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Reid et al. (1989) described a family in which 12 persons in 4 generations had diffuse cystic angiomatosis of bone. The affected individuals were asymptomatic. Roentgenographically, the lesions occurred throughout the length of long bones and were osteolytic, with a thin sclerotic rim. The cortex of the bone was rarely involved and showed no periosteal reaction. Growth plate closure and remodeling were unaffected. With age, increasing sclerosis occurred, resulting in complete obliteration of the cyst with irregular reactive trabeculations. Five of the affected individuals were female. There were several examples of male-to-male transmission. Cystic angiomatosis of bone includes both hemangiomatosis and lymphangiomatosis. The disorder is different from monocentric massive osteolysis, which goes by the name of Gorham (Gorham and Stout, 1955) and appears to be nonmendelian.
Devlin et al. (1996) studied a patient with Gorham-Stout disease (GSD) who had massive resorption of his mandible, which extended to the maxilla, zygoma, right parietal region, and cranium. They tested the effects of the patient's serum, sampled both early in the course of treatment and later after the osteolysis was 'stabilized.' It was 'stabilized' on the formation of osteoclast-like multinuclear cells (MNCs) in cultures of normal human marrow. The serum in 10% by volume dilution markedly increased the number of MNCs formed in cultures of normal serum as well as stimulated the formation of resorption pits by MNCs on dentine slices. Serum collected after further therapy did not enhance the number of MNCs formed in marrow cultures compared to those formed in normal serum. Elevated levels of IL6 (147620) were detected in the early GSD serum that were 7 times the upper limit of the normal range, and after further treatment, IL6 levels fell to one quarter of the pretreatment value. The levels of IL-1-beta (147720), tumor necrosis factor-alpha (191190), transforming growth factor-alpha (190170), PTH (168450), and PTH-related peptide (168470) were not increased in pretreatment serum. Moreover, the addition of neutralizing antibodies to IL6 to the normal human bone marrow cultures effectively blocked the increase in multinucleated cell formation induced by active GSD serum. In this patient mandibular osteolysis was said to have followed a blow to the chin at age 9 years. The patient was initially treated for suspected osteomyelitis, but there was no response to antibiotics. At the age of 10 years, biopsy of the right zygoma yielded findings consistent with the diagnosis of GSD. Daily subcutaneous injections of calcitonin resulted in a decline in the rate of bone resorption. The patient then received infusions of pamidronate every 3-4 months, and there was no further enlargement of the lytic lesions. Because of deformation of the softened skull base, he was placed on cervical traction with halo apparatus, and radiation therapy was administered. The first serum specimen was obtained after the calcitonin therapy and initial pamidronate treatments. The second specimen was obtained about 9 months later, after additional courses of pamidronate and the radiation therapy. A year after radiation therapy, a successful cervical fusion was performed.
Skel \- Diffuse cystic angiomatosis of bone Radiology \- Osteolytic lesions with a thin sclerotic rim throughout the length of long bones \- Increased sclerosis with age Misc \- Asymptomatic Inheritance \- Autosomal dominant ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| CYSTIC ANGIOMATOSIS OF BONE, DIFFUSE | c0029438 | 2,000 | omim | https://www.omim.org/entry/123880 | 2019-09-22T16:42:36 | {"mesh": ["D010015"], "omim": ["123880"], "orphanet": ["73"], "synonyms": ["Alternative titles", "GORHAM-STOUT DISEASE", "OSTEOLYSIS, MASSIVE"]} |
A number sign (#) is used with this entry because type IV syndactyly (SDTY4) is caused by heterozygous mutation in an SHH (600725) regulatory element (ZRS) that resides in intron 5 of the LMBR1 gene (605522).
Clinical Features
Haas (1940) reported this type of syndactyly in a mother and her 2 children. The syndactyly was complete, affecting the fingers of both hands, and there was polydactyly, with 6 metacarpals and 6 digits. Flexion of the fingers gave the hands a cup-shaped form. In contradistinction to the type of syndactyly in Apert syndrome (101200), there was no bone fusion. There was no mention of the condition of the feet and there were no associated malformations.
Gillessen-Kaesbach and Majewski (1991) described an affected 2-month-old girl with complete cutaneous syndactyly and hexadactyly of both hands. Partial cutaneous syndactyly of toes 2 and 3, involving the proximal segment, was present on both feet. Although neither parent had syndactyly, 2 brothers of the mother and the maternal grandmother showed complete bilateral cutaneous syndactyly of the second and third toes. Development was otherwise normal. Each hand had 1 supernumerary ray, which may have been pre- or postaxial.
Rambaud-Cousson et al. (1991) described type IV syndactyly with bilateral hexadactyly of the hands and feet in 6 members of 3 generations with 1 instance of male-to-male transmission. The proband also had unilateral absence of the tibia. The possibility was raised that syndactyly type IV with hexadactyly of the feet is in fact a complex entity which can include a variety of lower limb malformations.
Sato et al. (2007) reported a 5-generation Chinese family segregating autosomal dominant nonsyndromic syndactyly, which was clinically diagnosed as type IV because 1 of the 6 living affected members had complete syndactylism of all fingers and toes accompanied by polydactyly; flexion of the fingers together with cutaneous syndactyly gave his hands a cup-shaped appearance. This patient and 1 other in the family also had tibial hemimelia.
Mapping
Sato et al. (2007) performed linkage and haplotype analysis of a 5-generation Chinese family segregating autosomal dominant type IV syndactyly and obtained a maximum 2-point lod score of 1.613 for a 17.39-cM region on chromosome 7q36 flanked by markers D7S3070 and D7S559.
Molecular Genetics
In a 5-generation Chinese family diagnosed with type IV syndactyly mapping to chromosome 7q36, Sato et al. (2007) directly sequenced the SHH (600725) and LMBR1 (605522) genes, including the conserved ZPA regulatory sequence (ZRS) within intron 5 of LMBR1, but found no pathogenic mutations.
In a Han Chinese mother and daughter with type IV syndactyly, Sun et al. (2008) identified a 235-kb duplication in intron 5 of the LMBR1 gene (605522.0010) involving the ZRS. The duplication was not found in unaffected family members or in 50 unrelated Han Chinese controls.
In the Chinese family with type IV syndactyly and tibial hypoplasia previously studied by Sato et al. (2007), Wu et al. (2009) identified a 97-kb duplication involving the LMBR1 gene that segregated with the limb phenotype in the family and was not found in 50 unrelated ethnically matched controls. Wu et al. (2009) concluded that SDTY4 with tibial hypoplasia is a severe clinical subtype of SDTY4.
By array CGH analysis in the female patient with complete cutaneous syndactyly and hexadactyly of both hands who was originally reported by Gillessen-Kaesbach and Majewski (1991), Wieczorek et al. (2010) identified a 73-kb duplication involving the ZRS region of the LIMBR1 gene (605522.0016) that they designated arr7q36.3(156,265,512x2,156,265,453-156,354,638x3,156,354,579x2). Wieczorek et al. (2010) stated that because of the complex and repetitive nature of this genomic region, they were unable to determine the exact orientation of the duplication.
In affected individuals from 2 families with type IV syndactyly, Lohan et al. (2014) identified heterozygosity for microduplications in the ZRS region of LMBR1, measuring approximately 255 kb and 179 kb, respectively. Lohan et al. (2014) noted that the 255-kb duplication, present in a Peruvian boy who had complete syndactyly of the hands with no other anomalies, encompassed the entire LMBR1 gene as well as several exons of the adjacent RNF32 gene (610241).
INHERITANCE \- Autosomal dominant SKELETAL Hands \- Hexadactyly \- Cup-shaped hand \- 1-5 finger complete cutaneous syndactyly \- Separate triphalangeal thumb (in some patients) \- Separate hypoplastic thumb (in some patients) \- 6 metacarpals \- Pre- or postaxial polydactyly Feet \- Normal feet (majority of cases) \- Pre- or postaxial polydactyly (in some patients) \- Partial cutaneous 2-3 toe syndactyly SKIN, NAILS, & HAIR Nails \- Fused fingernails MOLECULAR BASIS \- Caused by mutation in the SHH ( 600725 ) regulatory element in the homolog of the mouse limb region 1 gene (LMBR1, 605522.0010 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| SYNDACTYLY, TYPE IV | c1861355 | 2,001 | omim | https://www.omim.org/entry/186200 | 2019-09-22T16:32:58 | {"doid": ["11193"], "mesh": ["C566092"], "omim": ["186200"], "orphanet": ["93405"], "synonyms": ["Alternative titles", "HAAS TYPE SYNDACTYLY", "POLYSYNDACTYLY, HAAS TYPE", "SD4"]} |
This article's lead section may be too short to adequately summarize its key points. Please consider expanding the lead to provide an accessible overview of all important aspects of the article. (September 2014)
Alcohol-related dementia (ARD) is a form of dementia caused by long-term, excessive consumption of alcoholic beverages, resulting in neurological damage and impaired cognitive function.[1]
## Contents
* 1 Terminology
* 2 Signs and symptoms
* 3 Pathophysiology
* 4 Diagnosis
* 4.1 Diagnostic criteria
* 5 Treatment
* 6 Epidemiology
* 7 Notable sufferers
* 8 References
* 9 External links
## Terminology[edit]
Alcohol-related dementia is a broad term currently preferred among medical professionals.[2] Many experts use the terms alcohol (or alcoholic) dementia to describe a specific form of ARD, characterized by impaired executive function (planning, thinking, and judgment).[3] Another form of ARD is known as wet brain (Wernicke–Korsakoff syndrome), characterized by short term memory loss and thiamine (vitamin B1) deficiency. ARD patients often have symptoms of both forms, i.e. impaired ability to plan, apathy, and memory loss. ARD may occur with other forms of dementia (mixed dementia). The diagnosis of ARD is widely recognized but rarely applied, due to a lack of specific diagnostic criteria.
On many non-medical websites, the terms wet brain and alcohol-related dementia are often used interchangeably, creating significant confusion. Additionally, the term alcohol-induced persistent dementia is another nonspecific name that is sometimes used.
## Signs and symptoms[edit]
Alcohol-related dementia presents as a global deterioration in intellectual function with memory not being specifically affected, but it may occur with other forms of dementia, resulting in a wide range of symptoms.[4] Certain individuals with alcohol-related dementia present with damage to the frontal lobes of their brain causing disinhibition, loss of planning and executive functions, and a disregard for the consequences of their behavior. Other types of alcohol-related dementia such as Korsakoff's Syndrome cause the destruction of certain areas of the brain, where changes in memory, primarily a loss of short-term memory,[5] are the main symptom. Most presentations of alcohol dementia are somewhere along the spectrum between a global dementia and Korsakoff's psychosis, and may include symptoms of both.[4]
Individuals affected by alcohol-related dementia may develop memory problems, language impairment, and an inability to perform complex motor tasks such as getting dressed. Heavy alcohol abuse also damages the nerves in arms and legs, i.e. peripheral neuropathy, as well as the cerebellum that controls coordination thereby leading to the development of cerebellar ataxia. These patients frequently have problems with sensation in their extremities and may demonstrate unsteadiness on their feet.[5]
Alcohol-related dementia can produce a variety of psychiatric problems including psychosis (disconnection from reality), depression, anxiety, and personality changes. Patients with alcoholic dementia often develop apathy, related to frontal lobe damage, that may mimic depression.[5] People with alcoholism are more likely to become depressed than people without alcoholism,[6] and it may be difficult to differentiate between depression and alcohol dementia.
## Pathophysiology[edit]
Alcohol has a direct effect on brain cells in the front part of the brain, resulting in poor judgment, difficulty making decisions, and lack of insight. Long-term alcohol abuse can often lead to poor nutrition problems causing parts of the brain to be damaged by vitamin deficiencies. These problems could also cause personality changes in some people.[7]
## Diagnosis[edit]
The signs and symptoms of alcohol-related dementia are essentially the same as the symptoms present in other types of dementia, making alcohol-related dementia difficult to diagnose. There are very few qualitative differences between alcohol dementia and Alzheimer's disease and it is therefore difficult to distinguish between the two.[8] Some of these warning signs may include memory loss, difficulty performing familiar tasks, poor or impaired judgment and problems with language. However the biggest indicator is friends or family members reporting changes in personality.[9]
A simple test for intellectual function, like the Folstein Mini-Mental Status Examination, is the minimum screen for dementia. The test requires 15–20 minutes to administer and is available in mental health centers.[10]
Diagnosing alcohol-related dementia can be difficult due to the wide range of symptoms and a lack of specific brain pathology.[5] The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) is a guide to aid doctors in diagnosing a range of psychiatric disorders, and may be helpful in diagnosing dementia.[11]
### Diagnostic criteria[edit]
The existence of alcohol-related dementia is widely acknowledged but not often used as a diagnosis, due to a lack of widely accepted, non-subjective diagnostic criteria; more research is needed.[2] Criteria for alcohol-induced persistent dementia in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) include the following:
A. The development of multiple cognitive deficits manifested by both:
1. Memory impairment (impaired ability to learn new information or to recall previously learned information)
2. One (or more) of the following cognitive disturbances:
* (a) Aphasia (language disturbance)
* (b) Apraxia (impaired ability to carry out motor activities despite intact motor function)
* (c) Agnosia (failure to recognize or identify objects despite intact sensory function)
* (d) Disturbance in executive functioning (i.e. planning, organizing, sequencing, abstracting)
B. The cognitive deficits in criteria A1 and A2 each cause significant impairment in social or occupational functioning and represent a significant decline from a previous level of functioning.
C. The deficits do not occur exclusively during the course of a delirium and persist beyond the usual duration of substance intoxication or withdrawal.
D. There is evidence from the history, physical examination, or laboratory findings that deficits are etiologically related to the persisting effects of substance use (e.g. drug of abuse; medication).[9]
There are problems with DSM diagnostic criteria, however. Firstly, they are vague and subjective. Furthermore, the criteria for diagnosis of dementia were inspired by the clinical presentation of Alzheimer's disease and are poorly adapted to the diagnosis of other dementias. This has led to efforts to develop better diagnostic models.[3]
Oslin (Int J Geriatr Psychiatry 1998) proposed alternative clinical diagnostic criteria which were validated. The criteria include a clinical diagnosis of dementia at least 60 days after last exposure to alcohol, significant alcohol use (i.e. minimum 35 standard drinks/week for males and 28 for women) for more than five years, and significant alcohol use occurring within three years of the initial onset of cognitive deficits.[2] Oslin proposed the new and refined diagnostic criteria for alcohol-related dementia because he hoped that the redefined classification system would bring more awareness and clarity to the relationship between alcohol use and dementia.[12]
Oslin's proposed classification of ARD:
* Definite alcohol-related dementia
At the current time there are no acceptable criteria to definitively define alcohol-related dementia.
* Probable alcohol-related dementia
A. The criteria for the clinical diagnosis of probable alcohol-related dementia include the following:
1. A clinical diagnosis of dementia at least 60 days after the last exposure to alcohol.
2. Significant alcohol use as defined by a minimum average of 35 standard drinks per week for men (28 for women) for greater than a period of five years. The period of significant alcohol use must occur within three years of the initial onset of dementia.
B. The diagnosis of alcohol-related dementia is supported by the presence of any of the following
1. Alcohol related hepatic, pancreatic, gastrointestinal, cardiovascular, or renal disease i.e. other end-organ damage.
2. Ataxia or peripheral sensory polyneuropathy (not attributed to other causes).
3. Beyond 60 days of abstinence, the cognitive impairment stabilizes or improves.
4. After 60 days of abstinence, any neuroimaging evidence of ventricular or sulcal dilatation improves.
5. Neuroimaging evidence of cerebellar atrophy, especially in the vermis.
C. The following clinical features cast doubt on the diagnosis of alcohol-related dementia
1. The presence of language impairment, especially dysnomia or anomia.
2. the presence of focal neurologic signs or symptoms (except ataxia or peripheral sensory polyneuropathy).
3. Neuroimaging evidence for cortical or subcortical infarction, subdural hematoma, or other focal brain pathology.
4. Elevated Hachinski Ischemia Scale score.
D. Clinical features that are neither supportive nor cast doubt on the diagnosis of alcohol-related dementia included:
1. Neuroimaging evidence of cortical atrophy.
2. The presence of periventricular or deep white matter lesions on neuroimaging in the absence of focal infarct(s).
3. The presence of the Apolipoprotein c4 allele.[12]
## Treatment[edit]
If the symptoms of alcohol dementia are caught early enough, the effects may be reversed. The person must stop drinking and start on a healthy diet, replacing the lost vitamins, including, but not limited to, thiamine.[8] Recovery is more easily achievable for women than men, but in all cases it is necessary that they have the support of family and friends and abstain from alcohol.[8]
## Epidemiology[edit]
The onset of alcohol dementia can occur as early as age 30,[8] although it is far more common that the dementia will reveal itself anywhere from age 50 to 70.[8] The onset and the severity of this type of dementia is directly correlated to the amount of alcohol that a person consumes over their lifetime.[citation needed]
Epidemiological studies show an association between long-term alcohol intoxication and dementia.[3] Alcohol can damage the brain directly as a neurotoxin,[3] or it can damage it indirectly by causing malnutrition, primarily a loss of thiamine (vitamin B1).[4] Alcohol abuse is common in older persons, and alcohol-related dementia is under-diagnosed.[5] A discredited[citation needed] French study, looking at other studies of thousands of subjects, found that moderate alcohol consumption (up to four glasses of wine per week) protected against dementia, whereas higher rates of consumption were found to increase the chances of getting it.[3]
## Notable sufferers[edit]
According to her family, the socialite Leonore Lemmon (fiancée of George Reeves) spent the last few years of her life with alcohol dementia, before dying in 1989.
The Australian entertainer and "King of Comedy" Graham Kennedy was suffering from alcohol-related dementia at time of his death in 2005.[13]
## References[edit]
1. ^ Ridley, Nicole J; Draper, Brian; Withall, Adrienne (25 January 2013). "Alcohol-related dementia: an update of the evidence". Alzheimer's Research & Therapy. 5 (1): 3. doi:10.1186/alzrt157. ISSN 1758-9193. PMC 3580328. PMID 23347747.
2. ^ a b c Warner, James; Gupta, Susham (2008). "Alcohol-related dementia: a 21st-century silent epidemic? - The British Journal of Psychiatry". The British Journal of Psychiatry. 193 (5): 351–353. doi:10.1192/bjp.bp.108.051425. PMID 18978310.
3. ^ a b c d e Derouesné, Christian; Pierucci‐Lagha, Amira (December 2003). "John Libbey Eurotext - Psychologie & NeuroPsychiatrie du vieillissement - Alcool et vieillissement". Psychologie & Neuropsychiatrie du Vieillissement. 1 (4): 237–249. Retrieved 21 October 2015.
4. ^ a b c "Alcohol-related dementia". Retrieved 21 October 2015.
5. ^ a b c d e Alcohol Induced Dementia
6. ^ "Alcohol - Special Subjects". Merck Manuals Consumer Version. Retrieved 21 October 2015.
7. ^ Buddy T. "Alcoholic Dementia". About.com Health. Retrieved 21 October 2015.
8. ^ a b c d e "What's Alcohol-Related Dementia?". health-cares.net. 18 July 2005.
9. ^ a b Moriyama Y.; Mimura M.; Kato M.; Kashima H. (2006). "Primary alcoholic dementia and alcohol-related dementia". Psychogeriatrics. 6 (3): 114–118. doi:10.1111/j.1479-8301.2006.00168.x.
10. ^ Fiodor, Kosova. "Dementia test". Dementia Test. Retrieved 7 June 2019.
11. ^ David Pingitore-Randy A. Sansone (1998-10-15). "Using DSM-IV Primary Care Version: A Guide to Psychiatric Diagnosis in Primary Care". American Family Physician. 58 (6): 1347–52. PMID 9803199. Retrieved 21 October 2015.
12. ^ a b Oslin, D. (1998). ALCOHOL RELATED DEMENTIA: PROPOSED CLINICAL CRITERIA. International Journal of Geriatric Psychiatry, 13(4), 203-212.
13. ^ Mangos, John (7 June 2005). "The King and I". The Bulletin. NineMSN.com. p. 31. Archived from the original on 19 June 2005. Retrieved 4 February 2008.
## External links[edit]
* Alcoholism & Substance Abuse: Alcohol Dementia
* Alzheimer's Society factsheet — What is Korsakoff's syndrome?
* Kato N (June 1991). "[Clinical concept of alcoholic dementia]". Arukoru Kenkyuto Yakubutsu Ison (in Japanese). 26 (3): 119–33. PMID 1892448.
* v
* t
* e
Psychoactive substance-related disorder
General
* SID
* Substance intoxication / Drug overdose
* Substance-induced psychosis
* Withdrawal:
* Craving
* Neonatal withdrawal
* Post-acute-withdrawal syndrome (PAWS)
* SUD
* Substance abuse / Substance-related disorders
* Physical dependence / Psychological dependence / Substance dependence
Combined
substance use
* SUD
* Polysubstance dependence
* SID
* Combined drug intoxication (CDI)
Alcohol
SID
Cardiovascular diseases
* Alcoholic cardiomyopathy
* Alcohol flush reaction (AFR)
Gastrointestinal diseases
* Alcoholic liver disease (ALD):
* Alcoholic hepatitis
* Auto-brewery syndrome (ABS)
Endocrine diseases
* Alcoholic ketoacidosis (AKA)
Nervous
system diseases
* Alcohol-related dementia (ARD)
* Alcohol intoxication
* Hangover
Neurological
disorders
* Alcoholic hallucinosis
* Alcoholic polyneuropathy
* Alcohol-related brain damage
* Alcohol withdrawal syndrome (AWS):
* Alcoholic hallucinosis
* Delirium tremens (DTs)
* Fetal alcohol spectrum disorder (FASD)
* Fetal alcohol syndrome (FAS)
* Korsakoff syndrome
* Positional alcohol nystagmus (PAN)
* Wernicke–Korsakoff syndrome (WKS, Korsakoff psychosis)
* Wernicke encephalopathy (WE)
Respiratory tract diseases
* Alcohol-induced respiratory reactions
* Alcoholic lung disease
SUD
* Alcoholism (alcohol use disorder (AUD))
* Binge drinking
Caffeine
* SID
* Caffeine-induced anxiety disorder
* Caffeine-induced sleep disorder
* Caffeinism
* SUD
* Caffeine dependence
Cannabis
* SID
* Cannabis arteritis
* Cannabinoid hyperemesis syndrome (CHS)
* SUD
* Amotivational syndrome
* Cannabis use disorder (CUD)
* Synthetic cannabinoid use disorder
Cocaine
* SID
* Cocaine intoxication
* Prenatal cocaine exposure (PCE)
* SUD
* Cocaine dependence
Hallucinogen
* SID
* Acute intoxication from hallucinogens (bad trip)
* Hallucinogen persisting perception disorder (HPPD)
Nicotine
* SID
* Nicotine poisoning
* Nicotine withdrawal
* SUD
* Nicotine dependence
Opioids
* SID
* Opioid overdose
* SUD
* Opioid use disorder (OUD)
Sedative /
hypnotic
* SID
* Kindling (sedative–hypnotic withdrawal)
* benzodiazepine: SID
* Benzodiazepine overdose
* Benzodiazepine withdrawal
* SUD
* Benzodiazepine use disorder (BUD)
* Benzodiazepine dependence
* barbiturate: SID
* Barbiturate overdose
* SUD
* Barbiturate dependence
Stimulants
* SID
* Stimulant psychosis
* amphetamine: SUD
* Amphetamine dependence
Volatile
solvent
* SID
* Sudden sniffing death syndrome (SSDS)
* Toluene toxicity
* SUD
* Inhalant abuse
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| Alcohol-related dementia | None | 2,002 | wikipedia | https://en.wikipedia.org/wiki/Alcohol-related_dementia | 2021-01-18T18:40:25 | {"wikidata": ["Q4713264"]} |
A number sign (#) is used with this entry because of evidence that this form of hypoplastic amelogenesis imperfecta (AI1J) is caused by homozygous mutation in the ACPT (606362) on chromosome 19q13.
Description
Amelogenesis imperfecta is an inherited defect of dental enamel formation that shows both clinical and genetic heterogeneity. In the hypoplastic type of AI, the enamel is of normal hardness but does not develop to normal thickness. The thinness of the enamel makes the teeth appear small. Radiographically, enamel contrasts normally from dentin. The surface of the enamel can vary, showing smooth, rough, pitted, or local forms (Witkop, 1988).
Clinical Features
Seymen et al. (2016) described 11 children, aged 1 to 11 years, from 6 consanguineous, apparently unrelated Turkish families with generalized amelogenesis imperfecta. All of the children had thin enamel with no dentin defect, and some had teeth that were sensitive to thermal stimuli. AI was noted in both deciduous and permanent teeth. There was wide interdental spacing in 3 of the families, and discoloration of teeth ranging from yellow to black in 4 of the families. No other medical conditions were present.
Inheritance
The transmission pattern of AI in the families described by Seymen et al. (2016) was consistent with autosomal recessive inheritance.
Molecular Genetics
Seymen et al. (2016) studied 6 unrelated consanguineous Turkish families with generalized hypoplastic amelogenesis imperfecta and identified homozygous or compound heterozygous mutations in the ACPT gene (606362.0001-606362.0005) that segregated with the disorder in the families. In silico analysis of the tertiary structure of the ACPT extracellular domain showed that the mutations would affect the activity of ACPT by altering the sizes and charges of key amino acid side chains, limiting accessibility of the catalytic core, and interfering with homodimerization.
INHERITANCE \- Autosomal recessive HEAD & NECK Teeth \- Thin enamel \- Normal dentin \- Enamel discolorization ranging from yellow to black \- Sensitivity to thermal stimuli (in some patients) \- Deep overbite (in some patients) \- Large interdental spacing due to thin enamel (in some patients) \- Dental caries (in some patients) MISCELLANEOUS \- Five unrelated consanguineous Turkish families have been described (last curated December 2016) MOLECULAR BASIS \- Caused by mutation in the testicular acid phosphatase gene (ACPT, 606362.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| AMELOGENESIS IMPERFECTA, TYPE IJ | c0399367 | 2,003 | omim | https://www.omim.org/entry/617297 | 2019-09-22T15:46:09 | {"mesh": ["C538240"], "omim": ["617297"], "orphanet": ["100031"]} |
A rare variety of migraine with aura characterized by the presence of a motor weakness during the aura. There are two main forms depending on the familial history: patients with at least one first- or second-degree relative who has aura including motor weakness have familial hemiplegic migraine (FHM); patients without such familial history have sporadic hemiplegic migraine (SHM).
## Epidemiology
The prevalence of hemiplegic migraine (HM) is one in 10,000, with FHM and SHM being equally frequent.
## Clinical description
Typical HM attacks are characterised by motor weakness that is always associated with other aura symptoms, the most frequent being sensory, visual and speech disorders. In addition, basilar-type symptoms occur in up to 70% of patients. Severe attacks may occur in both FHM and SHM with prolonged hemiplegia, confusion, coma, fever and seizures. The clinical spectrum also includes permanent cerebellar signs (nystagmus, ataxia, dysarthria) and less frequently various types of seizures and intellectual deficit.
## Etiology
The three causative genes identified so far encode ion-transporters (CACNA1A, ATP1A2 and SCNA1). Molecular diagnosis is now possible through screening of these three genes.
## Genetic counseling
FHM is transmitted in an autosomal dominant manner.
## Management and treatment
Treatment involves the same approaches used for other varieties of migraine with aura, with the exception that triptans are contraindicated in FHM/SHM. Based on new pathophysiological insights, preventive treatments using various antiepileptic agents seem promising.
## Prognosis
Prognosis is usually good.
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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
| Familial or sporadic hemiplegic migraine | c1832884 | 2,004 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=569 | 2021-01-23T18:45:35 | {"gard": ["10768"], "mesh": ["C536890"], "omim": ["141500", "602481", "607516", "609634"], "icd-10": ["G43.1"]} |
Keratitis-ichthyosis-deafness syndrome
Other names"Erythrokeratodermia progressiva Burns"[1]
Keratitis–ichthyosis–deafness syndrome (also known as "Ichthyosiform erythroderma, corneal involvement, and deafness," and "KID syndrome,") presents at birth/infancy and is characterized by progressive corneal opacification, either mild generalized hyperkeratosis or discrete erythematous plaques, and neurosensory deafness.[2]:483,513[3]:565
It is caused by a mutation in connexin 26.[4]
## See also[edit]
* Senter syndrome
* Ichthyosis hystrix
* List of cutaneous conditions
## References[edit]
1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 770. ISBN 978-1-4160-2999-1.
2. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0.
3. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
4. ^ "Hystrix-like ichthyosis with deafness". Genetics Home Reference. U.S. National Library of Medicine. Retrieved 8 August 2014.
## External links[edit]
Classification
D
* ICD-10: GroupMajor.minor
* ICD-9-CM: xxx
* OMIM: 148210 242150
* MeSH: C537363
* DiseasesDB: 32841
* v
* t
* e
Diseases of ion channels
Calcium channel
Voltage-gated
* CACNA1A
* Familial hemiplegic migraine 1
* Episodic ataxia 2
* Spinocerebellar ataxia type-6
* CACNA1C
* Timothy syndrome
* Brugada syndrome 3
* Long QT syndrome 8
* CACNA1F
* Ocular albinism 2
* CSNB2A
* CACNA1S
* Hypokalemic periodic paralysis 1
* Thyrotoxic periodic paralysis 1
* CACNB2
* Brugada syndrome 4
Ligand gated
* RYR1
* Malignant hyperthermia
* Central core disease
* RYR2
* CPVT1
* ARVD2
Sodium channel
Voltage-gated
* SCN1A
* Familial hemiplegic migraine 3
* GEFS+ 2
* Febrile seizure 3A
* SCN1B
* Brugada syndrome 6
* GEFS+ 1
* SCN4A
* Hypokalemic periodic paralysis 2
* Hyperkalemic periodic paralysis
* Paramyotonia congenita
* Potassium-aggravated myotonia
* SCN4B
* Long QT syndrome 10
* SCN5A
* Brugada syndrome 1
* Long QT syndrome 3
* SCN9A
* Erythromelalgia
* Febrile seizure 3B
* Paroxysmal extreme pain disorder
* Congenital insensitivity to pain
Constitutively active
* SCNN1B/SCNN1G
* Liddle's syndrome
* SCNN1A/SCNN1B/SCNN1G
* Pseudohypoaldosteronism 1AR
Potassium channel
Voltage-gated
* KCNA1
* Episodic ataxia 1
* KCNA5
* Familial atrial fibrillation 7
* KCNC3
* Spinocerebellar ataxia type-13
* KCNE1
* Jervell and Lange-Nielsen syndrome
* Long QT syndrome 5
* KCNE2
* Long QT syndrome 6
* KCNE3
* Brugada syndrome 5
* KCNH2
* Short QT syndrome
* KCNQ1
* Jervell and Lange-Nielsen syndrome
* Romano–Ward syndrome
* Short QT syndrome
* Long QT syndrome 1
* Familial atrial fibrillation 3
* KCNQ2
* BFNS1
Inward-rectifier
* KCNJ1
* Bartter syndrome 2
* KCNJ2
* Andersen–Tawil syndrome
* Long QT syndrome 7
* Short QT syndrome
* KCNJ11
* TNDM3
* KCNJ18
* Thyrotoxic periodic paralysis 2
Chloride channel
* CFTR
* Cystic fibrosis
* Congenital absence of the vas deferens
* CLCN1
* Thomsen disease
* Myotonia congenita
* CLCN5
* Dent's disease
* CLCN7
* Osteopetrosis A2, B4
* BEST1
* Vitelliform macular dystrophy
* CLCNKB
* Bartter syndrome 3
TRP channel
* TRPC6
* FSGS2
* TRPML1
* Mucolipidosis type IV
Connexin
* GJA1
* Oculodentodigital dysplasia
* Hallermann–Streiff syndrome
* Hypoplastic left heart syndrome
* GJB1
* Charcot–Marie–Tooth disease X1
* GJB2
* Keratitis–ichthyosis–deafness syndrome
* Ichthyosis hystrix
* Bart–Pumphrey syndrome
* Vohwinkel syndrome)
* GJB3/GJB4
* Erythrokeratodermia variabilis
* Progressive symmetric erythrokeratodermia
* GJB6
* Clouston's hidrotic ectodermal dysplasia
Porin
* AQP2
* Nephrogenic diabetes insipidus 2
See also: ion channels
This Genodermatoses article is a stub. You can help Wikipedia by expanding it.
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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
| Keratitis–ichthyosis–deafness syndrome | c1275089 | 2,005 | wikipedia | https://en.wikipedia.org/wiki/Keratitis%E2%80%93ichthyosis%E2%80%93deafness_syndrome | 2021-01-18T18:52:20 | {"gard": ["3113"], "mesh": ["C537363"], "umls": ["C1275089"], "orphanet": ["477"], "wikidata": ["Q1345746"]} |
Fracture of the lateral tibial plateau caused by the bumper of a car
See also: Tibial plateau fracture
Bumper fracture
SpecialtyOrthopedic
A bumper fracture is a fracture of the lateral tibial plateau caused by the bumper of a car coming into contact with the outer side of the knee when a person is standing. Specifically, it is caused by a forced valgus applied to the knee. This causes the lateral part of the distal femur and the lateral tibial plateau to come into contact, compressing the tibial plateau and causing the tibia to fracture. The name of the injury is because it was described as being caused by the impact of a car bumper on the lateral side of the knee while the foot is planted on the ground, although this mechanism is only seen in about 25% of tibial plateau fractures.[1]
Fracture of the neck of the fibula may also be found, and associated injury to the medial collateral ligament or cruciate ligaments occurs in about 10% of cases.[2][3]
## History[edit]
The term "bumper fracture" was coined in 1929 by Cotton and Berg.[4]
## References[edit]
1. ^ Tibial Plateau Fractures at eMedicine
2. ^ APLEY AG (August 1956). "Fractures of the lateral tibial condyle treated by skeletal traction and early mobilisation; a review of sixty cases with special reference to the long-term results". J Bone Joint Surg Br. 38-B (3): 699–708. doi:10.1302/0301-620X.38B3.699. PMID 13357593. Retrieved 2009-10-11.[permanent dead link]
3. ^ "Skeletal Trauma". www.med-ed.virginia.edu. Retrieved 13 October 2018.
4. ^ "Bumper Fracture of the Knee". www.mdedge.com. Retrieved 13 October 2018.
## External links[edit]
Classification
D
* ICD-10: S82.1
* MeSH: 68013978
External resources
* AO Foundation: 41-B1
* v
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* e
Fractures and cartilage damage
General
* Avulsion fracture
* Chalkstick fracture
* Greenstick fracture
* Open fracture
* Pathologic fracture
* Spiral fracture
Head
* Basilar skull fracture
* Blowout fracture
* Mandibular fracture
* Nasal fracture
* Le Fort fracture of skull
* Zygomaticomaxillary complex fracture
* Zygoma fracture
Spinal fracture
* Cervical fracture
* Jefferson fracture
* Hangman's fracture
* Flexion teardrop fracture
* Clay-shoveler fracture
* Burst fracture
* Compression fracture
* Chance fracture
* Holdsworth fracture
Ribs
* Rib fracture
* Sternal fracture
Shoulder fracture
* Clavicle
* Scapular
Arm fracture
Humerus fracture:
* Proximal
* Supracondylar
* Holstein–Lewis fracture
Forearm fracture:
* Ulna fracture
* Monteggia fracture
* Hume fracture
* Radius fracture/Distal radius
* Galeazzi
* Colles'
* Smith's
* Barton's
* Essex-Lopresti fracture
Hand fracture
* Scaphoid
* Rolando
* Bennett's
* Boxer's
* Busch's
Pelvic fracture
* Duverney fracture
* Pipkin fracture
Leg
Tibia fracture:
* Bumper fracture
* Segond fracture
* Gosselin fracture
* Toddler's fracture
* Pilon fracture
* Plafond fracture
* Tillaux fracture
Fibular fracture:
* Maisonneuve fracture
* Le Fort fracture of ankle
* Bosworth fracture
Combined tibia and fibula fracture:
* Trimalleolar fracture
* Bimalleolar fracture
* Pott's fracture
Crus fracture:
* Patella fracture
Femoral fracture:
* Hip fracture
Foot fracture
* Lisfranc
* Jones
* March
* Calcaneal
This article about an injury is a stub. You can help Wikipedia by expanding it.
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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
| Bumper fracture | None | 2,006 | wikipedia | https://en.wikipedia.org/wiki/Bumper_fracture | 2021-01-18T18:42:24 | {"wikidata": ["Q4997333"]} |
A rare disorder of sex development (DSD) associated with anomalies in gonadal development that result in the presence of female external and internal genitalia despite the 46,XY karyotype.
## Epidemiology
The prevalence is unknown.
## Clinical description
Patients present during adolescence or early adulthood with normal female external genitalia but lack pubertal development although adrenarche is normal. Completely undeveloped streak gonads are present and are associated with an increased risk of abdominal tumours (most commonly dysgerminoma; see this term), which may be the presenting feature in some cases. Stature is normal or above normal, and features of Turner syndrome (see this term) are absent.
## Etiology
Although the etiology is not completely understood, 46,XY CGD results from failure of testicular development due to disruption of the underlying genetic pathways and several genes have been implicated: SRY (gene deletion of or loss-of-function mutations; Yp11.3), NR5A1 (9q33) and DHH (homozygous or compound heterozygous mutations; 12q13.1). In addition, patients with partial duplications of Xp (including the NR0B1 gene) and chromosome 9p deletions (involving the DMRT1 and DMRT2 genes) may also present with isolated 46, XY CGD. Mutations in the CBX2 gene have been rarely reported, namely in a patient with development of ovarian tissue despite 46,XY karyotype. Mutations in the MAP3K1 gene (mapped on chromosome 5q) that cause downstream alterations in the MAP kinase signaling pathway have recently been identified in two familial and two sporadic cases. Environmental factors (maternal progesterone intake during pregnancy), and impaired prenatal growth have also been associated with 46,XY CGD.
## Diagnostic methods
Diagnosis is made on the basis of the clinical findings together with cytogenetic analysis, endocrine investigations, molecular genetic studies, and sometimes surgical exploration with biopsy and removal of streak gonads.
## Differential diagnosis
The differential diagnosis should include hypergonadotropic ovarian dysgenesis (46,XX GD) and all forms of syndromic 46,XY CGD (for example, Frasier syndrome, campomelic dysplasia and 46,XY DSD with adrenal insufficiency; see these terms).
## Antenatal diagnosis
Prenatal diagnosis is feasible for families in which the genetic anomaly has been confirmed but is only recommended in syndromic cases.
## Genetic counseling
Although some cases of 46,XY CGD occur sporadically, genetic counseling may be offered to affected families and should be adapted depending on the mode of inheritance associated with the genetic anomaly identified.
## Management and treatment
Management should involve removal of streak gonadal tissue as there is a high risk for malignancy. Possible associated health issues (e.g. associated malformations) need to be addressed according to the genetic diagnosis. Hormone substitution is recommended at the time of puberty. Psychological support should also be offered to patients and their families. Infertility is an important management issue; however, pregnancy may be feasible through zygote egg donation.
## Prognosis
With appropriate management, the risk of malignancy is low and the psychological and clinical outcome for patients is good.
*[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 inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| 46,XY complete gonadal dysgenesis | c2936694 | 2,007 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=242 | 2021-01-23T19:09:01 | {"gard": ["5068"], "mesh": ["D006061"], "omim": ["154230", "233420", "300018", "400044", "612965", "613080", "613762", "616425"], "umls": ["C0018054", "C2936694"], "icd-10": ["Q99.1"], "synonyms": ["46,XY CGD", "46,XY pure gonadal dysgenesis", "Swyer syndrome"]} |
Angor animi
Differential diagnosisacute coronary syndrome
Angor animi (also referred to as angina animi,[1][2] Gairdner's disease[2] and also angina pectoris sine dolore[2]), in medicine, is a symptom defined as a patient's perception that they are in fact dying. Most cases of angor animi are found in patients suffering from acute coronary syndrome (cardiac related chest pain) such as myocardial infarction. It is, however, occasionally found in patients suffering from other conditions.[1] Pheochromocytoma also can present with angor animi, accompanied by other symptoms that include; headache, profuse sweating, palpitations and characteristically a pounding severe headache. Irukandji syndrome is also another reported cause.[3]
Angor animi is differentiated from a fear or desire for death,[1] since angor animi refers to a patient's actual and genuine belief that they are in fact dying.[1]
## Etymology[edit]
The phrase is derived from the two Latin terms which it is composed of, namely angor and animi.
Angor (different but related to the word anger), in modern English, refers to a great anxiety,[4] distress,[5] or mental anguish[5] often accompanied by a painful constriction and palpitations at the upper abdomen and lower thorax (chest).[4]
Animi means an animating spirit, intention or temper.[6]
## References[edit]
1. ^ a b c d angor animi. Online Medical Dictionary. CancerWeb. Centre for Cancer Education. Newcastle University. http://cancerweb.ncl.ac.uk/cgi-bin/omd?query=angor+animi(accessed: May 04, 2007)[dead link]
2. ^ a b c Gairdner's disease. Online Medical Dictionary. CancerWeb. Centre for Cancer Education. Newcastle University. http://cancerweb.ncl.ac.uk/cgi-bin/omd?query=Gairdner%27s+disease[permanent dead link] (accessed: May 04, 2007)
3. ^ Fenner, P.J. (2000). "Carukia barnesi and the 'Irukndji Syndrome'" (PDF). www.marine-medic.com.
4. ^ a b angor. Dictionary.com. Webster's Revised Unabridged Dictionary. MICRA, Inc. http://dictionary.reference.com/browse/angor (accessed: May 04, 2007)
5. ^ a b angor. Dictionary.com. Dictionary.com Unabridged (v 1.1). Random House, Inc. http://dictionary.reference.com/browse/angor (accessed: May 04, 2007).
6. ^ animi. Dictionary.com. Webster's Revised Unabridged Dictionary. MICRA, Inc. http://dictionary.reference.com/browse/animi (accessed: May 04, 2007)
This medical symptom article is a stub. You can help Wikipedia by expanding it.
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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
| Angor animi | c0549258 | 2,008 | wikipedia | https://en.wikipedia.org/wiki/Angor_animi | 2021-01-18T19:00:57 | {"umls": ["C0549258"], "wikidata": ["Q4763844"]} |
Hypermethioninemia due to glycine N-methyltransferase deficiency is a rare, genetic inborn error of metabolism characterized by a relatively benign clinical phenotype, with only mild to moderate hepatomegaly reported, in addition to laboratory studies revealing permanent, greatly increased hypermethioninemia, mild to moderate elevation of aminotransferases and highly elevated plasma S-adenosyl-methionine with normal S-adenosylhomocysteine and total homocysteine.
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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
| Hypermethioninemia due to glycine N-methyltransferase deficiency | c1847720 | 2,009 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=289891 | 2021-01-23T18:31:42 | {"gard": ["10764"], "mesh": ["C564683"], "omim": ["606664"], "umls": ["C1847720"], "icd-10": ["E72.1"], "synonyms": ["Glycine N-methyltransferase deficiency", "Hypermethioninemia due to GNMT deficiency"]} |
Subglottic stenosis
Neck AP x-ray of patient with post-intubation subglottic stenosis, as shown by the narrowing in the tracheal lumen marked by the arrow.
SpecialtyPulmonology
Subglottic stenosis is a congenital or acquired narrowing of the subglottic airway.[1] Although it is relatively rare, it is the third most common congenital airway problem (after laryngomalacia and vocal cord paralysis). Subglottic stenosis can present as a life-threatening airway emergency. It is imperative that the otolaryngologist be an expert at dealing with the diagnosis and management of this disorder. Subglottic stenosis can affect both children and adults.
## Contents
* 1 Types
* 2 Diagnosis
* 3 Management
* 4 Additional images
* 5 References
* 6 External links
## Types[edit]
Subglottic stenosis can be of three forms, namely congenital subglottic stenosis, idiopathic subglottic stenosis (ISS) and acquired subglottic stenosis. As the name suggests, congenital subglottic stenosis is a birth defect. Idiopathic subglottic stenosis is a narrowing of the airway due to an unknown cause. Acquired subglottic stenosis generally follows as an after-effect of airway intubation, and in extremely rare cases as a result of gastroesophageal reflux disease (GERD).[citation needed]
## Diagnosis[edit]
Subglottic stenosis is graded according to the Cotton-Myer classification system from one to four based on the severity of the blockage.[2]
Grade 1 – <50% obstruction
Grade 2 – 51–70% obstruction
Grade 3 – 71–99% obstruction
Grade 4 – no detectable lumen
## Management[edit]
Treatments to alleviate the symptoms of subglottic stenosis includes a daily dose of steroids such as prednisone, which reduces the inflammation of the area for better breathing. Other medications such as Methotrexate is also being tested by patients but results are pending.[citation needed]
## Additional images[edit]
Pre-surgical photographs of a 31-year-old female patient with subglottic stenosis caused by the formation of scar tissue resulting from chronic gastroesophageal reflux disease.
Post-surgical photographs of a 31-year-old female patient who has undergone a micro-direct laryngoscopy involving laser removal of scar tissue and balloon dilation of the airway.
## References[edit]
1. ^ "Subglottic Stenosis in Adults: Problem, Etiology, Pathophysiology". 2017-06-21. Cite journal requires `|journal=` (help)
2. ^ Myer Cm, 3rd; O'Connor, D. M.; Cotton, R. T. (April 1994). "Proposed grading system for subglottic stenosis based on endotracheal tube sizes". The Annals of Otology, Rhinology, and Laryngology. 103 (4 Pt 1): 319–23. doi:10.1177/000348949410300410. PMID 8154776. S2CID 12782910.
## External links[edit]
Classification
D
* ICD-10: Q31.8, J38.6
* v
* t
* e
Congenital malformations and deformations of respiratory system
Upper RT
Nose
* Choanal atresia
* Arrhinia
Larynx
* Laryngeal cyst
* Laryngocele
* Laryngomalacia
Lower RT
Trachea and bronchus
* Tracheomalacia
* Tracheal stenosis
* Bronchomalacia
* Tracheobronchomegaly
Lung
* Bronchiectasis
* Pulmonary hypoplasia
* Pulmonary sequestration
* Congenital cystic adenomatoid malformation
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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
| Subglottic stenosis | c0238441 | 2,010 | wikipedia | https://en.wikipedia.org/wiki/Subglottic_stenosis | 2021-01-18T18:57:17 | {"umls": ["C0238441"], "wikidata": ["Q7631147"]} |
Waardenburg syndrome type 1 is a genetic condition characterized by eyes that appear widely spaced, congenital hearing loss, and patchy pigment disturbances of the iris, hair and skin. Mutations in the PAX3 gene cause the symptoms observed in this condition. Treatment is symptomatic and supportive. Waardenburg syndrome type 1 is inherited in an autosomal dominant manner.
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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
| Waardenburg syndrome type 1 | c1847800 | 2,011 | gard | https://rarediseases.info.nih.gov/diseases/5519/waardenburg-syndrome-type-1 | 2021-01-18T17:57:09 | {"mesh": ["D014849"], "omim": ["193500"], "umls": ["C1847800"], "orphanet": ["894"], "synonyms": ["WS1", "Waardenburg's syndrome type 1"]} |
Pseudomonas hot-foot syndrome
SpecialtyDermatology
Pseudomonas hot-foot syndrome is a self-limited cutaneous condition that occurs on the plantar surface of children after swimming in pool water that has high concentrations of P. aeruginosa.[1][2] The condition typically presents as plantar purple-red nodules.[3]
## See also[edit]
* Pseudomonal pyoderma
* List of cutaneous conditions
## References[edit]
1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
2. ^ http://content.nejm.org/cgi/content/full/345/5/335
3. ^ Jain, Sima (2017). dermatology.
This dermatology article is a stub. You can help Wikipedia by expanding it.
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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
| Pseudomonas hot-foot syndrome | None | 2,012 | wikipedia | https://en.wikipedia.org/wiki/Pseudomonas_hot-foot_syndrome | 2021-01-18T19:06:41 | {"wikidata": ["Q7255050"]} |
Agnosia is characterized by an inability to recognize and identify objects and/or persons. Symptoms may vary, according to the area of the brain that is affected. It can be limited to one sensory modality such as vision or hearing; for example, a person may have difficulty in recognizing an object as a cup or identifying a sound as a cough. Agnosia can result from strokes, traumatic brain injury, dementia, a tumor, developmental disorders, overexposure to environmental toxins (e.g., carbon monoxide poisoning), or other neurological conditions. Visual agnosia may also occur in association with other underlying disorders. People with agnosia may retain their cognitive abilities in other areas. Treatment of primary agnosia is symptomatic and supportive; when it is caused by an underlying disorder, treatment of the disorder may reduce symptoms and help prevent further brain damage.
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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
| Agnosia | c0001816 | 2,013 | gard | https://rarediseases.info.nih.gov/diseases/8/agnosia | 2021-01-18T18:02:14 | {"mesh": ["D000377"], "synonyms": ["Primary visual agnosia", "Monomodal visual amnesia", "Visual amnesia"]} |
SYNGAP1-related non-syndromic intellectual disability is a condition that primarily affects the central nervous system. It is characterized by moderate to severe intellectual disability that is usually apparent in the first few years of life. Some affected people may also experience seizures and/or autism spectrum disorder. This condition is caused by changes (mutations) in the SYNGAP1 gene. Almost all reported cases are due to de novo mutations; however, the condition can be passed down to future generations in an autosomal dominant manner. Treatment is based on the signs and symptoms present in each person.
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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
| SYNGAP1-related non-syndromic intellectual disability | c2675473 | 2,014 | gard | https://rarediseases.info.nih.gov/diseases/12558/syngap1-related-non-syndromic-intellectual-disability | 2021-01-18T17:57:27 | {"mesh": ["C567234"], "omim": ["612621"], "synonyms": ["MRD5 ", "Syngap1 Gene Mutation Linked To Intellectual Disability, Schizophrenia and Autism ", "SYNGAP1-related NSID", "SYNGAP1 syndrome", "Autosomal dominant intellectual disability 5"]} |
Cantu et al. (1975) reported 3 affected males in a sibship of 13, from second-cousin parents, who had what the authors termed lethal faciocardiomelic dysplasia. They were all of low birth weight, had microretrognathia, microstomia, and microglossia, hypoplasia of the radius and ulna with radial deviation of the hands, simian creases and hypoplasia of fingers I and V, hypoplasia of the fibula and tibia with talipes and wide space between toes I and II, and severe cardiac malformation which may have been responsible for death of all 3 in the first week or so of life.
Cardiac \- Congenital heart malformation HEENT \- Micrognathia \- Retrognathia \- Microstomia \- Microglossia Limbs \- Radial hypoplasia \- Ulnar hypoplasia \- Radial deviation of hands \- Simian creases \- Hypoplasia of fingers I and V \- Fibular hypoplasia \- Tibial hypoplasia \- Talipes \- Wide space between toes I and II Growth \- Low birth weight \- Neonatal death Inheritance \- Autosomal recessive ▲ 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
| FACIOCARDIOMELIC DYSPLASIA, LETHAL | c1856891 | 2,015 | omim | https://www.omim.org/entry/227270 | 2019-09-22T16:27:59 | {"mesh": ["C565578"], "omim": ["227270"], "orphanet": ["1972"]} |
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (November 2013)
Urinothorax
Bilateral pleural effusions which later turned out to be urinothorax.
SpecialtyPulmonology
SymptomsSimilar to pleural effusion
Causesobstruction
Urinothorax (pl. urinothoraces) means urine in the fluid-filled cavity that surrounds the lungs.[1] It is an extremely rare cause of pleural effusion.[2] It is secondary to obstructive uropathy whereby urine forms a collection in the pleural cavity. The urine arrives in the pleural space either retroperitoneally (under the peritoneum) under the posterior diaphragm, or via the retro peritoneal lymphatics. It remains a rare, possibly under-diagnosed, differential in the case of transudative pleural effusion. Respiratory symptoms are usually mild.[3]
## Contents
* 1 Symptoms
* 2 Causes
* 3 Diagnosis
* 4 Treatment
* 5 References
## Symptoms[edit]
The defining characteristics of people affected by urinothorax are poorly defined. Symptoms include difficulty breathing, abdominal pain, chest pain, and reduced urination.[4]
## Causes[edit]
It is either caused by an obstruction (obstructive uropathy), caused by trauma, or iatrogenic. Traumatic cases tend to occur on one side, while obstructive cases tend to be bilateral.[2]
## Diagnosis[edit]
The pleural fluid is most often straw-colored, and it has a distinct smell like ammonia. Primary factors for diagnosing urinothorax include low protein and high LDH content.[5] Low glucose levels and acidity are also described, but not reliable ways to diagnose or rule out urinothorax.[2]
The most important chemical diagnostic factor of the fluid is that the ratio of creatinine to serum is more than 1 and usually more than 10.[5]
## Treatment[edit]
Treatment mainly consists of relieving urinary obstruction if it is present. If respiratory symptoms are minimal or nonexistent, thoracentesis may not be needed, as urinothoraces can resolve on their own in some cases after resolution of the underlying condition.[2]
## References[edit]
1. ^ Salcedo, Jose R. (April 1986). "Urinothorax: Report of 4 Cases and Review of the Literature". Journal of Urology. 135 (4): 805–808. doi:10.1016/S0022-5347(17)45862-9. PMID 3514964.
2. ^ a b c d Wei, Benjamin; Takayama, Hiroo; Bacchetta, Matthew D. (2009). "Urinothorax: An uncommon cause of pleural effusion". Respiratory Medicine CME. 2 (4): 179–180. doi:10.1016/j.rmedc.2009.01.009.
3. ^ Wunderle, Kathryn; Kim, Suil; Chiovaro, Joseph (15 March 2017). "Urinothorax: A Rare Case of Pleural Effusion". Journal of General Internal Medicine. 32 (9): 1058–1059. doi:10.1007/s11606-017-4032-z. PMC 5570734. PMID 28299602.
4. ^ Toubes, María E.; Lama, Adriana; Ferreiro, Lucía; Golpe, Antonio; Álvarez-Dobaño, José M.; González-Barcala, Francisco J.; San José, Esther; Rodríguez-Núñez, Nuria; Rábade, Carlos; Lourido, Tamara; Valdés, Luis (May 2017). "Urinothorax: a systematic review". Journal of Thoracic Disease. 9 (5): 1209–1218. doi:10.21037/jtd.2017.04.22. PMC 5465116. PMID 28616270.
5. ^ a b Chandra, Alka; Pathak, Amrendra; Kapur, Anu; Russia, Neha; Bhasin, Nikhil (2014). "Urinothorax: A rare cause of severe respiratory distress". Indian Journal of Critical Care Medicine. 18 (5): 320–322. doi:10.4103/0972-5229.132501. PMC 4047695. PMID 24914262.
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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
| Urinothorax | None | 2,016 | wikipedia | https://en.wikipedia.org/wiki/Urinothorax | 2021-01-18T18:57:28 | {"wikidata": ["Q16984194"]} |
"Delusions of grandeur" redirects here. For other uses, see Delusions of grandeur (disambiguation).
For other uses, see Megalomania (disambiguation).
Not to be confused with grandiosity or illusory superiority.
Subtype of delusion
Grandiose delusions
Other namesExpansive delusions
People suffering from grandiose delusions wrongly hold themselves at an extraordinarily high status in their mind.
SpecialtyPsychiatry
Grandiose delusions (GD), also known as delusions of grandeur or expansive delusions,[1] are a subtype of delusion that occur in patients suffering from a wide range of psychiatric diseases, including two-thirds of patients in manic state of bipolar disorder, half of those with schizophrenia, patients with the grandiose subtype of delusional disorder, and a substantial portion of those with substance abuse disorders.[2][3] GDs are characterized by fantastical beliefs that one is famous, omnipotent, wealthy, or otherwise very powerful. The delusions are generally fantastic and typically have a religious, science fictional, or supernatural theme. There is a relative lack of research into GD, in contrast to persecutory delusions and auditory hallucinations. About 10% of healthy people experience grandiose thoughts but do not meet full criteria for a diagnosis of GD.[3]
## Contents
* 1 Signs and symptoms
* 1.1 Positive functions
* 1.2 Comorbidity
* 1.2.1 Schizophrenia
* 1.2.2 Bipolar disorder
* 2 Cause
* 3 Anatomical aspects
* 4 Diagnosis
* 5 Treatment
* 6 Epidemiology
* 6.1 Prevalence
* 7 See also
* 8 References
## Signs and symptoms[edit]
According to the DSM-IV-TR diagnostic criteria for delusional disorders, grandiose-type symptoms include astronomically exaggerated beliefs of:
* self-worth
* power[4]
* knowledge
* identity
* exceptional relationship to a deity or famous person.[5]
For example, a patient who has fictitious beliefs about his or her power or authority may believe himself or herself to be a ruling monarch who deserves to be treated like royalty.[6] There are substantial differences in the degree of grandiosity linked with grandiose delusions in different patients. Some patients believe they are God, the Queen of the United Kingdom, a president's son, a famous rock star, and so on. Others are not as expansive and think they are skilled athletes or great inventors.[7]
Expansive delusions may be maintained by auditory hallucinations, which advise the patient that they are significant, or confabulations, when, for example, the patient gives a thorough description of their coronation or marriage to the king. Grandiose and expansive delusions may also be part of fantastic hallucinosis in which all forms of hallucinations occur.[7]
### Positive functions[edit]
Grandiose delusions frequently serve a very positive function for the person by sustaining or increasing their self-esteem. As a result, it is important to consider what the consequences of removing the grandiose delusion are on self-esteem when trying to modify the grandiose delusion in therapy.[4] In many instances of grandiosity it is suitable to go for a fractional rather than a total modification, which permits those elements of the delusion that are central for self-esteem to be preserved. For example, a person who believes they are a senior secret service agent gains a great sense of self-esteem and purpose from this belief, thus until this sense of self-esteem can be provided from elsewhere, it is best not to attempt modification.[4]
### Comorbidity[edit]
#### Schizophrenia[edit]
Main article: Schizophrenia
Schizophrenia is a mental disorder distinguished by a loss of contact with reality and the occurrence of psychotic behaviors, including hallucinations and delusions (unreal beliefs which endure even when there is contrary evidence).[8] Delusions may include the false and constant idea that the person is being followed or poisoned, or that the person’s thoughts are being broadcast for others to listen to. Delusions in schizophrenia often develop as a response to the individual attempting to explain their hallucinations.[8] Patients who experience recurrent auditory hallucinations can develop the delusion that other people are scheming against them and are dishonest when they say they do not hear the voices that the delusional person believes that he or she hears.[8]
Specifically, grandiose delusions are frequently found in paranoid schizophrenia, in which a person has an extremely exaggerated sense of his or her significance, personality, knowledge, or authority. For example, the person may possibly declare to own a major corporation and kindly offer to write a hospital staff member a check for $5 million if they would only help them escape from the hospital.[9] Other common grandiose delusions in schizophrenia include religious delusions such as the belief that one is Jesus Christ.[10]
#### Bipolar disorder[edit]
Main article: Bipolar disorder
Bipolar I disorder can lead to severe affective dysregulation, or mood states that sway from exceedingly low (depression) to exceptionally high (mania).[11] In hypomania or mania, some bipolar patients can suffer grandiose delusions. In its most severe manifestation, days without sleep, or auditory and other hallucinations, or uncontrollable racing thoughts can reinforce these delusions. In mania, this illness not only affects emotions but can also lead to impulsivity and disorganized thinking which can be harnessed to increase their sense of grandiosity. Protecting this delusion can also lead to extreme irritability, paranoia and fear. Sometimes their anxiety can be so over-blown that they believe others are jealous of them and, thus, are undermining their "extraordinary abilities," persecuting them or even scheming to seize what they already have.[12]
Scott Stapp of Creed, who suffered grandiose delusions as a result of bipolar disorder
The vast majority of bipolar patients rarely experience delusions. Typically, when experiencing or displaying a stage of heightened excitability called mania, they can experience, joy, rage, a flattened state in which life has no meaning[clarification needed] and sometimes even a mixed state of intense emotions which can cycle out of control along with thoughts or beliefs that are grandiose in nature. Some of these grandiose thoughts can be expressed as strong beliefs that the patient is very rich or famous or has super-human abilities, or can even lead to severe suicidal ideations.[13] In the most severe form, in what was formerly labeled as megalomania, the bipolar patient may hear voices which support these grandiose beliefs. In their delusions, they can believe that they are, for example, a king, a creative genius, or can even exterminate the world's poverty because of their extreme generosity.[14]
## Cause[edit]
There are two alternate causes for developing grandiose delusions:[15][further explanation needed]
* Delusion-as-defense: defense of the mind against lower self-esteem and depression.
* Emotion-consistent: result of exaggerated emotions.
## Anatomical aspects[edit]
Grandiose delusions may be related to lesions of the frontal lobe.[16] Temporal lobe lesions have been mainly reported in patients with delusions of persecution and of guilt, while frontal and frontotemporal involvement have been described in patients with grandiose delusions, Cotard’s syndrome, and delusional misidentification syndrome.[17]
## Diagnosis[edit]
Patients with a wide range of mental disorders which disturb brain function experience different kinds of delusions, including grandiose delusions.[18] Grandiose delusions usually occur in patients with syndromes associated with secondary mania, such as Huntington's disease,[19] Parkinson's disease,[20] and Wilson's disease.[21] Secondary mania has also been caused by substances such as L-DOPA and isoniazid which modify the monoaminergic neurotransmitter function.[22] Vitamin B12 deficiency,[23] uremia,[24] hyperthyroidism[25] as well as the carcinoid syndrome[26] have been found to cause secondary mania, and thus grandiose delusions.
In diagnosing delusions, the MacArthur-Maudsley Assessment of Delusions Schedule is used to assess the patient.[27]
## Treatment[edit]
In patients suffering from schizophrenia, grandiose and religious delusions are found to be the least susceptible to cognitive behavioral interventions.[27] Cognitive behavioral intervention is a form of psychological therapy, initially used for depression,[28] but currently used for a variety of different mental disorders, in hope of providing relief from distress and disability.[29] During therapy, grandiose delusions were linked to patients' underlying beliefs by using inference chaining.[jargon][28][30] Some examples of interventions performed to improve the patient's state were focus on specific themes, clarification of patient's neologisms, and thought linkage.[30] During thought linkage, the patient is asked repeatedly by the therapist to explain his/her jumps in thought from one subject to a completely different one.[30]
Patients suffering from mental disorders that experience grandiose delusions have been found to have a lower risk of having suicidal thoughts and attempts.[31]
## Epidemiology[edit]
In researching over 1000 individuals of a vast range of backgrounds, Stompe and colleagues (2006) found that grandiosity remains as the second most common delusion after persecutory delusions.[3] A variation in the occurrence of grandiosity delusions in schizophrenic patients across cultures has also been observed.[32][33] In research done by Appelbaum et al. it has been found that GDs appeared more commonly in patients with bipolar disorder (59%) than in patients with schizophrenia (49%), followed by presence in substance misuse disorder patients (30%) and depressed patients (21%).[34]
A relationship has been claimed between the age of onset of bipolar disorder and the occurrence of GDs. According to Carlson et al. (2000), grandiose delusions appeared in 74% of the patients who were 21 or younger at the time of the onset, while they occurred only in 40% of individuals 30 years or older at the time of the onset.[35]
### Prevalence[edit]
Research suggests that the severity of the delusions of grandeur is directly related to a higher self-esteem in individuals and inversely related to any individual’s severity of depression and negative self-evaluations.[36] Lucas et al. found that there is no significant gender difference in the establishment of grandiose delusion.[37] However, there is a claim that ‘the particular content of Grandiose delusions’ may be variable across both genders.[38] Also, it has been noted that the presence of GDs in people with at least grammar or high school education was greater than lesser educated persons. Similarly, the presence of grandiose delusions in individuals who are the eldest is greater than in individuals who are the youngest of their siblings.[37]
## See also[edit]
Wikiquote has quotations related to: Grandiose delusions
* God complex
* Illusory superiority
* Megalomania
* Messiah complex
* Organic personality disorder
* Persecutory delusions
## References[edit]
1. ^ Ray Corsini (2016). The Dictionary of Psychology. Taylor & Francis. p. 985. ISBN 978-1-317-70570-3.
2. ^ Diagnostic and Statistical Manual of Mental Disorders Fourth edition Text Revision (DSM-IV-TR) American Psychiatric Association (2000)
3. ^ a b c Knowles, R; McCarthy-Jones, S; Rowse, G (2011). "Grandiose delusions: A review and theoretical integration of cognitive and affective perspectives". Clinical Psychology Review. 31 (4): 684–696. doi:10.1016/j.cpr.2011.02.009. PMID 21482326. cites Stompe, T; Karakula, H; Rudalevičiene, P; Okribelashvili, N; Chaudhry, HR; Idemudia, EE; et al. (2006). "The pathoplastic effect of culture on psychotic symptoms in schizophrenia". World Cultural Psychiatry Research Review: 157–163.
4. ^ a b c Nelson, H.E. (2005). Cognitive-Behavioural Therapy with Delusions and Hallucinations: A Practice Manual. Nelson Thornes. p. 339. ISBN 9780748792566. Retrieved 5 August 2012.
5. ^ Sadock, B. J.; Sadock, VA (2008). "11.3 Delusional Disorder and Shared Psychotic Disorder". Kaplan and Sadock's Concise Textbook of Clinical Psychiatry. Lippincott Williams & Wilkins. DIAGNOSIS AND CLINICAL FEATURES, Mental Status, Table 11.3–1 DSM-IV-TR Diagnostic Criteria for Delusional Disorder, p. 184. ISBN 9780781787468. "Grandiose type: delusions of inflated worth, power, knowledge, identity, or special relationship to a deity or famous person"
6. ^ Davies, J.L.; Janosik E.H. (1991). Mental Health and Psychiatric Nursing: A Caring Approach. Boston, MA: Jones & Bartlett Learning. p. 760. ISBN 9780867204421.
7. ^ a b Casey, P.R.; Brendan K. (2007). Fish's Clinical Psychopathology: Signs and Symptoms in Psychiatry. UK: RCPsych Publications. p. 138. ISBN 9781904671329..
8. ^ a b c Magill's Encyclopedia of Social Science: Psychology. California: Salem Press, Inc. 2003. pp. 718–719.
9. ^ Noll, R. (2009). The Encyclopedia of Schizophrenia and Other Psychotic Disorders. New York: Facts on File, Inc. p. 122. ISBN 9780816075089.
10. ^ Hunsley, J.; Mash E.J. (2008). A Guide to Assessment that Work. Oxford University Press. p. 676. ISBN 9780198042457.
11. ^ Barlow, D.H. (2007). Clinical Handbook of Psychological Disorders: A Step by Step Treatment Manual. New York: Guilford. p. 722. ISBN 9781606237656.
12. ^ Kantor, M. (2004). Understanding Paranoia: A Guide for Professionals, Families, and Sufferers. West Port: Greenwoord. p. 252. ISBN 9780275981525.
13. ^ Isaac, G. (2001). Bipolar Not Adhd: Unrecognized Epidemic of Manic Depressive Illness in Children. Lincoln: Writers Club Press. p. 184. ISBN 9781475906493.
14. ^ Fieve, R. R. (2009). Bipolar Breakthrough: The Essential Guide to Going Beyond Moodswings to Harness Your Highs, Escape the Cycles of Recurrent Depression, and Thrive with Bipolar II. Rodale. p. 288. ISBN 9781605296456.
15. ^ Smith, N.; Freeman D.; Kuipers E. (2005). "Grandiose Delusions: An Experimental Investigation of the Delusion as Defense". Journal of Nervous and Mental Disease. 193 (7): 480–487. doi:10.1097/01.nmd.0000168235.60469.cc. PMID 15985843. S2CID 22462383.
16. ^ Omar, Rohani; Sampson, Elizabeth L.; Loy, Clement T.; Mummery, Catherine J.; Fox, Nick C.; Rossor, Martin N.; Warren, Jason D. (April 2009). "Delusions in frontotemporal lobar degeneration". Journal of Neurology. 256 (4): 600–607. doi:10.1007/s00415-009-0128-7. ISSN 0340-5354. PMC 2756566. PMID 19365594.
17. ^ Tonkonogy, Joseph M; Tonkonogiĭ, TM; Puente, AE (2009). "5 Disturbances in the Recognition of the Social World". Localization of Clinical Syndromes in Neuropsychology and Neuroscience. New York, NY: Springer Publishing Company. Conclusion, p. 288. ISBN 9780826119681. "2\. Temporal lobe lesions have been primarily reported in patients with delusions of persecution and of guilt, while frontal and frontotemporal involvement have described [sic] in patients with grandiose delusions, Cotard’s syndrome, and delusional misidentification syndrome."
18. ^ Cummings, Jeffrey L. (1985). "Organic delusions: phenomenology, anatomical correlations and review". The British Journal of Psychiatry. 146 (2): 184–197. doi:10.1192/bjp.146.2.184. PMID 3156653.
19. ^ McHugh, P.R; Folstein, M.F (1975). "Psychiatric syndromes in Huntington's chorea". Psychiatric Aspectes of Neurological Disease.
20. ^ Bromberg, W. (1930). "Mental states in chronic encephalitis". Psychiatric Quarterly. 4 (4): 537–566. doi:10.1007/bf01563408. S2CID 33819397.
21. ^ Pandy, R.S.; Sreenivas, K.N.; Paith N.M.; Swamy H.S. (1981). "Dopamine beta-hydroxylase in a patient with Wilson's disease and mania". The American Journal of Psychiatry. 138 (12): 1628–1629. doi:10.1176/ajp.138.12.1628. PMID 7304799.
22. ^ Lin, J-T Y.; Ziegler, D. (1976). "Psychiatric symptoms with initiation of carbidopa-levodopa treatment". Neurology. 26 (7): 679–700. doi:10.1212/wnl.26.7.699. PMID 945518. S2CID 19413218.
23. ^ Goggans, F.C. (1983). "A case of mania secondary to vitamin B12 deficiency". The American Journal of Psychiatry. 141 (2): 300–301. doi:10.1176/ajp.141.2.300. PMID 6691503.
24. ^ Cooper, A.T. (1967). "Hypomanic psychosis precipitated by hemodialysis". Comprehensive Psychiatry. 8 (3): 168–172. doi:10.1016/s0010-440x(67)80020-8. PMID 6046067.
25. ^ Jefferson, J.W.; Marshall J.R. "Neuropsychiatric Features of Medical Disorders". New York: Plenum :Medical Book Company.
26. ^ Lehmann, J. (1966). "Mental disturbances followed by stupor in a patient with carcinoidosis". Acta Psychiatrica Scandinavica. 42 (2): 153–161. doi:10.1111/j.1600-0447.1966.tb01921.x. PMID 5958539. S2CID 144556510.
27. ^ a b Appelbaum, P.S.; Clark Robbins, P.; Roth, L. H. (1999). "Dimensional approach to delusions: Comparison across types and diagnoses". The American Journal of Psychiatry. 156 (12): 1938–1943. doi:10.1176/ajp.156.12.1938 (inactive 2021-01-15). PMID 10588408.CS1 maint: DOI inactive as of January 2021 (link)
28. ^ a b Beck, A.T.; Rush A.J.; Shaw B.F.; Emergy G (1979). "Cognitive Therapy of Depression". New York, NY. Guilford Press.
29. ^ Salkovskis, P.M. (1996). Frontiers of Cognitive Therapy. New York: Guillford.
30. ^ a b c Sensky, T.; et al. (2000). "A randomized controlled trial of Cognitive-Behavioral Therapy for Persistent Symptoms in Schizophrenia resistant to medication". Archives of General Psychiatry. 57 (2): 165–172. doi:10.1001/archpsyc.57.2.165. PMID 10665619.
31. ^ Oquendo, M.A.; et al. (2000). "Suicidal behavior in bipolar mood disorder: clinical characteristics of attempters and nonattempters". Journal of Affective Disorders. 59 (2): 107–117. doi:10.1016/s0165-0327(99)00129-9. PMID 10837879.
32. ^ Stompe, T.; et al. (2007). "Paranoid-hallucinatory syndromes in schizophrenia results of the international study on psychotic symptoms". World Cultural Psychiatry Review: 63–68.
33. ^ Suhail, K. (2003). "Phenomenology of delusions in Pakistani patients: effect of gender and social class". Psychopathology. 36 (4): 195–199. doi:10.1159/000072789. PMID 14504453. S2CID 38400554.
34. ^ Knowles et al. (2011) cites Appelbaum, P.S.; Clark Robbins, P.; Roth, L. H. (1999). "Dimensional approach to delusions: Comparison across types and diagnoses". The American Journal of Psychiatry. 156 (12): 1938–1943. doi:10.1176/ajp.156.12.1938 (inactive 2021-01-15). PMID 10588408.CS1 maint: DOI inactive as of January 2021 (link)
35. ^ Knowles et al. (2011) cites Carlson, GA; Bromet, EJ; Sievers, S (2000). "Phenomenology and outcome of subjects with early- and adult-onset psychotic mania". American Journal of Psychiatry. 157 (2): 213–219. doi:10.1176/appi.ajp.157.2.213. PMID 10671389.
36. ^ Smith, N.; et al. (2006). "Emotion and psychosis: Links between depression, self-esteem, negative schematic beliefs and delusions and hallucinations". Schizophrenia Research. 86 (1): 181–188. doi:10.1016/j.schres.2006.06.018. PMID 16857346. S2CID 31993235.
37. ^ a b Lucas, C.J.; et al. (1962). "A social and clinical study of delusions in schizophrenia". The Journal of Mental Science. 108 (457): 747–758. doi:10.1192/bjp.108.457.747. PMID 13931397.
38. ^ Knowles et al. (2011) cites Rudalevičienė, P; Stompe, T; Narbekovas, A; Raškauskienė, N; Bunevičius, R (2008). "Are religious delusions related to religiosity in schizophrenia?". Medicina (Kaunas). 44 (7): 529–535. doi:10.3390/medicina44070068. PMID 18695349.
*[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
| Grandiose delusions | c0233681 | 2,017 | wikipedia | https://en.wikipedia.org/wiki/Grandiose_delusions | 2021-01-18T18:50:05 | {"wikidata": ["Q987664"]} |
Not to be confused with Anencephaly.
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Encephalopathy
SpecialtyNeurology
Encephalopathy (/ɛnˌsɛfəˈlɒpəθi/; from Ancient Greek: ἐνκέφαλος "brain" + πάθος "suffering") means any disorder or disease of the brain, especially chronic degenerative conditions.[1] In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of overall brain dysfunction; this syndrome has many possible organic and inorganic causes.
## Contents
* 1 Signs and symptoms
* 2 Types
* 2.1 Toxicity from chemotherapy
* 3 Diagnosis
* 4 Treatment
* 5 Prognosis
* 6 Terminology
* 7 See also
* 8 References
* 9 Further reading
* 10 External links
## Signs and symptoms[edit]
The hallmark of encephalopathy is an altered mental state or delirium. Characteristic of the altered mental state is impairment of the cognition, attention, orientation, sleep–wake cycle and consciousness.[2] An altered state of consciousness may range from failure of selective attention to drowsiness.[3] Hypervigilance may be present; with or without: cognitive deficits, headache, epileptic seizures, myoclonus (involuntary twitching of a muscle or group of muscles) or asterixis ("flapping tremor" of the hand when wrist is extended).[3]
Depending on the type and severity of encephalopathy, common neurological symptoms are loss of cognitive function, subtle personality changes, and an inability to concentrate. Other neurological signs may include dysarthria, hypomimia, problems with movements (they can be clumsy or slow), ataxia, tremor.[2] Other neurological signs may include involuntary grasping and sucking motions, nystagmus (rapid, involuntary eye movement), jactitation (restlessness while in bed),[citation needed] and respiratory abnormalities such as Cheyne-Stokes respiration (cyclic waxing and waning of tidal volume), apneustic respirations and post-hypercapnic apnea. Focal neurological deficits are less common.[3]
Wernicke encephalopathy can co-occur with Korsakoff alcoholic syndrome, characterized by amnestic-confabulatory syndrome: retrograde amnesia, anterograde amnesia, confabulations (invented memories), poor recall and disorientation.[4]
Anti-NMDA receptor encephalitis is the most common autoimmune encephalitis. It can cause paranoid and grandiose delusions, agitation, hallucinations (visual and auditory), bizarre behavior, fear, short-term memory loss, and confusion.[5]
HIV encephalopathy can lead to dementia.
## Types[edit]
There are many types of encephalopathy. Some examples include:
* Mitochondrial encephalopathy: Metabolic disorder caused by dysfunction of mitochondrial DNA. Can affect many body systems, particularly the brain and nervous system.
* Glycine encephalopathy: A genetic metabolic disorder involving excess production of glycine.
* Hepatic encephalopathy: Arising from advanced cirrhosis of the liver.
* Hypoxic ischemic encephalopathy: Permanent or transitory encephalopathy arising from severely reduced oxygen delivery to the brain.
* Static encephalopathy: Unchanging, or permanent, brain damage, usually caused by prenatal exposure to ethanol.
* Uremic encephalopathy: Arising from high levels of toxins normally cleared by the kidneys—rare where dialysis is readily available.
* Wernicke's encephalopathy: Arising from thiamine (B1) deficiency, usually in the setting of alcoholism.
* Hashimoto's encephalopathy: Arising from an auto-immune disorder.
* Anti-NMDA receptor encephalitis: An auto-immune encephalitis.
* Hyperammonemia: a condition caused by high levels of ammonia, which is due to inborn errors of metabolism (including urea cycle disorder or multiple carboxylase deficiency), a diet with excessive levels of protein, deficiencies of specific nutrients such as arginine or biotin, or organ failure.
* Hypertensive encephalopathy: Arising from acutely increased blood pressure.
* Chronic traumatic encephalopathy: a progressive degenerative disease associated with multiple concussions and other forms of brain injury
* Lyme encephalopathy: Arising from Lyme disease bacteria, including Borrelia burgdorferi.
* Toxic encephalopathy: A form of encephalopathy caused by chemicals, often resulting in permanent brain damage.
* Toxic-metabolic encephalopathy: A catch-all for brain dysfunction caused by infection, organ failure, or intoxication.
