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Neurofibromatosis type 3
Other namesNeurofibromatosis mixed type
SpecialtyNeurosurgery
Neurofibromatosis type 3 (also known as "Neurofibromatosis mixed type") resembles von Recklinghausen's disease, but also presents with cutaneous neurofibromas.[1]:552
## See also[edit]
* Neurofibromatosis
* Skin lesion
## References[edit]
1. ^ 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: Q85.0
* OMIM: 601321
* MeSH: C536641
External resources
* Orphanet: 93921
This Genodermatoses article is a stub. You can help Wikipedia by expanding it.
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*[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
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*[MSNs]: medium spiny neurons
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*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
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*[GER]: Germany
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*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
| Neurofibromatosis type 3 | c0917817 | 5,100 | wikipedia | https://en.wikipedia.org/wiki/Neurofibromatosis_type_3 | 2021-01-18T18:28:38 | {"mesh": ["D017253"], "wikidata": ["Q16929881"]} |
Pulp necrosis is a clinical diagnostic category indicating the death of cells and tissues in the pulp chamber of a tooth with or without bacterial invasion.[1] It is often the end result of many cases of dental trauma, caries and irreversible pulpitis.
In the initial stage of the infection, the pulp chamber is partially necrosed for a period of time and if left untreated, the area of cell death expands until the entire pulp necroses. The most common clinical signs present in a tooth with a necrosed pulp would be a grey discoloration of the crown and/or periapical radiolucency. This altered translucency in the tooth is due to disruption and cutting off of the apical neurovascular blood supply.[2]
Sequelae of a necrotic pulp include acute apical periodontitis, dental abscess or radicular cyst and discolouration of the tooth.[citation needed] Tests for a necrotic pulp include: vitality testing using a thermal test or an electric pulp tester. Discolouration may be visually obvious, or more subtle.
Treatment usually involves endodontics or extraction.[citation needed]
## Contents
* 1 Histopathology
* 1.1 Odontoblasts
* 1.2 Inflammation
* 2 Aetiology and Causes
* 2.1 Causes
* 2.1.1 Dental Caries
* 2.1.2 Dental Trauma
* 2.1.3 Dental Treatment
* 2.1.4 Pulpitis
* 3 Signs and symptoms
* 3.1 Pain
* 3.2 Crown discolouration
* 3.3 Abscess and/or fistula
* 3.4 Internal root resorption
* 4 Diagnosis
* 4.1 Thermal Tests
* 4.2 Pulse Oximeter Test
* 4.3 3-Tesla Magnetic Resonance Imaging
* 5 Management & Treatment
* 6 References
## Histopathology[edit]
The dental pulp is located in the centre of a tooth, made up of living connective tissue and cells.[3] It is surrounded by a rigid, hard and dense layer of dentine[3] which limits the ability of the pulp to tolerate excessive build up of fluid. Normal interstitial fluid pressure in the pulp ranges from 5-20mm Hg, marked increases in pressure in the pulp due to inflammation can go up to 60mm Hg.[4] The rise in pressure is commonly associated with an inflammatory exudate causing local collapse of the venous part of microcirculation. Tissues get starved of oxygen thus causing venules and lymphatics collapse which may lead to localized necrosis.[5] A common clinical sign associated with the histopathology will be varying levels of suppuration and purulence.[6]
Following the spread of local inflammation, chemical mediators such as IL-8, IL-6 and IL-1[7] are released from necrotic tissues leading to further inflammation and odema, which advances to total necrosis of the pulp.[5]
Further stages of destruction of pulp necrosis often leads to periapical pathosis, causing bone resorption (visible on radiographs) following bacterial invasion. The apical periodontal ligament (PDL) space widens and becomes continuous with apical radiolucency; the lamina dura of the apical area will also be lost.[7] The periapical lesion will enlarged with time and consequently, the pulp will be diagnosed as necrotic.
The pulp can respond (reversible pulpitis, irreversible pulpitis, partial necrosis, total necrosis) in a variety of ways to irritants. This response depends on the severity and duration of the irritant involved. If the irritant is severe or persists for a sustained amount of time it can cause the odontoblasts to die and cause initiation of an inflammatory response.
### Odontoblasts[edit]
The odontoblast cell bodies decrease in number and size before any inflammatory changes occur. The outward flow of tubular fluid can cause the nuclei of odontoblasts to be aspirated into the dentinal tubules. The odontoblasts may also be permanently damaged which causes them to release tissue injury factors which can then influence adjacent odontoblasts and underlying connective tissue. Odontoblasts can undergo vacuolization, a decrease in the number and size of the endoplasmic reticulum, and degeneration of mitochondria. It is unknown by which process (apoptosis or necrosis) the odontoblasts die.
### Inflammation[edit]
Lymphocytes, plasma cells and macrophages comprise the initial inflammatory infiltrate. In response to bacterial assault and tissue injury non-specific inflammatory mediators are released. These inflammatory mediators include histamine, bradykinin, serotonin, interleukins (IL) and metabolites of arachidonic acid. They can interact with neuropeptides (substance P) and calcitonin gene-related peptide (CGRP) during the inflammatory response. Destruction of the nerve fibres causes neuropeptides to be released into pulp. The neuropeptides can cause an increase vascular permeability and vasodilation. The filtration of serum proteins and fluid from the vessel causes the tissue to become oedematous. The tissue pressure increases as the blood volume and interstitial fluid volume rises. The thin-walled venules are compressed and the resistance to flow in these vessels increases. This is accompanied with a decrease in blood flow causing an aggregation of red blood cells and subsequent increase in blood viscosity. This tissue also becomes ischaemic which suppresses the cellular metabolism in the area of the pulp that is affected. This causes necrosis.[8] Necrosis is a histological term that means death of the pulp.[9] It does not occur suddenly unless there has been trauma. The pulp may be partially necrotic for some time. The area of cell death enlarges until the entire pulp is necrotic. Bacteria invade the pulp which causes the root canal system to become infected.[10] Teeth that have total pulpal necrosis are usually asymptomatic except for those that have inflammation which has progressed to the periradicular tissues.
## Aetiology and Causes[edit]
Pulp necrosis arises due to the cellular death within the pulp chamber – this can occur with or without the involvement of bacteria.[1] It is the result of various connective tissue disease progressions which occur in stages; normal healthy tissue becomes inflamed (i.e. pulpitis) which if left untreated leads to necrosis and infection and finally resulting in loss of pulp tissue (i.e. pulpless canals)[11]
### Causes[edit]
* Dental Caries
* Dental Trauma
* Dental Treatment
* Pulpitis
* Infection
#### Dental Caries[edit]
The influx of bacteria and growth of a carious lesion (if gross and left untreated) inevitably leads to the centre of the tooth – the pulp chamber. Once this tissue damaging process reaches the pulp it results in irreversible changes – necrosis and pulpal infection.[12][13]
#### Dental Trauma[edit]
When a tooth is displaced from its normal position as a result of dental trauma, it can result in pulp necrosis due to the apical blood supply being compromised. This might be due to displacement of the tooth through avulsion or luxation. Furthermore, if the tooth is severely damaged, it could lead to inflammation of the apical periodontal ligament, and subsequently pulp necrosis.[11]
#### Dental Treatment[edit]
Pulpal necrosis can also occur as a result of dental treatments such as iatrogenic damage due to overzealous crown preparation – this may be due to excessive thermal insult and close proximity to the pulp during tooth preparation – or rapid orthodontic work causing excessive force.
#### Pulpitis[edit]
Pulpitis is stated to be one of the stages of disease progression which leads to pulpal necrosis. This inflammation can be reversible or irreversible. Due to the enclosed nature of the pulp chamber - unlike normal inflammation - when inflamed, the increased pressure cannot be displaced to other tissues, resulting in pressure on the nerve of said tooth and tissues adjacent.[14] In irreversible pulpitis where the inflammation of pulpal tissues are not reversible, pulpal blood supply will become compromised and therefore necrosis of pulpal tissues will occur.
## Signs and symptoms[edit]
Pulp necrosis may or may not arise with symptoms.
Signs and symptoms of pulpal necrosis include;
* Pain[11]
* Crown discolouration[15]
* Abscess and/or fistula
* Internal root resorption
* Increased tooth mobility
There are additional signs of pulp necrosis which may be detected during radiographic assessment:-;
* Untreated caries
* Extensive/deep restoration
* Previous pulp capping
However, in some cases there may be no radiographic signs. For example, pulp necrosis caused by dental trauma which may only manifest/present itself with time, resulting in clinical changes.[11]
### Pain[edit]
The pain associated with pulp necrosis is often described as spontaneous.[15] Hot temperatures are reported to have exacerbating factors, and cold temperatures are said to soothe this pain. In some cases, the pain presents as a long dull ache as this is due to necrosis of the apical nerves being the last part of the pulp to necrose. Therefore the pain is from the apical nerves, which have residual vitality remaining when the majority of the pulp is necrosed due to the supply of blood to the more medial parts of the apical nerve.[11]
### Crown discolouration[edit]
In some cases of pulp necrosis there is a yellow, grey or brown crown discolouration. Dark coronal discoloration is believed to be an early sign of pulp degeneration.[16] Teeth with said discolouration need to be treated with special care and further investigations are required before pulp necrosis can be diagnosed.[11]
### Abscess and/or fistula[edit]
Alterations in the gingiva such as fistulas or abscesses and radiographic signs such as periapical lesions and external root resorption are used in some studies to diagnose pulp necrosis however other studies state that these factors alone are not enough to diagnose a necrotic pulp.[11]
### Internal root resorption[edit]
Internal root resorption may be an indication of pulpal necrosis though it is not possible to diagnose accurately with radiographic presentation of this alone. This is because the pulp tissue apical to the resorptive lesion will still be vital to allow active resorption to take place, it provides the clastic cells with nutrients via a viable blood supply.[11]
## Diagnosis[edit]
There are a plethora of ways to diagnose pulp necrosis in a tooth. The diagnosis of pulp necrosis can be based on the following observations: negative vitality, a periapical radiolucency, a grey tooth discoloration and even peri-apical lesions.[17] This altered translucency in the tooth is due to disruption and cutting off of the apical neurovascular blood supply.[18]
### Thermal Tests[edit]
Thermal testing is a common and traditional way used to detect pulp necrosis. These tests can exist in the form of a cold or hot test, which aims to stimulate nerves in the pulp by the flow of dentine liquid at changes in temperature. The liquid flow leads to movement of the odontoblast processes and mechanical stimulation of pulpal nerves.[19]
The cold test can be done by soaking a cotton pellet into 1,1,1,2 tetrofluoroethane, also known as Endo ice refrigerant spray. The cotton pellet will then be placed onto the middle third of the intact tooth surface. The clinical study done by Gopikrishna indicated the tooth to be diagnosed as having necrotic pulp if subjects felt no sensation after two 15-second applications every two minutes.[20] It is worthy to note that a control test should be performed on the adjacent tooth to ensure further accuracy of results.
### Pulse Oximeter Test[edit]
The pulse oximeter test is a more accurate way to test for necrotic pulps as it primarily tests for vascular health of the pulp as compared to its nervous response.[21] This method involves taking measurements of blood oxygen saturation levels, making it non-invasive and an objective way to record patient response regarding pulpal diagnosis.[20] In a study conducted in primary and immature permanent teeth, results clearly reflected that pulse oximetry can readily differentiate between vital and non-vital, necrosed teeth.
The pulse oximeter consists of a probe containing 2 light-emitting diodes, one of which transmits red light to measure the absorption of oxygenated haemoglobin, and the other transmitting infrared light, measuring the absorption of deoxygenated haemoglobin. As both oxygenated and deoxygenated haemoglobin absorb different amounts of red and infrared light, relationships between pulsatile changes in blood volume and light absorption values can establish saturation of arterial blood. In addition, using absorption curves for both oxygenated and deoxygenated haemoglobin can determine the oxygen saturation levels.[22] For the purposes of evaluating pulp vitality, it is imperative that the probes fit the anatomical contours and shape of the measured teeth.[23]
A study was done to assess the accuracy of pulse oximetry in comparison to thermal and electrical tests. Customized pulse oximeter dental probes were placed on the crown of the tooth, with oxygen saturation values recorded after 30 seconds of monitoring each tooth. The values were taken as a positive response (ie vital pulp) within the range of 75-85% oxygen saturation and a negative response below 75%, indicating pulp necrosis.[20]
Another critically appraised topic[24] also suggests that a pulse oximeter is more accurate than cold testing in diagnosing pulp necrosis, however comments raised regarding the validity of the evidence stated that the pulse oximeter adaptors were built by the respective authors causing some degree of bias in the experiments.[24]
### 3-Tesla Magnetic Resonance Imaging[edit]
MRI scans have been used to detect and evaluate several head and neck regions including the Temporomandibular Joint, salivary glands, floor of the mouth, etc. In the clinical study completed by Alexandre T. Assaf, MRI scans were used to detect pulp vitality after trauma in children. The absence of re-perfusion of the dental pulp suggests the lack of revitalization of the affected teeth and hence necrosis of the pulp. In this study, MRI scans prove to be a promising tool to avoid excessive root treatment on traumatized teeth. However, a major flaw in this study is a small sample size of 7.[25]
## Management & Treatment[edit]
The most basic treatment for teeth with pulpal necrosis is root canal treatment. This involves the use of biologically accepted mechanical and chemical treatment of the root system, followed by the placement of a root filling, allowing healing of the periradicular tissues to occur.
Pulpal regeneration can be considered if the following criteria are met:
1. Incomplete root development and incomplete apex closure
2. Apexogenesis is not applicable as there is apical closure
Pulpal regeneration involves the removal of the necrotic pulp followed by the placement of medicament into the root canal system until it is non-symptomatic. Apical bleeding is then induced to create a clot at the apex which will be sealed by Mineral Trioxide Aggregate.[26]
In an immature permanent tooth pulpal necrosis causes the development of the root to stop. This causes the walls of the root to become fragile and thin which can make these teeth more prone to cervical root fracture and ultimately the tooth may be lost. These teeth in the past were treated with the calcium hydroxide apexification technique. A disadvantage of this was that it required multiple visits over a prolonged time and there could be an increased risk of cervical root fracture due to an increase in exposure to calcium hydroxide. The apical barrier technique with mineral trioxide aggregate was then used. The advantage of this technique over apexification was that it shortened the number of appointments and the healing outcomes were better. A disadvantage of both these techniques was that it did not allow the root to mature and so regenerative endodontic procedures (REPs) were utilised. A systematic review conducted by Kahler, et al (2017) showed similar clinical outcomes for teeth treated with REPs versus calcium hydroxide apexification/MTA apical barrier technique. They suggested that it should be considered as a first line treatment option in immature teeth with pulpal necrosis. They did state that a thorough discussion with the patient would be necessary as teeth treated with REP’s can show variable root maturation and adverse outcomes.[27]
## References[edit]
1. ^ a b "Dental Pulp Necrosis MeSH Descriptor Data 2018". National Library of Medicine. 6 July 2009. Retrieved 2018-10-24.
2. ^ Lauridsen E, Hermann NV, Gerds TA, Ahrensburg SS, Kreiborg S, Andreasen JO (October 2012). "Combination injuries 3. The risk of pulp necrosis in permanent teeth with extrusion or lateral luxation and concomitant crown fractures without pulp exposure". Dental Traumatology. 28 (5): 379–85. doi:10.1111/j.1600-9657.2011.01100.x. PMID 22233180.
3. ^ a b "Dental Pulp Cavity Definition".
4. ^ Berggreen E, Bletsa A, Heyeraas KJ (September 2007). "Circulation in normal and inflamed dental pulp". Endodontic Topics. 17 (1): 2–11. doi:10.1111/j.1601-1546.2010.00249.x.
5. ^ a b Soames JV, Southam JC (2005). Oral pathology (4th ed.). Oxford: Oxford University Press. ISBN 978-0-19-852794-7. OCLC 57006193.
6. ^ "Pulp Therapy for Primary and Immature Permanent Teeth". Pediatric Dentistry. 39 (6): 325–333. September 2017. PMID 29179372.
7. ^ a b Rechenberg DK, Galicia JC, Peters OA (2016-11-29). "Biological Markers for Pulpal Inflammation: A Systematic Review". PLOS ONE. 11 (11): e0167289. Bibcode:2016PLoSO..1167289R. doi:10.1371/journal.pone.0167289. PMC 5127562. PMID 27898727.
8. ^ Yu, C; Abbott, PV (2007). "An overview of the dental pulp: its functions and responses to injury". Australian Dental Journal. 52: 4–16.
9. ^ Goodell, GC; Tordik, PA; Moss, D (December 2005). "Pulpal and periradicular diagnosis". Clinical. 27.
10. ^ Levin, LG; et al. (December 2009). "Identify and Define All Diagnostic Terms for Pulpal Health and Disease States". Journal of Endodontics. 35 (12): 1645–1657. doi:10.1016/j.joen.2009.09.032. PMID 19932339.
11. ^ a b c d e f g h Abbott PV, Yu C (March 2007). "A clinical classification of the status of the pulp and the root canal system". Australian Dental Journal. 52 (1 Suppl): S17-31. doi:10.1111/j.1834-7819.2007.tb00522.x. PMID 17546859.
12. ^ Smaïl-Faugeron V, Glenny AM, Courson F, Durieux P, Muller-Bolla M, Fron Chabouis H (May 2018). "Pulp treatment for extensive decay in primary teeth". The Cochrane Database of Systematic Reviews. 5: CD003220. doi:10.1002/14651858.CD003220.pub3. PMC 6494507. PMID 29852056.
13. ^ Bjørndal L (July 2008). "The caries process and its effect on the pulp: the science is changing and so is our understanding". Journal of Endodontics. 34 (7 Suppl): S2–5. doi:10.1016/j.joen.2008.02.037. PMID 18565367.
14. ^ Hargreaves KM, Goodis HE, Tay FR, Seltzer S (February 2012). Seltzer and Bender's Dental Pulp. Hanover Park, IL: Quintessence Pub. ISBN 978-0-86715-480-1. OCLC 794664259.
15. ^ a b Aldrigui JM, Cadioli IC, Mendes FM, Antunes JL, Wanderley MT (November 2013). "Predictive factors for pulp necrosis in traumatized primary incisors: a longitudinal study". International Journal of Paediatric Dentistry. 23 (6): 460–9. doi:10.1111/ipd.12019. PMID 23331274.
16. ^ Moccelini BS, de Alencar NA, Bolan M, Magno MB, Maia LC, Cardoso M (June 2018). "Pulp necrosis and crown discoloration: a systematic review and meta-analysis". International Journal of Paediatric Dentistry. 28 (5): 432–442. doi:10.1111/ipd.12372. PMID 29896799.
17. ^ JACOBSEN, INGEBORG (August 1980). "Criteria for diagnosis of pulp necrosis in traumatized permanent incisors". European Journal of Oral Sciences. 88 (4): 306–312. doi:10.1111/j.1600-0722.1980.tb01231.x. ISSN 0909-8836.
18. ^ Lauridsen, Eva; Hermann, Nuno Vibe; Gerds, Thomas Alexander; Ahrensburg, Søren Steno; Kreiborg, Sven; Andreasen, Jens Ove (2012-01-11). "Combination injuries 3. The risk of pulp necrosis in permanent teeth with extrusion or lateral luxation and concomitant crown fractures without pulp exposure". Dental Traumatology. 28 (5): 379–385. doi:10.1111/j.1600-9657.2011.01100.x. ISSN 1600-4469. PMID 22233180.
19. ^ Peterson, K.; Söderström, C.; Kiani-Anaraki, M.; Lévy, G. (June 1999). "Evaluation of the ability of thermal and electrical tests to register pulp vitality". Dental Traumatology. 15 (3): 127–131. doi:10.1111/j.1600-9657.1999.tb00769.x. ISSN 1600-4469.
20. ^ a b c Gopikrishna, Velayutham; Tinagupta, Kush; Kandaswamy, Deivanayagam (April 2007). "Evaluation of Efficacy of a New Custom-Made Pulse Oximeter Dental Probe in Comparison With the Electrical and Thermal Tests for Assessing Pulp Vitality". Journal of Endodontics. 33 (4): 411–414. doi:10.1016/j.joen.2006.12.003. ISSN 0099-2399. PMID 17368329.
21. ^ Munshi, A.; Hegde, Amitha; Radhakrishnan, Sangeeth (January 2003). "Pulse oximetry: a diagnostic instrument in pulpal vitality testing". Journal of Clinical Pediatric Dentistry. 26 (2): 141–145. doi:10.17796/jcpd.26.2.2j25008jg6u86236. ISSN 1053-4628.
22. ^ Jafarzadeh, Hamid; Rosenberg, Paul A. (March 2009). "Pulse Oximetry: Review of a Potential Aid in Endodontic Diagnosis". Journal of Endodontics. 35 (3): 329–333. doi:10.1016/j.joen.2008.12.006. ISSN 0099-2399. PMID 19249589.
23. ^ Dastmalchi, Nafiseh; Jafarzadeh, Hamid; Moradi, Saeed (September 2012). "Comparison of the Efficacy of a Custom-made Pulse Oximeter Probe with Digital Electric Pulp Tester, Cold Spray, and Rubber Cup for Assessing Pulp Vitality". Journal of Endodontics. 38 (9): 1182–1186. doi:10.1016/j.joen.2012.06.012. ISSN 0099-2399. PMID 22892732.
24. ^ a b Mainkar, Anshul; Kim, Sahng G. (May 2018). "Diagnostic Accuracy of 5 Dental Pulp Tests: A Systematic Review and Meta-analysis". Journal of Endodontics. 44 (5): 694–702. doi:10.1016/j.joen.2018.01.021. ISSN 0099-2399. PMID 29571914.
25. ^ Assaf, Alexandre T.; Zrnc, Tomislav A.; Remus, Chressen C.; Khokale, Arun; Habermann, Christian R.; Schulze, Dirk; Fiehler, Jens; Heiland, Max; Sedlacik, Jan (September 2015). "Early detection of pulp necrosis and dental vitality after traumatic dental injuries in children and adolescents by 3-Tesla magnetic resonance imaging". Journal of Cranio-Maxillofacial Surgery. 43 (7): 1088–1093. doi:10.1016/j.jcms.2015.06.010. ISSN 1010-5182. PMID 26165761.
26. ^ "Guide to Clinical Endodontics 6th edition". American Association of Endodontics. 2016.
27. ^ Kahler, B; et al. (July 2017). "An Evidence-based view of the Efficacy of Treatment Approaches for Immature Permanent Teeth with Pulp Necrosis Health and Disease States". Journal of Endodontics. 43 (7): 1052–1057. doi:10.1016/j.joen.2017.03.003. PMID 28511779.
* Medicine portal
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*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
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*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
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*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
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| Pulp necrosis | c0011407 | 5,101 | wikipedia | https://en.wikipedia.org/wiki/Pulp_necrosis | 2021-01-18T19:07:23 | {"mesh": ["D003790"], "umls": ["C0011407"], "wikidata": ["Q2507106"]} |
A number sign (#) is used with this entry because frontometaphyseal dysplasia-1 (FMD1) is caused by gain-of-function mutations in the gene encoding filamin A (FLNA; 300017) on chromosome Xq28.
Description
Frontometaphyseal dysplasia-1 is 1 of 4 otopalatodigital syndromes caused by mutations in the FLNA gene. The disorders, which include otopalatodigital syndrome-1 (OPD1; 311300), otopalatodigital syndrome-2 (OPD2; 304120), and Melnick-Needles syndrome (MNS; 309350), constitute a phenotypic spectrum. At the mild end of the spectrum, males with OPD1 have cleft palate and mild skeletal anomalies with conductive deafness caused by ossicular anomalies. FMD1 is characterized by a generalized skeletal dysplasia, deafness, and urogenital defects. Males with OPD2 have disabling skeletal anomalies in addition to variable malformations in the hindbrain, heart, intestines, and kidneys that frequently lead to perinatal death. The most severe phenotype, MNS, is characterized by a skeletal dysplasia in the heterozygote. Affected males exhibit severe malformations similar to those observed in individuals with OPD2, resulting in prenatal lethality or death in the first few months of life (review by Robertson, 2005). Verloes et al. (2000) suggested that these disorders constitute a single entity, which they termed 'frontootopalatodigital osteodysplasia.'
### Genetic Heterogeneity of Frontometaphyseal Dysplasia
Frontometaphyseal dysplasia-2 (FMD2; 617137) is caused by mutation in the MAP3K7 gene (602614) on chromosome 6q15.
Clinical Features
Gorlin and Cohen (1969) described a male patient with extraordinarily marked frontal hyperostosis giving great prominence to the supraciliary ridges, underdeveloped mandible, cryptorchidism, subluxated radial heads, and metaphyseal dysplasia resembling that in Pyle disease (metaphyseal dysplasia). This may be the disorder present in the case described by Walker (1969). Striking overgrowth of bone in the superciliary region was repaired by removal of excess bone.
Holt et al. (1972) reported 2 unrelated patients. Danks et al. (1972) studied an isolated case in which progressive contracture of the fingers and lysis and fusion of carpal bones were features. The patient had progressive osteosclerosis also. Fibroblasts showed metachromasia. All 3 patients were males.
Weiss et al. (1976) observed the disorder in a black male whose mother had the same disorder. The thumbs in the son were strikingly broad. 'Metaphyseal' is a misnomer since striking diaphyseal changes with lack of molding of the shafts of the long bones are found.
Kassner et al. (1976) reported an affected 8-year-old whose mother was thought to have mild metaphyseal dysplasia and several minor skeletal abnormalities that have occurred in patients with the syndrome; they also described the disorder in maternal half brothers.
Medlar and Crawford (1978) described an affected male who presented with scoliosis and had 2 of 3 sibs with significant scoliosis and similar facial abnormalities.
Ullrich et al. (1979) reported the radiographic findings in a severely affected boy and his mildly affected mother.
Abuelo and Ehrlich (1981) described a typically affected male whose mother showed no evidence of the disorder in her facial features. However, x-rays revealed marked hyperostosis of the mandible, scoliosis, and other abnormalities.
Gorlin and Winter (1980) pointed out that dorsiflexion of the wrists and extension of the elbows are reduced, with very limited pronation and supination. Flexion deformities of the fingers and ulnar deviation of the wrists are progressive. Missing permanent teeth and retained deciduous teeth have been noted in most patients.
Beighton and Hamersma (1980) raised the question of whether osteodysplasty of Melnick and Needles is the same as frontometaphyseal dysplasia. They suggested that the disorder in males may be labeled frontometaphyseal dysplasia and that in females called osteodysplasty.
Fitzsimmons et al. (1982) reported 4 cases in 1 family: grandmother, mother, son and daughter. The male had obstructive uropathy at birth; the authors found reports of associated renal abnormalities in 3 other males. The male also had severe congenital stridor from subglottic stenosis and a tracheal web. Both children had recurrent respiratory tract infections.
Superti-Furga and Gimelli (1987) reexamined the patient reported as having FMD by Danks et al. (1972) and concluded that the findings were consistent with the diagnosis of otopalatodigital syndrome. A review of 10 male subjects with frontometaphyseal dysplasia and 13 male subjects with the OPD syndrome from the literature revealed substantial phenotypic overlap between the 2 disorders, which share an X-linked inheritance pattern. They suggested that these may be the same disorder.
On the basis of experience with 2 newborn sons of an affected mother, Glass and Rosenbaum (1995) commented on the difficulties in diagnosing FMD in the neonatal period. In both boys, bone density was generally increased, but most markedly so in the skull base. The coronal skull sutures were partially fused. The metaphyses of all the long bones were flared. As in the mother, the ribs were unusually shaped and there was an anterior bony spur from the mandible. Both boys died neonatally of severe congenital heart disease.
Franceschini et al. (1997) described a male infant in whom frontometaphyseal dysplasia was complicated by esophageal atresia with distal tracheoesophageal fistula. In a review of the literature they noted that malformation of the bronchial tree, respiratory distress and wheezing, narrowing of the subglottic area, and subglottic stenosis with anterior web had been reported in individual cases previously.
Morava et al. (2003) described 2 families in which both males and females showed the facial and skeletal characteristics of FMD in association with severe progressive scoliosis. Some also had hearing loss and urogenital anomalies, leading Morava et al. (2003) to suggest that these were examples of frontootopalatodigital osteodysplasia as described by Verloes et al. (2000).
Inheritance
Gorlin and Winter (1980) marshalled evidence for X-linked inheritance with severe manifestations in males and variable manifestations in females.
Molecular Genetics
Robertson et al. (2003) demonstrated gain-of-function mutations in the filamin A gene in patients with frontometaphyseal dysplasia; see, e.g., 300017.0011 (D1159A) and 300017.0015 (S1186L).
Giuliano et al. (2005) identified the S1186L mutation in the FLNA gene in affected members of a 3-generation family with FMD.
Robertson et al. (2006) performed clinical and molecular analysis of 23 unrelated probands with FMD. No mutation in the FLNA gene was identified in 10 of the 23 patients (43%), suggesting genetic heterogeneity.
### Associations Pending Confirmation
See 605101.0001 for discussion of a possible assotiation between FMD and variation in the TAB2 gene.
INHERITANCE \- X-linked recessive HEAD & NECK Face \- Coarse facies \- Prominent supraorbital ridges \- Small pointed chin Ears \- Progressive mixed conductive and sensorineural hearing loss Eyes \- Hypertelorism \- Downslanting palpebral fissures Nose \- Wide nasal bridge Mouth \- High palate Teeth \- Selective tooth agenesis \- Delayed tooth eruption \- Retained deciduous teeth \- Malocclusion CARDIOVASCULAR Heart \- Mitral valve prolapse RESPIRATORY Airways \- Subglottic tracheal narrowing \- Congenital stridor Lung \- Cor pulmonale CHEST Ribs Sternum Clavicles & Scapulae \- Winged scapulae \- Irregular rib contours \- "Coat hanger" deformity of lower ribs GENITOURINARY Kidneys \- Hydronephrosis Ureters \- Hydroureter SKELETAL Skull \- Incomplete sinus development \- Wide foramen magnum \- Antegonial notching of mandible \- Hypoplastic condyloid process Spine \- Wide interpedicular distance \- Scoliosis \- Cervical vertebral fusion \- Anteriorly placed odontoid process Pelvis \- Flared pelvis \- Coxa valga Limbs \- Elbow contractures \- Knee and ankle contractures \- Erlenmeyer-flask appearance of femur and tibia \- Genu valgum \- Increased density of long bone diaphyses Hands \- Finger and wrist contractures \- Arachnodactyly \- Wide and elongated phalanges \- Partial fusion of carpals Feet \- Large feet \- Partial fusion of tarsals SKIN, NAILS, & HAIR Hair \- Hirsutism of buttocks and thighs MUSCLE, SOFT TISSUES \- Muscle wasting (especially legs and arms) NEUROLOGIC Central Nervous System \- Mental retardation MISCELLANEOUS \- Variable expression in females Otopalatodigital syndrome type I (OPD1, 311300 ) is an allelic disorder \- Otopalatodigital syndrome type II (OPD2, 304120 ) is an allelic disorder \- Melnick-Needles syndrome (MNS, 309350 ) is an allelic disorder \- Periventricular heterotopia ( 300049 ) is an allelic disorder MOLECULAR BASIS \- Caused by mutation in the filamin A gene (FLNA, 300017.0011 ) ▲ Close
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*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
| FRONTOMETAPHYSEAL DYSPLASIA 1 | c0265293 | 5,102 | omim | https://www.omim.org/entry/305620 | 2019-09-22T16:18:19 | {"mesh": ["C538064"], "omim": ["305620"], "orphanet": ["1826"], "synonyms": ["Alternative titles", "FMD"], "genereviews": ["NBK1393"]} |
In the ts546 temperature-sensitive rodent cell line, the arrest of cell division, when the cells are grown at nonpermissive temperatures, is in metaphase (Ming, 1984). Baserga et al. (1982) showed that the complementing human gene is on chromosome 6.
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*[AA]: Adrenergic agonist
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*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
| TEMPERATURE SENSITIVITY COMPLEMENTATION, CELL CYCLE SPECIFIC, ts546 | c1861243 | 5,103 | omim | https://www.omim.org/entry/187330 | 2019-09-22T16:32:48 | {"omim": ["187330"]} |
A number sign (#) is used with this entry because neuronal ceroid lipofuscinosis-13 (CLN13) is caused by homozygous or compound heterozygous mutation in the CTSF gene (603539) on chromosome 11q13.
Description
Neuronal ceroid lipofuscinosis-13 is an autosomal recessive neurodegenerative disorder characterized by adult onset of progressive cognitive decline and motor dysfunction leading to dementia and often early death. Some patients develop seizures. Neurons show abnormal accumulation of autofluorescent material (summary by Smith et al., 2013).
Adult-onset neuronal ceroid lipofuscinosis is sometimes referred to as Kufs disease.
For a discussion of genetic heterogeneity of neuronal ceroid lipofuscinosis (CLN), see CLN1 (256730).
Clinical Features
Smith et al. (2013) reported 2 Italian sibs, born of unrelated parents, with adult onset of CLN. At age 20 years, the proband developed a progressive cerebellar syndrome manifest as tremor, ataxia, and dysarthria. She later developed tonic-clonic seizures and progressive cognitive impairment with emotional lability turning into dementia. She died at age 42. Neuropathologic examination showed diffuse cerebral atrophy with neuronal loss and astrogliosis. There was abundant autofluorescent material in the cytoplasm of neurons in the cerebral cortex, thalamus, striatum, brainstem nuclei, and Purkinje cells. This storage material was immunoreactive for ubiquitin and contained fingerprint profiles. The patient's older sister developed depression associated with cognitive decline at age 32 years. She had rare seizures from age 41, and later showed ataxia, dysarthria, and pyramidal and extrapyramidal signs. She was bedridden at age 51. Brain MRI showed diffuse cerebral atrophy; skin biopsy was unremarkable. An unrelated woman, born of consanguineous French Canadian parents, had occasional focal seizures in her twenties. At age 35, she showed progressive dementia with mood disturbance and motor features, including tremor, ataxia, and extrapyramidal rigidity with mild hyperreflexia. In her forties, she had dementia and became wheelchair-bound. Brain biopsy showed autofluorescent material in neurons. A 35-year-old Australian woman had a similar disorder, with cognitive decline and dysarthria followed by at least 1 seizure and mild ataxia with tremor.
Di Fabio et al. (2014) reported an Italian family in which 4 individuals had Kufs disease. The proband presented with tonic-clonic seizures at age 23. From age 30, she showed progressive cognitive decline associated with myoclonic jerks, facial dyskinesia, axial hypotonia, postural tremor, hyperreflexia, and extensor plantar responses with frontal release signs. At age 40, she was wheelchair-bound and totally dependent for activities of daily living. Brain imaging showed severe cortical and cerebellar atrophy and periventricular hyperintensities on T2-weighted images. The patient's deceased mother and living cousin had a similar disease course, with onset of seizures in their twenties or early thirties, followed by progressive cognitive decline, behavioral and personality changes, and dementia. An affected aunt had later onset of similar symptoms in her mid-sixties. Skin fibroblasts from 2 of the patients showed aggresome-like osmiophilic cytoplasmic inclusions suggestive of NCL, and Western blot analysis of 1 patient's cells showed increased expression of polyubiquitinated proteins. Two additional deceased family members reportedly had a phenotype consistent with the disorder. Di Fabio et al. (2014) noted that the transmission pattern in this family initially resembled an autosomal dominant disorder, but the family was from an isolated community with a high degree of inbreeding (Fondi, in central Italy), and detailed family history was consistent with autosomal recessive inheritance.
Inheritance
The transmission pattern of CLN13 in the families reported by Smith et al. (2013) was consistent with autosomal recessive inheritance.
Molecular Genetics
In affected members of 2 unrelated families with Kufs disease, Smith et al. (2013) identified homozygous or compound heterozygous mutations in the CTSF gene (603539.0001-603539.0003). The mutations, which were found by linkage analysis combined with exome sequencing, segregated with the disorder and were not found in several large control databases. Sequencing of the CTSF gene in 22 unrelated probands with suspected Kufs disease identified compound heterozygous mutations (603539.0004-603539.0005) in 1 patient. Molecular modeling predicted that the mutations were pathogenic, and Smith et al. (2013) noted that Ctsf-null mice develop a similar neurodegenerative disorder (Tang et al., 2006). The findings implicated CTSF dysfunction in this disorder.
In affected members of an Italian family with CLN13, Di Fabio et al. (2014) identified a homozygous splice site mutation in the CTSF gene (603539.0006).
Animal Model
Tang et al. (2006) found that Ctsf-null mice developed normally, but had onset of a progressive neurologic disorder between 12 and 16 months of age. Mutant mice showed progressive difficulty walking, with hind leg weakness, decline in motor coordination, and general wasting. Other features included tonic hind leg extension, poor balance, tremor, and spasticity. Some mice had seizures. Ctsf-null mice died within 4 to 6 months of symptom onset. Postmortem examination showed substantial gliosis in the brain and spinal cord, neuronal loss, and an accumulation of cytoplasmic eosinophilic and autofluorescent granules in neurons and glial cells. Ultrastructural analysis confirmed membrane-bound lamellar inclusions in fingerprint patterns, consistent with lipofuscin. The phenotype was reminiscent of human adult-onset neuronal ceroid lipofuscinosis.
INHERITANCE \- Autosomal recessive NEUROLOGIC Central Nervous System \- Cognitive decline, progressive \- Dementia \- Motor abnormalities \- Tremor \- Ataxia \- Dysarthria \- Cerebellar signs \- Extrapyramidal signs \- Myoclonus \- Perioral dyskinesias \- Hyperreflexia \- Extensor plantar responses \- Primitive reflexes \- Seizures \- Cerebral atrophy, diffuse \- Cerebellar atrophy \- Accumulation of autofluorescent material in neurons Behavioral Psychiatric Manifestations \- Behavioral changes \- Emotional lability \- Depression LABORATORY ABNORMALITIES \- Skin fibroblasts show osmiophilic cytoplasmic inclusions MISCELLANEOUS \- Adult onset \- Progressive disorder MOLECULAR BASIS \- Caused by mutation in the cathepsin F gene (CTSF, 603539.0001 ) ▲ Close
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*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
| CEROID LIPOFUSCINOSIS, NEURONAL, 13 | c0022797 | 5,104 | omim | https://www.omim.org/entry/615362 | 2019-09-22T15:52:28 | {"doid": ["0110727"], "mesh": ["D009472"], "omim": ["615362"], "orphanet": ["352709", "79262"], "synonyms": ["Alternative titles", "CEROID LIPOFUSCINOSIS, NEURONAL, 13, KUFS TYPE"]} |
A rare multiple congenital anomalies syndrome characterized by greater hight, mild to moderate intellectual disability and distinctive facial appereance like round face, heavy, horizontal eyebrows and narrow palpebral fissures.
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*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
| Tall stature-intellectual disability-facial dysmorphism syndrome | c4014545 | 5,105 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=404443 | 2021-01-23T17:58:17 | {"omim": ["615879"], "icd-10": ["Q87.3"], "synonyms": ["DNMT3A-related overgrowth syndrome", "Tatton-Brown-Rahman overgrowth syndrome"]} |
B4GALT1-CDG is a congenital disorder of glycosylation characterised by macrocephaly due to Dandy-Walker malformation, hydrocephaly, hypotonia, myopathy and coagulation anomalies. To date, only one case has been reported. The syndrome is associated with mutations in the GALT1 gene (localised to region q13 of chromosome 9) leading to a deficiency in the Golgi apparatus enzyme beta-1,4-galactosyl transferase.
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*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
| B4GALT1-CDG | c2931009 | 5,106 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79332 | 2021-01-23T19:08:48 | {"gard": ["9841"], "mesh": ["C535753"], "omim": ["607091"], "umls": ["C2931009"], "icd-10": ["E77.8"], "synonyms": ["Beta-1,4-galactosyltransferase deficiency", "CDG syndrome type IId", "CDG-IId", "CDG2D", "Carbohydrate deficient glycoprotein syndrome type IId", "Congenital disorder of glycosylation type 2d", "Congenital disorder of glycosylation type IId"]} |
Aquadynia
SpecialtyDermatology
Aquadynia is a variant of aquagenic pruritus, and characterized by a widespread burning pain that lasts 15 to 45 minutes after water exposure.[1]:56
## See also[edit]
* Aquagenic pruritus
* Pruritus
* Skin lesion
## References[edit]
1. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
This cutaneous condition article is a stub. You can help Wikipedia by expanding it.
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*[AA]: Adrenergic agonist
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*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
| Aquadynia | None | 5,107 | wikipedia | https://en.wikipedia.org/wiki/Aquadynia | 2021-01-18T19:04:42 | {"wikidata": ["Q4782671"]} |
Fear of the sea or large open water
Thalassophobia
The Atlantic Ocean depicted as a deep body of water.
SpecialtyClinical Psychology
DurationMore than six months
TreatmentSystemic Desensitisation, Exposure Therapy, Counselling, Cognitive Behavioural Therapy (CBT), Medication
Thalassophobia (Greek: θάλασσα, thalassa, "sea" and φόβος, phobos, "fear")[1] is the persistent and intense fear of deep bodies of water such as the sea, oceans, pools or lakes. Though very closely related, thalassophobia should not be mistaken with aquaphobia which is classified as the fear of water itself. Thalassophobia can include fear of being in deep bodies of water, fear of the vast emptiness of the sea, of sea waves, sea creatures, and fear of distance from land.[2] The causes of thalassophobia are not clear and are of much interest to researchers and medical professionals as they can vary greatly from one individual to another.[3] Researchers believe that the fear of large bodies of water are (to an extent) evolutionary to humans and related to popular culture influences which induce fright and distress through multiple forums including movies, social media and mass media.[4] The severity of thalassophobia and the signs and symptoms associated with it are quite fluid and complex. Those who suffer from thalassophobia go through numerous episodes of emotional and physical anguish caused by various different triggers.[5] In terms of treatment options, experts say that the best time for providing therapeutics to patients is during childhood when thalassophobia is known to be at its peak.[6]
## Contents
* 1 Causes
* 1.1 Evolutionary context
* 1.2 Mythology and contemporary popular culture
* 1.3 Past experiences and genetics
* 2 Diagnosis and symptoms
* 3 Treatment
* 4 See also
* 5 References
## Causes[edit]
### Evolutionary context[edit]
It is thought that the fear of large bodies of water is an evolutionary and ancestral trait passed on from generation to generation. Humans prefer certainty to risk and adapt based on learning history and situational variables.[7][4] A 2016 study by Nicholas Carlton establishes that the ‘Fear of Unknown’ is an evolutionary mechanism that has driven the survival of the human race since the beginning.[8] Showing fear towards deep bodies of water is in effect justified since ancestors to the human race understood that their survival was reliant on remaining in territorial land and not aquatic environments.[7] This in return developed into a fundamental fear passing down from generation to generation in order to ensure the survival of human kind.[9]
Martin Antony, Professor of Psychology at Ryerson University and co-author of The Anti-Anxiety Workbook, states that "From an evolutionary perspective, it makes sense that humans would develop a tendency to fear and avoid deep water because of all the associated risks". He continues by commenting on the genetic aspect of fears, saying; "We are essentially 'programmed' through evolution to fear some situations (e.g., heights, deep water, snakes) more easily than others (e.g., flowers, teddy bears)" [10]
### Mythology and contemporary popular culture[edit]
Myslivny bozi dar lake in Czech Republic
In Judeo-Christian mythology, the sea is often depicted as a space of disaster and punishment. This is evident in the first book of the Bible (Genesis), through stories such as those of Noah's Ark. Texts like William Shakespeare's The Tempest featured a shipwreck as the driving force behind its narrative and gave the sea an "otherworldly" and "evil" personification. Authors of Beasts of the Deep: Sea Creatures and Popular Culture Sean Harrington and Jon Hackett believe that these narratives are a driving force for the widespread fear of oceans.[4] Literature of the gothic and supernatural have gravitated towards the sea as a fertile environment, and as a result create an unpleasant and fearful image in the minds of audiences.[7] This is thought to be true for both ancient and contemporary societies. The 1975 blockbuster film Jaws is often referenced as being an influential motion picture which drove the modern movement of thalassophobia. The mainstream media also affects the collective emotions of the public.[7] News reports of great white sharks, electric eels or other dangerous sea predators attacking swimmers in the ocean induce fear in viewers and are thought to have great influence.[11] Similarly, real cases of ships like the Titanic sinking with their passengers drowning have been made terrifyingly realistic through their movie versions. People who are very afraid of violent death or particularly of drowning are also more likely to develop thalassophobia. These cultural influences (both ancient and modern) are thought to have added to the prevalence of the fear of deep bodies of water throughout time.[4]
### Past experiences and genetics[edit]
A negative or past traumatic event can also trigger a deep fear of oceans.[12] Traumatic experiences of being frightened while swimming, or almost drowning are also leading causes of thalassophobia. In addition to this, observing others, particularly parental figures and other influential adults, who also had a fear of deep water are considered contributing factors for developing thalassophobia later in life.[13] Scientists also believe that genetics and biological heredity plays a major role in attaining a fear of seas, oceans and lakes.[13] Such genetic factors include having a family member with thalassophobia, personal mental state such as being negative, sensitive or anxious, and even hearing terrifying stories on water accidents. Personal experiences and one's upbringing are all factors that could potentially be the cause of thalassophobia.
## Diagnosis and symptoms[edit]
Thalassophobia is characterised by certain physical and emotional traits exhibited by an individual. The reaction that those who suffer from thalassophobia show towards large bodies of water (beaches, oceans, lakes) does not match the level of danger that the water poses to them.[14] Hence, they illustrate abnormal behaviour under situations or environments which trigger their fear. Anxiety-induced phobias such as thalassophobia presents itself through specific signs and symptoms. Individuals with a moderate fear of deep bodies of water may experience agitation and restlessness on a day-to-day basis.[5]
Common emotional symptoms of thalassophobia include:[12]
* Constant worrying
* Trouble falling or staying asleep (possibly insomnia)
* Panic and anxiety attacks
* Having a sense of imminent doom
* Needing to escape
* Feeling detached from the situation
* Being overwhelmed
Common physical symptoms of thalassophobia include:[6]
* Shortness of breath
* Sweating
* Shaking or trembling at the sight of the sea
* Weeping or running away when near deep bodies of water
* Nausea
* Dizziness
* Rapid breathing
* Screaming and/or shouting at the sight of the sea
According to the 'Diagnostic and Statistical Manual of Mental Disorders (fifth edition)' (DSM-5) which is a manual for assessment and diagnosis of mental disorders developed by the American Psychiatric Association; in order to be diagnosed with a phobia of deep bodies of water:[14]
* The individual's fear of deep water must be persistent, excessive and unreasonable
* The individual must feel this fear every time they are exposed to deep or open water
* The individual either avoids the ocean or other open bodies of water or endure them with intense fear
* The individual's fear of large bodies of water interferes with their normal functioning
* The individual's fear has been present for six months or longer
The prevalence and frequency of thalassophobia or any phobia is unknown for the most part. Researchers have concluded that the severity and prevalence of thalassophobia is in a constant state of change amongst different demographics and many may not be aware that they suffer from mild thalassophobia.[4]
## Treatment[edit]
Individuals who suffer from thalassophobia often improve their symptoms from specific strategies and procedures employed by therapists and medical professionals. It is extremely important to note that if left untreated, thalassophobia could lead to other mental disorders such as post-traumatic stress disorder, anxiety, depression and/or panic attacks.
* Cognitive Behavioural Therapy (CBT)
Thalassophobia can be managed through a psychological tool known as Cognitive Behavioural Therapy (CBT). CBT is a type of psychotherapeutic treatment that helps patients learn how to identify and manipulate disturbing thought patterns into positive and realistic behaviours.[15] Psychologists and therapists employ CBT to inflict a negative influence on certain behaviour and emotions so that they will be replaced by more appropriate and realistic reactions. A meta-analysis study in 2013 found that CBT has a positive effect in changing the neural pathways and activation of the brain on patients with phobias, resulting in more controlled behaviour when exposed to the fear.[16]
* Systematic Desensitisation
Systematic desensitisation is a treatment in which patients who suffer from certain phobias are exposed to increasingly more anxiety-provoking stimuli and taught relaxation techniques simultaneously.[12] Majority of individuals who have thalassophobia actively avoid the situation they are afraid of, which in return creates a false and even more frightening fake reality. Systematic desensitisation techniques allows patients to confront their fear with controlled emotions and realistic views.[6] It involves three steps, the first involves learning muscle relaxation techniques followed by patients being asked to create a list of fearful scenarios, ranking them in terms of their intensity. Finally, the patients are instructed to face their fear on a gradual spectrum. The focus of this technique is to focus on relaxation as they put themselves through stressful situations until the environment/event no longer causes discomfort.[17] The underlying theory behind systemic desensitisation is classical conditioning which aims to replace feelings of fear and anxiety with a state of calm. Relaxation techniques taught for dealing with thalassophobia through systemic desensitisation include diaphragmatic breathing, progressive muscle relaxation, meditation and mindfulness.[13]
* Exposure Therapy
Exposure therapy is the act of an individual coming into close contact with the situation or environment that triggers their phobia in a safe way. The overall goal of exposure therapy is to prove to the patient that a situation, object or environment is not as dangerous or worrisome as they might believe. This treatment also allows patients to feel more confident in their ability to cope with the situation that frightens them; should they face the situation they are afraid of.[3] In the case of thalassophobia, exposure therapy is employed to lessen the fear and anxiety associated with large bodies of water. There are several variation of exposure therapy and psychologists may use different techniques to achieve optimal results. These variations include:[18]
In vivo exposure: This is a technique whereby patients are instructed to directly face a feared object, situation or activity in real life. Those who suffer from thalassophobia are often instructed to enter the water at beaches, lakes or ponds. The downside of in vivo exposure is that participants have high dropout rates and poor treatment acceptance compared to other therapy options.
Interoceptive exposure: Deliberately inducing physical sensations that are harmless, yet feared. For instance, individuals with thalassophobia are often shown images of the sea, oceans or lakes or video footage of people in water. This induces a reaction which can then be changed or manipulated by the therapist.[3]
Virtual reality exposure: In certain circumstances, virtual reality technology can be employed when in vivo exposure is not practical. This could include when an individual doesn't reside near beaches, oceans or lakes. It can also include when some other factor inhibits the patient from entering such environments (including health, personal or religious factors).
Imaginal exposure: Vividly imagining the feared situation, object or environment. This technique is commonly used for those who have had a past traumatic experience or witnessed an event leading to their diagnosis of thalassophobia. It allows individuals to reduce their feelings of fear in regards to certain triggers.[12]
* Medication
Most patients improve or completely eliminate all their symptoms of thalassophobia through therapy; however, some might require a combination of therapy and medication to accurately treat their symptoms.[13] Medication cannot cure phobias such as thalassophobia however, it can help reduce symptoms of anxiety and fear. Selective serotonin re-uptake inhibitors (commonly known as SSRIs) are a type of antidepressants which can be prescribed by a qualified physician. Other common medication used for treating thalassophobia include beta blocker (which assists by blocking the flow of adrenaline that occurs when one is anxious) and benzodiazepines (fast-acting anti-anxiety medication). Benzodiazepines should only be prescribed only when other therapeutic or medicinal options have not worked as they are sedative and addicting.[19]
## See also[edit]
* Aquaphobia
* List of phobias
## References[edit]
1. ^ "thalass(o)-, comb. form". OED Online. Oxford University Press. June 2018. Retrieved August 7, 2018. "from Greek θάλασσα sea, and θαλάσσιος marine, formative elements of learned words. ... thalassophobia [is] a morbid dread of the sea."
2. ^ Snyder, Kari (2003). "Attack of the Water Monster". Boating. New York: Hachette Filipacchi Media. 76 (4): 44. ISSN 0006-5374. "Thalassophobia is the fear of the sea and can be associated with the fear of water or waves, fear of the vast emptiness, or fear of distance from land."
3. ^ a b c "Thalassophobia: Causes and treatments for the fear of the ocean". www.medicalnewstoday.com. 2020-11-19. Retrieved 2020-11-24.
4. ^ a b c d e Beasts of the deep : sea creatures and popular culture. Hackett, Jon, Harrington, Seán. Herts, United Kingdom. 2 February 2018. ISBN 978-0-86196-939-5. OCLC 1024275039.CS1 maint: others (link)
5. ^ a b "Thalassophobia: Signs, Symptoms, & Treatments". Choosing Therapy. Retrieved 2020-11-25.
6. ^ a b c "What Is Thalassophobia And How Can You Cope with It? | Betterhelp". www.betterhelp.com. Retrieved 2020-11-25.
7. ^ a b c d The spaces and places of horror. Pascuzzi, Francesco, Waters, Sandra. Wilmington, DE. 16 January 2020. ISBN 978-1-62273-863-2. OCLC 1122452212.CS1 maint: others (link)
8. ^ Carleton, R. Nicholas (2016-06-01). "Fear of the unknown: One fear to rule them all?". Journal of Anxiety Disorders. 41: 5–21. doi:10.1016/j.janxdis.2016.03.011. ISSN 0887-6185. PMID 27067453.
9. ^ Garcia, René (2017-09-01). "Neurobiology of fear and specific phobias". Learning & Memory. 24 (9): 462–471. doi:10.1101/lm.044115.116. ISSN 1072-0502. PMC 5580526. PMID 28814472.
10. ^ "Thalassophobia: Do You Fear the Deep Ocean?". HowStuffWorks. 2020-08-26. Retrieved 2020-11-24. "From an evolutionary perspective, it makes sense that humans would develop a tendency to fear and avoid deep water because of all the associated risks. We are essentially 'programmed' through evolution to fear some situations (e.g., heights, deep water, snakes) more easily than others (e.g., flowers, teddy bears)."
11. ^ Phobias : the psychology of irrational fear. Milosevic, Irena (Clinical psychologist), McCabe, Randi E. Santa Barbara, California. 2015. ISBN 978-1-61069-575-6. OCLC 895030322.CS1 maint: others (link)
12. ^ a b c d "Fear of the Ocean: What You Need to Know to Overcome It & Feel Better". Healthline. 2019-07-30. Retrieved 2020-11-25.
13. ^ a b c d "Thalassophobia: Do You Fear the Deep Ocean?". HowStuffWorks. 2020-08-26. Retrieved 2020-11-25.
14. ^ a b teo (2019-10-10). "Thalassophobia - fear of sea, sea travel, large bodies of water, emptiness of sea". FearOf.org. Retrieved 2020-11-25.
15. ^ PaulLee. "Thalassophobia". TranceForm Psychology. Retrieved 2020-11-25.
16. ^ Ipser, Jonathan C.; Singh, Leesha; Stein, Dan J. (2013). "Meta-analysis of functional brain imaging in specific phobia: Imaging meta-analysis of specific phobia". Psychiatry and Clinical Neurosciences. 67 (5): 311–322. doi:10.1111/pcn.12055. PMID 23711114.
17. ^ "Systematic Desensitization - A Treatment for Phobias | Simply Psychology". www.simplypsychology.org. Retrieved 2020-11-25.
18. ^ "What Is Exposure Therapy?". www.apa.org. Retrieved 2020-11-25.
19. ^ "CTRN: Change That's Right Now | Drugs & Medication". Retrieved 2020-11-25.
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
| Thalassophobia | None | 5,108 | wikipedia | https://en.wikipedia.org/wiki/Thalassophobia | 2021-01-18T18:28:42 | {"wikidata": ["Q3656219"]} |
"ESUS" redirects here. For other uses, see ESUS (disambiguation).
Embolic stroke of undetermined source (ESUS) is a type of ischemic stroke with an unknown origin, defined as a non-lacunar brain infarct without proximal arterial stenosis or cardioembolic sources.[1] As such, it forms a subset of cryptogenic stroke, which is part of the TOAST-classification.[2] The following diagnostic criteria define an ESUS:[1]
* Stroke detected by CT or MRI that is not lacunar
* No major-risk cardioembolic source of embolism
* Absence of extracranial or intracranial atherosclerosis causing 50% luminal stenosis in arteries supplying the area of ischaemia
* No other specific cause of stroke identified (e.g., arteritis, dissection, migraine/vasospasm, drug misuse)
## Contents
* 1 Causes
* 2 Diagnosis
* 2.1 Cryptogenic stroke vs ESUS
* 3 Management
* 4 Epidemiology
* 5 References
* 6 Further reading
## Causes[edit]
The following factors are suggested as pathogenesis of ESUS:[3]
* Subclinical atrial fibrillation: Detectable in ~2.7-30% of ESUS patients, depending on duration and modality of ECG monitoring.
* Patent foramen ovale (PFO): Deep vein thrombosis may result in paradoxical embolism in patients with PFO. About 40% of patients with cryptogenic stroke have PFO compared with 25% of the general population. However, the actual embolic source can often not be identified.
* Non-stenotic arterial plaques: Complicated plaques with signs indicative of intra-plaque haemorrhage in an ipsilateral carotid artery are detected in 1 in 4 of patients with cryptogenic stroke.[4][5] Aortic arch atherosclerosis is believed to be a specific cause of ESUS, particularly with plaques >4 mm diameter.[3][6]
* Further cardiopathies: the risk of ischaemic stroke is increased by supraventricular tachycardias. This also applies to patients with elevated NT-proBNP levels and patients with atrial enlargement in cardiac ultrasound.
* Other causes: Arterial dissections, infection-related vasculopathies (esp. Varicella zoster virus), thrombophilia, cancer-related thrombosis, migraine, Fabry disease and other genetic, autoimmune or rheumatic causes.
## Diagnosis[edit]
ESUS is a diagnosis of exclusion based on radiological and cardiological examinations. For exclusion of haemorrhagic or lacunar strokes CT or MRI imaging is needed. Both procedures also allow detection of embolic pattern of ischemic lesions. 12-lead ECG and cardiac monitoring for at least 24 h with automated rhythm detection are mandated to exclude atrial fibrillation; echocardiography (TTE and/or TEE) is used to detect other major-risk cardioembolic sources (e.g., intracardiac thrombi, or ejection fraction <30%). For imaging of both the extracranial and intracranial arteries supplying the area of brain ischaemia, examination methods like catheter, MR/CT angiography or cervical duplex plus transcranial Doppler ultrasonography are required. They allow an exclusion of large vessel stenosis (≥ 50%).[1]
### Cryptogenic stroke vs ESUS[edit]
Cryptogenic stroke is also an ischemic stroke with more than one probable cause or strokes with incomplete diagnostic workup.[2] ESUS has a clearer definition, with an established minimum diagnostic requirements; this is not required in defining a cryptogenic stroke. ESUS is an embolic stroke for which no probable cause can be identified after a standard diagnostic evaluation.
## Management[edit]
Due to the lack of data, there are no specific treatment guidelines for ESUS. Current guidelines recommend antiplatelet therapy for patients with non-cardioembolic ischemic stroke.[7][8][9] However, it is widely believed that there is a substantial overlap between ESUS and cardioembolic stroke so there may be a rationale for anticoagulation.[1][10] This approach is currently tested in clinical trials.
## Epidemiology[edit]
On average, ESUS accounts for about 1 in 6 ischemic strokes (17% (range 9 – 25%)) according to a systematic literature review of 9 studies.[11] Patients with ESUS tend to be relatively young and experience mild strokes. However, ESUS is associated with high recurrence rates. Of 2045 ESUS patients (identified by 8 studies)
* 58% were male,
* the mean age was 65 years,
* the average annualized rate of stroke recurrence was 4.5%
* mean NIHSS at stroke onset was 5.
The stroke recurrence rate was 29.0% over 5 years in patients with ESUS, which is similar to patients with cardioembolic stroke (26.8%), but significantly higher than all types of non-cardioembolic stroke. However, mortality was significantly lower in patients with ESUS than cardioembolic stroke.[12][13]
## References[edit]
1. ^ a b c d Hart RG, Diener HC, Coutts SB, Easton JD, Granger CB, O'Donnell MJ, Sacco RL, Connolly SJ (April 2014). "Embolic strokes of undetermined source: the case for a new clinical construct". The Lancet. Neurology. 13 (4): 429–38. doi:10.1016/S1474-4422(13)70310-7. PMID 24646875.
2. ^ a b Adams HP, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE (January 1993). "Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment". Stroke. 24 (1): 35–41. doi:10.1161/01.STR.24.1.35. PMID 7678184.
3. ^ a b Nouh A, Hussain M, Mehta T, Yaghi S (2016). "Embolic Strokes of Unknown Source and Cryptogenic Stroke: Implications in Clinical Practice". Frontiers in Neurology. 7: 37. doi:10.3389/fneur.2016.00037. PMC 4800279. PMID 27047443.
4. ^ Freilinger TM, Schindler A, Schmidt C, Grimm J, Cyran C, Schwarz F, et al. (April 2012). "Prevalence of nonstenosing, complicated atherosclerotic plaques in cryptogenic stroke". JACC: Cardiovascular Imaging. 5 (4): 397–405. doi:10.1016/j.jcmg.2012.01.012. PMID 22498329.
5. ^ Gupta A, Gialdini G, Lerario MP, Baradaran H, Giambrone A, Navi BB, et al. (June 2015). "Magnetic resonance angiography detection of abnormal carotid artery plaque in patients with cryptogenic stroke". Journal of the American Heart Association. 4 (6): e002012. doi:10.1161/JAHA.115.002012. PMC 4599540. PMID 26077590.
6. ^ Amarenco P, Cohen A, Tzourio C, Bertrand B, Hommel M, Besson G, et al. (December 1994). "Atherosclerotic disease of the aortic arch and the risk of ischemic stroke". The New England Journal of Medicine. 331 (22): 1474–9. doi:10.1056/NEJM199412013312202. PMID 7969297.
7. ^ European Stroke Organisation (ESO) Executive Committee, Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, et al. (July 2014). "Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association". Stroke. 45 (7): 2160–236. doi:10.1161/STR.0000000000000024. PMID 24788967.
8. ^ Lansberg MG, O'Donnell MJ, Khatri P, Lang ES, Nguyen-Huynh MN, Schwartz NE, et al. (February 2012). "Antithrombotic and thrombolytic therapy for ischemic stroke: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines". Chest. 141 (2 Suppl): e601S–e636S. doi:10.1378/chest.11-2302. PMC 3278065. PMID 22315273.
9. ^ European Stroke Organisation (ESO) Executive Committee; ESO Writing Committee, Ringleb PA, Bousser MG, Ford G, Bath P, Brainin M, et al. (2008). "Guidelines for management of ischaemic stroke and transient ischaemic attack 2008". Cerebrovascular Diseases. 25 (5): 457–507. doi:10.1159/000131083. PMID 18477843.
10. ^ Kamel H, Healey JS (February 2017). "Cardioembolic Stroke". Circulation Research. 120 (3): 514–526. doi:10.1161/CIRCRESAHA.116.308407. PMC 5312810. PMID 28154101.
11. ^ Hart RG, Catanese L, Perera KS, Ntaios G, Connolly SJ (April 2017). "Embolic Stroke of Undetermined Source: A Systematic Review and Clinical Update". Stroke. 48 (4): 867–872. doi:10.1161/STROKEAHA.116.016414. PMID 28265016.
12. ^ Ntaios G, Papavasileiou V, Milionis H, Makaritsis K, Manios E, Spengos K, Michel P, Vemmos K (January 2015). "Embolic strokes of undetermined source in the Athens stroke registry: a descriptive analysis". Stroke. 46 (1): 176–81. doi:10.1161/STROKEAHA.114.007240. PMID 25378429.
13. ^ Ntaios G, Papavasileiou V, Milionis H, Makaritsis K, Vemmou A, Koroboki E, et al. (August 2015). "Embolic Strokes of Undetermined Source in the Athens Stroke Registry: An Outcome Analysis". Stroke. 46 (8): 2087–93. doi:10.1161/STROKEAHA.115.009334. PMID 26159795.
## Further reading[edit]
* Spence JD (September 2016). "Cryptogenic Stroke". The New England Journal of Medicine. 375 (11): e26. doi:10.1056/NEJMc1609156. PMID 27626543.
* Amin H, Greer DM (January 2014). "Cryptogenic stroke-the appropriate diagnostic evaluation". Current Treatment Options in Cardiovascular Medicine. 16 (1): 280. doi:10.1007/s11936-013-0280-3. PMID 24352977.
* Diener HC, Bernstein R, Hart R (September 2017). "Secondary Stroke Prevention in Cryptogenic Stroke and Embolic Stroke of Undetermined Source (ESUS)". Current Neurology and Neuroscience Reports. 17 (9): 64. doi:10.1007/s11910-017-0775-5. PMID 28707135.
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
| Embolic stroke of undetermined source | c3888970 | 5,109 | wikipedia | https://en.wikipedia.org/wiki/Embolic_stroke_of_undetermined_source | 2021-01-18T19:01:15 | {"umls": ["C3888970"], "wikidata": ["Q55610805"]} |
Median arcuate ligament syndrome (MALS) is a rare disorder characterized by chronic, recurrent abdominal pain related to compression of the celiac artery (which supplies blood to the upper abdominal organs) by the median arcuate ligament (a muscular fibrous band of the diaphragm). It usually presents with symptoms of abdominal pain, weight loss, and an abdominal bruit (abnormal sound of a blood vessel when blocked or narrowed). The cause is not fully understood; however, it is suspected that there could be a combination of vascular (blood supply) and neurogenic (neurological) components involved. Diagnosis is usually confirmed with imaging such as CT angiography, MRI, ultrasound, and arteriography. Surgery is currently the only treatment option and involves releasing the ligament.
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
| Median arcuate ligament syndrome | c1861783 | 5,110 | gard | https://rarediseases.info.nih.gov/diseases/12308/median-arcuate-ligament-syndrome | 2021-01-18T17:59:11 | {"mesh": ["D000074742"], "synonyms": ["MALS", "Celiac artery compression syndrome", "Celiac axis syndrome", "Dunbar syndrome"]} |
Dental fear
Other namesDental anxiety, dental phobia, odontophobia
Cycle of dental fear
Dental fear is a normal emotional reaction to one or more specific threatening stimuli in the dental situation.[1][2] However, dental anxiety is indicative of a state of apprehension that something dreadful is going to happen in relation to dental treatment, and it is usually coupled with a sense of losing control.[1] Similarly, dental phobia denotes a severe type of dental anxiety, and is characterised by marked and persistent anxiety in relation to either clearly discernible situations or objects (e.g. drilling, local anaesthetic injections) or to the dental setting in general.[1] The term ‘dental fear and anxiety’ (DFA) is often used to refer to strong negative feelings associated with dental treatment among children, adolescents and adults, whether or not the criteria for a diagnosis of dental phobia are met. Dental phobia can include fear of dental procedures, dental environment or setting, fear of dental instruments or fear of the dentist as a person.[3] People with dental phobia often avoid the dentist and neglect oral health, which may lead to painful dental problems and ultimately force a visit to the dentist. The emergency nature of this appointment may serve to worsen the phobia. This phenomenon may also be called the cycle of dental fear.[3] Dental anxiety typically starts in childhood.[1] There is the potential for this to place strains on relationships and negatively impact on employment.[4]
## Contents
* 1 Signs and symptoms
* 2 Cause
* 3 Diagnosis
* 4 Management
* 4.1 Psychocognitive
* 4.1.1 Modelling
* 4.1.2 Tell-show-do
* 4.1.3 Behavioural techniques
* 4.1.4 Cognitive behavioural therapy
* 4.1.5 Environment changes
* 4.1.6 Hypnosis
* 4.1.7 Progressive muscle relaxation
* 4.1.8 Systematic desensitisation
* 4.2 Medication
* 4.2.1 Premedication
* 4.2.2 Conscious sedation
* 4.2.3 General anaesthesia
* 5 Epidemiology
* 6 See also
* 7 References
## Signs and symptoms[edit]
As with all types of fear and phobias, dental fear can manifest as single or combination of emotional, physiological, cognitive and behavioural symptoms.[5]
Emotional response
* Feeling of fear
* Feeling of anxiety
* Apprehension
* Panic
Physiological response
* Increased heart rate
* Breathlessness
* Sweating
* Nausea
* Shaking
Cognitive response
* "I don't like the feeling of this..."
* "I am choking to death"
* "I am having a heart attack"
* "I am going to die"
* "Feeling of swollen face"
* "I am not able to breathe"
Behavioural response
* Agitation
* High vigilance
## Cause[edit]
See also: Phobia
Research suggests that there is a complex set of factors that lead to the development and maintenance of significant dental anxiety or dental phobia, which can be grouped as genetic, behavioural and cognitive factors.[6] In comparison to other phobias, literature on odontophobia is relatively limited. There are several theories been proposed, however a 2014 review describes 5 pathways which relate specifically to development dental fear and anxiety: Cognitive Conditioning, Vicarious, Verbal Threat, Informative, and Parental. It is important to note, however, that there may be a variety of background factors common to all general fear and anxiety conditions that may be at play and affect these more specific pathways.[6]
Conditioning
Conditioning is defined as the process by which a person learns through personal experience that an event or stimulus will result in a detrimental outcome, e.g. "if I visit the dentist, it is going to be sore". As, expected dental fear is associated with previous traumatic experiences, especially their first one.[1] It is believed to be the most commonly used pathway for patients to develop dental fear and anxiety.[6]
Informative
This indirect pathway relates to fear acquisition through gaining information and becoming bias to the dental environment from dental phobic elders, negative connotations advertised by media (e.g. television, movies), and friends with personal negative experiences.[6]
Vicarious
The vicarious pathway suggests that fear is acquired through imagination of the feelings, experience or actions of another person. Whether this pathway occurs on its own or in combination with others is still unknown. It has been suggested that dental fear in the very young is passed through this pathway through observation of expressions of fear by elders/parents at the dentist.[6]
Verbal threat
This pathway can be seen as similar to the informative pathway, however it is more reliant on the emotion of fear elicited by "word of mouth" and is heavily modulated by the messenger. In essence the verbal threat pathway is the fear induced when an authority figure threatens an individual with a painful experience. In the case of dental fear, the painful and/or negative experiences linked to dental visits. Although, at a glance, the verbal threat and informative pathway are similar, in odontophobia the two pathways differ in that the verbal threat pathway occurs when a “visit to the dentist” is literally used as a form of punishment for bad behaviour. This does not occur in the informative pathway.[6]
Parental modelling
There is a significant relationship between child and parental dental fear,[7] especially that of the mothers.[6] it has been suggested that this relationship is strongest in children 8 years or younger.[6] However, it is important to note the parental modelling pathway may overlap with the informative or vicarious pathways are all linked in some way.
## Diagnosis[edit]
Several methods have been developed to diagnose dental fear and anxiety. In addition to identifying the patients with dental fear, different categories of dental fear have been established.[3][8] These include:
* Dental fear survey (DFS) which incapsulates 20 items in relation to various situations, feelings and reaction to dental work which is used to diagnose dental fear.
* Modified child dental anxiety scale (MCDAS), used for children and it has 8 items with a voting system from 1–5 where 1 is not worried and 5 is very worried.
* The index of dental anxiety and fear (IDAF-4C+), used for adults and it is separated into 8 item module and then a further 10 item module.
* Corahs dental anxiety scale 1–4 questions and then 1–26 question. This scale has a ranking system and the second section with 26 questions has 1–4 options ranging from 'low' to 'don't know' which is used to assess dental concern. The first section with 1–4 questions has 5 Likert scale options which are worth 1–5 points with the possible amount of maximum points is 20. Then depending on the result you rate the dental anxiety. 9–12 being moderate 13–14 being high, and 15–20 being severe.
