cases of advanced, recurrent, or metastasized disease, or if the tumor is inoperable, chemotherapy and radiation are the standard of care,[31] although the overall success rates with these remains low.[32] In January 2020, The U.S. Food and Drug Administration approved Tazverik (tazemetostat), a compound that blocks the EZH2 methyltransferase for the treatment epithelioid sarcoma in patients aged 16 years and older with either metastatic or locally advanced (unable to be completely removed surgically) disease.[33] ## Prognosis[edit] The 5-year survival rate for epithelioid sarcoma patients is 50-70%, and the 10-year survival rate is 42-55%. Children with epithelioid sarcoma tend to have slightly better outcomes than adults, with 5 year survival rates around 65%.[7] Pediatric patients also tend to display less lymphatic spread and metastasis.[7] In addition to stage and grade of the tumor, gender, site, age at diagnosis, tumor size and microscopic pathology have all been shown to affect prognosis.[9][34] Advanced stage and grade are associated with worse outcomes. Females tend to have more favorable outcomes than males, proximal cases show worse outcomes than distal cases, and younger age is associated with more positive outcomes. Tumors more than 2 cm in diameter and tumors with necrosis and vascular invasion have been correlated with a worse outcome.[34] The gold standard for chemotherapy is a combination of doxorubicin and ifosfamide. However, recent studies have suggested that the addition of ifosfamide to doxorubicin does not necessarily lead to an increase in overall survival.[35] Etoposide, vincristine, dactinomycin, and cyclophosphamide have also traditionally been given.[31] Newer chemotherapies, such as gemcitabine and pazopanib, are currently being tested in clinical trials.[citation needed] Radiation therapy is also a treatment option when tumors are deemed inoperable or wide surgical margins are not achievable. Radiation therapy in combination with chemotherapy has so far resulted in only minimal improvements to response rates. Trials with brachytherapy (an internal radiation treatment that delivers a high dose of radiation directly to the tumor and is thought to have fewer long-term side effects) have produced some positive results.[citation needed] ## Research[edit] Epithelioid sarcoma (especially advanced stage, recurrent, or metastasized disease) has been shown to be resistant to traditional cancer therapies, necessitating further exploration of novel treatment methods and techniques. Because of the relatively poor response of epithelioid sarcoma to traditional cancer treatments (surgery, chemotherapy, and radiation), new treatment strategies are being looked to.[citation needed] ### Chemotherapy[edit] New chemotherapies are being explored in current clinical trials for epithelioid sarcoma, although, thus far, none has shown significant improvement over the efficacy of doxorubicin/ifosfamide. These new agents include gemcitabine, pazopanib, cixutumumab, temozolomide, dasatanib, bevacizumab, taxanes, and vinorelbine.[31] Aldoxorubicin is a new pro-drug of doxorubicin. Doxorubicin is the standard of care for advanced or metastic epithelioid sarcoma, but has dose-limiting toxicities, namely acute and chronic cardiac toxicity.[36][37] Doxorubicin has achieved response rates in the 12-23% range for patients with soft tissue sarcomas. Aldoxorubicin is a new version of doxorubicin that is designed to safely deliver a higher dose of the drug directly to the tumor, resulting in increased efficacy and less toxicity. It works by entering the bloodstream, binding to the albumin in the blood, traveling throughout the body, and releasing a doxorubicin payload when it encounters the acidic microenvironment of a tumor.[38] Several phase I and II studies are ongoing, and, thus far at least, little if any cardiac toxicity has been observed. A maximum tolerated dose of aldoxorubicin has been established at 3.5 times the MTD of doxorubicin, and studies have indicated increased response rates for patients with soft tissue sarcomas. What is unknown at this time are the potential long-term side-effects of this increased dose of doxorubicin. Several studies have shown increased risk of the development of secondary cancers associated with exposure to high-dose anthracyclines (such as doxorubicin).[39] TH-302 is another novel prodrug in current development. It targets tumor hypoxia, a common event in tumorigenesis where the tumor microenvironment is depleted of oxygen and becomes hypoxic.[40] Hypoxic niches in tumors tend to harbor slower-growing cancer cells,[41] making many chemotherapies ineffective in these areas. TH-302 directly targets these deep hypoxic regions, and once within them, it releases a cytotoxic payload of bromo-isophosphoramide mustard directly to the cancer cells.[40] Given that epithelioid sarcoma is a slow-growing tumor, it is reasonable to hypothesize that ES tumors would be highly hypoxic and show a favorable response to TH-302. Several studies have observed increased efficacy of TH-302 when the hypoxic tumor microenvironment has been exasperated.[42] Several phase I, II, and III trials with TH-302 and TH-302 in combination with doxorubicin are ongoing, and promising results have thus far been observed.[43] Two phase 3 trials failed in 2015. ### Immunotherapies[edit] Immunotherapy is the strategy of using the body's own immune system to fight cancer. It usually involves “training” or “tweaking” the immune system so that it can better recognize and reject cancer cells. Different immunotherapies can include manipulation of the body's T-cells, NK cells, or Dendritic cells so they are more effective against cancer cells. They can also include the administration of laboratory-produced antibodies specific to tumor antigens to create or boost an immune response.[citation needed] Vaccine therapy is perhaps the immunotherapeutic strategy with the most ongoing exploration in sarcomas at the current time,[44] although, thus far at least, little evidence has emerged indicating that active vaccination alone can lead to tumor regression.[45] Multiple techniques and treatment strategies are currently being studied in an effort to improve the objective response rate of vaccine therapy.[44] Vaccines can deliver various tumor-associated factors (tumor antigens) to the immune system, resulting in a natural antibody and T-cell response to the tumor.[44][46] Adoptive immunotherapy seeks to expand a population of the body's T-cells that will recognize a specific tumor antigen. T-cells can be harvested and then expanded and genetically manipulated to recognize certain tumor markers.[44][46] In one case, a patient with advanced epithelioid sarcoma who had failed multiple therapies showed a strong response to expanded lymphocytes and natural killer cells.[47] Immune checkpoint inhibitors have recently shown promise against several cancers and may hold promise against sarcomas as well. Tumors often evolve during disease progression, and they can develop an expression of inhibitory proteins that deter recognition by the immune system and allow the tumor to escape immune surveillance.[45] By targeting these inhibitory proteins, a pathway is opened for the immune system to recognize the tumor. Two of these inhibitory proteins that have been studied recently are CTLA-4 and PD1,[45] and drugs targeting these proteins are in development and showing some promise. ### Anti-angiogenic therapies[edit] Several anti-angiogenic agents are being explored in epithelioid sarcoma,[citation needed] a cancer that likely relies on angiogenesis for survival and progression. These agents interfere with various pro-angiogenic factors, several of which are known to be over-expressed in epithelioid sarcoma[16][23] (VEGF and EGFR for example).[48][49] Tumors require a blood supply to provide them with oxygen and nutrients necessary for their survival. As tumors expand and grow, they send out various signals (such as HIF1) that encourage new blood vessel development to the tumor.[50] Anti-angiogenic agents, such as bevacizumab, attempt to slow or block the growth of tumors by essentially cutting off their blood supply. ### Targeted therapies[edit] Given the multiple genetic abnormalities and disrupted biological pathways observed in epithelioid sarcoma, drugs targeting these unique tumor characteristics are being looked at for more effective treatments. #### Tyrosine kinase inhibitors[edit] Tyrosine kinase inhibitors (such as sunitinib, pazopanib, and dasatinib) have shown some effect against several cancer types, most notably Imatinib-mesylate in gastrointestinal stromal tumors (GISTs).[51] Tyrosine kinase (a subclass of protein kinases) is an enzyme that transfers a phosphate group from an ATP molecule to a protein in a cell.[52] It functions as an “on” or “off” switch for many cellular functions, including signaling within the cell, and cell division. Tyrosine kinases can contain mutations that cause them to become constitutively active,[53] or stuck in the “on” position, resulting in unregulated cell division (a hallmark of cancer). Tyrosine kinase Inhibitors block the action of these enzymes. Tyrosine kinase inhibitors have been shown to inhibit the VEGF, EGFR, and MET,[52] pathways that are frequently over-expressed in epithelioid sarcoma. They also can be used against the c-KIT and JAK-STAT signaling pathways,[52] which are involved in many cancers and may be involved in epithelioid sarcoma. Temsirolimus is a tyrosine kinase inhibitor that blocks the effects of the mTOR protein and inhibits the mTOR pathway. Because of crosstalk between cell signaling pathways, it has been shown that, while interfering with the mTOR pathway alone produces only limited results in halting tumorigenesis, inhibiting both the mTOR and the EGFR pathways concurrently shows an increased effect.[22] #### SINE[edit] Selective inhibitors of nuclear export (SINE) compounds, such as selinexor and CBS9106, are being investigated in several sarcomas and have recently shown promising results across a broad spectrum of both hematological malignancies and solid tumors.[54][55] These compounds work by blocking the export of tumor suppressor genes from the cell's nucleus to the cell's cytoplasm,[54][56] where they are rendered nonfunctional.[57] Exportin 1 (a.k.a. XPO1 or CRM1) is a nuclear export protein responsible for the export of over 200 proteins, including the vast majority of tumor suppressor proteins.[54] For tumor suppressor genes to carry out their normal function (appropriately initiating apoptosis), they must be located in the nucleus of the cell.[57] Many cancer cells have been shown to express high levels of exportin1,[54][56] resulting in the increased export of tumor suppressor proteins out of the nucleus and therefore counteracting the natural apoptic processes that protect the body from cancer. SINE compounds prevent the transport of these tumor suppressor proteins out of the nucleus, allowing them to function normally and encourage apoptosis. Recently, researchers have observed a synergistic effect when using SINE compounds in combination with traditional chemotherapies (such as doxorubicin).[58] It has been demonstrated that a loss of INI1 expression can result in the “unmasking” of a nuclear export signal,[59] resulting in the transport of tumor suppressor proteins out of the nucleus of the cell, thus favoring tumorigenesis. It is therefore reasonable to suspect that a SINE inhibitor would show efficacy against epithelioid sarcoma, as the disease is characterized by a loss of INI1 function. #### HDAC inhibitors[edit] Histone deacetylase (HDAC) inhibitors, such as vorinostat, have shown some promise in epithelioid sarcoma. Researchers in Texas are investigating whether or not HDAC inhibitors can reverse the loss of INI1 function that is characteristic of epithelioid sarcoma.[6] HDAC inhibitors work by blocking events involved in DNA replication and, therefore, in cell division.[60] Blocking HDAC has been shown to encourage cancer cells to enter apoptosis.[6] Several dietary phytochemicals have been shown to be effective HDAC inhibitors.[61] These include sulphorphane, indole-3-carbinol, and phenethyl isothiocyanates, found in broccoli, kale, and watercress, and epigallocatecehin-3-gallate, found in green tea.[citation needed] #### CDK inhibitors[edit] Because of the association (see above) with cyclin D1 CDK inhibitors are being studied. palbociclib is a CDK inhibitor (approved for some breast cancer). Other experimental CDK inhibitors include abemaciclib and ribociclib. ### Targeting the cancer stem cell[edit] Cancer stem cells (or cancer-initiating cells) are thought to be a small population of cells within the tumor that are directly responsible for tumor formation. They are thought to be resistant to treatment and to have the ability to form all the cells needed for tumor development. They are suspected to be a major contributing factor in cancer progression and relapse after treatment. Certain “stem-like” cells have been found in epithelioid sarcoma that are marked by CD109 (cluster of differentiation 109),[25] providing a potentially drug-able target on the cancer stem cell for the disease. Certain challenges to targeting CD109 do exist, however, as CD109 is expressed in other areas of the body and not only in tumor cells.[citation needed] ### Oncolytic viral therapy[edit] Oncolytic viral therapy is an emerging cancer therapy that attempts to infect cancer cells with a genetically engineered virus that can penetrate the DNA of the cell. The virus then 1.) does direct damage to the cancer cell, 2.) is spread throughout the cells of the tumor via cellular (DNA) multiplication (tumor cell division and replication), and 3.) provides a target for a direct immune response from the patient.[17][62] It has been noted that the therapeutic potential of oncolytic virotherapy is not a simple consequence of the cytopathic effect but strongly relies on the induction of an endogenous immune response against transformed cells.[62][63] Superior anticancer effects have been observed when oncolytic viruses are engineered to express (or be co-administered with) immunostimulatory molecules such as GM-CSF.[63] Telomelysin (OBP-301) is an adenovirus that targets telomerase,[64] an enzyme that is expressed in practically all cancer cells but not in normal cells. OBP-301 has been studied in epithelioid sarcoma and shown to promote apoptosis and cell death [.[64] #### CGTG-102[edit] CGTG-102 (developed by Oncos Therapeutics) is an adenovirus currently in orphan drug status for soft tissue sarcomas. It is modified to selectively replicate in p16/Rb-defective cells, which include most human cancer cells. In addition, CGTG-102 codes for the granulocyte–macrophage colony-stimulating factor (GM-CSF),[63][65] a potent immunostimulatory molecule. While the CGTG-102 oncolytic adenovirus has shown efficacy as a single agent against several soft tissue sarcomas, it would also be appealing to use in combination with other regimes, as oncolytic viruses have demonstrated very little overlap in side effects with traditional therapies such as chemotherapy and radiation.[62][63] CGTG-102 has recently been studied in combination with doxorubicin, and a synergistic effect was observed.[66] At least part of doxorubicin's mechanism of action is as an inducer of immunogenic cell death, and it has been suggested that immune response contributes to its overall anti-tumor activity. Doxorubicin has been shown to increase adenoviral replication in soft tissue sarcoma cells as well,[66] potentially contributing to the observed synergistic effect in the virus/doxorubicin combination. ## Additional images[edit] * Intermed. mag. * High mag. * High mag. 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"Secondary Sarcomas in Childhood Cancer Survivors: A Report From the Childhood Cancer Survivor Study". Journal of the National Cancer Institute. 99 (4): 300–8. doi:10.1093/jnci/djk052. PMID 17312307. 40. ^ a b Meng, F.; Evans, J. W.; Bhupathi, D.; Banica, M.; Lan, L.; Lorente, G.; Duan, J.-X.; Cai, X.; Mowday, A. M.; Guise, C. P.; Maroz, A.; Anderson, R. F.; Patterson, A. V.; Stachelek, G. C.; Glazer, P. M.; Matteucci, M. D.; Hart, C. P. (2012). "Molecular and Cellular Pharmacology of the Hypoxia-Activated Prodrug TH-302". Molecular Cancer Therapeutics. 11 (3): 740–51. doi:10.1158/1535-7163.MCT-11-0634. PMID 22147748. S2CID 11701323. 41. ^ Wilson, William R.; Hay, Michael P. (2011). "Targeting hypoxia in cancer therapy". Nature Reviews Cancer. 11 (6): 393–410. doi:10.1038/nrc3064. PMID 21606941. S2CID 36040922. 42. ^ Wojtkowiak, Jonathan W; Cornnell, Heather C; Matsumoto, Shingo; Saito, Keita; Takakusagi, Yoichi; Dutta, Prasanta; Kim, Munju; Zhang, Xiaomeng; Leos, Rafael; Bailey, Kate M; Martinez, Gary; Lloyd, Mark C; Weber, Craig; Mitchell, James B; Lynch, Ronald M; Baker, Amanda F; Gatenby, Robert A; Rejniak, Katarzyna A; Hart, Charles; Krishna, Murali C; Gillies, Robert J (2015). "Pyruvate sensitizes pancreatic tumors to hypoxia-activated prodrug TH-302". Cancer & Metabolism. 3 (1): 2. doi:10.1186/s40170-014-0026-z. PMC 4310189. PMID 25635223. 43. ^ Chawla, S. P.; Cranmer, L. D.; Van Tine, B. A.; Reed, D. R.; Okuno, S. H.; Butrynski, J. E.; Adkins, D. R.; Hendifar, A. E.; Kroll, S.; Ganjoo, K. N. (2014). "Phase II Study of the Safety and Antitumor Activity of the Hypoxia-Activated Prodrug TH-302 in Combination With Doxorubicin in Patients With Advanced Soft Tissue Sarcoma". Journal of Clinical Oncology. 32 (29): 3299–306. doi:10.1200/JCO.2013.54.3660. PMC 4588714. PMID 25185097. 44. ^ a b c d Wilky, Breelyn; Goldberg, John M. (April 14, 2014). "Immunotherapy in sarcoma: A new frontier". Discovery Medicine. 17 (94): 201–6. PMID 24759624. 45. ^ a b c Hu, James S; Skeate, Joseph G; Kast, Wijbe Martin (2014). "Immunotherapy in sarcoma: A brief review". Sarcoma Research International. 1 (1): id1003. 46. ^ a b Pedrazzoli, Paolo; Secondino, Simona; Perfetti, Vittorio; Comoli, Patrizia; Montagna, Daniela (2011). "Immunotherapeutic Intervention against Sarcomas". Journal of Cancer. 2: 350–6. doi:10.7150/jca.2.350. PMC 3119402. PMID 21716856. 47. ^ Ratnavelu, Kananathan; Subramani, Baskar; Pullai, Chithra Ramanathan; Krishnan, Kohila; Sugadan, Sheela Devi; Rao, Manjunath Sadananda; Veerakumarasivam, Abhi; Deng, Xuewen; Hiroshi, Terunuma (2013). "Autologous immune enhancement therapy against an advanced epithelioid sarcoma: A case report". Oncology Letters. 5 (5): 1457–1460. doi:10.3892/ol.2013.1247. PMC 3678875. PMID 23761810. 48. ^ Ciardiello, F; Troiani, T; Bianco, R; Orditura, M; Morgillo, F; Martinelli, E; Morelli, MP; Cascone, T; Tortora, G (2006). "Interaction between the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor (VEGF) pathways: a rational approach for multi-target anticancer therapy". Annals of Oncology. 17 (Suppl 7): vii109–14. doi:10.1093/annonc/mdl962. PMID 16760272. 49. ^ Hirata, Akira; Ogawa, Soh-ichiro; Kometani, Takuro; Kuwano, Takashi; Naito, Seiji; Kuwano, Michihiko; Ono, Mayumi (2002). "ZD1839 (Iressa) induces antiangiogenic effects through inhibition of epidermal growth factor receptor tyrosine kinase". Cancer Research. 62 (9): 2554–60. PMID 11980649. 50. ^ Carmeliet, Peter; Dor, Yuval; Herbert, Jean-Marc; Fukumura, Dai; Brusselmans, Koen; Dewerchin, Mieke; Neeman, Michal; Bono, Françoise; Abramovitch, Rinat; Maxwell, Patrick; Koch, Cameron J.; Ratcliffe, Peter; Moons, Lieve; Jain, Rakesh K.; Collen, Désiré; Keshet, Eli (1998). "Role of HIF-1α in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis". Nature. 394 (6692): 485–90. Bibcode:1998Natur.394..485C. doi:10.1038/28867. PMID 9697772. S2CID 4419118. 51. ^ Demetri, GD (2002). "Identification and treatment of chemoresistant inoperable or metastatic GIST: experience with the selective tyrosine kinase inhibitor imatinib mesylate (STI571)". European Journal of Cancer. 38 (Suppl 5): S52–9. doi:10.1016/s0959-8049(02)80603-7. PMID 12528773. 52. ^ a b c Arora, Amit; Scholar, Eric M. (2005). "Role of Tyrosine Kinase Inhibitors in Cancer Therapy". Journal of Pharmacology and Experimental Therapeutics. 315 (3): 971–9. doi:10.1124/jpet.105.084145. PMID 16002463. S2CID 33720. 53. ^ Lengyel, Ernst; Sawada, Kenjiro; Salgia, Ravi (2007). "Tyrosine Kinase Mutations in Human Cancer". Current Molecular Medicine. 7 (1): 77–84. doi:10.2174/156652407779940486. PMID 17311534. 54. ^ a b c d Gerecitano, John (2014). "SINE (selective inhibitor of nuclear export) – translational science in a new class of anti-cancer agents". Journal of Hematology & Oncology. 7: 67. doi:10.1186/s13045-014-0067-3. PMC 4197302. PMID 25281264. 55. ^ Sakakibara, K.; Saito, N.; Sato, T.; Suzuki, A.; Hasegawa, Y.; Friedman, J. M.; Kufe, D. W.; VonHoff, D. D.; Iwami, T.; Kawabe, T. (2011). "CBS9106 is a novel reversible oral CRM1 inhibitor with CRM1 degrading activity". Blood. 118 (14): 3922–31. doi:10.1182/blood-2011-01-333138. PMID 21841164. S2CID 16936188. 56. ^ a b Gravina, Giovanni; Senapedis, William; McCauley, Dilara; Baloglu, Erkan; Shacham, Sharon; Festuccia, Claudio (2014). "Nucleo-cytoplasmic transport as a therapeutic target of cancer". Journal of Hematology & Oncology. 7: 85. doi:10.1186/s13045-014-0085-1. PMC 4272779. PMID 25476752. 57. ^ a b Hill, Richard; Cautain, Bastien; de Pedro, Nuria; Link, Wolfgang (2014). "Targeting nucleocytoplasmic transport in cancer therapy". Oncotarget. 5 (1): 11–28. doi:10.18632/oncotarget.1457. PMC 3960186. PMID 24429466. 58. ^ Turner, Joel G.; Dawson, Jana; Cubitt, Christopher L.; Baz, Rachid; Sullivan, Daniel M. (2014). "Inhibition of CRM1-dependent nuclear export sensitizes malignant cells to cytotoxic and targeted agents". Seminars in Cancer Biology. 27: 62–73. doi:10.1016/j.semcancer.2014.03.001. PMC 4108511. PMID 24631834. 59. ^ Craig, Errol; Zhang, Zhi‐Kai; Davies, Kelvin P.; Kalpana, Ganjam V. (2002). "A masked NES in INI1/hSNF5 mediates hCRM1-dependent nuclear export: implications for tumorigenesis". The EMBO Journal. 21 (1–2): 31–42. doi:10.1093/emboj/21.1.31. PMC 125819. PMID 11782423. 60. ^ Demicco, Elizabeth G.; Maki, Robert G.; Lev, Dina C.; Lazar, Alexander J. (2012). "New Therapeutic Targets in Soft Tissue Sarcoma". Advances in Anatomic Pathology. 19 (3): 170–80. doi:10.1097/PAP.0b013e318253462f. PMC 3353406. PMID 22498582. 61. ^ Rajendran, Praveen; Ho, Emily; Williams, David E; Dashwood, Roderick H (2011). "Dietary phytochemicals, HDAC inhibition, and DNA damage/repair defects in cancer cells". Clinical Epigenetics. 3 (1): 4. doi:10.1186/1868-7083-3-4. PMC 3255482. PMID 22247744. 62. ^ a b c Pol, Jonathan G; Rességuier, Julien; Lichty, Brian D (2012). "Oncolytic viruses: a step into cancer immunotherapy". Virus Adaptation and Treatment. 4: 1–21. doi:10.2147/VAAT.S12980. 63. ^ a b c d Hemminki, Akseli (2014). "Oncolytic Immunotherapy: Where Are We Clinically?". Scientifica. 2014: 1–7. doi:10.1155/2014/862925. PMC 3914551. PMID 24551478. 64. ^ a b Li, Gui-Dong; Kawashima, Hiroyuki; Ogose, Akira; Ariizumi, Takashi; Hotta, Tetsuo; Kuwano, Ryozo; Urata, Yasuo; Fujiwara, Toshiyoshi; Endo, Naoto (2013). "Telomelysin shows potent antitumor activity through apoptotic and non-apoptotic cell death in soft tissue sarcoma cells". Cancer Science. 104 (9): 1178–88. doi:10.1111/cas.12208. PMC 7656541. PMID 23718223. S2CID 33300842. 65. ^ Bramante, Simona; Koski, Anniina; Kipar, Anja; Diaconu, Iulia; Liikanen, Ilkka; Hemminki, Otto; Vassilev, Lotta; Parviainen, Suvi; Cerullo, Vincenzo; Pesonen, Saila K; Oksanen, Minna; Heiskanen, Raita; Rouvinen-Lagerström, Noora; Merisalo-Soikkeli, Maiju; Hakonen, Tiina; Joensuu, Timo; Kanerva, Anna; Pesonen, Sari; Hemminki, Akseli (2014). "Serotype chimeric oncolytic adenovirus coding for GM-CSF for treatment of sarcoma in rodents and humans". International Journal of Cancer. 135 (3): 720–30. doi:10.1002/ijc.28696. PMID 24374597. S2CID 22657446. 66. ^ a b Siurala, Mikko; Bramante, Simona; Vassilev, Lotta; Hirvinen, Mari; Parviainen, Suvi; Tähtinen, Siri; Guse, Kilian; Cerullo, Vincenzo; Kanerva, Anna; Kipar, Anja; Vähä-Koskela, Markus; Hemminki, Akseli (2015). "Oncolytic adenovirus and doxorubicin-based chemotherapy results in synergistic antitumor activity against soft-tissue sarcoma". International Journal of Cancer. 136 (4): 945–54. doi:10.1002/ijc.29048. PMID 24975392. S2CID 27535394. ## Further reading[edit] * Laskin, William B.; Miettinen, Markku (2003). "Epithelioid sarcoma: new insights based on an extended immunohistochemical analysis". Archives of Pathology & Laboratory Medicine. 127 (9): 1161–8. doi:10.1043/1543-2165(2003)127<1161:ESNIBO>2.0.CO;2 (inactive 2021-01-15). PMID 12946229.CS1 maint: DOI inactive as of January 2021 (link) ## External links[edit] Classification D * ICD-O: M8804/3 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Epithelioid sarcoma	c0205944	3,843	wikipedia	https://en.wikipedia.org/wiki/Epithelioid_sarcoma	2021-01-18T19:00:38	{"gard": ["10181"], "mesh": ["D012509"], "umls": ["C0205944"], "orphanet": ["293202"], "wikidata": ["Q5383708"]}
Camptodactyly - fibrous tissue hyperplasia - skeletal dysplasia syndrome is an extremely rare chondrodysplastic malformation syndrome that is characterized by the combination of arachnodactyly, becoming evident at around the age of 10, camptodactyly (hammertoes) and scoliosis. A mild facial dysmorphism including a broad nose and flaring nostrils, and a mild intellectual disability were also noted. Camptodactyly - fibrous tissue hyperplasia - skeletal dysplasia syndrome has been described once in 3 siblings and is suspected to follow autosomal recessive transmission. There have been no further descriptions in the literature since 1972. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Camptodactyly-fibrous tissue hyperplasia-skeletal dysplasia syndrome	c1859357	3,844	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1321	2021-01-23T18:56:33	{"gard": ["1064"], "mesh": ["C537974", "C537287"], "omim": ["211930"], "umls": ["C1859357"], "icd-10": ["Q87.2"], "synonyms": ["Goodman camptodactyly"]}
Enchondroma Micrograph of an enchondroma. H&E stain. An enchondroma is a benign cartilage tumour found inside bones. Typically, enchondroma is discovered on an X-ray scan. Enchondromas have a characteristic appearance on Magnetic Resonance Imaging (MRI) as well. They have also been reported to cause increased uptake on PET examination. ## Contents * 1 Symptoms * 1.1 Associated conditions * 2 Cause * 3 Pathophysiology * 4 Diagnosis * 5 Treatment * 6 See also * 7 References * 8 External links ## Symptoms[edit] X-ray showing an enchondroma in the femur. MRI T1 showing an enchondroma in the femur. Individuals with an enchondroma often have no symptoms at all. The following are the most common symptoms of an enchondroma. However, each individual may experience symptoms differently. Symptoms may include:[citation needed] * Pain that may occur at the site of the tumor if the tumor is very large, or if the affected bone has weakened causing a fracture of the affected bone * Enlargement of the affected finger * Slow bone growth in the affected area The symptoms of enchondroma may resemble other medical conditions or problems. Always consult your physician for a diagnosis. ### Associated conditions[edit] An enchondroma may occur as an individual tumor or several tumors. The conditions that involve multiple lesions include the following:[citation needed] * Ollier disease (enchondromatosis) - when multiple sites in the body develop the tumors. Ollier disease is very rare. * Maffucci's syndrome \- a combination of multiple tumors and angiomas (benign tumors made up of blood vessels). ## Cause[edit] While the exact cause of enchondroma is not known, it is believed to occur either as an overgrowth of the cartilage that lines the ends of the bones, or as a persistent growth of original, embryonic cartilage.[citation needed] ## Pathophysiology[edit] Enchondroma is a type of benign bone tumor that originates from cartilage. The exact etiology of it is not known. An enchondroma most often affects the cartilage that lines the inside of the bones. The bones most often involved with this benign tumor are the miniature long bones of the hands and feet. It may, however, also involve other bones such as the femur, humerus, or tibia. While it may affect an individual at any age, it is most common in adulthood. The occurrence between males and females is equal. It is not very likely that the enchondroma will grow back in the same spot; the rate is less than ten percent.[citation needed] ## Diagnosis[edit] Because an individual with an enchondroma has few symptoms, diagnosis is sometimes made during a routine physical examination, or if the presence of the tumor leads to a fracture. In addition to a complete medical history and physical examination, diagnostic procedures for enchondroma may include the following:[citation needed] * x-ray - On plain film, an enchondroma may be found in any bone formed from cartilage. They are lytic lesions that usually contain calcified chondroid matrix (a "rings and arcs" pattern of calcification), except in the phalanges. They may be central, eccentric, expansile or nonexpansile. Differentiating an enchondroma from a bone infarct on plain film may be difficult. Generally, an enchondroma commonly causes endosteal scalloping while an infarct will not. An infarct usually has a well-defined, sclerotic serpentine border, while an enchondroma will not. When differentiating an enchondroma from a chondrosarcoma, the radiographic image may be equivocal; however, periostitis is not usually seen with an uncomplicated enchondroma.[citation needed] * radionuclide bone scan \- a nuclear imaging method to evaluate any degenerative and/or arthritic changes in the joints; to detect bone diseases and tumors; to determine the cause of bone pain or inflammation. This test is to rule out any infection or fractures. * magnetic resonance imaging (MRI)[1] \- a diagnostic procedure that uses a combination of large magnets, radiofrequencies, and a computer to produce detailed images of organs and structures within the body. This test is done to rule out any associated abnormalities of the spinal cord and nerves. * computed tomography scan (Also called a CT or CAT scan.) - a diagnostic imaging procedure that uses a combination of x-rays and computer technology to produce cross-sectional images (often called slices), both horizontally and vertically, of the body. A CT scan shows detailed images of any part of the body, including the bones, muscles, fat, and organs. CT scans are more detailed than general x-rays. ## Treatment[edit] Specific treatment for enchondroma is determined by a physician based on the age, overall health, and medical history of the patient. Other considerations include: * extent of the disease * tolerance for specific medications, procedures, or therapies * expectations for the course of the disease * opinion or preference of the patient Treatment may include: * surgery (in some cases, when bone weakening is present or fractures occur) * bone grafting - a surgical procedure in which healthy bone is transplanted from another part of the patient's body into the affected area. If there is no sign of bone weakening or growth of the tumor, observation only may be suggested. However, follow-up with repeat x-rays may be necessary. Some types of enchondromas can develop into malignant, or cancerous, bone tumors later. Careful follow-up with a physician may be recommended. ## See also[edit] * List of radiographic findings associated with cutaneous conditions ## References[edit] 1. ^ Wang XL, De Beuckeleer LH, De Schepper AM, Van Marck E (2001). "Low-grade chondrosarcoma vs enchondroma: challenges in diagnosis and management". European Radiology. 11 (6): 1054–1057. doi:10.1007/s003300000651. PMID 11419152. ## External links[edit] * Enchondroma Radiology Classification D * ICD-O: 9220/0 * MeSH: D002812 * DiseasesDB: 33380 External resources * eMedicine: article/389224 * v * t * e Tumours of bone and cartilage Diaphysis * Multiple myeloma * Epithelia * Adamantinoma * Primitive neuroectodermal tumor * Ewing family * Ewing's sarcoma Metaphysis Osteoblast * Osteoid osteoma * Osteoblastoma * Osteoma/osteosarcoma Chondroblast * Chondroma/ecchondroma/enchondroma * Enchondromatosis * Extraskeletal chondroma * Chondrosarcoma * Mesenchymal chondrosarcoma * Myxoid chondrosarcoma * Osteochondroma * Osteochondromatosis * Chondromyxoid fibroma Fibrous * Ossifying fibroma * Fibrosarcoma Epiphysis Chondroblast * Chondroblastoma Myeloid * Giant-cell tumor of bone Other Notochord * Chordoma * v * t * e Osteochondrodysplasia Osteodysplasia// osteodystrophy Diaphysis * Camurati–Engelmann disease Metaphysis * Metaphyseal dysplasia * Jansen's metaphyseal chondrodysplasia * Schmid metaphyseal chondrodysplasia Epiphysis * Spondyloepiphyseal dysplasia congenita * Multiple epiphyseal dysplasia * Otospondylomegaepiphyseal dysplasia Osteosclerosis * Raine syndrome * Osteopoikilosis * Osteopetrosis Other/ungrouped * FLNB * Boomerang dysplasia * Opsismodysplasia * Polyostotic fibrous dysplasia * McCune–Albright syndrome Chondrodysplasia/ chondrodystrophy (including dwarfism) Osteochondroma * osteochondromatosis * Hereditary multiple exostoses Chondroma/enchondroma * enchondromatosis * Ollier disease * Maffucci syndrome Growth factor receptor FGFR2: * Antley–Bixler syndrome FGFR3: * Achondroplasia * Hypochondroplasia * Thanatophoric dysplasia COL2A1 collagen disease * Achondrogenesis * type 2 * Hypochondrogenesis SLC26A2 sulfation defect * Achondrogenesis * type 1B * Autosomal recessive multiple epiphyseal dysplasia * Atelosteogenesis, type II * Diastrophic dysplasia Chondrodysplasia punctata * Rhizomelic chondrodysplasia punctata * Conradi–Hünermann syndrome Other dwarfism * Fibrochondrogenesis * Short rib – polydactyly syndrome * Majewski's polydactyly syndrome * Léri–Weill dyschondrosteosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Enchondroma	c1704356	3,845	wikipedia	https://en.wikipedia.org/wiki/Enchondroma	2021-01-18T18:44:07	{"gard": ["6335"], "mesh": ["D002812"], "wikidata": ["Q1340037"]}
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(November 2019) (Learn how and when to remove this template message) Angioid streaks Bruchs membrane SpecialtyOphthalmology ComplicationsLoss of vision[1] Diagnostic methodFFA, ICGA Angioid streaks, also called Knapp streaks or Knapp striae are small breaks in Bruch's membrane, an elastic tissue containing membrane of the retina that may become calcified and crack.[2] Up to 50% of angioid streak cases are idiopathic.[3] It may occur secondary to blunt trauma, or it may be associated with many systemic diseases.[4] The condition is usually asymptomatic, but decrease in vision may occur due to choroidal neovascularization.[5] ## Contents * 1 Clinical features * 2 Signs * 3 Diagnosis * 4 Management * 5 History * 6 External links * 7 References ## Clinical features[edit] Angioid streaks are often associated with pseudoxanthoma elasticum, but have been found to occur in conjunction with other disorders, including Paget's disease, sickle cell disease and Ehlers-Danlos Syndrome. These streaks can have a negative impact on vision due to choroidal neovascularization or choroidal rupture. Also, vision can be impaired if the streaks progress to the fovea and damage the retinal pigment epithelium. ## Signs[edit] Retinal fundus examination may reveal grey or dark red spoke like lesions around optic disk and radiating outward from peripapillary area. Peau d'orange (orange skin), also known as leopard skin pattern may be seen in association with pseudoxanthoma elasticum. Optic disc drusen may also seen.[1] ## Diagnosis[edit] The diagnosis is mainly clinical, however fundus fluorescein angiography shows that the streaks appear hyperfluorescent (window defect) in the early phase.[1] Indocyanine green angiography can also be used for diagnosing angioid streaks and their associated ocular pathologies.[6] ## Management[edit] Management of angioid streaks starts with complete medical checkup to rule out underlying systemic associations. The condition is usually asymptomatic and at first do not need any treatment.[3] Secondary ocular complications like choroidal neovascularization lead to vision loss, and/or metamorphopsia.[3] If choroidal neovascularization is present, treatment options like anti-VEGF medication, laser photocoagulation, photodynamic therapy, transpupillary thermotherapy, macular translocation surgery etc. may be needed.[3] ## History[edit] They were first described by Robert Walter Doyne in 1889 in a patient with retinal hemorrhages. In 1892, ophthalmologist Hermann Jakob Knapp called them "angioid streaks"[4] because of their resemblance to blood vessels. From histopathological research in the 1930s, they were discovered to be caused by changes at the level of Bruch's membrane. Presently, it is believed that its pathology may be a combination of elastic degeneration of Bruch's membrane, iron deposition in elastic fibers from hemolysis with secondary mineralization, and impaired nutrition due to stasis and small vessel occlusion. ## External links[edit] * eMedicine article on Angioid streaks * Photos of Angioid streaks ## References[edit] 1. ^ a b c John F., Salmon (2020). "Acquired macular disorders". Kanski's clinical ophthalmology : a systematic approach (9th ed.). Edinburgh: Elsevier. pp. 607–609. ISBN 978-0-7020-7713-5. OCLC 1131846767. 2. ^ DermAtlas Archived June 7, 2012, at the Wayback Machine \- Johns Hopkins 3. ^ a b c d Tripathy, Koushik; Quint, Jessilin M. (2020-06-01). "Angioid Streaks (Knapp Streaks)". StatPearls. StatPearls Publishing. 4. ^ a b "Angioid Streaks - EyeWiki". eyewiki.aao.org. 5. ^ "Retina". The Wills eye manual : office and emergency room diagnosis and treatment of eye disease (7th ed.). Philadelphia, PA: Wolters Kluwer. 2017. ISBN 978-1-4963-5366-5. OCLC 951081880. 6. ^ Creig S, Hoyt; David, Taylor. Pediatric ophthalmology and strabismus (4th ed.). Saunders/Elsevier. p. 524. ISBN 9780702046919. Classification D * MeSH: D000793 External resources * eMedicine: article/1190444 This article about the eye is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Angioid streaks	c0002982	3,846	wikipedia	https://en.wikipedia.org/wiki/Angioid_streaks	2021-01-18T19:10:12	{"mesh": ["D000793"], "umls": ["C0002982"], "wikidata": ["Q4763261"]}