* Transmissible spongiform encephalopathy: A collection of diseases all caused by prions, and characterized by "spongy" brain tissue (riddled with holes), impaired locomotion or coordination, and a 100% mortality rate. Includes bovine spongiform encephalopathy (mad cow disease), scrapie, and kuru among others.
* Neonatal encephalopathy (hypoxic-ischemic encephalopathy): An obstetric form, often occurring due to lack of oxygen in bloodflow to brain-tissue of the fetus during labour or delivery.
* Salmonella encephalopathy: A form of encephalopathy caused by food poisoning (especially out of peanuts and rotten meat) often resulting in permanent brain damage and nervous system disorders.
* Encephalomyopathy: A combination of encephalopathy and myopathy. Causes may include mitochondrial disease (particularly MELAS) or chronic hypophosphatemia, as may occur in cystinosis.[6]
* Creutzfeldt–Jakob disease (CJD; transmissible spongiform encephalopathy).
* HIV encephalopathy (encephalopathy associated with HIV infection and AIDS, characterized by atrophy and ill-defined white matter hyperintensity).
* Sepsis-associated encephalopathy (this type can occur in the setting of apparent sepsis, trauma, severe burns, or trauma, even without clear identification of an infection).
* Epileptic encephalopathies:
* Early infantile epileptic encephalopathy (acquired or congenital abnormal cortical development).
* Early myoclonic epileptic encephalopathy (possibly due to metabolic disorders).
* Gluten encephalopathy: Focal abnormalities of the white matter (generally area of low perfusion) are appreciated through magnetic resonance. Migraine is the most common symptom reported.[7]
### Toxicity from chemotherapy[edit]
Chemotherapy medication, for example, fludarabine can cause a permanent severe global encephalopathy.[8] Ifosfamide can cause a severe encephalopathy (but it can be reversible with stopping use of the drug and starting the use of methylene blue).[8] Bevacizumab and other anti–vascular endothelial growth factor medication can cause posterior reversible encephalopathy syndrome.[8]
## Diagnosis[edit]
Blood tests, cerebrospinal fluid examination by lumbar puncture (also known as spinal tap), brain imaging studies, electroencephalography (EEG), and similar diagnostic studies may be used to differentiate the various causes of encephalopathy.
Diagnosis is frequently clinical. That is, no set of tests give the diagnosis, but the entire presentation of the illness with nonspecific test results informs the experienced clinician of the diagnosis.
## Treatment[edit]
Treatment varies according to the type and severity of the encephalopathy. Anticonvulsants may be prescribed to reduce or halt any seizures. Changes to diet and nutritional supplements may help some people. In severe cases, dialysis or organ replacement surgery may be needed.
Sympathomimetic drugs can increase motivation, cognition, motor performance and alertness in persons with encephalopathy caused by brain injury, chronic infections, strokes, brain tumors.[9]
When the encephalopathy is caused by untreated celiac disease or non-celiac gluten sensitivity, the gluten-free diet stops the progression of brain damage and improves the headaches.[7]
## Prognosis[edit]
Treating the underlying cause of the disorder may improve or reverse symptoms. However, in some cases, the encephalopathy may cause permanent structural changes and irreversible damage to the brain. These permanent deficits can be considered a form of stable dementia. Some encephalopathies can be fatal.
## Terminology[edit]
Encephalopathy is a difficult term because it can be used to denote either a disease or finding (i.e., an observable sign in a person).
When referring to a finding, encephalopathy refers to permanent (or degenerative)[10] brain injury, or a reversible one. It can be due to direct injury to the brain, or illness remote from the brain. The individual findings that cause a clinician to refer to a person as having encephalopathy include intellectual disability, irritability, agitation, delirium, confusion, somnolence, stupor, coma and psychosis. As such, describing a person as having a clinical picture of encephalopathy is not a very specific description.
When referring to a disease, encephalopathy refers to a wide variety of brain disorders with very different etiologies, prognoses and implications. For example, prion diseases, all of which cause transmissible spongiform encephalopathies, are invariably fatal, but other encephalopathies are reversible and can have a number of causes including nutritional deficiencies and toxins.
## See also[edit]
* Brain damage
* Neuroscience
* Neurological disorder
* Psychoorganic syndrome
## References[edit]
1. ^ The British Medical Association (BMA) (2002). Illustrated Medical Dictionary. A Dorling Kindersley Book. p. 199. ISBN 978-0-75-133383-1.
2. ^ a b Manfred Oehmichen; Roland N. Auer; Hans Günter König (2006). Forensic Neuropathology and Associated Neurology. Springer Science & Business Media. p. 611. ISBN 978-3-540-28995-1.
3. ^ a b c A.J. Larner (2016). A Dictionary of Neurological Signs. Springer. p. 112. ISBN 978-3-319-29821-4.
4. ^ American Psychiatric Association (2006). American Psychiatric Association Practice Guidelines for the Treatment of Psychiatric Disorders: Compendium 2006. American Psychiatric Pub. p. 210. ISBN 978-0-89042-385-1.
5. ^ Bost C, Pascual O, Honnorat J (2016). "Autoimmune encephalitis in psychiatric institutions: current perspectives". Neuropsychiatr Dis Treat. 12: 2775–2787. doi:10.2147/NDT.S82380. PMC 5089825. PMID 27822050.
6. ^ Müller M, Baumeier A, Ringelstein E, Husstedt I (2008). "Long-term tracking of neurological complications of encephalopathy and myopathy in a patient with nephropathic cystinosis: a case report and review of the literature". J Med Case Rep. 2: 235. doi:10.1186/1752-1947-2-235. PMC 2491650. PMID 18644104.
7. ^ a b Losurdo G, Principi M, Iannone A, Amoruso A, Ierardi E, Di Leo A, et al. (2018). "Extra-intestinal manifestations of non-celiac gluten sensitivity: An expanding paradigm". World J Gastroenterol (Review). 24 (14): 1521–1530. doi:10.3748/wjg.v24.i14.1521. PMC 5897856. PMID 29662290.
8. ^ a b c Ed. Stephen L. Hauser, S. Andrew Josephson (2013). Harrison's Neurology in Clinical Medicine (3rd ed.). p. 438. ISBN 978-0-07-181501-7.
9. ^ Benjamin J. Sadock; Virginia A. Sadock (2008). Kaplan & Sadock's Concise Textbook of Clinical Psychiatry. Lippincott Williams & Wilkins. p. 78. ISBN 978-0-7817-8746-8.
10. ^ "encephalopathy" at Dorland's Medical Dictionary
* Adapted from: Office of Communications and Public Liaison (9 November 2010). "NINDS Encephalopathy Information Page". National Institute of Neurological Disorders and Stroke, National Institutes of Health. Archived from the original on 2009-03-23. Retrieved 2005-09-01.
## Further reading[edit]
* The Diagnosis of Stupor and Coma by Plum and Posner, ISBN 0-19-513898-8, remains one of the best detailed observational references to the condition.
## External links[edit]
Classification
D
* ICD-10: G93.4
* ICD-9-CM: 348.30
* MeSH: D001927
* v
* t
* e
Diseases of the nervous system, primarily CNS
Inflammation
Brain
* Encephalitis
* Viral encephalitis
* Herpesviral encephalitis
* Limbic encephalitis
* Encephalitis lethargica
* Cavernous sinus thrombosis
* Brain abscess
* Amoebic
Brain and spinal cord
* Encephalomyelitis
* Acute disseminated
* Meningitis
* Meningoencephalitis
Brain/
encephalopathy
Degenerative
Extrapyramidal and
movement disorders
* Basal ganglia disease
* Parkinsonism
* PD
* Postencephalitic
* NMS
* PKAN
* Tauopathy
* PSP
* Striatonigral degeneration
* Hemiballismus
* HD
* OA
* Dyskinesia
* Dystonia
* Status dystonicus
* Spasmodic torticollis
* Meige's
* Blepharospasm
* Athetosis
* Chorea
* Choreoathetosis
* Myoclonus
* Myoclonic epilepsy
* Akathisia
* Tremor
* Essential tremor
* Intention tremor
* Restless legs
* Stiff-person
Dementia
* Tauopathy
* Alzheimer's
* Early-onset
* Primary progressive aphasia
* Frontotemporal dementia/Frontotemporal lobar degeneration
* Pick's
* Dementia with Lewy bodies
* Posterior cortical atrophy
* Vascular dementia
Mitochondrial disease
* Leigh syndrome
Demyelinating
* Autoimmune
* Inflammatory
* Multiple sclerosis
* For more detailed coverage, see Template:Demyelinating diseases of CNS
Episodic/
paroxysmal
Seizures and epilepsy
* Focal
* Generalised
* Status epilepticus
* For more detailed coverage, see Template:Epilepsy
Headache
* Migraine
* Cluster
* Tension
* For more detailed coverage, see Template:Headache
Cerebrovascular
* TIA
* Stroke
* For more detailed coverage, see Template:Cerebrovascular diseases
Other
* Sleep disorders
* For more detailed coverage, see Template:Sleep
CSF
* Intracranial hypertension
* Hydrocephalus
* Normal pressure hydrocephalus
* Choroid plexus papilloma
* Idiopathic intracranial hypertension
* Cerebral edema
* Intracranial hypotension
Other
* Brain herniation
* Reye syndrome
* Hepatic encephalopathy
* Toxic encephalopathy
* Hashimoto's encephalopathy
Both/either
Degenerative
SA
* Friedreich's ataxia
* Ataxia–telangiectasia
MND
* UMN only:
* Primary lateral sclerosis
* Pseudobulbar palsy
* Hereditary spastic paraplegia
* LMN only:
* Distal hereditary motor neuronopathies
* Spinal muscular atrophies
* SMA
* SMAX1
* SMAX2
* DSMA1
* Congenital DSMA
* Spinal muscular atrophy with lower extremity predominance (SMALED)
* SMALED1
* SMALED2A
* SMALED2B
* SMA-PCH
* SMA-PME
* Progressive muscular atrophy
* Progressive bulbar palsy
* Fazio–Londe
* Infantile progressive bulbar palsy
* both:
* Amyotrophic lateral sclerosis
* v
* t
* e
Organ failure
General
* Heart failure
* Respiratory failure
* Liver failure
* Acute
* Chronic
* Renal failure
* Acute
* Chronic
* Encephalopathy
Multiple
* Multiple organ dysfunction syndrome
*[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 inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| Encephalopathy | c0085584 | 2,018 | wikipedia | https://en.wikipedia.org/wiki/Encephalopathy | 2021-01-18T18:47:38 | {"mesh": ["D001927"], "umls": ["C0085584", "C0006111"], "wikidata": ["Q576349"]} |
For general phenotypic information and a discussion of genetic heterogeneity of juvenile myoclonic epilepsy, see 254770.
Clinical Features
Ratnapriya et al. (2010) reported a 4-generation family from southern India in which 6 living members had juvenile myoclonic epilepsy. Age at onset ranged from 12 to 20 years, and all had myoclonic seizures with secondary generalized tonic-clonic seizures. Two patients had a history of febrile seizures, and 2 had absence seizures. EEG showed generalized 4-6 Hz polyspike and wave discharges characteristic of a generalized epilepsy. Features included repetitive myoclonic seizures involving upper extremities, often after awakening, and at least 1 patient reported that seizures were precipitated by alcohol, sleep deprivation, and flashing lights. Three patients exhibited a photoparoxysmal response. Two clinically unaffected individuals had an abnormal EEG.
Inheritance
The transmission pattern of juvenile myoclonic epilepsy in the family reported by Ratnapriya et al. (2010) was consistent with autosomal dominant inheritance.
Mapping
By genomewide linkage analysis followed by fine-mapping of an Indian family with juvenile myoclonic epilepsy, Ratnapriya et al. (2010) identified a locus on chromosome 2q33-q36 (maximum 2-point lod score of 3.32 at D2S2248, multipoint lod score of 3.59 for the region between D2S2322 and D2S2228). Haplotype analysis delineated a 29-cM candidate region between markers D2S116 and D2S2390 on chromosome 2q33-q36. No mutations were detected in the SLC4A3 (106195), SLC11A1 (600266), SLC23A3, or KCNE4 (607775) genes.
INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Seizures, myoclonic \- Generalized tonic-clonic seizure \- Febrile seizures (in some) \- Absence seizures (in some) \- Photoparoxysmal response (in some) \- EEG shows generalized polyspike and wave discharges (4-6 Hz) MISCELLANEOUS \- Onset between ages 12 and 20 years \- Seizures occur upon awakening \- Seizures may be precipitated by sleep deprivation, alcohol consumption, or flashing lights \- One Indian family has been reported (as of October 2011) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| EPILEPSY, JUVENILE MYOCLONIC, SUSCEPTIBILITY TO, 9 | c0270853 | 2,019 | omim | https://www.omim.org/entry/614280 | 2019-09-22T15:55:52 | {"doid": ["0111328"], "mesh": ["D020190"], "omim": ["614280"], "orphanet": ["307"]} |
Complication of chronic kidney disease
Chronic kidney disease-mineral and bone disorder
SpecialtyNephrology
Chronic kidney disease–mineral and bone disorder (CKD-MBD) is one of the many complications associated with chronic kidney disease. It represents a systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following:[1][2]
* Abnormalities of calcium, phosphorus (phosphate), parathyroid hormone, or vitamin D metabolism
* Abnormalities in bone turnover, mineralization, volume, linear growth, or strength
* Vascular or other soft-tissue calcification
CKD-MBD explains, at least in part, the high morbidity and mortality of CKD patients, linking kidney and bone disease with cardiovascular complications. It is a matter of discussion whether CKD-MBD may be considered a real syndrome or not.[3]
CKD-MBD broadens the "old" concept of "renal osteodystrophy", which now should be restricted to describing the bone pathology associated with CKD.[1][2] Thus, renal osteodystrophy is currently considered one measure of the skeletal component of the systemic disorder of CKD–MBD that is quantifiable by histomorphometry of bone biopsy.[1][4] New guidelines have been recently released.[5]
## Contents
* 1 Pathophysiology
* 2 Diagnosis
* 3 Treatment
* 4 References
* 5 External links
## Pathophysiology[edit]
It is well-known that as kidney function declines, there is a progressive deterioration in mineral homeostasis, with a disruption of normal serum and tissue concentrations of phosphorus and calcium, and changes in circulating levels of hormones.[2] These include parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH) vitamin D; calcidiol), 1,25-dihydroxyvitamin D (1,25(OH)2 vitamin D; calcitriol), and other vitamin D metabolites, fibroblast growth factor 23 (FGF-23), and growth hormone.[2] Beginning in CKD stage 3, the ability of the kidneys to appropriately excrete a phosphate load is diminished, leading to hyperphosphatemia, elevated PTH (secondary hyperparathyroidism), and decreased 1,25(OH)2 vitamin D with associated elevations in the levels of FGF-23.[2] The conversion of 25(OH) vitamin D to 1,25(OH)2 vitamin D is impaired, reducing intestinal calcium absorption and increasing PTH.[2] The kidney fails to respond adequately to PTH, which normally promotes phosphaturia and calcium reabsorption, or to FGF-23, which also enhances phosphate excretion.[2] In addition, there is evidence at the tissue level of a downregulation of vitamin D receptor and of resistance to the actions of PTH. Therapy is generally focused on correcting biochemical and hormonal abnormalities in an effort to limit their consequences.[2]
The mineral and endocrine functions disrupted in CKD are critically important in the regulation of both initial bone formation during growth (bone modeling) and bone structure and function during adulthood (bone remodeling).[2] As a result, bone abnormalities are found almost universally in patients with CKD requiring dialysis (stage 5D), and in the majority of patients with CKD stages 3–5.[2] More recently, there has been an increasing concern of extraskeletal calcification that may result from the deranged mineral and bone metabolism of CKD and from the therapies used to correct these abnormalities.[2][6]
Numerous cohort studies have shown associations between disorders of mineral metabolism and fractures, cardiovascular disease, and mortality.[2] These observational studies have broadened the focus of CKD-related mineral and bone disorders (MBDs) to include cardiovascular disease (which is the leading cause of death in patients at all stages of CKD).[2] All three of these processes (abnormal mineral metabolism, abnormal bone, and extraskeletal calcification) are closely interrelated and together make a major contribution to the morbidity and mortality of patients with CKD.[2] The traditional definition of renal osteodystrophy did not accurately encompass this more diverse clinical spectrum, based on serum biomarkers, noninvasive imaging, and bone abnormalities. The absence of a generally accepted definition and diagnosis of renal osteodystrophy prompted Kidney Disease: Improving Global Outcomes (KDIGO)] to sponsor a controversies conference, entitled Definition, Evaluation, and Classification of Renal Osteodystrophy, in 2005. The principal conclusion was that the term CKD–Mineral and Bone Disorder (CKD–MBD) should now be used to describe the broader clinical syndrome encompassing mineral, bone, and calcific cardiovascular abnormalities that develop as a complication of CKD.[1][2]
## Diagnosis[edit]
This section is empty. You can help by adding to it. (January 2019)
## Treatment[edit]
Treatment efforts may involve many clinical and diagnostic manoeuvers, such as trying to decrease phosphate,[7] normalize vitamin D (calcidiol levels) or decrease PTH and/or alkaline phosphatase levels.[8] However, there is an important lack of randomized clinical studies and recent guidelines (KDIGO 2017) have been recently released on the topic. Although it was previously considered, normalization of calcemia is not included in modern treatment goals since the availability of calcimimetics.[5]
## References[edit]
1. ^ a b c d Moe S, Drueke T, Cunningham J, et al. (2006). "Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO)". Kidney International. 69 (11): 1945–1953. doi:10.1038/sj.ki.5000414. PMID 16641930.
2. ^ a b c d e f g h i j k l m n o KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) (2009). "Introduction and definition of CKD–MBD and the development of the guideline statements" (PDF). Kidney International Supplements. 76 (Suppl 113): S3–S8. doi:10.1038/ki.2009.189. PMID 26746396. Archived from the original (PDF) on 2016-12-13.
3. ^ Cozzolino M, Ureña-Torres P, Vervloet MG, Brandenburg V, Bover J, Goldsmith D, Larsson TE, Massy ZA, Mazzaferro S, CKD-MBD Working Group of ERA-EDTA (2014). "Is chronic kidney disease-mineral bone disorder (CKD-MBD) really a syndrome?". Nephrol Dial Transplant. 29 (10): 1815–20. doi:10.1093/ndt/gft514. PMID 24516228.
4. ^ Torres PU, Bover J, Mazzaferro S, de Vernejoul MC, Cohen-Solal M (2014). "When, how, and why a bone biopsy should be performed in patients with chronic kidney disease". Semin Nephrol. 34 (6): 612–25. doi:10.1016/j.semnephrol.2014.09.004. PMID 25498380.
5. ^ a b "KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD)" (PDF). 7 (1). July 2017. Cite journal requires `|journal=` (help)
6. ^ Bover J, Evenepoel P, Ureña-Torres P, Vervloet MG, Brandenburg V, Mazzaferro S, Covic A, Goldsmith D, Massy ZA, Cozzolino M, CKD-MBD Working Group of ERA-EDTA (2015). "Pro: Cardiovascular calcifications are clinically relevant". Nephrol Dial Transplant. 30 (3): 345–51. doi:10.1093/ndt/gfv020. PMID 25712934.
7. ^ Ketteler, Markus; Block, Geoffrey A.; Evenepoel, Pieter; Fukagawa, Masafumi; Herzog, Charles A.; McCann, Linda; Moe, Sharon M.; Shroff, Rukshana; Tonelli, Marcello A.; Toussaint, Nigel D.; Vervloet, Marc G.; Leonard, Mary B. (20 February 2018). "Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease–Mineral and Bone Disorder: Synopsis of the Kidney Disease: Improving Global Outcomes 2017 Clinical Practice Guideline Update". Annals of Internal Medicine. 168 (6): 422–430. doi:10.7326/M17-2640. PMID 29459980.
8. ^ Bover, J.; Ureña-Torres, P.; Lloret, M. J.; Ruiz-García, C.; DaSilva, I.; Diaz-Encarnacion, M. M.; Mercado, C.; Mateu, S.; Fernández, E.; Ballarin, J. (1 June 2016). "Integral pharmacological management of bone mineral disorders in chronic kidney disease (part I): from treatment of phosphate imbalance to control of PTH and prevention of progression of cardiovascular calcification". Expert Opinion on Pharmacotherapy. 17 (9): 1247–1258. doi:10.1080/14656566.2016.1182155. hdl:10459.1/63216. PMID 27156993.
## External links[edit]
* Chronic Kidney Disease-Mineral and Bone Disorder (NIDDKD)
* Current Concepts and Management Strategies in Chronic Kidney Disease-Mineral and Bone Disorder (Medscape)
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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
| Chronic kidney disease-mineral and bone disorder | c1527410 | 2,020 | wikipedia | https://en.wikipedia.org/wiki/Chronic_kidney_disease-mineral_and_bone_disorder | 2021-01-18T18:31:46 | {"mesh": ["D012080"], "umls": ["CL505711"], "wikidata": ["Q25339734"]} |
Necrotizing autoimmune myopathy (NAM) is a rare form of idiopathic inflammatory myopathy characterized clinically by acute or subacute proximal muscle weakness, and histopathologically by myocyte necrosis and regeneration without significant inflammation.
## Epidemiology
The prevalence and annual incidence of NAM are not known but the disorder is very rare. About 300 cases have been reported to date.
## Clinical description
Age of onset ranges from 30 to 70 years of age in reported cases. The main presenting feature of NAM is subacute severe symmetrical proximal myopathy, with a markedly elevated creatine kinase (CK) level. Its presentation is similar to that of polymyositis (see this term) with upper and lower limb weakness causing difficulty in moving from a sitting position, climbing stairs, or lifting objects The neck flexor, pharyngeal, and respiratorymuscles may also be involved. Other manifestations include fatigue, weight loss dysphagia and dyspnea. Interstitial lung disease (see this term) and cardiac involvement have also been reported. The course is often severe but may be self-limiting and recovery may occur within weeks to months of discontinuing the causative agent, if identified.
## Etiology
The disease is thought to be related to an immune response possibly triggered by drug therapy (statins), connective tissue diseases, or cancer. The exact mechanism underling the disorder is not known but some autoantibodies appear to be a likely cause. Malignancy may be involved.
## Diagnostic methods
Diagnosis is based on the clinical picture and on muscle biopsy showing minimal or no inflammatory infiltrates and marked muscle necrosis, unlike other inflammatory myopathies. Electromyography (EMG) shows myopathic findings. Creatine kinase (CK) levels are often more than 10 times above the upper limit of normal at the time of onset of muscle weakness. Magnetic resonance imaging (MRI) may show diffuse or patchy edema within muscles. Anti-SRP and anti-HMGCoAR autoantibodies are frequently associated with this condition. Currently, seronegative NAM represents 20-30% of the cases.
## Management and treatment
Treatment of the underlying cause, if identified, is essential (statin discontinuation, or malignancy). NAM patients generally respond well to multiple-agent, long-term immunosuppressive therapies starting by high dose corticosteroids. Intravenous immunoglobulin (IVIg) appears to be effective. Rituximab has also shown beneficial effects. Response to therapy should be assessed clinically on the basis of muscle strength and biologically on CK levels.
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*[AA]: Adrenergic agonist
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*[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
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| Immune-mediated necrotizing myopathy | c3267047 | 2,021 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=206569 | 2021-01-23T18:29:57 | {"umls": ["C3267047"], "icd-10": ["G72.4"], "synonyms": ["Anti-HMG-CoA myopathy", "Anti-SRP myopathy", "Autoimmune necrotizing myositis", "IMNM", "Immune myopathy with myocyte necrosis", "NAM"]} |
Weaver-Williams syndrome is a multiple congenital anomalies syndrome characterized by moderate-to-severe intellectual disability, decreased muscle mass, microcephaly, facial dysmorphism (prominent ears, midfacial hypoplasia, small mouth and cleft palate), clinodactyly of the fingers, delayed osseous maturation and generalized bone hypoplasia. The syndrome has been described in a brother and sister and an autosomal recessive mode of inheritance has been suggested. There have been no further descriptions in the literature since 1977.
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*[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
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| Weaver-Williams syndrome | None | 2,022 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3448 | 2021-01-23T19:12:24 | {"gard": ["5545"], "icd-10": ["Q87.8"]} |
## Description
Polycystic dysgenetic disease of the parotid gland (PDDP) is a rare benign condition of the parotid gland. The disorder presents often in childhood or young adulthood, but may occur later in life. It occurs most commonly in females. Features include fluctuating and nontender swelling of the parotid gland bilaterally, without defects in salivary function. Histology shows replacement of the lobular portion of the parotid gland by multiple epithelial-lined cysts arising from the intercalated ducts. The cysts often contain altered salivary secretions, including spheroliths or microliths; eosinophilic congophilic deposits have also been described. Chronic inflammation is not present. The condition is thought to result from a developmental defect of the intercalated duct system. Surgery may be indicated for diagnosis or for cosmetic reasons (summary by Smyth et al., 1993; Layfield and Gopez, 2002; Eley et al., 2011).
Clinical Features
Seifert et al. (1981) first delineated dysgenetic (primary) polycystic disease of the parotid glands as a distinct entity. The disorder was found in 2 unrelated patients out of a series 5,739 cases of salivary gland disturbances, 360 of which were nontumorous cysts of the salivary gland. A 6-year-old girl had painless, recurrently swollen parotid glands bilaterally, although palpation revealed tenderness. Biopsy showed that the gland lobules were permeated with variably sized cysts lined with flattened or cuboidal epithelial cells, some of which showed degenerative changes. Some of the cysts showed spur-like or incomplete septa. There were multiple spheroliths with concentric and radial patterns in the lumens of the cysts. Rests of glandular parenchyma were present between the cysts. The girl's father reportedly had similar changes in the parotid gland until age 12 years. The other patient was a 65-year-old woman with a 9-year history of progressive swelling of the right parotid gland. Sialography showed extended spherical ectasias in the vicinity of the peripheral duct segments. Pathology showed that the gland lobules were interspersed with duct cysts bound by flat epithelium and containing flaky lumps of secretory material. Remnants of gland acini could be seen among the cysts. Seifert et al. (1981) suggested that the cystic changes resulted from a developmental abnormality of the intercalated duct system of the gland, particularly a disturbance of branching and canalization of the terminal salivary duct buds. The differential diagnosis includes congenital sialectasias of the parotid gland, salivary duct cysts, and lymphoepithelial cysts.
Dobson and Ellis (1987) reported a 23-year-old woman with bilateral polycystic disease of the parotid gland. She had a history of fluctuating swelling since childhood. Sialogram showed fine punctate mottling of the gland with normal Stensen ducts. Secretory products within the cysts showed congophilic deposits, consistent with amyloid.
Batsakis et al. (1988) described the histologic findings in 3 additional unrelated women with the disorder. Two had bilateral parotid swelling since childhood, whereas 1 had unilateral swelling in 1 gland since puberty and developed involvement of the other gland as a young adult. The microscopic changes were virtually identical in all 3 cases: the functional acinar parenchyma of the glands was nearly completely replaced by honeycombed, latticework-like cystic changes. Small clusters of functional acini and ducts appeared as islands amid variably sized cysts. The cystic spaces were lined by flattened or cuboidal epithelial cells. Some of the cells showed hydropic changes and were sloughed into the cysts. In a review of the disorder, Batsakis et al. (1988) noted that secretory products within the cysts can range from a watery fluid to inspissated proteinaceous secretions, which may form laminated microliths or spheroliths. Dysplastic and inflammatory changes are absent, although there may be a mild inflammatory reaction to extravasated fluid.
Smyth et al. (1993) reported a mother and daughter with the condition. The daughter presented at age 18 years with bilateral, preauricular, painless swellings. The right-sided swelling began about 2 years prior to presentation, whereas the left-sided swelling had been present since early childhood. Imaging showed multiple cysts confined to the parotid glands. Parotidectomy and subsequent histologic examination showed that most of the gland was replaced by a gelatinous material surrounding multiple cystic spaces containing a mucinous fluid. There were numerous cysts of variable sizes, most lined by low simple squamous epithelium. Cysts were empty or contained inspissated material, mostly amorphous, but sometimes the material was keratin-like material or contained dystrophic calcified foci. The mother had a similar history of progressive swelling of the left parotid gland that began in adolescence; she had had 4 separate operations. There was no history of right-sided facial swelling in the mother.
Brown et al. (1995) reported a 31-year-old pregnant woman who presented at 4 months of pregnancy with bilateral painless swelling of the parotid glands with no other features. She had a history of recurrent episodes of swollen parotids as a child. MRI after the birth showed well-circumscribed glands with multiple cysts. Sialogram showed stretching of the intraglandular ductal system with no evidence of sialectasis or duct irregularity. Biopsy showed numerous small cysts lined with flattened to cuboidal epithelial cells, many of which were vacuolated or sloughed into the cyst lumen. Residual normal-appearing acini were scattered among the cysts. A needle aspirate showed an amyloid-like material, which was shown on biopsy to represent eosinophilic spheroliths.
Layfield and Gopez (2002) reported a 21-year-old man with the condition. Fine needle aspiration showed small numbers of epithelial cell clusters with a polygonal shape. Most had low columnar to cuboidal appearance with basely situated nuclei; some of the cells contained vacuoles. Parotidectomy showed near total replacement of the acinar tissue with a honeycomb of cystic spaces of various sizes and shapes. The cysts were lined by flattened to cuboidal epithelial cells. Some of the cysts contained multilaminated spheroliths. His father reportedly had the same condition. Layfield and Gopez (2002) discussed the differential diagnosis and cytologic features of various cystic lesions of the parotid gland.
Eley et al. (2011) reported an 8-year-old boy with recurrent nontender parotid swelling. He had a history of atopy with asthma, eczema, hay fever, and a nut allergy. Biopsy showed cystic dilation of the terminal ducts throughout the tissue, consistent with PDDP. The authors emphasized the benign nature of the condition.
Inheritance
Ficarra et al. (1996) reported histologically confirmed dysgenetic polycystic disease of the parotid gland in a woman, her mother, and her maternal grandmother, suggesting autosomal dominant inheritance.
History
Mihalyka (1962) reported the case of a 67-year-old woman with a 40-year history of bilateral recurrent nontender swelling of the parotid salivary glands, unrelated to meals. However, the diagnosis could not be substantiated because no histology was reported (Smyth et al., 1993). Marie et al. (1967) described the condition in 5 patients in 3 generations.
Mandel and Kaynar (1991) reported a 14-year-old girl with unilateral swelling of the parotid gland that spontaneously resolved. She had reduced salivary flow and radiographs showed small calcifications. Sialogram showed cystic pools connected to intact ductal structures, as well as several stones. However, Smyth et al. (1993) and Brown et al. (1995) concluded that the patient reported by Mandel and Kaynar (1991) did not have polycystic parotid disease. There was no histopathologic analysis, and the sialoceles were connected to intact ductal structures, which is more consistent with acquired salivary duct cysts or congenital sialectasis. Also, the patient had a marked reduction in salivary flow, which is not a feature of polycystic parotid disease.
INHERITANCE \- Autosomal dominant HEAD & NECK Mouth \- Parotid gland swelling, bilateral \- Normal acini are replaced with honeycombed cysts \- Cysts may contain watery secretions or spheroliths and microliths \- Cysts lined by cuboidal or flattened epithelial cells \- Epithelial cells may be sloughed into cysts \- Lack of inflammation MISCELLANEOUS \- Occurs much more commonly in women \- Onset in young adulthood \- Childhood onset may occur \- Nontender \- Benign condition ▲ Close
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*[c.]: circa
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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
| PAROTID SALIVARY GLANDS, POLYCYSTIC DYSGENETIC DISEASE OF | c3551133 | 2,023 | omim | https://www.omim.org/entry/600343 | 2019-09-22T16:16:15 | {"omim": ["600343"]} |
A number sign (#) is used with this entry because hypokalemic periodic paralysis type 2 (HOKPP2) is caused by heterozygous mutation in the SCN4A gene (603967).
Mutations in the SCN4A gene can also cause hyperkalemic periodic paralysis (HYPP; 170500).
For a general phenotypic description and a discussion of genetic heterogeneity of HOKPP, see HOKPP1 (170400), which is caused by mutation in the CACNL1A3 gene (CACNA1S; 114208).
Clinical Features
Bulman et al. (1999) reported 2 cousins with HOKPP. The proband experienced a first paralytic attack at age 14 on awakening in the morning, and was found to have a serum potassium of 2.2 mmol/L. Myotonia was not present. Similar paralytic episodes involving either his legs or all 4 limbs recurred with variable frequency, ranging from 1 to 2 times per week to once every 2 months. Potassium supplementation was effective. His cousin had a similar phenotype.
Sugiura et al. (2000) reported an unusual HOKPP phenotype in a Japanese family. Affected members showed heat-induced myotonia and cold-induced paralysis with hypokalemia. Myotonia lessened with exercise and was alleviated by cold, which distinguished the disorder from paramyotonia congenita (PMC; 168300). Treatment with acetazolamide alleviated the myotonia, but slightly worsened the paralysis. Patients showed seasonal swings with myotonia in the summer and paralysis in the winter, with hypokalemia during the paralytic attacks.
Venance et al. (2004) reported a sporadic patient with HOKPP2, confirmed by mutation in the SCN4A gene (603967.0020), who responded well to acetazolamide. The authors noted the variability in response to the drug in HOKPP, and suggested that carbonic anhydrase inhibitors should be considered in patients with SCN4A-associated HOKPP.
In a review of 71 patients from 56 kindreds with HOKPP, Miller et al. (2004) found that 64% of kindreds had mutations in either the CACNA1S or SCN4A genes. The arg1239-to-his (R1239H; 114208.0001) and arg528-to-his (R528H; 114208.0003) mutations of the CACNA1S gene were the most common mutations, each found in 42% of kindreds. Five kindreds had SCN4A mutations. No mutations were identified in 20 kindreds. HOKPP patients with mutations had a significantly earlier age at disease onset (10 years) compared to those without mutations (22 years); however, 2 patients with mutations presented at ages 23 and 26 years, respectively. Among those with mutations, the disease was most severe during the teenage years, and 72% of patients had residual muscle weakness. Muscle biopsies showed vacuolar changes in 80% of patients with CACNA1S mutations; these changes were not seen in any patients without mutations. Treatment with acetazolamide was beneficial in 85% of those with mutations and 100% of those without mutations. In a diagnostic flow chart for the periodic paralyses, Miller et al. (2004) indicated that HOKPP shows onset in childhood to adolescence and is characterized by infrequent but severe attacks, often lasting up to 24 hours, and decreased serum potassium. Myotonia is not a feature.
Molecular Genetics
Studying families in which linkage to the CACNL1A3 gene had been excluded, Bulman et al. (1999) identified a mutation in the SCN4A gene (603967.0015), and Jurkat-Rott et al. (2000) identified other mutations (603967.0016 and 603967.0017) in the same gene. The clinical picture did not differ from that of HOKPP caused by mutations in the CACNL1A3 gene.
In a Japanese family with an unusual temperature-dependent HOKPP phenotype, Sugiura et al. (2000) identified a mutation in the SCN4A gene (P1158S; 603967.0021).
Davies et al. (2001) found that 11 of 36 families with HOKPP harbored mutations in the CACNA1S gene (114208.0001 and 114208.0003), whereas only 1 family had a mutation in the SCN4A gene (603967.0020), suggesting that SCN4A mutations are an uncommon cause of HOKPP in the U.K. Among 58 independent index cases of HOKPP, Sternberg et al. (2001) found that 40 were linked to the CACNA1S gene and 5 to the SCN4A gene, all of which were in the same codon (see, e.g., 603967.0016). Thirteen families remained without known mutations, indicating genetic heterogeneity.
Matthews et al. (2009) identified mutations in the CACNA1S or SCN4A gene in 74 (almost 90%) of 83 patients with HOKPP. All of the mutations, including 3 novel mutations, affected arginine residues in the S4 voltage sensing region in 1 of the transmembrane domains of each gene. The most common mutations affected residues arg528 (25 cases) and arg1239 (39 cases) in CACNA1S (see, e.g., R1239H; 114208.0001 and R528H; 114208.0003). The most common mutations in SCN4A affected residues arg672 (see, e.g., 603967.0016) and arg1132. The findings supported the hypothesis that loss of positive charge in S4 voltage sensors is important to the pathogenesis of this disorder. (Sokolov et al., 2007).
Pathogenesis
In muscle fibers of patients with HOKPP, Rudel et al. (1984) determined that the basic defects were a reduced excitability and an increased sodium conductance, and that these defects were aggravated by reduction of the extracellular potassium concentration.
In a commentary, Ruff (2000) reviewed the evidence that HOKPP is caused by membrane depolarization triggering sodium channel inactivation, which renders the muscle membrane inexcitable. In addition, SCN4A mutations may also result in decreased density of membrane sodium channels, also decreasing overall current. HOKPP resulting from calcium channel mutations (CACNA1S) represent an 'indirect channelopathy': membrane depolarization results from hypokalemia activating a pathologic depolarizing current and from decreased inward rectifier potassium channel conductance.
By in vitro studies, Kuzmenkin et al. (2002) showed that 2 mutations in the voltage sensor region of the SCN4A gene (R669H 603967.0015 and R672H; 603967.0016) showed enhanced inactivation. The inactivation defects could be alleviated by decreased pH, which may explain why some patients have relief by some physical exercise.
Sokolov et al. (2007) showed that 3 mutations in gating charge-carrying arginine residues in an S4 segment that cause HOKPP induced a hyperpolarization-activated cationic leak through the voltage sensor of the skeletal muscle Nav1.4 channel (SCN4A). This cation leak would substantially increase resting membrane conductance and sodium influx into HOKPP skeletal muscle fibers, resulting in a gain of function effect that contributes to the dominant inheritance, depolarization, reduced rate of rise and amplitude of the action potential, cytopathology, and episodic paralysis correlated with decreased serum potassium. The mutant channels showed similar permeability to sodium, potassium, and cesium ions, but the organic monovalent cations tetraethylammonium and N-methyl-D-glucamine were much less permeant. Sokolov et al. (2007) concluded that their results revealed gating pore current in naturally occurring disease mutations of an ion channel and showed a clear correlation between mutations that cause gating pore current and HOKPP. In addition, the findings contrasted with the well-established paradigm in which alterations in control of ion conductance through the central pore of ion channels impair cell function. Sokolov et al. (2007) postulated that their observations might be generalizable to other ion channelopathies.
Francis et al. (2011) demonstrated that an R1132Q mutation (603967.0030) in the domain III voltage sensor domain of SCN4A found in a family with HOKPP created an anomalous gating pore current similar to that observed by Sokolov et al. (2007). This current is sufficient to depolarize and render the muscle fiber inexcitable particularly during low external potassium. The findings suggested a mechanism for loss of sarcolemmal excitability during attacks of weakness in HOKPP. In contrast, the R1148C mutation (603967.0003) causing PMC (168300) did not result in gating pore abnormalities.
INHERITANCE \- Autosomal dominant MUSCLE, SOFT TISSUES \- Flaccid weakness or paralysis, episodic attacks \- Attacks last 4 to 24 hours \- Attacks precipitated by hypokalemia, administration of glucose or insulin, heavy carbohydrate consumption, stress, fatigue, rest after exercise \- Attacks may present during or after sleep \- Attacks relieved by potassium administration \- Attacks usually decrease or disappear after age 40 years \- Progressive interictal weakness is common \- Myotonia is usually not seen \- Vacuolar myopathy may occur \- Tubular aggregates in muscle fibers may occur \- Acetazolamide may worsen symptoms LABORATORY ABNORMALITIES \- Hypokalemia occurs during paralytic attacks MISCELLANEOUS \- Onset usually in second decade (may occur earlier) \- One-third of cases are sporadic \- Variable phenotype \- Reduced penetrance in females \- Allelic disorder to hyperkalemic periodic paralysis (HYPP, 170500 ) MOLECULAR BASIS \- Caused by mutation in the alpha subunit of the type IV voltage-gated sodium channel gene (SCN4A, 603967.0015 ). ▲ 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
| HYPOKALEMIC PERIODIC PARALYSIS, TYPE 2 | c0238358 | 2,024 | omim | https://www.omim.org/entry/613345 | 2019-09-22T15:58:54 | {"doid": ["14452"], "mesh": ["D020514"], "omim": ["613345"], "orphanet": ["681"]} |
Mild phenylketonuria is a rare form of phenylketouria (PKU variant), an inborn error of amino acid metabolism, characterized by symptoms of PKU of mild to moderate severity. Patients with blood phenylalanine concentrations of 600-1,200 micromol/L are considered to have mild PKU. Clinical signs include reduced cognitive function and behavioral and developmental disorders. It is caused by certain mutations in the PAH gene which result in slightly higher activity of the phenylalanine hydroxylase compared with the classic phenylketonuria where there is a complete or near-complete deficiency of phenylalanine hydroxylase activity. Inheritance is autosomal recessive. Treatment is with a diet low in phenylalanine (patients can have up to 400-600 mg/day of phenylalanine).
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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
| Mild phenylketonuria | None | 2,025 | gard | https://rarediseases.info.nih.gov/diseases/10324/mild-phenylketonuria | 2021-01-18T17:59:03 | {"umls": ["C0543528"], "orphanet": ["79253"], "synonyms": ["Mild PKU", "mPKU", "Variant phenylketonuria", "Variant PKU"]} |
A number sign (#) is used with this entry because of evidence that ectodermal dysplasia/skin fragility syndrome is caused by homozygous or compound heterozygous mutation in the plakophilin-1 gene (PKP1; 601975) on chromosome 1q32.
Clinical Features
McGrath et al. (1997, 1999) described a boy with a unique skin disorder comprising trauma-induced skin fragility and congenital ectodermal dysplasia affecting hair, nails, and sweat glands. The proband reported by McGrath et al. (1997) was a 6-year-old boy with unrelated parents. There was no family history of skin blistering or other significant abnormalities. At birth, all of his skin was lobster pink, with blistering on the soles. Over the first 48 hours, he developed more severe blistering and desquamation on his face, limbs, and buttocks. His hair was noted to be short and sparse, and his nails were thickened and dystrophic. Subsequently, his skin continued to show fragility, with trauma-induced tearing and blisters on the pressure points of the soles after prolonged standing or walking. Light microscopy of the skin revealed thickening of the epidermis and extensive widening of keratinocyte intercellular spaces, extending from the first suprabasal layer upward. Electron microscopy showed a loss of keratinocyte-keratinocyte adhesion, and desmosomes, particularly in the lower suprabasal layers, were small and reduced in number. There was complete absence of immunostaining for plakophilin-1 in the skin. The proband was found to be a compound heterozygote for a premature termination codon on each of the 2 alleles of the PKP1 gene (see 601975.0001 and 601975.0002).
McGrath (2000) reported observations on 2 further unrelated cases of this syndrome. In one of these patients, a 17 year old, the scalp hair started to regrow a little after the age of 7 years, and the abnormality of sweating became much less marked. Most notable, however, was the painful, disabling cracking and hyperkeratosis of the palms and soles, also seen in the 3 other cases. The affected toddlers and children had to be carried about by their parents, and the 17-year-old patient, who had normal intelligence like the others, had gone through school in a wheelchair due to the effects of the disease on the soles of the feet. All 4 patients, who were from different families, showed loss of plakophilin-1.
Using immunohistochemistry and quantitative electron microscopy, McMillan et al. (2003) examined suprabasal desmosomes from 3 PKP1-deficient patients, an unaffected carrier with a PKP1-heterozygous acceptor splice site mutation, and 5 healthy control subjects. Compared with those in controls, desmosomes in PKP1-null patients were reduced dramatically both in size (49%) and frequency (61%) in the lower suprabasal layers (p less than 0.01). In the lower suprabasal compartment of the heterozygous carrier, corresponding reductions were 37% and 20%, respectively (p less than 0.01). Surprisingly, in the PKP1-null patients' upper suprabasal layer, desmosome size was larger (59%, p less than 0.01) than the control value, and showed increased desmoglein-1 (125670) and PKP2 (602861) staining. The upper suprabasal layer desmosome frequency in PKP1-null patients was similar to that seen in the lower suprabasal compartment but reduced by 43% compared to controls. The carrier showed no difference in the upper suprabasal layer desmosome size and frequency compared with the controls (p greater than 0.05). The PKP1-null patients showed poorly developed inner and outer desmosomal plaques. Thus, both the patients and unaffected carrier showed reductions in the lower suprabasal layer desmosome size and number, despite only PKP1-null patients exhibiting any phenotype. These findings attest to the molecular recruiting and stabilizing roles of PKP1 in desmosome formation, particularly in the lower suprabasal compartment.
Molecular Genetics
In a patient with ectodermal dysplasia/skin fragility syndrome, McGrath et al. (1997) identified compound heterozygosity for premature termination codons in the PKP1 gene (601975.0001-601975.0002).
In a 17-year-old patient with ectodermal dysplasia/skin fragility syndrome, Whittock et al. (2000) identified a homozygous splice site mutation in the PKP1 gene (601975.0003).
*[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 inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| ECTODERMAL DYSPLASIA/SKIN FRAGILITY SYNDROME | c1858302 | 2,026 | omim | https://www.omim.org/entry/604536 | 2019-09-22T16:11:54 | {"mesh": ["C536183"], "omim": ["604536"], "orphanet": ["158668"], "synonyms": ["Alternative titles", "MCGRATH SYNDROME"]} |
Oligomeganephronia is a developmental anomaly of the kidneys, and the most severe form of renal hypoplasia (see this term), characterized by a reduction of 80% in nephron number and a marked hypertrophy of the glomeruli and tubules.
## Epidemiology
Prevalence is unknown. The male to female ratio is of 3:1.
## Clinical description
Oligomeganephronia is usually detected on routine ultrasound screening with small but normal shaped kidneys. Birth weight is often below the average value. Patients may present at birth with polyuria/polydipsia or signs of renal dysfunction such as anemia. During the first year of life, the usual symptom is persistent anorexia with vomiting, fever, and height-weight growth delay. Renal failure typically occurs during childhood or adolescence. Adult-onset oligomeganephronia has been reported in some rare cases.
## Etiology
The etiology of oligomeganephronia is not fully understood, but is hypothesized to be caused by premature termination of nephrogenesis. This may be linked to the same factors as renal hypoplasia, but with a more severe reduction in nephron numbers. Such factors include intrauterine growth restriction, maternal diseases (diabetes, hypertension), maternal drug intake (inhibitors of the renin-angiotensin system or non-steroidal anti-inflammatory drugs (NSAIDs)) or intoxication (smoking and alcohol). Premature birth (before the 36th week) is also a risk factor due to incomplete nephrogenesis. Oligomeganephronia can occur as part of a multi-organ syndrome such as renal coloboma syndrome (see this term), which is caused by mutations in the PAX2 gene (10q24.31), or can be caused by chromosomal disorders including 22q11 deletion syndrome or Wolf-Hirschhorn syndrome (see this term).
## Diagnostic methods
Diagnosis can be suspected by bilateral small and echogenic kidneys on ultrasound. CT-scan may, in addition to small normal-shaped kidneys, show a thickened cortex and medulla with striated nephrograms. The diagnosis is confirmed histologically by a reduced number of nephrons, hypertrophic glomeruli with diameters being two to three times the normal size, hypertrophic tubules and thickening of Bowman's capsule. Both kidneys are symmetrically affected.
## Differential diagnosis
Differential diagnosis includes renal dysplasia, nephronophthisis, (see these terms), medullary cystic kidney disease, renal infarction or ischemic renal disease, and diffuse renal parenchymal disease.
## Antenatal diagnosis
Antenatal ultrasonographic screening is becoming routine and allows detection of oligomeganephronia from midway through gestation.
## Genetic counseling
Most cases are sporadic, but familial occurrence has been described.
## Management and treatment
Angiotensin-converting-enzyme inhibitors may slow the progression of the disease. Once having reached the stage of terminal renal failure, management includes a dialysis-transplantation program.
## Prognosis
With the increasing metabolic demands on the kidney during growth, a decline in renal function is seen resulting in chronic renal failure at a mean age of 10 years (range 6 months to 20 years).
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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
| Oligomeganephronia | c0431694 | 2,027 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2260 | 2021-01-23T18:12:53 | {"gard": ["4066"], "icd-10": ["Q60.4"], "synonyms": ["Oligomeganephronic renal hypoplasia"]} |
A number sign (#) is used with this entry because of evidence that SHORT syndrome can be caused by heterozygous mutation in the PIK3R1 gene (171833) on chromosome 5q13.
Description
'Short,' the mnemonic designation for this syndrome, is an acronym: S = stature; H = hyperextensibility of joints or hernia (inguinal) or both; O = ocular depression; R = Rieger anomaly; T = teething delay. The name was given by Gorlin (1975), who described the syndrome in 2 brothers.
Dyment et al. (2013) noted that the features listed in the acronym for SHORT syndrome do not capture the full range of the clinical phenotype, which can include a recognizable facial gestalt consisting of triangular facies, lack of facial fat, and hypoplastic nasal alae with overhanging columella, as well as near-universal partial lipodystrophy, insulin resistance, nephrocalcinosis, and hearing deficits. Notably, both developmental milestones and cognition are normal for individuals with SHORT syndrome.
Clinical Features
Sensenbrenner et al. (1975) described a 6-year-old girl with Rieger anomaly, short stature, and partial lipodystrophy of the face and upper limbs. She also had delayed dental eruption, delayed bone age, and hyperextensibility of the joints. Gorlin (1975) reported the same condition in 2 brothers, aged 11 and 4 years. Gorlin (1975) suggested autosomal recessive inheritance because of possible consanguinity in 1 set of parents.
Aarskog et al. (1983) described a family from the Lofoten Islands of Norway in which 4 persons in 3 generations had nonprogressive lipodystrophy present from infancy affecting primarily the face and buttocks. Affected persons also had the Rieger anomaly, midface hypoplasia, retarded bone age, and hypotrichosis. Of 2 sisters, 1 had glucose intolerance at age 55 years, and the other had insulinopenic diabetes mellitus at age 39 years. Aarskog et al. (1983) suggested that the disorder in their family was distinct from SHORT syndrome because of the absence of joint hypermobility and less extensive lipodystrophy in their patients.
Toriello et al. (1985) reported a patient with SHORT syndrome characterized by lipoatrophy, delayed speech development, clinodactyly, and short stature. The boy also had deafness, which the authors noted had not previously been reported in the SHORT syndrome. Stratton et al. (1989) reported a brother and sister with short stature, delayed bone age, developmental delay, congenital hip dislocation, and iridocorneal abnormalities with onset of glaucoma at or soon after birth. Many of the features resembled those of the SHORT syndrome, but triangular face and lipoatrophy were not present.
Schwingshandl et al. (1993) described a girl with most of the typical features of SHORT syndrome who, at age 14 years, developed nonketotic hyperglycemia. At the age of 16.5 years, diabetes mellitus with severe insulin resistance was diagnosed. From an early age, the patient had had partial lipodystrophy, as well as megalocornea and a peculiar progeria-like face. At age 6 years, bilateral sensorineural hearing loss was detected.
Verge et al. (1994) also described insulin-resistant diabetes in SHORT syndrome. They suggested that defective function of insulin receptors in adipose tissue may explain the paucity of fat storage in this disorder.
Bankier et al. (1995) described the association of triangular face, deep-set eyes, micrognathia, small facial bones, and narrow body build in 3 members of an English family and in an unrelated Australian girl. Absence of iridal stroma was found in the Australian girl and in the English mother; the son of the English woman also had sensorineural deafness. Bankier et al. (1995) noted that the symptom complex was similar to the SHORT syndrome, although all 4 patients had low-normal height and did not manifest joint hyperextensibility. Reardon and Temple (2008) reported that 1 of the female patients reported by Bankier et al. (1995) developed nephrocalcinosis as an adult. The affected son of this patient, who was diagnosed with SHORT syndrome in the neonatal period, had nephrocalcinosis and increased serum and urinary calcium at 2 months of age.
Sorge et al. (1996) described a 9-year-old Italian boy with short stature, partial lipodystrophy, minor facial anomalies, mild hyperextensibility of joints, ocular depression, Rieger anomaly, and delay in speech development and dental eruption. Because the father and sister showed a striking similarity to the propositus, Sorge et al. (1996) suggested an autosomal dominant gene with variable expression in this family. The sister had bilateral and symmetrical lens opacities, a feature that had not been reported previously in affected subjects or their relatives. Sorge et al. (1996) suggested that the disorder reported by Aarskog et al. (1983) was the same disorder.
Brodsky et al. (1996) added congenital glaucoma as a feature of the SHORT syndrome. Their patient was a 9-year-old boy who had enlarged cloudy corneas, Rieger anomaly, and elevated intraocular pressure at birth. He also had bilateral sensorineural hearing loss, short stature, and mild developmental delay. The face had a triangular configuration with prominent forehead, deeply set eyes, thin nasal alae, and a proportionately small middle and lower face. The face and chest showed diminished subcutaneous fat, and the hands had thin, dry, wrinkled skin, producing a progeroid appearance. A paternal uncle reportedly had a similar appearance.
Koenig et al. (2003) described a mother and son with short stature, progeroid facies, Rieger anomaly, teething delay, mild developmental retardation, particularly speech delay, and a slight build with lack of subcutaneous fat. Resistance to insulin was suggested by an oral glucose tolerance test in the mother, whereas the test was normal in the son at the age of 2 years. After reviewing the reported cases of SHORT syndrome, Koenig et al. (2003) concluded that 5 familial cases in different generations, equally affected male and female patients, and male-to-male transmission support autosomal dominant inheritance, possibly with germline mosaicism in the cases of affected sibs and unaffected parents.
Reardon and Temple (2008) reported 3 patients, including a mother and son previously reported by Bankier et al. (1995), with a clinical diagnosis of SHORT syndrome who all developed nephrocalcinosis. Two of the patients had nephrocalcinosis in infancy and also showed increased serum and urinary calcium. Reardon and Temple (2008) postulated that disordered calcium metabolism may be a previously unreported feature of SHORT syndrome.
Reis et al. (2011) studied a 6-year-old Caucasian girl with a diagnosis of SHORT syndrome, whose ocular features included Rieger anomaly, congenital glaucoma, microcornea, and nystagmus. She had short stature, poor weight gain, and macrocephaly, as well as hyperextensible joints, delayed eruption of teeth, decreased subcutaneous fat in the upper trunk and head, and dysmorphic facial features including prominent forehead, sunken eyes, small chin, and hypoplastic nares. Her hearing was normal, hands and feet were small with normal structure, and umbilicus was described as 'a bit pouchy' with mildly increased skin. Brain MRI showed normal structures.
Avila et al. (2016) reviewed the clinical features of 32 individuals, including 8 newly ascertained patients, with genetically confirmed SHORT syndrome. The major features described in the SHORT acronym were not universally seen, and only half (52%) had 4 or more of the classic features. The most common features included intrauterine and postnatal growth restriction, lipoatrophy, and a characteristic facial gestalt characterized by a progeroid appearance with prominent forehead, triangular face, deep-set eyes, hypoplastic alae nasi, midface hypoplasia, small chin, low-set ears, and downturned mouth. Hyperextensible joints or inguinal hernia was found in only 10 of 29 cases, and Rieger anomaly was only found in 13 of 30 cases, although some patients had other anterior chamber defects. Insulin resistance was found in 13 of 17 patients, and diabetes was found in 9 of 14. Three patients had cardiac anomalies and 5 had sensorineural deafness. Avila et al. (2016) concluded that cardinal features of the disorder warranting monitoring include lipoatrophy and insulin resistance, and that minor features of SHORT syndrome should include teething delay, thin wrinkled skin, speech delay, sensorineural deafness, hyperextensibility of joints, and inguinal hernia.
Cytogenetics
In a mother with Rieger syndrome (180500) and polycystic ovaries (see 184700) and a son manifesting SHORT syndrome, Karadeniz et al. (2004) identified a t(1;4)(q31.2;q25) translocation. Because Rieger syndrome can be caused by mutation in the PITX2 gene (601542) on chromosome 4q25, Karadeniz et al. (2004) suggested that the 2 syndromes may represent a single condition reflecting variable expression of this gene.
In a 6-year-old Caucasian girl with the complete constellation of features comprising SHORT syndrome, in whom screening of PITX2 showed normal sequence and copy number, Reis et al. (2011) identified heterozygosity for a 2.263-Mb deletion on chromosome 14q22.1-q22.2, encompassing BMP4 (112262) and 13 other genes. The minimum deleted interval was chr14:51,402,258-53,665,008 and the maximum interval was chr14:51,400,039-53,667,259 (NCBI36). Quantitative PCR confirmed deletion of 1 copy of BMP4 and the presence of both copies of the OTX2 gene (600037). The patient's mother, who had high myopia but otherwise normal ocular and systemic features, showed no evidence of BMP4 deletion; the unaffected father was unavailable for testing. Reis et al. (2011) suggested that SHORT syndrome might be a contiguous gene deletion syndrome requiring deletion of 1 or more other genes in addition to BMP4.
Molecular Genetics
By whole-exome sequencing in 2 unrelated patients with SHORT syndrome, Thauvin-Robinet et al. (2013) identified de novo mutations in the PIK3R1 gene (171833.0002 and 171833.0003). Screening PIK3R1 for mutations in 4 more affected individuals from 3 families, including a patient previously studied by Bonnel et al. (2000), revealed a recurrent substitution (R649W; 171833.0004) in all 4 patients. Thauvin-Robinet et al. (2013) then sequenced PIK3R1 in a heterogeneous clinical group of 14 additional unrelated individuals with severe insulin resistance and/or generalized lipoatrophy associated with dysmorphic features and growth retardation, who had not previously been diagnosed with SHORT syndrome and who were negative for mutation in known lipodystrophy-associated genes. Three of the 14 patients had mutations in PIK3R1, including 1 with the recurrent R649W substitution and another with a 1-bp duplication at R649 (171833.0005).
In a 3-generation Norwegian family with SHORT syndrome originally described by Aarskog et al. (1983), Chudasama et al. (2013) performed whole-exome sequencing and identified a heterozygous missense mutation in the PIK3R1 gene (R649W) that segregated with disease in the family and was not found in 340 Norwegian controls. Sanger sequencing of DNA from a German mother and son with SHORT syndrome, originally reported by Koenig et al. (2003), revealed that they were also heterozygous for the PIK3R1 R649W mutation. Haplotype analysis showed that the mutations resided on different backgrounds in the 2 families, indicating that they stemmed from 2 independent mutational events.
Dyment et al. (2013) performed whole-exome sequencing in a girl with SHORT syndrome and her unaffected parents and identified a frameshift mutation in the PIK3R1 gene (171833.0006) that segregated with disease. Analysis of PIK3R1 in 3 more SHORT probands revealed the R649W mutation in an affected mother and 2 sons from an English family, originally reported by Bankier et al. (1995) and restudied by Reardon and Temple (2008), and in another patient. A PIK3R1 nonsense mutation was identified in the third patient. In a 10-year-old boy diagnosed with SHORT syndrome, previously studied by Reardon and Temple (2008), no disease-causing variant was detected by whole-exome sequencing; coverage for PIK3R1 was excellent, and there was no evidence of any structural variant. Dyment et al. (2013) noted that although the boy showed several core features of SHORT syndrome, his facial features appeared to be distinct from those of mutation-positive individuals. The authors suggested that SHORT syndrome is a highly specific diagnosis that relies heavily on the facial gestalt.
### Associations Pending Confirmation
For discussion of a possible association between SHORT syndrome and variation in the PRKCE gene, see 176975.0001.
INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature \- Birth length less than 3rd percentile Weight \- Birth weight less than 3rd percentile Other \- Intrauterine growth retardation HEAD & NECK Face \- Triangular face \- Chin dimple \- Micrognathia \- Prominent forehead \- Midface hypoplasia Ears \- Hearing loss, sensorineural \- Large ears Eyes \- Deep-set eyes \- Rieger anomaly \- Telecanthus \- Glaucoma \- Megalocornea \- Cataracts \- Myopia Nose \- Hypoplastic nasal alae \- Wide nasal bridge Mouth \- Downturned corners of the mouth Teeth \- Delayed dental eruption \- Hypodontia \- Malocclusion GENITOURINARY External Genitalia (Male) \- Inguinal hernia SKELETAL \- Joint laxity \- Delayed bone age Limbs \- Large epiphyses \- Gracile diaphyses Hands \- Clinodactyly SKIN, NAILS, & HAIR Skin \- Dimples (chin, buttocks) \- Thin, wrinkled skin MUSCLE, SOFT TISSUES \- Lipoatrophy (lower face, upper limb, buttock) NEUROLOGIC Central Nervous System \- Normal intelligence \- Speech delay ENDOCRINE FEATURES \- Glucose intolerance \- Insulin resistant diabetes LABORATORY ABNORMALITIES \- Hyperglycemia MISCELLANEOUS \- SHORT is an acronym for Short stature, Hyperextensibility of joints/hernia, Ocular depression, Rieger anomaly, Teething delay \- De novo mutation identified in some patients MOLECULAR BASIS \- Caused by mutation in the phosphatidylinositol 3-kinase, regulatory, 1 gene (PIK3R1, 171833.0002 ) ▲ 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 inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| SHORT SYNDROME | c0878684 | 2,028 | omim | https://www.omim.org/entry/269880 | 2019-09-22T16:22:25 | {"mesh": ["C537327"], "omim": ["269880"], "orphanet": ["3163"], "synonyms": ["Alternative titles", "SHORT STATURE, HYPEREXTENSIBILITY, HERNIA, OCULAR DEPRESSION, RIEGER ANOMALY, AND TEETHING DELAY", "LIPODYSTROPHY, PARTIAL, WITH RIEGER ANOMALY AND SHORT STATURE"], "genereviews": ["NBK201365"]} |
This article is about a neuromuscular disorder of boys caused by a genetic defect in the UBA1 gene. For other conditions with similar name, see Spinal muscular atrophies.
X-linked spinal muscular atrophy type 2
Other namesSpinal muscular atrophy with arthrogryposis
This condition is inherited in an X-linked recessive manner
SpecialtyNeurology
X-linked spinal muscular atrophy type 2 (SMAX2, XLSMA), also known as arthrogryposis multiplex congenita X-linked type 1 (AMCX1), is a rare neurological disorder involving death of motor neurons in the anterior horn of spinal cord resulting in generalised muscle wasting (atrophy). The disease is caused by a mutation in UBA1 gene and is passed in an X-linked recessive manner by carrier mothers to affected sons.[1][2]
Affected babies have general muscle weakness, weak cry and floppy limbs; consequently, the condition is usually apparent at or even before birth. Symptoms resemble the more severe forms of the more common spinal muscular atrophy (SMA); however, SMAX2 is caused by a different genetic defect and only genetic testing can correctly identify the disease.[citation needed]
The disorder is usually fatal in infancy or early childhood due to progressive respiratory failure, although survival into teenage years have been reported.[3] As with many genetic disorders, there is no known cure to SMAX2. Appropriate palliative care may be able to increase quality of life and extend lifespan.[citation needed]
## Contents
* 1 See also
* 2 References
* 3 Further reading
* 4 External links
## See also[edit]
* Spinal muscular atrophies
* Arthrogryposis
## References[edit]
1. ^ Ramser, J.; Ahearn, M. E.; Lenski, C.; Yariz, K. O.; Hellebrand, H.; Von Rhein, M.; Clark, R. D.; Schmutzler, R. K.; Lichtner, P.; Hoffman, E. P.; Meindl, A.; Baumbach-Reardon, L. (2008). "Rare Missense and Synonymous Variants in UBE1 Are Associated with X-Linked Infantile Spinal Muscular Atrophy". The American Journal of Human Genetics. 82 (1): 188–193. doi:10.1016/j.ajhg.2007.09.009. PMC 2253959. PMID 18179898.
2. ^ Dressman, D.; Ahearn, M. E.; Yariz, K. O.; Basterrecha, H.; Martínez, F.; Palau, F.; Barmada, M. M.; Clark, R. D.; Meindl, A.; Wirth, B.; Hoffman, E. P.; Baumbach-Reardon, L. (2007). "X-linked infantile spinal muscular atrophy: Clinical definition and molecular mapping". Genetics in Medicine. 9 (1): 52–60. doi:10.1097/GIM.0b013e31802d8353. PMID 17224690.
3. ^ Kobayashi, H.; Baumbach, L.; Matise, T. C.; Schiavi, A.; Greenberg, F.; Hoffman, E. (1995). "A gene for a severe lethal form of X-linked arthrogryposis (X-linked infantile spinal muscular atrophy) maps to human chromosome Xp11.3–q11.2". Human Molecular Genetics. 4 (7): 1213–1216. doi:10.1093/hmg/4.7.1213. PMID 8528211.
## Further reading[edit]
* Dlamini, N.; Josifova, D. J.; Paine, S. M. L.; Wraige, E.; Pitt, M.; Murphy, A. J.; King, A.; Buk, S.; Smith, F.; Abbs, S.; Sewry, C.; Jacques, T. S.; Jungbluth, H. (2013). "Clinical and neuropathological features of X-linked spinal muscular atrophy (SMAX2) associated with a novel mutation in the UBA1 gene". Neuromuscular Disorders. 23 (5): 391–398. doi:10.1016/j.nmd.2013.02.001. PMID 23518311.
* Baumbach-Reardon L.; Sacharow S.; Ahearn M. E. "Spinal Muscular Atrophy, X-Linked Infantile." 30 Oct 2008 [Updated 13 Sep 2012]. In: Pagon R. A.; Adam M. P.; Ardinger H. H.; et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2014. Available from: www.ncbi.nlm.nih.gov/books/NBK2594.
## External links[edit]
Classification
D
* ICD-10: G12.1
* OMIM: 301830
* MeSH: C535380
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Nervous system
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* Pelizaeus–Merzbacher disease
* SMAX2
Skin and related tissue
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* Becker's muscular dystrophy/Duchenne
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No primary system
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* v
* t
* e
Disorders of translation and posttranslational modification
Translation
* Ribosome: Diamond–Blackfan anemia
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* Initiation factor: Leukoencephalopathy with vanishing white matter
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Posttranslational modification
Protein folding
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* chaperonins: 3-Methylglutaconic aciduria 5
Protein targeting
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Ubiquitin
* E1: X-linked spinal muscular atrophy 2
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* Aneurysmal bone cyst
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SUMO
* OFC10
Other
* Multiple sulfatase deficiency
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## Summary
### Clinical characteristics.
Factor V Leiden thrombophilia is characterized by a poor anticoagulant response to activated protein C (APC) and an increased risk for venous thromboembolism (VTE). Deep vein thrombosis (DVT) is the most common VTE, with the legs being the most common site. Thrombosis in unusual locations is less common. Evidence suggests that heterozygosity for the Leiden variant has at most a modest effect on risk for recurrent thrombosis after initial treatment of a first VTE. It is unlikely that factor V Leiden thrombophilia (i.e., heterozygosity or homozygosity for the Leiden variant) is a major factor contributing to pregnancy loss and other adverse pregnancy outcomes (preeclampsia, fetal growth restriction, and placental abruption). The clinical expression of factor V Leiden thrombophilia is influenced by the following:
* The number of Leiden variants (heterozygotes have a slightly increased risk for venous thrombosis; homozygotes have a much greater thrombotic risk)
* Coexisting genetic thrombophilic disorders, which have a supra-additive effect on overall thrombotic risk
* Acquired thrombophilic disorders: antiphospholipid antibody (APLA) syndrome, paroxysmal nocturnal hemoglobinuria, myeloproliferative disorders, and increased levels of clotting factors
* Circumstantial risk factors including but not limited to pregnancy, central venous catheters, travel, combined oral contraceptive (COC) use and other combined contraceptives, oral hormone replacement therapy (HRT), selective estrogen receptor modulators (SERMs), obesity, leg injury, and advancing age
### Diagnosis/testing.
Factor V Leiden thrombophilia is suspected in individuals with a history of venous thromboembolism (VTE) manifest as deep vein thrombosis (DVT) or pulmonary embolism, especially in women with a history of VTE during pregnancy or in association with use of estrogen-containing contraceptives, and in individuals with a personal or family history of recurrent thrombosis. The diagnosis of factor V Leiden thrombophilia is established in a proband by identification of a heterozygous or homozygous c.1691G>A variant (referred to as the factor V Leiden variant in F5, the gene encoding factor V) in conjunction with coagulation tests such as the APC resistance assay.
### Management.
Treatment of manifestations: The first acute thrombosis is treated according to standard guidelines. The duration of oral anticoagulation therapy should be based on an assessment of the risks for VTE recurrence and anticoagulant-related bleeding.
Prevention of primary manifestations: In the absence of a history of thrombosis, long-term prophylactic anticoagulation is not routinely recommended for asymptomatic Leiden variant heterozygotes. A short course of prophylactic anticoagulation when circumstantial risk factors are present may prevent initial thrombosis in Leiden variant heterozygotes.
Surveillance: Periodic reevaluation of individuals on long-term anticoagulation to assess risks (bleeding) vs benefits.
Agents/circumstances to avoid:
* Women heterozygous for the Leiden variant and a history of VTE should avoid estrogen-containing contraception and HRT.
* Women homozygous for the Leiden variant with or without prior VTE should avoid estrogen-containing contraception and HRT.
* While asymptomatic women heterozygous for the Leiden variant should be counseled to consider alternative forms of contraception and control of menopausal symptoms, those electing use of:
* Oral contraceptives should avoid third-generation and other progestins with a higher thrombotic risk.
* Short-term HRT for severe menopausal symptoms should avoid oral formulations.
Evaluation of relatives at risk: Although the genetic status of apparently asymptomatic at-risk family members can be established using molecular genetic testing, the indications for testing of at-risk family members are unresolved. In the absence of evidence that early identification of the Leiden variant leads to interventions that can reduce morbidity or mortality, decisions regarding testing should be made on an individual basis. However, if the results are likely to affect management, clarification of Leiden variant status may be indicated in at-risk female relatives considering hormonal contraception or pregnancy or in families with a strong history of recurrent venous thrombosis at a young age.
### Genetic counseling.
Factor V Leiden thrombophilia (i.e., predisposition to the development of venous thrombosis) is inherited in an autosomal dominant manner. Homozygosity for the Leiden variant (and a much greater risk for venous thrombosis) are inherited in an autosomal recessive manner. Because of the high prevalence of the factor V Leiden allele in the general population, the genetic status of both parents and/or the reproductive partner of an affected individual needs to be evaluated before information regarding potential risks to sibs or offspring can be provided. Once the Leiden variant has been identified in a family member, prenatal testing for pregnancies at increased risk and preimplantation genetic diagnosis are possible. Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis of this genetic change, which is common in the general population and is predisposing to, but not predictive of, thrombosis.
## Diagnosis
### Suggestive Findings
Factor V Leiden thrombophilia should be suspected in individuals with the following
* A history of first and recurrent venous thromboembolism (VTE) manifest as deep vein thrombosis (DVT) or pulmonary embolism (PE), especially in women with a history of VTE during pregnancy or in association with use of estrogen-containing contraceptives
* A family history of recurrent thrombosis
### Establishing the Diagnosis
The diagnosis of factor V Leiden thrombophilia is established in a proband by identification of a heterozygous or homozygous c.1691G>A variant (referred to as the factor V Leiden variant in F5, the gene encoding factor V; see Table 1) in conjunction with coagulation tests such as the APC resistance assay.
#### APC Resistance Assay
The original APC resistance assay involves performing an aPTT on the individual's plasma in the presence and absence of exogenous APC; the two results are expressed as a ratio (aPTT +APC/aPTT-APC). The APC-resistant phenotype is characterized by a minimal prolongation of the aPTT in response to APC and a correspondingly low ratio.
The modified "second generation" assay involves diluting the patient's plasma in factor V-deficient plasma containing a heparin neutralizer (which increases the specificity and sensitivity of detection of factor V Leiden thrombophilia to almost 100%) [Kadauke et al 2014].
Note: The second generation APC resistance assay: (1) is cost effective, highly accurate, and detects causes of APC resisance other than factor V Leiden thrombophilia and (2) is used to detect "pseudohomozygous" factor V Leiden thrombophilia (defined as heterozygosity for both the factor V Leiden variant and a second F5 pathogenic variant that causes a factor V deficiency) (see Genotype-Phenotype Correlations) or "pseudo wild-type" factor V Leiden thrombophilia (defined as the combination of a Leiden variant with a normal APC resistance ratio) [Prüller et al 2013, Kadauke et al 2014, Van Cott et al 2016].
Molecular genetic testing is recommended in individuals receiving direct thrombin inhibitors or direct factor Xa inhibitors, which may interfere with results of the APC resistance assay [Kadauke et al 2014], and in individuals with the following laboratory findings:
* Positive APC-resistance assay values: to confirm the diagnosis and to distinguish factor V Leiden variant heterozygotes from homozygotes
* Borderline APC resistance assay values: to confirm the diagnosis
* Very low APC resistance assay values to differentiate:
* Leiden variant heterozygotes
* Leiden variant homozygotes
* "Pseudohomozygotes"
* Strong lupus inhibitors and a markedly prolonged baseline aPTT
#### Factor V Leiden Variant Testing
The growing consensus is that factor V Leiden variant testing should not be performed on a routine basis and should only be considered when the results will affect clinical management [Chong et al 2012, Canadian Agency for Drugs and Technologies in Health 2015, Stevens et al 2016] for the following reasons:
* No randomized controlled trial has evaluated the effect of thrombophilia testing on the rate of recurrence after a first VTE.
* Analysis of a large cohort of indviduals with VTE suggested that thrombophilia testing at the time of the first VTE did not reduce the risk of recurrence [Coppens et al 2008].
* Not testing patients with VTE for inherited thrombophilia is included in the "Choosing Wisely Campaign" recommended by several professional societies [Hicks et al 2013, Hillis et al 2015].
Factor V Leiden variant testing may be considered in the following individuals when the results of testing would affect clinical management:
* Persons with a first unprovoked VTE who are planning to stop anticoagulation
* Female relatives of persons with VTE or hereditary thrombophilia considering estrogen contraception or hormone replacement
* Female relatives of persons with VTE or hereditary thrombophilia contemplating prophylactic anticoagulation during pregnancy
Factor V Leiden variant testing should not be performed on the following individuals:
* Adults with VTE provoked by major transient risk factors
* Adults with unprovoked VTE while on long-term anticoagulation
* Persons with arterial thrombosis
* Women with unexplained pregnancy loss
* Neonates and children with asymptomatic central venous catheter-related thrombosis
* Asymptomatic adult family members of individuals known to have a Leiden variant
Factor V Leiden variant testing should not be performed in the following circumstances:
* Routine testing:
* During pregnancy
* Prior to the use of oral contraceptives, hormone replacement therapy (HRT), or selective estrogen receptor modulators (SERMs)
* In asymptomatic children
* Prenatal or newborn testing
Molecular genetic testing approaches can include targeted analysis for the factor V Leiden variant (see Table 1) or a multigene panel that includes the factor V Leiden variant and other genes of interest (see Differential Diagnosis). Note: The genes included and sensitivity of multigene panels vary by laboratory and over time. 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 Factor V Leiden Thrombophilia
View in own window
Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method
F5Targeted analysis for c.1691G>A100%
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.
## Clinical Characteristics
### Clinical Description
#### Clinical Manifestations of Factor V Leiden Thrombophilia
Venous thromboembolism (VTE) is the primary clinical manifestation of factor V Leiden thrombophilia. Deep vein thrombosis (DVT) is the most common VTE. The most common site for DVT is the legs, but upper-extremity thrombosis also occurs. Superficial venous thrombosis may also occur.
Pulmonary embolism (PE). Some evidence suggests that PE is less common than DVT in individuals with the Leiden variant. Multiple studies and a meta-analysis consistently found a higher risk of DVT than PE in individuals with a Leiden variant [Dentali et al 2012, van Langevelde et al 2012]. The different effect on the risk of DVT and PE is referred to as "the factor V Leiden paradox"; the mechanism is still not well understood.
Thrombosis in unusual locations such as cerebral veins and splanchnic veins may also occur, but less commonly.
Risk for VTE in adults. The clinical expression of the Leiden variant varies [Campello et al 2016]: many individuals with the Leiden variant never develop thrombosis [Heit et al 2005] and those who do typically experience their first thrombotic event as adults; however, some have recurrent thromboembolism before age 30 years.
Heterozygosity for the Leiden variant is not associated with an increase in mortality or reduction in normal life expectancy even in the presence of a history of VTE [Hille et al 1997, Heijmans et al 1998, Pabinger et al 2012].
While individuals homozygous for the Leiden variant have a higher risk for thrombosis than heterozygotes, the clinical course of an acute thrombotic episode is not more severe or more resistant to anticoagulation in homozygotes than in heterozygotes.
Heterozygotes. The relative risk for venous thrombosis is increased approximately three- to eightfold in Leiden variant heterozygotes. Lower relative risks are reported in heterozygotes identified from general population screening [Juul et al 2004, Heit et al 2005].
The risk for VTE is increased in Leiden variant heterozygotes:
* Three- to eightfold [Rosendaal & Reitsma 2009]
* Four- to fivefold in two large meta-analyses [Gohil et al 2009, Simone et al 2013]
Despite the increase in relative risk, the overall annual incidence of a first VTE is low in heterozygotes, approximately 0.5% [Middeldorp 2011].
A heterozygous Leiden variant was associated with the following:
* A sixfold increased risk for primary upper-extremity thrombosis (not related to malignancy or a venous catheter) [Martinelli et al 2004]
* A sixfold increased risk of superficial vein thrombosis not associated with varicose veins, malignancy, or autoimmune disorders [Martinelli et al 1999]
* Increased risk of venous thrombosis at unusual sites [Martinelli et al 2014]
* A fourfold increased risk of cerebral venous thrombosis [Dentali et al 2006]
A Leiden variant:
* May increase the risk of splanchic vein thrombosis;
* Was associated with an 11-fold increased risk of Budd-Chiari syndrome in case-control studies [Janssen et al 2000];
* Confers a threefold increased risk of portal vein thrombosis (meta-analysis by Dentali et al [2008]).
Homozygotes. Compared to heterozygotes, homozygotes have a higher thrombotic risk and tend to develop thrombosis at a younger age.