* Spielberger State Trait Anxiety Index (STA): an instrument for measuring anxiety in adults. It differentiates between temporary condition of "state anxiety" and the more general and long-lasting quality of "trait anxiety". It can also help differentiate between anxiety and depression[9]
* Anxiety Sensitivity Index (ASI): a 16-item scale that focuses on apprehension about the symptoms of anxiety itself[10]
* Seattle System: consists of four diagnostic types in which such individuals are categorised according to the main source of their dear regarding dental treatment[3]
* Type 1: simple conditioned phobia—fear of dental procedures
* Type 2: fear of catastrophe—anxiety about somatic reactions during dental treatment, e.g. fainting, panic attack, heart attack
* Type 3: Generalized anxiety—nervous person in general
* Type 4: distrust of dentists—fear of the dentist
## Management[edit]
Dental fear varies across a continuum, from very mild fear to severe. Therefore, in a dental setting, it is also the case where the technique and management that works for one patient might not work for another. Some individuals may require a tailored management and treatment approach.[5]
The management of people with dental fear can be done using shorter term methods such as hypnosis and general anesthetic, or longer term methods such as cognitive behavioral therapy and the development of coping skills. Short term methods have been proven to be ineffective for long-term treatment of the phobia, since many return to a pattern of treatment avoidance afterwards. Psychological approaches are more effective at maintaining regular dental care, but demand more knowledge from the dentist and motivation from the patient[3]
Similarly, distraction techniques can also be utilised to divert the patient's attention to allow them to avoid supposed negativity and be more comfortable. This can be achieved through television or movies, or a physical distraction such as focusing on another body part such as wiggling the toes or fingers.[5]
### Psychocognitive[edit]
#### Modelling[edit]
Modelling is a form of psycho-behavioural therapy used to alleviate dental fear. Commonly used in paediatric dentistry, it involves the showing of a procedure under a simulated environment. It allows the patient to observe the behaviour of a friend, family member, or other patient when put in a similar situation, therefore, accommodating for the learning of new coping mechanisms.[5] Modelling can be presented live using a parent or actor as well as virtually through pre-recorded films.[4]
#### Tell-show-do[edit]
Tell-show-do is a common non-pharmacological practice used to manage behaviour such as dental fear, especially in paediatric dentistry.[5] The purpose of this intervention is to promote a positive attitude towards dentistry and to build a relationship with the patient to improve compliance. The patient is gradually introduced to the treatment. Firstly, the dentist "tells" the patient what the dental procedure will be using words. In 'show' phase, the patient is familiarized with dental treatment using demonstrations. Lastly, in 'do' phase, the dentist proceeds with the treatment following the same procedure and demonstrations illustrated to the patient.[11]
#### Behavioural techniques[edit]
A technique known as behavioral control involves the person giving a signal to the clinician when to stop the procedure. This could be simply raising a hand to let the clinician know, however, the signal that is chosen will be discussed prior. This technique provides the people with a sense of control over the appointment and as so, instills trust in the dentist.[4]
#### Cognitive behavioural therapy[edit]
Cognitive behavioral therapy (CBT) appears to decrease dental fear and improve the frequency people go to the dentist.[12] Other measures that may be useful include distraction, guided imagery, relaxation techniques, and music therapy.[4][13] Behavior techniques are believed to be sufficient for the majority of people with mild anxiety.[14] The quality of the evidence to support this, however, is low.[15]
#### Environment changes[edit]
It has been suggested that the ambience created by the dental practice can play a significant role in initiating dental fear and anxiety by triggering sensory stimuli. It has been suggested that the front of house staff, e.g. receptionist and dental nurses contribute to elicit a better cognitive and emotional experience for anxious patients by showing a positive and caring attitude and by adopting good communication techniques.[5] Anxious patients should not be made to wait too long in waiting rooms, so that they have less time to recall and absorb negative feelings. There is some small evidence that the waiting areas with soft music playing and dimmer lights and cooler in temperature produces a more calming effect. It as also been stipulated that masking strong clinical smells like eugenol with more pleasant smells can help to reduce anxiety, however this is more likely to be effective in moderate rather than severe anxiety.[5]
#### Hypnosis[edit]
Hypnosis may be useful in certain people.[4] Hypnosis may improve a person's level of cooperation and decrease gagging.[16]
#### Progressive muscle relaxation[edit]
Ideally done in a sitting position, this relaxation technique for certain muscle groups can be implemented in the waiting room. The major muscles groups include
* feet, calves, thighs, and buttocks
* hands, forearms, and biceps
* chest, stomach, and lower back; and
* head, face, throat, and shoulders[5]
The steps according to Edmund Jacobson are as follows:
1. Gently inhale, hold and exhale, being aware of the rise and fall of the chest.
2. Slightly extend and stretch toes towards knees, hold briefly and then let go. Recognize the difference in sensation.
3. Press heels of feet into the floor, hold and let go.
4. Press knees together hold briefly before letting them drift apart. Be aware of the change.
5. Squeeze buttocks together, hold before letting go.
6. Pull in stomach muscles towards the spine, hold briefly before releasing. Feel the difference.
7. Gently pull shoulders towards ears, enough to feel some tension in them, hold briefly before letting go.
8. Press upper arms and elbows into sides of the body, hold and then let go. Recognize a difference in feeling.
9. Gently clench hands, hold and let go.
10. Extend head forward slightly, hold briefly before releasing the tension and allowing for the head to return to the resting position.
11. Press the lips together before letting go until they are barely touching. Purse lips and let go, feeling the tension being let go.
12. Push the tongue to the roof of the mouth, hold briefly before letting it drop loosely.[5]
#### Systematic desensitisation[edit]
Desensitisation in dentistry refers to the gradual exposure of a new procedure to the patient in order to calm their anxiety. It is based on the principle that a patient can overcome their anxiety if they are gradually exposed to the feared stimuli, whether imagined or real, in a controlled and systematic way. Exposure to the feared stimuli or situation is recognised as a central treatment component for specific phobias.[17][18]
### Medication[edit]
Pharmacological techniques to manage dental fear range from conscious sedation to general anaesthesia; these are often used and work best in conjunction with behavioural (non-pharmacological) techniques.[19]
#### Premedication[edit]
Premedication refers to medication given prior to initiation of dental treatment.[20] Benzodiazepines, a class of sedative drugs, are commonly used as premedication, in the form of a tablet, to aid anxiety management before dental treatment.[21] Benzodiazepines are however addictive and subject to abuse, therefore only the minimum number of tablets required should be prescribed. Patients may also be required to be accompanied to their dental appointment by an escort.[22] In the UK, temazepam used to be the drug of choice however, lately, midazolam has become much more popular. In children, a recent meta-analysis comparing oral midazolam against placebo showed some improvement in co-operation in children using midazolam.[21] One of the disadvantages of oral premedication is that it is not titratable (i.e. it is difficult to adjust the dose to control the level of sedation desired) and therefore this technique should be only be used when other titratable sedation techniques are inappropriate.[13]
#### Conscious sedation[edit]
Conscious sedation refers to the use of a single or combination of drugs to help relax and reduce pain during a medical or dental procedure. There are a range of techniques and drugs that can be used ; these need to be tailored to the individual need of the patient taking into account the medical history, the skill and training of the dentist/sedationist and the facilities and equipment available.
#### General anaesthesia[edit]
General anaesthesia for dentistry can only be carried out in a hospital setting.[23]
The use of general anaesthesia to reduce the pain and anxiety associated with dental treatment should be discouraged and general anaesthesia should be undertaken only when absolutely necessary.[5]
## Epidemiology[edit]
Individuals who are highly anxious about undergoing dental treatment comprise approximately one in six of the population.[4] Middle aged women appear to have higher rates of dental anxiety compared to men.[4]
## See also[edit]
* Medicine portal
* Psychology portal
* Fear of medical procedures
* List of phobias
* Dental braces
* Prosthodontics
* Oral and maxillofacial surgery
* Prosthodontics
* Dental implant
## References[edit]
1. ^ a b c d e Seligman LD, Hovey JD, Chacon K, Ollendick TH (July 2017). "Dental anxiety: An understudied problem in youth". Clinical Psychology Review. 55: 25–40. doi:10.1016/j.cpr.2017.04.004. PMID 28478271.
2. ^ Anthonappa RP, Ashley PF, Bonetti DL, Lombardo G, Riley P (2017). "Non-pharmacological interventions for managing dental anxiety in children". Cochrane Database of Systematic Reviews. doi:10.1002/14651858.CD012676.
3. ^ a b c d e Moore R (1991). The Phenomenon of Dental Fear - Studies in Clinical Diagnosis, Measurement and Treatment (Ph.D. thesis). Fællestrykeriet, Aarhus University; Aarhus Denmark. doi:10.13140/rg.2.1.3647.5363/1.
4. ^ a b c d e f g Armfield JM, Heaton LJ (December 2013). "Management of fear and anxiety in the dental clinic: a review". Australian Dental Journal. 58 (4): 390–407, quiz 531. doi:10.1111/adj.12118. PMID 24320894.
5. ^ a b c d e f g h i j Appukuttan DP (March 2016). "Strategies to manage patients with dental anxiety and dental phobia: literature review". Clinical, Cosmetic and Investigational Dentistry. 8: 35–50. doi:10.2147/CCIDE.S63626. PMC 4790493. PMID 27022303.
6. ^ a b c d e f g h Carter AE, Carter G, Boschen M, AlShwaimi E, George R (November 2014). "Pathways of fear and anxiety in dentistry: A review". World Journal of Clinical Cases. 2 (11): 642–53. doi:10.12998/wjcc.v2.i11.642. PMC 4233415. PMID 25405187.
7. ^ Themessl-Huber M, Freeman R, Humphris G, MacGillivray S, Terzi N (March 2010). "Empirical evidence of the relationship between parental and child dental fear: a structured review and meta-analysis". International Journal of Paediatric Dentistry. 20 (2): 83–101. doi:10.1111/j.1365-263X.2009.00998.x. PMID 20384823.
8. ^ De Jongh A, Adair P, Meijerink-Anderson M (April 2005). "Clinical management of dental anxiety: what works for whom?". International Dental Journal. 55 (2): 73–80. doi:10.1111/j.1875-595X.2005.tb00037.x. PMID 15880961.
9. ^ "The State-Trait Anxiety Inventory (STAI)". American Psychological Association. Retrieved 2019-02-19.
10. ^ Gilbert C (2014). "Chapter 6.4 – Psychological assessment of breathing problems". In Chaitow L, Dinah Bradley D, Gilbert C (eds.). Recognizing and Treating Breathing Disorders (2nd ed.). Elsevier. pp. 129–136. doi:10.1016/b978-0-7020-4980-4.00011-3. ISBN 978-0-7020-4980-4.
11. ^ "Non-pharmacological Behaviour Management". Royal College of Surgeons. Retrieved 2020-01-30.
12. ^ Newton T, Asimakopoulou K, Daly B, Scambler S, Scott S (September 2012). "The management of dental anxiety: time for a sense of proportion?". British Dental Journal. 213 (6): 271–4. doi:10.1038/sj.bdj.2012.830. PMID 22996472.
13. ^ a b Ibbetson R, Blayney M, Rookes V, Cowpe J, Craig D, Felix D, et al. (Intercollegiate Advisory Committee for Sedation in Dentistry) (2015). Standards for Conscious Sedation in the Provision of Dental Care (PDF). United Kingdom: RCS Publications. p. 11. OCLC 915494772.
14. ^ Department of Health. Salaried Primary Dental Care Services: Toolkit for Commissioners. p9. London: Department of Health, 2009
15. ^ Wide Boman U, Carlsson V, Westin M, Hakeberg M (June 2013). "Psychological treatment of dental anxiety among adults: a systematic review". European Journal of Oral Sciences. 121 (3 Pt 2): 225–34. doi:10.1111/eos.12032. PMID 23659254.
16. ^ Allison N (October 2015). "Hypnosis in modern dentistry: Challenging misconceptions". Faculty Dental Journal. 6 (4): 172–175. doi:10.1308/rcsfdj.2015.172.
17. ^ ten Berg M (February 2008). "Dental fear in children: clinical consequences. Suggested behaviour management strategies in treating children with dental fear". European Archives of Paediatric Dentistry. 9 Suppl 1 (S1): 41–6. doi:10.1007/BF03262655. PMID 18328248.
18. ^ Klinberg G (February 2008). "Dental anxiety and behaviour management problems in paediatric dentistry--a review of background factors and diagnostics". European Archives of Paediatric Dentistry. 9 Suppl 1 (S1): 11–5. doi:10.1007/BF03262650. PMID 18328243.
19. ^ Milgrom P, Heaton LJ (January 2007). "Enhancing sedation treatment for the long- term: pre-treatment behavioural exposure". SAAD Digest. 23: 29–34. PMID 17265912.
20. ^ "BNF is only available in the UK". NICE. Retrieved 2020-02-19.
21. ^ a b Ashley PF, Chaudhary M, Lourenço-Matharu L (December 2018). "Sedation of children undergoing dental treatment". The Cochrane Database of Systematic Reviews. 12: CD003877. doi:10.1002/14651858.CD003877.pub5. PMC 6517004. PMID 30566228. Retrieved 2020-02-19.
22. ^ Richards D (June 2012). "SDCEP Dental Prescribing app". Evidence-Based Dentistry. 13 (2): 61–2. doi:10.1038/sj.ebd.6400867. PMID 22722422.
23. ^ Lim MA, Borromeo GL (June 2017). "The use of general anesthesia to facilitate dental treatment in adult patients with special needs". Journal of Dental Anesthesia and Pain Medicine. 17 (2): 91–103. doi:10.17245/jdapm.2017.17.2.91. PMC 5564153. PMID 28879336.
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
| Dental fear | None | 5,111 | wikipedia | https://en.wikipedia.org/wiki/Dental_fear | 2021-01-18T18:28:19 | {"mesh": ["D016854"], "wikidata": ["Q143472"]} |
Maternally-inherited mitochondrial dystonia is a rare neurological mitochondrial DNA-related disorder characterized clinically by progressive pediatric-onset dystonia with variable degrees of severity.
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
| Mitochondrial DNA-related dystonia | None | 5,112 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=254851 | 2021-01-23T18:01:53 | {"icd-10": ["E88.8"], "synonyms": ["Maternally-inherited mitochondrial dystonia", "mtDNA-related dystonia"]} |
Nervous system disease located in nerves or nerve cells
Not to be confused with Nephropathy or Neuropathology.
Peripheral neuropathy
Micrograph showing a vasculitic peripheral neuropathy; plastic embedded; Toluidine blue stain
SpecialtyNeurology
Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland or organ function depending on which nerves are affected; in other words, neuropathy affecting motor, sensory, or autonomic nerves result in different symptoms. More than one type of nerve may be affected simultaneously. Peripheral neuropathy may be acute (with sudden onset, rapid progress) or chronic (symptoms begin subtly and progress slowly), and may be reversible or permanent.
Common causes include systemic diseases (such as diabetes or leprosy), hyperglycemia-induced glycation,[1][2][3] vitamin deficiency, medication (e.g., chemotherapy, or commonly prescribed antibiotics including metronidazole and the fluoroquinolone class of antibiotics (Ciprofloxacin, Levaquin, Avelox etc.)), traumatic injury, including ischemia, radiation therapy, excessive alcohol consumption, immune system disease, coeliac disease, non-celiac gluten sensitivity, or viral infection. It can also be genetic (present from birth) or idiopathic (no known cause).[4][5][6][7] In conventional medical usage, the word neuropathy (neuro-, "nervous system" and -pathy, "disease of")[8] without modifier usually means peripheral neuropathy.
Neuropathy affecting just one nerve is called "mononeuropathy" and neuropathy involving nerves in roughly the same areas on both sides of the body is called "symmetrical polyneuropathy" or simply "polyneuropathy". When two or more (typically just a few, but sometimes many) separate nerves in disparate areas of the body are affected it is called "mononeuritis multiplex", "multifocal mononeuropathy", or "multiple mononeuropathy".[4][5][6]
Neuropathy may cause painful cramps, fasciculations (fine muscle twitching), muscle loss, bone degeneration, and changes in the skin, hair, and nails. Additionally, motor neuropathy may cause impaired balance and coordination or, most commonly, muscle weakness; sensory neuropathy may cause numbness to touch and vibration, reduced position sense causing poorer coordination and balance, reduced sensitivity to temperature change and pain, spontaneous tingling or burning pain, or skin allodynia (severe pain from normally nonpainful stimuli, such as light touch); and autonomic neuropathy may produce diverse symptoms, depending on the affected glands and organs, but common symptoms are poor bladder control, abnormal blood pressure or heart rate, and reduced ability to sweat normally.[4][5][6]
## Contents
* 1 Classification
* 1.1 Mononeuropathy
* 1.2 Polyneuropathy
* 1.3 Mononeuritis multiplex
* 1.4 Autonomic neuropathy
* 1.5 Neuritis
* 2 Signs and symptoms
* 3 Causes
* 4 Diagnosis
* 5 Treatment
* 5.1 Medications
* 5.1.1 Antidepressants
* 5.1.2 Antiepileptics
* 5.1.3 Opioids
* 5.1.4 Others
* 5.2 Medical devices
* 5.3 Diet
* 5.4 Counselling
* 5.5 Alternative medicine
* 6 Research
* 7 See also
* 8 References
* 9 Further reading
* 10 External links
## Classification[edit]
Peripheral neuropathy may be classified according to the number and distribution of nerves affected (mononeuropathy, mononeuritis multiplex, or polyneuropathy), the type of nerve fiber predominantly affected (motor, sensory, autonomic), or the process affecting the nerves; e.g., inflammation (neuritis), compression (compression neuropathy), chemotherapy (chemotherapy-induced peripheral neuropathy). The affected nerves are found in an EMG / NCS test and the classification is applied upon completion of the exam.[9]
### Mononeuropathy[edit]
See also: Compression neuropathy and Ulnar neuropathy
Mononeuropathy is a type of neuropathy that only affects a single nerve.[10] Diagnostically, it is important to distinguish it from polyneuropathy because when a single nerve is affected, it is more likely to be due to localized trauma or infection.
The most common cause of mononeuropathy is physical compression of the nerve, known as compression neuropathy. Carpal tunnel syndrome and axillary nerve palsy are examples. Direct injury to a nerve, interruption of its blood supply resulting in (ischemia), or inflammation also may cause mononeuropathy.
### Polyneuropathy[edit]
Main article: Polyneuropathy
"Polyneuropathy" is a pattern of nerve damage that is quite different from mononeuropathy, often more serious and affecting more areas of the body. The term "peripheral neuropathy" sometimes is used loosely to refer to polyneuropathy. In cases of polyneuropathy, many nerve cells in various parts of the body are affected, without regard to the nerve through which they pass; not all nerve cells are affected in any particular case. In distal axonopathy, one common pattern is that the cell bodies of neurons remain intact, but the axons are affected in proportion to their length; the longest axons are the most affected. Diabetic neuropathy is the most common cause of this pattern. In demyelinating polyneuropathies, the myelin sheath around axons is damaged, which affects the ability of the axons to conduct electrical impulses. The third and least common pattern affects the cell bodies of neurons directly. This usually picks out either the motor neurons (known as motor neuron disease) or the sensory neurons (known as sensory neuronopathy or dorsal root ganglionopathy).
The effect of this is to cause symptoms in more than one part of the body, often symmetrically on left and right sides. As for any neuropathy, the chief symptoms include motor symptoms such as weakness or clumsiness of movement; and sensory symptoms such as unusual or unpleasant sensations such as tingling or burning; reduced ability to feel sensations such as texture or temperature, and impaired balance when standing or walking. In many polyneuropathies, these symptoms occur first and most severely in the feet. Autonomic symptoms also may occur, such as dizziness on standing up, erectile dysfunction, and difficulty controlling urination.
Polyneuropathies usually are caused by processes that affect the body as a whole. Diabetes and impaired glucose tolerance are the most common causes. Hyperglycemia-induced formation of advanced glycation end products (AGEs) is related to diabetic neuropathy.[11] Other causes relate to the particular type of polyneuropathy, and there are many different causes of each type, including inflammatory diseases such as Lyme disease, vitamin deficiencies, blood disorders, and toxins (including alcohol and certain prescribed drugs).
Most types of polyneuropathy progress fairly slowly, over months or years, but rapidly progressive polyneuropathy also occurs. It is important to recognize that at one time it was thought that many of the cases of small fiber peripheral neuropathy with typical symptoms of tingling, pain, and loss of sensation in the feet and hands were due to glucose intolerance before a diagnosis of diabetes or pre-diabetes. However, in August 2015, the Mayo Clinic published a scientific study in the Journal of the Neurological Sciences showing "no significant increase in...symptoms...in the prediabetes group", and stated that "A search for alternate neuropathy causes is needed in patients with prediabetes." [12]
The treatment of polyneuropathies is aimed firstly at eliminating or controlling the cause, secondly at maintaining muscle strength and physical function, and thirdly at controlling symptoms such as neuropathic pain.
### Mononeuritis multiplex[edit]
Mononeuritis multiplex, occasionally termed polyneuritis multiplex, is simultaneous or sequential involvement of individual noncontiguous nerve trunks,[13] either partially or completely, evolving over days to years and typically presenting with acute or subacute loss of sensory and motor function of individual nerves. The pattern of involvement is asymmetric, however, as the disease progresses, deficit(s) becomes more confluent and symmetrical, making it difficult to differentiate from polyneuropathy.[14] Therefore, attention to the pattern of early symptoms is important.
Mononeuritis multiplex also may cause pain, which is characterized as deep, aching pain that is worse at night and frequently in the lower back, hip, or leg. In people with diabetes mellitus, mononeuritis multiplex typically is encountered as acute, unilateral, and severe thigh pain followed by anterior muscle weakness and loss of knee reflex.[medical citation needed]
Electrodiagnostic medicine studies will show multifocal sensory motor axonal neuropathy.
It is caused by, or associated with, several medical conditions:
* Diabetes mellitus
* Vasculitides: polyarteritis nodosa,[15][16] granulomatosis with polyangiitis[16] and eosinophilic granulomatosis with polyangiitis.[16] This results in vasculitic neuropathy.
* Immune-mediated diseases, such as rheumatoid arthritis,[17] systemic lupus erythematosus (SLE)
* Infections: leprosy, lyme disease, parvovirus B19,[18] HIV[19]
* Sarcoidosis[20]
* Cryoglobulinemia[21]
* Reactions to exposure to chemical agents, including trichloroethylene and dapsone[medical citation needed]
* Rarely, following the sting of certain jellyfish, such as the sea nettle[medical citation needed]
### Autonomic neuropathy[edit]
Autonomic neuropathy is a form of polyneuropathy that affects the non-voluntary, non-sensory nervous system (i.e., the autonomic nervous system), affecting mostly the internal organs such as the bladder muscles, the cardiovascular system, the digestive tract, and the genital organs. These nerves are not under a person's conscious control and function automatically. Autonomic nerve fibers form large collections in the thorax, abdomen, and pelvis outside the spinal cord. They have connections with the spinal cord and ultimately the brain, however. Most commonly autonomic neuropathy is seen in persons with long-standing diabetes mellitus type 1 and 2. In most—but not all—cases, autonomic neuropathy occurs alongside other forms of neuropathy, such as sensory neuropathy.
Autonomic neuropathy is one cause of malfunction of the autonomic nervous system, but not the only one; some conditions affecting the brain or spinal cord also may cause autonomic dysfunction, such as multiple system atrophy, and therefore, may cause similar symptoms to autonomic neuropathy.
The signs and symptoms of autonomic neuropathy include the following:
* Urinary bladder conditions: bladder incontinence or urine retention
* Gastrointestinal tract: dysphagia, abdominal pain, nausea, vomiting, malabsorption, fecal incontinence, gastroparesis, diarrhoea, constipation
* Cardiovascular system: disturbances of heart rate (tachycardia, bradycardia), orthostatic hypotension, inadequate increase of heart rate on exertion
* Respiratory system: impairments in the signals associated with regulation of breathing and gas exchange (central sleep apnea, hypopnea, bradypnea).[22]
* Other areas: hypoglycemia unawareness, genital impotence, sweat disturbances
### Neuritis[edit]
Neuritis is a general term for inflammation of a nerve[23] or the general inflammation of the peripheral nervous system. Symptoms depend on the nerves involved, but may include pain, paresthesia (pins-and-needles), paresis (weakness), hypoesthesia (numbness), anesthesia, paralysis, wasting, and disappearance of the reflexes.
Causes of neuritis include:
* Physical injury
* Infection
* Diphtheria
* Herpes zoster (shingles)
* Leprosy
* Lyme disease
* Chemical injury such as chemotherapy
* Radiation therapy
Types of neuritis include:
* Brachial neuritis
* Cranial neuritis such as Bell's palsy
* Optic neuritis
* Vestibular neuritis
* Wartenberg's migratory sensory neuropathy
* Underlying conditions including: :
* Alcoholism
* Autoimmune disease, especially multiple sclerosis and Guillain–Barré syndrome
* Beriberi (vitamin B1 deficiency)
* Cancer
* Celiac disease[24]
* Non-celiac gluten sensitivity[7]
* Diabetes mellitus (Diabetic neuropathy)
* Hypothyroidism
* Porphyria
* Vitamin B12 deficiency
* Vitamin B6 excess[25]
## Signs and symptoms[edit]
Those with diseases or dysfunctions of their nerves may present with problems in any of the normal nerve functions. Symptoms vary depending on the types of nerve fiber involved.[26][citation needed] In terms of sensory function, symptoms commonly include loss of function ("negative") symptoms, including numbness, tremor, impairment of balance, and gait abnormality.[27] Gain of function (positive) symptoms include tingling, pain, itching, crawling, and pins-and-needles. Motor symptoms include loss of function ("negative") symptoms of weakness, tiredness, muscle atrophy, and gait abnormalities; and gain of function ("positive") symptoms of cramps, and muscle twitch (fasciculations).[28]
In the most common form, length-dependent peripheral neuropathy, pain and parasthesia appears symmetrically and generally at the terminals of the longest nerves, which are in the lower legs and feet. Sensory symptoms generally develop before motor symptoms such as weakness. Length-dependent peripheral neuropathy symptoms make a slow ascent of the lower limbs, while symptoms may never appear in the upper limbs; if they do, it will be around the time that leg symptoms reach the knee.[29] When the nerves of the autonomic nervous system are affected, symptoms may include constipation, dry mouth, difficulty urinating, and dizziness when standing.[28]
A user-friendly, disease-specific, quality-of-life scale can be used to monitor how someone is doing living with the burden of chronic, sensorimotor polyneuropathy. This scale, called the Chronic, Acquired Polyneuropathy - Patient-reported Index (CAP-PRI), contains only 15 items and is completed by the person affected by polyneuropathy. The total score and individual item scores can be followed over time, with item scoring used by the patient and care-provider to estimate clinical status of some of the more common life domains and symptoms impacted by polyneuropathy.
CAP-PRI (Patient instructions: For each item , choose “Not at all” (0 points), “A little bit” (1 point), or “A lot” (2 points). Consider the past week when answering. Complete scale periodically to follow clinical status, for example, a few weeks after starting a new medication or with some change in clinical status.)
1\. I am frustrated by my neuropathy.
2\. I am bothered by pain from neuropathy.
3\. I am off balance when walking because of my neuropathy.
4\. I have trouble getting dressed because of my neuropathy.
5\. I have trouble sleeping because of my neuropathy.
6\. I am bothered by limitations in performing my work (include work at home) because of my neuropathy.
7\. I have trouble driving because of my neuropathy.
8\. I am dependent on others because of my neuropathy.
9\. I am depressed about my neuropathy.
10\. I am falling because of my neuropathy.
11\. I am preoccupied with my neuropathy.
12\. I am unable to do all the leisure activities that I want to do because of my neuropathy.
13\. I am worn out because of my neuropathy.
14\. I have trouble eating because of my neuropathy.
15\. I have trouble doing activities around the house.
## Causes[edit]
The causes are grouped broadly as follows:
* Surgery: LASIK (corneal neuropathy - 20 to 55% of people).[30]
* Genetic diseases: Friedreich's ataxia, Fabry disease,[31] Charcot-Marie-Tooth disease,[32] hereditary neuropathy with liability to pressure palsy
* Hyperglycemia-induced formation of advanced glycation end products (AGEs)[11][33][34]
* Metabolic and endocrine diseases: diabetes mellitus,[31] chronic kidney failure, porphyria, amyloidosis, liver failure, hypothyroidism
* Toxic causes: drugs (vincristine, metronidazole, phenytoin, nitrofurantoin, isoniazid, ethyl alcohol, statins),[medical citation needed] organic herbicides TCDD dioxin, organic metals, heavy metals, excess intake of vitamin B6 (pyridoxine). Peripheral neuropathies also may result from long term (more than 21 days) treatment with linezolid.[medical citation needed]
* Adverse effects of fluoroquinolones: irreversible neuropathy is a serious adverse reaction of fluoroquinolone drugs[35]
* Inflammatory diseases: Guillain–Barré syndrome,[31] systemic lupus erythematosus, leprosy, multiple sclerosis,[31] Sjögren's syndrome, Babesiosis, Lyme disease,[31] vasculitis,[31] sarcoidosis,[36]
* Vitamin deficiency states: Vitamin B12 (Methylcobalamin),[31] vitamin A, vitamin E, vitamin B1 (thiamin)
* Physical trauma: compression, automobile accident, sports injury, sports pinching, cutting, projectile injuries (for example, gunshot wound), strokes including prolonged occlusion of blood flow, electric discharge, including lightning strikes[medical citation needed]
* Effect of chemotherapy – see Chemotherapy-induced peripheral neuropathy[31]
* Exposure to Agent Orange[37]
* Others: electric shock, HIV,[31][38] malignant disease, radiation, shingles, MGUS (Monoclonal gammopathy of undetermined significance).[39]
## Diagnosis[edit]
Peripheral neuropathy may first be considered when an individual reports symptoms of numbness, tingling, and pain in feet. After ruling out a lesion in the central nervous system as a cause, diagnosis may be made on the basis of symptoms, laboratory and additional testing, clinical history, and a detailed examination.
During physical examination, specifically a neurological examination, those with generalized peripheral neuropathies most commonly have distal sensory or motor and sensory loss, although those with a pathology (problem) of the nerves may be perfectly normal; may show proximal weakness, as in some inflammatory neuropathies, such as Guillain–Barré syndrome; or may show focal sensory disturbance or weakness, such as in mononeuropathies. Classically, ankle jerk reflex is absent in peripheral neuropathy.
A physical examination will involve testing the deep ankle reflex as well as examining the feet for any ulceration. For large fiber neuropathy, an exam will usually show an abnormally decreased sensation to vibration, which is tested with a 128-Hz tuning fork, and decreased sensation of light touch when touched by a nylon monofilament.[29]
Diagnostic tests include electromyography (EMG) and nerve conduction studies (NCSs), which assess large myelinated nerve fibers.[29] Testing for small-fiber peripheral neuropathies often relates to the autonomic nervous system function of small thinly- and unmyelinated fibers. These tests include a sweat test and a tilt table test. Diagnosis of small fiber involvement in peripheral neuropathy may also involve a skin biopsy in which a 3 mm-thick section of skin is removed from the calf by a punch biopsy, and is used to measure the skin intraepidermal nerve fiber density (IENFD), the density of nerves in the outer layer of the skin.[27] Reduced density of the small nerves in the epidermis supports a diagnosis of small-fiber peripheral neuropathy.
Laboratory tests include blood tests for vitamin B-12 levels, a complete blood count, measurement of thyroid stimulating hormone levels, a comprehensive metabolic panel screening for diabetes and pre-diabetes, and a serum immunofixation test, which tests for antibodies in the blood.[28]
## Treatment[edit]
The treatment of peripheral neuropathy varies based on the cause of the condition, and treating the underlying condition can aid in the management of neuropathy. When peripheral neuropathy results from diabetes mellitus or prediabetes, blood sugar management is key to treatment. In prediabetes in particular, strict blood sugar control can significantly alter the course of neuropathy.[27] In peripheral neuropathy that stems from immune-mediated diseases, the underlying condition is treated with intravenous immunoglobulin or steroids. When peripheral neuropathy results from vitamin deficiencies or other disorders, those are treated as well.[27]
A 2009 Cochrane review states that there is no evidence from randomised trials on any form of treatment for neuralgic amyotrophy[40]
### Medications[edit]
A range of medications that act on the central nervous system have been used to symptomatically treat neuropathic pain. Commonly used medications include tricyclic antidepressants (such as nortriptyline,[41] amitriptyline.[42] imapramine,[43] and desipramine,[44]) serotonin-norepinephrine reuptake inhibitor (SNRI) medications (duloxetine,[45] venlafaxine,[46] and milnacipran[47]) and antiepileptic medications (gabapentin,[48] pregabalin,[49] oxcarbazepine[50] zonisamide[51] levetiracetam,[52] lamotrigine,[53] topiramate,[54] clonazepam,[55] phenytoin,[56] lacosamide,[57] sodium valproate[58] and carbamazepine[59]). Opioid and opiate medications (such as buprenorphine,[60] morphine,[61] methadone,[62] fentanyl,[63] hydromorphone,[64] tramadol[65] and oxycodone[66]) are also often used to treat neuropathic pain.
As is revealed in many of the Cochrane systematic reviews listed below, studies of these medications for the treatment of neuropathic pain are often methodologically flawed and the evidence is potentially subject to major bias. In general, the evidence does not support the usage of antiepileptic and antidepressant medications for the treatment of neuropathic pain. Better designed clinical trials and further review from non-biased third parties are necessary to gauge just how useful for patients these medications truly are. Reviews of these systematic reviews are also necessary to assess for their failings.
It is also often the case that the aforementioned medications are prescribed for neuropathic pain conditions for which they had not been explicitly tested on or for which controlled research is severely lacking; or even for which evidence suggests that these medications are not effective.[67][68][69] The NHS for example explicitly state that amitriptyline and gabapentin can be used for treating the pain of sciatica.[70] This is despite both the lack of high quality evidence that demonstrates efficacy of these medications for that symptom,[42][48] and also the prominence of generally moderate to high quality evidence that reveals that antiepileptics in specific, including gabapentin, demonstrate no efficacy in treating it.[71]
#### Antidepressants[edit]
In general, according to Cochrane's systematic reviews, antidepressants have shown to either be ineffective for the treatment of neuropathic pain or the evidence available is inconclusive.[41][44][72][73] Evidence also tends to be tainted by bias or issues with the methodology.[74][75]
Cochrane systematically reviewed the evidence for the antidepressants nortriptyline, desipramine, venlafaxine and milnacipran and in all these cases found scant evidence to support their use for the treatment of neuropathic pain. All reviews were done between 2014 and 2015.[41][44][72][73]
A 2015 Cochrane systematic review of amitriptyline found that there was no evidence supporting the use of amitriptyline that did not possess inherent bias. The authors believe amitriptyline may have an effect in some patients but that the effect is overestimated.[74] A 2014 Cochrane systematic review of imipramine notes that the evidence suggesting benefit were "methodologically flawed and potentially subject to major bias."[75]
A 2017 Cochrane systematic review assessed the benefit of antidepressant medications for several types of chronic non-cancer pains (including neuropathic pain) in children and adolescents and the authors found the evidence inconclusive.[76]
#### Antiepileptics[edit]
A 2017 Cochrane systematic review found that daily dosages between (1800 - 3600) mg of gabapentin could provide good pain relief for pain associated with diabetic neuropathy only. This relief occurred for roughly (30 - 40)% of treated patients, while placebo had a (10 - 20)% response. Three of the seven authors of the review had conflicts of interest declared.[48] In a 2019 Cochrane review of pregabalin the authors conclude that there is some evidence of efficacy in the treatment of pain deriving from post-herpetic neuralgia, diabetic neuropathy and post-traumatic neuropathic pain only. They also warned that many patients treated will have no benefit. Two of the five authors declared receiving payments from pharmaceutical companies.[49]
A 2017 Cochrane systematic review found that oxcarbazepine had little evidence to support its use for treating diabetic neuropathy, radicular pain and other neuropathies. The authors also call for better studies.[50] In a 2015 Cochrane systematic review the authors found a lack of evidence showing any effectiveness of zonisamide for the treatment of pain deriving from any peripheral neuropathy.[51] A 2014 Cochrane review found that studies of levetiracetam showed no indication for its effectiveness at treating pain from any neuropathy. The authors also found that the evidence was possibly biased and that some patients experienced adverse events.[77]
A 2013 Cochrane systematic review concluded that there was high quality evidence to suggest that lamotrigine is not effective for treating neuropathic pain, even at high dosages (200 - 400) mg.[78] A 2013 Cochrane systematic review of topimirate found that the included data had a strong likelihood of major bias; despite this, it found no effectiveness for the drug in treating the pain associated with diabetic neuropathy. It had not been tested for any other type of neuropathy.[54] Cochrane reviews from 2012 of clonazepam and phenytoin uncovered no evidence of sufficient quality to support their use in chronic neuropathic pain."[79][80]
A 2012 Cochrane systematic review of lacosamide found it very likely that the drug is ineffective for treating neuropathic pain. The authors caution against positive interpretations of the evidence.[81] For sodium valproate the authors of a 2011 Cochrane review found that "three studies no more than hint that sodium valproate may reduce pain in diabetic neuropathy". They discuss how there is a probable overestimate of effect due to the inherent problems with the data and conclude that the evidence does not support its usage.[82] In a 2014 systematic review of carbamazepine the authors believe the drug to be of benefit for some people. No trials were considered greater than level III evidence; none were longer than 4 weeks in length or were deemed as having good reporting quality.[83]
A 2017 Cochrane systematic review aiming to assess the benefit of antiepileptic medications for several types of chronic non-cancer pains (including neuropathic pain) in children and adolescents found the evidence inconclusive. Two of the ten authors of this study declared receiving payments from pharmaceutical companies.[84]
#### Opioids[edit]
A Cochrane review of buprenorphine, fentanyl, hydromorphone and morphine, all dated between 2015 and 2017, and all for the treatment of neuropathic pain, found that there was insufficient evidence to comment on their efficacy. Conflicts of interest were declared by the authors in this review.[60][61][63][64] A 2017 Cochrane review of methadone found very low quality evidence, three studies of limited quality, of its efficacy and safety. They could not formulate any conclusions about its relative efficacy and safety compared to a placebo.[62]
For tramadol, Cochrane found that there was only modest information about the benefits of its usage for neuropathic pain. Studies were small, had potential risks of bias and apparent benefits increased with risk of bias. Overall the evidence was of low or very low quality and the authors state that it "does not provide a reliable indication of the likely effect".[65] For oxycodone the authors found very low quality evidence showing its usefulness in treating diabetic neuropathy and postherpetic neuralgia only. One of the four authors declared receiving payments from pharmaceutical companies.[66]
More generally, a 2013 review examining the overall efficacy of opioid therapy for the treatment of neuropathic pain found studies were often subject to bias and that their efficacy and safety was not deducible with the evidence available.[85] A 2017 Cochrane review examining opioid therapy as a treatment for many non-cancer pain syndromes (including neuropathic pain) concluded, "There was no evidence from randomised controlled trials to support or refute the use of opioids to treat chronic non-cancer pain in children and adolescents."[86]
#### Others[edit]
A 2016 Cochrane review of paracetamol for the treatment of neuropathic pain concluded that its benefit alone or in combination with codeine or dihydrocodeine is unknown.[87]
Few studies have examined whether nonsteroidal anti-inflammatory drugs are effective in treating peripheral neuropathy.[88]
There is some evidence that symptomatic relief from the pain of peripheral neuropathy may be obtained by application of topical capsaicin. Capsaicin is the factor that causes heat in chili peppers. However, the evidence suggesting that capsaicin applied to the skin reduces pain for peripheral neuropathy is of moderate to low quality and should be interpreted carefully before using this treatment option.[89]
Evidence supports the use of cannabinoids for some forms of neuropathic pain.[90] A 2018 Cochrane review of cannabis-based medicines for the treatment of chronic neuropathic pain included 16 studies. All of these studies included THC as a pharmacological component of the test group. The authors rated the quality of evidence as very low to moderate. The primary outcome was quoted as, "Cannabis-based medicines may increase the number of people achieving 50% or greater pain relief compared with placebo" but "the evidence for improvement in Patient Global Impression of Change (PGIC) with cannabis to be of very low quality". The authors also conclude, "The potential benefits of cannabis-based medicine... might be outweighed by their potential harms."[91]
A 2014 Cochrane review of topical lidocaine for the treatment of various peripheral neuropathies found its usage supported by a few low quality studies. The authors state that there are no high quality randomised control trials demonstrating its efficacy or safety profile.[92]
A 2015 Cochrane review of topical clonidine for the treatment of diabetic neuropathy included two studies of 8 and 12 weeks in length; both of which compared topical clonidine to placebo and both of which were funded by the same drug manufacturer. The review found that topical clonidine may provide some benefit versus placebo. However, the authors state that the included trials are potentially subject to significant bias and that the evidence is of low to moderate quality.[93]
A 2007 Cochrane review of aldose reductase inhibitors for the treatment of the pain deriving from diabetic polyneuropathy found it no better than placebo.[94]
### Medical devices[edit]
Transcutaneous electrical nerve stimulation (TENS) therapy is often used to treat various types of neuropathy. A 2010 review of three trials, for the treatment of diabetic neuropathy explicitly, involving a total of 78 patients found some improvement in pain scores after 4 and 6, but not 12 weeks of treatment and an overall improvement in neuropathic symptoms at 12 weeks.[95] Another 2010 review of four trials, for the treatment of diabetic neuropathy, found significant improvement in pain and overall symptoms, with 38% of patients in one trial becoming asymptomatic. The treatment remains effective even after prolonged use, but symptoms return to baseline within a month of cessation of treatment.[96]
These older reviews can be balanced with a more recent 2017 review of TENS for neuropathic pain by Cochrane which concluded that, "This review is unable to state the effect of TENS versus sham TENS for pain relief due to the very low quality of the included evidence... The very low quality of evidence means we have very limited confidence in the effect estimate reported." A very low quality of evidence means, 'multiple sources of potential bias' with a 'small number and size of studies'.[97]
### Diet[edit]
According to a single review (2019), strict gluten-free diet is an effective treatment when neuropathy is caused by gluten sensitivity, with or without the presence of digestive symptoms or intestinal injury.[7]
### Counselling[edit]
A 2015 review on the treatment of neuropathic pain with psychological therapy concluded that, "There is insufficient evidence of the efficacy and safety of psychological interventions for chronic neuropathic pain. The two available studies show no benefit of treatment over either waiting list or placebo control groups."[98]
### Alternative medicine[edit]
A 2019 Cochrane review of the treatment of herbal medicinal products for people suffering neuropathic pain for at least three months concluded that, "There was insufficient evidence to determine whether nutmeg or St John's wort has any meaningful efficacy in neuropathic pain conditions.The quality of the current evidence raises serious uncertainties about the estimates of effect observed, therefore, we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect." [99]
A 2017 Cochrane review on the usage of acupuncture as a treatment for neuropathic pain concludes, "Due to the limited data available, there is insufficient evidence to support or refute the use of acupuncture for neuropathic pain in general, or for any specific neuropathic pain condition when compared with sham acupuncture or other active therapies." Also, "Most studies included a small sample size (fewer than 50 participants per treatment arm) and all studies were at high risk of bias for blinding of participants and personnel." Also, the authors state, "we did not identify any study comparing acupuncture with treatment as usual."[100]
A 2018 Cochrane review on acupuncture and related interventions for the treatment of carpal tunnel syndrome concluded that, "Acupuncture and laser acupuncture may have little or no effect in the short term on symptoms of carpal tunnel syndrome (CTS) in comparison with placebo or sham acupuncture." It was also noted that all studies had an unclear or high overall risk of bias and that all evidence was of low or very low quality.[101]
Alpha lipioc acid (ALA) with benfothiamine is a proposed pathogenic treatment for painful diabetic neuropathy only.[102] The results of two systematic reviews state that oral ALA produced no clinically significant benefit, intravenous ALA administered over the course of three weeks may improve symptoms and that long term treatment has not been investigated.[103]
## Research[edit]
A 2008 literature review concluded that, "based on principles of evidence-based medicine and evaluations of methodology, there is only a 'possible' association [of celiac disease and peripheral neuropathy], due to lower levels of evidence and conflicting evidence. There is not yet convincing evidence of causality."[104]
A 2019 review concluded that "gluten neuropathy is a slowly progressive condition. About 25% of the patients will have evidence of enteropathy on biopsy (CD [celiac disease]) but the presence or absence of an enteropathy does not influence the positive effect of a strict gluten-free diet."[7]
Stem-cell therapy is also being looked at as a possible means to repair peripheral nerve damage, however efficacy has not yet been demonstrated.[105][106][107]
## See also[edit]
* Scrambler therapy
* Giant axonal neuropathy
## References[edit]
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2. ^ Singh VP, Bali A, Singh N, Jaggi AS (February 2014). "Advanced glycation end products and diabetic complications". The Korean Journal of Physiology & Pharmacology. 18 (1): 1–14. doi:10.4196/kjpp.2014.18.1.1. PMC 3951818. PMID 24634591.
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104. ^ Grossman G (April 2008). "Neurological complications of coeliac disease: what is the evidence?". Practical Neurology. 8 (2): 77–89. doi:10.1136/jnnp.2007.139717. PMID 18344378. S2CID 28327166.
105. ^ Sayad Fathi S, Zaminy A (September 2017). "Stem cell therapy for nerve injury". World Journal of Stem Cells. 9 (9): 144–151. doi:10.4252/wjsc.v9.i9.144. PMC 5620423. PMID 29026460.
106. ^ Xu W, Cox CS, Li Y (2011). "Induced pluripotent stem cells for peripheral nerve regeneration". Journal of Stem Cells. 6 (1): 39–49. PMID 22997844.
107. ^ Zhou JY, Zhang Z, Qian GS (2016). "Mesenchymal stem cells to treat diabetic neuropathy: a long and strenuous way from bench to the clinic". Cell Death Discovery. 2: 16055. doi:10.1038/cddiscovery.2016.55. PMC 4979500. PMID 27551543.
## Further reading[edit]
* Latov N (2007). Peripheral Neuropathy: When the Numbness, Weakness, and Pain Won't Stop. New York: American Academy of Neurology Press Demos Medical. ISBN 978-1-932603-59-0.
* "Practice advisory for the prevention of perioperative peripheral neuropathies: a report by the American Society of Anesthesiologists Task Force on Prevention of Perioperative Peripheral Neuropathies". Anesthesiology. 92 (4): 1168–82. April 2000. doi:10.1097/00000542-200004000-00036. PMID 10754638.
## External links[edit]
Classification
D
* ICD-10: G64, G90.0
* ICD-9-CM: 356.0, 356.8
* MeSH: D010523
* DiseasesDB: 9850
External resources
* MedlinePlus: 000593
* Patient UK: Peripheral neuropathy
* Peripheral Neuropathy from the US NIH
* Peripheral Neuropathy at the Mayo Clinic
* 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
* t
* e
Diseases of the autonomic nervous system
General
* Dysautonomia
* Autonomic dysreflexia
* Autonomic neuropathy
* Pure autonomic failure
Hereditary
* Hereditary sensory and autonomic neuropathy
* Familial dysautonomia
* Congenital insensitivity to pain with anhidrosis
Orthostatic intolerance
* Orthostatic hypotension
* Postural orthostatic tachycardia syndrome
Other
* Horner's syndrome
* Multiple system atrophy
* v
* t
* e
Neuropathic pain and fibromyalgia pharmacotherapies
Monoaminergics
* SNRIs (e.g., duloxetine, milnacipran)
* TCAs (e.g., amitriptyline, nortriptyline, dosulepin)
* Opioid MRIs (e.g., tapentadol, tramadol)
Ion channel blockers
* Anticonvulsants (e.g., gabapentin, pregabalin, mirogabalin, carbamazepine, oxcarbazepine, lacosamide, lamotrigine)
* Local anesthetics (e.g., lidocaine)
* Mexiletine
* TCAs (e.g., amitriptyline, nortriptyline, desipramine)
* Ziconotide
Others
* Alpha lipoic acid
* Benfotiamine
* Botulinum toxin A
* Bupropion
* Cannabinoids (e.g., cannabis, dronabinol, nabilone)
* NMDA receptor antagonists (e.g., ketamine, dextromethorphan, methadone)
* Opioids (e.g., hydrocodone, morphine, oxycodone, methadone, buprenorphine, tramadol, tapentadol)
* Sodium oxybate (GHB)
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Peripheral neuropathy | c0031117 | 5,113 | wikipedia | https://en.wikipedia.org/wiki/Peripheral_neuropathy | 2021-01-18T18:55:46 | {"mesh": ["D010523"], "umls": ["C0031117", "C1335029", "C0442874"], "icd-9": ["356.0", "356.8"], "icd-10": ["G64", "G90.0"], "orphanet": ["98496"], "wikidata": ["Q945238"]} |
## Description
Celiac disease, also known as celiac sprue and gluten-sensitive enteropathy, is a multifactorial disorder of the small intestine that is influenced by both environmental and genetic factors. It is characterized by malabsorption resulting from inflammatory injury to the mucosa of the small intestine after the ingestion of wheat gluten or related rye and barley proteins (summary by Farrell and Kelly, 2002).
For additional information and a discussion of genetic heterogeneity of celiac disease, see 212750.
Mapping
The form of susceptibility to celiac disease here designated CELIAC11 is influenced by genetic variation in the 3q28 region, within a linkage disequilibrium (LD) block near the LPP (600700) gene.
To identify risk variants contributing to celiac disease susceptibility other than those in the HLA-DQ region (see CELIAC1, 212750) Hunt et al. (2008) genotyped 1,020 of the most strongly associated non-HLA markers identified by van Heel et al. (2007) in an additional 1,643 cases of celiac disease and 3,406 controls. Multiple correlated single-nucleotide polymorphisms (SNPs) within a 70-kb LD block on chromosome 3q28, e.g., rs1464510 (P overall = 5.33 x 10(-9)), showed association with celiac disease. This block is either 5-prime of the LPP gene (600700) or intronic for other possible isoforms of LPP. The LPP gene shows very high expression in the small intestine and may have a structural role at sites of cell adhesion in maintaining cell shape and motility.
In an Italian cohort involving 538 patients with celiac disease and 593 healthy controls, Romanos et al. (2009) confirmed moderate association at rs1464510 (p = 0.0348).
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| CELIAC DISEASE, SUSCEPTIBILITY TO, 11 | c2677603 | 5,114 | omim | https://www.omim.org/entry/612009 | 2019-09-22T16:02:30 | {"omim": ["612009"], "synonyms": ["Alternative titles", "GLUTEN-SENSITIVE ENTEROPATHY, SUSCEPTIBILITY TO, 11"]} |
A rare renal disease characterized by excess urinary calcium excretion in the absence of an underlying systemic disease. The condition leads to an increased risk for the formation of kidney stones and nephrocalcinosis, as well as reduced bone mineral density with increased incidence of fractures.
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Idiopathic hypercalciuria | c0543800 | 5,115 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2197 | 2021-01-23T18:20:21 | {"omim": ["143870", "607258"], "umls": ["C0543800"], "icd-10": ["E83.5"]} |
A rare form of salmonellosis caused by Salmonella enterica serovar Paratyphi A, characterized by typical symptoms of enteric fever including high fever, headache, abdominal pain and intestinal symptoms, dry cough, chills, and rashes, followed by a long period of recovery. The infection can be complicated by intestinal hemorrhage and perforation, as well as cardiac involvement, and may even be fatal. Transmission of the pathogen is via the fecal-oral route, with humans as the sole reservoir of infection.
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Paratyphoid fever | c0030528 | 5,116 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=443227 | 2021-01-23T17:55:01 | {"mesh": ["D010284"], "umls": ["C0030528"], "icd-10": ["A01.1", "A01.2", "A01.3", "A01.4"]} |
Bladder sphincter dyssynergia
Urodynamic trace of detrusor sphincter dyssynergia
SpecialtyUrology
Bladder sphincter dyssynergia (also known as detrusor sphincter dyssynergia (DSD) (the ICS standard terminology agreed 1998)[1] and neurogenic detrusor overactivity (NDO)) is a consequence of a neurological pathology such as spinal injury[2] or multiple sclerosis.[3] which disrupts central nervous system regulation of the micturition (urination) reflex resulting in dyscoordination of the detrusor muscles of the bladder and the male or female external urethral sphincter muscles. In normal lower urinary tract function, these two separate muscle structures act in synergistic coordination. But in this neurogenic disorder, the urethral sphincter muscle, instead of relaxing completely during voiding, dyssynergically contracts causing the flow to be interrupted and the bladder pressure to rise.[4]
## Contents
* 1 Presentation
* 2 Pathology
* 3 Treatment
* 4 References
* 5 Further reading
* 6 External links
## Presentation[edit]
People with this condition generally experience daytime and night time wetting, urinary retention, and often have a history of urinary tract and bladder infections. Constipation and encopresis are often associated with this condition.
## Pathology[edit]
The pathophysiology of the condition results from neuronal plasticity associated with bladder afferents and motor neurons innervating the external urethral sphincter.
## Treatment[edit]
Botulinum A toxin is a valuable alternative for patients who do not want surgical methods.[5]
## References[edit]
1. ^ Stöhrer M, Goepel M, Kondo A, Kramer G, Madersbacher H, Millard R, Rossier A, Wyndaele JJ (1999). "The standardization of terminology in neurogenic lower urinary tract dysfunction: with suggestions for diagnostic procedures. International Continence Society Standardization Committee". Neurourology and Urodynamics. 18 (2): 139–58. doi:10.1002/(SICI)1520-6777(1999)18:2<139::AID-NAU9>3.0.CO;2-U. PMID 10081953.
2. ^ Karsenty G, Reitz A, Wefer B, Boy S, Schurch B (October 2005). "Understanding detrusor sphincter dyssynergia--significance of chronology". Urology. 66 (4): 763–8. doi:10.1016/j.urology.2005.04.061. PMID 16230135.
3. ^ Stankovich EI, Borisov VV, Demina TL (2004). "[Tamsulosin in the treatment of detrusor-sphincter dyssynergia of the urinary bladder in patients with multiple sclerosis]". Urologiia (4): 48–51. PMID 15457955. Urination disorders occur in 80% patients with multiple sclerosis (MS). The most common of them is detrusor-sphincter dyssynergia (DSD),
4. ^ Corcos J, Schick E (2004). Textbook of the neurogenic bladder: adults and children. Informa Health Care. pp. 163–168. ISBN 978-1-84184-206-6.
5. ^ Schurch B, Hodler J, Rodic B (October 1997). "Botulinum A toxin as a treatment of detrusor-sphincter dyssynergia in patients with spinal cord injury: MRI controlled transperineal injections". Journal of Neurology, Neurosurgery, and Psychiatry. 63 (4): 474–6. doi:10.1136/jnnp.63.4.474. PMC 2169779. PMID 9343126.
## Further reading[edit]
* Libo LM, Arnold GE, Woodside JR, Borden TA, Hardy TL (June 1983). "EMG biofeedback for functional bladder-sphincter dyssynergia: a case study". Biofeedback and Self-Regulation. 8 (2): 243–53. doi:10.1007/BF00998854. PMID 6357288.
## External links[edit]
Classification
D
* ICD-9-CM: 596.55
* Pressure Flow Study, Department of Urology, Southern General Hospital, Glasgow
* v
* t
* e
Diseases of the urinary tract
Ureter
* Ureteritis
* Ureterocele
* Megaureter
Bladder
* Cystitis
* Interstitial cystitis
* Hunner's ulcer
* Trigonitis
* Hemorrhagic cystitis
* Neurogenic bladder dysfunction
* Bladder sphincter dyssynergia
* Vesicointestinal fistula
* Vesicoureteral reflux
Urethra
* Urethritis
* Non-gonococcal urethritis
* Urethral syndrome
* Urethral stricture
* Meatal stenosis
* Urethral caruncle
Any/all
* Obstructive uropathy
* Urinary tract infection
* Retroperitoneal fibrosis
* Urolithiasis
* Bladder stone
* Kidney stone
* Renal colic
* Malakoplakia
* Urinary incontinence
* Stress
* Urge
* Overflow
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Bladder sphincter dyssynergia | c0341747 | 5,117 | wikipedia | https://en.wikipedia.org/wiki/Bladder_sphincter_dyssynergia | 2021-01-18T19:01:10 | {"umls": ["C0341747"], "wikidata": ["Q13629899"]} |
Orofaciodigital syndrome type 11 is an extremely rare, sporadic form of Orofaciodigital syndrome (OFDS; see this term) with only a few reported cases, and characterized by facial (blepharophimosis, bulbous nasal tip, broad nasal bridge, downslanting palpebral fissures and low set ears) and skeletal (post-axial polydactyly and fusion of vertebrae) malformations along with severe intellectual disability, deafness and congenital heart defects.
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Orofaciodigital syndrome type 11 | c2752048 | 5,118 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=141000 | 2021-01-23T18:17:30 | {"gard": ["4118"], "mesh": ["C557821"], "omim": ["612913"], "umls": ["C2752048"], "icd-10": ["Q87.0"], "synonyms": ["OFD11", "Oral-facial-digital syndrome type 11", "Oral-facial-digital syndrome, Gabrielli type", "Orofaciodigital syndrome, Gabrielli type"]} |
Xeroderma pigmentosum, which is commonly known as XP, is an inherited condition characterized by an extreme sensitivity to ultraviolet (UV) rays from sunlight. This condition mostly affects the eyes and areas of skin exposed to the sun. Some affected individuals also have problems involving the nervous system.
The signs of xeroderma pigmentosum usually appear in infancy or early childhood. Many affected children develop a severe sunburn after spending just a few minutes in the sun. The sunburn causes redness and blistering that can last for weeks. Other affected children do not get sunburned with minimal sun exposure, but instead tan normally. By age 2, almost all children with xeroderma pigmentosum develop freckling of the skin in sun-exposed areas (such as the face, arms, and lips); this type of freckling rarely occurs in young children without the disorder. In affected individuals, exposure to sunlight often causes dry skin (xeroderma) and changes in skin coloring (pigmentation). This combination of features gives the condition its name, xeroderma pigmentosum.
People with xeroderma pigmentosum have a greatly increased risk of developing skin cancer. Without sun protection, about half of children with this condition develop their first skin cancer by age 10. Most people with xeroderma pigmentosum develop multiple skin cancers during their lifetime. These cancers occur most often on the face, lips, and eyelids. Cancer can also develop on the scalp, in the eyes, and on the tip of the tongue. Studies suggest that people with xeroderma pigmentosum may also have an increased risk of other types of cancer, including brain tumors. Additionally, affected individuals who smoke cigarettes have a significantly increased risk of lung cancer.
The eyes of people with xeroderma pigmentosum may be painfully sensitive to UV rays from the sun. If the eyes are not protected from the sun, they may become bloodshot and irritated, and the clear front covering of the eyes (the cornea) may become cloudy. In some people, the eyelashes fall out and the eyelids may be thin and turn abnormally inward or outward. In addition to an increased risk of eye cancer, xeroderma pigmentosum is associated with noncancerous growths on the eye. Many of these eye abnormalities can impair vision.
About 30 percent of people with xeroderma pigmentosum develop progressive neurological abnormalities in addition to problems involving the skin and eyes. These abnormalities can include hearing loss, poor coordination, difficulty walking, movement problems, loss of intellectual function, difficulty swallowing and talking, and seizures. When these neurological problems occur, they tend to worsen with time.
Researchers have identified at least eight inherited forms of xeroderma pigmentosum: complementation group A (XP-A) through complementation group G (XP-G) plus a variant type (XP-V). The types are distinguished by their genetic cause. All of the types increase skin cancer risk, although some are more likely than others to be associated with neurological abnormalities.
## Frequency
Xeroderma pigmentosum is a rare disorder; it is estimated to affect about 1 in 1 million people in the United States and Europe. The condition is more common in Japan, North Africa, and the Middle East.
## Causes
Xeroderma pigmentosum is caused by mutations in genes that are involved in repairing damaged DNA. DNA can be damaged by UV rays from the sun and by toxic chemicals such as those found in cigarette smoke. Normal cells are usually able to fix DNA damage before it causes problems. However, in people with xeroderma pigmentosum, DNA damage is not repaired normally. As more abnormalities form in DNA, cells malfunction and eventually become cancerous or die.
Many of the genes related to xeroderma pigmentosum are part of a DNA-repair process known as nucleotide excision repair (NER). The proteins produced from these genes play a variety of roles in this process. They recognize DNA damage, unwind regions of DNA where the damage has occurred, snip out (excise) the abnormal sections, and replace the damaged areas with the correct DNA. Inherited abnormalities in the NER-related genes prevent cells from carrying out one or more of these steps. The POLH gene also plays a role in protecting cells from UV-induced DNA damage, although it is not involved in NER; mutations in this gene cause the variant type of xeroderma pigmentosum.
The major features of xeroderma pigmentosum result from a buildup of unrepaired DNA damage. When UV rays damage genes that control cell growth and division, cells can either die or grow too fast and in an uncontrolled way. Unregulated cell growth can lead to the development of cancerous tumors. Neurological abnormalities are also thought to result from an accumulation of DNA damage, although the brain is not exposed to UV rays. Researchers suspect that other factors damage DNA in nerve cells. It is unclear why some people with xeroderma pigmentosum develop neurological abnormalities and others do not.
Inherited mutations in at least eight genes have been found to cause xeroderma pigmentosum. More than half of all cases in the United States result from mutations in the XPC, ERCC2, or POLH genes. Mutations in the other genes generally account for a smaller percentage of cases.
### Learn more about the genes associated with Xeroderma pigmentosum
* ERCC2
* ERCC3
* POLH
* XPA
* XPC
Additional Information from NCBI Gene:
* DDB2
* ERCC4
* ERCC5
## 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Xeroderma pigmentosum | c0268135 | 5,119 | medlineplus | https://medlineplus.gov/genetics/condition/xeroderma-pigmentosum/ | 2021-01-27T08:25:11 | {"gard": ["7910"], "omim": ["278700", "610651", "278720", "278730", "278740", "278760", "278780", "278750"], "synonyms": []} |
Selective IgM deficiency (SIgMD) is a rare immune disorder in which a person has no immunoglobulin M (IgM) antibodies, or too little IgM, with normal levels of IgG and IgA antibodies. IgM is the first antibody the immune system makes to fight a new infection. Therefore, when a person does not have enough IgM, the body may have difficulty fighting infections. SIgMD can occur in infants, children, or adults. The disorder may occur as a primary disorder (on its own) or more commonly, as a secondary disorder (associated with another underlying disease or condition). SIgMD may occur in association with some cancers, autoimmune diseases, allergic diseases, and gastrointestinal diseases.
Symptoms of SIgMD may include repeated viral, bacterial, or fungal infections, such as ear infections, bronchitis, sinusitis, and pneumonia. Infections may be life-threatening. Repeated infections are common in infants with SIgMD. In some people, diarrhea or a skin rash is the first symptom. Others do not have symptoms specific to SIgMD and are diagnosed when being evaluated for another condition. The diagnosis is made by blood tests showing low or absent IgM and normal levels of other antibodies, as well as diagnosing or ruling out underlying conditions that can cause low levels of IgM.
The cause of SIgMD is still unclear. SIgMD usually occurs in only one person in a family, but familial cases have occasionally been reported. It may occur in some people with chromosome disorders such as 22q11.2 deletion syndrome.
There are no official treatment recommendations since information about SIgMD is limited. Treatment options depend on the severity of symptoms and whether a person has an associated underlying disease. Treatment may include prompt treatment of infections, taking measures to prevent infections, prophylactic antibiotics, and immune globulin 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Selective IgM deficiency | c0154275 | 5,120 | gard | https://rarediseases.info.nih.gov/diseases/12547/selective-igm-deficiency | 2021-01-18T17:57:46 | {"icd-10": ["D80.4"], "orphanet": ["331235"], "synonyms": ["Selective immunoglobulin M deficiency", "SIgMD"]} |
A very rare and mild form of spondylocostal dysostosis characterized by vertebral and costal segmentation defects, often with a reduction in the number of ribs.
*[v]: View this template
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*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Autosomal dominant spondylocostal dysostosis | c4083048 | 5,121 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1797 | 2021-01-23T17:03:20 | {"gard": ["12806"], "omim": ["122600"], "icd-10": ["Q76.4"], "synonyms": ["Autosomal dominant spondylocostal dysplasia"]} |
A number sign (#) is used with this entry because of evidence that dilated cardiomyopathy-1JJ (CMD1JJ) is caused by heterozygous mutation in the LAMA4 gene (600133) on chromosome 6q21.
For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200).
Molecular Genetics
Knoll et al. (2007) sequenced the LAMA4 gene in 180 Caucasian patients with severe dilated cardiomyopathy (CMD) and identified heterozygosity for a nonsense (R1073X; 600133.0001) and a missense (P943L; 600133.0002) mutation in 2 patients, respectively. Genotyping for these mutations in an additional 374 Caucasian CMD patients identified 1 more patient with the P943L mutation. Neither mutation was found in 362 well-characterized Caucasian controls, and screening the LAMA4 gene by SSCP in an additional 200 Japanese CMD patients revealed no variants. Immunohistochemistry on myocardial biopsy samples revealed a significant loss of endothelial cells in the woman carrying the R1073X mutation, who had been diagnosed at 29 years of age and was a candidate for heart transplantation with an ejection fraction of only 20%. There was a more modest but still significant loss of endothelial cells in myocardial biopsies from the 2 men carrying the P943L mutation, who were diagnosed at ages 53 years and 68 years and had ejection fractions of 29% and 31%, respectively.
INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Cardiomyopathy, dilated, severe \- Markedly decreased ejection fraction \- Loss of endothelial cells seen on myocardial biopsy MOLECULAR BASIS \- Caused by mutation in the alpha-4 laminin gene (LAMA4, 600133.0001 ) ▲ 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| CARDIOMYOPATHY, DILATED, 1JJ | c0340427 | 5,122 | omim | https://www.omim.org/entry/615235 | 2019-09-22T15:52:46 | {"doid": ["0110438"], "mesh": ["C536231"], "omim": ["615235"], "orphanet": ["154"]} |
Paratyphoid fever
Other namesParatyphoid
Rose colored spots on the chest of a person with typhoid fever which are similar to those of paratyphoid
SpecialtyInfectious disease
SymptomsFever, headache, rash, weakness[1][2]
Usual onset6–30 days post exposure[1][3]
DurationWeeks to months[1]
CausesSalmonella enterica spread by food or water contaminated with feces[1]
Risk factorsPoor sanitation, crowded populations[4]
Diagnostic methodCulturing the bacteria or detecting its DNA in the blood, stool, or bone marrow[1][3]
PreventionHandwashing, clean water[1]
TreatmentAntibiotics[1]
Frequency529,000[5]
Deaths29,200[6]
Paratyphoid fever, also known simply as paratyphoid, is a bacterial infection caused by one of the three types of Salmonella enterica.[1] Symptoms usually begin 6–30 days after exposure and are the same as those of typhoid fever.[1][3] Often, a gradual onset of a high fever occurs over several days.[1] Weakness, loss of appetite, and headaches also commonly occur.[1] Some people develop a skin rash with rose-colored spots.[2] Without treatment, symptoms may last weeks or months.[1] Other people may carry the bacteria without being affected; however, they are still able to spread the disease to others.[3] Typhoid and paratyphoid are of similar severity.[3] Paratyphoid and typhoid fever are types of enteric fever.[7]
Paratyphoid is caused by the bacterium Salmonella enterica of the serotypes Paratyphi A, Paratyphi B, or Paratyphi C growing in the intestines and blood.[1] They are usually spread by eating or drinking food or water contaminated with the feces of an infected person.[1] They may occur when a person who prepares food is infected.[2] Risk factors include poor sanitation as is found among poor crowded populations.[4] Occasionally, they may be transmitted by sex.[1] Humans are the only animals infected.[1] Diagnosis may be based on symptoms and confirmed by either culturing the bacteria or detecting the bacterial DNA in the blood, stool, or bone marrow.[1][3] Culturing the bacteria can be difficult.[3] Bone-marrow testing is the most accurate.[4] Symptoms are similar to that of many other infectious diseases.[3] Typhus is a different disease.[8]
While no vaccine is available specifically for paratyphoid, the typhoid vaccine may provide some benefit.[1][2] Prevention includes drinking clean water, better sanitation, and better handwashing.[1] Treatment of the disease is with antibiotics such as azithromycin.[1] Resistance to a number of other previously effective antibiotics is common.[1]
Paratyphoid affects about six million people a year.[1][9] It is most common in parts of Asia and rare in the developed world.[1][2] Most cases are due to Paratyphi A rather than Paratyphi B or C.[3] In 2015, paratyphoid fever resulted in about 29,200 deaths, down from 63,000 deaths in 1990.[10][6] The risk of death is between 10 and 15% without treatment, while with treatment, it may be less than 1%.[3]
## Contents
* 1 Signs and symptoms
* 2 Cause
* 2.1 Transmission
* 2.2 Paratyphoid B
* 2.3 Paratyphoid C
* 2.4 Carriers
* 3 Pathophysiology
* 4 Prevention
* 5 Treatments
* 6 Prognosis
* 7 Epidemiology
* 8 References
* 9 Further reading
## Signs and symptoms[edit]
Rose spots on abdomen of a person with typhoid fever
Paratyphoid fever resembles typhoid fever. Infection is characterized by a sustained fever, headache, abdominal pain, malaise, anorexia, a nonproductive cough (in early stage of illness), a relative bradycardia (slow heart rate), and hepatosplenomegaly (an enlargement of the liver and spleen). About 30% of Caucasians develop rosy spots on the central body. In adults, constipation is more common than diarrhea.[citation needed]
Only 20 to 40% of people initially have abdominal pain. Nonspecific symptoms such as chills, sweating, headache, loss of appetite, cough, weakness, sore throat, dizziness, and muscle pains are frequently present before the onset of fever. Some very rare symptoms are psychosis (mental disorder), confusion, and seizures.[citation needed]
## Cause[edit]
Paratyphoid fever is caused by any of three serovars of Salmonella enterica subsp. enterica: S. Paratyphi A, S. Paratyphi B (invalid alias S. schottmuelleri), S. Paratyphi C (invalid alias S. hirschfeldii).[citation needed]
### Transmission[edit]
They are usually spread by eating or drinking food or water contaminated with the feces of an infected person.[1] They may occur when a person who prepares food is infected.[2] Risk factors include poor sanitation as is found among poor crowded populations.[4] Occasionally, they may be transmitted by sex. Humans are the only animals infected.[1]
### Paratyphoid B[edit]
Paratyphoid B is more frequent in Europe. It can present as a typhoid-like illness, as a severe gastroenteritis or with features of both. Herpes labialis, rare in true typhoid fever, is frequently seen in paratyphoid B. Rarely a subdural empyema can occur.[11] Diagnosis is with isolation of the agent in blood or stool and demonstration of antibodies antiBH in the Widal test. The disease responds well to chloramphenicol or co-trimoxazole.[citation needed]
### Paratyphoid C[edit]
Paratyphoid C is a rare infection, generally seen in the Far East. It presents as a septicaemia with metastatic abscesses. Cholecystitis is possible in the course of the disease. Antibodies to paratyphoid C are not usually tested and the diagnosis is made with blood cultures. Chloramphenicol therapy is generally effective.[citation needed]
### Carriers[edit]
Humans and, occasionally, domestic animals are the carriers of paratyphoid fever. Members of the same family can be transient or permanent carriers. In most parts of the world, short-term fecal carriers are more common than urinary carriers. The chronic urinary carrier state occurs in those who have schistosomiasis (parasitic blood fluke).[citation needed]
Continuing to shed Salmonella Paratyphi is possible for up to one year, and during this phase, a person is considered to be a carrier. The chronic carrier state may follow acute illness, or mild or even subclinical infections. Chronic carriers are most often women who were infected in their middle age.[citation needed]
## Pathophysiology[edit]
After ingestion, if the immune system is unable to stop the infection, the bacteria multiply and then spread to the bloodstream, after which the first signs of disease are observed in the form of fever. They penetrate further to the bone marrow, liver, and bile ducts, from which bacteria are excreted into the bowel contents. In the second phase of the disease, the bacteria penetrate the immune tissue of the small intestine, and the initial symptoms of small-bowel movements begin.[citation needed]
## Prevention[edit]
Providing basic sanitation and safe drinking water and food are the keys for controlling the disease. In developed countries, enteric fever rates decreased in the past when treatment of municipal water was introduced, human feces were excluded from food production, and pasteurization of dairy products began.[4] In addition, children and adults should be carefully educated about personal hygiene. This would include careful handwashing after defecation and sexual contact, before preparing or eating food, and especially the sanitary disposal of feces. Food handlers should be educated in personal hygiene prior to handling food or utensils and equipment. Infected individuals should be advised to avoid food preparation. Sexually active people should be educated about the risks of sexual practices that permit fecal-oral contact.[12]
Those who travel to countries with poor sanitation should receive a live attenuated typhoid vaccine—Ty21a (Vivotif), which, in addition to the protection against typhoid fever, may provide some protection against paratyphoid fever caused by the S. enterica serotypes A and B.[4] In particular, a reanalysis of data from a trial conducted in Chile showed the Ty21a vaccine was 49% effective (95% CI: 8–73%) in preventing paratyphoid fever caused by the serotype B.[13] Evidence from a study of international travelers in Israel also indicates the vaccine may prevent a fraction of infections by the serotype A, although no trial confirms this.[14] This cross-protection by a typhoid vaccine is most likely due to O antigens shared between different S. enterica serotypes.[14]
Exclusion from work and social activities should be considered for symptomatic, and asymptomatic people who are food handlers, healthcare/daycare staff who are involved in patient care and/or child care, children attending unsanitary daycare centers, and older children who are unable to implement good standards of personal hygiene. The exclusion applies until two consecutive stool specimens are taken from the infected patient and are reported negative.[citation needed]
## Treatments[edit]
Control requires treatment of antibiotics and vaccines prescribed by a doctor. Major control treatments for paratyphoid fever include ciprofloxacin for 10 days, ceftriaxone/cefotaxime for 14 days, or aziththromycin.[citation needed]
## Prognosis[edit]
Those diagnosed with Type A of the bacterial strain rarely die from it except in rare cases of severe intestinal complications. With proper testing and diagnosis, the mortality rate falls to less than 1%. Antibiotics such as azithromycin are particularly effective in treating the disease.[15]
## Epidemiology[edit]
Factors outside the household, such as unclean food from street vendors and flooding, help distribute the disease from person to person.[12] Because of poverty and poor hygiene and insanitary conditions, the disease is more common in less-industrialized countries, principally owing to the problem of unsafe drinking water, inadequate sewage disposal, and flooding.[16] Occasionally causing epidemics, paratyphoid fever is found in large parts of Asia, Africa, and Central and South America. Many of those infected get the disease in Asian countries. About 16 million cases occur a year, which result in about 25,000 deaths worldwide.[17]
## 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 Anna E. Newton (2014). "3 Infectious Diseases Related To Travel". CDC health information for international travel 2014 : the yellow book. ISBN 9780199948499. Archived from the original on 2015-07-02.