Polydactyly myopia syndrome is characterized by postaxial polydactyly (the presence of an extra digit on the side of the hand or foot by the pinky or small toe) and progressive myopia. This condition was originally described in 9 persons in 4 generations of a family in Hungary in 1986. Family history suggests autosomal dominant inheritance. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Polydactyly myopia syndrome	c1868117	3,847	gard	https://rarediseases.info.nih.gov/diseases/4413/polydactyly-myopia-syndrome	2021-01-18T17:58:15	{"mesh": ["C536331"], "omim": ["174310"], "orphanet": ["2917"], "synonyms": ["PMS", "Postaxial Polydactyly with progressive myopia", "Czeizel Brooser syndrome", "Postaxial polydactyly-progressive myopia syndrome"]}
For the juvenile onset form see Systemic-onset juvenile idiopathic arthritis. Adult-onset Still's disease SpecialtyRheumatology Adult-onset Still's disease (AOSD) is a form of Still's disease, a rare systemic autoinflammatory disease characterized by the classic triad of fevers, joint pain, and a distinctive salmon-colored bumpy rash. The disease is considered a diagnosis of exclusion.[1] Levels of the iron-binding protein ferritin may be extremely elevated with this disorder. AOSD may present in a similar manner to other inflammatory diseases and to autoimmune diseases, which must be ruled out before making the diagnosis. Prognosis is usually favorable but manifestations of the disease affecting the lungs, heart, or kidneys may occasionally cause severe life-threatening complications.[2] It is treated first with corticosteroids such as prednisone. Medications that block the action of interleukin-1, such as Anakinra, can be effective treatments when standard steroid treatments are insufficient.[3] ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 3 Diagnosis * 3.1 Classification * 4 Treatment * 5 Epidemiology * 6 History * 7 Research directions * 8 See also * 9 References * 10 External links ## Signs and symptoms[edit] The disease typically presents with joint pain, high fevers, a salmon-pink macular or maculopapular rash, enlargement of the liver and spleen, swollen lymph nodes, and a neutrophil-predominant increased white blood cell count in the blood.[1] Tests for rheumatoid factor and anti-nuclear antibodies are usually negative and serum ferritin is markedly elevated. Patients experiencing a flare-up from Adult-onset Still's disease usually report extreme fatigue, swelling of the lymph nodes and, less commonly, fluid accumulation in the lungs and heart. In rare cases, AOSD can cause life-threatening complications, including hemophagocytic lymphohistiocytosis, IVDC, fulminant hepatitis, or disabling conditions such as aseptic meningitis and sensorineural hearing loss.[4][5][6][1] ## Pathophysiology[edit] The cause of adult-onset Still's disease is unknown, but it presumably involves interleukin-1 (IL-1), since medications that block the action of IL-1β are effective treatments. Interleukin-18 is expressed at high levels.[2][7][8] ## Diagnosis[edit] The diagnosis is clinical, not based upon serology.[9] At least seven sets of diagnostic criteria have been devised, however the Yamaguchi criteria have the highest sensitivity. Diagnosis requires at least five features, with at least two of these being major diagnostic criteria.[10] Major criteria Minor criteria Fever of at least 39 °C for at least one week Sore throat Arthralgias or arthritis for at least two weeks Lymphadenopathy Nonpruritic salmon-colored rash (usually over trunk or extremities while febrile) Hepatomegaly or splenomegaly Leukocytosis (10,000/microL or greater), with granulocyte predominance Abnormal liver function tests Negative tests for antinuclear antibody and rheumatoid factor ### Classification[edit] People with AOSD generally experience one of two patterns in the disease: * a debilitating pattern of fevers, pain, and other systemic symptoms, or * a somewhat less aggressive pattern, in which the main symptom is arthritis and chronic joint pain.[3] One set of 21 adult-onset Still's disease patients were divided into four types, according to clinical course patterns. These included monocyclic systemic disease, polycyclic systemic disease, chronic articular monocyclic systemic disease, and chronic articular polycyclic systemic disease. People with chronic articular disease and polyarticular disease were at higher risk to develop disabling arthritis.[11] ## Treatment[edit] Adult-onset Still's disease is treated with anti-inflammatory medications. Steroids such as prednisone are used to treat severe symptoms of Still's. Other commonly used medications include hydroxychloroquine, penicillamine, azathioprine, methotrexate, etanercept, anakinra, tocilizumab cyclophosphamide, adalimumab, rituximab, and infliximab.[12] Newer medications target interleukin-1 (IL-1), particularly IL-1β.[13] A randomized, multicenter trial reported better outcomes in a group of 12 patients treated with anakinra than in a group of 10 patients taking other disease-modifying antirheumatic drugs.[14] On June 2020 FDA approved Ilaris (canakinumab) for the treatment of AOSD, this is the first FDA approved treatment for AOSD.[15] Canakinumab is another anti-IL1 drug which selectively binds IL-1β and rilonacept which blocks both IL-1A and IL-1β.[16] The monoclonal anti-IL6 antibody tocilizumab is another treatment option as effective as anakinra.[17] The condition "juvenile-onset Still's disease" is now usually grouped under juvenile rheumatoid arthritis. However, there is some evidence that the two conditions are closely related.[18][19] ## Epidemiology[edit] Adult-onset Still's Disease is rare and has been described all over the world. The number of new cases per year is estimated to be 1.6 per 1,000,000 population.[1] The number of people currently affected is estimated at 1.5 cases per 100,000–1,000,000 population.[citation needed] Onset is most common in two age ranges, between ages 16–25 and between ages of 36–46 years.[20] ## History[edit] Still's disease is named after English physician Sir George Frederic Still (1861–1941).[21][22] The adult-onset version was characterized by E. G. Bywaters in 1971.[1] ## Research directions[edit] Researchers are investigating whether levels of a protein named calprotectin could be used to improve diagnosis and monitoring.[23] ## See also[edit] * Juvenile idiopathic arthritis * The Big Sick ## References[edit] 1. ^ a b c d e Akkara Veetil BM, Yee AH, Warrington KJ, Aksamit AJ Jr, Mason TG (December 2012). "Aseptic meningitis in adult onset Still's disease". Rheumatol Int. 32 (12): 4031–4. doi:10.1007/s00296-010-1529-8. PMID 20495923. S2CID 19431424. 2. ^ a b Colafrancesco, Serena; Priori, Roberta; Alessandri, Cristiano; Perricone, Carlo; Pendolino, Monica; Picarelli, Giovanna; Valesini, Guido (2012). "IL-18 Serum Level in Adult Onset Still's Disease: A Marker of Disease Activity". International Journal of Inflammation. 2012: 1–6. doi:10.1155/2012/156890. PMC 3385601. PMID 22762008. 3. ^ a b Gerfaud-Valentin, Mathieu; Jamilloux, Yvan; Iwaz, Jean; Sève, Pascal (July 2014). "Adult-onset Still's disease". Autoimmunity Reviews. 13 (7): 708–722. doi:10.1016/j.autrev.2014.01.058. ISSN 1873-0183. PMID 24657513. 4. ^ Fauter, M.; Gerfaud-Valentin, M.; Delplanque, M.; Georgin-Lavialle, S.; Sève, P.; Jamilloux, Y. (2020-01-07). "[Adult-onset Still's disease complications]". La Revue de Médecine Interne. 41 (3): 168–179. doi:10.1016/j.revmed.2019.12.003. ISSN 1768-3122. PMID 31924392. 5. ^ Mitrovic, Stéphane; Fautrel, Bruno (2018). "Complications of adult-onset Still's disease and their management". Expert Review of Clinical Immunology. 14 (5): 351–365. doi:10.1080/1744666X.2018.1465821. ISSN 1744-8409. PMID 29658384. S2CID 4895740. 6. ^ Néel, Antoine; Wahbi, Anaïs; Tessoulin, Benoit; Boileau, Julien; Carpentier, Dorothée; Decaux, Olivier; Fardet, Laurence; Geri, Guillaume; Godmer, Pascal; Goujard, Cécile; Maisonneuve, Hervé (2018-04-11). "Diagnostic and management of life-threatening Adult-Onset Still Disease: a French nationwide multicenter study and systematic literature review". Critical Care (London, England). 22 (1): 88. doi:10.1186/s13054-018-2012-2. ISSN 1466-609X. PMC 5896069. PMID 29642928. 7. ^ Sugiura, T; Kawaguchi, Y; Harigai, M; Terajima-Ichida, H; Kitamura, Y; Furuya, T; Ichikawa, N; Kotake, S; Tanaka, M; Hara, M; Kamatani, N (Nov 2002). "Association between adult-onset Still's disease and interleukin-18 gene polymorphisms". Genes and Immunity. 3 (7): 394–9. doi:10.1038/sj.gene.6363922. PMID 12424620. 8. ^ Jamilloux, Y; Gerfaud-Valentin, M; Martinon, F; Belot, A; Henry, T; Sève, P (February 2015). "Pathogenesis of adult-onset Still's disease: new insights from the juvenile counterpart". Immunologic Research. 61 (1–2): 53–62. doi:10.1007/s12026-014-8561-9. PMID 25388963. S2CID 44588159. 9. ^ Efthimiou P, Kontzias A, Ward CM, Ogden NS (June 2007). "Adult-onset Still's disease: can recent advances in our understanding of its pathogenesis lead to targeted therapy?". Nat Clin Pract Rheumatol. 3 (6): 328–35. doi:10.1038/ncprheum0510. PMID 17538564. S2CID 30465113. 10. ^ Yamaguchi M, Ohta A, Tsunematsu T, Kasukawa R, Mizushima Y, Kashiwagi H, Kashiwazaki S, Tanimoto K, Matsumoto Y, Ota T (1992). "Preliminary criteria for classification of adult Still's disease". J. Rheumatol. 19 (3): 424–30. PMID 1578458. 11. ^ Cush, JJ; Medsger TA Jr; Christy, WC; Herbert, DC; Cooperstein, LA (Feb 1987). "Adult-onset Still's disease. Clinical course and outcome". Arthritis and Rheumatism. 30 (2): 186–194. doi:10.1002/art.1780300209. PMID 3827959. 12. ^ Jamilloux, Y; Gerfaud-Valentin, M; Henry, T; Sève, P (22 December 2014). "Treatment of adult-onset Still's disease: a review". Therapeutics and Clinical Risk Management. 11: 33–43. doi:10.2147/TCRM.S64951. PMC 4278737. PMID 25653531. 13. ^ Vastert, Sebastiaan J.; Jamilloux, Yvan; Quartier, Pierre; Ohlman, Sven; Osterling Koskinen, Lisa; Kullenberg, Torbjörn; Franck-Larsson, Karin; Fautrel, Bruno; de Benedetti, Fabrizio (2019-11-01). "Anakinra in children and adults with Still's disease". Rheumatology (Oxford, England). 58 (Supplement_6): vi9–vi22. doi:10.1093/rheumatology/kez350. ISSN 1462-0332. PMC 6878842. PMID 31769856. 14. ^ Nordström D; Knight A; Luukkainen R; van Vollenhoven R; et al. (Oct 2012). "Beneficial effect of interleukin 1 inhibition with anakinra in adult-onset Still's disease. An open, randomized, multicenter study". J. Rheumatol. 39 (10): 2008–11. doi:10.3899/jrheum.111549. PMID 22859346. S2CID 207614974. 15. ^ Commissioner, Office of the (2020-06-16). "FDA Approves First Treatment for Adult Onset Still's Disease, a Severe and Rare Disease". FDA. Retrieved 2020-06-21. 16. ^ Cecilia Giampietro; Bruno Fautrel (2012). "Review Article: Anti-Interleukin-1 Agents in Adult Onset Still's Disease". International Journal of Inflammation. 2012 (317820): 317820. doi:10.1155/2012/317820. PMC 3350963. PMID 22611515. 17. ^ Al-Homood, I. A. (2014-01-01). "Biologic treatments for adult-onset Still's disease". Rheumatology. 53 (1): 32–38. doi:10.1093/rheumatology/ket250. ISSN 1462-0324. PMID 23864171. 18. ^ Luthi F, Zufferey P, Hofer MF, So AK (2002). ""Adolescent-onset Still's disease": characteristics and outcome in comparison with adult-onset Still's disease". Clin. Exp. Rheumatol. 20 (3): 427–30. PMID 12102485. 19. ^ Jamilloux, Y.; Georgin-Lavialle, S.; Sève, P.; Belot, A.; Fautrel, B. (2019). "[It is time to reconcile systemic juvenile idiopathic arthritis and adult-onset Still's disease]". La Revue de Médecine Interne. 40 (10): 635–636. doi:10.1016/j.revmed.2019.06.001. ISSN 1768-3122. PMID 31221454. 20. ^ Owlia MB, Mehrpoor G (2009). "Adult – onset Still's disease : A review" (PDF). Indian J Med Sci. 63 (5): 207–21. doi:10.4103/0019-5359.53169. PMID 19584494. 21. ^ synd/1773 at Who Named It? 22. ^ G. F. Still. A special form of joint disease met with in children. Doctoral dissertation, Cambridge, 1896. 23. ^ Kopeć-Mędrek, Magdalena; Widuchowska, Małgorzata; Kucharz, Eugeniusz J. (2016). "Calprotectin in rheumatic diseases: a review". Reumatologia. 54 (6): 306–309. doi:10.5114/reum.2016.64907. ISSN 0034-6233. PMC 5241367. PMID 28115781. ## External links[edit] * "Adult-onset Still's disease \|". Genetic and Rare Diseases Information Center (GARD). Classification D * ICD-10: M06.1 * ICD-9-CM: 714.2 * MeSH: D016706 * DiseasesDB: 34295 External resources * MedlinePlus: 000450 * Orphanet: 829 * v * t * e Diseases of joints General * Arthritis * Monoarthritis * Oligoarthritis * Polyarthritis Symptoms * Joint pain * Joint stiffness Inflammatory Infectious * Septic arthritis * Tuberculosis arthritis Crystal * Chondrocalcinosis * CPPD (Psudogout) * Gout Seronegative * Reactive arthritis * Psoriatic arthritis * Ankylosing spondylitis Other * Juvenile idiopathic arthritis * Rheumatoid arthritis * Felty's syndrome * Palindromic rheumatism * Adult-onset Still's disease Noninflammatory * Hemarthrosis * Osteoarthritis * Heberden's node * Bouchard's nodes * Osteophyte [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Adult-onset Still's disease	c0085253	3,848	wikipedia	https://en.wikipedia.org/wiki/Adult-onset_Still%27s_disease	2021-01-18T18:34:00	{"gard": ["436"], "mesh": ["D016706"], "umls": ["C0085253"], "icd-9": ["714.2"], "orphanet": ["829"], "wikidata": ["Q1187697"]}
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder that leads to the premature death and impaired production of blood cells. It can occur at any age, but is usually diagnosed in young adulthood. People with PNH have recurring episodes of symptoms due to hemolysis, which may be triggered by stresses on the body such as infections or physical exertion. This results in a deficiency of various types of blood cells and can cause signs and symptoms such as fatigue, weakness, abnormally pale skin (pallor), shortness of breath, and an increased heart rate. People with PNH may also be prone to infections and abnormal blood clotting (thrombosis) or hemorrhage, and are at increased risk of developing leukemia. It is caused by acquired, rather than inherited, mutations in the PIGA gene; the condition is not passed down to children of affected individuals. Sometimes, people who have been treated for aplastic anemia may develop PNH. The treatment of PNH is largely based on symptoms; stem cell transplantation is typically reserved for severe cases of PNH with aplastic anemia or those whose develop leukemia. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Paroxysmal nocturnal hemoglobinuria	c0024790	3,849	gard	https://rarediseases.info.nih.gov/diseases/7337/paroxysmal-nocturnal-hemoglobinuria	2021-01-18T17:58:26	{"mesh": ["D006457"], "omim": ["300818", "615399"], "umls": ["C0024790"], "orphanet": ["447"], "synonyms": ["PNH", "Marchiafava-Micheli disease"]}
Aural cholesteatoma is an abnormal accumulation of keratin-producing squamous epithelium in the middle ear, epitympanum, mastoid, or petrous apex (Arriaga, 1994). The misnomer 'cholesteatoma' originated from the erroneous assumption that the mass represented a cystic tumor of cholesterol and fat. The original term has been retained, despite suggestions that the more pathologically accurate term 'keratoma' be adopted. Most cholesteatomas are acquired in the setting of recurrent otitis media (166760). Primary or congenital cholesteatomas are rare, representing approximately 2 to 5% of cases in several large series. Graham and Allanson (1999) described congenital cholesteatoma and malformations of the facial nerve in association with the branchiootorenal syndrome (BOR; 113650). They reviewed information on the incidence, clinical characteristics, diagnosis, and pathogenesis of congenital cholesteatoma. The evidence for mendelian inheritance was minimal. Shaoul et al. (1999) described a 6-year-old boy with adenomatous polyposis coli and congenital cholesteatoma; see 175100.0023. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	CHOLESTEATOMA, CONGENITAL	c0395886	3,850	omim	https://www.omim.org/entry/604183	2019-09-22T16:12:30	{"mesh": ["C562858"], "omim": ["604183"]}
This article needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed. Find sources: "Hydrothorax" – news · newspapers · books · scholar · JSTOR (July 2019) Hydrothorax SpecialtyRespirology Hydrothorax is a type of pleural effusion in which transudate accumulates in the pleural cavity. This condition is most likely to develop secondary to congestive heart failure, following an increase in hydrostatic pressure within the lungs. More rarely, hydrothorax can develop in 10% of patients with ascites which is called hepatic hydrothorax. It is often difficult to manage in end-stage liver failure and often fails to respond to therapy. Pleural effusions may also develop following the accumulation of other fluids within the pleural cavity; if the fluid is blood it is known as hemothorax (as in major chest injuries), if the fluid is pus it is known as pyothorax (resulting from chest infections), and if the fluid is lymph it is known as chylothorax (resulting from rupture of the thoracic duct). ## Contents * 1 Treatment * 2 See also * 3 References * 4 External links ## Treatment[edit] Treatment of hydrothorax is difficult for several reasons. The underlying condition needs to be corrected; however, often the source of the hydrothorax is end stage liver disease and correctable only by transplant. Chest tube placement should not occur. Other measures such as a TIPS procedure are more effective as they treat the cause of the hydrothorax, but have complications such as worsened hepatic encephalopathy. ## See also[edit] * Pleural effusion * Pneumothorax ## References[edit] ## External links[edit] Classification D * ICD-10: J94.8 * ICD-9-CM: 511.8 * MeSH: D006876 * DiseasesDB: 10122 * v * t * e Diseases of the respiratory system Upper RT (including URTIs, common cold) Head sinuses Sinusitis nose Rhinitis Vasomotor rhinitis Atrophic rhinitis Hay fever Nasal polyp Rhinorrhea nasal septum Nasal septum deviation Nasal septum perforation Nasal septal hematoma tonsil Tonsillitis Adenoid hypertrophy Peritonsillar abscess Neck pharynx Pharyngitis Strep throat Laryngopharyngeal reflux (LPR) Retropharyngeal abscess larynx Croup Laryngomalacia Laryngeal cyst Laryngitis Laryngopharyngeal reflux (LPR) Laryngospasm vocal cords Laryngopharyngeal reflux (LPR) Vocal fold nodule Vocal fold paresis Vocal cord dysfunction epiglottis Epiglottitis trachea Tracheitis Laryngotracheal stenosis Lower RT/lung disease (including LRTIs) Bronchial/ obstructive acute Acute bronchitis chronic COPD Chronic bronchitis Acute exacerbation of COPD) Asthma (Status asthmaticus Aspirin-induced Exercise-induced Bronchiectasis Cystic fibrosis unspecified Bronchitis Bronchiolitis Bronchiolitis obliterans Diffuse panbronchiolitis Interstitial/ restrictive (fibrosis) External agents/ occupational lung disease Pneumoconiosis Aluminosis Asbestosis Baritosis Bauxite fibrosis Berylliosis Caplan's syndrome Chalicosis Coalworker's pneumoconiosis Siderosis Silicosis Talcosis Byssinosis Hypersensitivity pneumonitis Bagassosis Bird fancier's lung Farmer's lung Lycoperdonosis Other * ARDS * Combined pulmonary fibrosis and emphysema * Pulmonary edema * Löffler's syndrome/Eosinophilic pneumonia * Respiratory hypersensitivity * Allergic bronchopulmonary aspergillosis * Hamman-Rich syndrome * Idiopathic pulmonary fibrosis * Sarcoidosis * Vaping-associated pulmonary injury Obstructive / Restrictive Pneumonia/ pneumonitis By pathogen * Viral * Bacterial * Pneumococcal * Klebsiella * Atypical bacterial * Mycoplasma * Legionnaires' disease * Chlamydiae * Fungal * Pneumocystis * Parasitic * noninfectious * Chemical/Mendelson's syndrome * Aspiration/Lipid By vector/route * Community-acquired * Healthcare-associated * Hospital-acquired By distribution * Broncho- * Lobar IIP * UIP * DIP * BOOP-COP * NSIP * RB Other * Atelectasis * circulatory * Pulmonary hypertension * Pulmonary embolism * Lung abscess Pleural cavity/ mediastinum Pleural disease * Pleuritis/pleurisy * Pneumothorax/Hemopneumothorax Pleural effusion Hemothorax Hydrothorax Chylothorax Empyema/pyothorax Malignant Fibrothorax Mediastinal disease * Mediastinitis * Mediastinal emphysema Other/general * Respiratory failure * Influenza * Common cold * SARS * Coronavirus disease 2019 * Idiopathic pulmonary haemosiderosis * Pulmonary alveolar proteinosis * v * t * e Disorders of volume state Volume contraction * dehydration * hypovolemia Hypervolemia * Edema * Anasarca * Cerebral edema * Pulmonary edema * Angioedema * Lymphedema Other * Cause of fluid collection * Exudate * Transudate * By site * Hydrothorax * Ascites * Hydrosalpinx * Hyperemia This medical sign article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Hydrothorax	c0020312	3,851	wikipedia	https://en.wikipedia.org/wiki/Hydrothorax	2021-01-18T18:50:33	{"mesh": ["D006876"], "umls": ["C0020312"], "icd-9": ["511.8"], "icd-10": ["J94.8"], "wikidata": ["Q1505538"]}
## Clinical Features Tariq et al. (2006) reported a consanguineous family from a region bordering Pakistan and India in which 4 sibs had nonsyndromic, prelingual profound hearing impairment involving all frequencies. Mapping By genomewide linkage analysis followed by fine mapping in a consanguineous family segregating autosomal recessive deafness, Tariq et al. (2006) identified a locus, termed DFNB65, on chromosome 20q13.2-q13.32 (maximum multipoint lod score of 3.3 at marker D20S840). Haplotype analysis defined a 4.3-Mb (10.5-cM) region between D20S480 and D20S430. Molecular Genetics ### Exclusion Studies Tariq et al. (2006) excluded mutation in the BMP7 gene (112267) in affected members of a family with deafness mapping to chromosome 20q13.2-q13.32. INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Deafness, profound \- Deafness affects all frequencies MISCELLANEOUS \- Prelingual onset ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	DEAFNESS, AUTOSOMAL RECESSIVE 65	c1853248	3,852	omim	https://www.omim.org/entry/610248	2019-09-22T16:04:55	{"doid": ["0110516"], "mesh": ["C565211"], "omim": ["610248"], "orphanet": ["90636"], "synonyms": ["Autosomal recessive isolated neurosensory deafness type DFNB", "Autosomal recessive isolated sensorineural deafness type DFNB", "Autosomal recessive non-syndromic neurosensory deafness type DFNB"]}
Corneal abrasion A corneal abrasion after staining with fluorescein, it is the green mark on the eye. SpecialtyEmergency medicine SymptomsEye pain, light sensitivity[1] Usual onsetRapid[2] DurationLess than 3 days[1] CausesMinor trauma, contact lens use[1] Diagnostic methodSlit lamp exam[1] Differential diagnosisCorneal ulcer, globe rupture[1] PreventionEye protection[1] Frequency3 per 1,000 per year (United States)[1] Corneal abrasion is a scratch to the surface of the cornea of the eye.[3] Symptoms include pain, redness, light sensitivity, and a feeling like a foreign body is in the eye.[1] Most people recover completely within three days.[1] Most cases are due to minor trauma to the eye such as that which can occur with contact lens use or from fingernails.[1] About 25% of cases occur at work.[1] Diagnosis is often by slit lamp examination after fluorescein dye has been applied.[1] More significant injuries like a corneal ulcer, globe rupture, recurrent erosion syndrome, and a foreign body within the eye should be ruled out.[1] Prevention includes the use of eye protection.[1] Treatment is typically with antibiotic ointment.[1] In those who wear contact lenses a fluoroquinolone antibiotic is often recommended.[1] Paracetamol (acetaminophen), NSAIDs, and eye drops such as cyclopentolate that paralysis the pupil can help with pain.[1] Evidence does not support the usefulness of eye patching for those with simple abrasions.[4] About 3 per 1,000 people are affected a year in the United States.[1] Males are more often affected than females.[1] The typical age group affected is those in their 20s and 30s.[1] Complications can include bacterial keratitis, corneal ulcer, and iritis.[1] Complications may occur in up to 8% of people.[5] ## Contents * 1 Signs and symptoms * 1.1 Complications * 2 Causes * 3 Diagnosis * 3.1 Prevention * 4 Treatment * 4.1 Foreign body * 4.2 Medications * 4.3 Patching * 5 Animals * 6 References * 7 External links ## Signs and symptoms[edit] Signs and symptoms of corneal abrasion include pain, trouble with bright lights, a foreign-body sensation, excessive squinting, and reflex production of tears. Signs include epithelial defects and edema, and often redness of the eye. The vision may be blurred, both from any swelling of the cornea and from excess tears. Crusty buildup from excess tears may also be present. ### Complications[edit] Complications are the exception rather than the rule from simple corneal abrasions. It is important that any foreign body be identified and removed, especially if containing iron as rusting will occur. Occasionally the healed epithelium may be poorly adherent to the underlying basement membrane in which case it may detach at intervals giving rise to recurrent corneal erosions. ## Causes[edit] Corneal abrasions are generally a result of trauma to the surface of the eye. Common causes include being poked by a finger, walking into a tree branch, and wearing old contact lenses.[citation needed] A foreign body in the eye may also cause a scratch if the eye is rubbed. Injuries can also be incurred by "hard" or "soft" contact lenses that have been left in too long. Damage may result when the lenses are removed, rather than when the lens is still in contact with the eye. In addition, if the cornea becomes excessively dry, it may become more brittle and easily damaged by movement across the surface. Soft contact lens wear overnight has been extensively linked to gram negative keratitis (infection of the cornea) particularly by a bacterium known as Pseudomonas aeruginosa which forms in the eye's biofilm as a result of extended soft contact lens wear. When a corneal abrasion occurs either from the contact lens itself or another source, the injured cornea is much more susceptible to this type of bacterial infection than a non-contact lens user's would be. This is an optical emergency as it is sight (in some cases eye) threatening. Contact lens wearers who present with corneal abrasions should never be pressure patched because it has been shown through clinical studies that patching creates a warm, moist dark environment that can cause the cornea to become infected or cause an existing infection to be greatly accelerated on its destructive path. Corneal abrasions are also a common and recurrent feature in people who suffer specific types of corneal dystrophy, such as lattice corneal dystrophy. Lattice dystrophy gets its name from an accumulation of amyloid deposits, or abnormal protein fibers, throughout the middle and anterior stroma. During an eye examination, the doctor sees these deposits in the stroma as clear, comma-shaped overlapping dots and branching filaments, creating a lattice effect. Over time, the lattice lines will grow opaque and involve more of the stroma. They will also gradually converge, giving the cornea a cloudiness that may also reduce vision. In some people, these abnormal protein fibers can accumulate under the cornea's outer layer—the epithelium. This can cause erosion of the epithelium. This condition is known as recurrent epithelial erosion. These erosions: (1) Alter the cornea's normal curvature, resulting in temporary vision problems; and (2) Expose the nerves that line the cornea, causing severe pain. Even the involuntary act of blinking can be painful. ## Diagnosis[edit] Although corneal abrasions may be seen with ophthalmoscopes, slit lamp microscopes provide higher magnification which allow for a more thorough evaluation. To aid in viewing, a fluorescein stain that fills in the corneal defect and glows with a cobalt blue-light is generally instilled first. A careful search should be made for any foreign body, in particular looking under the eyelids. Injury following use of hammers or power-tools should always raise the possibility of a penetrating foreign body into the eye, for which urgent ophthalmology opinion should be sought. ### Prevention[edit] Prevention is the best method to avoid recurrence of corneal abrasions. Protective eyewear should be worn by people who work with hazardous machinery, metal, wood, or chemicals, as well as those who perform yard work or participate in certain contact sports. The appropriate type of protective eyewear depends on the specific circumstances, but all should provide shielding, good visibility, and a comfortable fit. Some examples include polycarbonate glasses or goggles, plastic safety glasses, face shields, and welding helmets. Specifically, welders should use a helmet with a lens that blocks UV light to avoid UV keratitis. It is important to notice that people with one eye are especially vulnerable to potentially blinding injuries, and should pay special attention to protecting their eyes. In these cases, protective eyewear can ensure some degree of safety while also allowing people to participate in their normal day-to-day activities. Ensuring both a proper contact lens fit and the compliance of the person with care measures can prevent contact lens-related complications.[6] As it has been stated previously, these can cause both mechanic damage to the cornea and be a risk factor for the development of microbial keratitis. Thus, an emphasis should be placed on reducing lens contamination by using effective disinfecting solutions, as well as antimicrobial contact lenses and cases. It is important to avoid swimming with contact lenses, because this increases the frequency of bacterial infections, primarily from Staphylococcus epidermidis and other organisms found in contaminated water. Finally, people who use contact lenses can also avoid both mechanical and infectious trauma by not using contacts beyond the length of their intended use. ## Treatment[edit] The treatment of corneal abrasions aims to prevent bacterial superinfection, speed healing, and provide symptomatic relief.[7] If a foreign body is found, it needs to be removed. ### Foreign body[edit] * Positioning: The person is laid in a comfortable position with the affected eye closest to the physician. Loupes can be used if available and the eye can be illuminated with a medical light or, alternatively, with an ophtalmoscope held in the non-dominant hand. The person is then asked to focus on a particular point on the ceiling so that the foreign body sits as centrally between the eyelids as possible. This accounts for a more sterile procedure by keeping the eyelashes as far as possible, and reduces the chance of eliciting a blink reflex. If necessary, the eyelids can be kept open using an eyelid speculum, the examiner’s fingertips, a cotton tip or an assistant. * Anaesthetic and pupil dilator: Local anaesthetic is instilled into both eyes in order to reduce blepharospasm. Topical oxybuprocaine 0.4% is the preferred choice as it has an onset of action of 20 seconds and a half-life of 20 minutes. A drop of topical pupil dilator such a cyclopentolate 1%, if available, can be helpful to reduce ciliary spasm after removal of the foreign body. Atropine is generally avoided due to its long-lasting mydriatic effects. * Removal techniques: There are mainly two types of techniques, the choice of which will depend on the nature of the foreign body. The first technique is the cotton tip removal, which is indicated in superficial foreign bodies with no surrounding corneal reaction, and the second is the hypodermic needle or nº15 blade removal with which the complete foreign body and any surrounding rust ring can be removed. * Irrigation of the ocular surface and upper and lower fornices can be performed after the procedure to wash out any residual loose foreign body material. A 10 mL ampoule of sterile saline is usually sufficient. ### Medications[edit] Current recommendations stress the need to use topical and/or oral analgesia and topical antibiotics. One review has found that eye drops to numb the surface of the eye such as tetracaine improve pain; however, their safety is unclear.[8] Another review did not find evidence of benefit and concluded there was not enough data on safety.[9] Topical nonsteroidal anti-inflammatory drugs (NSAIDs) are useful to reduce the pain caused by corneal abrasions.[10] Diclofenac and ketorolac are the most used, one drop four times a day. It is worth noting, however, that diclofenac may delay wound healing and ketorolac should be avoided in people who wear contact lenses. Some studies do not recommend using topical NSAIDs due to the risk of corneal toxicity. There is no direct evidence regarding the use of oral analgesics, but because pain relief is the main concern for people with corneal abrasions, these are prescribed according to individual's characteristics. Topical antibiotics are used to prevent concomitant infections, which result in slower healing of corneal abrasions.[11] Ointments are considered the first-line treatment, as they are more lubricating than drops. If the person uses contact lenses, an antibiotic with anti-pseudomonal activity is preferred (ciprofloxacin, gentamycin or ofloxacin), and the use of contact lenses should be discontinued until the abrasion has healed and the antibiotic treatment has ended. This is because contact lens wearers are often colonized with Pseudomonas aeruginosa, which may cause corneal perforations and subsequent permanent vision loss. If the mechanism of injury involves contact lenses, fingernails or organic/ plant matter, antibiotic prophylaxis should be provided with topical fluoroquinolone drops 4 times a day, and a fluoroquinolone ointment, typically ciprofloxacin, at night. If the abrasion was caused by another mechanism, the recommended treatment includes antibiotic ointments (erythromycin, bacitracin or bacitracin/polymyxin B every 2 or 4 hours) or antibiotic drops, usually polymyxin B and trimethoprim 4 times a day. ### Patching[edit] Eye patching is not generally recommended as they do not help with healing or pain.[4] Furthermore, it can result in decreased oxygen delivery, increased moisture and a higher chance of an infection. Another measure that is no longer recommended is the use of mydriatics, formerly used to relieve the pain caused by ciliary muscle spasm.[12] ## Animals[edit] Main article: Corneal ulcers in animals ## References[edit] 1. ^ a b c d e f g h i j k l m n o p q r s t u Ahmed F, House RJ, Feldman BH (September 2015). "Corneal Abrasions and Corneal Foreign Bodies". Primary Care. 42 (3): 363–75. doi:10.1016/j.pop.2015.05.004. PMID 26319343. 2. ^ Leik MT (2013). Family Nurse Practitioner Certification Intensive Review: Fast Facts and Practice Questions, Second Edition (2 ed.). Springer Publishing Company. p. 112. ISBN 9780826134257. Archived from the original on 2016-11-07. 3. ^ "Corneal Abrasion". nei.nih.gov. National Eye Institute. Archived from the original on 2016-11-07. Retrieved 2016-11-06. 4. ^ a b Lim CH, Turner A, Lim BX (July 2016). "Patching for corneal abrasion". The Cochrane Database of Systematic Reviews. 7: CD004764. doi:10.1002/14651858.CD004764.pub3. PMC 6457868. PMID 27457359. 5. ^ Smolin G, Foster CS, Azar DT, Dohlman CH (2005). Smolin and Thoft's The Cornea: Scientific Foundations and Clinical Practice. Lippincott Williams & Wilkins. p. 798. ISBN 9780781742061. Archived from the original on 2016-11-07. 6. ^ Szczotka-Flynn LB, Pearlman E, Ghannoum M (March 2010). "Microbial contamination of contact lenses, lens care solutions, and their accessories: a literature review". Eye & Contact Lens. 36 (2): 116–29. doi:10.1097/icl.0b013e3181d20cae. PMC 3482476. PMID 20168237. 7. ^ Fowler GC (2011), "Corneal Abrasions and Removal of Corneal or Conjunctival Foreign Bodies", Pfenninger and Fowler's Procedures for Primary Care, Elsevier, pp. 433–439, doi:10.1016/b978-0-323-05267-2.00066-2, ISBN 9780323052672 8. ^ Swaminathan A, Otterness K, Milne K, Rezaie S (November 2015). "The Safety of Topical Anesthetics in the Treatment of Corneal Abrasions: A Review". The Journal of Emergency Medicine. 49 (5): 810–5. doi:10.1016/j.jemermed.2015.06.069. PMID 26281814. 9. ^ Puls HA, Cabrera D, Murad MH, Erwin PJ, Bellolio MF (November 2015). "Safety and Effectiveness of Topical Anesthetics in Corneal Abrasions: Systematic Review and Meta-Analysis". The Journal of Emergency Medicine. 49 (5): 816–24. doi:10.1016/j.jemermed.2015.02.051. PMID 26472608. 10. ^ Calder LA, Balasubramanian S, Fergusson D (May 2005). "Topical nonsteroidal anti-inflammatory drugs for corneal abrasions: meta-analysis of randomized trials". Academic Emergency Medicine. 12 (5): 467–73. doi:10.1197/j.aem.2004.10.026. PMID 15860701. 11. ^ "UpToDate Inc". 12. ^ "BestBets: Mydriatics in corneal abrasion". Archived from the original on 2008-09-02. ## External links[edit] Classification D * ICD-10: S05.0 * ICD-9-CM: 918.1 * DiseasesDB: 3108 External resources * eMedicine: oph/247 emerg/828 * v * t * e Nonmusculoskeletal injuries of head (head injury) and neck Intracranial * see neurotrauma Extracranial/ facial trauma eye: * Black eye * Eye injury * Corneal abrasion ear: * Perforated eardrum Either/both * Penetrating head injury [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Corneal abrasion	c0010032	3,853	wikipedia	https://en.wikipedia.org/wiki/Corneal_abrasion	2021-01-18T18:54:50	{"icd-9": ["918.1"], "icd-10": ["S05.0"], "wikidata": ["Q3510332"]}