The risk for VTE is increased in Leiden variant homozygotes:
* Nine- to 80-fold [Rosendaal & Reitsma 2009]
* Nine- to 12-fold [Gohil et al 2009, Simone et al 2013]
Risk for VTE in children. The cause of VTE in children is multifactorial and results from the interaction between acquired clinical risk factors (see Table 2), one or more underlying medical conditions, and an inherited predisposition to thrombophilia [Klaassen et al 2015, van Ommen & Nowak-Göttl 2017].
The most important clinical risk factor for thrombosis in children is a central venous catheter (CVC). A Leiden variant was associated with CVC-related VTE in some [Neshat-Vahid et al 2016] but not all studies [Thom et al 2014].
A Leiden variant significantly increased the risk of cerebral venous thrombosis in children (odds ratio 2.74); see meta-analysis by Kenet et al [2010].
A Leiden variant was also reported to increase the risk of neonatal cerebral vein thrombosis [Kenet et al 2010, Laugesaar et al 2010].
In a prospective study, asymptomatic children – family members of symptomatic probands with the Leiden variant who were themselves heterozygous or homozygous for the Leiden variant – had no thrombotic complications during follow up that averaged five years [Tormene et al 2002]. Thus, the available data suggest that asymptomatic children with a Leiden variant are at low risk for thrombosis except in the setting of strong circumstantial risk factors (see Table 2).
Risk for VTE in pregnancy. Normal pregnancy is associated with a five- to tenfold increased risk of developing VTE.
Women heterozygous for the Leiden variant have a five to eight times greater risk of pregnancy-related VTE than women without the variant [Robertson et al 2006, Bleker et al 2014, Gerhardt et al 2016]. The risk is higher in women from families with a history of thrombosis and in women older than age 34 years. The highest risk of VTE occurs during the first six weeks post partum.
While heterozygosity for the Leiden variant increases the relative risk for pregnancy-associated VTE, the absolute risk is low in the absence of other predisposing factors. VTE is estimated to occur in 1% of pregnancies in women who are Leiden variant heterozygotes. The absolute risk increases to 3% in those with a positive family history of VTE [Bleker et al 2014, Campello et al 2016].
In women homozygous for the Leiden variant the relative risk is increased 17- to 34-fold [Robertson et al 2006, Gerhardt et al 2016]. The absolute risk of developing pregnancy-related VTE is estimated at 2.2%-4.8% of pregnancies. The risk is higher (14%) in homozygotes with a positive family history and in those older than age 34 years [Bleker et al 2014, Gerhardt et al 2016].
Women doubly heterozygous for the Leiden variant and the 20210G>A F2 variant are reported to have an eight- to 47-fold increased relative risk of pregnancy-related VTE [Jacobsen et al 2010, Gerhardt et al 2016]. The probability of VTE during pregnancy and the puerperium is lower (5.5%) in doubly heterozygous women younger than age 35 years than in older women (8.2%) [Gerhardt et al 2016].
#### Recurrent Thrombosis
In adults heterozygous for a Leiden variant alone. Evidence suggests that a heterozygous Leiden variant has at most a modest effect on risk for recurrent thrombosis after initial treatment of a first VTE.
A modest, approximately 1.5-fold increased risk of VTE recurrence was identified in several meta-analyses [Marchiori et al 2007, Segal et al 2009]; however, in several prospective cohort studies of unselected individuals with a first VTE the recurrence risk was not increased in Leiden variant heterozygotes [Christiansen et al 2005, Lijfering et al 2010].
The reported risk may be higher in studies of families prone to thrombosis than in unselected individuals. In a prospective study of families with a strong history of thrombosis, the incidence of recurrent VTE was 3.5 per 100 person-years in persons with the Leiden variant (heterozygotes and homozygotes) [Vossen et al 2005]; however, a large family study found the rate of recurrent VTE in relatives with a Leiden variant to be similar to those reported in the general population (7% after 2 years, 11% after 5 years, and 25% after 10 years) [Lijfering et al 2009].
In Leiden variant homozygotes and heterozygotes with other risk factors. Risks for recurrent VTE in Leiden variant homozygotes and double heterozygotes for the Leiden variant and the F2 20210G>A variant vary widely between studies.
Similar rates of VTE recurrence for both Leiden variant homozygotes and heterozygotes were found in a recent study [Perez Botero et al 2016], whereas an earlier systematic review found that homozygosity for the Leiden variant conferred a 2.6-fold increased risk of recurrent VTE [Segal et al 2009].
Not all studies found a high risk for recurrence in Leiden variant homozygotes and double heterozygotes even when the analysis was restricted to those with a first unprovoked VTE [Lijfering et al 2010].
The risk of VTE is unknown in individuals with the rare combination of Leiden variant and prothrombin 20210G>A variants (i.e., homozygous Leiden variant / heterozygous 20210G>A, homozygous Leiden variant / homozygous 20210G>A). In a retrospective study, the risk of recurrence was 13% at one year and 22% at five years, similar to that expected in individuals with an unprovoked VTE without thrombophilia. However, the recurrence risk in this group was significantly higher than expected after a first VTE provoked by a transient risk factor (6% at 1 year and 26% at 5 years) [Lim et al 2016].
In children. In children, inherited thrombophilia appears to have at most a modest effect on the risk of recurrence, similar to findings in adults [Klaassen et al 2015].
In pregnant women. During pregnancy women with a prior history of VTE have an increased recurrence risk, ranging from 0% to 15% in published studies. The risk is higher in women with a prior unprovoked episode or an estrogen-related VTE, and in those with coexisting genetic or acquired risk factors (Table 2). No studies have specifically evaluated the risk for recurrent VTE in pregnant women who have the Leiden variant.
In subgroup analysis of a prospective study of the safety of withholding anticoagulation during pregnancy in 125 women with a history of VTE, Brill-Edwards et al [2000] found the following:
* Women with a prior unprovoked VTE and thrombophilia (especially factor V Leiden thrombophilia) had the highest recurrence rate during pregnancy (20% of pregnancies).
* A Leiden variant was associated with an increased risk of antepartum recurrence (odds ratio 10).
* Women with either thrombophilia or a prior unprovoked VTE (but not both) had recurrence rates of 13% and 7.7%, respectively.
#### Obstetric Complications
It is unlikely that a factor V Leiden thrombophilia (i.e., heterozygosity or homozygosity for the Leiden variant) is a major factor contributing to pregnancy loss and other adverse pregnancy outcomes (preeclampsia, fetal growth restriction, and placental abruption). At most, factor V Leiden thrombophilia is one of multiple largely unknown genetic and environmental predisposing factors contributing to these complications.
Pregnancy loss. Available data suggest that Leiden variant heterozygosity is at most a weak contributor to recurrent or late pregnancy loss. A meta-analysis evaluating only prospective cohort studies reported a slightly increased risk of pregnancy loss in women with the Leiden variant (4.2%) compared to those without the variant (3.2%) (odds ratio 1.52) [Rodger et al 2010]. A meta-analysis found that heterozygosity for the Leiden variant is associated with a twofold increased risk for a late unexplained fetal loss and a fourfold higher risk for loss in the second trimester compared to the first trimester [Robertson et al 2006]. Although maternal homozygosity for the Leiden variant was associated with stillbirth, presence of the Leiden variant was not associated with stillbirths in the subset of stillbirths resulting from placental insufficiency [Silver et al 2016].
Preeclampsia, fetal growth restriction, and placental abruption may also involve impaired placental perfusion; however, their association with inherited thrombophilia is more controversial [Greer et al 2014]. For example:
* A systematic review focused on prospective cohort studies found no significant association of preeclampsia or placental abruption with factor V Leiden thrombophilia [Rodger et al 2010].
* A Danish case-cohort study found that heterozygosity for the Leiden variant increased the risk of severe preeclampsia (odds ratio 1.6), severe fetal growth restriction (odds ratio 1.5), and symptomatic placental abruption (odds ratio 1.7) [Lykke et al 2012].
Such conflicting results may reflect the varying diagnostic and selection criteria, different ethnic groups, and small number of cases included. However, given that preeclampsia and placental abruption are heterogeneous disorders, it is unlikely that a single thrombophilic variant (such as the Leiden variant) plays a major causal role.
#### Arterial Thrombosis NOT Convincingly Associated with the Leiden Variant
The available evidence indicates that presence of a Leiden variant is not a major risk factor for arterial thrombosis of any sort, including myocardial infarction and stroke in fetuses, children, and adults, the majority of which occur in the presence of established cardiovascular risk factors (including hypertension, hyperlipidemia, diabetes mellitus, and smoking). For more information click here (pdf).
#### Clinical Expression of Factor V Leiden Thrombophilia
In addition to the number of Leiden variants (discussed above), the clinical expression of factor V Leiden thrombophilia is influenced by family history, coexisting genetic abnormalities, acquired thrombophilic disorders, and circumstantial risk factors.
A positive family history. Individuals with a Leiden variant who have a first-degree relative with a history of thrombosis had a threefold increased risk for VTE compared to those with a Leiden variant with a negative family history [Bezemer et al 2009]. The risk was increased to fivefold in those with a relative with a VTE before age 50 years and to 18-fold with two or more affected relatives. The family history had additional value in predicting risk even in those with a Leiden variant, suggesting the presence of unknown genetic risk factors.
Coexisting genetic abnormalities. The combination of Leiden variant heterozygosity and most other thrombophilic disorders (including protein C deficiency, protein S deficiency, antithrombin deficiency, and the F2 thrombophilia variant [c.*97G>A, commonly known as 20210G>A]) has a supra-additive effect on overall thrombotic risk [Ridker et al 1997a] (see Differential Diagnosis). For example:
* Individuals heterozygous for either the Leiden variant or the F2 thrombophilia variant had a four- to fivefold increased thrombotic risk, compared to double heterozygotes, who had a 20-fold increased thrombotic risk [Emmerich et al 2001].
* The F2 thrombophilia variant was four- to fivefold more common in Leiden variant homozygotes with VTE than in controls without a Leiden variant and with no thrombotic history [Ehrenforth et al 2004].
Acquired thrombophilic disorders include antiphospholipid antibody (APLA) syndrome, paroxysmal nocturnal hemoglobinuria, myeloproliferative disorders, and increased levels of clotting factors. Despite the following observations, the effect of these acquired disorders on Leiden variant-associated thrombotic risk is not well defined.
* Leiden variant heterozygotes with factor VIII levels greater than150% of normal had a two- to threefold increased incidence of VTE than heterozygotes for a Leiden variant alone [Lensen et al 2001]. The reason for the association of high FVIII levels with VTE is unknown; factor VIII, an acute phase reactant, is high in the presence of inflammation and estrogen. Although suspected, a genetic basis has not been identified.
* A Leiden variant was reported to contribute to increased risk for thrombotic complications in persons with polycythemia vera and essential thrombocytosis [Trifa et al 2014].
#### Circumstantial Risk Factors for VTE
Circumstantial risk factors for VTE in Leiden variant heterozygotes or homozygotes are summarized in Table 2. Other risk factors that to date have not been studied in Leiden variant heterozygotes are the newer forms of combined hormonal contraception, transdermal and vaginal ring contraception, for which the risk of VTE is at least as great as the risk associated with combined oral contraceptives (COCs) [Dore et al 2010, Lidegaard et al 2012].
### Table 2.
Circumstantial Risk Factors: Increased Risk for Thrombophilia in Persons with the Factor V Leiden Variant (heterozygosity and homozygosity not specified)
View in own window
CircumstanceRelative Risk for VTECommentCitation
Malignancy 1Unknown: probably modestIn persons w/cancer, no indication for:
* Testing for the Leiden variant;
* Prophylaxis
Farge et al [2013], Kovac et al [2015], Pabinger et al [2015]
Central venous catheter use2x-3x ↑ relative riskVan Rooden et al [2004]
5x ↑ relative risk in those w/cancerDentali et al [2008]
Travel2x ↑ relative riskRisk ↑:
* W/travel duration;
* In those w/thrombophilia
Chandra et al [2009]
8x ↑ relative risk when traveling ≥4 uninterrupted hrsCannegieter et al [2006]
COCs 1Much ↑ during 1st yr of use than subsequent yrsMartinelli et al [2016]
↑ in COC w/desogestrel or drospirenone than COC w/levonorgestrelBergendal et al [2014]
Unopposed progesterone contraceptionInjectable medroxyprogesterone assoc w/16x ↑ riskBergendal et al [2014]
Low-dose oral form has lowest thrombotic risk of hormonal contraceptionTepper et al [2016]
Oral HRT 17x-25x ↑ relative riskRisk ↑ w/↑ estrogen doseStraczek et al [2005], Douketis et al [2011]
Transdermal HRT 1Lower relative risk than oral HRTPreliminary data suggest may not ↑ thrombotic riskStraczek et al [2005], Canonico et al [2010], ACOG [2013a]
SERMS 1Not well definedRisk likely >2x ↑ over risk assoc w/SERMS aloneBarrett-Connor et al [2006], Nelson [2013]
Obesity (BMI >30 kg/m2)5x-12x ↑ relative riskRisk ↑ w/BMISeverinsen et al [2010], Ribeiro et al [2016]
Overweight (BMI >25 - <30 kg/m2)4x-10x ↑ relative riskRisk ↑ w/BMISeverinsen et al [2010], Ribeiro et al [2016]
Organ transplantationNot well definedGhisdal et al [2010], Pereboom et al [2011], Parajuli et al [2016]
Minor leg injury23x-50x ↑ riskvan Stralen et al [2008], van Adrichem et al [2014]
SurgeryUnclearAny excess risk conferred by Leiden variant heterozygosity likely small, compared to risk assoc w/surgeryJoseph et al [2005], Charen et al [2015], van Adrichem et al [2015]
AgeAfter age 45 yrs lifetime risk = 17% (vs 8% in general population)↑ age is an independent risk factor for VTE.Bell et al [2016]
Risk ↑ w/age, BMI, smoking, +FHJuul et al [2004]
Highest risk in persons age >70 yrs w/+FHKarasu et al [2016]
+
FH= positive family history; COCs = combined oral contraceptives; HRT = hormone replacement therapy; SERMS = selective estrogen receptor modulators
1\.
See text that follows table for more details.
Malignancy. To what extent inherited thrombophilia increases the risk of VTE in persons with cancer remains controversial [Decousus et al 2007, Pabinger et al 2015]. Because malignancy is such a strong thrombotic risk factor, it may obscure the effect of mild thrombophilic disorders including factor V Leiden. Thrombophilia status was not considered in recent guidelines for prophylaxis and treatment of VTE in patients with cancer [Farge et al 2013].
Combined oral contraceptive (COC) use substantially increases the relative risk for VTE in women heterozygous for the Leiden variant.
The supra-additive effect of both a Leiden variant and use of COC was confirmed in multiple studies in which odds ratios for VTE ranged from 11 to 41 [Wu et al 2005, Dayan et al 2011, Bergendal et al 2014, van Vlijmen et al 2016]. For women who are either homozygous for the Leiden variant or doubly heterozygous for the Leiden variant and the prothrombin 20210G>A variant the odds ratios for VTE ranged from 17 to 110 [Mohllajee et al 2006, van Vlijmen et al 2016].
Despite the marked increase in relative risk for VTE, the absolute incidence of VTE may be low because of the low baseline risk for VTE in young women.The incidence of VTE in COC users with either a Leiden variant or the prothrombin 20210G>A variant ranged 0.49 to 2.0 VTE/100 pill-years compared to 0.19 to 0/100 pill-years in COC users without these variants. The absolute VTE risk is substantially higher in COC users doubly heterozygous for the Leiden variant and the prothrombin 20210G>A variant or homozygous for either variant (0.86 vs 0.19/100 pill years) [van Vlijmen et al 2011, van Vlijmen et al 2016].
The thrombotic risk of COC is at least as high in women older than age 50 years as in younger users [Roach et al 2013]. However, since the incidence of VTE increases with age, the absolute risk for VTE in women older than age 50 years is much higher than in younger COC users.
Oral hormone replacement therapy (HRT) is associated with a two- to fourfold increased relative risk for VTE in healthy postmenopausal users of HRT compared to non-users [Renoux et al 2010, Eisenberger & Westhoff 2014]. Data comparing the VTE risk of combined estrogen/progestin HRT and unopposed estrogen are inconclusive [Eisenberger & Westhoff 2014].
The risk increases with higher estrogen doses and may differ with the particular estrogen and progestin components [Renoux et al 2010, Canonico et al 2011, Smith et al 2014].
The risk of HRT is threefold increased in postmenopausal women with a factor V Leiden or prothrombin 20210G>A variant than in HRT users without thrombophilia [Roach et al 2013].
Transdermal HRT. Multiple observational studies consistently found that transdermal HRT did not increase the risk of VTE [Canonico et al 2010, Sweetland et al 2012, ACOG 2013a]. There is also evidence that transdermal estrogen is associated with a lower thrombotic risk than oral estrogen in women with inherited thrombophilic variants including the Leiden variant [Canonico et al 2010]. Women with a Leiden variant using transdermal estrogen had a risk similar to that of non-users with the variant. Among women with a Leiden variant the use of oral estrogen was associated with a fourfold increased risk for VTE over transdermal estrogen [Straczek et al 2005]. However, no prospective randomized trials have confirmed the safety of transdermal HRT in women with inherited thrombophilia.
Selective estrogen receptor modulators (SERMS). The risk for VTE in women with the Leiden variant who use SERMS is not well defined. Limited data suggest that SERMs such as tamoxifen and raloxifene are associated with a twofold increased risk for VTE, similar to the risk for HRT [Barrett-Connor et al 2006]. The thrombotic risk conferred by tamoxifen was higher than raloxifene in trials for primary prevention of breast cancer [Nelson 2013]. In light of the interaction of factor V Leiden with HRT, the risk is likely higher than that associated with SERMS alone.
### Genotype-Phenotype Correlations
Other F5 variants may affect clinical outcome in an individual heterozygous for the Leiden variant.
* An F5 null variant in trans with the Leiden variant results in "pseudo-homozygous" APC resistance, which is indistinguishable from homozygous Leiden thrombophilia and may result in a more severe hypercoagulable state [Brugge et al 2005, Duckers et al 2011]. Coinheritance of an F5 null variant is estimated in approximately 1:1,000 individuals heterozygous for a Leiden variant [Simioni et al 2005].
* The F5 haplotype HR2, defined by the R2 variant (p.His1327Arg), may confer mild APC resistance. The HR2 haplotype in trans with the Leiden variant may confer greater thrombotic risk [Faioni et al 1999, de Visser et al 2000, Mingozzi et al 2003], but was not associated with a significantly higher risk for early or late pregnancy loss than presence of the Leiden variant alone [Zammiti et al 2006].
### Penetrance
See Clinical Description.
### Prevalence
Factor V Leiden thrombophilia is the most common inherited form of thrombophilia. The prevalence varies by population.
Heterozygosity for the Leiden variant occurs in 3%-8% of the general US and European populations. The highest heterozygosity rate is found in Europe; the Leiden variant is extremely rare in Asian, African, and indigenous Australian populations.
* Within Europe, prevalence varies from 10%-15% in southern Sweden and Greece to 2%-3% in Italy and Spain.
* In the US, prevalence reflects the world distribution of the Leiden variant [Ridker et al 1997b], which is present in:
* 5.2% of Americans of European origin;
* 2.2% of Hispanic Americans;
* 1.2% of African Americans;
* 0.45% of Asian Americans;
* 1.25% of Native Americans.
The frequency of homozygosity for the Leiden variant is approximately 1:5,000.
The Leiden variant is present in:
* Approximately 15%-20% of individuals with a first DVT;
* Up to 50% of individuals with recurrent venous thromboembolism or an estrogen-related thrombosis.
## Differential Diagnosis
The differential diagnosis of venous thromboembolism includes several other inherited thrombophilic disorders, including those caused by other variants in F5 (discussed here) and acquired thrombophilic disorders (outside of the scope of this GeneReview).
Prothrombin-related thrombophilia is characterized by venous thromboembolism (VTE) manifest most commonly in adults as deep-vein thrombosis (DVT) in the legs or pulmonary embolism. The clinical expression of prothrombin-related thrombophilia is variable; many individuals heterozygous or homozygous for the F2 thrombophilia variant (c.*97G>A, commonly known as 20210G>A) never develop thrombosis, and while most heterozygotes who develop thrombotic complications remain asymptomatic until adulthood, some have recurrent thromboembolism before age 30 years. The relative risk for DVT in adults heterozygous for this variant is two- to fivefold increased; in children, the relative risk for thrombosis is three- to fourfold increased. Factors that predispose to thrombosis in prothrombin-related thrombophilia include: the number of c.*97G>A alleles; presence of coexisting genetic abnormalities including factor V Leiden; and acquired thrombophilic disorders (e.g., antiphospholipid antibodies). Circumstantial risk factors for thrombosis include pregnancy and oral contraceptive use.
Inherited abnormalities or deficiencies of the natural anticoagulant proteins C, S, and antithrombin are approximately tenfold less common than the Leiden variant, with a combined prevalence of less than 1%-2% of the population. Anticoagulant protein deficiencies are found in 1%-3% of individuals with a first VTE.
Hereditary dysfibrinogenemias (OMIM 616004) are rare and infrequently cause thrombophilia and thrombosis.
See Thrombophilia: OMIM Phenotypic Series to view genes associated with this phenotype in OMIM.
## Management
### Evaluations Following Initial Diagnosis
To assess the risk for thrombosis in an individual found to have the factor V Leiden variant, the following evaluations are recommended:
* For individuals heterozygous for the Leiden variant: the following testing for other inherited or acquired thrombophilic disorders is recommended by experts (but is not a hard-and-fast rule) given that double heterozygosity for the Leiden variant and F2 thrombophilia variant 20210G>A occurs more commonly than protein C, S, and AT deficiencies (which are rare and unlikely to be found except in those with "high risk features" such as a strong family history) and antiphospholipid antibody (APLA) syndrome can occur at any age in anyone:
* DNA testing F2 thrombophilia variant (c.*97G>A, commonly known as 20210G>A)
* Multiple phospholipid-dependent coagulation assays for a lupus inhibitor
* Serologic assays for anticardiolipin antibodies and anti-beta2-glycoprotein 1 antibodies
* For high-risk individuals (i.e., those with a history of recurrent VTE, especially at young age, or those with strong family history of VTE at young age) evaluation should also include assays of:
* Protein C activity
* Antithrombin activity
* Protein S activity or free protein S antigen
Note: Measurement of the following is NOT recommended:
* Plasma concentration of homocysteine since no data support a change in duration of anticoagulation or the use of vitamin supplementation in individuals with hyperhomocysteinemia and a history of VTE
* MTHFR variants as no clinical rationale for this testing exists
* Factor VIII and other clotting factor levels [Moll 2015]
### Treatment of Manifestations
#### Treatment of VTE in Adults
The management of individuals with factor V Leiden thrombophilia depends on the clinical circumstances.
The first acute thrombosis should be treated according to standard guidelines [Kearon et al 2012, Kearon et al 2016]. For initial treatment of VTE, current guidelines suggest a new oral anticoagulant (dabigatran, edoxaban, rivaroxaban, or apixaban) over warfarin because of a lower bleeding risk and greater convenience [Kearon et al 2016]. Of note, low molecular-weight heparin (LMWH) is given before dabigatran and edoxaban but not before rivaroxaban or apixaban.
For patients not treated with one of the new oral anticoagulants, administration of warfarin is started concurrently with LMWH or fondaparinux (except during pregnancy) and monitored with the international normalized ratio (INR). A target international normalized ratio (INR) of 2.5 (therapeutic range 2.0-3.0) provides effective anticoagulation, even in individuals homozygous for the Leiden variant [Kearon et al 2008, Tzoran et al 2017]. LMWH and warfarin therapy should be overlapped for at least five days, and until the INR has been within the therapeutic range on two consecutive measurements over two days.
LMWH and warfarin are both safe in breastfeeding women (see Pregnancy Management for issues with anticoagulants).
The duration of oral anticoagulation therapy should be based on an assessment of the risks for VTE recurrence and anticoagulant-related bleeding. Recurrence risk is determined by the clinical circumstances of the first event (provoked or unprovoked), adequacy of early treatment, and individual risk factors.
* Heterozygosity for the Leiden variant alone is not an indication for long-term anticoagulation in the absence of other risk factors, according to the American College of Chest Physicians guidelines on antithrombotic therapy and prevention of thrombosis [Kearon et al 2012, Kearon et al 2016] as well as other clinical guidelines and expert opinion [Baglin et al 2010, Bauer 2010, National Clinical Guideline Centre 2012].
* Anticoagulation for at least three months is recommended for persons with DVT and/or PE associated with a transient (reversible) risk factor [Kearon et al 2012, Kearon et al 2016].
Long-term oral anticoagulation is recommended for individuals with a first or recurrent unprovoked (i.e., idiopathic) proximal DVT of the leg or pulmonary embolism (PE) who have a low or moderate bleeding risk [Kearon et al 2016]. The decision should be based on an assessment of potential risks and benefits regardless of Leiden variant status [EGAPP Working Group 2011].
Long-term anticoagulation is occasionally considered in individuals homozygous for the Leiden variant or with multiple thrombophilic disorders, particularly in the presence of additional risk factors (e.g., obesity) as the potential benefits from long-term anticoagulation may outweigh the bleeding risks [De Stefano & Rossi 2013].
#### Treatment of VTE in Children
The treatment recommendations for adults (which concluded that presence of a Leiden variant should not influence the intensity or duration of anticoagulation) are generally followed in children as well [Chalmers et al 2011, Heleen van Ommen & Middeldorp 2011, Monagle et al 2012].
Children with a first VTE should receive initial treatment with either unfractionated heparin (UFH) or LMWH for at least five days. LMWH is favored over warfarin for continued therapy, especially in very young children and those with complex medical problems. Recommendations on the duration of antithrombotic therapy are based on the nature of the thrombotic event (spontaneous or provoked) [Chalmers et al 2011, Monagle et al 2012].
Anticoagulation is recommended:
* For at least three months following a VTE provoked by a clinical risk factor that has resolved;
* At least three months and until the risk factor has resolved in children with an ongoing but potentially reversible risk factor;
* For 6-12 months after a first unprovoked VTE.
Expert opinion emphasizes the importance of a careful risk/benefit assessment in each individual [Heleen van Ommen & Middeldorp 2011].
### Prevention of Primary Manifestations
In the absence of a history of thrombosis, long-term anticoagulation is not routinely recommended for asymptomatic individuals who are heterozygous for the Leiden variant because the 1%-3%/year risk for major bleeding from warfarin is greater than the estimated less than 1%/year risk for thrombosis.
Because the initial thrombosis in 50% of Leiden variant heterozygotes occurs in association with other circumstantial risk factors (Table 2), a short course of prophylactic anticoagulation during exposure to hemostatic stresses may prevent some of these episodes. However, currently no evidence confirms the benefit of primary prophylaxis for asymptomatic Leiden variant heterozygotes. Factors that may influence decisions about the indication for and duration of anticoagulation include age, family history, and other coexisting risk factors.
Selected Leiden variant heterozygotes who do not require long-term anticoagulation may benefit from evaluation prior to exposure to circumstantial risk factors such as surgery or pregnancy. Recommendations for prophylaxis at the time of surgery and other high-risk situations are available in consensus guidelines [Guyatt et al 2012].
### Surveillance
Individuals on long-term anticoagulation require periodic reevaluation of their clinical course to confirm that the benefits of anticoagulation continue to outweigh the risk of bleeding.
### Agents/Circumstances to Avoid
Women with a history of VTE who are heterozygous for the Leiden variant should avoid estrogen-containing contraception and hormone replacement therapy (HRT).
Women homozygous for the Leiden variant with or without prior VTE should avoid estrogen-containing contraception and HRT.
Asymptomatic women heterozygous for the Leiden variant:
* Should be counseled on the risks of estrogen-containing contraception and HRT use and should be encouraged to consider alternative forms of contraception and control of menopausal symptoms;
* Electing to use oral contraceptives should avoid third-generation and other progestins with a higher thrombotic risk;
* Electing short-term hormone replacement therapy for severe menopausal symptoms should use a low-dose transdermal preparation, which has a lower thrombotic risk than oral formulations [Canonico et al 2007, Canonico et al 2010, Sweetland et al 2012].
### Evaluation of Relatives at Risk
Although the genetic status of apparently asymptomatic at-risk family members can be established using molecular genetic testing for the Leiden variant, the indications for family testing are unresolved.
* In the absence of evidence that early identification of the Leiden variant leads to interventions that can reduce morbidity or mortality, decisions regarding testing should be made on an individual basis.
* Clarification of Leiden variant status may be considered in at-risk female relatives considering hormonal contraception or pregnancy or in families with a strong history of recurrent venous thrombosis at a young age if the results are likely to affect management.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Pregnancy Management
#### Prevention of Thrombosis During Pregnancy
No consensus exists on the optimal management of factor V Leiden thrombophilia during pregnancy; guidelines are derived from studies in non-pregnant individuals [Baglin et al 2010, Bates et al 2012]. All women with inherited thrombophilia should undergo individualized risk assessment in order to base decisions about anticoagulation on the number and type of thrombophilic defects, coexisting risk factors, and personal and family history of thrombosis.
For pregnant women with a prior single episode of VTE provoked by a transient risk factor not related either to pregnancy or to the use of estrogen, clinical vigilance during pregnancy is suggested [Bates et al 2012].
LMWH is the preferred antithrombotic agent for prophylaxis and treatment during pregnancy [Bates et al 2012, ACOG 2013b].
The oral direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban are contraindicted during pregnancy and breastfeeding because of (1) absence of data on fetal and neonatal safety and (2) animal studies that showed reproductive toxicity [Ageno et al 2012].
Prophylactic anticoagulation during pregnancy is recommended for all women:
* With a history of unprovoked VTE including those heterozygous for the Leiden variant. LMWH should be given during pregnancy, followed by a six-week course of anticoagulation post partum [Bates et al 2012, ACOG 2013b];
* Heterozygous for the Leiden variant with a prior pregnancy or estrogen-related thrombosis who are also at increased risk for recurrence [Pabinger et al 2005, Bates et al 2012, ACOG 2013b].
Prophylactic anticoagulation during pregnancy is suggested for asymptomatic women who:
* Are homozygous for the Leiden variant;
* Are double heterozygotes for the Leiden variant and the prothrombin 20210G>A variant;
* Have other combined thrombophilic defects;
* Also have a positive family history for VTE.
In the absence of a positive family history for VTE, antepartum clinical vigilance and postpartum prophylaxis with LMWH is suggested as the greatest thrombotic risk is in the initial postpartum period [Bates et al 2012, ACOG 2013b].
Prophylactic anticoagulation during pregnancy is not routinely recommended in asymptomatic women heterozygous for the Leiden variant with no history of thrombosis. All women with a Leiden variant should be warned about potential thrombotic complications and counseled regarding the risks and benefits of anticoagulation during pregnancy [Bates et al 2012, ACOG 2013b].
#### Prevention of Thrombosis During the Postpartum Period
A six-week course of postpartum prophylaxis with LMWH is recommended for [Bates et al 2012, ACOG 2013b]:
* All women heterozygous for the Leiden variant with a prior history of VTE;
* Women heterozygous for the Leiden variant and a positive family history of VTE;
* All asymptomatic homozygous women.
#### Other
Unexplained pregnancy loss. Current consensus guidelines and expert opinion recommend against the use of antithrombotic therapy outside of clinical trials in women with inherited thrombophilia and unexplained pregnancy loss because of the absence of high-quality evidence confirming benefit [Baglin et al 2010, Bates et al 2012, ACOG 2013b, Middeldorp 2013, Skeith et al 2016].
Pregnancy complications. Current guidelines recommend against antithrombotic prophylaxis for women with inherited thrombophilia and a history of other pregnancy complications such as preeclampsia or placental abruption [Bates et al 2012, ACOG 2013b].
### Therapies Under Investigation
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. Note: There may not be clinical trials for 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 inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| Factor V Leiden Thrombophilia | c1861171 | 2,030 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1368/ | 2021-01-18T21:27:10 | {"mesh": ["C566056"], "synonyms": ["Hereditary Resistance to Activated Protein C"]} |
Chronic hiccup is a rare movement disorder characterized by involuntary spasmodic contractions of the inspiratory muscles synchronized with larynx closure lasting for more than 48 hours.
## Epidemiology
The disorder is thought to affect approximately 1/100,000 individuals. Chronic hiccup affect males more often than females.
## Clinical description
The involuntary spasmodic contractions of the inspiratory muscles followed by the rapid closure of the vocal cords known as hiccups usually last for no more than a few minutes or at most a few hours with spontaneous resolution, and can affect people of any age. In rare pathological cases, hiccups may last for more than two days (chronic /persistent hiccup). Recurrent episodes over long periods are also called chronic hiccup. Clinical repercussions of these episodes may include dehydration, weight loss and malnutrition due to difficulty eating, sleep disorders, depression and exhaustion.
## Etiology
The hiccup is poorly understood. According to experimental data it is probably a coordinated ventilatory movement mixing branchial ventilation, suction and deglutition components. Chronic hiccup is mainly an esophageal and gastric disorder. Other causes may include fever, brain lesions/tumors, cardiovascular disorders (stroke, myocardial infarction), renal failure, metabolic imbalance, peripheral nerve stimulation, or other injuries, drugs (chemotherapy, benzodiazepines, corticosteroids, barbiturates, morphine, and anesthetics), and alcohol. Other triggers include placement of medical instruments, certain foods and beverages, spices and tobacco. Cases also sometimes develop in a context of surgery (pleural, peritoneal or intracranial).
## Diagnostic methods
Clinical diagnosis is usually straightforward given the nature of the involuntary spasms. Imaging or laboratory tests to identify the underlying cause should focus primarily on the esophagus.
## Differential diagnosis
Hiccups are extremely specific and can rarely be mistaken for another condition.
## Management and treatment
Many anecdotal treatments have been described with varying success. Management should ideally focus on identifying and treating the underlying cause, especially esophageal. No specific treatments have proven efficacy in the absence of controlled studies. Pharmacological approaches that have been attempted in cases where no gastroesophageal treatment works include baclofen, chlorpromazine, carbamazepine, haloperidol, metoclopramide, gabapentin, serotoninergic agonists, prokinetics, lidocaine, nifedipine, carvedilol and marijuana. Alternative therapy includes hypnosis and acupuncture. Phrenic nerve blockade is of little benefit since it yields only partial relief at the expense of respiratory insufficiency. Long-term treatment of the frequent esophageal cause can be very useful.
## Prognosis
Persistent hiccups can reduce quality of life. Very long intractable disease may be debilitating.
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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
| Chronic hiccup | c0744898 | 2,031 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=396 | 2021-01-23T17:51:28 | {"gard": ["6657"]} |
A number sign (#) is used with this entry because of evidence that this late-onset form of autosomal recessive congenital ichthyosis (ARCI8) can be caused by homozygous mutation in the LIPN gene (613924) on chromosome 10q23.
Description
Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of disorders of keratinization characterized primarily by abnormal skin scaling over the whole body. These disorders are limited to skin, with approximately two-thirds of patients presenting severe symptoms. The main skin phenotypes are lamellar ichthyosis (LI) and nonbullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur (summary by Fischer, 2009). Neither histopathologic findings nor ultrastructural features clearly distinguish between NCIE and LI. In addition, mutations in several genes have been shown to cause both lamellar and nonbullous ichthyosiform erythrodermal phenotypes (Akiyama et al., 2003). At the First Ichthyosis Consensus Conference in Soreze in 2009, the term 'autosomal recessive congenital ichthyosis' (ARCI) was designated to encompass LI, NCIE, and harlequin ichthyosis (ARCI4B; 242500) (Oji et al., 2010).
NCIE is characterized by prominent erythroderma and fine white, superficial, semiadherent scales. Most patients present with collodion membrane at birth and have palmoplantar keratoderma, often with painful fissures, digital contractures, and loss of pulp volume. In half of the cases, a nail dystrophy including ridging, subungual hyperkeratosis, or hypoplasia has been described. Ectropion, eclabium, scalp involvement, and loss of eyebrows and lashes seem to be more frequent in NCIE than in lamellar ichthyosis (summary by Fischer et al., 2000). In LI, the scales are large, adherent, dark, and pigmented with no skin erythema. Overlapping phenotypes may depend on the age of the patient and the region of the body. The terminal differentiation of the epidermis is perturbed in both forms, leading to a reduced barrier function and defects of lipid composition in the stratum corneum (summary by Lefevre et al., 2006).
In later life, the skin in ARCI may have scales that cover the entire body surface, including the flexural folds, and the scales are highly variable in size and color. Erythema may be very mild and almost invisible. Some affected persons exhibit scarring alopecia, and many have secondary anhidrosis (summary by Eckl et al., 2005).
For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive congenital ichthyosis, see ARCI1 (242300).
Clinical Features
Israeli et al. (2011) studied a consanguineous Arab Muslim pedigree in which the index patient, whose skin appeared normal at birth, developed widespread ichthyosis at 5 years of age. At 14 years of age, the entire surface of her skin was covered with fine whitish scales, whereas her face was slightly erythematous. Photographs of her legs demonstrated 'diffuse lamellar ichthyosis.' Skin biopsy revealed hyperkeratosis and acanthosis without epidermolytic changes or intracytoplasmic vacuoles. Six additional family members were similarly affected, including a brother, paternal aunt and uncle, and 3 cousins. Her first-cousin parents and 3 sibs were unaffected.
Mapping
In a consanguineous Arab Muslim pedigree segregating an autosomal recessive late-onset autosomal recessive congenital ichthyosis of the lamellar type, Israeli et al. (2011) performed homozygosity mapping and identified 5 regions of homozygosity greater than 2 Mb in size. Fine mapping using microsatellite typing suggested linkage to chromosome 10q23 and excluded all other candidate loci. Recombination events narrowed the critical region to a 10.8-Mb interval bound by markers D10S1174 and D10S520.
Molecular Genetics
In a consanguineous Arab Muslim pedigree with late-onset ARCI of the lamellar type mapping to chromosome 10q23, Israeli et al. (2011) sequenced 28 candidate genes and identified homozygosity for a 2-bp deletion in the LIPN gene (613924.0001) that segregated with disease in the family.
INHERITANCE \- Autosomal recessive SKIN, NAILS, & HAIR Skin \- Ichthyosis, diffuse lamellar \- Fine whitish scales over entire surface of skin \- Slight erythema of face Skin Histology \- Hyperkeratosis \- Orthokeratosis \- Hypergranulosis \- Acanthosis MISCELLANEOUS \- Skin appears normal at birth, with development of generalized ichthyosis in childhood MOLECULAR BASIS \- Caused by mutation in the lipase N gene (LIPN, 613924.0001 ) ▲ 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
| ICHTHYOSIS, CONGENITAL, AUTOSOMAL RECESSIVE 8 | c3553029 | 2,032 | omim | https://www.omim.org/entry/613943 | 2019-09-22T15:57:01 | {"doid": ["0060717"], "mesh": ["D017490"], "omim": ["613943"], "icd-10": ["Q80.2"], "orphanet": ["313"], "synonyms": ["ICHTHYOSIS, LAMELLAR, 4, FORMERLY", "LI", "Congenital lamellar ichthyosis", "Alternative titles", "LAMELLAR ICHTHYOSIS, LATE-ONSET", "Classic lamellar ichthyosis"], "genereviews": ["NBK1420"]} |
A number sign (#) is used with this entry because Bardet-Biedl syndrome-4 (BBS4) is caused by homozygous mutation in the BBS4 gene (600374) on chromosome 15q24.
Description
BBS4 is a rare multisystemic disorder characterized primarily by retinal dystrophy, obesity, polydactyly, and renal dysfunction that accounts for less than 3% of BBS (Katsanis et al., 2002). Anosmia has been described in patients with BBS4 (Iannaccone et al., 2005), as well as polydactyly confined to the hands (Carmi et al., 1995).
For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (209900).
Clinical Features
Iannaccone et al. (2005) described 3 patients with BBS4 from an Italian family (Mykytyn et al., 2001). The proband had a history of retinal degeneration with early-onset night blindness and reduced visual acuity (20/100 by age 12), obesity, syndactyly of the right hand, and dental abnormalities. He had cryptorchidism but not hypogenitalism, and borderline intelligence but not overt mental retardation. He had completed high school and was employed. He was anosmic. His sister had retinal degeneration with early-onset night blindness and poor visual acuity, polydactyly of the right foot, brachydactyly, clinodactyly of the fifth finger in both hands, mild obesity, delayed secondary sexual development, and dental abnormalities. Her degree of cognitive impairment made her ineligible for olfactory testing. The cousin of these sibs also had a history of retinal degeneration with early-onset night blindness; he also had syndactyly of the right hand, mild obesity, and cystic changes in the left kidney. Like the proband, he had cryptorchidism without hypogenitalism, and normal intelligence. He had markedly reduced olfactory function. Iannaccone et al. (2005) concluded that the BBS4 gene plays a role in olfaction, supporting the hypothesis that ciliary dysfunction is an important aspect of BBS pathogenesis. They suggested that the spectrum of clinical manifestations associated with BBS be broadened to include decreased olfaction.
Genotype/Phenotype Correlations
Carmi et al. (1995) compared the clinical manifestations of BBS in 3 unrelated, extended Arab-Bedouin kindreds in which linkage had been demonstrated to chromosomes 3 (BBS3; 600151), 15 (BBS4), and 16 (BBS2; 615981). Observed differences included the limb distribution of the postaxial polydactyly and the extent and age-association of obesity. It appeared that the chromosome 3 locus is associated with polydactyly of all 4 limbs, while polydactyly of the chromosome 15 type is mostly confined to the hands. The chromosome 15 type is associated with early-onset morbid obesity, while the chromosome 16 type appears to present the 'leanest' end of BBS.
Mapping
Carmi et al. (1995) used a DNA pooling approach with DNA samples from a highly inbred Bedouin kindred to identify a Bardet-Biedl syndrome locus on chromosome 15. Homozygosity mapping using pooled DNA samples assumes that all or most of the affected individuals share a common chromosomal region inherited from a common ancestral founder. The pooled DNA was used as a PCR template with primers for short tandem repeat polymorphisms (STRPs). Pools consisting of DNA from unaffected sibs and parents of affected individuals were used as controls. Markers not linked to the disease locus are expected to show similar allele frequencies in the affected and controlled pools as a result of independent assortment. On the other hand, STRPs in linkage disequilibrium with the disease phenotype show a shift in allele frequencies toward a single homozygous allele in the affected DNA pool. Following identification of linked loci by linkage disequilibrium (homozygosity mapping), individual members of the pedigree were genotyped using the STRP markers. All 8 STRPs resulted in a positive lod score. Carmi et al. (1995) commented that the locus on chromosome 15 in the q22.3-q23 region is not near any of the known human retinopathy loci and is not in the region of syntenic homology with any of the known mouse obesity loci. The phenotype of the patients in the chromosome 15 kindred was very similar to that described for the previously linked loci. Identification of the genes involved in these 4 genetic forms of BBS may aid in the understanding of common disorders such as obesity, hypertension, and diabetes.
Molecular Genetics
Mykytyn et al. (2001) identified 3 homozygous mutations (e.g., 600374.0001, 600374.0002) in the BBS4 gene in 5 consanguineous families. They also identified a heterozygous BBS4 mutation in a small nonconsanguineous family.
Katsanis et al. (2002) detected mutation in the BBS4 gene (e.g., 600374.0003, 600374.0004) in 5 of 177 BBS families in a multiethnic patient cohort.
INHERITANCE \- Autosomal recessive GROWTH Weight \- Obesity HEAD & NECK Eyes \- Retinal degeneration \- Retinitis pigmentosa \- Night blindness Nose \- Impaired olfaction (in some patients) Teeth \- Dental abnormalities (in some patients) GENITOURINARY External Genitalia (Male) \- Cryptorchidism \- Hypogenitalism \- Hypogonadism Kidneys \- Renal cysts \- Renal anomalies SKELETAL Hands \- Polydactyly \- Brachydactyly \- Syndactyly Feet \- Polydactyly NEUROLOGIC Central Nervous System \- Mental retardation (in some patients) MOLECULAR BASIS \- Caused by mutation in the BBS4 gene (BBS4, 600374.0001 ) ▲ 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
| BARDET-BIEDL SYNDROME 4 | c0752166 | 2,033 | omim | https://www.omim.org/entry/615982 | 2019-09-22T15:50:29 | {"doid": ["0110126"], "mesh": ["D020788"], "omim": ["615982"], "orphanet": ["110"]} |
Distal trisomy 22q is a rare chromosomal anomaly syndrome, resulting from the partial duplication of the long arm of chromosome 22, with variable phenotype principally characterized by varying degrees of intellectual disabilty and developmental delay, pre- and postnatal growth deficiency, hypotonia, and craniofacial dysmorphism (incl. microcephaly, hypertelorism, narrow and upslanted palpebral fissures, epicanthic folds, low-set dysplastic ears, broad and depressed nasal bridge, cleft lip an/or palate, long philtrum, retro/micrognathia). Congenital heart defects, as well as cerebral, skeletal, renal and genital anomalies, have also been reported.
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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
| Distal trisomy 22q | c4706936 | 2,034 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=96109 | 2021-01-23T18:15:17 | {"icd-10": ["Q92.3"], "synonyms": ["Distal duplication 22q", "Telomeric duplication 22q", "Trisomy 22qter"]} |
Periorbital cellulitis
Other namesPreseptal cellulitis
Periorbital cellulitis caused by a dental infection (also causing maxillary sinusitis)
SpecialtyOphthalmology
Periorbital cellulitis (not to be confused with orbital cellulitis, which is posterior to the orbital septum), is an inflammation and infection of the eyelid and portions of skin around the eye anterior to the orbital septum.[1] It may be caused by breaks in the skin around the eye, and subsequent spread to the eyelid; infection of the sinuses around the nose (sinusitis); or from spread of an infection elsewhere through the blood.
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Diagnosis
* 4 Treatment
* 5 See also
* 6 References
* 7 External links
## Signs and symptoms[edit]
Periorbital cellulitis must be differentiated from orbital cellulitis, which is an emergency and requires intravenous (IV) antibiotics. In contrast to orbital cellulitis, patients with periorbital cellulitis do not have bulging of the eye (proptosis), limited eye movement (ophthalmoplegia), pain on eye movement, or loss of vision. If any of these features is present, one must assume that the patient has orbital cellulitis and begin treatment with IV antibiotics. CT scan may be done to delineate the extension of the infection.
Affected individuals may experience the following; swelling, redness, discharge, pain, shut eye, conjunctival infection, fever (mild), slightly blurred vision, teary eyes, and some reduction in vision.
Typical signs include periorbital erythema, induration, tenderness and warmth.[2]
## Causes[edit]
Staphylococcus aureus, Streptococcus pneumoniae, other streptococci, and anaerobes are the most common causes, depending on the origin of the infection.[3]
The advent of the Haemophilus influenzae vaccine has dramatically decreased the incidence.[4]
## Diagnosis[edit]
Tests include blood work (CBC) to rule out infectious cause. Also perform a CT scan, x ray of the anterior skull to view the sinuses, MRI scan and finally a soft tissue ultrasound of the orbital region.
## Treatment[edit]
Antibiotics are aimed at gram positive bacteria. Medical attention should be sought if symptoms persist beyond 2–3 days.
## See also[edit]
* Orbital cellulitis
* Cellulitis
## References[edit]
1. ^ http://www.healthatoz.com/healthatoz/Atoz/common/standard/transform.jsp?requestURI=/healthatoz/Atoz/ency/orbital_and_periorbital_cellulitis.jsp Archived 2008-06-26 at the Wayback Machine
2. ^ Givner, Laurence B. (1 December 2002). "Periorbital versus orbital cellulitis". The Pediatric Infectious Disease Journal. 21 (12): 1157–1158. doi:10.1097/00006454-200212000-00014. PMID 12488668.
3. ^ Botting, A.M.; McIntosh, D.; Mahadevan, M. (2008). "Paediatric pre- and post-septal peri-orbital infections are different diseases". International Journal of Pediatric Otorhinolaryngology. 72 (3): 377–383. doi:10.1016/j.ijporl.2007.11.013. PMID 18191234.
4. ^ Donahue S, Schwartz G (1998). "Preseptal and orbital cellulitis in childhood. A changing microbiologic spectrum". Ophthalmology. 105 (10): 1902–5, discussion 1905–6. doi:10.1016/S0161-6420(98)91038-7. PMID 9787362.
## External links[edit]
Classification
D
* ICD-10: L03.2
* ICD-9-CM: 373.13
* DiseasesDB: 31304
External resources
* MedlinePlus: 000976
* eMedicine: emerg/415 oph/206
* v
* t
* e
* Diseases of the human eye
Adnexa
Eyelid
Inflammation
* Stye
* Chalazion
* Blepharitis
* Entropion
* Ectropion
* Lagophthalmos
* Blepharochalasis
* Ptosis
* Blepharophimosis
* Xanthelasma
* Ankyloblepharon
Eyelash
* Trichiasis
* Madarosis
Lacrimal apparatus
* Dacryoadenitis
* Epiphora
* Dacryocystitis
* Xerophthalmia
Orbit
* Exophthalmos
* Enophthalmos
* Orbital cellulitis
* Orbital lymphoma
* Periorbital cellulitis
Conjunctiva
* Conjunctivitis
* allergic
* Pterygium
* Pseudopterygium
* Pinguecula
* Subconjunctival hemorrhage
Globe
Fibrous tunic
Sclera
* Scleritis
* Episcleritis
Cornea
* Keratitis
* herpetic
* acanthamoebic
* fungal
* Exposure
* Photokeratitis
* Corneal ulcer
* Thygeson's superficial punctate keratopathy
* Corneal dystrophy
* Fuchs'
* Meesmann
* Corneal ectasia
* Keratoconus
* Pellucid marginal degeneration
* Keratoglobus
* Terrien's marginal degeneration
* Post-LASIK ectasia
* Keratoconjunctivitis
* sicca
* Corneal opacity
* Corneal neovascularization
* Kayser–Fleischer ring
* Haab's striae
* Arcus senilis
* Band keratopathy
Vascular tunic
* Iris
* Ciliary body
* Uveitis
* Intermediate uveitis
* Hyphema
* Rubeosis iridis
* Persistent pupillary membrane
* Iridodialysis
* Synechia
Choroid
* Choroideremia
* Choroiditis
* Chorioretinitis
Lens
* Cataract
* Congenital cataract
* Childhood cataract
* Aphakia
* Ectopia lentis
Retina
* Retinitis
* Chorioretinitis
* Cytomegalovirus retinitis
* Retinal detachment
* Retinoschisis
* Ocular ischemic syndrome / Central retinal vein occlusion
* Central retinal artery occlusion
* Branch retinal artery occlusion
* Retinopathy
* diabetic
* hypertensive
* Purtscher's
* of prematurity
* Bietti's crystalline dystrophy
* Coats' disease
* Sickle cell
* Macular degeneration
* Retinitis pigmentosa
* Retinal haemorrhage
* Central serous retinopathy
* Macular edema
* Epiretinal membrane (Macular pucker)
* Vitelliform macular dystrophy
* Leber's congenital amaurosis
* Birdshot chorioretinopathy
Other
* Glaucoma / Ocular hypertension / Primary juvenile glaucoma
* Floater
* Leber's hereditary optic neuropathy
* Red eye
* Globe rupture
* Keratomycosis
* Phthisis bulbi
* Persistent fetal vasculature / Persistent hyperplastic primary vitreous
* Persistent tunica vasculosa lentis
* Familial exudative vitreoretinopathy
Pathways
Optic nerve
Optic disc
* Optic neuritis
* optic papillitis
* Papilledema
* Foster Kennedy syndrome
* Optic atrophy
* Optic disc drusen
Optic neuropathy
* Ischemic
* anterior (AION)
* posterior (PION)
* Kjer's
* Leber's hereditary
* Toxic and nutritional
Strabismus
Extraocular muscles
Binocular vision
Accommodation
Paralytic strabismus
* Ophthalmoparesis
* Chronic progressive external ophthalmoplegia
* Kearns–Sayre syndrome
palsies
* Oculomotor (III)
* Fourth-nerve (IV)
* Sixth-nerve (VI)
Other strabismus
* Esotropia / Exotropia
* Hypertropia
* Heterophoria
* Esophoria
* Exophoria
* Cyclotropia
* Brown's syndrome
* Duane syndrome
Other binocular
* Conjugate gaze palsy
* Convergence insufficiency
* Internuclear ophthalmoplegia
* One and a half syndrome
Refraction
* Refractive error
* Hyperopia
* Myopia
* Astigmatism
* Anisometropia / Aniseikonia
* Presbyopia
Vision disorders
Blindness
* Amblyopia
* Leber's congenital amaurosis
* Diplopia
* Scotoma
* Color blindness
* Achromatopsia
* Dichromacy
* Monochromacy
* Nyctalopia
* Oguchi disease
* Blindness / Vision loss / Visual impairment
Anopsia
* Hemianopsia
* binasal
* bitemporal
* homonymous
* Quadrantanopia
subjective
* Asthenopia
* Hemeralopia
* Photophobia
* Scintillating scotoma
Pupil
* Anisocoria
* Argyll Robertson pupil
* Marcus Gunn pupil
* Adie syndrome
* Miosis
* Mydriasis
* Cycloplegia
* Parinaud's syndrome
Other
* Nystagmus
* Childhood blindness
Infections
* Trachoma
* Onchocerciasis
*[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 inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| Periorbital cellulitis | c0149754 | 2,035 | wikipedia | https://en.wikipedia.org/wiki/Periorbital_cellulitis | 2021-01-18T18:53:55 | {"umls": ["C0149754"], "icd-9": ["373.13"], "icd-10": ["L01.1"], "wikidata": ["Q7168676"]} |
A number sign (#) is used with this entry because fragile X (FXS) is caused by mutation in the FMR1 gene (309550). The vast majority of cases are caused by a trinucleotide (CGG)n repeat expansion (309550.0004) of greater than 200 repeats.
See also fragile X tremor/ataxia syndrome (FXTAS; 300623), which is caused by expanded FMR1 (CGG)n repeats that range in size from 55 to 200 repeats and are referred to as 'premutations.'
Description
Fragile X syndrome is characterized by moderate to severe mental retardation, macroorchidism, and distinct facial features, including long face, large ears, and prominent jaw. In most cases, the disorder is caused by the unstable expansion of a CGG repeat in the FMR1 gene and abnormal methylation, which results in suppression of FMR1 transcription and decreased protein levels in the brain (Devys et al., 1993).
### Reviews
Fragile X syndrome accounts for about one-half of cases of X-linked mental retardation and is the second most common cause of mental impairment after trisomy 21 (190685) (Rousseau et al., 1995).
McCabe et al. (1999) summarized the proceedings of a workshop on the fragile X syndrome held in December 1998.
Jacquemont et al. (2007) provided a review of fragile X syndrome, which they characterized as a neurodevelopmental disorder, and FXTAS, which they characterized as a neurodegenerative disorder.
Clinical Features
Lubs (1969) reported a family in which 4 males spanning 3 generations had mental retardation. Cytogenetic studies showed an unusual constriction of the long arm of the X chromosome in 10 to 33% of cells. In a follow-up report of the same family, Lubs et al. (1984) noted that affected individuals had large testes, low-set large ears, and asymmetric facial features with prominent angle of the jaw.
Cantu et al. (1976) reported 4 male sibs with congenital bilateral macroorchidism and severe mental retardation. Detailed endocrinologic evaluation, including sperm analysis, indicated normal testicular function.
Mattei et al. (1981) reported 20 patients from 15 unrelated families with fragile X syndrome. In all 19 affected male and 1 affected female proband, the fragile X site was detected in 10-61% of lymphocyte or fibroblast cells; there seemed to be no correlation between the frequency of the fragile site and clinical severity. Three sisters of probands were mildly affected, but carrier females were unaffected. Affected male individuals showed characteristic facies, including long face, high forehead, midface hypoplasia, large mouth with long upper middle incisors, thick lips, high-arched palate, large jaw with prominent chin, and large, poorly formed ears. None of 14 prepubertal males showed macroorchidism. Mental retardation was very variable, but language development was usually very delayed. Motor development was often delayed. Most showed unusual behavior, with alternating anxiety and hilarity, disordered hyperactivity, and aggressiveness.
Lubs et al. (1984) reported a large African American kindred in which 10 males had mental retardation and macroorchidism associated with the abnormal X chromosome marker. Other variable clinical features included asymmetric facies and large hands. Six females were similarly affected. Meryash et al. (1984) studied 18 affected males, aged 18 to 69 years. Of 15 subjects, 13 had macroorchidism. Average height was less than published standards. Of the 18 subjects, 17 had absolute or relative macrocephaly and 12 were dolichocephalic.
Jacobs (1982) encountered a man and Daker et al. (1981) reported 2 brothers with marXq28 and average intelligence. Similarly, Fryns and Van Den Berghe (1982) presented a kindred in which the fragile X chromosome was transmitted by at least 3 normal males. These men died at ages 68, 72, and 76 years and had a normal phenotype with normal intelligence; one was an administrator and 2 were officers. Voelckel et al. (1988) reported 3 brothers with the fragile X; only 2 were mentally retarded. Johnson et al. (1991) described a large kindred with 10 mentally retarded, fragile X-positive males, and 2 normal transmitting males. Pellissier et al. (1991) also described a kindred with 2 normal transmitter brothers.
Loesch and Hay (1988) presented the clinical findings on 113 fragile X female heterozygotes from 44 families. In 85% of a subsample of 92 adult females, the nonverbal IQ score was 85 or less. Verbal ability deficits were much less common. Typical facial characteristics, irregular teeth, and hypermobility of finger joints occurred in approximately 40% of adult females, but facial abnormalities were less common in children. Although the frequency of miscarriages was increased, a moderate increase in the number of children was found in female carriers with borderline intellectual impairment. The question of whether ovarian size is increased in females with the fragile X was addressed by Goodman et al. (1987).
A Prader-Willi-like subphenotype of the fragile X syndrome was described by de Vries et al. (1993). Clinical features included extreme obesity with a full, round face, small, broad hands and feet, and regional skin hyperpigmentation. Unlike the Prader-Willi syndrome (176270), the patients lacked the neonatal hypotonia and feeding problems during infancy followed by hyperphagia during toddlerhood. In a group of 26 patients with suspected Prader-Willi syndrome but without detectable molecular abnormalities of chromosome 15, one fragile X patient was found. General overgrowth was described in 4 fragile X patients, all of whom came from families with other affected relatives who showed the classic Martin-Bell phenotype (de Vries et al., 1995). Schrander-Stumpel et al. (1994) found the FMR1 mutation in a 3-year-old boy with unexplained extreme obesity and delayed motor and speech development. They compared the clinical features with those in 9 reported patients with the fragile X syndrome and extreme obesity. They suggested that behavioral characteristics such as hyperkinesis, autistic-like behavior, and apparent speech and language deficits may help point toward the diagnosis of the fragile X syndrome.
Limprasert et al. (2000) described unilateral macroorchidism in a boy with fragile X syndrome and discussed the possible explanations.
Backes et al. (2000) evaluated a group of boys with fragile X syndrome, ascertained by molecular genetic methods, to determine a cognitive and behavioral profile. The cognitive phenotype revealed a general intelligence corresponding to mild to moderately severe mental retardation. Psychiatric comorbidity was high, and attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder, enuresis, and encopresis predominated. No significant correlation between the specific features of the phenotype and genotype were found.
Other Features
Stigmata of connective tissue abnormalities in fragile X syndrome have been reported, including finger joint hypermobility, instability of other joints (Opitz et al., 1984; Hagerman et al., 1984), and mitral valve prolapse (Pyeritz et al., 1982). Hagerman and Synhorst (1984) not only confirmed mitral valve prolapse but also demonstrated mild dilatation of the ascending aorta.
Davids et al. (1990) found that of 150 male patients with the fragile X syndrome, 75 had flat feet, 85 had excessive laxity of joints, and 10 had scoliosis. In 29 of the patients, flat feet had been evaluated or treated by an orthopedic surgeon before the diagnosis of fragile X syndrome had been made.
Langenbeck et al. (1984) found that mean corpuscular hemoglobin was increased in this disorder and asked whether this was a reflection of a defect in folate metabolism.
Rodewald et al. (1987) described ganglioglioma of the cauda equina in a 17-year-old male with familial Martin-Bell syndrome. Because of the association of neoplasms with autosomal chromosome abnormalities, Rodewald et al. (1987) suggested that this may be more than coincidence. However, they found no published reports of tumors associated with Martin-Bell syndrome.
Fryns (1993) noted periorbital hyperpigmentation and scrotal hyperpigmentation about the time of puberty.
Reiss et al. (1994) showed that the volume of the hippocampus was enlarged in fragile X patients compared to controls. Furthermore, there was an age-related increase in the volume of the hippocampus and an age-related decrease in the volume of the superior temporal gyrus. In another study, Reiss et al. (1991) showed that fragile X males had a significantly decreased size of the posterior cerebellar vermis and increased size of the fourth ventricle, when compared with age- and sex-matched groups of fragile X-negative, developmentally disabled subjects and individuals with normal IQ. Reiss et al. (1991) showed that young fragile X females had decreased size of the posterior cerebellar vermis and increased size of the fourth ventricle, when compared with normal age-, sex-, and IQ-matched females. The findings were intermediate between those of the fragile X males and the non-fragile X control groups.
Jakala et al. (1997) found that males with the full fragile X (fM) mutation showed worse cognitive performance than did males with the premutation (pM); deficits in females with the fM were qualitatively similar but less severe than in males with the fM. In a visual memory test, both fM groups were impaired. Hippocampal volumes normalized for intracranial or brain area did not significantly differ between fM and pM groups. Minor abnormalities in temporal lobe structures were found by MRI in fM subjects.
Lachiewicz et al. (2000) compared physical characteristics of young boys with fragile X with those of a control group. After adjustment for multiple comparisons, only 4 of 42 characteristics studied differed significantly in their distributions between the 2 groups. These included adverse response to touch on the skin, difficulty touching the tongue to the lips, soft skin over the dorsum of the hand, and hallucal crease. Ten other characteristics were identified that may also have predictive value for fragile X syndrome.
Gould et al. (2000) compared sleep patterns and endogenous melatonin profiles in 13 boys with fragile X to 8 age-matched normal controls. Results showed greater variability in total sleep time, difficulty in sleep maintenance, and significantly greater nocturnal melatonin production in the boys with fragile X.
Koekkoek et al. (2005) observed a severe defect in eyeblink conditioning in 6 patients with fragile X syndrome, indicating a deficit in cerebellar motor learning. Fmr1-null mice also showed deficits in classic delay eyeblink conditioning, and Fmr1-null mouse cerebellar Purkinje cells showed elongated irregular dendritic spines and enhanced long-term depression induction at the parallel fiber synapses that innervate these spines. The findings indicated that a lack of FMRP leads to cerebellar dysfunction.
Moro et al. (2006) reported 2 unrelated boys with fragile X syndrome who had periventricular heterotopia on brain MRI. One had 3 heterotopic nodules, and the other had a single nodule. The findings suggested that abnormal neuronal migration contributes to the neurologic phenotype.
Gothelf et al. (2008) compared the neuroanatomy of 84 children and adolescents with fragile X syndrome to 72 control individuals using various MR imaging methods. Although there was no difference between the groups for total brain volume, separate analysis for different brain regions showed that patients had significantly smaller cortical lobes, significantly increased size of the caudate nucleus, and decreased size of the posterior cerebellar vermis, amygdala, and superior temporal gyrus compared to controls. The combination of a large caudate with small posterior cerebellar vermis, amygdala, and superior temporal gyrus could distinguish children with fragile X syndrome from control subjects with high sensitivity and specificity. Large caudate and small posterior cerebellar vermis were associated with lower FMRP levels and more pronounced cognitive deficits and aberrant behaviors, including autistic features. Gothelf et al. (2008) suggested that abnormal development of the prefrontal-striatal pathway and the orbitofrontal-amygdala circuit characterizes a neuroanatomic phenotype associated with fragile X syndrome.
In a systematic chart review of over 500 patients with fragile X syndrome, Berry-Kravis et al. (2015) found that male patients had significantly reduced levels of total cholesterol, low density lipoprotein (LDL), and high density lipoprotein (HDL) compared to matched controls. These findings were not related to body mass index (BMI).
### Male Premutation Carriers
Some boys with expanded FMR1 (CGG)n repeats that range in size from 55 to 200 repeats, referred to as 'premutations,' may exhibit similar, but possibly milder, clinical features to those with full expansions. Aziz et al. (2003) reported the clinical features of 10 boys with FMR1 CGG expansions between 45 and 198 repeats. Most had increased testicular volume and enlarged outer canthal distance, and most exhibited variable defects in social impairment, speech and language deficits, autistic features, hyperactivity, and/or developmental abnormalities.
Chonchaiya et al. (2012) examined 50 boys with FMR1 premutations for seizures and autistic features. Twenty-five boys were found to carry a premutation after direct referral for developmental issues ('probands'), and 25 additional boys were found to carry a FMR1 premutation after testing following identification of a family member with either the full mutation or a premutation ('non-probands'). The mean age of both groups was 9 years. All individuals with the premutation had increased FMR1 mRNA compared to sibs without a premutation. The probands with a premutation were significantly more likely to have features of autism spectrum disorder (68%) and seizures (28%) compared to controls (1.7% and 1% for autism spectrum disorder and seizures, respectively). Although none of the non-probands with premutations had seizures, 28% had features of autism spectrum disorder. Chonchaiya et al. (2012) concluded that boys with the FMR1 premutation should be assessed for autistic features and seizures.
### Female Premutation Carriers
For a discussion of premature ovarian failure (POF) associated with premutation in the FMR1 gene, see POF1 (311360).
Rousseau et al. (1991) observed an age-dependent phenomenon: the full fragile X mutation was found preferentially on the inactive X in leukocytes in adult females but not in younger ones. This phenomenon was not observed in female carriers of a premutation, who have little phenotypic expression. Preliminary data suggested that young females who show preferential presence of a full mutation on the active X in leukocytes may be at increased risk for mental retardation. There is a known decrease with age of the expression of the fragile site.
Steyaert et al. (2003) used the Sonneville Visual Attentions Task (SVAT) method to assess reaction time on different tasks in 3 groups of female subjects: premutation carriers, full mutation carriers, and control subjects. Their findings supported earlier findings that the fragile X premutation may affect neurocognitive function, in particular aspects of attention.
Hundscheid et al. (2003) investigated whether premutation carriers have an increased risk for diseases other than POF. Among 264 women from fragile X families, they found no statistically significant differences in the occurrence of diseases known to be associated with menopause, such as cardiovascular diseases and osteoporosis; however, lower bone mineral density was observed only in premutation carriers. Once a premutation carrier experiences premature ovarian failure, she is at risk for early estrogen deprivation which, if not treated, may lead to premature decrease in bone density.
Hunter et al. (2008) found no significant differences in neuropsychologic testing scores between 63 males under the age of 50 who were carriers of intermediate (20 to 55 repeats) or premutation (55 to 199 repeats) FMR1 alleles compared to 75 male controls. A comparison of 389 female intermediate or premutation allele carriers showed an association with increasing repeat length and self-reported attention difficulties compared to 117 female controls, but there were no differences in the other neuropsychologic testing scores.
Pathogenesis
Colak et al. (2014) demonstrated that FMR1 (309550) silencing is mediated by the FMR1 mRNA. The FMR1 mRNA contains the transcribed CGG-repeat tract as part of the 5-prime untranslated region, which hybridizes to the complementary CGG-repeat portion of the FMR1 gene to form an RNA/DNA duplex. Disrupting the interaction of the mRNA with the CGG-repeat portion of the FMR1 gene prevents promoter silencing. Colak et al. (2014) concluded that their data linked trinucleotide repeat expansion to a form of RNA-directed gene silencing mediated by direct interactions of the trinucleotide repeat RNA and DNA.
Cytogenetics
Lubs (1969) first described an abnormality of the distal long arm of the X chromosome, Xq, in 4 mentally retarded males from a single family. A secondary constriction of the chromosome gave the appearance of large satellites. Lubs (1969) suggested that either the anomalous region itself or a closely linked recessive gene might account for X-linked mental retardation. This observation went unconfirmed for years until cytogeneticists reverted to a folate-deficient medium for tissue culture such as Lubs (1969) employed. Appearance of this secondary constriction, referred to as a 'fragile site,' was localized to Xq27-q28 and was shown to be dependent on folate deficiency in the culture medium, which leads to deficiency of thymidine monophosphate (Giraud et al., 1976; Harvey et al., 1977; Sutherland, 1977). Sutherland was in Melbourne when he made his initial observations on the fragile X. When he went to Adelaide, he upgraded his laboratory, changing from 199 to F10 culture medium to give better chromosomes for banding. The failure to find the fragile X with the new medium led to his discovery of the critical role of folate (Gerald, 1983).
At least 12 other heritable secondary constrictions ('fragile sites') on other chromosomes were proved by the early 1980s (Sutherland, 1981; Hecht et al., 1982), but none had an association with a particular phenotype. In all pedigrees of marXq28 studied, no crossing-over between the marker and mental retardation had occurred. This suggested that the marker, rather than being closely linked to a gene causing mental retardation, is a direct cytologic indicator of the genetic mutation causing this phenotype (Kaiser-McCaw et al., 1980).
Turner et al. (1978) suggested labeling the marker 'secondary constriction Xq27'; however, convention requires that 'a break suspected at an interface between two bands is identified arbitrarily by the higher of the two band numbers' (ISCN, 1978; section 2.4.4.2). Brookwell and Turner (1983) again concluded that the fragile site is in band Xq27, close to the q27-q28 interface.
Lubs (1969) and Martin et al. (1980) found that the fragile X marker was not preferentially inactivated in female heterozygotes.
In a survey of retarded females who had no obvious physical abnormalities, Turner et al. (1980) found that 7% expressed marXq28 in lymphocytes. Among obligate heterozygotes, the likelihood of detecting marXq28 correlated with severity of retardation (Howard-Peebles and Stoddard, 1980; Jacobs et al., 1980). In 2 heterozygous sisters who were slow learners, Uchida and Joyce (1982) found that the fragile X was active in approximately 70% of cells, whereas 2 heterozygous relatives of normal intelligence had the fragile X active in approximately 30 to 50% of cells.
An earlier suggestion that the proportion of cells exhibiting marXq28 decreases with increasing heterozygote age (Sutherland, 1979; Jacobs et al., 1980; Turner et al., 1980) may have been an artifact due to ascertaining fewer retarded women in older age groups (Jacobs et al., 1982).
Inheritance
See review by Nussbaum and Ledbetter (1986).
In 4 of 27 large fragile X pedigrees, Fryns (1984) found strong evidence of transmission by normal males.
By analysis of multiple families with fragile X syndrome, Sherman et al. (1985) identified multiple special inheritance characteristics that differed from other X-linked traits. All mothers of affected sons were carriers; no new mutations were predicted. The risk of fragile X syndrome in offspring depended upon the sex and phenotype of the carrier parent. Daughters of nonpenetrant transmitting males were rarely affected, whereas daughters of normal carrier females had a higher chance of having affected daughters. Cognitively impaired females had a higher risk of having affected offspring. Mothers and daughters of transmitting males who were phenotypically similar had sons and daughters who expressed the gene differently. The gene seemed to be more penetrant in the offspring of daughters of transmitting males than in offspring of mothers of transmitting males. Sherman et al. (1985) suggested that a premutation exists which generates a definitive mutation only when transmitted by a female and that there is a submicroscopic rearrangement at Xq27.3 which per se causes no trouble but generates a significant genetic imbalance when involved in a recombinational event with the other X chromosome.
Pembrey et al. (1985) advanced a premutation hypothesis to explain unusual characteristics of the genetics of this disorder: transmission occurs through normal males; the heterozygous daughters of such males are never mentally retarded and have few or no fragile sites, and by contrast in the next generation, a third of heterozygous females are mentally subnormal with an average of 29% fragile sites (Sherman et al., 1985). This came to be called the Sherman paradox (Fu et al., 1991).
Winter and Pembrey (1986) analyzed linkage relationships of flanking genetic markers in daughters of normal transmitting males. There was a significant reduction in recombination in meioses giving rise to affected grandsons of normal transmitting males, as compared to families with no apparent normal transmitting males. One interpretation offered was interference related to a recombinational event leading to the full fragile X mutation.
Weaver and Sherman (1987) gave guidelines for counseling families with the Martin-Bell syndrome. Because of the peculiarities of the pedigrees, it is necessary to give different estimates for the risk among the sons and daughters of normal carrier mothers, mentally impaired carrier mothers, and normal transmitting males. Among the sons, the probability for mental impairment is 0.38, 0.5, and 0, respectively, and the chance of a son being a mentally normal carrier is 0.12, 0, and 0, respectively. Among the daughters, the risk of being a mentally impaired carrier is 0.16, 0.28, and 0, respectively, and the chance of being a mentally normal carrier is about 0.34, 0.22, and 1.0, respectively. Given a sporadic case in a male with no fragile X demonstrable in the mother, the estimates for occurrence in a brother of the proband vary from 9 to 27%, depending on the theoretical model used; the estimated risk in first cousins varies from 0.01 to 0.05.
Having excluded a mutation rate in male germ cells of the magnitude required by an exclusive mutation hypothesis to explain the high incidence of the fragile X syndrome, Vogel et al. (1990) proceeded to demonstrate an increased fitness of heterozygous females by a comparison with the reproductive performance of 'adequate' controls (mothers and grandparents of Down syndrome patients). Estimates ranged between 1.11 and 1.36. A higher incidence of dizygotic twinning suggested a biologic component for this increased fertility. On the other hand, the fragile X families had a significantly lower social status than the controls, suggesting a sociopsychologic component of their higher fertility.
Oberle et al. (1991) found that the transition from a premutation to a full mutation occurred only after passage through a female.
Yu et al. (1992) found that all individuals with the fragile X genotype had a parent with an amplified p(CCG)n repeat, indicating that few, if any, cases of fragile X syndrome are not familial.
Tabolacci et al. (2008) reported a 10-year-old boy with a normal CGG tract in the FMR1 gene and no fragile X syndrome phenotype; however, his 2 brothers were affected with fragile X syndrome due to an expanded allele. The mother carried a premutation allele of about 190 CGG. The 10-year-old unaffected boy was found to have an allele of 43 repeats with an unusual configuration detected using 2 different restriction enzymes, and the boy was not mosaic. Haplotype analysis proved that the rearranged allele originated from the maternal expanded allele, indicating contraction of the expanded CGG tract and reversion to a normal size FMR1 allele.
### Imprinting
Laird (1987) proposed that abnormal chromosome imprinting is involved in inheritance of the fragile X syndrome. Two independent events are required for expression of the syndrome: the fragile X mutation and X chromosome inactivation in pre-oogonial cells. According to this model, the fragile X mutation leads to an imprint, or stable inactivation of a gene or genes at the fragile X site because the mutation prevents reactivation of a mutant fragile X chromosome that had been inactivated in a female for dosage compensation. This block to reactivation leads to mental retardation in progeny by reducing the level of products from the unreactivated region in the male's cells, and for a heterozygous female, in somatic cells in which the normal X chromosome has been inactivated. The basis of this localized block to complete reactivation of a fragile X chromosome was proposed to be late replication of DNA at the fragile site (Laird et al., 1987).
From an analysis of data on fragile X, Laird et al. (1990) concluded that 2 progenitor cells for human oogonia may be present at the time of the initial event that leads to chromosome imprinting. The estimate was based on the fact that one-half of the female's primary oocytes would, on the average, be expected to show imprinting if X-chromosome inactivation is the initial step. The population genetic predictions of the 'X-inactivation imprinting' model indicate that the fraction of carrier males who are nonpenetrant (nonimprinted) would be about 0.5 at equilibrium (Sved and Laird, 1990). Sved and Laird (1988) suggested that this predicted fraction is higher than the reported fraction of 0.2 (Sherman et al., 1985) because of an unusual ascertainment bias.
Laird (1991) explained the cytogenetic disappearance of the fragile X site in the few daughters of affected males that have been reported as a consequence of erasure of the imprint when it is passed through males. Erasure of chromosome imprinting often occurs when the imprinted chromosome is passed through the parental gender opposite from the gender that established the imprint. Reimprinting apparently can occur, however, in primary oocytes of these daughters.
Follette and Laird (1992) examined the stability of the imprinted state, defining stability as 100% penetrance of the syndrome in sons who receive an imprinted chromosome from the mother. In a preliminary estimate, they concluded that the fragile X imprint was stable in 46 of 48 female meioses, giving a tentative estimate of about 96% for the stability of the imprint.
Kirkilionis et al. (1992) presented the pedigree of a large family that illustrated dramatically the Sherman paradox and was compatible with the predictions of the Laird X-inactivation imprinting model.
Zeesman et al. (2004) reported a family in which a fragile X mosaic male, with both premutation and full mutation alleles in his peripheral blood leukocytes, had a daughter with both premutation and partially methylated full mutation alleles and a significant developmental disability. The sperm cells in the father contained only alleles in the premutation range; because the daughter had both premutation and full mutation alleles, the expansion to full mutation must have occurred postzygotically. The authors believed this to be the first report of a paternally derived full mutation expressed in a female. Steinbach and Steinbach (2005) disputed the conclusion of Zeesman et al. (2004) of paternal transmission of fragile X syndrome, and Tassone et al. (2005) provided a response.
Mapping
In 6 of 18 informative Sardinian pedigrees with fragile X syndrome, Filippi et al. (1983) found close linkage with G6PD (305900) and deutan colorblindness (CBD; 303800), both linked to Xq28. The maximum likelihood estimate of recombination was 6% with 90% fiducial limits between 2.5 and 19.5% and odds favoring linkage of 428:1. There was no linkage between G6PD and the Renpenning form of X-linked mental retardation (RENS1; 309500) on Xp11.
Camerino et al. (1983) found close linkage between the factor IX locus (F9; 300746) on Xq27 and fragile X syndrome in a large affected family (lod score of 4.02 at a theta of 0.05 for Xq27). In addition, they demonstrated transmission of the disorder through a phenotypically normal male. They observed no meiotic recombination out of 17 opportunities.