2. ^ a b c d e f Jeremy Hawker (2012). "3.56". Communicable disease control and health protection handbook (3rd ed.). Chichester, West Sussex, UK: Wiley-Blackwell. ISBN 9781444346947. Archived from the original on 2017-09-08.
3. ^ a b c d e f g h i j Alan J. Magill (2013). Hunter's tropical medicine and emerging infectious diseases (9th ed.). London: Saunders/Elsevier. pp. 568–572. ISBN 9781455740437. Archived from the original on 2017-09-08.
4. ^ a b c d e f Crump, JA; Mintz, ED (15 January 2010). "Global trends in typhoid and paratyphoid Fever". Clinical Infectious Diseases. 50 (2): 241–6. doi:10.1086/649541. PMC 2798017. PMID 20014951.
5. ^ GBD 2015 Disease and Injury Incidence and Prevalence, Collaborators. (8 October 2016). "Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1545–1602. doi:10.1016/S0140-6736(16)31678-6. PMC 5055577. PMID 27733282.
6. ^ a b GBD 2015 Mortality and Causes of Death, Collaborators. (8 October 2016). "Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1459–1544. doi:10.1016/s0140-6736(16)31012-1. PMC 5388903. PMID 27733281.
7. ^ Wain, J; Hendriksen, RS; Mikoleit, ML; Keddy, KH; Ochiai, RL (21 March 2015). "Typhoid fever". Lancet. 385 (9973): 1136–45. doi:10.1016/s0140-6736(13)62708-7. PMID 25458731. S2CID 1499916.
8. ^ Cunha BA (March 2004). "Osler on typhoid fever: differentiating typhoid from typhus and malaria". Infect. Dis. Clin. North Am. 18 (1): 111–25. doi:10.1016/S0891-5520(03)00094-1. PMID 15081508.
9. ^ Global Burden of Disease Study 2013, Collaborators (22 August 2015). "Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013". Lancet. 386 (9995): 743–800. doi:10.1016/s0140-6736(15)60692-4. PMC 4561509. PMID 26063472.
10. ^ GBD 2013 Mortality and Causes of Death, Collaborators (17 December 2014). "Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013". Lancet. 385 (9963): 117–71. doi:10.1016/S0140-6736(14)61682-2. PMC 4340604. PMID 25530442.
11. ^ Williams, V; Lakshmikantha, KM; Nallasamy, K; Sudeep, KC; Baranwal, AK; Jayashree, M (November 2018). "Subdural empyema due to Salmonella paratyphi B in an infant: a case report and review of literature". Child's Nervous System. 34 (11): 2317–2320. doi:10.1007/s00381-018-3825-7. PMID 29748704. S2CID 13689184.
12. ^ a b Bhan MK, Bahl R, Bhatnagar S (2005). "Typhoid and paratyphoid fever". Lancet. 366 (9487): 749–62. doi:10.1016/S0140-6736(05)67181-4. PMID 16125594. S2CID 28367429.
13. ^ Levine, M. M.; Ferreccio, C.; Black, R. E.; Lagos, R.; Martin, O. S.; Blackwelder, W. C. (2007). "Ty21a Live Oral Typhoid Vaccine and Prevention of Paratyphoid Fever Caused by Salmonella enterica Serovar Paratyphi B". Clinical Infectious Diseases. 45: S24–S28. doi:10.1086/518141. PMID 17582564.
14. ^ a b Whitaker, J. A.; Franco-Paredes, C.; Del Rio, C.; Edupuganti, S. (2009). "Rethinking Typhoid Fever Vaccines: Implications for Travelers and People Living in Highly Endemic Areas". Journal of Travel Medicine. 16 (1): 46–52. doi:10.1111/j.1708-8305.2008.00273.x. PMID 19192128.
15. ^ "Medical Conditions and Medical Information: ADAM Medical Library of Health Condi". Healthatoz.com. Archived from the original on 2009-02-08. Retrieved 2011-10-06.
16. ^ "Water-related Diseases." Communicable Diseases 2001. World Health Organization. 31 Oct 2008 <"Archived copy". Archived from the original on 2008-11-14. Retrieved 2008-11-15.CS1 maint: archived copy as title (link)>.
17. ^ Rubin, Raphael., David S. Strayer., Emanuel Rubin., Jay M. McDonald. Rubin's Pathology. 5th ed. 2007
## Further reading[edit]
Wikipedia's health care articles can be viewed offline with the Medical Wikipedia app.
* "Typhoid and Paratyphoid Fever." Communicable Disease Management Protocol. November 2001 https://www.gov.mb.ca/health/publichealth/cdc/protocol/typhoid.pdf.
* "Typhoid and Paratyphoid Fever." Public Health Notifiable Disease Management Guidelines. Disease Control and Prevention. Alberta Health and Wellness: June 2013 https://web.archive.org/web/20130925214850/http://www.health.alberta.ca/documents/Guidelines-Paratyphoid-Fever-2013.pdf
Classification
D
* ICD-10: A01.1-A01.4
* ICD-9-CM: 002
* MeSH: D010284
* DiseasesDB: 33218
External resources
* Patient UK: Paratyphoid fever
* 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]: 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Paratyphoid fever | c0030528 | 5,123 | wikipedia | https://en.wikipedia.org/wiki/Paratyphoid_fever | 2021-01-18T18:34:22 | {"mesh": ["D010284"], "umls": ["C0343375", "C0030528", "C0343376", "C0343377"], "orphanet": ["443227"], "wikidata": ["Q705906"]} |
Early changes of acroosteolysis can be detected by x-ray. In this radiograph there is dissolution and fragmentation of the bone in several of the terminal phalanges.~CDC
Acroosteolysis is resorption of the distal bony phalanges. Acroosteolysis has two patterns of resorption in adults: diffuse and bandlike.
The diffuse pattern of resorption has a widely diverse differential diagnosis which includes: pyknodysostosis, collagen vascular disease and vasculitis, Raynaud's neuropathy, trauma, epidermolysis bullosa, psoriasis, frostbite, sarcoidosis, hypertrophic osteoarthropathy, acromegaly, and advanced leprosy.[1][2][3]
The bandlike pattern of resorption may be seen with polyvinyl chloride exposure and Hadju-Cheney syndrome.[1]
A mnemonic commonly used for acro-osteolysis is PINCHFO.[4] Pyknodysostosis, Psoriasis, Injury (thermal burn, frostbite), Neuropathy (diabetes), Collagen vascular disease (scleroderma, Raynaud's), Hyperparathyroidism, Familial (Hadju-Cheney, progeria), Occupational (polyvinyl exposure),
Acroosteolysis may be associated with minimal skin changes or with ischemic skin lesions that may result in digital necrosis.[5]:665
## See also[edit]
* Nail anatomy
## References[edit]
1. ^ a b Yu, Joseph. Musculoskeletal Imaging, Case Review Series. 2008.
2. ^ Romero, Belinchón; Ramos Rincón, J.M.; Reyes Rabellc, F. "Nail Involvement in Leprosy". ACTAS Dermo-Sifiliograficas. Academia Española de Dermatología y Veneralogía. Archived from the original on 28 April 2015. Retrieved 28 June 2014.
3. ^ Baran, Robert; de Berker, David A. R.; Holzberg, Mark; Thomas, Luc (July 23, 2012). Baran and Dawber's Diseases of the Nails and their Management (4th ed.). Wiley. ISBN 978-0470657355. Retrieved 28 June 2014.
4. ^ http://radiopaedia.org/articles/pinch-fo
5. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0.
This condition of the skin appendages 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Acroosteolysis | c0917990 | 5,124 | wikipedia | https://en.wikipedia.org/wiki/Acroosteolysis | 2021-01-18T19:08:19 | {"mesh": ["D030981"], "wikidata": ["Q4676384"]} |
Benign essential blepharospasm (BEB) is a progressive neurological disorder characterized by abnormal blinking or spasms of the eyelids. It is a form of dystonia, a group of movement disorders involving uncontrolled tensing of the muscles (contractions), rhythmic shaking (tremors), and other involuntary movements. BEB occurs in both men and women, although it is especially common in middle-aged women.
Initial symptoms include an increased frequency of blinking, dry eyes, and eye irritation. As the condition progresses, spasms of the muscles surrounding the eyes cause involuntary winking or squinting and increasing difficulty keeping eyes open, which can lead to vision impairment. In more than half of all people with BEB, the symptoms affect other facial muscles and muscles in other areas of the body. When people with BEB also experience involuntary muscle spasms affecting the tongue and jaw, this is known as Meige syndrome. The cause of BEB is unknown; however, some cases appear to run through families. Although there is no cure for BEB, symptoms can be treated using various methods including botulinum toxin injections.
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Benign essential blepharospasm | c4692845 | 5,125 | gard | https://rarediseases.info.nih.gov/diseases/5909/benign-essential-blepharospasm | 2021-01-18T18:01:50 | {"omim": ["606798"], "orphanet": ["93955"], "synonyms": ["BEB", "OBSOLETE: Benign essential blepharospasm", "Primary blepharospasm", "Blepharospasm"]} |
A number sign (#) is used with this entry because immunodeficiency-32A (IMD32A) is caused by heterozygous mutation in the IRF8 gene (601565) on chromosome 16q24.1.
Immunodeficiency-32B (IMD32B; 614894), an autosomal recessive disorder, is allelic.
Description
Autosomal dominant IRF8 deficiency, or IMD32A, causes an abnormal peripheral blood myeloid phenotype with a marked loss of CD11C (ITGAX; 151510)-positive/CD1C (188340) dendritic cells, resulting in selective susceptibility to mycobacterial infections (Hambleton et al., 2011).
Clinical Features
Hambleton et al. (2011) reported 2 unrelated individuals of Italian descent living in Brazil and Chile who had histories of multiple episodes of disseminated, but curable, BCG disease. The patients were otherwise healthy, with no other unusual infections. Both were born to nonconsanguineous parents. Analysis of patient peripheral blood mononuclear cells showed selective depletion of CD11C-positive/CD1C-positive circulating dendritic cells and weak production of IL12 (see IL12B; 161561) following stimulation.
Mapping
Autosomal dominant CD11C-positive/CD1C-positive dendritic cell deficiency is caused by mutation in the IRF8 gene, which Chiquet et al. (2007) mapped to chromosome 16q24.1.
Molecular Genetics
In the 2 unrelated individuals with BCG disease, who lacked known mutations associated with susceptibility to mycobacterial disease, Hambleton et al. (2011) identified a de novo thr80-to-ala (T80A; 601565.0002) mutation in the IRF8 gene. The T80A mutation was not detected in 1,064 healthy controls. The mutant protein showed weak IL12B promoter transactivation in transfected mouse macrophages. Hambleton et al. (2011) proposed that depletion of IL12-producing CD1C-positive dendritic cells contributes to susceptibility to mycobacterial disease.
INHERITANCE \- Autosomal dominant IMMUNOLOGY \- Primary immunodeficiency \- Recurrent infections (disseminated mycobacterial infection after BCG immunization) \- Loss of IL-12-producing circulating CD11c+/CD1c+ myeloid dendritic cells MISCELLANEOUS \- Two unrelated patients have been reported (last curated September 2013) MOLECULAR BASIS \- Caused by mutation in the interferon regulatory factor 8 gene (IRF8, 601565.0002 ) ▲ 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| IMMUNODEFICIENCY 32A | c3808589 | 5,126 | omim | https://www.omim.org/entry/614893 | 2019-09-22T15:53:47 | {"omim": ["614893"], "orphanet": ["319600"], "synonyms": ["CD11C-POSITIVE/CD1C-POSITIVE DENDRITIC CELL DEFICIENCY, AUTOSOMAL DOMINANT", "MSMD due to partial interferon regulatory factor 8 deficiency", "Mendelian susceptibility to mycobacterial diseases due to partial interferon regulatory factor 8 deficiency", "Alternative titles", "MSMD due to partial IRF8 deficiency", "IMMUNODEFICIENCY 32A, MYCOBACTERIOSIS, AUTOSOMAL DOMINANT", "IRF8 DEFICIENCY, AUTOSOMAL DOMINANT"]} |
Primary erythermalgia is characterized by intermittent attacks of red, warm, painful burning extremities. It spontaneously arises during early childhood and adolescence in the absence of any detectable underlying disorder.
## Epidemiology
It may occur sporadically or as an inherited disease, but less than 30 kindreds with familial primary erythermalgia have been reported in the literature so far.
## Clinical description
Clinically, it is characterized by episodes of symmetrical red congestion, vasodilatation, and burning pain in both the feet and lower legs provoked by exercise, long standing and exposure to warmth that usually compels patients not to wear socks or closed shoes even in winter and to search for relief by immersion of feet in ice-cold water.
## Etiology
The gene for autosomal dominant erythermalgia, SCN9a, is located on chromosome 2q. SCN9a is a 26 exon gene encoding the voltage-gated sodium channel alpha subunit Nav1.7. This channel is found mainly in dorsal root ganglia and sympathetic ganglia neurons. All mutations detected so far are missense and lead to a gain of function by lowering the activation threshold of Nav1.7, resulting in hyperexcitability of pain signaling neurons.
## Diagnostic methods
The molecular diagnosis relies on sequencing of all coding exons of SCN9a. All mutations so far detected are private mutations (i.e. all families have their own unique mutations). Clinical diagnostic criteria are: attacks of local red congestion and vasodilation with increased local skin temperature and burning pain; a bilateral and symmetric distribution of symptoms; onset and aggravation of symptoms in response to distress, exercise and heat; relief provided by cold, rest and elevation of the affected extremities; the absence of a primary or associated disease; the condition being refractory to treatment.
## Differential diagnosis
Differential diagnosis includes erythromelalgia and secondary erythermalgia. In erythromelalgia, the burning pain and red congestion are usually unilateral or asymmetrically distributed with preferential involvement of one or more toes, the forefoot soles or fingertips. The platelet count is always elevated > 400 x 10 9/L, and aspirin relieves symptoms. Secondary erythermalgia is acquired, mostly develops at a later age and is invariably linked with the use of drugs or underlying disease (vasculitis, neuropathy). In contrast to erythromelalgia, the platelet count in both secondary and inherited primary erythermalgia is normal.
## Genetic counseling
In familial cases, the disorder is inherited as an autosomal dominant trait. Genetic counselling should be adapted according to the family history of the patient and affected parents should be informed of the 50% risk of reoccurrence.
## Management and treatment
Analgesic therapy for the neuropathic pain is problematic. However, voltage-gated sodium channels are potential targets for local anesthetics (lidocaine), systemic antiarrhythmics (mexiletine) and antiepileptic drugs such as phenytoin. In several patients, oral mexiletine (600 mg daily) rapidly improved symptoms suggesting that blocking the voltage-gated sodium channels is a valid therapeutic option.
## Prognosis
Prognosis depends on the severity of the disease. In severe cases the burning pain leads to an urgent need to cool the affected extremities. As a consequence, the affected skin from the limb (mostly the feet) can macerate resulting in skin fissures, skin infections and, possibly life-threatening sepsis. Amputation may be required in case of repeated infections. The very severe burning pain can lead to profound psychological consequences and depression.
*[v]: View this template
*[t]: Discuss this template
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*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Primary erythromelalgia | c0014805 | 5,127 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=90026 | 2021-01-23T16:58:24 | {"gard": ["6377"], "mesh": ["D004916"], "omim": ["133020"], "umls": ["C0014805"], "icd-10": ["I73.8"], "synonyms": ["Primary erythermalgia"]} |
A number sign (#) is used with this entry because of evidence that susceptibility to migraine with aura-13 (MGR13) is conferred by heterozygous mutation in the KCNK18 gene (613655) on chromosome 10q25.
Clinical Features
Lafreniere et al. (2010) reported a large 4-generation family in which migraine with aura was transmitted in an autosomal dominant pattern. The female proband had onset in her early teens of migraine headaches with visual aura. The visual aura was characterized by bilateral slowly enlarging scotoma with a scintillating edge, typically lasting 20 to 30 minutes, and followed by a throbbing lateralized or holocranial headache. The headache had a duration of 24 to 48 hours and was associated with sensitivity to lights, sounds, and smells, as well as nausea and occasional vomiting. Headaches also occurred in isolation without a preceding aura. Triggers included fatigue, alcohol, and bright lights. There was no clear association with the menstrual cycle, but the migraines were less frequent after menopause. Seven additional affected individuals in the family described similar migraine episodes with aura.
Molecular Genetics
In affected members of a family with autosomal dominant transmission of migraine with aura, Lafreniere et al. (2010) identified a heterozygous truncating mutation in the KCNK18 gene (613655.0001), which encodes the TWIK-related spinal cord K+ (TRESK) channel. The gene was chosen for direct sequencing by a candidate gene approach method, since two-pore domain (K2P) potassium channels are associated with neuronal excitability and modulation of pain. The mutation segregated only with the 8 affected family members. Sequencing of the KCNK18 gene detected a deleterious mutation in only 1 of 621 migraine probands, suggesting that KCNK18 mutations are a rare cause of this disorder.
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*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| MIGRAINE WITH OR WITHOUT AURA, SUSCEPTIBILITY TO, 13 | c3150908 | 5,128 | omim | https://www.omim.org/entry/613656 | 2019-09-22T15:58:01 | {"omim": ["613656"]} |
Usher syndrome is a genetic disorder characterized by sensorineural hearing loss or deafness and progressive vision loss due to retinitis pigmentosa. Sensorineural hearing means it is caused by abnormalities of the inner ear. Retinitis pigmentosa is an eye disease that affects the layer of light-sensitive tissue at the back of the eye (the retina). Vision loss occurs as the light-sensing cells of the retina gradually deteriorate. Night vision loss begins first, followed by blind spots that develop in the side (peripheral) vision, that can enlarge and merge to produce tunnel vision (loss of all peripheral vision). In some cases, vision is further impaired by clouding of the lens of the eye (cataracts). Three major types of Usher syndrome have been described - types I, II, and III. The different types are distinguished by their severity and the age when signs and symptoms appear. All three types are inherited in an autosomal recessive manner. Treatment for the hearing loss may include hearing aids or surgery for a cochlear implant. Vitamin A palmitate is useful for treating the vision loss in people with Usher syndrome type II.
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Usher syndrome type 3A | c1568248 | 5,129 | gard | https://rarediseases.info.nih.gov/diseases/5442/usher-syndrome-type-3a | 2021-01-18T17:57:13 | {"mesh": ["D052245"], "omim": ["276902"], "umls": ["C1568248"], "synonyms": ["USH3A", "USH3"]} |
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Omphalitis of newborn
SpecialtyNeonatology
Omphalitis of newborn is the medical term for inflammation of the umbilical cord stump in the neonatal newborn period, most commonly attributed to a bacterial infection.[1] Typically immediately after an infant is born, the umbilical cord is cut with a small remnant (often referred to as the stump) left behind. Normally the stump separates from the skin within 3–45 days after birth.[2] A small amount of pus-like material is commonly seen at the base of the stump and can be controlled by keeping the stump open to air to dry.[3] Certain bacteria can grow and infect the stump during this process and as a result significant redness and swelling may develop, and in some cases the infection can then spread through the umbilical vessels to the rest of the body.[3] While currently an uncommon anatomical location for infection in the newborn in the United States, it has caused significant morbidity and mortality both historically and in areas where health care is less readily available. In general, when this type of infection is suspected or diagnosed, antibiotic treatment is given, and in cases of serious complications surgical management may be appropriate.[3]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Diagnosis
* 4 Prevention
* 5 Treatment
* 6 Epidemiology
* 7 References
* 8 External links
## Signs and symptoms[edit]
Clinically, neonates with omphalitis present within the first two weeks of life with signs and symptoms of a skin infection (cellulitis) around the umbilical stump (redness, warmth, swelling, pain), pus from the umbilical stump, fever, fast heart rate (tachycardia), low blood pressure (hypotension), somnolence, poor feeding, and yellow skin (jaundice). Omphalitis can quickly progress to sepsis and presents a potentially life-threatening infection. In fact, even in cases of omphalitis without evidence of more serious infection such as necrotizing fasciitis, mortality is high (in the 10% range).
## Causes[edit]
Omphalitis is most commonly caused by bacteria. The culprits usually are Staphylococcus aureus, Streptococcus, and Escherichia coli.[2] The infection is typically caused by a combination of these organisms and is a mixed Gram-positive and Gram-negative infection. Anaerobic bacteria can also be involved.[4]
## Diagnosis[edit]
In a normal umbilical stump, you first see the umbilicus lose its characteristic bluish-white, moist appearance and become dry and black[2] After several days to weeks, the stump should fall off and leave a pink fleshy wound which continues to heal as it becomes a normal umbilicus.[2]
For an infected umbilical stump, diagnosis is usually made by the clinical appearance of the umbilical cord stump and the findings on history and physical examination. There may be some confusion, however, if a well-appearing neonate simply has some redness around the umbilical stump. In fact, a mild degree is common, as is some bleeding at the stump site with detachment of the umbilical cord. The picture may be clouded even further if caustic agents have been used to clean the stump or if silver nitrate has been used to cauterize granulomata of the umbilical stump.
## Prevention[edit]
During the 1950s there were outbreaks of omphalitis that then led to anti-bacterial treatment of the umbilical cord stump as the new standard of care.[5] It was later determined that in developed countries keeping the cord dry is sufficient, (known as "dry cord care") as recommended by the American Academy of Pediatrics.[2] The umbilical cord dries more quickly and separates more readily when exposed to air[2] However, each hospital/birthing center has its own recommendations for care of the umbilical cord after delivery. Some recommend not using any medicinal washes on the cord. Other popular recommendations include triple dye, betadine, bacitracin, or silver sulfadiazine. With regards to the medicinal treatments, there is little data to support any one treatment (or lack thereof) over another. However one recent review of many studies supported the use of chlorhexidine treatment as a way to reduce risk of death by 23% and risk of omphalitis by anywhere between 27-56% in community settings in underdeveloped countries.[6] This study also found that this treatment increased the time that it would take for the umbilical stump to separate or fall off by 1.7 days.[6] Lastly this large review also supported the notion that in hospital settings no medicinal type of cord care treatment was better at reducing infections compared to dry cord care.[6]
## Treatment[edit]
Treatment consists of antibiotic therapy aimed at the typical bacterial pathogens in addition to supportive care for any complications which might result from the infection itself such as hypotension or respiratory failure. A typical regimen will include intravenous antibiotics such as from the penicillin-group which is active against Staphylococcus aureus and an aminoglycoside for activity against Gram-negative bacteria. For particularly invasive infections, antibiotics to cover anaerobic bacteria may be added (such as metronidazole). Treatment is typically for two weeks and often necessitates insertion of a central venous catheter or peripherally inserted central catheter.
## Epidemiology[edit]
The current incidence in the United States is somewhere around 0.5% per year; overall, the incidence rate for developed world falls between 0.2–0.7%. In developing countries, the incidence of omphalitis varies from 2 to 7 for 100 live births.[7] There does not appear to be any racial or ethnic predilection.
Like many bacterial infections, omphalitis is more common in those patients who have a weakened or deficient immune system or who are hospitalized and subject to invasive procedures. Therefore, infants who are premature, sick with other infections such as blood infection (sepsis) or pneumonia, or who have immune deficiencies are at greater risk. Infants with normal immune systems are at risk if they have had a prolonged birth, birth complicated by infection of the placenta (chorioamnionitis), or have had umbilical catheters.
## References[edit]
1. ^ Jones, Kevin, MD, Neayland, Beverly, MD. "Brief Review of Omphalitis" (PDF). dead link. UNSOM Department of Pediatrics. Archived from the original (PDF) on 27 March 2014. Retrieved 23 July 2013.CS1 maint: multiple names: authors list (link)
2. ^ a b c d e f Cunningham, F. Williams Obstetrics:The Newborn (24 ed.). McGraw-Hill.
3. ^ a b c Rosenberg. Current Diagnosis & Treatment: Pediatrics (22e ed.).
4. ^ Fleisher, Gary R. Textbook of Pediatric Emergency Medicine. Philadelphia: Lippincott Williams & Wilkins, 2006, p. 928.
5. ^ Janssen, PA; Selwood, BL; Dobson, SR; Peacock, D; Thiessen, PN (January 2003). "To dye or not to dye: a randomized, clinical trial of a triple dye/alcohol regime versus dry cord care". Pediatrics. 111 (1): 15–20. doi:10.1542/peds.111.1.15. PMID 12509548.
6. ^ a b c Imdad, A; Bautista, RM; Senen, KA; Uy, ME; Mantaring JB, 3rd; Bhutta, ZA (31 May 2013). "Umbilical cord antiseptics for preventing sepsis and death among newborns". The Cochrane Database of Systematic Reviews. 5 (5): CD008635. doi:10.1002/14651858.CD008635.pub2. PMID 23728678.
7. ^ Bugaje, Mairo Adamu; et al. "Omphalitis" (PDF). Paediatric Surgery: A Comprehensive Text For Africa. Retrieved 23 July 2013.
## External links[edit]
Classification
D
* ICD-10: P38
* ICD-9-CM: 771.4
* DiseasesDB: 34512
External resources
* eMedicine: ped/1641
* v
* t
* e
Conditions originating in the perinatal period / fetal disease
Maternal factors
complicating pregnancy,
labour or delivery
placenta
* Placenta praevia
* Placental insufficiency
* Twin-to-twin transfusion syndrome
chorion/amnion
* Chorioamnionitis
umbilical cord
* Umbilical cord prolapse
* Nuchal cord
* Single umbilical artery
presentation
* Breech birth
* Asynclitism
* Shoulder presentation
Growth
* Small for gestational age / Large for gestational age
* Preterm birth / Postterm pregnancy
* Intrauterine growth restriction
Birth trauma
* scalp
* Cephalohematoma
* Chignon
* Caput succedaneum
* Subgaleal hemorrhage
* Brachial plexus injury
* Erb's palsy
* Klumpke paralysis
Affected systems
Respiratory
* Intrauterine hypoxia
* Infant respiratory distress syndrome
* Transient tachypnea of the newborn
* Meconium aspiration syndrome
* Pleural disease
* Pneumothorax
* Pneumomediastinum
* Wilson–Mikity syndrome
* Bronchopulmonary dysplasia
Cardiovascular
* Pneumopericardium
* Persistent fetal circulation
Bleeding and
hematologic disease
* Vitamin K deficiency bleeding
* HDN
* ABO
* Anti-Kell
* Rh c
* Rh D
* Rh E
* Hydrops fetalis
* Hyperbilirubinemia
* Kernicterus
* Neonatal jaundice
* Velamentous cord insertion
* Intraventricular hemorrhage
* Germinal matrix hemorrhage
* Anemia of prematurity
Gastrointestinal
* Ileus
* Necrotizing enterocolitis
* Meconium peritonitis
Integument and
thermoregulation
* Erythema toxicum
* Sclerema neonatorum
Nervous system
* Perinatal asphyxia
* Periventricular leukomalacia
Musculoskeletal
* Gray baby syndrome
* muscle tone
* Congenital hypertonia
* Congenital hypotonia
Infections
* Vertically transmitted infection
* Neonatal infection
* rubella
* herpes simplex
* mycoplasma hominis
* ureaplasma urealyticum
* Omphalitis
* Neonatal sepsis
* Group B streptococcal infection
* Neonatal conjunctivitis
Other
* Miscarriage
* Perinatal mortality
* Stillbirth
* Infant mortality
* Neonatal withdrawal
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Omphalitis of newborn | c0158947 | 5,130 | wikipedia | https://en.wikipedia.org/wiki/Omphalitis_of_newborn | 2021-01-18T18:37:49 | {"icd-9": ["771.4"], "icd-10": ["P38"], "wikidata": ["Q586878"]} |
A number sign (#) is used with this entry because of evidence that Wilms tumor-2 (WT2) is caused by mutation of the H19/IGF2-imprinting control region (ICR1; 616186) on chromosome 11p15. ICR1 controls imprinted expression of H19 (103280) and IGF2 (147470).
ICR1 and a neighboring imprinted gene cluster are implicated in Beckwith-Wiedemann syndrome (BWS; 130650), of which Wilms tumor is a common feature.
For a general phenotypic description and discussion of genetic heterogeneity of Wilms tumor, see WT1 (194070).
Mapping
Using a range of probes for chromosome 11, Mannens et al. (1988) demonstrated that loss of heterozygosity in Wilms tumors may involve chromosome 11p15.5 in addition to 11p13. Jeanpierre et al. (1990) found loss of maternal alleles from the 11p15 area of the maternal chromosome in Wilms tumor tissue and a constitutional deletion of 11p13 of the maternal chromosome. The authors noted that there have been other instances in which the 11p region involved in loss of heterozygosity (11p15) is different from the region involved in hereditary predisposition (11p13).
Koufos et al. (1989) studied patients with sporadic Wilms tumors, not associated with BWS, and found that a subset of the tumors had attained somatic homozygosity through mitotic recombination, with the smallest shared region of overlap being distal to the beta-globin complex at 11p15.5. The data suggested that there is a second locus, distinct from that on 11p13, that plays a role in the Wilms tumor. See also Henry et al. (1989).
Reeve et al. (1989) found loss of allelic heterozygosity at polymorphic 11p15 loci in Wilms tumor cells from 5 patients. In cells of 1 tumor, mitotic recombination had occurred distal to the gamma-globin gene on 11p15.5. Wadey et al. (1990) found that some Wilms tumors had allele loss restricted to 11p15 or to 11p13 and distal sequences.
Dowdy et al. (1991) provided in vivo functional evidence for the existence of this second genetic locus involved in suppressing the tumorigenic phenotype of Wilms tumor: they constructed a chromosome 11 that had one or the other region deleted, and this chromosome was introduced into the tumorigenic Wilms tumor cell line G401. When assayed for tumor-forming activity in nude mice, the 11p13-deleted, but not the 11p15.5-p14.1-deleted chromosome, retained its ability to suppress tumor formation.
Molecular Genetics
Using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) of the 11p15 growth regulatory region, Scott et al. (2008) identified constitutional abnormalities at chromosome 11p15 in 13 (3%) of 437 individuals with sporadic Wilms tumor without features of overgrowth syndromes. Six patients had paternal uniparental disomy of 11p15 and 6 had hypermethylation at the H19 differentially methylated region (DMR) (see ICR1, 616186). There were 2 familial cases. In 1 family, 2 sibs had a microdeletion of the H19 DMR (616186.0002) that was inherited from the unaffected mother; 1 sib had isolated Wilms tumor and the other had features of BWS. In a second family, a mother and 2 daughters had a microinsertion in the H19 DMR (616186.0003), inherited from the unaffected grandmother. No abnormalities were detected in 220 controls. Analysis of tumor tissue showed that the level of H19 DMR hypermethylation was greater in tumor compared to lymphocytes, suggesting that the tumors developed by clonal expansion of cells harboring the 11p15 defect. There was no evidence of additional tumor-specific 11p15 abnormalities affecting the wildtype allele.
INHERITANCE \- Autosomal dominant \- Somatic mutation GENITOURINARY Kidneys \- Nephroblastoma (Wilms tumor) NEOPLASIA \- Nephroblastoma (Wilms tumor) MISCELLANEOUS \- Most case are sporadic MOLECULAR BASIS \- Caused by mutation in the H19 gene (H19, 103290.0002 ) ▲ 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| WILMS TUMOR 2 | c0027708 | 5,131 | omim | https://www.omim.org/entry/194071 | 2019-09-22T16:31:46 | {"mesh": ["D009396"], "omim": ["194071"], "orphanet": ["654"], "genereviews": ["NBK1294"]} |
Childhood hepatocellular carcinoma (childhood HCC) is a rare type of malignant (cancerous) tumor that forms in the cells and tissues of the liver. Childhood HCC is usually found in older children and adolescents (10-14 years), but has been found in children younger than 5. Symptoms may include a mass in the abdomen, a swollen and painful abdomen, weight loss, poor appetite, yellowing of the skin and eyes (jaundice), vomiting, fever, itchy skin, and a decreased number of red blood cells (anemia). The cause of childhood HCC is not well understood; however, underlying disorders that cause liver dysfunction (ex. hepatitis B) and congenital or genetic disorders that affect the liver (ex. tyrosinemia type 1) may increase the risk for childhood HCC to occur. Treatment options vary depending on a variety of factors including the stage of the cancer and may include surgery to remove the tumor and chemotherapy.
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Childhood hepatocellular carcinoma | c0279606 | 5,132 | gard | https://rarediseases.info.nih.gov/diseases/9331/childhood-hepatocellular-carcinoma | 2021-01-18T18:01:29 | {"omim": ["114550"], "umls": ["C0279606"], "orphanet": ["33402"], "synonyms": ["Childhood Carcinoma of Liver Cell", "Childhood Hepatoma", "Childhood Liver Cell Carcinoma", "Pediatric Carcinoma of Liver Cell", "Pediatric Hepatocellular Carcinoma", "Pediatric Hepatoma", "Pediatric Liver Cell Carcinoma"]} |
Granulocytosis
SpecialtyHematology
In medicine, granulocytosis is the presence of an increased number of granulocytes in the peripheral blood. Often, the word refers to an increased neutrophil granulocyte count (neutrophilia), but granulocytosis formally refers to the combination of neutrophilia, eosinophilia, and basophilia.[1] Leukocytosis refers to an increase in the number of all white blood cells.
## Contents
* 1 Causes
* 2 Diagnosis
* 3 Prognostic
* 4 See also
* 5 References
* 6 External links
## Causes[edit]
Granulocytosis can be a feature of a number of diseases, including:[citation needed]
* Infection, especially bacterial
* Malignancy, most notably leukemia (it is the main feature of chronic myelogenous leukemia, CML)
* Autoimmune disease
## Diagnosis[edit]
Diagnosis of granulocytosis is usually done by obtaining a complete blood count.[citation needed]
## Prognostic[edit]
In cardiovascular disease, increased white blood cell counts have been shown to indicate a worse prognosis.[citation needed]
## See also[edit]
* Agranulocytosis
* Bandemia
* Complete blood count
## References[edit]
1. ^ George, Tracy I. (8 December 2012). "Malignant or benign leukocytosis". ASH Education Program Book. pp. 475–484. doi:10.1182/asheducation-2012.1.475. Retrieved 13 March 2019.
## External links[edit]
Classification
D
* DiseasesDB: 8995
* v
* t
* e
Diseases of monocytes and granulocytes
Monocytes and macrophages
↑
-cytosis:
* Monocytosis
* Histiocytosis
* Chronic granulomatous disease
↓
-penia:
* Monocytopenia
Granulocytes
↑
-cytosis:
* granulocytosis
* Neutrophilia
* Eosinophilia/Hypereosinophilic syndrome
* Basophilia
* Bandemia
↓
-penia:
* Granulocytopenia/agranulocytosis (Neutropenia/Severe congenital neutropenia/Cyclic neutropenia
* Eosinopenia
* Basopenia)
Disorder of phagocytosis
Chemotaxis and degranulation
* Leukocyte adhesion deficiency
* LAD1
* LAD2
* Chédiak–Higashi syndrome
* Neutrophil-specific granule deficiency
Respiratory burst
* Chronic granulomatous disease
* Neutrophil immunodeficiency syndrome
* Myeloperoxidase deficiency
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Granulocytosis | c1282609 | 5,133 | wikipedia | https://en.wikipedia.org/wiki/Granulocytosis | 2021-01-18T18:54:46 | {"umls": ["C0861145", "C1282609"], "wikidata": ["Q3775781"]} |
A number sign (#) is used with this entry because Griscelli syndrome type 2 (GS2), which is characterized by hypomelanosis with immunologic abnormalities with or without neurologic impairment, is caused by mutation in the RAB27A gene (603868).
For a discussion of phenotypic and genetic heterogeneity of Griscelli syndrome, see Griscelli syndrome type 1 (GS1; 214450).
Clinical Features
Griscelli et al. (1978) described 2 unrelated patients with a disorder resembling the Chediak-Higashi syndrome (CHS; 214500). Features were partial albinism, frequent pyogenic infections, and acute episodes of fever, neutropenia, and thrombocytopenia. The pigmentary dilution was characterized by large clumps of pigment in the hair shafts and an accumulation of melanosomes in melanocytes. Despite an adequate number of T and B lymphocytes, the patients were hypogammaglobulinemic, deficient in antibody production, and incapable of delayed skin hypersensitivity and skin graft rejection. Their leukocytes did not stimulate normal lymphocytes. A defect of helper T-cells was postulated. One patient was an 11-year-old North African girl with unrelated parents with a brother and sister with silvery hair who had died at 30 and 18 months of age, respectively. Differences from CHS were morphologic normality of polymorphonuclear leukocytes; the giant granules of CHS were not found. The morphologic characteristics of the hypopigmentation also distinguished the disorder from CHS, as well as from other pigmentary anomalies of man. Another difference was normal leukocyte specific protease activity, which is very low in CHS.
In a review, Klein et al. (1994) stated that Griscelli syndrome can be distinguished from Chediak-Higashi syndrome by pathognomonic histologic features. The prognosis is poor unless early bone marrow transplantation is carried out. They stated that since the original description, only 19 patients had been described. They reported the clinical and biologic features, therapy, and outcome in 7 cases.
In 8 Saudi Arabian kindreds, Harfi et al. (1992) described a disorder characterized by partial albinism with immunodeficiency and progressive demyelination of brain white matter, referred to as PAID syndrome. Although the authors originally considered this syndrome to be distinct from both Chediak-Higashi syndrome and Griscelli syndrome, de Saint Basile (2007) stated that 1 of the Saudi Arabian kindreds reported by Harfi et al. (1992) was found to have a mutation in the RAB27A gene.
Gogus et al. (1995) described 3 Turkish patients with Griscelli syndrome: a girl with consanguineous parents and 2 brothers who were born to another consanguineous couple. The girl and one boy had serious neurologic problems, with spasticity, rigidity, and convulsions. Despite therapy, both patients died. Hemorrhagic areas and lymphohistiocytic infiltration were found in all sections of the brain. Focal spongy degeneration was found in the cortex. Erythrophagocytosis was present in almost every organ.
Mancini et al. (1998) described a patient with Griscelli syndrome who presented with hepatosplenomegaly, hepatitis, pancytopenia, and silvery hair in the newborn period. Her parents were Hispanic and distantly related. Petechiae and hepatosplenomegaly were noted at birth, and multiple platelet and packed red blood cell transfusions were required. Bilirubin peaked at 26.5 mg/dL at 4 weeks of age. Hepatitis and pancytopenia gradually improved, necessitating only occasional transfusions for blood products. Treatment preliminary to bone marrow transplantation was initiated; however, she presented at 15 weeks of age with spasticity and seizures and it was decided that she was not a suitable candidate for transplantation.
The 16 patients with Griscelli syndrome in whom Menasche et al. (2000) identified mutations in the RAB27A gene came from consanguineous families, except a pair of brothers, whose parents originated, however, from the same village in Mauritius (603868.0003). The patients exhibited various degrees of skin hypopigmentation and a silvery-gray sheen of the hair with large pigment aggregates in hair shafts. In all of these patients, at least 1 episode of hemophagocytic syndrome had occurred, characterized by acute onset of uncontrolled lymphocyte and macrophage activation, resulting in infiltration and hemophagocytosis in multiple organs. The first episode of hemophagocytic syndrome occurred at 8 years in one, 3 years in the 2 Mauritian brothers and another patient, and before 6 months in all the others. During the course of the hemophagocytic syndrome, some of the patients presented with convulsions and/or cerebellar manifestations, thought to be the consequence of leukocyte brain infiltration.
Menasche et al. (2000) made a useful clinical distinction between Griscelli syndrome type 1 (214450) due to mutation in the MYO5A gene and GS2 due to mutation in the RAB27A gene. GS1 is associated with a primary neurologic impairment; immune features such as susceptibility to infections and occurrence of hemophagocytic syndrome are absent. GS2 has no primary neurologic features but is associated with an uncontrolled T lymphocyte and macrophage activation syndrome, often associated with the hemophagocytic syndrome, leading to death in the absence of bone marrow transplantation. Menasche et al. (2000) suggested that the convulsions and/or cerebral manifestations with which some of their GS2 patients with RAB27A mutations presented during the course of hemophagocytic syndrome were most likely the consequence of leukocyte brain infiltration.
Hurvitz et al. (1993) reported studies of 4 members of a highly consanguineous kindred with pigmentation and histologic findings consistent with Griscelli syndrome but without recurrent infections. These patients exhibited a range of neurologic involvement from mild cognitive delay with a convulsive disorder in one patient to a fatal degenerative course in 3 others. Anikster et al. (2002) restudied this family, a Muslim Arab kindred whose members had highly variable neurologic involvement, along with the hemophagocytic syndrome and immunologic abnormalities. This family included 4 affected children: a brother (the proband) and sister in one family, and their 2 female first cousins. All 4 individuals died in childhood, at ages 11.5 years, 10 months, 6 years, and 2 years, respectively. All had silvery hair. Skin biopsies revealed normal numbers of melanocytes containing normally sized melanin granules; Hurvitz et al. (1993) had suggested that no melanosomes were transferred to the surrounding keratinocytes. The 3 females presented with recurrent vomiting; the sister of the proband had an acute febrile illness, and 1 of her cousins presented with lethargy. All 3 deteriorated neurologically after their initial presentation, as indicated by regression of mental and physical function. The clinical course of the proband was characterized by periodic episodes of seizures, from the age of 1 year, and by mild cognitive delay. At the age of 2 years 10 months, he experienced an episode similar to the accelerated phase described by Griscelli et al. (1978) and recovered completely. He was well and had no recurrent infections and his neurologic status was stable until age 8 years. He was not monitored between the ages of 8 years and 10.5 years, after which he was repeatedly admitted to a local hospital because of prolonged fever, severe hepatosplenomegaly, and pancytopenia. His condition deteriorated, and he developed ascites, generalized edema, and jaundice and died at the age of 11.5 years.
Aksu et al. (2003) reported an 11-year-old girl with GS2 confirmed by identification of a mutation in the RAB27A gene (603868.0007). In addition to hypomelanosis, she had multiple immunologic abnormalities such as hypogammaglobulinemia and leukopenia, but no hemophagocytosis. Degenerative white matter disease was also present. Aksu et al. (2003) noted that the presence of white matter disease and the absence of hemophagocytosis in their patient were unusual for a patient with mutation in the RAB27A gene, and extended the phenotypic spectrum of Griscelli syndrome.
Diagnosis
Durandy et al. (1993) successfully undertook the prenatal diagnosis of 2 hereditary syndromes associating albinism and immune defects: Chediak-Higashi syndrome and Griscelli syndrome. Because the genes responsible for these diseases had not yet been mapped and the immune abnormalities were too subtle to be diagnosed in utero, prenatal diagnosis was made on morphologic grounds. In the case of CHS, it was based on light-microscopic examination of the hair shaft and on light- and electron-microscopic study of polymorphonuclear cells. In the Griscelli syndrome, only examination of the hair was feasible. The diagnosis was negative in 12 fetuses at risk and positive in 4.
Mapping
In 4 patients with Griscelli syndrome, Pastural et al. (2000) found that the MYO5A gene was expressed, and no mutation was detected in the coding sequence of the gene, even in the alternatively spliced region for which exon-intron boundaries were characterized. Linkage analysis performed in 15 Griscelli families studied to that time confirmed the original localization to 15q21. However, fine haplotype analysis in 3 families strongly suggested the existence of a second locus for Griscelli syndrome less than 7.3 cM from the MYO5A gene.
Molecular Genetics
Menasche et al. (2000) demonstrated that the non-MYO5A locus defined by Pastural et al. (2000) in the 15q21 region is that for RAB27A (603868) and detected causative mutations in that gene.
Anikster et al. (2002) performed mutation analysis of the MYO5A and RAB27A genes in the family originally described by Hurvitz et al. (1993). The patients had normal MYO5A genes but exhibited a homozygous 67.5-kb deletion (603868.0004) that eliminated RAB27A mRNA and immunocytofluorescence-detectable protein. The RAB27A and MYO5A genes are less than 1.6 cM from each other on 15q21. Furthermore, their gene products interact and function in vesicle trafficking. Anikster et al. (2002) proposed that all patients with RAB27A mutations have Griscelli syndrome and that neurologic complications in these individuals occur secondarily to lymphocytic and histiocytic infiltration of the brain (Gogus et al., 1995). They further proposed that patients with MYO5A mutations have Elejalde syndrome, also known as neuroectodermal melanolysosomal disease (256710), a condition characterized by mild hypopigmentation and severe, primary neurologic abnormalities. Menasche et al. (2002), Huizing et al. (2002), and Bahadoran et al. (2003, 2003) also suggested the identity of Elejalde syndrome, at least in some patients, and Griscelli syndrome type 1.
Using retroviral vector-mediated gene transfer of RAB27A into CD8+ T cells from a patient with Griscelli syndrome type 2 and compound heterozygosity for mutations in RAB27A (see 603868.0008), Bizario et al. (2004) demonstrated rescue of the cytotoxic function of the patient's mutant cells and concluded that RAB27A GTPase plays an essential role in lytic granule release.
INHERITANCE \- Autosomal recessive SKIN, NAILS, & HAIR Skin \- Skin hypopigmentation \- Accumulation of melanosomes in melanocytes Hair \- Silver-gray hair \- Melanin pigment aggregation in hair shafts NEUROLOGIC Central Nervous System \- Variable neurologic deterioration (likely result of hemophagocytic syndrome) \- Seizures \- Cerebellar signs \- Spasticity IMMUNOLOGY \- Hemophagocytic syndrome (HS) characterized by acute onset of uncontrolled T-lymphocyte and macrophage activation \- Lymphohistiocytic infiltration and hemophagocytosis in multiple organs \- T-cells show reduced cytotoxicity and reduced cytolytic granule exocytosis \- Deficiency of delayed skin hypersensitivity \- Humoral deficiency (likely result of T-cell abnormalities) \- Frequent pyogenic infections MISCELLANEOUS \- Onset in infancy or early childhood \- Death in childhood \- Multiorgan failure may result from HS \- See also Griscelli syndrome type 1 ( 214450 ) for a similar disorder without immunological abnormalities and Griscelli syndrome type 3 ( 609227 ) for a similar disorder without neurologic or immunologic abnormalities MOLECULAR BASIS \- Caused by mutations in the Ras-associated protein RAB27A gene (RAB27A, 603868.0001 ) ▲ 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| GRISCELLI SYNDROME, TYPE 2 | c1868679 | 5,134 | omim | https://www.omim.org/entry/607624 | 2019-09-22T16:08:59 | {"doid": ["0060833"], "mesh": ["C537302"], "omim": ["607624"], "orphanet": ["79477", "381"], "synonyms": ["Alternative titles", "GRISCELLI SYNDROME WITH HEMOPHAGOCYTIC SYNDROME", "PARTIAL ALBINISM AND IMMUNODEFICIENCY SYNDROME", "PAID SYNDROME"]} |
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Mucopolysaccharidosis
A 16-year-old male with rapidly progressing MPS-VI, showing characteristic facial features and skeletal abnormalities
SpecialtyEndocrinology
Mucopolysaccharidoses are a group of metabolic disorders caused by the absence or malfunctioning of lysosomal enzymes needed to break down molecules called glycosaminoglycans (GAGs). These long chains of sugar carbohydrates occur within the cells that help build bone, cartilage, tendons, corneas, skin and connective tissue. GAGs (formerly called mucopolysaccharides) are also found in the fluids that lubricate joints.
Individuals with mucopolysaccharidosis either do not produce enough of one of the eleven enzymes required to break down these sugar chains into simpler molecules, or they produce enzymes that do not work properly. Over time, these GAGs collect in the cells, blood and connective tissues. The result is permanent, progressive cellular damage which affects appearance, physical abilities, organ and system functioning.
The mucopolysaccharidoses are part of the lysosomal storage disease family, a group of more than 40 genetic disorders that result when the lysosome organelle in animal cells malfunctions. The lysosome can be thought of as the cell's recycling center because it processes unwanted material into other substances that the cell can utilize. Lysosomes break down this unwanted matter via enzymes, highly specialized proteins essential for survival. Lysosomal disorders like mucopolysaccharidosis are triggered when a particular enzyme exists in too small an amount or is missing altogether.
## Contents
* 1 Signs and symptoms
* 2 Genetics
* 3 Diagnosis
* 3.1 Types
* 3.2 Overview table
* 3.3 MPS I
* 3.4 MPS II
* 3.5 MPS III
* 3.6 MPS IV
* 3.7 MPS VI
* 3.8 MPS VII
* 3.9 MPS IX
* 4 Treatment
* 5 See also
* 6 References
* 7 External links
## Signs and symptoms[edit]
A child with an unspecified MPS disorder, showing characteristic facial features
Corneal clouding in a 30-year-old male with MPS-VI. Several other MPS disorders may also present with corneal clouding
The mucopolysaccharidoses share many clinical features but have varying degrees of severity. These features may not be apparent at birth but progress as storage of GAGs affects bone, skeletal structure, connective tissues, and organs. Neurological complications may include damage to neurons (which send and receive signals throughout the body) as well as pain and impaired motor function. This results from compression of nerves or nerve roots in the spinal cord or in the peripheral nervous system, the part of the nervous system that connects the brain and spinal cord to sensory organs such as the eyes and to other organs, muscles, and tissues throughout the body.
Depending on the mucopolysaccharidosis subtype, affected individuals may have normal intellect or have cognitive impairments, may experience developmental delay, or may have severe behavioral problems. Many individuals have hearing loss, either conductive (in which pressure behind the eardrum causes fluid from the lining of the middle ear to build up and eventually congeal), neurosensory (in which tiny hair cells in the inner ear are damaged), or both. Communicating hydrocephalus—in which the normal reabsorption of cerebrospinal fluid is blocked and causes increased pressure inside the head—is common in some of the mucopolysaccharidoses. Surgically inserting a shunt into the brain can drain fluid. The eye's cornea often becomes cloudy from intracellular storage, and glaucoma and degeneration of the retina also may affect the patient's vision.
Physical symptoms generally include coarse or rough facial features (including a flat nasal bridge, thick lips, and enlarged mouth and tongue), short stature with disproportionately short trunk (dwarfism), dysplasia (abnormal bone size and/or shape) and other skeletal irregularities, thickened skin, enlarged organs such as liver (hepatomegaly) or spleen (splenomegaly), hernias, and excessive body hair growth. Short and often claw-like hands, progressive joint stiffness, and carpal tunnel syndrome can restrict hand mobility and function. Recurring respiratory infections are common, as are obstructive airway disease and obstructive sleep apnea. Many affected individuals also have heart disease, often involving enlarged or diseased heart valves.
Another lysosomal storage disease often confused with the mucopolysaccharidoses is mucolipidosis. In this disorder, excessive amounts of fatty materials known as lipids (another principal component of living cells) are stored, in addition to sugars. Persons with mucolipidosis may share some of the clinical features associated with the mucopolysaccharidoses (certain facial features, bony structure abnormalities, and damage to the brain), and increased amounts of the enzymes needed to break down the lipids are found in the blood.
## Genetics[edit]
Mucopolysaccharidosis has an autosomal recessive pattern of inheritance.
It is estimated that 1 in 25,000 babies born in the United States will have some form of the mucopolysaccharidoses.[1] Most mucopolysaccharidoses are autosomal recessive disorders, meaning that only individuals inheriting the defective gene from both parents are affected. (The exception is MPS II, or Hunter syndrome, in which the mother alone passes along the defective gene to a son.) When both people in a couple have the defective gene, each pregnancy carries with it a one in four chance that the child will be affected. The parents and siblings of an affected child may have no sign of the disorder. Unaffected siblings and select relatives of a child with one of the mucopolysaccharidoses may carry the recessive gene and could pass it to their own children.
## Diagnosis[edit]
Diagnosis often can be made through clinical examination and urine tests (excess mucopolysaccharides are excreted in the urine). Enzyme assays (testing a variety of cells or body fluids in culture for enzyme deficiency) are also used to provide definitive diagnosis of one of the mucopolysaccharidoses. Prenatal diagnosis using amniocentesis and chorionic villus sampling can verify if a fetus either carries a copy of the defective gene or is affected with the disorder. Genetic counseling can help parents who have a family history of the mucopolysaccharidoses determine if they are carrying the mutated gene that causes the disorders.
### Types[edit]
Seven distinct clinical types and numerous subtypes of the mucopolysaccharidoses have been identified. Although each mucopolysaccharidosis (MPS) differs clinically, most patients generally experience a period of normal development followed by a decline in physical and/or mental function. (Note: MPS-V and MPS-VIII are no longer in use as designations for any disease.)
### Overview table[edit]
Main mucopolysaccharidoses Type[2] Common name
Other names OMIM Gene Locus Deficient enzyme Accumulated products Symptoms Incidence
MPS IH Hurler syndrome 607014 IDUA 4p16.3 α-L-iduronidase Heparan sulfate
Dermatan sulfate Intellectual disability, micrognathia, coarse facial features, macroglossia, retinal degeneration, corneal clouding, cardiomyopathy, hepatosplenomegaly 1:100,000[3]
MPS IH/S Hurler–Scheie syndrome 607015
MPS IS Scheie syndrome
Formerly: Mucopolysaccharidosis type V 607016
MPS II Hunter syndrome 309900 IDS Xq28 Iduronate sulfatase Heparan sulfate
Dermatan sulfate Intellectual disability (similar, but milder, symptoms to MPS I). This type exceptionally has X-linked recessive inheritance 1:100,000-1:150,000 males[1]
MPS IIIA Sanfilippo syndrome A
Sulfamidase deficiency 252900 SGSH 17q25.3 Heparan sulfamidase Heparan sulfate Developmental delay, severe hyperactivity, spasticity, motor dysfunction, death by the second decade 1:280,000[4] – 1:50,000[5]
MPS IIIB Sanfilippo syndrome B
NAGLU deficiency 252920 NAGLU 17q21.2 N-acetylglucosaminidase
MPS IIIC Sanfilippo syndrome C 252930 HGSNAT 8p11.21 Heparan-α-glucosaminide N-acetyltransferase
MPS IIID Sanfilippo syndrome D 252940 GNS 12q14.3 N-acetylglucosamine 6-sulfatase
MPS IVA Morquio syndrome A 253000 GALNS 16q24.3 Galactose-6-sulfate sulfatase Keratan sulfate
Chondroitin 6-sulfate Severe skeletal dysplasia, short stature, motor dysfunction 1 in 75,000[4]
MPS IVB Morquio syndrome B 253010 GLB1 3p22.3 β-galactosidase Keratan sulfate
MPS V See MPS IS (Scheie syndrome) above
MPS VI Maroteaux–Lamy syndrome
ARSB deficiency 253200 ARSB 5q14.1 N-acetylgalactosamine-4-sulfatase Dermatan sulfate Severe skeletal dysplasia, short stature, motor dysfunction, kyphosis, heart defects
MPS VII Sly syndrome
GUSB deficiency 253220 GUSB 7q11.21 β-glucuronidase Heparan sulfate
Dermatan sulfate
Chondroitin 4,6-sulfate Hepatomegaly, skeletal dysplasia, short stature, corneal clouding, developmental delay <1:250,000[1]
MPS IX Natowicz syndrome
Hyaluronidase deficiency 601492 HYAL1 3p21.31 Hyaluronidase Hyaluronic acid Nodular soft-tissue masses around joints, episodes of painful swelling of the masses, short-term pain, mild facial changes, short stature, normal joint movement, normal intelligence
### MPS I[edit]
MPS I is divided into three subtypes based on severity of symptoms. All three types result from an absence of, or insufficient levels of, the enzyme alpha-L-iduronidase. Children born to an MPS I parent carry the defective gene.
* MPS I H (also called Hurler syndrome or α-L-iduronidase deficiency), is the most severe of the MPS I subtypes. Developmental delay is evident by the end of the first year, and patients usually stop developing between ages 2 and 4. This is followed by progressive mental decline and loss of physical skills. Language may be limited due to hearing loss and an enlarged tongue. In time, the clear layers of the cornea become clouded and retinas may begin to degenerate. Carpal tunnel syndrome (or similar compression of nerves elsewhere in the body) and restricted joint movement are common.
Affected children may be quite large at birth and appear normal but may have inguinal (in the groin) or umbilical (where the umbilical cord passes through the abdomen) hernias. Growth in height may be faster than normal but begins to slow before the end of the first year and often ends around age 3. Many children develop a short body trunk and a maximum stature of less than 4 feet. Distinct facial features (including flat face, depressed nasal bridge, and bulging forehead) become more evident in the second year. By age 2, the ribs have widened and are oar-shaped. The liver, spleen, and heart are often enlarged. Children may experience noisy breathing and recurring upper respiratory tract and ear infections. Feeding may be difficult for some children, and many experience periodic bowel problems. Children with Hurler syndrome often die before age 10 from obstructive airway disease, respiratory infections, and cardiac complications.
* MPS I S, Scheie syndrome, is the mildest form of MPS I. Symptoms generally begin to appear after age 5, with diagnosis most commonly made after age 10. Children with Scheie syndrome have normal intelligence or may have mild learning disabilities; some may have psychiatric problems. Glaucoma, retinal degeneration, and clouded corneas may significantly impair vision. Other problems include carpal tunnel syndrome or other nerve compression, stiff joints, claw hands and deformed feet, a short neck, and aortic valve disease. Some affected individuals also have obstructive airway disease and sleep apnea. Persons with Scheie syndrome can live into adulthood.
* MPS I H-S, Hurler–Scheie syndrome, is less severe than Hurler syndrome alone. Symptoms generally begin between ages 3 and 8. Children may have moderate intellectual disability and learning difficulties. Skeletal and systemic irregularities include short stature, marked smallness in the jaws, progressive joint stiffness, compressed spinal cord, clouded corneas, hearing loss, heart disease, coarse facial features, and umbilical hernia. Respiratory problems, sleep apnea, and heart disease may develop in adolescence. Some persons with MPS I H-S need continuous positive airway pressure during sleep to ease breathing. Life expectancy is generally into the late teens or early twenties.
Although no studies have been done to determine the frequency of MPS I in the United States, studies in British Columbia estimate that 1 in 100,000 babies born has Hurler syndrome. The estimate for Scheie syndrome is one in 500,000 births and for Hurler-Scheie syndrome it is one in 115,000 births.
### MPS II[edit]
MPS II, Hunter syndrome or iduronate sulfatase deficiency, is caused by lack of the enzyme iduronate sulfatase. Hunter syndrome has two clinical subtypes and (since it shows X-linked recessive inheritance) is the only one of the mucopolysaccharidoses in which the mother alone can pass the defective gene to a son. The incidence of Hunter syndrome is estimated to be 1 in 100,000 to 150,000 male births.
### MPS III[edit]
MPS III, Sanfilippo syndrome, is marked by severe neurological symptoms. These include progressive dementia, aggressive behavior, hyperactivity, seizures, some deafness and loss of vision, and an inability to sleep for more than a few hours at a time. This disorder tends to have three main stages. During the first stage, early mental and motor skill development may be somewhat delayed. Affected children show a marked decline in learning between ages 2 and 6, followed by eventual loss of language skills and loss of some or all hearing. Some children may never learn to speak. In the syndrome's second stage, aggressive behavior, hyperactivity, profound dementia, and irregular sleep may make children difficult to manage, particularly those who retain normal physical strength. In the syndrome's last stage, children become increasingly unsteady on their feet and most are unable to walk by age 10.
Thickened skin and mild changes in facial features, bone, and skeletal structures become noticeable with age. Growth in height usually stops by age 10. Other problems may include narrowing of the airway passage in the throat and enlargement of the tonsils and adenoids, making it difficult to eat or swallow. Recurring respiratory infections are common.
There are four distinct types of Sanfilippo syndrome, each caused by alteration of a different enzyme needed to completely break down the heparan sulfate sugar chain. Little clinical difference exists between these four types but symptoms appear most severe and seem to progress more quickly in children with type A. The average duration of Sanfilippo syndrome is 8 to 10 years following onset of symptoms. Most persons with MPS III live into their teenage years, and some live longer.
* Sanfilippo A is the most severe of the MPS III disorders and is caused by the missing or altered enzyme heparan N-sulfatase. Children with Sanfilippo A have the shortest survival rate among those with the MPS III disorders.
* Sanfilippo B is caused by the missing or deficient enzyme alpha-N-acetylglucosaminidase.
* Sanfilippo C results from the missing or altered enzyme acetyl-CoAlpha-glucosaminide acetyltransferase.
* Sanfilippo D is caused by the missing or deficient enzyme N-acetylglucosamine 6-sulfatase.
The incidence of Sanfilippo syndrome (for all four types combined) is about one in 70,000 births.
### MPS IV[edit]
MPS IV, Morquio syndrome, is estimated to occur in 1 in 700,000 births. Its two subtypes result from the missing or deficient enzymes N-acetylgalactosamine-6-sulfatase (GALNS) (Type A) or beta-galactosidase (Type B) needed to break down the keratan sulfate sugar chain. Clinical features are similar in both types but appear milder in Morquio Type B. Onset is between ages 1 and 3. Neurological complications include spinal nerve and nerve root compression resulting from extreme, progressive skeletal changes, particularly in the ribs and chest; conductive and/or neurosensitive loss of hearing and clouded corneas. Intelligence is normal unless hydrocephalus develops and is not treated.
Physical growth slows generally around the age of 18 months, and stops completely by the age of 8. Skeletal abnormalities include a bell-shaped chest, a flattening or curvature of the spine, shortened long bones, and dysplasia of the hips, knees, ankles, and wrists. The bones that stabilize the connection between the head and neck can be malformed (odontoid hypoplasia); in these cases, a surgical procedure called spinal cervical bone fusion can be lifesaving. Restricted breathing, joint stiffness, and heart disease are also common. Children with the more, severe form of Morquio syndrome may not live beyond their twenties or thirties.
### MPS VI[edit]
Children with MPS VI, Maroteaux–Lamy syndrome, usually have normal intellectual development but share many of the physical symptoms found in Hurler syndrome. Caused by the deficient enzyme N-acetylgalactosamine 4-sulfatase, Maroteaux-Lamy syndrome has a variable spectrum of severe symptoms. Neurological complications include clouded corneas, deafness, thickening of the dura (the membrane that surrounds and protects the brain and spinal cord), and pain caused by compressed or traumatized nerves and nerve roots.
Growth is normal at first but stops suddenly around age 8. By age 10 children have developed a shortened trunk, crouched stance, and restricted joint movement. In more severe cases, children also develop a protruding abdomen and forward-curving spine. Skeletal changes (particularly in the pelvic region) are progressive and limit movement. Many children also have umbilical or inguinal hernias. Nearly all children have some form of heart disease.
An enzyme replacement therapy was tested on patients with MPS VI and was successful in that it improved growth and joint movement. An experiment was then carried out to see whether an injection of the missing enzyme into the hips would help the range of motion and pain.
### MPS VII[edit]
MPS VII, Sly syndrome, one of the least common forms of the mucopolysaccharidoses, is estimated to occur in fewer than one in 250,000 births. The disorder is caused by deficiency of the enzyme beta-glucuronidase. In its rarest form, Sly syndrome causes children to be born with hydrops fetalis, in which extreme amounts of fluid are retained in the body. Survival is usually a few months or less. Most children with Sly syndrome are less severely affected. Neurological symptoms may include mild to moderate intellectual disability by age 3, communicating hydrocephalus, nerve entrapment, corneal clouding, and some loss of peripheral and night vision. Other symptoms include short stature, some skeletal irregularities, joint stiffness and restricted movement, and umbilical and/or inguinal hernias. Some patients may have repeated bouts of pneumonia during their first years of life. Most children with Sly syndrome live into the teenage or young adult years.
### MPS IX[edit]
As of 2001, only one case of MPS IX (Online Mendelian Inheritance in Man (OMIM): 601492) had been reported. The disorder results from hyaluronidase deficiency. Symptoms included nodular soft-tissue masses located around joints, with episodes of painful swelling of the masses and pain that ended spontaneously within 3 days. Pelvic radiography showed multiple soft-tissue masses and some bone erosion. Other traits included mild facial changes, acquired short stature as seen in other MPS disorders, and normal joint movement and intelligence.
## Treatment[edit]
Currently there is no cure for these disorders. Medical care is directed at treating systemic conditions and improving the person's quality of life. Physical therapy and daily exercise may delay joint problems and improve the ability to move.
Changes to the diet will not prevent disease progression, but limiting milk, sugar, and dairy products has helped some individuals experiencing excessive mucus.
Surgery to remove tonsils and adenoids may improve breathing among affected individuals with obstructive airway disorders and sleep apnea. Sleep studies can assess airway status and the possible need for nighttime oxygen. Some patients may require surgical insertion of an endotrachial tube to aid breathing. Surgery can also correct hernias, help drain excessive cerebrospinal fluid from the brain, and free nerves and nerve roots compressed by skeletal and other abnormalities. Corneal transplants may improve vision among patients with significant corneal clouding.
Enzyme replacement therapy has proven useful in reducing non-neurological symptoms and pain. Currently BioMarin Pharmaceutical produces enzyme replacement therapies for MPS type I and VI. Aldurazyme is an enzymatic replacement therapy for alpha-L-iduronidase produced by BioMarin for use in Type I MPS.[6] In May 2005, galsulfase[Naglazyme®], a recombinant enzyme replacement therapy also produced by Biomarin was approved for MPS VI (Marateaux-Lamy syndrome).[7] In July 2006, the United States Food and Drug Administration approved a synthetic version of I2S produced by Shire Pharmaceuticals Group, called Elaprase, as a treatment for MPS type II (Hunter syndrome). Vestronidase alfa (Mepsevii) is a recombinant human lysosomal beta glucuronidase for MPS VII (Sly syndrome) approved in the United States in November 2017 (Ultragenyx).[8]
Bone marrow transplantation (BMT) and umbilical cord blood transplantation (UCBT) have had limited success in treating the mucopolysaccharidoses. Abnormal physical characteristics, except for those affecting the skeleton and eyes, may be improved, but neurologic outcomes have varied. BMT and UCBT are high-risk procedures and are usually performed only after family members receive extensive evaluation and counseling.
## See also[edit]
* Alder-Reilly anomaly — a morphologic abnormality of white blood cells associated with mucopolysaccharidosis
* Lysosomal storage disease
## References[edit]
1. ^ a b c "Mucopolysaccharidoses Face Sheet". National Institute of Neurological Disorders and Stroke. 15 Nov 2017. Archived from the original on 18 August 2016. Retrieved 11 May 2018.
2. ^ Marks DB, Swanson T, Kim SI, Glucksman M (2007). Biochemistry and molecular biology. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 978-0-7817-8624-9.
3. ^ eMedicine Specialties > Mucopolysaccharidosis Type I Author: Maryam Banikazemi. Updated: Apr 14, 2009
4. ^ a b Nelson J (December 1997). "Incidence of the mucopolysaccharidoses in Northern Ireland". Human Genetics. 101 (3): 355–8. doi:10.1007/s004390050641. PMID 9439667. S2CID 23099247.
5. ^ Poorthuis BJ, Wevers RA, Kleijer WJ, Groener JE, de Jong JG, van Weely S, et al. (1999). "The frequency of lysosomal storage diseases in The Netherlands". Human Genetics. 105 (1–2): 151–6. doi:10.1007/s004390051078. PMID 10480370.
6. ^ "Aldurazyme (laronidase) for MPS I and approved in April 2003". BioMarin. Retrieved 12 June 2015.
7. ^ "Naglazyme". Drugs@FDA: FDA-Approved Drugs.
8. ^ "MEPSEVIITM (vestronidase alfa-vjbk)" (PDF). Highlights of Prescribing Information. U.S. Food and Drug Administration.
## External links[edit]
Classification
D
* ICD-10: E76
* ICD-9-CM: 277.5
* MeSH: D009083
* v
* t
* e
Lysosomal storage diseases: Inborn errors of carbohydrate metabolism (Mucopolysaccharidoses)
Catabolism
* MPS I
* Hurler Syndrome, Hurler-Scheie Syndrome, Scheie Syndrome
* MPS II: Hunter Syndrome
* MPS III: Sanfilippo Syndrome
* MPS IV: Morquio Syndrome
* MPS VI: Maroteaux-Lamy Syndrome
* MPS VII: Sly Syndrome
* MPS IX: Hyaluronidase deficiency
Authority control
* LCCN: sh85088232
* NDL: 01134892
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Mucopolysaccharidosis | c0026703 | 5,135 | wikipedia | https://en.wikipedia.org/wiki/Mucopolysaccharidosis | 2021-01-18T19:01:41 | {"gard": ["7065"], "mesh": ["D009083"], "umls": ["C0026703"], "orphanet": ["79213"], "wikidata": ["Q1479681"]} |
Griscelli syndrome type 2
Other namesHypopigmentation-immunodeficiency with or without neurologic impairment syndrome
This condition is inherited in an autosomal recessive manner
Griscelli syndrome type 2 (also known as "partial albinism with immunodeficiency") is a rare autosomal recessive syndrome characterized by variable cutenous albinism, silver colored metallic looking hair, frequent bacterial or viral infections, neutropenia, and thrombocytopenia.[1]:866
## Contents
* 1 Presentation
* 2 Genetics
* 3 Diagnosis
* 3.1 Differential diagnosis
* 4 Treatment
* 5 History
* 6 See also
* 7 References
* 8 External links
## Presentation[edit]
All types of Griscelli syndrome have distinctive skin and hair coloring.
Type 1 is associated with neurological abnormalities. These include delayed development, intellectual disability, seizures, hypotonia and eye abnormalities.
Type 2 - unlike type 1 - is not associated with primary neurological disease but is associated with an uncontrolled T lymphocyte expansion and macrophage activation syndrome. It is often associated with the hemophagocytic syndrome. This latter condition may be fatal in the absence of bone marrow transplantation.
Persons with type 3 have the typical light skin and hair coloring but are otherwise normal.
## Genetics[edit]
There are three types of Griscelli syndrome.
Type 1 is associated with mutations in the MYO5A gene
Type 2 is associated with mutations in RAB27A gene.
Both these genes are located on the long arm of chromosome 15 (15q21).
Type 3 is associated with mutations in the MLPH gene.
All types are inherited in an autosomal recessive fashion.