A number sign (#) is used with this entry because of evidence that anterior segment dysgenesis-2 (ASGD2) is caused by homozygous, compound heterozygous, or heterozygous mutation in the FOXE3 gene (601094) on chromosome 1p33. Description Anterior segment dysgeneses are a heterogeneous group of developmental disorders affecting the anterior segment of the eye, including the cornea, iris, lens, trabecular meshwork, and Schlemm canal. The clinical features of ASGD include iris hypoplasia, an enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, an abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface (summary by Cheong et al., 2016). Anterior segment dysgenesis is sometimes divided into subtypes, including aniridia (see 106210), Axenfeld and Rieger anomalies, iridogoniodysgenesis, Peters anomaly, and posterior embryotoxon (Gould and John, 2002). Some patients with ASGD2 have been reported with a congenital primary aphakia subtype. Congenital primary aphakia is a rare developmental disorder characterized by absence of the lens, the development of which is normally induced during the fourth to fifth week of human embryogenesis. This original failure leads, in turn, to complete aplasia of the anterior segment of the eye, which is the diagnostic histologic criterion for CPAK. In contrast, in secondary aphakia, lens induction occurs and the lens vesicle develops to some degree, but is progressively resorbed perinatally, resulting in less severe ocular defects (summary by Valleix et al., 2006). Clinical Features Doucette et al. (2011) studied a 4-generation family from Newfoundland, originally reported by Green and Johnson (1986), in which 11 cases of mild to severe forms of anterior segment dysgenesis segregated as an autosomal dominant trait across 6 sibships. The proband was noted to have bilateral dense corneal opacities at birth; examination under anesthesia revealed corneal opacification of the right eye temporally and hazy cornea nasally, with fine adhesions from the collarette of the iris to the cornea obscuring the angle. The left cornea was more densely opaque with a large central adhesion from the cornea to the lens and peripheral adhesions from the iris to the cornea. Both globes were of normal size, but he had bilateral microcornea. At 6 months of age, the proband underwent left corneal transplant; examination of the corneal tissue showed absent Descemet membrane, partial absence of Bowman membrane, and thinning of the central cornea, consistent with Peters anomaly. Reexamination of the proband at 30 years of age showed a phthisical left eye due to postoperative complications; there was no other facial dysmorphism, and no extraocular features were seen. The proband's father had small posterior subcapsular and central nuclear cataracts noted at 7 years of age; examination at 27 years of age revealed bilateral microcornea, with scleralization and vascularization of the cornea. Gonioscopy showed fine iris processes extending over the trabecular network. He underwent cataract extractions at ages 39 and 40 years because of decreasing visual acuity. Three paternal aunts had lens opacities documented in childhood and underwent cataract extractions in their second or third decades; all 3 had microcornea and mild to moderate scleralization of the cornea with varying degrees of vascularization. In addition, 3 paternal cousins underwent cataract extractions at ages 16 to 40 years; the cataracts were originally described as anterior polar, anterior cortical, nuclear, and posterior subcapsular. There was no evidence that either of the deceased paternal grandparents had any form of anterior segment dysgenesis: both were reported to have normal-sized corneas, and lens opacities that developed and resulted in cataract extraction in the eighth decade of life were attributed to the aging process. Doucette et al. (2011) suggested that one might have had a subclinical phenotype or that gonadal mosaicism might have been present. Khan et al. (2016) studied a large consanguineous family (PKCC139) in which 3 sibs and their cousin had ASGD. The authors stated that the affected individuals displayed classic ocular signs of Peters anomaly such as bilateral corneal opacities, developmental glaucoma, iris-retina coloboma, anterior segment dysgenesis, and iridolenticular adhesions. Nystagmus was observed in 3 of the 4 patients. Khan et al. (2016) noted that these features were present with 'variable degrees of penetrance' in the patients. Valleix et al. (2006) analyzed a consanguineous family in which 3 sibs had bilateral aphakia, microphthalmia, and complete agenesis of the ocular anterior segment. Two sibs exhibited sclerocornea, and 1 had megacornea. Inheritance The transmission pattern of ASGD in the family reported by Green and Johnson (1986) was consistent with autosomal dominant inheritance. The transmission pattern of ASGD in the consanguineous family reported by Khan et al. (2016) was consistent with autosomal recessive inheritance. Molecular Genetics In a mother and daughter with a prominent anterior Schwalbe line (posterior embryotoxon) and cataract, Semina et al. (2001) identified heterozygosity for a single-nucleotide insertion in the FOXE3 gene (601094.0001). The mutation was not found in 180 control chromosomes. To identify the genetic cause of congenital primary aphakia in 3 affected sibs, Valleix et al. (2006) sequenced 7 candidate genes chosen on the basis of either animal models or spatial and temporal patterns of expression. They identified homozygosity for a null mutation in the FOXE3 gene (C240X; 601094.0002). The findings indicated a possible critical role for FOXE3 very early in the lens developmental program, perhaps earlier than any role recognized elsewhere for this gene. Anjum et al. (2010) studied a large consanguineous Pakistani family with congenital primary aphakia mapping to chromosome 1p33, noting that affected individuals were initially tested for mutation in genes associated with autosomal recessive cataract to exclude the possibility that surgical cataract removal had resulted in the aphakic eyes. Sequencing of the FOXE3 gene identified homozygosity for the C240X mutation in 5 affected individuals; their unaffected parents were heterozygous for the mutation. Haplotype analysis between an affected individual from this family and 1 from the family with the same mutation reported by Valleix et al. (2006) demonstrated different haplotypes segregating in the 2 families, indicating that the mutation likely arose independently in each family. In a large 4-generation Newfoundland family segregating an autosomal dominant form of variable anterior segment dysgenesis, previously reported by Green and Johnson (1986), Doucette et al. (2011) analyzed 9 functional candidate genes and identified a heterozygous non-stop mutation in the FOXE3 gene (X320L; 601094.0003) that segregated with disease. The mutation was not found in 141 ethnically matched controls. In a large consanguineous family (PKCC139) with ASGD mapping to chromosome 1p34.1-p32.3, Khan et al. (2016) sequenced the candidate gene FOXE3 and identified homozygosity for a nonsense mutation (C240X; 601094.0004) that segregated with disease and was not found in 384 ethnically matched control chromosomes or in public variant databases. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Congenital primary aphakia \- Microphthalmia \- Anterior segment of eye aplasia \- Absent iris \- Sclerocornea \- Nystagmus \- Iridolenticular adhesions \- Iris-retina coloboma \- Elevated intraocular pressure \- Peters anomaly \- Microcornea \- Cataracts \- Corneal opacities of variable size and density \- Iris adhesions \- Absent Descemet membrane on histopathology (reported in 1 patient) \- Partial absence of Bowman membrane on histopathology (reported in 1 patient) \- Thinning of central cornea on histopathology (reported in 1 patient) MISCELLANEOUS \- Variable features may be present MOLECULAR BASIS \- Caused by mutation in the forkhead box E3 gene (FOXE3, 601094.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	ANTERIOR SEGMENT DYSGENESIS 2	c1853230	3,854	omim	https://www.omim.org/entry/610256	2019-09-22T16:04:54	{"doid": ["11367"], "mesh": ["C537786"], "omim": ["610256"], "orphanet": ["83461"], "synonyms": ["Alternative titles", "APHAKIA, CONGENITAL PRIMARY", "CPA"]}
Combined oxidative phosphorylation deficiency 1 is a severe condition that primarily impairs neurological and liver function. Most people with combined oxidative phosphorylation deficiency 1 have severe brain dysfunction (encephalopathy) that worsens over time; they also have difficulty growing and gaining weight at the expected rate (failure to thrive). In some cases, affected individuals have abnormal muscle tone (increased or decreased), developmental delay, seizures, loss of sensation in the limbs (peripheral neuropathy), and an unusually small head (microcephaly). Liver disease is common in people with combined oxidative phosphorylation deficiency 1, with individuals quickly developing liver failure. Individuals with this condition also usually have a potentially life-threatening buildup of a chemical called lactic acid in the body (lactic acidosis). The neurological features of combined oxidative phosphorylation deficiency 1 are largely due to brain abnormalities that include thinning of the tissue that connects the two halves of the brain (corpus callosum hypoplasia) and loss of brain tissue called white matter (leukodystrophy), particularly in an area of the brain called the basal ganglia, which normally helps control movement. Individuals with combined oxidative phosphorylation deficiency 1 usually do not survive past early childhood, although some people live longer. ## Frequency Combined oxidative phosphorylation deficiency 1 is likely a rare disorder, although its prevalence is unknown. At least 12 affected individuals have been described in the scientific literature. ## Causes Combined oxidative phosphorylation deficiency 1 is caused by mutations in the GFM1 gene. This gene provides instructions for making an enzyme called mitochondrial translation elongation factor G1. This enzyme is found in cell structures called mitochondria, which are the energy-producing centers in cells. While instructions for making most of the body's proteins are found in DNA that is stored in the nucleus of cells (nuclear DNA), a few proteins and other molecules are produced from DNA that is stored in mitochondria (mtDNA). Mitochondrial translation elongation factor G1 is involved in the production of proteins from mtDNA genes through a process called translation. The enzyme's role in translation is to coordinate the movements of mtRNA molecules, which are the protein blueprints created from mtDNA. This function allows assembly of proteins to continue until it is complete. Genes on mtDNA provide instructions for proteins that are primarily involved in the process of converting the energy from food into a form cells can use (oxidative phosphorylation). GFM1 gene mutations reduce or eliminate mitochondrial translation elongation factor G1 function. As a result, fewer mitochondrial proteins involved in oxidative phosphorylation are produced. (The process of oxidative phosphorylation involves five groups of proteins, or complexes. The condition is called combined oxidative phosphorylation deficiency 1 because it impairs the function of more than one of these complexes.) Organs that have high energy demands, such as the brain and liver, are particularly affected by the resulting impairment of oxidative phosphorylation. A shortage of energy in these tissues leads to cell death, causing the neurological and liver problems in people with combined oxidative phosphorylation deficiency 1. It is thought that other tissues that require a lot of energy, such as the heart and other muscles, are not affected in this condition because they have additional enzymes that can perform the process of mitochondrial protein production. ### Learn more about the gene associated with Combined oxidative phosphorylation deficiency 1 * GFM1 ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Combined oxidative phosphorylation deficiency 1	c1836797	3,855	medlineplus	https://medlineplus.gov/genetics/condition/combined-oxidative-phosphorylation-deficiency-1/	2021-01-27T08:25:53	{"mesh": ["C563797"], "omim": ["609060"], "synonyms": []}
Red ear syndrome A red ear syndrome attack, with affected ear on the left Red ear syndrome (RES) is a rare disorder of unknown etiology which was originally described in 1994. The defining symptom of red ear syndrome is redness of one or both external ears, accompanied by a burning sensation.[1] A variety of treatments have been tried with a limited success.[1] Red ears are also often a classic symptom of relapsing polychondritis (RP), a rare autoimmune disease that attacks various cartilage areas (and sometimes other connective tissue areas) in the body; research estimates that RP affects 3-5 people per million. Red ears in RP indicate inflamed cartilage (and sometimes the skin of the outer ear along with the cartilage) and often cause moderate to extreme pain during “flares” of the disease, which can be acute and/or chronic. Red ears in RP can be bilateral or unilateral, and are described as “earlobe sparing” due to the lack of cartilage in the earlobe. Prolonged inflammation can eventually result in deteriorated ear cartilage (often described as “cauliflower ear” or “floppy ear”), and even partial or total loss of hearing. ## Contents * 1 Characteristics * 2 Causes * 3 Management * 4 Epidemiology * 5 References ## Characteristics[edit] Attacks of skin redness and burning sensation or pain in one or both external ears are the only common symptoms.[1] Pain is often most pronounced at the ear lobe, and sometimes radiates to the jawbone and cheek.[1] The pain is normally mild, but has occasionally been described as severe.[1] The attacks can last seconds or hours, with 30 minutes to an hour being typical.[1] Most patients have daily attacks, ranging from 20 a day to a few a year.[1] ## Causes[edit] It is believed this syndrome may represent an auriculo-autonomic headache or be part of the group of disorders known as trigeminal autonomic cephalgias, which includes cluster headaches.[2][3] It is more often associated with migraine in younger people, while late-onset RES may result from pathology of the upper cervical spine or trigeminal autonomic cephalgia.[1] ## Management[edit] Red ear syndrome has proven difficult to treat.[1] The most widely attempted medication is gabapentin, with one case series finding that seven of eight patients on gabapentin showed improvement in attack frequency and ear color.[1] Smaller studies have reported limited success in certain patients using amitriptyline, flunarizine, imipramine, verapamil, and propranolol.[1] Appropriate medication may differ depending on the underlying cause of the individual's symptoms.[4] Using an ice pack to cool the ear during an attack can provide relief.[1] ## Epidemiology[edit] Red ear syndrome is considered rare, but the prevalence is unknown.[1] There are only about 101 cases described in the medical literature, with a male-to-female ratio of 1:1.25.[1] It has been reported in patients from ages 4 to 92, with an average onset at age 42.[1] ## References[edit] 1. ^ a b c d e f g h i j k l m n o Lambru, G.; Miller, S. & Matharu, M. S. (2013). "The red ear syndrome". The Journal of Headache and Pain. 14 (1): 83. doi:10.1186/1129-2377-14-83. PMC 3850925. 2. ^ Purdy RA, Dodick DW (August 2007). "Red ear syndrome". Curr Pain Headache Rep. 11 (4): 313–6. doi:10.1007/s11916-007-0210-8. PMID 17686397. 3. ^ Brill TJ, Funk B, Thaçi D, Kaufmann R (December 2009). "Red ear syndrome and auricular erythromelalgia: the same condition?". Clin. Exp. Dermatol. 34 (8): e626–8. doi:10.1111/j.1365-2230.2009.03342.x. PMID 19489849. 4. ^ Ryan, S.; Wakerley, B. R. & Davies, P. (2012). "Red ear syndrome: A review of all published cases (1996–2010)". Cephalalgia. 33 (3): 190–201. doi:10.1177/0333102412468673. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Red ear syndrome	c4324534	3,856	wikipedia	https://en.wikipedia.org/wiki/Red_ear_syndrome	2021-01-18T18:29:32	{"umls": ["CL519458"], "wikidata": ["Q7305317"]}
8q21.11 microdeletion syndrome encompasses heterozygous overlapping microdeletions on chromosome 8q21.11 resulting in intellectual disability, facial dysmorphism comprising a round face, ptosis, short philtrum, Cupid's bow and prominent low-set ears, nasal speech and mild finger and toe anomalies. ## Epidemiology The prevalence is unknown but 8q21.11 microdeletion syndrome is rare. To date, 13 cases, of which 5 from the same family, have been clinically and molecularly characterized without a notable gender discrepancy. ## Clinical description Very frequent facial anomalies in patients with 8q21.11 microdeletions include a round face with full cheeks, ptosis, short philtrum, small mouth with downturned corners and a Cupid's bow of the upper lip, low-set and prominent ears and nasal speech. Mild to moderate intellectual disability is present in all affected individuals. Mild finger and toe anomalies such as camptodactyly, syndactyly of the 3rd and 4th fingers, and broadening of the first rays are relatively common. Most also suffer from hypotonia. Other features comprise a high forehead, short palpebral fissures, wide nasal bridge, underdeveloped alae, micrognathia, short neck, hearing loss and ophthalmic manifestations including strabismus, sclerocornea and microphthalmia. ## Etiology The syndrome is caused by a heterozygous deletion at chromosome region 8q21.11, reported in the majority of patients. The constant microdeletion overlap region contains the ZFHX4 gene, a microRNA gene of unknown function, as well as a pseudogene and in 7 cases heterozygous deletions of PEX2 were noted. Microdeletions appear de novo or are inherited from affected parents in an autosomal dominant manner. ## Diagnostic methods Diagnosis is based on clinical manifestations leading to cytogenetic analysis. The 8q21.11 microdeletion can be detected using a range of molecular techniques including array based comparative genomic hybridization (array CGH) and fluorescence in situ hybridization (FISH). ## Differential diagnosis Differential diagnosis includes Schilbach-Rott syndrome, auriculo-condylar (question mark ear) syndrome, Frydman syndrome, Kabuki syndrome (see these terms). The syndrome also bares resemblance with distal 22q11.2 microdeletion syndrome and 10p13 microdeletion syndrome. The entity should not be confused with the 8q22.1 microdeletion (see this term) found in patients with Nablus mask-like facial syndrome. ## Antenatal diagnosis Antenatal diagnosis of 8q21.11 microdeletion is possible by amniocentesis or chorionic villus sampling and cytogenetic analysis. Preimplantation genetic diagnosis should be available for at risk couples. ## Genetic counseling Cytogenetic testing and genetic counseling should be offered to parents of affected individuals, informing them of the 50% risk of recurrence. Although the 8q21.11 microdeletion occurs sporadically, most deletions appearing de novo, a small number of patients have been inherited from affected parents. ## Management and treatment Management involves assessment, developmental therapies and a regular follow-up by a primary care physician and if required by appropriate specialists. Affected children almost invariably need special education. Early diagnosis and access to therapies with attention to speech and language, motor development and cognition are recommended. ## Prognosis Prognosis depends on clinical features. Adult affected individuals, despite their learning difficulties specifically regarding abstract thinking and planning ahead, function normally in everyday life. Fertility and life expectancy does not seem to be reduced. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	8q21.11 microdeletion syndrome	c3280231	3,857	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=284160	2021-01-23T19:06:32	{"omim": ["614230"], "icd-10": ["Q93.5"], "synonyms": ["Del(8)(q21.11)", "Deletion 8q21.11", "Monosomy 8q21.11"]}
Hyperbetaalaninemia is a very rare metabolic condition. Hyperbetaalaninemia refers to the build-up of protein building blocks, called beta amino acids, in the body. The excess beta amino acids are neurotoxic to the body. Signs and symptoms of hyperbetaalaninemia include convulsions (rapid and uncontrollable shaking), lethargy, and encephalopathy. Hyperbetaalaninemia is thought to be due to a loss of a functional form of the enzyme, beta-alanine-alpha-ketoglutarate transaminase. Treatment with oral pyridoxine was demonstrated to be helpful in one case. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Hyperbetaalaninemia	c0268630	3,858	gard	https://rarediseases.info.nih.gov/diseases/10267/hyperbetaalaninemia	2021-01-18T17:59:56	{"mesh": ["C562684"], "omim": ["237400"], "umls": ["C0268630"], "orphanet": ["309147"], "synonyms": ["Hyperalaninemia", "Hyper-beta-alaninemia"]}
## Summary ### Clinical characteristics. Cerebral cavernous malformations (CCMs) are vascular malformations in the brain and spinal cord comprising closely clustered, enlarged capillary channels (caverns) with a single layer of endothelium without mature vessel wall elements or normal intervening brain parenchyma. The diameter of CCMs ranges from a few millimeters to several centimeters. CCMs increase or decrease in size and increase in number over time. Hundreds of lesions may be identified, depending on the person's age and the quality and type of brain imaging used. Although CCMs have been reported in infants and children, the majority become evident between the second and fifth decades with findings such as seizures, focal neurologic deficits, nonspecific headaches, and cerebral hemorrhage. Up to 50% of individuals with FCCM remain symptom free throughout their lives. Cutaneous vascular lesions are found in 9% of those with familial cerebral cavernous malformations (FCCM; see Diagnosis/testing) and retinal vascular lesions in almost 5%. ### Diagnosis/testing. The diagnosis of familial cerebral cavernous malformation (FCCM) is established in a proband with either or both of the following: * Multiple CCMs, or one CCM and at least one other family member with one or more CCMs * A heterozygous pathogenic variant in KRIT1, CCM2, or PDCD10 ### Management. Treatment of manifestations: Surgical removal of lesions associated with intractable seizures or focal deficits from recurrent hemorrhage or mass effect may be considered. Treatment of seizures and epilepsy is symptomatic. Headaches are managed symptomatically and prophylactically. Acute and chronic neurologic deficits may be managed through rehabilitation. Surveillance: Brain MRI imaging with gradient echo (GRE) or susceptibility-weighted imaging (SWI) is indicated in individuals experiencing new neurologic symptoms. Agents/circumstances to avoid: Agents that increase risk of hemorrhage: aspirin, NSAIDs, heparin, and sodium warfarin (Coumadin®). Note: When these medications are necessary for treatment of life-threatening thrombosis, careful consideration and close medical monitoring of dosage are warranted. Radiation to the central nervous system may lead to new lesion formation. Evaluation of relatives at risk: Asymptomatic at-risk relatives of all ages may be evaluated by molecular genetic testing (if the family-specific pathogenic variant is known) to allow early diagnosis and monitoring of those at high risk of developing CCMs. Symptomatic relatives may undergo brain MRI with special sequences (GRE or SWI) to determine presence, size, and location of lesions. Pregnancy management: Baseline MRI one year prior to delivery is recommended to determine lesion locations; pregnant women with FCCM who have had recent brain or spinal cord hemorrhage, epilepsy, or migraine require closer monitoring during pregnancy; individulas with FCCM are at a higher risk for symptomatic cerebral hemorrhage during pregnancy than those with sporadic CCM; seizure is the most common symptom of CCM hemorrhage during pregnancy; exposure to antiepileptic medication during pregnancy may increase the risk for adverse fetal outcome but is generally recommended because the fetal risk is typically less than that associated with fetal exposure to an untreated maternal seizure disorder. ### Genetic counseling. Familial CCM is inherited in an autosomal dominant manner. The proportion of affected individuals with a de novo pathogenic variant is unknown. Each child of an individual with FCCM has a 50% chance of inheriting the pathogenic variant. Prenatal testing for pregnancies at increased risk is possible if the pathogenic variant has been identified in the family. ## Diagnosis ### Suggestive Findings Familial cerebral cavernous malformation (FCCM) should be suspected in individuals with the following clinical findings, brain imaging, histopathology, and family history. Clinical findings * Seizure disorder with onset at any age, but most typically between the second and fifth decades * Focal neurologic deficits * Nonspecific headaches * Cerebral hemorrhage * Vascular skin lesions (capillary malformations, hyperkeratotic cutaneous capillary venous malformations, venous malformations, red macules, and/or nodular venous malformations) * Retinal cavernomas and rare choroidal hemangiomas Brain imaging. Brain MRI using either gradient echo (GRE) or susceptibility-weighted imaging (SWI) demonstrating one or more cerebral cavernous malformations [Bulut et al 2014]: * The characteristic lesion is of mixed signal intensity with a central reticulated core surrounded by a dark ring, which is presumed to be hemosiderin deposition from prior hemorrhage [Rigamonti et al 1987] (see Table 2). * Lesions may appear as black dots, mixed signal intensity, or with rims of hemosiderin, fresh hemorrhage, or edema [Al-Shahi Salman et al 2008, de Souza et al 2008, Nikoubashman et al 2013, Nikoubashman et al 2015]. Note: Intravenous gadolinium contrast administration is not needed for identification of cavernous malformations, but is useful in identifying complex vascular malformations with arterial and venous components (which on rare occasion are associated with CCMs) and other types of vascular brain malformations including telangiectasias, arteriovenous malformations, and aneurysms. Histopathology * Closely clustered enlarged capillary channels (caverns) ranging from two to 55 mm (mean: 8 mm) with a single layer of endothelium without normal mature vessel wall elements or intervening brain parenchyma * Thrombosis and intra- and extralesional hemorrhage. Edema may surround lesions with recent hemorrhage. Family history. Two or more family members (including the proband) with cerebral cavernous malformations (CCM). Note: Individuals with a single CCM may have familial CCM; therefore, the presence of a single CCM in an individual with no family history of CCM (i.e., a simplex case) does not exclude the diagnosis of familial CCM (FCCM). ### Establishing the Diagnosis The diagnosis of familial cerebral cavernous malformation (FCCM) is established in a proband with either or both of the following: * Multiple CCMs, or one CCM and at least one other family member with one or more CCMs * A heterozygous pathogenic variant in KRIT1, CCM2, or PDCD10 identified by molecular genetic testing (see Table 1) Molecular testing approaches can include serial single-gene testing, use of a multigene panel, and genomic testing. Serial single-gene testing. Sequence analysis of KRIT1, CCM2, and PDCD10 is performed first (either sequentially or concurrently) followed by gene-targeted deletion/duplication analysis if no pathogenic variant is found. Several founder pathogenic variants that are useful for stratifying genetic testing in specific populations have been identified: * In individuals with ancestry from northern Mexico and the American Southwest, the pathogenic p.Gln455Ter variant in KRIT1 is common. * Gene-targeted deletion/duplication analysis for the CCM2 exon 2-10 deletion may be performed as part of the first tier of the testing strategy in individuals from the US, where up to 22% of affected individuals will have this pathogenic variant [Liquori et al 2007, Stahl et al 2008]. * In individuals of Ashkenazi Jewish descent a recurrent pathogenic variant in CCM2, c.30+5_30+6delGCinsTT, has been identified in multiple unrelated kindreds [Gallione et al 2011]. A multigene panel that includes KRIT1, CCM2, and PDCD10 and other genes of interest (see Differential Diagnosis) may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. ### Table 1. Molecular Genetic Testing Used in Familial Cerebral Cavernous Malformation View in own window Gene 1Proportion of FCCM Attributed to Pathogenic Variants in This Gene 2Proportion of Pathogenic Variants 3 Detected by Test Method Sequence analysis 4Gene-targeted deletion/duplication analysis 5 KRIT153%-65%85%-95% 65%-15% 6 CCM220%40%-70% 630%-60% 6, 7 PDCD1010%-16%80%-90% 60%-10% 6 Unknown 8NA 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. Following stringent inclusion criteria for familial CCM (multiple lesions and/or family history), a causative heterozygous pathogenic variant in either KRIT1, CCM2, or PDCD10 is detected in at least 75% of affected families [Denier et al 2006, Liquori et al 2007, D'Angelo et al 2011, Riant et al 2013, Spiegler et al 2014], with some authors reporting 97% detection rates [Cigoli et al 2014]. 3\. See Molecular Genetics for information on allelic variants detected in this gene. 4\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 6\. Pathogenic alleles detected by Riant et al [2013] by gene and methodology: KRIT: 68/80 alleles by sequencing and 12/80 alleles by del/dup; CCM2: 16/23 alleles by sequencing and 7/23 alleles by del/dup; PDCD10: 16/19 by sequencing and 3/19 alleles by del/dup. Pathogenic alleles detected by Liquori et al [2007] by gene and methodology: KRIT: 23/24 alleles by sequencing and 1/24 alleles by del/dup; CCM2: 10/24 alleles by sequencing and 14/24 alleles by del/dup; PDCD10: 4/4 by sequencing and 0/24 alleles by del/dup. 7\. Variability in the detection rate of deletion/duplication testing results from the high prevalence of a founder CCM2 deletion (exons 2-10) in the US. This deletion was rare in an Italian population [Liquori et al 2007, Liquori et al 2008]. 8\. Based on exclusion of a PDCD10 (CCM3 locus) pathogenic variant in a large family whose phenotype is linked to the CCM3 locus but not to the CCM1 (KRIT1) or CCM2 (CCM2) loci, Liquori et al [2006] proposed a putative CCM4 locus at 3q26.3-q27.2. However, with high rates of pathogenic variant detection in affected individuals the existence of a CCM4 locus is unlikely. ## Clinical Characteristics ### Clinical Description Neurologic findings. In familial CCM, up to 50% of individuals with a heterozygous pathogenic variant in either KRIT1, CCM2, or PDCD10 are clinically asymptomatic, although at least half of these individuals have identifiable CCM lesions on head imaging [Battistini et al 2007, Fischer et al 2013]. However, based on CCMs ascertained on autopsy, approximately 90% of individuals with either sporadic CCM or FCCM were asymptomatic [Otten et al 1989]. Cerebral cavernous malformation (CCM) has been reported in infants and children, but the majority of individuals with FCCM present with symptoms between the second and fifth decades. In one study, 9% of individuals were symptomatic before age ten years, 62%-72% between ages ten and 40 years, and 19% after age 40 years [Gunel et al 1996]. A more recent study of affected individuals found that 20% were younger than age ten years and 33% younger than age 18 years at the time of referral for genetic testing; the age of symptom onset was not cited [Spiegler et al 2014]. Clinically affected individuals most often present with seizures (40%-70%), focal neurologic deficits (35%-50%), nonspecific headaches (10%-30%), and cerebral hemorrhage (32%) [Denier et al 2004b]. Five percent of individuals with intractable temporal lobe epilepsy have CCM [Spencer et al 1984], although it is unknown how many of these individuals have FCCM. Central nervous system hemorrhages may be intralesional or extend beyond the lesion [Al-Shahi Salman et al 2008]. In children, hemorrhage and an aggressive presentation were thought to be more likely than in adults [Lee et al 2008]; however, Al-Holou et al [2012] evaluated hemorrhage risk in affected individuals younger than age 25 years and found that it was similar to the rates in adults. In general, symptom onset in children with FCCM is earlier than in children with sporadic (i.e., non-genetic) CCM [Acciarri et al 2009]. Cavernous malformation can lead to death from intracranial hemorrhage or from complications of surgery [Acciarri et al 2009] particularly when found in the brain stem [Bhardwaj et al 2009, Abla et al 2010]. Of note, severe hemorrhage from CCM is less common than hemorrhage from arteriovenous malformations (AVM) [Selman et al 2000]. Brain MRI. Either gradient echo (GRE) or susceptibility-weighted imaging (SWI) is the imaging modality of choice. While larger, complex lesions are visible on routine T1\- and T2\- weighted MRI sequences, GRE MRI sequences reveal up to triple the number of lesions and SWI MRI sequences reveal an additional doubling or tripling [Cooper et al 2008, de Souza et al 2008]. Use of these sensitive imaging techniques may reveal hundreds of lesions [Petersen et al 2010]. Four characteristic types of lesions have been described [Zabramski et al 1994] by MRI and histology (see Table 2). Dividing CCM into these radiologic and histologic types is clinically useful in predicting hemorrhage risk [Nikoubashman et al 2015]. ### Table 2. Classification of CCM by MRI and Histopathology View in own window LesionMR SignalHistopathologyClinical Correlation Type 1 * SE T1: hyperintense core * SE T2: hyperintense core or hypointense core Subacute hemorrhageAcute hemorrhage; high frequency of bleeding relapse Type 2 * SE T1: reticulated mixed signal core * SE T2: reticulated mixed signal core w/surrounding hypointense rim Lesions w/hemorrhages & thromboses of varying ages Type 3 * SE T1: iso- or hypointensity * SE T2: hypointense lesion w/hypointense rim magnifying size of lesion Chronic hemorrhage w/hemosiderin staining in & around lesion Type 4 * SE T1: not seen * SE T2: not seen * GRE: punctate hypointense lesion * SWI: punctuate hypointense lesion Tiny CCM or telangiectasiaPossibly represent true new lesions Zabramski et al [1994], de Souza et al [2008] Specific MRI sequences and programs: GRE = gradient echo MRI; SE = spin echo MRI; SWI = susceptibility-weighted imaging MRI The medical significance of small lesions (classified as type 4) seen on MRI (sometimes referred to as cerebral dot-like cavernomas or black spot lesions) is unclear. For these lesions, a mean bleeding rate of 0.7% per lesion–year was found over a period of 5.5 years in 18 children with either an inherited or a de novo heterozygous pathogenic variant in KRIT1 or PDCD10. Of the ten inidividuals who had hemorrhages, only two were symptomatic [Nikoubashman et al 2013, Nikoubashman et al 2015]. FCCM is a dynamic disease on neuroimaging studies. Brunereau et al [2000] and Labauge et al [2001] determined that new lesions appear at a rate of between 0.2 and 0.4 lesions per patient-year. In both FCCM and sporadic CCM lesions may change in size and signal characteristics over time. It had been assumed that individuals with familial CCM generally have multiple lesions while individuals who represent simplex cases (i.e., a single occurrence of a CCM in a family) have a single lesion; however, in a study of 138 individuals (62 symptomatic and 76 asymptomatic) with a heterozygous KRIT1 pathogenic variant, Denier et al [2004b] found that 26 (20%) appeared to have only one lesion when evaluated with T2-weighted MRI sequences. Further examination with GRE sequence MRI of 12 of the apparently symptom-free individuals revealed multiple lesions in eight (66%) and a single detectable lesion in four (33%). Additionally, eight of the symptom-free individuals showed no lesion at all. Thus, approximately 13% of individuals with a heterozygous KRIT1 pathogenic variant had only one lesion detected when examined with T2-weighted MRI and about 2% had only one lesion detected when examined with GRE sequence MRI. Since lesions are more readily identifiable using SWI, the number of clinically asymptomatic affected individuals is likely to increase as longitudinal