Szabo et al. (1984) determined that the G6PD locus is distal to the fragile X locus on Xq27.3. Although both G6PD and F9 have been linked to fragile X, F9 has been shown to segregate independently from deutan and protan (CBP; 303900) color blindness in some families. Szabo et al. (1984) concluded that the Xq27 region is a 'hotspot' for meiotic recombination; that the microscopically detectable change in fragile X syndrome is probably a minute chromosomal aberration resulting from an inaccurate recombination event; and that recombination is suppressed at the Xq27.3 region in heterozygous females.
Using intragenic RFLPs of factor IX in the study of 3 families with the fragile X syndrome, Forster-Gibson et al. (1985) found a minimum of 4 recombinations in 9 meioses. A maximum lod score of 2.75 at theta 0.20 was estimated. The authors concluded that the genetic distance between fragile X and factor IX was too great for factor IX probes to be useful for carrier detection of fragile X syndrome.
Warren et al. (1985) reported a family in which 2 brothers with fragile X mental retardation had different factor IX RFLPs, indicating that a recombinational event occurred between the 2 loci. Brown et al. (1985) found that pedigrees with nonpenetrant males showed tight linkage to factor IX, whereas the linkage was loose in those pedigrees with full penetrance in males. Giannelli et al. (1987) found that families with nonpenetrant carrier males showed tighter linkage to factor IX than did the others and suggested the existence of 2 fragile X loci. In a multilocus linkage analysis of 147 families, Brown et al. (1988) found significant variation in the recombination distance between F9 and FRAXA. Heterogeneity testing showed that 20% of the families had tight F9-FRAXA linkage, whereas 80% demonstrated loose linkage, with an average recombination distance of 0.35. On average, the multipoint distances found were DXS51-F9, 6.9%; F9-FRAXA, 22.4%; FRAXA-DXS52, 12.7%; and DXS52-DXS15, 2.2%. In 14 families with fragile X and 9 normal pedigrees from the CEPH collection, Thibodeau et al. (1988) also observed genetic heterogeneity between the fragile X locus and the F9 locus, with recombination frequencies of DXS51-F9, 0%; F9-DXS52, 45%; DXS51-FRAXA, 15%; F9-FRAXA, 18%; DXS98-FRAXA, 36%; and DXS52-FRAXA, 15%. The authors proposed the relative order for the 5 loci as DXS51, F9, DXS98--FRAXA--DXS52.
Using a 275-kb fragment of human DNA isolated in a yeast artificial chromosome (YAC) and thought to span the fragile site, Yu et al. (1991) derived 2 probes that spanned the fragile site as demonstrated by in situ hybridization. Mapping delineated further the sequences that appeared to span the fragile site to about 15 kb. A 5-kb EcoRI fragment was found to contain fragile site breakpoints. When this fragment was used as a probe on the chromosomal DNA of normal and fragile X individuals, alterations in the mobility of the sequences were found only in fragile X DNA. These sequences were of an increased size and varied within families, indicating that the region was unstable. The results were consistent with those of Oberle et al. (1991).
Richards et al. (1991) used microsatellite markers to position the fragile X locus within the multipoint map of the X chromosome to a position 3.7 cM distal to DXS297 and 1.2 cM proximal to DXS296. They described 2 polymorphic microsatellite AC repeat markers, FRAXAC1 and FRAXAC2, physically located within 10 kb and on either side of the (CCG)n repeat responsible for the fragile site. The 2 markers showed strong linkage disequilibrium and have heterozygosity of 44 and 71%, respectively. No recombination was observed either between these markers in 40 CEPH pedigrees or with FMR1 in affected pedigrees.
Diagnosis
Jacky and Dill (1980) detected the fragile X chromosome in cultured lymphocytes and fibroblasts from affected patients. Glover (1981), Tommerup et al. (1981), and Jacobs et al. (1982) demonstrated that pharmacologic inhibition of thymidylate synthetase (TYMS; 188350) was effective in inducing the fragile X marker in cell cultures. Snyder et al. (1984) showed that culture conditions that promote expression of the fragile X site do not affect expression of lymphocyte HPRT but do cause a marked reduction in G6PD activity.
Sutherland (1989) indicated that there is a fragile site (FRAXD) located at Xq27.2, separate from the classic FRAXA site at Xq27.3 which is responsible for mental retardation. The FRAXD is inducible by high doses of aphidicolin. Ramos et al. (1992) concluded that the fragile site at Xq27.2 can be demonstrated in normal persons under the conditions of thymidylate stress routinely used for cytogenetic diagnosis of the fragile X syndrome. Furthermore, this fragile site is present at low levels (1-2%) in all persons who express it and, therefore, its expression is unlikely to cause false-positive diagnoses of the syndrome. Lesions at Xq26 are also seen at low levels in lymphocytes of persons without the syndrome.
Griffiths and Strachan (1991) described a technique, based on a culture system reported by Wheater and Roberts (1987), that enabled the cytogeneticist to do fra(X) screening and prometaphase banding on the same specimen.
Using restriction enzymes, Oberle et al. (1991) detected abnormally large-sized fragments and abnormal methylation around the fragile X site in affected males and carrier females. Some affected males appeared to be mosaics, with coexistence of a large methylated fragment and a smaller normal unmethylated fragment. Rare apparent false negatives were considered to be the result of genetic heterogeneity or misdiagnosis.
Rousseau et al. (1991) concluded that direct DNA diagnosis of the fragile X syndrome is efficient and reliable. Southern analysis of EcoRI and EagI digests of DNA distinguished clearly in a single test between the normal genotype, the premutation, and the full mutation. All 103 affected males and 31 of 59 females with full mutations had mental retardation. Fifteen percent of those with full mutations had some cells carrying only the premutation. All of the mothers of affected children were carriers of either a premutation or a full mutation. Because of the certainty of DNA diagnosis, this method replaced cytogenetic detection of the fragile X chromosome, which carries a rate of misdiagnosis of about 5% for both false positives and the more frequent false negative conclusion, and diagnosis by the linkage principle, which gives a probabilistic result rather than an absolute one. Jacobs (1991), however, stated that the cytogenetic marker still had an honorable role to play in the diagnosis of fragile X syndrome. It was reliable for virtually all males and for the majority of affected females and was the most efficient and cost effective methodology at that time.
Mandel et al. (1992) reported on the Fifth International Workshop on the Fragile X and X-Linked Mental Retardation held near Strasbourg, France, in August 1991. In addition to their summary, over 50 papers on the fragile X syndrome and 18 papers related to other X-linked mental retardation syndromes presented at the conference were published in the American Journal of Medical Genetics. Mandel et al. (1992) reviewed the hypothesis of Patricia Jacobs which postulated 3 mutations: a change from a normal insert (N) to a small insert that is at low risk of converting to a large insert (S); a change from that type of small insert to a small insert at high risk of converting to a large insert (S*); and a change from the high risk small insert to a large insert (L) which is associated with clinical abnormality. Cytogenetic screening of the mentally handicapped for the fra(X) was equivalent to testing for individuals with a large insert (L) as there was no evidence that a small insert (S) has a deleterious effect on the phenotype. The consensus was that in diagnostic laboratories cytogenetics is still the method of choice, with subsequent molecular investigation of those patients found or suspected of being fra(X) positive; no consensus was reached on the relative merits of cytogenetics and molecular techniques for screening. Mulley et al. (1992) reported a high success rate with the direct molecular diagnosis of fragile X using the pfxa3 probe which detects amplification of an unstable DNA element consisting of variable length CCG repeats.
Snow et al. (1993) found that PCR followed by DNA sequencing of the FMR1 gene allowed the most accurate determination of CGG repeat numbers up to approximately 130 repeats. Turner et al. (1996) suggested that the clinical definition of fragile X syndrome be redefined in males as a mental handicap associated with absolute or relative deficiency of the FMR1 protein. In the absence of a readily available protein test, analysis of the trinucleotide repeat size has been used for diagnosis. An increase in the size of the trinucleotide repeat over a particular value initiates methylation of the FMR gene promoter site and suppression of FMR1 gene transcription. Testing can identify individuals who lack FMR1 protein as a consequence of deletion of the gene but will not identify those individuals whose FMR1 protein is defective through mutation.
Willemsen et al. (1995, 1997) developed a diagnostic method using mouse monoclonal antibodies against the FMR1 protein that allowed for detection of the fragile X syndrome in a blood smear. This noninvasive test required only 1 or 2 drops of blood and could be used to screen large groups of mentally retarded persons and neonates. Willemsen et al. (1999) modified the antibody test for application to hair roots. Mentally retarded female patients with a full mutation showed FMR protein expression in only some of their hair roots (less than 55%), and no overlap with normal female controls was observed.
Storm et al. (1998) noted that incomplete EcoRI digestion may lead to false diagnosis of fragile X syndrome and suggested that HindIII digest be used instead of EcoRI to identify premutation vs normal fragment length in genomic DNA.
Abrams et al. (1999) examined olfactory neuroblasts from 2 mentally retarded, autistic brothers with fragile X expansion mutations in leukocytes. Olfactory neurons were chosen for study because they are accessible neurons that undergo regeneration and are closely linked to the brain. In both subjects, the genotype in neuroblasts was highly, but not perfectly, consistent with that observed in leukocytes. The results suggested that FMR1 mutation patterns in leukocytes are a good, albeit potentially fallible, reflection of such patterns in the brain and demonstrated the feasibility of using olfactory neuron samples to evaluate FMR1 mutations in humans in vivo.
Stoll (2001) presented 11 children under the age of 8 years and noted the difficulties in diagnosis of fragile X syndrome at this age. The author emphasized the importance of fragile X DNA testing in all children with mental retardation, autism, or significant developmental delay without a clear etiology.
MacKenzie et al. (2006) reported a 46-year-old male patient with a typical fragile X syndrome phenotype who was found to be a somatic mosaic for the FMR1 repeat expansion. Analysis of peripheral blood detected a premutation allele of 58 CGG repeats, whereas skin fibroblasts yielded a full mutation allele of 500 CGG repeats. The authors suggested that the proband may have inherited a full mutation that has undergone selective contraction, given his age at molecular diagnosis. MacKenzie et al. (2006) concluded that testing of ectodermally derived tissues may provide improved diagnosis for fragile X syndrome.
Coffee et al. (2009) reported the development of an assay for newborn screening of fragile X syndrome. The assay showed 100% specificity and 100% sensitivity for detecting FMR1 methylation on dried blood spots, thus successfully distinguishing normal males from those with the full mutation. The assay could also detect excess FMR1 methylation in 82% of females with full mutations, although the methylation status did not correlate with intellectual disability. With amelogenin PCR used for detecting the presence of a Y chromosome, this assay also detected males with Klinefelter syndrome (47,XXY). Among 64 males with FMR1 methylation, 7 were found to have full-mutation fragile X syndrome and 57 had Klinefelter syndrome. In their study of 36,124 newborn males, Coffee et al. (2009) estimated the incidence of fragile X syndrome to be 1 in 5,161 newborn males, and that of Klinefelter syndrome to be 1 in 633.
### Carrier Females
Toledano-Alhadef et al. (2001) tested 14,334 Israeli women of childbearing age for fragile X carrier status between 1992 and 2000. These women were either preconceptional or pregnant and had no family history of mental retardation. They identified 207 carriers of an allele with more than 50 repeats, representing a prevalence of 1:69. There were 127 carriers with more than 54 repeats, representing a prevalence of 1:113. Three asymptomatic women carried the full-mutation allele. Among the premutation and full-mutation carriers, 177 prenatal diagnoses were performed. Expansion occurred in 30 fetuses, 5 of which had an expansion to the full mutation. The authors recommended wide-scale screening to identify female carriers.
In 34 female full mutation carriers and unaffected female control relatives, Willemsen et al. (2003) found a correlation between cognitive function and the percentage of hair roots that expressed the FMRP protein. Cognitive function in the female carriers was much more strongly determined by the absence of FMRP than by genetic background.
Angkustsiri et al. (2008) described a 23-year-old woman with the full fragile X mutation who had no dysmorphic features and above-average intelligence combined with significant impairments due to anxiety and learning disability. Her brother had fragile X syndrome, her mother was a premutation carrier, and her maternal grandfather was the first patient diagnosed with the fragile X tremor/ataxia syndrome (FXTAS; 300623 and Hagerman et al., 2001). Angkustsiri et al. (2008) concluded that women with fragile X syndrome can present primarily with learning and emotional problems and that clinicians should consider the diagnosis in these women regardless of their IQ, particularly if there are physical features or a family history consistent with fragile X syndrome.
### Prenatal Diagnosis
Jenkins et al. (1982) detected the fragile X marker in cultured amniocytes, enabling successful prenatal diagnosis. Jenkins et al. (1984) described prenatal diagnosis of 3 cases of fragile X syndrome based on cytogenetic analysis of cultured amniocytes. The testes of 2 positive fetuses appeared large for gestational age.
Sutherland et al. (1991) reported prenatal diagnosis of fragile X syndrome in a male fetus using direct analysis of an unstable sequence in DNA obtained by chorionic villus sampling. They used a probe referred to as pfxa3 to detect an abnormal 2.3-kb band in the fetus. Normal carrier males usually have a fragile X band that is between 1.1 and 1.6 kb. Yamauchi et al. (1993) used the diagnostic DNA probe pPCRfx1 to confirm that an at-risk fetus was a heterozygous female carrier.
Dreesen et al. (1995) approached preimplantation testing for the fragile X syndrome by genotyping the polymorphic DXS548 AC-repeat locus, which is closely linked to the FMR1 gene, in unfertilized oocytes and extruded polar bodies. They concluded that a PCR procedure could be performed within 16 hours after blastomere biopsy and that for carrier females heterozygous at the DXS548 locus, preimplantation testing with DXS548 is a possible alternative to prenatal testing.
Molecular Genetics
### Nomenclature of Expanded Trinucleotide Repeats
The repeat involved in the fragile X syndrome is variously referred to here as (CGG)n or (CCG)n. The identical repeat found in the cloned FRAXE gene (309548) was referred to as (GCC)n by Knight et al. (1993). There are only 10 different trinucleotide repeats, but each can be written in a number of ways. Sutherland (1993) favored the convention that lists the motif in alphabetical order in the 5-prime to 3-prime direction. Consistent with this, he uses the (CCG)n designation. He preferred, furthermore, the designation (AGC)n for the other clinically significant dinucleotide repeat found in myotonic dystrophy (DM1; 160900), Huntington disease (143100), Kennedy disease (SMAX1; 313200), and SCA1 (164400); (CAG)n is the designation most often used. Sutherland (1993) suggested that the same convention can apply to dinucleotides. He wrote: 'It must be very confusing for newcomers to the literature to find (AC)n, (CA)n, (GT)n, and (TG)n repeats, when the cognoscenti know these are synonyms.'
### Fragile X Syndrome
Kremer et al. (1991) demonstrated that the presence of an unstable expanded trinucleotide repeat sequence, designated p(CGG)n (309550.0004), in the FMR1 gene is the basis of fragile X syndrome. The authors showed that normal X chromosomes have about 40 +/- 25 copies of p(CCG)n and that within these limits the sequence is a stable DNA polymorphism. The fragile X genotype was characterized by an increased amount of unstable DNA that maps to the repeat.
Pieretti et al. (1991) found absence of FMR1 mRNA in lymphoblastoid cell lines and leukocytes derived from patients with fragile X syndrome, whereas it was normally expressed in normal controls and carriers.
Devys et al. (1992) noted that there are 2 main types of mutations involved in fragile X syndrome. Premutations, which do not cause mental retardation, are characterized by an elongation of 70 to 500 bp with little or no somatic heterogeneity and without abnormal methylation. Full mutations are associated with high risk of mental retardation and consist of a 600 bp or more amplification, often with extensive somatic heterogeneity and abnormal DNA methylation.
De Boulle et al. (1993) identified a missense mutation in the FMR1 gene (I304N; 309550.0001) in a patient with a severe form of fragile X mental retardation, confirming that abnormality of the FMR1 gene underlies fragile X syndrome.
Russo et al. (1998) described a female with borderline cognitive impairment who was compound heterozygous for a full FMR1 mutation and a premutation. The parents came from the same small village in Italy. The proband's mother and aunt reported that they had undergone premature ovarian failure at 35 years of age (see POF1, 311360). Mila et al. (1996) reported a compound heterozygous Spanish female. Linden et al. (1999) reported a 15-year-old girl with fragile X syndrome who was compound heterozygous for a full expansion (363 repeats) and a premutation (103 repeats) in the FMR1 gene. Both parents carried premutations (98 repeats in the father, 146 repeats in the mother). Cognitively, this woman was functioning in the mid range of involvement for fragile X females. She attended regular classes and received supplemental assistance for her learning disabilities. She experienced behavioral characteristics typical of females with fragile X syndrome including severe shyness, anxiety, panic episodes, mood swings, and attention deficits. She responded well to appropriate treatment including fluoxetine for anxiety, methylphenidate for attention problems, and educational therapy.
Gronskov et al. (2011) identified a truncating mutation in the FMR1 gene (S27X; 309550.0005) in a man with classic features of fragile X syndrome. He had mental retardation, early-onset seizures, poor language development, and autistic tendencies. Dysmorphic features included an elongated face, high and broad forehead, low-set large ears, prognathia, and enlarged testes. Neurologic examination showed hypotonia and hypermobility, with hyperextensible joints. Western blot analysis of patient lymphoblastoid cells showed no FMRP protein expression. His mother, who also carried the mutation, had mild to moderate intellectual disability, hypermotor behavior, and automatisms. Gronskov et al. (2011) noted that the frequency of point mutations in the FMR1 gene is unknown, since most screening techniques look for the expanded repeat.
### Reviews
D'Hulst and Kooy (2009) provided a review of fragile X syndrome, with a focus on molecular genetics.
Population Genetics
Jacobs (1982) indicated that a reasonable estimate of frequency of fragile X syndrome is 0.5 per 1,000 males. Although many of the cases first ascertained were of northern European descent, affected males have since been found in most ethnic groups.
In Sweden, Blomquist et al. (1982) found that 6 of 96 Swedish boys with IQ less than 50 born between 1959 and 1970 had fraXq28. Blomquist et al. (1985) found the fragile X in 13 (16%) of 83 boys but none of 129 girls with infantile autism.
Webb et al. (1986) performed a population study of school children in the city of Coventry, England, and, using cytogenetic studies, gave an overall prevalence for fragile X syndrome in males and females of 1:952. Morton et al. (1997) reevaluated the 29 children diagnosed with fragile X syndrome by Webb et al. (1986) and confirmed the presence of the FMR1 gene expansion in only 7 of the children, giving a revised prevalence of 1:2,720 to 1:5,714, depending on whether the 4 children lost to follow-up are included. On the basis of molecular genetic analysis, Turner et al. (1996) reported that a prevalence of 1:4,000 or 2.4:10,000 was more realistic than the 1:1,000 reported by Webb et al. (1986).
Filippi et al. (1991) reported findings in a very large Sardinian kindred spanning 6 generations and including 13 patients with Martin-Bell syndrome, several instances of normal transmitting males or females, and the G6PD Mediterranean (305900.0006) mutant segregating in some of its branches. All the fragile X patients and the 15 obligate heterozygous women could be traced through their X-chromosome lineage to a woman in the first generation who must have been heterozygous for a silent premutation at the fragile X locus. Filippi et al. (1991) concluded that this premutation had been converted into a full mutation at least 9 times during the gametogenesis of this ancestor's X-related descendants, of whom 4 were males.
Morton and Macpherson (1992) proposed a model in which the fragile X mutation is postulated to occur as a multistep process. This attractive model provides a framework in which the seemingly contradictory observations of a mutation old enough to establish a founder effect and an apparently high new mutation rate are united. Morton and Macpherson (1992) suggested that 4 types of alleles occur in the fragile X syndrome (see table in the review by Chakravarti, 1992). The 4 types of alleles were as follows: N = normal, with a frequency of 0.9751; S = stable insert with a frequency of 0.0225 and a mean age of about 90 generations; Z = unstable insert with a frequency of 0.0014 and a mean age of 2 generations; and L = mutation with a frequency of 0.0010 and a mean age of 1.4 generations. Thus myotonic dystrophy (DM1; 160900) and fragile X appear to share both the phenomenon of anticipation and the phenomenon of founder effect.
Richards and Sutherland (1992) referred to the amplification mutation involving (CCG)n in the fragile X syndrome and the trinucleotide repeats in myotonic dystrophy and Kennedy disease as 'dynamic mutations.' In studies using 2 polymorphic CA repeats located close to the 'mutation target' for the fragile X syndrome, Oudet et al. (1993) observed significant differences in allelic and haplotypic distributions between normal and fragile X chromosomes, indicating that a limited number of primary events may have been at the origin of most present-day fragile X chromosomes in Caucasian populations. They proposed a putative scheme with 6 founder chromosomes from which most of the observed fragile X-linked haplotypes can be derived directly or by a single event at one of the marker loci. Such founder chromosomes may have carried a number of CGG repeats in an upper-normal range, from which recurrent multistep expansion mutations have arisen. The diversity of haplotypes at the fragile X locus may reflect genetic heterogeneity but may also be explained by mutations in the markers themselves.
Richards et al. (1992) presented haplotype evidence for a founder effect in the fragile X mutation. They found clear evidence of linkage disequilibrium between fragile X and 2 polymorphic microsatellite markers that flank FMR1 and are within 10 kb of the (CCG)n repeat. These markers have 5 to 7 alleles, show no recombination with each other, and define 15 haplotypes. In an analysis of 134 fragile X chromosomes from unrelated affected individuals in Australia and the United States, they found that 58% of the fragile X mutations occurred on the 3 backgrounds that account for 18% of normal chromosomes. Correspondingly, the single most common normal haplotype, which has a frequency of 50%, carries only 18% of fragile X mutations. The data argued for the expected occurrence of multiple, independent mutations, but also indicated the unexpectedly long history of some of these fragile X mutations. Using the FRAXAC1 polymorphic marker in the study of a large number of patients, Hirst et al. (1993) found its allele distribution to be strikingly different on fragile X chromosomes, confirming earlier observations and giving further support to the suggestion of a fragile X founder effect (Richards et al., 1992).
Haataja et al. (1994) presented evidence for a founder effect of fragile X syndrome in Finland arising from a common ancestor in the 16th century.
In a study of 122 Israeli families affected with the fragile X syndrome diagnosed in 7 genetic centers, Dar et al. (1995) found that Tunisian Jews, who comprise only 4% of the general population, accounted for 21% of the fragile X families, suggesting founder effect.
Rousseau et al. (1995) reported a population frequency of 1 in 259 for female carriers of an allele of more than 54 repeats.
The CGG repeat, which is normally polymorphic in length, is frequently interrupted by AGG triplets, which are believed to stabilize the repeat. The absence of AGG triplets, leading to long tracts of perfect CGG repeats, may give rise to predisposed alleles. Kunst et al. (1996) determined the repeat length of 345 chromosomes from 9 populations from various parts of the world and used automated DNA sequencing to assess 14 of them. They found that the FMR1 alleles were very heterogeneous, although the level of variation correlated with the age and/or genetic history of a particular population. Native American alleles, interrupted by 3 AGG repeats, exhibited marked stability over 7,000 years. However, in older African populations, parsimony analysis predicted the occasional loss of an AGG, leading to more perfect CGG repeats.
Studies of (CGG)n repeat structures of selected human populations showed a high degree of conservation of the canonical (CGG)9AGG interruption pattern in different populations and confirmed the proposed stabilizing effect of AGG interruptions (Eichler and Nelson, 1996). In the native population of Greenland, Larsen et al. (1999) found a narrow distribution of (CGG)n allele sizes, similar to that reported for Asian populations. DNA sequencing of alleles with 36 CGG repeats revealed an AGG(CGG)6 insertion previously reported exclusively in Asian populations and a high frequency of 2 other sequence patterns. The data confirmed the Asian origin of the Greenlandic (Eskimo) population and indicated that some (CGG)n alleles have remained stable for 15,000 to 30,000 years, since the population of the New World arrived from Asia via the Bering Strait. The findings added new evidence for the 'out of Asia' theory of the colonization of the New World (Cavalli-Sforza et al., 1994). Studies in Native Americans (Amerinds) had not shown the (CGG)6AGG insertion. This may be due to the relatively small sample sizes in these studies, but may also be caused either by a later migration of the Eskimo population compared with the Amerind and the Na-dene populations (as proposed in the '3 migrations theory' Greenberg et al., 1986 or by genetic bottlenecks during the population of the New World (Wallace and Torroni, 1992)).
Goldman et al. (1997) reported that the prevalence of FRAXA syndrome among institutionalized South African blacks was similar to that reported in the literature for institutionalized white populations. Crawford et al. (1999) found that the prevalence of the FRAXA full mutation in African American males was approximately the same as that in Caucasian American males.
Beresford et al. (2000) reported molecular analysis of 177 males with mental handicap and 1,226 random alleles from Guthrie newborn screening samples in Nova Scotia. No FMR1 premutations or mutations were found. Beresford et al. (2000) also noted that only 1 case of fragile X had been reported in this region since 1980, in an individual who had moved from elsewhere in Canada. Beresford et al. (2000) concluded that the fragile X syndrome was rare in Nova Scotia, a phenomenon they found remarkable given the high prevalence of other rare heritable disorders in the region and that the population has tens of thousands of founders from multiple founding groups.
Larsen et al. (2001) analyzed the AGG interspersion pattern of the (CGG)n repeat and the haplotype distribution of 2 closely located microsatellite markers in 3 circumarctic populations: Norwegians, Saami, and Nenets. The data indicated the existence of chromosomes of Asian origin in the Saami and Nenets populations. Haplotype analysis of Norwegian fragile X males compared to other populations showed that the fragile X founder haplotypes may vary between populations and that the CGG expansion associated with fragile X syndrome may originate from subpopulations of unstable alleles within the normal population.
Several population-based studies in Caucasians of mostly northern European descent established that the prevalence of the fragile X syndrome is probably between 1 in 6,000 and 1 in 4,000 males. Crawford et al. (2002) presented the final results of a 4-year study in the metropolitan area of Atlanta, Georgia, establishing the prevalence of the fragile X syndrome and the frequency of CGG repeat variants in a large Caucasian and African American population. They found that one-quarter to one-third of the children identified with the fragile X syndrome attending Atlanta public schools were not diagnosed before the age of 10 years. Also, a revised prevalence for the syndrome revealed a higher point estimate for African American males (1/2,545; 95% CI 1/5,208-1/1,289) than reported previously, although confidence intervals included the prevalence estimated for Caucasians from this and other studies (1/3,717; 95% CI 1/7,692-1/1,869).
Mingroni-Netto et al. (2002) studied the distribution of CGG repeats and DXS548/FRAXAC1 haplotypes in normal South American populations of different ethnic backgrounds. They found that some rare alleles that seem nearly absent in Europe occurred in higher frequencies among African Brazilians, which suggested a general trend for higher genetic diversity among Africans. Thus, the rarer alleles could be African in origin and would have been lost or possibly not present in the groups that gave rise to Europeans.
Dombrowski et al. (2002) screened 10,572 independent French Canadian males for premutation-size FMR1 alleles and identified 13 who carried alleles of more than 54 repeats, which corresponded to a population frequency of 1 in 813. Haplotype analysis of the 13 identified male carriers revealed that the prevalence of the major fragile X mutation-associated haplotype was increased among FMR1 alleles of 40 to 54 repeats. Although sequencing of highly unstable premutation alleles from fragile X families revealed only pure CGG tracts, 48 of 49 males from the general population with 40 or more triplets had 1 to 2 AGG interruptions. This suggests that the loss of an AGG interruption in the triplet repeat array may not be necessary for expansion of normal alleles of 29 to 30 triplets to intermediate size. The authors concluded that loss of AGG interruptions appears to be a late event that may lead to greatly increased instability and may be related to the haplotype background of specific FMR1 alleles.
Biancalana et al. (2004) reported the molecular diagnosis of fragile X syndrome in France during the 5-year period from 1997 to 2001: 477 families were diagnosed with fragile X syndrome, representing 2.8% of tested male probands and 1% of tested female probands.
Fatima et al. (2014) found the FMR1 full mutation in 15 (6.5%) of 229 Pakistani boys and in 1 (0.9%) of 104 girls with intellectual disability. The overall frequency among intellectually disabled children in this population was 4.8%.
History
The X-linked mental retardation reported by Martin and Bell (1943) is the same as the fragile X syndrome. Opitz et al. (1984) referred to this disorder as the 'Martin-Bell syndrome' on the assumption that the family reported from the Queen Square Hospital in London by J. Purdon Martin and Julia Bell (Martin and Bell, 1943) had that disorder. Although macroorchidism was not mentioned by Martin and Bell (1943), one of the patients was described as having a 'big face and jaw;' furthermore, at least 9 of the affected males were maternal grandsons of 2 unaffected brothers. All but 1 of the mothers of affected males were daughters of these 2 brothers, the other being their sister. Martin and Bell (1943) hypothesized that some controlling factor caused suppression of the disease in the 2 grandfathers without affecting their liability to transmit it. For a superb biography of Julia Bell (1879-1979), see Bundey (1996).
Richards et al. (1981) followed up on the Martin-Bell kindred, demonstrating that it was indeed the fragile X syndrome. The original index patient was then aged 56. All 4 affected males who had adequate karyotyping showed the fragile X syndrome in 17 to 50% of their cells. The other major contribution of Julia Bell was in the defining of many hereditary disorders, such as the forms of brachydactyly, on the basis of massive collections of pedigrees in the famous Treasury of Human Inheritance. She also collaborated with J. B. S. Haldane in the first estimation of linkage in the human, that of colorblindness and hemophilia (Bell and Haldane, 1937).
According to Opitz and Sutherland (1984), Escalante, a graduate student with Frota-Pessoa in Sao Paulo, Brazil, and Drs. Bryan and Gillian Turner in Sydney, Australia, independently noted the association of macroorchidism with X-linked mental retardation in the late 1960s. Escalante et al. (1971) published their findings (which they had reported in 1969 at the Warsaw Congress of the International Association for the Scientific Study of Mental Deficiency) in the Journal de Genetique Humaine. While visiting the Drs. Turner in Sydney, McKusick (1970) examined several patients with mental retardation and macroorchidism.
Antibiotics such as Bactrim (Roche) and Septra (Burroughs Wellcome) contain trimethoprim, which can lower folate levels by inhibition of dihydrofolate reductase. Hecht and Glover (1983) urged avoidance of trimethoprim and other folate antagonists in pregnant women who are at risk for having a child with the fragile X syndrome. Lejeune et al. (1982) described severe clinical regression of psychomotor development in a 2-year-old boy with the fragile X syndrome while on trimethoprim.
Froster-Iskenius et al. (1984) raised the possibility of an autosomal suppressor system to account for the transmission of the marker X syndrome by unaffected males. Steinbach (1986) and Israel (1987) also postulated an autosomal suppressor gene or modifier to explain the occurrence of mentally normal males who transmit the fragile X gene to their daughters and the fact that while about one-third of all female carriers have mental impairment, mothers and daughters of these mentally normal transmitting males are rarely, if ever, mentally impaired. Steinbach (1986) designated the modifier genes as D and N, the equivalent of Israel's s and S, respectively. Essentially the models were identical: normal male transmitters of fragile X were suggested to be homozygous for S (or N), while normal female transmitters are either homozygous for S or heterozygous, Ss (ND). Sherman (1987) found the Israel model attractive.
Thode et al. (1988) were unable to corroborate the existence of a form of the Martin-Bell syndrome with no detectable fragile X. They identified 32 men with the phenotype who were fragile X negative but concluded that they did not fit the full criteria.
Klauck et al. (1997) concluded from molecular genetic studies of 141 patients from 105 simplex and 18 multiplex families that an association of autism with fragile X is nonexistent and that the Xq27.3 region is not a candidate for autism.
Animal Model
For a discussion of animal models of fragile X syndrome, see 309550.
INHERITANCE \- X-linked dominant HEAD & NECK Head \- Macrocephaly Face \- Coarse facies \- Large forehead \- Long face \- Prominent jaw Ears \- Large ears CARDIOVASCULAR Heart \- Mitral valve prolapse CHEST Ribs Sternum Clavicles & Scapulae \- Pectus excavatum GENITOURINARY External Genitalia (Male) \- Macroorchidism, postpubertal \- Congenital macroorchidism (in some patients) SKELETAL Spine \- Scoliosis Limbs \- Joint laxity Feet \- Pes planus NEUROLOGIC Central Nervous System \- Mental retardation (moderate to severe in males) \- Seizures \- Abnormal head movements \- Periventricular heterotopia Behavioral Psychiatric Manifestations \- Hyperactive behavior \- Poor eye contact \- Autistic features LABORATORY ABNORMALITIES \- Folate-dependent fragile site at Xq28 MISCELLANEOUS \- Incomplete penetrance \- 50% of females have learning disability or mild mental retardation \- Prevalence approximately 1 in 4,000 males \- Most cases (98%) caused by expanded trinucleotide repeat (CGG)n in the FMR1 gene ( 309550.0004 ) \- Repeat is unstable if > 52 repeats \- Symptomatic if > 200 repeats \- Some boys with premutations (55 to 200 repeats) may show milder features, including autistic features MOLECULAR BASIS \- Caused by mutation in the FMR1 gene (FMR1, 309550.0001 ) ▲ 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
| FRAGILE X SYNDROME | c0016667 | 2,036 | omim | https://www.omim.org/entry/300624 | 2019-09-22T16:19:54 | {"doid": ["14261"], "mesh": ["D005600"], "omim": ["300624"], "icd-9": ["759.83"], "icd-10": ["Q99.2"], "orphanet": ["908", "449291"], "synonyms": ["Alternative titles", "FRAGILE X MENTAL RETARDATION SYNDROME", "MENTAL RETARDATION, X-LINKED, ASSOCIATED WITH marXq28", "X-LINKED MENTAL RETARDATION AND MACROORCHIDISM", "MARKER X SYNDROME", "MARTIN-BELL SYNDROME"], "genereviews": ["NBK1384"]} |
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart condition in which the muscle of the right ventricle of the heart is replaced by fat and/or scar tissue. The condition is progressive and over time the right ventricle loses the ability to pump blood. Individuals with ARVC often develop abnormal heart rhythms known as arrhythmias, which can increase the risk of sudden cardiac arrest or death. Other symptoms of ARVC include chest palpitations, dizziness, fainting and shortness of breath. Often, sudden cardiac death can be the first sign of ARVC. ARVC is caused by genetic mutations in genes that instruct proteins to link one heart cell to the next. There is also some evidence that ARVC could be caused by an infection of the heart muscle. Treatment options can vary by patient and may include anti-arrhythmogenic medication, implantable cardioverter defibrillators and catheter ablation.
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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
| Arrhythmogenic right ventricular cardiomyopathy | c0349788 | 2,037 | gard | https://rarediseases.info.nih.gov/diseases/5847/arrhythmogenic-right-ventricular-cardiomyopathy | 2021-01-18T18:02:02 | {"mesh": ["D019571"], "omim": ["107970"], "umls": ["C0349788"], "orphanet": ["247"], "synonyms": ["ARVD", "ARVC", "Arrhythmogenic right ventricular dysplasia"]} |
Subcortical band heterotopia is a condition in which nerve cells (neurons) do not move (migrate) to their proper locations in the fetal brain during early development. (Heterotopia means "out of place.") Normally, the neurons that make up the outer surface of the brain (cerebral cortex) are distributed in a well-organized and multi-layered way. In people with subcortical band heterotopia, some neurons that should be part of the cerebral cortex do not reach it. These neurons stop their migration process in areas of the brain where they are not supposed to be and form band-like clusters of tissue. Since these bands are located beneath the cerebral cortex, they are said to be subcortical. In most cases, the bands are symmetric, which means they occur in the same places on the right and left sides of the brain.
The abnormal brain development causes neurological problems in people with subcortical band heterotopia. The signs and symptoms of the condition depend on the size of the bands and the lack of development of the cerebral cortex. The signs and symptoms can vary from severe intellectual disability and seizures that begin early in life and affect both sides of the brain (generalized seizures) to normal intelligence with seizures occurring later in life and affecting only one side of the brain (focal seizures). Some affected individuals also have weak muscle tone (hypotonia), loss of fine motor skills such as using utensils, or behavioral problems. Subcortical band heterotopia is typically found when brain imaging is done following the onset of seizures, usually in adolescence or early adulthood.
## Frequency
More than 200 cases of subcortical band heterotopia have been reported in the scientific literature. Most affected individuals are female.
## Causes
Mutations in the DCX or PAFAH1B1 gene cause subcortical band heterotopia. Both genes provide instructions for making proteins that are involved in the movement of neurons to their proper locations in the developing brain, a process called neuronal migration. Neuronal migration is essential for normal brain development and function.
Most individuals with subcortical band heterotopia have DCX gene mutations. These mutations impair the protein's function or alter the protein's structure or stability. PAFAH1B1 gene mutations are less common. Mutations in this gene reduce the protein's function.
Altered structure or function of the proteins produced by the DCX or PAFAH1B1 gene impairs important interactions that are needed for neuronal migration. Without proper neuronal migration, neurons in the developing brain can be misplaced, forming abnormal bands of tissue beneath the cerebral cortex.
### Learn more about the genes associated with Subcortical band heterotopia
* DCX
* PAFAH1B1
## Inheritance Pattern
The inheritance pattern of subcortical band heterotopia depends on its genetic cause.
When subcortical band heterotopia is caused by mutations in the DCX gene, it is inherited in an X-linked pattern. The DCX gene is located on the X chromosome, which is one of the two sex chromosomes. In females, who have two copies of the X chromosome, one altered copy of the gene in each cell can lead to the condition, sometimes with less severe symptoms than affected males. In males, who have only one X chromosome, a mutation in the only copy of the gene in each cell usually causes a more severe condition called isolated lissencephaly sequence (ILS). Most males with subcortical band heterotopia have a DCX gene mutation that is not inherited and is present in only some of the body's cells, a situation known as mosaicism. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
When subcortical band heterotopia is caused by a PAFAH1B1 gene mutation, it is generally not inherited but arises from a mutation in the body's cells that occurs after conception, which leads to mosaicism. This alteration is called a somatic mutation. PAFAH1B1 gene mutations that occur in all of the body's cells (germline mutations) usually cause ILS.
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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
| Subcortical band heterotopia | c0431375 | 2,038 | medlineplus | https://medlineplus.gov/genetics/condition/subcortical-band-heterotopia/ | 2021-01-27T08:25:38 | {"gard": ["1904"], "mesh": ["D054221"], "omim": ["607432", "300067"], "synonyms": []} |
Chondronectin is a distinct glycoprotein similar in structure and function to fibronectin. It is present in plasma in the concentration of about 20 micrograms per ml. In tissues, it is limited to cartilage and vitreous, which are also the sites of type II collagen, and functions in relation to chondrocytes and type II collagen in the way that fibronectin functions in relation to other cells and types I and III collagen (Kleinman et al., 1981). It also binds chondroitin sulfate and heparin (Kleinman, 1982).
*[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
| CHONDRONECTIN | c3887693 | 2,039 | omim | https://www.omim.org/entry/118670 | 2019-09-22T16:43:20 | {"omim": ["118670"]} |
This article is about the animal disease. For other uses, see Blackleg (disambiguation).
Early signs: swelling of the thigh, with leg up and tail raised (arrows)
Recovered calf after removing of all necrotic tissue
Blackleg, black quarter, quarter evil, or quarter ill (Latin: gangraena emphysematosa) is an infectious bacterial disease most commonly caused by Clostridium chauvoei, a Gram-positive bacterial species. It is seen in livestock all over the world, usually affecting cattle, sheep, and goats. It has been seen occasionally in farmed bison and deer.[1] The acute nature of the disease makes successful treatment difficult, and the efficacy of the commonly used vaccine is disputed.[2]
## Contents
* 1 Susceptibility
* 2 Causative agent
* 3 Clinical presentations
* 4 Vaccination and prevention
* 5 See also
* 6 References
* 7 External links
## Susceptibility[edit]
Most losses due to blackleg occur when the cattle are between the ages of six months and two years, although it can occur when they are as young as two months. Typically, cattle that have a high feed intake and are well-conditioned tend to be the most susceptible to blackleg. Furthermore, many blackleg cases occur during the hot and humid summer months or after a sudden cold period, but cases can occur at any time during the year.[3]
## Causative agent[edit]
Blackleg is caused by infection with Clostridium bacteria. The most common causative agent is C. chauvoei, but the disease can also be caused by C. septicum, C. sordelli, and C. novyi.[4][5] C. chauvoei is Gram-positive, rod-shaped, anaerobic, and motile, and can produce environmentally persistent spores when conditions are not ideal for growth. These spores can remain in the soil for years in an inactive state, and return to their infectious form when consumed by grazing livestock. Contaminated pasture is a predominant source of these organisms, which are also found naturally in the intestines of animals.[6] Cases can occur over many years in areas where soil or manure is contaminated with the bacteria, and it is exceedingly difficult to remove the spores from the environment.
C. chauvoei can produce a large amount of gas as a metabolic byproduct when growing and reproducing, hence the alternate name gas gangrene, present in humans.[7] This gas builds up in infected tissue, usually large muscles, and causes the tissue to make a crackling or popping sound when pressed. Large gas-filled blisters can also form, which can be extremely painful as they build up in the tissues.[citation needed]
## Clinical presentations[edit]
When infection begins, the animal may develop a fever, and the affected limb can feel hot to the touch. The limb usually swells significantly, and the animal can develop lameness on the affected leg. Crepitation (the sensation of air under the skin) can be noticed in many infections, as the area seems to crackle under pressure.[8]
Once clinical signs develop, the animal may only live a short while, sometimes as few as 12 hours. Occasionally, cattle succumb to the disease without showing any symptoms, and only a necropsy reveals the cause. During a necropsy, a diagnosis is usually made very quickly, as the affected muscle is usually mottled with black patches, which are dead tissue, killed by the toxins the bacteria release when they infect live tissue. If viewed under a microscope, small rod-like bacteria can be seen to confirm the diagnosis.[citation needed]
## Vaccination and prevention[edit]
The use of a seven-way clostridial vaccination is the most common and cost effective preventative measure taken against blackleg,[5] but its efficacy is disputed.[2] Burning the upper layer of soil to eradicate left-over spores is the best way to stop the spread of blackleg from diseased cattle. Diseased cattle should be isolated. Treatment is generally unrewarding due to the rapid progression of the disease, but penicillin is the drug of choice for treatment. Treatment is only effective in the early stages and as a control measure.[citation needed]
## See also[edit]
* Gas gangrene
* Clostridium vaccine
## References[edit]
1. ^ MacKintosh, C; Haigh, J. C; Griffin, F (2002). "Bacterial diseases of farmed deer and bison". Revue Scientifique et Technique. 21 (2): 249–63. doi:10.20506/rst.21.2.1341. PMID 11974613.
2. ^ a b Uzal, Francisco A (2012). "Evidence-Based Medicine Concerning Efficacy of Vaccination Against Clostridium chauvoei Infection in Cattle". Veterinary Clinics of North America: Food Animal Practice. 28 (1): 71–7, viii. doi:10.1016/j.cvfa.2011.12.006. PMID 22374118.
3. ^ Sarah Robson; J. M. Wilson. "Blackleg in Cattle". 5m Publishing. Retrieved 18 February 2013.
4. ^ https://www.zoetis.com.au/_locale-assets/faq/faqs-blackleg.pdf[full citation needed]
5. ^ a b http://ucanr.edu/sites/UCCE_LR/files/152026.pdf[full citation needed]
6. ^ Clostridial diseases: Blackleg. The Merck Veterinary Manual. Available from http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/50704.htm Retrieved 2012-03-20.
7. ^ Nagano, N; Isomine, S; Kato, H; Sasaki, Y; Takahashi, M; Sakaida, K; Nagano, Y; Arakawa, Y (2008). "Human Fulminant Gas Gangrene Caused by Clostridium chauvoei". Journal of Clinical Microbiology. 46 (4): 1545–7. doi:10.1128/JCM.01895-07. PMC 2292918. PMID 18256217.
8. ^ Irsik, M.B. Blackleg in cattle. University of Florida, Institute of Food and Agricultural Sciences. Available from http://edis.ifas.ufl.edu/vm120 Archived 2012-02-07 at the Wayback Machine. Retrieved 2012-03-22.
## External links[edit]
* Blackleg and Other Clostridial Diseases
Wikimedia Commons has media related to Blackleg (disease).
*[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
| Blackleg (disease) | None | 2,040 | wikipedia | https://en.wikipedia.org/wiki/Blackleg_(disease) | 2021-01-18T18:32:25 | {"wikidata": ["Q699921"]} |
Familial cold autoinflammatory syndrome is a condition that causes episodes of fever, skin rash, and joint pain after exposure to cold temperatures. These episodes usually begin in infancy and occur throughout life.
People with this condition usually experience symptoms after cold exposure of an hour or more, although in some individuals only a few minutes of exposure is required. Symptoms may be delayed for up to a few hours after the cold exposure. Episodes last an average of 12 hours, but may continue for up to 3 days.
In people with familial cold autoinflammatory syndrome, the most common symptom that occurs during an episode is an itchy or burning rash. The rash usually begins on the face or extremities and spreads to the rest of the body. Occasionally swelling in the extremities may occur.
In addition to the skin rash, episodes are characterized by fever, chills, and joint pain, most often affecting the hands, knees, and ankles. Redness in the whites of the eye (conjunctivitis), sweating, drowsiness, headache, thirst, and nausea may also occur during an episode of this disorder.
## Frequency
Familial cold autoinflammatory syndrome is a very rare condition, believed to have a prevalence of less than 1 per million people.
## Causes
Mutations in the NLRP3 and NLRP12 genes cause familial cold autoinflammatory syndrome. The NLRP3 gene (also known as CIAS1) provides instructions for making a protein called cryopyrin, and the NLRP12 gene provides instructions for making the protein monarch-1.
Cryopyrin and monarch-1 belong to a family of proteins called nucleotide-binding domain and leucine-rich repeat containing (NLR) proteins. These proteins are involved in the immune system, helping to regulate the process of inflammation. Inflammation occurs when the immune system sends signaling molecules and white blood cells to a site of injury or disease to fight microbial invaders and facilitate tissue repair. When this has been accomplished, the body stops (inhibits) the inflammatory response to prevent damage to its own cells and tissues.
Cryopyrin is involved in the assembly of a molecular complex called an inflammasome, which helps start the inflammatory process. Mutations in the NLRP3 gene result in a hyperactive cryopyrin protein that inappropriately triggers an inflammatory response.
Monarch-1 is involved in the inhibition of the inflammatory response. Mutations in the NLRP12 gene appear to reduce the ability of the monarch-1 protein to inhibit inflammation.
Impairment of the body's mechanisms for controlling inflammation results in the episodes of skin rash, fever, and joint pain seen in familial cold autoinflammatory syndrome. It is unclear why episodes are triggered by cold exposure in this disorder.
### Learn more about the genes associated with Familial cold autoinflammatory syndrome
* NLRP12
* NLRP3
## Inheritance Pattern
This condition is inherited in an autosomal dominant pattern from an affected parent; one copy of the altered gene in each cell is sufficient to cause the disorder.
*[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 inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| Familial cold autoinflammatory syndrome | c0343068 | 2,041 | medlineplus | https://medlineplus.gov/genetics/condition/familial-cold-autoinflammatory-syndrome/ | 2021-01-27T08:25:32 | {"gard": ["9535"], "mesh": ["D056587"], "omim": ["120100", "611762"], "synonyms": []} |
Hereditary site-specific ovarian cancer syndrome refers to ovarian cancer caused by germline mutations in various genes, usually associated with additional cancer risks. The most common are breast and ovarian cancer syndrome (HBOC) due to mutations in BRCA1 and BRCA2 genes and hereditary nonpolyposis colorectal cancer (HNPCC) due to mutations in DNA mismatch-repair genes. Mutations in STK11 gene, causing Peutz-Jeghers syndrome, are also associated with a risk of ovarian cancer (typically sex cord stromal tumors). Mutations in other genes, including RAD51C, RAD51D, PALB2, confer an elevated ovarian cancer risk in a minority of patients.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| Hereditary site-specific ovarian cancer syndrome | None | 2,042 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=213524 | 2021-01-23T17:49:11 | {"icd-10": ["C56"]} |
Alport syndrome is a genetic condition characterized by kidney disease, hearing loss, and eye abnormalities. Most affected individuals experience progressive loss of kidney function, usually resulting in end-stage kidney disease. People with Alport syndrome also frequently develop sensorineural hearing loss in late childhood or early adolescence. The eye abnormalities characteristic of this condition seldom lead to vision loss. In 80% of cases, Alport syndrome is inherited in an X-linked manner and is caused by mutations in the COL4A5 gene. In the remaining cases, it may be inherited in either an autosomal recessive, or rarely in an autosomal dominant manner. In these cases, the condition is caused by mutations in the COL4A3 or COL4A4 genes. Diagnosis of the condition is based on family history of the condition, clinical signs, and specific testing such as a kidney biopsy. The diagnosis can be confirmed by genetic testing. Treatment may include use of a hearing aid, hemodialysis and peritoneal dialysis to treat those with end-stage renal failure, and kidney 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 inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| Alport syndrome | c1567741 | 2,043 | gard | https://rarediseases.info.nih.gov/diseases/5785/alport-syndrome | 2021-01-18T18:02:11 | {"mesh": ["D009394"], "omim": ["301050"], "orphanet": ["63"], "synonyms": ["Alport syndrome, X-linked", "Hemorrhagic familial nephritis", "Hemorrhagic hereditary nephritis", "Congenital hereditary hematuria"]} |
Imerslund-Grasbeck syndrome (IGS) is a rare condition characterized by vitamin B12 deficiency, often causing megaloblastic anemia. IGS usually appears in childhood. Other features may include failure to thrive, infections, and neurological damage. Mild proteinuria (with no signs of kidney disease) is present in about half of affected individuals. IGS is caused by mutations in either the CUBN or AMN gene and is inherited in an autosomal recessive manner. Treatment includes life-long vitamin B12 injections, with which affected individuals can stay healthy for decades.
*[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
| Imerslund-Grasbeck syndrome | c1306856 | 2,044 | gard | https://rarediseases.info.nih.gov/diseases/7006/imerslund-grasbeck-syndrome | 2021-01-18T17:59:49 | {"omim": ["261100"], "orphanet": ["35858"], "synonyms": ["IGS", "Pernicious anemia, juvenile, due to selective intestinal malabsorption of vitamin B12, with proteinuria", "Enterocyte cobalamin malabsorption", "Defect of enterocyte intrinsic factor receptor", "Familial megaloblastic anemia", "Selective cobalamin malabsorption with proteinuria", "Gräsbeck-Imerslund disease", "Megaloblastic anemia 1"]} |
A nonprogressive disorder with multiple mild flexion contractures developing in infancy was described in 2 brothers by Fenichel et al. (1971). Motor strength was normal. Lower limb tendon reflexes were exaggerated but plantar responses were flexor. Associated findings were borderline normal intelligence, speech defect, choreic movements of the outstretched hands, normal cranial nerve, sensory and cerebellar functions, and EEGs indicating paroxysmal disorder. CPK was elevated in the younger boy. Muscle biopsies showed decreased fiber size, especially of the ATPase positive type (A fibers), increased amounts of PAS positive material, and 'Ringbinden,' without typical myopathic or neuropathic changes. The authors interpreted the findings as the result of a primary cerebral disorder.
INHERITANCE \- Autosomal recessive SKELETAL Spine \- Lordosis MUSCLE, SOFT TISSUES \- Muscle biopsy with small A-fibers, increased PAS-positive material, and ringbinden (disoriented myofibrils) NEUROLOGIC Central Nervous System \- Dystonia \- Abnormal gait \- Hyperreflexia \- Chorea of hands \- Language delay \- EEG with focal discharge MISCELLANEOUS \- Childhood onset ▲ 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
| DYSTONIA WITH RINGBINDEN | c1857089 | 2,045 | omim | https://www.omim.org/entry/224550 | 2019-09-22T16:28:27 | {"mesh": ["C565608"], "omim": ["224550"]} |
## Description
Langerhans cell histiocytosis (LCH) is a rare disorder characterized by the dysregulated proliferation of Langerhans cells and subsequent organ infiltration. Clinical manifestations range from a spontaneously healing isolated osteolytic lesion to a lymphoma-like syndrome with fatal multiorgan failure, in the absence of any cellular evidence of malignancy. Although the disease can present at any age, the peak age at diagnosis is between 1 and 3 years (summary by Arico et al., 1999).
Egeler and D'Angio (1995) presented a classification of histiocytosis syndromes in children: class I, Langerhans cell histiocytosis (LCH); class II, histiocytosis of mononuclear macrophages other than Langerhans cells, including familial hemophagocytic lymphohistiocytosis (267700); and class III, malignant histiocytic disorders, including histiocytic lymphoma.
Clinical Features
The Langerhans cell is a dendritic cell (DC) of the epidermis that was first described by a medical student, Paul Langerhans, who thought it was part of the nervous system (Langerhans, 1868). Birbeck et al. (1961) found that the Langerhans cell displays a unique electron-microscopic morphology. The discoveries that these cells are not confined to skin and that they make up a sizable portion of the cellular infiltrate in histiocytosis X (246400), along with other evidence, suggested that they play an immunologic role in protecting against environmental antigens.
LCH is a rare disorder in which granulomatous deposits occur at multiple sites within the body, but which often involves the hypothalamopituitary axis (HPA). Although diabetes insipidus (DI) is a well-recognized complication, the frequency of anterior pituitary and other nonendocrine hypothalamic (NEH) involvement had not been well defined, particularly in adult patients with the disease. Kaltsas et al. (2000) evaluated the frequency and progression of LCH-related anterior pituitary and other NEH dysfunction and their responses to treatment in 12 adult patients with histologically proven LCH and DI. The median age at diagnosis of DI was 34 years (range, 2-47 years); DI was the presenting symptom in 4 patients, whereas the remaining 8 each developed DI 1-20 years (median, 2 years) after the diagnosis of LCH. Eight patients developed one or more anterior pituitary hormonal deficiencies at a median of 4.5 years (range, 2-22 years) after the diagnosis of DI; GH (139250) deficiency developed in 8 patients (median, 2 years; range 2-22 years), FSH/LH (see 136530) deficiency in 7 patients (median, 7 years; range, 2-22 years), and TSH (see 188540) and ACTH (see 176830) deficiency in 5 patients (median, 10 years; range, 3-16 and 3-19 years), respectively; 5 patients developed panhypopituitarism. In addition, 7 patients with anterior pituitary dysfunction also developed symptoms of other NEH dysfunctions at a median of 10 years (range, 1-23 years): 5 morbid obesity (body mass index greater than 35), 5 short-term memory deficits, 4 sleeping disorders, 2 disorders of thermoregulation, and 1 adipsia. The authors concluded that in their adult patients with hypothalamic LCH and DI, anterior pituitary hormonal deficiencies developed in 8 of 12 (67%) patients; these occurred over the course of 20 years. They were frequently accompanied by structural changes of the HPA, although these were often subtle in nature. In addition, symptoms of NEH dysfunction developed in up to 90% of such patients and complicated management. Patients with LCH and DI, particularly those with multisystem disease and a structural lesion on radiology, should undergo regular and prolonged endocrine assessment to establish anterior pituitary deficiency and provide appropriate hormonal replacement.
Population Genetics
The reported incidence of childhood Langerhans cell histiocytosis ranges from 3.5 to 7 cases per million children per year. These figures may be spuriously low because of the failure to diagnose and report cases with a mild course or spontaneous healing of isolated lesions (cited by Arico et al., 1999).
Inheritance
Although LCH is usually considered a sporadic nonhereditary disorder, familial clustering has been described in a limited number of cases, particularly in twins reported or known to be monozygotic. Arico et al. (1999) conducted a survey to examine the possible familial nature of LCH. They identified 9 families with more than 1 affected relative: 5 with LCH-concordant twin pairs, and 4 with LCH in sibs or cousins. Three twin pairs not concordant for LCH were also studied. Because of variable confidence for twin monozygosity, they termed the twin pairs 'presumed monozygotic,' or pMZ. Overall, 4 of 5 pMZ twin pairs and 1 of 3 dizygotic (DZ) pairs were concordant for LCH. The pMZ twins had simultaneous and early disease onset (mean age, 5.4 months); onset was at 21 months in the DZ pair. Clinical features were similar in the pMZ pairs. One pair of DZ twins had disseminated LCH. The 3 healthy twins (1 pMZ, 2 DZ) remained asymptomatic 0.3, 5.9, and 4.7 years, respectively, after disease onset in their cotwins. Of the 2 families with affected nontwin sibs, one had parental consanguinity and the other possible consanguinity. Potential consanguinity was also present in 1 of the 2 families with affected first cousins.
Pathogenesis
Coury et al. (2008) detected high levels of soluble RANKL (TNFSF11; 602642) and IL17A (603149), but not IL1B (147720), IL22 (605330), or TNF (191160), in serum from patients with LCH. Immunohistochemical analysis demonstrated IL17A-positive DCs in LCH patient skin and bone lesions and in multinucleated giant cells (MGCs). Intracytoplasmic flow cytometry and ELISA identified DCs, and not T cells, as the source of IL17A in LCH. IL17A stimulation induced fusion of healthy DCs in vitro. LCH DCs behaved similarly to IL17A-stimulated healthy DCs, and transwell assays confirmed that IL17A secreted from LCH DCs was functional. Gene chip analysis showed that IL17A was responsible for expression of TRAP (ACP5; 171640), MMP9 (120361), and MMP12 (601046) by MGCs in healthy DCs. Healthy DCs treated with IL17A and LCH DCs and MGCs displayed overactivation of TRAP. IgG autoantibody to IL17A was also detected in LCH serum. Coury et al. (2008) proposed that IL17A has a major role in LCH severity and may be a therapeutic target in the disease.
In a follow-up study to Coury et al. (2008), Allen and McClain (2009) reported that they were unable to detect IL17A mRNA by RT-PCR in CD207 (604862)-positive Langerhans cells or CD3-positive T cells isolated by flow cytometry from 14 LCH biopsy samples. In addition, they could not detect significant levels of serum IL17A in LCH patients. In response, Arico et al. (2009) pointed out that they (i.e., Coury et al. (2008)) had detected IL17A in CD207-negative DCs, the majority cell population in LCH lesions, using different sets of antibodies from those used by Allen and McClain (2009). They also stated that their serum ELISA assay used a capture antibody able to outcompete autoantibodies to IL17A that are present in LCH sera. Both studies showed that serum IL17A concentrations did not correlate with LCH activity and that Th17 cells were not present in LCH lesions. Indirectly, there may also be concurrence between the studies in the statement by Arico et al. (2009) that LCH is a DC-related disease rather than a Langerhans cell-related disease.
*[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
| LANGERHANS CELL HISTIOCYTOSIS | c0019621 | 2,046 | omim | https://www.omim.org/entry/604856 | 2019-09-22T16:11:42 | {"doid": ["2571"], "mesh": ["D006646"], "omim": ["604856"], "icd-10": ["C96.6", "C96.5"], "orphanet": ["389"], "synonyms": ["Alternative titles", "LCH"]} |
20p12.3 microdeletion syndrome is a recently described syndrome characterized by Wolff-Parkinson-White syndrome (see this term), variable developmental delay and facial dysmorphism.
## Epidemiology
It has been clinically and molecularly characterized in 3 patients.
## Clinical description
Dysmorphic features include macrocephaly, hypertelorism, down-slanting palpebral fissures and microstomia.
## Etiology
This syndrome is caused by an interstitial deletion encompassing 20p12.3. All these deletions except one occurred de novo and were characterized by comparative genomic hybridization (CGH) microarray and fluorescence in situ hybridization (FISH). They have a variable size with the smallest region of overlap including only one gene, BMP2, which is a good candidate gene for explaining the phenotype of Wolff-Parkinson-White syndrome.
*[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 inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| 20p12.3 microdeletion syndrome | c4304539 | 2,047 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=261295 | 2021-01-23T19:09:59 | {"gard": ["12492"], "icd-10": ["Q93.5"], "synonyms": ["Del(20)(p12.3)", "Monosomy 20p12.3"]} |
Junctional ectopic tachycardia
Other namesHis bundle tachycardia
SpecialtyCardiology
CausesPost-cardiac surgery
Differential diagnosisAV nodal re-entrant tachycardia
TreatmentCorrection of acidosis and electrolyte disturbances, antiarrhythmic medication, catheter ablation
MedicationAmiodarone, propranolol, verapamil, flecainide, propafenone
Junctional ectopic tachycardia (JET) is a rare syndrome of the heart that manifests in patients recovering from heart surgery.[1] It is characterized by cardiac arrhythmia, or irregular beating of the heart, caused by abnormal conduction from or through the atrioventricular node (AV node).[2][3] In newborns and infants up to 6 weeks old, the disease may also be referred to as His bundle tachycardia or congenital JET.
## Contents
* 1 Pathophysiology
* 2 Diagnosis
* 3 Treatment
* 4 Epidemiology
* 5 Etymology
* 6 References
* 7 External links
## Pathophysiology[edit]
In normal individuals, electrical activity in the heart is initiated in the sinoatrial (SA) node (located in the right atrium), propagates to the atrioventricular (AV) node, and then through the bundle of His to the ventricles of the heart. (See electrical conduction system of the heart).
The AV node acts as a gatekeeper, limiting the electrical activity that reaches the ventricles of the heart. This function of the AV node is important, because if the signals generated in the atria of the heart were to increase in rate (as they do during atrial fibrillation or atrial flutter), the AV node will limit the electrical activity that conducts to the ventricles. For instance, if the atria are electrically activated at 300 beats per minute, half those electrical impulses are blocked by the AV node, so that the ventricles are activated at 150 beats per minute (giving a pulse of 150 beats per minute). Another important property of the AV node is that it slows down individual electrical impulses. This is manifest on the ECG as the PR interval, which is about less than 200 milliseconds, the time from activation of the atria (manifest as the P wave) and activation of the ventricles (manifest as the QRS complex).[citation needed]
Individuals with JET have a "short-circuit" in their heart, where the electricity bypasses the AV node, causing the heart to beat faster than normal. The cause of the arrhythmia, the ectopic focus, is usually near the AV node in the triangle of Koch (a rough triangle with points at the coronary sinus, the tendon of Todaro, and the tricuspid valve).[4]
Patients of heart surgery may experience an accelerated narrow complex tachycardia, usually within the first 24–48 hours (but occasionally longer) after surgery. There may be atrio-ventricular disassociation with more ventricular signals than atrial signals. The cause of JET is felt to be due to manipulation of the tissue surrounding the AV node during surgery, however debate exists regarding the exact cause, as it is seen after procedures even without significant manipulation of this area.[citation needed]
JET-like symptoms can also manifest congenitally and in the first six months of life. This syndrome, which may also referred to as His bundle tachycardia, is resistant to therapy and can be difficult to treat.[3][5]
## Diagnosis[edit]
JET in a 2-month-old girl following cardiac surgery. In this case the right bundle branch block was present during tachycardia and during normal sinus rhythm.
JET is most commonly diagnosed using a 12-lead ECG. The appearance is usually of a tachycardia with rapid, regular ventricular rates of 170-260 beats per minute.[6] The QRS complexes are usually narrow, but may be broad if a bundle branch block is present. There may a 1:1 relationship between atria and ventricular activity with a short RP interval, or atrioventricular dissociation with slower atrial than ventricular rates if the AV node is unable to conduct from the ventricles to the atria.[7]
The differential diagnosis of JET includes other forms of supraventricular tachycardia, most commonly atrioventricular nodal reentrant tachycardia (AVNRT). These can be distinguished using adenosine. The response to adenosine in JET is a temporary loss of conduction to the atria leading to continuation of the tachycardia but with atrioventricular dissociation.[6] In contrast, administration of adenosine in AVNRT will usually terminate the arrhythmia.[8] The diagnosis can be conclusively proven by performing an invasive electrophysiological study.[8]
## Treatment[edit]
Treatment is aimed at slowing the rate by correcting acidosis, correcting electrolytes (especially magnesium and calcium), cooling the patient, and antiarrhythmic medications.[6] Occasionally pacing of the atrium at a rate higher than the JET may allow improved cardiac function by allowing atrial and ventricular synchrony.[6]
Medications used to treat JET include beta-adrenoceptor blockers such as propranolol, calcium channel antagonists such as verapamil, and antiarrhythmics such as flecainide, amiodarone, and propafenone.[7] Amiodarone is frequently used in the short term in children experiencing JET following heart surgery, although propanolol, flecainide and propafenone are more commonly recommended for long term use due to the frequency of side effects associated with amiodarone.[7]
In those who experience recurrent episodes of JET, an alternative to long term medical therapy is catheter ablation.[7] In this procedure, the small area in which the cells initiating JET are found can be destroyed by heating or freezing the tissue.[9] This is accomplished using wires passed to the heart via the femoral vein through a small puncture in the groin.[9] The main risk of this procedure is accidental damage to the AV node. This occurs more frequently when treating JET than other forms of supraventricular tachycardia, requiring treatment with a pacemaker in 5-10% of ablations for JET.[7] The risk is lower if the tissue is frozen rather than heated.[7]
For those at risk of developing JET such as children undergoing heart surgery, treatment can also be given prophylactically. A meta-analysis of 9 studies found that sedation with dexmedetomidine reduced the risk of JET occurring post-operatively.[10]
## Epidemiology[edit]
JET is most commonly seen in children following cardiac surgery. The arrhythmia affects 2-22% of children depending on the type of surgery performed, with higher rates seen following repair of Tetralogy of Fallot, and lower rates following the repair of ventricular septal defects and arterial switch operations.[6]
## Etymology[edit]
Junctional ectopic tachycardia derives its name from the problem it causes. "Junctional" is used as the abnormal tissue driving the ventricular rate is located close junction between the atria and ventricles, known as the AV node. Ectopic (from the Greek ektopos, meaning "out of place") refers to the fact that the ventricles are being triggered by tissue that is not the normal pacemaker tissue within the heart. Tachycardia (from the Greek takhys, meaning "swift", and kardia, meaning heart) means a swift heart rate.[11]
By this definition, junctional ectopic tachycardia is an abnormally swift heart rhythm due to cells firing within the heart near the AV node.
## References[edit]
1. ^ Sarubbi B, Vergara P, D'Alto M, Calabro R (2003). "Congenital junctional ectopic tachycardia: presentation and outcome". Indian Pacing Electrophysiol J. 3 (3): 143–7. PMC 1502046. PMID 16943912. Retrieved 21 December 2008.
2. ^ "Supraventricular Tachycardia, Junctional Ectopic Tachycardia: Overview - eMedicine". Retrieved 21 December 2008.
3. ^ a b Campbell, R. W. F.; Wren, C. (1987). "His bundle tachycardia- arrhythmogenic and antiarrhythmic effects of therapy". European Heart Journal. 8 (6): 647–650. doi:10.1093/oxfordjournals.eurheartj.a062336. PMID 3113958. Retrieved 29 August 2011.
4. ^ Zhivadinovik J, Lazarova D, Gjorgov N (2006). "Dimensions of the Triangle of Koch" (PDF). Bratisl Lek Listy. 107 (4): 107–9. PMID 16796135. Retrieved 31 January 2013.
5. ^ Sarubbi B, Musto B, Ducceschi V, D'Onofrio A, Cavallaro C, Vecchione F, Musto C, Calabro R (2002). "Congenital junctional ectopic tachycardia in children and adolescents: a 20 year experience based study". Heart. 88 (2): 188–190. doi:10.1136/heart.88.2.188. PMC 1767240. PMID 12117855.
6. ^ a b c d e Haas, N. A.; Plumpton, K.; Justo, R.; Jalali, H.; Pohlner, P. (May 2004). "Postoperative junctional ectopic tachycardia (JET)". Zeitschrift für Kardiologie. 93 (5): 371–380. doi:10.1007/s00392-004-0067-3. ISSN 0300-5860. PMID 15160272.
7. ^ a b c d e f Brugada, Josep; Katritsis, Demosthenes G.; Arbelo, Elena; Arribas, Fernando; Bax, Jeroen J.; Blomström-Lundqvist, Carina; Calkins, Hugh; Corrado, Domenico; Deftereos, Spyridon G.; Diller, Gerhard-Paul; Gomez-Doblas, Juan J. (31 August 2019). "2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC)". European Heart Journal. doi:10.1093/eurheartj/ehz467. ISSN 1522-9645. PMID 31504425.
8. ^ a b Josephson, Mark E. (10 August 2015). Josephson's clinical cardiac electrophysiology : techniques and interpretations. Preceded by: Josephson, Mark E. (Fifth ed.). Baltimore, MD. ISBN 9781496326614. OCLC 938434294.
9. ^ a b Handbook of cardiac electrophysiology : a practical guide to invasive EP studies and catheter ablation. Murgatroyd, Francis D. London: ReMEDICA Pub. 2002. ISBN 9781901346374. OCLC 48363139.CS1 maint: others (link)
10. ^ Li, Xin; Zhang, Chengxin; Dai, Di; Liu, Haiyuan; Ge, Shenglin (September 2018). "Efficacy of dexmedetomidine in prevention of junctional ectopic tachycardia and acute kidney injury after pediatric cardiac surgery: A meta-analysis". Congenital Heart Disease. 13 (5): 799–807. doi:10.1111/chd.12674. ISSN 1747-0803. PMID 30260073.
11. ^ "Tachycardia". Online Etymology Dictionary. Retrieved 29 August 2011.
## External links[edit]
Classification
D
* MeSH: D013613
* v
* t
* e
Cardiovascular disease (heart)
Ischaemic
Coronary disease
* Coronary artery disease (CAD)
* Coronary artery aneurysm
* Spontaneous coronary artery dissection (SCAD)
* Coronary thrombosis
* Coronary vasospasm
* Myocardial bridge
Active ischemia
* Angina pectoris
* Prinzmetal's angina
* Stable angina
* Acute coronary syndrome
* Myocardial infarction
* Unstable angina
Sequelae
* hours
* Hibernating myocardium
* Myocardial stunning
* days
* Myocardial rupture
* weeks
* Aneurysm of heart / Ventricular aneurysm
* Dressler syndrome
Layers
Pericardium
* Pericarditis
* Acute
* Chronic / Constrictive
* Pericardial effusion
* Cardiac tamponade
* Hemopericardium
Myocardium
* Myocarditis
* Chagas disease
* Cardiomyopathy
* Dilated
* Alcoholic
* Hypertrophic
* Tachycardia-induced
* Restrictive
* Loeffler endocarditis
* Cardiac amyloidosis
* Endocardial fibroelastosis
* Arrhythmogenic right ventricular dysplasia
Endocardium /
valves
Endocarditis
* infective endocarditis
* Subacute bacterial endocarditis
* non-infective endocarditis
* Libman–Sacks endocarditis
* Nonbacterial thrombotic endocarditis
Valves
* mitral
* regurgitation
* prolapse
* stenosis
* aortic
* stenosis
* insufficiency
* tricuspid
* stenosis
* insufficiency
* pulmonary
* stenosis
* insufficiency
Conduction /
arrhythmia
Bradycardia
* Sinus bradycardia
* Sick sinus syndrome
* Heart block: Sinoatrial
* AV
* 1°
* 2°
* 3°
* Intraventricular
* Bundle branch block
* Right
* Left
* Left anterior fascicle
* Left posterior fascicle
* Bifascicular
* Trifascicular
* Adams–Stokes syndrome
Tachycardia
(paroxysmal and sinus)
Supraventricular
* Atrial
* Multifocal
* Junctional
* AV nodal reentrant
* Junctional ectopic
Ventricular
* Accelerated idioventricular rhythm
* Catecholaminergic polymorphic
* Torsades de pointes
Premature contraction
* Atrial
* Junctional
* Ventricular
Pre-excitation syndrome
* Lown–Ganong–Levine
* Wolff–Parkinson–White
Flutter / fibrillation
* Atrial flutter
* Ventricular flutter
* Atrial fibrillation
* Familial
* Ventricular fibrillation
Pacemaker
* Ectopic pacemaker / Ectopic beat
* Multifocal atrial tachycardia
* Pacemaker syndrome
* Parasystole
* Wandering atrial pacemaker
Long QT syndrome
* Andersen–Tawil
* Jervell and Lange-Nielsen
* Romano–Ward
Cardiac arrest
* Sudden cardiac death
* Asystole
* Pulseless electrical activity
* Sinoatrial arrest
Other / ungrouped
* hexaxial reference system
* Right axis deviation
* Left axis deviation
* QT
* Short QT syndrome
* T
* T wave alternans
* ST
* Osborn wave
* ST elevation
* ST depression
* Strain pattern
Cardiomegaly
* Ventricular hypertrophy
* Left
* Right / Cor pulmonale
* Atrial enlargement
* Left
* Right
* Athletic heart syndrome
Other
* Cardiac fibrosis
* Heart failure
* Diastolic heart failure
* Cardiac asthma
* Rheumatic fever
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| Junctional ectopic tachycardia | c0039235 | 2,048 | wikipedia | https://en.wikipedia.org/wiki/Junctional_ectopic_tachycardia | 2021-01-18T18:59:10 | {"gard": ["2706"], "mesh": ["D013613"], "umls": ["C0039235"], "orphanet": ["3283"], "wikidata": ["Q3513620"]} |
## Summary
### Clinical characteristics.
SCN8A-related epilepsy with encephalopathy is characterized by developmental delay, seizure onset in the first 18 months of life (mean 4 months), and intractable epilepsy characterized by multiple seizure types (generalized tonic-clonic seizures, infantile spasms, and absence and focal seizures). Epilepsy syndromes can include Lennox-Gastaut syndrome, West syndrome, and epileptic encephalopathies (e.g., Dravet syndrome). Hypotonia and movement disorders including dystonia, ataxia, and choreoathetosis are common. Psychomotor development varies from normal prior to seizure onset (with subsequent slowing or regression after seizure onset) to abnormal from birth. Intellectual disability, present in all, ranges from mild to severe (in ~50% of affected individuals). Autistic features are noted in some. Sudden unexpected death in epilepsy (SUDEP) of unknown cause has been reported in approximately 10% of published cases. To date SCN8A-related epilepsy with encephalopathy has been reported in the literature in about 50 individuals.
### Diagnosis/testing.
The diagnosis is established in a proband with encephalopathy and epilepsy and identification of a de novo pathogenic variant in SCN8A on molecular genetic testing.
### Management.
Treatment of manifestations: Seizure control should be managed by a pediatric neurologist with expertise in epilepsy management who is familiar with the pharmacotherapy for SCN8A-related epilepsy with encephalopathy and aware of how it differs from treatment of similar disorders. Vigorous attempts to control seizures are warranted. Several studies suggest a favorable response to sodium channel blockers.
Surveillance: Periodic evaluation for neurologic, cognitive, and/or behavioral deterioration; monitoring with EEG and other modalities such as video EEG telemetry or ambulatory EEG when new or different seizure types are suspected. Because of the increased risk of SUDEP, some families use oxygen monitoring during sleep.
Agents/circumstances to avoid: Several families of affected individuals report worsening of seizures with levetiracetam.
### Genetic counseling.
SCN8A-related epilepsy with encephalopathy is expressed in an autosomal dominant manner. Most affected individuals have a de novo pathogenic variant and typically do not reproduce. While the risk to future pregnancies is presumed to be low, some parents of an affected child may wish to consider prenatal testing or preimplantation genetic testing in future pregnancies as the risk may be slightly greater than in the general population because of the possibility of parental germline mosaicism.
## Diagnosis
### Suggestive Findings
SCN8A-related epilepsy with encephalopathy should be suspected in individuals with early-onset epileptic encephalopathy (i.e., refractory seizures and cognitive slowing or regression associated with ongoing epileptiform activity), particularly those with the following epilepsy features, seizure types, and/or epilepsy syndromes.
Epilepsy features
* Seizure onset in the first 18 months of life (mean age 4 months)
* Focal clonic seizures evolving into bilateral convulsive seizures
* Development of multiple seizure types
* Motor abnormalities including hypotonia
* Movement disorders including dystonia, ataxia, choreoathetosis
Seizure types
* Intractable childhood epilepsy with generalized tonic-clonic seizures
* Infantile spasms
* Absence and focal seizures
Epilepsy syndromes
* Lennox-Gastaut syndrome
* West syndrome
* Early-onset epilepsy with hypotonia, movement disorders, and/or intellectual disability (e.g., Dravet syndrome)
### Establishing the Diagnosis
The diagnosis of SCN8A-related epilepsy with encephalopathy is established in a proband with encephalopathy and epilepsy by identification of a de novo pathogenic variant in SCN8A through molecular genetic testing (see Table 1).
Molecular genetic testing approaches can include targeted gene testing (multigene panel) or genomic testing (comprehensive genomic sequencing).
Targeted gene testing requires the clinician to develop a hypothesis about which specific gene(s) are likely to be involved, whereas genomic testing may not. Because the phenotypes of many genetic epileptic encephalopathies overlap, most children with SCN8A encephalopathy with epilepsy are diagnosed by following recommended testing (multigene panel) or testing to consider (comprehensive genomic sequencing). Note that testing of SCN8A alone (i.e., single-gene testing) is rarely used.
#### Recommended Testing
A multigene panel that includes SCN8A and other genes of interest (see Differential Diagnosis) is the recommmmended approach. 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.
#### Testing to Consider
Comprehensive genomic testing (when available) including exome sequencing and genome sequencing may be considered if the phenotype is indistinguishable from other inherited disorders (or the phenotype alone is insufficient to support focused gene testing). For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
### Table 1.
Molecular Genetic Testing Used in SCN8A-Related Encephalopathy with Epilepsy
View in own window
Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method
SCN8ASequence analysis 3100% 4
Gene-targeted deletion/duplication analysis 5Unknown, none reported to date 4
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. 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 the first 100 individuals with SCN8A-related encephalopathy with epilepsy, all SCN8A pathogenic variants were missense variants with the exception of one splice site variant predicted to cause an in-frame deletion [Rauch et al 2012; Veeramah et al 2012; Carvill et al 2013; Allen et al 2013; de Kovel et al 2014; Estacion et al 2014; Ohba et al 2014; Vaher et al 2014; Blanchard et al 2015; Dyment et al 2015; Fitzgerald et al 2015, Fung et al 2015; Kong et al 2015a; Larsen et al 2015; Mercimek-Mahmutoglu et al 2015; Olson et al 2015; Singh et al 2015; Takahashi et al 2015; Wagnon et al 2015a; Boerma et al 2016; M Hammer, unpublished data].