## Diagnosis[edit]
### Differential diagnosis[edit]
This includes Chediak-Higashi syndrome and Elejalde syndrome (neuroectodermal melanolysosomal disease).
## Treatment[edit]
This section is empty. You can help by adding to it. (September 2017)
## History[edit]
This syndrome was first described in 1978.[2] In 2000 types 1 and 2 were distinguished.[3]
## See also[edit]
* Griscelli syndrome
## References[edit]
1. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
2. ^ Griscelli C, Durandy, A, Guy-Grand D, Daguillard F, Herzog C, Prunieras M (1978) A syndrome associating partial albinism and immunodeficiency. Am J Med 65:691-702
3. ^ Menasche G, Pastural E, Feldmann J, Certain S, Ersoy F, Dupuis S, Wulffraat N, Bianchi D, Fischer A, Le Deist F, de Saint Basile G (2000) Mutations in RAB27A cause Griscelli syndrome associated with haemophagocytic syndrome. Nature Genet 25:173-176
## External links[edit]
Classification
D
* ICD-10: E70.3
* OMIM: 607624
* MeSH: C537302
External resources
* Orphanet: 79477
This cutaneous condition article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
* 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
* v
* t
* e
Deficiencies of intracellular signaling peptides and proteins
GTP-binding protein regulators
GTPase-activating protein
* Neurofibromatosis type I
* Watson syndrome
* Tuberous sclerosis
Guanine nucleotide exchange factor
* Marinesco–Sjögren syndrome
* Aarskog–Scott syndrome
* Juvenile primary lateral sclerosis
* X-Linked mental retardation 1
G protein
Heterotrimeic
* cAMP/GNAS1: Pseudopseudohypoparathyroidism
* Progressive osseous heteroplasia
* Pseudohypoparathyroidism
* Albright's hereditary osteodystrophy
* McCune–Albright syndrome
* CGL 2
Monomeric
* RAS: HRAS
* Costello syndrome
* KRAS
* Noonan syndrome 3
* KRAS Cardiofaciocutaneous syndrome
* RAB: RAB7
* Charcot–Marie–Tooth disease
* RAB23
* Carpenter syndrome
* RAB27
* Griscelli syndrome type 2
* RHO: RAC2
* Neutrophil immunodeficiency syndrome
* ARF: SAR1B
* Chylomicron retention disease
* ARL13B
* Joubert syndrome 8
* ARL6
* Bardet–Biedl syndrome 3
MAP kinase
* Cardiofaciocutaneous syndrome
Other kinase/phosphatase
Tyrosine kinase
* BTK
* X-linked agammaglobulinemia
* ZAP70
* ZAP70 deficiency
Serine/threonine kinase
* RPS6KA3
* Coffin-Lowry syndrome
* CHEK2
* Li-Fraumeni syndrome 2
* IKBKG
* Incontinentia pigmenti
* STK11
* Peutz–Jeghers syndrome
* DMPK
* Myotonic dystrophy 1
* ATR
* Seckel syndrome 1
* GRK1
* Oguchi disease 2
* WNK4/WNK1
* Pseudohypoaldosteronism 2
Tyrosine phosphatase
* PTEN
* Bannayan–Riley–Ruvalcaba syndrome
* Lhermitte–Duclos disease
* Cowden syndrome
* Proteus-like syndrome
* MTM1
* X-linked myotubular myopathy
* PTPN11
* Noonan syndrome 1
* LEOPARD syndrome
* Metachondromatosis
Signal transducing adaptor proteins
* EDARADD
* EDARADD Hypohidrotic ectodermal dysplasia
* SH3BP2
* Cherubism
* LDB3
* Zaspopathy
Other
* NF2
* Neurofibromatosis type II
* NOTCH3
* CADASIL
* PRKAR1A
* Carney complex
* PRKAG2
* Wolff–Parkinson–White syndrome
* PRKCSH
* PRKCSH Polycystic liver disease
* XIAP
* XIAP2
See also intracellular signaling peptides and proteins
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Griscelli syndrome type 2 | c1868679 | 5,136 | wikipedia | https://en.wikipedia.org/wiki/Griscelli_syndrome_type_2 | 2021-01-18T18:39:45 | {"gard": ["4483"], "mesh": ["C537302"], "umls": ["C1868679"], "orphanet": ["79477"], "wikidata": ["Q5609615"]} |
Insulitis is an inflammation of the islets of Langerhans, a collection of endocrine tissue located in the pancreas.[1][2][3] The islets containing the pancreatic β-cells, and in some cases, the exocrine tissues, become infiltrated by T and B lymphocytes, macrophages and dendritic cells.[4][5][6] This innate immune cell and lymphocyte infiltration can result in destruction of the insulin producing beta cells of the islets,[7] and clinical diabetes. Insulitis is often studied in the multiple low dose streptozotocin (MLDS) mouse model or the non-obese diabetic (NOD) mouse model of type 1 diabetes. The chemokine family of proteins may play a key role in promoting leukocytic infiltration into the pancreas prior to pancreatic beta-cell destruction.[8]
## References[edit]
1. ^ Campbell-Thompson ML, Atkinson MA, Butler AE, Chapman NM, Frisk G, Gianani R, Giepmans BN, von Herrath MG, Hyöty H, Kay TW, Korsgren O, Morgan NG, Powers AC, Pugliese A, Richardson SJ, Rowe PA, Tracy S, In't Veld PA (Nov 2013). "The diagnosis of insulitis in human type 1 diabetes". Diabetologia. 56 (11): 2541–3. doi:10.1007/s00125-013-3043-5. PMID 24006089.
2. ^ Coppieters KT, Dotta F, Amirian N, Campbell PD, Kay TW, Atkinson MA, Roep BO, von Herrath MG (2012). "Demonstration of islet-autoreactive CD8 T cells in insulitic lesions from recent onset and long-term type 1 diabetes patients". J Exp Med. 209 (1): 51–60. doi:10.1084/jem.20111187. PMC 3260877. PMID 22213807.
3. ^ Willcox A, Richardson SJ, Bone AJ, Foulis AK, and Morgan NG (Feb 2009). "Analysis of islet inflammation in human type 1 diabetes". Clin Exp Immunol. 155 (2): 173–81. doi:10.1111/j.1365-2249.2008.03860.x. PMC 2675247. PMID 19128359.
4. ^ Campbell-Thompson M; Fu Ann; Wasserfall Clive; Kaddis John; Schatz Desmond; Pugliese Alberto; Atkinson Mark (Nov 2015). "Insulitis and beta cell mass in the natural history of type 1 diabetes". Diabetes. 65 (3): 719–731. doi:10.2337/db15-0779. PMC 4764143. PMID 26581594.
5. ^ Rodriguez-Calvo T, Ekwall O, Amirian N, Zapardiel-Gonzalo J, von Herrath MG (2014). "Increased Immune Cell Infiltration of the Exocrine Pancreas: A Possible Contribution to the Pathogenesis of Type 1 Diabetes". Diabetes. 63 (11): 3880–3890. doi:10.2337/db14-0549. PMC 4207385. PMID 24947367.
6. ^ Campbell-Thompson M, Rodriguez-Calvo R, Battaglia M (Oct 2015). "Abnormalities of the exocrine pancreas in type 1 diabetes". Curr Diab Rep. 15 (10): 79. doi:10.1007/s11892-015-0653-y. PMC 5072278. PMID 26318606.
7. ^ Foulis AK, Stewart JA (June 1984). "The pancreas in recent-onset type 1 (insulin-dependent) diabetes mellitus: insulin content of islets, insulitis and associated changes in the exocrine acinar tissue". Diabetologia. 26 (6): 456–61. doi:10.1007/bf00262221. PMID 6381192.
8. ^ Burke SJ, Collier JJ (May 2015). "Transcriptional regulation of chemokine genes: a link to pancreatic islet inflammation?". Biomolecules. 5 (2): 1020–34. doi:10.3390/biom5021020. PMC 4496708. PMID 26018641.
* v
* t
* e
Disease of the pancreas and glucose metabolism
Diabetes
* Types
* type 1
* type 2
* gestational
* MODY 1 2 3 4 5 6
* Complications
* See Template:Diabetes
Abnormal blood glucose levels
* Hyperglycaemia
* Oxyhyperglycemia
* Hypoglycaemia
* Whipple's triad
Insulin disorders
* Insulin resistance
* Hyperinsulinism
* Rabson–Mendenhall syndrome
Other pancreatic disorders
* Insulinoma
* Insulitis
This article about an endocrine, nutritional, or metabolic disease 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Insulitis | c3686577 | 5,137 | wikipedia | https://en.wikipedia.org/wiki/Insulitis | 2021-01-18T18:36:23 | {"wikidata": ["Q922215"]} |
Running injuries
Other namesRunning-related injuries (RRI)
SpecialtySports medicine
Running injuries (or running-related injuries, RRI) affect about half of runners annually. The frequencies of various RRI depend on the type of running, such as speed and mileage. Some injuries are acute, caused by sudden overstress, such as side stitch, strains, and sprains. Many of the common injuries that affect runners are chronic, developing over longer periods as the result of overuse. Common overuse injuries include shin splints, stress fractures, Achilles tendinitis, Iliotibial band syndrome, Patellofemoral pain (runner's knee), and plantar fasciitis.
Proper running form is important in injury prevention. A major aspect of running form is foot strike pattern. The way in which the foot makes contact with the ground determines how the force of the impact is distributed throughout the body. Different types of modern running shoes are created to adjust the foot strike pattern in an effort to reduce the risk of injury. In recent years, barefoot running has increased in popularity in many Western countries, because of claims that it reduces the risk of injury. However, this has not been proven and is still debated.[1][better source needed]
## Contents
* 1 Acute injuries
* 1.1 Side stitch
* 1.2 Strains
* 1.3 Sprains
* 2 Overuse injuries
* 2.1 Causes and prevention
* 2.2 Shin splints
* 2.3 Stress fractures
* 2.4 Achilles tendinitis
* 2.5 Patellofemoral pain syndrome
* 2.6 Iliotibial band syndrome
* 2.7 Plantar fasciitis
* 3 Footwear
* 3.1 Traditional running shoes
* 3.2 Barefoot running
* 3.2.1 Endurance running hypothesis
* 3.3 Minimalist footwear
* 4 References
* 5 External links
## Acute injuries[edit]
### Side stitch[edit]
A side stitch is an intense stabbing abdominal pain under the lower edge of the ribcage that occurs during exercise. It is also called a side ache, side cramp, muscle stitch, or simply a stitch, and the medical term is Exercise-related Transient Abdominal Pain (ETAP). It sometimes extends to shoulder tip pain, and commonly occurs during running, swimming, and horseback riding. Approximately two-thirds of runners will experience at least one episode of a stitch each year. The precise cause is unclear, although it most likely involves irritation of the abdominal lining, and the condition is more likely after consuming a meal or a sugary beverage. If the pain is present only when exercising and is completely absent at rest, in an otherwise healthy person, it does not require investigation. Typical treatment strategies involve deep breathing and/or manual pressure on the affected area.[2][3][4]
### Strains[edit]
A strain is an injury that occurs to a muscle, tendon, or both. Generally, the muscle or tendon overstretches and partially tears, under more physical stress than it can withstand,[5] often from a sudden increase in duration, intensity, or frequency of an activity. Strains most commonly occur in the foot, leg, or back.[6] Immediate treatment typically includes five steps abbreviated as PRICE: protection, rest, ice, compression, elevation.[7]
### Sprains[edit]
A sprain, also known as a torn ligament, is the stretching or tearing of ligaments within a joint, often caused by an injury abruptly forcing the joint beyond its functional range of motion. Ligaments are tough, inelastic fibers made of collagen that connect two or more bones to form a joint.[8] Sprains can occur at any joint but most commonly occur in the ankle, knee, or wrist.[9] The majority of sprains are mild, causing minor swelling and bruising that can be resolved with conservative treatment, typically summarized as RICE: rest, ice, compression, elevation. However, severe sprains involve complete tears, ruptures, or fractures, often leading to joint instability, severe pain, and decreased functional ability. These sprains require surgical fixation, prolonged immobilization, and physical therapy.[10]
## Overuse injuries[edit]
### Causes and prevention[edit]
Pronation, neutral, and supination placements of the right ankle. The ankle and foot naturally pronate and supinate by about 5 degrees while walking or running. The red arrows indicate excessive pronation.
In general, overuse injuries are the result of repetitive impact between the foot and the ground. With improper running form, the force of the impact can be distributed abnormally throughout the feet and legs. Running form tends to worsen with fatigue. When moving at a constant pace along a straight path, a symmetrical gait is considered to be normal. Asymmetry is considered to be a risk factor for injury. One study attempted to quantify the change in running form between a rested and fatigued state by measuring asymmetrical running gait in the lower limbs. The results showed that "knee internal rotation and knee stiffness became more asymmetrical with fatigue, increasing by 14% and 5.3%, respectively."[11] These findings suggest that focusing on proper running form, particularly when fatigued, could reduce the risk of running-related injuries. Running in worn-out shoes may also increase the risk of injury, and altering the footwear might be helpful. These injuries can also arise due to a sudden increase in the intensity or amount of exercise.
### Shin splints[edit]
A shin splint, also known as Medial Tibial Stress Syndrome (MTSS), is pain along the inside edge of the shinbone (tibia) due to inflammation of tissue in the area. Generally this is between the middle of the lower leg to the ankle. The pain may be dull or sharp, and is generally brought on by high-impact exercise that overloads the tibia. Groups that are commonly affected include runners (especially on concrete or asphalt), dancers, gymnasts, and military personnel. Rates of shin splints in at-risk groups range from 4% to 35%. The condition occurs more often in women. Shin splints are generally treated by rest followed by a gradual return to exercise over a period of weeks.[12][13]
### Stress fractures[edit]
A stress fracture is a fatigue-induced bone fracture caused by repeated stress over time. Instead of resulting from a single severe impact, stress fractures are the result of accumulated injury from repeated submaximal loading, such as running or jumping. Because of this mechanism, stress fractures are common overuse injuries in athletes.[14]
Stress fractures can be described as small cracks in the bone, or "hairline fractures". Stress fractures of the foot are sometimes called "march fractures" because of the injury's prevalence among heavily marching soldiers.[15] Stress fractures most frequently occur in weight-bearing bones of the lower extremities, such as the tibia and fibula (bones of the lower leg), metatarsal and navicular bones (bones of the foot). Less common are stress fractures to the femur, pelvis, and sacrum. Treatment usually consists of rest followed by a gradual return to exercise over a period of months.[14]
### Achilles tendinitis[edit]
Achilles tendinitis is inflammation of the Achilles tendon, resulting in pain along the back of the leg near the heel. There are two types of Achilles tendinitis, insertional and noninsertional. Noninsertional Achilles tendinitis is the type that more commonly affects runners. In this case, inflammation is occurring in the middle portion of the tendon, whereas insertional Achilles tendinitis is inflammation located where the tendon connects (inserts) to the heel bone. Having tight calf muscles may also increase the risk of Achilles tendinitis. Stretching the calves before starting heavy exercise may help relieve tightness in the muscles.[16]
### Patellofemoral pain syndrome[edit]
Patellofemoral pain syndrome is associated with pain in the knee and around the patella (kneecap). It is sometimes referred to as runner's knee, but this term is also used for other overuse injuries that involve knee pain. It can be caused by a single incident but is often the result of overuse or a sudden increase in physical activity.
### Iliotibial band syndrome[edit]
Diagram indicating the location of the iliotibial band and pain associated with iliotibial band syndrome
Iliotibial band syndrome (ITBS) is defined as inflammation of the iliotibial band on the outside of the knee. This inflammation occurs a result of the iliotibial band and the outside of the knee joint rubbing together. The resulting pain typically is initially mild and worsens if running continues. Recurrence is a common issue with iliotibial band syndrome, as pain goes away with a period of rest, but symptoms can easily come back as the runner returns to training. During recovery, the muscles on the outside of the hip can be stretched to reduce tightness in the band.
### Plantar fasciitis[edit]
The plantar fascia extends from the heel bone to the toes, and helps support the arch of the foot.[17] Plantar fasciitis is a common cause of heel pain and affects about two million people in the United States. Though once considered an inflammatory condition, plantar fasciitis is now characterized as a degenerative pathology. Intrinsic risk factors include obesity and limited ankle flexibility. Extrinsic risk factors include deconditioning, hard surfaces, inadequate stretching and poor footwear.[18]
## Footwear[edit]
### Traditional running shoes[edit]
So-called "traditional" running shoes are designed to give more support and cushion the landing to reduce the effects of impact. They allow for more-comfortable running on hard surfaces such as asphalt and also protect the foot when stepping on rocks or other potentially sharp objects. However, the cushioning provided in traditional running shoes is thought to encourage a foot strike pattern where the heel lands first. Heel striking generates a relatively large amount of impact force that can put different parts of the lower extremities under excessive stress.
### Barefoot running[edit]
Barefoot running has been promoted as one method of reducing the risk of running-related injuries. Barefoot running is thought to improve running form by encouraging forefoot striking. The collision of the forefoot with the ground generates a significantly smaller impact force in comparison to striking heel first.[19] However, barefoot running leaves the foot unprotected from stepping on sharp objects. Although running barefoot may reduce the risk of running-related injuries, it is important to take time while switching from running with shoes.
Beginning to run barefoot without reducing intensity or mileage of training can actually cause muscle or tendon injury. Changing one's style of running shoe or switching to barefoot running will most likely alter the foot strike pattern, meaning that the force of impact will be absorbed differently. Injuries are more likely to occur in novice barefoot runners. This may be a result of not yet having fully adapted to a new style of running, and therefore running with inconsistent technique. To measure this, a study was conducted involving runners who habitually run with a rearfoot strike while wearing shoes. Of the runners involved in the study, 32% used a heel strike pattern in initial attempts at running barefoot. Running barefoot while heel striking leads to increased muscle activation and impact accelerations.[20] The findings suggest that an inconsistency in running technique among novice barefoot runners may put them at a higher risk of injury in comparison to running with shoes.
#### Endurance running hypothesis[edit]
According to the endurance running hypothesis, long-distance running may have played a significant role in the lifestyle and evolution of early hominins. Before developing more-advanced hunting tools such as the bow and arrow, early humans are thought to have used endurance running for scavenging and hunting. Persistence hunting is "a form of pursuit hunting in which [the hunter uses] endurance running during the midday heat to drive [prey] into hyperthermia and exhaustion so they can easily be killed".[21] Unlike many medium-to-large mammals that use panting as a form of evaporative cooling, hominins rely on sweating, allowing evaporation to occur on a much larger surface area. In this way, sweating results in better thermoregulation that allows the hominin to outlast the prey during the chase. This is one potential explanation for the loss of most body hair in humans. Those individuals with less body hair would be able to better thermoregulate while running to avoid overheating. For this species to exist under the endurance running hypothesis, running most likely did not result in the frequency of injuries that it does today, because such an injury to early hominins likely led to starvation. This example would imply that recent ancestors of humans experienced selective pressure to adapt to barefoot running for long periods of time.
### Minimalist footwear[edit]
As an intermediate option between traditional running shoes and running barefoot, "minimalist" shoes lack thickly cushioned heels and are designed to encourage forefoot striking.[22] Compared to traditional running shoes, one study observed that high-speed runners in minimalist shoes experienced a significant redistribution of mechanical work from the knee to the ankle.[23] Therefore, minimalist shoes may be beneficial for runners who have experienced a knee injury in the past, although the shoes might increase the risk of ankle and calf injuries. As with barefoot running, runners who switch to minimalist shoes should not start out at full training intensity.
## References[edit]
1. ^ Davies, George J.; Wallace, Lynn A.; Malone, Terry R. (January 1981). "Mechanisms of Selected Knee Injuries". Physical Therapy. 60 (12): 1590–1595. doi:10.1093/ptj/60.12.1590. PMID 7454785. Retrieved 10 February 2017.
2. ^ Morton, Darren P.; Callister, Robin (February 2000). "Characteristics and etiology of exercise-related transient abdominal pain". Medicine & Science in Sports & Exercise. 32 (2): 432–438. doi:10.1097/00005768-200002000-00026. PMID 10694128.
3. ^ Morton, Darren P.; Callister, Robin (January 2015). "Exercise-Related Transient Abdominal Pain (ETAP)". Sports Medicine. 45 (1): 23–35. doi:10.1007/s40279-014-0245-z. PMID 25178498. S2CID 18088581.
4. ^ Wetsman, Nicole (20 October 2017). "When you get a stitch in your side, what's really going on?". Popular Science. Retrieved 30 November 2020.
5. ^ "Sprains and Strains: In-Depth". National Institutes of Health. January 2015. Retrieved 1 December 2020.
6. ^ Mulcahey, Mary K. (June 2020). "Sprains, Strains and Other Soft-Tissue Injuries". OrthoInfo. American Academy of Orthopaedic Surgeons. Retrieved 1 December 2020.
7. ^ Järvinen, T.A.H.; et al. (April 2007). "Muscle injuries: optimising recovery". Best Practice and Research in Clinical Rheumatology. 21 (2): 317–331. doi:10.1016/j.berh.2006.12.004. PMID 17512485.
8. ^ Bahr, Roald; Alfredson, Håkan; Järvinen, Markku; Järvinen, Tero; Khan, Karim; Kjaer, Michael; Matheson, Gordon; Maehlum, Sverre (2012-06-22), Bahr, Roald (ed.), "Types and Causes of Injuries", The IOC Manual of Sports Injuries, Wiley-Blackwell, pp. 1–24, doi:10.1002/9781118467947.ch1, ISBN 978-1-118-46794-7
9. ^ Hartshorne, Henry. "Sprained Joints". The Home Cyclopedia Of Health And Medicine. Retrieved 1 December 2020.
10. ^ "Ligament Sprain". Physiopedia. Retrieved 1 December 2020.
11. ^ Radzak, Kara N.; Putnam, Ashley M.; Tamura, Kaori; Hetzler, Ronald K.; Stickley, Christopher D. (January 2017). "Asymmetry between lower limbs during rested and fatigued state running gait in healthy individuals". Gait & Posture. 51: 268–274. doi:10.1016/j.gaitpost.2016.11.005. ISSN 1879-2219. PMID 27842295.
12. ^ Alaia, Michael J. (August 2019). "Shin Splints". OrthoInfo. American Academy of Orthopaedic Surgeons. Retrieved 30 November 2020.
13. ^ Reshef, N; Guelich, DR (April 2012). "Medial tibial stress syndrome". Clinics in Sports Medicine. 31 (2): 273–290. doi:10.1016/j.csm.2011.09.008. PMID 22341017.
14. ^ a b Behrens, Steve; Deren, Matson; Fadale, Monchik (March–April 2013). "Stress Fractures of the Pelvis and Legs in Athletes: A Review". Sports Health: A Multidisciplinary Approach. 5 (2): 165–174. doi:10.1177/1941738112467423. PMC 3658382. PMID 24427386.
15. ^ Payne, Jacqueline (26 March 2018). "Metatarsal Fractures". Patient.info. Retrieved 30 November 2020.
16. ^ Kadakia, Anish R. (June 2010). "Achilles Tendinitis". OrthoInfo. American Academy of Orthopaedic Surgeons. Retrieved 30 November 2020.
17. ^ Petraglia, Federica; Ramazzina, Ileana; Costantino, Cosimo (10 May 2017). "Plantar fasciitis in athletes: diagnostic and treatment strategies. A systematic review". Muscles, Ligaments and Tendons Journal. 7 (1): 107–118. doi:10.11138/mltj/2017.7.1.107. PMC 5505577. PMID 28717618.
18. ^ Schwartz, Emily N.; Su, John (Winter 2014). "Plantar fasciitis: a concise review". The Permanente Journal. 18 (1): 105–117. doi:10.7812/TPP/13-113. PMC 3951039. PMID 24626080.
19. ^ Lieberman, Daniel. "Running Barefoot: Biomechanics of Foot Strike". Harvard University. Retrieved 9 February 2017.
20. ^ Lucas-Cuevas, Angel Gabriel; Priego Quesada, José Ignacio; Giménez, José Vicente; Aparicio, Inma; Jimenez-Perez, Irene; Pérez-Soriano, Pedro (November 2016). "Initiating running barefoot: Effects on muscle activation and impact accelerations in habitually rearfoot shod runners". European Journal of Sport Science. 16 (8): 1145–1152. doi:10.1080/17461391.2016.1197317. ISSN 1536-7290. PMID 27346636. S2CID 23392717.
21. ^ Carrier, David R.; Kapoor, A. K.; Kimura, Tasuku; Nickels, Martin K.; Satwanti; Scott, Eugenie C.; So, Joseph K.; Trinkaus, Erik (August–October 1984). "The Energetic Paradox of Human Running and Hominid Evolution [and Comments and Reply]". Current Anthropology. 25 (4): 483–495. doi:10.1086/203165. JSTOR 2742907.
22. ^ Lieberman, Daniel. "Running Barefoot: Heel Striking & Running Shoes". Harvard University. Retrieved 30 November 2020.
23. ^ Fuller, Joel T.; Buckley, Jonathan D.; Tsiros, Margarita D.; Brown, Nicholas A. T.; Thewlis, Dominic (1 October 2016). "Redistribution of Mechanical Work at the Knee and Ankle Joints During Fast Running in Minimalist Shoes". Journal of Athletic Training. 51 (10): 806–812. doi:10.4085/1062-6050-51.12.05. ISSN 1938-162X. PMC 5189234. PMID 27834504.
## External links[edit]
Classification
D
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Running injuries | None | 5,138 | wikipedia | https://en.wikipedia.org/wiki/Running_injuries | 2021-01-18T18:50:12 | {"wikidata": ["Q30314084"]} |
The clinical manifestations of mental retardation, spastic diplegia, and congenital deafness in various degrees are known as the neurologic type of endemic cretinism, which occurs in countries with high goiter endemicity. Maternal iodine deficiency has been established as a major cause. On the basis of studies of 70 families with endemic cretinism from Highland Ecuador, Held et al. (1990) suggested that an autosomal recessive predisposition is a major etiologic factor. A segregation analysis of 49 families yielded an estimate of P = 0.245. Half sibs were all unaffected and no significant birth order effect was observed among 101 probands. Because the neurologic type of endemic cretinism represents a defined subset of the iodine deficiency disorders, Held et al. (1990) suggested the designation fetal iodine deficiency disorder (FIDD) rather than cretinism.
FIDD is the principal form of endemic cretinism, and the most common cause of preventable mental deficiency in the world. However, not everyone at risk develops FIDD and familial aggregation is common, suggesting that genetic factors may be involved. The apolipoprotein E (APOE; 107741) gene encodes a lipoprotein that possesses a thyroid hormone-binding domain, and the APOE genotype might affect the efficiency with which thyroid hormone influences neuronal cell growth during the first and second trimesters of fetal development. In each of 3 iodine-deficient areas in central China, Wang et al. (2000) found that APOE4 genotypes were significantly enriched in FIDD probands, being 16% versus 6% in controls. They suggested that this may contribute to the low frequency of the APOE4 gene in Chinese compared with Caucasian populations.
Neuro \- Mental retardation \- Spastic diplegia Neck \- Goiter Inheritance \- Autosomal recessive predisposition Endocrine \- Hypothyroidism Lab \- Fetal iodine deficiency \- Maternal iodine deficiency Ears \- Congenital deafness ▲ Close
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*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| FETAL IODINE DEFICIENCY DISORDER | c0342200 | 5,139 | omim | https://www.omim.org/entry/228355 | 2019-09-22T16:27:53 | {"mesh": ["D003409"], "omim": ["228355"], "icd-10": ["E00.1"], "orphanet": ["1910"], "synonyms": ["Alternative titles", "ENDEMIC CRETINISM"]} |
Motor speech disorder cause by damage to motor systems
Dysarthria
SpecialtyNeurology, neuropsychology
Dysarthria is a motor speech disorder resulting from neurological injury of the motor component of the motor–speech system[1] and is characterized by poor articulation of phonemes.[2] In other words, it is a condition in which problems effectively occur with the muscles that help produce speech, often making it very difficult to pronounce words. It is unrelated to problems with understanding language (that is, dysphasia or aphasia),[3] although a person can have both. Any of the speech subsystems (respiration, phonation, resonance, prosody, and articulation) can be affected, leading to impairments in intelligibility, audibility, naturalness, and efficiency of vocal communication.[4] Dysarthria that has progressed to a total loss of speech is referred to as anarthria. The term dysarthria is from New Latin, dys- "dysfunctional, impaired" and arthr- "joint, vocal articulation".[5][6]
Neurological injury due to damage in the central or peripheral nervous system may result in weakness, paralysis, or a lack of coordination of the motor–speech system, producing dysarthria.[1] These effects in turn hinder control over the tongue, throat, lips or lungs; for example, swallowing problems (dysphagia) are also often present in those with dysarthria. Cranial nerves that control the muscles relevant to dysarthria include the trigeminal nerve's motor branch (V), the facial nerve (VII), the glossopharyngeal nerve (IX), the vagus nerve (X), and the hypoglossal nerve (XII).
Dysarthria does not include speech disorders from structural abnormalities, such as cleft palate and must not be confused with apraxia of speech, which refers to problems in the planning and programming aspect of the motor–speech system.[4] Just as the term "articulation" can mean either "speech" or "joint movement", so is the combining form of arthr- the same in the terms "dysarthria", "dysarthrosis", and "arthropathy"; the term "dysarthria" is conventionally reserved for the speech problem and is not used to refer to arthropathy, whereas "dysarthrosis" has both senses but usually refers to arthropathy.
## Contents
* 1 Causes
* 2 Diagnosis
* 2.1 Classification
* 3 Treatment
* 4 See also
* 5 References
* 6 Further reading
* 7 External links
## Causes
There are many potential causes of dysarthria. They include toxic, metabolic, degenerative diseases, traumatic brain injury, or thrombotic or embolic stroke.[citation needed]
Degenerative diseases include parkinsonism, amyotrophic lateral sclerosis (ALS), multiple sclerosis,[7] Huntington's disease, Niemann-Pick disease, and Friedreich's ataxia.[citation needed] Toxic and metabolic conditions include: Wilson's disease, hypoxic encephalopathy such as in drowning, and central pontine myelinolysis.[7]
These result in lesions to key areas of the brain involved in planning, executing, or regulating motor operations in skeletal muscles (i.e. muscles of the limbs), including muscles of the head and neck (dysfunction of which characterises dysarthria). These can result in dysfunction, or failure of: the motor or somatosensory cortex of the brain, corticobulbar pathways, the cerebellum, basal nuclei (consisting of the putamen, globus pallidus, caudate nucleus, substantia nigra etc.), brainstem (from which the cranial nerves originate), or the neuromuscular junction (in diseases such as myasthenia gravis) which block the nervous system's ability to activate motor units and effect correct range and strength of movements.[citation needed]
Causes:[citation needed]
* Brain tumor
* Cerebral palsy
* Guillain–Barré syndrome
* Hypothermia
* Lyme disease
* Stroke
* Idiopathic intracranial hypertension (formerly known as pseudotumor cerebri)
* Tay–Sachs disease, and late-onset Tay–Sachs disease (LOTS)
## Diagnosis
### Classification
Dysarthrias are classified in multiple ways based on the presentation of symptoms. Specific dysarthrias include spastic (resulting from bilateral damage to the upper motor neuron), flaccid (resulting from bilateral or unilateral damage to the lower motor neuron), ataxic (resulting from damage to cerebellum), unilateral upper motor neuron (presenting milder symptoms than bilateral UMN damage), hyperkinetic and hypokinetic (resulting from damage to parts of the basal ganglia, such as in Huntington's disease or Parkinsonism), and the mixed dysarthrias (where symptoms of more than one type of dysarthria are present). The majority of dysarthric patients are diagnosed as having 'mixed' dysarthria, as neural damage resulting in dysarthria is rarely contained to one part of the nervous system — for example, multiple strokes, traumatic brain injury, and some kinds of degenerative illnesses (such as amyotrophic lateral sclerosis) usually damage many different sectors of the nervous system.[citation needed]
Ataxic dysarthria is an acquired neurological and sensorimotor speech deficit. It is a common diagnosis among the clinical spectrum of ataxic disorders.[8] Since regulation of skilled movements is a primary function of the cerebellum, damage to the superior cerebellum and the superior cerebellar peduncle is believed to produce this form of dysarthria in ataxic patients.[9] Growing evidence supports the likelihood of cerebellar involvement specifically affecting speech motor programming and execution pathways, producing the characteristic features associated with ataxic dysarthria. This link to speech motor control can explain the abnormalities in articulation and prosody, which are hallmarks of this disorder.[10] Some of the most consistent abnormalities observed in patients with ataxia dysarthria are alterations of the normal timing pattern, with prolongation of certain segments and a tendency to equalize the duration of syllables when speaking. As the severity of the dysarthria increases, the patient may also lengthen more segments as well as increase the degree of lengthening of each individual segment.[11]
Common clinical features of ataxic dysarthria include abnormalities in speech modulation, rate of speech, explosive or scanning speech, slurred speech, irregular stress patterns, and vocalic and consonantal misarticulations.[12][13]
Ataxic dysarthria is associated with damage to the left cerebellar hemisphere in right-handed patients.[14]
Dysarthria may affect a single system; however, it is more commonly reflected in multiple motor–speech systems. The etiology, degree of neuropathy, existence of co-morbidities, and the individual's response all play a role in the effect the disorder has on the individual's quality of life. Severity ranges from occasional articulation difficulties to verbal speech that is completely unintelligible.[1]
Individuals with dysarthria may experience challenges in the following:
* Timing
* Vocal quality
* Pitch
* Volume
* Breath control
* Speed
* Strength
* Steadiness
* Range
* Tone[1][4]
Examples of specific observations include a continuous breathy voice, irregular breakdown of articulation, monopitch, distorted vowels, word flow without pauses, and hypernasality.[4]
## Treatment
Articulation problems resulting from dysarthria are treated by speech language pathologists, using a variety of techniques. Techniques used depend on the effect the dysarthria has on control of the articulators. Traditional treatments target the correction of deficits in rate (of articulation), prosody (appropriate emphasis and inflection, affected e.g. by apraxia of speech, right hemisphere brain damage, etc.), intensity (loudness of the voice, affected e.g. in hypokinetic dysarthrias such as in Parkinson's), resonance (ability to alter the vocal tract and resonating spaces for correct speech sounds) and phonation (control of the vocal folds for appropriate voice quality and valving of the airway). These treatments have usually involved exercises to increase strength and control over articulator muscles (which may be flaccid and weak, or overly tight and difficult to move), and using alternate speaking techniques to increase speaker intelligibility (how well someone's speech is understood by peers). With the speech language pathologist, there are several skills that are important to learn; safe chewing and swallowing techniques, avoiding conversations when feeling tired, repeat words and syllables over and over in order to learn the proper mouth movements, and techniques to deal with the frustration while speaking. Depending on the severity of the dysarthria, another possibility includes learning how to use a computer or flip cards in order to communicate more effectively.[3]
More recent techniques based on the principles of motor learning (PML), such as LSVT (Lee Silverman voice treatment)[15] speech therapy and specifically LSVT may improve voice and speech function in PD.[16] For Parkinson's, aim to retrain speech skills through building new generalised motor programs, and attach great importance to regular practice, through peer/partner support and self-management. Regularity of practice, and when to practice, are the main issues in PML treatments, as they may determine the likelihood of generalization of new motor skills, and therefore how effective a treatment is.[citation needed]
Augmentative and alternative communication (AAC) devices that make coping with a dysarthria easier include speech synthesis and text-based telephones. These allow people who are unintelligible, or may be in the later stages of a progressive illness, to continue to be able to communicate without the need for fully intelligible speech.[citation needed]
## See also
* Lists of language disorders
## References
1. ^ a b c d O'Sullivan, S. B.; Schmitz, T. J. (2007). Physical Rehabilitation (5th ed.). Philadelphia: F. A. Davis Company.[page needed]
2. ^ Duffy, Joseph (2005). Motor Speech Disorders: Substrates, Eifferential Eiagnosis, and Management. St. Louis, Mo: Elsevier Mosby. ISBN 0323024521.
3. ^ a b "Dysarthria". PubMed Health.
4. ^ a b c d MacKenzie, C (2011). "Dysarthria in stroke: A narrative review of its description and the outcome of intervention". International Journal of Speech-Language Pathology. 13 (2): 125–36. doi:10.3109/17549507.2011.524940. PMID 21480809.
5. ^ "Definition of DYSARTHRIA". www.merriam-webster.com. Retrieved 2020-03-07.
6. ^ Company, Houghton Mifflin Harcourt Publishing. "The American Heritage Dictionary entry: dysarthria". www.ahdictionary.com. Retrieved 2020-03-07.
7. ^ a b Duffy, Joseph R. (2005). Motor speech disorders : substrates, differential diagnosis, and management (PDF) (2nd ed.). St. Louis: Elsevier Mosby. p. 275. ISBN 9780323024525.
8. ^ Eigentler, A; Rhomberg, J; Nachbauer, W; Ritzer, I; et al. (2011). "The scale for the assessment and rating of ataxia correlates with dysarthria assessment in Friedreich's ataxia". Journal of Neurology. 259 (3): 420–6. doi:10.1007/s00415-011-6192-9. PMID 21805332.
9. ^ Caplan, Louis R. (2012). "Ataxia in Patients with Brain Infarcts and Hemorrhages". In Subramony, Sankara H.; Dürr, Alexandra (eds.). Ataxic Disorders. Handbook of Clinical Neurology. 103. pp. 147–60. doi:10.1016/B978-0-444-51892-7.00008-5. ISBN 978-0-444-51892-7. PMID 21827886.
10. ^ Spencer, K; Slocomb, D (2007). "The neural basis of ataxic dysarthria". The Cerebellum. 6 (1): 58–65. doi:10.1080/14734220601145459. PMID 17366266.
11. ^ Kent, RD; Netsell, R; Abbs, JH (September 1979). "Acoustic characteristics of dysarthria associated with cerebellar disease". J Speech Hear Res. 22 (3): 627–48. doi:10.1044/jshr.2203.627. PMID 502519. Archived from the original on 2012-07-16.
12. ^ Ogawa, K; Yoshihashi, H; Suzuki, Y; Kamei, S; et al. (2010). "Clinical study of the responsible lesion for dysarthria in the cerebellum". Internal Medicine. 49 (9): 861–4. doi:10.2169/internalmedicine.49.2913. PMID 20453409.
13. ^ Wang, Y-T; Kent, RD; Duffy, JR; Thomas, JE (2009). "Analysis of Diadochokinesis in Ataxic Dysarthria Using the Motor Speech Profile Program™". Folia Phoniatrica et Logopaedica. 61 (1): 1–11. doi:10.1159/000184539. PMC 2790744. PMID 19088478.
14. ^ Lechtenberg, R.; Gilman, S. (1978). "Speech Disorders in Cerebellar Disease" (PDF). Ann. Neurol. 3 (4): 285–290. doi:10.1002/ana.410030402. hdl:2027.42/50292. PMID 666268.
15. ^ Fox, C; Ramig, L; Ciucci, M; Sapir, S; et al. (2006). "The Science and Practice of LSVT/LOUD: Neural Plasticity-Principled Approach to Treating Individuals with Parkinson Disease and Other Neurological Disorders". Seminars in Speech and Language. 27 (4): 283–99. doi:10.1055/s-2006-955118. PMID 17117354.
16. ^ The National Collaborating Centre for Chronic Conditions, ed. (2006). "Other key interventions". Parkinson's Disease. London: Royal College of Physicians. pp. 135–46. ISBN 1-86016-283-5.
## Further reading
* Haines, Duane (2004). Neuroanatomy: an atlas of structures, sections, and systems. Hagerstown, MD: Lippincott Williams & Wilkins. ISBN 0-7817-4677-9.
* Duffy, Joseph R (2005). Motor Speech Disorders: Substrates, Differential Diagnosis, And Management (2nd ed.). Saint Louis: C.V. Mosby. ISBN 0-323-02452-1.
* Hustad, KC; Lee, J (2008). "Changes in Speech Production Associated with Alphabet Supplementation". Journal of Speech, Language, and Hearing Research. 51 (6): 1438–50. doi:10.1044/1092-4388(2008/07-0185). PMID 18664687.
* Hustad, KC (2006). "Estimating the Intelligibility of Speakers with Dysarthria". Folia Phoniatrica et Logopaedica. 58 (3): 217–28. doi:10.1159/000091735. PMID 16636569.
* Hustad, KC (2006). "A Closer Look at Transcription Intelligibility for Speakers with Dysarthria: Evaluation of Scoring Paradigms and Linguistic Errors Made by Listeners". American Journal of Speech-Language Pathology. 15 (3): 268–77. doi:10.1044/1058-0360(2006/025). PMID 16896176.
## External links
Classification
D
* ICD-10: R47.1
* ICD-9-CM: 784.5
* MeSH: D004401
* DiseasesDB: 4015
External resources
* MedlinePlus: 007470
Look up dysarthria in Wiktionary, the free dictionary.
* Online Speech and Voice Disorder Support (VoiceMatters.net)
* American Speech-Language-Hearing Association
* News About Dysarthria
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Dysarthria | c0013362 | 5,140 | wikipedia | https://en.wikipedia.org/wiki/Dysarthria | 2021-01-18T18:33:59 | {"mesh": ["D004401"], "umls": ["C0013362"], "icd-9": ["784.5"], "icd-10": ["R47.1"], "wikidata": ["Q225957"]} |
A number sign (#) is used with this entry because of evidence that calcification of joints and arteries (CALJA) is caused by homozygous or compound heterozygous mutation in the NT5E gene (129190) on chromosome 6q14.
Description
Adult-onset calcification of the lower extremity arteries, including the iliac, femoral, and tibial arteries, and hand and foot capsule joints is an autosomal recessive condition that represents only the second mendelian disorder of isolated calcification (see generalized arterial calcification of infancy (GACI), 208000). Age of onset has been reported as early as the second decade of life, usually involving intense joint pain or calcification in the hands (St. Hilaire et al., 2011).
Clinical Features
Sharp (1954) described a family in which 2 of 4 sibs from a first-cousin marriage displayed calcification of joint structures and arteries of an unusual type. The remaining 2 sibs and the son and daughter of one of the severely affected sibs seemed to show a milder form of the disorder affecting only arteries. Two previously reported sporadic cases were noted. Ball (1978) stated that at autopsy in 1967, one of the severely affected sibs, F.W., a 62-year-old male, showed widespread calcification of the media of the aorta and of the iliac, femoral and tibial arteries, with bilateral gangrene of the feet; calcification of the mitral and aortic valve rings and membranous portion of the interventricular septum; ossification of intervertebral discs and interspinous ligaments; calcific deposits in the capsule of metacarpophalangeal joints and lateral ligaments of the knees; and excessive bone formation in attachment of quadriceps tendon to the patella. Thus, there was evidence of both dystrophic calcification and ectopic ossification.
St. Hilaire et al. (2011) studied 3 families with calcification of the lower extremity arteries and hand and foot joints. In the first family, there were 5 affected sibs, born of unaffected third-cousin parents of English descent. The proband was a 54-year-old woman with a 20 year history of intermittent claudication and markedly reduced ankle/brachial blood pressure indices. Contrast-enhanced magnetic resonance angiography revealed extensive occlusion of the iliac, femoropopliteal, and tibial arteries, with extensive collateralization. Plain radiography of the lower extremities revealed heavy calcification with areas of arteriomegaly; chest x-ray showed no vascular calcifications above the diaphragm. Radiography also revealed juxtaarticular joint-capsule calcifications of the fingers, wrists, ankles, and feet. All 4 of her sibs had disabling intermittent claudication and similar calcifications on radiography, and 1 sister also had radiographs showing vascular and periarticular calcifications in the shoulders, elbows, hands, hips, and knees; notably absent were calcifications in the coronary arteries, except in 1 brother who had moderate coronary calcifications. Four of the sibs had joint pain and swelling; past evaluations for rheumatoid arthritis and other joint-related autoimmune disorders were negative. The second family consisted of 3 affected Italian sisters whose unaffected parents were distantly related. The proband was a 68-year-old woman who had a history of joint pain in the hands unresponsive to corticosteroids, in whom radiographs of the lower limbs revealed calcifications. Her 70- and 73-year-old sisters had lower extremity pain and similar calcifications. The proband of the third family was a 44-year-old woman with an English father and French mother, in whom dystrophic calcifications were noted in wrist films at 26 years of age; at age 41 years, swelling and severe pain in the hands and wrists were diagnosed as pseudogout. She developed mild paresthesias of the lower extremities at 42 years of age, and evaluation revealed extensive calcifications of the distal arteries, with sparing of the carotid and coronary arteries and the aorta. None of the 9 affected patients and none of their parents or children had abnormal bone morphologic characteristics, type 2 diabetes mellitus, or decreased renal function.
Mapping
In a consanguineous family of English descent in which 5 sibs were affected with calcification of the lower extremity arteries and hand and foot joints, St. Hilaire et al. (2011) performed homozygosity mapping and identified a single 22.4-Mb region of homozygosity on chromosome 6q14, for which they obtained a lod score of 4.81 by parametric multipoint linkage analysis.
Molecular Genetics
In 5 affected sibs from a consanguineous family of English descent with calcifications of arteries and joints mapping to chromosome 6q14, St. Hilaire et al. (2011) analyzed 3 candidate genes and identified homozygosity for a nonsense mutation in the NT5E gene (S221X; 129190.0001). Analysis of NT5E in 3 affected Italian sisters revealed homozygosity for a missense mutation (C358Y; 129190.0002), and the proband from a third family was found to be a compound heterozygote for S221X and a frameshift mutation (129190.0003). The mutations segregated with disease in all 3 families, and none was present in 400 alleles from ethnically matched controls.
INHERITANCE \- Autosomal recessive CARDIOVASCULAR Heart \- Mitral valve ring calcification (in some patients) \- Aortic valve ring calcification (in some patients) Vascular \- Abdominal aorta, calcification of \- Iliac, femoral, tibial, and popliteal artery calcification \- Coronary and carotid arteries spared (in most patients) \- Claudication \- Arteriomegaly, diffuse, secondary to femoropopliteal occlusion SKELETAL \- Dystrophic calcification \- Ectopic ossification Spine \- Intervertebral disc and interspinous ligament calcification (in some patients) Limbs \- Vascular and periarticular calcifications (shoulders, elbows, hips, and knees) \- Tendon calcification (knee, lateral ligament and quadriceps) Hands \- Hands, vascular and periarticular calcification of \- Fingers, periarticular joint capsule calcification of \- Metacarpophalangeal calcification Feet \- Periarticular joint capsule calcifications MOLECULAR BASIS \- Caused by mutation in the ecto-5-prime nucleotidase gene (NT5E, 129190.0001 ) ▲ 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| CALCIFICATION OF JOINTS AND ARTERIES | c1859372 | 5,141 | omim | https://www.omim.org/entry/211800 | 2019-09-22T16:30:16 | {"mesh": ["C565891"], "omim": ["211800"], "orphanet": ["289601"], "synonyms": ["Alternative titles", "ARTERIAL CALCIFICATION DUE TO DEFICIENCY OF CD73", "Calcification of joints and arteries", "CALJA"]} |
A number sign (#) is used with this entry because Usher syndrome type IIIA (USH3A) is caused by homozygous or compound heterozygous mutation in the CLRN1 gene (606397) on chromosome 3q25.
Mutation in the same gene can cause a form of nonsyndromic retinitis pigmentosa (RP61; 614180).
Description
Usher syndrome type III is characterized by postlingual, progressive hearing loss, variable vestibular dysfunction, and onset of retinitis pigmentosa symptoms, including nyctalopia, constriction of the visual fields, and loss of central visual acuity, usually by the second decade of life (Karjalainen et al., 1985; Pakarinen et al., 1995).
For a discussion of phenotypic heterogeneity of Usher syndrome, see USH1 (276900).
### Genetic Heterogeneity of Usher syndrome Type III
Usher syndrome type IIIB (614504) is caused by mutation in the HARS gene (142810) on chromosome 5q31.3.
Clinical Features
Karjalainen et al. (1985) described this distinct type of Usher syndrome as being characterized by progressive hearing loss and vestibular hypoactivity. Smith et al. (1992) described a family in the French Acadian population of southwestern Louisiana in which 2 males had a clinical phenotype like that in the family reported by Karjalainen et al. (1985). Both Usher syndrome type I (276900) and Usher syndrome type II (276901) are frequent among the Louisiana Acadians but this family appeared to have a separate form.
Shinkawa and Nadol (1986) studied the inner ear of a patient with type III Usher syndrome who died at age 52 of metastatic cancer. They found hair cell loss in the basal turn, severe loss of spiral ganglion cells, widespread neural degeneration in the cochlea, and discrete collections of degenerating supporting cells in the organ of Corti. The pattern of neural degeneration bore some similarity to abnormalities in the retina in retinitis pigmentosa.
Aller et al. (2004) did not consider progressive hearing loss to be the definitive parameter in distinguishing Usher syndrome type III from Usher syndrome types I and II. They noted that 3 patients reported by Adato et al. (2002) with a mutation in the CLRN1 gene (606397.0006) had profound stable deafness and vestibular hyporeflexia.
Malm et al. (2011) evaluated visual function, comprising both the severity of the rod cone degeneration and the function in the macular region, in 12 patients genotyped as Usher syndrome 1B, 1D, 1F, 2A, 2C, or 3A, including 3 families with affected sibs, and confirmed phenotypic heterogeneity between sibs with the same genotype and between patients with different genotypes. In all patients examined with ERG, the 30 Hz flicker response revealed remaining cone function. Optical coherence tomography (OCT) demonstrated loss of foveal depression with distortion of the foveal architecture in the macula of all patients. The foveal thickness ranged from 159 to 384 micrometers and was not correlated with retinal function.
Population Genetics
Usher syndrome type III has been estimated to comprise 2% of all Usher syndrome cases; however, based on clinical criteria, 42% of patients with Usher syndrome in Finland are thought to have USH3, suggesting gene enrichment by a founder effect (Sankila et al. (1994, 1995)). Joensuu et al. (2001) identified the Finnish founder mutation (606397.0001).
Mapping
In Finnish families segregating Usher syndrome type III, Sankila et al. (1994, 1995) excluded previous chromosomal sites at which Usher syndrome had been mapped. Using highly polymorphic microsatellite markers for a systematic search for the USH3 locus by genetic linkage analyses of 11 multiply affected families, they assigned the disease locus to 3q21-q25. Of 20 parental disease chromosomes, 15 had identical alleles at 3 marker loci covering a 3-cM genetic distance, including the putative USH3 locus. They stated that this was the fifth distinctive form of Usher syndrome to be identified.
Joensuu et al. (1996) typed a total of 32 pedigrees from a geographically isolated Finnish founder population for polymorphisms in the USH3 region of chromosome 3. By analysis of linkage disequilibrium and historical recombinations in 77 USH3 chromosomes, the location of the Finnish USH3 mutation was narrowed to an interval of approximately 1 cM between markers D3S1299 and D3S3625. The profilin-2 gene (PFN2; 176590) was mapped to the vicinity but was excluded as a candidate for USH3 by sequencing.
Gasparini et al. (1998) reported linkage analysis of an Italian family with Usher syndrome type III and confirmed linkage at 3q24-q25 with a maximum lod score obtained with marker D3S1299 (maximum lod = 2.43 at theta = 0.00).
Molecular Genetics
In the 2 Finnish families reported by Sankila et al. (1995) and Joensuu et al. (1996) and the Italian family reported by Gasparini et al. (1998) with Usher syndrome type III, Joensuu et al. (2001) identified mutations in the CLRN1 gene (606397.0001-606397.0003).
Adato et al. (1999) studied a nonconsanguineous Jewish Yemenite family with 2 affected and 6 healthy sibs, originally reported by Adato et al. (1997), in which the 2 affected brothers had different Usher syndrome phenotypes: one had typical USH3 phenotype, whereas the other had typical USH1 (276900) phenotype. Adato et al. (1999) found a double mutation of the MYO7A gene (276903), which is responsible for USH1B, on 1 maternal chromosome in the brother with the more severe USH1 phenotype; the mother and 2 unaffected sibs also carried the double mutation. The authors suggested a possible synergistic interaction between MYO7A and the USH3 gene product that might increase the severity of the deafness as part of the clinical symptoms associated with USH3. In the course of their study of this family, Adato et al. (1999) narrowed the assignment of the USH3 gene to the interval between D3S1299 and D3S3625. Adato et al. (2002) restudied this family and identified homozygosity for a 23-bp deletion of the CLRN1 gene (606397.0007) in the 2 affected brothers with different Usher syndrome phenotypes. Adato et al. (2002) noted that the mother and 2 sibs who carried only the double mutation in MYO7A were healthy, whereas in the context of a homozygous CLRN1-null mutation, the presence of 1 null mutation in the MYO7A gene mimicked haploinsufficiency, illustrating a departure from the monogenic model for Usher syndrome.
Fields et al. (2002) described 4 novel disease-causing mutations in the CLRN1 gene, including one that appeared to be relatively common in the Ashkenazi Jewish population (N48K; 606397.0004). Adato et al. (2002) detected the N48K missense mutation in 6 affected individuals from 4 unrelated families of Eastern European Jewish origin; shared microsatellite and SNP haplotypes on carrier chromosomes suggested the existence of a founder effect for this mutation.
In a cohort of 40 Ashkenazi Jewish patients with Usher syndrome, Ness et al. (2003) found that the 16 (40%) who were clinically classified as having Usher syndrome type III were homozygous for the N48K mutation. The carrier frequency of N48K was 0.7% (95% CI, 0.0-1.6%) among Ashkenazi Jews in the New York area, with a predicted Usher syndrome type III prevalence of 1.2 per 100,000. Despite the genetic homogeneity of Usher syndrome type III in this group, there was a wide range of phenotypic severity displayed by the N48K homozygotes. Age at onset of the auditory phenotype varied from infancy to more than 35 years. A 56-year-old woman had onset of the ocular phenotype in early childhood ending with no useful vision, whereas hearing loss began after age 35 years, progressing to moderate to severe.
Aller et al. (2004) screened for mutations in the CLRN1 gene in Spanish patients with Usher syndrome and found mutations in only 2 families. They identified 1 patient with Usher syndrome type III who was homozygous for a C40G mutation (606397.0008). They noted that only 1 other mutation had been reported in the USH3A gene in Spanish families with Usher syndrome (606397.0006). These 2 families accounted for only 1.7% of Spanish families with Usher syndrome.
Animal Model
Geng et al. (2009) developed a Clrn1 -/- mouse model for Usher syndrome type III. Clrn1 was expressed as early as embryonic day 16.5 in the auditory and vestibular hair cells and associated ganglionic neurons, with its expression being higher in outer hair cells than inner hair cells. Clrn1 -/- mice showed early-onset hearing loss that rapidly progressed to severe levels. Two to 3 weeks after birth (postnatal day 14 to 21), Clrn1-null mice showed elevated auditory-evoked brainstem response (ABR) thresholds and prolonged peak and interpeak latencies. By postnatal day 21, approximately 70% of Clrn1-null mice had no detectable ABR, and by postnatal day 30, these mice were deaf. Distortion product otoacoustic emissions were not recordable from Clrn1 -/- mice. Vestibular function in Clrn1-null mice mirrored the cochlear phenotype, although it deteriorated more gradually than cochlear function. Disorganization of outer hair cell stereocilia was seen as early as postnatal day 2 and by postnatal day 21 outer hair cell loss was observed. Geng et al. (2009) concluded that CLRN1 is necessary for hair cell function and associated neural activation.
INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Hearing loss, sensorineural, progressive post-lingual \- Vestibular dysfunction, variable Nose \- Retinitis pigmentosa \- Nyctalopia \- Progressive restriction of visual feilds \- Reduction of central visual acuity MISCELLANEOUS \- Increased frequency in Finland \- USH3 cases account for 40% of all Usher patients in Finland MOLECULAR BASIS \- Caused by mutation in the USH3A gene (USH3A, 606397.0001 ) ▲ 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| USHER SYNDROME, TYPE IIIA | c0271097 | 5,142 | omim | https://www.omim.org/entry/276902 | 2019-09-22T16:21:25 | {"doid": ["0110841"], "mesh": ["D052245"], "omim": ["276902"], "orphanet": ["886", "231183"], "synonyms": ["Alternative titles", "USHER SYNDROME, TYPE III"]} |
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: "Aggressive fibromatosis" – news · newspapers · books · scholar · JSTOR (March 2018)
Aggressive fibromatosis
Desmoid tumor as seen on CT scan
SpecialtyOncology
Aggressive fibromatosis is a rare condition marked by the presence of desmoid tumors. Desmoid tumors arise from cells called fibroblasts, which are found throughout the body and provide structural support, protection to the vital organs, and play a critical role in wound healing. These tumors tend to occur in women in their thirties, but can occur in anyone at any age. They can be either relatively slow-growing or malignant. However, aggressive fibromatosis is locally aggressive and can cause life-threatening problems or even death when they compress vital organs such as intestines, kidneys, lungs, blood vessels, or nerves. Most cases are sporadic, but some are associated with familial adenomatous polyposis (FAP). Approximately 10% of individuals with Gardner's syndrome, a type of FAP with extracolonic features, have desmoid tumors.[1]
Histologically they resemble very low-grade fibrosarcomas,[2] but they are very locally aggressive and tend to recur even after complete resection. There is a tendency for recurrence in the setting of prior surgery; in one study, two-thirds of patients with desmoid tumors had a history of prior abdominal surgery.[3]
## Contents
* 1 Risk factor
* 2 Diagnosis
* 2.1 Classification
* 3 Treatment
* 4 References
* 5 External links
## Risk factor[edit]
Risk factors for desmoid disease amongst FAP patients include female sex, a 3' APC mutation, a positive family history, and a history of previous abdominal surgery.[4]
## Diagnosis[edit]
### Classification[edit]
Desmoid tumor
Desmoid fibromatosis, H&E stain. Banal fibroblasts infiltrate the adjacent tissue in fascicles. Mitoses may be infrequent.
Desmoid tumors may be classified as extra-abdominal, abdominal wall, or intra-abdominal (the last is more common in patients with FAP). It is thought that the lesions may develop in relation to estrogen levels or trauma/operations.[citation needed]
A 3' APC mutation is the most significant risk factor for intra-abdominal desmoid development amongst FAP patients.[5] FAP patients presenting with an abdominal wall desmoid pre-operatively are at an increased risk of developing an intra-abdominal desmoid post-operatively.[6]
Desmoid tumours of the breast are rare. Although benign, they can mimic breast cancer on physical examination, mammography and breast ultrasound and can also be locally invasive. Even though they occur sporadically, they can also be seen as a part of Gardner's syndrome. A high index of suspicion and a thorough triple examination protocol is necessary to detect rare lesions like a desmoid tumour which can masquerade as breast carcinoma. Desmoid tumour of the breast may present a difficulty in the diagnosis especially where imaging studies are not conclusive and suggest a more ominous diagnosis.[7]
## Treatment[edit]
Treatment may consist of watchful waiting, complete surgical removal, radiation therapy, antiestrogens (ex. Tamoxifen), NSAIDs, chemotherapy, or microwave ablation.
Patients with desmoid tumors should be evaluated by a multi-disciplinary team of surgeons, medical oncologists, radiation oncologists, and geneticists. There is no cure for desmoid tumors; when possible, patients are encouraged to enlist in clinical trials.[8]
A biopsy is always indicated as the definitive method to determine nature of the tumour. Management of these lesions is complex, the main problem being the high rates of recurrence in FAP associated disease. Conversely, for intra-abdominal fibromatosis without evidence of FAP, although extensive surgery may still be required for local symptoms, the risk of recurrence appears to be lower.[9] Wide surgical resection with clear margins is the most widely practiced technique with radiation, chemotherapy, or hormonal therapy being used to reduce the risk of recurrence.[7]
Current experimental studies are being done with Gleevec (Imatinib) and Nexavar (sorafenib) for treatment of desmoid tumors, and show promising success rates.
## References[edit]
1. ^ Nieuwenhuis MH, De Vos Tot Nederveen Cappel W, Botma A, et al. (February 2008). "Desmoid tumors in a Dutch cohort of patients with familial adenomatous polyposis". Clinical Gastroenterology and Hepatology. 6 (2): 215–9. doi:10.1016/j.cgh.2007.11.011. PMID 18237870.
2. ^ "desmoid" at Dorland's Medical Dictionary
3. ^ Lynch HT, Fitzgibbons R (December 1996). "Surgery, desmoid tumors, and familial adenomatous polyposis: case report and literature review". The American Journal of Gastroenterology. 91 (12): 2598–601. PMID 8946994.
4. ^ Sinha A, Clark SK (2010). "Risk factors predicting desmoid occurrence in patients with familial adenomatous polyposis: a meta-analysis". Colorectal Disease. 13 (11): 1222–1229. doi:10.1111/j.1463-1318.2010.02345.x. PMID 20528895. S2CID 26117431.
5. ^ Sinha A, Clark SK (June 2010). "Risk factors predicting intra-abdominal desmoids in familial adenomatous polyposis: a single centre experience". Techniques in Coloproctology. 14 (2): 141–6. doi:10.1007/s10151-010-0573-4. PMID 20352275. S2CID 24922322.
6. ^ Sinha A, Clark SK (2010). "Surgical prophylaxis in familial adenomatous polyposis: do pre-existing desmoids outside the abdominal cavity matter?". Familial Cancer. 9 (3): 407–11. doi:10.1007/s10689-010-9342-9. PMID 20428953. S2CID 20685381.
7. ^ a b Rammohan A, Wood JJ (2012). "Desmoid tumour of the breast as a manifestation of Gardner's syndrome". International Journal of Surgery Case Reports. 3 (5): 139–142. doi:10.1016/j.ijscr.2012.01.004. PMC 3312056. PMID 22370045.
8. ^ "About Desmoid Tumors". Archived from the original on 2015-07-27. Retrieved 2015-08-04.
9. ^ Wilkinson MJ, Fitzgerald JE, Thomas JM, Hayes AJ, Strauss DC (2012). "Surgical resection for non-familial adenomatous polyposis-related intra-abdominal fibromatosis". British Journal of Surgery. 99 (5): 706–13. doi:10.1002/bjs.8703. PMID 22359346. S2CID 205512855.
## External links[edit]
Classification
D
* ICD-10: D48.1
* MeSH: D018222
* DiseasesDB: 29794
External resources
* eMedicine: article/1060887
* v
* t
* e
Soft tissue disorders
Capsular joint
Synoviopathy
* Synovitis/Tenosynovitis
* Calcific tendinitis
* Stenosing tenosynovitis
* Trigger finger
* De Quervain syndrome
* Transient synovitis
* Ganglion cyst
* osteochondromatosis
* Synovial osteochondromatosis
* Plica syndrome
* villonodular synovitis
* Giant-cell tumor of the tendon sheath
Bursopathy
* Bursitis
* Olecranon
* Prepatellar
* Trochanteric
* Subacromial
* Achilles
* Retrocalcaneal
* Ischial
* Iliopsoas
* Synovial cyst
* Baker's cyst
* Calcific bursitis
Noncapsular joint
Symptoms
* Ligamentous laxity
* Hypermobility
Enthesopathy/Enthesitis/Tendinopathy
upper limb
* Adhesive capsulitis of shoulder
* Impingement syndrome
* Rotator cuff tear
* Golfer's elbow
* Tennis elbow
lower limb
* Iliotibial band syndrome
* Patellar tendinitis
* Achilles tendinitis
* Calcaneal spur
* Metatarsalgia
* Bone spur
other/general:
* Tendinitis/Tendinosis
Nonjoint
Fasciopathy
* Fasciitis: Plantar
* Nodular
* Necrotizing
* Eosinophilic
Fibromatosis/contracture
* Dupuytren's contracture
* Plantar fibromatosis
* Aggressive fibromatosis
* Knuckle pads
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Aggressive fibromatosis | c0079218 | 5,143 | wikipedia | https://en.wikipedia.org/wiki/Aggressive_fibromatosis | 2021-01-18T18:36:55 | {"gard": ["1820"], "mesh": ["D018222"], "umls": ["C0079218"], "icd-10": ["D48.1"], "wikidata": ["Q475086"]} |
A rare genetic skeletal muscle disease characterized by childhood onset of exercise-induced progressive impairment of muscle relaxation, stiffness, cramps, and myalgia, predominantly in the arms, legs, and face (eyelids), and, biochemically, by a reduced sarcoplasmic reticulum Ca(2+)-ATPase activity. Symptoms improve after a few minutes of rest and may be exacerbated by cold. The term Brody syndrome refers to a clinically distinguishable subset of patients without ATP2A1 mutations, with adolescence or adult onset and selective muscular involvement, in which myalgia is more common.
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Brody myopathy | c1832918 | 5,144 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=53347 | 2021-01-23T18:33:16 | {"gard": ["9158"], "mesh": ["C536607"], "omim": ["601003"], "umls": ["C1832918"], "icd-10": ["G71.8"]} |
Not to be confused with Cytokine release syndrome.
highly morbid or fatal immune reaction
A cytokine storm, also called hypercytokinemia, is a physiological reaction in humans and other animals in which the innate immune system causes an uncontrolled and excessive release of pro-inflammatory signaling molecules called cytokines. Normally, cytokines are part of the body's immune response to infection, but their sudden release in large quantities can cause multisystem organ failure and death.[1] Cytokine storms can be caused by a number of infectious and non-infectious etiologies, especially viral respiratory infections such as H5N1 influenza, SARS-CoV-1,[2][3] and SARS-CoV-2 (COVID-19 agent). Other causative agents include the Epstein-Barr virus, cytomegalovirus, and group A streptococcus, and non-infectious conditions such as graft-versus-host disease.[4] The viruses can invade lung epithelial cells and alveolar macrophages to produce viral nucleic acid, which stimulates the infected cells to release cytokines and chemokines, activating macrophages, dendritic cells, and others.[5]
Cytokine storm syndrome is diverse set of conditions that can result in cytokine storm. Cytokine storm syndromes include familiar hemophagocytic lymphohistiocytosis, Epstein-Barr virus–associated hemophagocytic lymphohistiocytosis, systemic or non-systemic juvenile idiopathic arthritis–associated macrophage activation syndrome, NLRC4 macrophage activation syndrome, cytokine release syndrome and sepsis.[6]
## Contents
* 1 Cytokine storms versus cytokine release syndrome
* 2 Research
* 3 History
* 3.1 Relationship to COVID-19
* 4 References
## Cytokine storms versus cytokine release syndrome[edit]
The term "cytokine storm" is often loosely used interchangeably with cytokine release syndrome (CRS) but is more precisely a differentiable syndrome that may represent a severe episode of cytokine release syndrome or a component of another disease entity, such as macrophage activation syndrome. When occurring as a result of a therapy, CRS symptoms may be delayed until days or weeks after treatment. Immediate-onset (fulminant) CRS appears to be a cytokine storm.[7]
## Research[edit]
Nicotinamide (a form of vitamin B3) is a potent inhibitor of proinflammatory cytokines.[8][9]
Magnesium decreases inflammatory cytokine production by modulation of the immune system.[10][11]
## History[edit]
The first reference to the term cytokine storm in the published medical literature appears to be by James Ferrara in 1993 during a discussion of graft vs. host disease; a condition in which the role of excessive and self-perpetuating cytokine release had already been under discussion for many years.[12][13][14] The term next appeared in a discussion of pancreatitis in 2002, and in 2003 it was first used in reference to a reaction to an infection.[12]
It is believed that cytokine storms were responsible for the disproportionate number of healthy young adult deaths during the 1918 influenza pandemic, which killed 17 to 50 million people. In this case, a healthy immune system may have been a liability rather than an asset.[15] Preliminary research results from Taiwan also indicated this as the probable reason for many deaths during the SARS epidemic in 2003.[16] Human deaths from the bird flu H5N1 usually involve cytokine storms as well.[17] Cytokine storm has also been implicated in hantavirus pulmonary syndrome.[18]
In 2006, a study at Northwick Park Hospital in England resulted in all 6 of the volunteers given the drug theralizumab becoming critically ill, with multiple organ failure, high fever, and a systemic inflammatory response.[19][20] Parexel, a company conducting trials for pharmaceutical companies, in one of its documents, wrote about the trial and said theralizumab could cause a cytokine storm—the dangerous reaction the men experienced.[21]
### Relationship to COVID-19[edit]
During the COVID-19 pandemic, some doctors attributed many deaths to cytokine storms.[22][23] Severe symptoms of acute respiratory distress syndrome (ARDS) with high mortality in COVID-19 patients are caused by a cytokine storm.[24] SARS-CoV-2 activates the innate immune system and results in a release of a large number of cytokines, including IL-6, which can increase vascular permeability and cause a migration of fluid and blood cells into the alveoli as well as the consequent symptoms such as dyspnea and respiratory failure.[25] The higher mortality is being linked to the result of ARDS aggravation and the tissue damage that can result in organ-failure and/or death.[26]
ARDS was shown to be the cause of mortality in 70% of COVID-19 deaths.[27] In a cytokine plasma level analysis of those with severe Sars-CoV-2, the levels of many interleukins and cytokines are extremely elevated, showing evidence of a cytokine storm in those most harshly affected.[26] Additionally, postmortem examination of patients with COVID-19 has shown large accumulation of inflammatory cells in lung tissues, including macrophages and T-helper cells.[28]
Early recognition of this cytokine storm in COVID-19 patients is crucial to ensure the best outcome, allowing for treatment with a variety of biological agents that target the cytokines to reduce their levels.
Due to the increased levels of cytokines and interferons in those with severe Sars-CoV-2, both are being investigated as potential therapies for COVID-19. An animal study done on mice found that those producing early strong interferon responses to SARS-CoV, which also originated from bats, were more likely to live, while other cases were likely to experience a highly morbid overactive immune system.[29][30] The high mortality rate of COVID-19 in older populations were linked to the impact of age on interferon responses.
Short-term use of dexamethasone, a synthetic corticosteroid, has been demonstrated to reduce the severity of inflammation and lung damage induced by the cytokine storm; it inhibits the severe cytokine storm, or the hyperinflammatory phase in patients with COVID-19.[31]
Trials continue to identify causes of cytokine storms in COVID-19 cases.[32][33] One possible cause is the delayed type I INF response, because it leads to accumulation of pathogenic monocytes. High viremia is also associated with exacerbated type I INF response and worse prognosis.[34] Diabetes, hypertension, and cardiovascular disease are all risk factors of cytokine storms in COVID-19 patients.[35]
## References[edit]
1. ^ Farsalinos, Konstantinos; Barbouni, Anastasia; Niaura, Raymond (2020). "Systematic review of the prevalence of current smoking among hospitalized COVID-19 patients in China: Could nicotine be a therapeutic option?". Internal and Emergency Medicine. 15 (5): 845–852. doi:10.1007/s11739-020-02355-7. PMC 7210099. PMID 32385628.
2. ^ Wong, Jonathan P.; Viswanathan, Satya; Wang, Ming; Sun, Lun-Quan; Clark, Graeme C.; D'Elia, Riccardo V. (February 2017). "Current and future developments in the treatment of virus-induced hypercytokinemia". Future Medicinal Chemistry. 9 (2): 169–178. doi:10.4155/fmc-2016-0181. ISSN 1756-8927. PMC 7079716. PMID 28128003.
3. ^ Liu, Qiang; Zhou, Yuan-hong; Yang, Zhan-qiu (January 2016). "The cytokine storm of severe influenza and development of immunomodulatory therapy". Cellular & Molecular Immunology. 13 (1): 3–10. doi:10.1038/cmi.2015.74. PMC 4711683. PMID 26189369.
4. ^ Tisoncik, Jennifer R.; Korth, Marcus J.; Simmons, Cameron P.; Farrar, Jeremy; Martin, Thomas R.; Katze, Michael G. (2012). "Into the Eye of the Cytokine Storm". Microbiology and Molecular Biology Reviews. 76 (1): 16–32. doi:10.1128/MMBR.05015-11. ISSN 1092-2172. PMC 3294426. PMID 22390970.
5. ^ Song, Peipei; Li, Wei; Xie, Jianqin; Hou, Yanlong; You, Chongge (October 2020). "Cytokine storm induced by SARS-CoV-2". Clinica Chimica Acta; International Journal of Clinical Chemistry. 509: 280–287. doi:10.1016/j.cca.2020.06.017. ISSN 0009-8981. PMC 7283076. PMID 32531256.