studies using SWI are published. Some studies have identified an increasing number of lesions in families by generation: five to 12 lesions in children and adolescents; 20 lesions in parents; and more than 100 lesions in grandparents [Horowitz & Kondziolka 1995]. This is likely related to ascertainment bias; it has not been borne out by subsequent studies. Brunereau et al [2000] and Labauge et al [2001] determined that in familial CCM 76%-86% of lesions were supratentorial and 16%-24% infratentorial. Of the infratentorial lesions, almost half occurred in the brain stem. Brain stem lesions are frequently associated with symptoms [Fritschi et al 1994]. Spinal cord lesions are considered rare, reportedly occurring in fewer than 5% of affected individuals [Deutsch et al 2000, Badhiwala et al 2014]. In one large family with a known heterozygous KRIT1 pathogenic variant, spinal cavernous angiomas, either alone or associated with vertebral hemangiomas, were found in five of eight individuals studied using spinal MRI [Toldo et al 2009]. Cohen-Gadol et al [2006] found that 40% of persons presenting with a spinal CM had a similar intracranial lesion (CCM). In this same study 40% of persons with both spinal and intracranial CMs were simplex cases. Molecular genetic testing was not done in this study; however, multiplicity of spinal cord cavernous malformations are strongly suggestive of FCCM. Other. Vascular lesions found outside of the central nervous system have been reported in association with multiple intracranial cavernomas (cavernous malformations) with and without confirmed heterozygous pathogenic variants in KRIT1, CCM2, or PDCD10. * Vascular skin lesions have been reported in 9% of individuals with a heterozygous pathogenic variant in KRIT1 and less commonly in individuals with a heterozygous pathogenic variant in CCM2 or PDCD10 [Eerola et al 2000, Zlotoff et al 2007, Sirvente et al 2009, Toldo et al 2009, Kurlemann 2012, Campione et al 2013, Brownlee & Roxburgh 2014, Cigoli et al 2014, Bilo et al 2016]. * In the 38 individuals with FCCM and cutaneous vascular malformations reported by Sirvente et al [2009], the skin lesions were classified as capillary malformations (13); hyperkeratotic cutaneous capillary venous malformation (15); venous malformations (8); and unclassified (2). * Bluish nodules and other subcutaneous nodules have been described in the venous malformations. * Some affected individuals have skin lesions removed secondary to bleeding, pain, protrusion, concern about cosmesis, or concern for malignancy. * Retinal vascular lesions, reported in 5% of affected individuals, may include retinal cavernomas and (rarely) choroidal hemangiomas [Wood et al 1957, Sarraf et al 2000, Labauge et al 2006]. * Liver cavernoma have been reported in two Italian families with a heterozygous pathogenic variant in CCM2 but have not been confirmed to occur with an increased frequency in individuals with FCCM compared to individuals in the general population [Drigo et al 1994, Toldo et al 2009]. * Renal angioma has been reported in one affected individual of Italian descent [Battistini et al 2007]. * Atrial myxoma [Ardeshiri et al 2008, Sharma et al 2011] is rare and has not yet been definitively attributed to FCCM [Dobyns et al 1987, Drigo et al 1994, Labauge et al 1999, Eerola et al 2000, Chen et al 2002, Toldo et al 2009, Lanfranconi et al 2014]. ### Phenotype Correlations by Gene The clinical course of FCCM varies within and between families; therefore, the following are generalizations. KRIT1. Individuals with a heterozygous pathogenic variant in KRIT1 may have a less severe clinical phenotype than those with a heterozygous pathogenic variant in either CCM2 or PDCD10 [Gault et al 2006]. * Up to 50% of persons with FCCM caused by a heterozygous pathogenic variant in KRIT1 ultimately become symptomatic. * Skin lesions may be more common in persons with a heterozygous KRIT1 pathogenic variant [Sirvente et al 2009, Campione et al 2013]. CCM2. Individuals with a heterozygous pathogenic variant in CCM2 have fewer brain lesions on GRE MRI, and the rate of lesion development is slower than in individuals with a heterozygous pathogenic variant in KRIT1 [Denier et al 2006]. PDCD10. Individuals with a heterozygous pathogenic variant in PDCD10 are most likely to present with hemorrhage and to have symptom onset before age 15 years [Denier et al 2006, Shenkar et al 2015]. * Individuals with pathogenic variants in this gene generally have the most severe clinical phenotype [Riant et al 2013, Shenkar et al 2015], including a higher risk of the following: * Lesion burden * Skin lesions * Scoliosis * Brain tumors (meningioma, astrycytoma, acoustic neuroma) * Cognitive disability unrelated to lesion burden or hemorrhage ### Penetrance KRIT1. Among 64 families with 202 individuals who were heterozygous for a KRIT1 pathogenic variant [Denier et al 2004b]: * 62% were symptomatic; * 58% of those who were at least age 50 years had symptoms related to CCM; * 45 of 53 symptom-free individuals had lesions on MRI (3 had indications of a type 4 lesion; see Table 2) and five had no clinical or MRI findings of CCM. Note: SWI MRI, the most sensitive imaging technique for identifying CCMs, was not performed in this study. PDCD10. Penetrance may be decreased in families with a heterozygous pathogenic variant in PDCD10 compared to families with a heterozygous pathogenic variant in KRIT1 [Denier et al 2006]. Penetrance may be specific to the pathogenic variant [Gianfrancesco et al 2007]. ### Prevalence Based on autopsy studies, approximately 0.4%-0.5% of the general population have either sporadic CCM or FCCM [Otten et al 1989, Del Curling et al 1991, Robinson et al 1991]. The fairly common occurrence of asymptomatic vascular lesions in individuals with FCCM suggests that the population incidence of FCCM has been routinely underestimated [Verlaan et al 2002a, Johnson et al 2004]. There is a high incidence of FCCM in individuals of Mexican descent who have the pathogenic p.Gln455Ter variant in KRIT1 – a finding that could be attributable to inheritance from a common ancestor [Johnson et al 1995, Gunel et al 1996]. ## Differential Diagnosis CCMs represent 5%-15% of all cerebral vascular malformations [Rigamonti et al 1988]. Other vascular malformations occurring in the brain that should be distinguishable from CCM by neuroimaging and clinical manifestations: * Arteriovenous malformations * Venous malformations * Telangiectases * Vascular tumors such as hemangioblastomas (including those seen in Von Hippel-Lindau syndrome) * Vascular malformations associated with Sturge-Weber syndrome (OMIM 185300) [Mohr & Pile-Spellman 2005] The finding of developmental venous anomalies (DVA) in association with CCM decreases the likelihood that an individual has FCCM [Petersen et al 2010]. The following acquired conditions may lead to brain imaging findings similar to those seen in individuals with CCM: * Hypertensive angiopathy * Trauma * Multiple hemorrhagic metastases * Myloid angiopathy (with lacunar stroke) * Pneumocephalus [Palma et al 2009] * Cysticercosis ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs of an individual diagnosed with familial cerebral cavernous malformation (FCCM), the following evaluations are recommended: * MRI imaging of the brain and/or spinal cord if not already performed * Cerebral angiography may be considered to better define a complex lesion with arterial or venous components identified on brain MRI; however, caution should be used as cerebral angiography carries a small but appreciable risk of stroke. * In those with epilepsy: * Electoencephalogram (EEG) and/or video-EEG * Wada testing (to determine which hemisphere is language dominant) * Magnetoencephalography to confirm the localization of the epilepsy and to exclude other epileptogenic lesions * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations Recurrent hemorrhage or mass effect. Surgical removal of lesions associated with intractable seizures or focal deficits from recurrent hemorrhage or mass effect has traditionally been recommended [Heros & Heros 2000, Selman et al 2000, Folkersma & Mooij 2001]; however, a recent large prospective study in Scotland reported that surgical excision increased the overall risk of short-term neurologic disability, symptomatic intracranial hemorrhage, and new focal neurosurgical deficits [Moultrie et al 2014], calling this practice into question. * Neuropsychological testing may be considered prior to any neurosurgical procedure. * Microsurgical techniques rely on intraoperative examination for precise localization. * Even when a large number of lesions are present, a surgical approach may be justified. Gamma knife surgery or radiosurgery, while effective, appears to increase the risk of recurrent hemorrhage and remains unproven [Wang et al 2010, Steiner et al 2010]. Very large single lesions can be difficult to ablate, especially in the brain stem. In these instances, radiosurgery may be an option [Monaco et al 2010]. * In a group of individuals with symptomatic cavernous malformations studied in Japan, radiosurgery using varying doses of radiation for deep lesions was compared with conservative (nonsurgical) management. Doses less than 15 Gray (Gy) were associated with the lowest level of complications. Complications were also lower when the lesions were of smaller size, with overall hemorrhage rates reduced initially but reverting to a rate similar to that of the natural history after the first two years post-radiosurgery [Kida et al 2015]. * A study that carefully reviewed post-radiosurgery changes in individuals with CCM or AVM found that more than 30% developed radiation necrosis [Blamek et al 2010]. Seizures. Standard treatment for focal seizures using antiepileptic medication with early evaluation for surgical resection is appropriate (see Recurrent hemorrhage or mass effect). Headaches. Standard treatment and management of headaches is indicated unless the headache is severe, prolonged, or progressive, or associated with new or worsening neurologic deficits. In this circumstance, urgent brain imaging could lead to surgical management. Neurologic deficits. Rehabilitation is indicated for those with temporary or permanent neurologic deficits. ### Surveillance Brain MRI imaging with GRE or SWI is indicated in individuals experiencing new neurologic symptoms. Interpretation can be difficult because new hemorrhages may be asymptomatic. ### Agents/Circumstances to Avoid Limited evidence suggests an increased risk of hemorrhage with certain analgesic medications such as nonsteroidal anti-inflammatory drugs (ibuprofen, naproxen) and aspirin. Individuals with headaches and other pain should avoid these medications if suitable substitutes are available. Other medications that increase risk of hemorrhage (e.g., heparin, sodium warfarin [Coumadin®]) should be avoided or, when such medications are necessary for treatment of life-threatening thrombosis, should be closely monitored by the affected individual's medical team [Schneble et al 2012, Flemming et al 2013, Erdur et al 2014]. The use of narcotic pain medications is also discouraged in chronic pain conditions because of the potential for addiction and because of their association with rebound headaches. Radiation to the central nervous system is associated with de novo lesion formation in FCCM [Larson et al 1998, Nimjee et al 2006, Golden et al 2015]. The pathology of these lesions appears to be histologically different from the cavernomas found prior to radiation [Cha et al 2015]. ### Evaluation of Relatives at Risk It is appropriate to evaluate both symptomatic and apparently asymptomatic older and younger at-risk relatives of an affected individual in order to identify as early as possible those who would benefit from initiation of screening and preventive measures. Evaluations can include: * Molecular genetic testing if the pathogenic variant in the family is known. * Brain and/or spinal cord MRI imaging including GRE or SWI if the pathogenic variant in the family is not known See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management Pregnant women with FCCM who have had recent brain or spinal cord hemorrhage, epilepsy, or migraine will require closer observation during pregnancy. Baseline MRI one year prior to delivery is recommended to determine lesion locations [De Jong et al 2012, Witiw et al 2012, Yamada et al 2013]. Simonazzi et al [2014] reported six women with CCM who had symptoms such as seizure or focal neurologic deficit during pregnancy or within six weeks post-delivery. Reviewing the literature they found ten further cases in which pregnancy outcome was published. Of the 16 women, hemorrhage occured in ten. Preterm delivery occurred in four of six cases, one because of neurologic symptoms at 30 weeks. Cæsarean (C-)section was performed in nine cases, eight of which were for concern over CCM. Affected women and obstetricians are frequently concerned that the risk of increased blood pressure and intrathoracic pressure during stage 3 labor (pushing phase) could lead to CCM hemorrhage. However, in a study of 168 pregnancies (64 women), 28 with sporadic CCM and 36 with FCCM, only five symptomatic cerebral hemorrhages were reported, most commonly manifesting as seizures. Nineteen deliveries in this study were by C-section, mostly due to fear of possible intracranial hemorrhage. The risk of CCM hemorrhage was higher in the familial cases (3.6% compared with 1.8% in sporadic cases) [Kalani & Zabramski 2013]. In general, women with epilepsy or a seizure disorder from any cause are at greater risk for mortality during pregnancy than pregnant women without a seizure disorder; use of antiepileptic medication during pregnancy reduces this risk. However, exposure to antiepileptic medication may increase the risk for adverse fetal outcome (depending on the drug used, the dose, and the stage of pregnancy at which medication is taken). Nevertheless, the risk of an adverse outcome to the fetus from medication exposure is often less than that associated with exposure to an untreated maternal seizure disorder. Therefore, use of antiepileptic medication during pregnancy is typically recommended. Discussion of the risks and benefits of using a given antiepileptic drug during pregnancy should ideally take place prior to conception. Transitioning to a lower-risk medication prior to pregnancy may be possible [Sarma et al 2016]. See MotherToBaby for further information on medication use during pregnancy. ### Therapies Under Investigation Recent advances in the understanding of the pathobiology and molecular signaling of the CCM proteins (see Molecular Genetics) has identified several pathways which may be amenable to drug targeting. These are being investigation in in vitro assays and in live animal models. Fasudil, a specific Rho kinase inhibitor, has been demonstrated in Krit1(+/-) and Ccm2 (+/-) mouse models of FCCM to reduce both lesion size and number, as well as to lesson hemorrhage, proliferation, and inflammation [Stockton et al 2010, McDonald et al 2012]. Fasudil is approved in Japan for treatment of vasodilation; it is not currently available with FDA approval in the United States. Statin medications are nonspecific Rho kinase inhibitors and may be suitable for repurposing to treat CCM lesions. Strong in vitro data [Whitehead et al 2009] led to simvastatin being studied in people with CCM who are eligible to take this medication for other indications such as hyperlipidemia. This trial is in the final data collection and analysis phase (ClinicalTrials.gov identifier: NCT01764451). However, a Ccm2 knockout mouse model treated with simvastatin did not show a significant decrease in lesion burden, raising questions about dosing and efficacy of statin drug therapy [Gibson et al 2015]. A further proof-of-concept human trial is planned for atorvastatin therapy (ClinicalTrials.gov identifier: NCT02603328). The chemotherapeutic drug sorafenib [Wüstehube et al 2010] has been investigated in murine models of FCCM caused by mutation of KRIT1 with the finding of reduced capillary sprouting. Loss of function of KRIT1 leads to an increase in signaling of the TGFβ pathway leading to an inappropriate endothelial-to-mesenchymal cellular transition (EndMT): endothelial cells change to become more proliferative, with increased invasiveness and sprouting. Chemical inhibition of TGFβ decreases both the size and number of CCM lesions in mouse models [Maddaluno et al 2013]. Furthermore, inhibition of upstream Wnt/B-Catenin signaling related to EndMT with the drug sulindac restores junctional integrity between endothelia, and also reduces number and size of CCM lesions in a Pdcd10 knockout mouse model [Bravi et al 2015]. Sulindac is used clinically in humans for other indications, including for the treatment of colon cancer. A repurposing drug screen identified vitamin D3 (cholecalciferol) and tempol (a superoxide scavenger) as potential therapeutic drugs for CCM. Both of these molecules reduced lesion number in mouse models of CCM [Gibson et al 2015]. Vitamin D3 inhibits the signaling activation of RHOA, while tempol targets superoxide, suggesting a role for oxidative stress in CCM disease pathogenesis. Search ClinicalTrials.gov in the US and www.ClinicalTrialsRegister.eu in Europe for access to information on clinical studies for a wide range of diseases and conditions. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Cerebral Cavernous Malformation, Familial	c2931263	3,859	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1293/	2021-01-18T21:36:10	{"mesh": ["C536610"], "synonyms": ["Familial Cavernous Hemangioma", "Familial Cerebral Cavernous Angioma", "Familial Cerebral Cavernous Malformation"]}
A number sign (#) is used with this entry because of evidence that Adams-Oliver syndrome-2 (AOS2) is caused by homozygous or compound heterozygous mutation in the DOCK6 gene (614194) on chromosome 19p13. Description Adams-Oliver syndrome-2 is an autosomal recessive multiple congenital anomaly syndrome characterized by aplasia cutis congenita (ACC) and terminal transverse limb defects, in association with variable involvement of the brain, eyes, and cardiovascular systems (summary by Shaheen et al., 2011). For a discussion of genetic heterogeneity of Adams-Oliver syndrome, see AOS1 (100300). Clinical Features Koiffmann et al. (1988) reported a Brazilian family with Adams-Oliver syndrome suggesting autosomal recessive inheritance. The proband, born of unaffected first cousins, had a congenital scalp defect with hypoplastic fingers and toes. Among 7 sibs, 3 sisters and 2 brothers were normal, whereas 2 brothers born with the same scalp defect died as a consequence of bleeding from this abnormal area. Orstavik et al. (1995) reported 2 sibs with aplasia cutis congenita, transverse limb anomalies, and congenital vitreoretinal abnormalities: the sister had retinal nonattachment and the brother had a falciform fold in his left eye. The authors concluded that these patients had a more severe phenotype than typical Adams-Oliver syndrome, and suggested that they may represent a new severe variant of the disorder. The healthy parents were unrelated but came from the same small town, and Orstavik et al. (1995) stated that autosomal recessive inheritance seemed most likely. Klinger and Merlob (1998) reported a brother and sister with AOS. The brother had scalp aplasia cutis congenita and cutis marmorata; his sister had these features associated with terminal lower limb defects, including short upper limbs, short feet, and brachydactyly of toes 2 to 4. Oligohydramnios had been a feature of both pregnancies. The authors also pointed out the report of Kahn and Olmedo (1950) as another example of recessive inheritance. Tekin et al. (1999) reported a Turkish family with 2 affected sibs and unaffected consanguineous parents as evidence of recessive inheritance in at least some families. Amor et al. (2000) reported 2 sibs, born of consanguineous parents, with cortical malformations and scalp and limb defects consistent with AOS. Both sibs showed global developmental delay, and brain imaging showed polymicrogyria and dilatation of the cerebral ventricles. One child developed lymphedema of 1 leg. Amor et al. (2000) suggested that the sibs had a rare variant of AOS with autosomal recessive inheritance. Unay et al. (2001) described a 7-year-old Turkish girl, born of unaffected double first-cousin parents, who presented with seizures and focal alopecia. Her psychomotor development was severely delayed. Dysmorphic features included bitemporal depression, prominent ears, and micrognathia. There was an 8.5-cm diameter area of alopecia in the left frontotemporal region without any underlying bone defect; the remainder of the skin was normal. Her right hand was short, with flexed fingers, and there were only 2 phalanges of digits 2, 3, and 5; on the left, the middle and distal phalanges were absent from all fingers. There was interdigital webbing between toes 2, 3, and 4. Heart was normal by ECG and echocardiography. EEG demonstrated diffuse and slow right hemispheric complex activity due to cerebral cortical dysfunction; CT scan of the brain showed multiple calcifications in the walls of the ventricles. Unay et al. (2001) stated that the triad of microcephaly, epilepsy, and mental retardation is an extremely rare finding in AOS, and that this patient represented the third such reported case. Temtamy et al. (2007) reported 3 probands with AOS from 3 unrelated consanguineous Egyptian families. The patients had typical skull and limb anomalies with cutis marmorata telangiectatica congenita. The parents were unaffected, and there was a history of similarly affected sibs in 2 of the families. Additional rare manifestations were observed, including microcephaly, psychomotor retardation, epilepsy, eye anomalies, and atrophic skin lesions. MRI of the brain in 1 patient revealed retrocerebellar cyst and mild asymmetric cerebellar hypoplasia, features not previously reported in AOS. Temtamy et al. (2007) stated that their findings provided further evidence of clinical and genetic heterogeneity and supported the presence of an autosomal recessive variant of Adams-Oliver syndrome. Prothero et al. (2007) reported a male infant, born of consanguineous Afghan parents, with microcephaly, cutis aplasia of the scalp, a wide anterior fontanel, hypoplastic distal phalanges of all 4 limbs, and hypoplastic nails, most marked in his hands and left foot. There were some mild facial dysmorphic features, including posteriorly rotated ears, deep-set eyes, and micrognathia. Ophthalmic examination showed bilateral falciform retinal folds involving the macula. Brain MRI showed periventricular calcifications, slight ventricular dilation, and hypoplasia of the corpus callosum. At 1 year, he had severe developmental delay with truncal hypotonia and increased tone in all 4 limbs. McGoey and Lacassie (2008) reported 2 sisters with Adams-Oliver syndrome who had central nervous system abnormalities. The proband was born with rudimentary fingers, hypoplastic nails, and near total adactyly of 1 foot and syndactyly of the other. She also had 2 hair whorls, micrognathia, high-pitched cry, sacrococcygeal dimple, cutis marmorata, and microcephaly. She developed seizures at age 7 months, at which time MRI showed near total agenesis of the corpus callosum and periventricular gliosis with calcifications. Her older sister was born with terminal transverse limb defects, including bilateral shortening of the radioulnar bones with hypoplastic digits at the elbows and near total adactyly of the feet. Facial features included hypertelorism, epicanthal folds, blue sclerae, and micrognathia. She also had seizures, developmental delay, microcephaly, and periventricular calcifications. McGoey and Lacassie (2008) reviewed previous reports of autosomal recessive inheritance of Adams-Oliver syndrome, stating that 12 patients from 9 kindreds had been reported. The authors postulated that central nervous system abnormalities may be more common in the recessive form compared to the classic autosomal dominant form. Balasubramanian and Collins (2009) reported 2 sibs with probable AOS. They were born to nonconsanguineous unaffected parents and had 2 healthy older sibs, suggesting autosomal recessive inheritance. The younger girl was more severely affected than her older brother, and the diagnosis of AOS in the 2 affected sibs only became apparent after she was born. The sister was born with microcephaly, scalp and abdominal wall defects, abnormally small fingers and toes, widely spaced nipples, and brain MRI abnormalities, including thin corpus callosum and periventricular leukomalacia. The brother showed a milder presentation with intrauterine growth retardation, microcephaly, cardiac defects, mild distal limb anomalies, and periventricular calcification. He was reported to have mild developmental delay at age 6 months. Shaheen et al. (2011) described 2 probands with AOS from 2 unrelated consanguineous Arab families. One patient was an 11-month-old girl with severe and global developmental delay and recurrent seizures, who had 4 normal sibs and 1 cousin who was said to be similarly affected. In addition to a large area of cutis aplasia of the scalp and absence of distal phalanges and nails of the hands and feet, examination revealed microcephaly, optic atrophy, and axial hypotonia with appendicular hypertonia. Echocardiography was normal. Brain CT showed hydrocephalus with dilation of the lateral ventricles and multiple small periventricular and subependymal calcifications. The other patient was a 3.5-year-old girl with terminal reduction defects of the hands and feet, cutis aplasia of the scalp, and speech delay, in whom echocardiography, EEG, and eye examination were normal. Both sets of parents were healthy. Sukalo et al. (2015) studied 12 patients from 10 families with molecularly proven AOS2. Limb defects ranged from minimal hypoplasia of terminal phalanges to severe transverse reduction defects. In addition to aplasia cutis congenita of the scalp, 4 patients had areas of ACC on the abdomen. All patients from whom sufficient data could be obtained were reported to have developmental delay or mental retardation, ranging from mild to severe. A broad range of additional neurologic abnormalities were reported in most cases, including cerebral palsy, spasticity, contractures, and epilepsy. Only 1 of the 7 patients who were more than 4 years old had achieved the ability to walk without support. Brain MRI or CT scan was performed in 7 patients, and was abnormal in all cases. The most frequent changes included ventriculomegaly, periventricular leukomalacia and/or calcifications, and hypoplasia or atrophy of the corpus callosum. Head circumference measurements were available for 8 patients and were in the microcephalic range for all. Ocular anomalies included microphthalmia and retinal detachment, and visual impairment was present in all patients for whom clinical information was available. In contrast, cardiac anomalies were observed in only 3 cases. Sukalo et al. (2015) noted that AOS2 appears to be strongly associated with structural brain abnormalities, ocular anomalies, and intellectual disability, and suggested that it represents a variant of AOS with a particularly poor prognosis. Inheritance The transmission pattern of Adams-Oliver syndrome in the families reported by Shaheen et al. (2011) was consistent with autosomal recessive inheritance. Molecular Genetics By combining autozygome data with next-generation sequencing in an 11-month-old Arab girl with autosomal recessive AOS, Shaheen et al. (2011) identified a homozygous 4-bp deletion in the DOCK6 gene (614194.0001), which was found in heterozygosity in her unaffected parents. Analysis of DOCK6 in a 3.5-year-old Arab girl with AOS revealed a homozygous 1-bp duplication (614194.0002) that segregated with disease in her family. In affected individuals from 2 consanguineous Arab families with AOS who shared a region of homozygosity overlapping the DOCK6 gene, Shaheen et al. (2013) identified homozygous mutations in DOCK6 (614914.0003 and 614914.0004, respectively). In 14 affected individuals from 12 unrelated families with AOS, Stittrich et al. (2014) screened for variants in AOS-associated genes and identified 1 individual who was compound heterozygous for mutations in the DOCK6 gene. Sukalo et al. (2015) analyzed the DOCK6 gene in 88 AOS patients from 78 unrelated families and identified probands from 10 families with biallelic mutations, including compound heterozygosity for a missense mutation (V263D; 614194.0005) and a splice site mutation (614194.0006) in the 2 sibs originally reported by Orstavik et al. (1995), and homozygosity for a missense mutation (E1052K; 614194.0007) in the Afghan male infant previously reported by Prothero et al. (2007). The overall proportion of DOCK6-related AOS across the complete cohort was 13%, with a frequency of 29% among families suggestive of autosomal recessive inheritance and 2% among sporadic cases. Sukalo et al. (2015) stated that AOS2 is strongly associated with cerebral and ocular anomalies in addition to aplasia cutis congenita and transverse terminal limb defects, and suggested that DOCK6 should be the primary candidate gene for investigation in patients with such a constellation of features. INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Microcephaly \- Macrocephaly (rare) \- Aplasia cutis congenita of the scalp Face \- Mild facial dysmorphism \- Low hair line \- Bitemporal depression (rare) Ears \- Low-set ears \- Prominent ears (rare) Eyes \- Hypertelorism \- Small palpebral fissures \- Strabismus (rare) \- Microphthalmia (rare) \- Cataract, congenital (rare) \- Rod dystrophy (rare) \- Vitreoretinal abnormalities, congenital (rare) \- Optic atrophy (rare) Nose \- Depressed nasal bridge \- Bulbous nasal tip Mouth \- Micrognathia SKELETAL Limbs \- Terminal transverse defects, asymmetric (minimal to absence of a limb) Hands \- Shortened digits \- Single palmar creases Feet \- Shortened digits \- Webbing, interdigital SKIN, NAILS, & HAIR Skin \- Aplasia cutis congenita of the scalp \- Aplasia cutis congenita of the abdomen (in some patients) \- Cutis marmorata \- Prominent veins on scalp, trunk, and/or extremities Nails \- Hypoplastic nails Hair \- Low anterior hairline MUSCLE, SOFT TISSUES \- Lymphedema, of upper and/or lower extremity (rare) NEUROLOGIC Central Nervous System \- Psychomotor retardation \- Seizures \- Hypotonia \- Calcifications of cerebral ventricles \- Dilation of cerebral ventricles \- Polymicrogyria (rare) \- Cerebral atrophy (rare) \- Cerebellar hypoplasia, mild asymmetric (rare) \- Retrocerebellar cyst (rare) PRENATAL MANIFESTATIONS Amniotic Fluid \- Oligohydramnios MISCELLANEOUS \- Limb reduction defects typically involve the distal phalanges or entire digit, with rare involvement of more proximal limb structures \- Wide variability in severity of limb defects MOLECULAR BASIS \- Caused by mutation in the dedicator of cytokinesis-6 gene (DOCK6, 614194.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	ADAMS-OLIVER SYNDROME 2	c0265268	3,860	omim	https://www.omim.org/entry/614219	2019-09-22T15:56:00	{"doid": ["0060227"], "omim": ["614219"], "orphanet": ["974"], "genereviews": ["NBK355754"]}
A number sign (#) is used with this entry because of evidence that spastic quadriplegic cerebral palsy-3 (CPSQ3) is caused by homozygous mutation in the ADD3 gene (601568) on chromosome 10q24. One such family has been reported. For a discussion of genetic heterogeneity of CPSQ, see CPSQ1 (603513). Clinical Features Kruer et al. (2013) reported 4 sibs, born of consanguineous Jordanian parents, with a neurodevelopmental disorder characterized by variable spasticity and cognitive impairment. Three patients developed severe spastic quadriplegia in the first months or years of life. All had cognitive impairment and poor speech. One patient developed seizures by age 2 that responded to medication. One patient was slightly less severely affected, with spastic diplegia and borderline intellectual function at age 7 years. All 4 patients had borderline microcephaly. More variable features included pyramidal signs, dysarthria, dysphagia, exotropia, supranuclear gaze palsy, strabismus, and nystagmus. One of the patients was dependent for all activities of daily living at age 16 years. Brain imaging was abnormal in all 4 patients: all had some T2-weighted hyperintensities, and the patient with seizures also had gray matter heterotopia. Three patients also had transient conjugated hyperbilirubinemia during illness, which was attributed to a homozygous S1342Y mutation in the ABCC2 gene (601107), resulting in Dubin-Johnson syndrome (DJS; 237500). Inheritance The transmission pattern of CPSQ3 in the family reported by Kruer et al. (2013) was consistent with autosomal recessive inheritance. Molecular Genetics In 4 sibs, born of consanguineous Jordanian parents, with CPSQ3, Kruer et al. (2013) identified a homozygous missense mutation in the ADD3 gene (G367D; 601568.0001) that was responsible for the neurologic phenotype. The mutation, which was found by a combination of homozygosity mapping and whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Lysates from patient fibroblasts showed a significant increase in actin polymerization compared to controls, consistent with impaired actin capping activity and a loss of function. Compared to controls, mutant fibroblast showed a lack of neurite-like processes and increased proliferation and migration. The mutation also impaired the ability of mutant ADD3 to associate with the ADD1 (102680) subunit. Overall, the biologic studies implicated abnormalities of components of the dynamic cytoskeleton and process outgrowth in neuromotor dysfunction. Animal Model Kruer et al. (2013) found that knockdown of the Add3 homolog in Drosophila resulted in lesions in the brain lamina and medulla, as well as impaired locomotion, consistent with a role in normal neuromotor function. INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Microcephaly, borderline Eyes \- Nystagmus \- Strabismus \- Supranuclear gaze palsy \- Exotropia ABDOMEN Gastrointestinal \- Dysphagia NEUROLOGIC Central Nervous System \- Global developmental delay \- Spastic quadriplegia \- Spastic diplegia \- Pyramidal tract signs \- Cognitive impairment \- Poor speech \- Seizures (1 patient) \- Gray matter heterotopia (in 1 patient) \- T2-weighted hyperintensities (in 2 patients) MISCELLANEOUS \- Onset in infancy \- Variable severity \- One consanguineous Jordanian family with 4 affected sibs has been reported (last curated June 2016) MOLECULAR BASIS \- Caused by mutation in the adducin 3 gene (ADD3, 601568.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	CEREBRAL PALSY, SPASTIC QUADRIPLEGIC, 3	c2751938	3,861	omim	https://www.omim.org/entry/617008	2019-09-22T15:47:14	{"mesh": ["C567853"], "omim": ["603513", "617008"], "orphanet": ["210141"], "synonyms": ["Inherited congenital spastic quadriplegia", "Spastic quadriplegic cerebral palsy"]}
Typhoid or typhoid fever is a reportable, fecal-oral, potentially fatal infectious disease, caused by the bacteria Salmonella typhi and characterized by a non-focal fever. ## Epidemiology The prevalence of typhoid is unknown but it is most commonly found in Asia, Africa and South America where access to properly treated drinking water may be limited. It is rare in Europe and Western countries and generally only occurs when imported from an endemic location. The annual incidence in Europe is estimated to be less than 1/30,000 persons/year. ## Clinical description Symptoms usually appear 1-7 days after ingestion of the bacteria and include high fever (39 to 40°C), chills, constipation or diarrhea, headache, stomach pain, malaise, rash of flat rose-colored spots on the chest and hepato-splenomegaly. Temperature rises for 2-3 days and remains elevated for another 10-14 days accompanied by bradycardia and prostration. In severe cases, delirium, stupor and coma can occur. In 1-2% of patients, intestinal lesions can lead to bleeding and death. Others may develop pneumonia in the second to third week. Intestinal hemorrhage and perforation (usually in the terminal ileum) is a serious complication that can occur 2-3 weeks after infection, and usually occurs in developing countries where treatment is not always available. The convalescence period may last several months. Patients can remain carriers after symptoms disappear. With treatment most patients recover after 5-7 days of therapy and death is extremely uncommon. ## Etiology Typhoid is caused by several serovars of Salmonella enterica, a Gram-negative bacterium, with S. typhi being the most common. It is transmitted by the fecal-oral route from human to human when food or water is contaminated with feces of infected individuals. There is no known zoonotic reservoir. Once ingested, S. typhi multiply inside macrophages and spread throughout the body in the bloodstream where they travel to the bone marrow, liver and gallbladder and are shed in the bile and feces. Asymptomatic carriers can spread the disease as a consequence of gallbladder colonization. ## Diagnostic methods Diagnosis of typhoid is suspected in patients with fever who have recently travelled to an area where the disease is endemic. The only methodology currently able to categorically confirm a diagnosis of typhoid involves a microbiological culture of blood or bone marrow to detect S. typhi or other typhoidal organisms. The Widal test, an agglutination test, is used only in developing countries as it is rapid, inexpensive and does not require a specialized laboratory, but it lacks sensitivity and specificity. ## Differential diagnosis Other viral, bacterial or parasitic pathogens that cause diseases similar to typhoid include malaria, dengue fever, leptospirosis, typhus group rickettsia (see these terms), and influenza. ## Management and treatment Typhoid is treated with antimicrobials, typically fluoroquinolones, which are essential for bacterial clearance. Patients usually begin to recover after 2-3 days but must complete the course of treatment to prevent relapse or latent retention of the infection. If intestinal perforation occurs, surgical intervention is necessary immediately. When travelling to countries where typhoid is endemic, vaccinations are recommended. The two licensed vaccines currently available are the oral live attenuated vaccine Ty21a and the parenteral Vi polysaccharide vaccine. Travelers should take care to avoid unsafe drinking water and food prepared in unsanitary conditions. Any cases of typhoid should immediately be reported. Food should not be prepared by people who have been infected with typhoid recently as they may still be carriers. ## Prognosis Prognosis is good and complications rarely occur if treated quickly with antibiotics. In untreated cases the fatality rate can be as high as 20%. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Typhoid	c0041466	3,862	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99745	2021-01-23T17:12:57	{"gard": ["9564"], "mesh": ["D014435"], "umls": ["C0041466"], "icd-10": ["A01.0"], "synonyms": ["Typhoid fever", "Typhoidal salmonellosis"]}