5\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.
## Clinical Characteristics
### Clinical Description
SCN8A pathogenic variants have been associated with developmental delay prior to and/or after onset of seizures, intellectual disability without seizures, and epileptic encephalopathy.
SCN8A-related epilepsy with encephalopathy is an early-onset, intractable epilepsy characterized by multiple seizure types and developmental delay. To date 50 individuals with a de novo SCN8A pathogenic variant have been reported [Rauch et al 2012, Veeramah et al 2012, Allen et al 2013, Carvill et al 2013, de Kovel et al 2014, Estacion et al 2014, Ohba et al 2014, Vaher et al 2014, Blanchard et al 2015, Dyment et al 2015, Fitzgerald et al 2015, Fung et al 2015, Kong et al 2015a, Larsen et al 2015, Mercimek-Mahmutoglu et al 2015, Olson et al 2015, Singh et al 2015, Takahashi et al 2015, Wagnon et al 2015a, Boerma et al 2016].
The most common clinical features of SCN8A-related epilepsy with encephalopathy are described below. Of note, sudden setbacks of unknown cause are common.
Seizures. In 48 of the 50 affected individuals reported to date age of onset of seizures ranged from the first day of life to age 22 months (median age: 4 months; mean age: 4.7 months). Of note, prenatal onset of seizures may occur as some mothers reported unusual "drumming" movements in the later stages of pregnancy [Singh et al 2015].
Initial seizure type varies, and most affected individuals develop additional seizure types, including the following:
* Focal clonic seizures evolving to a bilateral convulsive seizure
* Afebrile generalized tonic clonic seizures
* Tonic seizures
* Infantile spasms
* Myoclonic seizures
Although both convulsive and non-convulsive status epilepticus appear to be common [Larsen et al 2015], they are not as common as in Dravet syndrome.
Seizure frequencies range from hundreds per day to fewer than one per month.
Most affected individuals have refractory seizures and require polytherapy (see Treatment of Manifestations).
Psychomotor development varies from normal prior to seizure onset (with subsequent slowing or regression after seizure onset) to abnormal from birth [Larsen et al 2015]. Many affected individuals experience marked slowing or arrest in development either for no apparent reason or after an event that occurred before the developmental decline, such as a change in seizure type or change in medication.
Approximately half of affected children learn to sit and walk unassisted; the remainder are non-ambulatory. Ataxia and sudden loss of mobility are common in those who are ambulatory.
The oldest patient of whom the authors are aware is 47 years old; the majority of diagnosed individuals are younger than age 20 years. For the several who are in their teens, cognitive and motor disabilities persist.
Language is frequently affected. The majority of affected individuals speak few or no words.
Intellectual disability ranges from mild to severe, with about half of affected individuals having severe intellectual disability. Autistic features are noted in some [Larsen et al 2015].
Movement abnormalities including hypotonia, dystonia, choreoathetosis, ataxia, spasticity, and increased startle have been described in some affected individuals.
Startle and sleep problems. Many children are hyper-alert as infants (i.e., more awake and aware of their surroundings than typical infants) and are easily startled. For example, Singh et al [2015] reported a newborn with jittery movements shortly after birth and a pathologically exaggerated startle response to tactile and acoustic stimuli, findings that prompted a suspicion of hyperekplexia. The hyper-alert sleep appears to make it difficult for the infant to settle into a deep, healthy sleep. These findings have been anecdotally reported in several other individuals with SCN8A-related encephalopathy with epilepsy.
Associated medical problems, reported in some affected individuals, can include the following:
* Autonomic nervous system dysfunction, including difficulty with temperature regulation and tachypnea
* Hearing problems
* Bone fractures, often associated with prolonged seizures
* Laryngomalacia
* Scoliosis
* Microcephaly
* Cortical visual impairment
* Gum hyperplasia secondary to antiepileptic drugs (AEDs)
Sudden unexpected death in epilepsy (SUDEP) has been reported in approximately 10% of published cases [Veeramah et al 2012, Estacion et al 2014, Kong et al 2015a, Larsen et al 2015]. The cause of SUDEP is unknown, but may be related to prolonged seizures, cardiac abnormalities, or brain stem dysfunction. SUDEP can occur at any age.
EEG. Early on the EEG may be normal or exhibit focal or multifocal epileptiform activity. The EEG tends to evolve over time, often showing moderate to severe background slowing and focal or multifocal sharp waves or spikes, most often in the temporal regions. Some show almost continuous delta slowing in the temporo-parietal-occipital regions, with superimposed beta frequencies and bilateral asynchronous spikes or sharp waves [Larsen et al 2015].
Brain MRI is usually normal at the onset of seizures; however, abnormal findings may include cerebral atrophy and hypoplasia of the corpus callosum. Some affected individuals have been shown to have developed cerebral or cerebellar atrophy in follow-up studies [Larsen et al 2015, Singh et al 2015].
### Genotype-Phenotype Correlations
There is no obvious correlation between the position of an SCN8A pathogenic variant and the seizure onset, seizure type, or clinical severity. Most pathogenic variants are located in the transmembrane segments of the channel.
Notable similarities in age of onset and movement impairment were reported in two severely affected, unrelated individuals with the same de novo pathogenic variant p.Ile1327Val [Vaher et al 2014, Singh et al 2015]; in contrast, however, multiple individuals with the pathogenic variant p.Arg1617Gln had different ages of onset and disease severity [Wagnon & Meisler 2015].
### Penetrance
Penetrance for SCN8A-related epilepsy with encephalopathy is unknown but assumed to be complete.
* All SCN8A pathogenic variants identified to date have been de novo or inherited from a parent with a somatic mosaic pathogenic variant that included the germline.
* None of the SCN8A pathogenic variants have been seen in unaffected individuals, including controls in various studies and the ExAC database of ~60,000 genomes (exac.broadinstitute.org).
### Prevalence
The prevalence of SCN8A-related epilepsy with encephalopathy is not known.
The frequency of SCN8A pathogenic variants among individuals with epileptic encephalopathy was 13/1557 (close to 1%) in four independent studies, each of which included several hundred individuals [Allen et al 2013, Carvill et al 2013, Larsen et al 2015, Mercimek-Mahmutoglu et al 2015].
## Differential Diagnosis
The clinical features associated with a SCN8A pathogenic variant overlap significantly with other genetic (and non-genetic) epileptic encephalopathies. The differential diagnosis should include all genes known to be associated with early infantile epileptic encephalopathy (>30 have been identified; see OMIM Phenotypic Series).
Structural abnormalities of the brain that cause epileptic encephalopathy should be included in the differential diagnosis and can be identified by brain MRI.
Treatable neurometabolic disorders causing early infantile-onset epileptic encephalopathy that should be considered in the differential diagnosis include:
* Pyridoxine-dependent epilepsy
* Pyridoxamine 5'-phosphate oxidase deficiency (OMIM 610090)
* Biotinidase deficiency
* Glucose transporter 1 deficiency syndrome
* Creatine deficiency syndromes
* Holocarboxylase synthetase deficiency (OMIM 253270)
* Serine biosynthesis disorders including:
* Phosphoglycerate dehydrogenase deficiency (OMIM 601815)
* Phosphoserine aminotransferase deficiency (OMIM 610992)
* Phosphoserine phosphate deficiency (OMIM 614023)
Dravet syndrome is an infantile epileptic encephalopathy characterized by hemiclonic or generalized seizures that are often triggered by fever. More than 80% of individuals with Dravet syndrome have a de novo pathogenic variant in SCN1A (a related sodium channel gene) that results in loss of function due to protein truncation (60%) or pathogenic missense variants that inactivate the channel [Marini et al 2011]. The distinction between epilepsy caused by mutation of SCN1A and epilepsy caused by mutation of SCN8A is important because sodium channel blockers should be avoided in Dravet syndrome whereas they may be beneficial in SCN8A-related epilepsy with encephalopathy (see Treatment of Manifestations).
Distinctions between SCN8A-related epilepsy with encephalopathy and Dravet syndrome include:
* Age of onset. The mean age of onset is similar but the range of 0 days to 22 months in SCN8A-related epilepsy with encephalopathy is broader than that seen in Dravet syndrome.
* Febrile seizures. Susceptibility to seizures with fever is common in Dravet syndrome, but rare in SCN8A-related encephalopathy with epilepsy.
* Infantile spasms. Many patients with SCN8A-related epilepsy with encephalopathy present with spasms, which are not a feature of Dravet syndrome.
* Myoclonic seizures. Patients with SCN8A-related epilepsy with encephalopathy rarely have myoclonic seizures, which are common in Dravet syndrome.
* Hypotonia and movement disorders are common in patients with SCN8A-related encephalopathy with epilepsy, but are not typical of Dravet syndrome.
* EEG findings. Generalized spike wave, a hallmark of Dravet syndrome after age one to two years, is not typical in SCN8A-related encephalopathy with epilepsy.
* Medications. Sodium channel blockers such as carbamazepine, oxcarbazepine, and phenytoin appear to be the most efficacious antiepileptic drug (AED) for SCN8A-related epilepsy with encephalopathy [Larsen et al 2015, Boerma et al 2016], while many patients with Dravet syndrome do worse on sodium channel blockers.
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with a SCN8A-related encephalopathy with epilepsy, the following evaluations are recommended:
* Neurologic examination including:
* EEG, which may provide an assessment of the overall degree of epileptic encephalopathy and seizure type
* Brain MRI if not previously performed
* Cognitive and behavioral neuropsychological evaluation
* ECG to assess for cardiac arrhythmias, which have been identified in some patients with mutation of genes encoding other sodium channel subunits and may increase the risk of sudden unexpected death in epilepsy (SUDEP)
* Consultation with a clinical geneticist and/or genetic counselor
### Treatment of Manifestations
No published treatment guidelines exist.
Seizure control should be managed by a pediatric neurologist with expertise in epilepsy management who is familiar with the pharmacotherapy for SCN8A-related epilepsy with encephalopathy and how it differs from treatment of similar disorders (e.g., Dravet syndrome; see SCN1A-Related Seizure Disorders and Differential Diagnosis).
Vigorous attempts to control seizures with drug polytherapy are warranted because children with SCN8A-related epilepsy with encephalopathy are at risk for sudden unexplained death in epilepsy (SUDEP) as well as prolonged acute seizures that may cause permanent injury [Chipaux et al 2010, Takayanagi et al 2010].
Sodium channel blockers. Several studies suggest that patients with SCN8A-related epilepsy with encephalopathy respond favorably to the class of antiepileptic drugs (AEDs) that block sodium channels; these include phenytoin, valproate, carbamazepine, lacosamide, lamotrigine, rufinamide, and oxcarbazepine [Kong et al 2015b, Larsen et al 2015, Boerma et al 2016]. The effectiveness of sodium channel blockers is consistent with the activating effects of most SCN8A pathogenic variants [Wagnon & Meisler 2015, Wagnon et al 2015a, Wagnon et al 2015b]. Most patients are maintained on multiple medications with incomplete seizure control. One study of four patients reported a positive response to high doses of phenytoin [Boerma et al 2016].
Other AEDs
* Clobazam, part of the standard of care for epilepsy in Europe, is now FDA-approved for the treatment of seizures in Lennox-Gastaut syndrome [Selmer et al 2009].
* Phenobarbital, while effective for seizure control, is poorly tolerated because of its effects on cognition.
* Levetiracetam (Keppra®) has been reported by several families to be ineffective or occasionally associated with an increase in seizure frequency [M Hammer, unpublished data].
Other. When seizures are not responsive to conventional AEDs, the following drugs/treatment modalities may be effective based on anecdotal information:
* Corticosteroids
* Immunoglobulins
* Vagus nerve stimulator
* Ketogenic diet
* Cannabinoids
Sleep hygiene. As described for Dravet syndrome, sleep deprivation and illness can exacerbate SCN8A-related seizures; thus, good sleep hygiene should be encouraged. Comorbidity with sleep apnea can also occur frequently in individuals with epilepsy [Malow et al 2000], and can influence seizure control, behavior, and cognition. Polysomnography should be considered if obstructive or central sleep apnea is suspected.
Caregivers. For information on non-medical interventions and coping strategies for parents or caregivers of children diagnosed with epilepsy, see Epilepsy & My Child Toolkit.
### Surveillance
Evaluate periodically for neurologic, cognitive, and/or behavioral deterioration.
Monitor with EEG and other modalities (e.g., video EEG telemetry or ambulatory EEG) when new or different seizure types are suspected.
Because of the increased risk of SUDEP, some families use oxygen monitoring during sleep.
### Agents/Circumstances to Avoid
Several families of affected individuals report worsening of seizures with levetiracetam (Keppra®) [M Hammer, unpublished data].
### Evaluation of Relatives at Risk
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Therapies Under Investigation
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. Note: There may not be clinical trials for this 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 inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| SCN8A-Related Epilepsy with Encephalopathy | c3281191 | 2,049 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK379665/ | 2021-01-18T20:59:40 | {"synonyms": ["Early-Infantile Epileptic Encephalopathy 13 (EIEE13)"]} |
Lemierre syndrome is a rare, potentially lethal, oropharyngeal infectious disease occurring in immunocompetent adolescents and young adults that is mainly due to Fusobacterium necrophorum and that is characterized by septic thrombophlebitis of the internal jugular vein that leads to septic, usually pulmonary, embolism, associated with ENT (ear, nose, and throat) infection that manifests with fever, neck pain, and tonsillopharyngitis.
*[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
| Lemierre syndrome | c0343525 | 2,050 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=137839 | 2021-01-23T18:03:13 | {"gard": ["6882"], "mesh": ["D057831"], "umls": ["C0343525"], "icd-10": ["I80.8"], "synonyms": ["Lemierre postanginal sepsis", "Postanginal sepsis secondary to orophyngeal infection", "Septic phlebitis of the internal jugular vein"]} |
A number sign (#) is used with this entry because of evidence that a syndrome involving cutaneous telangiectasia, mild developmental anomalies of hair, teeth, and nails, and a predisposition to cancer, predominantly oropharyngeal, is caused by heterozygous mutation in the ATR gene (601215) on chromosome 3q23. One such family has been reported.
Description
Patients with this syndrome develop cutaneous telangiectases in infancy with patchy alopecia over areas of affected skin, thinning of the lateral eyebrows, and mild dental and nail anomalies. Affected individuals are at increased risk of developing oropharyngeal cancer, and other malignancies have been reported as well (Tanaka et al., 2012).
Clinical Features
Tanaka et al. (2012) reported a family with 24 affected individuals over 4 generations. All those with the disorder had telangiectases that appeared during infancy (before 18 months of age) in both sun-exposed and sun-protected skin. Other clinical features included thinning of the lateral eyebrows and patchy alopecia in areas of skin with prominent telangiectases. Thin dental enamel and dental caries in both primary and secondary dentition were also noted, and some patients had mild dystrophic nail changes as well, including longitudinal ridging, thin nails prone to cracking, onycholysis, and onychomycosis. In addition, 10 of the 24 cases developed oropharyngeal cancer, typically in the third decade of life or later. Other reported malignancies included nonmelanoma skin cancer (basal cell carcinoma, squamous cell carcinoma, and sebaceous carcinoma) in 3 individuals, breast cancer in 1, and cervical cancer in 1.
Mapping
Using DNA from 7 affected and 6 unaffected members of a large 4-generation family segregating autosomal dominant cutaneous telangiectasia and predisposition to cancer, Tanaka et al. (2012) performed parametric linkage analysis and obtained a lod score of 2.7 on chromosome 3q22-q24 for an approximately 116 to 155 cM interval between SNPs rs722813 and rs952032. Fine mapping using microsatellite markers and SNP array data narrowed the candidate region to an approximately 16.8-cM interval at 3q22-q24, between rs712984 and rs951465.
Molecular Genetics
In a large 4-generation family segregating cutaneous telangiectasia and predisposition to cancer mapping to chromosome 3q22-q24, Tanaka et al. (2012) analyzed 42 candidate genes and identified a heterozygous missense mutation in the ATR gene (Q2144R; 601215.0002) that segregated with the disease and was not found in 220 ethnically matched control chromosomes.
INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Thinning of lateral eyebrows Nose \- Beaked nose (in some patients) Mouth \- Oropharyngeal cancer Teeth \- Thin dental enamel of both primary and secondary dentition \- Dental caries of both primary and secondary dentition \- Loss of multiple teeth \- Misshapen incisors (in some patients) SKIN, NAILS, & HAIR Skin \- Telangiectases in both sun-exposed and sun-protected areas \- Nonmelanoma skin cancer (in some patients) Nails \- Longitudinal ridging (in some patients) Hair \- Thinning of lateral eyebrows \- Alopecia, patchy, over areas of prominent telangiectases NEOPLASIA \- Oropharyngeal cancer \- Nonmelanoma skin cancer (in some patients) \- Breast cancer (rare) \- Cervical cancer (rare) MOLECULAR BASIS \- Caused by mutation in the ataxia-telangiectasia and RAD3-related gene (ATR, 601215.0002 ) ▲ 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 inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| CUTANEOUS TELANGIECTASIA AND CANCER SYNDROME, FAMILIAL | c3281203 | 2,051 | omim | https://www.omim.org/entry/614564 | 2019-09-22T15:54:52 | {"omim": ["614564"], "orphanet": ["313846"], "synonyms": ["Alternative titles", "TELANGIECTASIA, CUTANEOUS, AND CANCER SYNDROME, FAMILIAL"]} |
Larsen-like syndrome, B3GAT3 type is a rare, genetic, primary bone dysplasia characterized by laxity, dislocations and contractures of the joints, short stature, foot deformities (e.g. clubfeet), broad tips of fingers and toes, short neck, dysmorphic facial features (hypertelorism, downslanting palpebral fissures, upturned nose with anteverted nares, high arched palate) and various cardiac malformations. Severe disease is associated with multiple fractures, osteopenia, arachnodactyly and blue sclerae. A broad spectrum of additional features, including scoliosis, radio-ulnar synostosis, mild developmental delay, and various eye disorders (glaucoma, amblyopia, hyperopia, astigmatism, ptosis), are also reported.
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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
| Larsen-like syndrome, B3GAT3 type | c3278404 | 2,052 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=284139 | 2021-01-23T18:19:39 | {"omim": ["245600"], "icd-10": ["Q74.8"], "synonyms": ["Multiple joint dislocations-short stature-craniofacial dysmorphism-congenital heart defects syndrome"]} |
Oculoosteocutaneous syndrome is characterised by congenital anodontia, a small maxilla, short stature with shortened metacarpals and metatarsals, sparse hair, albinoidism and multiple ocular anomalies. It has been described in three siblings (one brother and two sisters). Transmission is autosomal recessive.
*[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 inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| Oculoosteocutaneous syndrome | c1859385 | 2,053 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2713 | 2021-01-23T18:22:11 | {"mesh": ["C565893"], "omim": ["211370"], "umls": ["C1859385"], "icd-10": ["Q87.5"]} |
A number sign (#) is used with this entry because of evidence that the phenotype of hereditary increase of red blood cell ATP is caused by heterozygous mutation in the PKLR (609712) on chromosome 1q22.
Clinical Features
Brewer (1965) in the United States and Zurcher et al. (1965) in Holland described high erythrocyte adenosine triphosphate as a dominantly inherited trait. 'High red cell ATP syndrome' may be a heterogeneous category. For example, pyrimidine-5-prime-nucleotidase deficiency (266120) hemolytic anemia shows this feature. Max-Audit et al. (1980) described a family in which 4 persons had polycythemia and pyruvate kinase hyperactivity. They showed low 2,3-diphosphoglycerate (2,3-DPG) and high adenosine triphosphate (ATP) levels. The PK electrophoretic patterns in these persons were abnormal by the presence of several additional bands.
Molecular Genetics
Beutler et al. (1997) restudied the family described by Zurcher et al. (1965) and by SSCP analysis found a band shift in exon 2 of the red cell pyruvate kinase gene resulting from a point mutation at nucleotide 110. Beutler (1997) verified the mutation as a G-to-A transition resulting in a gly37-to-glu amino acid substitution (609712.0008). The mutation was present in heterozygous state. Beutler et al. (1997) stated it is possible that different mutations in the PKLR gene are responsible for the finding in other families with elevated red cell ATP levels, because the enzyme kinetics in other families have been different from those in the family reported by Zurcher et al. (1965).
Inheritance \- Autosomal dominant Lab \- High erythrocyte adenosine triphosphate \- Pyruvate kinase hyperactivity \- Low 2,3-diphosphoglycerate (2,3-DPG) \- Additional PK electrophoretic bands Heme \- Polycythemia ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| ADENOSINE TRIPHOSPHATE, ELEVATED, OF ERYTHROCYTES | c1863224 | 2,054 | omim | https://www.omim.org/entry/102900 | 2019-09-22T16:45:17 | {"mesh": ["C566310"], "omim": ["102900"], "synonyms": ["Alternative titles", "PYRUVATE KINASE HYPERACTIVITY"]} |
Wikipedia list article
Main article: Mass psychogenic illness
In sociology and psychology, mass hysteria (also known as mass psychogenic illness, collective hysteria, group hysteria, or collective obsessional behavior) is a phenomenon that transmits collective illusions of threats, whether real or imaginary, through a population and society as a result of rumors and fear.[1][2]
In medicine, the term is used to describe the spontaneous manifestation—or production of chemicals in the body—of the same or similar hysterical physical symptoms by more than one person.[3][4]
A common type of mass hysteria occurs when a group of people believes that it is suffering from a similar disease or ailment,[5] sometimes referred to as mass psychogenic illness or epidemic hysteria.[6]
## Contents
* 1 Middle Ages
* 2 1500−1800
* 3 1800−1950
* 4 1950−2000
* 5 2000s
* 6 See also
* 7 References
* 8 Further reading
* 9 External links
## Middle Ages
According to an account which was written by an author in 1784, a nun who lived in a German convent in the 1400s began to bite her companions, the behavior soon spread through other convents in Germany, Holland and Italy.[7]
According to an 1844 book which cited an unnamed medical textbook, a nun who lived in a French convent during an unspecified time in the Middle Ages inexplicably began to meow like a cat, shortly leading the other nuns in the convent to meow as well. Eventually all of the nuns in the convent would meow together for a certain period of time every day, leaving the surrounding community astonished. This did not stop until the police threatened to whip the nuns.[8]
## 1500−1800
* The dancing plague of 1518 was a case of dancing mania that occurred in Strasbourg, Alsace (then part of the Holy Roman Empire) in July 1518. Numerous people took to dancing for days.
* The Irish Fright took place in England and parts of Wales in December 1688 during the Glorious Revolution. False reports that Irish soldiers were burning and massacring English towns prompted a mass panic in at least nineteen counties, with thousands of people arming themselves and preparing to resist non-existent groups of marauding Irishmen.[9]
* Salem witch trials (1692−1693) – In colonial Massachusetts, adolescent girls Abigail Williams, Betty Parris, Ann Putnam, Jr., and Elizabeth Hubbard began to have fits that were described by a minister as "beyond the power of Epileptic Fits or natural disease to effect."[10] The events resulted in the Salem witch trials, a series of hearings which resulted in the execution of 20 citizens and the death of five other citizens of Salem Village, Massachusetts (present day Danvers, Massachusetts) and nearby towns who were accused of practicing witchcraft.[11] The episode is one of America's most notorious cases of mass hysteria, and it has been used in political rhetoric and popular literature as a vivid cautionary tale about the dangers of isolationism, religious extremism, false accusations and lapses in due process.[12]
* Würzburg 1749 – An outbreak of screaming, squirming, and trance in a nunnery led to the execution of a suspected witch.[13]
* The Great Fear was a general panic that took place between 17 July and 3 August 1789, at the start of the French Revolution.[14]
## 1800−1950
* Spring-heeled Jack – England, starting in 1837
* Basel and Groß Tinz "Writing Tremor Epidemic" (1892, 1904) – The right hand of a ten-year-old girl in Groß Tinz began trembling, which developed into full-body seizures that spread to 19 other students. A similar epidemic affected 20 in Basel, Switzerland. Twelve years later, the Basel school experienced another outbreak that affected 27 students. Legend of the first outbreak was said to have played a role.[15]
* Montreal (1894) – Sixty students at a ladies' seminary suffered an outbreak of fits and seizures, some for as long as 2 months.[15]
* Meissen "Trembling Disease" (1905–06) – An estimated 237 children were afflicted between October 1905 and May 1906.[15]
* Halifax Slasher (1938) – The Halifax Slasher was the name given to a supposed attacker of residents, mostly women, of the town of Halifax, England in November 1938. The week-long scare began after two women claimed to have been attacked by a mysterious man with a mallet and "bright buckles" on his shoes.[16] Further reports of attacks by a man wielding a knife or a razor followed. The situation became so serious that Scotland Yard was called in to assist the Halifax police.[17] On November 29 one of the alleged victims admitted that he had inflicted the damage upon himself for attention. Others soon had similar admissions, and the Yard investigation concluded that none of the attacks had been real. Five local people were subsequently charged with public mischief offenses, and four were sent to prison.[16]
* "War of the Worlds" radio broadcast (1938) – Newspaper headlines reported that thousands of American's were plunged into panic over an Orson Welles radio play, convinced that America was under a deadly Martian attack.[18]
* Bellevue, Louisiana (1939) – A girl developed a leg twitch at the annual homecoming high school dance. Attacks worsened and spread to friends over the next several weeks.[15]
* Mad Gasser of Mattoon, Illinois, 1940s
## 1950−2000
* Seattle windshield pitting epidemic of 1954
* Tanganyika laughter epidemic (1962) – began on January 30, 1962, at a mission-run boarding school for girls in Kashasha, Tanzania. The laughter started with three girls and spread haphazardly throughout the school, affecting 95 of the 159 pupils, aged 12–18.[19][20] Symptoms lasted from a few hours to 16 days in those affected. The teaching staff were not affected but reported that students were unable to concentrate on their lessons. The school was forced to close down on March 18, 1962.[21] After the school was closed and the students were sent home, the epidemic spread to Nshamba, a village that was home to several of the girls.[21] In April and May, 217 people had laughing attacks in the village, most of them school children and young adults. The Kashasha school was reopened on May 21, only to be closed again at the end of June. In June, the laughing epidemic spread to Ramashenye girls' middle school, near Bukoba, affecting 48 girls. Another outbreak occurred in Kanyangereka and two nearby boys schools were closed.[19]
* June bug epidemic (1962) – The June bug epidemic serves as a classic example of hysterical contagion. In 1962 a mysterious disease broke out in a dressmaking department of a US textile factory. The symptoms included numbness, nausea, dizziness, and vomiting. Word of a bug in the factory that would bite its victims and cause them to develop the above symptoms quickly spread.[22] Soon 62 employees developed this mysterious illness, some of whom were hospitalized. The news media reported on the case. After research by company physicians and experts from the US Public Health Service Communicable Disease Center, it was concluded that the case was one of mass hysteria. While the researchers believed some workers were bitten by the bug, anxiety was probably the cause of the symptoms. No evidence was ever found for a bug which could cause the above flu-like symptoms, nor did all workers demonstrate bites.
* Welsh, Louisiana (1962) – With students' sexual activity under close scrutiny by school officials, and following rumors of mandatory pregnancy tests, 21 girls and one boy in grades six to eleven were affected by seizures and other symptoms over six months.[15]
* Blackburn, England (1965) – In October 1965 at a girls' school in Blackburn, several girls complained of dizziness.[23] Some fainted. Within a couple of hours, 85 girls from the school were rushed by ambulance to a nearby hospital after fainting. Symptoms included swooning, moaning, chattering of teeth, hyperpnea, and tetany.[23] A medical analysis of the event about one year later found that outbreaks began among the 14-year-olds, but that the heaviest incidence moved to the youngest age groups.[23] There was no evidence of pollution of food or air.[23] The younger girls proved more susceptible, but disturbance was more severe and lasted longer in the older girls.[23] Using the Eysenck Personality Inventory, those affected had higher scores for extroversion and neuroticism.[23] It was considered that the epidemic was hysterical, that a previous polio epidemic had rendered the population emotionally vulnerable, and that a three-hour parade, producing 20 faints on the day before the first outbreak, had been the specific trigger.[23]
* Mount Pleasant, Mississippi (1976) – School officials suspected drug use after 15 students fell to the ground writhing, but no drugs were found and hysteria is assumed to be the culprit. At one point, one third of the school's 900 students stayed home for fear of being "hexed".[15]
* Malaysia (1970s–1980s) – Mass hysteria occurred in Malaysia from the 1970s to the 1980s. It affected school-age girls and young women working in factories. The locals have explained this outbreak as "spirits" having possessed the girls and young women.[24][25][26]
* Hollinwell incident (1980) – Around 300 people, mostly children, but including adults and babies, suddenly suffered fainting attacks, nausea and other symptoms. The Hollinwell incident remains one of the prime examples of mass hysteria.
* The 1983 West Bank fainting epidemic was a series of incidents in March 1983 in which 943 Palestinian teenage girls, mostly schoolgirls, and a small number of IDF women soldiers fainted or complained of feeling nauseous in the West Bank. Israel was accused of using chemical warfare to sterilize West Bank women while IDF sources speculated that a toxic substance had been employed by Palestinian militants to stir up unrest,[27] but investigators concluded that even if some environmental irritant had originally been present, the wave of complaints was ultimately a product of mass hysteria. This conclusion was supported by a Palestinian health official, who said that while 20% of the early cases may have been caused by the inhalation of some kind of gas, the remaining 80% were psychosomatic.[28]
* Day-care sex-abuse hysteria was a moral panic that occurred primarily in the 1980s and early 1990s featuring charges against day-care providers of several forms of child abuse, including Satanic ritual abuse.[29][30]
* San Diego (1988) – The US Navy evacuated 600 men from barracks; 119 were sent to San Diego hospitals with complaints of breathing difficulty. No evidence of toxins, food poisoning, or any other cause was found.[31]
* Kosovo student poisoning 1990 – Zoran Radovanović, a professor in the Faculty of Medicine in Kuwait argues in an article for the European Journal of Epidemiology that the "Kosovo Student Poisoning" that affected at least four thousand, mostly ethnic Albanians, was a product of mass hysteria.
* Ganesha drinking milk miracle, 1995
* Belgium (June 1999) – Soft drink giant Coca-Cola withdrew 30 million units of its product from sale after more than a hundred people in Belgium and northern France complained of cramps, nausea and other problems after consuming the soft drinks. Testing found no evidence of tainted product and the incident was reported to be a panic, perhaps fueled by the discovery of dioxins in Belgian meat, which had brought down the national government earlier that year.[32]
* Many UFO reports may be the result of mass hysteria.[33]
## 2000s
* North Carolina (2002) – Ten girls developed seizures and other symptoms at a rural high school in North Carolina. Symptoms persisted for five months across various grade levels. Incidents tended to happen outside of class, with half of all incidents estimated to have occurred around lunch hour. Half of the affected were cheerleaders or former cheerleaders.[34][35]
* "Strawberries with Sugar virus" (2006) – In May 2006, an outbreak of the so-dubbed Morangos com Açúcar Virus (Strawberries with Sugar virus) was reported in Portuguese schools, named after the popular teen girl's show Morangos com Açúcar (Strawberries With Sugar). 300 or more students at 14 schools reported similar symptoms to those experienced by the characters in a then recent episode where a life-threatening virus affected the school depicted in the show.[36][37] Symptoms included rashes, difficulty breathing, and dizziness. The belief that there was a medical outbreak forced some schools to temporarily close. The Portuguese National Institute for Medical Emergency eventually dismissed the illness as mass hysteria.[36][37]
* Mexico City (2006–2007) – Between October 2006 and June 2007,[38] near Chalco, a working-class suburb of Mexico City, mass hysteria resulted in an outbreak of unusual symptoms suffered by more than 500 adolescent female students at Children's Village School (Villa de las Ninas), a Catholic boarding-school.[39][40] The afflicted students had difficulty walking and were feverish and nauseated, some becoming partially paralyzed.[38]
* Vinton, Virginia (2007) – An outbreak of twitching, headaches and dizziness affected at least nine girls and one teacher at William Byrd High School. The episode lasted for months amid other local public health scares.[34]
* Afghanistan (2009–) – Starting around 2009, a spate of apparent poisonings at girls' schools across Afghanistan began to be reported, with symptoms including dizziness, fainting, and vomiting. The United Nations, World Health Organization and NATO's International Security Assistance Force carried out investigations of the incidents over multiple years, but never found any evidence of toxins or poisoning in the hundreds of blood, urine, and water samples they tested. The conclusion of the investigators was that the girls were suffering from mass psychogenic illness.[41][42] Despite these findings, Afghan officials often blame the incidents on the Taliban, accusing them of contaminating the school's water supply or using poison gas.[42]
* Brunei (2010) – In April and May 2010, incidents of mass hysteria occurred at two all-girls secondary schools in Brunei.[43] The most recent notable event happened on the 24 April 2014 in a public secondary school. The phenomenon caused a wave of panic among many parents, educators, and members of the community. Some of the students affected by the phenomenon claimed to have been possessed by spirits, or jinn, displaying histrionic symptoms such as screaming, shaking, fainting, and crying.
* LeRoy, New York (2011–12) – 12 high school girls developed Tourette-like symptoms in 2011. Their school was tested for toxins, and all other factors for their symptoms were ruled out. The case, and some of the girls and their parents, gained national media attention. In January 2012, several more students and a 36-year-old adult female came forward with similar symptoms. They were all diagnosed with conversion disorder.[44][45]
* Sri Lanka (2012) – From November 15–20, 2012, incidents of mass hysteria occurred at 15 schools in Sri Lanka. More than 1,900 school children of 15 schools in Sri Lanka and five teachers were treated for a range of symptoms that included skin rashes, vomiting, vertigo, and cough due to allergic reactions believed to be mass hysteria. It originated at the Jinaraja Balika Vidyala in Gampola, Central Province on November 15, 2012 when 1,100 students were admitted to hospital with a range of symptoms that included skin rashes, vomiting, vertigo and coughing. Later, authorities had to close down the school for 3 days. After that on November 16–19 there were more reports of students from other parts of the country showing similar symptoms.[46][unreliable source?]
* Charlie Charlie panic (2015) – Four teens in Tunja, Colombia were hospitalized, and several in the Dominican Republic were considered "possessed by Satan" after playing the Charlie Charlie Challenge viral game.[47]
* 2016 clown sightings – Sightings of people in evil clown costumes in the United States, Canada, and 18 other countries were dismissed as a case of mass hysteria, stating that a fear of clowns (which is common in children and adults) may be an underlying cause.[48] The website Vox likewise claimed that "The Great Clown Panic of 2016 has been perpetuated by pretty much everyone except actual clowns."[49]
* Recurrent epidemic of mass hysteria (2016–2018) Nepal: A unique phenomenon of “recurrent epidemic of mass hysteria” was reported from a school of Pyuthan district of western Nepal in 2018. After a 9-year-old school girl developed crying and shouting episodes, quickly other children of the same school were also affected resulting in 47 affected students (37 females, 10 males) in the same day. Since 2016 similar episodes of mass psychogenic illness has been occurring in the same school every year. In 2016, twelve students were affected and in 2017, a total of 18 students of the same school were affected showing various symptoms in a single day. Hence it was thought to be a unique case of recurrent mass hysteria.[50][51]
* Emirates Flight 203, September 2018 – 106 of 521 passengers on a 14-hour flight from Dubai to New York reported symptoms including coughing, sneezing, fever, or vomiting. The pilot notified airport ground staff, and personnel from the U.S. Centers for Disease Control and Prevention met and quarantined the plane in New York and evaluated passengers, 11 of whom were sent to the hospital. A few passengers on the "flight from hell" turned out to have common colds or flu, with the other passengers coming to the belief that they were also sick after observing those around them.[52][53]
* In August 2019 the BBC reported that schoolgirls at the Ketereh national secondary school (SMK Ketereh) in Kelantan, Malaysia, started screaming, with some claiming to have seen 'a face of pure evil'. Professor Simon Wessely a former president of the Royal College of Psychiatrists, suggested it was a form of 'collective behaviour'. Robert Bartholomew, a medical sociologist, suggested it was due to the stricter implementation of Islamic law in the school. The school responded to the outbreak by cutting down the trees around the school, believing they were home to supernatural spirits.[54]
* Starehe Girls Centre, Kenya (October 2019) – 52 students were isolated with an unknown disease, showing symptoms of a high-pitched cough, sneezing and low-grade fever, a number that later rose to 68.[55] As the number rose, the school's administration shut the school down and instructed parents to pick up their daughters. Specimens collected from the affected students showed only two cases of rhinovirus, a virus that is the predominant cause of the common cold. After carrying out psychological assessments on the students, a team of mental health specialists dispatched by Kenya's Ministry of Health to the school concluded that the 'mysterious' disease was a case of mass hysteria.
* Mass hysteria occurred during the COVID-19 pandemic. For example, violence broke out in Ukraine over fear of the virus from quarantined evacuees from China. Ukraine authorities blamed the violence on a disinformation campaign targeting the country and spread over social media.[56]
## See also
* Body-centred countertransference
* Conversion disorder
* Folie à deux (from the French for "a madness shared by two")
* Hysterical contagion
* Psychochemical weaponry
## References
1. ^ Wolf, M. (1976). Witchcraft and Mass Hysteria in Terms of Current Psychological Theories, (are caused by the use of medical/experimental delusions). Journal of Practical Nursing and Mental Health Services 14: 23–28.
2. ^ Bartholomew, Robert E. (2001). Little Green Men, Meowing Nuns and Head-Hunting Panics: A Study of Mass Psychogenic Illness and Social Delusion. McFarland & Company.
3. ^ Bartholomew, Robert E.; Wesley, Simon (2002). "Protean nature of mass sociogenic illness: From possessed nuns to chemical and biological terrorism fears". British Journal of Psychiatry. Royal College of Psychiatrists. 180 (4): 300–306. doi:10.1192/bjp.180.4.300. PMID 11925351. "Mass sociogenic illness mirrors prominent social concerns, changing in relation to context and circumstance (including hysteria from the topic at hands). Prior to the 1900, reports are dominated by episodes of motor symptom's typified by de-sociation, hormonics and psychologist agitated and incubated in an environment of preexisting tension. Nineteenth-century reports feature anxiety symptoms that are triggered by sudden exposure to an anxiety-generating agent (chemicals), most commonly an variety of food poisoning rumours."
4. ^ Waller, John (18 September 2008). "Falling down". The Guardian. London. "The recent outbreak of fainting in a school in Tanzania bears all the hallmarks of mass hysteria, says John Waller. But what causes it and why is it still happening around the world today?"
5. ^ Bartholomew, Robert E.; Erich Goode (May–June 2000). "Mass Delusions and Hysterias: Highlights from the Past Millennium". Committee for Skeptical Inquiry. 24 (3). Archived from the original on 2013-10-21. Retrieved 2010-04-12.
6. ^ Mass, Weir E. "Mass sociogenic- illness." CMAJ 172 (2005): 36. Web. 14 Dec. 2009.
7. ^ Zimmermann, Johann Georg (1784). Über die Einsamkeit (in German). 2. Leipzig: Weidmanns Erben und Reich. pp. 71–73.
8. ^ Hecker, J. F. (1844). The Epidemics of the Middle Ages (First ed.). p. 118.
9. ^ Jones, George Hilton (1982). "The Irish Fright of 1688: Real Violence and Imagined Massacre". Historical Research. 55 (132): 148–153. doi:10.1111/j.1468-2281.1982.tb01154.x. ISSN 0950-3471.
10. ^ "Salem Witch Trials".
11. ^ Trask, Richard B. (2013), The Witchcraft Delusion: A Brief Guide, Danvers Archival Center
12. ^ Adams, G. (2009), The Specter of Salem: Remembering the Witch Trials in Nineteenth-Century America, University of Chicago Press
13. ^ "Dancing plagues and mass hysteria". July 31, 2009. Retrieved July 1, 2015.
14. ^ John Merriman (1996). A History of Modern Europe from the French Revolution to the Present, volume 2, p. 482.
15. ^ a b c d e f Bartholomew, Robert E.; Rickard, Bob (2014). Mass Hysteria in Schools: A Worldwide History Since 1566. ISBN 978-1476614267. Retrieved July 1, 2010.
16. ^ a b "Life's Like That".
17. ^ BBC. "Radio 4 Making History".
18. ^ "75 Years Ago, 'War Of The Worlds' Started A Panic. Or Did It?". NPR.
19. ^ a b Provine, Robert R. (January–February 1996). "Laughter". American Scientist. 84 (1): 38–47.
20. ^ Rankin, A.M.; Philip, P.J. (May 1963). "An epidemic of laughing in the Bukoba district of Tanganyika". Central African Journal of Medicine. 9: 167–70. PMID 13973013.
21. ^ a b "Laughter". Radiolab. Retrieved 2011-01-12.
22. ^ Alan C. Kerckhoff & Kurt W. Back (1968) The June Bug: a study of hysterical contagion, Appleton-Century-Crofts
23. ^ a b c d e f g Moss, P. D. and C. P. McEvedy. "An epidemic of overbreathing among schoolgirls." British Medical Journal 2(5525) (1966):1295–1300. Web. 17 Dec. 2009.
24. ^ "Mass hysteria hits Malaysian school". Asian Economic News. Kuala Lumpur. Kyodo. July 16, 2001. Archived from the original on July 18, 2012. Retrieved 9 May 2012.
25. ^ http://smj.sma.org.sg/1604/1604smj11.pdf
26. ^ Ong, Aihwa (Feb 1988). "The Production of Possession: Spirits and the Multinational Corporation in Malaysia". American Ethnologist. Medical Anthropology. University of California, Berkeley: Blackwell Publishing. 15 (1): 28–42. doi:10.1525/ae.1988.15.1.02a00030. JSTOR 645484.
27. ^ David K. Shipler (April 4, 1983). "More Schoolgirls in West Bank Fall Sick". The New York Times. Jerusalem. Retrieved 6 May 2011.
28. ^ "Ailing Schoolgirls". Time. Apr 18, 1983. Retrieved 9 May 2012.
29. ^ "Innocence Lost, The Plea". Frontline. Retrieved 2009-03-20.
30. ^ Miller, L (2001-07-06). "Parole Board recommends Amirault's commutation". Associated Press. Archived from the original on 2007-11-04. Retrieved 2007-10-31. "The Amiraults always insisted they were innocent, the victims of a sex-abuse hysteria that swept the country in the 1980s and questionable testimony from child witnesses."
31. ^ "117 of Ill Recruits Returned to Base". September 5, 1988. Retrieved July 21, 2015.
32. ^ Dillner, Luisa (6 July 1999). "A case of mass hysteria". The Guardian. Guardian News & Media Limited. Retrieved 24 February 2019.
33. ^ How UFO Reports Change With the Technology of the Times | Smithsonian Magazine
34. ^ a b Bartholomew, Robert E.; Rickard, Bob (2014). Mass Hysteria in Schools: A Worldwide History Since 1566. ISBN 978-1476614267. Retrieved July 19, 2015.
35. ^ "Episodic Neurological Dysfunction Due to Mass Hysteria" (PDF). February 24, 2012. Retrieved July 19, 2015.
36. ^ a b "Teenagers hit by soap opera virus". CNN-IBN. May 19, 2006. Retrieved July 1, 2010.
37. ^ a b "Teens suffer soap opera virus". China Daily. May 19, 2006. Retrieved July 1, 2010.
38. ^ a b Hernandez, Daniel (20 May 2020). "The haunting of Girlstown". Vox. Retrieved 25 May 2020.
39. ^ Malkin, Elisabeth (April 16, 2007). "Mysterious illness strikes teenage girls in Mexico". The New York Times. Retrieved November 7, 2010.
40. ^ Zavala, Nashyiela Loa (2010). "The expulsion of evil and its return: An unconscious fantasy associated with a case of mass hysteria in adolescents". International Journal of Psychoanalysis. 91 (5): 1157–78. doi:10.1111/j.1745-8315.2010.00322.x. PMID 20955250.
41. ^ "Poisonings' at Afghan girls' schools likely mass hysteria – not Taliban, says report". 4 July 2012. Retrieved 5 January 2016.
42. ^ a b "Are the Taliban Poisoning Afghan Schoolgirls? The Evidence". 9 July 2012. Retrieved 5 January 2016.
43. ^ Bandial, Quratul-Ain (May 13, 2010). "Mass hysteria: product of 'jinn' or anxiety?". The Brunei Times. Brunei-Muara. Archived from the original on 22 April 2012. Retrieved 9 May 2012.
44. ^ "12 girls at NY high school develop involuntary tics". Washington Post. Archived from the original on 2012-01-23.
45. ^ McGowan, Kate (2012-01-29). "LeRoy Woman Discloses 'Conversion Disorder', Talks Exclusively to YNN". YNN. Retrieved 9 May 2012.
46. ^ "Sri Lanka Mass Hysteria at Schools".
47. ^ "'Charlie Charlie' game summoning Mexican demon goes viral, causing damage real and fake".
48. ^ Angela Chen (7 October 2016). "The 2016 clown panic: 10 questions asked and answered". theverge.com. Retrieved 1 November 2016.
49. ^ Aja Romano (12 October 2016). "The great clown panic of 2016 is a hoax. But the terrifying side of clowns is real". vox.com. Retrieved 3 November 2016.
50. ^ "४८ विद्यार्थीमा मास हिस्टेरिया भएपछि एक महिनाका लागि विद्यालय बन्द". https://swasthyakhabar.com/. Retrieved 2020-06-14. External link in `|website=` (help)
51. ^ Poudel, Reet; Aich, Tapas Kumar; Bhandary, Krishma; Thapa, Dipendra; Giri, Rajesh (2020-05-01). "Recurrent mass hysteria in schoolchildren in Western Nepal". Indian Journal of Psychiatry. 62 (3): 316. doi:10.4103/psychiatry.IndianJPsychiatry_571_19. ISSN 0019-5545.
52. ^ A Flight From Dubai Carrying Dozens Of Sick Passengers Was Quarantined In New York
53. ^ On the Media – Plague of Suspicion
54. ^ Chen, Heather (11 August 2019). "The mystery of screaming schoolgirls in Malaysia". BBC News. Retrieved 17 August 2019.
55. ^ Agutu, Nancy (4 October 2019). "Starehe girls diagnosed with mass hysteria". The Star. Retrieved 5 October 2019.
56. ^ "Hysteria over coronavirus sparks violent protests in Ukraine". ABC News. Retrieved 2020-05-24.
## Further reading
* Bartholomew, Robert E. (2001). Little Green Men, Meowing Nuns and Head-hunting Panics: A Study of Mass Psychogenic Illnesses and Social Delusion. McFarland.
* Bartholomew, Robert E; Evans, Hilary. (2009). Outbreak! The Encyclopedia of Extraordinary Social Behavior. Anomalist Books.
* Craft, Amos Norton. (1881). Epidemic Delusions: Containing an Exposé of the Superstitions and Frauds which Underlie Some Ancient and Modern Delusions, Including Especial Reference to Modern Spiritualism. New York: Phillips & Hunt.
* Fleischer, Jeff. (2011). The Latest Craze: A Short History of Mass Hysterias. Fall River Press.
* Mackay, Charles. (1856 edition). Memoirs of Extraordinary Popular Delusions and the Madness of Crowds. London, New York: G. Routledge and Sons.
* Verma, S. K; Srivastava, D. K. (2003). A Study on Mass Hysteria (Monkey Men?) Victims In East Delhi. Indian Journal of Medical Sciences 57: 355–360.
## External links
* Six hundred girls in Mexico suffer from collective hysteria
* Sri Lanka Mass Hysteria
* Mass hysteria – Skeptic's Dictionary
* Mass Delusions and Hysterias: Highlights from the Past Millennium – Skeptical Inquirer
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*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| List of mass hysteria cases | None | 2,055 | wikipedia | https://en.wikipedia.org/wiki/List_of_mass_hysteria_cases | 2021-01-18T19:09:59 | {"wikidata": ["Q847836"]} |
Subepidermal calcified nodule
Other namesSolitary congenital nodular calcification[1] and Winer's nodular calcinosis[1])
Histologic sample of subepidermal calcified nodule
SpecialtyDermatology
Subepidermal calcified nodule is a type of Calcinosis cutis. It's a cutaneous condition characterized by calcification of the skin resulting from the deposition of calcium and phosphorus, occurring most frequently as one or a few skin lesions on the scalp or face of children.[2]:528 Lesions may also appear on the ear and eyelid.[citation needed]
## See also[edit]
* Ectopic calcification
* Calcinosis cutis
* Skin lesion
* List of cutaneous conditions
## References[edit]
Wikimedia Commons has media related to Subepidermal calcified nodule.
1. ^ a b Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
2. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6.
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This cutaneous condition article is a stub. You can help Wikipedia by expanding it.
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*[c.]: circa
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| Subepidermal calcified nodule | c0546395 | 2,056 | wikipedia | https://en.wikipedia.org/wiki/Subepidermal_calcified_nodule | 2021-01-18T18:57:49 | {"umls": ["C0546395"], "wikidata": ["Q7631121"]} |
Spontaneous flow of milk from the breast
Galactorrhea
SpecialtyObstetrics
Galactorrhea (also spelled galactorrhoea) (galacto- \+ -rrhea) or lactorrhea (lacto- \+ -rrhea) is the spontaneous flow of milk from the breast, unassociated with childbirth or nursing.
Galactorrhea is reported to occur in 5–32% of women. Much of the difference in reported incidence can be attributed to different definitions of galactorrhea.[1] Although frequently benign, it may be caused by serious underlying conditions and should be properly investigated.[2] Galactorrhea also occurs in males, newborn infants and adolescents of both sexes.[3]
## Contents
* 1 Causes
* 2 Neonatal milk
* 3 See also
* 4 References
* 5 External links
## Causes[edit]
Galactorrhea can take place as a result of dysregulation of certain hormones. Hormonal causes most frequently associated with galactorrhea are hyperprolactinemia and thyroid conditions with elevated levels[a] of thyroid-stimulating hormone (TSH) or thyrotropin-releasing hormone (TRH). No obvious cause is found in about 50% of cases.[1]
Lactation requires the presence of prolactin, and the evaluation of galactorrhea includes eliciting a history for various medications or foods (methyldopa, opioids, antipsychotics, serotonin reuptake inhibitors, as well as licorice[4]) and for behavioral causes (stress, and breast and chest wall stimulation), as well as evaluation for pregnancy, pituitary adenomas (with overproduction of prolactin or compression of the pituitary stalk), and hypothyroidism. Adenomas of the anterior pituitary are most often prolactinomas. Overproduction of prolactin leads to cessation of menstrual periods and infertility, which may be a diagnostic clue. Galactorrhea may also be caused by hormonal imbalances owing to birth control pills.
Galactorrhea is also a side effect associated with the use of the second-generation H2 receptor antagonist cimetidine (Tagamet). Galactorrhea can also be caused by antipsychotics that cause hyperprolactinemia by blocking dopamine receptors responsible for control of prolactin release. Of these, risperidone is the most notorious for causing this complication.[5] Case reports suggest proton-pump inhibitors have been shown to cause galactorrhea.
## Neonatal milk[edit]
Main article: Witch's milk
Neonatal milk or witch's milk is milk secreted from the breasts of approximately 5% of newborn infants. It is considered a normal variation and no treatment or testing is necessary. In folklore, witch's milk was believed to be a source of nourishment for witches' familiar spirits.[6]
## See also[edit]
* Lactation failure
* Galactagogue
* Mammoplasia
* Hypothalamic–pituitary–prolactin axis
## References[edit]
1. ^ a b Sakiyama, R.; Quan, M. (1983). "Galactorrhea and hyperprolactinemia". Obstetrical & Gynecological Survey. 38 (12): 689–700. doi:10.1097/00006254-198312000-00001. PMID 6361641. S2CID 2846310.
2. ^ Whitman-Elia, G. F.; Windham, N. Q. (2000). "Galactorrhea may be clue to serious problems. Patients deserve a thorough workup". Postgraduate Medicine. 107 (7): 165–168, 171. doi:10.3810/pgm.2000.06.1129. PMID 10887453.
3. ^ Rohn, R. D. (1984). "Galactorrhea in the adolescent". Journal of Adolescent Health. 5 (1): 37–49. doi:10.1016/s0197-0070(84)80244-2. PMID 6420385.
4. ^ Karimi, H; Nourizad, S; Momeni, M; Rahbar, H; Momeni, M; Farhadi, K (2013). "Burns, hypertrophic scar and galactorrhea". Journal of Injury & Violence Research. 5 (2): 117–9. doi:10.5249/jivr.v5i2.314. PMC 3683415. PMID 23456048.
5. ^ Popli, A (March 1998). "Risperidone-induced galactorrhea associated with a prolactin elevation". Ann Clin Psychiatry. 10 (1): 31–3. doi:10.3109/10401239809148815. PMID 9622047.
6. ^ Potts, Malcolm (1999). Ever Since Adam and Eve: The Evolution of Human Sexuality. p. 145. ISBN 0-521-64404-6.
1. ^ which may also suggest Pituitary disease
## External links[edit]
Classification
D
* ICD-10: N64.3, O92.6
* ICD-9-CM: 611.6, 676.6
* MeSH: D005687
* DiseasesDB: 6314
External resources
* Patient UK: Galactorrhea
Look up galactorrhea in Wiktionary, the free dictionary.
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Breast disease
Inflammation
* Mastitis
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*[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
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*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
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| Galactorrhea | c3665358 | 2,057 | wikipedia | https://en.wikipedia.org/wiki/Galactorrhea | 2021-01-18T18:53:15 | {"mesh": ["D005687"], "umls": ["C0235660", "C3665358"], "icd-9": ["611.6"], "icd-10": ["O92.6", "N64.3"], "wikidata": ["Q278515"]} |
Bartholin's cyst
Other namesBartholinitis, Bartholin's duct cyst, Bartholin's abscess
Bartholin's cyst of the right side
SpecialtyGynecology
SymptomsSwelling of one side of the vagina, pain[1]
ComplicationsAbscess[2]
Usual onsetChildbearing age[2]
CausesTypically unknown[1]
Diagnostic methodBased on symptoms and examination[1]
Differential diagnosisSebaceous cyst, hernia, hidradenitis suppurativa, folliculitis, vulvar cancer[3][4]
TreatmentPlacement of a Word catheter, incision and drainage, marsupialization, sitz baths[3][1]
Frequency2% of women[2]
A Bartholin's cyst occurs when a Bartholin's gland within the labia becomes blocked.[1] Small cysts may result in minimal symptoms. Larger cysts may result in swelling on one side of the vagina, as well as pain during sex or walking.[1] If the cyst becomes infected, an abscess can occur, which is typically red and very painful.[2] If there are no symptoms, no treatment is needed.[2][1] Bartholin's cysts affect about 2% of women at some point in their life.[2] They most commonly occur during childbearing years.[2]
When the cyst becomes uncomfortable or painful, drainage is recommended.[2] The preferred method is the insertion of a Word catheter for four weeks, as recurrence following simple incision and drainage is common.[2][3] A surgical procedure known as marsupialization may be used or, if the problems persist, the entire gland may be removed.[2] Removal is sometimes recommended in those older than 40 to ensure cancer is not present.[2] Antibiotics are not generally needed to treat a Bartholin's cyst.[2]
The cause of a Bartholin's cyst is typically unknown.[1] An abscess results from a bacterial infection, but it is not usually a sexually transmitted infection (STI).[5] Rarely, gonorrhea may be involved.[1][4] Diagnosis is typically based on symptoms and examination.[1] In women over the age of 40, a tissue biopsy is often recommended to rule out cancer.[3][1]
The cyst is named after Caspar Bartholin who accurately described the glands in 1677.[6] The underlying mechanism of the cyst was determined in 1967 by 20th Century obstetrician Samuel Buford Word.[7][6][8]
## Contents
* 1 Signs and symptoms
* 2 Pathophysiology
* 3 Diagnosis
* 4 Treatment
* 5 Prognosis
* 6 Epidemiology
* 7 References
* 8 External links
## Signs and symptoms[edit]
Most Bartholin's cysts do not cause any symptoms, although some may cause pain during walking, sitting,[2] or sexual intercourse (dyspareunia).[9] They are usually between 1 and 4 cm, and are located just medial to the labia minora. Most Bartholin's cysts only affect the left or the right side (unilateral). While small cysts are usually not painful, larger cysts can cause significant pain.[citation needed]
## Pathophysiology[edit]
A Bartholin's gland cyst develops when the duct that drains the gland becomes blocked.[9] Blockage may be caused by an infection or a mucus plug.[9] The secretions from the Bartholin's gland are retained, forming a cyst.[2]
## Diagnosis[edit]
Other conditions that may present similarly include hidradenoma papilliferum, lipomas, epidermoid cysts and Skene's duct cysts, among others conditions.[2] In women who are more than 40 years, a biopsy may be recommended to rule out cancer.[2]
## Treatment[edit]
If the Bartholin's cysts is not painful or uncomfortable, treatment may not be necessary. Small, asymptomatic cysts can be observed over time to assess their development. In cases that require intervention, a catheter may be placed to drain the cyst, or the cyst may be surgically opened to create a permanent pouch (marsupialization). Intervention has a success rate of 85%, regardless of the method used, to alleviate swelling and discomfort.[10]
Catheterization is a minor procedure that can be performed locally as an outpatient procedure. A small tube with a balloon on the end (known as a Word catheter) may be inserted into the cyst.[2] The balloon is then inflated to keep it in place. The catheter stays in place for 2 to 4 weeks, draining the fluid and causing a normal gland opening to form, after which the catheter is removed.[11] The catheters do not generally impede normal activity, but sexual intercourse is generally abstained from while the catheter is in place.[12]
Cysts may also be opened permanently, a procedure called marsupialization,[13] which involves opening the gland through an incision to ensure that the secretion channel remains open.If a cyst is infected, it may break open and start to heal on its own after 3 to 4 days. Nonprescription pain medication such as ibuprofen relieves pain, and a sitz bath may increase comfort and use pain. Warm compresses can also speed up healing. If a Bartholin gland abscess comes back several times, the gland and duct can be surgically removed.[citation needed]
## Prognosis[edit]
While Bartholin cysts can be quite painful, they are not life-threatening. New cysts cannot absolutely be prevented from forming, but surgical or laser removal of a cyst makes it less likely that a new one will form at the same site. Those with a cyst are more likely than those without a cyst to get one in the future. They can recur every few years or more frequently. Many women who have marsupialization done find that the recurrences may slow, but do not actually stop.[citation needed]
## Epidemiology[edit]
Two percent of women will have a Bartholin's gland cyst at some point in their lives.[2] They occur at a rate of 0.55 per 1000 person-years and in women aged 35–50 years at a rate of 1.21 per 1000 person-years.[14] The incidence of Bartholin duct cysts increases with age until menopause, and decreases thereafter.[14] Hispanic women may be more often affected than white women and black women.[2] The risk of developing a Bartholin's gland cyst increases with the number of childbirths.[2]
## References[edit]
1. ^ a b c d e f g h i j k "Bartholin Gland Cysts". Merck Manuals Professional Edition. Retrieved 12 September 2018.
2. ^ a b c d e f g h i j k l m n o p q r s t Omole, Folashade; Simmons, Barbara J.; Hacker Yolanda (2003). "Management of Bartholin's duct cyst and gland abscess". American Family Physician. 68 (1): 135–40. PMID 12887119.
3. ^ a b c d Lee, MY; Dalpiaz, A; Schwamb, R; Miao, Y; Waltzer, W; Khan, A (May 2015). "Clinical Pathology of Bartholin's Glands: A Review of the Literature". Current Urology. 8 (1): 22–5. doi:10.1159/000365683. PMC 4483306. PMID 26195958.
4. ^ a b Ferri, Fred (2017). Ferri's clinical advisor 2018 : 5 books in 1. Elsevier Canada. p. 175. ISBN 978-0323280495.
5. ^ Marx, John A. Marx (2014). "Skin and Soft Tissue Infections". Rosen's emergency medicine : concepts and clinical practice (8th ed.). Philadelphia, PA: Elsevier/Saunders. pp. Chapter 137. ISBN 978-1455706051.
6. ^ a b Knaus, John V.; Isaacs, John H. (2012). Office Gynecology: Advanced Management Concepts. Springer Science & Business Media. p. 266. ISBN 9781461243403.
7. ^ Baskett, Thomas F (2019). Mr. United Kingdom: Cambridge University Press. pp. 455–457. ISBN 978-1108421706.
8. ^ Williams Gynecology (2 ed.). McGraw Hill Professional. 2012. p. 1063. ISBN 9780071804653.
9. ^ a b c Eilber, Karyn Schlunt; Raz, Shlomo (September 2003). "Benign Cystic Lesions of the Vagina: A Literature Review". The Journal of Urology. 170 (3): 717–722. doi:10.1097/01.ju.0000062543.99821.a2. PMID 12913681.
10. ^ Bartholin's cyst from BestPractice, BMJ Publishing Group. Last updated: Apr 26, 2013
11. ^ Bourne, Tom (2007). "Mr". Australian and New Zealand Journal of Obstetrics & Gynaecology. 47: 137–140 – via Academia.edu.
12. ^ Reif, P; Elsayed, H (2015). "Quality of life and sexual activity during treatment of Bartholin's cyst or abscess with a Word catheter". European Journal of Obstetrics, Gynaecology and Reproductive Biology. 190: 76–80. doi:10.1016/j.ejogrb.2015.03.008. PMID 25800788.
13. ^ Haider Z, Condous G, Kirk E, Mukri F, Bourne T (April 2007). "The simple outpatient management of Bartholin's abscess using the Word catheter: a preliminary study". Aust N Z J Obstet Gynaecol. 47 (2): 137–140. doi:10.1111/j.1479-828X.2007.00700.x. PMID 17355304. S2CID 36752877.
14. ^ a b Yuk, Jin-Sung; Kim, Yong-Jin; Hur, Jun-Young; Shin, Jung-Ho (2013). "Incidence of Bartholin duct cysts and abscesses in the Republic of Korea". International Journal of Gynecology & Obstetrics. 122 (1): 62–4. doi:10.1016/j.ijgo.2013.02.014. PMID 23618035. S2CID 23981470.
## External links[edit]
Classification
D
* ICD-10: N75.0
* ICD-9-CM: 616.2
External resources
* MedlinePlus: 001489
* v
* t
* e
Female diseases of the pelvis and genitals
Internal
Adnexa
Ovary
* Endometriosis of ovary
* Female infertility
* Anovulation
* Poor ovarian reserve
* Mittelschmerz
* Oophoritis
* Ovarian apoplexy
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* Follicular cyst of ovary
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Fallopian tube
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Endometrium
* Asherman's syndrome
* Dysfunctional uterine bleeding
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* Flow
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Myometrium
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Parametrium
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Cervix
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General
* Hematometra / Pyometra
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Vagina
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Other / general
* Pelvic congestion syndrome
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External
Vulva
* Bartholin's cyst
* Kraurosis vulvae
* Vestibular papillomatosis
* Vulvitis
* Vulvodynia
Clitoral hood or clitoris
* Persistent genital arousal 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 inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| Bartholin's cyst | c0004767 | 2,058 | wikipedia | https://en.wikipedia.org/wiki/Bartholin%27s_cyst | 2021-01-18T18:54:07 | {"umls": ["C0004767"], "wikidata": ["Q574406"]} |
Squamous odontogenic tumors (SOTs) are very rare benign locally infiltrative odontogenic neoplasms of epithelial origin. Only some 50 cases have been documented. They occur mostly from 20-40 and are more common in males. Treatment is by simple enucleation and local curettage, and recurrence is rare.[1]
## Clinical appearance[edit]
Clinically, they are initially slow growing and asymptomatic but may cause mobility or displacement of teeth. They may occur anywhere in the jaws but are more common in the posterior mandible and anterior maxilla. They are usually intrabony, but some peripheral cases have been observed. Radiographically, they are small unilocular or larger multilocular well defined non-corticated radiolucencies, triangular or crescent in shape, with the base apically between adjacent roots of vital teeth. They are often misdiagnosed as periodontitis. SOT should be suspected where isolated periodontal defects occur without obvious risk factors.[2]
## Histology[edit]
Lesions are non-encapsulated with islands of well differentiated squamous epithelium that commonly contain microcysts and calcifications in a dense fibrous connective tissue stroma. The pathogenesis is unclear but they appear to arise from the gingival epithelium or cell rests of Malassez or Serres. This presentation is similar to that of squamous cell carcinomas; however, the epithelium of SOT is highly differentiated.[3]
## References[edit]
1. ^ Badni M, Nagaraja A, Kamath V. Squamous odontogenic tumor: A case report and review of literature. J Oral Maxillofac Pathol. 2012;16(1):113-7.
2. ^ Kahn, Michael A. Basic Oral and Maxillofacial Pathology. Volume 1. 2001.
3. ^ Mardones Ndo R, Gamba Tde O, Flores IL, de Almeida SM, Lopes SL. Squamous Odontogenic Tumor: Literature Review Focusing on the Radiographic Features and Differential Diagnosis. Open Dent J. 2015;9:154-8. Published 2015 May 15. doi:10.2174/1874210601509010154
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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
| Squamous odontogenic tumor | c1458142 | 2,059 | wikipedia | https://en.wikipedia.org/wiki/Squamous_odontogenic_tumor | 2021-01-18T18:36:27 | {"mesh": ["D051527"], "wikidata": ["Q7581957"]} |
## 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
Attempting to overcome the problem confronting whole genome screens arising from genetic heterogeneity in a study of susceptibility to celiac disease, Woolley et al. (2002) performed a genomewide scan in a Finnish subpopulation expected to be more homogeneous than the general population of Finland. The families in their study originated from the northeastern part of Finland, the Koilliskaira region, which had been relatively isolated since its founding in the 16th century. Genealogic studies confirmed that the families studied shared a common ancestor in the 16th century. Nine families with a total of 23 patients were genotyped for 399 microsatellite markers and the data were analyzed with parametric linkage analysis using 2 dominant and 1 recessive model. A region on chromosome 15q11-q13 was implicated with a lod score of 3.14 using a highly penetrant dominant model. Addition of more markers and one more sib pair increased the lod score to 3.74. This result gave preliminary evidence for existence of a susceptibility factor in this chromosomal region.
*[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
| CELIAC DISEASE, SUSCEPTIBILITY TO, 5 | c1846631 | 2,060 | omim | https://www.omim.org/entry/607202 | 2019-09-22T16:09:32 | {"omim": ["607202"], "synonyms": ["Alternative titles", "GLUTEN-SENSITIVE ENTEROPATHY, SUSCEPTIBILITY TO, 5", "GSES"]} |
A pure form of hereditary spastic paraplegia characterized by slowly progressive spastic paraplegia of lower extremities with an age of onset ranging from childhood to adulthood and patients presenting with spastic gait, increased tendon reflexes in lower limbs, extensor plantar response, weakness and atrophy of lower limb muscles and, in rare cases, pes cavus. No abnormalities are noted on magnetic resonance imaging.
*[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
| Autosomal dominant spastic paraplegia type 42 | c2675528 | 2,061 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=171863 | 2021-01-23T17:03:24 | {"mesh": ["C567262"], "omim": ["612539"], "umls": ["C2675528"], "icd-10": ["G11.4"], "synonyms": ["SPG42"]} |
Hemolytic uremic syndrome, atypical, childhood is a disease that causes abnormal blood clots to form in small blood vessels in the kidneys. These clots can cause serious medical problems if they restrict or block blood flow, including hemolytic anemia, thrombocytopenia, and kidney failure. It is often caused by a combination of environmental and genetic factors. Genetic factors involve genes that code for proteins that help control the complement system (part of your body’s immune system). Environmental factors include viral or bacterial infections, certain medications (such as anticancer drugs), chronic diseases, cancers, and organ transplantation. Most cases are sporadic. Less than 20 percent of all cases have been reported to run in families. When the disorder is familial, it can have an autosomal dominant or an autosomal recessive pattern of inheritance.
Atypical hemolytic-uremic syndrome differs from a more common condition called typical hemolytic-uremic syndrome. The two disorders have different causes and symptoms.
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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
| Hemolytic uremic syndrome, atypical, childhood | None | 2,062 | gard | https://rarediseases.info.nih.gov/diseases/9432/hemolytic-uremic-syndrome-atypical-childhood | 2021-01-18T18:00:06 | {"synonyms": ["Atypical childhood HUS"]} |
Episodic ataxia is a group of related conditions that affect the nervous system and cause problems with movement. People with episodic ataxia have recurrent episodes of poor coordination and balance (ataxia). During these episodes, many people also experience dizziness (vertigo), nausea and vomiting, migraine headaches, blurred or double vision, slurred speech, and ringing in the ears (tinnitus). Seizures, muscle weakness, and paralysis affecting one side of the body (hemiplegia) may also occur during attacks. Additionally, some affected individuals have a muscle abnormality called myokymia during or between episodes. This abnormality can cause muscle cramping, stiffness, and continuous, fine muscle twitching that appears as rippling under the skin.
Episodes of ataxia and other symptoms can begin anytime from early childhood to adulthood. They can be triggered by environmental factors such as emotional stress, caffeine, alcohol, certain medications, physical activity, and illness. The frequency of attacks ranges from several per day to one or two per year. Between episodes, some affected individuals continue to experience ataxia, which may worsen over time, as well as involuntary eye movements called nystagmus.
Researchers have identified at least seven types of episodic ataxia, designated type 1 through type 7. The types are distinguished by their pattern of signs and symptoms, age of onset, length of attacks, and, when known, genetic cause.
## Frequency
Episodic ataxia is uncommon, affecting less than 1 in 100,000 people. Only types 1 and 2 have been identified in more than one family, and type 2 is by far the most common form of the condition.
## Causes
Episodic ataxia can be caused by mutations in several genes that play important roles in the nervous system. Three of these genes, KCNA1, CACNA1A, and CACNB4, provide instructions for making proteins that are involved in the transport of charged atoms (ions) across cell membranes. The movement of these ions is critical for normal signaling between nerve cells (neurons) in the brain and other parts of the nervous system. Mutations in the KCNA1, CACNA1A, and CACNB4 genes are responsible for episodic ataxia types 1, 2, and 5, respectively.
Mutations in the SLC1A3 gene have been found to cause episodic ataxia type 6. This gene provides instructions for making a protein that transports a brain chemical (neurotransmitter) called glutamate. Neurotransmitters, including glutamate, allow neurons to communicate by relaying chemical signals from one neuron to another.
Researchers believe that mutations in the KCNA1, CACNA1A, CACNB4, and SLC1A3 genes alter the transport of ions and glutamate in the brain, which causes certain neurons to become overexcited and disrupts normal communication between these cells. Although changes in chemical signaling in the brain underlie the recurrent attacks seen in people with episodic ataxia, it is unclear how mutations in these genes cause the specific features of the disorder.
The genetic causes of episodic ataxia types 3, 4, and 7 have not been identified. Researchers are looking for additional genes that can cause episodic ataxia.
### Learn more about the genes associated with Episodic ataxia
* CACNA1A
* CACNB4
* KCNA1
* SLC1A3
## 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.
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.
*[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 inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| Episodic ataxia | c1866039 | 2,063 | medlineplus | https://medlineplus.gov/genetics/condition/episodic-ataxia/ | 2021-01-27T08:25:54 | {"gard": ["9851"], "mesh": ["C566601"], "omim": ["601949", "160120", "108500", "606554", "606552", "611907", "600111"], "synonyms": []} |
Papillary thyroid cancer
Papillary thyroid carcinoma.
SpecialtyENT surgery
Papillary thyroid cancer or papillary thyroid carcinoma[1] is the most common type of thyroid cancer,[2] representing 75 percent to 85 percent of all thyroid cancer cases.[1] It occurs more frequently in women and presents in the 20–55 year age group. It is also the predominant cancer type in children with thyroid cancer, and in patients with thyroid cancer who have had previous radiation to the head and neck.[3] It is often well-differentiated, slow-growing, and localized, although it can metastasize.
## Contents
* 1 Diagnosis
* 1.1 Markers
* 1.2 Pathology
* 1.3 Associated mutations
* 2 Treatment
* 3 Prognosis
* 3.1 MACIS
* 3.2 Stage
* 4 Epidemiology
* 5 References
* 6 External links
## Diagnosis[edit]
Papillary thyroid carcinoma is usually discovered on routine examination as an asymptomatic thyroid nodule that appears as a neck mass. In some instances, the mass may have produced local symptoms. This mass is normally referred to a fine needle aspiration biopsy (FNA) for investigation. FNA accuracy is very high and it is a process widely used in these cases. Other investigation methods include ultrasound imaging and nuclear scan. The ultrasound is a useful test to distinguish solid from cystic lesions and to identify calcifications.[4] The thyroid ultrasound is also very effective to discover microcarcinomas, which refer to very small carcinomas (<1 cm).
Papillary thyroid carcinomas are also discovered when a hard nodule is found in multinodular goiter, when enlarged cervical lymph nodes are detected, or when there are unidentified metastatic lesions elsewhere in the body.[5] Expanding lesions found in the thyroid gland, especially if they are painful, should be examined as they may indicate the presence of papillary thyroid carcinoma. Other clinical signs that could indicate papillary thyroid are fixation to the trachea, a firm neck mass, damage to recurrent laryngeal or cervical sympathetic nerves. Five percent of the population can have thyroid nodules, and the majority will be benign.[6]
Appropriate workup includes an ultrasound of the neck, followed by lab studies. Patients will usually meet with both an endocrinologist and a surgeon (head and neck surgeon or endocrine surgeon).
### Markers[edit]
Thyroglobulin can be used as a tumor marker for well-differentiated papillary thyroid cancer.[7][8] HBME-1 staining may be useful for differentiating papillary carcinomas from follicular carcinomas; in papillary lesions it tends to be positive.[9]
Reduced expression of ATP5E is significantly associated with the diagnosis of papillary thyroid cancer and may serve as an early tumor marker of the disease.[10]
### Pathology[edit]
Gross appearance of papillary carcinoma of thyroid gland
Papillary thyroid cancer gets its name from the papillae among its cells, visible on microscopy. Features include:
* Characteristic Orphan Annie eye nuclear inclusions (nuclei with uniform staining, which appear empty due to powdery chromatin and marginal micronucleoli)[11] and psammoma bodies on light microscopy. The former is useful in identifying the follicular variant of papillary thyroid carcinomas.[12]
* Lymphatic spread is more common than hematogenous spread
* Multifocality is common
* The so-called Lateral Aberrant Thyroid is actually a lymph node metastasis from papillary thyroid carcinoma.[13]
* Papillary microcarcinoma is a subset of papillary thyroid cancer defined as measuring less than or equal to 1 cm.[14] The highest incidence of papillary thyroid microcarcinoma in an autopsy series was reported by Harach et al. in 1985, who found 36 of 101 consecutive autopsies to have an incidental microcarcinoma.[15] Michael Pakdaman et al. report the highest incidence in a retrospective surgical series at 49.9 percent of 860 cases.[16] Management strategies for incidental papillary microcarcinoma on ultrasound (and confirmed on FNAB) range from total thyroidectomy with radioactive iodine ablation to observation alone. Harach et al. suggest using the term "occult papillary tumor" to avoid giving patients distress over having cancer. It was Woolner et al. who first arbitrarily coined the term "occult papillary carcinoma" in 1960, to describe papillary carcinomas ≤ 1.5 cm in diameter.[17]
Several variants are recognized, although classical papillary thyroid carcinoma is the most frequent; microscopic, follicular variant, diffuse sclerosing variant, tall cell variant, columnar cell variant, hobnail variant, among others. The encapsulated follicular variant, specifically when noninvasive, has been newly reclassified as the noninvasive follicular thyroid neoplasm with papillary-like nuclear features.[18]
Although papillary carcinoma has a propensity to invade lymphatics, it is less likely to invade blood vessels.[19] These kinds of tumors are most commonly unencapsulated, and they have a high tendency to metastasize locally to lymph nodes, which may produce cystic structures near the thyroid that are difficult to diagnose because of the paucity of malignant tissue.[5][20] Furthermore, papillary tumors may metastasize to the lungs and produce a few nodules or the lung fields may exhibit a snowflake appearance throughout.
Other characteristics of the papillary carcinoma is that E.M. shows increased mitochondria, increased RER, as well as increased apical microvilli. Moreover, papillary carcinomas have an indolent growth, and 40 percent of cases spread out of the capsule.[21]
* Micrograph of papillary thyroid carcinoma demonstrating prominent papillae with fibrovascular cores. H&E stain.
* Micrograph showing that the papillae in papillary thyroid carcinoma are composed of cuboidal cells. H&E stain.
* Nuclear grooves (arrows indicate one of them)
* Micrograph (high power view) showing nuclear changes in papillary thyroid carcinoma (PTC), which include groove formation, optical clearing, eosinophilic inclusions and overlapping of nuclei. H&E stain.
* Micrograph (high power view) of PTC demonstrating nuclear clearing and overlapping nuclei. H&E stain.
* Micrograph of metastatic papillary thyroid carcinoma to a lymph node. H&E stain.
* Micrograph of papillary thyroid carcinoma, tall cell variant - high magnification. H&E stain.
* Micrograph of papillary thyroid carcinoma, tall cell variant - intermediate magnification. H&E stain.
### Associated mutations[edit]
Mutations associated with papillary thyroid cancer are mainly two forms of chromosomal translocation and one form of point mutation. These alterations lead to activation of a common carcinogenic pathway—the MAPK/ERK pathway.
Chromosomal translocations involving the RET proto-oncogene (encoding a tyrosine kinase receptor that plays essential roles in the development of neuroendocrine cells) located on chromosome 10q11 occur in approximately a fifth of papillary thyroid cancers. The fusion oncoproteins generated are termed RET/PTC proteins (ret/papillary thyroid carcinoma), and constitutively activate RET and the downstream MAPK/ERK pathway.[1] The frequency of ret/PTC translocations is significantly higher in papillary cancers arising in children and after radiation exposure.[1] The gene NTRK1 (encoding the TrkA receptor), located on chromosome 1q, is similarly translocated in approximately 5 percent to 10 percent of papillary thyroid cancers.[1]
Approximately a third to a half of papillary thyroid carcinomas harbor point mutations in the BRAF oncogene, also activating the MAPK/ERK pathway.[1] In those cases the BRAF mutations found were V600E mutation. After performing a multivariate analysis, it was found that the absence of tumor capsule was the only parameter associated (P=0.0005) with BRAF V600E mutation.[5] According to recent studies, papillary cancers carrying the common V600E mutation tend to have a more aggressive long-term course. BRAF mutations are frequent in papillary carcinoma and in undifferentiated cancers that have developed from papillary tumors.