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9. ^ Yanez M, Jhanji M, Murphy K, Gower RM, Sajish M, Jabbarzadeh E (2019). "Nicotinamide Augments the Anti-Inflammatory Properties of Resveratrol through PARP1 Activation". Sci Rep. 9 (1): 10219. Bibcode:2019NatSR...910219Y. doi:10.1038/s41598-019-46678-8. PMC 6629694. PMID 31308445.CS1 maint: multiple names: authors list (link)
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13. ^ Ferrara JL, Abhyankar S, Gilliland DG (February 1993). "Cytokine storm of graft-versus-host disease: a critical effector role for interleukin-1". Transplantation Proceedings. 25 (1 Pt 2): 1216–7. PMID 8442093.
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15. ^ Osterholm MT (May 2005). "Preparing for the next pandemic". The New England Journal of Medicine. 352 (18): 1839–42. CiteSeerX 10.1.1.608.6200. doi:10.1056/NEJMp058068. PMID 15872196.
16. ^ Huang KJ, Su IJ, Theron M, Wu YC, Lai SK, Liu CC, Lei HY (February 2005). "An interferon-gamma-related cytokine storm in SARS patients". Journal of Medical Virology. 75 (2): 185–94. doi:10.1002/jmv.20255. PMC 7166886. PMID 15602737.
17. ^ Haque A, Hober D, Kasper LH (October 2007). "Confronting potential influenza A (H5N1) pandemic with better vaccines". Emerging Infectious Diseases. 13 (10): 1512–8. doi:10.3201/eid1310.061262. PMC 2851514. PMID 18258000.
18. ^ Mori M, Rothman AL, Kurane I, Montoya JM, Nolte KB, Norman JE, et al. (February 1999). "High levels of cytokine-producing cells in the lung tissues of patients with fatal hantavirus pulmonary syndrome". The Journal of Infectious Diseases. 179 (2): 295–302. doi:10.1086/314597. PMID 9878011.
19. ^ The Lancet Oncology (February 2007). "High stakes, high risks". The Lancet. Oncology. 8 (2): 85. doi:10.1016/S1470-2045(07)70004-9. PMID 17267317.
20. ^ Yiu, Hao Hong; Graham, Andrea L.; Stengel, Robert F. (1 October 2012). "Dynamics of a Cytokine Storm". PLOS ONE. 7 (10): e45027. Bibcode:2012PLoSO...745027Y. doi:10.1371/journal.pone.0045027. PMC 3462188. PMID 23049677.
21. ^ Coghlan A (2006-08-14). "Mystery over drug trial debacle deepens". Health. New Scientist. Retrieved 2009-04-29.
22. ^ Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ (March 2020). "COVID-19: consider cytokine storm syndromes and immunosuppression". Lancet. 395 (10229): 1033–1034. doi:10.1016/S0140-6736(20)30628-0. PMC 7270045. PMID 32192578.
23. ^ Ruan Q, Yang K, Wang W, Jiang L, Song J (March 2020). "Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China". Intensive Care Medicine. 46 (5): 846–848. doi:10.1007/s00134-020-05991-x. PMC 7080116. PMID 32125452.
24. ^ Hojyo S, Uchida M, Tanaka K, Hasebe R, Tanaka Y, Murakami M, Hirano T (October 2020). "How covid-19 induces cytokine storm with high mortality". Inflammation and Regeneration. 40 (37): 37. doi:10.1186/s41232-020-00146-3. PMC 7527296. PMID 33014208.
25. ^ Farsalinos, Konstantinos; Barbouni, Anastasia; Niaura, Raymond (2020-05-09). "Systematic review of the prevalence of current smoking among hospitalized COVID-19 patients in China: could nicotine be a therapeutic option?". Internal and Emergency Medicine. 15 (5): 845–852. doi:10.1007/s11739-020-02355-7. ISSN 1828-0447. PMC 7210099. PMID 32385628.
26. ^ a b Ragad, Dina (16 June 2020). "The COVID-19 Cytokine Storm; What we know so far". Front. Immunol. 11: 1446. doi:10.3389/fimmu.2020.01446. PMC 7308649. PMID 32612617.
27. ^ Hojyo, Shintaro; Uchida, Mona; Tanaka, Kumiko; Hasebe, Rie; Tanaka, Yuki; Murakami, Masaaki; Hirano, Toshio (2020-10-01). "How COVID-19 induces cytokine storm with high mortality". Inflammation and Regeneration. 40: 37. doi:10.1186/s41232-020-00146-3. ISSN 1880-9693. PMC 7527296. PMID 33014208.
28. ^ Tang, Yujun; Liu, Jiajia; Zhang, Dingyi; Xu, Zhenghao; Ji, Jinjun; Wen, Chengping (2020-07-10). "Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies". Frontiers in Immunology. 11: 1708. doi:10.3389/fimmu.2020.01708. ISSN 1664-3224. PMC 7365923. PMID 32754163.
29. ^ Channappanavar, Rudragouda; Perlman, Stanley (2017). "Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology". Seminars in Immunopathology. 39 (5): 529–539. doi:10.1007/s00281-017-0629-x. ISSN 1863-2297. PMC 7079893.
30. ^ Velasquez-Manoff, Moises (2020-08-11). "How Covid Sends Some Bodies to War With Themselves". The New York Times. ISSN 0362-4331. Retrieved 2020-12-28.
31. ^ Sharun, Khan; Tiwari, Ruchi; Dhama, Jaideep; Dhama, Kuldeep (October 2020). "Dexamethasone to combat cytokine storm in COVID-19: Clinical trials and preliminary evidence". International Journal of Surgery. 82: 179–181. doi:10.1016/j.ijsu.2020.08.038. PMC 7472975. PMID 32896649.
32. ^ Hermine, Olivier; Mariette, Xavier; Tharaux, Pierre-Louis; Resche-Rigon, Matthieu; Porcher, Raphaël; Ravaud, Philippe; CORIMUNO-19 Collaborative Group (20 October 2020). "Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia: A Randomized Clinical Trial". JAMA Internal Medicine. doi:10.1001/jamainternmed.2020.6820. PMC 7577198. PMID 33080017.
33. ^ Gupta, Shruti; Wang, Wei; Hayek, Salim S.; Chan, Lili; Mathews, Kusum S.; Melamed, Michal L.; Brenner, Samantha K.; Leonberg-Yoo, Amanda; Schenck, Edward J.; Radbel, Jared; Reiser, Jochen; Bansal, Anip; Srivastava, Anand; Zhou, Yan; Finkel, Diana; Green, Adam; Mallappallil, Mary; Faugno, Anthony J.; Zhang, Jingjing; Velez, Juan Carlos Q.; Shaefi, Shahzad; Parikh, Chirag R.; Charytan, David M.; Athavale, Ambarish M.; Friedman, Allon N.; Redfern, Roberta E.; Short, Samuel A. P.; Correa, Simon; Pokharel, Kapil K.; Admon, Andrew J.; Donnelly, John P.; Gershengorn, Hayley B.; Douin, David J.; Semler, Matthew W.; Hernán, Miguel A.; Leaf, David E.; STOP-COVID Investigators (20 October 2020). "Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19". JAMA Internal Medicine. doi:10.1001/jamainternmed.2020.6252. PMC 757720. PMID 33080002.
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35. ^ Mangalmurti, Nilam; Hunter, Christopher A. (14 July 2020). "Cytokine Storms: Understanding COVID-19". Immunity. 53 (1): 19–25. doi:10.1016/j.immuni.2020.06.017. PMC 7321048. PMID 32610079 – via ScienceDirect.
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Cytokine storm | c0919747 | 5,145 | wikipedia | https://en.wikipedia.org/wiki/Cytokine_storm | 2021-01-18T18:31:17 | {"umls": ["C0919747"], "wikidata": ["Q1076369"]} |
A number sign (#) is used with this entry because Bernard-Soulier syndrome (BSS) has been found to be caused by mutation in the GP1BA gene (606672), the GP1BB gene (138720), or the GP9 gene (173515); the forms of BSS caused by homozygous or compound heterozygous mutation in these genes are here referred to as types A1, B, and C, respectively.
See also autosomal dominant Bernard-Soulier syndrome (BSSA2; 153670), which can be caused by heterozygous mutation in the GP1BA gene. It is much less common than autosomal recessive Bernard-Soulier syndrome.
Description
Bernard-Soulier syndrome is an autosomal recessive bleeding disorder caused by a defect in or deficiency of the platelet membrane von Willebrand factor (VWF; 613160) receptor complex, glycoprotein Ib (GP Ib). GP Ib is composed of 4 subunits encoded by 4 separate genes: GP1BA, GP1BB, GP9, and GP5 (173511).
### Genetic Heterogeneity of Platelet-Type Bleeding Disorders
Inherited platelet disorders are a heterogeneous group of bleeding disorders affecting platelet number, function, or both. Functional defects can involve platelet receptors, signaling pathways, cytoskeletal proteins, granule contents, activation, or aggregation (review by Cox et al., 2011 and Nurden and Nurden, 2011).
Platelet-type bleeding disorders include Bernard-Soulier syndrome (BDPLT1); Glanzmann thrombasthenia (BDPLT2; 273800), caused by mutation in the ITGA2B (607759) or ITGB3 (173470) gene; pseudo-von Willebrand disease (BDPLT3; 177820), caused by mutation in the GP1BA gene (606672); gray platelet syndrome (BDPLT4; 139090), caused by mutation in the NBEAL2 gene (614169); Quebec platelet disorder (BDPLT5; 601709), caused by tandem duplication of the PLAU gene (191840); May-Hegglin anomaly (BDPLT6; 155100), caused by mutation in the MYH9 gene (160775); Scott syndrome (BDPLT7; 262890), caused by mutation in the TMEM16F gene (608663); BDPLT8 (609821), caused by mutation in the P2RY12 gene (600515); BDPLT9 (614200), associated with deficiency of the glycoprotein Ia/IIa receptor (see ITGA2; 192974); glycoprotein IV deficiency (BDPLT10; 608404), caused by mutation in the CD36 gene (173510); BDPLT11 (614201), caused by mutation in the GP6 gene (605546); BDPLT12 (605735), associated with a deficiency of platelet COX1 (176805); susceptibility to BDPLT13 (614009), caused by mutation in the TBXA2R gene (188070); BDPLT14 (614158), associated with deficiency of thromboxane synthetase (TBXAS1; 274180); BDPLT15 (615193), caused by mutation in the ACTN1 gene (102575); BDPLT16 (187800), caused by mutation in the ITGA2B (607759) or ITGB3 (173470) gene; BDPLT17 (187900), caused by mutation in the GFI1B gene (604383); BDPLT18 (615888), caused by mutation in the RASGRP2 gene (605577); BDPLT19 (616176), caused by mutation in the PRKACG gene (176893); BDPLT20 (616913), caused by mutation in the SLFN14 gene (614958); BDPLT21 (617443), caused by mutation in the FLI1 gene (193067); and BDPLT22 (618462), caused by mutation in the EPHB2 gene (600997).
See reviews by Rao (2003), Cox et al. (2011), and Nurden and Nurden (2011).
For a discussion of the genetic heterogeneity of hereditary thrombocytopenia, see THC1 (313900).
Clinical Features
Bernard-Soulier syndrome and other platelet disorders have some similar clinical features, including mucosal bleeding, purpuric skin bleeding, epistaxis, and menorrhagia. In BSS, bleeding time is prolonged (in some cases longer than 20 minutes), platelets are large, and there is no platelet aggregation in response to ristocetin or addition of von Willebrand factor. Thrombocytopenia may or may not be present (Lopez et al., 1998).
Bernard and Soulier (1948) described a congenital bleeding disorder in patients who had unusually large platelets and a moderate degree of thrombocytopenia. All had a markedly prolonged bleeding time. The same abnormality was described in a family by Kanska et al. (1963). Cullum et al. (1967) described 2 brothers from a consanguineous family of Sicilian origin with a bleeding disorder characterized by thrombocytopenia, abnormally large platelets, prolonged bleeding time, low platelet thromboplastic activity, and normal clotting retraction. All 5 of the brothers' children had abnormal platelet morphology. Multiple other members of the extended family had abnormal platelets without the full bleeding disorder. The authors concluded that the 2 affected brothers were homozygous and the other members with isolated abnormal platelet morphology were heterozygotes. The phospholipid content of platelets was increased. Cullum et al. (1967) suggested that abnormally rapid removal of the bizarre platelets may be responsible for thrombocytopenia. Weiss et al. (1974) studied 2 black first cousins with the disorder.
Clinical Management
In the case of a Swedish patient with Bernard-Soulier syndrome, Waldenstrom et al. (1991) found that the parents had common ancestors in the 17th century. In this and another patient, bleeding time was shortened by infusion of dDAVP (1-deamino-8D-arginine vasopressin), although it was not completely normalized.
Pathogenesis
Grottum and Solum (1969) found reduced electrophoretic mobility of BSS platelets due to a marked decrease in the concentration of sialic acid on their membranes.
Weiss et al. (1974) noted that the adhesion of BSS platelets to rabbit aortic subendothelium was impaired. The authors suggested that there may be a reduced or abnormal glycoprotein involved, and they presented evidence suggesting that platelets in this syndrome lack a receptor for the von Willebrand factor.
In 2 patients with the Bernard-Soulier syndrome, Nurden and Caen (1975) were unable to find more than traces of a 155,000 molecular mass glycoprotein in membrane fraction from platelets. Previously reported findings of sialic acid content and reduced electrophoretic mobility of Bernard-Soulier platelets were consistent. Caen et al. (1976) confirmed a defect in BSS platelet adhesion to rabbit aorta subendothelium. The factor VIII-von Willebrand protein was apparently normal on Bernard-Soulier platelets when studied by an immuno-electron-microscopic technique; however, a reduced content of a major platelet glycoprotein was found by two methods.
In 3 patients with the Bernard-Soulier syndrome, Kunicki et al. (1978) could not detect the platelet membrane receptor for quinidine and quinine-dependent antibodies. The platelets were likewise deficient in glycoproteins Ib and Is. In normal platelets, apparently, complete cleavage of the glycoproteins had little effect on antibody receptor activity, suggesting the presence of a second membrane defect in BSS.
Hagen et al. (1980) stated that there was clear evidence that there is a defect in von Willebrand receptor in the Bernard-Soulier syndrome (see also Moake et al., 1980), and that the normal receptor is glycoprotein I (Nurden and Caen, 1975). Heterozygotes (e.g., parents) have a decrease in glycoprotein I but no impairment of platelet function and no abnormal bleeding.
Montgomery et al. (1983) demonstrated that an assay using monoclonal antibodies raised in the mouse can recognize the deficiency of glycoprotein Ib in the Bernard-Soulier syndrome and of the glycoprotein IIb/IIIa in Glanzmann thrombasthenia (GTA; 273800).
Stricker et al. (1985) described acquired Bernard-Soulier syndrome in a patient with a lymphoproliferative disorder. They demonstrated an IgG antibody that inhibited aggregation of normal platelets by ristocetin and by von Willebrand factor. By Western blotting, they found that the antibody bound specifically to an antigen of MW 210,000 present in normal platelets but missing in BSS platelets.
Molecular Genetics
In a patient with autosomal recessive Bernard-Soulier syndrome, Ware et al. (1990) identified a homozygous nonsense mutation in the GP1BA gene (606672.0001), which encodes the alpha chain of the GP Ib receptor.
By RFLP analysis, Finch et al. (1990) ruled out the GP1BA gene as the site of the mutation in a BSS family with 2 affected sibs. The authors suggested that the cause of BSS in this family was due to other genes encoding platelet membrane glycoproteins, including GP1BB, GP IX, and possibly GP V, which may result in failure of assembly and cell surface expression of the von Willebrand factor receptor complex. This suggestion came from the observation that other membrane complexes such as platelet GP IIb-IIIa (273800, 173470) and the T-cell receptor/CD3 complex (186790, 186830, 186740) require coordinate expression of multiple subunits for normal receptor assembly.
In a male patient with the velocardiofacial syndrome caused by a deletion in chromosome 22q and symptoms of BSS, Ludlow et al. (1996) identified a mutation in the upstream promoter of the GP1BB gene (138720.0003). Thus, in this patient, BSS resulted from deletion of 1 copy of the gene and mutation in the other copy.
In a family with BSS, Wright et al. (1993) identified compound heterozygous mutations in the GP9 gene (173515.0001, 173515.0002). The authors suggested that abnormal GP IX prevented stable assembly of the GP Ib complex.
Noda et al. (1995) reported 2 BSS patients: one had a mutation in the GP9 gene and the other had a mutation in the GP1BA gene. They noted that abnormality of a single component of the receptor complex resulted in heterogeneous surface expression of all the components.
In 2 Japanese sisters with giant platelets, mild childhood bleeding, and impaired ristocetin aggregation, Kunishima et al. (1997) identified compound heterozygosity for mutations in the GP1BB gene (138720.0001-138720.0002). The authors suggested that the phenotype caused by mutations in the subunits of the GP Ib complex could span the spectrum from a normal phenotype, to isolated giant platelet disorder, to full-blown Bernard-Soulier syndrome.
Animal Model
Ware et al. (2000) disrupted the Gp1ba gene of the mouse and described a murine model recapitulating the hallmark characteristics of human Bernard-Soulier syndrome. Using transgenic technology, they rescued the murine BSS phenotype by expression of the human glycoprotein Ib-alpha subunit on the surface of circulating mouse platelets.
Kato et al. (2004) found that Gp1bb-null mice had macrothrombocytopenia and a severe bleeding phenotype. Electron microscopy showed increased size of the alpha-granules compared to control alpha-granules, possibly resulting from disruption of the neighboring Sept5 gene (602724), approximately 250 nucleotides 5-prime to the Gp1bb gene. Sept5 protein levels in platelets from Gp1bb-null mice were 2- to 3-fold increased compared to controls.
INHERITANCE \- Autosomal recessive HEAD & NECK Nose \- Epistaxis ABDOMEN Gastrointestinal \- Hemorrhage GENITOURINARY Internal Genitalia (Female) \- Menorrhagia SKIN, NAILS, & HAIR Skin \- Purpura HEMATOLOGY \- Congenital bleeding diathesis \- Large platelets \- Mild thrombocytopenia LABORATORY ABNORMALITIES \- Prolonged bleeding time \- Reduced platelet glycoprotein Ib complex \- Normal platelet aggregation with ADP, collagen, epinephrine \- Absent platelet agglutination in presence of ristocetin MOLECULAR BASIS \- Caused by mutation in the platelet glycoprotein Ib, alpha polypeptide, gene (GP1BA, 606672.0001 ) \- Caused by mutation in the platelet glycoprotein Ib, beta polypeptide, gene (GP1BB, 138720.0001 ) \- Caused by mutation in the platelet glycoprotein IX gene (GP9, 173515.0001 ) ▲ 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| BERNARD-SOULIER SYNDROME | c0005129 | 5,146 | omim | https://www.omim.org/entry/231200 | 2019-09-22T16:27:34 | {"doid": ["2217"], "mesh": ["D001606"], "omim": ["231200"], "orphanet": ["274"], "synonyms": ["Alternative titles", "BLEEDING DISORDER, PLATELET-TYPE, 1", "PLATELET GLYCOPROTEIN Ib DEFICIENCY", "GLYCOPROTEIN Ib, PLATELET, DEFICIENCY OF", "VON WILLEBRAND FACTOR RECEPTOR DEFICIENCY"]} |
L1 syndrome is a mild to severe congenital disorder with hydrocephalus of varying degrees of severity, intellectual disability, spasticity of the legs, and adducted thumbs. It includes several conditions, some more severe than others: X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS) - the most severe of all; MASA syndrome (intellectual disability, aphasia (delayed speech), spastic paraplegia (shuffling gait), adducted thumbs); SPG1 (X-linked complicated hereditary spastic paraplegia type 1) X-linked complicated corpus callosum agenesis. It is inherited in an X-linked manner; therefore, it only affects males. It is caused by alterations (mutations) in L1CAM gene. The diagnosis is made in males who have the clinical and neurologic findings and a family history consistent with X-linked inheritance and is confirmed by a genetic test showing the L1CAM gene mutation. The treatment involves doing a surgery for the hydrocephalus.
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| L1 syndrome | c0795953 | 5,147 | gard | https://rarediseases.info.nih.gov/diseases/12524/l1-syndrome | 2021-01-18T17:59:32 | {"mesh": ["C536029"], "orphanet": ["275543"], "synonyms": ["Corpus callosum hypoplasia-retardation-adducted thumbs-spasticity-hydrocephalus syndrome", "CRASH syndrome", "L1CAM syndrome"]} |
Pseudo-pelade of Brocq is a rare hair abnormality characterized by onset in adulthood of soft, irregular, flesh-toned patches of alopecia primarily in the parietal and vertex portions of the scalp, without follicular hyperkeratosis or perifollicular inflammation.
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Pseudopelade of Brocq | c0086873 | 5,148 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=129 | 2021-01-23T16:54:21 | {"gard": ["4536"], "mesh": ["C531609", "D000505"], "umls": ["C0086873"], "icd-10": ["L66.0"]} |
A number sign (#) is used with this entry because Joubert syndrome-15 (JBTS15) is caused by homozygous mutation in the CEP41 gene (610523) on chromosome 7q32. Digenic inheritance has also been reported; see MOLECULAR GENETICS.
Description
Joubert syndrome-15 is an autosomal recessive developmental disorder characterized by ataxia, hypotonia, delayed psychomotor development, and variable mental retardation. Other features, such as polydactyly, breathing abnormalities, and oculomotor apraxia, are variable (summary by Lee et al., 2012).
For a phenotypic description and a discussion of genetic heterogeneity of Joubert syndrome, see 213300.
Clinical Features
Lee et al. (2012) reported 8 patients from 3 consanguineous families with Joubert syndrome. All patients had hypotonia, ataxia, psychomotor delay with mental retardation, and the molar tooth sign on brain imaging. More variable features included postaxial polydactyly, breathing abnormalities, and oculomotor apraxia. Seven of the patients did not have hepatic or renal involvement; 2 had retinal involvement.
Inheritance
The transmission pattern of Joubert syndrome-15 in the families reported by Lee et al. (2012) was consistent with autosomal recessive inheritance.
Mapping
By linkage analysis of a consanguineous Egyptian family with Joubert syndrome, Lee et al. (2012) mapped a novel locus, which they termed JBTS15, to a 5-Mb region on chromosome 7q31.33-q32.3 between markers rs766240 and rs4728251 (maximum multipoint lod score of 3.71).
Molecular Genetics
In affected members of 3 consanguineous families with Joubert syndrome-15, 2 of Egyptian origin and 1 Portuguese, Lee et al. (2012) identified 3 different homozygous loss-of-function mutations in the CEP41 gene (610523.0001-610523.0003). The first mutation was found by linkage analysis followed by candidate gene sequencing in 1 of the families. Heterozygous CEP41 mutations (see, e.g., 610523.0004-610523.0007) were found in 5 additional patients with Joubert syndrome, and 3 of them were found to carry heterozygous mutations in other genes associated with ciliopathies (KIF7, 611254.0007 and CC2D2A, 612013.0007 and 612013.0009). These findings indicated digenic inheritance, and suggested that CEP41 may act as a modifier in the broader class of ciliopathies. Extensive studies in zebrafish and patient fibroblasts suggested that CEP41 mutations cause a defect in the posttranslational modification and glutamylation of tubulin by interfering with the proper transport of TTLL6 (610849), an evolutionarily conserved polyglutamylase enzyme, between the basal body and cilium. The findings implicated tubulin posttranslational modification in the pathogenesis of human ciliary dysfunction.
INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Oculomotor apraxia (variable) \- Retinopathy (rare) RESPIRATORY \- Breathing abnormalities (variable) ABDOMEN Liver \- Liver abnormalities, mild (1 patient) GENITOURINARY External Genitalia (Male) \- Ambiguous genitalia (1 patient) \- Micropenis Kidneys \- Nephronophthisis (1 patient) SKELETAL Hands \- Polydactyly (variable) MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Hypotonia \- Ataxia \- Delayed psychomotor development \- Mental retardation \- Molar tooth sign MOLECULAR BASIS \- Caused by mutation in the 41-kD centrosomal protein gene (CEP41, 610523.0001 ) ▲ 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| JOUBERT SYNDROME 15 | c3280897 | 5,149 | omim | https://www.omim.org/entry/614464 | 2019-09-22T15:55:10 | {"doid": ["0110984"], "omim": ["614464", "213300"], "orphanet": ["475", "220493"], "synonyms": ["Cerebelloparenchymal disorder IV", "JS-O", "Classic Joubert syndrome", "Joubert-Boltshauser syndrome", "Joubert syndrome type A", "CPD IV", "Pure Joubert syndrome", "Joubert syndrome with retinopathy"], "genereviews": ["NBK1325"]} |
## Clinical Features
The typical setting-sun phenomenon consists of a downward rotation of the eyes with upper eyelid retraction and a rim of sclera visual above each iris. Haverkamp and Weimann (1995) described a family with 2 affected sisters and with 2 affected males and an affected female in a sibship related as first cousins through unaffected females ('maternal first cousins'). The episodes of the setting-sun signs became less frequent with time and disappeared after the first month of life. The only other description of familial benign setting-sun phenomenon was by Cernerud (1975). Haverkamp and Weimann (1995) interpreted the phenomenon as inherited delayed maturation of the visual-motor system. This phenomenon should be differentiated from the sporadic occurrence of isolated setting-sun sign in preterm babies.
Inheritance
Haverkamp and Weimann (1995) suggested multifactorial or autosomal dominant inheritance of setting sun phenomenon with variable expression.
Eyes \- Downward eye rotation with upper eyelid retraction and a rim of sclera visible above each iris Inheritance \- Multifactorial vs. 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| SETTING-SUN PHENOMENON, FAMILIAL BENIGN | c1833577 | 5,150 | omim | https://www.omim.org/entry/600598 | 2019-09-22T16:16:02 | {"mesh": ["C563470"], "omim": ["600598"]} |
## Description
Craniometadiaphyseal dysplasia (CRMDD) is characterized clinically by macrocephaly with frontal prominence, dental hypoplasia, and increased bone fragility. Diagnostic radiologic features include thin bones in the superior part of calvaria with prominent wormian bones, diaphyseal widening of the long tubular bones in early childhood with wide undermineralized metaphyses in older individuals, widened ribs and clavicles, and broadening of short tubular bones with increased transparency and thin cortices (summary by Dhar et al., 2010).
Clinical Features
The first case of craniometadiaphyseal dysplasia was reported by Schwarz (1960) as an example of craniometaphyseal dysplasia in an 18-year-old girl who was short, with frontal bossing, prominent mandible, and dental caries. She had a history of multiple fractures, severe scoliosis, bowing of the lower limbs, bilateral cubitus valgus with dislocated radial heads, coxa valga deformity, and deformities of the chest, pelvis, and elbows.
Williams et al. (1989) and Langer et al. (1991) described the same brother and sister, born to clinically normal, first-cousin parents of Polish ancestry, who presented with a large head, prominent forehead, delayed closure of a large anterior fontanel, mild downward slant of palpebral fissures, malar hypoplasia, high-arched palate, and hypoplastic teeth; characteristic skull changes including multiple wormian bones; wide long tubular bones without normal metaphyseal flaring; wide short tubular bones without normal diaphyseal constriction and sometimes with actual diaphyseal expansion; and wide ribs and clavicles. Langer et al. (1991) called this condition craniometadiaphyseal dysplasia, wormian bone type, and distinguished it from craniometaphyseal dysplasia (see CMDR, 218400). Although after infancy, the long tubular bones appear the same in both disorders, the skull changes of CRMDD, e.g., thin bone in the superior part of the calvaria and prominent wormian bones, are not present in CMDR. The short tubular bones are strikingly different in the 2 disorders. In infants with CMDR, the diaphyses of the long tubular bones are sclerotic, but the modeling is normal.
Santolaya et al. (1998) described a 4-year-old Moroccan boy, the first child of first-cousin parents, with craniometadiaphyseal dysplasia, wormian bone type. The patient had a large head with prominent forehead, skull changes showing multiple wormian bones, wide long tubular bones without the usual metaphyseal flare, wide short tubular bones without the normal diaphyseal constriction, and wide ribs and clavicles.
Dhar et al. (2010) provided a 25-year follow-up of the brother reported at the age of 8 years by Williams et al. (1989) and reviewed other reported cases. They recommended that patients with this condition get evaluated with bone density scans and hearing and ophthalmologic examinations on a regular basis because nerve impingement secondary to progressive bone deformities can be a problem.
Inheritance
Parental consanguinity in the families with craniometadiaphyseal dysplasia reported by Langer et al. (1991) and Santolaya et al. (1998) is consistent with autosomal recessive inheritance.
History
Gorlin et al. (1969) had suggested that the patient reported by Schwarz (1960) as an example of craniometaphyseal dysplasia and the patient reported by Lelek (1961) as an example of Camurati-Engelmann disease had the same distinct disorder. They proposed the designation Schwarz-Lelek syndrome. However, Hennekam et al. (2010) suggested that the patient reported by Lelek (1961) had craniometaphyseal dysplasia (see 122860).
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature HEAD & NECK Head \- Macrocephaly \- Large anterior fontanel \- Delayed closure of the anterior fontanel \- Prominent forehead Face \- Malar hypoplasia Ears \- Low-set ears Eyes \- Large eyes \- Downslanting palpebral fissure Mouth \- High palate \- Prognathism, mild Teeth \- Natal teeth \- High-arched palate \- Small teeth \- Crowded teeth \- Dental caries CHEST External Features \- Chest deformity secondary to scoliosis Ribs Sternum Clavicles & Scapulae \- Wide clavicles \- Wide ribs SKELETAL \- Fractures \- Poor diaphyseal constriction long tubular bones \- Poor metaphyseal flaring long tubular bones \- Wide short tubular bones \- Thin cortex osteopenia Skull \- Delayed ossification of cranial vault in infancy \- Multiple wormian bones \- Sclerosis of skull base, minor \- Absent paranasal sinuses and mastoids \- Occipital bony protuberance Spine \- Scoliosis Pelvis \- Distorted pelvis \- Wide pubis \- Wide ischia Limbs \- Lower limb bowing \- Cubitus valgus \- Coxa valga LABORATORY ABNORMALITIES \- Increased alkaline phosphatase ▲ Close
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*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| CRANIOMETADIAPHYSEAL DYSPLASIA | c0265292 | 5,151 | omim | https://www.omim.org/entry/269300 | 2019-09-22T16:22:28 | {"mesh": ["C537519"], "omim": ["269300"], "orphanet": ["85184"], "synonyms": []} |
negative attitudes and discrimination toward vegetarian and vegan people
Part of a series on
Discrimination
General forms
* Age
* Class (Caste)
* Physical Disability
* Education
* Economic
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* Genetics
* Hair texture
* Height
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* Looks
* Race / Ethnicity / Nationality
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Specific forms
Social
* Acephobia
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* Anti-albinism
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Manifestations
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* age
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Countermeasures
* Affirmative action
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* Human rights
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Related topics
* Allophilia
* Anti-cultural, anti-national, and anti-ethnic terms
* Bias
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* Dehumanization
* Diversity
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* autism
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* Second-generation gender bias
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* Social exclusion
* Social model of disability
* Social stigma
* Stereotype
* threat
* The talk
* White privilege
* v
* t
* e
Vegaphobia is an aversion to vegan people.[a] It is in the 21st century that it began to frame the phenomenon in the sociological sphere and makes its appearance veganphobia In 2020, a disproportionate talk about veganism in British national newspapers" took place in the United Kingdom, which examined 397 articles containing the terms "vegan", "vegans" and "veganism". The researchers found that 74.3% of the items are classified as "negatives"; 20.2% "neutral" and only 5.5% "positive". Negative items were in order of frequency: ridiculing veganism; characterize veganism as asceticism; affirming that veganism is difficult or impossible to sustain; describe veganism as a fashion; portray vegans as sentimentalists; defining vegans as hostile.[1]
Laura Wright claims that media organisations and wider discourse routinely mischaracterise vegan diets[7] and highlights situations where media outlets report the death of children from a 'vegan diet' rather than the neglect that was the actual cause.[8] However, Christophe Traïni writes that some vegan activists may present themselves "as members of an oppressed minority rebelling against 'vegephobia'".[9]
However, the application of the term "vegaphobia"—and the extent to which it can be compared to other forms of discrimination—remains a divisive issue,[6] with Sophie Wilkinson of Grazia opining that "...discrimination is about being treated differently for who you are, not for what you choose to do." and that discrimination against vegans (unlike sexism, racism, homophobia, etc.) doesn't tend to go beyond the level of microaggressions.[10]
At the 2013 International Animal Rights Conference, actress and producer Jola Cora, discussed the topic in a presentation called "Vegaphobia, what is it?"[11]
In 2018, a survey of British and American vegans from the weight-loss application Lifesum found eight out of ten respondents to have experienced some form of anti-vegan prejudice.[6]
## Bibliography[edit]
* Guadagnucci, Lorenzo (2012). Restiamo animali (in Italian). Terre di mezzo. ISBN 978-88-6189-224-8.
* Charles Patterson (2003). Un'eterna Treblinka. Il massacro degli animali e l'Olocausto (in Italian). Editori Riuniti. ISBN 978-8835953241.
* Horta, Oscar (2018). "Discrimination against vegans". Res Publica 24 (3): 359-73. doi:10.1007%2Fs11158-017-9356-3.
* Mannucci, Erica Joy (2008). La cena di Pitagora. Storia del vegetarianismo dall'antica Grecia a Internet (in Italian). Carocci editore. ISBN 978-88-430-4574-7.
* Cole, Matthew (2011). Vegafobia: discorsi dispregiativi sul veganismo nei giornali nazionali britannici (in Italian).
* Sigler, Pierre. L'exploitation animale est une question de société (in French).
* Oliver, David. Vegephobia is Speciesism.
## Notes[edit]
1. ^ [1][2][3][4][5][6]
## References[edit]
1. ^ a b Cole, Matthew; Morgan, Karen (1 March 2011). "Vegaphobia: derogatory discourses of veganism and the reproduction of speciesism in UK national newspapers". The British Journal of Sociology. 62 (1): 134–153. doi:10.1111/j.1468-4446.2010.01348.x. PMID 21361905.
2. ^ "Vegephobia, what is it? Why is it important to fight it? (Jola Cora) [IARC2013]". ar-conference.org.
3. ^ Griffin, Nathan Stephens (20 July 2017). Understanding Veganism: Biography and Identity. Springer. pp. 24, 47, 120. ISBN 9783319521022.
4. ^ Jones, R. C: (2016) Veganisms. In Castricano, J. & Simonsen, R. R. Critical Perspectives on Veganism. Palgrave Macmillan. p. 25
5. ^ Khara, Tani (7 November 2018). "Why do vegans have such bad reputations?". Australian Broadcasting Corporation. Retrieved 20 July 2019.
6. ^ a b c Krishnan, Manisha (26 November 2018). "There's a Term For Hating On Vegans And It's Vegaphobia". Vice Media. Retrieved 20 July 2019.
7. ^ Wright, Laura (2015). The Vegan Studies Project : Food, Animals, and Gender in the Age of Terror. EBSCOhost: University of Georgia Press.
8. ^ Laura Wright (1 October 2015). The Vegan Studies Project: Food, Animals, and Gender in the Age of Terror. University of Georgia Press. pp. 89–. ISBN 978-0-8203-4854-4.
9. ^ Traïni, Christophe; Throssell, Katharine. "Between disgust and moral indignation". Revue Française de Science Politique. 62 (4) – via cairn-int.info.
10. ^ Wilkinson, Sophie (3 December 2018). "No, Vegan-Based Discrimination Is Nonsense". Grazia. Retrieved 20 July 2019.
11. ^ VeganKanal (12 September 2013). "Vegephobia, what is it? Jola Cora at IARC 2013 Luxembourg" – via YouTube.
* v
* t
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Animal rights
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* Category ( 85 )
* v
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Veganism and vegetarianism
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Vegan
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Books,
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* An Essay on Abstinence from Animal Food, as a Moral Duty (1802)
* Vegetable Cookery (1812)
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* Moral Inquiries on the Situation of Man and of Brutes (1824)
* Nature's Own Book (1835)
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* What is Vegetarianism? (1886)
* Shelley's Vegetarianism (1891)
* Behind the Scenes in Slaughter-Houses (1892)
* Why I Am a Vegetarian (1895)
* Figs or Pigs? (1896)
* Thirty-nine Reasons Why I Am a Vegetarian (1903)
* The Meat Fetish (1904)
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* Ten Talents (1968)
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Related
* Vegetarian and vegan symbolism
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[[Category:Vega
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Vegaphobia | None | 5,152 | wikipedia | https://en.wikipedia.org/wiki/Vegaphobia | 2021-01-18T18:57:03 | {"wikidata": ["Q40800461"]} |
A rare, acquired, dermis elastic tissue disease characterized by asymptomatic, well-demarcated, symmetric patches and/or plaques of finely wrinkled skin arranged parallel to skin cleavage lines (type I), associated with perifollicular papular protrusions (type II) or with persistent reticular erythema (type III), occurring predominantly on the shoulders, trunk, back, and proximal extremities, associating, on histopathology, a selective loss of elastic tissue in the midreticular dermis. Erythema and/or urticaria may or may not precede wrinkly 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Mid-dermal elastolysis | None | 5,153 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=228299 | 2021-01-23T17:23:44 | {} |
A number sign (#) is used with this entry because of evidence that Reis-Bucklers corneal dystrophy (CDRB, or CDB1) is caused by heterozygous mutation in the TGFBI gene (601692) on chromosome 5q31.
The TGFBI gene is mutant in several other forms of corneal dystrophy, including Thiel-Behnke corneal dystrophy (CDTB, or CDB2; 602082), lattice type I corneal dystrophy (CDL1; 122200), lattice type IIIA corneal dystrophy (CDL3A; 608471), Avellino corneal dystrophy (ACD; 607541), and Groenouw type I corneal dystrophy (CDGG1; 121900).
Clinical Features
Paufique and Bonnet (1966) described a family with members in 3 generations affected by Reis-Buckler corneal dystrophy. Most of the affected persons also had strabismus. The cornea presented a 'dusty' opacity and a rough map-like surface with a peripheral condensation ring separated from the limbus by a narrow strip of normal cornea. The lesions are primarily in Bowman membrane with secondary involvement of the epithelium and superficial part of the stroma. Relapsing corneal erosions occur between ages 8 and 20 and again in more severe form at about 40 or 50 years. The ultrastructure was described by Rice et al. (1968) and Akiya and Brown (1971). Almost every epithelial cell, but especially the basal cells, showed degenerative changes, i.e., swollen mitochondria, large vacuoles, swelling and disruption of the endoplasmic reticulum. Bowman membrane was almost completely replaced by masses of disoriented collagen fibrils and smaller electron-dense fibrils whose composition and origin have not been determined.
Moller (1989) concluded that Reis-Bucklers corneal dystrophy may be the same entity as Groenouw type I granular corneal dystrophy.
To clarify whether Thiel-Behnke corneal dystrophy is a separate entity from Reis-Bucklers corneal dystrophy, Kuchle et al. (1995) examined 28 corneal specimens with a clinically suspected diagnosis of corneal dystrophy of the Bowman layer by light and electron microscopy and reviewed the literature. Eight specimens came from patients with a honeycomb-shaped pattern of opacities at the level of the Bowman layer. Study of these 8 specimens disclosed destruction of Bowman layer, a subepithelial fibrocellular tissue with an undulant configuration, absence of the epithelial basement membrane in many areas, and the presence of 'curly' collagen fibers with a diameter of 9 to 15 nm. Kuchle et al. (1995) concluded that 2 distinct autosomal dominant CDBs exist and proposed the designation CDB type I (geographic or 'true' Reis-Bucklers dystrophy) and CDB type II (honeycomb-shaped or Thiel-Behnke dystrophy). Eight corneas were characterized as CDB type II. Visual loss is significantly greater in CDB I, and recurrences after keratoplasty or keratectomy seem to be earlier and more extensive in CDB I. Most cases previously reported as Reis-Bucklers dystrophy were thought by Kuchle et al. (1995) to be CDB II.
Kobayashi and Sugiyama (2007) used in vivo laser confocal microscopy to investigate microstructures in patients with genetically confirmed Thiel-Behnke or Reis-Bucklers corneal dystrophy. In the Thiel-Behnke type, the deposits in the epithelial basal cell layer showed homogeneous reflectivity with round edges accompanying dark shadows. In contrast, deposits in the Reis-Bucklers type in the same cell layer showed extremely high reflectivity from small granular materials without any shadows in all cases. In each dystrophy, the Bowman layer was replaced totally with pathologic materials; the reflectivity of those materials is much higher in the Reis-Bucklers type than in the Thiel-Behnke type.
Clinical Management
Dinh et al. (1999) reviewed 50 excimer laser phototherapeutic keratectomy (PTK) procedures. Preoperative diagnoses included Reis-Bucklers dystrophy, granular dystrophy, anterior basement membrane dystrophy (121820), lattice dystrophy, and Schnyder crystalline dystrophy (121800). The authors concluded that PTK can restore and preserve useful visual function for a significant period of time in patients with anterior corneal dystrophies. Even though corneal dystrophies are likely to recur eventually after PTK, successful retreatment with PTK is possible.
Molecular Genetics
In 6 families with various forms of corneal dystrophy, Munier et al. (1997) identified missense mutations in the TGFBI gene. All the mutations occurred at the CpG dinucleotide of 2 arginine codons: arg555 to trp (R555W; 601692.0001) in a family with CDGG1, arg555 to gln (R555Q; 601692.0002) in a family with CDTB, arg124 to cys (R124C; 601692.0003) in 2 families with CDL1, and arg124 to his (R124H; 601692.0004) in 2 families with ACD. The observations established a common molecular origin of several 5q31-linked corneal dystrophies. The family with CDTB was initially described as having Reis-Buckler corneal dystrophy, but in a later report (Munier et al., 2002) the phenotype was reclassified as CDTB.
Okada et al. (1998) described an arg124-to-leu mutation (R124L; 601692.0007) mutation in a 25-year-old man with progressive subepithelial geographic opacities of the cornea. This was thought to be an example of 'true' Reis-Bucklers corneal dystrophy with geographic opacities rather than honeycomb-shaped opacities (CDTB).
Kim et al. (2002) studied the molecular properties of wildtype and mutant BIGH3 proteins: specifically, the R124L (CDRB), R124C (CDL1), R124H (ACD), R555W (CDGG1), and R555Q (CDTB) mutations commonly found in 5q31-linked corneal dystrophies. They found that the mutations did not significantly affect the fibrillar structure, interactions with other extracellular matrix proteins, or adhesion activity in cultured corneal epithelial cells. In addition, the mutations apparently produced degradation products similar to those of wildtype BIGH3. BIGH3 polymerizes to form a fibrillar structure and strongly interacts with type I collagen (see 120150), laminin (see 150320), and fibronectin (135600).
Tanhehco et al. (2006) reported 2 unrelated cases of Reis-Bucklers corneal dystrophy caused by spontaneous mutations in the TGFBI gene. Both children had had multiple corneal erosions, and neither had a family history of corneal dystrophy. Analysis of the TGFBI gene identified the R124L mutation in both children. The mutation was not found in any of the parents.
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*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| CORNEAL DYSTROPHY, REIS-BUCKLERS TYPE | c0339278 | 5,154 | omim | https://www.omim.org/entry/608470 | 2019-09-22T16:07:49 | {"doid": ["0060453"], "mesh": ["C535476"], "omim": ["608470"], "orphanet": ["98961"], "synonyms": ["Alternative titles", "REIS-BUCKLERS CORNEAL DYSTROPHY", "CORNEAL DYSTROPHY OF BOWMAN LAYER, TYPE I", "CORNEAL DYSTROPHY, GEOGRAPHIC", "GRANULAR CORNEAL DYSTROPHY, TYPE III"]} |
A number sign (#) is used with this entry because of evidence that Townes-Brocks syndrome-1 (TBS1) is caused by heterozygous mutation in the gene encoding the SALL1 putative transcription factor (602218) on chromosome 16q12.
There is also evidence that a Townes-Brocks-branchiootorenal-like syndrome is caused by heterozygous mutation in the SALL1 gene.
Description
Townes-Brocks syndrome-1 (TBS1) is characterized by the triad of imperforate anus, dysplastic ears, and thumb malformations. Minor features of the condition include hearing loss, foot malformations, renal impairment with or without renal malformations, genitourinary malformations, and congenital heart disease (Webb et al., 2017).
### Genetic Heterogeneity of Townes-Brocks Syndrome
Townes-Brocks syndrome-2 (TBS2; 617466) is caused by mutation in the DACT1 gene (607861) on chromosome 14q23.
Clinical Features
Townes and Brocks (1972) observed a father and 5 of his 7 children who had imperforate anus, triphalangeal thumbs, and other anomalies of the hands and feet, including fusion of metatarsals, absent bones, and supernumerary thumbs. Other features included mild sensorineural deafness, and lop ears. Reid and Turner (1976) described the same syndrome.
Kurnit et al. (1978) described autosomal dominant inheritance of a syndrome of anal stenosis, other anal abnormalities, deformed external ears and perceptive deafness, renal anomalies, including hypoplastic kidney, and radial dysplasia (REAR syndrome). The features are those of the VATER syndrome (192350), which has been subsequently expanded into the VACTERL syndrome (acronym for vertebral anomalies, anal atresia, congenital cardiac disease, tracheoesophageal fistula, renal anomalies, radial dysplasia, and other limb defects).
Walpole and Hockey (1982) reported cases. Monteiro de Pina-Neto (1984) reported a case in which congenital heart defect was also present and proposed that the cases of Silver et al. (1972) were instances of this syndrome rather than the Holt-Oram syndrome (142900).
Aylsworth (1985) observed the Townes-Brocks syndrome in a mother and 2 children. De Vries-Van der Weerd et al. (1988) described TBS in a father and son. The son, the proband, showed the full spectrum of anomalies, including imperforate anus, prominent perineal raphe, rectoperineal fistula, triphalangeal thumb, preaxial hexadactyly, syndactyly, clinodactyly, preauricular protuberances, hypoplastic 'satyr' ears, sensorineural hearing loss, and urorenal anomalies. In contrast, the father showed only limb anomalies, sensorineural hearing loss, and renal anomalies. Anorectal malformations, which are present in most patients with TBS, were absent in the father.
Ferraz et al. (1989) reported a sporadic case. The patient's 'satyr ear' and CT scans of the deformities in the ossicles of the ear were pictured. The cardiac lesion was ventricular septal defect. At birth the girl had been noted to have type I imperforate anus with rectovaginal fistula, bilateral supernumerary digits on the radial side of the thumb base, and incomplete soft tissue syndactyly between fingers 2 and 3 on the right. Bilateral symmetric mixed deafness was discovered at age 6 years. The maternal grandfather may have been affected, since he had deafness, polycystic kidneys, and a short proximal phalanx of the left fifth finger.
In a review of the Townes-Brocks syndrome, O'Callaghan and Young (1990) pointed out that patients may have a prominent midline perineal raphe extending from the site of the anal orifice to the scrotum. They pictured the feet of a mother and son, both showing hypoplastic third toes overlapped by the second and fourth toes, as well as a 'satyr' form of lopped ear.
Cameron et al. (1991) suggested that there may be an increase of mental retardation in persons with TBS. Ishikiriyama et al. (1996) also saw a boy with both TBS and mental retardation.
Serville et al. (1993) listed the main features of TBS as follows: abnormal placement of the anus, anal atresia or stenosis; auricular pits, fistulas, or tags; conductive and sensorineural deafness; dysplastic ears; hypoplastic or bifid thumbs; deviation of distal phalanges of the thumbs; triphalangeal thumbs; and cardiac and renal abnormalities. They noted that neither of the patients reported by Friedman et al. (1987) had thumb anomalies, but pointed to the fact that clinical variability is known in TBS.
Johnson et al. (1996) described a 3-generation family in which the grandmother and mother were thought to have Goldenhar syndrome (164210), but the birth of a grandson with typical features of TBS redirected the diagnosis to that possibility. The mother was of short stature with small ears, preauricular and tragal tags on the right and postauricular tag on the left, facial asymmetry, epibulbar dermoids bilaterally, micrognathia, and macrostomia with lateral extension more prominent on the right. The thumbs were triphalangeal with a previously removed, rudimentary, supernumerary digit that had been attached to the right thumb. Midline clefting of the uterus was reported. The anus was normal. The IQ at age 10 was 84; microcephaly was noted at the age of 24 years. The grandmother had small ears with preauricular tags, epibulbar dermoid on the right, and micrognathia without facial asymmetry. The thumbs were triphalangeal and the great toe on the left was bifid representing syndactyly of toes 1 and 2 or absence of 2. Genitourinary abnormalities included urethrostenosis and septate uterus. The anus showed redundant skin. Height was 147 cm. The grandson was born with an imperforate anus covered by a thin membrane requiring a minor surgical procedure. The left side of the face was smaller than the right. The ears were small with overfolding of the helix more prominent on the right which showed a small preauricular tag. Other findings were epibulbar dermoid on the left, triphalangeal thumbs with ulnar deviation.
Newman et al. (1997) reported a case of Townes-Brock syndrome in a male who presented at the age of 23 years with end-stage renal failure. He had severe hypertension and bilaterally small kidneys by ultrasound scan. Surgery had been performed after birth to correct anal stenosis. At that time the ears were noted to be low set with overfolded helices and bilateral preauricular tags, bilateral preaxial hexadactyly of the hands, and syndactyly of the third and fourth toes. Bilateral sensorineural deafness was noted at 3 years of age.
Kohlhase et al. (1998) reported 2 half-sibs with TBS, born of the same mother. Photographs illustrated the presence of duplicated triphalangeal left thumb and duplicated triphalangeal right thumb combined with a third dysplastic thumb. Dysplastic ears were also illustrated. The affected mother displayed low birth weight and presented with imperforate anus, preauricular tags, microtia and dysplastic ears, sensorineural hearing loss, bifid right thumb, and rudimentary bifid left thumb. Her son had imperforate anus type 3 with rectoperineal fistula, microtia and dysplastic ears, sensorineural hearing loss, bifid left and distally broadened right thumb. His sister likewise showed imperforate anus type 3 with rectovaginal fistula, preauricular tags, microtia and dysplastic ears, sensorineural hearing loss, bifid triphalangeal left thumb, and triple triphalangeal right thumb.
Doray et al. (1999) described 2 unrelated, apparently sporadic cases of Townes-Brocks syndrome.
Surka et al. (2001) described a 3-generation family in which 7 individuals had TBS confirmed by genetic analysis (602218.0008). Cardiac anomalies seen in this family included lethal truncus arteriosus in 1 patient and a lethal complicated defect that included pulmonary valve atresia in a second. These severe cardiac anomalies had not previously been reported in a familial case of TBS. On the basis of this family and a review of the literature, Surka et al. (2001) suggested that cardiac evaluation is warranted in all patients with this disorder. The authors stated that hypoplastic thumbs were observed in 2 individuals in their family and therefore should be considered a feature of TBS. In fact, the thumb anomalies as indicated by the photographs were bilateral triphalangeal thumbs in at least 2 individuals, a right hypoplastic thumb with absent distal phalanx and left preaxial polydactyly and triphalangeal thumb in one, and left preaxial polydactyly and triphalangeal thumb in another. A severely affected child who died at the age of 3 days from cardiac malformations had bilateral preaxial polydactyly.
Botzenhart et al. (2005) reported 13 unrelated families with TBS confirmed by genetic analysis. Rare phenotypic features included hypothyroidism, gastroesophageal reflux, vaginal aplasia with bifid uterus, cryptorchidism, bifid scrotum without hypospadia scrotalis, unilateral chorioretinal coloboma with loss of vision, Duane anomaly, dorsal hypoplasia of the corpus callosum, and umbilical hernia.
Sudo et al. (2010) reported a Japanese family in which the 4-year-old female proband had bilateral preauricular tags, bilateral preaxial polydactyly, syndactyly of the right toe, overriding toes of the left foot, anteriorly placed and stenosed anus, mild bilateral sensorineural hearing loss, ventricular septal defect, and small right kidney. Her mother and her maternal uncle, grandfather, and great aunt were also affected. Her mother had right preaxial polydactyly, anterior placement of the anus, small right kidney, and mild sensorineural hearing loss, whereas her uncle had right preaxial polydactyly, imperforate anus, and mild hearing loss. Her grandfather and great aunt had only unilateral preaxial polydactyly and deafness. The proband and her mother were found to be heterozygous for a frameshift mutation in the SALL1 gene. Sudo et al. (2010) noted that there was an anticipation-like increase in severity of the phenotype with each succeeding generation in this family, and stated that similar increases in clinical severity had been observed in other TBS families, frequently in patients who inherited the disease from their mothers.
Inheritance
Autosomal dominant inheritance of TBS is well established, with multiple cases of male-to-male transmission reported by Townes and Brocks (1972), Reid and Turner (1976), Kurnit et al. (1978) and de Vries-Van der Weerd et al. (1988).
Pathogenesis
Bozal-Basterra et al. (2018) showed that TBS-derived primary fibroblasts exhibit changes in SALL1 localization, a higher rate of ciliogenesis, abnormally elongated cilia, aberrant cilia disassembly, and SHH signaling defects. Through proximity proteomics, Bozal-Basterra et al. (2018) identified 2 main ciliogenesis suppressors, CCP110 (609544) and CEP97 (615864), as interactors of TBS-causing truncated SALL1. The higher rate of ciliogenesis detected in TBS-derived primary fibroblasts is consistent with an observed lower amount of CCP110 and CEP97 at the mother centriole in these fibroblasts compared with controls. The authors noted that truncated SALL1, alone or with full-length SALL1, sequesters CCP110 and CEP97, disrupting cilia formation and function. Bozal-Basterra et al. (2018) concluded that TBS might be considered a ciliopathy.
Cytogenetics
Serville et al. (1993) described TBS in an infant with a 2-break reciprocal translocation between chromosomes 5 and 16. They noted that Friedman et al. (1987) described father and daughter with this syndrome associated with a pericentric inversion of chromosome 16 with breakpoints at p11.2 and q12.1. Since 16p12.1 was the location of 1 of the breakpoints in the patient reported by Serville et al. (1993), they suggested that this may be the location of the gene for TBS.
Molecular Genetics
In 2 half-sibs with TBS, born of the same mother, and a sporadic TBS patient, Kohlhase et al. (1998) identified 2 different heterozygous mutations in the SALL1 gene (602218.0001; 602218.0002).
In a father and 2 daughters with features overlapping those of Townes-Brocks syndrome and branchiootorenal syndrome (113650), Engels et al. (2000) identified a mutation in the SALL1 gene (602218.0007). The daughters had dysplastic ears, hypoplastic kidneys with impaired renal function, gastroesophageal reflux, hypermetropia, and mild developmental delay. The father showed impaired renal function, dysplastic ears, and gastroesophageal reflux. None of the affected family members had anal or hand malformations. Engels et al. (2000) considered this family to demonstrate phenotypic overlap between the 2 conditions.
In 3 members of a nonconsanguineous German family who had only some features of Townes-Brocks syndrome, Albrecht et al. (2004) identified a mutation in the SALL1 gene (602218.0009). Characteristic features of TBS included preauricular tags, overfolded helices, hypospadias, and impaired renal function; 1 brother had only hypospadias and underriding third toes. None of the affected family members had the characteristic anal or hand malformations of TBS. Albrecht et al. (2004) considered the disorder in their patients to be different from that described by Engels et al. (2000).
Powell and Michaelis (1999) reviewed the clinical features and molecular basis of Townes-Brocks syndrome.
Botzenhart et al. (2005) stated that 35 mutations had been identified in the SALL1 gene. Most mutations occur 5-prime to or within the region encoding the first double zinc finger.
Kosaki et al. (2007) analyzed the SALL1 gene in 2 sisters, 1 with a Townes-Brocks syndrome phenotype and the other exhibiting features of Goldenhar syndrome (see hemifacial microsomia, 164210), and identified heterozygosity for a mutation (L419X; 602218.0010). Their mother, who had dysplastic external ears but was otherwise normal, also carried the mutation. The authors noted that Johnson et al. (1996) had previously reported an affected family member with a Goldenhar syndrome-like phenotype in a 3-generation TBS family.
Genotype/Phenotype Correlations
Furniss et al. (2007) reported a heterozygous mutation in the SALL1 gene (995delC; 602218.0011) in a patient with a relatively severe form of Townes-Brocks syndrome. The patient had bilateral preaxial polydactyly, imperforate anus, rectal atresia, hypospadias, and overfolded helices. The mutation was found to be resistant to nonsense-mediated decay. Furniss et al. (2007) concluded that the phenotype was caused by a truncated SALL1 protein acting in a dominant-negative manner. These findings were in contrast to another SALL1 mutation (602218.0012) that did undergo nonsense-mediated decay and was associated with a milder phenotype of Townes-Brocks syndrome.
INHERITANCE \- Autosomal dominant HEAD & NECK Head \- Microcephaly Ears \- Overfolding of superior helix \- Large ears \- Preauricular tags \- Preauricular pits \- Microtia \- Satyr ear \- Sensorineural hearing loss Eyes \- Chorioretinal coloboma (rare) \- Duane anomaly (rare) CARDIOVASCULAR Heart \- Tetralogy of Fallot \- Ventricular septal defect ABDOMEN Gastrointestinal \- Duodenal atresia \- Imperforate anus \- Anal stenosis \- Anterior placement of anus \- Rectovaginal/rectoperineal fistula \- Gastroesophageal reflux \- Umbilical hernia GENITOURINARY External Genitalia (Male) \- Hypospadias \- Bifid scrotum \- Prominent midline perineal raphe Internal Genitalia (Male) \- Cryptorchidism Internal Genitalia (Female) \- Rectovaginal fistula \- Vaginal aplasia \- Bifid uterus Kidneys \- Hypoplastic kidneys \- Multicystic kidneys \- Dysplastic kidneys \- Renal failure Ureters \- Vesicoureteral reflux Bladder \- Urethral valves SKELETAL Hands \- Broad thumb \- Bifid thumb \- Triphalangeal thumb \- Preaxial polydactyly \- Pseudoepiphyses of second metacarpal \- Fusion of triquetrum and hamate \- Absent triquetrum and navicular bones \- 2-3 and 3-4 finger syndactyly Feet \- Fusion of metatarsals \- Short metatarsals \- Absent/hypoplastic third toe \- Fifth toe clinodactyly \- 3-4 toe syndactyly NEUROLOGIC Central Nervous System \- Mental retardation (rarely noted) ENDOCRINE FEATURES \- Hypothyroidism (rare) MOLECULAR BASIS \- Caused by mutation in the sal-like 1 gene (SALL1, 602218.0001 ) ▲ Close
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*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| TOWNES-BROCKS SYNDROME 1 | c0265246 | 5,155 | omim | https://www.omim.org/entry/107480 | 2019-09-22T16:44:54 | {"doid": ["0050887"], "mesh": ["C536974"], "omim": ["107480"], "orphanet": ["857"], "synonyms": ["Alternative titles", "RENAL-EAR-ANAL-RADIAL SYNDROME", "REAR SYNDROME", "ANUS, IMPERFORATE, WITH HAND, FOOT, AND EAR ANOMALIES", "DEAFNESS, SENSORINEURAL, WITH IMPERFORATE ANUS AND THUMB ANOMALIES"], "genereviews": ["NBK1445"]} |
A number sign (#) is used with this entry because of evidence that rare cases of primary bile acid malabsorption (PBAM) are caused by compound heterozygous mutation in the SLC10A2 gene (601295) on chromosome 13q33.
Description
Primary bile acid malabsorption is an intestinal disorder associated with chronic watery diarrhea, excess fecal bile acids, and steatorrhea. Bile acid malabsorption has been classified into 3 main types depending on the etiology. Types 1 and 3 are secondary disorders: type 1 is due to ileal dysfunction resulting from Crohn disease or ileal resection, and type 3 is secondary to other conditions, including cholecystectomy, post-vagotomy, celiac disease, and pancreatic insufficiency. Type 2 bile acid malabsorption is a primary congenital disorder, including the rare type due to mutations in the SLC10A2 gene (review by Pattni and Walters, 2009).
Clinical Features
Hess Thaysen and Pedersen (1976) described several patients who had chronic lifelong watery diarrhea and excessive bile acid loss, without other ileal pathology. The diarrhea resolved upon bile acid sequestration with cholestyramine.
Heubi et al. (1979, 1982) reported a case study of a boy who presented 48 hours after birth with severe diarrhea, steatorrhea, and malabsorption, requiring parenteral nutrition. Intestinal absorption of bile acid was nearly absent and resulted in a small bile acid pool size, a low interluminal bile acid concentration, and severe malabsorption of water and fat. Ileal biopsies showed no active bile acid transport. The findings were consistent with a congenital transport defect that includes absence of active ileal bile acid transport presenting as diarrhea in infancy. In a follow-up of this patient, Oelkers et al. (1997) stated that he had consistently low plasma LDL cholesterol levels and no family history of the disorder. Heubi et al. (1982) described an apparent familial defect in active ileal bile acid transport.
At the other extreme, a child with marked bile acid malabsorption but with almost normal growth and development, nearly normal fat absorption, and a moderately well-maintained bile acid pool, was described by Jonas et al. (1986). This patient had a 15-fold increase in bile acid synthesis that was adequate to maintain pool size, interluminal bile acids, and fat absorption. This report indicated that the clinical phenotype apparently can vary from severe diarrhea, fat malabsorption, and malnutrition, to modest diarrhea without significant fat malabsorption. In a review, Small (1997) suggested that the bile acid malabsorption and the variable severity could represent mutations in any of the main players involved in ileal bile transport.
Molecular Genetics
Small et al. (1972) suggested that a genetic defect in the predicted bile acid receptor in the ileum would lead to diarrhea and/or steatorrhea and suggested that bile acid turnover and fecal bile acid excretion be studied in patients with unexplained diarrhea.
In the patient with PBAM reported by Heubi et al. (1979, 1982), Oelkers et al. (1997) identified compound heterozygosity for 2 mutant SLC10A2 alleles (601295.0001 and 601295.0002). In vitro functional expression assays in transfected COS cells showed that the mutant proteins had abolished transport activity for conjugated bile acids. The findings of Oelkers et al. (1997) established that SLC10A2 mutations can cause PBAM and underscored the role of the ileal sodium/bile acid cotransporter in intestinal reclamation of bile acids. The patient's unaffected son was heterozygous for 1 of the alleles, consistent with autosomal recessive inheritance.
Heterogeneity
Montagnani et al. (2006) reported a 3-generation Swedish family in which 3 individuals had chronic diarrhea, especially after meals. The patients' ages were 67, 39, and 18 years. The 2 older patients reported onset as an adult and as a teenager, respectively. Treatment of 2 patients with cholestyramine resulted in clinical improvement. Two patients studied showed decreased retention of a radiolabeled bile acid and increased levels of a bile acid synthesis precursor, consistent with a diagnosis of 'idiopathic bile acid malabsorption.' Mutation analysis excluded mutations in the SLC10A2, NR1H4 (603826), and PPARA (170998) genes. The findings argued against defective ileal uptake of bile acids as the cause of bile acid malabsorption in these patients. Montagnani et al. (2001) also excluded mutations in the SLC10A2 gene in 13 patients with adult-onset idiopathic bile acid malabsorption.
INHERITANCE \- Autosomal recessive GROWTH Other \- Poor growth \- Failure to thrive ABDOMEN Gastrointestinal \- Watery diarrhea, chronic \- Steatorrhea \- Increased fecal bile acid \- Bile acid malabsorption in the ileum LABORATORY ABNORMALITIES \- Decreased LDL cholesterol MISCELLANEOUS \- Onset in infancy \- Variable severity \- Rare disorder MOLECULAR BASIS \- Caused by mutation in the solute carrier family 10 (sodium/bile acid cotransporter family), member 2 gene (SLC10A2, 601295.0001 ) ▲ Close
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*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| BILE ACID MALABSORPTION, PRIMARY | c2750087 | 5,156 | omim | https://www.omim.org/entry/613291 | 2019-09-22T15:59:04 | {"mesh": ["C567652"], "omim": ["613291"]} |
For the pupillary defect, see Marcus Gunn pupil.
Marcus Gunn phenomenon
Other namesMarcus Gunn jaw-winking or Trigemino-oculomotor synkinesis
Nerves of the orbit, and the ciliary ganglion. Side view. (Trigeminal nerve and oculomotor nerve both visible)
SpecialtyOphthalmology neurology
Marcus Gunn phenomenon is an autosomal dominant condition with incomplete penetrance, in which nursing infants will have rhythmic upward jerking of their upper eyelid. This condition is characterized as a synkinesis: when two or more muscles that are independently innervated have either simultaneous or coordinated movements.[1][2]
Common physiologic examples of synkineses occur during sucking, chewing, or conjugate eye movements. There are also several abnormal cranial nerve synkineses, both acquired and congenital. Marcus Gunn jaw-winking is an example of a pathologic congenital synkinesis.
First described by the ophthalmologist Marcus Gunn in 1883,[3] this condition presents in approximately 5% of neonates with congenital ptosis. This condition has been associated with amblyopia (in 54% of cases), anisometropia (26%), and strabismus (56%).
## Contents
* 1 Presentation
* 1.1 Behavioral and social implications
* 2 Pathophysiology
* 3 Treatment
* 4 Inverse Marcus Gunn phenomenon
* 5 References
* 6 External links
## Presentation[edit]
An affected young woman demonstrating The Marcus Gunn Jaw Wink Phenomenon. The woman cannot control her eyelids while sucking on a straw. This is a particularly mild case.
### Behavioral and social implications[edit]
Although treatment may be unnecessary, there may be social implications, especially in young children when venturing from a supportive home environment to a public environment (e.g., starting school). Continued support, including monitoring behavior and educating the child about his or her appearance as seen by others, is encouraged. Gradual or sudden withdrawal from interaction with others is a sign that may or may not be related to such behavior. Studies are being conducted to elucidate these implications.[citation needed]
## Pathophysiology[edit]
It has been postulated that the synkinesis is due to damage to cranial nerve nuclei, caused by peripheral nerve injury and the nuclear lesion releases evolutionarily older [neural] mechanisms with their tendency toward associated movements, and so primitive reflexes are not inhibited.
Marcus Gunn jaw-winking is an exaggeration of a very weak physiologic co-contraction that has been disinhibited secondary to a congenital brain stem lesion. The stimulation of the trigeminal nerve by contraction of the pterygoid muscles of jaw results in the excitation of the branch of the oculomotor nerve that innervates the levator palpebrae superioris ipsilaterally (on the same side of the face), so the patient will have rhythmic upward jerking of their upper eyelid.
There are two major groups of trigemino-oculomotor synkineses:
1) External pterygoid-levator synkinesis is when the eyelid raises upon:
* Jaw thrust to opposite side (homolateral external pterygoid)
* Jaw is projected forward (bilateral external pterygoid)
* Mouth is opened widely
2) Internal pterygoid-levator synkinesis is when the eyelid raises upon teeth clenching
External pterygoid-levator synkinesis is the more common group.
## Treatment[edit]
Treatment is usually unnecessary. In severe cases, surgery with a bilateral levator excision and frontalis brow suspension may be used.[4]
## Inverse Marcus Gunn phenomenon[edit]
Inverse Marcus Gunn phenomenon is a rare condition[5] that causes the eyelid to fall upon opening of the mouth. In this case, trigeminal innervation to the pterygoid muscles of the jaw is associated with an inhibition of the branch of the oculomotor nerve to the levator palpebrae superioris, as opposed to stimulation in Marcus Gunn jaw-winking.
## References[edit]
1. ^ Yamada K, Hunter DG, Andrews C, Engle EC (September 2005). "A novel KIF21A mutation in a patient with congenital fibrosis of the extraocular muscles and Marcus Gunn jaw-winking phenomenon". Arch. Ophthalmol. 123 (9): 1254–9. doi:10.1001/archopht.123.9.1254. PMID 16157808.[permanent dead link]
2. ^ Cates CA, Tyers AG (2008). "Results of levator excision followed by fascia lata brow suspension in patients with congenital and jaw-winking ptosis". Orbit. 27 (2): 83–9. doi:10.1080/01676830701376072. PMID 18415867.
3. ^ Gunn RM. Congenital ptosis with peculiar associated movements of the affected lid. Trans Ophthal Soc UK. 1883;3:283-7.
4. ^ Ibrahim HA (2007). "Use of the levator muscle as a frontalis sling". Ophthal Plast Reconstr Surg. 23 (5): 376–80. doi:10.1097/IOP.0b013e3181379e20. PMID 17881988.
5. ^ Prakash MV, Radhakrishnan M, Yogeshwari A, Nazir W, Maragatham K, Natarajan K (June 2002). "Inverse Marcus Gunn phenomenon". Indian J Ophthalmol. 50 (2): 142–4. PMID 12194575.
## External links[edit]
Classification
D
* ICD-10: Q07.8
* OMIM: 154600
* MeSH: C535908 C535908, C535908
External resources
* eMedicine: article/1213228
* v
* t
* e
Congenital malformations and deformations of eyes
Adnexa
Eyelid
* Ptosis
* Ectropion
* Entropion
* Distichia
* Blepharophimosis
* Ablepharon
* Marcus Gunn phenomenon
Lacrimal apparatus
* Congenital lacrimal duct obstruction
Globe
Entire eye
* Anophthalmia (Cystic eyeball, Cryptophthalmos)
* Microphthalmia
Lens
* Ectopia lentis
* Aphakia
Iris
* Aniridia
Anterior segment
* Axenfeld–Rieger syndrome
Cornea
* Keratoglobus
* Megalocornea
Other
* Buphthalmos
* Coloboma (Coloboma of optic nerve)
* Hydrophthalmos
* Norrie disease
*[v]: View this template
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*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Marcus Gunn phenomenon | c0266521 | 5,157 | wikipedia | https://en.wikipedia.org/wiki/Marcus_Gunn_phenomenon | 2021-01-18T19:09:03 | {"gard": ["6972"], "mesh": ["C535908"], "umls": ["C0266521"], "orphanet": ["91412"], "wikidata": ["Q1476789"]} |
Alpers syndrome is a progressive neurologic disorder that begins during childhood and is complicated in many instances by serious liver disease. Symptoms include increased muscle tone with exaggerated reflexes (spasticity), seizures, and loss of cognitive ability (dementia). Most often Alpers syndrome is caused by mutations in the POLG gene.
*[v]: View this template
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*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Alpers syndrome | c0205710 | 5,158 | gard | https://rarediseases.info.nih.gov/diseases/5783/alpers-syndrome | 2021-01-18T18:02:11 | {"mesh": ["D002549"], "omim": ["203700"], "orphanet": ["726"], "synonyms": ["Alpers disease", "Alpers diffuse degeneration of cerebral gray matter with hepatic cirrhosis", "Alpers progressive infantile poliodystrophy", "Poliodystrophia cerebri progressiva", "Progressive cerebral poliodystrophy", "Diffuse cerebral degeneration in infancy", "Alpers-Huttenlocher syndrome", "Neuronal degeneration of childhood with liver disease, progressive", "PNDC", "Infantile poliodystrophy"]} |
## Description
The atherogenic lipoprotein phenotype (ALP) is a common heritable trait characterized by a preponderance of small, dense low density lipoprotein (LDL) particles (subclass pattern B), increased levels of triglyceride-rich lipoproteins, reduction in high density lipoprotein, and a 3-fold increased risk of myocardial infarction (summary by Nishina et al., 1992).
The so-called atherogenic lipoprotein phenotype was shown by Austin et al. (1988) to be independently associated with an increased risk for coronary artery disease. Allayee et al. (1998) concluded, furthermore, that there is a genetically based association between familial combined hyperlipidemia (FCHL; 144250) and small, dense LDL particles and that the genetic determinants for LDL particle size are shared, at least in part, among FCHL families and the more general population at risk for coronary artery disease. Juo et al. (1998) concluded from a bivariate segregation analysis of small, dense LDL particles and elevated apolipoprotein B levels (APOB; 107730), which are commonly found together in members of FCHL families, that the 2 traits share a common major gene plus individual polygenic components. The common major gene was estimated to explain 37% of the variance of adjusted LDL particle size and 23% of the variance of adjusted apoB levels.