For other uses, see Locoweed (disambiguation). Plant that produces swainsonine, a phytotoxin harmful to livestock Locoweed (also crazyweed and loco) is a common name in North America for any plant that produces swainsonine, a phytotoxin harmful to livestock. Worldwide, swainsonine is produced by a small number of species, most in three genera of the flowering plant family Fabaceae: Oxytropis and Astragalus in North America,[1] and Swainsona in Australia. The term locoweed usually refers only to the North American species of Oxytropis and Astragalus, but this article includes the other species as well. Some references may list Datura stramonium as locoweed.[2] Locoweed is relatively palatable to livestock, and some individual animals will seek it out. Livestock poisoned by chronic ingestion of large amounts of swainsonine develop a medical condition known as locoism (also swainsonine disease,[3] swainsonine toxicosis, locoweed disease, and loco disease; North America) and pea struck[4] (Australia). Locoism is reported most often in cattle, sheep, and horses, but has been reported also in elk and deer. It is the most widespread poisonous plant problem in the western United States.[1] Agricultural Research Service and New Mexico State University scientists have been collaborating since 1990 to help solve the problem that locoweed presents to livestock farmers. The research involved identifying the fungal species that produces the locoweed toxins, pinpointing levels of toxicity in animals once they have ingested locoweed, observing the effects of locoweed toxins on livestock's reproduction and grazing preferences, etc. Together, the scientists assembled a grazing management scheme to help farmers avoid the poisonous locoweed.[5] Most of the 2000 species of Astragalus, including many that are commonly known as locoweeds, do not produce swainsonine. Some species, including a few that produce swainsonine, accumulate selenium. This has led to confusion between swainsonine poisoning and selenium poisoning due to this genus. ## Contents * 1 History and etymology * 2 Taxa producing swainsonine * 3 Epidemiology * 4 Pathology * 5 Diagnosis * 6 Prevention * 7 See also * 8 References * 9 External links ## History and etymology[edit] The first technical account (in English) of locoism was published in 1873, in the United States. Linguists have documented locoism in use among English speakers by 1889, and both loco and locoweed in use by 1844.[6] Loco, a loanword from Spanish, is understood by most English-speaking users in the sense of crazy, and this appears to have also been the sense understood by vaqueros.[6] In Spanish, however, loco has an older, different sense. In Spain, where the native Astragalus species are not known to cause locoism, for centuries loco has been applied to some of these species in the sense of rambling: common names include yerba loca (hierba loca; rambling herb) and chocho loco (rambling lupine). Locoweed is a compound of loco and weed.[citation needed] Although some authors claim it is incorrect to use loco as a noun (in place of locoweed), this usage has a long history.[citation needed] The presence of a toxin in locoweed was demonstrated in 1909. Initially, the toxin was reported to be barium, but that was soon disproved. Swainsonine, first isolated from Swainsona, was shown to be responsible for pea struck in 1979, and was reported in both Oxytropis and Astragalus in 1982.[7] Since 1982, swainsonine has been isolated from still more plants, some of which also are reported to cause locoism or medical conditions similar to locoism. The first report of locoism in South America, involving Astragalus pehuenches, was published in 2000.[8] ## Taxa producing swainsonine[edit] Swainsonine is produced by a small number of species, including species in several genera of plants and two genera of fungi. Oxytropis sericea in bloom Astragalus lentiginosus in fruit Swainsona galegifolia Oxytropis is distributed throughout western North America, particularly in the Great Plains and Rocky Mountains. However, most species of Oxytropis have narrow habitat requirements and within those habitats are abundant only in unusually wet years.[1] The species most frequently encountered by livestock are O. lambertii (Lambert locoweed, purple locoweed, woolly locoweed) and especially Oxytropis sericea (white locoweed, white point locoweed, white point loco). Swainsonine has also been found in O. campestris (in Canada).[9] Some species of Astragalus (milkvetch) are also referred to as locoweed. These are primarily species which grow in areas with high selenium content in the soil.[citation needed] Swainsonine has been found in:[9] * A. earlei (Big Bend loco) * A. mollissimus (purple woolly loco) * A. pubentissimus (green river milkvetch) * A. lentiginosis (spotted locoweed, freckled milkvetch) * A. wootoni (garbancillo) * A. nothoxys (Sheep milkvetch) * A. tephrodes (ashen milkvetch) * A. humistratus (ground cover milkvetch) In Argentina, locoism (locoismo) was first reported in 2000. A flock of sheep grazing a pasture with Astragalus pehuenches was poisoned and 220 sheep (73%) died.[8] Although this was the first report of locoism in South America,[8] swainsonine had been isolated previously from A. pehuenches and several other species in Argentina and Peru.[8][10] In the Old World, native plants causing locoism have not been reported. Astragalus lusitanicus in Morocco was suspected,[11] but has been shown be neither a producer of swainsonine nor an accumulator of selenium. Its toxicity is suspected to be due to a novel alkaloid.[12] In Australia, species of Swainsona (Darling pea) that cause pea struck include:[9][13] * S. luteola * S. greyana * S. galegifolia (smooth Darling pea) Astragalus and Oxytropis are 2 of 20 genera (and 78 names of genera) in the tribe Galegeae, subtribe Astragalinae. Some authorities include Swainsona in the subtribe.[14] Formerly, Swainsona was in another subtribe, Coluteinae, that has been combined into Astragalinae. Swainsonine has also been isolated from Sida carpinifolia and Ipomoea carnea, and both species have been reported to cause locoism.[15] Embellisia, a fungus isolated from Oxytropis lambertii, has also been shown to produce swainsonine and to cause locoism in rats.[16] Rhizoctonia leguminicola, a fungal plant pathogen that may occur on red clover, also produces swainsonine. Although intoxication due to this fungus resembles locoism, it has additional signs and symptoms due to the production of other toxins.[17] ## Epidemiology[edit] Locoweed is eaten during the early spring and late fall, when it is often the only green plant available to grazing animals.[citation needed] ## Pathology[edit] Intoxication with swainsonine has several kinds of effect. Livestock that graze for several weeks on locoweed (and little else) develop a lysosomal storage disease similar to genetic mannosidosis.[18] Swainsonine inhibits a lysosomal enzyme, alpha-mannosidase.[19] This results in abnormal accumulation of the molecules normally processed by the enzyme, and this accumulation leads to vacuolation of most tissues. Vacuolation is most obvious in neurons and epithelial cells. The vacuolation resolves shortly after poisoning is discontinued, but if the vacuolation is so severe that it destroys cells, it may result in some neurologic damage that is irreversible and permanent.[18] The damage is highly varied. In cattle at high altitude, complications of locoism can include congestive heart failure.[20] ## Diagnosis[edit] Diagnosis of clinical poisoning is generally made by documenting exposure, identifying the neurologic signs, and analyzing serum for alpha-mannosidase activity and swainsonine.[18] In mule deer, clinical signs of locoism are similar to chronic wasting disease. Histological signs of vacuolation provide a differential diagnosis.[21] Sub-clinical intoxication has been investigated in cattle grazing on Astragalus mollissimus. As the estimated intake of swainsonine increased, blood serum alpha-mannosidase activity and albumin decreased, and alkaline phosphatase and thyroid hormone increased.[22] ## Prevention[edit] Because O. sericea is both frequently encountered and relatively palatable to livestock, it is an important cause of economic losses in livestock production. Keeping livestock away from locoweed infested pasture in spring and fall when grass and other forbs are not actively growing is recommended. Another suggested remedy is to provide palatable supplemental nutrients if animals are to be kept in infested pasture. These remedies take into account livestock preference for locoweed during seasons when grass is dry and not very nutritious.[23] Conditioned food aversion has been used experimentally to discourage livestock from eating it.[24][25] In horses, a small study has shown promising results using lithium chloride as the aversive agent.[25] ## See also[edit] * List of plants poisonous to equines * Nutrition disorder * Locoweed is a street name for marijuana . ## References[edit] 1. ^ a b c Ralphs MH, James LF (February 1999). "Locoweed grazing". Journal of Natural Toxins. 8 (1): 47–51. PMID 10091127. 2. ^ https://www.flickr.com/photos/alanenglish/417160351/ 3. ^ Jones et al. (1997), page 39. 4. ^ Pritchard DH, Huxtable CR, Dorling PR (March 1990). "Swainsonine toxicosis suppresses appetite and retards growth in weanling rats". Research in Veterinary Science. 48 (2): 228–30. doi:10.1016/S0034-5288(18)30995-0. PMID 2110378. 5. ^ http://www.ars.usda.gov/is/pr/2010/100621.htm 6. ^ a b Robert N. Smead & Richard W. Slatta (2004). Vocabulario Vaquero/cowboy Talk: A Dictionary Of Spanish Terms From The American West. University of Oklahoma Press. p. 197. ISBN 978-0-8061-3631-8. page 115 7. ^ Keeler and Tu (1983), page 454. 8. ^ a b c d C.A. Robles; C. Saber; M. Jefrey (2000). "Intoxicación por Astragalus pehuenches (locoismo) en ovinos Merino de la Patagonia Argentina" [Astragalus pehuenches (locoweed) poisoning in a Merino sheep flock in Patagonia Region, Argentina]. Revista de Medicina Veterinaria. 81 (5): 380–384. 9. ^ a b c Jones et al. (1997), page 752. 10. ^ Michael JP (December 1997). "Indolizidine and quinolizidine alkaloids". Natural Product Reports. 14 (6): 619–36. doi:10.1039/NP9971400619. PMID 9418297. 11. ^ Abdennebi EH, el Ouazzani N, Lamnaouer D (December 1998). "Clinical and analytical studies of sheep dosed with various preparations of Astragalus lusitanicus". Veterinary and Human Toxicology. 40 (6): 327–31. PMID 9830691. 12. ^ Ouazzani N, Lamnaouer D, Abdennebi EH (1999). "Toxicology of Astragalus lusitanicus Lam". Thérapie. 54 (6): 707–10. PMID 10709444. 13. ^ Les Tanner (August 2003). "Poisonous plant: Darling pea (Swainsona spp.)" (PDF). Northern Inland Weeds Advisory Committee. Archived from the original (PDF) on 2005-06-15. Retrieved 2009-05-11. 14. ^ "GRIN Genera of Fabaceae subtribe Astragalinae". Germplasm Resources Information Network. 2003. Archived from the original on 2008-10-15. Retrieved 2009-05-12. 15. ^ Carod-Artal FJ (2003). "[Neurological syndromes linked with the intake of plants and fungi containing a toxic component (I). Neurotoxic syndromes caused by the ingestion of plants, seeds and fruits]". Revista de Neurología (in Spanish). 36 (9): 860–71. PMID 12717675. Retrieved 2009-05-13. 16. ^ McLain-Romero J, Creamer R, Zepeda H, Strickland J, Bell G (July 2004). "The toxicosis of Embellisia fungi from locoweed (Oxytropis lambertii) is similar to locoweed toxicosis in rats". Journal of Animal Science. 82 (7): 2169–74. doi:10.2527/2004.8272169x. PMID 15309966. 17. ^ Croom WJ, Hagler WM, Froetschel MA, Johnson AD (May 1995). "The involvement of slaframine and swainsonine in slobbers syndrome: a review". Journal of Animal Science. 73 (5): 1499–1508. doi:10.2527/1995.7351499x. PMID 7665382. 18. ^ a b c Stegelmeier BL, James LF, Panter KE, Ralphs MH, Gardner DR, Molyneux RJ, Pfister JA (February 1999). "The pathogenesis and toxicokinetics of locoweed (Astragalus and Oxytropis spp.) poisoning in livestock". Journal of Natural Toxins. 8 (1): 35–45. PMID 10091126. 19. ^ Jones et al. (1997), page 31. 20. ^ "High-mountain Disease: Introduction". The Merck Veterinary Manual. 2008. Retrieved May 11, 2009. 21. ^ Stegelmeier BL, James LF, Gardner DR, Panter KE, Lee ST, Ralphs MH, Pfister JA, Spraker TR (September 2005). "Locoweed (Oxytropis sericea)-induced lesions in mule deer (Odocoileius hemionus)". Veterinary Pathology. 42 (5): 566–78. doi:10.1354/vp.42-5-566. PMID 16145203. 22. ^ Stegelmeier BL, Ralphs MH, Gardner DR, Molyneux RJ, James LF (October 1994). "Serum alpha-mannosidase activity and the clinicopathologic alterations of locoweed (Astragalus mollissimus) intoxication in range cattle". Journal of Veterinary Diagnostic Investigation. 6 (4): 473–9. doi:10.1177/104063879400600412. PMID 7858027. 23. ^ "ARS and New Mexico Scientists Take a Long Look at Livestock and Locoweed" by Ann Perry, June 21, 2010 Agricultural Research Service, accessed September 29, 2010 24. ^ Ralphs MH, Provenza FD (November 1999). "Conditioned food aversions: principles and practices, with special reference to social facilitation". Proceedings of the Nutrition Society. 58 (4): 813–20. doi:10.1017/S002966519900110X. PMID 10817148. 25. ^ a b Pfister JA, Stegelmeier BL, Cheney CD, Ralphs MH, Gardner DR (January 2002). "Conditioning taste aversions to locoweed (Oxytropis sericea) in horses". Journal of Animal Science. 80 (1): 79–83. doi:10.2527/2002.80179x. ISSN 0021-8812. PMID 11831531. Retrieved 2018-01-28. * Jones, T. C.; R. D. Hunt; N. W. King (1997). Veterinary pathology (6th ed.). Wiley-Blackwell. p. 1392. ISBN 9780683044812. * Keeler, R. F.; A. T. Tu, eds. (1983). Plant and fungal toxins. Marcel Dekker. p. 934. ISBN 978-0-8247-1893-0. ## External links[edit] Look up loco or weed in Wiktionary, the free dictionary. Look up locoweed in Wiktionary, the free dictionary. * White Locoweed - Kansas State University * Purple LocoWeed - Kansas State University * Purple Locoweed - United States Department of Agriculture * Locoweed - ARS/USDA * Astragalus species of locoweed - Utah State University * v * t * e * Poisoning * Toxicity * Overdose History of poison Inorganic Metals Toxic metals * Beryllium * Cadmium * Lead * Mercury * Nickel * Silver * Thallium * Tin Dietary minerals * Chromium * Cobalt * Copper * Iron * Manganese * Zinc Metalloids * Arsenic Nonmetals * Sulfuric acid * Selenium * Chlorine * Fluoride Organic Phosphorus * Pesticides * Aluminium phosphide * Organophosphates Nitrogen * Cyanide * Nicotine * Nitrogen dioxide poisoning CHO * alcohol * Ethanol * Ethylene glycol * Methanol * Carbon monoxide * Oxygen * Toluene Pharmaceutical Drug overdoses Nervous * Anticholinesterase * Aspirin * Barbiturates * Benzodiazepines * Cocaine * Lithium * Opioids * Paracetamol * Tricyclic antidepressants Cardiovascular * Digoxin * Dipyridamole Vitamin poisoning * Vitamin A * Vitamin D * Vitamin E * Megavitamin-B6 syndrome Biological1 Fish / seafood * Ciguatera * Haff disease * Ichthyoallyeinotoxism * Scombroid * Shellfish poisoning * Amnesic * Diarrhetic * Neurotoxic * Paralytic Other vertebrates * amphibian venom * Batrachotoxin * Bombesin * Bufotenin * Physalaemin * birds / quail * Coturnism * snake venom * Alpha-Bungarotoxin * Ancrod * Batroxobin Arthropods * Arthropod bites and stings * bee sting / bee venom * Apamin * Melittin * scorpion venom * Charybdotoxin * spider venom * Latrotoxin / Latrodectism * Loxoscelism * tick paralysis Plants / fungi * Cinchonism * Ergotism * Lathyrism * Locoism * Mushrooms * Strychnine 1 including venoms, toxins, foodborne illnesses. * Category * Commons * WikiProject [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Locoweed	c0275191	3,863	wikipedia	https://en.wikipedia.org/wiki/Locoweed	2021-01-18T18:47:41	{"umls": ["C0275191"], "wikidata": ["Q1128527"]}
For a general phenotypic description and a discussion of genetic heterogeneity of glioma, see GLM1 (137800). Mapping Working from the hypothesis that coinheritance of low-risk variants contributes to the 2-fold increased risk of glioma in relatives of individuals with primary brain tumors, Shete et al. (2009) conducted a metaanalysis of 2 glioma genomewide association studies by genotyping 550,000 tagged SNPs in a total of 1,878 cases and 3,670 controls, with validation in 3 additional independent series totaling 2,545 cases and 2,953 controls. The strongest association was achieved with the single-nucleotide polymorphism (SNP) rs4295627 (OR = 1.36, 95% CI 1.29-1.43, P = 2.34 x 10(-18)), which localizes to chromosome 8q24.21 in intron 3 of the CCDC26 gene (613040), a retinoic acid modulator of differentiation and death. In a 2-stage study using tag SNP genotyping and imputation, pooled next-generation sequencing using long-range PCR, and subsequent validation SNP genotyping and involving 1,657 cases and 1,301 controls, Jenkins et al. (2012) identified 7 low frequency SNPs at 8q24.21 that were strongly associated with glioma risk (p = 1 x 10(-25) to 1 x 10(-14)). The most strongly associated SNP, rs55705857G, remained highly significant after individual adjustment for the other top 6 SNPs and the 2 SNPs identified by Shete et al. (2009), rs4295627 and rs891835. After stratifying by histologic and tumor genetic subtype, the most significant associations of rs55705857 were with oligodendroglial tumors (OR = 6.3, p = 2.2 x 10(-28)) and gliomas with mutant IDH1 (147700) (OR = 5.1, p = 1.1 x 10(-31)) or IDH2 (147650) (OR = 4.8, p = 6.6 x 10(-22)). Strong associations were observed for astrocytomas with mutated IDH1 or IDH2 (grades 2-4) (OR = 5.16-6.66, p = 4.7 x 10(-12) to 2.2 x 10(-8)) but not for astrocytomas with wildtype IDH1 and IDH2. The conserved sequence block that includes rs55705857 is consistently modeled as a microRNA. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	GLIOMA SUSCEPTIBILITY 7	c0017638	3,864	omim	https://www.omim.org/entry/613032	2019-09-22T15:59:55	{"mesh": ["D005910"], "omim": ["613032"], "orphanet": ["182067"]}
"CTCL" redirects here. For the book by Loren Pope, see Colleges That Change Lives. Cutaneous T cell lymphoma Micrograph showing cutaneous T-cell lymphoma. H&E stain. SpecialtyHematology and oncology Cutaneous T cell lymphoma (CTCL) is a class of non-Hodgkin lymphoma, which is a type of cancer of the immune system. Unlike most non-Hodgkin lymphomas (which are generally B cell related), CTCL is caused by a mutation of T cells. The cancerous T cells in the body initially migrate to the skin, causing various lesions to appear. These lesions change shape as the disease progresses, typically beginning as what appears to be a rash which can be very itchy and eventually forming plaques and tumors before spreading to other parts of the body. ## Contents * 1 Signs and symptoms * 2 Cause * 3 Diagnosis * 3.1 Classification * 4 Treatment * 5 Epidemiology * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] The presentation depends if it is mycosis fungoides or Sézary syndrome, the most common, though not the only types. Among the symptoms for the aforementioned types are: enlarged lymph nodes, an enlarged liver and spleen, and non-specific dermatitis.[1] ## Cause[edit] The cause of CTCL is unknown. ## Diagnosis[edit] A point-based algorithm for the diagnosis for early forms of cutaneous T cell lymphoma was proposed by The International Society for Cutaneous Lymphomas in 2005.[2] ### Classification[edit] Cutaneous T-cell lymphoma may be divided into the several subtypes.[3]:727–740 Mycosis fungoides is the most common form of CTCL and is responsible for half of all cases.[4] A WHO-EORTC classification has been developed.[5][6] * Pagetoid reticulosis * Sézary syndrome * Granulomatous slack skin * Lymphomatoid papulosis * Pityriasis lichenoides chronica * Pityriasis lichenoides et varioliformis acuta * CD30+ cutaneous T-cell lymphoma * Secondary cutaneous CD30+ large cell lymphoma * Non-mycosis fungoides CD30− cutaneous large T-cell lymphoma * Pleomorphic T-cell lymphoma * Lennert lymphoma * Subcutaneous T-cell lymphoma * Angiocentric lymphoma * Blastic NK-cell lymphoma ## Treatment[edit] Romidepsin There is no cure for CTCL, but there are a variety of treatment options available and some CTCL patients are able to live normal lives with this cancer, although symptoms can be debilitating and painful, even in earlier stages. FDA approved treatments include the following:[7] * (1999) Denileukin diftitox (Ontak) * (2000) Bexarotene (Targretin) a retinoid * (2006) Vorinostat (Zolinza) a hydroxymate histone deacetylase (HDAC) inhibitor * (2009) Romidepsin (Istodax) a cyclic peptide histone deacetylase (HDAC) inhibitor * (2018) Poteligeo (mogamulizumab-kpkc) Histone deacetylase (HDAC) inhibitors are shown to have antiproliferative and cytotoxic properties against CTCL.[8]Other (off label) treatments include: * Topical and oral corticosteroids * Bexarotene (Targretin) gel and capsules * Carmustine (BCNU, a nitrosourea) * Mechlorethamine (Nitrogen Mustard) * Phototherapy (Broad & Narrow Band UVB or PUVA) * Local and Total Skin Electron Therapy (TSET) * Conventional Radiation Therapy * Photopheresis * Interferons * Alemtuzumab (Campath-1H) * Methotrexate * Pentostatin and other purine analogues (Fludarabine, 2-deoxychloroadenosine) * Liposomal doxorubicin (Doxil) * Gemcitabine (Gemzar) * Cyclophosphamide * Bone marrow / stem cells * Allogenic transplantation * Forodesine (Inhibits Purine Nucleoside phosphorylase) In 2010, the U.S. Food and Drug Administration granted orphan drug designation for a topical treatment for pruritus in cutaneous T-cell lymphoma to a pharmaceutical company called Elorac.[9] ## Epidemiology[edit] Of all cancers involving lymphocytes, 2% of cases are cutaneous T cell lymphomas.[10] CTCL is more common in men and in African-American people.[7] The incidence of CTCL in men is 1.6 times higher than in women.[7] There is some evidence of a relationship with human T-lymphotropic virus (HTLV) with the adult T-cell leukemia/lymphoma subtype.[7] No definitive link between any viral infection or environmental factor has been definitely shown with other CTCL subtypes.[7] ## See also[edit] * Cutaneous B-cell lymphoma * List of cutaneous conditions ## References[edit] 1. ^ "Cutaneous T-Cell Lymphoma: Practice Essentials, Background, Pathophysiology". 2016-06-02. Cite journal requires `\|journal=` (help) 2. ^ Pimpinelli, Nicola; Olsen, Elise A.; Santucci, Marco; Vonderheid, Eric; Haeffner, Andreas C.; Stevens, Seth; Burg, Guenter; Cerroni, Lorenzo; Dreno, Brigitte (December 2005). "Defining early mycosis fungoides" (PDF). Journal of the American Academy of Dermatology. 53 (6): 1053–1063. doi:10.1016/j.jaad.2005.08.057. hdl:2158/311708. PMID 16310068. 3. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. 4. ^ Sidiropoulos, KG; Martinez-Escala, ME; Yelamos, O; Guitart, J; Sidiropoulos, M (December 2015). "Primary cutaneous T-cell lymphomas: a review". Journal of Clinical Pathology (Review). 68 (12): 1003–10. doi:10.1136/jclinpath-2015-203133. PMID 26602417. 5. ^ Willemze, R.; Jaffe, ES.; Burg, G.; Cerroni, L.; Berti, E.; Swerdlow, SH.; Ralfkiaer, E.; Chimenti, S.; et al. (May 2005). "WHO-EORTC classification for cutaneous lymphomas". Blood. 105 (10): 3768–85. doi:10.1182/blood-2004-09-3502. hdl:2434/566817. PMID 15692063. 6. ^ Khamaysi, Z.; Ben-Arieh, Y.; Izhak, OB.; Epelbaum, R.; Dann, EJ.; Bergman, R. (Feb 2008). "The applicability of the new WHO-EORTC classification of primary cutaneous lymphomas to a single referral center". Am J Dermatopathol. 30 (1): 37–44. doi:10.1097/DAD.0b013e31815f9841. PMID 18212543. 7. ^ a b c d e Devata, S; Wilcox, RA (June 2016). "Cutaneous T-Cell Lymphoma: A Review with a Focus on Targeted Agents". American Journal of Clinical Dermatology (Review). 17 (3): 225–37. doi:10.1007/s40257-016-0177-5. PMID 26923912. 8. ^ Beigi, Pooya Khan Mohammad (2017). "Treatment". Clinician's Guide to Mycosis Fungoides. Springer International Publishing. pp. 23–34. doi:10.1007/978-3-319-47907-1_6. ISBN 9783319479064. 9. ^ Elorac, Inc. Announces Orphan Drug Designation for Novel Topical Treatment for Pruritus in Cutaneous T-cell Lymphoma (CTCL) Archived 2010-12-30 at the Wayback Machine website 10. ^ Turgeon, Mary Louise (2005). Clinical hematology: theory and procedures. Hagerstown, MD: Lippincott Williams & Wilkins. p. 283. ISBN 978-0-7817-5007-3. "Frequency of lymphoid neoplasms. (Source: Modified from WHO Blue Book on Tumour of Hematopoietic and Lymphoid Tissues. 2001, p. 2001.)" ## External links[edit] Classification D * ICD-10: C84.0, C84.1 * ICD-9-CM: 202.1, 202.2 * ICD-O: M9700/3, M9701/3 * MeSH: D016410 * DiseasesDB: 8595 External resources * eMedicine: med/3486 * DermNet dermal-infiltrative/cutaneous-t-cell-lymphoma * v * t * e Leukaemias, lymphomas and related disease B cell (lymphoma, leukemia) (most CD19 * CD20) By development/ marker TdT+ * ALL (Precursor B acute lymphoblastic leukemia/lymphoma) CD5+ * naive B cell (CLL/SLL) * mantle zone (Mantle cell) CD22+ * Prolymphocytic * CD11c+ (Hairy cell leukemia) CD79a+ * germinal center/follicular B cell (Follicular * Burkitt's * GCB DLBCL * Primary cutaneous follicle center lymphoma) * marginal zone/marginal zone B-cell (Splenic marginal zone * MALT * Nodal marginal zone * Primary cutaneous marginal zone lymphoma) RS (CD15+, CD30+) * Classic Hodgkin lymphoma (Nodular sclerosis) * CD20+ (Nodular lymphocyte predominant Hodgkin lymphoma) PCDs/PP (CD38+/CD138+) * see immunoproliferative immunoglobulin disorders By infection * KSHV (Primary effusion) * EBV * Lymphomatoid granulomatosis * Post-transplant lymphoproliferative disorder * Classic Hodgkin lymphoma * Burkitt's lymphoma * HCV * Splenic marginal zone lymphoma * HIV (AIDS-related lymphoma) * Helicobacter pylori (MALT lymphoma) Cutaneous * Diffuse large B-cell lymphoma * Intravascular large B-cell lymphoma * Primary cutaneous marginal zone lymphoma * Primary cutaneous immunocytoma * Plasmacytoma * Plasmacytosis * Primary cutaneous follicle center lymphoma T/NK T cell (lymphoma, leukemia) (most CD3 * CD4 * CD8) By development/ marker * TdT+: ALL (Precursor T acute lymphoblastic leukemia/lymphoma) * prolymphocyte (Prolymphocytic) * CD30+ (Anaplastic large-cell lymphoma * Lymphomatoid papulosis type A) Cutaneous MF+variants * indolent: Mycosis fungoides * Pagetoid reticulosis * Granulomatous slack skin aggressive: Sézary disease * Adult T-cell leukemia/lymphoma Non-MF * CD30-: Non-mycosis fungoides CD30− cutaneous large T-cell lymphoma * Pleomorphic T-cell lymphoma * Lymphomatoid papulosis type B * CD30+: CD30+ cutaneous T-cell lymphoma * Secondary cutaneous CD30+ large-cell lymphoma * Lymphomatoid papulosis type A Other peripheral * Hepatosplenic * Angioimmunoblastic * Enteropathy-associated T-cell lymphoma * Peripheral T-cell lymphoma not otherwise specified (Lennert lymphoma) * Subcutaneous T-cell lymphoma By infection * HTLV-1 (Adult T-cell leukemia/lymphoma) NK cell/ (most CD56) * Aggressive NK-cell leukemia * Blastic NK cell lymphoma T or NK * EBV (Extranodal NK-T-cell lymphoma/Angiocentric lymphoma) * Large granular lymphocytic leukemia Lymphoid+ myeloid * Acute biphenotypic leukaemia Lymphocytosis * Lymphoproliferative disorders (X-linked lymphoproliferative disease * Autoimmune lymphoproliferative syndrome) * Leukemoid reaction * Diffuse infiltrative lymphocytosis syndrome Cutaneous lymphoid hyperplasia * Cutaneous lymphoid hyperplasia * with bandlike and perivascular patterns * with nodular pattern * Jessner lymphocytic infiltrate of the skin General * Hematological malignancy * leukemia * Lymphoproliferative disorders * Lymphoid leukemias * v * t * e Medicine Specialties and subspecialties Surgery * Cardiac surgery * Cardiothoracic surgery * Colorectal surgery * Eye surgery * General surgery * Neurosurgery * Oral and maxillofacial surgery * Orthopedic surgery * Hand surgery * Otolaryngology * ENT * Pediatric surgery * Plastic surgery * Reproductive surgery * Surgical oncology * Transplant surgery * Trauma surgery * Urology * Andrology * Vascular surgery Internal medicine * Allergy / Immunology * Angiology * Cardiology * Endocrinology * Gastroenterology * Hepatology * Geriatrics * Hematology * Hospital medicine * Infectious disease * Nephrology * Oncology * Pulmonology * Rheumatology Obstetrics and gynaecology * Gynaecology * Gynecologic oncology * Maternal–fetal medicine * Obstetrics 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Medical school * Bachelor of Medicine, Bachelor of Surgery * Bachelor of Medical Sciences * Master of Medicine * Master of Surgery * Doctor of Medicine * Doctor of Osteopathic Medicine * MD–PhD Related topics * Alternative medicine * Allied health * Dentistry * Podiatry * Pharmacy * Physiotherapy * Molecular oncology * Nanomedicine * Personalized medicine * Public health * Rural health * Therapy * Traditional medicine * Veterinary medicine * Physician * Chief physician * History of medicine * Book * Category * Commons * Wikiproject * Portal * Outline [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Cutaneous T cell lymphoma	c0079773	3,865	wikipedia	https://en.wikipedia.org/wiki/Cutaneous_T_cell_lymphoma	2021-01-18T19:09:02	{"gard": ["6226"], "mesh": ["D016410"], "umls": ["C0079773"], "icd-9": ["202.1", "202.2"], "icd-10": ["C84.8", "C84.1", "C84.0"], "orphanet": ["171901"], "wikidata": ["Q5196687"]}
A rare multiple congenital anomalies/dysmorphic syndrome characterized by the association of congenital hypoparathyroidism, nephropathy, congenital lymphedema, mitral valve prolapse and brachytelephalangy. Additional features include mild facial dysmorphism, hyperthricoses, and nail abnormalities. There have been no further descriptions in the literature since 1993. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Dahlberg-Borer-Newcomer syndrome	c1855477	3,866	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1563	2021-01-23T19:03:48	{"gard": ["237"], "mesh": ["C535769"], "omim": ["247410"], "umls": ["C1855477"], "icd-10": ["Q87.8"], "synonyms": ["Dahlberg syndrome", "Lymphedema-hypoparathyroidism syndrome"]}
Roseola vaccinia SpecialtyDermatology Roseola vaccinia is a cutaneous condition characterized by a prominent rim of erythema surrounding the site of vaccinia injection.[1]:393 ## See also[edit] * Vaccinia * Skin lesion ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. * v * t * e Skin infections, symptoms and signs related to viruses DNA virus Herpesviridae Alpha HSV * Herpes simplex * Herpetic whitlow * Herpes gladiatorum * Herpes simplex keratitis * Herpetic sycosis * Neonatal herpes simplex * Herpes genitalis * Herpes labialis * Eczema herpeticum * Herpetiform esophagitis Herpes B virus * B virus infection VZV * Chickenpox * Herpes zoster * Herpes zoster oticus * Ophthalmic zoster * Disseminated herpes zoster * Zoster-associated pain * Modified varicella-like syndrome Beta * Human herpesvirus 6/Roseolovirus * Exanthema subitum * Roseola vaccinia * Cytomegalic inclusion disease Gamma * KSHV * Kaposi's sarcoma Poxviridae Ortho * Variola * Smallpox * Alastrim * MoxV * Monkeypox * CPXV * Cowpox * VV * Vaccinia * Generalized vaccinia * Eczema vaccinatum * Progressive vaccinia * Buffalopox Para * Farmyard pox: Milker's nodule * Bovine papular stomatitis * Pseudocowpox * Orf * Sealpox Other * Yatapoxvirus: Tanapox * Yaba monkey tumor virus * MCV * Molluscum contagiosum Papillomaviridae HPV * Wart/plantar wart * Heck's disease * Genital wart * giant * Laryngeal papillomatosis * Butcher's wart * Bowenoid papulosis * Epidermodysplasia verruciformis * Verruca plana * Pigmented wart * Verrucae palmares et plantares * BPV * Equine sarcoid Parvoviridae * Parvovirus B19 * Erythema infectiosum * Reticulocytopenia * Papular purpuric gloves and socks syndrome Polyomaviridae * Merkel cell polyomavirus * Merkel cell carcinoma RNA virus Paramyxoviridae * MeV * Measles Togaviridae * Rubella virus * Rubella * Congenital rubella syndrome ("German measles" ) * Alphavirus infection * Chikungunya fever Picornaviridae * CAV * Hand, foot, and mouth disease * Herpangina * FMDV * Foot-and-mouth disease * Boston exanthem disease Ungrouped * Asymmetric periflexural exanthem of childhood * Post-vaccination follicular eruption * Lipschütz ulcer * Eruptive pseudoangiomatosis * Viral-associated trichodysplasia * Gianotti–Crosti syndrome This infection-related cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Roseola vaccinia	None	3,867	wikipedia	https://en.wikipedia.org/wiki/Roseola_vaccinia	2021-01-18T18:39:55	{"wikidata": ["Q7368625"]}
Hypertelorism-microtia-facial clefting syndrome, or HMC syndrome, is a very rare syndrome characterized by the combination of hypertelorism, cleft lip and palate and microtia. ## Epidemiology Nine cases have been reported in the literature in seven families. ## Clinical description Some patients have associated cardiac or renal congenital malformations. Short stature and intellectual deficiency are common. ## Antenatal diagnosis Antenatal diagnosis is possible by ultrasonographic monitoring. ## Genetic counseling The reported cases support autosomal recessive inheritance. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Hypertelorism-microtia-facial clefting syndrome	c0220742	3,868	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2213	2021-01-23T18:50:28	{"gard": ["897"], "mesh": ["C537632"], "omim": ["239800"], "umls": ["C0220742"], "icd-10": ["Q87.0"], "synonyms": ["Bixler-Christian-Gorlin syndrome", "HMC syndrome"]}
A rare syndromic trigonocephaly characterized by marked malformations of the head and face (essentially acrocephaly), broad depressed nasal bridge, narrow maxillae, abnormalities of the hands and feet (polydactyly, brachydactyly, syndactyly, clinodactyly, camptodactyly, ulnar deviation), obesity and congenital heart disease. This disease is considered a variant of Carpenter syndrome without intellectual disability. There have been no further descriptions in the literature since 1992. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Goodman syndrome	c0265303	3,869	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=65798	2021-01-23T18:52:47	{"gard": ["2549"], "mesh": ["C537287"], "omim": ["201020"], "umls": ["C0265303"], "icd-10": ["Q87.0"], "synonyms": ["ACPS4", "Acrocephalopolysyndactyly type 4"]}
Epidermolysis bullosa simplex due to BP230 deficiency is a rare, hereditary, basal epidermolysis bullosa simplex characterized by mild, predominantly acral, trauma-induced skin fragility, resulting in blisters. Blisters mostly affect the feet, including the dorsal side, and are often several centimetres big. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Epidermolysis bullosa simplex due to BP230 deficiency	c3809470	3,870	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=412181	2021-01-23T19:02:56	{"omim": ["615425"], "icd-10": ["Q81.0"], "synonyms": ["DST-related epidermolysis bullosa simplex", "EBS-AR BP230"]}
Congenital cataract-progressive muscular hypotonia-hearing loss-developmental delay syndrome is a rare, genetic, mitochondrial myopathy disorder characterized by congenital cataract, progressive muscular hypotonia that particularly affects the lower limbs, reduced deep tendon reflexes, sensorineural hearing loss, global development delay and lactic acidosis. Muscle biopsy reveals reduced complex I, II and IV respiratory chain activity. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Congenital cataract-progressive muscular hypotonia-hearing loss-developmental delay syndrome	c2751320	3,871	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=330054	2021-01-23T17:09:54	{"gard": ["10522"], "mesh": ["C567769"], "omim": ["613076"], "umls": ["C2751320"], "icd-10": ["G71.3"], "synonyms": ["Congenital cataract-progressive muscular hypotonia-deafness-developmental delay syndrome"]}