Many more changes in gene expression are currently being investigated. Previous studies demonstrated the dysregulation of different microRNAs in thyroid cancer. For example, downregulation of miR-369-3p and consequent upregulation of its target TSPAN13 appear to be involved in the pathophysiology of PTC.[22]
Mitochondrial mutations: MtDNA(mitochondrial) haplogroups, characterized by unique sets of non pathological mtDNA polymorphisms can modulate the pathogenesis of different diseases in specific populations because of its influence on the expression of genes related to ROS production and OXPHOS coupling efficiency and the regulation of apoptosis.[23] In Asian populations, haplogroup D4a is associated with an increased risk of thyroid cancer [24] while in European populations, Haplogroup K is considered to be protective of Thyroid cancer.[25]
## Treatment[edit]
Surgery remains the mainstay of treatment for papillary thyroid cancer. The Revised 2009 American Thyroid Association guidelines for papillary thyroid cancer state that the initial procedure should be near-total or total thyroidectomy. Thyroid lobectomy alone may be sufficient treatment for small (<1 cm), low-risk, unifocal, intrathyroidal papillary carcinomas in the absence of prior head and neck irradiation or radiologically or clinically involved cervical nodal metastasis.[26]
* Minimal disease (diameter up to 1.0 centimeters) - hemithyroidectomy (or unilateral lobectomy) and isthmectomy may be sufficient. There is some discussion whether this is still preferable over total thyroidectomy for this group of patients.
* Gross disease (diameter over 1.0 centimeters) - total thyroidectomy, and central compartment lymph node removal is the therapy of choice. Additional lateral neck nodes can be removed at the same time if an ultrasound guided FNA and thyroglobulin TG cancer washing was positive on the pre-operative neck node ultrasound evaluation.
Arguments for total thyroidectomy are:[27]
* Reduced risk of recurrence, if central compartment nodes are removed at the original surgery.
* 30-85% of papillary carcinoma is multifocal disease. Hemithyroidectomy may leave disease in the other lobe. However, multifocal disease in the remnant lobe may not necessarily become clinically significant or serve as a detriment to patient survival.
* Ease of monitoring with thyroglobulin (sensitivity for picking up recurrence is increased in presence of total thyroidectomy, and ablation of the remnant normal thyroid by low dose radioiodine 131 after following a low iodine diet (LID).
* Ease of detection of metastatic disease by thyroid and neck node ultrasound.
* Post-operative complications at high-volume thyroid surgery centers with experienced surgeons are comparable to that of hemithyroidectomy.
Arguments for hemithyroidectomy:
* Most patients have low-risk cancer with an excellent prognosis, with similar survival outcomes in low-risk patients who undergo total thyroidectomy versus hemithyroidectomy.
* Less likelihood of patient requiring lifelong thyroid hormone replacement after surgery.
Thyroid total body scans are less reliable at finding recurrence than TG and ultrasound.
Papillary tumors tend to be more aggressive in patients over age 45. In such cases, it might be required to perform a more extensive resection including portions of the trachea. Also, the sternocleidomastoid muscle, jugular vein, and accessory nerve are to be removed if such procedure allows apparently complete tumor resection. If a significant amount of residual tumor is left in the neck, external radiotherapy has been indicated and has proven useful especially in those cases when the residual tumor does not take up radioiodine.
After surgical thyroid removal, the patient waits around 4–6 weeks to then have radioiodine therapy. This therapy is intended to both detect and destroy any metastasis and residual tissue in the thyroid. The treatment may be repeated 6–12 months after initial treatment of metastatic disease where disease recurs or has not fully responded.[28]
Patients are administered hormone replacement levothyroxine for life after surgery, especially after total thyroidectomy. Chemotherapy with cisplatin or doxorubicin has proven limited efficacy, however, it could be helpful for patients with bone metastases to improve their quality of life. Patients are also prescribed levothyroxine and radioiodine after surgery. Levothyroxine influences growth and maturation of tissues and it is involved in normal growth, metabolism, and development. In case of metastases, patients are prescribed antineoplastic agents which inhibit cell growth and proliferation and help in palliating symptoms in progressive disease.
After successful treatment, 35 percent of the patients may experience a recurrence within a 40-year span. Also, patients may experience a high incidence of nodule metastasis, with 35 percent cases of cervical node metastases. Approximately 20 percent of patients will develop multiple tumors within the thyroid gland.[29]
There is ongoing discussion regarding the best management regarding the optimal surgical procedure for papillary thyroid cancer. Prognosis of patients with papillary thyroid cancer is found to be dependent on the patient's age, the size of the tumor, presence of metastatic disease, and the presence of tumor invasion into adjacent tissues near the thyroid gland. Recent studies have examined a more conservative approach to surgery and have demonstrated that hemithyroidectomy may be acceptable for patients with low-risk papillary thyroid cancer with tumor size 1 cm to 4 cm with no presence of invasion to tissues surrounding the thyroid or metastasis. Studies examining large databases of patients with papillary thyroid cancer have concluded that there is no survival advantage for patients with stage I papillary thyroid cancer size 1–4 cm receiving total thyroidectomy versus hemithyroidectomy.[30] In light of this data, choosing the optimal course of surgical and medical management of papillary thyroid cancer should involve shared decision making from patient, endocrinologists, and surgeons.
## Prognosis[edit]
Depending on source, the overall 5-year survival rate for papillary thyroid cancer is 96 percent[31] or 97 percent,[32] with a 10-year survival rate of 93 percent.[31]
For a more specific prognosis for individual cases, there are at minimum 13 known scoring systems for prognosis; among the more often used are:
* AGES - Age, Grade, Extent of disease, Size
* AMES - Age, Metastasis, Extent of disease, Size
* MACIS - Metastasis, Age at presentation, Completeness of surgical resection, Invasion (extrathyroidal), Size[33] (this is a modification of the AGES system). It is probably the most reliable staging method available. Also known as the MAICS system.
* TNM staging \- Tumor, node, metastasis. Remarkable about the TNM staging for (differentiated) thyroid carcinoma is that the scoring is different according to age.
### MACIS[edit]
The MACIS system of estimating the prognosis of papillary thyroid cancer was developed by Clive S. Grant at the Mayo Clinic, and was based on careful evaluation of a large group of patients. It is probably the most reliable staging method available.[34]
It assigns scores to the main factors involved, and uses the sum of this score to calculate the prognosis:
Factors[34] Score[34]
Distant Metastasis: spread of the cancer to areas outside the neck Yes 3
No 0
Age at the time the tumor was discovered Less than 39 years 3.1
Over 40 years 0.08 x age
Invasion into surrounding areas of the neck as seen by the naked eye Yes 1
No 0
Completeness of surgical resection (or removal) of the tumor Incomplete 1
Complete 0
Size of the tumor 0.3 x size in cm
Sum of MACIS score[34] 20 yr Survival[34]
< 6.0 99%
6.0 - 6.99 89%
7.0 - 7.99 56%
> 8.0 24%
Most patients fall into the low-risk category (MACIS score less than 6.0) and are cured of the cancer at the time of surgery.[34]
Children with multiple lung metastases and/or a miliary aspect still have an excellent long-term prognosis if given adequate treatment.[35]
### Stage[edit]
Based on overall cancer staging into stages I to IV, papillary thyroid cancer has a 5-year survival rate of 100 percent for stages I and II, 93 percent for stage III and 51 percent for stage IV.[36]
## Epidemiology[edit]
According to Surveillance, Epidemiology, and End Results (SEER), the incidence of papillary cancer has increased from 4.8 to 14.9 per 100,000 from 1975 to 2012. Females are more likely to get papillary cancer when compared to males with incidence ratio of 2.5 to 1 where most of the cancers are diagnosed between 40 and 50 years old in females. However, death rates from papillary cancer remains static from 2003 to 2012 at 0.5 per 100,000 men and women. There was an increased incidence of papillary cancer from 1910 to 1960 due to the use of ionising radiation in treating childhood head and neck cancers.[37] The incidence decreased after radiation therapy was abandoned. Environmental exposures to radiation such as atomic bombings of Hiroshima and Nagasaki and Chernobyl disaster also causes an increase in childhood papillary thyroid cancer at 5 to 20 years after the exposure to radiation.[38] Family history of thyroid cancer syndrome such as familial adenomatous polyposis, Carney complex, Multiple endocrine neoplasia type 2 (MEN-2), Werner syndrome, and Cowden syndrome increases the risk of getting papillary cancer.[37]
## References[edit]
1. ^ a b c d e f Chapter 20 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K; Fausto, Nelson (2007). Robbins Basic Pathology. Philadelphia: Saunders. ISBN 978-1-4160-2973-1. 8th edition.
2. ^ Hu MI, Vassilopoulou-Sellin R, Lustig R, Lamont JP "Thyroid and Parathyroid Cancers" in Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (Eds) Cancer Management: A Multidisciplinary Approach. 11 ed. 2008.
3. ^ Dinets A, Hulchiy M, Sofiadis A, Ghaderi M, Höög A, Larsson C, Zedenius J (2012). "Clinical, Genetic and Immunohistochemical Characterization of 70 Ukrainian Adult Cases with Post-Chornobyl Papillary Thyroid Carcinoma". Eur J Endocrinol. 166 (6): 1049–60. doi:10.1530/EJE-12-0144. PMC 3361791. PMID 22457234.
4. ^ "Papillary Thyroid Carcinoma: An Overview". Archives of Pathology & Laboratory Medicine. 2006. Retrieved 2010-07-15.
5. ^ a b c "The Thyroid and its Diseases". Archived from the original on 2010-07-01. Retrieved 2010-07-15.
6. ^ Surgical Recall 7th Edition ISBN 978-1451192919
7. ^ Lin JD (2007). "Thyroglobulin and human thyroid cancer". Clin Chim Acta. 388 (1–2): 15–21. doi:10.1016/j.cca.2007.11.002. PMID 18060877.
8. ^ Tuttle RM, Leboeuf R, Martorella AJ (2007). "Papillary thyroid cancer: monitoring and therapy". Endocrinol. Metab. Clin. North Am. 36 (3): 753–78, vii. doi:10.1016/j.ecl.2007.04.004. PMID 17673127.
9. ^ Papotti M, Rodriguez J, De Pompa R, Bartolazzi A, Rosai J (April 2005). "Galectin-3 and HBME-1 expression in well-differentiated thyroid tumors with follicular architecture of uncertain malignant potential". Mod. Pathol. 18 (4): 541–46. doi:10.1038/modpathol.3800321. PMID 15529186.
10. ^ Hurtado-López, LM; Fernández-Ramírez, F; Martínez-Peñafiel, E; Carrillo Ruiz, JD; Herrera González, NE (16 June 2015). "Molecular Analysis by Gene Expression of Mitochondrial ATPase Subunits in Papillary Thyroid Cancer: Is ATP5E Transcript a Possible Early Tumor Marker?". Medical Science Monitor. 21: 1745–51. doi:10.12659/MSM.893597. PMC 4482184. PMID 26079849.
11. ^ "Papillary Carcinoma of Thyroid (Hi Pow)". University of Connecticut Health Center. Archived from the original on 2012-07-09. Retrieved 2008-09-14.
12. ^ Yang GC, Liebeskind D, Messina AV (2001). "Ultrasound-guided fine-needle aspiration of the thyroid assessed by Ultrafast Papanicolaou stain: data from 1135 biopsies with a two- to six-year follow-up". Thyroid. 11 (6): 581–89. doi:10.1089/105072501750302895. PMID 11442006.
13. ^ Escofet X, Khan AZ, Mazarani W, Woods WG (2007). "Lessons to be learned: a case study approach. Lateral aberrant thyroid tissue: is it always malignant?". J R Soc Health. 127 (1): 45–6. doi:10.1177/1466424007073207. PMID 17319317.
14. ^ Shaha AR (2007). "TNM classification of thyroid carcinoma". World J Surg. 31 (5): 879–87. doi:10.1007/s00268-006-0864-0. PMID 17308849.
15. ^ Harach HR, Franssila KO, Wasenius VM (1985). "Occult papillary carcinoma of the thyroid. A "normal" finding in Finland. A systematic autopsy study". Cancer. 56 (3): 531–8. doi:10.1002/1097-0142(19850801)56:3<531::AID-CNCR2820560321>3.0.CO;2-3. PMID 2408737.
16. ^ Pakdaman MN, Rochon L, Gologan O, Tamilia M, Garfield N, Hier MP, Black MJ, Payne RJ (2008). "Incidence and histopathological behavior of papillary microcarcinomas: Study of 429 cases". Otolaryngol Head Neck Surg. 139 (5): 718–22. doi:10.1016/j.otohns.2008.08.014. PMID 18984270.
17. ^ Woolner LB, Lemmon ML, Beahrs OH, Black BM, Keating FR (January 1960). "Occult papillary carcinoma of the thyroid gland: a study of 140 cases observed in a 30-year period". J. Clin. Endocrinol. Metab. 20: 89–105. doi:10.1210/jcem-20-1-89. PMID 13845950.
18. ^ Nikiforov YE, Seethala RR, Tallini G, Baloch ZW, Basolo F, Thompson LDR, Barletta J, Wenig BM, Ghuzlan AA, Kakudo K, Giordano TJ, Alves VA, Khanafshar E, Asa SL, El-Naggar AK, Gooding WE, Hodak SP, Lloyd RV, Maytal G, Mete O, Nikiforova MN, Nosé V, Papotti M, Poller DN, Sadow PM, Tischler AS, Tuttle RM, Wall KB, LiVolsi VA, Randolph GW, Ghossein RA (14 April 2016). "Nomenclature Revision for encapsulated follicular variant of papillary thyroid carcinoma: A Paradigm Shift to Reduce Overtreatment of Indolent Tumors". JAMA Oncol. 2 (8): 1023–9. doi:10.1001/jamaoncol.2016.0386. PMC 5539411. PMID 27078145.CS1 maint: uses authors parameter (link)
19. ^ "Thyroid, Papillary Carcinoma". Retrieved 2010-07-15.
20. ^ Grani, G; Fumarola, A (Jun 2014). "Thyroglobulin in Lymph Node Fine-Needle Aspiration Washout: A Systematic Review and Meta-analysis of Diagnostic Accuracy". The Journal of Clinical Endocrinology and Metabolism. 99 (6): 1970–82. doi:10.1210/jc.2014-1098. PMID 24617715.
21. ^ "Papillary Carcinomas". Archived from the original on April 19, 2010. Retrieved 2010-07-15.
22. ^ Li P, Dong M, Wang Z. Downregulation of TSPAN13 by miR-369-3p inhibits cell proliferation in papillary thyroid cancer (PTC). Bosn J of Basic Med Sci [Internet]. 2019May20 [cited 2020Apr.6];19(2):146-54. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/2865
23. ^ Bai RK, Leal SM, Covarrubias D, Liu A, Wong LJ. Mitochondrial genetic background modifies breast cancer risk. Cancer Res. 2007 May 15;67(10):4687-94. doi: https://doi.org/10.1158/0008-5472.CAN-06-3554. PMID: https://pubmed.ncbi.nlm.nih.gov/17510395/
24. ^ Fang, H., Shen, L., Chen, T. et al. Cancer type-specific modulation of mitochondrial haplogroups in breast, colorectal and thyroid cancer. BMC Cancer 10, 421 (2010). https://doi.org/10.1186/1471-2407-10-421
25. ^ Cocoş R, Schipor S, Badiu C, Raicu F. Mitochondrial DNA haplogroup K as a contributor to protection against thyroid cancer in a population from southeast Europe. Mitochondrion. 2018 Mar;39:43-50. DOI: https://doi.org/10.1016/j.mito.2017.08.012
26. ^ Cooper, David (November 2009). "Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer" (PDF). Thyroid. 19 (11): 1167–1214. doi:10.1089/thy.2009.0110. hdl:2027.42/78131. PMID 19860577.
27. ^ Udelsman, Robert (July 2005). "Is total thyroidectomy the best possible surgical management for well-differentiated thyroid cancer?". The Lancet Oncology. 6 (7): 529–531. doi:10.1016/s1470-2045(05)70247-3. PMID 15992702.
28. ^ "Treatment". Retrieved 2010-07-15.
29. ^ "Papillary Thyroid Carcinoma". Archived from the original on July 19, 2008. Retrieved 2010-07-15.
30. ^ Adam, Mohamed (January 2015). "Impact of extent of surgery on survival for papillary thyroid cancer patients younger than 45 years". J Clin Endocrinol Metab. 100 (1): 115–121. doi:10.1210/jc.2014-3039. PMC 5399499. PMID 25337927.
31. ^ a b Numbers from National Cancer Database in the US, from Page 10 in: Biersack, H-J; Grünwald, F, eds. (2005). Thyroid Cancer. Berlin: Springer. ISBN 978-3-540-22309-2. (Note: Book also states that the 14 percent 10-year survival for anaplastic thyroid cancer was overestimated)
32. ^ Rounded up to nearest natural number from 96.7 percent as given by eMedicine > Thyroid, Papillary Carcinoma Author: Luigi Santacroce. Coauthors: Silvia Gagliardi and Andrew Scott Kennedy. Updated: Sep 28, 2010
33. ^ "New York Thyroid Center: Prognosis Staging for Thyroid Cancer". Archived from the original on 2007-12-14. Retrieved 2007-12-22.
34. ^ a b c d e f New York Thyroid Center > Thyroid cancer > Prognosis staging Retrieved on April 30, 2010
35. ^ Vermeer-Mens, J. C. J.; Goemaere, N. N. T.; Kuenen-Boumeester, V.; De Muinck Keizer-Schrama, S. M. P. F.; Zwaan, C. M.; Devos, A. S.; De Krijger, R. R. (2006). "Childhood Papillary Thyroid Carcinoma with Miliary Pulmonary Metastases". Journal of Clinical Oncology. 24 (36): 5788–5789. doi:10.1200/JCO.2006.08.8732. PMID 17179115. [1]
36. ^ cancer.org > Thyroid Cancer By the American Cancer Society. In turn citing: AJCC Cancer Staging Manual (7th ed).
37. ^ a b Tuttle, RM; Ross, DS; Mulder, JE. "Papillary thyroid cancer". UpToDate. Retrieved 13 October 2017.
38. ^ Vaisman, F; Corbo, R; Vaisman, M (9 May 2011). "Thyroid Carcinoma in Children and Adolescents—Systematic Review of the Literature". Journal of Thyroid Research. 2011: 845362. doi:10.4061/2011/845362. PMC 3166725. PMID 21904689.
## External links[edit]
Classification
D
* ICD-10: C73
* ICD-9-CM: 193
* ICD-O: M8260/3
* OMIM: 603744
* MeSH: D013964
External resources
* MedlinePlus: 000331
* eMedicine: med/2464
* Thyroid cancer at DMOZ
* Cancer Management Handbook: Thyroid and Parathyroid Cancers
* Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer The American Thyroid Association Guidelines Taskforce (2015).
* v
* t
* e
Tumours of endocrine glands
Pancreas
* Pancreatic cancer
* Pancreatic neuroendocrine tumor
* α: Glucagonoma
* β: Insulinoma
* δ: Somatostatinoma
* G: Gastrinoma
* VIPoma
Pituitary
* Pituitary adenoma: Prolactinoma
* ACTH-secreting pituitary adenoma
* GH-secreting pituitary adenoma
* Craniopharyngioma
* Pituicytoma
Thyroid
* Thyroid cancer (malignant): epithelial-cell carcinoma
* Papillary
* Follicular/Hurthle cell
* Parafollicular cell
* Medullary
* Anaplastic
* Lymphoma
* Squamous-cell carcinoma
* Benign
* Thyroid adenoma
* Struma ovarii
Adrenal tumor
* Cortex
* Adrenocortical adenoma
* Adrenocortical carcinoma
* Medulla
* Pheochromocytoma
* Neuroblastoma
* Paraganglioma
Parathyroid
* Parathyroid neoplasm
* Adenoma
* Carcinoma
Pineal gland
* Pinealoma
* Pinealoblastoma
* Pineocytoma
MEN
* 1
* 2A
* 2B
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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
| Papillary thyroid cancer | c0238463 | 2,064 | wikipedia | https://en.wikipedia.org/wiki/Papillary_thyroid_cancer | 2021-01-18T18:34:53 | {"gard": ["12027"], "mesh": ["D000077273"], "umls": ["C0238463"], "icd-9": ["193"], "icd-10": ["C73"], "wikidata": ["Q2292945"]} |
Abnormal basal metabolic rate
SpecialtyEndocrinology
Abnormal basal metabolic rate refers to a high or low basal metabolic rate (BMR). It has numerous causes, both physiological (part of the body's normal function) and pathological (associated with disease).
## Contents
* 1 Causes
* 1.1 Physiological
* 1.2 Pathological
* 2 References
* 3 External links
## Causes[edit]
### Physiological[edit]
An abnormal basal metabolic rate is not necessarily indicative of disease; a number of physiological factors can alter the BMR by influencing cellular metabolic activity.[1] For instance, males are more likely than females to have a high BMR, and in women, the BMR may rise to abnormal levels during pregnancy or lactation.[2] An individual's BMR varies greatly with age: infants and children typically have a high BMR, required for growth, while the elderly have a low BMR.[1] Tall, thin people have a higher BMR than their shorter counterparts, even with the same weight, due to the greater surface area of their skin.[3] The metabolic rate also decreases during sleep and increases in exercise, and individuals who exercise regularly have a higher BMR than those who are sedentary.[1] Environmental temperature also has an effect: the BMR is increased in both heat and cold.[3]
### Pathological[edit]
A common pathological cause for a high BMR is fever, since a rise in body temperature increases the rate of cellular metabolic reactions.[1] It is estimated that for every degree Fahrenheit of rise in body temperature, the BMR increases by 7 percent.[3]
Thyroid disease also has a marked effect on BMR, since thyroid hormones regulate the rate of cellular metabolism.[3] Hyperthyroidism—in which there is an increase in the production of thyroid hormones—leads to a high BMR, while hypothyroidism—in which thyroid hormones are depleted—causes a low BMR.[1]
Prolonged periods of abnormal nutrition cause an adaptive change in BMR; this helps the body to maintain a stable body weight in response to the change in food supply. In prolonged malnutrition, the BMR declines, while in prolonged overnutrition, the BMR is increased.[1] Cancer sometimes causes an increase in BMR, perhaps because the cancer cells that form tumors have a high level of metabolic activity.[1]
## References[edit]
1. ^ a b c d e f g Bijlani, R. L.; Manjunatha, S. (2010). Understanding Medical Physiology (4th ed.). Jaypee Brothers. p. 383. ISBN 9789380704814.
2. ^ Lieberman, Michael; Marks, Allan D. (2009). Marks' Basic Medical Biochemistry: A Clinical Approach. Lippincott Williams & Wilkins. p. 8. ISBN 9780781770224.
3. ^ a b c d DeBruyne, Linda; Whitney, Eleanor; Pinna, Kathryn (2007). Nutrition and Diet Therapy. Cengage Learning. p. 150. ISBN 9780495119166.
## External links[edit]
Classification
D
* ICD-10: R94.8
* ICD-9-CM: 794.7
* v
* t
* e
Blood film findings
Red blood cells
Size
* Anisocytosis
* Macrocytosis
* Microcytosis
Shape
* Poikilocytosis
* Membrane abnormalities
* Acanthocyte
* Codocyte
* Elliptocyte
* Hereditary elliptocytosis
* Spherocyte
* Hereditary spherocytosis
* Dacrocyte
* Echinocyte
* Schistocyte
* Degmacyte
* Sickle cell/drepanocyte
* Sickle cell disease
* Stomatocyte
* Hereditary stomatocytosis
Colour
* Anisochromia
* Hypochromic anemia
* Polychromasia
Inclusion bodies
* Developmental
* Howell–Jolly body
* Basophilic stippling
* Pappenheimer bodies
* Cabot rings
* Hemoglobin precipitation
* Heinz body
Other
* Red cell agglutination
* Rouleaux
White blood cells
Lymphocytes
* Reactive lymphocyte
* Smudge cell
* Russell bodies
Granulocytes
* Hypersegmented neutrophil
* Arneth count
* Pelger–Huët anomaly
* Döhle bodies
* Toxic granulation
* Toxic vacuolation
* Critical green inclusion
* Alder–Reilly anomaly
* Jordans' anomaly
* Birbeck granules
* Left shift
Other
* Auer rod
* Metabolism portal
*[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 inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| Abnormal basal metabolic rate | c0476418 | 2,065 | wikipedia | https://en.wikipedia.org/wiki/Abnormal_basal_metabolic_rate | 2021-01-18T18:29:07 | {"umls": ["C0476418", "C2711647"], "wikidata": ["Q4668176"]} |
Medical condition
For other uses, see Dry.
This article provides insufficient context for those unfamiliar with the subject. Please help improve the article by providing more context for the reader. (November 2018) (Learn how and when to remove this template message)
This article needs attention from an expert in Medicine. The specific problem is: expansion required. WikiProject Medicine may be able to help recruit an expert. (November 2018)
Dryness is a medical condition in which there is local or more generalized decrease in normal lubrication of the skin or mucous membranes.
Examples of local dryness include dry mouth, dry eyes, dry skin and vaginal dryness. These often have specific causes and treatments. It is possible to have dry eyes without any other signs or symptoms, but this usually causes a syndrome of eye symptoms called keratoconjunctivitis sicca.
More generalized dryness can be caused by e.g. dehydration (that is, more general loss of body fluids),[1] anticholinergic drugs and Sjögren syndrome.
## References[edit]
1. ^ thefreedictionary.com > dehydration citing:
* Dorland's Medical Dictionary for Health Consumers. © 2007
* The American Heritage® Medical Dictionary Copyright © 2007
* Mosby's Medical Dictionary, 8th edition. © 2009
* Mosby's Dental Dictionary, 2nd edition. © 2008
This medical symptom article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| Dryness (medical) | c0854113 | 2,066 | wikipedia | https://en.wikipedia.org/wiki/Dryness_(medical) | 2021-01-18T18:58:26 | {"umls": ["C0854113", "C0151908"], "wikidata": ["Q5309747"]} |
Bent bone dysplasia syndrome is an often lethal skeletal disorder characterized by poor mineralization of the skull (calvarium), craniosynostosis, underdeveloped (hypoplastic) pubic bone (pubis) and clavicles, osteopenia, and bent long bones. Unusual facial features include low-set ears, widely spaced eyes (hypertelorism), midface hypoplasia, prematurely erupted fetal teeth, and small chin (micrognathia). This condition is associated with mutations in the FGFR2 gene.
*[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 inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| Bent bone dysplasia syndrome | c3281247 | 2,067 | gard | https://rarediseases.info.nih.gov/diseases/10965/bent-bone-dysplasia-syndrome | 2021-01-18T18:01:49 | {"omim": ["614592"], "synonyms": ["Bent bone dysplasia (BBD)-FGFR2 type"]} |
TARP syndrome is a rare developmental defect during embryogenesis syndrome characterized by Robin sequence (micrognathia, glossoptosis, and cleft palate), atrial septal defect, persistence of the left superior vena cava, and talipes equinovarus. The phenotype is variable, some patients present with further dysmorphic characteristics (e.g. hypertelorism, ear abnormalities) while others do not have any key findings. Additional features, such as syndactyly, polydactyly, or brain anomalies (e.g. cerebellar hypoplasia), have also been reported. The syndrome is almost invariably lethal with affected males either dying prenatally or living just a few months.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| TARP syndrome | c1839463 | 2,068 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2886 | 2021-01-23T17:54:45 | {"gard": ["10089"], "mesh": ["C536942"], "omim": ["311900"], "umls": ["C1839463"], "icd-10": ["Q87.8"], "synonyms": ["Pierre Robin sequence-congenital heart defect-talipes syndrome", "Pierre Robin syndrome-congenital heart defect-talipes syndrome", "Talipes equinovarus-atrial septal defect-Robin sequence-persistence of the left superior vena cava syndrome"]} |
A rare muscle disorder characterized by episodic attacks of muscle weakness associated with an increase in serum potassium concentration.
## Epidemiology
The prevalence is estimated at around 1/200,000.
## Clinical description
Attacks of muscle weakness generally begin during childhood (first decade). They vary in frequency, duration (a few minutes to hours) and severity (focal paresis to total paralysis). They generally involve the limb muscles and spare the facial and respiratory musculature. Episodes are triggered by rest after exercise, fasting and cold exposure. Other factors may include ingestion of potassium-rich food, stress, infection, glucocorticoids, anesthesia and pregnancy. Maintaining exercise alleviates symptoms. 12.5% of patients present with clinical moderate and permanent myotonia that frequently involves facial muscles (lid-lag sign, eye closure myotonia) while electrical myotonia can be demonstrated in at least 50% of patients on electromyography (EMG). When clinical and electrical myotonia are a feature of the disease, the condition is called hyperkalemic periodic paralysis with myotonia (see this term). Another particular form of the disease, periodica paramyotonia, shares features with paramyotonia congenita (see this term) i.e. weakness is preceded by muscle stiffness provoked by cold and exercise.
## Etiology
HyperPP is a sodium muscle channelopathy due to point mutations (Thr704Met and Met1592Val mutations in 80% of cases) in the SCN4A gene encoding the alpha subunit of the skeletal muscle voltage-gated sodium channel Nav1.4. These mutations lead to defective inactivation of the channel.
## Diagnostic methods
Diagnosis is based on clinical history, EMG and genetic tests. Hyperkalemia during attacks can be very mild and fugitive. Serum creatinine kinase (CK) levels can be slightly elevated. Classical EMG may record myotonic discharges and/or myopathic features. The prolonged exercise test is positive in 80% of cases (decrease of over 30% of the compound muscle actionpotential after exercise). Muscle biopsy may show non-specific results (muscle fibers atrophy with vacuoles).
## Differential diagnosis
Differential diagnoses include secondary hyperPP caused by renal or endocrine diseases, other familial periodic paralyses such as hypokalemic or normokalemic PP (see these terms) and non dystrophic myotonias such as paramyotonia congenita (see this term).
## Antenatal diagnosis
Prenatal diagnosis is theoretically possible if the disease-causing mutation in the family has been identified but is rarely performed because of the non life-threatening prognosis.
## Genetic counseling
Transmission is autosomal dominant with almost complete penetrance but variable expression in severity within and between families. Genetic counseling should be offered to affected families informing them of the 50% risk the child of an affected parent has of inheriting the disease-causing mutation.
## Management and treatment
Management of patients consists in medical therapy and avoidance of triggering factors. Gentle physical activity, ingestion of carbohydrate-rich drinks/snacks or inhaled salbutamol at the onset of attacks may abort them. Daily use of carbonic anhydrase inhibitors or thiazide diuretics helps in preventing attacks. Dietary advice includes regular meals (to prevent fasting) and avoidance of potassium-rich foods.
## Prognosis
With age (generally after 40 years of age), the frequency of the episodes declines but some patients may develop chronic myopathy of variable severity that may cause permanent muscle weakness.
*[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 inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| Hyperkalemic periodic paralysis | c0238357 | 2,069 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=682 | 2021-01-23T19:04:13 | {"gard": ["195"], "mesh": ["C535409", "D020513"], "omim": ["170500"], "umls": ["C0238357", "C2930895"], "icd-10": ["G72.3"], "synonyms": ["Adynamia episodica hereditaria", "Familial hyperPP", "Familial hyperkalemic periodic paralysis", "Gamstorp disease", "Gamstorp episodic adynamy", "HYPP", "HyperKPP", "HyperPP", "Hyperkalemic PP", "Primary hyperPP", "Primary hyperkalemic periodic paralysis"]} |
A rare, autosomal recessive, organic aciduria that is characterized by variable clinical presentation ranging from acute neonatal onset of metabolic decompensation to later onset of chronic, non-specific manifestations including failure to thrive and/or developmental delay. All patients are prone to intermittent, acute metabolic decompensation. During metabolic episodes, urine analysis demonstrates elevated isovaleric acid derivatives.
## Epidemiology
Accurate data on the prevalence is not readily available. Best estimates come from newborn screening studies that estimate prevalence at birth between 1/50,000-150,000.
## Clinical description
Patients present along a spectrum. Acute, neonatal presentation is characterized by onset in the first two weeks of life with vomiting, seizures, and lethargy, progressing to coma. Metabolic acidosis with an increased anion gap is apparent on laboratory evaluation. Hyperammonemia may occur. Later onset is relatively non-specific with failure to thrive and/or developmental delay. Patients who survived an early acute presentation are subsequently indistinguishable from those with the chronic phenotype. All patients are prone to intermittent acute episodes of decompensation with minor illnesses. Childhood onset metabolic acidosis is typically brought on by prolonged fasting, increased intake of protein-rich food or infections, and can be fatal if not treated immediately. The characteristic smell of isovaleric acid may be present, and is likened to sweaty feet/body sweat. Though severe developmental delay and neurologic sequelae are present in some patients, they are likely related to severe biochemical presentations.
## Etiology
Isovaleric academia (IVA) is caused by mutations in the IVD gene (15q15.1) encoding the enzyme isovaleryl-CoA dehydrogenase (IVDH) resulting in accumulation of isovaleric acid and its derivatives. Asymptomatic patients with specific mutations have been reported, especially when identified through newborn screening.
## Diagnostic methods
Where implemented, diagnosis is through newborn blood spot screening. Otherwise, in symptomatic individuals diagnosis is suspected based on the clinical presentation. Metabolite or molecular genetic testing confirms diagnosis. Characteristic urine metabolites includes elevated N‐isovalerylglycine, N‐isovalerylcarnitine and 3‐hydroxyisovaleric acid. Isovalerylcarnitine (''C5 carnitine'') is elevated in blood. The urine organic acids may normalize when a patient is well.
## Differential diagnosis
In acutely decompensating patients, the differential diagnosis includes other organic acidemias (including lactic acidosis), urea cycle defects, and sepsis. On newborn screening, ''C5-carnitine'' may also indicated 2-methylbutyryl-CoA dehydrogenase deficiency; urine organic acids readily differential the two disorders as does molecular testing.
## Antenatal diagnosis
Prenatal genetic testing is possible when the mutation of a proband has previously been determined.
## Genetic counseling
The pattern of inheritance is autosomal recessive; genetic counseling is recommended for affected families. The risk of disease transmission at each pregnancy is 25% when the parents are proven or obligate carriers.
## Management and treatment
Lifelong management is with a low protein diet. Children diagnosed with IVA should be referred to a metabolic dietician who can tailor the diet to support normal growth and development. Supplementing with artificial protein restricted in leucine may be required. L-carnitine and glycine may be prescribed to clear excess isovaleric acid. Emergency treatment in times of metabolic stress (including illness and fasting) is with an anabolic diet. Reducing, but not eliminating, natural protein in the diet for 12-24 hours may help, but only if additional other calories can be given to promote anabolism.
## Prognosis
Prognosis for patients diagnosed by newborn screening is excellent with the potential for normal neurodevelopmental outcome with appropriate metabolic management. Patients who present symptomatically can have significant neurologic sequelae including neurodevelopmental delay, especially if acidosis and hyperammonemia are severe.
*[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
| Isovaleric acidemia | c0268575 | 2,070 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=33 | 2021-01-23T17:17:31 | {"gard": ["465"], "mesh": ["C538167"], "omim": ["243500"], "umls": ["C0268575"], "icd-10": ["E71.1"], "synonyms": ["Isovaleric acid CoA dehydrogenase deficiency"]} |
Sandhoff disease is a lysosomal storage disorder from the GM2 gangliosidosis family and is characterised by central nervous system degeneration.
## Epidemiology
Prevalence in Europe is about 1/130 000.
## Clinical description
The clinical picture is identical to that of Tay-Sachs disease, with startle reactions, early blindness, progressive motor and mental deterioration, macrocephaly and cherry-red spots on the macula. Patients may have a doll-like face, hepatosplenomegaly and recurring respiratory tract infections. High levels of urinary oligosaccharides are found. Children develop normally during the first 3-6 months of life, after which the disease appears and evolves quickly. In cases with later onset, or in adult cases, signs may be those of spinocerebellous ataxia or dystonia. Intellectual capacities may or may not be affected.
## Etiology
It results from hexosaminidase A and B deficiency, linked to an abnormal beta subunit (while Tay-Sachs disease results from hexosaminidase A deficiency caused by an abnormal alpha subunit). This enzymatic defect leads to abnormal GM2 ganglioside storage in neurons and peripheral tissues. The causative gene is located on chromosome 5 (5q13).
## Genetic counseling
The condition is an autosomal recessive inherited trait.
## Management and treatment
There is no specific treatment available for this disease.
## Prognosis
Prognosis is poor, with death usually occurring by age of 4 years.
*[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
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*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| Sandhoff disease | c0036161 | 2,071 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=796 | 2021-01-23T18:11:08 | {"gard": ["2521", "7604"], "mesh": ["D012497"], "omim": ["268800"], "umls": ["C0036161"], "icd-10": ["E75.0"], "synonyms": ["GM2 gangliosidosis 0 variant", "Hexosaminidases A and B deficiency"]} |
In Sint Maarten, a Dutch Caribbean constituent country of the Kingdom of the Netherlands, foreign policy is set by the Netherlands but all other laws including those related to abortion are self-determined. Abortion in Sint Maarten is illegal, although it may be permissible in circumstances where a pregnancy threatens the woman's life. Despite its illegality, abortions are routinely performed by some medical practitioners and are ignored by authorities.
## Legislation[edit]
Sint Maarten's abortion law is modelled after Dutch common law which was adopted by the Netherlands' foreign colonies in 1918. This law, covered in Articles 308 to 311, prohibits the act of abortion with no exceptional circumstances. For a woman who procures her own abortion or a health practitioner who intentionally assists, the penalties range from three to 15 years of imprisonment, depending on whether the woman consents to the procedure, whether the woman dies as a result, and whether a qualified health professional is involved. Any woman "who intentionally causes the expulsion or the death of her fruit" can be imprisoned for up to three years, while assistants to abortion can be imprisoned for up to four years and six months if the woman consents to the procedure (increasing to six years if the woman dies) or up to 12 years if the woman does not give her permission (increasing to 15 years if the woman dies). The maximum sentences may be raised by a third if a health professional is involved—including doctors, midwives and pharmacists—and they may be banned from their profession. Although not explicitly stated in the articles relating to abortion law, the principle of necessity may be used as a justification for breaking criminal law if an abortion is required to save a pregnant woman's life.[1]
Although the Netherlands legalised abortion in 1981, the reform was not adopted by any of the former colonies in the Dutch Caribbean, including Sint Maarten, Aruba and Curaçao, which instead retain the old Dutch common law.[1] These three territories became autonomous countries in 2010, but there remains public apprehension about whether the Netherlands will continue to attempt to "impose its liberal values and legislation" on the Dutch Caribbean, with abortion law being a chief concern.[2]
## Access to abortion services[edit]
Although abortion is illegal in Sint Maarten, it is fairly commonplace as part of a system of "institutionalised tolerance".[3][4] Since the 1981 Dutch law allowed abortion, Sint Maarten physicians and officials have become more tolerant of abortion despite the fact that Sint Maarten's own law did not change. The Ministry of Health in the nearby island country of Curaçao has had an ongoing agreement with abortion providers in Sint Maarten, providing inspections of the facilities for quality of care.[3]
Abortion is more accessible in the neighbouring country of the Collectivity of Saint Martin—which forms the other half of the island Saint Martin—where medical abortion using misoprostol is legal until 14 weeks' gestation and is universally available to those without health insurance. It is therefore common for women in Sint Maarten seeking abortions to travel to Saint Martin, "just a walk away across the border".[3]
Overall, the abortion rate in the Dutch Antilles is similar to that of Dutch Antillean women living in the Netherlands; this is around eight times higher than the abortion rate amongst native Dutch women.[2]
## References[edit]
1. ^ a b Pheterson, Gail; Azize, Yamila (2010). "Safe Illegal Abortion: An Inter-Island Study in the Northeast Caribbean". University of Puerto Rico. Archived from the original on 19 August 2014. Retrieved 16 August 2014.
2. ^ a b Allen, Rose Mary (2010). "The Complexity of National Identity Construction in Curaçao, Dutch Caribbean" (PDF). European Review of Latin American and Caribbean Studies. 89.
3. ^ a b c Pheterson, Gail; Azize, Yamila (2008). "Abortion within and around the law in the Caribbean". Puerto Rico Health Sciences Journal. 27 (1).
4. ^ "Opinion: Abortion". Today. 28 January 2014. Archived from the original on 19 August 2014. Retrieved 16 August 2014.
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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
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| Abortion in Sint Maarten | None | 2,072 | wikipedia | https://en.wikipedia.org/wiki/Abortion_in_Sint_Maarten | 2021-01-18T18:53:41 | {"wikidata": ["Q18161468"]} |
Small, rough growth resembling a cauliflower or a solid blister
For other uses, see Wart (disambiguation).
Warts
Other namesVerrucae,[1] papillomas[2]
A large number of warts on the big toe
SpecialtyDermatology
SymptomsPainless, small, rough skin growth[1][3]
DurationMonths to years[1]
CausesHuman papillomavirus[1]
Risk factorsPublic showers, eczema[3]
Differential diagnosisCallus, seborrheic keratosis, squamous cell carcinoma[4]
TreatmentSalicylic acid, cryotherapy[1]
FrequencyVery common[2]
Warts are typically small, rough, hard growths that are similar in color to the rest of the skin.[1][3] They typically do not result in other symptoms, except when on the bottom of the feet, where they may be painful.[3] While they usually occur on the hands and feet, they can also affect other locations.[1] One or many warts may appear.[3] They are not cancerous.[3]
Warts are caused by infection with a type of human papillomavirus (HPV).[1] Factors that increase the risk include use of public showers, working with meat, eczema and a weak immune system.[1][3] The virus is believed to enter the body through skin that has been damaged slightly.[1] A number of types exist, including "common warts", plantar warts, "filiform warts", and genital warts.[3] Genital warts are often sexually transmitted.[5]
Without treatment, most types of warts resolve in months to years.[1] A number of treatments may speed resolution including salicylic acid applied to the skin and cryotherapy.[1] In those who are otherwise healthy, they do not typically result in significant problems.[1] Treatment of genital warts differs from that of other types.[3]
Warts are very common, with most people being infected at some point in their lives.[2] The estimated current rate of non-genital warts among the general population is 1–13%.[1] They are more common among young people.[1] The estimated rate of genital warts in sexually active women is 12%.[5] Warts have been described at least as far back as 400 BC by Hippocrates.[4]
## Contents
* 1 Types
* 2 Cause
* 3 Pathophysiology
* 4 Diagnosis
* 5 Prevention
* 5.1 Disinfection
* 6 Treatment
* 6.1 Medication
* 6.2 Procedures
* 6.3 Alternative medicine
* 7 History
* 8 Other animals
* 9 References
* 10 External links
## Types[edit]
A filiform wart on the eyelid.
A range of types of wart have been identified, varying in shape and site affected, as well as the type of human papillomavirus involved.[6][7] These include:
* Common wart (verruca vulgaris), a raised wart with roughened surface, most common on hands, but can grow anywhere on the body. Sometimes known as a Palmer wart or Junior wart.
* Flat wart (verruca plana), a small, smooth flattened wart, flesh-coloured, which can occur in large numbers; most common on the face, neck, hands, wrists and knees.
* Filiform or digitate wart, a thread- or finger-like wart, most common on the face, especially near the eyelids and lips.
* Genital wart (venereal wart, condyloma acuminatum, verruca acuminata), a wart that occurs on the genitalia.
* Periungual wart, a cauliflower-like cluster of warts that occurs around the nails.
* Plantar wart (verruca, verruca plantaris), a hard, sometimes painful lump, often with multiple black specks in the center; usually only found on pressure points on the soles of the feet.
* Mosaic wart, a group of tightly clustered plantar-type warts, commonly on the hands or soles of the feet.
## Cause[edit]
Main article: Human papilloma virus
Warts are caused by the human papilloma virus (HPV). There are about 130 known types of human papilloma viruses.[8] HPV infects the squamous epithelium, usually of the skin or genitals, but each HPV type is typically only able to infect a few specific areas on the body. Many HPV types can produce a benign growth, often called a "wart" or "papilloma", in the area they infect. Many of the more common HPV and wart types are listed below.
* Common warts – HPV types 2 and 4 (most common); also types 1, 3, 26, 29, and 57 and others.
* Cancers and genital dysplasia – "high-risk" HPV types are associated with cancers, notably cervical cancer, and can also cause some vulvar, vaginal,[9] penile, anal[10] and some oropharyngeal cancers. "Low-risk" types are associated with warts or other conditions.[11][12]
* High-risk: 16, 18 (cause the most cervical cancer); also 31, 33, 35, 39, 45, 52, 58, 59, and others.
* Plantar warts (verruca) – HPV type 1 (most common); also types 2, 3, 4, 27, 28, and 58[citation needed] and others.
* Anogenital warts (condylomata acuminata or venereal warts) – HPV types 6 and 11 (most common); also types 42, 44 and others.[13]
* Low-risk: 6, 11 (most common); also 13, 44, 40, 43, 42, 54, 61, 72, 81, 89, and others.
* Verruca plana (flat warts) – HPV types 3, 10, and 28.
* Butcher's warts – HPV type 7.
* Heck's disease (focal epithelial hyperplasia) – HPV types 13 and 32.
## Pathophysiology[edit]
Common warts have a characteristic appearance under the microscope. They have thickening of the stratum corneum (hyperkeratosis), thickening of the stratum spinosum (acanthosis), thickening of the stratum granulosum, rete ridge elongation, and large blood vessels at the dermoepidermal junction.
## Diagnosis[edit]
Micrograph (H&E stain) of a common wart (verruca vulgaris) showing the characteristic features (hyperkeratosis, acanthosis, hypergranulosis, rete ridge elongation, and large blood vessels at the dermoepidermal junction)
On dermatoscopic examination warts will commonly have fingerlike or knoblike extensions.[14]
## Prevention[edit]
Gardasil 6 is an HPV vaccine aimed at preventing cervical cancers and genital warts. Gardasil is designed to prevent infection with HPV types 16, 18, 6, and 11. HPV types 16 and 18 currently cause about 70% of cervical cancer cases,[11][12] and also cause some vulvar, vaginal,[9] penile and anal cancers.[10] HPV types 6 and 11 are responsible for 90% of documented cases of genital warts.[15]
Gardasil 9, approved in 2014 protects against HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.[16]
HPV vaccines do not currently protect against the virus strains responsible for plantar warts (verrucae).
### Disinfection[edit]
The virus is relatively hardy and immune to many common disinfectants. Exposure to 90% ethanol for at least 1 minute, 2% glutaraldehyde,[citation needed] 30% Savlon, and/or 1% sodium hypochlorite can disinfect the pathogen.[17]
The virus is resistant to drying and heat, but killed by 100 °C (212 °F) and ultraviolet radiation.[17]
## Treatment[edit]
Further information: Plantar wart § Treatment
There are many treatments and procedures associated with wart removal.[18] A review of various skin wart treatments concluded that topical treatments containing salicylic acid were more effective than placebo.[19] Cryotherapy appears to be as effective as salicylic acid, but there have been fewer trials.[19]
### Medication[edit]
* Salicylic acid can be prescribed by a dermatologist in a higher concentration than that found in over-the-counter products. Several over-the-counter products are readily available at pharmacies and supermarkets of roughly two types: adhesive pads treated with salicylic acid, and bottled concentrated salicylic acid solution.
* Imiquimod is a topical cream that helps the body's immune system fight the wart virus by encouraging interferon production. It has been approved by the U.S. Food and Drug Administration (FDA) for genital warts.[20]
* Cantharidin, found naturally in the bodies of many members of the beetle family Meloidae, causes dermal blistering. It is used either by itself or compounded with podophyllin. Not FDA approved, but available through Canada or select US compounding pharmacies.
* Bleomycin is not US FDA approved and can cause necrosis of digits and Raynaud syndrome.[21][22] The usual treatment is one or two injections.
* Dinitrochlorobenzene (DNCB), like salicylic acid, is applied directly to the wart. Studies show this method is effective with a cure rate of 80%.[medical citation needed] But DNCB must be used much more cautiously than salicylic acid; the chemical is known to cause genetic mutations, so it must be administered by a physician. This drug induces an allergic immune response resulting in inflammation that wards off the wart-causing virus.[23]
* Cidofovir is an antiviral drug which is injected into HPV lesions within the larynx (laryngeal papillomatosis) as an experimental treatment.[24]
* Verrutop verruca treatment is a topical solution made from a combination of organic acids, inorganic acids, and metal ions. This solution causes the production of nitrites which act to denature viral proteins and mummify the wart tissue. The difference between Verrutop and other acid treatments is that it does not damage the surrounding skin.
* Another product available over-the-counter that can aid in wart removal is silver nitrate in the form of a caustic pencil, which is also available at drug stores. In a placebo-controlled study of 70 patients, silver nitrate given over nine days resulted in clearance of all warts in 43% and improvement in warts in 26% one month after treatment compared to 11% and 14%, respectively, in the placebo group.[25] The instructions must be followed to minimize staining of skin and clothing. Occasionally pigmented scars may develop.
* Two viral warts on a middle finger, being treated with a mixture of acids (like salicylic acid) to remove them. A white precipitate forms on the area where the product was applied.
* Throat warts before and after carbon dioxide laser treatment.
### Procedures[edit]
Liquid nitrogen spray tank
* Keratolysis, of dead surface skin cells usually using salicylic acid, blistering agents, immune system modifiers ("immunomodulators"), or formaldehyde, often with mechanical paring of the wart with a pumice stone, blade etc.[26]
* Electrodesiccation[27]
* Cryosurgery or cryotherapy, which involves freezing the wart (generally with liquid nitrogen),[28] creating a blister between the wart and epidermal layer after which the wart and the surrounding dead skin fall off. An average of 3 to 4 treatments are required for warts on thin skin. Warts on calloused skin like plantar warts might take dozens or more treatments.[21]
* Surgical curettage of the wart
* Laser treatment – often with a pulse dye laser or carbon dioxide (CO2) laser. Pulse dye lasers (wavelength 582 nm) work by selective absorption by blood cells (specifically hemoglobin). CO2 lasers work by selective absorption by water molecules. Pulse dye lasers are less destructive and more likely to heal without scarring. CO2 laser works by vaporizing and destroying tissue and skin. Laser treatments can be painful, expensive (though covered by many insurance plans), and not extensively scarring when used appropriately. CO2 lasers will require local anaesthetic. Pulse dye laser treatment does not need conscious sedation or local anesthetic. It takes 2 to 4 treatments but can be many more for extreme cases. Typically, 10–14 days are required between treatments. Preventative measures are important.[21]
* Infrared coagulator – an intense source of infrared light in a small beam like a laser. This works essentially on the same principle as laser treatment. It is less expensive. Like the laser, it can cause blistering pain and scarring.[29]
* Intralesional immunotherapy with purified candida, MMR, and tuberculin (PPD) protein appears safe and effective.[30][31]
* Duct tape occlusion therapy involves placing a piece of duct tape over the wart. The mechanism of action of this technique still remains unknown. Despite several trials, evidence for the efficacy of duct tape therapy is inconclusive.[32][33] Despite the mixed evidence for efficacy, the simplicity of the method and its limited side-effects leads some researchers to be reluctant to dismiss it.[34]
This image shows throat warts (papillomas) before treatment and during the treatment process. Left to right: warts prior to treatment, warts on day of silver nitrate treatment, warts two days after treatment, warts four days after treatment, warts six days after treatment, and warts remaining nine days after treatment.
### Alternative medicine[edit]
Despite their appearance, toads do not cause warts
Daily application of the latex of Chelidonium majus is a traditional treatment.[35]
The acrid yellow sap of Greater Celandine is used as a traditional wart remedy.[36] The sap can be applied directly to the wart in a similar manner to concentrated salicylic acid solution, but in more modest quantities.
According to English folk belief, touching toads causes warts; according to a German belief, touching a toad under a full moon cures warts.[37] The most common Northern Hemisphere toads have glands that protrude from their skin that superficially resemble warts. Warts are caused by a virus, and toads do not harbor it.[38] A variety of traditional folk remedies and rituals claim to be able to remove warts.
In The Adventures of Tom Sawyer, Mark Twain has his characters discuss a variety of such remedies. Tom Sawyer proposes "spunk-water" (or "stump-water", the water collecting in the hollow of a tree stump) as a remedy for warts on the hand. You put your hand into the water at midnight and say:
> Barley-corn, barley-corn, injun-meal shorts,
> Spunk-water, spunk-water, swaller these warts
You then "walk away quick, eleven steps, with your eyes shut, and then turn around three times and walk home without speaking to anybody. Because if you speak the charm's busted." This is given as an example to Huckleberry Finn's planned remedy which involving throwing a dead cat into a graveyard as a devil or devils comes to collect a recently buried wicked person. Another remedy involved splitting a bean, drawing blood from the wart and putting it on one of the halves, and burying that half at a crossroads at midnight. The theory of operation is that the blood on the buried bean will draw away the wart.[39] Twain is recognized as an early collector and recorder of genuine American folklore.[40]
Similar practices are recorded elsewhere. In Louisiana, one remedy for warts involves rubbing the wart with a potato, which is then buried; when the "buried potato dries up, the wart will be cured".[41] Another remedy similar to Twain's is reported from Northern Ireland, where water from a specific well on Rathlin Island is credited with the power to cure warts.[42]
## History[edit]
A ~7 mm plantar wart surgically removed from the sole of a person's foot after other treatments failed.
Surviving ancient medical texts show that warts were a documented disease since at least the time of Hippocrates, who lived ca. 460 – c. 370 BC. In the book De Medecia by the Roman physician Aulus Cornelius Celsus, who lived c. 25 BC – c. 50 AD, different types of warts were described. Celsus described myrmecia, today recognized as plantar wart, and categorized acrochordon (a skin tag) as wart. In the 13th century warts were described in books published by the surgeons William of Saliceto and Lanfranc of Milan. The word verruca to describe a wart was introduced by the physician Daniel Sennert, who described warts in his 1636 book Hypomnemata physicae.[43]
But the cause of warts was disputed in the medical profession. In the early 18th century the physician Daniel Turner, who published the first book on dermatology, suggested that warts were caused by damaged nerves close to the skin. Mid 18th century the surgeon John Hunter popularized the believe that warts were caused by a bacterial syphilis infection. The surgeon Benjamin Bell documented that warts were caused by a disease entirely unrelated to syphilis and established a causal link between warts and cancer. In the 19th century the chief physician of Verona hospital established a link between warts and cervical cancer. But in 1874 it was noted by the dermatologist Ferdinand Ritter von Hebra that while various theories were advanced by the medical profession, the "influences causing warts are still very obscure".[44]
In 1907 the physician Giuseppe Ciuffo was the first to demonstrate that warts were caused by a virus infection. In 1976 the virologist Harald zur Hausen was the first to discover that warts were caused by the human papillomavirus (HPV). His continuous research established the evidence necessary to develop a HPV vaccine, which first became available in 2006.[45]
## Other animals[edit]
See also: Papillomavirus and Bovine papillomavirus
## References[edit]
1. ^ a b c d e f g h i j k l m n o Loo, SK; Tang, WY (12 June 2014). "Warts (non-genital)". BMJ Clinical Evidence. 2014. PMC 4054795. PMID 24921240.
2. ^ a b c "Papillomas (Warts) – National Library of Medicine". PubMed Health. Archived from the original on 2017-09-10. Retrieved 2016-11-06.
3. ^ a b c d e f g h i "Warts: Overview". U.S. National Library of Medicine. 30 July 2014. Archived from the original on 10 September 2017. Cite journal requires `|journal=` (help)
4. ^ a b Bope, Edward T.; Kellerman, Rick D. (2012). Conn's Current Therapy 2012. Elsevier Health Sciences. p. 275. ISBN 978-1455733057. Archived from the original on 2016-11-07.
5. ^ a b W Buck, Henry (13 August 2010). "Warts (genital)". BMJ Clinical Evidence. 2010. PMC 3217761. PMID 21418685.
6. ^ Anderson, Keith; Keith, Jeff; Novak, Patricia D.; Elliot, Michelle A. (2005). Mosby's Medical, Nursing & Allied Health Dictionary (5th ed.). C.V. Mosby. ISBN 978-0-323-03736-5. Archived from the original on 2017-01-07.
7. ^ "MedlinePlus: Warts". 2010. Archived from the original on 2013-05-16.
8. ^ De Villiers EM, Fauquet C, Broker TR, Bernard HU, Zur Hausen H (Jun 2004). "Classification of papillomaviruses". Virology. 324 (1): 17–27. doi:10.1016/j.virol.2004.03.033. PMID 15183049.
9. ^ a b "FDA Approves Expanded Uses for Gardasil to Include Preventing Certain Vulvar and Vaginal Cancers". FDA. 2008-09-12. Archived from the original on 2010-03-06.
10. ^ a b Cortez, Michelle Fay; Pettypiece, Shannon (2008-11-13). "Merck Cancer Shot Cuts Genital Warts, Lesions in Men". Bloomberg News. Retrieved 2013-05-17.
11. ^ a b Lowy DR, Schiller JT (2006). "Prophylactic human papillomavirus vaccines". J. Clin. Invest. 116 (5): 1167–73. doi:10.1172/JCI28607. PMC 1451224. PMID 16670757.
12. ^ a b Muñoz N, Bosch FX, Castellsagué X, Díaz M, de Sanjose S, Hammouda D, Shah KV, Meijer CJ (2004-08-20). "Against which human papillomavirus types shall we vaccinate and screen? The international perspective". Int J Cancer. 111 (2): 278–85. doi:10.1002/ijc.20244. PMID 15197783. S2CID 20679802.
13. ^ Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Mitchell, Richard (2007). "Chapter 19 The Female Genital System and Breast". Robbins Basic Pathology (8 ed.). Philadelphia: Saunders. ISBN 978-1-4160-2973-1.
14. ^ Dong, Huiting (2011). "Dermatoscopy of genital warts". Journal of the American Academy of Dermatology. 64 (5): 859–864. doi:10.1016/j.jaad.2010.03.028. PMID 21429619 – via Elsevier Science Direct.
15. ^ Steinbrook, Robert (2006). "The Potential of Human Papillomavirus Vaccines". New England Journal of Medicine. 354 (11): 1109–12. doi:10.1056/NEJMp058305. PMID 16540608.
16. ^ "Prescribing information Gardasil 9" (PDF). Food and Drug Administration. 2015. Archived (PDF) from the original on 2016-10-10.
17. ^ a b Human Papillomavirus Archived 2015-08-23 at the Wayback Machine. Public Health Agency of Canada
18. ^ Lipke MM (2006). "An armamentarium of wart treatments". Clin Med Res. 4 (4): 273–93. doi:10.3121/cmr.4.4.273. PMC 1764803. PMID 17210977.
19. ^ a b Kwok CS, Gibbs S, Bennett C, Holland R, Abbott R (Sep 12, 2012). Gibbs S (ed.). "Topical treatments for cutaneous warts". The Cochrane Database of Systematic Reviews. 9 (9): CD001781. doi:10.1002/14651858.CD001781.pub3. PMID 22972052. Archived from the original on 2013-07-04.
20. ^ Barclay L (2011-06-04). "Short-Acting Imiquimod Cream Approved for Genital Warts". Medscape. Archived from the original on 18 August 2011. Retrieved 10 August 2011.
21. ^ a b c Bacelieri R, Johnson SM (2005). "Cutaneous warts: An evidence-based approach to therapy". American Family Physician. 72 (4): 647–52. PMID 16127954. Archived from the original on 2014-04-21.
22. ^ Champion, R. H., et al. (1998). Rook's Textbook of Dermatology. Blackwell Science, p. 1044, ISBN 0-632-06429-3
23. ^ "Treating Warts". British Medical Journal. 2002-08-31. Archived from the original on 2010-11-03. Retrieved 2013-05-17.
24. ^ Soma, Marlene A; Albert, David M (2008). "Cidofovir: to use or not to use?". Current Opinion in Otolaryngology & Head and Neck Surgery. 16 (1): 86–90. doi:10.1097/MOO.0b013e3282f43408. PMID 18197029. S2CID 22895067.
25. ^ Sterling JC, Handfield-Jones S, Hudson PM (2001). "Guidelines for the management of cutaneous warts" (PDF). British Journal of Dermatology. 144 (1): 4–11. doi:10.1046/j.1365-2133.2001.04066.x. PMID 11167676. S2CID 20179474. Archived from the original (PDF) on 2012-03-03.
26. ^ Warts Archived 2008-05-17 at the Wayback Machine at About.com
27. ^ Stone KM, Becker TM, Hadgu A, Kraus SJ (1990). "Treatment of external genital warts: A randomised clinical trial comparing podophyllin, cryotherapy, and electrodesiccation". Genitourinary Medicine. 66 (1): 16–19. doi:10.1136/sti.66.1.16. PMC 1194434. PMID 2179111.
28. ^ "Cryotherapy for Warts". WebMD. Archived from the original on 2016-07-09.
29. ^ Halasz CL (1994). "Treatment of common warts using the infrared coagulator". The Journal of Dermatologic Surgery and Oncology. 20 (4): 252–56. doi:10.1111/j.1524-4725.1994.tb01620.x. PMID 8163746.
30. ^ Aldahan, AS; Mlacker, S; Shah, VV; Kamath, P; Alsaidan, M; Samarkandy, S; Nouri, K (May 2016). "Efficacy of intralesional immunotherapy for the treatment of warts: A review of the literature". Dermatologic Therapy. 29 (3): 197–207. doi:10.1111/dth.12352. PMID 26991521. S2CID 40536366.
31. ^ Salman, Samer (2019). "Intralesional Immunotherapy for the Treatment of Warts: A Network Meta-analysis". Journal of the American Academy of Dermatology. 80 (4): 922–930.e4. doi:10.1016/j.jaad.2018.07.003. PMID 30003983. S2CID 51617793 – via Elsevier Science Direct.
32. ^ Loo, SK; Tang, WY (12 June 2014). "Warts (non-genital)". BMJ Clinical Evidence. 2014. PMC 4054795. PMID 24921240.
33. ^ Kwok CS; Gibbs S; Bennett C; Holland R; Abbott R (12 Sep 2012). "Topical treatments for cutaneous warts". Cochrane Database Syst Rev. 9 (9): CD001781. doi:10.1002/14651858.CD001781.pub3. PMID 22972052.
34. ^ Stubbings A, Wacogne I (September 2011). "Question 3. What is the efficacy of duct tape as a treatment for verruca vulgaris?". Archives of Disease in Childhood. 96 (9): 897–99. doi:10.1136/archdischild-2011-300533. PMID 21836182. S2CID 206853952.
35. ^ Gilca, Marilena, et al. « Chelidonium majus–an integrative review: traditional knowledge versus modern findings » Forschende Komplementärmedizin/Research in Complementary Medicine2010; 17(5): 241-248.
36. ^ Greater Celandine For Warts Archived 2014-07-17 at the Wayback Machine. botanical-online.com
37. ^ Ley, Willy (December 1963). "The Names of the Constellations". For Your Information. Galaxy Science Fiction. pp. 90–99.
38. ^ Clark, Josh. "Do toads cause warts?". science.howstuffworks.com. p. 2. Archived from the original on October 16, 2012. Retrieved October 20, 2012.
39. ^ Mark Twain, The Adventures of Tom Sawyer, ch. 6
40. ^ LeMaster, J. R. (1993) The Mark Twain Encyclopedia (Taylor and Francis, pp. 293–94 Archived 2017-01-07 at the Wayback Machine, ISBN 0-8240-7212-X.
41. ^ Webb, Julie Yvonne (1971). "Louisiana Voodoo and Superstitions Relating to Health". HSMHA Health Reports. 86 (4): 291, 296–97. doi:10.2307/4594154. JSTOR 4594154. PMC 1937133. PMID 4324337.
42. ^ Ballard LM (2009). "An approach to traditional cures in Ulster". The Ulster Medical Journal. 78 (1): 26–33. PMC 2629017. PMID 19252727.
43. ^ Karamanou, Marianna; Agapitos, Emmanovil; Kousoulis, Antonis; Androutsos, George (17 August 2010). "From the humble wart to HPV: a fascinating story throughout centuries". Oncology Reviews. 4 (3): 133–135. doi:10.1007/s12156-010-0060-1. S2CID 72238300.
44. ^ Karamanou, Marianna; Agapitos, Emmanovil; Kousoulis, Antonis; Androutsos, George (17 August 2010). "From the humble wart to HPV: a fascinating story throughout centuries". Oncology Reviews. 4 (3): 133–135. doi:10.1007/s12156-010-0060-1. S2CID 72238300.
45. ^ Karamanou, Marianna; Agapitos, Emmanovil; Kousoulis, Antonis; Androutsos, George (17 August 2010). "From the humble wart to HPV: a fascinating story throughout centuries". Oncology Reviews. 4 (3): 133–135. doi:10.1007/s12156-010-0060-1. S2CID 72238300.
## External links[edit]
Look up wart in Wiktionary, the free dictionary.
* Wart photo library, Dermnet
Classification
D
* ICD-10: B07
* ICD-9-CM: 078.1
* MeSH: D014860
* DiseasesDB: 28410
External resources
* MedlinePlus: 000885
* eMedicine: emerg/641
* Patient UK: Wart
* v
* t
* e
Diseases of the skin and appendages by morphology
Growths
Epidermal
* Wart
* Callus
* Seborrheic keratosis
* Acrochordon
* Molluscum contagiosum
* Actinic keratosis
* Squamous-cell carcinoma
* Basal-cell carcinoma
* Merkel-cell carcinoma
* Nevus sebaceous
* Trichoepithelioma
Pigmented
* Freckles
* Lentigo
* Melasma
* Nevus
* Melanoma
Dermal and
subcutaneous
* Epidermal inclusion cyst
* Hemangioma
* Dermatofibroma (benign fibrous histiocytoma)
* Keloid
* Lipoma
* Neurofibroma
* Xanthoma
* Kaposi's sarcoma
* Infantile digital fibromatosis
* Granular cell tumor
* Leiomyoma
* Lymphangioma circumscriptum
* Myxoid cyst
Rashes
With
epidermal
involvement
Eczematous
* Contact dermatitis
* Atopic dermatitis
* Seborrheic dermatitis
* Stasis dermatitis
* Lichen simplex chronicus
* Darier's disease
* Glucagonoma syndrome
* Langerhans cell histiocytosis
* Lichen sclerosus
* Pemphigus foliaceus
* Wiskott–Aldrich syndrome
* Zinc deficiency
Scaling
* Psoriasis
* Tinea (Corporis
* Cruris
* Pedis
* Manuum
* Faciei)
* Pityriasis rosea
* Secondary syphilis
* Mycosis fungoides
* Systemic lupus erythematosus
* Pityriasis rubra pilaris
* Parapsoriasis
* Ichthyosis
Blistering
* Herpes simplex
* Herpes zoster
* Varicella
* Bullous impetigo
* Acute contact dermatitis
* Pemphigus vulgaris
* Bullous pemphigoid
* Dermatitis herpetiformis
* Porphyria cutanea tarda
* Epidermolysis bullosa simplex
Papular
* Scabies
* Insect bite reactions
* Lichen planus
* Miliaria
* Keratosis pilaris
* Lichen spinulosus
* Transient acantholytic dermatosis
* Lichen nitidus
* Pityriasis lichenoides et varioliformis acuta
Pustular
* Acne vulgaris
* Acne rosacea
* Folliculitis
* Impetigo
* Candidiasis
* Gonococcemia
* Dermatophyte
* Coccidioidomycosis
* Subcorneal pustular dermatosis
Hypopigmented
* Tinea versicolor
* Vitiligo
* Pityriasis alba
* Postinflammatory hyperpigmentation
* Tuberous sclerosis
* Idiopathic guttate hypomelanosis
* Leprosy
* Hypopigmented mycosis fungoides
Without
epidermal
involvement
Red
Blanchable
Erythema
Generalized
* Drug eruptions
* Viral exanthems
* Toxic erythema
* Systemic lupus erythematosus
Localized
* Cellulitis
* Abscess
* Boil
* Erythema nodosum
* Carcinoid syndrome
* Fixed drug eruption
Specialized
* Urticaria
* Erythema (Multiforme
* Migrans
* Gyratum repens
* Annulare centrifugum
* Ab igne)
Nonblanchable
Purpura
Macular
* Thrombocytopenic purpura
* Actinic/solar purpura
Papular
* Disseminated intravascular coagulation
* Vasculitis
Indurated
* Scleroderma/morphea
* Granuloma annulare
* Lichen sclerosis et atrophicus
* Necrobiosis lipoidica
Miscellaneous
disorders
Ulcers
*
Hair
* Telogen effluvium
* Androgenic alopecia
* Alopecia areata
* Systemic lupus erythematosus
* Tinea capitis
* Loose anagen syndrome
* Lichen planopilaris
* Folliculitis decalvans
* Acne keloidalis nuchae
Nail
* Onychomycosis
* Psoriasis
* Paronychia
* Ingrown nail
Mucous
membrane
* Aphthous stomatitis
* Oral candidiasis
* Lichen planus
* Leukoplakia
* Pemphigus vulgaris
* Mucous membrane pemphigoid
* Cicatricial pemphigoid
* Herpesvirus
* Coxsackievirus
* Syphilis
* Systemic histoplasmosis
* Squamous-cell carcinoma
* v
* t
* e
Skin infections, symptoms and signs related to viruses
DNA virus
Herpesviridae
Alpha
HSV
* Herpes simplex
* Herpetic whitlow
* Herpes gladiatorum
* Herpes simplex keratitis
* Herpetic sycosis
* Neonatal herpes simplex
* Herpes genitalis
* Herpes labialis
* Eczema herpeticum
* Herpetiform esophagitis
Herpes B virus
* B virus infection
VZV
* Chickenpox
* Herpes zoster
* Herpes zoster oticus
* Ophthalmic zoster
* Disseminated herpes zoster
* Zoster-associated pain
* Modified varicella-like syndrome
Beta
* Human herpesvirus 6/Roseolovirus
* Exanthema subitum
* Roseola vaccinia
* Cytomegalic inclusion disease
Gamma
* KSHV
* Kaposi's sarcoma
Poxviridae
Ortho
* Variola
* Smallpox
* Alastrim
* MoxV
* Monkeypox
* CPXV
* Cowpox
* VV
* Vaccinia
* Generalized vaccinia
* Eczema vaccinatum
* Progressive vaccinia
* Buffalopox
Para
* Farmyard pox: Milker's nodule
* Bovine papular stomatitis
* Pseudocowpox
* Orf
* Sealpox
Other
* Yatapoxvirus: Tanapox
* Yaba monkey tumor virus
* MCV
* Molluscum contagiosum
Papillomaviridae
HPV
* Wart/plantar wart
* Heck's disease
* Genital wart
* giant
* Laryngeal papillomatosis
* Butcher's wart
* Bowenoid papulosis
* Epidermodysplasia verruciformis
* Verruca plana
* Pigmented wart
* Verrucae palmares et plantares
* BPV
* Equine sarcoid
Parvoviridae
* Parvovirus B19
* Erythema infectiosum
* Reticulocytopenia
* Papular purpuric gloves and socks syndrome
Polyomaviridae
* Merkel cell polyomavirus
* Merkel cell carcinoma
RNA virus
Paramyxoviridae
* MeV
* Measles
Togaviridae
* Rubella virus
* Rubella
* Congenital rubella syndrome ("German measles" )
* Alphavirus infection
* Chikungunya fever
Picornaviridae
* CAV
* Hand, foot, and mouth disease
* Herpangina
* FMDV
* Foot-and-mouth disease
* Boston exanthem disease
Ungrouped
* Asymmetric periflexural exanthem of childhood
* Post-vaccination follicular eruption
* Lipschütz ulcer
* Eruptive pseudoangiomatosis
* Viral-associated trichodysplasia
* Gianotti–Crosti syndrome
* v
* t
* e
Skin cancer of the epidermis
Tumor
Carcinoma
BCC
* Forms
* Aberrant
* Cicatricial
* Cystic
* Fibroepithelioma of Pinkus
* Infltrative
* Micronodular
* Nodular
* Pigmented
* Polypoid
* Pore-like
* Rodent ulcer
* Superficial
* Nevoid basal cell carcinoma syndrome
SCC
* Forms
* Adenoid
* Basaloid
* Clear cell
* Signet-ring-cell
* Spindle-cell
* Marjolin's ulcer
* Bowen's disease
* Bowenoid papulosis
* Erythroplasia of Queyrat
* Actinic keratosis
Adenocarcinoma
* Aggressive digital papillary adenocarcinoma
* Extramammary Paget's disease
Ungrouped
* Merkel cell carcinoma
* Microcystic adnexal carcinoma
* Mucinous carcinoma
* Primary cutaneous adenoid cystic carcinoma
* Verrucous carcinoma
* Malignant mixed tumor
Benign
tumors
Acanthoma
* Forms
* Large cell
* Fissuring
* Clear cell
* Epidermolytic
* Melanoacanthoma
* Pilar sheath acanthoma
* Seboacanthoma
* Seborrheic keratosis
* Warty dyskeratoma
Keratoacanthoma
* Generalized eruptive
* Keratoacanthoma centrifugum marginatum
* Multiple
* Solitary
Wart
* Verruca vulgaris
* Verruca plana
* Plantar wart
* Periungual wart
Other
Epidermal nevus
* Syndromes
* Epidermal nevus syndrome
* Schimmelpenning syndrome
* Nevus comedonicus syndrome
* Nevus comedonicus
* Inflammatory linear verrucous epidermal nevus
* Linear verrucous epidermal nevus
* Pigmented hairy epidermal nevus syndrome
* Systematized epidermal nevus
* Phakomatosis pigmentokeratotica
Other nevus
* Nevus unius lateris
* Patch blue nevus
* Unilateral palmoplantar verrucous nevus
* Zosteriform speckled lentiginous nevus
Ungrouped
* Cutaneous horn
* v
* t
* e
Human papillomavirus
Related
diseases
Cancers
* Cervical cancer
* cancers
* Anal
* Vaginal
* Vulvar
* Penile
* Head and neck cancer (HPV-positive oropharyngeal cancer)
Warts
* * genital
* plantar
* flat
* Laryngeal papillomatosis
* Epidermodysplasia verruciformis
* Focal epithelial hyperplasia
* Papilloma
Others
Acrochordon (skin tags)
Vaccine
* HPV vaccines
* Cervarix
* Gardasil
Screening
* Pap test:
* stain
* Bethesda system
* Cytopathology
* Cytotechnology
* Experimental techniques:
* Speculoscopy
* Cervicography
Colposcopy
Biopsy histology
* Cervical intraepithelial neoplasia (CIN)
* Koilocyte
* Vaginal intraepithelial neoplasia (VAIN)
* Vulvar intraepithelial neoplasia (VIN)
Treatment
* Cervical conization
* Loop electrical excision procedure (LEEP)
History
* Georgios Papanikolaou
* Harald zur Hausen
*[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
| Wart | c3665596 | 2,073 | wikipedia | https://en.wikipedia.org/wiki/Wart | 2021-01-18T18:31:11 | {"mesh": ["D014860"], "umls": ["C3665596"], "icd-9": ["078.1"], "icd-10": ["B07"], "wikidata": ["Q101971"]} |
Pure mitochondrial myopathy is a rare mitochondrial disease characterized by exclusive skeletal muscle involvement, without clinical evidence of other organ involvement, manifesting with progressive limb weakness, proximal limb muscle atrophy, and eye muscle anomalies (e.g. ocular motility restriction, ptosis). Patients may present with lactic acidosis, diffuse myalgia and overall fatigability (particularly during/after physical activities), dysphagia, and diminished deep tendon reflexes.
*[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
| Pure mitochondrial myopathy | c4517289 | 2,074 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=254854 | 2021-01-23T16:53:19 | {"icd-10": ["G71.3"]} |
Aromatic l-amino acid decarboxylase (AADC) deficiency is an inherited disorder that affects the way signals are passed between certain cells in the nervous system.
Signs and symptoms of AADC deficiency generally appear in the first year of life. Affected infants may have severe developmental delay, weak muscle tone (hypotonia), muscle stiffness, difficulty moving, and involuntary writhing movements of the limbs (athetosis). They may be lacking in energy (lethargic), feed poorly, startle easily, and have sleep disturbances. People with AADC deficiency may also experience episodes called oculogyric crises that involve abnormal rotation of the eyeballs; extreme irritability and agitation; and pain, muscle spasms, and uncontrolled movements, especially of the head and neck.
AADC deficiency may affect the autonomic nervous system, which controls involuntary body processes such as the regulation of blood pressure and body temperature. Resulting signs and symptoms can include droopy eyelids (ptosis), constriction of the pupils of the eyes (miosis), inappropriate or impaired sweating, nasal congestion, drooling, reduced ability to control body temperature, low blood pressure (hypotension), backflow of acidic stomach contents into the esophagus (gastroesophageal reflux), low blood sugar (hypoglycemia), fainting (syncope), and cardiac arrest.
Signs and symptoms of AADC deficiency tend to worsen late in the day or when the individual is tired, and improve after sleep.
## Frequency
AADC deficiency is a rare disorder. Only about 100 people with this condition have been described in the medical literature worldwide; about 20 percent of these individuals are from Taiwan.
## Causes
Mutations in the DDC gene cause AADC deficiency. The DDC gene provides instructions for making the AADC enzyme, which is important in the nervous system. This enzyme helps produce dopamine and serotonin from other molecules. Dopamine and serotonin are neurotransmitters, which are chemical messengers that transmit signals between nerve cells, both in the brain and spinal cord (central nervous system) and in other parts of the body (peripheral nervous system).
Mutations in the DDC gene result in reduced activity of the AADC enzyme. Without enough of this enzyme, nerve cells produce less dopamine and serotonin. Dopamine and serotonin are necessary for normal nervous system function, and changes in the levels of these neurotransmitters contribute to the developmental delay, intellectual disability, abnormal movements, and autonomic dysfunction seen in people with AADC deficiency.