Mapping
Nishina et al. (1992) found close linkage between the atherogenic lipoprotein phenotype and the LDL receptor locus; maximum lod = 4.07 at theta = 0.04, assuming 100% penetrance of the ALP pattern B, and 4.27 at a recombination fraction of 0.0, assuming 90% penetrance of pattern B. The gene, which may be the same as the LDLR gene (606945), was symbolized ATHS (for atherosclerosis susceptibility). It appeared to be located distal to D19S76 near or at the LDL receptor locus.
Small dense LDL particles carry a 3-fold increased risk for coronary artery disease. By utilizing nonparametric quantitative sib-pair and relative-pair-analysis methods in coronary artery disease families, Rotter et al. (1996) confirmed linkage to the LDLR locus (P = 0.008). No evidence of linkage could be found to 6 candidate gene loci: APOB, APOA2, Lp(a), APOE, lipoprotein lipase, and high-density lipoprotein-binding protein (142695). Significant evidence for linkage was found with the CETP locus on chromosome 16 (118470) and the SOD1 locus on chromosome 6 (147450). A suggestion of linkage was found with the APOA1/APOC3/APOA4 cluster on chromosome 11.
### Associations Pending Confirmation
To determine whether genetic variation in the TNFR1 gene contributes to aging-related atherosclerosis, Zhang et al. (2010) performed a case-control association study of coronary artery disease (CAD) with 16 TNFR1 (191190) SNPs in 1,330 subjects from a coronary angiography database. Two TNFR1 SNPs were significantly associated with CAD in subjects older than 55 years, and this association was supported by analysis of a set of 759 independent CAD cases. In multiple linear regression analysis, accounting for TNFR1 SNP rs4149573 significantly altered the relationship between aging and CAD index among 1,811 subjects from the coronary angiography database. In a mouse model of atherosclerosis, Zhang et al. (2010) demonstrated that arterial wall aging-dependent acceleration of atherosclerosis was abrogated when arterial walls lacked TNFR1.
Molecular Genetics
Naggert et al. (1997) followed up on the family study showing tight linkage of the atherogenic lipoprotein phenotype to the LDL receptor locus (LDLR; 606945) on 19p13.2. To test whether a mutation in the structural portion of the LDLR gene could be responsible for the phenotype, they sequenced the exons of the receptor-binding domain for each pair of parents in the 11 pedigrees. For the remaining LDLR coding region, exons as well as cloned LDLR cDNAs were sequenced for selected members of the pedigrees. No mutations that changed the amino acid sequence of the LDLR were found. They concluded that a mutant allele of LDLR is not likely to be responsible for ALP.
Cardiac \- Increased myocardial infarction risk Lab \- Preponderance of small, dense low density lipoprotein (LDL) particles (subclass pattern B) \- Increased triglyceride-rich lipoproteins \- Reduced high density lipoprotein Inheritance \- Autosomal dominant \- ? same as LDLR ▲ Close
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*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| ATHEROSCLEROSIS SUSCEPTIBILITY | c1531719 | 5,159 | omim | https://www.omim.org/entry/108725 | 2019-09-22T16:44:40 | {"omim": ["108725"], "synonyms": ["Alternative titles", "ATHEROGENIC LIPOPROTEIN PHENOTYPE"]} |
## Clinical Features
Richards and Rundle (1959) described a family in which 5 of 13 offspring of a marriage of first cousins once removed had mental retardation, underdevelopment of secondary sex characteristics, deafness, ataxia, and peripheral muscle wasting. The onset of deafness and ataxia was in early infancy, and all were mute. Laboratory studies showed increased urinary excretion of beta-aminoisobutyric acid (see 210100), and low urinary excretion of neutral 17-ketosteroids. The condition progressed in childhood but eventually became static. Richards and Rundle (1959) found in the literature a description of a brother and sister who probably had the same condition (Koennecke, 1919).
Sylvester (1972) reported postmortem examination of 2 of the sibs reported by Richards and Rundle (1959). A woman had died at age 38 years of status epilepticus, and a man at age 29 years from bronchopneumonia. The ovaries were abnormal and consisted only of fibrous tissue without any follicles, and the testicles showed spermatogenic arrest. The inner ear and cochlea showed atrophy of the neuroepithelium and degeneration of spiral ganglion cells. The olivocerebellar, spinocerebellar, dorsal columns, and corticospinal tracts all showed myelin loss, and fibrous gliosis was present throughout the brainstem and cerebellum. Neuronal loss was found in the dentate nuclei. The neuropathologic findings suggested Roussy-Levy syndrome (180800). See Berman et al. (1974) and 208850 for a similar disorder.
Inheritance
The transmission pattern of the ataxia-deafness-mental retardation syndrome in the family reported by Richards and Rundle (1959) was consistent with autosomal recessive inheritance.
INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Sensorineural deafness GENITOURINARY \- Hypogonadism External Genitalia (Male) \- Spermatogenic arrest Internal Genitalia (Female) \- Ovaries lack follicles SKELETAL Feet \- Pes planus \- Pes cavus \- Pes equinovarus MUSCLE, SOFT TISSUES \- Muscle atrophy NEUROLOGIC Central Nervous System \- Delayed psychomotor development, severe \- Mental retardation \- Cerebellar ataxia \- Loss of independent ambulation \- Mutism \- Cerebellar degeneration \- Atrophy of the spinal cord and cerebellar tracts Peripheral Nervous System \- Areflexia Behavioral Psychiatric Manifestations \- Aggression \- Tantrums ENDOCRINE FEATURES \- Hypogonadotropic hypogonadism \- Primary amenorrhea LABORATORY ABNORMALITIES \- Low urinary excretion of neutral 17-ketosteroids MISCELLANEOUS \- Onset in infancy \- Progressive disorder ▲ 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| RICHARDS-RUNDLE SYNDROME | c0796136 | 5,160 | omim | https://www.omim.org/entry/245100 | 2019-09-22T16:26:05 | {"mesh": ["C535674"], "omim": ["245100"], "orphanet": ["1399"], "synonyms": ["Alternative titles", "ATAXIA-DEAFNESS-MENTAL RETARDATION SYNDROME"]} |
A number sign (#) is used with this entry because of evidence that mitochondrial complex I deficiency nuclear type 7 (MC1DN7) is caused by homozygous mutation in the NDUFV2 gene (600532) on chromosome 18p11.
For a discussion of genetic heterogeneity of mitochondrial complex I deficiency, see 252010.
Clinical Features
Benit et al. (2003) reported a male infant, born to first-cousin parents of African ancestry, with isolated complex I deficiency. The patient presented at 5 days of life with hypertrophic cardiomyopathy, truncal hypotonia, and encephalopathy.
Pagniez-Mammeri et al. (2009) reported a patient (patient 1) with MC1DN7 who presented with hypertrophic cardiomyopathy and encephalopathy.
Cameron et al. (2015) reported 5 patients from 2 unrelated families with MC1DN7. Two infant sibs in 1 family presented with hypertrophic cardiomyopathy and lactic acidosis and died in the first days or months of life. Muscle and fibroblasts tissues from the patients showed increased lactate:pyruvate ratios and/or isolated complex I deficiency. Brain imaging of 1 of the patients did not show evidence of Leigh syndrome. Three sibs in a second family with isolated complex I deficiency presented in infancy with seizures and developmental regression. Other variable features included spasticity, microcephaly, nystagmus, and optic atrophy. Brain imaging in these patients showed progressive brain atrophy and changes in the basal ganglia consistent with Leigh syndrome. One died at age 10 year, 1 was in a vegetative state by age 3 and was still alive at age 32, and the third died at 19 months of age.
Molecular Genetics
In a male infant, born to first-cousin parents of African ancestry, with isolated complex I deficiency, Benit et al. (2003) identified a 4-bp deletion of nucleotides 5 to 8 at the 5-prime end of IVS2 of the NDUFV2 gene, resulting in skipping of exon 2 (600532.0002). Benit et al. (2003) stated that whereas mutations in a number of genes encoding complex I subunits result in neurologic symptoms, hypertrophic cardiomyopathy and encephalopathy have been described previously only with a mutation in NDUFS2 (Loeffen et al., 2001; see 602985.0001).
Pagniez-Mammeri et al. (2009) identified a homozygous 4-bp deletion (IVS2+5_+8delGTAA) in the NDUFV2 gene (600532.0002) in a patient (patient 1) with MC1DN7 who presented with hypertrophic cardiomyopathy and encephalopathy. The mutation was the same as that reported by Benit et al. (2003) in an unrelated individual.
In 2 infant sibs with lethal MC1DN7 manifest as hypertrophic cardiomyopathy, Cameron et al. (2015) identified compound heterozygosity for 2 mutations in the NDUFV2 gene (c.IVS2+1delGTAA, 600532.0002 and c.669_670insG, 600532.0003). The mutations were found by whole-exome sequencing. Patient mitochondria showed 25% residual NDUFV2 protein levels compared to controls. Two sibs from another family with MC1DN7 manifest as early-onset seizures and Leigh syndrome were subsequently found to be homozygous for the c.IVS2+1delGTAA mutation by direct sequencing of the gene in 10 additional families. Parental DNA was not studied in either family.
INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive HEAD & NECK Head \- Microcephaly Eyes \- Nystagmus \- Optic atrophy CARDIOVASCULAR Heart \- Hypertrophic cardiomyopathy (in some patients) MUSCLE, SOFT TISSUES \- Hypotonia \- Skeletal muscle biopsy shows variation in fiber size \- Atrophic fibers \- Subsarcolemmal accumulation of mitochondria NEUROLOGIC Central Nervous System \- Encephalopathy \- Impaired psychomotor development \- Developmental regression \- Spasticity \- Seizures, early-onset (in some patients) \- Brain atrophy \- Abnormalities consistent with Leigh syndrome seen on brain imaging (in some patients) METABOLIC FEATURES \- Lactic acidosis LABORATORY ABNORMALITIES \- Mitochondrial respiratory complex I deficiency in various tissues \- Increased lactate:pyruvate ratio MISCELLANEOUS \- Onset in infancy \- Variable features \- Early death may occur MOLECULAR BASIS \- Caused by mutation in the NADH-ubiquinone oxidoreductase flavoprotein 2 gene (NDUFV2, 600532.0002 ) ▲ 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 7 | c2936907 | 5,161 | omim | https://www.omim.org/entry/618229 | 2019-09-22T15:43:02 | {"mesh": ["C537475"], "omim": ["618229"], "orphanet": ["2609", "255241"]} |
## Summary
### Clinical characteristics.
Citrullinemia type I (CTLN1) presents as a clinical spectrum that includes an acute neonatal form (the "classic" form), a milder late-onset form (the "non-classic" form), a form without symptoms or hyperammonemia, and a form in which women have onset of severe symptoms during pregnancy or post partum. Distinction between the clinical forms is based on clinical findings and is not clear-cut.
Infants with the acute neonatal form appear normal at birth. Shortly thereafter, they develop hyperammonemia and become progressively lethargic, feed poorly, often vomit, and may develop signs of increased intracranial pressure (ICP). Without prompt intervention, hyperammonemia and the accumulation of other toxic metabolites (e.g., glutamine) result in increased ICP, increased neuromuscular tone, spasticity, ankle clonus, seizures, loss of consciousness, and death. Children with the severe form who are treated promptly may survive for an indeterminate period of time, but usually with significant neurologic deficits.
The late-onset form may be milder than that seen in the acute neonatal form, for unknown reasons. The episodes of hyperammonemia are similar to those seen in the acute neonatal form, but the initial neurologic findings may be more subtle because of the older age of the affected individuals.
### Diagnosis/testing.
The diagnosis of CTLN1 is established in a proband with elevated plasma ammonia concentration (>150 µmol/L; may range to ≥2000-3000 µmol/L) and plasma citrulline concentration (usually >1000 µmol/L) and/or by the identification of biallelic pathogenic variants in ASS1 on molecular genetic testing.
### Management.
Treatment of manifestations: Acute management of hyperammonemia involves rapidly lowering plasma ammonia concentration using pharmacologic nitrogen scavenger therapy (sodium benzoate, sodium phenylacetate, and arginine) or hemodialysis, if scavenger therapy fails; reversal of catabolism via intravenous glucose infusion and intralipids or protein-free enteral nutrition, if tolerated; and control of intracranial pressure.
Chronic management involves lifelong dietary management to maintain plasma ammonia concentration lower than100 µmol/L and near-normal plasma glutamine concentration; oral administration of sodium phenylbutyrate or glycerol phenylbutyrate; L-carnitine to prevent systemic hypocarnitinemia. Liver transplantation, the only known cure for CTLN1, is best performed between age three months (and/or attainment of 5 kg body weight) and one year to decrease complications and improve survival; liver transplantation does not reverse any neurologic sequelae present at the time of transplant.
Prevention of secondary complications: Medical attention during intercurrent infections to prevent hyperammonemia; routine vaccinations including annual influenza vaccine.
Surveillance: Routine follow up in a metabolic clinic; monitoring for hyperammonemia and secondary deficiency of essential amino acids; monitoring older individuals for signs of impending hyperammonia (i.e., mood changes, headache, lethargy, nausea, vomiting, refusal to feed, ankle clonus) and elevated plasma glutamine concentration. Monitoring should be frequent in neonates and infants, based on disease severity, but may be extended to every six months to annually in older individuals, depending on clinical stability.
Agents/circumstances to avoid: Excess protein intake; exposure to communicable diseases.
Evaluation of relatives at risk: In utero diagnosis if the pathogenic variants in the family are known permits appropriate oral therapy beginning with the first feeds. Alternatively, sibs should be evaluated on day one of life by measurement of plasma concentrations of ammonia and citrulline; elevation of either above acceptable levels (ammonia >100 µmol/L or plasma citrulline >~100 µmol/L) is sufficient evidence to initiate treatment.
### Genetic counseling.
Citrullinemia type I is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal diagnosis for pregnancies at increased risk are possible if the pathogenic variants in the family are known.
## Diagnosis
Citrullinemia type I (CTLN1) results from deficiency of the enzyme argininosuccinate synthase, the third step in the urea cycle, in which citrulline is condensed with aspartate to form arginosuccinic acid (see Urea Cycle Disorders Overview Figure 1).
### Suggestive Findings
Citrullinemia type I (CTLN1) should be suspected in individuals with the following newborn screening results, clinical features (by age), and supportive laboratory findings.
#### Newborn Screening Results
Elevated citrulline is detected in dried blood spots on newborn screen by tandem mass spectroscopy (MS/MS). Note: As of this writing, all states include CTLN1 in their newborn screening programs.
#### Clinical Features
Neonatal presentation. Sign and symptoms classically occur within the first week of life while on a full protein diet:
* Increasing lethargy
* Somnolence
* Refusal to feed
* Vomiting
* Tachypnea
* Stroke
* Increased intracranial pressure (secondary to hyperammonemia) resulting in increased neuromuscular tone, spasticity, and ankle clonus
Non-classic presentation. Signs and symptoms may occur at any age and may not present as acutely as in the neonate:
* Recurrent lethargy and somnolence
* Intense headache
* Scotomas
* Migraine-like episodes
* Ataxia and slurred speech
* Intellectual disability
#### Supportive Laboratory Findings
Plasma ammonia concentration
* Neonate. Initial plasma ammonia concentration in the severe form may be 1000-3000 µmol/L (normal: 40-100 µmol/L).
* Late-onset. Chronic or recurrent hyperammonemia, often with a lower plasma concentration than in the classic form (adult upper limit of normal: <60 µmol/L).
Plasma quantitative amino acid analysis
* Citrulline. Usually >1000 µmol/L (normal: <50 µmol/L)
* Argininosuccinic acid. Absent
* Arginine and ornithine. Low to normal range; see Urea Cycle Disorders Overview Figure 3.
* Lysine, glutamine, and alanine. Increased; these are surrogate markers of hyperammonemia.
Urinary organic acids analysis. Normal, although orotic acid may be detected as part of urinary organic acid analysis by gas chromatography/mass spectrometry. However, the sensitivity depends on the extraction method.
### Establishing the Diagnosis
The diagnosis of CTLN1 is established in a proband with elevated plasma ammonia concentration (>150 µmol/L; may range to ≥2000-3000 µmol/L) and plasma citrulline concentration (usually >1000 µmol/L) and/or by the identification of biallelic pathogenic variants in ASS1 on molecular genetic testing (see Table 1).
Note: Determining the prognosis prospectively can be difficult in some individuals who fit the biochemical phenotype but may or may not have serious clinical illness.
Molecular genetic testing approaches can include single-gene testing and use of a multigene panel:
* Single-gene testing. Sequence analysis of ASS1 is performed first and followed by gene-targeted deletion/duplication analysis if only one or no pathogenic variant is found.
* A multigene panel that includes ASS1 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 Citrullinemia Type I
View in own window
Gene 1MethodProportion of Probands with Pathogenic Variants 2 Detectable by Method
ASS1Sequence analysis 396% 4, 5
Gene-targeted deletion/duplication analysis 6See footnote 7
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
See Molecular Genetics for information on allelic variants detected in this gene.
3\.
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.
4\.
In 80 individuals evaluated, both abnormal alleles were identified in 75 (94%), one abnormal allele in four (5%), and no abnormal alleles in one (1%).
5\.
Sequencing of genomic DNA from a variety of cells or cDNA from cultured fibroblasts detected 154 of 160 (96%) abnormal alleles [Häberle, personal communication].
6\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods that may be used 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.
7\.
Exon and multiexon deletions were reported by Engel et al [2009].
Argininosuccinate synthase (ASS) enzyme activity. Incorporation of radiolabeled citrulline into argininosuccinic acid is measured in cultured fibroblasts (see also Prenatal Testing and Preimplantation Genetic Diagnosis). ASS activity is also determined by a method based on the conversion of radiolabeled (14C)-aspartate to (14C)-argininosuccinate [Gao et al 2003]:
* The normal enzyme activity in fibroblasts is 0.8-3.8 nmol/min/mg protein, but this is specific to tissue, method, and laboratory.
* Enzyme assay is not widely used because the clinical presentation and relatively specific pattern of metabolites found in affected individuals are sufficient to establish the diagnosis.
## Clinical Characteristics
### Clinical Description
Citrullinemia type I (CTLN1) presents as a spectrum that includes a neonatal acute form (the "classic" form), a milder late-onset form (the "non-classic" form), a form in which women have onset of symptoms at pregnancy or post partum, and a form without symptoms or hyperammonemia.
Neonatal ("classic") form. The infant appears normal at birth. After an interval of one to a few days, the infant becomes progressively more lethargic, feeds poorly, may vomit, and may develop signs of increased intracranial pressure [Brusilow & Horwich 2001]. Fifty-six percent of infants with classic citrullinemia type I are symptomatic by age four days and 67% by age one week [Bachmann 2003a].
Children diagnosed and referred for appropriate treatment (see Management) survive for an indeterminate period of time, usually with significant neurologic deficits. All children with a peak plasma ammonia concentration greater than 480 µmol/L or an initial plasma ammonia concentration greater than 300 µmol/L have cognitive impairment [Bachmann 2003b]. The longest survival of an untreated infant with classic citrullinemia type I is 17 days.
Non-classic form. The clinical course may be similar to or milder than that seen in the acute neonatal form, but commences later in life for reasons that are not completely understood. However, specific ASS1 pathogenic variants may be associated with the non-classic form (see Genotype-Phenotype Correlations and Molecular Genetics). When episodes of hyperammonemia occur, they are similar to those seen in the acute neonatal form, but the neurologic findings may be more subtle because of the older age of the affected individuals. These can include intense headache, scotomas, migraine-like episodes, ataxia, slurred speech, lethargy, and somnolence. Individuals with hyperammonemia also display respiratory alkalosis and tachypnea [Brusilow & Horwich 2001]. Without prompt intervention, increased intracranial pressure occurs, with increased neuromuscular tone, spasticity, ankle clonus, seizures, loss of consciousness, and death.
Liver failure is now recognized as a primary presentation of CTLN1, contradicting established dogma of CNS symptoms as the primary finding [Salek et al 2010, Faghfoury et al 2011, Lee et al 2013, Rüegger et al 2014]. Hepatic dysfunction, when present, is frequently noted at the time of the initial hyperammonemic episode but has also developed in an affected individual who was not experiencing significant hyperammonemia (>250 µmol/L) at the time [Lee et al 2013].
Possible long-term complications. An individual with classic citrullinemia treated with chronic protein restriction and scavenger therapy (see Treatment of Manifestations) developed progressive hypertrophic cardiomyopathy (diagnosed at age 23 years) and bilateral cataracts (diagnosed at age 27 years) [Brunetti-Pierri et al 2012]. No additional individuals with classic CTLN1 have been identified with similar findings. As such, the necessity for cardiac and ophthalmologic surveillance remains controversial until more affected individuals have been studied.
Pregnancy. A healthy woman with untreated CTLN1 underwent two successful pregnancies [Potter et al 2004]; however, women with onset of severe symptoms during pregnancy or in the postpartum period have been reported [Gao et al 2003, Ruitenbeek et al 2003].
* Three women not known to have citrullinemia presented in hyperammonemic coma shortly after delivery; one died and two survived without neurologic sequelae [Häberle et al 2009].
* CTLN1 has been implicated in postpartum psychosis [Häberle et al 2010].
Individuals remaining asymptomatic up to at least age ten years have been reported; it appears that they could remain asymptomatic lifelong [Häberle et al 2002, Häberle et al 2003].
Neuroimaging. CT scan of infants with citrullinemia type I demonstrates cerebral atrophy, particularly in the cingulate gyrus, the insula, and the temporal lobes, as well as general cortical hypo-attenuation (i.e., the cortex appears darker than in unaffected individuals) [Albayram et al 2002].
Brain MRI findings in classic citrullinemia include restricted diffusion and T2 signal hyperintensities in the basal ganglia, thalami, and subcortical white matter of the bilateral temporal, parietal, and occipital cortex [Majoie et al 2004, Bireley et al 2012]. Multicystic encephalomalacia and cerebral atrophy have been seen as early as age three to four months in an individual with classic CTLN1 [Lee et al 2013].
### Genotype-Phenotype Correlations
Although certain pathogenic variants are identified with some phenotypes, the phenotype cannot be predicted in all instances [Engel et al 2009].
* Severe, classic citrullinemia type I typically results from 22 defined pathogenic variants [Engel et al 2009]. The pathogenic variant in exon 15, p.Gly390Arg, remains the most prevalent associated with the classic phenotype [Engel et al 2009, Laróvere et al 2009].
* Mild (i.e., late-onset) citrullinemia type I is associated with 12 pathogenic variants [Engel et al 2009].
### Nomenclature
The preferred terms for argininosuccinic acid synthetase deficiency are "citrullinemia type I" and "classic citrullinemia," which are used to avoid confusion with the genetically distinct disease, citrullinemia type II, also known as citrin deficiency.
### Prevalence
Citrullinemia type I has been estimated to occur in 1:57,000 births [Brusilow & Horwich 2001].
Newborn screening programs found CTLN1 in the following:
* In Korea: two in 44,300 newborns [Yoon et al 2003]
* In New England: one in 200,000 newborns [Marsden 2003]
* In Taiwan: five (2 severe and 3 mild) in a pilot program of 592,717 newborns; overall incidence 1:118,543 [Niu et al 2010]
* In Austria: 1:77,811 among 622,489 newborns [Kasper et al 2010]
* In Texas, New York, Michigan, California, Massachusetts, North Carolina and Wisconsin, estimated combined prevalence of CTLN1 and ASLD: one in 117,000 [Summar et al 2013]
## Differential Diagnosis
Conditions that may result in elevated citrulline on newborn screening are citrullinemia II (citrin deficiency), argininosuccinic aciduria, and pyruvate carboxylase deficiency.
Citrullinemia type II (CTLN2) is caused by citrin deficiency resulting from biallelic pathogenic variants in SLC25A13, which encodes the mitochondrial solute carrier protein, citrin. In citrin deficiency aspartate and glutamate fail to shuttle to and from the mitochondrion, leading to mild hyperammonemia and citrullinemia. Biallelic pathogenic variants in SLC25A13 also lead to intrahepatic cholestasis in the neonate [Saheki & Kobayashi 2002]. The clinical course in adults with citrullinemia type II is milder than that of CTLN1, possibly distinguishing it from milder late-onset citrullinemia type I. It is not known why CTLN2 is milder and later in onset than CTLN1; distinguishing between the two disorders is difficult. The prevalence of citrullinemia type II has not been reported.
It is critical to distinguish hyperammonemia caused by a defect in the urea cycle from the secondary hyperammonemia caused by an organic acidemia, which may cause inhibition of N-acetylglutamate synthase (see Urea Cycle Disorders Overview Figure 2).
Dihydrolipoamide dehydrogenase (DLD) deficiency has also been reported to display increased citrulline, ammonia and glutamine [Haviv et al 2014]. DLD deficiency is caused by biallelic pathogenic variants in DLD.
Classic citrullinemia type I shares the phenotype of the typical acute neonatal hyperammonemia displayed by other defects in the first four steps in the urea cycle pathway. The mild phenotype shares a later onset with other disorders such as late-onset ornithine transcarbamylase (OTC) deficiency. Urea Cycle Disorders Overview Figure 3 shows a diagnostic strategy to identify which steps in the urea cycle are defective in an individual with hyperammonemia.
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with citrullinemia type I (CTLN1), the following evaluations are recommended:
* Measurement of: concentration of plasma ammonia, amino acids, and electrolytes; blood gases; urinary organic acids; and urinary orotic acid
* Assessment of intracranial pressure and overall neurologic status
* Consultation with a clinical geneticist
### Treatment of Manifestations
As soon as a diagnosis of CTLN1 is made, acute (if needed) and chronic management should be initiated per established treatment guidelines [Batshaw et al 2001, Summar 2001, UCD Conference Group 2001]. See ACMG-ACT Sheet, ACMG Algorithm.
#### Acute Management of Hyperammonemia
Hallmarks of therapy include rapid lowering of the plasma ammonia concentration, reversal of catabolism, and avoidance and/or treatment of increased intracranial pressure [Häberle et al 2012].
Rapidly decreasing plasma ammonia concentration. When hyperammonemia is diagnosed or suspected, all protein intake should be withheld for a maximum of 24-48 hours. This time frame allows for the plasma ammonia concentration to be lowered via nitrogen scavenger therapy and/or dialysis and avoids an essential amino acid deficiency that would promote a catabolic state:
* Pharmacologic nitrogen scavenger therapy (sodium benzoate, sodium phenylacetate and arginine) should be given intravenously as soon as hyperammonemia is diagnosed in an individual known to have CTLN1. (For information pertaining to the mechanism of action of this treatment, see Scavenger Therapy.)
* Priming infusion (to be given continuously over 90 minutes):
* Sodium benzoate: 250 mg/kg or 5.5 g/m2
* Sodium phenylacetate: 250 mg/kg or 5.5 g/m2
* 10% arginine HCl: 600 mg/kg or 12.0 g/m2
* Sustaining infusion (to be given continuously over 24 hours):
* Sodium benzoate: 250 mg/kg or 5.5 g/m2
* Sodium phenylacetate: 250 mg/kg or 5.5 g/m2
* 10% arginine HCl: 600 mg/kg or 12.0 g/m2
* Note: Repeat boluses are not recommended unless the individual is receiving dialysis (see following).
* Dialysis is the most effective means of reducing plasma ammonia rapidly. Failure to control ammonia with scavenger therapy requires the emergency use of dialysis.
* Hemodialysis is the preferred method of dialysis and exceeds both peritoneal dialysis and hemofiltration in the rate of ammonia clearance.
* Scavenger therapy should be continued while dialysis is being performed.
* Note: Exchange transfusions have no place in hyperammonemic treatment.
Reversal of catabolism. An anabolic state should be promoted through the provision of IV glucose (and insulin in the event of hyperglycemia) and intralipids.
* Complete protein restriction should be limited to 24-48 hours to avoid a catabolic state.
* In small infants, 40 kcal/100 mL given as D10W can be significant in averting catabolism. As soon as possible, osmolar load permitting, the individual should receive total parenteral nutrition (TPN) providing 0.25 g/kg/day of protein and 50 kcal/kg/day, advancing (as plasma ammonia concentration allows) to 1.0-1.5 g/kg/day of protein and 100-120 kcal/kg/day. Standard TPN solutions of dextrose, aminosol, and intralipid are used.
Control of intracranial pressure. It is critical to monitor fluid balance, intake and output, and body weight.
* The affected individual should be maintained on the dry side of fluid balance: approximately 85 mL/kg of body weight per day in infants and appropriate corresponding fluid restriction in children and adults.
* Increased intracranial pressure is manifested by tension in the fontanelle, acute enlargement of the liver, edema, and worsening neurologic signs including fisting, scissoring, ankle clonus, and coma. Cerebral edema and ischemia may be documented by MRI.
#### Chronic Management
Chronic therapy for those with CTLN1 consists of lifelong protein restriction, medications (nitrogen scavenger therapy and carnitine), and possible liver transplantation based on the degree of metabolic control achieved with dietary modification and medication therapy.
Protein restriction. Lifelong dietary management is necessary and requires the services of a metabolic nutritionist.
Nitrogen scavenger therapy
* When the affected individual is able to tolerate solid food, the oral medication sodium phenylbutyrate (Buphenyl®, Ammonaps®), at a dose of 450-600 mg/kg/day divided into three doses, and arginine-free base of 400 and 700 mg/kg/day are begun. As children grow, doses change to 9.9-13 g/m2/day of sodium phenylbutyrate and 8.8-15.4 g/m2/day of arginine. For details of management, the reader is referred to Brusilow & Horwich [2001] and Häberle et al [2012].
* Glycerol phenylbutyrate (Ravicti®) is a more palatable option. The initial dosage for phenylbutyrate-naïve patients is 4.5-11.2 mL/m2/day (5-12.4 g/m2/day). If the individual is transitioning from sodium phenylbutyrate to glycerol phenylbutyrate, the daily dose of glycerol phenylbutyrate (mL) = daily dose of sodium phenylbutyrate (g) x 0.86.
* Success of therapy is defined by a plasma ammonia concentration lower than100 µmol/L and near-normal plasma glutamine concentration. Plasma arginine concentration may be up to 250% above upper normal limit for age.
* Treatment with L-carnitine has been advocated as auxiliary treatment to prevent systemic hypocarnitinemia, which may result from therapy with acylating agents.
Liver transplantation for urea cycle disorders is the only known curative therapy [Morioka et al 2005]. Transplantation eliminates the need for dietary protein restriction but does not reverse any neurologic sequelae that affected individuals may have at the time of transplant.
Liver transplantation should ideally be performed in affected individuals who are younger than age one year (prior to the development of any neurocognitive impairment) but older than age three months and/or above 5 kg body weight, to decrease complications and improve survival rates [Häberle et al 2012].
* Liver transplantation of four individuals with CTLN1 between the ages of six and 64 months showed better developmental outcomes when the transplant was performed at earlier ages [Kim et al 2013].
* Survival rates in those who underwent liver transplantation prior to age two years was between 90% and 95% five years post transplant [Bourdeaux et al 2007, Perito et al 2014].
Note: Although liver transplantation cures the ASS enzyme deficiency, arginine is extrahepatically synthesized and remains low post-transplantation, requiring ongoing supplementation.
* Living related-donor liver transplantation
* A successful living related-donor liver transplantation (240 g) from mother to six-year-old daughter has been reported. The allopurinol challenge test was normalized in this child, who previously had very brittle control with four to six hyperammonemic episodes per year [Ito et al 2003].
* A living related-donor liver transplantation from mother to son resulted in continued elevation in plasma concentration of citrulline (200-400 µmol/L). The mother, a heterozygote, had 28% residual ASS1 enzyme activity [Ando et al 2003].
### Prevention of Primary Manifestations
Prevention of hyperammonemia is achieved through lifelong protein restriction, nitrogen scavenger therapy, and possible liver transplantation based on metabolic control (see Treatment of Manifestations).
### Prevention of Secondary Complications
Intercurrent infections (particularly some viral exanthems) may induce a catabolic state. Affected individuals must be observed carefully during such episodes and medical attention sought to prevent hyperammonemia.
Age-appropriate immunizations including the influenza vaccine should be provided.
### Surveillance
Follow up in a metabolic clinic with a qualified metabolic nutritionist and clinical biochemical geneticist is required. Monitoring should include:
* Evaluation of early warning signs of impending hyperammonemic episodes including mood changes, headache, lethargy, nausea, vomiting, refusal to feed, and ankle clonus;
* Plasma ammonia and amino acid analysis to identify hyperammonemia and deficiency of essential amino acids and impending hyperammonemia, respectively. Plasma glutamine concentration may rise 48 hours in advance of increases in plasma ammonia concentration [Brusilow & Horwich 2001].
Monitoring should occur frequently in neonates and infants, based on disease severity.
As affected individuals become older (teenage years and adulthood), clinical and biochemical monitoring can be extended to every six months to annually depending on clinical stability.
### Agents/Circumstances to Avoid
Avoid the following:
* Excess protein intake
* Obvious exposure to communicable diseases
### Evaluation of Relatives at Risk
Because the long-term prognosis for individuals with citrullinemia type I depends on initial and peak plasma ammonia concentration, it is important that at-risk sibs be identified as soon as possible.
Evaluations can include:
* Molecular genetic testing if the pathogenic variants in the family are known; in utero diagnosis (which permits appropriate oral therapy beginning with first feeds), if possible, is preferred.
* Measurement of plasma concentrations of ammonia and citrulline on day one of life. Elevation of either above acceptable levels (ammonia >100 µmol/L or plasma citrulline >~100 µmol/L) is sufficient evidence to initiate treatment.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Pregnancy Management
Because women with onset of severe symptoms during pregnancy or in the postpartum period have been reported, scrupulous attention needs to be paid to diet and medication during these periods.
### Therapies Under Investigation
Gene therapy has been suggested; success has not been achieved to date.
Phase I and Phase II clinical trials to assess the safety and efficacy of human hepatocyte transplantation as either an alternative to liver transplantation or as a temporizing measure for individuals with CTLN1 awaiting transplantation has recently finished.
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions.
### Other
Ketoacids of essential amino acids were an early form of auxiliary waste nitrogen disposal enhancement, now replaced by the agents described in Treatment of Manifestations.
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Citrullinemia Type I | c0175683 | 5,162 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1458/ | 2021-01-18T21:34:49 | {"mesh": ["D020159"], "synonyms": ["Argininosuccinate Synthetase Deficiency", "Argininosuccinic Acid Synthetase Deficiency", "ASS Deficiency", "Classic Citrullinemia", "CTLN1"]} |
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: "Streff syndrome" – news · newspapers · books · scholar · JSTOR (June 2020)
Streff syndrome is a vision condition primarily exhibited by children under periods of visual or emotional stress.
## Contents
* 1 Presentation
* 2 Diagnosis
* 3 Treatment
* 4 Notes
## Presentation[edit]
Frequently patients will have reduced stereopsis, large accommodative lag on dynamic retinoscopy, and a reduced visual field (tubular or spiral field). Streff Syndrome was first described in 1962 by an optometrist, Dr. John Streff as Non-malingering syndrome. In 1962, Dr. Streff and Dr. Richard Apell expanded the concept to add early adaptive syndrome as a precursor to Streff syndrome. Dr. Streff believed the visual changes were induced by stress from reading. There is dispute on the taxonomy of functional vision defects. Some research indicates that Streff syndrome may be caused by a dysfunction in the magnocellular pathway of the retinal ganglion cells.[1] These cells are only 10% of the retinal nerve cells and register motion detection. Early Adaptive Syndrome
## Diagnosis[edit]
The diagnostic criteria for Streff syndrome are not well established, and the validity of this condition has not been recognized by The American Academy of Ophthalmology, The American Academy of Pediatric Ophthalmology, The American Academy of Optometry or The American academy of Pediatrics.
## Treatment[edit]
Most optometrists agree that Streff syndrome is a generalized reduction in visual performance that is not caused by structural damage. It is a disease involving vision distress primarily of the accommodation system. Hans Selye described stress, distress and eustress. It is most common in girls ages 8 to 14. Hand held reading material is often positioned excessively close. Reading aloud shows signs of elevated pitch and stumbling over common words. History of homework avoidance and falling class performance are often present. If the patient is directed to read aloud and +.50 lenses are then used, there is usually a dramatic improvement as observed by patient and parent. Abnormal results on color vision or visual field testing is not uncommon. Visual field often presents as constricted 'tubular' at multiple test distances. The poor visual performance is understood as distress, and treatments are usually to provide the patient with low powered reading glasses. The "relaxing" nature of reading glasses is believed to reduce the near vision stress and allow normal function. The emotional effects of chronic near vision stress are also reduced. The "non-Malingering" name is a refutation that the patient is malingering.
## Notes[edit]
1. ^ Nimesh P. The use of frequency doubling technology to determine magnocellular pathway deficiencies. Journal of Behavioral Optometry, Volume 15. Number 2, 2005
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Streff syndrome | None | 5,163 | wikipedia | https://en.wikipedia.org/wiki/Streff_syndrome | 2021-01-18T18:29:17 | {"wikidata": ["Q7623169"]} |
Epidermolysis bullosa simplex with muscular dystrophy (EBS-MD) is a basal subtype of epidermolysis bullosa simplex (EBS, see this term) characterized by generalized blistering associated with muscular dystrophy.
## Epidemiology
Prevalence is unknown, but more than 40 cases have been reported to date.
## Clinical description
Onset of blistering is usually as early as birth, whereas muscular dystrophy manifests between infancy and adulthood. Blisters are often hemorrhagic and heal with mild atrophic scarring and rare milia formation. Associated findings comprise markedly dystrophic nails, and focal keratoderma of the palms and soles. Extracutaneous involvement is usually present, including enamel hypoplasia with premature tooth decay, blistering in the oral cavity, pharynx and, rarely, larynx and trachea with inspiratory stridor and breathing difficulties requiring tracheotomy. Slowly progressive weakness of the head and limb muscles appears between the first year and the fourth decade of life and may confine the patient to a wheelchair. Additional neurological symptoms (ptosis, oculobulbar muscle weakness and fatigability) indicative of a myasthenic syndrome have been described in some patients.
## Etiology
EBS-MD is caused by mutations in the PLEC gene (8q24) encoding plectin. Plectin deficiency can be demonstrated in skin and muscle by analysis with specific antibodies.
## Genetic counseling
Transmission is autosomal recessive.
## Prognosis
From a prognostic point of view, immunohistochemical recognition of EBS-MD in infancy is particularly important, since in some patients the associated muscular dystrophy may not become apparent until later in childhood or adulthood. EBS-MD may have a fatal outcome.
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Epidermolysis bullosa simplex with muscular dystrophy | c2931072 | 5,164 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=257 | 2021-01-23T19:02:44 | {"gard": ["2137"], "mesh": ["C535955"], "omim": ["226670"], "umls": ["C2931072"], "icd-10": ["Q81.0"], "synonyms": ["EBS-MD", "Limb-girdle muscular dystrophy with epidermolysis bullosa simplex"]} |
Tritanopia is an extremely rare form of colour blindness characterised by a selective deficiency of blue vision.
## Epidemiology
It affects between 1 in 13,000 and 1 in 15,000 newborns.
## Clinical description
Red and green vision is unaffected.
## Etiology
It is associated with a deficiency or absence of blue-sensitive cone photoreceptor function. The disease is caused by point mutations in the gene encoding the blue-sensitive visual pigment.
## Genetic counseling
Tritanopia is transmitted as an autosomal dominant trait.
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Tritanopia | c0155017 | 5,165 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=88629 | 2021-01-23T18:46:38 | {"mesh": ["D003117"], "omim": ["190900"], "umls": ["C0155017"], "icd-10": ["H53.5"], "synonyms": ["Blue colour blindness", "Congenital tritanopia", "Tritan colour blindness"]} |
## Clinical Features
In 2 generations of a Northern Ireland family, Graham et al. (1988, 1991) described 7 males with clinical anophthalmia, of whom 3 were deceased at the time of study. The pattern was consistent with X-linked recessive inheritance, and multipoint linkage analysis suggested that gene was localized to the Xq27-q28 region; maximum lod = 1.9 at theta = 0.08. Clinically affected males with bilateral disease had fusion of the eyelid margins (ankyloblepharon) and radiologically demonstrable underdevelopment of the bony orbits. All males had mental retardation (IQ less than 50) and 1 male was born with preauricular skin tags and a cleft soft palate. No deafness was present and lack of limb, hand, dental, and urogenital abnormalities was considered to make Lenz microphthalmia syndrome (309800) unlikely. Although some early reports of 'anophthalmos' were probably instances of Norrie disease (310600), the linkage mapping, if valid, excludes that possibility in this family, since the Norrie disease gene is located at Xp11.4.
Forrester et al. (2001) mapped Lenz microphthalmia syndrome, which has many features similar to those in affected members of the family of Graham et al. (1991), to Xq27-q28.
Nomenclature
The term 'anophthalmia' has been misused in the medical literature. True or primary anophthalmia is rarely compatible with life; in such cases, the primary optic vesicle has stopped developing and the abnormal development involves major defects in the brain as well (Francois, 1961). The diagnosis can only be made histologically (Reddy et al., 2003; Morini et al., 2005; Smartt et al., 2005), but this is rarely done. In most published cases, the term 'anophthalmia' is used as a synonym for the more appropriate terms 'extreme microphthalmia' or 'clinical anophthalmia.'
INHERITANCE \- X-linked recessive HEAD & NECK Ears \- Preauricular skin tags Eyes \- Anophthalmia, clinical \- Ankyloblepharon \- Underdeveloped bony orbits Mouth \- Cleft palate NEUROLOGIC Central Nervous System \- Mental retardation (IQ less than 50) ▲ 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| MICROPHTHALMIA, SYNDROMIC 4 | c1844948 | 5,166 | omim | https://www.omim.org/entry/301590 | 2019-09-22T16:18:47 | {"mesh": ["C564457"], "omim": ["301590"], "orphanet": ["85275"], "synonyms": ["Alternative titles", "MICROPHTHALMIA WITH ANKYLOBLEPHARON AND MENTAL RETARDATION", "ANOP1, FORMERLY"]} |
## Summary
The purpose of this overview on hereditary dystonia is to help clinicians determine if an individual has a hereditary dystonia in order to provide information regarding recurrence risk and evaluation of relatives at risk.
### Goal 1.
Describe the clinical characteristics of dystonia.
### Goal 2.
Review the causes of hereditary dystonia.
### Goal 3.
Provide an evaluation strategy to determine the etiology of hereditary dystonia in a proband.
### Goal 4.
Review the differential diagnosis of hereditary dystonia (i.e., non-genetic causes of dystonia).
### Goal 5.
Provide information regarding recurrence risk and evaluation of relatives of a proband with hereditary dystonia who are at risk.
## Diagnosis
## Clinical Characteristics
## Differential Diagnosis
## Management
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Hereditary Dystonia Overview | None | 5,167 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1155/ | 2021-01-18T21:21:06 | {"synonyms": []} |
A number sign (#) is used with this entry because the Cromer blood group system is based on homozygous mutation in the CD55 gene (CD55; 125240) on chromosome 1q32.
Description
The Cromer blood group system (CROM) consists of 12 high-prevalence and 3 low-prevalence antigens that reside on decay-accelerating factor (DAF, or CD55; 125240), a regulator of complement activation. Nearly all Cromer antigens result from SNPs in the DAF gene. The red blood cells (RBCs) of people with the Cromer-null phenotype, Inab, lack DAF but do not appear to show increased susceptibility to hemolysis. Antibodies to Cromer antigens are rarely encountered, although evidence suggests that the antibodies may cause accelerated destruction of transfused RBCs. Cromer system antibodies are not associated with hemolytic disease of the newborn, because placenta is a rich source of fetally derived DAF, which is thought to absorb the antibodies (review by Storry et al., 2010).
The Inab phenotype is associated with CHAPLE syndrome (226300) in some individuals.
Clinical Features
### Inab Phenotype
Daniels et al. (1982) reported a 27-year-old Japanese man, designated 'Inab,' whose red blood cells failed to react with anti-Cr(a) sera and with 3 Cromer-related sera, designated BP, GT, and KTO. His serum reacted with all red blood cells tested except his own. The patient also had protein-losing enteropathy (see 226300) and an ileocecal tumor; after he underwent hemicolectomy, the protein-losing enteropathy was reported to have resolved. Daniels et al. (1982) suggested that the 'Inab' phenotype represented a null phenotype in the Cromer complex.
Walthers et al. (1983) described a 25-year-old Caucasian man (JF), with a history of Crohn disease (see 266600) and prior transfusions, whose erythrocytes typed Tc(a- b- c-) and Cr(a-) and were also negative for other high-frequency antigens, consistent with the Inab phenotype. The authors noted that this patient and the original Inab proband reported by Daniels et al. (1982) had a history of protein-losing enteropathy.
Lin et al. (1988) reported an 86-year-old Italian American woman and her 70-year-old brother who both exhibited the Inab phenotype but had no history of intestinal disease. The authors noted that the Inab phenotype appeared to be a heritable characteristic in this family.
### Dr(a-) Phenotype
Levene et al. (1984) described 2 Israeli sisters (MD and NL), born of Jewish parents from Bukhara, whose red cells had very weak Cr(a) and Tc(a) antigens and reacted only weakly with the antibody of the Cr(a-)Tc(a-) individual, Inab. Both sisters had an antibody, designated anti-Dr(a), to a high-frequency antigen absent from their own cells and Inab cells, but present on Cr(a-)Tc(a+) and Cr(a+)Tc(a-) cells. Levene et al. (1984) stated that this was the third example in which both Cr(a) and Tc(a) antigens were either absent or showed weakened expression on red cells, but the first case in which the unusual phenotype was shown to be inherited.
Levene et al. (1987) studied a 68-year-old Israeli woman, born in Samarkand in the Soviet Union, who had anti-Dr(a) in her serum and whose red cells were Dr(a-), as were those of 3 of her 4 children. All Dr(a-) cells had weakened expression of their Cr(a), Tc(a), Es(a), IFC, and other Cromer-related antigens. Anti-Dr(a) was inhibited by serums from Dr(a+) but not Dr(a-) members of the family. The proband was diagnosed with rectal carcinoma and underwent deep x-ray therapy and surgery. The authors noted that Samarkand is a neighboring city in the same region as Bukhara in the Uzbekskaya SSR in the southern part of the Soviet Union, from which the Dr(a-) family described by Levene et al. (1984) originated, but Levene et al. (1987) stated that there was no evidence to suggest that the 2 families were related.
Reid et al. (1991) reported a 38-year-old Russian woman (KZ), admitted to the hospital for surgery to correct a chronic intestinal disorder of unknown etiology, who they stated was the fourth proband with the Inab phenotype. Lublin et al. (1994) restudied patient KZ and demonstrated that her red cell phenotype was Dr(a-) rather than Inab. Whereas previously immunoblot showed no reaction with KZ red cell membranes, analysis of an immunoblot using murine MoAbs to different epitopes on DAF to increase sensitivity showed that KZ erythrocyte membranes reacted with murine MoAbs at a strength comparable to Dr(a-) membranes, but more weakly than control Dr(a+) membranes. In contrast, Inab phenotype membranes failed to react at all with the DAF MoAbs. Furthermore, flow cytometry studies showed that KZ reacted to the Dr(a+) but not the Dr(a-) variant of DAF, indicating that KZ antibody could distinguish the single amino acid difference between DR(a+) and Dr(a-) (see MOLECULAR GENETICS).
Reid et al. (1996) studied 2 cases in which strongly reactive Cromer system antibodies, anti-Cr(a) and anti-Dr(a), became undetectable during the second and third trimesters of pregnancy.
Molecular Genetics
### Inab Phenotype
The Inab phenotype, or Cromer null, in which RBCs lack all Cromer system antigens, is very rare. In the 27-year-old Japanese man in whom the Inab phenotype was first detected (Daniels et al., 1982), Lublin et al. (1994) demonstrated homozygosity for a nonsense mutation in exon 2 of the DAF gene (W53X; 125240.0001). The mutation truncated DAF near the N terminus, explaining the complete absence of surface DAF in the red cells of the individual.
In a 28-year-old Japanese woman, Wang et al. (1998) demonstrated that the Cromer Inab phenotype was due to homozygosity for a c.1579C-A transversion at the position 24 bp upstream of the 3-prime end of exon 2 of the CD55 gene (125240.0002). This substitution resulted in an mRNA with a 26-bp deletion, which introduced a frameshift and created a stop codon immediately downstream of the deletion. Translation of the mRNA would be terminated at the first amino acid of the second short consensus repeat (SCR2) domain of DAF. Wang et al. (1998) noted that this proband, like the Italian American woman and her brother with the Inab phenotype reported by Lin et al. (1988), did not have a history of intestinal disease.
In a Japanese woman (Osad family) with the Inab phenotype, who exhibited the characteristic anti-IFC antibody, Daniels et al. (1998) identified homozygosity for the W53X mutation in the DAF gene. She was not known to be related to the Japanese man in whom the phenotype was originally described. Her unaffected parents were heterozygous for the mutation; DNA from her unaffected children was not tested. The proband was also reported to have a capillary angioma of the small intestine.
### Dr(a-) Phenotype
In an Israeli woman of Russian ancestry (MD) with the Dr(a-) phenotype, originally described by Levene et al. (1984), Lublin et al. (1991) sequenced the coding region of membrane DAF and identified homozygosity for a missense mutation (S165L; 125240.0003). Sequencing of DNA from the identified region in 2 unrelated Dr(a-) individuals showed that both were homozygous for the same variant in the DAF gene. Lublin et al. (1991) designated the Dr(a-) allele of DAF 'Dr(b).'
In a Russian woman (KZ) with the Dr(a-) phenotype, previously studied by Reid et al. (1991), Lublin et al. (1994) identified homozygosity for the S165L substitution in the DAF gene. Analysis of the proband's cDNA yielded 2 products: a full-length 291-bp sequence with the S165L change, and a more abundant 247-bp product. The authors showed that the single nucleotide transition results in 2 changes: an amino acid substitution that is the basis for the antigenic variation, and an alternative splicing event that underlies the decreased expression of DAF in the Dr(a-) phenotype.
In a Japanese female blood donor (Kim) with the Dr(a-) phenotype, Daniels et al. (1998) identified homozygosity for the S165L substitution in the DAF gene.
### Exclusion Studies
Yazer et al. (2006) studied a 1.5-year-old Caucasian boy born with congenital cytomegalovirus disease causing blindness and deafness, who also had severe growth retardation and significant gastroesophageal reflux disease requiring a feeding tube. Routine pretransfusion testing in advance of cochlear implant surgery revealed an Inab phenotype and a potent panagglutinin that did not react with Dr(a-) or IFC erythrocytes. Flow cytometry initially indicated that the patient's red blood cells lacked CD55 (1.6% of that of control); however several months later, CD55-positive cells had increased to 28% of control, and the anti-IFC was virtually undetectable. Analysis of the exons 2 through 6 of the CD55 gene and their flanking intronic sequences revealed no mutations. Yazer et al. (2006) noted that in early reports of the Inab phenotype, the 4 unrelated probands had gastrointestinal abnormalities, but 6 other Inab phenotype individuals, including 2 transient Inab patients, did not show or have a history of gastrointestinal abnormalities.
INHERITANCE \- Autosomal recessive ABDOMEN Gastrointestinal \- Protein-losing enteropathy (in some patients) \- Gastrointestinal tumors (in some patients) HEMATOLOGY \- Red blood cells lack some ('Dr(A-)') or all ('Inab') of the Cromer blood group antigens NEOPLASIA \- Gastrointestinal tumors (in some patients) MISCELLANEOUS \- Some patients are clinically asymptomatic MOLECULAR BASIS \- Caused by mutation in the CD55 antigen gene (CD55, 125240.0001 ) ▲ 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| BLOOD GROUP, CROMER SYSTEM | None | 5,168 | omim | https://www.omim.org/entry/613793 | 2019-09-22T15:57:31 | {"omim": ["613793"], "synonyms": ["Alternative titles", "CROMER BLOOD GROUP SYSTEM"]} |
A rare acquired retinal disorder characterised by sequential focal degeneration of photoreceptors, retinal pigment epithelium and choroid, with the majority of patients experiencing sudden onset photopsia and acute scotomas. Although patients typically retain decent visual acuity, blind spot enlargement and retinal pigment epithelial disturbances tend to develop over time. Individuals also often complain of distortion of central vision, photophobia and difficulty with night vision, with more advanced cases reporting loss of peripheral vision.
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Acute zonal occult outer retinopathy | c0730298 | 5,169 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=284454 | 2021-01-23T18:26:37 | {"gard": ["8640"], "mesh": ["C538223"], "umls": ["C0730298"], "synonyms": ["AZOOR"]} |
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Find sources: "Cryptorchidism" – news · newspapers · books · scholar · JSTOR (November 2010) (Learn how and when to remove this template message)
Cryptorchidism
Cryptorchidism on scrotal ultrasound
SpecialtyMedical genetics
Cryptorchidism is the absence of one or both testes from the scrotum. The word is from the Greek κρυπτός (kryptos), meaning "hidden", and ὄρχις (orchis), meaning "testicle". It is the most common birth defect of the male genital tract.[1] About 3% of full-term and 30% of premature infant boys are born with at least one undescended testis. However, about 80% of cryptorchid testes descend by the first year of life (the majority within three months), making the true incidence of cryptorchidism around 1% overall. Cryptorchidism may develop after infancy, sometimes as late as young adulthood, but that is exceptional.
Cryptorchidism is distinct from monorchism, the condition of having only one testicle. Though the condition may occur on one or both sides, it more commonly affects the right testis.[2]
A testis absent from the normal scrotal position may be:
1. Anywhere along the "path of descent" from high in the posterior (retroperitoneal) abdomen, just below the kidney, to the inguinal ring
2. In the inguinal canal
3. Ectopic, having "wandered" from the path of descent, usually outside the inguinal canal and sometimes even under the skin of the thigh, the perineum, the opposite scrotum, or the femoral canal
4. Undeveloped (hypoplastic) or severely abnormal (dysgenetic)
5. Missing (also see anorchia).
About two-thirds of cases without other abnormalities are unilateral; most of the other third involve both testes. In 90% of cases, an undescended testis can be felt in the inguinal canal. In a small minority of cases, missing testes may be found in the abdomen or appear to be nonexistent (truly "hidden").
Undescended testes are associated with reduced fertility, increased risk of testicular germ-cell tumors, and psychological problems when the boy is grown. Undescended testes are also more susceptible to testicular torsion (and subsequent infarction) and inguinal hernias. Without intervention, an undescended testicle will usually descend during the first year of life, but to reduce these risks, undescended testes can be brought into the scrotum in infancy by a surgical procedure called an orchiopexy.[3]
Although cryptorchidism nearly always refers to congenital absence or maldescent, a testis observed in the scrotum in early infancy can occasionally "reascend" (move back up) into the inguinal canal. A testis which can readily move or be moved between the scrotum and canal is referred to as retractile.
Cryptorchidism, hypospadias, testicular cancer, and poor semen quality make up the syndrome known as testicular dysgenesis syndrome.
## Contents
* 1 Signs and symptoms
* 1.1 Infertility
* 1.2 Cancer risk
* 1.3 Psychological consequences
* 2 Causes
* 3 Mechanism
* 3.1 Normal development
* 3.2 Pathophysiology
* 4 Diagnosis
* 5 Treatment
* 6 Other animals
* 6.1 Dogs
* 6.2 Cats
* 6.3 Horses
* 7 References
* 8 External links
## Signs and symptoms[edit]
### Infertility[edit]
Many men who were born with undescended testes have reduced fertility, even after orchiopexy in infancy. The reduction with unilateral cryptorchidism is subtle, with a reported infertility rate of about 10%, compared with about 6% reported by the same study for the general population of adult men.
The fertility reduction after orchiopexy for bilateral cryptorchidism is more marked, about 38%, or six times that of the general population. The basis for the universal recommendation for early surgery is research showing degeneration of spermatogenic tissue and reduced spermatogonia counts after the second year of life in undescended testes. The degree to which this is prevented or improved by early orchiopexy is still uncertain.
### Cancer risk[edit]
One of the strongest arguments for early orchiopexy is reducing the risk of testicular cancer. About one in 500 men born with one or both testes undescended develops testicular cancer, roughly a four- to 40-fold increased risk. The peak incidence occurs in the third and fourth decades of life. The risk is higher for intra-abdominal testes and somewhat lower for inguinal testes, but even the normally descended testis of a man whose other testis was undescended has about a 20% higher cancer risk than those of other men.[citation needed]
The most common type of testicular cancer occurring in undescended testes is seminoma.[4] It is usually treatable if caught early, so urologists often recommend that boys who had orchiopexy as infants be taught testicular self-examination, to recognize testicular masses and seek early medical care for them. Cancer developing in an intra-abdominal testis would be unlikely to be recognized before considerable growth and spread, and one of the advantages of orchiopexy is that a mass developing in a scrotal testis is far easier to recognize than an intra-abdominal mass.
Orchidopexy was originally thought to result in easier detection of testicular cancer, but did not lower the risk of actually developing cancer. However, recent data have shown a paradigm shift. The New England Journal of Medicine published in 2007 that orchidopexy performed before puberty resulted in a significantly reduced risk of testicular cancer than if done after puberty.[5]
The risk of malignancy in the undescended testis is four to 10 times higher than that in the general population, and is about one in 80 with a unilateral undescended testis and one in 40 to one in 50 for bilateral undescended testes. The peak age for this tumor is 15–45 years old. The most common tumor developing in an undescended testis is a seminoma (65%); in contrast, after orchiopexy, seminomas represent only 30% of testicular tumors.[citation needed]
### Psychological consequences[edit]
A small body of research on the psychology of cryptorchidism attempts to determine whether this condition can cause lasting psychological problems. It consists of only a few case reports and small studies. This research also has serious methodological problems; major variables are completely uncontrolled, such as the small physical stature of many cryptorchid boys, and the psychological effects of corrective surgery.
Existing research indicates that boys with undescended testicles do not tend to be gender-disordered, effeminate, or prehomosexual. A disturbed self-image forms only when the family dynamics are destructive to developing male self esteem. Such pathogenic attitudes were found in parents who focused on the boy's genital defect as a sign of his presumed effeminacy. However, when the cryptorchism is surgically corrected, a healthy masculinity becomes possible. The basic sexual normality of these boys was confirmed in a small retrospective study that tested adolescent boys several years after their condition was surgically repaired. They had developed into fairly well-adjusted teenagers without special sexual or gender problems, and with no distinctive traits of psychopathological relevance.[6]
## Causes[edit]
In most full-term infant boys with cryptorchidism but no other genital abnormalities, a cause cannot be found, making this a common, sporadic, unexplained (idiopathic) birth defect. A combination of genetics, maternal health, and other environmental factors may disrupt the hormones and physical changes that influence the development of the testicles.
* Severely premature infants can be born before descent of testes. Low birth weight is also a known factor.[7]
* A contributing role of environmental chemicals called endocrine disruptors that interfere with normal fetal hormone balance has been proposed. The Mayo Clinic lists "parents' exposure to some pesticides" as a known risk factor.[7][8]
* Risk factors may include exposure to regular alcohol consumption during pregnancy (five or more drinks per week, associated with a three-fold increase in cryptorchidism, when compared to nondrinking mothers.[9] Cigarette smoking is also a known risk factor.[7]
* Family history of undescended testicles or other problems of genital development[7]
* Cryptorchidism occurs at a much higher rate in a large number of congenital malformation syndromes. Among the more common are Down syndrome,[7] Prader–Willi syndrome, and Noonan syndrome.
* In vitro fertilization, use of cosmetics by the mother, and pre-eclampsia have also been recognized as risk factors for development of cryptorchidism.[10]
In 2008, a study was published that investigated the possible relationship between cryptorchidism and prenatal exposure to a chemical called phthalate (DEHP), which is used in the manufacture of plastics. The researchers found a significant association between higher levels of DEHP metabolites in the pregnant mothers and several sex-related changes, including incomplete descent of the testes in their sons. According to the lead author of the study, a national survey found that 25% of U.S. women had phthalate levels similar to the levels that were found to be associated with sexual abnormalities.[11]
A 2010 study examined the prevalence of congenital cryptorchidism among offspring whose mothers had taken mild analgesics, primarily over-the-counter pain medications including ibuprofen (e.g. Advil) and paracetamol (acetaminophen).[12] Combining the results from a survey of pregnant women prior to their due date in correlation with the health of their children and an ex vivo rat model, the study found that pregnant women who had been exposed to mild analgesics had a higher prevalence of baby boys born with congenital cryptorchidism.[12]
New insight into the testicular descent mechanism has been hypothesized by the concept of a male programming window derived from animal studies. According to this concept, testicular descent status is "set" during the period from eight to 14 weeks of gestation in humans. Undescended testis is a result of disruption in androgen levels only during this programming window.[13]
## Mechanism[edit]
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### Normal development[edit]
The testes begin as an immigration of primordial germ cells into testicular cords along the gonadal ridge in the abdomen of the early embryo. The interaction of several male genes organizes this developing gonad into a testis rather than an ovary by the second month of gestation. During the third to fifth months, the cells in the testes differentiate into testosterone-producing Leydig cells, and anti-Müllerian hormone-producing Sertoli cells. The germ cells in this environment become fetal spermatogonia. Male external genitalia develop during the third and fourth months of gestation and the fetus continues to grow, develop, and differentiate. The testes remain high in the abdomen until the seventh month of gestation, when they move from the abdomen through the inguinal canals into the two sides of the scrotum. Movement has been proposed to occur in two phases, under the control of somewhat different factors. The first phase, movement across the abdomen to the entrance of the inguinal canal, appears controlled (or at least greatly influenced) by anti-Müllerian hormone (AMH). The second phase, in which the testes move through the inguinal canal into the scrotum, is dependent on androgens (most importantly testosterone). In rodents, androgens induce the genitofemoral nerve to release calcitonin gene-related peptide, which produces rhythmic contractions of the gubernaculum, a ligament which connects the testis to the scrotum, but a similar mechanism has not been demonstrated in humans. Maldevelopment of the gubernaculum, or deficiency or insensitivity to either AMH or androgen can, therefore, prevent the testes from descending into the scrotum. Some evidence suggests an additional paracrine hormone, referred to as descendin, may be secreted by the testes.
In many infants with inguinal testes, further descent of the testes into the scrotum occurs in the first six months of life. This is attributed to the postnatal surge of gonadotropins and testosterone that normally occurs between the first and fourth months of life.
Spermatogenesis continues after birth. In the third to fifth months of life, some of the fetal spermatogonia residing along the basement membrane become type A spermatogonia. More gradually, other fetal spermatogonia become type B spermatogonia and primary spermatocytes by the fifth year after birth. Spermatogenesis arrests at this stage until puberty.
Most normal-appearing undescended testes are also normal by microscopic examination, but reduced spermatogonia can be found. The tissue in undescended testes becomes more markedly abnormal ("degenerates") in microscopic appearance between two and four years after birth. Some evidence indicates early orchiopexy reduces this degeneration.
### Pathophysiology[edit]
At least one contributing mechanism for reduced spermatogenesis in cryptorchid testes is temperature. The temperature of testes in the scrotum is at least a few degrees cooler than in the abdomen. Animal experiments in the middle of the 20th century suggested that raising the temperature could damage fertility. Some circumstantial evidence suggests tight underwear and other practices that raise the testicular temperature for prolonged periods can be associated with lower sperm counts. Nevertheless, research in recent decades suggests that the issue of fertility is more complex than a simple matter of temperature. Subtle or transient hormone deficiencies or other factors that lead to a lack of descent also may impair the development of spermatogenic tissue.
The inhibition of spermatogenesis by ordinary intra-abdominal temperature is so potent that continual suspension of normal testes tightly against the inguinal ring at the top of the scrotum by means of special "suspensory briefs" has been researched as a method of male contraception, and was referred to as "artificial cryptorchidism" by one report.
An additional factor contributing to infertility is the high rate of anomalies of the epididymis in boys with cryptorchidism (over 90% in some studies). Even after orchiopexy, these may also affect sperm maturation and motility at an older age.
## Diagnosis[edit]
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Scrotal ultrasonography of undescended testis: (a) Normal testis in the scrotum (b) Atrophic and decreased echogenicity of the contralateral testis of the same patient seen in the inguinal region[citation needed]
The most common diagnostic dilemma in otherwise normal boys is distinguishing a retractile testis from a testis that will not descend spontaneously into the scrotum. Retractile testes are more common than truly undescended testes and do not need to be operated on. In normal males, as the cremaster muscle relaxes or contracts, the testis moves lower or higher ("retracts") in the scrotum. This cremasteric reflex is much more active in infant boys than older men. A retractile testis high in the scrotum can be difficult to distinguish from a position in the lower inguinal canal. Though various maneuvers are used to do so, such as using a cross-legged position, soaping the examiner's fingers, or examining in a warm bath, the benefit of surgery in these cases can be a matter of clinical judgment.
In the minority of cases with bilaterally nonpalpable testes, further testing to locate the testes, assess their function, and exclude additional problems is often useful. Scrotal ultrasound or magnetic resonance imaging performed and interpreted by a radiologist can often locate the testes while confirming absence of a uterus. At ultrasound, the undescended testis usually appears small, less echogenic than the contralateral normal testis and usually located in the inguinal region.[citation needed] With color Doppler ultrasonography, the vascularity of the undescended testis is poor.[citation needed]
A karyotype can confirm or exclude forms of dysgenetic primary hypogonadism, such as Klinefelter syndrome or mixed gonadal dysgenesis. Hormone levels (especially gonadotropins and AMH) can help confirm that hormonally functional testes are worth attempting to rescue, as can stimulation with a few injections of human chorionic gonadotropin to elicit a rise of the testosterone level. Occasionally, these tests reveal an unsuspected and more complicated intersex condition.
In the even smaller minority of cryptorchid infants who have other obvious birth defects of the genitalia, further testing is crucial and has a high likelihood of detecting an intersex condition or other anatomic anomalies. Ambiguity can indicate either impaired androgen synthesis or reduced sensitivity. The presence of a uterus by pelvic ultrasound suggests either persistent Müllerian duct syndrome (AMH deficiency or insensitivity) or a severely virilized genetic female with congenital adrenal hyperplasia. An unambiguous micropenis, especially accompanied by hypoglycemia or jaundice, suggests congenital hypopituitarism.
## Treatment[edit]
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The primary management of cryptorchidism is watchful waiting, due to the high likelihood of self-resolution. Where this fails, orchiopexy is effective if inguinal testes have not descended after 4–6 months. Surgery is often performed by a pediatric urologist or pediatric surgeon, but in many communities still by a general urologist or surgeon.
When the undescended testis is in the inguinal canal, hormonal therapy is sometimes attempted and very occasionally successful. The most commonly used hormone therapy is human chorionic gonadotropin (hCG). A series of hCG injections (10 injections over five weeks is common) is given and the status of the testis/testes is reassessed at the end. Although many trials have been published, the reported success rates range widely, from roughly 5% to 50%, probably reflecting the varying criteria for distinguishing retractile testes from low inguinal testes. Hormone treatment does have the occasional incidental benefits of allowing confirmation of Leydig cell responsiveness (proven by a rise of the testosterone by the end of the injections) or inducing additional growth of a small penis (via the testosterone rise). Some surgeons have reported facilitation of surgery, perhaps by enhancing the size, vascularity, or healing of the tissue. A newer hormonal intervention used in Europe is the use of GnRH analogs such as nafarelin or buserelin; the success rates and putative mechanism of action are similar to hCG, but some surgeons have combined the two treatments and reported higher descent rates. Limited evidence suggests that germ cell count is slightly better after hormone treatment; whether this translates into better sperm counts and fertility rates at maturity has not been established. The cost of either type of hormone treatment is less than that of surgery and the chance of complications at appropriate doses is minimal. Nevertheless, despite the potential advantages of a trial of hormonal therapy, many surgeons do not consider the success rates high enough to be worth the trouble, since the surgery itself is usually simple and uncomplicated.
In cases where the testes are identified preoperatively in the inguinal canal, orchiopexy is often performed as an outpatient and has a very low complication rate. An incision is made over the inguinal canal. The testis with accompanying cord structure and blood supply is exposed, partially separated from the surrounding tissues ("mobilized"), and brought into the scrotum. It is sutured to the scrotal tissue or enclosed in a "subdartos pouch". The associated passage back into the inguinal canal, an inguinal hernia, is closed to prevent reascent. In patients with intra-abdominal maldescended testis, laparoscopy is useful to see for oneself the pelvic structures, position of the testis and decide upon surgery (single or staged procedure ).
Surgery becomes more complicated if the blood supply is not ample and elastic enough to be stretched into the scrotum. In these cases, the supply may be divided, some vessels sacrificed with expectation of adequate collateral circulation. In the worst case, the testis must be "autotransplanted" into the scrotum, with all connecting blood vessels cut and reconnected (anastomosed).
When the testis is in the abdomen, the first stage of surgery is exploration to locate it, assess its viability, and determine the safest way to maintain or establish the blood supply. Multistage surgeries, or autotransplantation and anastomosis, are more often necessary in these situations. Just as often, intra-abdominal exploration discovers that the testis is nonexistent ("vanished"), or dysplastic and not salvageable.
The principal major complication of all types of orchiopexy is a loss of the blood supply to the testis, resulting in loss of the testis due to ischemic atrophy or fibrosis.
## Other animals[edit]
Cryptorchidism is seen in all domestic animals, most commonly in stallions, boars, and canines.[14] The prevalence of this condition can vary depending on species and breed. Evidence of this condition is more likely in companion animals and swine than ruminants.[15] The cause of this condition can vary from a combination of genetics, environment, and epigenetics.[14]
### Dogs[edit]
Inguinal cryptorchidism in a Chihuahua
Cryptorchidism is common in male dogs, occurring at a rate up to 10%.[16] This condition is one of the most common congenital defects in purebred dogs (11%), with 14% reported in Siberian Huskies.[17] Although the genetics are not fully understood, it is thought to be a recessive, and probably polygenetic, trait.[18] Some have speculated that it is a sex-limited autosomal recessive trait;[19] however, it is unlikely to be simple recessive.[18] Dog testes usually descend by 10 days of age and it is considered to be cryptorchidism if they do not descend by the age of eight weeks.[20] Cryptorchidism can be either bilateral (causing sterility) or unilateral, and inguinal or abdominal (or both). Because it is an inherited trait, affected dogs should not be bred and should be castrated. The parents should be considered carriers of the defect and a breeder should thoughtfully consider whether to breed the carrier parent or not. Littermates may be normal, carriers, or cryptorchid. Castration of the undescended teste(s) should be considered for cryptorchid dogs due to the high rate of testicular cancer, especially sertoli cell tumors.[20] The incidence of testicular cancer is 13.6 times higher in dogs with abdominally retained testicles compared with normal dogs.[16] Testicular torsion is also more likely in retained testicles. Surgical correction is by palpation of the retained testicle and subsequent exploration of the inguinal canal or abdomen, but showing altered dogs is against AKC rules, making this correction pointless for breeding stock. Orchiopexy is an option for pet dogs that will not be used for breeding.
Commonly affected breeds include:[19]
A retained testicle with cancer removed during necropsy of a dog
* Alaskan Klee Kai
* Boxer
* Chihuahua
* Dachshund (miniature)
* Bulldog
* Maltese
* Miniature Schnauzer
* Pekingese
* Pomeranian
* Poodle (toy and miniature)
* Pug
* Shetland Sheepdog
* Siberian Husky
* Whippet
* Yorkshire Terrier
### Cats[edit]
Cryptorchidism is rarer in cats than it is in dogs. In one study, 1.9% of intact male cats were cryptorchid.[21] Persians are predisposed.[22] Normally, the testicles are in the scrotum by the age of six to eight weeks. Male cats with one cryptorchid testicle may still be fertile; however, male cats with two cryptorchid testicles are most likely to be sterile.[23] Urine spraying is one indication that a cat with no observable testicles may not be neutered; other signs are the presence of enlarged jowls, thickened facial and neck skin, and spines on the penis (which usually regress within six weeks after castration).[24] Most cryptorchid cats present with an inguinal testicle.[25] Testicular tumors and testicular torsion are rare in cryptorchid cats, but castration is usually performed due to unwanted behavior such as urine spraying.