A rare form of chronic cutaneous lupus erythematosus characterized by erythematous, scaly papules and plaques preferentially occurring on sun-exposed skin areas (scalp, face, and ears) and exhibiting follicular plugging, pigmentary changes, and central atrophy, scarring, and telangiectasia. Skin biopsy shows a perivascular and periadnexal lymphocytic infiltrate and involvement of the dermoepidermal junction with thickening of the basement membrane and vacuolar degeneration of the basal cells. A small percentage of patients may develop systemic lupus erythematosus. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Discoid lupus erythematosus	c0024138	3,872	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=90281	2021-01-23T18:31:32	{"mesh": ["D008179"], "umls": ["C0024138"], "icd-10": ["L93.0"]}
A rare, syndromic, benign, epidemal nevus syndrome characterized by the association of a Becker nevus (i.e. circumscribed, unilateral, irregularly shaped, hyperpigmented macules, with or without hypertrichosis and/or acneiform lesions, occuring predominantly on the anterior upper trunk or scapular region) with ipsilateral breast hypoplasia or other, typically hypoplastic, skeletal, cutaneous, and/or muscular defects, such as pectoralis major hypoplasia, supernumerary nipples, vertebral defects, scoliosis, limb asymmetry, odontomaxillary hypoplasia and lipoatrophy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Becker nevus syndrome	c0263579	3,873	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=64755	2021-01-23T19:05:35	{"gard": ["3856", "5901"], "omim": ["604919"], "umls": ["C0263579", "C1858042"], "icd-10": ["D22.5"], "synonyms": ["Pigmentary hairy epidermal nevus"]}
A number sign (#) is used with this entry because of evidence that pain sensitivity quantitative trait locus-1 (PAINQTL1) is caused by a contiguous gene deletion on chromosome 1p33 affecting the FAAHP1 gene (618375). The pain insensitivity phenotype can be modified by the simultaneous presence of a polymorphism in the FAAH gene (602935), also on chromosome 1p33. One such family has been reported. Clinical Features Habib et al. (2019) reported a 66-year-old Caucasian woman with a lifelong history of insensitivity to pain, even after surgery, including hip replacement and shoulder surgery for osteoarthritis. She did not require analgesia for varicose vein and dental procedures and reported numerous burns and cuts without pain, which she stated healed quickly with little or no residual scarring. She could tolerate eating hot peppers with a short-lasting 'pleasant glow' in her mouth, but no discomfort. She described sweating normally in warm conditions. She also scored very low on tests for anxiety and reported never panicking in dangerous or fearful situations, although she had a long history of short memory lapses, such as forgetting words or location of keys. Physical examination showed multiple scars on the arms and on the back of her hands, and sensory testing demonstrated hyposensitivity to noxious heat in the hands and feet. Family history revealed that her deceased father had little requirement for pain killers; her son also reported some degree of pain insensitivity, but not to the same extent as the proband. The proband's mother and daughter appeared to perceive pain normally. Inheritance The transmission pattern of PAINQTL1 in the family reported by Habib et al. (2019) was consistent with autosomal dominant inheritance. Molecular Genetics In a 66-year-old Caucasian woman with pain insensitivity and a nonanxious disposition, Habib et al. (2019) identified an approximately 8-kb heterozygous microdeletion on chromosome 1, about 4.7 kb downstream of the 3-prime end of the FAAH gene. Molecular cloning identified novel 5-prime exons of an expressed FAAH pseudogene, termed FAAHP1 (FAAH-OUT), that mapped within the microdeletion. The microdeletion removed the promoter and first 2 exons of the FAAHP1 gene. The authors noted that the deleted region is flanked by ALU sequences, which may predispose it to deletion by unequal crossing over. The affected woman also carried a heterozygous hypomorphic polymorphism in the FAAH gene (P129T; 602935.0001) that reduces FAAH enzyme activity. The patient's son, who exhibited some pain insensitivity, carried the microdeletion but not the hypomorphic FAAH allele. The woman's unaffected mother and daughter did not carry the microdeletion, but both carried the FAAH polymorphism in heterozygous state. The proband had approximately triple the levels of various circulating fatty acid amides normally degraded by FAAH compared with controls who were either homozygous wildtype or heterozygous for the hypomorphic FAAH allele. The authors proposed that the microdeletion affects FAAH function either by removing a regulatory element for FAAH or by reducing expression of FAAH-OUT, which may regulate FAAH epigenetically or function as a microRNA decoy for FAAH. One Colombian male sequenced in the 1000 Genomes Project carried a similar microdeletion, but his pain sensitivity was unknown, and he was homozygous wildtype for the FAAH allele. The case provided new insights into the role of the endocannabinoid system in analgesia. INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Insensitivity to pain Behavioral Psychiatric Manifestations \- Non-anxious disposition \- Short memory lapses LABORATORY ABNORMALITIES \- Increased levels of circulating fatty acid amides MISCELLANEOUS \- Decreased need for analgesia during surgery \- Frequent painless injuries \- The phenotype can be modified by presence of a polymorphism in the FAAH gene ( 602935.0001 ) \- One family has been reported (last curated March 2019) MOLECULAR BASIS \- Caused by deletion affecting the fatty acid amine hydrolase pseudogene 1 gene (FAAHP1, 618375 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	PAIN SENSITIVITY QUANTITATIVE TRAIT LOCUS 1	c0344307	3,874	omim	https://www.omim.org/entry/618377	2019-09-22T15:42:13	{"omim": ["618377"], "synonyms": ["Alternative titles", "INSENSITIVITY TO PAIN"]}
CADDS is a rare, genetic, neurometabolic disease characterized by severe intrauterine growth retardation, failure to thrive, profound neonatal hypotonia, severe global development delay, elevated very long chain fatty acids in plasma, and neonatal cholestasis leading to hepatic failure and death. Other features include ocular abnormalities (e.g. blindness and cataracts), sensorineural deafness, seizures, and abnormal brain morphology (notably delayed CNS myelination and ventriculomegaly). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	CADDS	c1845408	3,875	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=369942	2021-01-23T19:00:58	{"gard": ["12472"], "mesh": ["C564508"], "omim": ["300475"], "umls": ["C1845408"], "icd-10": ["Q87.8"], "synonyms": ["Contiguous ABCD1 DXS1357E deletion syndrome", "Zellweger-like contiguous gene deletion syndrome"]}
This article has multiple issues. Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages) This article includes a list of references, related reading or external links, but its sources remain unclear because it lacks inline citations. Please help to improve this article by introducing more precise citations. (July 2018) (Learn how and when to remove this template message) This article needs more links to other articles to help integrate it into the encyclopedia. Please help improve this article by adding links that are relevant to the context within the existing text. (February 2017) (Learn how and when to remove this template message) (Learn how and when to remove this template message) Monostotic fibrous dysplasia Other namesMonostotic osteitis fibrosa SpecialtyRheumatology Monostotic fibrous dysplasia is a form of fibrous dysplasia where only one bone is involved. It comprises a majority of the cases of fibrous dysplasia (approximately 70–80%).[1] It is a rare bone disease characterized by the replacement of normal elements of the bone by fibrous connective tissue,[2] which can cause very painful swellings and bone deformities, and make bone abnormally fragile and prone to fracture.[3] A congenital, noninherited, benign anomaly of bone development in a single bone, it consists of the replacement of normal marrow and cancellous bone by immature bone with fibrous stroma. Monostotic fibrous dysplasia occurs with equal frequency in both sexes and normally develops early in life, with lesions frequently identified late in the first and early second decades. Most patients are asymptomatic, with the diagnosis often established after an incidental finding or with pain, swelling, or fracture. Lesions usually enlarge in proportion to skeletal growth and the abnormal replacement remain active only until skeletal maturity.[4] Monostotic fibrous dysplasia does not convert into the polyostotic type. When symptoms are present, they often are nonspecific, including pain, swelling, or pathologic fracture.[5] It most often affects the ribs (28%), proximal femur (23%), tibia, craniofacial bones (10-25%) and humerus (10-25%).[6] ## See also[edit] * Polyostotic fibrous dysplasia ## References[edit] 1. ^ Alves, Raphael Vicente; Souza, Anderson Rodrigo; Silva, Alessandra dos Santos; Cardim, Vera Lúcia Nocchi; Godoy, Roberto (September 2009). "Co-existing fibrous dysplasia and meningothelial meningioma". Arquivos de Neuro-Psiquiatria. 67 (3): 699–700. doi:10.1590/S0004-282X2009000400025. ISSN 1678-4227. 2. ^ Pereira, J. C. O.; Filho, R. C. L.; Silva, F. B. C.; Ruela, K. P. (2009). "Fibrous Dysplasia of Maxillary Sinus". Int. Arch. Otorhinolaryngol. 13 (2): 214–217. 3. ^ Singer, Frederick. "Fibrous Dysplasia". rarediseases.org. NORD (National Organization for Rare Disorders). Retrieved 29 November 2020. 4. ^ DiCaprio, Matthew R.; Enneking, William F. (August 2005). "Fibrous dysplasia. Pathophysiology, evaluation, and treatment". The Journal of Bone and Joint Surgery. American Volume. 87 (8): 1848–1864. ISSN 0021-9355. 5. ^ A. Mark Davies; Murali Sundaram; Steven L. J. James, eds. (2009). Imaging of Bone Tumors and Tumor-Like Lesions. Medical Radiology. Berlin, Heidelberg: Springer Berlin Heidelberg. p. 412. ISBN 978-3-540-77982-7. Retrieved 2020-11-29. 6. ^ Singh, Gagandeep. "Fibrous dysplasia \| Radiology Reference Article \| Radiopaedia.org". Radiopaedia. ## External links[edit] Classification D * ICD-10: M85.0 * ICD-9-CM: 733.29 * MeSH: D005358 * DiseasesDB: 32262 External resources * Orphanet: 93277 * v * t * e Bone and joint disease Bone Inflammation endocrine: * Osteitis fibrosa cystica * Brown tumor infection: * Osteomyelitis * Sequestrum * Involucrum * Sesamoiditis * Brodie abscess * Periostitis * Vertebral osteomyelitis Metabolic * Bone density * Osteoporosis * Juvenile * Osteopenia * Osteomalacia * Paget's disease of bone * Hypophosphatasia Bone resorption * Osteolysis * Hajdu–Cheney syndrome * Ainhum * Gorham's disease Other * Ischaemia * Avascular necrosis * Osteonecrosis of the jaw * Complex regional pain syndrome * Hypertrophic pulmonary osteoarthropathy * Nonossifying fibroma * Pseudarthrosis * Stress fracture * Fibrous dysplasia * Monostotic * Polyostotic * Skeletal fluorosis * bone cyst * Aneurysmal bone cyst * Hyperostosis * Infantile cortical hyperostosis * Osteosclerosis * Melorheostosis * Pycnodysostosis Joint Chondritis * Relapsing polychondritis Other * Tietze's syndrome Combined Osteochondritis * Osteochondritis dissecans Child leg: * hip * Legg–Calvé–Perthes syndrome * tibia * Osgood–Schlatter disease * Blount's disease * foot * Köhler disease * Sever's disease spine * * Scheuermann's_disease arm: * wrist * Kienböck's disease * elbow * Panner disease This article about a disease of musculoskeletal and connective tissue is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Monostotic fibrous dysplasia	c0016064	3,876	wikipedia	https://en.wikipedia.org/wiki/Monostotic_fibrous_dysplasia	2021-01-18T19:09:10	{"mesh": ["D005358"], "umls": ["C0016064"], "icd-9": ["733.29"], "icd-10": ["M85.0"], "orphanet": ["93277"], "wikidata": ["Q6901991"]}
## Clinical Features Ouvrier and Billson (1988), followed by Ahn et al. (1989), Deonna et al. (1990) and Echenne and Rivier (1992), described a 'new' paroxysmal disorder of childhood, the main features of which are bouts of tonic upward deviation of the eyes associated with ataxia. Long-term outcome is favorable, with no apparent neurologic sequelae. None of the reported patients had an underlying CNS lesion that could have caused the disease. The brain of one of the children who died accidentally was normal on examination (Ouvrier and Billson, 1988). Campistol et al. (1993) suggested that this is a familial disorder. They described a father-son and a mother-son combination; in a third family, the mother of the male proband had generalized epilepsy beginning at the age of 18 years. Campistol et al. (1993) pictured a 12-month-old infant during an episode of tonic upgaze accompanied by compensatory forward bending of the neck. The patients showed gross motor clumsiness and delayed acquisition of independent walking. Campistol et al. (1993) found that levodopa was beneficial. Inheritance Campistol et al. (1993) suggested that benign paroxysmal tonic upgaze of childhood with ataxia may be an autosomal dominant disorder. Misc \- Response to levodopa Neuro \- Episodic tonic upward deviation of eyes \- Episodic ataxia \- Clumsiness \- Delayed walking Neck \- Forward neck bending Inheritance \- Autosomal dominant ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	PAROXYSMAL TONIC UPGAZE, BENIGN CHILDHOOD, WITH ATAXIA	c1868576	3,877	omim	https://www.omim.org/entry/168885	2019-09-22T16:36:31	{"mesh": ["C566817"], "omim": ["168885"], "orphanet": ["1179"]}
Holmes tremor, first identified by Gordon Holmes in 1904, can be described as a wing-beating movement localized in the upper body that is caused by cerebellar damage.[1] Holmes tremor is a combination of rest, action, and postural tremors. Tremor frequency ranges from 2 to 5 Hertz and is aggravated with posture and movement.[1] It may arise from various underlying structural disorders including stroke, tumors, trauma, and other cerebellar lesions.[2] Because Holmes tremor is rare, much of the research is based on individual cases. The formation of tremors is due to two main factors: the over-excited rhythmic movement of neuronal loops and permanent structural changes from neurodegeneration. Two major neuronal networks, the corticostriatothalamocortical hap and the inferior olivary nucleus (ION) specifically target the development of the tremors.[1] When diagnosing a patient with Holmes tremor, one must look at the neurological signs and symptoms, as well as the possibility that the tremor is caused by medications or other stimulants. In most cases, the patient's history and a targeted neurological examination is enough to give a diagnosis. Treatment for Holmes tremor is dependent on the characteristics of the tremor. Because the disease is involved with the dopaminergic system, most treatments involve levodopa.[1] Drugs used to treat other types of tremors are applicable to the treatment of Holmes tremor; however, these drugs have a low success rate.[3] ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Risk factors * 2.2 Triggers * 2.3 Genetics/Genome * 3 Mechanism * 4 Diagnosis * 5 Treatment * 6 References * 7 Further reading ## Signs and symptoms[edit] Holmes tremor is typically characterized by a low frequency tremor (below 4.5 Hz) that has a repeated series of rest and intention tremors.[1] These tremors move slowly and are generally specific to an upper area of the body. They can consist of postural tremors in nearby muscles as well. These tremors involve uncontrollable shaking despite efforts to be still.[1] Holmes tremor is considered a rest-intention posture tremor. These irregular movements occur while muscles are at rest, but worsen during voluntary muscle contractions.[1] Symptoms usually appear delayed one to twenty-four months after the lesion is created.[1] ## Causes[edit] ### Risk factors[edit] Risk factors for Holmes tremor include excess exposure to heavy metals, such as mercury and lead, as well as an increased intake of various drugs and toxins.[1] Researchers found that raising the dose of antidepressants or neuroleptics elevate the risk for developing Holmes tremor.[1] Increasing intake of coffee, tea, or other stimulants can also cause for greater risk of development. Tremors depend on dosage and amount of exposure to these factors and will typically decrease dramatically if the intake is reduced. Hyperthyroidism and hyperglycemia also increase the likelihood of developing Holmes tremor.[1] ### Triggers[edit] Similar to the causes of most tremors, Holmes tremor is triggered by lesion damage to a circuit controlling a physiological task such as precision movements, motor learning, the control of muscle groups, etc. Holmes tremor specifically occurs as a delayed reaction to lesion damage of the dopaminergic and cerebellothalamic systems.[1] The most common cause of this lesion damage is brainstem stroke and trauma. The lesion damage to the dopamine pathways is associated with the neurological signs and symptoms.[1] ### Genetics/Genome[edit] Because brainstem stroke and lesions are typically the causes of Holmes tremor, there is little research supporting a genetic factor to the disease. However, one could be more susceptible to developing Holmes tremor if there is a familial history of stroke, substance abuse, or other disorders that increase risk.[2] ## Mechanism[edit] The pathophysiology of a tremor is not completely understood, but what is understood can be explained by two principles. First, the complete absence of structural changes in the neuronal loops results in hyperexcitability and rhythmic movement.[1] Second, is the permanent structural neurodegeneration. The corticostriatothalamocortical hap is a neuronal network that is associated with the integration of different muscle groups. It activates complex movement programs and guarantees continuous movement that cannot be terminated by small external influences. Another important circuit involving Holmes tremor is the Guillain-Mollaret Triangle, which includes the red nucleus, the inferior olivary nucleus (ION), and the dentate nucleus.[1] This circuit controls voluntary precision movements. The ION is the most important of these components in the formation of tremors.[1] In normal/healthy individuals' ION neurons, calcium channels regulate normal oscillatory depolarizations. This pacemaker affects processing and coordination of cerebellar precision movements and motor learning. Damages, both physical and chemical, to the ION affects the Guillain-Mollaret Triangle and leads to tremors. ## Diagnosis[edit] The physical characteristics of the tremor and the history of the patient will contribute to the diagnosis of Holmes tremor. A doctor will determine if the tremor is present during rest or voluntary muscle contraction and the frequency of the tremor. A Holmes tremor is generally made worse upon standing and upon intentional movements. Also, a Holmes tremor is not as rhythmic as other tremors.[3] To confirm the diagnosis of a Holmes tremor, a doctor will usually perform ancillary examinations. This includes measuring serum thyroid stimulating hormone levels to ensure the thyroid is functioning normally.[3] This rules out the possibility hyperthyroidism is causing a different type of tremor. An MRI can also be performed to look for structural lesions in areas such as the thalamus, midbrain tegmentum, and substantia nigra.[3] ## Treatment[edit] Treatment of a Holmes tremor can fail or is delayed because there are only a few diagnostic tools available. The treatment of choice is complete removal of the tumor.[2] Removing the tumor can result in elimination or better control of the tremors.[2] Other treatment options involve coping strategies such as avoiding movements or actions that worsen tremors.[1] Patients suffering from Holmes tremors can also benefit from using larger utensil handles and wrist weights.[1] There are also some pharmacological treatments, but they are not very effective.[1] ## References[edit] 1. ^ a b c d e f g h i j k l m n o p q r s Puschmann, A; Wszolek, ZK (2011). "Diagnosis and Treatment of Common Forms of Tremor" (PDF). Seminars in Neurology. 31 (1): 65–77. doi:10.1055/s-0031-1271312. PMC 3907068. PMID 21321834. 2. ^ a b c d Menon, B; Sasikala, P; Agrawal, A (2014). "Giant Middle Fossa Epidermoid Presenting as Holmes' tremor Syndrome". Journal of Movement Disorders. 7 (1): 22–24. doi:10.14802/jmd.14005. PMC 4051724. PMID 24926407. 3. ^ a b c d Buijink, A; Contarino, M; Koelman, J; Speelman, J; van Rootselaar, A (2012). "How to Tackle Tremor – Systematic Review of the Literature and Diagnostic Work-Up". Frontiers in Neurology. 3 (146): 146. doi:10.3389/fneur.2012.00146. PMC 3478569. PMID 23109928. ## Further reading[edit] * Brittain, John-Stuart; Ned Jenkinson; Petter Holland; Raed A Joundi; Alex L Green; Tipu Aziz (2011). "Development of Holmes' tremor following hemi-cerebellar infarction". Movement Disorders. 26 (10): 1957–1959. doi:10.1002/mds.23704. PMID 21542020. * Kim, M C; B C Son; Y Miyagi; J-K Kang (2002). "Vim thalamotomy for Holmes' tremor secondary to midbrain tumor". Journal of Neurology, Neurosurgery & Psychiatry. 73 (4): 453–455. doi:10.1136/jnnp.73.4.453. PMC 1738060. PMID 12235320. * Sheppard, Gordon M G; Erik Tauboll; Soren Jacob Bakke; Rolf Nyberg-Hansen (1997). "Midbrain Tremor and Hypertrophic Olivery Degeneration After Pontine Hemorrhage". Movement Disorders. 12 (3): 432–437. doi:10.1002/mds.870120327. PMID 9159743. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Holmes tremor	c0750940	3,878	wikipedia	https://en.wikipedia.org/wiki/Holmes_tremor	2021-01-18T18:38:04	{"mesh": ["D001259"], "wikidata": ["Q5883653"]}
Generalized basaloid follicular hamartoma syndrome is a rare, genetic skin disease characterized by multiple milium-like, comedone-like lesions and skin-colored to hyperpigmented, 1 to 2 mm-sized papules, associated with hypotrichosis and palmar/plantar pits. Lesions are usually first noticed on cheeks or neck and gradually increase in size and number to involve the scalp, face, ears, shoulders, chest, axillas, and upper arms. In severe cases, lower back, lower arms, and back of the legs can be involved. Mild hypohidrosis has also been reported. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Generalized basaloid follicular hamartoma syndrome	c1853919	3,879	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=168632	2021-01-23T18:54:42	{"mesh": ["C565284"], "omim": ["605827"], "umls": ["C1853919"], "icd-10": ["Q82.5"]}
A man urinating while cycling in the 1989 Race Across America Athletic incontinence (athletic leakage, athletic leaks, exercise-induced urinary incontinence) is the specific form of urinary incontinence that results from engaging in high-impact or strenuous activities. Unlike stress incontinence, which is defined as the loss of small amounts of urine associated with sneezing, laughing or exercising, athletic incontinence occurs exclusively during exercise.[1] Athletic incontinence is generally thought to be the result of decreased structural support of the pelvic floor due to increased abdominal pressure during high-impact exercise. As such exercises that build and develop the pelvic floor may be an important step to counteracting athletic incontinence.[2] In addition to high-impact exercise, this weakening can also stem from childbirth and age.[3] ## Prevalence[edit] Studies have shown that 30 percent to 40 percent of all women deal with athletic incontinence, with some studies reporting up to 69 percent of women as sufferers.[1][3][4] Athletes in high impact sports such as gymnastics and basketball are likely to suffer from incontinence, with over 60 percent of subjects in each sport reporting they suffer from athletic leaks during activity.[5] Rarely do sufferers of athletic incontinence seek treatment, with one study showing that over 95 percent of subjects had not sought professional advice on their condition.[6] Those who participated in the study claimed they didn’t seek help because they were embarrassed or thought it was a normal condition. ## See also[edit] * Treatment of urinary incontinence ## References[edit] 1. ^ a b Barten, Kelly (December 21, 2009). "Exercise-induced urinary incontinence (leaking urine while running) - it's more common than you think, and treatable". blog.oregonlive.com. Retrieved January 2, 2014. 2. ^ Bø, K (2004). "Urinary incontinence, pelvic floor dysfunction, exercise and sport". Sports Medicine. 34 (7): 451–64. doi:10.2165/00007256-200434070-00004. PMID 15233598. 3. ^ a b Robbins, Laura (December 21, 2009). "Stress Urinary Incontinence in the Female Athlete". blog.oregonlive.com/. Retrieved January 2, 2014. 4. ^ Krucoff, Carol (August 30, 1999). "Fitness : The Bane of Female Athletes Too, Incontinence Can Be Treated". Los Angeles Times. 5. ^ Nygaard IE, Thompson FL, Svengalis SL, Albright JP (September 1994). "Urinary incontinence in elite nulliparous athletes". Obstet Gynecol. 84 (3): 183–7. PMID 8041527. 6. ^ Phillips, Allan (January 17, 2013). "Pelvic Floor Dysfuction, Urinary Incontinence, and Female Athletes". pikeathletics.com. Retrieved January 2, 2014. * v * t * e Symptoms and signs relating to the urinary system Pain * Dysuria * Renal colic * Costovertebral angle tenderness * Vesical tenesmus Control * Urinary incontinence * Enuresis * Diurnal enuresis * Giggling * Nocturnal enuresis * Post-void dribbling * Stress * Urge * Overflow * Urinary retention Volume * Oliguria * Anuria * Polyuria Other * Lower urinary tract symptoms * Nocturia * urgency * frequency * Extravasation of urine * Uremia Eponymous * Addis count * Brewer infarcts * Lloyd's sign * Mathe's sign [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Athletic incontinence	None	3,880	wikipedia	https://en.wikipedia.org/wiki/Athletic_incontinence	2021-01-18T19:05:36	{"wikidata": ["Q17014021"]}
Odontoma-dysphagia syndrome is a malformation syndrome, characterized by odontomas (undifferentiated mass of the esophagus) and severe dysphagia. ## Epidemiology Less than ten cases have been reported so far. ## Clinical description Three of the reported patients manifested multiple odontomas. Occasionally, cardiac (stenosis of the intrathoracic descendent aorta, interstitial myocarditis), renal (pyelonephritis) and hepatic (hepatic sclerosis) involvement has been described. ## Etiology Hypertrophy and dysmotility of the esophageal smooth muscles is suggested to have causative role for dysphagia. ## Genetic counseling In several cases, autosomal dominant inheritance has been suspected. Currently, there are no genes associated with this condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Odontomatosis-aortae esophagus stenosis syndrome	c1834013	3,881	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2724	2021-01-23T18:44:14	{"gard": ["238"], "mesh": ["C537740"], "omim": ["164330"], "umls": ["C1834013"], "synonyms": ["Boder syndrome"]}
Genetic disorder resulting in abnormal enamel Amelogenesis imperfecta Amelogenesis imperfecta, hypoplastic type. Note the association of pitted enamel and open bite. SpecialtyDentistry Amelogenesis imperfecta (AI) is a congenital disorder which presents with a rare abnormal formation of the enamel[1] or external layer of the crown of teeth, unrelated to any systemic or generalized conditions.[2] Enamel is composed mostly of mineral, that is formed and regulated by the proteins in it. Amelogenesis imperfecta is due to the malfunction of the proteins in the enamel (ameloblastin, enamelin, tuftelin and amelogenin) as a result of abnormal enamel formation via amelogenesis.[3] People afflicted with amelogenesis imperfecta may have teeth with abnormal color: yellow, brown or grey; this disorder can afflict any number of teeth of both dentitions. Enamel hypoplasia manifests in a variety of ways depending on the type of AI an individual has (see below), with pitting and plane-form defects common.[4] The teeth have a higher risk for dental cavities and are hypersensitive to temperature changes as well as rapid attrition, excessive calculus deposition, and gingival hyperplasia.[5] The earliest known case of AI is in an extinct hominid species called Paranthropus robustus, with over a third of individuals displaying this condition.[6] ## Contents * 1 Genetics * 2 Diagnosis * 3 Treatment * 4 Epidemiology * 5 References * 6 Further reading * 7 External links ## Genetics[edit] Several gene expression is needed for enamel formation where the relevant matrix proteins & proteinases are transcribed for regular crystal growth & enamel mineralization. Mutations in the AMELX,[7] ENAM,[8] MMP20,[9] KLK-4,[10] FAM83H,[11] WDR72,[12] C4orf26,[13] SLC24A4[14][15] LAMB3[16] and ITGB6[17] genes have been found to cause amelogenesis imperfecta (non-syndromic form). AMELX and ENAM encode extracellular matrix proteins of the developing tooth enamel and KLK-4 and MMP20 encode proteases that help degrade organic matter from the enamel matrix during the maturation stage of amelogenesis. SLC24A4 encodes a calcium transporter that mediates calcium transport to developing enamel during tooth development. Less is known about the function of other genes implicated in amelogenesis imperfecta. Researchers expect that mutations in further genes are likely to be identified as causes of amelogenesis imperfecta. Types include: Type OMIM Gene Locus AI1B 104500 ENAM 4q21 AI1C 204650 ENAM 4q21 AI2A1 204700 KLK4 19q13.4 AI2A2 612529 MMP20 11q22.3-q23 AI2A3 613211 WDR72 15q21.3 AI2A4 614832 ODAPH 4q21.1 AI2A5 609840 SLC24A4 14q32.12 AI3 130900 FAM83H 8q24.3 AIH1 301200 AMELX Xp22.3-p22.1 AIGFS 614253 FAM20A 17q24.2 Amelogenesis imperfecta can have different inheritance patterns depending on the gene that is altered. Mutations in the ENAM gene are the most frequent known cause and are most commonly inherited in an autosomal dominant pattern. This type of inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. Amelogenesis imperfecta is also inherited in an autosomal recessive pattern; this form of the disorder can result from mutations in the ENAM, MMP20, KLK4, FAM20A, C4orf26 or SLC24A4 genes. Autosomal recessive inheritance means two copies of the gene in each cell are altered. About 5% of amelogenesis imperfecta cases are caused by mutations in the AMELX gene and are inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In most cases, males with an X-linked form of this condition experience more severe dental abnormalities than affected females. Recent genetic studies suggest that the cause of a significant proportion of amelogenesis imperfecta cases remains to be discovered.[citation needed] ## Diagnosis[edit] AI can be classified according to their clinical appearances:[18] Type 1 - Hypoplastic Enamel of abnormal thickness due to malfunction in enamel matrix formation. Enamel is very thin but hard & translucent, and may have random pits & grooves. Condition is of autosomal dominant, autosomal recessive, or x-linked pattern. Enamel differs in appearance from dentine radiographically as normal functional enamel.[19] Type 2 - Hypomaturation Enamel has sound thickness, with a pitted appearance. It is less hard compared to normal enamel, and are prone to rapid wear, although not as intense as Type 3 AI. Condition is of autosomal dominant, autosomal recessive, or x-linked pattern. Enamel appears to be comparable to dentine in its radiodensity on radiographs. Type 3 - Hypocalcified Enamel defect due to malfunction of enamel calcification, therefore enamel is of normal thickness but is extremely brittle, with an opaque/chalky presentation. Teeth are prone to staining and rapid wear, exposing dentine. Condition is of autosomal dominant and autosomal recessive pattern. Enamel appears less radioopaque compared to dentine on radiographs. Type 4 - Hypomature hypoplastic enamel with taurodontism Enamel has a variation in appearance, with mixed features from Type 1 and Type 2 AI. All Type 4 AI has taurodontism in common. Condition is of autosomal dominant pattern. Other common features may include an anterior open bite,[20] taurodontism, sensitivity of teeth. Differential diagnosis would include dental fluorosis, molar-incisor hypomineralization, chronological disorders of tooth development.[21] ## Treatment[edit] X-ray showing lack of enamel opacity and a pathological loss of enamel in patient with amelogenesis imperfecta Preventive and restorative dental care is very important as well as considerations for esthetic issues since the crown are yellow from exposure of dentin due to enamel loss.[5] The main objectives of treatment is pain relief, preserving patient's remaining dentition, and to treat and preserve the patient's occlusal vertical height.[19] Many factors are to be considered to decide on treatment options such as the classification and severity of AI, the patient's social history, clinical findings etc. There are many classifications of AI but the general management of this condition is similar. Full-coverage crowns are sometimes being used to compensate for the abraded enamel in adults, tackling the sensitivity the patient experiences. Usually stainless steel crowns are used in children which may be replaced by porcelain once they reach adulthood.[22] These aid with maintaining occlusal vertical dimension. Aesthetics may be addressed via placement of composite or porcelain veneers, depending on patient factors e.g. age. If the patient has primary or mixed dentition, lab-made composite veneers may be provided temporarily, to be replaced by permanent porcelain veneers once the patient has stabilized permanent dentition. The patient's oral hygiene and diet should be controlled as well as they play a factor in the success of retaining future restorations. In the worst-case scenario, the teeth may have to be extracted and implants or dentures are required. Loss of nerves in the affected teeth may occur. ## Epidemiology[edit] The exact incidence of amelogenesis imperfecta is uncertain. Estimates vary widely, from 1 in 700 people in northern Sweden to 1 in 14,000 people in the United States.[23] The prevalence of amelogenesis imperfecta in non-human animals has not been explored, however its presence has been noted.[24] This condition is neither caused by nor the equivalent of dental fluorosis. A manifestation of amelogenesis imperfecta known as "snow capping" is confined to the outer prismless enamel layer. It may superficially resemble dental fluorosis, and indeed "snow capping" may be used as a descriptive term in some incidents of dental fluorosis.[25][26] ## References[edit] 1. ^ Slootweg PJ (2007). Dental pathology: a practical introduction. Springer Science & Business Media. pp. 19–. ISBN 978-3-540-71690-7. Retrieved 28 December 2010. 2. ^ Kida M, Ariga T, Shirakawa T, Oguchi H, Sakiyama Y (November 2002). "Autosomal-dominant hypoplastic form of amelogenesis imperfecta caused by an enamelin gene mutation at the exon-intron boundary". Journal of Dental Research. 81 (11): 738–42. doi:10.1177/154405910208101103. PMID 12407086. 3. ^ Smith CE, Murillo G, Brookes SJ, Poulter JA, Silva S, Kirkham J, Inglehearn CF, Mighell AJ (August 2016). "Deletion of amelotin exons 3-6 is associated with amelogenesis imperfecta". Human Molecular Genetics. 25 (16): 3578–3587. doi:10.1093/hmg/ddw203. PMC 5179951. PMID 27412008. 4. ^ Crawford PJ, Aldred M, Bloch-Zupan A (April 2007). "Amelogenesis imperfecta". Orphanet Journal of Rare Diseases. 2 (1): 17. doi:10.1186/1750-1172-2-17. PMC 1853073. PMID 17408482. 5. ^ a b American Academy of Pediatric Dentistry, Guideline on Dental Management of Heritable Dental Developmental Anomalies, 2013, http://www.aapd.org/media/Policies_Guidelines/G_OHCHeritable.pdf 6. ^ Towle, Ian; Irish, Joel D. (2019). "A probable genetic origin for pitting enamel hypoplasia on the molars of Paranthropus robustus" (PDF). Journal of Human Evolution. 129: 54–61. doi:10.1016/j.jhevol.2019.01.002. PMID 30904040. 7. ^ Lagerström M, Dahl N, Nakahori Y, Nakagome Y, Bäckman B, Landegren U, Pettersson U (August 1991). "A deletion in the amelogenin gene (AMG) causes X-linked amelogenesis imperfecta (AIH1)". Genomics. 10 (4): 971–5. doi:10.1016/0888-7543(91)90187-j. PMID 1916828. 8. ^ Rajpar MH, Harley K, Laing C, Davies RM, Dixon MJ (August 2001). "Mutation of the gene encoding the enamel-specific protein, enamelin, causes autosomal-dominant amelogenesis imperfecta". Human Molecular Genetics. 10 (16): 1673–7. doi:10.1093/hmg/10.16.1673. PMID 11487571. 9. ^ Kim JW, Simmer JP, Hart TC, Hart PS, Ramaswami MD, Bartlett JD, Hu JC (March 2005). "MMP-20 mutation in autosomal recessive pigmented hypomaturation amelogenesis imperfecta". Journal of Medical Genetics. 42 (3): 271–5. doi:10.1136/jmg.2004.024505. PMC 1736010. PMID 15744043. 10. ^ Hart PS, Hart TC, Michalec MD, Ryu OH, Simmons D, Hong S, Wright JT (July 2004). "Mutation in kallikrein 4 causes autosomal recessive hypomaturation amelogenesis imperfecta". Journal of Medical Genetics. 41 (7): 545–9. doi:10.1136/jmg.2003.017657. PMC 1735847. PMID 15235027. 11. ^ Kim JW, Lee SK, Lee ZH, Park JC, Lee KE, Lee MH, Park JT, Seo BM, Hu JC, Simmer JP (February 2008). "FAM83H mutations in families with autosomal-dominant hypocalcified amelogenesis imperfecta". American Journal of Human Genetics. 