### Learn more about the gene associated with Aromatic l-amino acid decarboxylase deficiency
* DDC
## Inheritance Pattern
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| Aromatic l-amino acid decarboxylase deficiency | c1291564 | 2,075 | medlineplus | https://medlineplus.gov/genetics/condition/aromatic-l-amino-acid-decarboxylase-deficiency/ | 2021-01-27T08:25:38 | {"gard": ["770"], "omim": ["608643"], "synonyms": []} |
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (February 2017)
Maternal hypothyroidism is hypothyroidism in pregnant mothers.[1] Even with appropriate treatment, it may pose risks not only to the mother, but also to the fetus. Thyroid hormones, T4 and TSH, diffuse across the placenta traveling from the mother to fetus for 10–12 weeks before the fetus’s own thyroid gland can begin synthesizing its own thyroid hormones.[2] The mother continues to supply some T4 to the fetus even after he/she is able to synthesize his/her own. Infants with sporadic congenital hypothyroidism show T4 concentrations in the umbilical cord suggesting the mother is still providing 25-50 percent of T4. If these infants are not screened soon after birth for their hypothyroidism and treated, the infants can become permanently intellectually disabled, since they can’t meet their bodies demand for T4.[3]
One study showed infants born to treated hypothyroid mothers had abnormal thyroid function compared to matched controls.[2] Therefore, it is advised to monitor T4 levels throughout the pregnancy in case treatment dosages should be increased to accommodate both the mother’s and fetus’s thyroid hormone requirements. If the supply of T4 is insufficient the mother may be at risk for preeclampsia and preterm delivery.[3]
The infants may also be at risk for suppressed psychomotor development and slightly lower IQ.[3] In a study of induced hypothyroidism in pregnant rats they were able to find lower levels of growth hormone in both the blood and pituitary gland of the offspring.[4] This study also looked at neural development in rats and found that maternal hypothyroidism in rat mothers is related to deterioration, damage, disorganization and malformation of neurons and dendrites in the pups, which may result from an impaired antioxidant defense system and high levels of oxidative stress.[4]
## References[edit]
1. ^ "Hypothyroidism in Pregnancy". American Thyroid Association. Retrieved 2020-10-29.
2. ^ a b Blazer S.; Moreh-Waterman Y.; Miller-Lotan R.; Tamir A.; Hochberg Z. (2003). "Maternal hypothyroidism may affect fetal growth and neonatal thyroid function". Obstetrics & Gynecology. 102 (2): 232–241. doi:10.1016/s0029-7844(03)00513-1. PMID 12907094. S2CID 39487202.
3. ^ a b c Utiger Robert D (1999). "Editorial: Maternal Hypothyroidism and Fetal Development". The New England Journal of Medicine. 341 (8): 601–2. doi:10.1056/nejm199908193410809. PMID 10451467.
4. ^ a b Ahmed O.M.; Ahmed R.G.; El-Gareib A.W.; El-Bakry A.M.; El-Tawab S.M. Abd (2012). "Effects of experimentally induced maternal hypothyroidism and hyperthyroidism on the development of rat offspring: II—The developmental pattern of neurons in relation to oxidative stress and antioxidant defense system". International Journal of Developmental Neuroscience. 30 (6): 517–537. doi:10.1016/j.ijdevneu.2012.04.005. PMID 22664656. S2CID 32600950.
*[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
| Maternal hypothyroidism | c0262548 | 2,076 | wikipedia | https://en.wikipedia.org/wiki/Maternal_hypothyroidism | 2021-01-18T18:33:43 | {"umls": ["C0262548"], "wikidata": ["Q17006575"]} |
Short tarsus - absence of lower eyelashes is a very rare syndrome characterized by the association of thin and short upper and lower tarsus and absence of the lower eyelashes.
## Epidemiology
It has been described in 11 patients from a four generation family.
## Clinical description
There is no other unusual feature.
## Genetic counseling
Inheritance is autosomal dominant.
*[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
| Short tarsus-absence of lower eyelashes syndrome | c1838328 | 2,077 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2832 | 2021-01-23T17:33:35 | {"gard": ["296"], "mesh": ["C537036"], "omim": ["600269"], "umls": ["C1838328"], "icd-10": ["Q87.2"], "synonyms": ["Lopes-Gorlin syndrome"]} |
Dizziness resulting from unequal pressures in the middle ears
Alternobaric vertigo
SpecialtyOtorhinolaryngology, diving medicine
In aviation and underwater diving, alternobaric vertigo is dizziness resulting from unequal pressures being exerted between the ears due to one Eustachian tube being less patent than the other.[1][2][3]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Diagnosis
* 4 Management
* 5 See also
* 6 References
## Signs and symptoms[edit]
This section is empty. You can help by adding to it. (December 2018)
## Causes[edit]
This might have occurred due to barotrauma of descent, and/or the effects of nasal decongestants. It is due to unequal increase in middle ear pressures on ascent, is usually mild, and most often cleared by further ascent. When the pressures in both ears reach ambient levels, the stimulus for the dizziness stops.[2] Although most often mild, the vertigo can persist until the diver reaches the surface continuing the unequal pressures, which can damage the inner ear or ear drum.
Alternobaric vertigo is most pronounced when the diver is in the vertical position; the spinning is towards the ear with the higher pressure and tends to develop when the pressures differ by 60 cm of water or more.[4][5] Ear clearing may be a remedy. A similar vertigo can also occur as a result of unequal heating stimulation of one inner ear labyrinth over the other due to diving in a prone position in cold water - the undermost ear being stimulated.
## Diagnosis[edit]
In terms of diagnosis for alternobaric vertigo the medical history and physical examination, are important. Furthermore, Eustachian tube function testing is also performed[6]
## Management[edit]
This section is empty. You can help by adding to it. (December 2018)
## See also[edit]
* Underwater diving portal
* Vertigo – Type of dizziness where a person has the sensation of moving or surrounding objects moving
## References[edit]
1. ^ Wicks RE (January 1989). "Alternobaric vertigo: an aeromedical review". Aviat Space Environ Med. 60 (1): 67–72. PMID 2647073.
2. ^ a b Tjernström O (December 1974). "Function of the eustachian tubes in divers with a history of alternobaric vertigo". Undersea Biomed Res. 1 (4): 343–51. PMID 4469100. Retrieved 2008-07-04.
3. ^ Lundgren CEG, Tjernström O, Ornhagen H (September 1974). "Alternobaric vertigo and hearing disturbances in connection with diving: an epidemiologic study". Undersea Biomed Res. 1 (3): 251–8. PMID 4469094. Retrieved 2008-07-04.
4. ^ Edmonds, C. (1971). "Vertigo In Diving". Royal Australian Navy, School of Underwater Medicine. RANSUM-1-71. Retrieved 2008-04-25.
5. ^ Ross HE (December 1976). "The direction of apparent movement during transient pressure vertigo". Undersea Biomed Res. 3 (4): 403–10. PMID 10897867. Retrieved 2008-07-04.
6. ^ Francescon, Daniel; Cooper, Jeffrey S. (2018). "Diving, Alternobaric Vertigo". StatPearls. StatPearls Publishing. Retrieved 8 December 2018.
* v
* t
* e
Underwater diving
* Diving modes
* Atmospheric pressure diving
* Freediving
* Saturation diving
* Scuba diving
* Snorkeling
* Surface oriented diving
* Surface-supplied diving
* Unmanned diving
Diving equipment
* Cleaning and disinfection of personal diving equipment
* Human factors in diving equipment design
Basic equipment
* Diving mask
* Snorkel
* Swimfin
Breathing gas
* Bailout gas
* Bottom gas
* Breathing air
* Decompression gas
* Emergency gas supply
* Heliox
* Nitrox
* Oxygen
* Travel gas
* Trimix
Buoyancy and
trim equipment
* Buoyancy compensator
* Power inflator
* Dump valve
* Diving weighting system
* Ankle weights
* Integrated weights
* Trim weights
* Weight belt
Decompression
equipment
* Decompression buoy
* Decompression cylinder
* Decompression trapeze
* Dive computer
* Diving shot
* Jersey upline
* Jonline
Diving suit
* Atmospheric diving suit
* Dry suit
* Sladen suit
* Standard diving suit
* Rash vest
* Wetsuit
* Dive skins
* Hot-water suit
Helmets
and masks
* Anti-fog
* Diving helmet
* Free-flow helmet
* Lightweight demand helmet
* Orinasal mask
* Reclaim helmet
* Shallow water helmet
* Standard diving helmet
* Diving mask
* Band mask
* Full-face mask
* Half mask
Instrumentation
* Bottom timer
* Depth gauge
* Dive computer
* Dive timer
* Diving watch
* Helium release valve
* Pneumofathometer
* Submersible pressure gauge
Mobility
equipment
* Diving bell
* Closed bell
* Wet bell
* Diving stage
* Swimfin
* Monofin
* PowerSwim
* Towboard
Diver
propulsion
vehicle
* Advanced SEAL Delivery System
* Cosmos CE2F series
* Dry Combat Submersible
* Human torpedo
* Motorised Submersible Canoe
* Necker Nymph
* R-2 Mala-class swimmer delivery vehicle
* SEAL Delivery Vehicle
* Shallow Water Combat Submersible
* Siluro San Bartolomeo
* Wet Nellie
* Wet sub
Safety
equipment
* Alternative air source
* Octopus regulator
* Pony bottle
* Bolt snap
* Buddy line
* Dive light
* Diver's cutting tool
* Diver's knife
* Diver's telephone
* Through-water communications
* Diving bell
* Diving safety harness
* Emergency gas supply
* Bailout block
* Bailout bottle
* Lifeline
* Screw gate carabiner
* Emergency locator beacon
* Rescue tether
* Safety helmet
* Shark-proof cage
* Snoopy loop
* Navigation equipment
* Distance line
* Diving compass
* Dive reel
* Line marker
* Surface marker buoy
* Silt screw
Underwater
breathing
apparatus
* Atmospheric diving suit
* Diving cylinder
* Burst disc
* Diving cylinder valve
* Diving helmet
* Reclaim helmet
* Diving regulator
* Mechanism of diving regulators
* Regulator malfunction
* Regulator freeze
* Single-hose regulator
* Twin-hose regulator
* Full face diving mask
Open-circuit
scuba
* Scuba set
* Bailout bottle
* Decompression cylinder
* Independent doubles
* Manifolded twin set
* Scuba manifold
* Pony bottle
* Scuba configuration
* Sidemount
* Sling cylinder
Diving
rebreathers
* Carbon dioxide scrubber
* Carleton CDBA
* CDLSE
* Cryogenic rebreather
* CUMA
* DSEA
* Dolphin
* Electro-galvanic oxygen sensor
* FROGS
* Halcyon PVR-BASC
* Halcyon RB80
* IDA71
* Interspiro DCSC
* KISS
* LAR-5
* LAR-6
* LAR-V
* LARU
* Porpoise
* Ray
* Siebe Gorman CDBA
* Siva
* Viper
Surface-supplied
diving equipment
* Air line
* Diver's umbilical
* Diving air compressor
* Gas panel
* Hookah
* Scuba replacement
* Sea Trek
* Snuba
* Standard diving dress
Escape set
* Davis Submerged Escape Apparatus
* Momsen lung
* Steinke hood
* Submarine Escape Immersion Equipment
*
Diving
equipment
manufacturers
* AP Diving
* Apeks
* Aqua Lung America
* Aqua Lung/La Spirotechnique
* Beuchat
* René Cavalero
* Cis-Lunar
* Cressi-Sub
* Dacor
* DESCO
* Dive Xtras
* Divex
* Diving Unlimited International
* Drägerwerk
* Fenzy
* Maurice Fernez
* Technisub
* Oscar Gugen
* Heinke
* HeinrichsWeikamp
* Johnson Outdoors
* Mares
* Morse Diving
* Nemrod
* Oceanic Worldwide
* Porpoise
* Sub Sea Systems
* Shearwater Research
* Siebe Gorman
* Submarine Products
* Suunto
Diving support equipment
Access equipment
* Boarding stirrup
* Diver lift
* Diving bell
* Diving ladder
* Diving platform (scuba)
* Diving stage
* Downline
* Jackstay
* Launch and recovery system
* Messenger line
* Moon pool
Breathing gas
handling
* Air filtration
* Activated carbon
* Hopcalite
* Molecular sieve
* Silica gel
* Booster pump
* Carbon dioxide scrubber
* Cascade filling system
* Diver's pump
* Diving air compressor
* Diving air filter
* Water separator
* High pressure breathing air compressor
* Low pressure breathing air compressor
* Gas blending
* Gas blending for scuba diving
* Gas panel
* Gas reclaim system
* Gas storage bank
* Gas storage quad
* Gas storage tube
* Helium analyzer
* Nitrox production
* Membrane gas separation
* Pressure swing adsorption
* Oxygen analyser
* Oxygen compatibility
Decompression
equipment
* Built-in breathing system
* Decompression tables
* Diving bell
* Bell cursor
* Closed bell
* Clump weight
* Launch and recovery system
* Wet bell
* Diving chamber
* Diving stage
* Recreational Dive Planner
* Saturation system
Platforms
* Dive boat
* Canoe and kayak diving
* Combat Rubber Raiding Craft
* Liveaboard
* Subskimmer
* Diving support vessel
* HMS Challenger (K07)
Underwater
habitat
* Aquarius Reef Base
* Continental Shelf Station Two
* Helgoland Habitat
* Jules' Undersea Lodge
* Scott Carpenter Space Analog Station
* SEALAB
* Tektite habitat
Remotely operated
underwater vehicles
* 8A4-class ROUV
* ABISMO
* Atlantis ROV Team
* CURV
* Deep Drone
* Épaulard
* Global Explorer ROV
* Goldfish-class ROUV
* Kaikō ROV
* Kaşif ROUV
* Long-Term Mine Reconnaissance System
* Mini Rover ROV
* OpenROV
* ROV KIEL 6000
* ROV PHOCA
* Scorpio ROV
* Sea Dragon-class ROV
* Seabed tractor
* Seafox drone
* Seahorse ROUV
* SeaPerch
* SJT-class ROUV
* T1200 Trenching Unit
* VideoRay UROVs
Safety equipment
* Diver down flag
* Diving shot
* Hyperbaric lifeboat
* Hyperbaric stretcher
* Jackstay
* Jonline
* Reserve gas supply
General
* Diving spread
* Air spread
* Saturation spread
* Hot water system
* Sonar
* Underwater acoustic positioning system
* Underwater acoustic communication
Freediving
Activities
* Aquathlon
* Apnoea finswimming
* Freediving
* Haenyeo
* Pearl hunting
* Ama
* Snorkeling
* Spearfishing
* Underwater football
* Underwater hockey
* Underwater ice hockey
* Underwater rugby
* Underwater target shooting
Competitions
* Nordic Deep
* Vertical Blue
* Disciplines
* Constant weight (CWT)
* Constant weight without fins (CNF)
* Dynamic apnea (DYN)
* Dynamic apnea without fins (DNF)
* Free immersion (FIM)
* No-limits apnea (NLT)
* Static apnea (STA)
* Skandalopetra diving
* Variable weight apnea (VWT)
* Variable weight apnea without fins
Equipment
* Diving mask
* Diving suit
* Hawaiian sling
* Polespear
* Snorkel (swimming)
* Speargun
* Swimfins
* Monofin
* Water polo cap
Freedivers
* Deborah Andollo
* Peppo Biscarini
* Sara Campbell
* Derya Can Göçen
* Goran Čolak
* Carlos Coste
* Robert Croft
* Mandy-Rae Cruickshank
* Yasemin Dalkılıç
* Leonardo D'Imporzano
* Flavia Eberhard
* Şahika Ercümen
* Emma Farrell
* Francisco Ferreras
* Pierre Frolla
* Flavia Eberhard
* Mehgan Heaney-Grier
* Elisabeth Kristoffersen
* Loïc Leferme
* Enzo Maiorca
* Jacques Mayol
* Audrey Mestre
* Karol Meyer
* Stéphane Mifsud
* Alexey Molchanov
* Natalia Molchanova
* Dave Mullins
* Patrick Musimu
* Guillaume Néry
* Herbert Nitsch
* Umberto Pelizzari
* Annelie Pompe
* Michal Risian
* Stig Severinsen
* Tom Sietas
* Aharon Solomons
* Martin Štěpánek
* Walter Steyn
* Tanya Streeter
* William Trubridge
* Devrim Cenk Ulusoy
* Danai Varveri
* Alessia Zecchini
* Nataliia Zharkova
Hazards
* Barotrauma
* Drowning
* Freediving blackout
* Deep-water blackout
* Shallow-water blackout
* Hypercapnia
* Hypothermia
Historical
* Ama
* Octopus wrestling
* Swimming at the 1900 Summer Olympics – Men's underwater swimming
Organisations
* AIDA International
* Scuba Schools International
* Australian Underwater Federation
* British Freediving Association
* Confédération Mondiale des Activités Subaquatiques
* Fédération Française d'Études et de Sports Sous-Marins
* Performance Freediving International
Professional diving
Occupations
* Ama
* Commercial diver
* Commercial offshore diver
* Hazmat diver
* Divemaster
* Diving instructor
* Diving safety officer
* Diving superintendent
* Diving supervisor
* Haenyeo
* Media diver
* Police diver
* Public safety diver
* Scientific diver
* Underwater archaeologist
Military diving
* Army engineer diver
* Clearance diver
* Frogman
* List of military diving units
* Royal Navy ships diver
* Special Boat Service
* United States military divers
* U.S. Navy diver
* U.S.Navy master diver
* United States Navy SEALs
* Underwater Demolition Team
Underwater work
* Commercial offshore diving
* Dive leader
* Diver training
* Recreational diver training
* Hyperbaric welding
* Media diving
* Nondestructive testing
* Pearl hunting
* Police diving
* Potable water diving
* Public safety diving
* Scientific diving
* Ships husbandry
* Sponge diving
* Submarine pipeline
* Underwater archaeology
* Archaeology of shipwrecks
* Underwater construction
* Offshore construction
* Underwater demolition
* Underwater photography
* Underwater search and recovery
* Underwater videography
Salvage diving
* SS Egypt
* Kronan
* La Belle
* SS Laurentic
* RMS Lusitania
* Mars
* Mary Rose
* USS Monitor
* HMS Royal George
* Vasa
Diving contractors
* COMEX
* Helix Energy Solutions Group
Tools & equipment
* Abrasive waterjet
* Airlift
* Baited remote underwater video
* In-water surface cleaning
* Brush cart
* Cavitation cleaning
* Pressure washing
* Pigging
* Lifting bag
* Remotely operated underwater vehicle
* Thermal lance
* Tremie
* Water jetting
Underwater
weapons
* Limpet mine
* Speargun
* Hawaiian sling
* Polespear
Underwater
firearm
* Gyrojet
* Mk 1 Underwater Defense Gun
* Powerhead
* Underwater pistols
* Heckler & Koch P11
* SPP-1 underwater pistol
* Underwater revolvers
* AAI underwater revolver
* Underwater rifles
* ADS amphibious rifle
* APS underwater rifle
* ASM-DT amphibious rifle
Recreational diving
Specialties
* Altitude diving
* Cave diving
* Deep diving
* Ice diving
* Muck diving
* Open-water diving
* Rebreather diving
* Sidemount diving
* Solo diving
* Technical diving
* Underwater photography
* Wreck diving
Diver
organisations
* British Sub-Aqua Club (BSAC)
* Cave Divers Association of Australia (CDAA)
* Cave Diving Group (CDG)
* Comhairle Fo-Thuinn (CFT)
* Confédération Mondiale des Activités Subaquatiques (CMAS)
* Federación Española de Actividades Subacuáticas (FEDAS)
* Fédération Française d'Études et de Sports Sous-Marins (FFESSM)
* International Association for Handicapped Divers (IAHD)
* National Association for Cave Diving (NACD)
* Woodville Karst Plain Project (WKPP)
Diving tourism
industry
* Dive center
* Environmental impact of recreational diving
* Scuba diving tourism
* Shark tourism
* Sinking ships for wreck diving sites
Diving events
and festivals
* Diversnight
* Underwater Bike Race
Recreational
dive sites
Reef diving
regions
* Aliwal Shoal Marine Protected Area
* Arrecifes de Cozumel National Park
* Edmonds Underwater Park
* Great Barrier Reef
* iSimangaliso Marine Protected Area
* Poor Knights Islands
* Table Mountain National Park Marine Protected Area
Reef dive
sites
* Artificial reef
* Gibraltar Artificial Reef
* Shark River Reef
* Osborne Reef
* Fanadir
* Gamul Kebir
* Palancar Reef
* Underwater artworks
* Cancún Underwater Museum
* Christ of the Abyss
* Molinere Underwater Sculpture Park
Wreck diving
regions
* Chuuk Lagoon
* Edmonds Underwater Park
* Finger Lakes Underwater Preserve Association
* Maritime Heritage Trail – Battle of Saipan
* Michigan Underwater Preserves
* Robben Island Marine Protected Area
* Table Mountain National Park Marine Protected Area
* Tulagi
* Tulamben
* Whitefish Point Underwater Preserve
* Wreck Alley, San Diego
Wreck dive
sites
* HMS A1
* HMS A3
* USS Aaron Ward
* Abessinia
* Aeolian Sky
* Albert C. Field
* Andrea Doria
* Antilla
* Antilles
* Aquila
* USS Arkansas
* Bianca C.
* SS Binnendijk
* HMS Boadicea
* Booya
* HMSAS Bloemfontein
* Breda
* HMAS Brisbane
* HMHS Britannic
* Bungsberg
* HMAS Canberra
* Carl D. Bradley
* Carnatic
* SMS Dresden
* Dunraven
* Eastfield
* HMT Elk
* Ellengowan
* RMS Empress of Ireland
* HMS Falmouth
* Fifi
* SS Francisco Morazan
* Fujikawa Maru
* Fumizuki
* SATS General Botha
* USNS General Hoyt S. Vandenberg
* HMS Ghurka
* Glen Strathallan
* SAS Good Hope
* Gothenburg
* Herzogin Cecilie
* Hilma Hooker
* Hispania
* HMS Hood
* HMAS Hobart
* Igara
* James Eagan Layne
* Captain Keith Tibbetts
* King Cruiser
* SMS Kronprinz
* Kyarra
* HMS Laforey
* USAT Liberty
* Louis Sheid
* USS LST-507
* SMS Markgraf
* Mikhail Lermontov
* HMS M2
* Maine
* Maloja
* HMS Maori
* Marguerite
* SS Mauna Loa
* USAT Meigs
* Mendi
* USCGC Mohawk
* Mohegan
* RMS Moldavia
* HMS Montagu
* MV RMS Mulheim
* Nagato
* Oceana
* USS Oriskany
* Oslofjord
* P29
* P31
* Pedernales
* Persier
* HMAS Perth
* SAS Pietermaritzburg
* Piłsudski
* Pool Fisher
* HMS Port Napier
* Preußen
* President Coolidge
* PS Queen Victoria
* Radaas
* Rainbow Warrior
* RMS Rhone
* Rondo
* Rosehill
* Rotorua
* Royal Adelaide
* Royal Charter
* Rozi
* HMS Safari
* Salem Express
* USS Saratoga
* USS Scuffle
* HMS Scylla
* HMS Sidon
* USS Spiegel Grove
* Stanegarth
* Stanwood
* Stella
* HMAS Swan
* USS Tarpon
* Thesis
* Thistlegorm
* Toa Maru
* Torrey Canyon
* SAS Transvaal
* U-40
* U-352
* U-1195
* Um El Faroud
* Varvassi
* Walter L M Russ
* Washingtonian (1913)
* HMNZS Wellington
* USS Yancey
* Yongala
* Zenobia
* Zealandia
* Zingara
Cave diving
sites
* Blauhöhle
* Chinhoyi Caves
* Devil's Throat at Punta Sur
* Engelbrecht Cave
* Fossil Cave
* Jordbrugrotta
* Piccaninnie Ponds
* Pluragrotta
* Pollatoomary
* Sistema Ox Bel Ha
* Sistema Sac Actun
* Sistema Dos Ojos
* Sistema Nohoch Nah Chich
Freshwater
dives
* Dutch Springs
* Ewens Ponds
* Little Blue Lake
Training sites
* Capernwray Dive Centre
* Deepspot
* National Diving and Activity Centre
* Stoney Cove
Open ocean
diving
* Blue-water diving
* Black-water diving
Diving safety
* Human factors in diving equipment design
* Human factors in diving safety
* Life-support system
* Safety-critical system
* Scuba diving fatalities
Diving
hazards
* List of diving hazards and precautions
* Environmental
* Current
* Delta-P
* Entanglement hazard
* Overhead
* Silt out
* Wave action
* Equipment
* Freeflow
* Use of breathing equipment in an underwater environment
* Failure of diving equipment other than breathing apparatus
* Single point of failure
* Physiological
* Cold shock response
* Decompression
* Nitrogen narcosis
* Oxygen toxicity
* Seasickness
* Uncontrolled decompression
* Diver behaviour and competence
* Lack of competence
* Overconfidence effect
* Panic
* Task loading
* Trait anxiety
* Willful violation
Consequences
* Barotrauma
* Decompression sickness
* Drowning
* Hypothermia
* Hypoxia
* Hypercapnia
* Hyperthermia
Diving
procedures
* Ascending and descending
* Emergency ascent
* Boat diving
* Canoe and kayak diving
* Buddy diving
* buddy check
* Decompression
* Decompression practice
* Pyle stop
* Ratio decompression
* Dive briefing
* Dive log
* Dive planning
* Scuba gas planning
* Diver communications
* Diving hand signals
* Diving line signals
* Diver voice communications
* Diver rescue
* Diver training
* Doing It Right
* Drift diving
* Gas blending for scuba diving
* Night diving
* Solo diving
* Water safety
Risk
management
* Checklist
* Hazard identification and risk assessment
* Hazard analysis
* Job safety analysis
* Risk assessment
* Risk control
* Hierarchy of hazard controls
* Incident pit
* Lockout–tagout
* Permit To Work
* Redundancy
* Safety data sheet
* Situation awareness
Diving team
* Bellman
* Chamber operator
* Diver medical technician
* Diver's attendant
* Diving supervisor
* Diving systems technician
* Gas man
* Life support technician
* Stand-by diver
Equipment
safety
* Breathing gas quality
* Testing and inspection of diving cylinders
* Hydrostatic test
* Sustained load cracking
* Diving regulator
* Breathing performance of regulators
Occupational
safety and
health
* Approaches to safety
* Job safety analysis
* Risk assessment
* Toolbox talk
* Housekeeping
* Association of Diving Contractors International
* Code of practice
* Contingency plan
* Diving regulations
* Emergency procedure
* Emergency response plan
* Evacuation plan
* Hazardous Materials Identification System
* Hierarchy of hazard controls
* Administrative controls
* Engineering controls
* Hazard elimination
* Hazard substitution
* Personal protective equipment
* International Marine Contractors Association
* Occupational hazard
* Biological hazard
* Chemical hazard
* Physical hazard
* Psychosocial hazard
* Occupational hygiene
* Exposure assessment
* Occupational exposure limit
* Workplace health surveillance
* Safety culture
* Code of practice
* Diving safety officer
* Diving superintendent
* Health and safety representative
* Operations manual
* Safety meeting
* Standard operating procedure
Diving medicine
Diving
disorders
* List of signs and symptoms of diving disorders
* Cramp
* Motion sickness
* Surfer's ear
Pressure
related
* Alternobaric vertigo
* Barostriction
* Barotrauma
* Air embolism
* Aerosinusitis
* Barodontalgia
* Dental barotrauma
* Pulmonary barotrauma
* Compression arthralgia
* Decompression illness
* Dysbarism
Oxygen
* Freediving blackout
* Hyperoxia
* Hypoxia
* Oxygen toxicity
Inert gases
* Avascular necrosis
* Decompression sickness
* Isobaric counterdiffusion
* Taravana
* Dysbaric osteonecrosis
* High-pressure nervous syndrome
* Hydrogen narcosis
* Nitrogen narcosis
Carbon dioxide
* Hypercapnia
* Hypocapnia
Breathing gas
contaminants
* Carbon monoxide poisoning
Immersion
related
* Asphyxia
* Drowning
* Hypothermia
* Immersion diuresis
* Instinctive drowning response
* Laryngospasm
* Salt water aspiration syndrome
* Swimming-induced pulmonary edema
Treatment
* Demand valve oxygen therapy
* First aid
* Hyperbaric medicine
* Hyperbaric treatment schedules
* In-water recompression
* Oxygen therapy
* Therapeutic recompression
Personnel
* Diving Medical Examiner
* Diving Medical Practitioner
* Diving Medical Technician
* Hyperbaric nursing
Screening
* Atrial septal defect
* Effects of drugs on fitness to dive
* Fitness to dive
* Psychological fitness to dive
Research
Researchers in
diving physiology
and medicine
* Arthur J. Bachrach
* Albert R. Behnke
* Paul Bert
* George F. Bond
* Robert Boyle
* Albert A. Bühlmann
* John R. Clarke
* Guybon Chesney Castell Damant
* Kenneth William Donald
* William Paul Fife
* John Scott Haldane
* Robert William Hamilton Jr.
* Leonard Erskine Hill
* Brian Andrew Hills
* Felix Hoppe-Seyler
* Christian J. Lambertsen
* Simon Mitchell
* Charles Momsen
* John Rawlins R.N.
* Charles Wesley Shilling
* Edward D. Thalmann
* Jacques Triger
Diving medical
research
organisations
* Aerospace Medical Association
* Divers Alert Network (DAN)
* Diving Diseases Research Centre (DDRC)
* Diving Medical Advisory Council (DMAC)
* European Diving Technology Committee (EDTC)
* European Underwater and Baromedical Society (EUBS)
* National Board of Diving and Hyperbaric Medical Technology
* Naval Submarine Medical Research Laboratory
* Royal Australian Navy School of Underwater Medicine
* Rubicon Foundation
* South Pacific Underwater Medicine Society (SPUMS)
* Southern African Underwater and Hyperbaric Medical Association (SAUHMA)
* Undersea and Hyperbaric Medical Society (UHMS)
* United States Navy Experimental Diving Unit (NEDU)
Law
* Civil liability in recreational diving
* Diving regulations
* Duty of care
* List of legislation regulating underwater diving
* Investigation of diving accidents
* UNESCO Convention on the Protection of the Underwater Cultural Heritage
History of underwater diving
* History of decompression research and development
* History of scuba diving
* List of researchers in underwater diving
* Timeline of diving technology
* Underwater diving in popular culture
Archeological
sites
* SS Commodore
* USS Monitor
* Queen Anne's Revenge
* Whydah Gally
Underwater art
and artists
* The Diver
* Jason deCaires Taylor
Engineers
and inventors
* William Beebe
* Georges Beuchat
* John R. Clarke
* Jacques Cousteau
* Charles Anthony Deane
* John Deane
* Ted Eldred
* Henry Fleuss
* Émile Gagnan
* Joseph-Martin Cabirol
* Christian J. Lambertsen
* Yves Le Prieur
* John Lethbridge
* Ernest William Moir
* Joseph Salim Peress
* Auguste Piccard
* Willard Franklyn Searle
* Augustus Siebe
* Jacques Triger
Equipment
* Aqua-Lung
* RV Calypso
* SP-350 Denise
* Nikonos
* Porpoise regulator
* Standard diving dress
* Vintage scuba
Military and
covert operations
* Raid on Alexandria (1941)
* Sinking of the Rainbow Warrior
Scientific projects
* 1992 cageless shark-diving expedition
* Mission 31
Incidents
Dive boat incidents
* Sinking of MV Conception
* Fire on MV Red Sea Aggressor
Diver rescues
* Alpazat cave rescue
* Tham Luang cave rescue
Early diving
* John Day (carpenter)
* Charles Spalding
* Ebenezer Watson
Freediving fatalities
* Loïc Leferme
* Audrey Mestre
* Nicholas Mevoli
* Natalia Molchanova
Offshore
diving incidents
* Byford Dolphin diving bell accident
* Drill Master diving accident
* Star Canopus diving accident
* Stena Seaspread diving accident
* Venture One diving accident
* Waage Drill II diving accident
* Wildrake diving accident
Professional
diving fatalities
* Roger Baldwin
* John Bennett
* Victor F. Guiel Jr.
* Craig M. Hoffman
* Peter Henry Michael Holmes
* Johnson Sea Link accident
* Edwin Clayton Link
* Gerard Anthony Prangley
* Pier Skipness
* Robert John Smyth
* Albert D. Stover
* Richard A. Walker
* Lothar Michael Ward
* Joachim Wendler
* Bradley Westell
* Arne Zetterström
Scuba diving
fatalities
* Ricardo Armbruster
* Allan Bridge
* David Bright
* Berry L. Cannon
* Cotton Coulson
* Cláudio Coutinho
* E. Yale Dawson
* Deon Dreyer
* Milan Dufek
* Sheck Exley
* Maurice Fargues
* Fernando Garfella Palmer
* Guy Garman
* Steve Irwin
* Jim Jones
* Henry Way Kendall
* Artur Kozłowski
* Chris and Chrissy Rouse
* Kirsty MacColl
* Agnes Milowka
* François de Roubaix
* Dave Shaw
* Wesley C. Skiles
* Dewey Smith
* Rob Stewart
* Esbjörn Svensson
* Josef Velek
Publications
Manuals
* NOAA Diving Manual
* U.S. Navy Diving Manual
* Basic Cave Diving: A Blueprint for Survival
* Underwater Handbook
* Bennett and Elliott's physiology and medicine of diving
* Encyclopedia of Recreational Diving
* The new science of skin and scuba diving
* Professional Diver's Handbook
* Basic Scuba
Standards and
Codes of Practice
* Code of Practice for Scientific Diving (UNESCO)
* DIN 7876
* IMCA Code of Practice for Offshore Diving
* ISO 24801 Recreational diving services — Requirements for the training of recreational scuba divers
General non-fiction
* The Darkness Beckons
* Goldfinder
* The Last Dive
* Shadow Divers
* The Silent World: A Story of Undersea Discovery and Adventure
Research
* List of Divers Alert Network publications
Dive guides
*
Training and registration
Diver
training
* Competence and assessment
* Competency-based learning
* Refresher training
* Skill assessment
* Diver training standard
* Diving instructor
* Diving school
* Occupational diver training
* Commercial diver training
* Military diver training
* Public safety diver training
* Scientific diver training
* Recreational diver training
* Introductory diving
* Teaching method
* Muscle memory
* Overlearning
* Stress exposure training
Skills
* Combat sidestroke
* Diver navigation
* Diver trim
* Ear clearing
* Frenzel maneuver
* Valsalva maneuver
* Finning techniques
* Scuba skills
* Buddy breathing
* Low impact diving
* Diamond Reef System
* Surface-supplied diving skills
* Underwater searches
Recreational
scuba
certification
levels
Core diving skills
* Advanced Open Water Diver
* Autonomous diver
* CMAS* scuba diver
* CMAS** scuba diver
* Introductory diving
* Low Impact Diver
* Master Scuba Diver
* Open Water Diver
* Supervised diver
Leadership skills
* Dive leader
* Divemaster
* Diving instructor
* Master Instructor
Specialist skills
* Rescue Diver
* Solo diver
Diver training
certification
and registration
organisations
* European Underwater Federation (EUF)
* International Diving Regulators and Certifiers Forum (IDRCF)
* International Diving Schools Association (IDSA)
* International Marine Contractors Association (IMCA)
* List of diver certification organizations
* National Oceanic and Atmospheric Administration (NOAA)
* Nautical Archaeology Society
* Universal Referral Program
* World Recreational Scuba Training Council (WRSTC)
Commercial diver
certification
authorities
* Australian Diver Accreditation Scheme (ADAS)
* Commercial diver registration in South Africa
* Divers Institute of Technology
* Health and Safety Executive (HSE)
* Department of Employment and Labour
Commercial diving
schools
* Divers Academy International
* Norwegian diver school
Free-diving
certification
agencies
* AIDA International (AIDA)
* Confédération Mondiale des Activités Subaquatiques (CMAS)
* Performance Freediving International (PI)
* Scuba Schools International (SSI)
Recreational scuba
certification
agencies
* American Canadian Underwater Certifications (ACUC)
* American Nitrox Divers International (ANDI)
* Association nationale des moniteurs de plongée (ANMP)
* British Sub-Aqua Club (BSAC)
* Comhairle Fo-Thuinn (CFT)
* Confédération Mondiale des Activités Subaquatiques (CMAS)
* Federación Española de Actividades Subacuáticas (FEDAS)
* Fédération Française d'Études et de Sports Sous-Marins (FFESSM)
* Federazione Italiana Attività Subacquee (FIAS)
* Global Underwater Explorers (GUE)
* International Association for Handicapped Divers (IAHD)
* International Association of Nitrox and Technical Divers (IANTD)
* International Diving Educators Association (IDEA)
* Israeli Diving Federation (TIDF)
* National Academy of Scuba Educators (NASE)
* National Association of Underwater Instructors (NAUI)
* Nederlandse Onderwatersport Bond (NOB)
* Professional Association of Diving Instructors (PADI)
* Professional Diving Instructors Corporation (PDIC)
* Sub-Aqua Association (SAA)
* Scuba Diving International (SDI)
* Scuba Educators International (SEI)
* Scottish Sub Aqua Club (ScotSAC)
* Scuba Schools International (SSI)
* Türkiye Sualtı Sporları Federasyonu (TSSF)
* United Diving Instructors (UDI)
* YMCA SCUBA Program
Scientific diver
certification
authorities
* American Academy of Underwater Sciences (AAUS)
* CMAS Scientific Committee
Technical
certification
agencies
* American Nitrox Divers International (ANDI)
* British Sub-Aqua Club (BSAC)
* Confédération Mondiale des Activités Subaquatiques (CMAS)
* Diving Science and Technology (DSAT)
* Federazione Italiana Attività Subacquee (FIAS)
* International Association of Nitrox and Technical Divers (IANTD)
* Professional Association of Diving Instructors (PADI)
* Professional Diving Instructors Corporation (PDIC)
* Trimix Scuba Association (TSA)
* Technical Extended Range (TXR)
Cave
diving
* Cave Divers Association of Australia (CDAA)
* Cave Diving Group (CDG)
* Global Underwater Explorers (GUE)
* National Association for Cave Diving (NACD)
* National Speleological Society#Cave Diving Group (CDG)
* National Association of Underwater Instructors (NAUI)
* Technical Diving International (TDI)
Underwater sports
Surface snorkeling
* Finswimming
Snorkeling/breath-hold
* Spearfishing
* Underwater football
* Underwater hockey
* Australia
* Turkey
* Underwater rugby
* Colombia
* United States
* Underwater target shooting
Breath-hold
* Aquathlon
* Apnoea finswimming
* Freediving
* Underwater ice hockey
Open Circuit Scuba
* Immersion finswimming
* Sport diving
* Underwater cycling
* Underwater orienteering
* Underwater photography
Rebreather
* Underwater photography
Sports governing
organisations
and federations
* International
* AIDA International
* Confédération Mondiale des Activités Subaquatiques)
* National
* AIDA Hellas
* Australian Underwater Federation
* British Freediving Association
* British Octopush Association
* British Underwater Sports Association
* Comhairle Fo-Thuinn
* Federación Española de Actividades Subacuáticas
* Fédération Française d'Études et de Sports Sous-Marins
* South African Underwater Sports Federation
* Türkiye Sualtı Sporları Federasyonu
* Underwater Society of America)
Competitions
* 14th CMAS Underwater Photography World Championship
Underwater divers
Pioneers
of diving
* Eduard Admetlla i Lázaro
* Aquanaut
* James F. Cahill
* Jacques Cousteau
* Billy Deans
* Dottie Frazier
* Hans Hass
* Dick Rutkowski
* Teseo Tesei
* Arne Zetterström
Underwater
scientists
archaeologists and
environmentalists
* Michael Arbuthnot
* Robert Ballard
* George Bass
* Mensun Bound
* Louis Boutan
* Hugh Bradner
* Cathy Church
* Eugenie Clark
* James P. Delgado
* Sylvia Earle
* John Christopher Fine
* George R. Fischer
* Anders Franzén
* Honor Frost
* Fernando Garfella Palmer
* David Gibbins
* Graham Jessop
* Swietenia Puspa Lestari
* Pilar Luna
* Robert F. Marx
* Anna Marguerite McCann
* Innes McCartney
* Charles T. Meide
* David Moore
* Mark M. Newell
* Lyuba Ognenova-Marinova
* John Peter Oleson
* Mendel L. Peterson
* Richard Pyle
* William R. Royal
* Margaret Rule
* Gunter Schöbel
* Stephanie Schwabe
* Myriam Seco
* E. Lee Spence
* Robert Sténuit
* Peter Throckmorton
Scuba record
holders
* Pascal Bernabé
* Jim Bowden
* Mark Ellyatt
* Sheck Exley
* Nuno Gomes
* Claudia Serpieri
* Krzysztof Starnawski
Underwater
filmmakers
and presenters
* Samir Alhafith
* David Attenborough
* Ramón Bravo
* Jean-Michel Cousteau
* Richie Kohler
* Ivan Tors
* Andrew Wight
Underwater
photographers
* Tamara Benitez
* Georges Beuchat
* Adrian Biddle
* Jonathan Bird
* Eric Cheng
* Neville Coleman
* Jacques Cousteau
* John D. Craig
* Ben Cropp
* Bernard Delemotte
* David Doubilet
* John Christopher Fine
* Dermot FitzGerald
* Rodney Fox
* Ric Frazier
* Stephen Frink
* Peter Gimbel
* Monty Halls
* Hans Hass
* Henry Way Kendall
* Rudie Kuiter
* Joseph B. MacInnis
* Luis Marden
* Agnes Milowka
* Noel Monkman
* Steve Parish
* Zale Parry
* Pierre Petit
* Leni Riefenstahl
* Peter Scoones
* Brian Skerry
* Wesley C. Skiles
* E. Lee Spence
* Philippe Tailliez
* Ron Taylor
* Valerie Taylor
* Albert Tillman
* John Veltri
* Stan Waterman
* Michele Westmorland
* John Ernest Williamson
* J. Lamar Worzel
Underwater
explorers
* Caves
* Graham Balcombe
* Sheck Exley
* Martyn Farr
* Jochen Hasenmayer
* Jill Heinerth
* Jarrod Jablonski
* William Hogarth Main
* Tom Mount
* Jack Sheppard
* Bill Stone
* Reefs
* * Wrecks
* Leigh Bishop
* John Chatterton
* Clive Cussler
* Bill Nagle
* Aristotelis Zervoudis
Aquanauts
* Andrew Abercromby
* Joseph M. Acaba
* Clayton Anderson
* Richard R. Arnold
* Serena Auñón-Chancellor
* Michael Barratt (astronaut)
* Robert L. Behnken
* Randolph Bresnik
* Timothy J. Broderick
* Justin Brown
* Berry L. Cannon
* Scott Carpenter
* Gregory Chamitoff
* Steve Chappell
* Catherine Coleman
* Robin Cook
* Craig B. Cooper
* Fabien Cousteau
* Philippe Cousteau
* Timothy Creamer
* Jonathan Dory
* Pedro Duque
* Sylvia Earle
* Jeanette Epps
* Sheck Exley
* Albert Falco
* Andrew J. Feustel
* Michael Fincke
* Satoshi Furukawa
* Ronald J. Garan Jr.
* Michael L. Gernhardt
* Christopher E. Gerty
* David Gruber
* Chris Hadfield
* Jeremy Hansen
* José M. Hernández
* John Herrington
* Paul Hill
* Akihiko Hoshide
* Mark Hulsbeck
* Emma Hwang
* Norishige Kanai
* Les Kaufman
* Scott Kelly
* Karen Kohanowich
* Timothy Kopra
* Dominic Landucci
* Jon Lindbergh
* Kjell N. Lindgren
* Michael López-Alegría
* Joseph B. MacInnis
* Sandra Magnus
* Thomas Marshburn
* Matthias Maurer
* K. Megan McArthur
* Craig McKinley
* Jessica Meir
* Simone Melchior
* Dorothy Metcalf-Lindenburger
* Andreas Mogensen
* Karen Nyberg
* John D. Olivas
* Takuya Onishi
* Luca Parmitano
* Nicholas Patrick
* Tim Peake
* Thomas Pesquet
* Marc Reagan
* Garrett Reisman
* Kathleen Rubins
* Dick Rutkowski
* Tara Ruttley
* David Saint-Jacques
* Josef Schmid
* Robert Sheats
* Dewey Smith
* Steve Squyres
* Heidemarie Stefanyshyn-Piper
* Robert Sténuit
* Hervé Stevenin
* Nicole Stott
* James Talacek
* Daniel M. Tani
* Robert Thirsk
* Bill Todd
* Mark T. Vande Hei
* Koichi Wakata
* Rex J. Walheim
* Shannon Walker
* John Morgan Wells
* Joachim Wendler
* Douglas H. Wheelock
* Peggy Whitson
* Dafydd Williams
* Jeffrey Williams
* Sunita Williams
* Gregory R. Wiseman
* Kimiya Yui
Writers and journalists
* Michael C. Barnette
* Victor Berge
* Philippe Diolé
* Gary Gentile
* Bret Gilliam
* Bob Halstead
* Trevor Jackson
* Steve Lewis
* John Mattera
Rescuers
* Craig Challen
* Richard Harris
* Rick Stanton
* John Volanthen
Frogmen
* Lionel Crabb
Commercial salvors
* Keith Jessop
Science of underwater diving
Diving
physics
* Breathing performance of regulators
* Buoyancy
* Archimedes' principle
* Neutral buoyancy
* Concentration
* Diffusion
* Molecular diffusion
* Force
* Oxygen fraction
* Permeation
* Psychrometric constant
* Solubility
* Henry's law
* Saturation
* Solution
* Supersaturation
* Surface tension
* Hydrophobe
* Surfactant
* Temperature
* Torricellian chamber
* Underwater acoustics
* Modulated ultrasound
* Underwater vision
* Snell's law
* Underwater computer vision
* Weight
* Apparent weight
Gas laws
* Amontons's law
* Boyle's law
* Charles's law
* Combined gas law
* Dalton's law
* Gay-Lussac's law
* Ideal gas law
Pressure
* Absolute pressure
* Ambient pressure
* Atmospheric pressure
* Gauge pressure
* Hydrostatic pressure
* Metre sea water
* Partial pressure
Diving
physiology
* Artificial gills
* Cold shock response
* Diving reflex
* Equivalent narcotic depth
* Lipid
* Maximum operating depth
* Metabolism
* Physiological response to water immersion
* Tissue
* Underwater vision
Circulatory
system
* Blood shift
* Patent foramen ovale
* Perfusion
* Pulmonary circulation
* Systemic circulation
Decompression
theory
* Decompression models:
* Bühlmann decompression algorithm
* Haldane's decompression model
* Reduced gradient bubble model
* Thalmann algorithm
* Thermodynamic model of decompression
* Varying Permeability Model
* Equivalent air depth
* Equivalent narcotic depth
* Oxygen window in diving decompression
* Physiology of decompression
Respiration
* Blood–air barrier
* Breathing
* CO₂ retention
* Dead space
* Gas exchange
* Hypocapnia
* Respiratory exchange ratio
* Respiratory quotient
* Respiratory system
* Work of breathing
Diving
environment
Classification
* List of diving environments by type
* Altitude diving
* Benign water diving
* Confined water diving
* Deep diving
* Inland diving
* Inshore diving
* Muck diving
* Night diving
* Open-water diving
* Black-water diving
* Blue-water diving
* Penetration diving
* Cave diving
* Ice diving
* Wreck diving
* Recreational dive sites
* Underwater environment
Impact
* Environmental impact of recreational diving
* Low impact diving
Environmental
factors
* Algal bloom
* Currents:
* Current
* Longshore drift
* Ocean current
* Rip current
* Tidal race
* Undertow
* Upwelling
* Ekman transport
* Halocline
* Reef
* Coral reef
* Stratification
* Thermocline
* Tides
* Turbidity
* Wind wave
* Breaking wave
* Surf
* Surge
* Wave shoaling
Other
* Bathysphere
* Defense against swimmer incursions
* Diver detection sonar
* Offshore survey
* Underwater domain awareness
Awards and events
* Hans Hass Award
* International Scuba Diving Hall of Fame
* London Diving Chamber Dive Lectures
* NOGI Awards
Deep-submergence
vehicle
* Aluminaut
* DSV Alvin
* American submarine NR-1
* Bathyscaphe
* Archimède
* FNRS-2
* FNRS-3
* FNRS-4
* Harmony class bathyscaphe
* Sea Pole-class bathyscaphe
* Trieste II
* Deepsea Challenger
* Ictineu 3
* JAGO
* Jiaolong
* Konsul-class submersible
* DSV Limiting Factor
* Russian submarine Losharik
* Mir
* Nautile
* Pisces-class deep submergence vehicle
* DSV Sea Cliff
* DSV Shinkai
* DSV Shinkai 2000
* DSV Shinkai 6500
* DSV Turtle
* DSV-5 Nemo
Deep-submergence
rescue vehicle
* LR5
* LR7
* MSM-1
* Mystic-class deep-submergence rescue vehicle
* DSRV-1 Mystic
* DSRV-2 Avalon
* NATO Submarine Rescue System
* Priz-class deep-submergence rescue vehicle
* Russian deep submergence rescue vehicle AS-28
* Russian submarine AS-34
* ASRV Remora
* SRV-300
* Submarine Rescue Diving Recompression System
* Type 7103 DSRV
* URF (Swedish Navy)
Special
interest
groups
* Artificial Reef Society of British Columbia
* CMAS Europe
* Coral Reef Alliance
* Diving Equipment and Marketing Association
* Divers Alert Network
* Green Fins
* Historical Diving Society
* Karst Underwater Research
* Nautical Archaeology Program
* Nautical Archaeology Society
* Naval Air Command Sub Aqua Club
* Project AWARE
* Reef Check
* Reef Life Survey
* Rubicon Foundation
* Save Ontario Shipwrecks
* SeaKeys
* Sea Research Society
* Society for Underwater Historical Research
* Society for Underwater Technology
* Underwater Archaeology Branch, Naval History & Heritage Command
Submarine escape
and rescue
* Escape trunk
* International Submarine Escape and Rescue Liaison Office
* McCann Rescue Chamber
* Submarine Escape and Rescue system (Royal Swedish Navy)
* Submarine escape training facility
* Submarine Escape Training Facility (Australia)
* Submarine rescue ship
Neutral buoyancy
facilities for
Astronaut training
* Neutral Buoyancy Laboratory
* Neutral buoyancy pool
* Neutral buoyancy simulation as a training aid
* Neutral Buoyancy Simulator
* Space Systems Laboratory
* Yuri Gagarin Cosmonaut Training Center
Other
* Nautilus Productions
* Category
* Commons
* * Glossary
* Indexes: dive sites
* divers
* diving
* * Outline
* Portal
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| Alternobaric vertigo | c0413281 | 2,078 | wikipedia | https://en.wikipedia.org/wiki/Alternobaric_vertigo | 2021-01-18T18:36:24 | {"umls": ["C0413281"], "wikidata": ["Q4736617"]} |
A number sign (#) is used with this entry because autosomal recessive nonsyndromic mental retardation-18 is caused by homozygous mutation in the MED23 gene (605042) on chromosome 6q23.2.
Clinical Features
Hashimoto et al. (2011) reported a large Algerian consanguineous multiplex family in which 5 affected individuals presented with nonsyndromic intellectual disability. Two sisters were evaluated, age 39 and 41 years. The parents were healthy first cousins from Algeria. Pregnancy and delivery were uneventful. There were no postnatal infections, toxic exposures, or significant head trauma. The sisters were unable to read, write, or look after financial affairs, but they were independent for tasks of daily living. Mental retardation was estimated as mild to moderate. Physical exam of both patients showed normal height, weight, and head circumference. There were no dysmorphic features or malformations. Metabolic workup was unremarkable as was molecular testing which ruled out fragile X syndrome. High-resolution chromosome analysis was normal. Array CGH testing at 1-Mb resolution was normal as were bone X rays, cerebellar MRI, and EEG. Family history revealed that 2 additional sisters and 1 brother were affected with a similar condition.
Molecular Genetics
Hashimoto et al. (2011) identified a G-to-A transition at nucleotide 1850 of the MED23 gene, resulting in an arg-to-gln substitution at codon 617 (R617Q; 605042.0001). Arg617 is absolutely conserved across all MED23 orthologs from Xenopus to Drosophila and human. The mutation does not affect MED23 expression, protein stability or architecture, or composition of the whole Mediator complex. The mutation specifically impaired the response of JUN (165160) and FOS (164810) immediate-early genes to serum mitogens by altering the interaction between enhancer-bound transcription factors (TCF4, 602272 and ELK1, 311040, respectively) and Mediator. Transcriptional dysregulation of these genes was also observed in cells derived from patients presenting with other neurologic disorders linked to mutations in other Mediator subunits or proteins interacting with the Mediator complex. These findings highlighted the crucial role of Mediator in brain development and functioning and suggested that altered immediate-early gene expression might provide a molecular signature for cognitive deficits.
INHERITANCE \- Autosomal recessive NEUROLOGIC Central Nervous System \- Mental retardation, mild to moderate MISCELLANEOUS \- Normal metabolic screening and no malformations \- Based on 1 consanguineous Algerian family with 5 affected sibs ▲ 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
| MENTAL RETARDATION, AUTOSOMAL RECESSIVE 18 | c3280265 | 2,079 | omim | https://www.omim.org/entry/614249 | 2019-09-22T15:55:57 | {"doid": ["0060308"], "omim": ["614249"], "orphanet": ["88616"], "synonyms": ["AR-NSID", "NS-ARID"]} |
A number sign (#) is used with this entry because of evidence that phosphoserine aminotransferase deficiency (PSATD) is caused by compound heterozygous mutation in the PSAT1 gene (610936) on chromosome 9q21. One such family has been reported.
Description
Deficiency of phosphoserine aminotransferase (PSAT) is characterized biochemically by low plasma and cerebrospinal fluid (CSF) concentrations of serine and glycine and clinically by intractable seizures, acquired microcephaly, hypertonia, and psychomotor retardation. Outcome is poor once the individual becomes symptomatic, but treatment with serine and glycine supplementation from birth can lead to a normal outcome (Hart et al., 2007).
Clinical Features
Hart et al. (2007) identified PSAT deficiency in a brother and sister, the children of nonconsanguineous British parents, who showed low concentrations of serine and glycine in plasma and CSF. The index patient was healthy at birth, with head circumference and weight in the 9th percentile. At age 2 weeks he was admitted to the hospital with poor feeding and cyanotic episodes. At age 7 weeks he was experiencing jerking movements and posturing. At age 9 weeks he presented with severe, intractable seizures and slight hypertonia. His head circumference was less than the 0.4th percentile, whereas weight was in the 2nd percentile. His seizures could not be controlled despite multiple-anticonvulsant therapy. Extensive biochemical investigations revealed no abnormalities with the exception of low plasma and CSF concentrations of serine and glycine. Cranial imaging showed generalized atrophy, a hypoplastic cerebellar vermis, and poor white matter development. Treatment with serine begun at 11 weeks of age normalized plasma and CSF concentrations, but the clinical effect was limited. Severe seizure episodes continued, hypertonia worsened, and the patient died at age 7 months. In the proband's younger sister plasma and CSF samples in the neonatal period revealed low concentrations of serine and glycine, and supplementation with serine and glycine was begun in the first 24 hours of life. Her growth and development were normal at 3 years of age, with the exception of an apneic episode at age 2 weeks. Analysis of fibroblasts from the proband revealed phosphoserine aminotransferase activity that was low in comparison to that in controls (approximately 50% decreased), but not sufficiently so to conclude the presence of a deficiency disorder. Hart et al. (2007) also noted that plasma serine and glycine concentrations were only marginally below the reference range in the proband, emphasizing the importance of measuring serine and glycine in CSF as well as plasma.
Molecular Genetics
In 2 sibs with PSAT deficiency, Hart et al. (2007) identified compound heterozygosity for mutations in the PSAT1 gene: a frameshift mutation on the paternal allele (G107del; 610936.0001) and a missense mutation on the maternal allele (D100A; 610936.0002). Expression studies of the D100A mutant protein revealed a V(max) of only 15% of that of the wildtype protein.
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Microcephaly, acquired ABDOMEN Gastrointestinal \- Poor feeding NEUROLOGIC Central Nervous System \- Jerking movements \- Posturing \- Seizures, intractable \- Hypertonia \- Psychomotor retardation \- Brain imaging shows generalized atrophy \- Hypoplastic cerebellar vermis LABORATORY ABNORMALITIES \- Decreased plasma serine \- Decreased plasma glycine \- Decreased CSF serine \- Decreased CSF glycine MISCELLANEOUS \- Onset in infancy \- Treatment with serine and glycine replacement may alleviate features if started at birth \- Lack of treatment results in early death MOLECULAR BASIS \- Caused by mutation in the phosphoserine aminotransferase-1 gene (PSAT1, 610936.0001 ) ▲ 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
| PHOSPHOSERINE AMINOTRANSFERASE DEFICIENCY | c1970253 | 2,080 | omim | https://www.omim.org/entry/610992 | 2019-09-22T16:03:47 | {"doid": ["0050723"], "mesh": ["C567032"], "omim": ["610992"], "orphanet": ["284417"], "synonyms": ["Alternative titles", "PSAT DEFICIENCY"]} |
A rare, genetic distal myopathy disorder characterized by middle age-onset of distal leg muscle weakness, atrophy in the anterior compartment resulting in foot drop, without proximal or scapular skeletal muscle weakness. Rapidly progressive dementia, Paget disease of bone and hand weakness have been reported. Muscle biopsy shows pronounced myopathic changes with rimmed vacuoles.
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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
| Adult-onset distal myopathy due to VCP mutation | None | 2,081 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=329478 | 2021-01-23T18:11:38 | {"icd-10": ["G71.0"]} |
Ebstein's malformation is a rare congenital cardiac anomaly characterized by rotational displacement of the septal and inferior leaflets of the tricuspid valve such that they are hinged within the right ventricle, rather than as expected at the atrioventricular junction.
## Epidemiology
Prevalence is estimated at 1/50,000-1/200,000. Both sexes are equally affected.
## Clinical description
Clinical presentation is heterogeneous and depends on the severity of the lesion (extent of tethering of the antero-superior leaflet across the normal valvar orifice), and the degree of dysfunction of the right ventricle. Patients with minor forms of the disease remain asymptomatic or may present with an incidental murmur, exertional dyspnea, fatigue, or palpitations. Those with severe forms can present at various ages with arrhythmias, cyanosis, and sometimes cardiac failure. Those with the most severe malformations present as neonates, often with so-called ``wall-to-wall'' hearts. During adulthood, supraventricular tachycardia can also be observed, a proportion of patients also having Wolff-Parkinson-White syndrome (see this term). The malformation is often associated with other cardiac lesions, such as atrial or ventricular septal defects, patency of the arterial duct, and pulmonary stenosis.
## Etiology
Etiology is unknown. In some cases, maternal ingestion of lithium was associated with the disease.
## Diagnostic methods
Diagnosis is based on cross-sectional or 3D echocardiography, which reveals the rotational displacement of the leaflets, the extent of abnormal tethering of the antero-superior leaflet, the extent of thinning of the atrialized inlet component of the right ventricle, and the degree of regurgitation or stenosis of the abnormal valve. The electrocardiogram can reveal right atrial hypertrophy, right bundle branch block, and supraventricular tachycardia. Radiography shows any cardiomegaly, and cardiac MRI shows the full extent of the valvar abnormalities.
## Differential diagnosis
The major differential diagnosis, particularly during fetal life, is dysplasia of the leaflets of the tricuspid valve. This, as can Ebstein's malformation if associated with pulmonary atresia, can lead to gross thinning of the walls of the right ventricle which should not be confused with Uhl's anomaly (see this term). The severest forms of Ebstein's malformation can produce an imperforate tricuspid valve, which must be distinguished from tricuspid atresia (see this term).
## Antenatal diagnosis
Antenatal diagnosis is now possible with fetal echocardiography that reveals hydrops fetalis.
## Management and treatment
Medical treatment relies on inotropic agents (in case of cardiac failure) and antiarrhythmic drugs (in case of tachyarrhythmia). Definitive treatment is surgical and consists of reconstructive surgery prior to the onset of cardiac failure. If the valve is too malformed, replacement is the only option.
## Prognosis
Asymptomatic patients, and patients with mild forms of the disease, have a normal life expectancy. Patients with severe forms of the disease, particularly those presenting during the fetal period or as neonates, have an increased risk of death due to cardiac failure, including at birth or during physical exercise.
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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
| Ebstein malformation | c0013481 | 2,082 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1880 | 2021-01-23T19:02:11 | {"gard": ["6313"], "mesh": ["D004437"], "omim": ["224700"], "umls": ["C0013481"], "icd-10": ["Q22.5"], "synonyms": ["Ebstein anomaly of the tricuspid valve"]} |
Phacomatosis pigmentovascularis (PPV) is a disorder characterized by the co-existence of vascular and pigmentary birthmarks. Signs and symptoms may include port wine stain, melanocytic nevi (commonly known as moles), epidermal nevi, dermal melanocytosis (areas of blue-gray discoloration), nevus spilus, and patches of hyperpigmentation (areas of darker skin). Other skin features may include nevus anemicus (areas of lighter skin) and café au lait spots. About half of people with PPV have systemic involvement, which means they have features affecting other areas of the body. People with systemic involvement may have neurologic, ocular (eye), or muscular abnormalities. Several subtypes of PPV have been identified which are generally distinguished based on the specific type(s) of skin features present.
Isolated PPV is typically a sporadic disorder that occurs for the first time in people with no family history of PPV. Researchers have found that PPV can be caused by a somatic mutation in the GNA11 or GNAQ gene that is present only in the affected tissues of the body. These mutations are not present in the blood or in unaffected tissues, which means the disorder is likely due to non-inherited mutations that are randomly acquired after conception. In some cases of isolated PPV, the underlying cause remains unknown.
Treatment and long-term outlook (prognosis) of PPV largely depends whether there is systemic involvement and which body parts or organ systems are affected. Isolated PPV without systemic involvement typically does not require treatment. However, large skin lesions may cause problems with body image and self-esteem, so laser treatments may be considered to improve the appearance of skin lesions.
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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
| Phacomatosis pigmentovascularis | c1274879 | 2,083 | gard | https://rarediseases.info.nih.gov/diseases/4312/phacomatosis-pigmentovascularis | 2021-01-18T17:58:20 | {"mesh": ["C537894"], "umls": ["C1274879"], "synonyms": ["Association of cutaneous vascular malformations and different pigmentary disorders", "PPV", "Phakomatosis pigmentovascularis"]} |
This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.
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Saccharopinuria
Other namesHyperlysinemia type II[1]
Saccharopine
Saccharopinuria (an excess of saccharopine in the urine), also called saccharopinemia, saccharopine dehydrogenase deficiency or alpha-aminoadipic semialdehyde synthase deficiency,[2] is a variant form of hyperlysinemia.[3] It is caused by a partial deficiency of the enzyme saccharopine dehydrogenase, which plays a secondary role in the lysine metabolic pathway. Inheritance is thought to be autosomal recessive, but this cannot be established as individuals affected by saccharopinuria typically have only a 40% reduction in functional enzyme.[2]
## See also[edit]
* Hyperlysinemia
## References[edit]
1. ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Saccharopinuria". www.orpha.net. Retrieved 16 April 2019.
2. ^ a b Online Mendelian Inheritance in Man (OMIM): 268700
3. ^ Higashino, K. (1998). "Saccharopinuria (a variant form of familial hyperlysinemia)". Ryoikibetsu Shokogun Shirizu (18 Pt 1): 191–194. PMID 9590025.
## External links[edit]
* Saccharopinuria; Alpha-aminoadipic semialdehyde synthase deficiency at NIH's Office of Rare Diseases
Classification
D
* ICD-10: E72.3
* ICD-9-CM: 270.7
* OMIM: 268700
* MeSH: C537218
External resources
* Orphanet: 3124
* v
* t
* e
Inborn error of amino acid metabolism
K→acetyl-CoA
Lysine/straight chain
* Glutaric acidemia type 1
* type 2
* Hyperlysinemia
* Pipecolic acidemia
* Saccharopinuria
Leucine
* 3-hydroxy-3-methylglutaryl-CoA lyase deficiency
* 3-Methylcrotonyl-CoA carboxylase deficiency
* 3-Methylglutaconic aciduria 1
* Isovaleric acidemia
* Maple syrup urine disease
Tryptophan
* Hypertryptophanemia
G
G→pyruvate→citrate
Glycine
* D-Glyceric acidemia
* Glutathione synthetase deficiency
* Sarcosinemia
* Glycine→Creatine: GAMT deficiency
* Glycine encephalopathy
G→glutamate→
α-ketoglutarate
Histidine
* Carnosinemia
* Histidinemia
* Urocanic aciduria
Proline
* Hyperprolinemia
* Prolidase deficiency
Glutamate/glutamine
* SSADHD
G→propionyl-CoA→
succinyl-CoA
Valine
* Hypervalinemia
* Isobutyryl-CoA dehydrogenase deficiency
* Maple syrup urine disease
Isoleucine
* 2-Methylbutyryl-CoA dehydrogenase deficiency
* Beta-ketothiolase deficiency
* Maple syrup urine disease
Methionine
* Cystathioninuria
* Homocystinuria
* Hypermethioninemia
General BC/OA
* Methylmalonic acidemia
* Methylmalonyl-CoA mutase deficiency
* Propionic acidemia
G→fumarate
Phenylalanine/tyrosine
Phenylketonuria
* 6-Pyruvoyltetrahydropterin synthase deficiency
* Tetrahydrobiopterin deficiency
Tyrosinemia
* Alkaptonuria/Ochronosis
* Tyrosinemia type I
* Tyrosinemia type II
* Tyrosinemia type III/Hawkinsinuria
Tyrosine→Melanin
* Albinism: Ocular albinism (1)
* Oculocutaneous albinism (Hermansky–Pudlak syndrome)
* Waardenburg syndrome
Tyrosine→Norepinephrine
* Dopamine beta hydroxylase deficiency
* reverse: Brunner syndrome
G→oxaloacetate
Urea cycle/Hyperammonemia
(arginine
* aspartate)
* Argininemia
* Argininosuccinic aciduria
* Carbamoyl phosphate synthetase I deficiency
* Citrullinemia
* N-Acetylglutamate synthase deficiency
* Ornithine transcarbamylase deficiency/translocase deficiency
Transport/
IE of RTT
* Solute carrier family: Cystinuria
* Hartnup disease
* Iminoglycinuria
* Lysinuric protein intolerance
* Fanconi syndrome: Oculocerebrorenal syndrome
* Cystinosis
Other
* 2-Hydroxyglutaric aciduria
* Aminoacylase 1 deficiency
* Ethylmalonic encephalopathy
* Fumarase deficiency
* Trimethylaminuria
This genetic disorder article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| Saccharopinuria | c0268556 | 2,084 | wikipedia | https://en.wikipedia.org/wiki/Saccharopinuria | 2021-01-18T19:08:04 | {"gard": ["314"], "mesh": ["C537218", "D020167"], "umls": ["C0268556", "C2936921"], "icd-9": ["270.7"], "orphanet": ["3124"], "wikidata": ["Q7396610"]} |
Tarsal tunnel syndrome
Other namesPosterior tibial neuralgia
The mucous sheaths of the tendons around the ankle. Medial aspect.
SpecialtyNeurology
Tarsal tunnel syndrome (TTS), is a compression neuropathy and painful foot condition in which the tibial nerve is compressed as it travels through the tarsal tunnel.[1] This tunnel is found along the inner leg behind the medial malleolus (bump on the inside of the ankle). The posterior tibial artery, tibial nerve, and tendons of the tibialis posterior, flexor digitorum longus, and flexor hallucis longus muscles travel in a bundle through the tarsal tunnel. Inside the tunnel, the nerve splits into three segments. One nerve (calcaneal) continues to the heel, the other two (medial and lateral plantar nerves) continue on to the bottom of the foot. The tarsal tunnel is delineated by bone on the inside and the flexor retinaculum on the outside.
Patients with TTS typically complain of numbness in the foot radiating to the big toe and the first three toes, pain, burning, electrical sensations, and tingling over the base of the foot and the heel.[1] Depending on the area of entrapment, other areas can be affected. If the entrapment is high, the entire foot can be affected as varying branches of the tibial nerve can become involved. Ankle pain is also present in patients who have high level entrapments. Inflammation or swelling can occur within this tunnel for a number of reasons. The flexor retinaculum has a limited ability to stretch, so increased pressure will eventually cause compression on the nerve within the tunnel. As pressure increases on the nerves, the blood flow decreases.[1] Nerves respond with altered sensations like tingling and numbness. Fluid collects in the foot when standing and walking and this makes the condition worse. As small muscles lose their nerve supply they can create a cramping feeling.
## Contents
* 1 Symptoms
* 2 Causes
* 3 Risk factors
* 4 Diagnosis
* 5 Prevention
* 6 Treatment
* 6.1 Conservative treatment (nonsurgical)
* 6.2 Surgical treatment
* 7 Incidence
* 8 Athletic activities
* 8.1 Famous case
* 9 Society
* 10 See also
* 11 References
* 12 External links
## Symptoms[edit]
Some of the symptoms are:
* Pain and tingling in and around ankles and sometimes the toes
* Swelling of the feet and ankle area.
* Painful burning, tingling, or numb sensations in the lower legs. Pain worsens and spreads after standing for long periods; pain is worse with activity and is relieved by rest.
* Electric shock sensations
* Pain radiating up into the leg,[1] behind the shin, and down into the arch, heel, and toes
* Hot and cold sensations in the feet
* A feeling as though the feet do not have enough padding
* Pain while operating automobiles
* Pain along the Posterior Tibial nerve path
* Burning sensation on the bottom of foot that radiates upward reaching the knee
* "Pins and needles"-type feeling and increased sensation on the feet
* A positive Tinel's sign[1]
Tinel's sign is a tingling electric shock sensation that occurs when you tap over an affected nerve. The sensation usually travels into the foot but can also travel up the inner leg as well.
## Causes[edit]
3D still showing tarsal tunnel syndrome.
It is difficult to determine the exact cause of Tarsal Tunnel Syndrome. It is important to attempt to determine the source of the problem. Treatment and the potential outcome of the treatment may depend on the cause. Anything that creates pressure in the Tarsal Tunnel can cause TTS. This would include benign tumors or cysts, bone spurs, inflammation of the tendon sheath, nerve ganglions, or swelling from a broken or sprained ankle. Varicose veins (that may or may not be visible) can also cause compression of the nerve. TTS is more common in athletes and other active people. These people put more stress on the tarsal tunnel area. Flat feet may cause an increase in pressure in the tunnel region and this can cause nerve compression. Those with lower back problems may have symptoms. Back problems with the L4, L5 and S1 regions are suspect and might suggest a "Double Crush" issue: one "crush" (nerve pinch or entrapment) in the lower back, and the second in the tunnel area. In some cases, TTS can simply be idiopathic.[1]
This is an image of a normal arched foot.
When comparing to the normal arch image, this image of fallen arches, helps create a visualization of how the tibial nerve can be strained and compressed due to the curvature.
Rheumatoid Arthritis has also been associated with TTS.[2]
Neurofibromatosis can also cause TTS. This is a disease that results in the formation of pigmented, cutaneous neurofibromas. These masses, in a specific case, were shown to have the ability to invade the tarsal tunnel causing pressure, therefore resulting in TTS.[3]
Diabetes makes the peripheral nerve susceptible to nerve compression, as part of the double crush hypothesis.[4] In contrast to carpal tunnel syndrome due to one tunnel at the wrist for the median nerve, there are four tunnels in the medial ankle for tarsal tunnels syndrome.[5] If there is a positive Tinel sign when you tap over the inside of the ankle, such that tingling is felt into the foot, then there is an 80% chance that decompressing the tarsal tunnel will relieve the symptoms of pain and numbness in a diabetic with tarsal tunnel syndrome.[6]
## Risk factors[edit]
Anything compromising the tunnel of the posterior tibial nerve proves significant in the risk of causing TTS. Neuropathy can occur in the lower limb through many modalities, some of which include obesity and inflammation around the joints. By association, this includes risk factors such as RA, compressed shoes, pregnancy, diabetes and thyroid diseases[7]
## Diagnosis[edit]
Diagnosis is based upon physical examination findings. Patients' pain history and a positive Tinel's sign are the first steps in evaluating the possibility of tarsal tunnel syndrome. X-ray can rule out fracture. MRI can assess for space occupying lesions or other causes of nerve compression. Ultrasound can assess for synovitis or ganglia. Nerve conduction studies alone are not, but they may be used to confirm the suspected clinical diagnosis. Common causes include trauma, varicose veins, neuropathy and space-occupying anomalies within the tarsal tunnel. Tarsal tunnel syndrome is also known to affect both athletes and individuals that stand a lot.[1]
A Neurologist or a Physiatrist usually administers nerve conduction tests or supervises a trained technologist. During this test, electrodes are placed at various spots along the nerves in the legs and feet. Both sensory and motor nerves are tested at different locations. Electrical impulses are sent through the nerve and the speed and intensity at which they travel is measured. If there is compression in the tunnel, this can be confirmed and pinpointed with this test. Some doctors do not feel that this test is necessarily a reliable way to rule out TTS.[1] Some research indicates that nerve conduction tests will be normal in at least 50% of the cases.
Given the unclear role of electrodiagnostics in the diagnosis of tarsal tunnel syndrome, efforts have been made in the medical literature to determine which nerve conduction studies are most sensitive and specific for tibial mononeuropathy at the level of the tarsal tunnel. An evidence-based practice topic put forth by the professional organization, the American Association of Neuromuscular & Electrodiagnostic Medicine has determined that Level C, Class III evidence exists for the use of tibial motor nerve conduction studies, medial and lateral plantar mixed nerve conduction studies, and medial and lateral plantar sensory nerve conduction studies. The role of needle electromyography remains less defined.[8]
Tarsal Tunnel Syndrome (TTS) is most closely related to Carpal Tunnel Syndrome (CTS). However, the commonality to its counterpart is much less or even rare in prevalence[9] Studies have found that patients with rheumatoid arthritis (RA) show signs of distal limb neuropathy. The posterior tibial nerve serves victim to peripheral neuropathy and often show signs of TTS amongst RA patients. Therefore, TTS is a common discovery found in the autoimmune disorder of rheumatoid arthritis[10]
Increased pressure and high loads on the ankle joint can cause TTS, as can smaller than normal shoes. In this picture, most of the load is placed upon the knee and ankle joint.
## Prevention[edit]
The exact cause of Tarsal Tunnel Syndrome (TTS) can vary from patient to patient. However the same end result is true for all patients, the compression of the posterior tibial nerve and it branches as it travels around the medial malleolus causes pain and irritation for the patient.[11] There are many possible causes for compression of the tibial nerve therefore there are a variety of prevention strategies. One being immobilization, by placing the foot in a neutral position with a brace, pressure is relieved from the tibial nerve thus reducing patients pain.[12][13][14] Eversion, inversion, and plantarflexion all can cause compression of the tibial nerve therefore in the neutral position the tibial nerve is less agitated. Typically this is recommended for the patient to do while sleeping. Another common problem is improper footwear, having shoes deforming the foot due to being too tight can lead to increased pressure on the tibial nerve.[11] Having footwear that tightens the foot for extended periods of time even will lead to TTS. Therefore, by simply having properly fitted shoes TTS can be prevented.
## Treatment[edit]
Treatments typically include rest, manipulation, strengthening of tibialis anterior, tibialis posterior, peroneus and short toe flexors, casting with a walker boot, corticosteroid and anesthetic injections, hot wax baths, wrapping, compression hose, and orthotics. Medications may include various anti-inflammatories such as Anaprox, or other medications such as Ultracet, Neurontin and Lyrica. Lidocaine patches are also a treatment that helps some patients.
### Conservative treatment (nonsurgical)[edit]
There are multiple ways that tarsal tunnel can be treated and the pain can be reduced. The initial treatment, whether it be conservative or surgical, depends on the severity of the tarsal tunnel and how much pain the patient is in. There was a study done that treated patients diagnosed with tarsal tunnel syndrome with a conservative approach. Meaning that the program these patients were participated in consisted of physiotherapy exercises and orthopedic shoe inserts in addition to that program. There were fourteen patients that had supplementary tibial nerve mobilization exercises. They were instructed to sit on the edge of a table in a slumped position, have their ankle taken into dorsiflexion and ankle eversion then the knee was extended and flexed to obtain the optimal tibial nerve mobilization. Patients in both groups showed positive progress from both programs.[15] The medial calcaneal, medial plantar and lateral plantar nerve areas all had a reduction in pain after successful nonoperative or conservative treatment.[16] There is also the option of localized steroid or cortisone injection that may reduce the inflammation in the area, therefore relieving pain. Or just a simple reduction in the patient's weight to reduce the pressure in the area.[17]
Tarsal Tunnel release
### Surgical treatment[edit]
If non-invasive treatment measures fail, tarsal tunnel release surgery may be recommended to decompress the area. The incision is made behind the ankle bone and then down towards but not as far as the bottom of foot. The Posterior Tibial nerve is identified above the ankle. It is separated from the accompanying artery and vein and then followed into the tunnel. The nerves are released. Cysts or other space-occupying problems may be corrected at this time. If there is scarring within the nerve or branches, this is relieved by internal neurolysis. Neurolysis is when the outer layer of nerve wrapping is opened and the scar tissue is removed from within nerve. Following surgery, a large bulky cotton wrapping immobilizes the ankle joint without plaster. The dressing may be removed at the one-week point and sutures at about three weeks.
Complications may include bleeding, infection, and unpredictable healing. The incision may open from swelling. There may be considerable pain and cramping. Regenerating nerve fibers may create shooting pains. Patients may have hot or cold sensations and may feel worse than before surgery. Crutches are usually recommended for the first two weeks, as well as elevation to minimize swelling. The nerve will grow at about one inch per month. One can expect to continue the healing process over the course of about one year.