### Horses[edit]
In horses, cryptorchidism is sufficiently common that affected males (ridglings) are routinely gelded.
Rarely, cryptorchidism is due to the presence of a congenital testicular tumor such as a teratoma, which has a tendency to grow large.[26]
## References[edit]
1. ^ Wood, HM; Elder, JS (February 2009). "Cryptorchidism and testicular cancer: separating fact from fiction". The Journal of Urology. 181 (2): 452–61. doi:10.1016/j.juro.2008.10.074. PMID 19084853.
2. ^ Tamparo, Carol (2011). Diseases of the Human Body (Fifth ed.). Philadelphia, PA. pp. 125. ISBN 978-0-8036-2505-1.
3. ^ The A.D.A.M. Medical Encyclopedia
4. ^ Dähnert, Wolfgang (2011). Radiology Review Manual. 995.CS1 maint: location (link)
5. ^ Pettersson, Andreas; Lorenzo Richiardi; Agneta Nordenskjold; Magnus Kaijser; Olof Akre (May 3, 2007). "Age at Surgery for Undescended Testis and Risk of Testicular Cancer". NEJM. 356 (18): 1835–41. doi:10.1056/NEJMoa067588. hdl:2318/58479. PMID 17476009.
6. ^ Meyer-Bahlburg, et al (1974). Cryptorchism, development of gender identity and sex behavior. In Sex Differences in Behavior, ed. Friedman, Richart, & Vande Wiele. New York: Wiley
7. ^ a b c d e "Undescended testicle - Symptoms and causes". Mayo Clinic. Retrieved 2018-03-31.
8. ^ Andersen, HR; Schmidt, IM; Grandjean, P; Jensen, TK; Budtz-Jørgensen, E; Kjaerstad, MB; Baelum, J; Nielsen, JB; Skakkebaek, NE; Main, KM (April 2008). "Impaired reproductive development in sons of women occupationally exposed to pesticides during pregnancy". Environmental Health Perspectives. 116 (4): 566–72. doi:10.1289/ehp.10790. PMC 2290975. PMID 18414644.
9. ^ Rehmeyer, Julie (2 January 2007). "Drinking During Pregnancy Emerges As a Possible Male-Infertility Factor". Science News.
10. ^ Brouwers, Marijn M.; de Bruijne, Leonie M.; de Gier, Robert P.E.; Zielhuis, Gerhard A.; Feitz, Wouter F.J.; Roeleveld, Nel (2012). "Risk factors for undescended testis". Journal of Pediatric Urology. 8 (1): 59–66. doi:10.1016/j.jpurol.2010.11.001. PMID 21115274.
11. ^ Pelley, Janet (12 November 2008). "Plasticizer may make boys less masculine". Environmental Science & Technology. doi:10.1021/on.2008.11.12.154968 (inactive 2021-01-15). Retrieved 2019-01-20.CS1 maint: DOI inactive as of January 2021 (link)
12. ^ a b Kristensen, DM; Hass, U; Lesné, L; Lottrup, G; Jacobsen, PR; Desdoits-Lethimonier, C; Boberg, J; Petersen, JH; Toppari, J; Jensen, TK; Brunak, S; Skakkebaek, NE; Nellemann, C; Main, KM; Jégou, B; Leffers, H (January 2011). "Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat". Human Reproduction. 26 (1): 235–44. doi:10.1093/humrep/deq323. PMID 21059752.
13. ^ Welsh, M.; Saunders, P. T.; et al. (2008). "Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism". J Clin Invest. 118 (4): 1479–1490. doi:10.1172/jci34241. PMC 2267017. PMID 18340380.
14. ^ a b "Congenital and Inherited Anomalies of the Reproductive System - Merck Veterinary Manual". Merck Veterinary Manual. Retrieved 2017-12-05.
15. ^ Amann, R. P.; Veeramachaneni, D. N. R. (2007-03-01). "Cryptorchidism in common eutherian mammals". Reproduction. 133 (3): 541–561. doi:10.1530/rep-06-0272. ISSN 1470-1626. PMID 17379650.
16. ^ a b Miller NA, Van Lue SJ, Rawlings CA (2004). "Use of laparoscopic-assisted cryptorchidectomy in dogs and cats". J. Am. Vet. Med. Assoc. 224 (6): 875–8, 865. CiteSeerX 10.1.1.204.888. doi:10.2460/javma.2004.224.875. PMID 15070057.
17. ^ Zhao, X.; Du, Z.-Q.; Rothschild, M.f. (2010-08-01). "An association study of 20 candidate genes with cryptorchidism in Siberian Husky dogs". Journal of Animal Breeding and Genetics. 127 (4): 327–331. doi:10.1111/j.1439-0388.2010.00859.x. ISSN 1439-0388. PMID 20646120.
18. ^ a b Willis, Malcolm B. (1989). Genetics of the Dog (1st ed.). Howell Book House. ISBN 978-0-87605-551-9.
19. ^ a b Ettinger, Stephen J.; Feldman, Edward C. (1995). Textbook of Veterinary Internal Medicine (4th ed.). W.B. Saunders Company. ISBN 978-0-7216-6795-9.
20. ^ a b Meyers-Wallen, V.N. "Inherited Abnormalities of Sexual Development in Dogs and Cats". Recent Advances in Small Animal Reproduction. Retrieved 2006-08-10.
21. ^ Scott K, Levy J, Crawford P (2002). "Characteristics of free-roaming cats evaluated in a trap-neuter-return program". J Am Vet Med Assoc. 221 (8): 1136–38. doi:10.2460/javma.2002.221.1136. PMID 12387382.
22. ^ Griffin, Brenda (2005). "Diagnostic usefulness of and clinical syndromes associated with reproductive hormones". In August, John R. (ed.). Consultations in Feline Internal Medicine Vol. 5. Elsevier Saunders. ISBN 978-0-7216-0423-7.
23. ^ Eldredge, Debra M.; Carlson, Delbert G.; Carlson, Liisa D.; Giffin, James M. (2008). Cat Owner's Home Veterinary Handbook. Howell Book House. p. 421.
24. ^ Memon, M.; Tibary, A. (2001). "Canin and Feline Cryptorchidism" (PDF). Recent Advances in Small Animal Reproduction. Retrieved 2007-02-09.
25. ^ Yates D, Hayes G, Heffernan M, Beynon R (2003). "Incidence of cryptorchidism in dogs and cats". Vet Rec. 152 (16): 502–504. doi:10.1136/vr.152.16.502. PMID 12733559. S2CID 39651870.
26. ^ Jones, T. C.; R. D. Hunt & N. W. King (1997). Veterinary pathology (6th ed.). Wiley-Blackwell. p. 1392. ISBN 978-0-683-04481-2. p. 1210.
## External links[edit]
Wikimedia Commons has media related to Cryptorchidism.
* Kidshealth.org: Cryptorchidism
Classification
D
* ICD-10: Q53
* ICD-9-CM: 752.5
* OMIM: 219050
* MeSH: D003456
* DiseasesDB: 3218
External resources
* MedlinePlus: 000973
* eMedicine: med/2707 radio/201 ped/3080
* v
* t
* e
Male congenital anomalies of the genitalia, including Intersex and DSD
Internal
Testicle
* Cryptorchidism
* Polyorchidism
* Monorchism
* Anorchia
* Sertoli cell-only syndrome
* True hermaphroditism
* Mixed gonadal dysgenesis
* Swyer syndrome
Vas deferens
* Congenital absence of the vas deferens
Other
* Persistent Müllerian duct syndrome
External
Penis
* Hypospadias
* Epispadias
* Chordee
* Micropenis
* Penile agenesis
* Diphallia
* Penoscrotal transposition
Other
* Pseudohermaphroditism
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Cryptorchidism | c0010417 | 5,170 | wikipedia | https://en.wikipedia.org/wiki/Cryptorchidism | 2021-01-18T19:07:36 | {"mesh": ["D003456"], "umls": ["C0010417"], "wikidata": ["Q966052"]} |
Nuclear gene-encoded Leigh syndrome is a progressive neurological disease. It usually first becomes apparent in infancy with developmental delay or regression. Rarely, the disease begins in adolescence or adulthood. Symptoms progress to include generalized weakness, lack of muscle tone, spasticity, movement disorders, cerebellar ataxia, and peripheral neuropathy. Other signs and symptoms may include an increase in the heart muscle size (hypertrophic cardiomyopathy); excessive body hair (hypertrichosis); anemia; kidney or liver problems; and lung or heart failure. Nuclear gene-encoded Leigh syndrome (and Leigh-like syndrome, a term used for cases with similar features but that do not fulfill the diagnostic criteria for Leigh syndrome) may be caused by mutations in any of several genes and can be inherited in an autosomal recessive or X-linked manner. While treatment for some cases of Leigh-like syndrome may be available, management is generally supportive and focuses on the symptoms present.
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Nuclear gene-encoded Leigh syndrome | None | 5,171 | gard | https://rarediseases.info.nih.gov/diseases/12941/nuclear-gene-encoded-leigh-syndrome | 2021-01-18T17:58:39 | {"synonyms": []} |
## Clinical Features
Fred et al. (1962) described acute pulmonary edema precipitated in some persons at high altitude. Their 2 patients were both physicians who on one or more occasions were near death from pulmonary edema that developed when skiing at altitudes of 6,000 to 10,000 feet. The father of one of these, previously in good health, died at age 43 while mountain climbing, and acute pulmonary edema was thought to be the cause. Hultgren et al. (1961) also noted familial occurrence. Cardiac catheterization during the acute episode showed normal left atrial and pulmonary vein pressures but elevation of pulmonary artery pressure. Pulmonary edema, it was proposed, results from increased vasomotor activity of the pulmonary venous capillaries or venules. Cattle differ in their susceptibility to right-sided heart failure when pastured at high altitudes. (The heart failure is known as 'brisket disease' because of accumulation of edema in and over the parasternal muscles. It is due to pulmonary hypertension.) Weir et al. (1974) could demonstrate no difference in reactivity of pulmonary vasculature of susceptible and resistant animals. Conceivably a major portion of the adaption to altitude shown by Sherpas in the Himalayan mountains and by Amerindians in the Andes might be determined by 1 or 2 loci. Those occasional Sherpas or Andean Indians who get mountain sickness have a genetic disease (see chronic mountain sickness, 616182), but the 'disease' is the normal for those of us who live at lower altitudes.
In the Kyrghyz Republic, 90% of the territory is high mountains of the Tien Shan and Pamir ranges, and more than 200,000 people live at an altitude greater than 3,000 meters above sea level. There, as in other mountainous regions of the world, high altitude pulmonary hypertension (HAPH) is a major public health issue because up to 6% of the population develop severe pulmonary hypertension with right ventricular dysfunction (Mirrakhimov and Winslow, 1996).
Morrell et al. (1995) found that angiotensin I-converting enzyme (ACE; 106180) expression is increased in small pulmonary arteries of rats with hypoxia-induced pulmonary hypertension. Morrell et al. (1999) determined the ACE insertion/deletion (I/D) genotypes (106180.0001) in 37 Kyrghyz highland men during investigation for suspected HAPH. People with HAPH were found to have a 6-fold higher frequency of the I/I genotype compared with those without (p = 0.04). The odds ratio for HAPH among highlanders carrying the I allele was 3. The results were unexpected because it is the D allele that confers higher ACE enzyme concentrations (Rigat et al., 1990). Morrell et al. (1999) suggested that the likely explanation is that the I allele is in linkage disequilibrium with another important HAPH susceptibility gene within this population.
Pulmonary edema results from a persistent imbalance between the forces that drive water into the air space in the alveoli and the physiologic mechanisms that remove it. For many years, it was believed that Starling forces and lymphatic drainage accounted entirely for the removal of excess intraalveolar fluid, but it later became clear that an osmotic gradient created by vectorial transepithelial sodium transport plays an important part. Sodium enters the apical membrane of alveolar epithelial cells mainly through amiloride-sensitive cation channels and is transported across the basolateral membrane by ouabaine-inhibitable Na(+)/K(+)-ATPase (Matalon et al., 1996). Hummler et al. (1996) found that in mice deletion of the alpha subunit of the amiloride-sensitive epithelial sodium channel (SCNN1A; 600228) leads to neonatal death because of failure to clear the liquid from the lungs. Sartori et al. (2002) pointed out that beta-adrenergic agonists increased vectorial sodium transport in vitro, enhanced the clearance of alveolar fluid in the resected human lung and in several species of animals, and accelerated the resolution of pulmonary edema in animal models of lung injury. Among the physiologic mechanisms that remove water from the air, the absorption of liquid driven by active alveolar transepithelial sodium transport may be defective in patients predisposed to pulmonary edema. Sartori et al. (2002) assessed the effects of prophylactic inhalation of the beta-adrenergic agonist salmeterol on the incidence of pulmonary edema during exposure to high altitudes in 37 subjects who were susceptible to high altitude pulmonary edema. They also measured the nasal transepithelial potential difference, a marker of the transepithelial sodium and water transport in the distal airways, in 33 mountaineers who were prone to high altitude pulmonary edema and 33 mountaineers who were resistant to this condition. They found that the beta-adrenergic agonist reduced the risk of high altitude pulmonary edema. They pointed to this as evidence that sodium-dependent absorption of liquid from the airways may be defective in patients who are susceptible to high altitude pulmonary edema.
Molecular Genetics
### Associations Pending Confirmation
For discussion of a possible association between variation in the GUCY1A3 gene and protection against high-altitude pulmonary hypertension, see 139396.
Animal Model
In Sprague-Dawley rats undergoing hypoxia-induced pulmonary hypertension, Sebkhi et al. (2003) observed that pretreatment with the phosphodiesterase-5A (PDE5A; 603310)-inhibitor sildenafil significantly reduced the increase in pulmonary artery pressure in a dose-dependent manner (60 to 90% reduction). When begun after 14 days of hypoxia, sildenafil significantly reduced pulmonary artery pressure (30% reduction) and partially reversed pulmonary artery muscularization (approximately 40% reduction). Sebkhi et al. (2003) concluded that PDE5A inhibition attenuates the rise in pulmonary artery pressure and vascular remodeling when given before chronic exposure to hypoxia and when administered as a treatment during ongoing hypoxia-induced pulmonary hypertension.
INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Normal left atrial pressure Vascular \- Normal pulmonary vein pressures \- Elevated pulmonary artery pressure RESPIRATORY Lung \- High altitude acute pulmonary edema MISCELLANEOUS \- Crisis precipitated by high altitude exposure ▲ 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| PULMONARY EDEMA OF MOUNTAINEERS, SUSCEPTIBILITY TO | c0340552 | 5,172 | omim | https://www.omim.org/entry/178400 | 2019-09-22T16:35:24 | {"mesh": ["C535833"], "omim": ["178400"], "synonyms": ["Alternative titles", "HIGH ALTITUDE PULMONARY HYPERTENSION"]} |
This article is about the neurological syndrome. For the congenital disorder, see split hand.
Split hand syndrome
SpecialtyNeurological
In medicine, split hand syndrome is a neurological syndrome in which the hand muscles on the side of the thumb (lateral, thenar eminence) appear wasted, whereas the muscles on the side of the little finger (medial, hypothenar eminence) are spared. Anatomically, the abductor pollicis brevis and first dorsal interosseous muscle are more wasted than the abductor digiti minimi.[1]
If lesions affecting the branches of the ulnar nerve that run to the wasted muscles are excluded, the lesion is almost sure to be located in the anterior horn of the spinal cord at the C8-T1 level.[2] It has been proposed as a relatively specific sign for amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease).[1][3] It can also occur in other disorders affecting the anterior horn, such as spinal muscular atrophy, Charcot-Marie-Tooth disease, poliomyelitis and progressive muscular atrophy.[2][4] A slow onset and a lack of pain or sensorial symptoms are arguments against a lesion of the spinal root or plexus brachialis.[4] To an extent, these features can also be seen in normal aging (although technically, the apparent muscle wasting is sarcopenia rather than atrophy).[5]
The term split hand syndrome was first coined in 1994 by a researcher from the Cleveland Clinic called Asa J. Wilbourn.[6][7]
## Footnotes[edit]
1. ^ a b Kuwabara S, Sonoo M, Komori T, et al. (April 2008). "Dissociated small hand muscle atrophy in amyotrophic lateral sclerosis: frequency, extent, and specificity". Muscle Nerve. 37 (4): 426–30. doi:10.1002/mus.20949. PMID 18236469. S2CID 18500530.
2. ^ a b Split hand syndrome. Stedman's Medical Dictionary. Retrieved August 13, 2008.
3. ^ Kuwabara S, Mizobuchi K, Ogawara K, Hattori T (July 1999). "Dissociated small hand muscle involvement in amyotrophic lateral sclerosis detected by motor unit number estimates". Muscle Nerve. 22 (7): 870–3. doi:10.1002/(SICI)1097-4598(199907)22:7<870::AID-MUS9>3.0.CO;2-O. PMID 10398204. Archived from the original on 2013-01-05.
4. ^ a b Schelhaas HJ, van de Warrenburg BP, Kremer HP, Zwarts MJ (December 2003). "The "split hand" phenomenon: evidence of a spinal origin". Neurology. 61 (11): 1619–20. doi:10.1212/01.wnl.0000096009.50213.6c. PMID 14663056. S2CID 39361741.
5. ^ Voermans NC, Schelhaas HJ, Munneke M, Zwarts MJ (December 2006). "Dissociated small hand muscle atrophy in aging: the 'senile hand' is a split hand". Eur J Neurol. 13 (12): 1381–4. doi:10.1111/j.1468-1331.2006.01477.x. PMID 17116225. S2CID 26868415.
6. ^ Wilbourn AJ, Sweeney PJ (1994). "Dissociated wasting of medial and lateral hand muscles with motor neuron disease". Can J Neurol Sci. 21 (S2): S9.
7. ^ Wilbourn AJ (January 2000). "The "split hand syndrome"". Muscle Nerve. 23 (1): 138. doi:10.1002/(SICI)1097-4598(200001)23:1<138::AID-MUS22>3.0.CO;2-7. PMID 10590421. Archived from the original on 2013-01-05.
* v
* t
* e
Symptoms and signs relating to movement and gait
Gait
* Gait abnormality
* CNS
* Scissor gait
* Cerebellar ataxia
* Festinating gait
* Marche à petit pas
* Propulsive gait
* Stomping gait
* Spastic gait
* Magnetic gait
* Truncal ataxia
* Muscular
* Myopathic gait
* Trendelenburg gait
* Pigeon gait
* Steppage gait
* Antalgic gait
Coordination
* Ataxia
* Cerebellar ataxia
* Dysmetria
* Dysdiadochokinesia
* Pronator drift
* Dyssynergia
* Sensory ataxia
* Asterixis
Abnormal movement
* Athetosis
* Tremor
* Fasciculation
* Fibrillation
Posturing
* Abnormal posturing
* Opisthotonus
* Spasm
* Trismus
* Cramp
* Tetany
* Myokymia
* Joint locking
Paralysis
* Flaccid paralysis
* Spastic paraplegia
* Spastic diplegia
* Spastic paraplegia
* Syndromes
* Monoplegia
* Diplegia / Paraplegia
* Hemiplegia
* Triplegia
* Tetraplegia / Quadruplegia
* General causes
* Upper motor neuron lesion
* Lower motor neuron lesion
Weakness
* Hemiparesis
Other
* Rachitic rosary
* Hyperreflexia
* Clasp-knife response
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Split hand syndrome | None | 5,173 | wikipedia | https://en.wikipedia.org/wiki/Split_hand_syndrome | 2021-01-18T18:35:51 | {"wikidata": ["Q7578690"]} |
Type A insulin resistance syndrome is a rare disorder characterized by severe insulin resistance, a condition in which the body's tissues and organs do not respond properly to the hormone insulin. Insulin normally helps regulate blood sugar levels by controlling how much sugar (in the form of glucose) is passed from the bloodstream into cells to be used as energy. In people with type A insulin resistance syndrome, insulin resistance impairs blood sugar regulation and ultimately leads to a condition called diabetes mellitus, in which blood sugar levels can become dangerously high.
Severe insulin resistance also underlies the other signs and symptoms of type A insulin resistance syndrome. In affected females, the major features of the condition become apparent in adolescence. Many affected females do not begin menstruation by age 16 (primary amenorrhea) or their periods may be light and irregular (oligomenorrhea). They develop cysts on the ovaries and excessive body hair growth (hirsutism). Most affected females also develop a skin condition called acanthosis nigricans, in which the skin in body folds and creases becomes thick, dark, and velvety. Unlike most people with insulin resistance, females with type A insulin resistance syndrome are usually not overweight.
The features of type A insulin resistance syndrome are more subtle in affected males. Some males have low blood sugar (hypoglycemia) as the only sign; others may also have acanthosis nigricans. In many cases, males with this condition come to medical attention only when they develop diabetes mellitus in adulthood.
Type A insulin resistance syndrome is one of a group of related conditions described as inherited severe insulin resistance syndromes. These disorders, which also include Donohue syndrome and Rabson-Mendenhall syndrome, are considered part of a spectrum. Type A insulin resistance syndrome represents the mildest end of the spectrum: its features often do not become apparent until puberty or later, and it is generally not life-threatening.
## Frequency
Type A insulin resistance syndrome is estimated to affect about 1 in 100,000 people worldwide. Because females have more health problems associated with the condition, it is diagnosed more often in females than in males.
## Causes
Type A insulin resistance syndrome results from mutations in the INSR gene. This gene provides instructions for making a protein called an insulin receptor, which is found in many types of cells. Insulin receptors are embedded in the outer membrane surrounding the cell, where they attach (bind) to insulin circulating in the bloodstream. This binding triggers signaling pathways that influence many cell functions.
Most of the INSR gene mutations that cause type A insulin resistance syndrome lead to the production of a faulty insulin receptor that cannot transmit signals properly. Although insulin is present in the bloodstream, the defective receptors make it less able to exert its effects on cells and tissues. This severe resistance to the effects of insulin impairs blood sugar regulation and leads to diabetes mellitus. In females with type A insulin resistance syndrome, excess insulin in the bloodstream interacts with hormonal factors during adolescence to cause abnormalities of the menstrual cycle, ovarian cysts, and other features of the disorder.
This condition is designated as type A to distinguish it from type B insulin resistance syndrome. Although the two disorders have similar signs and symptoms, type B is not caused by INSR gene mutations; instead, it results from an abnormality of the immune system that blocks insulin receptor function.
### Learn more about the gene associated with Type A insulin resistance syndrome
* INSR
## Inheritance Pattern
Type A insulin resistance syndrome can have either an autosomal dominant or, less commonly, an autosomal recessive pattern of inheritance.
In autosomal dominant inheritance, one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.
In autosomal recessive inheritance, 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Type A insulin resistance syndrome | c0342278 | 5,174 | medlineplus | https://medlineplus.gov/genetics/condition/type-a-insulin-resistance-syndrome/ | 2021-01-27T08:25:36 | {"gard": ["3008"], "mesh": ["C562710"], "omim": ["610549"], "synonyms": []} |
Shwachman-Diamond syndrome (SDS) affects many parts of the body, particularly the bone marrow, pancreas, and skeletal system. Symptoms include the inability to digest food due to missing digestive enzymes, low muscle tone, and anemia. Other symptoms include skeletal findings and intellectual disability. Children with SDS may have feeding difficulties, slow growth, and frequent infections. People with SDS are at increased risk for blood cancers. Shwachman-Diamond syndrome can be caused by the SBDS, DNAJC21, EFL1, or SRP54 gene not working correctly. It can be inherited in either an autosomal recessive or autosomal dominant pattern. SDS is diagnosed is based on symptoms, blood tests, and genetic testing. Treatment may include enzyme and vitamin supplements, blood transfusion, granulocyte-colony stimulating factor (G-CSF), and hematopoietic stem cell transplantation.
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Shwachman-Diamond syndrome | c0272170 | 5,175 | gard | https://rarediseases.info.nih.gov/diseases/4863/shwachman-diamond-syndrome | 2021-01-18T17:57:43 | {"mesh": ["C537330"], "omim": ["260400"], "umls": ["C0272170"], "orphanet": ["811"], "synonyms": ["SDS", "Pancreatic insufficiency and bone marrow dysfunction", "Shwachman-Bodian syndrome", "Lipomatosis of pancreas, congenital", "Congenital lipomatosis of pancreas"]} |
AIDS dysmorphic syndrome, also called HIV embryopathy, is a cluster of facial malformations seen in children with perinatal HIV infection. Its status as a syndrome is disputed by the research community. Common symptoms of perinatal HIV infection include candidiasis, lymphocytic interstitial pneumonitis, hepatosplenomegaly, and lymphadenopathy.[1]
## References[edit]
1. ^ "AIDS Dysmorphic Syndrome - NORD (National Organization for Rare Disorders)". Retrieved 2015-09-21.
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| AIDS dysmorphic syndrome | None | 5,176 | wikipedia | https://en.wikipedia.org/wiki/AIDS_dysmorphic_syndrome | 2021-01-18T18:34:39 | {"gard": ["5765"], "wikidata": ["Q24975595"]} |
Hypokalemic sensory overstimulation
Hypokalemic sensory overstimulation is characterized by a subjective experience of sensory overload and a relative resistance to lidocaine local anesthesia. The sensory overload is treatable with oral potassium gluconate. Individuals with this condition are sometimes diagnosed as having attention deficit hyperactivity disorder (ADHD), raising the possibility that a subtype of ADHD has a cause that can be understood mechanistically and treated in a novel way.
It is not to be confused with hot tooth syndrome.
## Contents
* 1 Cause
* 2 Diagnosis
* 3 Treatment
* 4 References
## Cause[edit]
Hypokalemic sensory overstimulation is a term coined by MM Segal and colleagues to describe a syndrome of sensory overstimulation, ineffectiveness of the local anesthetic lidocaine, and in females, premenstrual syndrome.[1] This initial report was followed by discussion in a second article of tens of families with apparent autosomal dominant inheritance of this condition.[2] The similarities were described clinically to ADHD and mechanistically and therapeutically to disorders of ion channels, in particular to the muscle disorder hypokalemic periodic paralysis. Some females with premenstrual syndrome may have the same autosomal dominant disorder underlying their symptoms.[2]
## Diagnosis[edit]
A test for lidocaine ineffectiveness was briefly described in the 2014 paper[2] but the controlled trial has not yet been completed.[3]
## Treatment[edit]
The use of oral potassium and avoiding high carbohydrate meals can help treat it according to recent tests, following the same approach that is standard for the muscle disease hypokalemic periodic paralysis.[4][5]
Since this condition includes ineffectiveness of the sodium-channel blocker lidocaine, the amide-type local anesthetic used in dental care articaine was tested and found to be effective in one member of the family.[1] No data about other local anesthetics effective in these individuals for non-dental procedures has yet been published.
## References[edit]
1. ^ a b Segal, M. M; Rogers, G. F; Needleman, H. L; Chapman, C. A (2007). "Hypokalemic sensory overstimulation". Journal of Child Neurology. 22 (12): 1408–10. doi:10.1177/0883073807307095. PMID 18174562. S2CID 35659227.
2. ^ a b c Segal, Michael M (2014). "We Cannot Say Whether Attention Deficit Hyperactivity Disorder Exists, but We Can Find its Molecular Mechanisms". Pediatric Neurology. 51 (1): 15–16. doi:10.1016/j.pediatrneurol.2014.04.014. PMID 24938135.
3. ^ Clinical trial number NCT03563573 for "Single-dose Potassium Supplementation in Patients With ADHD for Whom the Anesthetic Lidocaine is Ineffective" at ClinicalTrials.gov
4. ^ "What causes ADHD? Some intriguing findings". 11 January 2008.
5. ^ Levitt, Jacob O. (21 April 2008). "Practical aspects in the management of hypokalemic periodic paralysis". Journal of Translational Medicine. 6 (1): 18. doi:10.1186/1479-5876-6-18. PMC 2374768. PMID 18426576.
* Medicine portal
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Anesthesia and anesthesiology
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* General
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Techniques
* Airway management
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* Dogliotti's principle
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* Intraoperative neurophysiological monitoring
* Nerve block
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Scientific principles
* Blood–gas partition coefficient
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Measurements
* ASA physical status classification system
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Instruments
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Complications
* Emergence delirium
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* Anesthesiologist
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History
* ACE mixture
* Helsinki Declaration for Patient Safety in Anaesthesiology
* History of general anesthesia
* History of neuraxial anesthesia
* History of tracheal intubation
Organizations
* American Association of Nurse Anesthetists
* American Society of Anesthesia Technologists & Technicians
* American Society of Anesthesiologists
* Anaesthesia Trauma and Critical Care
* Association of Anaesthetists of Great Britain and Ireland
* Royal College of Anaesthetists
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* Australian and New Zealand College of Anaesthetists
* Australian Society of Anaesthetists
* International Anesthesia Research Society
* Category
* 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Hypokalemic sensory overstimulation | None | 5,177 | wikipedia | https://en.wikipedia.org/wiki/Hypokalemic_sensory_overstimulation | 2021-01-18T19:09:26 | {"wikidata": ["Q48837404"]} |
Papillomatosis
SpecialtyDermatology
Papillomatosis of skin is skin surface elevation caused by hyperplasia and enlargement of contiguous dermal papillae.[1] These papillary projections of the epidermis form an undulating surface under microscopic examination.
## See also[edit]
* Skin lesion
* Skin disease
* List of skin diseases
* Papilloma
* Laryngeal papillomatosis
## References[edit]
1. ^ Kumar, Vinay; Fausto, Nelso; Abbas, Abul (2004) Robbins & Cotran Pathologic Basis of Disease (7th ed.). Saunders. Page 1230. ISBN 0-7216-0187-1.
## External links[edit]
Classification
D
* MeSH: D010212
* v
* t
* e
Skin lesion terminology
Macroscopic
Primary lesions
* flat
* Macule
* Patch
* elevated
* Papule
* Nodule
* Plaque
* fluid
* Vesicle
* Bulla
* Pustule
* Ulcer
* Erosion
* Telangiectasia
* Special initial lesions : Burrow
* Tunnel
* Comedo
* Scutulum
* Target lesion
* Herald patch
* Wheal
Secondary lesions
* Scale
* Crust
* Lichenification
* Excoriation
* Induration
* Atrophy
Microscopic
* keratin: Hyperkeratosis
* Parakeratosis
* Dyskeratosis
* Hypergranulosis
* Acanthosis
* Papillomatosis
* Acantholysis
* Spongiosis
* Hydropic swelling
* Exocytosis
* Vacuolization
* Erosion
* Ulceration
* Lentiginous
*[v]: View this template
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*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Papillomatosis | c0205875 | 5,178 | wikipedia | https://en.wikipedia.org/wiki/Papillomatosis | 2021-01-18T18:57:33 | {"mesh": ["D010212"], "wikidata": ["Q1223924"]} |
De Vries et al. (1962) presented evidence, based on 3 extensively studied families, that uric acid urolithiasis can be inherited as an autosomal dominant trait independent of gout. In these families no gout or hyperuricemia was found. Cases of this type had rather long been recognized and had been referred to by Henneman as 'idiopathic uric acid stone formers.' The familial nature had apparently not been recognized previously. Recognition of the disorder as familial may be important to its prevention. Oral alkalinization and high fluid intake will often dissolve stones already formed and can be depended on to prevent stone formation. Henneman et al. (1962) suggested that elderly Italian or Jewish patients are most likely to get into trouble with uric acid stones despite normal serum and urine concentrations of uric acid. Constant acidity of the urine and low ammonium excretion may be involved in pathogenesis.
GU \- Uric acid urolithiasis independent of gout Misc \- Response to oral alkalinization and high fluid intake Lab \- No hyperuricemia 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| UROLITHIASIS, URIC ACID, AUTOSOMAL DOMINANT | c2674049 | 5,179 | omim | https://www.omim.org/entry/191700 | 2019-09-22T16:32:07 | {"omim": ["191700"], "synonyms": ["Alternative titles", "NEPHROLITHIASIS, URIC ACID, AUTOSOMAL DOMINANT"]} |
Muenke syndrome is a condition characterized by the premature closure of certain bones of the skull (craniosynostosis) during development, which affects the shape of the head and face.
Many people with this disorder have a premature fusion of skull bones along the coronal suture, the growth line that goes over the head from ear to ear. Other parts of the skull may also be malformed. These changes can result in an abnormally shaped head, wide-set eyes, and flattened cheekbones. About 5 percent of affected individuals have an enlarged head (macrocephaly). People with Muenke syndrome may also have mild abnormalities of the hands or feet, and hearing loss has been observed in some cases. Most people with this condition have normal intellect, but developmental delay and learning problems are possible.
The signs and symptoms of Muenke syndrome vary among affected people, and some features overlap with those seen in other craniosynostosis syndromes. A small percentage of people with the gene mutation associated with Muenke syndrome do not have any of the characteristic features of the disorder.
## Frequency
Muenke syndrome occurs in about 1 in 30,000 newborns. This condition accounts for an estimated 4 percent of all cases of craniosynostosis.
## Causes
A particular mutation in the FGFR3 gene causes Muenke syndrome. The FGFR3 gene provides instructions for making a protein that is involved in the development and maintenance of bone and brain tissue. The mutation associated with Muenke syndrome causes the FGFR3 protein to be overly active, which interferes with normal bone growth and allows the bones of the skull to fuse before they should.
### Learn more about the gene associated with Muenke syndrome
* FGFR3
## Inheritance Pattern
This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Muenke syndrome | c1864436 | 5,180 | medlineplus | https://medlineplus.gov/genetics/condition/muenke-syndrome/ | 2021-01-27T08:24:51 | {"gard": ["7097"], "mesh": ["C537369"], "omim": ["602849"], "synonyms": []} |
Genitopatellar syndrome is a rare condition characterized by genital abnormalities, missing or underdeveloped kneecaps (patellae), intellectual disability, and abnormalities affecting other parts of the body.
The genital abnormalities in affected males typically include undescended testes (cryptorchidism) and underdevelopment of the scrotum. Affected females can have an enlarged clitoris (clitoromegaly) and small labia.
Missing or underdeveloped patellae is the most common skeletal abnormality associated with genitopatellar syndrome. Affected individuals may have additional skeletal problems, including joint deformities (contractures) involving the hips and knees or an inward- and upward-turning foot called a clubfoot. Bone abnormalities of the spine, ribs, collarbone (clavicle), and pelvis have also been reported.
Genitopatellar syndrome is also associated with delayed development and intellectual disability, which are often severe. Affected individuals may have an usually small head (microcephaly) and structural brain abnormalities, including underdeveloped or absent tissue connecting the left and right halves of the brain (agenesis of the corpus callosum).
People with genitopatellar syndrome may have distinctive facial features such as prominent cheeks and eyes, a nose with a rounded tip or a broad bridge, an unusually small chin (micrognathia) or a chin that protrudes (prognathism), and a narrowing of the head at the temples. Many affected infants have weak muscle tone (hypotonia) that leads to breathing and feeding difficulties. The condition can also be associated with abnormalities of the heart, kidneys, and teeth.
## Frequency
Genitopatellar syndrome is estimated to occur in fewer than 1 per million people. At least 18 cases have been reported in the medical literature.
## Causes
Genitopatellar syndrome is caused by mutations in the KAT6B gene. This gene provides instructions for making a type of enzyme called a histone acetyltransferase. These enzymes modify histones, which are structural proteins that attach (bind) to DNA and give chromosomes their shape. By adding a small molecule called an acetyl group to histones, histone acetyltransferases control the activity of certain genes. Little is known about the function of the histone acetyltransferase produced from the KAT6B gene. It appears to regulate genes that are important for early development, including development of the skeleton and nervous system.
The mutations that cause genitopatellar syndrome occur near the end of the KAT6B gene and lead to the production of a shortened histone acetyltransferase enzyme. Researchers suspect that the shortened enzyme may function differently than the full-length version, altering the regulation of various genes during early development. However, it is unclear how these changes lead to the specific features of genitopatellar syndrome.
### Learn more about the gene associated with Genitopatellar syndrome
* KAT6B
## Inheritance Pattern
This condition has an autosomal dominant inheritance pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. All reported cases have resulted from new mutations in the gene and have occurred in people with no history of the disorder in their 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Genitopatellar syndrome | c1853566 | 5,181 | medlineplus | https://medlineplus.gov/genetics/condition/genitopatellar-syndrome/ | 2021-01-27T08:25:43 | {"gard": ["10994"], "mesh": ["C565255"], "omim": ["606170"], "synonyms": []} |
A number sign (#) is used with this entry because encephalopathy due to defective mitochondrial and peroxisomal fission-1 (EMPF1) is caused by heterozygous mutation in the DNM1L gene (603850), encoding the dynamin-1-like protein, on chromosome 12p. Some patients have compound heterozygous DNM1L mutations.
Description
Encephalopathy due to defective mitochondrial and peroxisomal fission-1 is characterized by delayed psychomotor development and hypotonia that may lead to death in childhood. Many patients develop refractory seizures, consistent with an epileptic encephalopathy, and thereafter show neurologic decline. The age at onset, features, and severity are variable, and some patients may not have clinical evidence of mitochondrial or peroxisomal dysfunction (summary by Sheffer et al., 2016; Fahrner et al., 2016).
### Genetic Heterogeneity of Encephalopathy Due to Defective Mitochondrial And Peroxisomal Fission
See also EMPF2 (617086), caused by mutation in the MFF gene (614785) on chromosome 2q36.
Clinical Features
Waterham et al. (2007) reported a newborn girl, born of unrelated Caucasian parents of British ancestry, with a systemic disorder resulting in death in infancy. The mother noted diminished fetal movements during pregnancy. After birth, the infant was well for several days, but presented in the first week of life with poor feeding and neurologic impairment, including hypotonia, little spontaneous movement, no tendon reflexes, no response to light stimulation, and poor visual fixation. She was mildly dysmorphic, with microcephaly, deep-set eyes, and a pointed chin. Optic discs were pale and cupped, and MRI showed an abnormal gyral pattern in both frontal lobes that extended to the perisylvian areas and was associated with dysmyelination. Laboratory studies showed persistent lactic acidemia and mildly elevated plasma concentration of very long-chain fatty acids. She died suddenly at 37 days of age. Studies of patient fibroblasts did not show defects in mitochondrial oxidative phosphorylation or in mitochondrial complex activities, and muscle biopsy was essentially normal with no ragged-red fibers. However, immunofluorescence microscopic analyses showed fewer peroxisomes in fibroblasts compared to controls, and the peroxisomes varied markedly in size and were frequently arranged in rows. This arrangement was similar to that seen in mammalian cells overexpressing dominant-negative mutant DLP1 or those with DLP1 expression that had been downregulated owing to RNA interference (Koch et al., 2003; Li and Gould, 2003). Because such mammalian cells also showed a defect in mitochondrial fission (Smirnova et al., 2001; Yoon et al., 2001), Waterham et al. (2007) studied the mitochondria of fibroblasts from the patient using a fluorescent mitochondrial probe. Mitochondria in the patient's fibroblasts were elongated, tangled, tubular structures concentrated predominantly around the nucleus.
Sheffer et al. (2016) reported a 2-year-old boy, born of unrelated Arab parents, with a severe neurologic disorder characterized by neonatal hypotonia and respiratory insufficiency, delayed psychomotor development, and insensitivity to pain. At age 2 years, he could crawl, but not stand or speak. He had postnatal microcephaly, poor overall growth, athetoid movements, drooling, broad thumbs and big toes, and reduced muscle tone; there were no significant dysmorphic features. Brain imaging suggested delayed myelination. Plasma lactate was mildly increased, and patient fibroblasts showed isolated mitochondrial complex IV deficiency, as well as decreased ATP production and oxygen consumption (decreased by 30 and 40%, respectively). Mitochondria isolated from patient fibroblasts showed an elongated morphology, but peroxisomes appeared normal and there was no biochemical evidence of a peroxisomal defect.
Vanstone et al. (2016) reported a 7-year-old boy, born of unrelated Caucasian parents, with severely delayed psychomotor development and onset of refractory epilepsy at about 1 year of age. He had clonic, focal, and generalized tonic-clonic seizures, and experienced several episodes of status epilepticus. He was nonambulatory and had few words. He did not have significant dysmorphic features, and brain imaging was normal. Skeletal muscle biopsy showed the presence of concentric cristae and/or increased dense granules in some mitochondria, and many subsarcolemmal mitochondrial aggregates on electron microscopy. Confocal microscopy of patient fibroblasts showed hyperfusion of the mitochondrial network. However, respiratory chain enzymologies in muscle and skin fibroblasts and lactate/pyruvate ratio in fibroblasts were normal, as was serum lactate. There was no evidence of peroxisomal dysfunction. Vanstone et al. (2016) noted the diagnostic difficulties given that this patient had no clinical evidence of mitochondrial dysfunction on standard screening tests, and suggested that the disorder may result from abnormal mitochondrial distribution within neurons.
Fahrner et al. (2016) reported 2 unrelated boys who presented at 4 to 5 years of age with epileptic encephalopathy and subsequent neurologic decline after normal early development. Both children had metabolic insults prior to the sudden onset of status epilepticus: one patient developed seizures 2 weeks following a DTaP booster vaccination, whereas the other developed seizures after a viral illness and minor head trauma. Both had refractory epilepsy followed by developmental regression and progressive neurologic decline. One child had difficulty walking, dysphasia, and cognitive decline. The second child was wheelchair-bound with profound global developmental delay, myoclonus, and hypertonia; he had a tracheostomy and G-tube. Both patients continued to have seizures, and brain imaging showed progressive diffuse cerebral atrophy, particularly affecting the hippocampus, as well as nonspecific signal changes in the thalamus. Serum lactate was normal, and muscle biopsy of 1 patient was normal.
Chao et al. (2016) reported a boy with EMPF1 manifest as global developmental delay, hypotonia, and status epilepticus. He had normal development until 5 months of age, when he developed seizures followed by neurodevelopmental regression. Brain imaging showed progressive cerebral volume loss, demyelination, thinning of the corpus callosum, and T2-weighted hyperintense lesions in the cortex. Serum lactate levels were initially normal, but became elevated around 4 years of age. Muscle biopsy showed mild reduction of mitochondrial respiratory chain activities and mitochondrial pleomorphism. He died at 5 years of age due to severe status epilepticus with respiratory failure.
### Autosomal Recessive Inheritance
Yoon et al. (2016) reported 2 infant sibs, born of unrelated Filipino parents with EMPF resulting in death in infancy. Both presented at birth with profound hypotonia, absent respiratory effort, no spontaneous movements, and absent deep tendon reflexes. Brain imaging was normal in 1 infant, whereas it showed a profound hypoxic-ischemic insult in the other. Laboratory studies did not show increased serum lactate or biochemical evidence of a peroxisomal disorder. The patients died at ages 8 days and 3 weeks. Postmortem examination showed intracytoplasmic hyaline eosinophilic round globules in neurons in both the brain and spinal cord. Electron microscopy of hippocampal neurons and Purkinje cells of the cerebellum showed multiple giant mitochondria that contained elongated cristae arranged parallel to each other. Giant mitochondria were not identified in glial or nonneuronal cells. The spinal cord showed reduced myelin content and the posterior nerve roots were poorly myelinated; peripheral nerves also showed poor myelination with a marked reduction in numbers of myelinated axons. Examination of skeletal muscle showed no abnormalities. The myelination defects in the peripheral nervous system were consistent with the absence of deep tendon reflexes and profound muscle weakness in both patients. Whole-exome sequencing identified compound heterozygous truncating mutations in the DNM1L gene (603850.0004 and 603850.0005) in both sibs, consistent with a complete loss of function. Sural nerve samples revealed absent DNM1L protein in both patients compared to an age-matched control. Each unaffected parent was heterozygous for 1 of the mutations. The findings confirmed the central role of DNM1L and mitochondrial fission in normal human development and survival. Yoon et al. (2016) noted the autosomal recessive inheritance pattern in this family, resulting from loss-of-function mutations, which differed from previously reported patients with de novo heterozygous mutations in the DNM1L gene that presumably resulted in a gain of function.
Nasca et al. (2016) reported 2 brothers, aged 16 and 3 years, with a slowly progressive neurologic disorder characterized by delayed psychomotor development that became apparent at about 1 year of age. The patients had strabismus, oculomotor apraxia, dysarthria, dysmetria, hyperreflexia, pyramidal signs, and severe walking difficulties. Brain imaging of the older brother showed minor abnormalities in the subthalamic nucleus. Fibroblasts derived from the older patient showed isolated partial complex IV deficiency (53% of controls) and decreased mtDNA content (about 50% of controls), but muscle samples showed normal activities of all mitochondrial respiratory chain enzymes. Laboratory studies showed increased lactate beginning at age 12 years in the older brother; serum lactate was normal in the younger brother. There was no biochemical evidence of a peroxisomal defect. Targeted sequencing of a gene panel identified compound heterozygous mutations in the DNM1L gene: S36G (603850.0007) and a truncating mutation (603850.0005). Each unaffected parent carried 1 of the mutations in heterozygous state. Although immunofluorescence studies showed impairment of both mitochondria and peroxisomal dynamics, routine laboratory studies in the patients were not informative for these defects.
Molecular Genetics
In a newborn girl with a systemic lethal disorder and abnormal peroxisomes and mitochondria in fibroblast studies, Waterham et al. (2007) identified a de novo heterozygous mutation in the DNM1L gene (A395D; 603850.0001). The mutation was associated with a severe defect in the fission of both mitochondria and peroxisomes, indicating a dominant-negative effect.
In a 7-year-old boy, born of unrelated Caucasian parents, with EMPF1, Vanstone et al. (2016) identified a de novo heterozygous missense mutation in the DNM1L gene (G362D; 603850.0002). The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing.
In a 2-year-old boy, born of unrelated Arab parents, with EMPF1, Sheffer et al. (2016) identified a de novo heterozygous missense mutation in the DNM1L gene (G362S; 603850.0003). The mutation was found by exome sequencing and confirmed by Sanger sequencing. Transfection of the mutation into fibroblasts caused significantly altered mitochondrial morphology, with bulky clusters of mitochondria concentrated in a small area of the cell and absent in the remaining part. Transfected cells were also 60% smaller than control cells.
In 2 unrelated boys with onset of EMPF1 in childhood after normal early development, Fahrner et al. (2016) identified a de novo heterozygous missense mutation in the DNM1L gene (R403C; 603850.0006). The mutations were found by whole-exome sequencing. In vitro functional expression studies in mouse cells and yeast showed that the R403C mutation resulted in impaired self-assembly, decreased colocalization to the mitochondria, and defective mitochondrial fission in a dominant-negative manner. Fahrner et al. (2016) noted that higher-order oligomerization of DNM1L is critical for proper function because it facilitates recruitment to the mitochondrial surface and enhances GTP hydrolysis activity. The effects of this mutation were not as severe as those of A395D (603850.0001), which may explain the later onset of symptoms in these children.
In a boy with EMPF1, Chao et al. (2016) identified a de novo heterozygous missense mutation in the DNM1L gene (G350R; 603850.0008). The mutation, which was found by whole-exome sequencing, was not present in the father, but was present in maternal blood at a low level (6 to 8%), suggesting somatic mosaicism. Expression of the G350R mutation in Drosophila resulted in increased peroxisomal size, altered cellular distribution, decreased number of total peroxisomes per cell, abnormal mitochondrial morphology, and abnormal mitochondrial trafficking, with a dominant-negative effect.
INHERITANCE \- Autosomal dominant \- Autosomal recessive GROWTH Other \- Poor feeding \- Failure to thrive HEAD & NECK Head \- Microcephaly Face \- Pointed chin (patient A) Eyes \- Deep-set eyes (patient A) \- Optic atrophy (patient A) \- Cupped optic discs (patient A) \- Poor visual fixation \- Nystagmus \- Strabismus \- Oculomotor apraxia MUSCLE, SOFT TISSUES \- Hypotonia \- Skeletal muscle biopsy shows elongated mitochondria \- Abnormal mitochondrial concentric cristae \- Increased dense granules in mitochondria \- Subsarcolemmal mitochondrial aggregates \- Decreased mitochondrial complex IV activity \- Skeletal muscle biopsy may be normal NEUROLOGIC Central Nervous System \- Hypotonia \- Delayed psychomotor development \- Seizures (in some patients) \- Epileptic encephalopathy (in some patients) \- Status epilepticus (in some patients) \- Neurologic decline \- Pyramidal signs \- Cerebral atrophy \- Dysmyelination \- Abnormal gyral pattern in frontal lobes (1 patient) Peripheral Nervous System \- Areflexia METABOLIC FEATURES \- Lactic acidosis (in some patients) PRENATAL MANIFESTATIONS Movement \- Decreased fetal movement LABORATORY ABNORMALITIES \- Increased serum and CSF lactate (in some patients) \- Fibroblasts show decreased peroxisomes arranged in rows \- Fibroblasts show elongated, tangled, tubular mitochondria \- Defect in mitochondrial fission \- Defect in peroxisomal fission MISCELLANEOUS \- Onset in first days of life \- Some patients may have onset in mid-childhood \- Progressive disorder \- Variable features \- Variable severity \- Some patients may not have biochemical evidence of mitochondrial or peroxisomal dysfunction on standard screening MOLECULAR BASIS \- Caused by mutation in the dynamin 1-like gene (DNM1L, 603850.0001 ) ▲ 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| ENCEPHALOPATHY DUE TO DEFECTIVE MITOCHONDRIAL AND PEROXISOMAL FISSION 1 | c3280660 | 5,182 | omim | https://www.omim.org/entry/614388 | 2019-09-22T15:55:26 | {"omim": ["614388"], "orphanet": ["330050"], "synonyms": ["Alternative titles", "EMPF"]} |
A rare disorder of the anterior segment of the eye characterized by spontaneous separation of the anterior layer of the iris stroma from the posterior stroma and muscle layers. The anterior layer then splits into strands, and the free ends float freely in the anterior chamber. The condition usually affects patients in the seventh decade of life and is often associated with glaucoma. It may begin on one side but is typically a bilateral disease. The inferior part of the iris is most commonly involved.
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*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Isolated iridoschisis | None | 5,183 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=519392 | 2021-01-23T17:21:28 | {"icd-10": ["H21.2"]} |
Multiple system atrophy, parkinsonian type (MSA-p) is a form of multiple system atrophy (MSA; see this term) with predominant parkinsonian features (bradykinesia, rigidity, irregular jerky postural tremor, and postural instability).
## Epidemiology
MSA-p is observed predominantly in patients from the Western Hemisphere. 68% of MSA cases are MSA-p. Genders are equally distributed.
## Clinical description
The mean age of disease onset is 55 to 60 years. MSA-p is characterized by parkinsonism (bradykinesia, rigidity, irregular jerky tremor and postural instability) and autonomic failure in the form of bladder dysfunction (including early urinary incontinence) and/or orthostatic hypotension. The presence of autonomic failure is mandatory for the diagnosis of MSA-p. Additional features include dysphonia, dysphagia and other autonomic features (respiratory disturbances such as sleep apnea, stridor and inspiratory sighs, as well as constipation and sexual dysfunction). In the course of the disease, all patients with MSA-p display at least some cerebellar signs (gait and limb ataxia, oculomotor dysfunction, dysarthria). Abnormal postures (camptocormia (see this term), Pisa syndrome and disproportionate antecollis) are frequently observed. Neuropsychiatric features and sleep disturbances may be observed and include: rapid eye movement (REM) sleep behavior disorder (RBD), periodic limb movements in sleep (PLMS), depression, apathy and anxiety. In some cases, pyramidal signs (generalized hyper-reflexia with a positive Babinski sign) may also be observed. Patients with MSA-p may develop early-onset levodopa-induced orofacial and craniocervical dystonia.
## Etiology
The exact etiology of MSA-p is still unknown but the presence of cytoplasmic aggregates of α-synuclein, primarily in oligodendroglia, in combination with predominant neurodegeneration of the striatonigral pathway are the pathological hallmark features of MSA-p. Mutations in the COQ2 gene (4q21.23) (encoding an enzyme involved in the biosynthesis of coenzyme Q10) have been shown in multiplex families with MSA, while some variants were associated with an increased risk for sporadic MSA.
## Genetic counseling
MSA-p occurs sporadically. However, some familial cases of MSA have 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Multiple system atrophy, parkinsonian type | None | 5,184 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98933 | 2021-01-23T16:52:59 | {"icd-10": ["G23.2"], "synonyms": ["MSA, parkinsonian type", "MSA-p"]} |
A rare, inherited, non-syndromic ichthyosis characterized by congenital, generalized erythroderma with cutaneous blistering and erosions, resembling collodion presentation at birth, replaced by progressive hyperkeratosis later in life without palmoplantar involvement. The ultrastructural pathology consists of sparse keratin filaments and keratin clumps that show a nearly homogeneous, amorphous structure.
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Autosomal recessive epidermolytic ichthyosis | c4225407 | 5,185 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=512103 | 2021-01-23T17:20:34 | {"synonyms": ["AREI"]} |
Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is a condition that prevents the body from converting certain fats into energy, especially during periods without food (fasting).
Signs and symptoms of SCAD deficiency may appear during infancy or early childhood and can include vomiting, low blood sugar (hypoglycemia), a lack of energy (lethargy), poor feeding, and failure to gain weight and grow at the expected rate (failure to thrive). Other features of this disorder may include poor muscle tone (hypotonia), seizures, developmental delay, and a small head size (microcephaly).
The symptoms of SCAD deficiency may be triggered by fasting or illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe condition that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.
In some people with SCAD deficiency, signs and symptoms do not appear until adulthood. These individuals are more likely to have problems related to muscle weakness and wasting.
The severity of this condition varies widely, even among members of the same family. Some individuals are diagnosed with SCAD deficiency based on laboratory testing but never develop any symptoms of the condition.
## Frequency
This disorder is thought to affect approximately 1 in 35,000 to 50,000 newborns.
## Causes
Mutations in the ACADS gene cause SCAD deficiency. This gene provides instructions for making an enzyme called short-chain acyl-CoA dehydrogenase, which is required to break down (metabolize) a group of fats called short-chain fatty acids. Fatty acids are a major source of energy for the heart and muscles. During periods of fasting, fatty acids are also an important energy source for the liver and other tissues.
Mutations in the ACADS gene lead to a shortage (deficiency) of the SCAD enzyme within cells. Without sufficient amounts of this enzyme, short-chain fatty acids are not metabolized properly. As a result, these fats are not converted into energy, which can lead to the signs and symptoms of this disorder, such as lethargy, hypoglycemia, and muscle weakness. It remains unclear why some people with SCAD deficiency never develop any symptoms.
### Learn more about the gene associated with Short-chain acyl-CoA dehydrogenase deficiency
* ACADS
## 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
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*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Short-chain acyl-CoA dehydrogenase deficiency | c0342783 | 5,186 | medlineplus | https://medlineplus.gov/genetics/condition/short-chain-acyl-coa-dehydrogenase-deficiency/ | 2021-01-27T08:25:28 | {"gard": ["4822"], "mesh": ["C537596"], "omim": ["201470"], "synonyms": []} |
Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a hereditary renal phosphate-wasting disorder characterized by hypophosphatemia and hypercalciuria associated with rickets and/or osteomalacia.
## Epidemiology
HHRH has been described in several kindreds and in a few sporadic cases from Europe, North America and Japan.
## Clinical description
Other features include slow growth, short stature, skeletal deformities, muscle weakness and bone pain that are associated with normal or elevated plasma levels of calcitriol and hyperphosphaturia.
## Etiology
HHRH is caused by homozygous or compound heterozygous mutations in the SLC34A3 gene encoding a sodium-dependent phosphate transporter (NaPi-IIc/NPT2c).
## Genetic counseling
Transmission is autosomal recessive.
## Management and treatment
Treatment requires daily administration of phosphorus without calcitriol supplementation as this may increase 1,25(OH)2 vitamin D levels further leading to hyperabsorptive hypercalciuria.
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Hereditary hypophosphatemic rickets with hypercalciuria | c1853271 | 5,187 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=157215 | 2021-01-23T17:57:45 | {"mesh": ["C562793"], "omim": ["241530"], "umls": ["C1853271"], "icd-10": ["E83.3"], "synonyms": ["HHRH"]} |
Comedown or crashing is a phase of drug withdrawal that involves the deterioration in mood and energy that occurs when a psychoactive drug, typically a stimulant,[1] clears from the blood. The improvement and deterioration of mood (euphoria and dysphoria) are represented in the cognitive schema as high and low elevations; thus, after the drug has elevated the mood (a state known as a high), there follows a period of coming back down, which often has a distinct character from withdrawal in stimulants. Generally, a comedown ("down", "low", sometimes "crash") can happen to anyone as a transient symptom, but in people who are dependent on the drug (especially those addicted to it), it is an early symptom of withdrawal and thus can be followed by others.
Various drug classes, most especially stimulants and to a lesser degree opioids and sedatives, are subject to comedowns.[2] A milder analogous mood cycle can happen even with blood sugar levels (thus sugar highs and sugar lows), which is especially relevant to people with diabetes mellitus and to parents and teachers managing children's behavior, as well as in adults with ADHD. Stimulant comedowns are unique in that they often appear very abruptly after a period of focus or high, and are typically the more intensely dysphoric phase of withdrawal than that following complete elimination from the bloodstream. Besides general dysphoria, this phase can be marked by frustration, anger, anhedonia, social withdrawal, and other symptoms characteristic to a milder mixed episode in bipolar disorder. Alertness and other general stimulant effects are still present.
For example, in an MDMA (ecstasy) comedown, if the user experiences severe, persisting emotional distress, such as panic attacks, severe generalized anxiety, or insomnia following an MDMA session, a physician may prescribe a benzodiazepine (specifically, lorazepam) and/or sleep aid (e.g., zolpidem), to alleviate those effects.[3]
## See also[edit]
* Hangover
* Dysphoria
* Self-medication
* Cocaine withdrawal
## References[edit]
1. ^ "Stimulant Withdrawal". DrugAbuse.com. American Addiction Centers. Archived from the original on 13 November 2017. Retrieved 10 November 2018.
2. ^ "Cocaine Crashes and the Motivation to Use". Addiction.com. Addiction.com. Retrieved 10 November 2018.
3. ^ "An Open-Label, Multi-Site Phase 2 Study of the Safety and Effect of Manualized MDMA-Assisted Psychotherapy for the Treatment of Severe Posttraumatic Stress Disorder" (PDF). mapsbcorp.com. MAPS Public Benefit Corporation. Retrieved 25 March 2019.
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Comedown (drugs) | None | 5,188 | wikipedia | https://en.wikipedia.org/wiki/Comedown_(drugs) | 2021-01-18T18:42:46 | {"wikidata": ["Q5151412"]} |
Aceruloplasminemia is a disorder of iron metabolism. This disorder causes iron to build-up in the body. Signs and symptoms begin in adulthood. People with this disorder tend to develop anemia and diabetes in their 20's. As the condition progresses, movement problems are common, such as tremors, chorea, ataxia, eyelid twitching, and grimacing. Some experience psychiatric problems and dementia in their 40's and 50's. Eye examination may reveal changes in the retina, but these changes typically do not affect vision. Aceruloplasminemia is caused by mutations in the CP gene and are 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Aceruloplasminemia | c0878682 | 5,189 | gard | https://rarediseases.info.nih.gov/diseases/9499/aceruloplasminemia | 2021-01-18T18:02:23 | {"mesh": ["C536004"], "omim": ["604290"], "orphanet": ["48818"], "synonyms": ["Ceruloplasmin deficiency", "Familial apoceruloplasmin deficiency", "Hereditary ceruloplasmin deficiency", "Hypoceruloplasminemia", "Systemic hemosiderosis due to aceruloplasminemia"]} |
Canine subvalvular aortic stenosis (SAS) is an abnormal, congenital heart murmur caused by subaortic stenosis (SAS). There is a high incidence of this condition identified in large and giant breed dogs like the Rottweiler, Newfoundland, Golden Retriever, Boxer, German Shepherd, English Bulldog, Great Dane, German Shorthaired Pointer, and Bouvier des Flandres.[1]
It is a common congenital heart defect that consists of abnormal tissue located just below the aortic valve that creates an obstruction the heart has to overcome to pump blood out to the body. As a result, the heart muscle can become thickened. The blood is pumped at a higher speed and pressure across the stenosis into the aorta, creating a heart murmur.[1]
This genetic trait is polygenic. An animal might have the genes for SAS, yet have no actual sign of SAS. Also, an animal might have signs of subaortic stenosis, and yet offspring with SAS may not demonstrate clinical signs for a couple of generations. Any animal that has subaortic stenosis should not be bred because they can pass the defect on to future offspring.
## Contents
* 1 Symptoms
* 2 Diagnosis
* 3 Treatment
* 4 References
## Symptoms[edit]
In many cases, affected dogs do not show any signs. Aortic stenosis is often initially detected upon hearing a heart murmur during a routine physical examination by a veterinarian. In dogs with severe disease, you may observe signs related to heart dysfunction. These signs include lethargy, exercise intolerance, shortness of breath, and fainting. Signs of heart failure may also be seen in severe cases of aortic stenosis. These signs include coughing, increased breathing effort, and open-mouth breathing.[2]
Puppies and adult dogs diagnosed with subaortic stenosis can suffer from heart failure and sudden death. If a dog with SAS develops heart failure, medications can be prescribed to alleviate the clinical signs (sudden/strong lethargicism, continuous heavy panting, rise in temperature etc.)
## Diagnosis[edit]
SAS is diagnosed via echocardiogram with Doppler performed by a veterinary cardiologist. This allows visualization of the four heart chambers and valves as well as the anatomy of the subaortic area. Doppler allows estimation of the pressure created in the heart by the stenosis.[1]
An electrocardiogram (ECG) may be required in patients with an irregular heart rhythm.
Heart murmurs are graded on a scale of one to six, with one being very mild and six being very serious.[3] Murmurs can exist due to a large number of heart problems (infection, trauma, anemia, etc.). Conversely, some murmurs are benign and do not indicate cardiac pathology.
The Orthopedic Foundation for Animals (OFA) has established a Congenital Heart Registry whose guidelines were established by veterinary cardiologists. A dog which auscultates normally at 12 months of age is considered to be free of congenital heart disease; upon confirmation of this, OFA will issue a certificate.
## Treatment[edit]
Prognosis of canines with aortic stenosis depends on the severity of the disease. Mild stenosis usually does not affect longevity; however, the possibility of aortic endocarditis exists.
Administration of beta-blockers can decrease heart rate and prolong diastole and coronary filling, thereby reducing myocardial hypoxia and protect against arrhythmia. Dogs do clinically well on beta-blockers; however, a study proved no benefit in terms of survival versus untreated dogs with severe SAS.[4]
## References[edit]
1. ^ a b c "Subaortic Stenosis in Dogs & Cats | CVCA". Chesapeake Veterinary Cardiology Associates. Retrieved 2019-12-22.
2. ^ "Aortic Stenosis in Dogs". vca_corporate. Retrieved 2019-12-22.
3. ^ Burke A. "Heart Murmur in Dogs". American Kennel Club. Retrieved 2018-02-12.
4. ^ Eason BD, Fine DM, Leeder D, Stauthammer C, Lamb K, Tobias AH (May 2014). "Influence of beta blockers on survival in dogs with severe subaortic stenosis". Journal of Veterinary Internal Medicine. 28 (3): 857–62. doi:10.1111/jvim.12339. PMC 4895480. PMID 24597738.
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Subvalvular aortic stenosis (canine) | c0340375 | 5,190 | wikipedia | https://en.wikipedia.org/wiki/Subvalvular_aortic_stenosis_(canine) | 2021-01-18T18:32:15 | {"gard": ["5052"], "mesh": ["D001020"], "umls": ["C0340375"], "wikidata": ["Q7632441"]} |
Spondyloepimetaphyseal dysplasia, Irapa type is characterized by disproportionate short-trunked short stature, pectus carinatum, short arms, short and broad hands, short metatarsals, flat and broad feet, coxa vara, genu valgum, osteoarthritis, arthrosis and moderate-to-serious gait impairment.
## Epidemiology
The syndrome has been described among Venezuelan Indians of the Yukpa (Irapa) tribe and three sibs from a Mexican mestizo family.
## Etiology
Autosomal recessive inheritance has been suggested, but the causative gene has not yet been identified.
*[v]: View this template
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*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Spondyloepimetaphyseal dysplasia, Irapa type | c0432213 | 5,191 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93351 | 2021-01-23T17:14:47 | {"mesh": ["C562958"], "omim": ["271650"], "umls": ["C0432213"], "icd-10": ["Q77.7"], "synonyms": ["SEMD, Irapa type"]} |
Pure red cell aplasia (PRCA) is a rare condition that affects the bone marrow. Bone marrow contains stem cells which develop into the red blood cells that carry oxygen through the body, the white blood cells that fight infections, and the platelets that help with blood clotting. In people with PRCA, the bone marrow makes a reduced number of red blood cells (called anemia). As a result, affected people may experience fatigue, lethargy, and pale skin. PRCA has many different causes. A rare congenital form of PRCA, called Diamond Blackfan syndrome, is an inherited condition that is also associated with other physical abnormalities. PRCA can also be due to certain medications, infections, pregnancy, renal failure, and conditions such as thymomas, autoimmune disease (such as systemic lupus erythematosus), cancers of the blood, and solid tumors. In many cases, the cause of the condition is unknown (idiopathic). The treatment of PRCA aims to address the underlying cause of the condition and relieve the associated signs and symptoms.
*[v]: View this template
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*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Pure red cell aplasia | c0034902 | 5,192 | gard | https://rarediseases.info.nih.gov/diseases/7504/pure-red-cell-aplasia | 2021-01-18T17:58:02 | {"mesh": ["D012010"], "umls": ["C0034902"], "synonyms": ["PRCA"]} |
## Description
Primary lymphedema is caused by anatomic or functional defects in the lymphatic system, resulting in chronic swelling of body parts. There may be accompanying nail and skin changes, such as nail dysplasia or papillomatosis. Onset is usually at birth or in early childhood but can occur later, and the severity is variable (summary by Gordon et al., 2013 and Balboa-Beltran et al., 2014).
For a discussion of the genetic heterogeneity of lymphocytic malformation, see 153100.
Nomenclature
An early classification of primary lymphedema was based on age of onset. The first descriptions of familial lymphedema were published by Milroy (1892), who described early onset of the disorder, and Meige (1898), who described onset around the time of puberty. Lymphedema of early onset became classified as Milroy disease (type I; see 153100), and lymphedema after puberty as Meige disease or lymphedema praecox (type II). However, later reports showed that lymphedema could occur with early and late onset within the same family and that the features of the disorder could vary within a family. Primary lymphedema is here classified by molecular defect and mode of inheritance.
Clinical Features
Edema, particularly severe below the waist, develops about the time of puberty. Meige (1898) described 8 cases in 4 generations without male-to-male transmission. Goodman (1962) reported the condition in 2 sisters and a brother with presumed normal parents who were not known to be related.
Herbert and Bowen (1983) described a kindred with many cases of lymphedema of postpubertal onset. Involvement of the upper limbs (as well as the lower limbs), face, and larynx and, in one, a persistent pleural effusion were notable features. Scintilymphangiography indicated paucity or absence of lymph nodes in the axillae and above the inguinal ligaments. Chronic facial swelling resulted in a characteristic appearance of affected members including puffiness, shiny skin, deep creases, and, in some, excessive wrinkling. Emerson (1966) noted similar facial features and remarked on the possible erroneous diagnosis of myxedema.
Herbert and Bowen (1983) noted the difficulties of nosology. For example, because lymphedema and yellow nail syndrome has yellow or dystrophic nails as a variable feature, this could be the same disorder. They pointed also to the association of late-onset lymphedema with deafness (Emberger et al., 1979) and with primary pulmonary hypertension and cerebrovascular malformations (152900; Avasthey and Roy, 1968).
Figueroa et al. (1983) reported the association of cleft palate. In their family, the mother, with only lymphedema praecox of the legs, gave birth to 5 sons, 3 of whom had both lymphedema of the legs and cleft palate. A mild form of lymphedema affecting mainly the medial aspect of both ankles in a 21-year-old son was pictured.
Andersson et al. (1995) described a family in which 3 individuals, a grandmother, her son and her grandson, had onset of lymphedema in their mid-twenties or thirties. The grandson was 23 years old when he had his first episode of lymphedema, which was thought to be due to thrombophlebitis. During the ensuing decade, he had episodic waxing and waning of lymphedema of both lower limbs and was treated with anticoagulant therapy. At the age of 35, he developed lymphangiosarcoma on the inner right thigh and died of metastases some months later. Lymphangiosarcoma, usually associated with postmastectomy lymphedema, had not been described previously in late-onset hereditary lymphedema. Andersson et al. (1995) raised the question of whether a genetic predisposition to malignancy combined with the lymphedema was etiologically significant. There seemed to be an unusually high frequency of cancer (uterine, colon, lung, prostate, breast, and bone) in the proband's family.
Molecular Genetics
### Exclusion Studies
Finegold et al. (2001) reported a mutation in the FOXC2 gene (589insC; 602402.0007) in a family with supposed Meige lymphedema. Rezaie et al. (2008) disputed the clinical diagnosis of the family reported by Finegold et al. (2001). The family included patients with distichiasis, consistent with lymphedema-distichiasis syndrome (153400). Rezaie et al. (2008) did not identify mutations in the FOXC2 gene in 22 unrelated probands with Meige disease, i.e., lymphedema without distichiasis. One additional proband was found to carry a FOXC2 mutation, but further detailed ophthalmologic examination revealed accessory eyelashes in him and his affected family members, thus confirming the diagnosis of lymphedema-distichiasis. Rezaie et al. (2008) concluded that Meige disease is not caused by FOXC2 mutations. The authors also emphasized that the detection of distichiasis may be difficult to confirm and cannot be assumed to be absent from patient self-reports.
INHERITANCE \- Autosomal dominant HEAD & NECK Face \- Facial swelling (in some patients) Mouth \- Cleft palate (in some patients) SKIN, NAILS, & HAIR Nails \- Yellow nails (in some patients) MUSCLE, SOFT TISSUES \- Lymphedema, predominantly in the lower limbs \- Paucity or absence of lymph nodes in the axillae and above the inguinal ligaments seen on scintilymphangiography MISCELLANEOUS \- Onset around puberty ▲ Close
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*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| LYMPHATIC MALFORMATION 5 | c0238261 | 5,193 | omim | https://www.omim.org/entry/153200 | 2019-09-22T16:38:46 | {"doid": ["0070213"], "mesh": ["C562467"], "omim": ["153200"], "orphanet": ["90186"], "synonyms": ["Alternative titles", "MEIGE DISEASE", "MEIGE LYMPHEDEMA", "LYMPHEDEMA, LATE-ONSET", "LYMPHEDEMA PRAECOX", "LYMPHEDEMA, HEREDITARY, II, FORMERLY"]} |
This form appears to be distinct from the two types that are inherited as autosomal recessives (254780, 254800). Unlike those forms, no Lafora bodies were found at autopsy and only diffuse atrophy was present.
Neuro \- Myoclonic epilepsy Lab \- No Lafora bodies at autopsy \- only diffuse atrophy Inheritance \- Autosomal dominant form \- also autosomal recessive types ▲ Close
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*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| MYOCLONIC EPILEPSY, HARTUNG TYPE | c1834581 | 5,194 | omim | https://www.omim.org/entry/159600 | 2019-09-22T16:37:47 | {"mesh": ["C563550"], "omim": ["159600"]} |
A number sign (#) is used with this entry because of evidence that DFNA9 is caused by heterozygous mutation in the cochlin gene (COCH; 603196) on chromosome 14q12.
Description
DFNA9 is an autosomal dominant adult-onset form of progressive sensorineural hearing loss associated with variable vestibular dysfunction (summary by Robertson et al., 2006).