82 (2): 489–94. doi:10.1016/j.ajhg.2007.09.020. PMC 2427219. PMID 18252228. 12. ^ El-Sayed W, Parry DA, Shore RC, Ahmed M, Jafri H, Rashid Y, et al. (November 2009). "Mutations in the beta propeller WDR72 cause autosomal-recessive hypomaturation amelogenesis imperfecta". American Journal of Human Genetics. 85 (5): 699–705. doi:10.1016/j.ajhg.2009.09.014. PMC 2775821. PMID 19853237. 13. ^ Parry DA, Brookes SJ, Logan CV, Poulter JA, El-Sayed W, Al-Bahlani S, Al Harasi S, Sayed J, el Raïf M, Shore RC, Dashash M, Barron M, Morgan JE, Carr IM, Taylor GR, Johnson CA, Aldred MJ, Dixon MJ, Wright JT, Kirkham J, Inglehearn CF, Mighell AJ (September 2012). "Mutations in C4orf26, encoding a peptide with in vitro hydroxyapatite crystal nucleation and growth activity, cause amelogenesis imperfecta". American Journal of Human Genetics. 91 (3): 565–71. doi:10.1016/j.ajhg.2012.07.020. PMC 3511980. PMID 22901946. 14. ^ Parry DA, Poulter JA, Logan CV, Brookes SJ, Jafri H, Ferguson CH, et al. (February 2013). "Identification of mutations in SLC24A4, encoding a potassium-dependent sodium/calcium exchanger, as a cause of amelogenesis imperfecta". American Journal of Human Genetics. 92 (2): 307–12. doi:10.1016/j.ajhg.2013.01.003. PMC 3567274. PMID 23375655. 15. ^ Herzog CR, Reid BM, Seymen F, Koruyucu M, Tuna EB, Simmer JP, Hu JC (February 2015). "Hypomaturation amelogenesis imperfecta caused by a novel SLC24A4 mutation". Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology. 119 (2): e77–81. doi:10.1016/j.oooo.2014.09.003. PMC 4291293. PMID 25442250. 16. ^ Poulter JA, El-Sayed W, Shore RC, Kirkham J, Inglehearn CF, Mighell AJ (January 2014). "Whole-exome sequencing, without prior linkage, identifies a mutation in LAMB3 as a cause of dominant hypoplastic amelogenesis imperfecta". European Journal of Human Genetics. 22 (1): 132–5. doi:10.1038/ejhg.2013.76. PMC 3865405. PMID 23632796. 17. ^ Wang SK, Choi M, Richardson AS, Reid BM, Lin BP, Wang SJ, Kim JW, Simmer JP, Hu JC (April 2014). "ITGB6 loss-of-function mutations cause autosomal recessive amelogenesis imperfecta". Human Molecular Genetics. 23 (8): 2157–63. doi:10.1093/hmg/ddt611. PMC 3959820. PMID 24305999. 18. ^ Fonseca RB, Sobrinho LC, Neto AJ, Soares da Mota A, Soares CJ (2006). "Enamel hypoplasia or amelogenesis imperfecta – a restorative approach". Brazilian Journal of Oral Sciences. 5 (16): 941–3. 19. ^ a b Visram S, McKaig S (December 2006). "Amelogenesis imperfecta--clinical presentation and management: a case report". Dental Update. 33 (10): 612–4, 616. doi:10.12968/denu.2006.33.10.612. PMID 17209536. 20. ^ Bouvier D, Duprez JP, Bois D (1996). "Rehabilitation of young patients with amelogenesis imperfecta: a report of two cases". ASDC Journal of Dentistry for Children. 63 (6): 443–7. PMID 9017180. 21. ^ Crawford PJ, Aldred M, Bloch-Zupan A (April 2007). "Amelogenesis imperfecta". Orphanet Journal of Rare Diseases. 2: 17. doi:10.1186/1750-1172-2-17. PMC 1853073. PMID 17408482. 22. ^ Illustrated Dental Embryology, Histology, and Anatomy, Bath-Balogh and Fehrenbach, Elsevier, 2011, page 64 23. ^ Hoppenreijs TJ, Voorsmit RA, Freihofer HP (August 1998). "Open bite deformity in amelogenesis imperfecta. Part 1: An analysis of contributory factors and implications for treatment". Journal of Cranio-Maxillo-Facial Surgery. 26 (4): 260–6. doi:10.1016/s1010-5182(98)80023-1. PMID 9777506. 24. ^ Towle I, Irish JD, De Groote I (April 2018). "Amelogenesis imperfecta in the dentition of a wild chimpanzee" (PDF). Journal of Medical Primatology. 47 (2): 117–119. doi:10.1111/jmp.12323. PMID 29112236. S2CID 3801451. 25. ^ Chaudhary M, Dixit S, Singh A, Kunte S (July 2009). "Amelogenesis imperfecta: Report of a case and review of literature". Journal of Oral and Maxillofacial Pathology. 13 (2): 70–7. doi:10.4103/0973-029X.57673. PMC 3162864. PMID 21887005. 26. ^ Hu JC, Chan HC, Simmer SG, Seymen F, Richardson AS, Hu Y, Milkovich RN, Estrella NM, Yildirim M, Bayram M, Chen CF, Simmer JP (2012). "Amelogenesis imperfecta in two families with defined AMELX deletions in ARHGAP6". PLOS ONE. 7 (12): e52052. Bibcode:2012PLoSO...752052H. doi:10.1371/journal.pone.0052052. PMC 3522662. PMID 23251683. ## Further reading[edit] * Winter GB, Brook AH (January 1975). "Enamel hypoplasia and anomalies of the enamel". Dental Clinics of North America. 19 (1): 3–24. PMID 162891. * Simmer JP, Hu JC (September 2001). "Dental enamel formation and its impact on clinical dentistry". Journal of Dental Education. 65 (9): 896–905. doi:10.1002/j.0022-0337.2001.65.9.tb03438.x. PMID 11569606. * Aldred MJ, Savarirayan R, Crawford PJ (January 2003). "Amelogenesis imperfecta: a classification and catalogue for the 21st century". Oral Diseases. 9 (1): 19–23. doi:10.1034/j.1601-0825.2003.00843.x. PMID 12617253. * Nusier M, Yassin O, Hart TC, Samimi A, Wright JT (February 2004). "Phenotypic diversity and revision of the nomenclature for autosomal recessive amelogenesis imperfecta". Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 97 (2): 220–30. doi:10.1016/j.tripleo.2003.08.007. PMID 14970781. * Stephanopoulos G, Garefalaki ME, Lyroudia K (December 2005). "Genes and related proteins involved in amelogenesis imperfecta". Journal of Dental Research. 84 (12): 1117–26. doi:10.1177/154405910508401206. PMID 16304440. S2CID 17693799. ## External links[edit] Classification D * ICD-10: K00.5 * ICD-9-CM: 520.5 * MeSH: D000567 * DiseasesDB: 31408 External resources * MedlinePlus: 001578 * v * t * e Developmental tooth disease/tooth abnormality Quantity * Anodontia/Hypodontia * Hyperdontia Shape and size * Concrescence * Fusion * Gemination * Dens evaginatus/Talon cusp * Dens invaginatus * Enamel pearl * Macrodontia * Microdontia * Taurodontism * Supernumerary roots Formation * Dilaceration * Regional odontodysplasia * Turner's hypoplasia * Enamel hypoplasia * Ectopic enamel Other hereditary * Amelogenesis imperfecta * Dentinogenesis imperfecta * Dentin dysplasia * Regional odontodysplasia Other * Dental fluorosis * Tooth impaction * v * t * e X-linked disorders X-linked recessive Immune * Chronic granulomatous disease (CYBB) * Wiskott–Aldrich syndrome * X-linked severe combined immunodeficiency * X-linked agammaglobulinemia * Hyper-IgM syndrome type 1 * IPEX * X-linked lymphoproliferative disease * Properdin deficiency Hematologic * Haemophilia A * Haemophilia B * X-linked sideroblastic anemia Endocrine * Androgen insensitivity syndrome/Spinal and bulbar muscular atrophy * KAL1 Kallmann syndrome * X-linked adrenal hypoplasia congenita Metabolic * Amino acid: Ornithine transcarbamylase deficiency * Oculocerebrorenal syndrome * Dyslipidemia: Adrenoleukodystrophy * Carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency * Pyruvate dehydrogenase deficiency * Danon disease/glycogen storage disease Type IIb * Lipid storage disorder: Fabry's disease * Mucopolysaccharidosis: Hunter syndrome * Purine–pyrimidine metabolism: Lesch–Nyhan syndrome * Mineral: Menkes disease/Occipital horn syndrome Nervous system * X-linked intellectual disability: Coffin–Lowry syndrome * MASA syndrome * Alpha-thalassemia mental retardation syndrome * Siderius X-linked mental retardation syndrome * Eye disorders: Color blindness (red and green, but not blue) * Ocular albinism (1) * Norrie disease * Choroideremia * Other: Charcot–Marie–Tooth disease (CMTX2-3) * Pelizaeus–Merzbacher disease * SMAX2 Skin and related tissue * Dyskeratosis congenita * Hypohidrotic ectodermal dysplasia (EDA) * X-linked ichthyosis * X-linked endothelial corneal dystrophy Neuromuscular * Becker's muscular dystrophy/Duchenne * Centronuclear myopathy (MTM1) * Conradi–Hünermann syndrome * Emery–Dreifuss muscular dystrophy 1 Urologic * Alport syndrome * Dent's disease * X-linked nephrogenic diabetes insipidus Bone/tooth * AMELX Amelogenesis imperfecta No primary system * Barth syndrome * McLeod syndrome * Smith–Fineman–Myers syndrome * Simpson–Golabi–Behmel syndrome * Mohr–Tranebjærg syndrome * Nasodigitoacoustic syndrome X-linked dominant * X-linked hypophosphatemia * Focal dermal hypoplasia * Fragile X syndrome * Aicardi syndrome * Incontinentia pigmenti * Rett syndrome * CHILD syndrome * Lujan–Fryns syndrome * Orofaciodigital syndrome 1 * Craniofrontonasal dysplasia [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Amelogenesis imperfecta	c0002452	3,882	wikipedia	https://en.wikipedia.org/wiki/Amelogenesis_imperfecta	2021-01-18T19:03:03	{"gard": ["5791"], "mesh": ["D000567"], "umls": ["C0002452"], "orphanet": ["88661"], "wikidata": ["Q461854"]}
Iridogoniodysgenesis, dominant type Iridogoniodysgenesis, dominant type is inherited via autosomal dominant manner[1] Iridogoniodysgenesis, dominant type (type 1, IRID1) refers to a spectrum of diseases characterized by malformations of the irido-corneal angle of the anterior chamber of the eye. Iridogoniodysgenesis is the result of abnormal migration or terminal induction of neural crest cells. These cells lead to formation of most of the anterior segment structures of the eye (corneal stroma & endothelium, iris stroma, trabeculum).[2] ## Contents * 1 Symptoms and signs * 2 Cause * 3 Diagnosis * 4 Treatment * 5 History * 6 References * 7 External links ## Symptoms and signs[edit] Symptoms include iris hypoplasis, goniodysgenesis, and juvenile glaucoma. Glaucoma phenotype that maps to 6p25 results from mutations in the forkhead transcription factor gene FOXC1[citation needed] ## Cause[edit] This is transmitted through an autosomal dominant pattern with complete penetrance and variable expressivity. ## Diagnosis[edit] This section is empty. You can help by adding to it. (July 2017) ## Treatment[edit] Treatment of glaucoma in iridogoniodysgenesis is primarily surgical.[citation needed] It is listed as a "rare disease" by the Office of Rare Diseases (ORD).[3] This means that Iridogoniodysgenesis, dominant type, or a subtype of Iridogoniodysgenesis, dominant type, affects less than 200,000 people in the US population. ## History[edit] This was first reported by Berg (1932).[4] ## References[edit] 1. ^ "OMIM Entry - # 601631 - ANTERIOR SEGMENT DYSGENESIS 3; ASGD3". omim.org. Retrieved 21 July 2017. 2. ^ Dureau P.Iridogoniodysgenesis dominant type. Orphanet Encyclopedia. March 2004 3. ^ Iridogoniodysgenesis, dominant type at NIH's Office of Rare Diseases 4. ^ Berg, Fredrik (1932-12-01). "Erbliches Jugendliches Glaukom". Acta Ophthalmologica. 10 (4): 568–587. doi:10.1111/j.1755-3768.1932.tb07210.x. ISSN 1755-3768. S2CID 72041411. ## External links[edit] * Entrez Gene Classification D * OMIM: 601631 * DiseasesDB: 34611 * v * t * e Genetic disorders relating to deficiencies of transcription factor or coregulators (1) Basic domains 1.2 * Feingold syndrome * Saethre–Chotzen syndrome 1.3 * Tietz syndrome (2) Zinc finger DNA-binding domains 2.1 * (Intracellular receptor): Thyroid hormone resistance * Androgen insensitivity syndrome * PAIS * MAIS * CAIS * Kennedy's disease * PHA1AD pseudohypoaldosteronism * Estrogen insensitivity syndrome * X-linked adrenal hypoplasia congenita * MODY 1 * Familial partial lipodystrophy 3 * SF1 XY gonadal dysgenesis 2.2 * Barakat syndrome * Tricho–rhino–phalangeal syndrome 2.3 * Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome * Denys–Drash syndrome * Duane-radial ray syndrome * MODY 7 * MRX 89 * Townes–Brocks syndrome * Acrocallosal syndrome * Myotonic dystrophy 2 2.5 * Autoimmune polyendocrine syndrome type 1 (3) Helix-turn-helix domains 3.1 * ARX * Ohtahara syndrome * Lissencephaly X2 * MNX1 * Currarino syndrome * HOXD13 * SPD1 synpolydactyly * PDX1 * MODY 4 * LMX1B * Nail–patella syndrome * MSX1 * Tooth and nail syndrome * OFC5 * PITX2 * Axenfeld syndrome 1 * POU4F3 * DFNA15 * POU3F4 * DFNX2 * ZEB1 * Posterior polymorphous corneal dystrophy * Fuchs' dystrophy 3 * ZEB2 * Mowat–Wilson syndrome 3.2 * PAX2 * Papillorenal syndrome * PAX3 * Waardenburg syndrome 1&3 * PAX4 * MODY 9 * PAX6 * Gillespie syndrome * Coloboma of optic nerve * PAX8 * Congenital hypothyroidism 2 * PAX9 * STHAG3 3.3 * FOXC1 * Axenfeld syndrome 3 * Iridogoniodysgenesis, dominant type * FOXC2 * Lymphedema–distichiasis syndrome * FOXE1 * Bamforth–Lazarus syndrome * FOXE3 * Anterior segment mesenchymal dysgenesis * FOXF1 * ACD/MPV * FOXI1 * Enlarged vestibular aqueduct * FOXL2 * Premature ovarian failure 3 * FOXP3 * IPEX 3.5 * IRF6 * Van der Woude syndrome * Popliteal pterygium syndrome (4) β-Scaffold factors with minor groove contacts 4.2 * Hyperimmunoglobulin E syndrome 4.3 * Holt–Oram syndrome * Li–Fraumeni syndrome * Ulnar–mammary syndrome 4.7 * Campomelic dysplasia * MODY 3 * MODY 5 * SF1 * SRY XY gonadal dysgenesis * Premature ovarian failure 7 * SOX10 * Waardenburg syndrome 4c * Yemenite deaf-blind hypopigmentation syndrome 4.11 * Cleidocranial dysostosis (0) Other transcription factors 0.6 * Kabuki syndrome Ungrouped * TCF4 * Pitt–Hopkins syndrome * ZFP57 * TNDM1 * TP63 * Rapp–Hodgkin syndrome/Hay–Wells syndrome/Ectrodactyly–ectodermal dysplasia–cleft syndrome 3/Limb–mammary syndrome/OFC8 Transcription coregulators Coactivator: * CREBBP * Rubinstein–Taybi syndrome Corepressor: * HR (Atrichia with papular lesions) [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Iridogoniodysgenesis, dominant type	c1842031	3,883	wikipedia	https://en.wikipedia.org/wiki/Iridogoniodysgenesis,_dominant_type	2021-01-18T18:35:57	{"mesh": ["C535536"], "umls": ["C1842031"], "orphanet": ["98634", "91483"], "wikidata": ["Q17125601"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive nonsyndromic deafness-24 (DFNB24) is caused by homozygous mutation in the gene encoding radixin (RDX; 179410) on chromosome 11q22. Clinical Features Khan et al. (2007) reported 3 Pakistani families with isolated autosomal recessive sensorineural deafness. Two of the families were known to be consanguineous. The deafness showed prelingual onset and was bilateral and profound. None of the affected individuals had vestibular dysfunction or hyperbilirubinemia. Shearer et al. (2009) reported a consanguineous Iranian family with DFNB24. Affected individuals had congenital onset of severe to profound hearing loss and no evidence of liver dysfunction. Molecular Genetics In affected members of 3 Pakistani families with isolated autosomal recessive sensorineural deafness, Khan et al. (2007) identified 3 respective homozygous mutations in the RDX gene (179410.0001-179410.0003). In 4 affected members of a consanguineous Iranian family with DFNB24, Shearer et al. (2009) identified a homozygous splice site mutation in the RDX gene (179410.0004). INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Deafness, profound, sensorineural MISCELLANEOUS \- Prelingual onset MOLECULAR BASIS \- Caused by mutation in the radixin gene (RDX, 179410.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	DEAFNESS, AUTOSOMAL RECESSIVE 24	c1970239	3,884	omim	https://www.omim.org/entry/611022	2019-09-22T16:03:50	{"doid": ["0110482"], "mesh": ["C567027"], "omim": ["611022"], "orphanet": ["90636"], "synonyms": ["Autosomal recessive isolated neurosensory deafness type DFNB", "Autosomal recessive isolated sensorineural deafness type DFNB", "Autosomal recessive non-syndromic neurosensory deafness type DFNB"], "genereviews": ["NBK1434"]}
Carnitine palmitoyltransferase II deficiency Other namesCPT-II, CPT2 Carnitine SpecialtyEndocrinology Carnitine palmitoyltransferase II deficiency is an autosomal recessively inherited genetic metabolic disorder characterized by an enzymatic defect that prevents long-chain fatty acids from being transported into the mitochondria for utilization as an energy source. The disorder presents in one of three clinical forms: lethal neonatal, severe infantile hepatocardiomuscular and myopathic. First characterized in 1973 by DiMauro and DiMauro the adult myopathic form of this disease is triggered by physically strenuous activities and/or extended periods without food and leads to immense muscle fatigue and pain.[1] It is the most common inherited disorder of lipid metabolism affecting the skeletal muscle of adults, primarily affecting males. CPT II deficiency is also the most frequent cause of hereditary myoglobinuria. ## Contents * 1 Signs and symptoms * 1.1 Neonatal form * 1.2 Infantile form * 1.3 Adult form * 2 Biochemistry * 2.1 Enzyme structure * 2.2 Catalytic mechanism * 2.3 Biochemical significance of disease-causing mutations * 2.4 Enzyme activity and disease severity * 3 Pathophysiology * 3.1 Molecular genetics * 3.1.1 Amino acid consequences of some reported mutations * 4 Diagnosis * 5 Treatment * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] The three main types of carnitine palmitoyltransferase II deficiency classified on the basis of tissue-specific symptomatology and age of onset. Among the few people diagnosed with CPT2, some have unknown and/or novel mutations that place them outside these three categories while remaining positive for CPT2. ### Neonatal form[edit] The neonatal form is the least common clinical presentation of this disorder and is almost invariably fatal in rapid fashion regardless of intervention. Symptomatic onset has been documented just hours after birth to within 4 days of life. Affected newborns typically experience respiratory failure, low blood sugar, seizures, liver enlargement, liver failure, and heart enlargement with abnormal heart rhythms leading to cardiac arrest. In most cases, elements of abnormal brain and kidney development are apparent, sometimes even at prenatal ultrasound. Infants with the lethal neonatal form usually live no longer than a few months.[2] Neuronal migration defects have also been documented, to which the CNS pathology of the disorder is often attributed. ### Infantile form[edit] Symptomatic presentation usually occurs between 6 and 24 months of age, but the majority of cases have been documented in children less than 1 year of age. The infantile form involves multiple organ systems and is primarily characterized by hypoketotic hypoglycemia (recurring attacks of abnormally low levels of fat breakdown products and blood sugar) that often results in loss of consciousness and seizure activity. Acute liver failure, liver enlargement, and cardiomyopathy are also associated with the infantile presentation of this disorder. Episodes are triggered by febrile illness, infection, or fasting. Some cases of sudden infant death syndrome are attributed to infantile CPT II deficiency at autopsy. ### Adult form[edit] This exclusively myopathic form is the most prevalent and least severe phenotypic presentation of this disorder. Characteristic signs and symptoms include rhabdomyolysis (breakdown of muscle fibers and subsequent release of myoglobin), myoglobinuria, recurrent muscle pain, and weakness. The myoglobin release causes the urine to be red or brown and is indicatory of damage being done to the kidneys which ultimately could result in kidney failure.[3] Muscle weakness and pain typically resolves within hours to days, and patients appear clinically normal in the intervening periods between attacks. Symptoms are most often exercise-induced, but fasting, a high-fat diet, exposure to cold temperature, sleep deprivation, or infection (especially febrile illness) can also provoke this metabolic myopathy. In a minority of cases, disease severity can be exacerbated by three life-threatening complications resulting from persistent rhabdomyolysis: acute kidney failure, respiratory insufficiency, and episodic abnormal heart rhythms. Severe forms may have continual pain from general life activity. The adult form has a variable age of onset. The first appearance of symptoms usually occurs between 6 and 20 years of age but has been documented in patients as young as 8 months as well as in adults over the age of 50. Roughly 80% cases reported to date have been male. ## Biochemistry[edit] ### Enzyme structure[edit] The CPT system directly acts on the transfer of fatty acids between the cytosol and the inner mitochondrial matrix.[4] CPT II shares structural elements with other members of the carnitine acyltransferase protein family.[5] The crystal structure of rat CPT II was recently elucidated by Hsiao et al.[6] The human homolog of the CPT II enzyme shows 82.2% amino acid sequence homology with the rat protein.[7] Significant structural and functional information about CPT II has thus been derived from the crystallographic studies with the rat protein. In addition to similarities shared by the acyltransferases, CPT II also contains a distinct insertion of 30 residues in the amino domain that forms a relatively hydrophobic protrusion composed of two alpha helices and a small anti-parallel beta sheet.[6] It has been proposed that this segment mediates the association of CPT II with the inner mitochondrial membrane.[6] Moreover, the insert might also facilitate the shuttling of palmitoylcarnitines directly into the active site of CPT II after translocation across the inner membrane by virtue of its juxtaposition to the active site tunnel of the enzyme.[6] ### Catalytic mechanism[edit] CPT II catalyzes the formation of palmitoyl-CoA from palmitoylcarnitine imported into the matrix via the acylcarnitine translocase. The catalytic core of the CPT II enzyme contains three important binding sites that recognize structural aspects of CoA, palmitoyl, and carnitine.[8] Although kinetic studies are hindered by high substrate inhibition, strong product inhibition, very low Km values for the acyl-CoA substrates, and complex detergent effects with respect to micelle formation,[8] studies have shown that CPT II demonstrates a compulsory-order mechanism in which the enzyme must bind CoA before palmitoylcarnitine, and then the resulting product palmitoyl-CoA is the last substrate to be released from the enzyme. The carnitine binding site is made accessible by the conformational change induced in the enzyme by the binding of CoA.[8] This ordered mechanism is believed to be important so that the enzyme responds appropriately to the acylation state of the mitochondrial pool of CoA despite the fact that the concentrations of both CoA and acyl-CoA found in the matrix well exceed the measured km value of the enzyme (most CPT II will already have bound the CoA).[9] The histidine residue (at position 372 in CPT II) is fully conserved in all members of the carnitine acyltransferase family and has been localized to the enzyme active site, likely playing a direct role in the catalytic mechanism of the enzyme.[5] A general mechanism for this reaction is believed to involve this histidine acting as a general base. More specifically, this reaction proceeds as a general base-catalyzed nucleophilic attack of the thioester of acetyl-CoA by the hydroxyl group of carnitine.[10] ### Biochemical significance of disease-causing mutations[edit] The majority of the genetic abnormalities in CPT II deficient patients affect amino acid residues somewhat removed from the active site of the enzyme. Thus, these mutations are thought to compromise the stability of the protein rather than the catalytic activity of the enzyme.[6] Theories regarding the biochemical significance of the two most common mutations are noted below: * Ser113Leu Hsiao et al.[6] theorize that this mutation may disturb the hydrogen-bonding between Ser113 and Arg 498 and the ion-pair network between Arg498 and Asp376, thereby indirectly affecting the catalytic efficiency of the His372 residue. Isackson et al.[5] suggest that this mutation increases the thermolability of the enzyme, structurally destabilizing it. This is noteworthy in light of the fact that this mutation is associated with the exercise-induced adult form (i.e., rising core body temperature may exacerbate enzymatic defects leading to symptomatic presentation).[11] Rufer et al. speculate that mutation of serine to the bulkier, hydrophobic leucine alters a critical interaction with nearby Phe117, ultimately modifying the position and environment of the catalytically important residues Trp116 and Arg498, reducing enzyme activity.[12] * Pro50His This proline is 23 residues from the active site, and is located right below the hydrophobic membrane insert in the active CPT II enzyme.[6] Hsiao et al. speculate that this mutation indirectly compromises the association between CPT II and the inner mitochondrial membrane and disturbs the shuttling of the palmitoylcarnitine substrate into the active site of the enzyme.[6] ### Enzyme activity and disease severity[edit] The clinical significance of the biochemical consequences that result from the genetic abnormalities in patients with CPT II Deficiency is a contested issue. Rufer et al. support the theory that there is an association between level of enzyme activity and clinical presentation.[12] Multiple research groups have transfected COS-1 cells with different CPT II mutations and found varying levels of reduction in enzyme activity compared with controls: Phe352Cys reduced enzyme activity to 70% of wild-type, Ser113Leu reduced enzyme activity to 34% of wild-type, and several severe mutations reduced activity to 5-10% of wild-type.[5] However, most researchers are reluctant to accept the existence of a causal relationship between enzyme functionality and clinical phenotype.[5] Two groups[13][14] have recently reported a limited correlation (lacking in statistical significance) between the genotypic array and the clinical severity of the phenotype in their patient cohorts. There is a need for further explorations of this topic in order to fully assess the biochemical ramifications of this enzymatic deficiency. The rate of long-chain fatty acid oxidation in CPT II-deficient patients has been proposed to be a stronger predictor of clinical severity than residual CPT II enzyme activity. For example, one study found that although the level of residual CPT II activity in adult versus infantile onset groups overlapped, a significant decrease in palmitate oxidation was noted in the infantile group when compared to the adult group.[15] This group concluded that both the type and location of CPT2 mutation in combination with at least one secondary genetic factor modulate the long-chain fatty acid flux and, therefore, the severity of the disease.[15] ## Pathophysiology[edit] Carnitine is a hydrophilic natural substance acquired mostly through dietary meats and dairy products and is used by cells to transport hydrophobic fatty acids.[16] The "carnitine shuttle"[17] is composed of three enzymes that utilize carnitine to facilitate the import of hydrophobic long-chain fatty acids from the cytosol into the mitochondrial matrix for the production of energy via β-oxidation.[18] * Carnitine palmitoyltransferase I (CPT I) is localized to the outer mitochondrial membrane and catalyzes the esterification reaction between carnitine and palmitoyl-CoA to produce palmitoylcarnitine. Three tissue-specific isoforms (liver, muscle, brain) have been identified. * Carnitine-acylcarnitine translocase (CACT) is an integral inner mitochondrial membrane protein that transports palmitoylcarnitine from the intermembrane space into the matrix in exchange for a molecule of free carnitine that is subsequently moved back out of the mitochondria into the cytosol. * Carnitine palmitoyltransferase II (CPT II) is a peripheral inner mitochondrial membrane protein ubiquitously found as a monomeric protein in all tissues that oxidize fatty acids.[11] It catalyzes the transesterification of palmitoylcarnitine back into palmitoyl-CoA which is now an activated substrate for β-oxidation inside the matrix. ### Molecular genetics[edit] Carnitine palmitoyltransferase II deficiency has an autosomal recessive pattern of inheritance. CPT II deficiency has an autosomal recessive pattern of inheritance.[13] CPT2 is the gene that encodes the CPT II enzyme, and it has been mapped to chromosomal locus 1p32.[19] This gene is composed of 5 exons that encode a protein 658 amino acids in length.[13] To date, sixty disease-causing mutations within the coding sequence of CPT2 have been reported in the literature, of which 41 are thought to result in amino acid substitutions or deletions at critical residues.[5] #### Amino acid consequences of some reported mutations[edit] * Ser113Leu (338C>T) is the most common mild mutation observed in adult cases, it has an observed allelic frequency of 65% in adult cases,[13] and both homozygous and heterozygous cases have been documented. * Pro50His (149C>A) is also relatively common in the adult form, with an allelic frequency of 6.5%.[20] * Arg161Trp, Glu174Lys and Ile502Thr are other homozygous mild mutations associated with the adult form [5] * Arg151Gln and Pro227Leu are examples of severe homozygous mutations that have been associated with the mutisystemic infantile/neonatal form of the disorder.[5] * The 18 known severe mutations that result in prematurely truncated proteins lack residual CPT II activity are associated with the neonatal onset and are likely incompatible with life in most circumstances.[5] * Val368Ile and Met647Val are polymorphisms have been linked to CPT II deficiency.[5] These genetic abnormalities alone do not directly cause the disorder, but they seem to exacerbate the reduction in enzymatic efficiency when combined with one or more primary CPT2 mutations.[20] Recent research[15] found that mutations associated with a specific disease phenotype segregated to specific exons. In this study, infantile-onset cases had mutations in exon 4 or 5 of the CPT2 gene, while adult-onset cases had at least one mutation in exon 1 and/or exon 3. This group suggested that Ser113Leu (exon 3) and Pro50His (exon 1) might confer some sort of protective advantage against the development of the severe infantile phenotype in patients predisposed to develop the adult form of the disorder, since these two mutations have never been identified in cases of compound heterozygous infantile cases.[15] In support of this theory, an independent group reported two cases where mutations that have been shown to cause the infantile (Arg151Gln) or neonatal (Arg631Cys) forms when homozygous instead were associated with the milder, adult-onset phenotype when present as compound heterozygous mutations with Ser113Leu as the second mutation.[13] ## Diagnosis[edit] * Tandem mass spectrometry: non-invasive, rapid method; a significant peak at C16 is indicative of generalized CPT II deficiency[21][22] * Genetic testing and carrier testing to confirm deficiency using a skin enzyme test.[23] Pregnant women can also undergo testing via amniocentesis. * Enzymatic activity studies in fibroblasts and/or lymphocytes * Laboratory findings: most patients have low total and free carnitine levels and high acylcarnitine:free carnitine ratios. Adult patients often have serum and/or urine screen positive for the presence of myoglobin and serum creatine kinase and transaminase levels 20-400x higher than normal levels during an attack.[20] Signs of metabolic acidosis and significant hyperammonemia have been reported in infantile and neonatal cases.[20][16] ## Treatment[edit] Standard of care for treatment of CPT II deficiency commonly involves limitations on prolonged strenuous activity and the following stipulations: * The medium-chain fatty acid triheptanoin appears to be an effective therapy for adult-onset CPT II deficiency. * Restriction of lipid intake, increased carbohydrate intake[24] * Avoidance of fasting situations * Glucose infusions during infections to prevent catabolism * Avoidance of valproic acid, ibuprofen, diazepam, and general anesthesia [24] * Dietary modifications including replacement of long-chain with medium-chain triglycerides supplemented with L-carnitine * Rigorous meal schedule[23] * Avoidance of rigorous exercise.[23] ## See also[edit] * Carnitine O-palmitoyltransferase * Carnitine palmitoyltransferase I deficiency * Fasciculation * Myokymia * Primary carnitine deficiency ## References[edit] 1. ^ Research, Institute of Medicine (US) Committee on Military Nutrition; Marriott, Bernadette M. (1994). The Role of Carnitine in Enhancing Physical Performance. National Academies Press (US). 2. ^ "Carnitine palmitoyltransferase II deficiency, lethal neonatal (Concept Id: C1833518) - MedGen - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2019-12-12. 3. ^ Reference, Genetics Home. "CPT II deficiency". Genetics Home Reference. Retrieved 2019-12-12. 4. ^ Sigauke, Ellen; Rakheja, Dinesh; Kitson, Kimberly; Bennett, Michael J. (November 2003). "Carnitine Palmitoyltransferase II Deficiency: A Clinical, Biochemical, and Molecular Review". Laboratory Investigation. 83 (11): 1543–1554. doi:10.1097/01.LAB.0000098428.51765.83. ISSN 1530-0307. PMID 14615409. 5. ^ a b c d e f g h i j Isackson PJ, Bennett MJ, Vladutiu GD (December 2006). "Identification of 16 new disease-causing mutations in the CPT2 gene resulting in carnitine palmitoyltransferase II deficiency". Molecular Genetics and Metabolism. 89 (4): 323–31. doi:10.1016/j.ymgme.2006.08.004. PMID 16996287. 6. ^ a b c d e f g h Hsiao Y, Jogl G, Esser V, Tong L (2006). "Crystal structure of rat carnitine palmitoyltransferase II (CPT-II)". Biochem Biophys Res Commun. 346 (3): 974–80. doi:10.1016/j.bbrc.2006.06.006. PMC 2937350. PMID 16781677. 7. ^ Finocchiaro G; et al. (1991). "cDNA cloning, sequence analysis, and chromosomal localization of the gene for human carnitine palmitoyltransferase". Proc. Natl. Acad. Sci. USA. 88 (2): 661–5. Bibcode:1991PNAS...88..661F. doi:10.1073/pnas.88.2.661. PMC 50872. PMID 1988962. 8. ^ a b c Nic, Bhaird N; et al. (1993). "Comparison of the active sites of the purified carnitine acyltransferases from peroxisomes and mitochondria by using a reaction-intermediate analogue". Biochem J. 294 (3): 645–51. doi:10.1042/bj2940645. PMC 1134510. PMID 8379919. 9. ^ Ramsay R; et al. (2001). "Molecular enzymology of carnitine transfer and transport". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology. 1546 (1): 21–43. doi:10.1016/s0167-4838(01)00147-9. PMID 11257506. 10. ^ Wu D; et al. (2003). "Structure of Human Carnitine Acetyltransferase: Molecular Basis For Fatty Acyl Transfer". J Biol Chem. 278 (15): 13159–65. doi:10.1074/jbc.m212356200. PMID 12562770. 11. ^ a b Sigauke E; et al. (2003). "Carnitine Palmitoyltransferase II Deficiency: A Clinical, Biochemical, and Molecular Review". Laboratory Invest. 83 (11): 1543–54. doi:10.1097/01.LAB.0000098428.51765.83. PMID 14615409. 12. ^ a b Rufer A; et al. (2006). "The Crystal Structure of Carnitine Palmitoyltransferase 2 and Implications for Diabetes Treatment". Structure. 14 (4): 713–23. doi:10.1016/j.str.2006.01.008. PMID 16615913. 13. ^ a b c d e Corti S, Bordoni A, Ronchi D, et al. (March 2008). "Clinical features and new molecular findings in Carnitine Palmitoyltransferase II (CPT II) deficiency". Journal of the Neurological Sciences. 266 (1–2): 97–103. doi:10.1016/j.jns.2007.09.015. PMID 17936304. 14. ^ Wieser T; et al. (2003). "Carnitine palmitoyltransferase II deficiency: molecular and biochemical analysis of 32 patients". Neurology. 60 (8): 1351–3. doi:10.1212/01.wnl.0000055901.58642.48. PMID 12707442. S2CID 14849280. 15. ^ a b c d Thuillier L et al. (2003). Correlation between genotype, metabolic data, and clinical presentation in carnitine palmitoyltransferase 2 (CPT2) deficiency. Hum Metab, 21: 493-501. 16. ^ a b Longo N, Amat, San Filippo C, Pasquali M (2006). "Disorders of Carnitine Transport and the Carnitine Cycle". Am J Med Genet C Semin Med Genet. 142 (2): 77–85. doi:10.1002/ajmg.c.30087. PMC 2557099. PMID 16602102. 17. ^ Nelson DL and Cox MM (2005). "Fatty Acid Catabolism" in Lehninger Principles of Biochemistry, 4th Ed. New York: W.H. Freeman and Company, 631-55. 18. ^ Kerner J, Hoppel C (June 2000). "Fatty acid import into mitochondria". Biochim. Biophys. Acta. 1486 (1): 1–17. doi:10.1016/s1388-1981(00)00044-5. PMID 10856709. 19. ^ Gellera C; et al. (1994). "Assignment of the human carnitine palmitoyltransferase II gene (CPT1) to chromosome 1p32". Genomics. 24 (1): 195–7. doi:10.1006/geno.1994.1605. PMID 7896283. 20. ^ a b c d Bonnefont JP; et al. (2004). "Carnitine palmitoyltransferases 1 and 2: biochemical, molecular and medical aspects". Molecular Aspects of Medicine. 25 (5–6): 495–520. doi:10.1016/j.mam.2004.06.004. PMID 15363638. 21. ^ Brivet M et al. (1999). Defects in activation and transport of fatty acids. J Inher Metab Dis, 22: 428-441. 22. ^ Rettinger A et al. (2002). Tandem Mass Spectrometric Assay for the Determination of Carnitine Palmitoyltransferase II Activity in Muscle Tissue. Analyt Biochem, 302: 246-251. 23. ^ a b c "NEWBORN SCREENING". www.newbornscreening.info. Retrieved 2019-12-12. 24. ^ a b Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, Wieser T (1993). "Carnitine Palmitoyltransferase II Deficiency". PMID 20301431. Cite journal requires `\|journal=` (help)CS1 maint: uses authors parameter (link) ## External links[edit] Classification D * ICD-10: E71.314 * ICD-9-CM: 277.85 * OMIM: 255110 600649 608836 * MeSH: C535589 * DiseasesDB: 32534 External resources * eMedicine: ped/321 This article incorporates public domain text from The U.S. National Library of Medicine * GeneReviews/NCBI/NIH/UW entry on Carnitine Palmitoyltransferase II Deficiency * v * t * e Inborn error of lipid metabolism: dyslipidemia Hyperlipidemia * Hypercholesterolemia/Hypertriglyceridemia * Lipoprotein lipase deficiency/Type Ia * Familial apoprotein CII deficiency/Type Ib * Familial hypercholesterolemia/Type IIa * Combined hyperlipidemia/Type IIb * Familial dysbetalipoproteinemia/Type III * Familial hypertriglyceridemia/Type IV * Xanthoma/Xanthomatosis Hypolipoproteinemia Hypoalphalipoproteinemia/HDL * Lecithin cholesterol acyltransferase deficiency * Tangier disease Hypobetalipoproteinemia/LDL * Abetalipoproteinemia * Apolipoprotein B deficiency * Chylomicron retention disease Lipodystrophy * Barraquer–Simons syndrome Other * Lipomatosis * Adiposis dolorosa * Lipoid proteinosis * APOA1 familial renal amyloidosis * v * t * e Inborn error of lipid metabolism: fatty-acid metabolism disorders Synthesis * Biotinidase deficiency (BTD) Degradation Acyl transport * Carnitine * CPT1 * CPT2 * CDSP * CACTD * Adrenoleukodystrophy (ALD) Beta oxidation General * Acyl CoA dehydrogenase * Short-chain SCADD * Medium-chain MCADD * Long-chain 3-hydroxy LCHAD * Very long-chain VLCADD * Mitochondrial trifunctional protein deficiency (MTPD): Acute fatty liver of pregnancy Unsaturated * 2,4 Dienoyl-CoA reductase deficiency (DECRD) Odd chain * Propionic acidemia (PCC deficiency) Other * 3-hydroxyacyl-coenzyme A dehydrogenase deficiency (HADHD) * Glutaric acidemia type 2 (MADD) To acetyl-CoA * Malonic aciduria (MCD) Aldehyde * Sjögren–Larsson syndrome (SLS) [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Carnitine palmitoyltransferase II deficiency	c0342790	3,885	wikipedia	https://en.wikipedia.org/wiki/Carnitine_palmitoyltransferase_II_deficiency	2021-01-18T18:52:23	{"gard": ["1121"], "mesh": ["C535589"], "umls": ["C0342790"], "orphanet": ["157"], "wikidata": ["Q2033861"]}
Megalencephalic leukoencephalopathy with subcortical cysts Other namesVacuolating megalencephalic leukoencephalopathy with subcortical cysts Megalencephalic leukoencephalopathy with subcortical cysts (MLC, or Van der Knaap disease) is a form of hereditary CNS demyelinating disease. It belongs to a group of disorders called leukodystrophies. ## Contents * 1 Genetics * 2 History * 3 References * 4 External links ## Genetics[edit] It is associated with MLC1.[1][2] ## History[edit] A series of cases with megalencephalic leukodystrophy were described by the Indian neurologist Bhim Sen Singhal (1933-)in 1991.[3][4][5] However, it is sometimes referred to as Van der Knaap disease after the Dutch neurologist Marjo van der Knaap who described another series of cases with clinical and radiological features in 1995.[6][7][8] ## References[edit] 1. ^ Ilja Boor PK, de Groot K, Mejaski-Bosnjak V, et al. (June 2006). "Megalencephalic leukoencephalopathy with subcortical cysts: an update and extended mutation analysis of MLC1". Hum. Mutat. 27 (6): 505–12. doi:10.1002/humu.20332. PMID 16652334. S2CID 3174994. 2. ^ "Megalencephalic leukoencephalopathy with subcortical cysts - Genetics Home Reference". Retrieved 2009-03-11. 3. ^ Singhal, BS; Gursahani, RD; Udani, VP; Biniwale, AA (May 1996). "Megalencephalic leukodystrophy in an Asian Indian ethnic group". Pediatric Neurology. 14 (4): 291–6. doi:10.1016/0887-8994(96)00048-3. PMID 8805171. 4. ^ Batla, A; Pandey, S; Nehru, R (January 2011). "Megalencephalic leukoencephalopathy with subcortical cysts: A report of four cases". Journal of Pediatric Neurosciences. 6 (1): 74–7. doi:10.4103/1817-1745.84416 (inactive 2021-01-10). PMC 3173924. PMID 21977097.CS1 maint: DOI inactive as of January 2021 (link) 5. ^ Singhal BS, Gursahani RD, Biniwale AA, Udani VP. Tokyo, Japan: In Proceedings of the 8th Asian and Oceanian Congress of Neurology; 1991. Megalencephalic leukodystrophy in India; p. 72. 6. ^ van der Knaap, Marjo S.; Wevers, Ron A.; Kure, Shigeo; Gabreëls, Fons J. M.; Verhoeven, Nanda M.; van Raaij-Selten, Bertie; Jaeken, Jaak (2 July 2016). "Increased Cerebrospinal Fluid Glycine: A Biochemical Marker for a Leukoencephalopathy With Vanishing White Matter". Journal of Child Neurology. 14 (11): 728–731. doi:10.1177/088307389901401108. PMID 10593550. S2CID 25535446. 7. ^ van der Knaap, MS; Barth, PG; Stroink, H; van Nieuwenhuizen, O; Arts, WF; Hoogenraad, F; Valk, J (March 1995). "Leukoencephalopathy with swelling and a discrepantly mild clinical course in eight children". Annals of Neurology. 37 (3): 324–34. doi:10.1002/ana.410370308. PMID 7695231. S2CID 29580717. 8. ^ van der Knaap, Marjo S; Boor, Ilja; Estévez, Raúl (November 2012). "Megalencephalic leukoencephalopathy with subcortical cysts: chronic white matter oedema due to a defect in brain ion and water homoeostasis". The Lancet Neurology. 11 (11): 973–985. doi:10.1016/S1474-4422(12)70192-8. PMID 23079554. S2CID 31690619. ## External links[edit] Classification D * ICD-10: E75.2 * OMIM: 604004 * MeSH: C536141 * DiseasesDB: 33813 External resources * GeneReviews: Megalencephalic Leukoencephalopathy with Subcortical Cysts * Orphanet: 2478 * GeneReview/NIH/UW entry on Megalencephalic Leukoencephalopathy with Subcortical Cysts * v * t * e Diseases of the nervous system, primarily CNS Inflammation Brain * Encephalitis * Viral encephalitis * Herpesviral encephalitis * Limbic encephalitis * Encephalitis lethargica * Cavernous sinus thrombosis * Brain abscess * Amoebic Brain and spinal cord * Encephalomyelitis * Acute disseminated * Meningitis * Meningoencephalitis Brain/ encephalopathy Degenerative Extrapyramidal and movement disorders * Basal ganglia disease * Parkinsonism * PD * Postencephalitic * NMS * PKAN * Tauopathy * PSP * Striatonigral degeneration * Hemiballismus * HD * OA * Dyskinesia * Dystonia * Status dystonicus * Spasmodic torticollis * Meige's * Blepharospasm * Athetosis * Chorea * Choreoathetosis * Myoclonus * Myoclonic epilepsy * Akathisia * Tremor * Essential tremor * Intention tremor * Restless legs * Stiff-person Dementia * Tauopathy * Alzheimer's * Early-onset * Primary progressive aphasia * Frontotemporal dementia/Frontotemporal lobar degeneration * Pick's * Dementia with Lewy bodies * Posterior cortical atrophy * Vascular dementia Mitochondrial disease * Leigh syndrome Demyelinating * Autoimmune * Inflammatory * Multiple sclerosis * For more detailed coverage, see Template:Demyelinating diseases of CNS Episodic/ paroxysmal Seizures and epilepsy * Focal * Generalised * Status epilepticus * For more detailed coverage, see Template:Epilepsy Headache * Migraine * Cluster * Tension * For more detailed coverage, see Template:Headache Cerebrovascular * TIA * Stroke * For more detailed coverage, see Template:Cerebrovascular diseases Other * Sleep disorders * For more detailed coverage, see Template:Sleep CSF * Intracranial hypertension * Hydrocephalus * Normal pressure hydrocephalus * Choroid plexus papilloma * Idiopathic intracranial hypertension * Cerebral edema * Intracranial hypotension Other * Brain herniation * Reye syndrome * Hepatic encephalopathy * Toxic encephalopathy * Hashimoto's encephalopathy Both/either Degenerative SA * Friedreich's ataxia * Ataxia–telangiectasia MND * UMN only: * Primary lateral sclerosis * Pseudobulbar palsy * Hereditary spastic paraplegia * LMN only: * Distal hereditary motor neuronopathies * Spinal muscular atrophies * SMA * SMAX1 * SMAX2 * DSMA1 * Congenital DSMA * Spinal muscular atrophy with lower extremity predominance (SMALED) * SMALED1 * SMALED2A * SMALED2B * SMA-PCH * SMA-PME * Progressive muscular atrophy * Progressive bulbar palsy * Fazio–Londe * Infantile progressive bulbar palsy * both: * Amyotrophic lateral sclerosis This genetic disorder article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Megalencephalic leukoencephalopathy with subcortical cysts	c1858854	3,886	wikipedia	https://en.wikipedia.org/wiki/Megalencephalic_leukoencephalopathy_with_subcortical_cysts	2021-01-18T18:40:16	{"gard": ["3445"], "mesh": ["C536141"], "icd-10": ["E75.2"], "orphanet": ["2478"], "wikidata": ["Q3237080"]}
Congenital disorder of glycosylation type Ia (CDG-Ia) is an inherited condition that affects many parts of the body. The type and severity of problems associated with CDG-Ia vary widely among affected individuals, sometimes even among members of the same family. Signs and symptoms are typically evident in infancy and can include hypotonia, inverted nipples, an abnormal distribution of fat, strabismus, developmental delay, failure to thrive, seizures, and distinctive facial features. About 20 percent of affected infants do not survive the first year of life due to multiple organ failure. The most severe cases of CDG-Ia are characterized by hydrops fetalis. This condition is caused by mutations in the PMM2 gene and is inherited in an autosomal recessive fashion. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	PMM2-CDG (CDG-Ia)	c0349653	3,887	gard	https://rarediseases.info.nih.gov/diseases/9826/pmm2-cdg-cdg-ia	2021-01-18T17:58:17	{"mesh": ["C535739"], "omim": ["212065"], "umls": ["C0349653"], "orphanet": ["79318"], "synonyms": ["CDG 1A", "CDG1A", "Jaeken syndrome", "Carbohydrate-deficient glycoprotein syndrome type 1A", "Phosphomannomutase 2 deficiency", "Carbohydrate-deficient glycoprotein syndrome type 1A (formerly)", "Congenital disorder of glycosylation, type Ia ", "CDG syndrome type Ia", "CDG-Ia", "Carbohydrate deficient glycoprotein syndrome type Ia", "Congenital disorder of glycosylation type 1a", "Congenital disorder of glycosylation type Ia", "PMM2-CDG"]}
Hyperacusis is a hearing disorder that results in difficulty tolerating sounds that would not bother most people. This condition may occur due to many different causes, such as head injury, viral infections, or neurological disorders. In some people with hyperacusis, sounds are perceived as being much louder than they would be by someone without this disorder. Some people may have emotional reactions to sounds, such as being annoyed or afraid. Others experience pain with low-level sounds. People with hyperacusis can have only one or different combinations of these symptoms. Another very common symptom is ringing in the ears (tinnitus). Patients with hyperacusis typically first receive an otolaryngologic exam and hearing testing. These tests can be done by an Audiologist or an Otolaryngologist (ear, nose, and throat doctor). Treatment may involve a program of sound therapy to train the brain to better process everyday sounds. This type of treatment involves listening to low-level white noise to gradually improve the ability to hear sounds. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Hyperacusis	c0034880	3,888	gard	https://rarediseases.info.nih.gov/diseases/9655/hyperacusis	2021-01-18T17:59:56	{"mesh": ["D012001"], "synonyms": ["Low tolerance to sound"]}
For a phenotypic description and a discussion of genetic heterogeneity of juvenile myoclonic epilepsy (JME), see 254770. JME is a form of idiopathic generalized epilepsy (IGE; 600669). Clinical Features Kapoor et al. (2007) reported a family from southern India in which 8 individuals had juvenile myoclonic epilepsy inherited in an autosomal dominant pattern. The proband was a 32-year-old woman who developed morning myoclonic jerks at age 14 years and generalized tonic-clonic seizures at age 20. EEG recordings showed polyspike and wave discharges characteristic of a generalized epilepsy. Other affected members had a similar history. None had absence or febrile seizures. Response to medication was good. Mapping By genomewide linkage analysis of an Indian family with juvenile myoclonic seizures, Kapoor et al. (2007) identified a candidate locus, referred to here as EJM4, on chromosome 5q12-q14 (2-point lod score of 3.33 at D5S459; parametric multipoint lod score of 3.33 at D5S641 and D5S459). Haplotype analysis delineated a 25-Mb region between D5S624 and D5S428. INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Seizures, myoclonic \- Generalized tonic-clonic seizures \- EEG shows generalized polyspike and wave discharges (4-5 Hz) MISCELLANEOUS \- Onset between 9 and 16 years \- Myoclonic seizures occur on awakening or within 2 hours of awakening \- Good response to medication ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	MYOCLONIC EPILEPSY, JUVENILE, SUSCEPTIBILITY TO, 4	c0270853	3,889	omim	https://www.omim.org/entry/611364	2019-09-22T16:03:23	{"doid": ["0111327"], "mesh": ["D020190"], "omim": ["611364"], "orphanet": ["307"]}
This article includes a list of references, related reading or external links, but its sources remain unclear because it lacks inline citations. Please help to improve this article by introducing more precise citations. (March 2016) (Learn how and when to remove this template message) Moore's lightning streaks are lightning type streaks (photopsia) (seen to the temporal side) due to sudden head or eye movement in the dark. They are generally caused by shock waves in the vitreous humor hitting the retina or traction on the retina from fibers in the vitreous humor. The implication is that the vitreous is softer than normal, generally this is not a cause for alarm provided they are momentary, occur only in the dark, are due to sudden head movements (acceleration) and do not occur along with many new tiny black floating specks in the vision. Professional advice should be sought in cases of doubt, as retinal detachment, a serious condition, also can cause flashes in the eye. They are named after Robert Foster Moore (1878–1963), a British ophthalmologist. ## References[edit] * Moore R: Subjective lightning flashes. Am J Ophthalmol 23: 1255, 1940 * Verhoeff FH. "Are Moore's lightning streaks of serious portent?" Am J Ophthalmol. 1956 May;41(5):837–40. PMID 13313677. This article about the eye is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Moore's lightning streaks	None	3,890	wikipedia	https://en.wikipedia.org/wiki/Moore%27s_lightning_streaks	2021-01-18T18:33:26	{"wikidata": ["Q6908107"]}
Disorder of written expression SpecialtyNeurology Disorder of written expression is a type of learning disability in which a person’s writing ability falls substantially below normally expected range based on the individual’s age, educational background, and measured intelligence. Poor writing skills must interfere significantly with academic progress or daily activities that involves written expression[1] (spelling, grammar, handwriting, punctuation, word usage, etc.).[2] This disorder is also generally concurrent with disorders of reading and/or mathematics, as well as disorders related to behavior. Since it is so often associated with other learning disorders and mental problems, it is uncertain whether it can appear by itself.[3] The prevalence of disorder of written expression is estimated to be of a similar frequency to other learning disorders, between 3 - 5%.[citation needed] A diagnosis can be made based on results of several assessments.[4] ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Other disabilities * 3 Diagnosis * 4 Treatment * 5 References * 6 External links ## Signs and symptoms[edit] * Multiple spelling mistakes * Errors in grammar and punctuation * Exceptionally poor or illegible writing * Sentences that lack cohesion [5] * Reluctance or refusal to complete writing tasks * Anxiety or frustration (breaking pencils, tearing up homework assignments, )[6] ## Causes[edit] Specific causes of this disorder are unknown. The interaction of physical, psychological, and environmental factors is thought to contribute to the disorder of written expression. In neuropsychological and neurobiological research, some studies show evidence that abnormally high testosterone levels and abnormalities in cognitive processes (visual-motor, linguistic, attentional, and memory) are thought to play a role in learning disorder cases. The impact of brain injuries in both children and adults can impair any of these cognitive processes.[4] ### Other disabilities[edit] * Dyslexia * Reading disability * Expressive language disorder * Mathematics disorder * Developmental coordination disorder * Traumatic brain injury[7] ## Diagnosis[edit] * Oral and Written Language Scales (OWLS) * Test of Adolescent and Adult Language–3 (TOAL-3) * Test of Early Written Language * Test of Written Expression (TOWE) * Test of Written Language–3 (TOWL-3) * Woodcock Johnson Psychoeducational Battery–Revised, Tests of Achievement * Weschler Individual Achievement Test (WIAT) ## Treatment[edit] Although disorder for written expressions skills can be difficult and an enduring problem all throughout childhood into adulthood, different types of treatment and support can help individuals who have this disorder to employ strategies and skills in the home and school environment. This includes remedial education tailored to improve specific skills, providing special academic services in the learning environment, and addressing concurrent health and mental issues. It is sometimes necessary to foster motivational techniques to maintain motivation and minimize negative thoughts or feelings. Using whatever modifications are necessary to overcome fears of failure in the early stages of writing mediation is strongly encouraged because children with learning disabilities often experience low self-esteem and confidence, which may further interfere with learning and academic success.[8] ## References[edit] 1. ^ "A 15 Disorder of Written Expression". American Psychiatric Association DSM-5 Development. American Psychiatric Association. Retrieved 2 April 2012. 2. ^ "Disorder of Written Expression". Psych Central. Psych Central. Retrieved 2 April 2012. 3. ^ "Written Expression Learning Disorder (Overview)". Medscape Reference. WebMD LLC. 4. ^ a b "Written Expression Learning Disorder (Presentation)". Medscape Reference. WebMD LLC. Retrieved 2 April 2012. 5. ^ "Disorder of Written Expression". Encyclopedia of Mental Disorders. Advameg, Inc. Retrieved 2 April 2012. 6. ^ "Written Expression Learning Disorder (Workup)". Medscape Reference. WebMD LLC. Retrieved 2 April 2012. 7. ^ Wheeler, L., Nickerson, S., Long, K., & Silver, R. (2014). Expressive writing in people with traumatic brain injury and learning disability. Neurorehabilitation, 34(1), 29-37. doi:10.3233/NRE-131007 8. ^ "Written Expression Learning Disorder (Treatment)". Medscape Reference. WebMD LLC. Retrieved 2 April 2012. ## External links[edit] Classification D * ICD-10: F81.8 * ICD-9-CM: 315.2 * v * t * e Dyslexia and related specific developmental disorders Conditions Speech, language, and communication * Expressive language disorder * Infantile speech * Landau–Kleffner syndrome * Language disorder * Lisp * Mixed receptive-expressive language disorder * Specific language impairment * Speech and language impairment * Speech disorder * Speech error * Speech sound disorder * Stuttering * Tip of the tongue Learning disability * Dyslexia * Dyscalculia * Dysgraphia * Disorder of written expression Motor * Developmental coordination disorder * Developmental verbal dyspraxia Sensory * Auditory processing disorder * Sensory processing disorder Related topics * Dyslexia research * Irlen filters * Learning Ally * Learning problems in childhood cancer * Literacy * Management of dyslexia * Multisensory integration * Neuropsychology * Reading acquisition * Spelling * Writing system Lists * Dyslexia in fiction * Languages by Writing System * People with dyslexia [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Disorder of written expression	c0236825	3,891	wikipedia	https://en.wikipedia.org/wiki/Disorder_of_written_expression	2021-01-18T18:31:06	{"icd-9": ["315.2"], "icd-10": ["F81.1"], "wikidata": ["Q5282510"]}
## Clinical Features Onwukwe et al. (1973) described a family in which multiple members of 4 generations and by inference a fifth, in a pattern consistent with autosomal dominant inheritance (including male-to-male transmission), had persistent, asymptomatic, yellowish-white, translucent papules and plaques on the hands and feet, associated with fine-textured scalp hair and atopic diathesis. Histologic study of the translucent lesions showed orthohypergranulosis, acanthosis, and a relatively normal dermis. Onwukwe et al. (1973) suggested that this might be a new variant of familial punctate keratoderma. De Wit and Hulsmans (1986) observed a Suriname woman with abnormalities of palmar and plantar skin. Her father was reported to have similar changes confined to the feet. The index patient was observed to have both classical keratosis punctata palmaris et plantaris (175860) and papulotranslucent acrokeratoderma. Sracic et al. (2005) reported a 27-year-old female who developed white translucent papules bilaterally on her palms, and to a lesser extent, on her soles, at age 21 years. The palmar lesions became dramatically pronounced immediately after taking showers, and would lessen in severity after approximately 1 hour. She had fine-textured scalp hair, and her mother and brother had a history of asthma. There was no associated palmar hyperhidrosis or history of exposure to arsenic. The patient's maternal grandmother, mother, sister, and 2 half-brothers all had similar, though less severe, symptoms; her maternal grandmother, mother, and 1 half brother also had a history of Hailey-Hailey disease (BCPM; 169600). Hair \- Fine-textured scalp hair Inheritance \- Autosomal dominant Immunology \- Atopic diathesis Lab \- Skin lesions show orthohypergranulosis, acanthosis, and a relatively normal dermis Skin \- Persistent, asymptomatic, yellowish-white, translucent papules and plaques of hands and feet ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	ACROKERATODERMA, HEREDITARY PAPULOTRANSLUCENT	c1863343	3,892	omim	https://www.omim.org/entry/101840	2019-09-22T16:45:28	{"mesh": ["C566323"], "omim": ["101840"]}
HEC syndrome Other namesHydrocephalus-endocardial fibroelastosis-cataract syndrome HEC syndrome is a syndrome characterized by hydrocephalus, endocardial fibroelastosis and cataracts.[1] ## References[edit] 1. ^ Devi A, Eisenfeld L, Uphoff D, Greenstein R (1995). "New syndrome of hydrocephalus, endocardial fibroelastosis, and cataracts (HEC syndrome)". Am J Med Genet. 56 (1): 62–6. doi:10.1002/ajmg.1320560114. PMID 7747788. ## External links[edit] Classification D * ICD-10: Q87.8 * OMIM: 600559 * MeSH: C535855 External resources * Orphanet: 2119 * Online Mendelian Inheritance in Man (OMIM): 600559 This article about a disease, disorder, or medical condition is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	HEC syndrome	c1833607	3,893	wikipedia	https://en.wikipedia.org/wiki/HEC_syndrome	2021-01-18T18:39:19	{"gard": ["2620"], "mesh": ["C535855"], "umls": ["C1833607"], "orphanet": ["2119"], "wikidata": ["Q5629424"]}
Cataract-ataxia-deafness syndrome is characterised by mild intellectual deficit, congenital cataract, progressive sensorineural deafness and ataxia. It has been described in two sisters. The inheritance is likely to be autosomal recessive. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Cataract-ataxia-deafness syndrome	c0796123	3,894	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1368	2021-01-23T18:46:07	{"gard": ["1141"], "mesh": ["C538283"], "omim": ["212710"], "umls": ["C0796123"], "icd-10": ["G11.2"], "synonyms": ["Cataract-ataxia-hearing loss syndrome"]}
Subaortic course of innominate vein is a rare congential anomaly of the great veins characterized by an anomalous course of the left brachiocephalic vein, passing from left to right below the aortic arch and entering the superior vena cava below the orifice of the azygos vein. Patients are frequently asymptomatic and diagnosed incidentally on imaging studies. Other cardiac malformations may be associated. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Subaortic course of innominate vein	c4707821	3,895	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99113	2021-01-23T16:55:48	{"icd-10": ["Q26.8"], "synonyms": ["Subaortic course of brachiocephalic vein"]}
Extranodal nasal NK/T cell lymphoma (NKTCL) is a rare, malignant neoplasm mainly affecting men in the fifth decade of life, that usually arises in the nose, paranasal sinuses, orbits or upper airway, and that can present with a nasal mass, nasal bleeding, nasal obstruction, palate perforation (i.e. midline perforation of the hard palate), and mid-facial and/or upper airway destructive lesions. In advanced disease stages, which are associated with a poor prognosis, NKTCL may disseminate to other organs. A few cases of NKTCL presenting primarily in the lymph nodes have also been described. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Extranodal nasal NK/T cell lymphoma	c0018197	3,896	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=86879	2021-01-23T18:29:56	{"mesh": ["D054391", "D006103"], "umls": ["C0018197", "C0392788"], "icd-10": ["C86.0"], "synonyms": ["Angiocentric T-cell lymphoma", "Lethal midline granuloma", "NK/T-cell lymphoma", "NKTCL", "Nasal T/natural killer-cell lymphoma"]}
Papillary stenosis is a disturbance of the sphincter of Oddi, a muscular valve, that prevents the opening and release of bile or pancreatic fluids into the duodenum in response to food entering the duodenum. Obstruction of the valve can cause: * pancreatic pain * jaundice - bile leaking back into the blood stream. * attacks of pancreatitis ## Contents * 1 Causes * 2 Diagnosis and treatment * 3 See also * 4 External links * 5 References ## Causes[edit] * passage of stones * scarring * Gluten-sensitive enteropathy[1] * Autoimmune pancreatitis[2] ## Diagnosis and treatment[edit] * Endoscopic examination[3] * Usually treated surgically, usually involving papillotomy, that is, an incision in the sphincter. ## See also[edit] * Sphincter of Oddi dysfunction ## External links[edit] * Papillary Stenosis: Sphincter of Oddi Dysfunction ## References[edit] 1. ^ Patel RS, Johlin FC, Murray JA (1999). "Celiac disease and recurrent pancreatitis". Gastrointest. Endosc. 50 (6): 823–827. doi:10.1016/S0016-5107(99)70166-5. PMID 10570344. 2. ^ Löhr JM (2007). "What are the useful biological and functional markers of early-stage chronic pancreatitis?". J. Gastroenterol. 42. Suppl 17 (S17): 66–71. doi:10.1007/s00535-006-1932-9. PMID 17238031. 3. ^ Koch H, Classen M, Schaffner O, Demling L (1975). "Endoscopic papillotomy. Experimental studies and initial clinical experience". Scand. J. Gastroenterol. 10 (4): 441–4. doi:10.3109/00365528708996456. PMID 1153938. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Papillary stenosis	c0238340	3,897	wikipedia	https://en.wikipedia.org/wiki/Papillary_stenosis	2021-01-18T18:44:12	{"umls": ["C0941093"], "wikidata": ["Q7132988"]}
A number sign (#) is used with this entry because autosomal dominant hypogonadotropic hypogonadism-6 with or without anosmia (HH6) is caused by heterozygous mutation in the fibroblast growth factor-8 gene (FGF8; 600483) on chromosome 10q24, sometimes in association with mutation in another gene, e.g., FGFR1 (136350). Description Congenital idiopathic hypogonadotropic hypogonadism (IHH) is a disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. Idiopathic hypogonadotropic hypogonadism can be caused by an isolated defect in gonadotropin-releasing hormone (GNRH; 152760) release, action, or both. Other associated nonreproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss, occur with variable frequency. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism has been called 'Kallmann syndrome (KS),' whereas in the presence of a normal sense of smell, it has been termed 'normosmic idiopathic hypogonadotropic hypogonadism (nIHH)' (summary by Raivio et al., 2007). Because families have been found to segregate both KS and nIHH, the disorder is here referred to as 'hypogonadotropic hypogonadism with or without anosmia (HH).' For a discussion of genetic heterogeneity of hypogonadotropic hypogonadism with or without anosmia as well as a discussion of oligogenicity of this disorder, see 147950. Clinical Features Trarbach et al. (2010) identified 2 families with hypogonadotropic hypogonadism-6 with or without anosmia. The proband in the first family had HH6 with primary amenorrhea and moderate microsmia. Among the other 4 affected sibs, 2 had hypogonadotropic hypogonadism (a female with primary amenorrhea and a male with micropenis) and 2 females had pubertal delay; all 4 were normosmic. One of the affected sibs also had cleft lip and palate. In the second family, the proband had hypogonadotropic hypogonadism with micropenis, cryptorchidism, and azoospermia. His sister had hypogonadotropic hypogonadism with primary amenorrhea. Both were normosmic. Molecular Genetics Using a candidate gene approach, Falardeau et al. (2008) screened the FGF8 gene in 461 unrelated probands with idiopathic hypogonadotropic hypogonadism, including 193 normosmic patients, 237 anosmic patients, and 21 patients with adult-onset IHH. They identified 6 mutations in the FGF8 gene, in 2 familial cases of Kallmann syndrome (600483.0002 and 600483.0005, respectively), 1 familial case of IHH (600483.0004), 2 sporadic cases of IHH (600483.0001 and 600483.0003, respectively) and 1 case of adult-onset IHH (600483.0006). Probands harboring an FGF8 mutation were screened for other loci underlying IHH, and 2 probands with normosmic IHH (see 600483.0003 and 600483.0004, respectively) were found to carry additional mutations in the FGFR1 gene (see 136350.0023-136350.0025, respectively). None of the FGF8 mutations were found in 180 ethnically matched controls. Structural and in vitro biochemical analysis of the FGF8 mutations, all of which were at highly conserved residues, demonstrated loss of function for all 4 FGF8 isoforms in 4 mutations and loss of function for the FGF8 isoforms involved in GnRH neuronal development in 2 mutations. By sequencing the FGF8 gene in 2 unrelated probands from Brazil with hypogonadotropic hypogonadism-6, one with and one without anosmia, Trarbach et al. (2010) identified different heterozygous nonsense mutations (R127X, 600483.0007 and R129X, 600483.0008). Both patients had a family history of the disorder. Both mutations mapped to the core domain of the protein, affected all 4 FGF8 isoforms, and led to deletion of a large portion of the protein, predicted to result in nonfunctional FGF8 ligands. The mutations were not found in 150 Brazilian control individuals. INHERITANCE \- Autosomal dominant HEAD & NECK Nose \- Anosmia (in some patients) \- Hyposmia (in some patients) Mouth \- High-arched palate \- Cleft lip and palate CHEST Breasts \- No breast development GENITOURINARY External Genitalia (Male) \- Hypogonadism \- Micropenis Internal Genitalia (Male) \- Low testicular volume \- Undescended testes Internal Genitalia (Female) \- Primary amenorrhea \- Prepubertal uterus \- Small ovaries SKELETAL \- Delayed bone age \- Low bone density Limbs \- Eunuchoidal proportions Hands \- Hyperlaxity of digits NEUROLOGIC Central Nervous System \- Small pituitary gland \- Partial empty sella \- Hypoplastic olfactory bulbs and tracts (in some patients) ENDOCRINE FEATURES \- Delayed or absent puberty \- Low or undetectable serum estradiol (E2) levels \- Apulsatile luteinizing hormone (LH) secretion pattern \- Undetectable LH levels \- Low or undetectable follicle-stimulating hormone (FSH) levels \- Low or undetectable testosterone levels MISCELLANEOUS \- Intrafamilial phenotypic variability MOLECULAR BASIS \- Caused by mutation in the fibroblast growth factor-8 gene (FGF8, 600483.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	HYPOGONADOTROPIC HYPOGONADISM 6 WITH OR WITHOUT ANOSMIA	c0162809	3,898	omim	https://www.omim.org/entry/612702	2019-09-22T16:00:44	{"doid": ["0090086"], "mesh": ["D017436"], "omim": ["612702"], "orphanet": ["432", "478"], "synonyms": ["Gonadotropic deficiency", "Isolated congenital gonadotropin deficiency", "Normosmic idiopathic hypogonadotropic hypogonadism", "nIHH"], "genereviews": ["NBK1334"]}
This article may be too technical for most readers to understand. Please help improve it to make it understandable to non-experts, without removing the technical details. (February 2019) (Learn how and when to remove this template message) Robertsonian translocation (ROB) is a chromosomal abnormality wherein a certain type of a chromosome becomes attached to another. It is the most common form of chromosomal translocation in humans, affecting 1 out of every 1,000 babies born. It does not usually cause health difficulties, but can in some cases result in genetic disorders such as Down syndrome and Patau syndrome.[1] Robertsonian translocations result in a reduction in the number of chromosomes. ## Contents * 1 Mechanism * 2 Consequences * 3 Name * 4 References ## Mechanism[edit] Chromosome arms can have different length ratios. Robertsonian translocation occurs in acrocentric chromosome pairs (number `II` in the image), where the short arms are fairly short but not very short. A: Short arm (p arm) B: Centromere C: Long arm (q arm) D: Sister chromatids In humans, Robertsonian translocations occur in the five acrocentric chromosome pairs (chromosome pairs where the short arms are fairly short), namely 13, 14, 15, 21 and 22. The participating chromosomes break at their centromeres and the long arms fuse to form a single, large chromosome with a single centromere. A Robertsonian translocation is a type of translocation involving two homologous (paired) or non-homologous chromosomes (i.e. two different chromosomes, not belonging to a homologous pair). A feature of chromosomes that are commonly found to undergo such translocations is that they possess an acrocentric centromere, partitioning the chromosome into a large arm containing the vast majority of its genes, and a short arm with a much smaller proportion of genetic content. The short arms also join to form a smaller reciprocal product, which typically contains only nonessential genes also present elsewhere in the genome, and is usually lost within a few cell divisions. This type of translocation is cytologically visible, and can reduce chromosome number (from 23 to 22 pairs, in humans) if the smaller chromosome that results from a translocation is lost in the process of future cellular divisions. However, the smaller chromosome lost may carry so few genes (which are, in any case, also present elsewhere in the genome) that it can be lost without an ill effect to the individual.[2][3] ## Consequences[edit] In humans, when a Robertsonian translocation joins the long arm of chromosome 21 with the long arm of chromosomes 14 or 15, the heterozygous carrier is phenotypically normal because there are two copies of all major chromosome arms and hence two copies of all essential genes.[4] However, the progeny of this carrier may inherit an unbalanced trisomy 21, causing Down syndrome. About one in a thousand newborns have a Robertsonian translocation.[5] The most frequent forms of Robertsonian translocations are between chromosomes 13 and 14, 14 and 21, and 14 and 15.[1] A Robertsonian translocation in balanced form results in no excess or deficit of genetic material and causes no health difficulties. In unbalanced forms, Robertsonian translocations cause chromosomal deletions or addition and result in syndromes of multiple malformations, including trisomy 13 (Patau syndrome) and trisomy 21 (Down syndrome). A Robertsonian translocation results when the long arms of two acrocentric chromosomes fuse at the centromere and the two short arms are lost. If, for example, the long arms of chromosomes 13 and 14 fuse, no significant genetic material is lost—and the person is completely normal in spite of the translocation. Common Robertsonian translocations are confined to the acrocentric chromosomes 13, 14, 15, 21 and 22, because the short arms of these chromosomes encode for rRNA which is present in multiple copies. Most people with Robertsonian translocations have only 45 chromosomes in each of their cells, yet all essential genetic material is present, and they appear normal. Their children, however, may either be normal, carry the fusion chromosome (depending which chromosome is represented in the gamete), or they may inherit a missing or extra long arm of an acrocentric chromosome (phenotype affected). Genetic counseling and genetic testing is offered to families that may be carriers of chromosomal translocations. Rarely, the same translocation may be present homozygously if heterozygous parents with the same Robertsonian translocation have children. The result may be viable offspring with 44 chromosomes.[6] ## Name[edit] Robertsonian translocations are named after the American zoologist and cytogeneticist William Rees Brebner Robertson (1881–1941) who first described a Robertsonian translocation in grasshoppers in 1916.[2] They are also called whole-arm translocations or centric-fusion translocations. ## References[edit] 1. ^ a b Unique: Rare Chromosome Disorder Support Group 2. ^ a b Robertson WRB. Chromosome studies. I. Taxonomic relationships shown in the chromosomes of Tettigidae and Acrididae. V-shaped chromosomes and their significance in Acrididae, Locustidae and Gryllidae: chromosome and variation. J Morph 1916;27:179-331. 3. ^ Hartwell, Leland; Hood, Leroy; Goldberg, Michael; Reynolds, Ann; Silver, Lee (2011). Genetics From Genes to Genomes, 4e. New York: McGraw-Hill. pp. 443, 454. ISBN 9780073525266. 4. ^ Peter J. Russel; Essential Genetics 2003 5. ^ E. Therman, B. Susman and C. Denniston. The nonrandom participation of human acrocentric chromosomes in Robertsonian translocations. Annals of Human Genetics 1989;53:49-65. 6. ^ Martinez-Castro P, Ramos MC, Rey JA, Benitez J, Sanchez Cascos A (1984). "Homozygosity for a Robertsonian translocation (13q14q) in three offspring of heterozygous parents". Cytogenet Cell Genet. 38: 310–2. doi:10.1159/000132080. PMID 6510025. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Robertsonian translocation	c0333715	3,899	wikipedia	https://en.wikipedia.org/wiki/Robertsonian_translocation	2021-01-18T18:39:54	{"wikidata": ["Q2914875"]}

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