Clinical Features
Manolis et al. (1996) reported results of a genetic linkage analysis in a family with nonsyndromic postlingual progressive sensorineural hearing loss. In this family hearing loss was inherited as an autosomal dominant trait which begins at approximately 20 years of age and progresses to total deafness. Manolis et al. (1996) described unique temporal bone histopathologic findings in this family. Affected individuals were found to have mucopolysaccharide depositions in the channels of the cochlear and vestibular nerves. These depositions apparently caused strangulation and degeneration of dendritic fibers. Manolis et al. (1996) noted that others (Khetarpal et al., 1991; Khetarpal, 1993) had reported previous clinical evaluations of this family.
Based on the findings in the 3 affected families, including the family of Manolis et al. (1996), Robertson et al. (1998) described the hearing loss as having its onset between 20 and 30 years of age. Initially it was most profound at high frequencies and displayed variable progression to anacusis by 40 to 50 years of age. Some DFNA9 patients had received cochlear implants and others used hearing aids. A spectrum of clinical vestibular involvement, ranging from lack of symptoms to presence of vertigo, vestibular hypofunction as assessed by electronystagmography and histopathology, had been found.
Mapping
By linkage analysis in a family with nonsyndromic postlingual progressive sensorineural hearing loss, Manolis et al. (1996) demonstrated that the deafness localized to chromosome 14q12-q13. The maximum lod score (6.19 at theta = 0.0) was obtained with the marker D14S121.
Molecular Genetics
In the original family of Manolis et al. (1996) and 2 additional families with DFNA9 identified with the characteristic histopathologic findings of acidophilic ground substance in the cochlea and vestibular labyrinth, Robertson et al. (1998) described separate mutations in the COCH gene (603196.0001-603196.0003), which is expressed almost exclusively in the inner ear.
Fransen et al. (1999) identified a mutation in the COCH gene (P51S; 603196.0004) in 1 large Belgian and 2 small Dutch families with autosomal dominant nonsyndromic progressive sensorineural hearing loss associated with vestibular dysfunction. Greater than 25% of the patients affected with this mutation showed additional symptoms, including episodes of vertigo, tinnitus, aural fullness, and hearing loss. Fransen et al. (1999) suggested that the COCH gene may be one of the genetic factors contributing to Meniere disease (156000) and that the possibility of a COCH mutation should be considered in patients with Meniere disease symptoms.
Usami et al. (2003) performed COCH mutation analysis in a Japanese population of 23 patients from independent families with autosomal dominant hearing impairment, 4 of whom reported vestibular symptoms, and 20 Meniere disease patients. Usami et al. (2003) concluded that mutations in the COCH gene are responsible for a significant fraction of patients with autosomal dominant inherited hearing loss accompanied by vestibular symptoms, but not for dominant hearing loss without vestibular dysfunction or sporadic Meniere disease. They identified a novel point mutation in the COCH gene (603196.0006) in a patient with autosomal dominant hearing loss and vestibular symptoms.
Street et al. (2005) performed a genomewide scan and linkage analysis in an American pedigree with hearing loss and vestibular and oculomotor disturbances. A maximal pairwise lod score of 7.08 was obtained with marker D14S1021, and a mutation was identified in exon 12 of the COCH gene (603196.0007) that cosegregated with auditory dysfunction. Street et al. (2005) stated that this was the first mutation to be reported outside of the LCCL domain, which is encoded by exons 4 and 5. Hearing loss and vestibular dysfunction was present in a 17-year-old male in this family, the youngest reported age of onset in a DFNA9 family member.
Yuan et al. (2008) reported a large Chinese family with DFNA9 confirmed by genetic analysis (603196.0008). Age at onset ranged from the second to fifth decade of life, and there was some evidence of genetic anticipation, although the findings may have been due to bias. Most affected family members (82%) had tinnitus at the onset of hearing loss. Hearing loss first affected the high frequencies and later involved all frequencies. Overall, the patients displayed a downward sloping audiogram contour. Although none had clinical vestibular complaints, detailed studies showed evidence for subtle defects.
Hildebrand et al. (2009) reported a 5-generation American family in which members with nonsyndromic sensorineural deafness and vestibular impairment, excluding 2 thought to represent deafness phenocopies, had a P51S mutation in the COCH gene (603196.0004). In addition, 1 member with the P51S mutation had bilateral superior semicircular canal dehiscence (SCCD). The family was related to those reported by Fransen et al. (1999, 2001), providing further evidence of a founder mutation. Hildebrand et al. (2009) recommended high-resolution temporal bone CT in patients with DFNA9-related deafness and screening for COCH in sporadic or familial cases of superior semicircular canal dehiscence.
In 3 unrelated patients with SCCD and no family history of the disorder or of deafness, Crovetto et al. (2012) excluded mutations in the coding exons and intron-exon boundaries of the COCH gene.
Pathogenesis
In mouse and human inner ear, Robertson et al. (2006) found that cochlin immunostaining was restricted to tissues of mesodermal origin; neuroectodermally derived structures clearly lacked cochlin expression. Robertson et al. (2006) found that temporal bones from patients with DFNA9 showed large amounts of cochlin-immunoreactive eosinophilic acellular deposits contained throughout the spiral ligament, limbus, and osseous spiral lamina. Coch-null mice showed no such material, suggesting that DFNA9-associated mutations result in a dominant-negative effect. Robertson et al. (2006) suggested that the obstruction of these channels in DFNA9 results in secondary neuronal damage and hearing loss.
Animal Model
Makishima et al. (2005) found that Coch -/- mice with no detectable cochlin in the inner ear had auditory brainstem responses to click and pure-tone stimuli indistinguishable from those of wildtype mice. A lacZ reporter assay revealed Coch mRNA expression in nonsensory epithelial and stromal regions of the cochlea and vestibular labyrinth in the mutant mice. Makishima et al. (2005) concluded that DFNA9 may not be caused by COCH haploinsufficiency but by a dominant-negative or gain-of-function effect in nonsensory regions of the inner ear.
INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Hearing loss, postlingual \- Vestibular involvement (variable) \- Vertigo \- Tinnitus \- Downward sloping audiogram \- Superior semicircular canal dehiscence (SCCD) \- Temporal bone shows deposition of cochlin-positive eosinophilic extracellular ground substance in the channels of the cochlear and vestibular nerves \- Atrophy of cochlear and vestibular fibrocytes MISCELLANEOUS \- Onset in young adulthood \- Progressive disorder MOLECULAR BASIS \- Caused by mutation in the cochlin gene (COCH, 603196.0001 ) ▲ Close
*[v]: View this template
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*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| DEAFNESS, AUTOSOMAL DOMINANT 9 | c1832425 | 5,195 | omim | https://www.omim.org/entry/601369 | 2019-09-22T16:14:57 | {"doid": ["0110593"], "mesh": ["C563335"], "omim": ["601369"], "orphanet": ["90635"], "synonyms": ["Autosomal dominant isolated neurosensory deafness type DFNA", "Autosomal dominant isolated neurosensory hearing loss type DFNA", "Autosomal dominant isolated sensorineural deafness type DFNA", "Autosomal dominant isolated sensorineural hearing loss type DFNA", "Autosomal dominant non-syndromic neurosensory deafness type DFNA", "Autosomal dominant non-syndromic neurosensory hearing loss type DFNA", "Autosomal dominant non-syndromic sensorineural hearing loss type DFNA"], "genereviews": ["NBK1434"]} |
Tinea imbricata (TI) produces a superficial skin infection with unmistakable clinical appearance. It is a chronic disorder common in parts of Papua New Guinea and Oceania. It has also been reported in Mexico and South America. A familial pattern suggested to Serjeantson and Lawrence (1977) autosomal recessive inheritance of susceptibility. In married couples, no concordance beyond that expected by chance was observed and segregation in different types of matings was compatible with recessive inheritance. Ravine et al. (1980) analyzed 228 pedigrees from a Papua New Guinea population and concluded that autosomal recessive inheritance is likely. The frequency of the susceptibility gene was estimated to be 0.49. The possibility of autosomal dominant inheritance with reduced penetrance could not be excluded. The causative fungus is Trichophyton concentricum. The significance of inherited susceptibility is indicated by the fact that although the disease is found extensively throughout the tropics, it is absent from Africa and northern Australia. Workers have observed a much higher prevalence in some races than in others living in the same country under closely related environmental circumstances.
Inheritance \- Autosomal recessive Lab \- Trichophyton concentricum infection Skin \- Tinea imbricata (TI) susceptibility ▲ 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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| TINEA IMBRICATA, SUSCEPTIBILITY TO | c0276742 | 5,196 | omim | https://www.omim.org/entry/275240 | 2019-09-22T16:21:40 | {"mesh": ["D014006"], "omim": ["275240"], "icd-10": ["B35.0"]} |
## Description
The XG blood group system is the only blood group system assigned to the X chromosome. The system consists of 2 antigens, Xg(a) and CD99, which are encoded by 2 adjacent genes, XG and CD99 (313470). Xg(a) may be expressed only on red blood cells, whereas CD99 is expressed on all tissue cells. The expression level of CD99 on red blood cells is directly related to the presence or absence of Xg(a). Both anti-Xg(a) and anti-CD99 are rare. Anti-Xg(a) is considered clinically insignificant, and the clinical significance of anti-CD99 is unknown (review by Johnson, 2011).
Clinical Features
Mann et al. (1962) identified the first Xg(a) antiserum in a patient with hereditary hemorrhagic telangiectasia (see 187300) who had received many transfusions (Mann et al., 1962). The antigen is well developed at birth. Evidence suggested that homozygotes react as strongly with anti-Xg(a) as hemizygotes and more strongly than heterozygotes.
Inheritance
Mann et al. (1962) demonstrated that the Xg(a) antigen behaves as an X-linked dominant.
Population Genetics
Mann et al. (1962) found the Xg(a) antigen in 89% of 188 Caucasian females and in 62% of 154 males. In the few Blacks tested, the phenotype frequencies seem to be about the same as in Caucasians.
The efficient estimate of the frequency of the Xg(a) allele in Caucasians, making use of the data on females as well as males, is 0.651 (Sanger et al., 1962).
Mapping
In her review, Johnson (2011) stated that the XG gene, which encodes Xg(a), spans the pseudoautosomal boundary between the 2 regions of the X chromosome at Xp22.3. The MIC2 gene, which encodes CD99, is located in the pseudoautosomal region at chromosome Xp22.2, adjacent to the XG gene.
Ellis et al. (1994) proposed that the observed XG polymorphism may be due to variation in an XG regulator (XGR; 314705) that may be situated between the XG gene and the MIC2 gene (see MOLECULAR GENETICS).
Molecular Genetics
Ellis et al. (1994) demonstrated that XG, which they called PBDX, a gene found to span the pseudoautosomal boundary on the X chromosome, is the XG blood group gene. Using rabbit polyclonal and mouse monoclonal antibodies raised against a peptide derived from the N-terminal domain of the predicted mature PBDX, they identified the Xg(a) antigen. By its identity with PBDX, therefore, Xg(a) was recognized as a cell-surface antigen 48% homologous to CD99. Ellis et al. (1994) concluded that the XG polymorphism is defined by a difference in the level of the Xg antigen on the surface of the erythrocyte rather than a difference in the amino acid sequences of the protein products encoded by the Xg(a) allele and an alternative Xg(a)-negative allele. They proposed a model in which the observed XG polymorphism may be due to variation in an XG regulator (XGR; 314705) that may be situated between the XG locus proximally and the MIC2 locus distally.
Data on gene frequencies of XG allelic variants were tabulated by Roychoudhury and Nei (1988).
History
The Xg(a) blood group proved useful to genetics, especially for study of linkage (summary by Race and Sanger, 1975) and determination where nondisjunction occurs leading to X chromosome aneuploidy. Evidence on lyonization of the Xg locus was conflicting. Evidence for lyonization came from a study of X-linked hypochromic anemia (300751) by Lee et al. (1968). Lawler and Sanger (1970) found that a group of females with Philadelphia-chromosome-positive myeloid leukemia cases had the frequency of Xg types expected of females. This could mean either that the Xg locus is not subject to inactivation or that all Ph-positive cells are not monoclonal. Also assumed, of course, was that the erythroid cells in the patients studied were derived from a Ph-positive cell and that no red cells derived from Ph-negative precursors persisted. Data on linkage of the Xg locus with many other loci are summarized by Race and Sanger (1975). Ducos et al. (1971) studied a chimera twin pair in whom 2 red cell populations were easily separable because of differences in their ABO blood groups. One population was Xg(a+), the other Xg(a-). Thus the important point was established that the Xg antigen is made in the red cell precursors and not secondarily acquired by red cells. Xg can, therefore, give information on lyonization.
The Xg locus cannot be on the distal third of the long arm of the X chromosome, because Pearson (1973) observed a family in which the mother was Xg(a+) and had a balanced translocation of the distal third of the Xq onto 3p, the karyologically normal father was Xg(a-), and an unbalanced daughter with deleted distal third of the long arm of one X chromosome (derived from the mother) was Xg(a+). Bernstein et al. (1977) presented evidence from an X-Y translocation suggesting that the Xg locus is at the distal end of Xp and that an X-linked mental retardation locus is in the same region. From the study of a boy nullisomic for the terminal portion of Xp, Ferguson-Smith and Aitken (1982) concluded that the order of loci is STS (300747)--11cM--Xg--?2cM--Xk--OA. The boy showed sulfatase-deficient ichthyosis and was Xg(a-), although the family findings suggest that he should be Xg(a+), but he did not have chronic granulomatous disease or ocular albinism. On the other hand, Ropers et al. (1982) suggested the order Xg--H-Y repressor--STS--Xk. That the Xg locus is near one end of the X chromosome was suggested by the fact that it shows lack of linkage with so many loci. (The genetic length of the X chromosome is about 200 cM.) Race and Sanger (1975) pointed out that when the 3-generation linkage data for deutan (303800), protan (303900), G6PD (305900) and classic hemophilia (306700) (on the one hand) versus Xg (on the other) are pooled, the score is 236 nonrecombinants and 193 recombinants: a recombination fraction of 45% (chi square 4.3, expecting 50% recombination).
Positive evidence that Xg is in the Xp2 region comes mainly from 2 sources. In the first place, Evans et al. (1979) reported morphologic studies suggesting that about 70% of nonmosaic cases of XX males have arisen by Xp-Yp interchange in paternal meiosis. In such cases, the short arm of one X is longer, by 0.4% to 22.9%, than the short arm of the other X chromosome, and its banding profile is altered. Evans et al. (1979) found a Y-specific fragment in the DNA digest from 1 of 3 XX males with Xp+ whom they studied. Combined with this morphologic and biochemical evidence for Xp-Yp interchange are the data on Xg blood group in XX males and their parents. In 9 of 12 cases the XX male failed to inherit the Xg+ gene from his father, suggesting that the Xg locus was lost in the process of Xp-Yp interchange. These cases were not studied morphologically; thus the cases without anomaly of Xg inheritance may have had a cause other than interchange, e.g., occult mosaicism, transfer of Y material to an autosome, or perhaps an autosomal recessive gene for sex reversal. (De la Chapelle et al. (1979) could not corroborate heteromorphism of the X chromosomes in 46,XX males.) During meiosis the X and Y chromosomes show terminal association of their short arms, including an electron microscopically demonstrable synaptinemal complex. This may predispose to X-Y interchange. There should be XY individuals who are Xg-positive, even though the mother is Xg-negative, as a result of transfer of their father's Xg+ gene to the Y chromosome that he gave that particular offspring. Such persons might or might not have an abnormality of sexual development.
A second web of evidence that Xg is on Xp2 comprises (a) the linkage of Xg to X-linked ichthyosis (308100), (b) the demonstration of steroid sulfatase deficiency as the fundamental defect in X-linked ichthyosis, and (c) the assignment of the steroid sulfatase locus to Xp22-Xpter by study of deleted X chromosomes in mouse-man somatic cell hybrids (Mohandas et al., 1980). Both the Xg locus (Race and Sanger, 1975) and the steroid sulfatase locus (Mohandas et al., 1980) do not, it seems, participate in lyonization. Thus, the distal part of the short arm of the X chromosome appears to have 2 properties different from the rest of the X: pairing with the Y and absence of inactivation. Boyd et al. (1981) studied an instructive family in which the Xg(a-) mother had a 46Xt(X;Y)(p24;q11) karyotype and had transmitted her X-Y translocation chromosome to both her son and her daughter. The mother and daughter were monosomic for the region Xq24-Xqter and the son nullisomic for the same region. The maternal grandfather was Xg(a+) and neither grandparent carried the translocation chromosome. Thus, in origin of the translocation, the Xg locus was lost. The son showed generalized ichthyosis and zero steroid sulfatase activity. His mother had activity like that of normal males. Thus, the STS locus must have been involved also in the deletion of Xp. Ferguson-Smith et al. (1964) had predicted, on the basis of karyotype-phenotype correlations, that a region of Xp must escape inactivation and contain the Xg locus. Ropers et al. (1983) estimated the genetic length of the short arm of the X chromosome to be about 75-90 cM (the Xg-centromere segment). Sarfarazi et al. (1983) found no linkage between Xg and a proximal Xp DNA polymorphic marker called L1.28 (DXS7) and no close linkage between Xg and a more distal RFLP (lambda-RC8, or DXS9). Curry et al. (1984) found that the steroid sulfatase, Xg, and MIC2X loci as well as the locus for X-linked chondrodysplasia punctata (302950) were apparently absent in males with deletion of Xp22.32.
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*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| BLOOD GROUP, XG SYSTEM | None | 5,197 | omim | https://www.omim.org/entry/314700 | 2019-09-22T16:17:04 | {"omim": ["314700"], "synonyms": ["Alternative titles", "XG BLOOD GROUP SYSTEM"]} |
Distal myopathy 2 is a condition characterized by weakness of specific muscles that begins in adulthood. It is a form of muscular dystrophy that specifically involves muscles in the throat, lower legs, and forearms. Muscles farther from the center of the body, like the muscles of the lower legs and forearms, are known as distal muscles.
Muscle weakness in the ankles is usually the first symptom of distal myopathy 2. The weakness can also affect muscles in the hands, wrists, and shoulders. At first, the muscle weakness may be on only one side of the body, but both sides are eventually involved. This muscle weakness can slowly worsen and make actions like walking and lifting the fingers difficult.
Another characteristic feature of distal myopathy 2 is weakness of the vocal cords and throat. This weakness initially causes the voice to sound weak or breathy (hypophonic). Eventually, the voice becomes gurgling, hoarse, and nasal. The weakness can also cause difficulty swallowing (dysphagia).
## Frequency
The prevalence of distal myopathy 2 is unknown. At least two families with the condition have been described in the scientific literature.
## Causes
A mutation in the MATR3 gene has been identified in people with distal myopathy 2. This gene provides instructions for making a protein called matrin 3, which is found in the nucleus of the cell as part of the nuclear matrix. The nuclear matrix is a network of proteins that provides structural support for the nucleus and aids in several important nuclear functions.
The function of the matrin 3 protein is unknown. This protein can attach to (bind) RNA, which is a chemical cousin of DNA. Some studies indicate that matrin 3 binds and stabilizes a type of RNA called messenger RNA (mRNA), which provides the genetic blueprint for proteins. Matrin 3 may also bind certain abnormal RNAs that might lead to nonfunctional or harmful proteins, thereby blocking the formation of such proteins. Other studies suggest that the matrin 3 protein may be involved in cell survival.
The MATR3 gene mutation identified in people with distal myopathy 2 changes a single protein building block (amino acid) in the matrin 3 protein. The effect of this mutation on the function of the protein is unknown, although one study suggests that the mutation may change the location of the protein in the nucleus. Researchers are working to determine how this gene mutation leads to the signs and symptoms of distal myopathy 2.
### Learn more about the gene associated with Distal myopathy 2
* MATR3
## Inheritance Pattern
Distal myopathy 2 is inherited in an autosomal dominant pattern, which means one copy of the altered MATR3 gene in each cell is sufficient to cause the disorder.
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*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Distal myopathy 2 | c3807521 | 5,198 | medlineplus | https://medlineplus.gov/genetics/condition/distal-myopathy-2/ | 2021-01-27T08:24:57 | {"gard": ["1887"], "omim": ["606070"], "synonyms": []} |
Paraphilia involving a sexual fixation on non-human animal
For plant pollination carried by animals, see Zoophily.
Roman oil lamp depicting a zoophilic act, 1st–3rd century A.D.
Pan having sex with a goat, statue from Villa of the Papyri, Herculaneum (catalogued 1752)
Zoophilia is a paraphilia involving a sexual fixation on non-human animals. Bestiality is cross-species sexual activity between humans and non-human animals. The terms are often used interchangeably, but some researchers make a distinction between the attraction (zoophilia) and the act (bestiality).[1]
Although sex with animals is not outlawed in some countries, in most countries, bestiality is illegal under animal abuse laws or laws dealing with buggery or crimes against nature.
## Contents
* 1 Terminology
* 1.1 General
* 1.2 Zoophilia
* 1.3 Zoosexuality
* 1.4 Bestiality
* 2 Extent of occurrence
* 3 Perspectives on zoophilia
* 3.1 Research perspectives
* 3.2 Historical and cultural perspectives
* 3.3 Religious perspectives
* 4 Legal status
* 4.1 Pornography
* 5 Health and safety
* 6 Zoophiles
* 6.1 Non-sexual zoophilia
* 6.2 Zoophile community
* 7 Debate over zoophilia or zoophilic relations
* 7.1 Arguments against bestiality
* 7.2 Arguments for bestiality
* 8 Mentions in the media
* 9 See also
* 10 References and footnotes
* 11 External links
## Terminology
### General
Three key terms commonly used in regards to the subject—zoophilia, bestiality, and zoosexuality—are often used somewhat interchangeably. Some researchers distinguish between zoophilia (as a persistent sexual interest in animals) and bestiality (as sexual acts with animals), because bestiality is often not driven by a sexual preference for animals.[1] Some studies have found a preference for animals is rare among people who engage in sexual contact with animals.[2] Furthermore, some zoophiles report they have never had sexual contact with an animal.[3] People with zoophilia are known as "zoophiles", though also sometimes as "zoosexuals", or even very simply "zoos".[1][4] Zooerasty, sodomy, and zooerastia[5] are other terms closely related to the subject but are less synonymous with the former terms, and are seldom used. "Bestiosexuality" was discussed briefly by Allen (1979), but never became widely established.[citation needed] Ernest Bornemann (1990, cited by Rosenbauer, 1997) coined the separate term zoosadism for those who derive pleasure – sexual or otherwise – from inflicting pain on animals. Zoosadism specifically is one member of the Macdonald triad of precursors to sociopathic behavior.[6]
### Zoophilia
The term zoophilia was introduced into the field of research on sexuality in Psychopathia Sexualis (1886) by Krafft-Ebing, who described a number of cases of "violation of animals (bestiality)",[7] as well as "zoophilia erotica",[8] which he defined as a sexual attraction to animal skin or fur. The term zoophilia derives from the combination of two nouns in Greek: ζῷον (zṓion, meaning "animal") and φιλία (philia, meaning "(fraternal) love"). In general contemporary usage, the term zoophilia may refer to sexual activity between human and non-human animals, the desire to engage in such, or to the specific paraphilia (i.e., the atypical arousal) which indicates a definite preference for non-human animals over humans as sexual partners. Although Krafft-Ebing also coined the term zooerasty for the paraphilia of exclusive sexual attraction to animals,[9] that term has fallen out of general use.
### Zoosexuality
Hokusai's (1760–1849) The Dream of the Fisherman's Wife.
The term zoosexual was proposed by Hani Miletski in 2002[4] as a value-neutral term. Usage of zoosexual as a noun (in reference to a person) is synonymous with zoophile, while the adjectival form of the word – as, for instance, in the phrase "zoosexual act" – may indicate sexual activity between a human and a non-human animal. The derivative noun "zoosexuality" is sometimes used by self-identified zoophiles in both support groups and on internet-based discussion forums to designate sexual orientation manifesting as romantic or emotional involvement with, or sexual attraction to, non-human animals.[4][10]
### Bestiality
Japanese ukiyo-e woodblock print from Utagawa Kunisada's series, "Eight Canine Heroes of the House of Satomi", 1837.
An 18th-century Indian miniature depicting women practising zoophilia in the bottom register.
The legal term bestiality has three common pronunciations: [ˌbestʃiˈæləti] or [ˌbistʃiˈæləti] in the United States,[11] and [ˌbestiˈæləti] in the United Kingdom.[12] Some zoophiles and researchers draw a distinction between zoophilia and bestiality, using the former to describe the desire to form sexual relationships with animals, and the latter to describe the sex acts alone.[13] Confusing the matter yet further, writing in 1962, Masters used the term bestialist specifically in his discussion of zoosadism.
Stephanie LaFarge, an assistant professor of psychiatry at the New Jersey Medical School, and Director of Counseling at the ASPCA, writes that two groups can be distinguished: bestialists, who rape or abuse animals, and zoophiles, who form an emotional and sexual attachment to animals.[14] Colin J. Williams and Martin Weinberg studied self-defined zoophiles via the internet and reported them as understanding the term zoophilia to involve concern for the animal's welfare, pleasure, and consent, as distinct from the self-labelled zoophiles' concept of "bestialists", whom the zoophiles in their study defined as focused on their own gratification. Williams and Weinberg also quoted a British newspaper saying that zoophilia is a term used by "apologists" for bestiality.[15]
## Extent of occurrence
The Kinsey reports rated the percentage of people who had sexual interaction with animals at some point in their lives as 8% for men and 3.6% for women, and claimed it was 40–50% in people living near farms,[9] but some later writers dispute the figures, because the study lacked a random sample in that it included a disproportionate number of prisoners, causing sampling bias. Martin Duberman has written that it is difficult to get a random sample in sexual research, and that even when Paul Gebhard, Kinsey's research successor, removed prison samples from the figures, he found the figures were not significantly changed.[16]
By 1974, the farm population in the USA had declined by 80 percent compared with 1940, reducing the opportunity to live with animals; Hunt's 1974 study suggests that these demographic changes led to a significant change in reported occurrences of bestiality. The percentage of males who reported sexual interactions with animals in 1974 was 4.9% (1948: 8.3%), and in females in 1974 was 1.9% (1953: 3.6%). Miletski believes this is not due to a reduction in interest but merely a reduction in opportunity.[17]
Nancy Friday's 1973 book on female sexuality, My Secret Garden, comprised around 190 fantasies from different women; of these, 23 involve zoophilic activity.[18]
In one study, psychiatric patients were found to have a statistically significant higher prevalence rate (55 percent) of reported bestiality, both actual sexual contacts (45 percent) and sexual fantasy (30 percent) than the control groups of medical in-patients (10 percent) and psychiatric staff (15 percent).[19] Crépault and Couture (1980) reported that 5.3 percent of the men they surveyed had fantasized about sexual activity with an animal during heterosexual intercourse.[20] In a 2014 study, 3% of women and 2.2% of men reported fantasies about having sex with an animal.[21] A 1982 study suggested that 7.5 percent of 186 university students had interacted sexually with an animal.[22]
Sexual arousal from watching animals mate is known as faunoiphilia.[23] A frequent interest in and sexual excitement at watching animals mate is cited as an indicator of latent zoophilia by Massen (1994).[citation needed]
## Perspectives on zoophilia
Art by Franz von Bayros depicting oral sex between an adolescent and a deer
### Research perspectives
Zoophilia has been partly discussed by several sciences: psychology (the study of the human mind), sexology (a relatively new discipline primarily studying human sexuality), ethology (the study of animal behavior), and anthrozoology (the study of human–animal interactions and bonds).
In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), zoophilia is placed in the classification "other specified paraphilic disorder"[24] ("paraphilias not otherwise specified" in the DSM-III and IV[25][26][27][28]). The World Health Organization takes the same position, listing a sexual preference for animals in its ICD -10 as "other disorder of sexual preference".[29] In the DSM-5, it rises to the level of a diagnosable disorder only when accompanied by distress or interference with normal functioning.[24][30]
Zoophilia may also be covered to some degree by other fields such as ethics, philosophy, law, animal rights and animal welfare. It may also be touched upon by sociology which looks both at zoosadism in examining patterns and issues related to sexual abuse and at non-sexual zoophilia in examining the role of animals as emotional support and companionship in human lives, and may fall within the scope of psychiatry if it becomes necessary to consider its significance in a clinical context. The Journal of Forensic and Legal Medicine (Vol. 18, February 2011) states that sexual contact with animals is almost never a clinically significant problem by itself;[31] it also states that there are several kinds of zoophiles:[31]
* Human-animal role-players
* Romantic zoophiles
* Zoophilic fantasizers
* Tactile zoophiles
* Fetishistic zoophiles
* Sadistic bestials
* Opportunistic zoophiles
* Regular zoophiles
* Exclusive zoophiles
Additionally, zoophiles in categories 2, 3, and 8 (romantic zoophiles, zoophilic fantasizers, and regular zoophiles) are the most common, while zoophiles found in categories 6 and 7 (sadistic bestials and opportunistic zoophiles) are the least common.[31]
Zoophilia may reflect childhood experimentation, sexual abuse or lack of other avenues of sexual expression. Exclusive desire for animals rather than humans is considered a rare paraphilia, and sufferers often have other paraphilias[32] with which they present. Zoophiles will not usually seek help for their condition, and so do not come to the attention of psychiatrists for zoophilia itself.[33]
The first detailed studies of zoophilia date from prior to 1910. Peer reviewed research into zoophilia in its own right started around 1960. However, a number of the most oft-quoted studies, such as Miletski, were not published in peer-reviewed journals. There have been several significant modern books, from Masters (1962) to Beetz (2002);[34] their research arrived at the following conclusions:
* Most zoophiles have (or have also had) long term human relationships as well or at the same time as zoosexual ones, and that zoosexual partners are usually dogs and/or horses (Masters, Miletski, Beetz)[34][35]
* Zoophiles' emotions and care for animals can be real, relational, authentic and (within animals' abilities) reciprocal, and not just a substitute or means of expression.[36] Beetz believes zoophilia is not an inclination which is chosen.[34]
* Society in general at present is considerably misinformed about zoophilia, its stereotypes, and its meaning.[34] The distinction between zoophilia and zoosadism is a critical one to these researchers, and is highlighted by each of these studies. Masters (1962), Miletski (1999) and Weinberg (2003) each comment significantly on the social harm caused by misunderstandings regarding zoophilia: "This destroy[s] the lives of many citizens".[34]
Beetz also states the following:
> The phenomenon of sexual contact with animals is starting to lose its taboo: it is appearing more often in scholarly publications, and the public are being confronted with it, too. ... Sexual contact with animals – in the form of bestiality or zoophilia – needs to be discussed more openly and investigated in more detail by scholars working in disciplines such as animal ethics, animal behavior, anthrozoology, psychology, mental health, sociology, and the law.[37]
More recently, research has engaged three further directions: the speculation that at least some animals seem to enjoy a zoophilic relationship assuming sadism is not present, and can form an affectionate bond.[38] Similar findings are also reported by Kinsey (cited by Masters), and others earlier in history. Miletski (1999) notes that information on sex with animals on the internet is often very emphatic as to what the zoophile believes gives pleasure and how to identify what is perceived as consent beforehand. For instance, Jonathan Balcombe says animals do things for pleasure. But he himself says pet owners will be unimpressed by this statement, as this is not news to them.[39]
Beetz described the phenomenon of zoophilia/bestiality as being somewhere between crime, paraphilia and love, although she says that most research has been based on criminological reports, so the cases have frequently involved violence and psychiatric illness. She says only a few recent studies have taken data from volunteers in the community.[40] As with all volunteer surveys and sexual ones in particular, these studies have a potential for self-selection bias.[41]
Medical research suggests that some zoophiles only become aroused by a specific species (such as horses), some zoophiles become aroused by multiple species (which may or may not include humans), and some zoophiles are not attracted to humans at all.[2][42]
Researchers who observed a monkey trying to mate with a deer in 2017 (interspecies sex) said that it may provide clues into why humans have interspecies sex.[43][44][45]
### Historical and cultural perspectives
Main article: Historical and cultural perspectives on zoophilia
The taboo of zoophilia has led to stigmatised groups being accused of it, as with blood libel. This German illustration shows Jews performing bestiality on a Judensau, while Satan watches.
Instances of this behavior have been found in the Bible.[46] In a cave painting from at least 8000 BC in the Northern Italian Val Camonica a man is shown about to penetrate an animal. Raymond Christinger interprets that as a show of power of a tribal chief,[47] and so we do not know if this practice was then more acceptable, and if the scene depicted was usual or unusual or whether it was symbolic or imaginary.[48] The "Cambridge Illustrated History of Prehistoric Art" says the scene may be humorous, as the penetrating man seems to be waving cheerfully with his hand at the same time. Potters seem to have spent time depicting the practice, but this may be because they found the idea amusing.[49] Dr "Jacobus X", said to be the pen name of a French author, said this was clearly "before any known taboos against sex with animals existed".[50] Marc Epprecht states that authors such as Jacobus X do not deserve respect because their methodology is based on hearsay, and was designed for voyeuristic titillation of the reader.[51] Masters said that since pre-historic man is prehistoric it goes without saying that we know little of his sexual behaviour;[52] depictions in cave paintings may only show the artist's subjective preoccupations or thoughts.
Pindar, Herodotus, and Plutarch claimed the Egyptians engaged in ritual congress with goats.[53] Such claims about other cultures do not necessarily reflect anything about which the author had evidence, but may be a form of propaganda or xenophobia, similar to blood libel.[citation needed]
Bestiality was accepted in some North American and Middle Eastern indigenous cultures.[54] Sexual intercourse between humans and non-human animals was not uncommon among certain Native American indigenous peoples, including the Hopi.[55][56] Voget describes the sexual lives of young Native Americans as "rather inclusive", including bestiality.[55] In addition, the Copper Inuit people had "no aversion to intercourse with live animals".[55]
Several cultures built temples (Khajuraho, India) or other structures (Sagaholm, barrow, Sweden) with zoophilic carvings on the exterior, however at Khajuraho, these depictions are not on the interior, perhaps depicting that these are things that belong to the profane world rather than the spiritual world, and thus are to be left outside.[citation needed]
In the Church-oriented culture of the Middle Ages, zoophilic activity was met with execution, typically burning, and death to the animals involved either the same way or by hanging, as "both a violation of Biblical edicts and a degradation of man as a spiritual being rather than one that is purely animal and carnal".[57] Some witches were accused of having congress with the devil in the form of an animal. As with all accusations and confessions extracted under torture in the witch trials in Early Modern Europe, their validity cannot be ascertained.[53]
### Religious perspectives
Passages in Leviticus 18 (Lev 18:23: "And you shall not lie with any beast and defile yourself with it, neither shall any woman give herself to a beast to lie with it: it is a perversion." RSV) and 20:15–16 ("If a man lies with a beast, he shall be put to death; and you shall kill the beast. If a woman approaches any beast and lies with it, you shall kill the woman and the beast; they shall be put to death, their blood is upon them." RSV) are cited by Jewish, Christian, and Muslim theologians as categorical denunciation of bestiality. However, the teachings of the New Testament have been interpreted by some as not expressly forbidding bestiality.[58]
In Part II of his Summa Theologica, medieval philosopher Thomas Aquinas ranked various "unnatural vices" (sex acts resulting in "venereal pleasure" rather than procreation) by degrees of sinfulness, concluding that "the most grievous is the sin of bestiality".[59] Some Christian theologians extend Matthew's view that even having thoughts of adultery is sinful to imply that thoughts of committing bestial acts are likewise sinful.
Man having intercourse with a horse, pictured on the exterior of a temple in Khajuraho.
There are a few references in Hindu scriptures to religious figures engaging in symbolic sexual activity with animals such as explicit depictions of people having sex with animals included amongst the thousands of sculptures of "Life events" on the exterior of the temple complex at Khajuraho. The depictions are largely symbolic depictions of the sexualization of some animals and are not meant to be taken literally.[60] According to the Hindu tradition of erotic painting and sculpture, having sex with an animal is believed to be actually a human having sex with a god incarnated in the form of an animal.[61] However, in some Hindu scriptures, such as the Bhagavata Purana and the Devi Bhagavata Purana, having sex with animals, especially the cow, leads one to hell, where one is tormented by having one's body rubbed on trees with razor-sharp thorns.[62]
## Legal status
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Main article: Legality of bestiality by country or territory
In many jurisdictions, all forms of zoophilic acts are prohibited; others outlaw only the mistreatment of animals, without specific mention of sexual activity. In the United Kingdom, Section 63 of the Criminal Justice and Immigration Act 2008 (also known as the Extreme Pornography Act) outlaws images of a person performing or appearing to perform an act of intercourse or oral sex with an animal (whether dead or alive).[63] Despite the UK Ministry of Justice's explanatory note on extreme images saying "It is not a question of the intentions of those who produced the image. Nor is it a question of the sexual arousal of the defendant",[64] "it could be argued that a person might possess such an image for the purposes of satire, political commentary or simple grossness," according to The Independent.[65]
Many new laws banning sex with animals have been made recently, such as in New Hampshire,[66] Ohio,[citation needed] Germany,[67] Sweden,[68] Denmark,[69]Thailand,[70] Costa Rica,[71] Bolivia,[72] and Guatemala.[73] The number of jurisdictions around the world banning it has grown in the 2000s and 2010s.
The only EU countries where zoophilia remains legal are Finland, Hungary, and Romania.[74] It is also legal in Malta but not desired to remain so.[75]
Laws on zoophilia are sometimes triggered by specific incidents.[76] While some laws are very specific, others employ vague terms such as "sodomy" or "bestiality", which lack legal precision and leave it unclear exactly which acts are covered. In the past, some bestiality laws may have been made in the belief that sex with an animal could result in monstrous offspring, as well as offending the community. Current anti-cruelty laws focus more specifically on animal welfare while anti-bestiality laws are aimed only at offenses to community "standards".[77] Notable legal views include Sweden, where a 2005 report by the Swedish Animal Welfare Agency for the government expressed concern over the increase in reports of horse-ripping incidents. The agency believed current animal cruelty legislation was not sufficient in protecting animals from abuse and needed updating, but concluded that on balance it was not appropriate to call for a ban.[78] In New Zealand, the 1989 Crimes Bill considered abolishing bestiality as a criminal offense, and instead viewing it as a mental health issue, but they did not, and people can still be prosecuted for it. Under Section 143 of the Crimes Act 1961, individuals can serve a sentence of seven years duration for animal sexual abuse and the offence is considered 'complete' in the event of 'penetration'.[79] In Canada, a clarification of the anti-bestiality law was made in 2016 which legalizes most forms of sexual contact with animals other than penetration.[80]
Some countries once had laws against single males living with female animals, such as alpacas.[citation needed] Copulating with a female alpaca is still specifically against the law in Peru.[81]
As of 2017, bestiality is illegal in 45 U.S. states. Most state bestiality laws were enacted between 1999 and 2017.[82][83] Until 2005, there was a farm near Enumclaw, Washington that was described as an "animal brothel", where people paid to have sex with animals. After an incident on 2 July 2005, when a man was pronounced dead in the emergency room of the Enumclaw community hospital after his colon ruptured due to having had anal sex with a horse, the farm garnered police attention. The state legislature of the State of Washington, which had been one of the few states in the United States without a law against bestiality, within six months passed a bill making bestiality illegal.[84][85] Arizona,[86] Alaska,[87] Florida,[88] Alabama,[89] New Jersey,[90] New Hampshire,[66] Ohio,[91] Texas,[92] Vermont,[93] and Nevada[94] have banned sex with animals between 2006 and the present, with the latter 5 all banning it in 2017. When such laws are proposed, they are never questioned or debated.[95][96] Laws which prohibit non-abusive bestiality have been criticized for being discriminatory, unjust and unconstitutional.[97][98]
### Pornography
Main articles: Obscenity and Legal status of Internet pornography
See also: Category:Animal pornography.
Wikimedia Commons has media related to Zoophilia in art.
Ancient Greek sodomising a goat", plate XVII from 'De Figuris Veneris' by F.K. Forberg, illustrated by Édouard-Henri Avril.
Pornography involving sex with animals is widely illegal, even in most countries where bestiality itself is not explicitly outlawed.[citation needed]
In the United States, zoophilic pornography would be considered obscene if it did not meet the standards of the Miller Test and therefore is not openly sold, mailed, distributed or imported across state boundaries or within states which prohibit it. Under U.S. law, 'distribution' includes transmission across the Internet. Production and mere possession appears to be legal, however. U.S. prohibitions on distribution of sexual or obscene materials are as of 2005[update] in some doubt, having been ruled unconstitutional in United States v. Extreme Associates (a judgement which was overturned on appeal, December 2005).
Similar restrictions apply in Germany (see above). In New Zealand the possession, making or distribution of material promoting bestiality is illegal.
The potential use of media for pornographic movies was seen from the start of the era of silent film. Polissons and Galipettes (re-released 2002 as "The Good Old Naughty Days") is a collection of early French silent films for brothel use, including some animal pornography, dating from around 1905 – 1930.
Material featuring sex with animals is widely available on the Internet, due to its ease of production.[citation needed] Prior to the advent of mass-market magazines such as Playboy, so-called Tijuana Bibles were a form of pornographic tract popular in America, sold as anonymous underground publications typically comprising a small number of stapled comic-strips representing characters and celebrities.[99] The promotion of "stars" began with the Danish Bodil Joensen, in the period of 1969–72, along with other porn actors such as the Americans Linda Lovelace (Dogarama, 1969), Chessie Moore (multiple films, c. 1994), Kerri Downs (three films, 1998) and Calina Lynx (aka Kelly G'raffe) (two films, 1998). Another early film to attain great infamy was "Animal Farm", smuggled into Great Britain around 1980 without details as to makers or provenance.[100] The film was later traced to a crude juxtaposition of smuggled cuts from many of Bodil Joensen's 1970s Danish movies.
Into the 1980s, the Dutch took the lead, creating figures like "Wilma" and the "Dutch Sisters". In the 1980s, "bestiality" was featured in Italian adult films with actresses like Denise Dior, Francesca Ray, and Marina Hedman, manifested early in the softcore flick Bestialità in 1976.
Today, in Hungary, where production faces no legal limitations, zoophilic materials have become a substantial industry that produces a number of films and magazines, particularly for Dutch companies such as Topscore and Book & Film International, and the genre has stars such as "Hector", a great dane dog starring in several films. Many Hungarian mainstream performers also appeared anonymously in animal pornography in their early careers, including for example, Suzy Spark.[101]
In Japan, animal pornography is used to bypass censorship laws, often featuring Japanese and Swedish[citation needed] female models performing fellatio on animals, because oral penetration of a non-human penis is not in the scope of Japanese mosaic censor. Sakura Sakurada is an AV idol known to have appeared in animal pornography, specifically in the AV The Dog Game in 2006. While primarily underground, there are a number of animal pornography actresses who specialize in bestiality movies. A box-office success of the 1980s, 24 Horas de Sexo Explícito featured zoophilia.
In the United Kingdom, Section 63 of the Criminal Justice and Immigration Act 2008 criminalises possession of realistic pornographic images depicting sex with animals (see extreme pornography), including fake images and simulated acts, as well as images depicting sex with dead animals, where no crime has taken place in the production. The law provides for sentences of up to two years in prison; a sentence of 12 months was handed down in one case in 2011.[102]
Pornography of this sort has become the business of certain spammers such as Jeremy Jaynes and owners of some fake TGPs, who use the promise of "extreme" material as a bid for users' attention.
## Health and safety
Main article: Zoonosis
Infections that are transmitted from animals to humans are called zoonoses. Some zoonoses may be transferred through casual contact, but others are much more readily transferred by activities that expose humans to the semen, vaginal fluids, urine, saliva, feces and blood of animals. Examples of zoonoses are Brucellosis, Q fever, leptospirosis, and toxocariasis. Therefore, sexual activity with animals is, in some instances, a high risk activity. Allergic reactions to animal semen may occur, including anaphylaxis. Bites and other trauma from penetration or trampling may occur.
## Zoophiles
### Non-sexual zoophilia
The love of animals is not necessarily sexual in nature. In psychology and sociology the word "zoophilia" is sometimes used without sexual implications. Being fond of animals in general, or as pets, is accepted in Western society, and is usually respected or tolerated. However, the word zoophilia is used to mean a sexual preference towards animals, which makes it[103] a paraphilia. Some zoophiles may not act on their sexual attraction to animals. People who identify as zoophiles may feel their love for animals is romantic rather than purely sexual, and say this makes them different from those committing entirely sexually motivated acts of bestiality.[104]
### Zoophile community
Several companies (e.g., Bad Dragon) sell dildos in the shape of animal penises, both realistic and fantastical. This one is based on a wolf's penis.
An online survey which recruited participants over the internet concluded that prior to the arrival of widespread computer networking, most zoophiles would not have known other zoophiles, and for the most part, zoophiles engaged in bestiality secretly, or told only trusted friends, family or partners. The internet and its predecessors made people able to search for information on topics which were not otherwise easily accessible and to communicate with relative safety and anonymity. Because of the diary-like intimacy of blogs and the anonymity of the internet, zoophiles had the ideal opportunity to "openly" express their sexuality.[105] As with many other alternate lifestyles, broader networks began forming in the 1980s when participating in networked social groups became more common at home and elsewhere.[106] Such developments in general were described by Markoff in 1990; the linking of computers meant that people thousands of miles apart could feel the intimacy akin to being in a small village together.[107] The popular newsgroup alt.sex.bestiality, said to be in the top 1% of newsgroup interest (i.e. number 50 out of around 5000), – and reputedly started in humor[108] – along with personal bulletin boards and talkers, chief among them Sleepy's multiple worlds, Lintilla, and Planes of Existence, were among the first group media of this kind in the late 1980s and early 1990s. These groups rapidly drew together zoophiles, some of whom also created personal and social websites and internet forums. By around 1992–1994, the wide social net had evolved.[109] This was initially centered around the above-mentioned newsgroup, alt.sex.bestiality, which during the six years following 1990 had matured into a discussion and support group.[110][111][112][113] The newsgroup included information about health issues, laws governing zoophilia, bibliography relating to the subject, and community events.[114]
Weinberg and Williams observe that the internet can socially integrate an incredibly large number of people. In Kinsey's day contacts between animal lovers were more localized and limited to male compatriots in a particular rural community. Further, while the farm boys Kinsey researched might have been part of a rural culture in which sex with animals was a part, the sex itself did not define the community. The zoophile community is not known to be particularly large compared to other subcultures which make use of the internet, so Weinberg and Williams surmised its aims and beliefs would likely change little as it grew. Those particularly active on the internet may not be aware of a wider subculture, as there is not much of a wider subculture, Weinberg and Williams felt the virtual zoophile group would lead the development of the subculture.[106]
Websites aim to provide support and social assistance to zoophiles (including resources to help and rescue abused or mistreated animals), but these are not usually well publicized. Such work is often undertaken as needed by individuals and friends, within social networks, and by word of mouth.[115]
Zoophiles tend to experience their first zoosexual feelings during adolescence, and tend to be secretive about it, hence limiting the ability for non-Internet communities to form.[116]
## Debate over zoophilia or zoophilic relations
Leda and the Swan, copy of a lost Michelangelo.
Because of its controversial nature, people have developed arguments both for[117] and against[118] zoophilia. Arguments for and against zoosexual activity from a variety of sources, including religious, moral, ethical, psychological, medical and social.
### Arguments against bestiality
Bestiality is seen by the government of the United Kingdom as profoundly disturbed behavior (as indicated by the UK Home Office review on sexual offences in 2002).[119] Andrea Beetz states there is evidence that there can be violent zoosadistic approaches to sex with animals. Beetz argues that animals might be traumatized even by a non-violent, sexual approach from a human;[120] however, Beetz also says that in some cases, non-abusive bestiality can be reciprocally pleasurable for both the human and non-human animal.[120]
An argument from human dignity is given by Wesley J. Smith, a senior fellow and Intelligent Design proponent at the Center for Science and Culture of the conservative Christian Discovery Institute: – "such behavior is profoundly degrading and utterly subversive to the crucial understanding that human beings are unique, special, and of the highest moral worth in the known universe—a concept known as 'human exceptionalism' ... one of the reasons bestiality is condemned through law is that such degrading conduct unacceptably subverts standards of basic human dignity and is an affront to humankind's inestimable importance and intrinsic moral worth."[121]
One of the primary critiques of bestiality is that it is harmful to animals and necessarily abusive, because animals are unable to give or withhold consent.[122]
The Humane Society of the United States (HSUS) has said that as animals do not have the same capacity for thinking as humans, they are unable to give full consent. The HSUS takes the position that all sexual activity between humans and animals is abusive, whether it involves physical injury or not.[123] In his 1993 article, Dr. Frank Ascione stated that "bestiality may be considered abusive even in cases when physical harm to an animal does not occur." In a 1997 article, Piers Beirne, Professor of Criminology at the University of Southern Maine, points out that 'for genuine consent to sexual relations to be present...both participants must be conscious, fully informed and positive in their desires.'[124][125]
### Arguments for bestiality
Book illustration depicting dog with woman, Isfahan, Iran, 15th century.
Some defenders of bestiality argue that the issue of sexual consent is irrelevant because many legal human practices (such as semen collection, artificial insemination, hunting, laboratory testing, and slaughtering animals for meat) do not involve the consent of the animal.[126] Brian Cutteridge states the following regarding this argument:
> "Animal sexual autonomy is regularly violated for human financial gain through procedures such as [artificial insemination and slaughter]. Such procedures are probably more disturbing physically and psychologically than acts of zoophilia would be, yet the issue of consent on the part of the animal is never raised in the discussion of such procedures. To confine the 'right' of any animal strictly to acts of zoophilia is thus to make a law [against zoophilia] based not on reason but on moral prejudice, and to breach the constitutional rights of zoophiles to due process and equality before the law. [...] Laws which criminalize zoophilia based on societal abhorrence of such acts rather than any real harm caused by such acts are an unjust and unconstitutional infringement on individual liberty."[97]
Hani Miletski believes that "Animals are capable of sexual consent – and even initiation – in their own way."[127] It is not an uncommon practice for dogs to attempt to copulate with ("hump") the legs of people of both genders.[128] Rosenberger (1968) emphasizes that as far as cunnilingus is concerned, dogs require no training, and even Dekkers (1994) and Menninger (1951) admit that sometimes animals take the initiative and do so impulsively.[120] Those supporting zoophilic activity feel animals sometimes even seem to enjoy the sexual attention[129] or voluntarily initiate sexual activity with humans.[130] Animals such as dogs can be willing participants in sexual activity with humans, and "seem to enjoy the attention provided by the sexual interaction with a human."[97] Animal owners normally know what their own pets like or do not like. Most people can tell if an animal does not like how it is being petted, because it will move away. An animal that is liking being petted pushes against the hand, and seems to enjoy it. To those defending bestiality this is seen as a way in which animals give consent, or the fact that a dog might wag its tail.[131]
Utilitarian philosopher and animal liberation author Peter Singer argues that bestiality is not unethical so long as it involves no harm or cruelty to the animal[132] (see Harm principle). In the article "Heavy Petting,"[133] Singer argues that zoosexual activity need not be abusive, and that relationships could form which were mutually enjoyed. Singer and others have argued that people's dislike of bestiality is partly caused by irrational speciesism and anthropocentrism.[134][135] Because interspecies sex occurs in nature,[136] and because humans are animals,[137] supporters argue that zoosexual activity is not "unnatural" and is not intrinsically wrong.[98][138]
Research has proven that non-human animals can and do have sex for non-reproductive purposes (and for pleasure).[139] In 2006, a Danish Animal Ethics Council report concluded that ethically performed zoosexual activity is capable of providing a positive experience for all participants, and that some non-human animals are sexually attracted to humans[140] (for example, dolphins).[141]
Some zoophiles claim that they are not abusive towards animals:[96]
> "In other recent surveys, the majority of zoophiles scoffed at the notion that they were abusive toward animals in any way—far from it, they said. Many even consider themselves to be animal welfare advocates in addition to zoophiles."[96]
## Mentions in the media
Because of its controversial nature, different countries vary in the discussion of bestiality. Often sexual matters are the subject of legal or regulatory requirement. In 2005 the UK broadcasting regulator (OFCOM) updated its code stating that freedom of expression is at the heart of any democratic state. Adult audiences should be informed as to what they will be viewing or hearing, and the young, who cannot make a fully informed choice for themselves, should be protected. Hence a watershed and other precautions were set up for explicit sexual material, to protect young people. Zoophile activity and other sexual matters may be discussed, but only in an appropriate context and manner.[142]
After the Films, Videos, and Publications Classification Act in 1993, the IPT was replaced with bodies designed to allow both more debate and increased consistency, and possession and supply of material that it is decided are objectionable was made a criminal offence.
## See also
Human/nonhuman interaction
* Semen collection from male animals
* Semen collection from bulls
* Semen collection from male dogs
* Anthrozoology
* Animal loss
* Exogamy
* Human–animal bonding
* Sexual imprinting
* Animal marriage
Animal studies
* Non-human animal sexuality
* Non-reproductive sexual behavior in animals
* Animal cognition
* Animal communication
* Bonding in mammals
Human sexuality
* Animal roleplay#Erotic scenarios
* Fur fetishism
* Bestiality in ancient Rome
* Sexual norm
* Sodomy
* Paraphilia
Ethics, morality and philosophy
* Wisdom of repugnance
* Argument from incredulity
* Anthropocentrism
* Human exceptionalism
* Religion and sexuality
* Zoophile rights by country or territory
* Great Ape personhood
Animal welfare
* Animal welfare
* Animal abuse
* Animal rights
Other
* Historical and cultural perspectives on zoophilia
* John Travers (a zoosadist)
* Timeline of zoophilia
## References and footnotes
1. ^ a b c Ranger, R.; Fedoroff, P. (2014). "Commentary: Zoophilia and the Law". Journal of the American Academy of Psychiatry and the Law Online. 42 (4): 421–426. PMID 25492067.
2. ^ a b Earls, C. M.; Lalumiere, M. L. (2002). "A Case Study of Preferential Bestiality (Zoophilia)". Sexual Abuse: A Journal of Research and Treatment. 14 (1): 83–88. doi:10.1177/107906320201400106. PMID 11803597. S2CID 43450855.
3. ^ Maratea, R. J. (2011). "Screwing the pooch: Legitimizing accounts in a zoophilia on-line community". Deviant Behavior. 32 (10): 938. doi:10.1080/01639625.2010.538356. S2CID 145637418.
4. ^ a b c Beetz, Andrea M. (2010). "Bestiality and Zoophilia: A Discussion of Sexual Contact With Animals". In Ascione, Frank (ed.). The International Handbook of Animal Abuse and Cruelty: Theory, Research, and Application. ISBN 978-1-55753-565-8.
5. ^ "zooerastia definition". Dictionary.com. Retrieved 13 December 2011.
6. ^ MacDonald, J. M. (1963). "The Threat to Kill". American Journal of Psychiatry. 120 (2): 125–30. doi:10.1176/ajp.120.2.125. Retrieved 19 January 2013.
7. ^ Richard von Krafft-Ebing: Psychopathia Sexualis, p. 561.
8. ^ Richard von Krafft-Ebing: Psychopathia Sexualis, p. 281.
9. ^ a b D. Richard Laws and William T. O'Donohue: Books.Google.co.uk, Sexual Deviance, page 391. Guilford Press, 2008. ISBN 978-1-59385-605-2.
10. ^ "What is zoosexuality". Zoosexuality.org. Retrieved 3 December 2011.
11. ^ "Pronunciation of bestiality". MacMillan Dictionary. Retrieved 3 January 2018.
12. ^ "Pronunciation of bestiality". MacMillan Dictionary. Retrieved 3 January 2018.
13. ^ "Sexuality.about.com". Sexuality.about.com. Retrieved 13 May 2012.
14. ^ Melinda Roth (15 December 1991). "All Opposed, Say Neigh". Riverfront Times. Retrieved 24 January 2009.
15. ^ Williams CJ, Weinberg MS (December 2003). "Zoophilia in men: a study of sexual interest in animals". Archives of Sexual Behavior. 32 (6): 523–35. doi:10.1023/A:1026085410617. PMID 14574096. S2CID 13386430.
16. ^ Richard Duberman: KinseyInstitute.org Archived 11 January 2009 at the Wayback Machine, Kinsey's Urethra The Nation, 3 November 1997, pp. 40–43. Review of Alfred C. Kinsey: A Public/Private Life. By James H. Jones.
17. ^ Hunt 1974, cited and re-examined by Miletski (1999)
18. ^ Nancy Friday (1998) [1973]. "What do women fantasize about? The Zoo". My Secret Garden (Revised ed.). Simon and Schuster. pp. 180–185. ISBN 978-0-671-01987-7.
19. ^ Alvarez, WA; Freinhar, JP (1991). "A prevalence study of bestiality (zoophilia) in psychiatric in-patients, medical in-patients, and psychiatric staff". International Journal of Psychosomatics. 38 (1–4): 45–7. PMID 1778686.
20. ^ Crépault, Claude; Couture, Marcel (1980). "Men's erotic fantasies". Archives of Sexual Behavior. 9 (6): 565–81. doi:10.1007/BF01542159. PMID 7458662. S2CID 9021936.
21. ^ Joyal, C. C.; Cossette, A.; Lapierre, V. (2014). "What Exactly Is an Unusual Sexual Fantasy?". The Journal of Sexual Medicine. 12 (2): 328–340. doi:10.1111/jsm.12734. PMID 25359122.
22. ^ Story, MD (1982). "A comparison of university student experience with various sexual outlets in 1974 and 1980". Adolescence. 17 (68): 737–47. PMID 7164870.
23. ^ Aggrawal, Anil. Forensic and medico-legal aspects of sexual crimes and unusual sexual practices. CRC Press, 2008.
24. ^ a b American Psychiatric Association, ed. (2013). "Other Specified Paraphilic Disorder, 302.89 (F65.89)". Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. American Psychiatric Publishing. p. 705.
25. ^ Diagnostic and Statistical Manual of Mental Disorders: DSM-IV. Washington, DC: American Psychiatric Association. 2000. ISBN 978-0-89042-025-6. OCLC 43483668.
26. ^ Milner, J. S.; Dopke, C. A. (2008). "Paraphilia Not Otherwise Specified: Psychopathology and theory". In Laws, D. R.; O'Donohue, W. T. (eds.). Sexual Deviance, Second Edition: Theory, Assessment, and Treatment. New York: The Guilford Press. pp. 384–418. ISBN 978-1-59385-605-2. OCLC 152580827.
27. ^ Money, John (1988). Lovemaps: Clinical Concepts of Sexual/Erotic Health and Pathology, Paraphilia, and Gender Transposition in Childhood, Adolescence, and Maturity. Buffalo, N.Y: Prometheus Books. ISBN 978-0-87975-456-3. OCLC 19340917.
28. ^ Seto, MC; Barbaree HE (2000). "Paraphilias". In Hersen, M.; Van Hasselt, V. B. (eds.). Aggression and violence: an introductory text. Boston: Allyn & Bacon. pp. 198–213. ISBN 978-0-205-26721-7. OCLC 41380492.
29. ^ "International Statistical Classification of Diseases and Related Health Problems 10, F65.8 Other disorders of sexual preference". Who.int. Retrieved 13 May 2012.
30. ^ Miletski, H. (2015). "Zoophilia – Implications for Therapy". Journal of Sex Education and Therapy. 26 (2): 85–86. doi:10.1080/01614576.2001.11074387. S2CID 146150162.
31. ^ a b c Aggrawal, Anil (2011). "A new classification of zoophilia". Journal of Forensic and Legal Medicine. 18 (2): 73–8. doi:10.1016/j.jflm.2011.01.004. PMID 21315301.
32. ^ D. Richard Laws; William T. O'Donohue (January 2008). Sexual Deviance: Theory, Assessment, and Treatment. Guilford Press. p. 391. ISBN 978-1-59385-605-2.
33. ^ Richard W. Roukema (13 August 2008). What Every Patient, Family, Friend, and Caregiver Needs to Know About Psychiatry, Second Edition. American Psychiatric Pub. p. 133. ISBN 978-1-58562-750-9.
34. ^ a b c d e Beetz 2002, section 5.2.4 – 5.2.7.
35. ^ Anil Aggrawal (22 December 2008). Forensic and Medico-legal Aspects of Sexual Crimes and Unusual Sexual Practices. CRC Press. p. 257. ISBN 978-1-4200-4309-9. Retrieved 13 May 2012.
36. ^ (Masters, Miletski, Weinberg, Beetz)
37. ^ Anthony L. Podberscek; Andrea M. Beetz (1 September 2005). Bestiality and Zoophilia: Sexual Relations with Animals. Berg. p. 94. ISBN 978-0-85785-222-9. Retrieved 13 May 2012.
38. ^ Masters, 1962.
39. ^ Jonathan Balcombe (29 May 2006). "Animals can be happy too". The Guardian. London. Retrieved 13 May 2012.
40. ^ "Bestiality/Zoophilia: A Scarcely-Investigated Phenomenon Between Crime, Paraphilia, and Love". Scie-SocialCareOnline.org.uk. Archived 15 November 2010 at the Wayback Machine
41. ^ Joseph W. Slade (2001). Pornography and Sexual Representation: A Reference Guide. Greenwood Publishing Group. p. 980. ISBN 978-0-313-31521-3.
42. ^ Bhatia, MS; Srivastava, S; Sharma, S (2005). "1. An uncommon case of zoophilia: A case report". Medicine, Science, and the Law. 45 (2): 174–75. doi:10.1258/rsmmsl.45.2.174. PMID 15895645. S2CID 5744962.
43. ^ Devlin, Hannah (10 January 2017). "Snow monkey attempts sex with deer in rare example of interspecies mating". The Guardian. Retrieved 12 March 2018.
44. ^ "Monkey Tries to Mate With Deer in First Ever Video". Nationalgeographic.com. 11 January 2017. Retrieved 12 March 2018.
45. ^ Wenzke, Marissa. "Sex between snow monkey and deer shows different species may mate if they're 'deprived', study says". Mashable.com. Retrieved 12 March 2018.
46. ^ Aggrawal, Anil (2009). "References to the paraphilias and sexual crimes in the Bible". Journal of Forensic and Legal Medicine. 16 (3): 109–14. doi:10.1016/j.jflm.2008.07.006. PMID 19239958.
47. ^ Archaeometry.org, Link to web page and photograph, archaeometry.org
48. ^ Lynne Bevan (2006). Worshippers and warriors: reconstructing gender and gender relations in the prehistoric rock art of Naquane National Park, Valcamonica, Brecia, northern Italy. Archaeopress. ISBN 978-1-84171-920-7.
49. ^ Paul G. Bahn (1998). The Cambridge Illustrated History of Prehistoric Art. Cambridge University Press. p. 188. ISBN 978-0-521-45473-5.
50. ^ Abuses Aberrations and Crimes of the Genital Sense, 1901.
51. ^ Marc Epprecht (2006). ""Bisexuality" and the politics of normal in African Ethnography". Anthropologica. 48 (2): 187–201. doi:10.2307/25605310. JSTOR 25605310.
52. ^ Masters, Robert E. L., Forbidden Sexual Behavior and Morality, p. 5.
53. ^ a b Vern L. Bullough; Bonnie Bullough (1 January 1994). Human Sexuality: An Encyclopedia. Taylor & Francis. p. 61. ISBN 978-0-8240-7972-7.
54. ^ Judith Worell (September 2001). "Cross-Cultural Sexual Practices". Encyclopedia of Women and Gender: Sex Similarities and Differences and the Impact of Society on Gender. Academic Press. p. 298. ISBN 978-0-12-227245-5.
55. ^ a b c Voget, F. W. (1961) "Sex life of the American Indians", in Ellis, A. & Abarbanel, A. (Eds.) The Encyclopaedia of Sexual Behavior, Volume 1. London: W. Heinemann, pp. 90–109.
56. ^ Talayesva, Don C; Simmons, Leo William (1942). Sun Chief: The Autobiography of a Hopi Indian. Yale University Press. p. 78. ISBN 9780300002270. Retrieved 12 December 2012.
57. ^ Masters (1962)
58. ^ Plummer, Keith (2001). To beast or not to beast: does the law of Christ forbid zoophilia?. 53rd National Conference of the Evangelical Theological Society. Colorado Springs, CO.
59. ^ Fordham.edu Aquinas on Unnatural Sex
60. ^ Swami Satya Prakash Saraswati, The Critical and Cultural Study of the Shatapatha Brahmana, p. 415.
61. ^ Podberscek, Anthony L.; Beetz, Andrea M. (1 September 2005). Bestiality and Zoophilia: Sexual Relations with Animals. Berg. p. 12. ISBN 978-0-85785-222-9. Retrieved 4 January 2013.
62. ^ Mani, Vettam (1975). Puranic Encyclopaedia: A Comprehensive Dictionary With Special Reference to the Epic and Puranic Literature. Delhi: Motilal Banarsidass. pp. 368–70. ISBN 978-0-8426-0822-0. OCLC 2198347.
63. ^ "Section 63 – Possession of extreme pornographic images". Criminal Justice and Immigration Act 2008. 2008.
64. ^ "Extreme Pornography". Crown Prosecution Service. Retrieved 23 September 2015.
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67. ^ "§ 3 TierSchG - dejure.org". Dejure.org. Retrieved 20 October 2018.
68. ^ "Sweden Joins An Increasing Number of European Countries That Ban Bestiality". Webpronews.com. Retrieved 16 November 2017.
69. ^ "Flertal for lovændring: Nu bliver sex med dyr ulovligt". 21 April 2015. Retrieved 20 October 2018.
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72. ^ "LEY No 700 del 01 de Junio de 2015 " Derechoteca". Derechoteca.com. Retrieved 16 November 2017.
73. ^ "Transdoc :: Ley de Protección y Bienestar Animal :: transdoc.com". Transdoc.com. Retrieved 16 November 2017.
74. ^ "Denmark passes law to ban bestiality". BBC Newsbeat. 22 April 2015. Retrieved 18 August 2018.
75. ^ https://lovinmalta.com/news/maltese-law-encouraging-animal-sex-tourism-and-risks-becoming-bestiality-hotspot/
76. ^ Howard Fischer: Lawmakers hope to outlaw bestiality, Arizona Daily Star, 28 March 2006. In Arizona, the motive for legislation was a "spate of recent cases."
77. ^ Posner, Richard, A Guide to America's Sex Laws, The University of Chicago Press, 1996. ISBN 978-0-226-67564-0. Page 207.
78. ^ "TheLocal.se". TheLocal.se. 26 January 2012. Archived from the original on 15 May 2013. Retrieved 13 May 2012.
79. ^ "Crimes Act 1961 No 43 (as at 01 October 2012), Public Act – New Zealand Legislation". Legislation.govt.nz. 1 October 2012. Retrieved 4 January 2013.
80. ^ "Her Majesty the Queen v. D.L.W." Office of the Registrar of the Supreme Court of Canada (ORSCC). 2 May 2016. Retrieved 20 June 2016.
81. ^ Fred Leavitt (1 January 2003). The Real Drug Abusers. Rowman & Littlefield. p. 195. ISBN 978-0-7425-2518-4. "female alpaca peru copulate."
82. ^ "Michigan State University College of Law". Animallaw.info. Retrieved 4 January 2013.
83. ^ "Table of State Animal Sexual Assault Laws | Animal Legal & Historical Center". Animallaw.info. 24 June 2016. Retrieved 17 April 2017.
84. ^ Johnston, Lynda and Longhurst, Robyn Space, Place, and Sex Lanham, Maryland:2010 Rowman & Littlefield Publishers, p. 110.
85. ^ "Man dies after sex with horse". News24, 19 July 2005.
86. ^ "Sheriff says Craigslist facilitates bestiality". The Washington Times. 16 March 2011. Retrieved 4 January 2013.
87. ^ Sessions, David (27 January 2010). "Bill to Criminalize Bestiality Advances in Alaska Legislature". Politics Daily. Archived from the original on 8 September 2012. Retrieved 10 February 2020.CS1 maint: unfit URL (link)
88. ^ Mandell, Nina (6 May 2011). "Legislation outlawing bestiality makes it to Florida governor's desk". Daily News. New York.
89. ^ "SB 151 - Alabama 2014 Regular Session". Openstate.org. Retrieved 17 April 2017.
90. ^ "New Jersey A3012 - 2014-2015 - Regular Session". Retrieved 17 April 2017.
91. ^ "Ohio SB195 - 2015-2016 - 131st General Assembly". Legiscan.com. Retrieved 16 November 2017.
92. ^ "Texas: Crackdown on animal cruelty, bestiality, starts 1 Sept". Star-telegram.com. Retrieved 12 March 2018.
93. ^ "No. 62. An act relating to criminal justice" (PDF). Legislature.vermont.gov. Retrieved 20 October 2018.
94. ^ "AB391". Leg.state.nv.us. Retrieved 12 March 2018.
95. ^ "Senate again passes bestiality bill | Florida Politics | Sun Sentinel blog". Weblogs.sun-sentinel.com. 24 March 2011. Retrieved 4 January 2013.
96. ^ a b c Bering, Jesse (24 March 2010). "Animal Lovers: Zoophiles Make Scientists Rethink Human Sexuality | Bering in Mind, Scientific American Blog Network". Scientific American. Retrieved 4 January 2013.
97. ^ a b c "Inter-disciplinary.net" (PDF). Archived from the original (PDF) on 22 July 2012. Retrieved 13 May 2012.
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99. ^ An example digitized Tijuana Bible entitled The Pet from the 1960s is linked at tijuanabibles.org page link (also see full size and search).
100. ^ "The Dark Side of Porn Season 2 (2006) - Documentary / TV-Show". Crimedocumentary.com. Retrieved 28 May 2018.
101. ^ EuroBabeIndex.com, Suzy Spark
102. ^ ‘Acts of depravity’ found on dad’s computer, Reading Post, 26 January 2011.
103. ^ W. Edward Craighead; Charles B. Nemeroff, eds. (11 November 2002). The Corsini Encyclopedia of Psychology and Behavioral Science. John Wiley & Sons. p. 1050. ISBN 978-0-471-27083-6.
104. ^ David Delaney (2003). Law and Nature. Cambridge University Press. p. 252. ISBN 978-1-139-43700-4.
105. ^ Montclair, 1997, cited by Miletski, 1999, p .35.
106. ^ a b Weinberg and Williams
107. ^ Markoff, 1990.
108. ^ Miletski p. 35.
109. ^ Miletski (1999)
110. ^ Milteski (1999), p. 35.
111. ^ Andriette, 1996.
112. ^ Fox, 1994.
113. ^ Montclair, 1997.
114. ^ Donofrio, 1996.
115. ^ Miletski (1999), p. 22.
116. ^ Thomas Francis (20 August 2009). "Those Who Practice Bestiality Say They're Part of the Next Sexual Rights Movement – Page 2 – News – Broward/Palm Beach – New Times Broward-Palm Beach". Broward/Palm Beach. Retrieved 13 May 2012.
117. ^ Pablo Stafforini. "Heavy Petting, by Peter Singer". Utilitarian.net. Archived from the original on 6 June 2012. Retrieved 13 May 2012.
118. ^ "Bestiality and Lack of Consent " StopBestiality". Stopbestiality.wordpress.com. Retrieved 13 May 2012.
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122. ^ Regan, Tom. Animal Rights, Human Wrongs. Rowman & Littlefield, 2003, pp. 63–4, 89.
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125. ^ Ascione, Frank R. (1993). "Children Who are Cruel to Animals: A Review of Research and Implications for Developmental Psychopathology". Anthrozoös: A Multidisciplinary Journal of the Interactions of People and Animals. 6 (4): 226–47. doi:10.2752/089279393787002105.
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127. ^ Miltski, 1999, p. 50.
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## External links
Look up zoophilia, zoosexuality, or bestiality in Wiktionary, the free dictionary.
Wikimedia Commons has media related to Zoophilia.
* Encyclopedia of Human Sexuality entry for "Bestiality" at Sexology Department of Humboldt University, Berlin.
* Zoophilia References Database Bestiality and zoosadism criminal executions.
* Animal Abuse Crime Database search form for the U.S. and UK.
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* BNF: cb12405379f (data)
* GND: 4181721-7
* NDL: 00575090
*[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 inhibitor
*[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
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
| Zoophilia | c0152186 | 5,199 | wikipedia | https://en.wikipedia.org/wiki/Zoophilia | 2021-01-18T19:08:33 | {"umls": ["C0152186"], "wikidata": ["Q8392"]} |
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