Many patients report good results. Some, however, experience no improvement or a worsening of symptoms. In the Pfeiffer article (Los Angeles, 1996),[full citation needed] fewer than 50% of the patients reported improvement, and there was a 13% complication rate. This is a staggering percentage of complications for what is a fairly superficial and minor surgical procedure.
Tarsal tunnel can greatly impact patients' quality of life. Depending on the severity, the ability to walk distances people normally take for granted (such as grocery shopping) may become compromised. Proper pain management and counseling is often required.
Results of surgery can be maximized if all four of the medial ankle tunnels are released and you walk with a walker the day after surgery. Success can be improved to 80%.[18]
## Incidence[edit]
Though TTS is rare, its cause can be determined in 70% of reported cases. In the workplace TTS is considered a musculoskeletal disorder and accounts for 1.8 million cases a year, which accumulates to about $15–$20 billion a year[19] New studies indicate an occurrence of TTS in sports placing high loads on the ankle joint (3). This can be seen in figure 1. TTS occurs more dominantly in active adults, with a higher pervasiveness among women. Active adults that experience more jumping and landing on the ankle joint are more susceptible (see figure 2). Though athletics and sport are correlations, cases are individualistically assessed because of the oddity.
## Athletic activities[edit]
The athletic population tends to put themselves at greater risk of TTS due to the participation in sports that involve the lower extremities. Strenuous activities involved in athletic activities put extra strain on the ankle and therefore can lead to the compression of the tibial nerve.[20] Activities that especially involve sprinting and jumping have a greater risk of developing TTS. This is due to the ankle being put in eversion, inversion, and plantarflexion at high velocities. Examples of sports that can lead to TTS include basketball, track, soccer, lacrosse, snowboarding, and volleyball.[21] Participation in these sports should be done cautiously due to the high risk of developing TTS. However athletes will tend to continue to participate in these activities therefore proper stretching, especially in lower extremities, prior to participation can assist in the prevention of developing TTS.
Placing the foot in Eversion (top left), Inversion (bottom left), or Plantar flexion(right) all put strain on the tibial nerve. These positions should be avoided to prevent the development of TTS and can be done so by using a brace to place the foot in a neutral position.
### Famous case[edit]
According to South Korea's National Intelligence Service, North Korean leader Kim Jong Un had surgery to correct TTS in his right ankle, the source of a pronounced limp. Kim's disappearance from public for six weeks around the suspected surgery created worldwide speculation about the future of Kim and North Korea.[22]
## Society[edit]
As stated earlier, musculoskeletal disorders can cost up to $15–$20 billion in direct costs or $45–$55 billion in indirect expenses. This is about $135 million a day[19] Tests that confirm or correct TTS require expensive treatment options like x-rays, CT-scans, MRI and surgery. 3 former options for TTS detect and locate, while the latter is a form of treatment to decompress tibial nerve pressure[23] Since surgery is the most common form of TTS treatment, high financial burden is placed upon those diagnosed with the rare syndrome.
## See also[edit]
* Carpal tunnel syndrome
* Cuboid syndrome
## References[edit]
1. ^ a b c d e f g h Yates, Ben (2009). Merriman's Assessment of the Lower Limb (3rd ed.). New York: Churchill Livingstone. ISBN 978-0-08-045107-7.
2. ^ Baylan SP, Paik SW, Barnert AL, Ko KH, Yu J, Persellin RH (1981). "Prevalence of the tarsal tunnel syndrome in rheumatoid arthritis". Rheumatol Rehabil. 20 (3): 148–50. doi:10.1093/rheumatology/20.3.148. PMID 7280489.
3. ^ Mirick, Anika L., Gerald B. Bornstein, and Laura W. Bancroft. "Radiologic Case Study." Orthopedics 36.81 (2013): 154–57. Web. 22 Apr. 2014.
4. ^ Dellon AL, Mackinnon SE, Seiler WA (1988). "Susceptibility of the diabetic nerve to chronic compression". Ann Plast Surg. 20 (2): 117–119. doi:10.1097/00000637-198802000-00004.
5. ^ Mackinnon SE, Dellon AL (1987). "Homologies between the tarsal and carpal tunnels: Implications for treatment of the tarsal tunnel syndrome". Contemp Orthop. 14: 75–79.
6. ^ Lee C, Dellon AL (2004). "Prognostic ability of Tinel sign in determining outcome for decompression surgery decompression surgery in diabetic and non-diabetic neuropathy". Ann Plast Surg. 53 (6): 523–27. doi:10.1097/01.sap.0000141379.55618.87.
7. ^ Beltran L. S.; Bencardino J.; Ghazikhanian V.; Beltran J. (2010). "Entrapment Neuropathies III: Lower Limb". Seminars in Musculoskeletal Radiology. 14 (5): 501–511. doi:10.1055/s-0030-1268070. PMID 21072728.
8. ^ "Usefulness of electrodiagnostic techniques in the evaluation of suspected tarsal tunnel syndrome: An evidence-based review". aanem.org/getmedia/51417557-424c-4c29-be6a-5bbaff64517c/TarsalTunnel.pdf.aspx. Retrieved 15 February 2015.
9. ^ Ahmad, M. M., Tsang, K. K., Mackenney, P. J., & Adedapo, A. O. (2012). Tarsal tunnel syndrome: A literature review. Foot & Ankle Surgery (Elsevier Science), 18(3), 149–152.
10. ^ Baylan, S. P., S. W. Paik, A. L. Barnert, K. H. Ko, J. Yu, and R. H. Persellin. "Prevalence Of The Tarsal Tunnel Syndrome In Rheumatoid Arthritis." Rheumatology 20.3 (1981): 148–150.
11. ^ a b Low, Hu L., and George Stephenson. "These Boots Weren't Made for Walking: Tarsal Tunnel Syndrome." Canadian Medical Association Journal 176.10 (2007): 1415–416.
12. ^ Gondring, William H., Elly Trepman, and Byron Shields. "Tarsal Tunnel Syndrome: Assessment of Treatment Outcome with an Anatomic Pain Intensity Scale."Foot and Ankle Surgery 15.3 (2009): 133–38.
13. ^ Bracilovic, A., A. Nihal, V. L. Houston, A. C. Beatle, Z. S. Rosenberg, and E. Trepman. "Effect of Foot and Ankle Position on Tarsal Tunnel Compartment Volume." Foot and Ankle International 27.6 (2006): 421–37.
14. ^ Nakasa, Tomoyuki, Kohei Fukuhara, Nobuo Adachi, and Mitsuo Ochi. "Painful Os Intermetatarseum in Athletes: Report of Four Cases and Review of the Literature." Archives of Orthopaedic and Trauma Surgery 127.4 (2007): 261–64. Print.
15. ^ Kavlak Y, Uygur F (2011). "Effects of nerve mobilization exercise as an adjunct to the conservative treatment for patients with tarsal tunnel syndrome". J Manipulative Physiol Ther. 34 (7): 441–8. doi:10.1016/j.jmpt.2011.05.017. PMID 21875518.
16. ^ Gondring WH1, Trepman E, Shields B. (2008). Tarsal tunnel syndrome: assessment of treatment outcome with an anatomic pain intensity scale. Foot Ankle Surg. 15(3):133-8
17. ^ Edwards William G.; Lincoln C. Robert; Bassett Frank H.; Goldner J. Leonard (1969). "The Tarsal Tunnel Syndrome Diagnosis and Treatment". JAMA. 207 (4): 716–720. doi:10.1001/jama.1969.03150170042009.
18. ^ Mullick T, Dellon AL. Results of decompression of four medial ankle tunnels in the treatment of tarsal tunnels syndrome. J Reconstr Microsurg. 2008;24:119–126.
19. ^ a b . Jeffress, Charles N. "Work-related Musculoskeletal Disorders (MSDs)." Work-related Musculoskeletal Disorders (MSDs). Occupational Safety & Health Administration, n.d. Web. 11 May 2014.
20. ^ Kinoshita, M. "Tarsal Tunnel Syndrome in Athletes." American Journal of Sports Medicine 34.8 (2006): 1307–312.
21. ^ Ramani, William, David H. Perrin, and Tim Whiteley. "Tarsal Tunnel Syndrome: Case Study of a Male Collegiate Athlete." Journal of Sports Rehabilitation 6 (n.d.): 364-70.
22. ^ http://www.cnn.com/2014/10/28/world/asia/kim-jong-un-cyst/index.html?hpt=wo_c2
23. ^ Manasseh, N., Cherian, V., & Abel, L. (2009). Malunited calcaneal fracture fragments causing tarsal tunnel syndrome: A rare cause. Foot & Ankle Surgery (Elsevier Science), 15(4), 207–209.
## External links[edit]
Classification
D
* ICD-10: G57.5
* ICD-9-CM: 355.5
* MeSH: D013641
* DiseasesDB: 32754
External resources
* eMedicine: orthoped/565
* Patient UK: Tarsal tunnel syndrome
* v
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* 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
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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
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* See Template:Cranial nerve disease
Polyneuropathy and Polyradiculoneuropathy
HMSN
* Charcot–Marie–Tooth disease
* Dejerine–Sottas disease
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* Complex regional pain syndrome
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| Tarsal tunnel syndrome | c0039319 | 2,085 | wikipedia | https://en.wikipedia.org/wiki/Tarsal_tunnel_syndrome | 2021-01-18T18:49:02 | {"gard": ["7733"], "mesh": ["D013641"], "umls": ["C0039319"], "wikidata": ["Q1410673"]} |
Movement disorder that causes involuntary tremors
Essential tremor
Other namesIdiopathic tremor
Archimedean spiral drawings from a man with a unilateral essential tremor. The spiral on the left was drawn by the subject using the left hand, and the one on the right using the right hand.
SpecialtyNeurology
Usual onsetAny age, but typically after 40[1]
CausesUnknown[1]
Risk factorsFamily history, exposure to particular toxins[2]
Diagnostic methodBased on symptoms[3]
Differential diagnosisCerebellar tremor, dystonic tremor, multiple sclerosis, Parkinson's disease[4]
TreatmentMedications, surgery[5]
MedicationBeta blockers, primidone, anti-epileptics, topiramate, gabapentin, levetiracetam, benzodiazepines[5]
FrequencyAnnual incidence of 23.7 per 100,000 (2010)[6]
Essential tremor (ET), also called benign tremor, familial tremor, and idiopathic tremor, is a medical condition characterized by involuntary rhythmic contractions and relaxations (oscillations or twitching movements) of certain muscle groups in one or more body parts of unknown cause.[7] It typically is symmetrical, and affects the arms, hands, or fingers; but sometimes involves the head, vocal cords, or other body parts. [5] Essential tremor is either an action (intention) tremor—it intensifies when one tries to use the affected muscles during voluntary movements such as eating and writing—or it is a postural tremor, present with sustained muscle tone. This means that it is distinct from a resting tremor, such as that caused by Parkinson's disease, which is not correlated with movement.[8]
Essential tremor is a progressive[9][10][11] neurological disorder, and the most common movement disorder. Its onset is usually after age 40, but it can occur at any age.[1] The cause is unknown. Diagnosis is by observing the typical pattern of the tremor coupled with the exclusion of known causes of such a tremor.
While essential tremor is distinct from Parkinson's disease, which causes a resting tremor, essential tremor is nevertheless sometimes misdiagnosed as Parkinson's disease.[5] Some patients have been found to have both essential tremors and resting tremors.[5]
Treatments for essential tremor include medications, typically given sequentially to determine which is most effective coupled with which has the least troublesome side effects. Clostridium botulinum toxin (Botox) injections and ultrasound are also sometimes used for cases refractory to medications.
## Contents
* 1 Signs and symptoms
* 2 Cause
* 2.1 Genetic
* 2.2 Toxins
* 3 Pathophysiology
* 4 Diagnosis
* 5 Terminology
* 6 Treatment
* 6.1 General measures
* 6.2 Oral medications
* 6.2.1 First-line
* 6.2.2 Second-line
* 6.2.3 Third-line
* 6.2.4 Fourth-line
* 6.3 Botulinum injection
* 6.4 Ultrasound
* 7 Prognosis
* 8 Epidemiology
* 9 Society and culture
* 10 Research
* 11 See also
* 12 References
* 13 External links
## Signs and symptoms[edit]
In mild cases, ET can manifest as the inability to stop the tongue or hands from shaking, the ability to sing only in vibrato, and difficulty doing small, precise tasks such as threading a needle. Even simple tasks such as cutting in a straight line or using a ruler can range from difficult to impossible, depending on the severity of the condition. In disabling cases, ET can interfere with a person's activities of daily living, including feeding, dressing, and taking care of personal hygiene. Essential tremor generally presents as a rhythmic tremor (4–12 Hz) that occurs only when the affected muscle is exerting effort. Any sort of physical or mental stress tends to make the tremor worse.[3]
The tremor may also occur in the head (neck), jaw, and voice, as well as other body regions, with the general pattern being that the tremor begins in the arms and then spreads to these other regions in some people. Women are more likely to develop the head tremor than are men. Other types of tremor may also occur, including postural tremor of the outstretched arms, intention tremor of the arms, and rest tremor in the arms.[12] Some people may have unsteadiness and problems with gait and balance.[citation needed]
ET-related tremors do not occur during sleep, but people with ET sometimes complain of an especially coarse tremor upon awakening that becomes noticeably less coarse within the first few minutes of wakefulness. Tremor and disease activity/intensity can worsen in response to fatigue, strong emotions, low blood sugar, cold and heat, caffeine, lithium salts, some antidepressants, and other factors. Typically, the tremor worsens in "performance" situations, such as when writing a cheque for payment at a store or giving a presentation.
Parkinson's disease and parkinsonism can also occur simultaneously with ET.[5] The degree of tremor, rigidity, and functional disability did not differ from patients with idiopathic Parkinson's disease. Hand tremor predominated (as it did in Parkinson’s disease), and occurred in nearly all cases, followed by head tremor, voice tremor, neck, face, leg, tongue, and trunk tremor. Most other tremors occurred in association with hand tremor. More severe tremors, a lower sleep disorder frequency, and a similar prevalence of other non-motor symptoms also can occur.[13]
Walking difficulties in essential tremor are common. About half of patients have associated dystonia, including cervical dystonia, writer's cramp, spasmodic dysphonia, and cranial dystonia, and 20% of the patients had associated parkinsonism. Olfactory dysfunction (loss of sense of smell) is common in Parkinson’s disease, and has also been reported to occur in patients with essential tremor. A number of patients with essential tremor also exhibit many of the same neuropsychiatric disturbances seen in idiopathic Parkinson's disease.[14]
Essential tremor with tremor onset after the age of 65 has been associated with mild cognitive impairment,[15] as well as dementia; although the link between these conditions, if any, is still not understood.[16][17]
Essential tremor has two tremor components, central and peripheral. These two tremor components were identified by measuring the tremor of ET patients once with no weights on their hands and then with 1-lb weights on their hands. The addition of the weights resulted in a tremor spectrum with two peaks, one that maintained the same frequency (the central tremor) and one that decreased in frequency (the peripheral tremor). Only with the addition of the weights was the peripheral tremor distinguishable from the central tremor.[18]
## Cause[edit]
### Genetic[edit]
The underlying cause of essential tremor is not clear, but many cases seem to be familial.[19] About half of the cases are due to a genetic mutation and the pattern of inheritance is most consistent with autosomal dominant transmission. No genes have been identified yet, but genetic linkage has been established with several chromosomal regions.[20][21]
### Toxins[edit]
Some environmental factors, including toxins, are also under active investigation, as they may play a role in the disease's cause.[22]
## Pathophysiology[edit]
In terms of pathophysiology, clinical, physiological and imaging studies point to an involvement of the cerebellum and/or cerebellothalamocortical circuits.[23] Changes in the cerebellum could also be mediated by alcoholic beverage consumption. Purkinje cells are especially susceptible to ethanol excitotoxicity.[24] Impairment of Purkinje synapses is a component of cerebellar degradation that could underlie essential tremor.[24] Some cases have Lewy bodies in the locus ceruleus.[25][26][27] ET cases that progress to Parkinson's disease are less likely to have had cerebellar problems.[28] Recent neuroimaging studies[29] have suggested that the efficiency of the overall brain functional network in ET is disrupted.
Recent post mortem studies have evidenced alterations in (leucine-rich repeat and Ig domain containing 1 (LINGO1) gene[30][31] and GABA receptors[32] in the cerebellum of people with essential tremor. HAPT1 mutations have also been linked to ET, as well as to Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy.[33]
In 2012, the National Toxicology Program concluded that sufficient evidence exists of an association between blood lead exposure at levels <10 μg/dl and essential tremor in adults, and limited evidence at blood lead levels <5 μg/dl.[34]
## Diagnosis[edit]
Usually, the diagnosis is established on clinical grounds. Tremors can start at any age, from birth through advanced ages (senile tremor).[35][36] Any voluntary muscle in the body may be affected, although the tremor is most commonly seen in the hands and arms and slightly less commonly in the neck (causing the person's head to shake), tongue, and legs. A resting tremor of the hands is sometimes present.[14][37] Tremor occurring in the legs might be diagnosable as orthostatic tremor.
ET occurs within multiple neurological disorders besides Parkinson's disease. This includes migraine disorders, where co-occurrences between ET and migraines have been examined.[38]
## Terminology[edit]
This type of tremor is often referred to as "kinetic tremor". Essential tremor has been known as "benign essential tremor", but the adjective "benign" has been removed in recognition of the sometimes disabling nature of the disorder.[39][40]
## Treatment[edit]
### General measures[edit]
Not all individuals with ET require treatment, but many treatment options are available depending on symptom severity.[5] Caffeine and stress should be avoided, and adequate good-quality sleep is recommended.[5]
### Oral medications[edit]
#### First-line[edit]
When symptoms are sufficiently troublesome to warrant treatment, the first medication choices are beta blockers such as propranolol or alternately, nadolol and timolol. Atenolol and pindolol are not effective for tremor.[5] The anti-epileptic primidone may also be effective.[5]
Propranolol and primidone only have tremor-reducing effects on about half of ET patients, and the effects are moderate.[18]
#### Second-line[edit]
Second-line medications are the anti-epileptics topiramate, gabapentin (as monotherapy) or levetiracetam, or benzodiazepines such as alprazolam.
#### Third-line[edit]
Third-line medications are clonazepam and mirtazapine.[5]
#### Fourth-line[edit]
Theophylline has been used by some practitioners to treat ET, though it may also induce tremor. However, its use is debated due to conflicting data on its efficacy.[41] Some evidence shows that low doses may lead to improvement.[42][43]
Ethanol has shown superior efficacy to those of benzodiazepines in small trials. It improves tremor in small doses and its effects are usually noticeable within 20 minutes for 3–5 hours, but occasionally appears in a rebound tremor augmentation later.[44]
Some systematic reviews of medications for the treatment of ET have been conducted. A 2017 review of topiramate found limited data and low quality evidence to support its efficacy and the occurrence of treatment-limiting adverse effects,[45] a 2017 review of zonisamide found insufficient information to assess efficacy and safety,[46] and a 2016 review of pregabalin determined the effects to be uncertain due to the low quality of evidence.[47]
### Botulinum injection[edit]
When medications do not control the tremor or the person does not tolerate medication, C. botulinum toxin,[48][49][50][51] deep brain stimulation, or occupational therapy can be helpful.[5] The electrodes for deep brain stimulation are usually placed in the "tremor center" of the brain, the ventral intermediate nucleus of the thalamus.
### Ultrasound[edit]
Additionally, MRI-guided high-intensity focused ultrasound is a nonsurgical treatment option for people with essential tremor who are medication refractory.[52][53] MRI-guided high-intensity focused ultrasound does not achieve healing, but can improve the quality of life.[53] While its long-term effects are not yet established, the improvement in tremor score from baseline was durable at 1 year and 2 years following the treatment.[54] To date, reported adverse events and side effects have been mild to moderate. Possible adverse events include gait difficulties, balance disturbances, paresthesias, headache, skin burns with ulcerations, skin retraction, scars, and blood clots.[52][53][55] This procedure is contraindicated in pregnant women, persons who have non-MRI compatible implanted metallic devices, allergy to MR contrast agents, cerebrovascular disease, abnormal bleeding, hemorrhage and/or blood clotting disorders, advanced kidney disease or on dialysis, heart conditions, severe hypertension, and ethanol or substance abuse, among others.[53] The US Food and Drug Administration (FDA) approved Insightec’s Exablate Neuro system to treat essential tremor in 2016.[53]
Another treatment for essential tremor is a surgical option; deep brain stimulation is used.
## Prognosis[edit]
Although essential tremor is often mild, people with severe tremor have difficulty performing many of their routine activities of daily living.[39][40] ET is generally progressive in most cases (sometimes rapidly, sometimes very slowly), and can be disabling in severe cases.[56][57][58]
## Epidemiology[edit]
ET is one of the most common neurological diseases, with a prevalence around 4% in persons age 40 and older and considerably higher among persons in their 60s, 70s, 80s, with an estimated 20% of individuals in their 90s and over.[59] Aside from enhanced physiological tremor, it is the most common type of tremor and one of the most commonly observed movement disorders.[60]
## Society and culture[edit]
Actress Katharine Hepburn (1907–2003) had an essential tremor, which she inherited from her grandfather,[61] that caused her head—and sometimes her hands—to shake.[62][63][64] The tremor was noticeable by the time of her performance in the 1979 film The Corn is Green, when critics mentioned the "palsy that kept her head trembling".[65] Hepburn's tremor worsened in her later life.[63]
In 2010, musician Daryl Dragon of The Captain and Tennille was diagnosed with essential tremor, with the condition becoming so severe that Dragon was forced to retire from music.[citation needed]
Director-writer-producer-comedian Adam McKay was diagnosed with essential tremor.[66]
Downton Abbey Creator Julian Fellowes has the condition as does the character Charlie Carson [67]
## Research[edit]
Harmaline is a widely used model of essential tremor (ET) in rodents.[68] Harmaline is thought to act primarily on neurons in the inferior olive. Olivocerebellar neurons exhibit rhythmic excitatory action when harmaline is applied locally.[68] Harmane or harmaline has been implicated not only in essential tremors, but is also found in greater quantities in the brain fluid of Parkinson's disease sufferers as well as cancer.[69][70][71] Higher levels of the neurotoxin are associated with greater severity of the tremors.[2][72] Harmane is particularly abundant in meats, and certain cooking practices (e.g., long cooking times) increase its concentration,[73][74][75] however, at least one study has shown that harmane blood concentrations do not go up after meat consumption in ET patients with already elevated harmane levels, where as the control group's harmane levels increase accordingly, suggesting that another factor, like a metabolic defect, may be responsible for the higher harmane levels in E.T. patients.[76]
Caprylic acid is being researched as a possible treatment for essential tremor. It has currently been approved by the FDA and designated as GRAS, and is used as a food additive and has been studied as part of a ketogenic diet for treatment of epilepsy in children. Research on caprylic acid as a possible treatment for ET begun because researchers recognized that ethanol was effective in reducing tremor, and because of this, they looked into longer-chain alcohols reducing tremor. They discovered that 1-octanol reduced tremor and did not have the negative side effects of ethanol. Pharmacokinetic research on 1-octanol lead to the discovery that 1-octanol metabolized into caprylic acid in the body and that caprylic acid actually was the tremor-reducing agent.[77] Many studies of the effects of caprylic acid on essential tremor have been done, including a dose-escalation study on ET patients[78] and a study testing the effects of caprylic acid on central and peripheral tremor.[18] The dose-escalation study examined doses of 8 mg/kg to 128 mg/kg and determined that these concentrations were safe with mild side effects. The maximum tolerated dose was not reached in this study. The study testing the effects of caprylic acid on central and peripheral tremors determined that caprylic acid reduced both.
## See also[edit]
* Intention tremor
## References[edit]
1. ^ a b c Kivi R (2012-08-07). "What is essential tremor?". Healthline. Retrieved 17 June 2018.
2. ^ a b Louis ED, Zheng W, Mao X, Shungu DC (August 2007). "Blood harmane is correlated with cerebellar metabolism in essential tremor: a pilot study". Neurology. 69 (6): 515–20. doi:10.1212/01.wnl.0000266663.27398.9f. PMID 17679670. S2CID 7612446.
3. ^ a b "Essential Tremor Treatment at the Johns Hopkins Movement Disorders Center in Baltimore, MD". hopkinsmedicine.org. Retrieved October 27, 2014.
4. ^ Bhidayasiri R (December 2005). "Differential diagnosis of common tremor syndromes". Postgraduate Medical Journal. 81 (962): 756–62. doi:10.1136/pgmj.2005.032979. PMC 1743400. PMID 16344298.
5. ^ a b c d e f g h i j k l Abboud H, Ahmed A, Fernandez HH (December 2011). "Essential tremor: choosing the right management plan for your patient". Cleveland Clinic Journal of Medicine. 78 (12): 821–8. doi:10.3949/ccjm.78a.10178. PMID 22135272. S2CID 58374.
6. ^ Zesiewicz TA, Chari A, Jahan I, Miller AM, Sullivan KL (September 2010). "Overview of essential tremor". Neuropsychiatric Disease and Treatment. 6: 401–8. doi:10.2147/ndt.s4795. PMC 2938289. PMID 20856604.
7. ^ "tremor" at Dorland's Medical Dictionary
8. ^ "LINGO1 variant responsible for essential tremors and Parkinson's disease". news-medical.net. 2009-09-02. Retrieved October 27, 2014.
9. ^ Shukla AW. "Essential Tremor Information". Unified Health. Retrieved 17 June 2018.
10. ^ Louis ED. "Essential Tremor". National Organization for Rare Disorders. Retrieved 17 June 2018.
11. ^ Gironell A, Ribosa-Nogué R, Gich I, Marin-Lahoz J, Pascual-Sedano B (2015). "Severity stages in essential tremor: a long-term retrospective study using the glass scale". Tremor and Other Hyperkinetic Movements. 5: 299. doi:10.7916/D8DV1HQC. PMC 4361372. PMID 25793146.
12. ^ Louis ED (September 2001). "Clinical practice. Essential tremor". The New England Journal of Medicine. 345 (12): 887–91. doi:10.1056/nejmcp010928. PMID 11565522.
13. ^ Ryu DW, Lee SH, Oh YS, An JY, Park JW, Song IU, Lee KS, Kim JS (2017-05-16). "Clinical Characteristics of Parkinson's Disease Developed from Essential Tremor". Journal of Parkinson's Disease. 7 (2): 369–376. doi:10.3233/JPD-160992. PMID 28409750.
14. ^ a b Rajput AH, Rozdilsky B, Ang L, Rajput A (May 1993). "Significance of parkinsonian manifestations in essential tremor". The Canadian Journal of Neurological Sciences. 20 (2): 114–7. doi:10.1017/s031716710004765x. PMID 8334571. INIST:4838591.
15. ^ Benito-León J, Louis ED, Mitchell AJ, Bermejo-Pareja F (2011). "Elderly-onset essential tremor and mild cognitive impairment: a population-based study (NEDICES)". Journal of Alzheimer's Disease. 23 (4): 727–35. doi:10.3233/JAD-2011-101572. PMID 21304183.
16. ^ Benito-León J, Louis ED, Bermejo-Pareja F (May 2006). "Elderly-onset essential tremor is associated with dementia". Neurology. 66 (10): 1500–5. doi:10.1212/01.wnl.0000216134.88617.de. PMID 16717208. S2CID 34434554.
17. ^ Klein RD, Kincaid RL, Hodgson AS, Harrison JH, Hillers JK, Cronrath JD (October 1987). "Dietary fiber and early weaning on growth and rumen development of calves". Journal of Dairy Science. 70 (10): 2095–104. doi:10.3168/jds.S0022-0302(87)80259-X. PMC 2824583. PMID 18043006.
18. ^ a b c Cao H, Thompson-Westra J, Hallett M, Haubenberger D (July 2018). "The response of the central and peripheral tremor component to octanoic acid in patients with essential tremor". Clinical Neurophysiology. 129 (7): 1467–1471. doi:10.1016/j.clinph.2018.03.016. PMC 6530908. PMID 29678370.
19. ^ Deng H, Le W, Jankovic J (June 2007). "Genetics of essential tremor". Brain. 130 (Pt 6): 1456–64. doi:10.1093/brain/awm018. PMID 17353225.
20. ^ Higgins JJ, Pho LT, Nee LE (November 1997). "A gene (ETM) for essential tremor maps to chromosome 2p22-p25". Movement Disorders. 12 (6): 859–64. doi:10.1002/mds.870120605. PMID 9399207. S2CID 2614579.
21. ^ Gulcher JR, Jónsson P, Kong A, Kristjánsson K, Frigge ML, Kárason A, Einarsdóttir IE, Stefánsson H, Einarsdóttir AS, Sigurthoardóttir S, Baldursson S, Björnsdóttir S, Hrafnkelsdóttir SM, Jakobsson F, Benedickz J, Stefánsson K (September 1997). "Mapping of a familial essential tremor gene, FET1, to chromosome 3q13". Nature Genetics. 17 (1): 84–7. doi:10.1038/ng0997-84. PMID 9288103. S2CID 1506516.
22. ^ Louis ED (September 2001). "Etiology of essential tremor: should we be searching for environmental causes?". Movement Disorders. 16 (5): 822–9. doi:10.1002/mds.1183. PMID 11746611. S2CID 38809483.
23. ^ Louis ED, Vonsattel JP (January 2008). "The emerging neuropathology of essential tremor". Movement Disorders. 23 (2): 174–82. doi:10.1002/mds.21731. PMC 2692583. PMID 17999421.
24. ^ a b Mostile G, Jankovic J (October 2010). "Alcohol in essential tremor and other movement disorders". Movement Disorders. 25 (14): 2274–84. doi:10.1002/mds.23240. PMID 20721919. S2CID 39981956.
25. ^ Louis ED (October 2009). "Essential tremors: a family of neurodegenerative disorders?". Archives of Neurology. 66 (10): 1202–8. doi:10.1001/archneurol.2009.217. PMC 2762114. PMID 19822775.
26. ^ Louis ED (2014). "'Essential tremor' or 'the essential tremors': is this one disease or a family of diseases?". Neuroepidemiology. 42 (2): 81–9. doi:10.1159/000356351. PMC 3945103. PMID 24335621.
27. ^ Louis ED, Faust PL, Vonsattel JP, Honig LS, Rajput A, Robinson CA, Rajput A, Pahwa R, Lyons KE, Ross GW, Borden S, Moskowitz CB, Lawton A, Hernandez N (December 2007). "Neuropathological changes in essential tremor: 33 cases compared with 21 controls". Brain. 130 (Pt 12): 3297–307. doi:10.1093/brain/awm266. PMID 18025031.
28. ^ Ghika A, Kyrozis A, Potagas C, Louis ED (2015). "Motor and Non-motor Features: Differences between Patients with Isolated Essential Tremor and Patients with Both Essential Tremor and Parkinson's Disease". Tremor and Other Hyperkinetic Movements. 5: 335. doi:10.7916/D83777WK. PMC 4548968. PMID 26336614.
29. ^ Benito-León J, Sanz-Morales E, Melero H, Louis ED, Romero JP, Rocon E, Malpica N (November 2019). "Graph theory analysis of resting-state functional magnetic resonance imaging in essential tremor". Human Brain Mapping. 40 (16): 4686–4702. doi:10.1002/hbm.24730. PMC 6865733. PMID 31332912.
30. ^ Delay C, Tremblay C, Brochu E, Paris-Robidas S, Emond V, Rajput AH, Rajput A, Calon F (November 2014). "Increased LINGO1 in the cerebellum of essential tremor patients". Movement Disorders. 29 (13): 1637–47. doi:10.1002/mds.25819. PMID 24531928. S2CID 27331090.
31. ^ Kuo SH, Tang G, Louis ED, Ma K, Babji R, Balatbat M, Cortes E, Vonsattel JP, Yamamoto A, Sulzer D, Faust PL (June 2013). "Lingo-1 expression is increased in essential tremor cerebellum and is present in the basket cell pinceau". Acta Neuropathologica. 125 (6): 879–89. doi:10.1007/s00401-013-1108-7. PMC 3663903. PMID 23543187.
32. ^ Paris-Robidas S, Brochu E, Sintes M, Emond V, Bousquet M, Vandal M, Pilote M, Tremblay C, Di Paolo T, Rajput AH, Rajput A, Calon F (January 2012). "Defective dentate nucleus GABA receptors in essential tremor". Brain. 135 (Pt 1): 105–16. doi:10.1093/brain/awr301. PMID 22120148.
33. ^ Vilariño-Güell C, Soto-Ortolaza AI, Rajput A, Mash DC, Papapetropoulos S, Pahwa R, Lyons KE, Uitti RJ, Wszolek ZK, Dickson DW, Farrer MJ, Ross OA (February 2011). "MAPT H1 haplotype is a risk factor for essential tremor and multiple system atrophy". Neurology. 76 (7): 670–2. doi:10.1212/WNL.0b013e31820c30c1. PMC 3053340. PMID 21321341.
34. ^ "NTP monograph on health effects of low-level lead" (PDF). NTP Monograph. US Department of Health and Human Services (1): xiii, xv–148. June 2012. PMID 23964424.
35. ^ Louis ED, Dure LS, Pullman S (September 2001). "Essential tremor in childhood: a series of nineteen cases". Movement Disorders. 16 (5): 921–3. doi:10.1002/mds.1182. PMID 11746623. S2CID 30848508.
36. ^ Bain PG, Findley LJ, Thompson PD, Gresty MA, Rothwell JC, Harding AE, Marsden CD (August 1994). "A study of hereditary essential tremor". Brain. 117 (4): 805–24. doi:10.1093/brain/117.4.805. PMID 7922467.
37. ^ Cohen O, Pullman S, Jurewicz E, Watner D, Louis ED (2003). "Rest tremor in essential tremor patients: Prevalence, clinical correlates, and electrophysiological characteristics". Arch Neurol. 60 (3): 405–410. doi:10.1001/archneur.60.3.405. PMID 12633153.
38. ^ Biary N, Koller W, Langenberg P (December 1990). "Correlation between essential tremor and migraine headache". Journal of Neurology, Neurosurgery, and Psychiatry. 53 (12): 1060–2. doi:10.1136/jnnp.53.12.1060. PMC 488315. PMID 2292698.
39. ^ a b Bain PG, Mally J, Gresty M, Findley LJ (November 1993). "Assessing the impact of essential tremor on upper limb function". Journal of Neurology. 241 (1): 54–61. doi:10.1007/bf00870673. PMID 8138823. S2CID 9502687.
40. ^ a b Louis ED, Barnes L, Albert SM, Cote L, Schneier FR, Pullman SL, Yu Q (September 2001). "Correlates of functional disability in essential tremor". Movement Disorders. 16 (5): 914–20. doi:10.1002/mds.1184. PMID 11746622. S2CID 9540572.
41. ^ Zesiewicz TA, Elble R, Louis ED, Hauser RA, Sullivan KL, Dewey RB, Ondo WG, Gronseth GS, Weiner WJ (June 2005). "Practice parameter: therapies for essential tremor: report of the Quality Standards Subcommittee of the American Academy of Neurology". Neurology. 64 (12): 2008–20. doi:10.1212/01.WNL.0000163769.28552.CD. PMID 15972843.
42. ^ Mally J, Stone TW (June 1991). "The effect of theophylline on essential tremor: the possible role of GABA". Pharmacology Biochemistry and Behavior. 39 (2): 345–9. doi:10.1016/0091-3057(91)90190-D. PMID 1946576. S2CID 1344534.
43. ^ Mally J, Stone TW (October 1995). "Efficacy of an adenosine antagonist, theophylline, in essential tremor: comparison with placebo and propranolol". Journal of the Neurological Sciences. 132 (2): 129–32. doi:10.1016/0022-510X(95)00128-O. PMID 8543937. S2CID 21810329.
44. ^ Ondo W (2016). "Essential Tremor: What We Can Learn from Current Pharmacotherapy". Tremor and Other Hyperkinetic Movements. 6: 356. doi:10.7916/D8K35TC3. PMC 4790207. PMID 26989572.
45. ^ Bruno E, Nicoletti A, Quattrocchi G, Allegra R, Filippini G, Colosimo C, Zappia M (April 2017). "Topiramate for essential tremor". The Cochrane Database of Systematic Reviews. 4: CD009683. doi:10.1002/14651858.CD009683.pub2. PMC 6478240. PMID 28409827.
46. ^ Bruno E, Nicoletti A, Filippini G, Quattrocchi G, Colosimo C, Zappia M (August 2017). "Zonisamide for essential tremor". The Cochrane Database of Systematic Reviews. 8: CD009684. doi:10.1002/14651858.CD009684.pub2. PMC 6483684. PMID 28836659.
47. ^ Bruno E, Nicoletti A, Quattrocchi G, Filippini G, Colosimo C, Zappia M (October 2016). "Pregabalin for essential tremor". The Cochrane Database of Systematic Reviews. 10: CD009682. doi:10.1002/14651858.CD009682.pub2. PMC 6461190. PMID 27763691.
48. ^ Zakin E, Simpson D (November 2017). "Botulinum Toxin in Management of Limb Tremor". Toxins. 9 (11): 365. doi:10.3390/toxins9110365. PMC 5705980. PMID 29125566.
49. ^ Samotus O, Rahimi F, Lee J, Jog M (2016). "Functional Ability Improved in Essential Tremor by IncobotulinumtoxinA Injections Using Kinematically Determined Biomechanical Patterns - A New Future". PLOS ONE. 11 (4): e0153739. Bibcode:2016PLoSO..1153739S. doi:10.1371/journal.pone.0153739. PMC 4839603. PMID 27101283.
50. ^ Samotus O, Lee J, Jog M (2017). "Long-term tremor therapy for Parkinson and essential tremor with sensor-guided botulinum toxin type A injections". PLOS ONE. 12 (6): e0178670. Bibcode:2017PLoSO..1278670S. doi:10.1371/journal.pone.0178670. PMC 5460844. PMID 28586370.
51. ^ Samotus O, Kumar N, Rizek P, Jog M (January 2018). "Botulinum Toxin Type A Injections as Monotherapy for Upper Limb Essential Tremor Using Kinematics". The Canadian Journal of Neurological Sciences. 45 (1): 11–22. doi:10.1017/cjn.2017.260. PMID 29157315.
52. ^ a b Rohani M, Fasano A (2017). "Focused Ultrasound for Essential Tremor: Review of the Evidence and Discussion of Current Hurdles". Tremor and Other Hyperkinetic Movements. 7: 462. doi:10.7916/D8Z89JN1. PMC 5425801. PMID 28503363.
53. ^ a b c d e FDA News Release. "FDA approves first MRI-guided focused ultrasound device to treat essential tremor", FDA, July 11, 2016
54. ^ Chang JW, Park CK, Lipsman N, Schwartz ML, Ghanouni P, Henderson JM, Gwinn R, Witt J, Tierney TS, Cosgrove GR, Shah BB, Abe K, Taira T, Lozano AM, Eisenberg HM, Fishman PS, Elias WJ (December 2017). "A Prospective Trial of Magnetic Resonance guided Focused Ultrasound Thalamotomy for Essential Tremor: Results at the 2-year Follow-up". Annals of Neurology. 83 (1): 107–114. doi:10.1002/ana.25126. PMID 29265546. S2CID 4437809.
55. ^ Hedera P (February 2017). "Emerging strategies in the management of essential tremor". Therapeutic Advances in Neurological Disorders (Review). 10 (2): 137–148. doi:10.1177/1756285616679123. PMC 5367648. PMID 28382111.
56. ^ Critchley M (1949). "Observations on essential (heredofamilial) tremor". Brain. 72 (2): 113–139. doi:10.1093/brain/72.2.113. PMID 18136705.
57. ^ Busenbark KL, Nash J, Nash S, Hubble JP, Koller WC (1991). "Is essential tremor benign?". Neurology. 41 (12): 1982–1983. doi:10.1212/wnl.41.12.1982. PMID 1745359. S2CID 41199748.
58. ^ Louis ED, Ford B, Barnes LF (2000). "Clinical subtypes of essential tremor". Arch Neurol. 57 (8): 1194–1198. doi:10.1001/archneur.57.8.1194. PMID 10927801.
59. ^ Louis ED, Ferreira JJ (April 2010). "How common is the most common adult movement disorder? Update on the worldwide prevalence of essential tremor". Movement Disorders. 25 (5): 534–41. doi:10.1002/mds.22838. PMID 20175185. S2CID 32051975.
60. ^ Benito-León J, Louis ED (December 2006). "Essential tremor: emerging views of a common disorder". Nature Clinical Practice Neurology. 2 (12): 666–78, quiz 2p following 691. doi:10.1038/ncpneuro0347. PMID 17117170. S2CID 5902956.
61. ^ Healy, David (director) (January 18, 1993). Katharine Hepburn: All About Me. Turner Home Entertainment.
62. ^ Claiborne RC (July 22, 2003). "Q & A; Head and Hand Tremors". The New York Times. Retrieved November 3, 2013.
63. ^ a b Berg AS (2004) [2003]. Kate Remembered: Katharine Hepburn, a personal biography. London: Pocket. p. 260. ISBN 978-0-7434-1563-7.
64. ^ Conova S (January 29, 2003). "Stopping essential tremor". In Vivo. Columbia University Health Sciences. 2 (2).
65. ^ Dickens H (1990) [1971]. The Films of Katharine Hepburn. New York City, NY: Carol Publishing Group. p. 31. ISBN 978-0-8065-1175-7.
66. ^ Goodyear D. "Hollywood Shadows". The New Yorker. Retrieved 2018-12-13.
67. ^ "Downton Abbey creator reveals reason he gave Mr Carson a tremor". Breaking News.ie. November 19, 2019. Retrieved August 20, 2020.
68. ^ a b Miwa H (2007). "Rodent models of tremor". Cerebellum. 6 (1): 66–72. doi:10.1080/14734220601016080. PMID 17366267. S2CID 24179439.
69. ^ Kuhn W, Müller T, Grosse H, Rommelspacher H (1996). "Elevated levels of harman and norharman in cerebrospinal fluid of parkinsonian patients". Journal of Neural Transmission. 103 (12): 1435–40. doi:10.1007/bf01271257. PMID 9029410. S2CID 21230301.
70. ^ Pfau W, Skog K (March 2004). "Exposure to beta-carbolines norharman and harman". Journal of Chromatography B. 802 (1): 115–26. doi:10.1016/j.jchromb.2003.10.044. PMID 15036003.
71. ^ Louis ED, Pellegrino KM, Factor-Litvak P, Rios E, Jiang W, Henchcliffe C, Zheng W (September 2008). "Cancer and blood concentrations of the comutagen harmane in essential tremor". Movement Disorders. 23 (12): 1747–51. doi:10.1002/mds.22084. PMC 2597456. PMID 18709680.
72. ^ Louis ED, Factor-Litvak P, Gerbin M, Slavkovich V, Graziano JH, Jiang W, Zheng W (March 2011). "Blood harmane, blood lead, and severity of hand tremor: evidence of additive effects". Neurotoxicology. 32 (2): 227–32. doi:10.1016/j.neuro.2010.12.002. PMC 3073713. PMID 21145352.
73. ^ Louis ED, Jiang W, Gerbin M, Viner AS, Factor-Litvak P, Zheng W (2012). "Blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor: repeat observation in cases and controls in New York". Journal of Toxicology and Environmental Health. Part A. 75 (12): 673–83. doi:10.1080/15287394.2012.688485. PMC 3412610. PMID 22757671.
74. ^ Louis ED, Zheng W, Jiang W, Bogen KT, Keating GA (June 2007). "Quantification of the neurotoxic beta-carboline harmane in barbecued/grilled meat samples and correlation with level of doneness". Journal of Toxicology and Environmental Health. Part A. 70 (12): 1014–9. doi:10.1080/15287390601172015. PMC 4993204. PMID 17497412.
75. ^ Louis ED, Keating GA, Bogen KT, Rios E, Pellegrino KM, Factor-Litvak P (2008). "Dietary epidemiology of essential tremor: meat consumption and meat cooking practices". Neuroepidemiology. 30 (3): 161–6. doi:10.1159/000122333. PMC 2821442. PMID 18382115.
76. ^ Louis ED, Zheng W, Applegate L, Shi L, Factor-Litvak P (August 2005). "Blood harmane concentrations and dietary protein consumption in essential tremor". Neurology. 65 (3): 391–6. doi:10.1212/01.wnl.0000172352.88359.2d. PMC 4993192. PMID 16087903.
77. ^ Haubenberger D, McCrossin G, Lungu C, Considine E, Toro C, Nahab FB, Auh S, Buchwald P, Grimes GJ, Starling J, Potti G, Scheider L, Kalowitz D, Bowen D, Carnie A, Hallett M (March 2013). "Octanoic acid in alcohol-responsive essential tremor: a randomized controlled study". Neurology. 80 (10): 933–40. doi:10.1212/WNL.0b013e3182840c4f. PMC 3653213. PMID 23408867.
78. ^ Voller B, Lines E, McCrossin G, Tinaz S, Lungu C, Grimes G, Starling J, Potti G, Buchwald P, Haubenberger D, Hallett M (April 2016). "Dose-escalation study of octanoic acid in patients with essential tremor". The Journal of Clinical Investigation. 126 (4): 1451–7. doi:10.1172/JCI83621. PMC 4811161. PMID 26927672.
## External links[edit]
Classification
D
* ICD-10: G25.0
* ICD-9-CM: 333.1
* OMIM: 190300 602134
* MeSH: D020329
* SNOMED CT: 609558009
External resources
* MedlinePlus: 000762
* eMedicine: neuro/129
* Essential tremor at Curlie
* v
* t
* e
Diseases of the nervous system, primarily CNS
Inflammation
Brain
* Encephalitis
* Viral encephalitis
* Herpesviral encephalitis
* Limbic encephalitis
* Encephalitis lethargica
* Cavernous sinus thrombosis
* Brain abscess
* Amoebic
Brain and spinal cord
* Encephalomyelitis
* Acute disseminated
* Meningitis
* Meningoencephalitis
Brain/
encephalopathy
Degenerative
Extrapyramidal and
movement disorders
* Basal ganglia disease
* Parkinsonism
* PD
* Postencephalitic
* NMS
* PKAN
* Tauopathy
* PSP
* Striatonigral degeneration
* Hemiballismus
* HD
* OA
* Dyskinesia
* Dystonia
* Status dystonicus
* Spasmodic torticollis
* Meige's
* Blepharospasm
* Athetosis
* Chorea
* Choreoathetosis
* Myoclonus
* Myoclonic epilepsy
* Akathisia
* Tremor
* Essential tremor
* Intention tremor
* Restless legs
* Stiff-person
Dementia
* Tauopathy
* Alzheimer's
* Early-onset
* Primary progressive aphasia
* Frontotemporal dementia/Frontotemporal lobar degeneration
* Pick's
* Dementia with Lewy bodies
* Posterior cortical atrophy
* Vascular dementia
Mitochondrial disease
* Leigh syndrome
Demyelinating
* Autoimmune
* Inflammatory
* Multiple sclerosis
* For more detailed coverage, see Template:Demyelinating diseases of CNS
Episodic/
paroxysmal
Seizures and epilepsy
* Focal
* Generalised
* Status epilepticus
* For more detailed coverage, see Template:Epilepsy
Headache
* Migraine
* Cluster
* Tension
* For more detailed coverage, see Template:Headache
Cerebrovascular
* TIA
* Stroke
* For more detailed coverage, see Template:Cerebrovascular diseases
Other
* Sleep disorders
* For more detailed coverage, see Template:Sleep
CSF
* Intracranial hypertension
* Hydrocephalus
* Normal pressure hydrocephalus
* Choroid plexus papilloma
* Idiopathic intracranial hypertension
* Cerebral edema
* Intracranial hypotension
Other
* Brain herniation
* Reye syndrome
* Hepatic encephalopathy
* Toxic encephalopathy
* Hashimoto's encephalopathy
Both/either
Degenerative
SA
* Friedreich's ataxia
* Ataxia–telangiectasia
MND
* UMN only:
* Primary lateral sclerosis
* Pseudobulbar palsy
* Hereditary spastic paraplegia
* LMN only:
* Distal hereditary motor neuronopathies
* Spinal muscular atrophies
* SMA
* SMAX1
* SMAX2
* DSMA1
* Congenital DSMA
* Spinal muscular atrophy with lower extremity predominance (SMALED)
* SMALED1
* SMALED2A
* SMALED2B
* SMA-PCH
* SMA-PME
* Progressive muscular atrophy
* Progressive bulbar palsy
* Fazio–Londe
* Infantile progressive bulbar palsy
* both:
* Amyotrophic lateral sclerosis
*[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
| Essential tremor | c0270736 | 2,086 | wikipedia | https://en.wikipedia.org/wiki/Essential_tremor | 2021-01-18T18:47:00 | {"gard": ["5910"], "mesh": ["D020329"], "umls": ["C0270736"], "orphanet": ["862"], "wikidata": ["Q693519"]} |
Coloboma of the optic nerve is a congenital eye abnormality in which the optic nerve (which carries images of what the eye sees to the brain) is incompletely formed. The condition may occur in one or both eyes. The degree of visual impairment varies widely depending on the severity and structures involved. Serous detachments of the retina commonly occur in affected people, with a high risk for extensive retinal detachment. The coloboma may be associated with other features, such as a small eye (microphthalmia) with or without a cyst; small cornea (microcornea); or coloboma of other eye structures. Although the condition is present from birth, diagnosis may be delayed since the coloboma is inside the eye and not visible by simple inspection. Coloboma of the optic nerve may occur sporadically, may be due to a genetic mutation and be inherited, or may occur as a feature of an underlying syndrome or other genetic condition. There is no treatment to correct an optic nerve coloboma, but low vision aids may be helpful for some people.
*[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
| Coloboma of optic nerve | c0155299 | 2,087 | gard | https://rarediseases.info.nih.gov/diseases/8502/coloboma-of-optic-nerve | 2021-01-18T18:01:13 | {"mesh": ["C535970"], "omim": ["120430"], "umls": ["C0155299"], "synonyms": ["Optic nerve head pits, bilateral congenital", "Congenital coloboma of the optic nerve", "Optic nerve coloboma"]} |
Bleeding on probing (BoP) which is also known as bleeding gums or gingival bleeding is a term used by dentists and dental hygienists when referring to bleeding that is induced by gentle manipulation of the tissue at the depth of the gingival sulcus, or interface between the gingiva and a tooth. BoP is a sign of periodontal inflammation and indicates some sort of destruction and erosion to the lining of the sulcus[1] or the ulceration of sulcular epithelium.[2] The blood comes from lamina propria after the ulceration of the lining.[2] BoP seems to be correlated with Periodontal Inflamed Surface Area (PISA).[3]
## Contents
* 1 Causes
* 2 Diagnosis
* 3 Treatment
* 4 References
## Causes[edit]
There are many possible causes of gingival bleeding. The main cause of gingival bleeding is the formation and accumulation of plaque at the gum line due to improper brushing and flossing of teeth. The hardened form of plaque is calculus. An advanced form of gingivitis as a result of formation of plaque is periodontitis. Other conditions associated with gingival bleeding include:[4]
* Tooth and/or gum infection
* Diabetes mellitus[5]
* Hypertension[6][7]
* Idiopathic thrombocytopenic purpura
* Leukemia
* Malnutrition
* Aspirin and anticoagulants therapy [8]
* Hormonal imbalances during puberty and pregnancy
* Iron overload
Other less common causes are:
* vitamin C deficiency (scurvy) and vitamin K deficiency
* dengue fever[9]
## Diagnosis[edit]
An examination by the dentist or dental hygienist should be sufficient to rule out the issues such as malnutrition and puberty. Additional corresponding diagnosis tests to certain potential disease may be required. This includes oral glucose tolerance test for diabetes mellitus, blood studies, human gonadotrophin levels for pregnancy,[5] and X-rays for teeth and jaw bones.[4]
In order to determine the periodontal health of a patient, the dentist or dental hygienist records the sulcular depths of the gingiva and observes any bleeding on probing. This is often accomplished with the use of a periodontal probe. Alternatively, dental floss may also be used to assess the Gingival bleeding index. It is used as an initial evaluation on patient's periodontal health especially to measure gingivitis. The number of bleeding sites is used to calculate the gingival bleeding score.[10]
Peer-reviewed dental literature thoroughly establishes that bleeding on probing is a poor positive predictor of periodontal disease, but conversely lack of bleeding is a very strong negative predictor. The clinical interpretation of this research is that while BOP presence may not indicate periodontal disease, continued absence of BOP is a strong predictor (approximately 98%) of continued periodontal health.[11]
## Treatment[edit]
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* Corresponding treatments for diagnosed diseases should be taken as first priority.
* Dentist or hygienists should be visited once every three months for plaque removal.
* Soft-bristle toothbrush is recommended for brushing your teeth. Hard-bristled toothbrushes may be softened by leaving under hot running water (very hot) before brushing every time, followed by gentle brushing.[12]
* Flossing twice a day can prevent the building up of plaques.
* Tobacco should be avoided as tobacco can aggravate the bleeding gums.
* A balanced healthy diet should also be taken into account.[4]
* Physiotherapy programme using over-the-counter toothpaste with triclosan should be used with home care.
If there is persistent continuation of inflammation and bleeding, a prescription of antiplaque rinse would be useful.[5]
## References[edit]
1. ^ CARRANZA'S CLINICAL PERIODONTOLOGY, 9th edition, 2002. page 447
2. ^ a b Gingival bleeding URL assessed on November 21, 2009
3. ^ Pietropaoli, Davide; Del Pinto, Rita; Ferri, Claudio; Marzo, Giuseppe; Giannoni, Mario; Ortu, Eleonora; Monaco, Annalisa (February 2020). "Association between periodontal inflammation and hypertension using periodontal inflamed surface area and bleeding on probing". Journal of Clinical Periodontology. 47 (2): 160–172. doi:10.1111/jcpe.13216. ISSN 0303-6979.
4. ^ a b c MedlinePlus: Bleeding gums URL assessed on November 21, 2009
5. ^ a b c Charles R. Craig, Robert E. Stitzel (2004) In Modern Pharmacology with clinical applications (Edition 6). Lippincott Williams & Wilkins. p. 506. ISBN 0-7817-3762-1. Google Book Search. Retrieved on November 21, 2009.
6. ^ Pietropaoli, Davide; Del Pinto, Rita; Ferri, Claudio; Marzo, Giuseppe; Giannoni, Mario; Ortu, Eleonora; Monaco, Annalisa (2020). "Association between periodontal inflammation and hypertension using periodontal inflamed surface area and bleeding on probing". Journal of Clinical Periodontology. 47 (2): 160–172. doi:10.1111/jcpe.13216. ISSN 1600-051X. PMID 31680283.
7. ^ Pietropaoli, Davide; Monaco, Annalisa; D'Aiuto, Francesco; Muñoz Aguilera, Eva; Ortu, Eleonora; Giannoni, Mario; Czesnikiewicz-Guzik, Marta; Guzik, Tomasz J.; Ferri, Claudio; Del Pinto, Rita (2020-06-22). "Active gingival inflammation is linked to hypertension". Journal of Hypertension. doi:10.1097/HJH.0000000000002514. ISSN 1473-5598. PMID 32576741.
8. ^ Howstuffworks Bleeding gums Archived 2017-10-12 at the Wayback Machine URL assessed on November 21, 2009
9. ^ Hayes, E. B.; Gubler, D. J. Pediatr. Infect. Dis. J., 1992, 11, 311- 317.
10. ^ Gingival Bleeding Index of Carter and Barnes URL assessed on November 21, 2009
11. ^ Absence of bleeding on probing. An indicator of periodontal stability. J Clin Periodontol. 1990 Nov;17(10):714-21.
12. ^ "Mermaid Clinic-in Gum disease and periodontal disease". Retrieved January 17, 2017.
* v
* t
* e
Dentistry involving supporting structures of teeth (Periodontology)
Anatomy
* Periodontium
* Alveolar bone
* Biologic width
* Bundle bone
* Cementum
* Free gingival margin
* Gingiva
* Gingival fibers
* Gingival sulcus
* Junctional epithelium
* Mucogingival junction
* Periodontal ligament
* Sulcular epithelium
* Stippling
Disease
Diagnoses
* Chronic periodontitis
* Localized aggressive periodontitis
* Generalized aggressive periodontitis
* Periodontitis as a manifestation of systemic disease
* Periodontosis
* Necrotizing periodontal diseases
* Abscesses of the periodontium
* Combined periodontic-endodontic lesions
Infection
* A. actinomycetemcomitans
* Capnocytophaga sp.
* F. nucleatum
* P. gingivalis
* P. intermedia
* T. forsythia
* T. denticola
* Red complex
* Entamoeba gingivalis (amoebic)
* Trichomonas tenax
Other
* Calculus
* Clinical attachment loss
* Edentulism
* Fremitus
* Furcation defect
* Gingival enlargement
* Gingival pocket
* Gingival recession
* Gingivitis
* Horizontal bony defect
* Linear gingival erythema
* Occlusal trauma
* Periodontal pocket
* Periodontal disease
* Periodontitis
* Plaque
* Vertical bony defect
Treatment and prevention
* Periodontal examination
* Ante's law
* Brushing
* Bleeding on probing
* Chlorhexidine gluconate
* Flossing
* Hydrogen peroxide
* Mouthwash
* Oral hygiene
* Tetracycline
* Triclosan
* Host modulatory therapy
Treatment
Conventional therapy
* Debridement
* Scaling and root planing
* Full mouth disinfection
* Full mouth ultrasonic debridement
Surgery
* Apically positioned flap
* Bone graft
* Coronally positioned flap
* Crown lengthening
* Free gingival graft
* Gingival grafting
* Gingivectomy
* Guided bone regeneration
* Guided tissue regeneration
* Enamel matrix derivative
* Implant placement
* Lateral pedicle graft
* Open flap debridement
* Pocket reduction surgery
* Socket preservation
* Sinus lift
* Subepithelial connective tissue graft
* Tools
* Curette
* Membrane
* Probe
* Scaler
Important personalities
* Tomas Albrektsson
* Frank Beube
* Per-Ingvar Brånemark
* Robert Gottsegen
* Gary Greenstein
* Jan Lindhe
* Brian Mealey
* Preston D. Miller
* Willoughby D. Miller
* Carl E. Misch
* John Mankey Riggs
* Jay Seibert
* Jørgen Slots
* Paul Roscoe Stillman
* Dennis P. Tarnow
* Hom-Lay Wang
* James Leon Williams
* W. J. Younger
Other specialties
* Endodontology
* Orthodontology
* Prosthodontology
*[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
| Bleeding on probing | c2698524 | 2,088 | wikipedia | https://en.wikipedia.org/wiki/Bleeding_on_probing | 2021-01-18T18:28:13 | {"wikidata": ["Q4925923"]} |
Autosomal recessive spastic paraplegia type 66 is a rare, complex hereditary spastic paraplegia disorder characterized by infantile onset of progressive lower limb spasticity, severe gait disturbances leading to a non-ambulatory state, absent deep tendon reflexes and amyotrophy. Additional signs include severe sensorimotor neuropathy, pes equinovarus and mild intellectual disability. Cerebellar and corpus callosum hypoplasia, as well as colpocephaly, are observed on neuroimaging.
*[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
| Autosomal recessive spastic paraplegia type 66 | None | 2,089 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=401815 | 2021-01-23T17:00:55 | {"icd-10": ["G11.4"], "synonyms": ["SPG66"]} |
## Description
Optic atrophy-8 (OPA8) is an autosomal dominant neurologic disorder characterized by progressive visual loss during the first or second decade of life. Some patients may have additional features, mainly late-onset sensorineural hearing loss.
For a discussion of genetic heterogeneity of optic atrophy, see OPA1 (165500).
Clinical Features
Carelli et al. (2011) reported a large multigenerational kindred from the Italian region of Emilia-Romagna in which 53 individuals had with optic neuropathy. Five affected adults were studied in detail. Onset of visual loss occurred between 6 and 21 years of age, and symptoms included central scotoma, diffuse reduction in the retinal nerve fiber layer, and abnormal visual evoked potentials. Electroretinogram was normal in all patients. Two patients had bilateral sensorineural hearing loss for high frequencies, and 3 had abnormal brainstem auditory evoked potentials. Somatosensory evoked potentials were also increased, suggesting some involvement of the dorsal columns. In addition, all 5 patients had mitral valve prolapse or insufficiency. Although mitochondrial integrity and respiratory enzyme analyses were normal, muscle biopsy showed subsarcolemmal accumulations of mitochondria and a slight increase in mtDNA content. Patient fibroblasts grown in galactose medium were unable to increase ATP content compared to controls, and showed an abnormally high rate of fusion activity, suggestive of mitochondrial dysfunction. Ophthalmologic investigations of 11 additional affected family members showed optic atrophy with central scotoma and reduced visual acuity. Carelli et al. (2011) noted that the patients had preferential involvement of the papillomacular bundle with temporal atrophy, which is a typical feature of mitochondrial optic neuropathies.
Inheritance
The transmission pattern of OPA8 in the family reported by Carelli et al. (2011) was consistent with autosomal dominant inheritance.
Mapping
By genomewide linkage analysis of a large Italian kindred with OPA8, Carelli et al. (2011) found significant linkage to a 6.94-cM region on chromosome 16q21-q22 (maximum 2-point lod score of 8.84 at D16S752). Genomic screening of candidate genes in this region did not reveal any mutations.
INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Hearing loss, sensorineural (in some patients) \- Abnormal brainstem auditory evoked potentials (in some patients) Eyes \- Optic atrophy \- Central scotoma \- Visual loss \- Diffuse reduction in retinal nerve fiber layer \- Abnormal pattern visual evoked potentials CARDIOVASCULAR Heart \- Mitral valve prolapse (in some patients) \- Mitral valve insufficiency (in some patients) MUSCLE, SOFT TISSUES \- Subsarcolemmal accumulation of mitochondria seen on skeletal muscle biopsy \- Mildly increased mtDNA NEUROLOGIC Central Nervous System \- Increased conduction time of somatosensory evoked potentials (in some patients) LABORATORY ABNORMALITIES \- Fibroblasts show some mitochondrial abnormalities, such as increased mitochondrial fusion MISCELLANEOUS \- Onset of visual loss in the first or second decades \- Hearing loss occurs later if at all \- One large Italian kindred has been reported (last curated November 2015) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| OPTIC ATROPHY 8 | c1832466 | 2,090 | omim | https://www.omim.org/entry/616648 | 2019-09-22T15:48:21 | {"mesh": ["C535351"], "omim": ["616648"], "orphanet": ["1215"]} |
Involuntary muscle spasm prevents vaginal penetration.
Not to be confused with Vaginitis.
Vaginismus
Other namesVaginism, genito-pelvic pain disorder[1]
Muscles included
SpecialtyGynecology
SymptomsPain with sex[2]
Usual onsetWith first sexual intercourse[3]
CausesFear of pain[3]
Risk factorsHistory of sexual assault, endometriosis, vaginitis, prior episiotomy[2]
Diagnostic methodBased on the symptoms and examination[2]
Differential diagnosisDyspareunia[4]
TreatmentBehavior therapy, gradual vaginal dilatation[2]
PrognosisGenerally good with treatment[5]
Frequency0.5% of women[2]
Vaginismus is a condition in which involuntary muscle spasm interferes with vaginal intercourse or other penetration of the vagina.[2] This often results in pain with attempts at sex.[2] Often, it begins when vaginal intercourse is first attempted.[3]
The formal diagnostic criteria specifically requires interference during vaginal intercourse and a desire for intercourse. However, the term vaginismus is sometimes used more broadly to refer to any muscle spasms occurring during the insertion of some or all types of objects into the vagina, sexually motivated or otherwise, including the usage of speculums and tampons.[6][7]
The underlying cause is generally a fear that penetration will hurt.[3] Risk factors include a history of sexual assault, endometriosis, vaginitis, or a prior episiotomy.[2] Diagnosis is based on the symptoms and examination.[2] It requires there to be no anatomical or physical problems and a desire for penetration on the part of the woman.[3][8]
Treatment may include behavior therapy such as graduated exposure therapy and gradual vaginal dilatation.[2][3] Surgery is not generally indicated.[5] Botulinum toxin (botox), a muscle spasm treatment, is being studied.[2] Estimates of how common the condition is vary.[9] One textbook estimates that 0.5% of women are affected.[2] Outcomes are generally good with treatment.[5]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 2.1 Primary vaginismus
* 2.2 Secondary vaginismus
* 3 Mechanism
* 4 Diagnosis
* 5 Treatment
* 5.1 Psychological
* 5.2 Physical
* 5.3 Neuromodulators
* 6 Epidemiology
* 7 See also
* 8 References
* 9 Further reading
## Signs and symptoms[edit]
Severity and pain during vaginal penetration varies.[10]
## Causes[edit]
### Primary vaginismus[edit]
Vaginismus occurs when penetrative sex or other vaginal penetration cannot be experienced without pain. It is commonly discovered among teenage girls and women in their early twenties, as this is when many girls and young women first attempt to use tampons, have penetrative sex, or undergo a Pap smear. Awareness of vaginismus may not happen until vaginal penetration is attempted. Reasons for the condition may be unknown.[11]
A few of the main factors that may contribute to primary vaginismus include:
* chronic pain conditions and harm-avoidance behaviour[12]
* negative emotional reaction towards sexual stimulation, e.g. disgust both at a deliberate level and also at a more implicit level[13]
* strict conservative moral education, which also can elicit negative emotions[14]
Primary vaginismus is often unknown cause.[15]
Vaginismus has been classified by Lamont[16] according to the severity of the condition. Lamont describes four degrees of vaginismus: In first degree vaginismus, the person has spasm of the pelvic floor that can be relieved with reassurance. In second degree, the spasm is present but maintained throughout the pelvis even with reassurance. In third degree, the person elevates the buttocks to avoid being examined. In fourth degree vaginismus (also known as grade 4 vaginismus), the most severe form of vaginismus, the person elevates the buttocks, retreats and tightly closes the thighs to avoid examination. Pacik expanded the Lamont classification to include a fifth degree in which the person experiences a visceral reaction such as sweating, hyperventilation, palpitations, trembling, shaking, nausea, vomiting, losing consciousness, wanting to jump off the table, or attacking the doctor.[17]
Although the pubococcygeus muscle is commonly thought to be the primary muscle involved in vaginismus, Pacik identified two additionally-involved spastic muscles in people who were treated under sedation. These include the entry muscle (bulbocavernosum) and the mid-vaginal muscle (puborectalis). Spasm of the entry muscle accounts for the common complaint that people often report when trying to have intercourse: "It's like hitting a brick wall".[11]
### Secondary vaginismus[edit]
Secondary vaginismus occurs when a person who has previously been able to achieve penetration develops vaginismus. This may be due to physical causes such as a yeast infection or trauma during childbirth, while in some cases it may be due to psychological causes, or to a combination of causes. The treatment for secondary vaginismus is the same as for primary vaginismus, although, in these cases, previous experience with successful penetration can assist in a more rapid resolution of the condition. Peri-menopausal and menopausal vaginismus, often due to a drying of the vulvar and vaginal tissues as a result of reduced estrogen, may occur as a result of "micro-tears" first causing sexual pain then leading to vaginismus.[18]
## Mechanism[edit]
Specific muscle involvement is unclear, but the condition may involve the pubococcygeus muscle, levator ani, bulbocavernosus, circumvaginal, or perivaginal muscles.[9]
## Diagnosis[edit]
The diagnosis of vaginismus, as well as other diagnoses of female sexual dysfunction, can be made when "symptoms are sufficient to result in personal distress."[19] The DSM-IV-TR defines vaginismus as "recurrent or persistent involuntary spasm of the musculature of the outer third of the vagina that interferes with sexual intercourse, causing marked distress or interpersonal difficulty".[19]
## Treatment[edit]
A Cochrane review found little high quality evidence regarding the treatment of vaginismus in 2012.[20] Specifically it is unclear if systematic desensitisation is better than other measures including nothing.[20]
### Psychological[edit]
According to a 2011 study those with vaginismus are twice as likely to have a history of childhood sexual interference and held less positive attitudes about their sexuality, whereas no correlation was noted for lack of sexual knowledge or (non-sexual) physical abuse.[21]
### Physical[edit]
Dilators for treating vaginismus
Often, when faced with a person experiencing painful intercourse, a gynecologist will recommend Kegel exercises and provide some additional lubricants.[22][23][24][25] Strengthening the muscles that unconsciously tighten during vaginismus may be extremely counter-intuitive for some people. Although vaginismus has not been shown to affect a person's ability to produce lubrication, providing additional lubricant can be helpful in achieving successful penetration. This is due to the fact that women may not produce natural lubrication if anxious or in pain. Treatment of vaginismus may involve the use Hegar dilators (sometimes called vaginal trainers), progressively increasing the size of the dilator inserted into the vagina.[26][27]
### Neuromodulators[edit]
Botulinum toxin A (Botox) has been considered as a treatment option, under the idea of temporarily reducing the hypertonicity of the pelvic floor muscles. Although no random controlled trials have been done with this treatment, experimental studies with small samples have shown it to be effective, with sustained positive results through 10 months.[9][28] Similar in its mechanism of treatment, lidocaine has also been tried as an experimental option.[9][29]
Anxiolytics and antidepressants are other pharmacotherapies that have been offered to people in conjunction with other psychotherapy modalities, or if these people's experience high levels of anxiety from their condition.[9] Evidence for these medications; however, is limited.[9]
## Epidemiology[edit]
Estimates of how common the condition is vary.[9] A 2016 textbook estimated about 0.5% of women are affected,[2] while rates in Morocco and Sweden were estimated at 6%.[30]
Among those who attend clinics for sexual dysfunction rates may be as high as 12 to 47%.[2][31]
## See also[edit]
* Medicine portal
* Hymen
* Penis captivus
* Vulvodynia
## References[edit]
1. ^ Maddux, James E.; Winstead, Barbara A. (2012). Psychopathology: Foundations for a Contemporary Understanding. Taylor & Francis. p. 332. ISBN 9781136482847.
2. ^ a b c d e f g h i j k l m n Ferri, Fred F. (2016). Ferri's Clinical Advisor 2017 E-Book: 5 Books in 1. Elsevier Health Sciences. p. 1330. ISBN 9780323448383.
3. ^ a b c d e f "Vaginismus". Merck Manuals Professional Edition. April 2013. Retrieved 15 October 2018.
4. ^ Domino, Frank J. (2010). The 5-Minute Clinical Consult 2011. Lippincott Williams & Wilkins. p. 1394. ISBN 9781608312597.
5. ^ a b c "Vaginismus". NHS. 2018-01-11. Retrieved 15 October 2018.
6. ^ "Vaginismus". NHS. Retrieved July 7, 2020.
7. ^ Nazario, Brunilda, MD. (2012). "Women's Health: Vaginismus". WebMD. Retrieved December 22, 2016.
8. ^ Braddom, Randall L. (2010). Physical Medicine and Rehabilitation E-Book. Elsevier Health Sciences. p. 665. ISBN 978-1437735635.
9. ^ a b c d e f g Lahaie, MA; Boyer, SC; Amsel, R; Khalifé, S; Binik, YM (Sep 2010). "Vaginismus: a review of the literature on the classification/diagnosis, etiology and treatment". Women's Health (London, England). 6 (5): 705–19. doi:10.2217/whe.10.46. PMID 20887170.
10. ^ Reissing, Elke; Yitzchak Binik; Samir Khalife (May 1999). "Does Vaginismus Exist? A Critical Review of the Literature". The Journal of Nervous and Mental Disease. 187 (5): 261–274. doi:10.1097/00005053-199905000-00001. PMID 10348080.
11. ^ a b Pacik PT (December 2009). "Botox treatment for vaginismus". Plast. Reconstr. Surg. 124 (6): 455e–6e. doi:10.1097/PRS.0b013e3181bf7f11. PMID 19952618.
12. ^ Borg, Charmaine; Peters, L. M.; Weijmar Schultz, W.; de Jong, P. J. (February 2012). "Vaginismus: Heightened Harm Avoidance and Pain Catastrophizing Cognitions". Journal of Sexual Medicine. 9 (2): 558–567. doi:10.1111/j.1743-6109.2011.02535.x. PMID 22024378.
13. ^ Borg, Charmaine; Peter J. De Jong; Willibrord Weijmar Schultz (June 2010). "Vaginismus and Dyspareunia: Automatic vs. Deliberate: Disgust Responsivity". Journal of Sexual Medicine. 7 (6): 2149–2157. doi:10.1111/j.1743-6109.2010.01800.x. PMID 20367766.
14. ^ Borg, Charmaine; Peter J. de Jong; Willibrord Weijmar Schultz (Jan 2011). "Vaginismus and Dyspareunia: Relationship with General and Sex-Related Moral Standards". Journal of Sexual Medicine. 8 (1): 223–231. doi:10.1111/j.1743-6109.2010.02080.x. PMID 20955317.
15. ^ "Vaginismus". Sexual Pain Disorders and Vaginismus. Armenian Medical Network. 2006. Retrieved 2008-01-07.
16. ^ Lamont, JA (1978). "Vaginismus". Am J Obstet Gynecol. 131 (6): 633–6. doi:10.1016/0002-9378(78)90822-0. PMID 686049.
17. ^ Pacik, PT.; Cole, JB. (2010). When Sex Seems Impossible. Stories of Vaginismus and How You Can Achieve Intimacy. Odyne Publishing. pp. 40–7.
18. ^ Pacik, Peter (2010). When Sex Seems Impossible. Stories of Vaginismus & How You Can Achieve Intimacy. Manchester, NH: Odyne. pp. 8–16. ISBN 978-0-9830134-0-2. Archived from the original on 2012-02-19. Retrieved 2011-12-29.
19. ^ a b American College of Obstetricians Gynecologists Committee on Practice Bulletins-Gynecology (April 2011). "Practice Bulletin No. 119: Female Sexual Dysfunction". Obstetrics & Gynecology. 117 (4): 996–1007. doi:10.1097/aog.0b013e31821921ce. ISSN 0029-7844. PMID 21422879.
20. ^ a b Melnik, T; Hawton, K; McGuire, H (12 December 2012). "Interventions for vaginismus". The Cochrane Database of Systematic Reviews. 12: CD001760. doi:10.1002/14651858.CD001760.pub2. PMC 7072531. PMID 23235583.
21. ^ Reissing ED, Binik YM, Khalifé S, Cohen D, Amsel R (2003). "Etiological correlates of vaginismus: sexual and physical abuse, sexual knowledge, sexual self-schema, and relationship adjustment". J Sex Marital Ther. 29 (1): 47–59. doi:10.1080/713847095. PMID 12519667. S2CID 46659017.
22. ^ "When sex hurts – vaginismus". The Society of Obstetricians and Gynecologists of Canada. n.d. Archived from the original on 2013-10-20.
23. ^ Herndon, Jaime (November 30, 2015). "Vaginismus". Healthline. George Kruick, MD. Retrieved December 22, 2016.
24. ^ Nazario, Brunilda, MD. (2012). "Women's Health: Vaginismus". WebMD. Retrieved December 22, 2016.
25. ^ "When sex gives more pain than pleasure". Harvard Health Publications. Harvard Health. May 2012. Retrieved December 22, 2016.
26. ^ Doleys, Daniel (6 December 2012). Behavioral Medicine. Springer Science & Business Media. p. 377. ISBN 9781468440706.
27. ^ nhs, nhs (2015). "NHS Choices Vaginal Trainers to treat vaginismus". NHS Choices Vaginismus treatment. NHS.
28. ^ Pacik PT (2011). "Vaginismus: A Review of Current Concepts and Treatment using Botox Injections, Bupivacaine Injections and Progressive Dilation Under Anesthesia". Aesthetic Plastic Surgery Journal. 35 (6): 1160–1164. doi:10.1007/s00266-011-9737-5. PMID 21556985. S2CID 8754988.
29. ^ Melnik, T; Hawton, K; McGuire, H (Dec 12, 2012). "Interventions for vaginismus". The Cochrane Database of Systematic Reviews. 12: CD001760. doi:10.1002/14651858.CD001760.pub2. PMC 7072531. PMID 23235583.
30. ^ Lewis RW, Fugl-Meyer KS, Bosch R, et al. (July 2004). "Epidemiology/risk factors of sexual dysfunction". J Sex Med. 1 (1): 35–9. CiteSeerX 10.1.1.565.3552. doi:10.1111/j.1743-6109.2004.10106.x. PMID 16422981.
31. ^ Reissing ED, Binik YM, Khalifé S (May 1999). "Does vaginismus exist? A critical review of the literature". J. Nerv. Ment. Dis. 187 (5): 261–74. doi:10.1097/00005053-199905000-00001. PMID 10348080.
## Further reading[edit]
* Crowley T, Richardson D, Goldmeier D (January 2006). "Recommendations for the management of vaginismus: BASHH Special Interest Group for Sexual Dysfunction". Int J STD AIDS. 17 (1): 14–8. doi:10.1258/095646206775220586. PMID 16409672. S2CID 14152533.
Classification
D
* ICD-10: F52.5, N94.2
* ICD-9-CM: 306.51 625.1
* MeSH: D052065
* DiseasesDB: 13701
External resources
* MedlinePlus: 001487
* v
* t
* e
Mental and behavioral disorders
Adult personality and behavior
Gender dysphoria
* Ego-dystonic sexual orientation
* Paraphilia
* Fetishism
* Voyeurism
* Sexual maturation disorder
* Sexual relationship disorder
Other
* Factitious disorder
* Munchausen syndrome
* Intermittent explosive disorder
* Dermatillomania
* Kleptomania
* Pyromania
* Trichotillomania
* Personality disorder
Childhood and learning
Emotional and behavioral
* ADHD
* Conduct disorder
* ODD
* Emotional and behavioral disorders
* Separation anxiety disorder
* Movement disorders
* Stereotypic
* Social functioning
* DAD
* RAD
* Selective mutism
* Speech
* Stuttering
* Cluttering
* Tic disorder
* Tourette syndrome
Intellectual disability
* X-linked intellectual disability
* Lujan–Fryns syndrome
Psychological development
(developmental disabilities)
* Pervasive
* Specific
Mood (affective)
* Bipolar
* Bipolar I
* Bipolar II
* Bipolar NOS
* Cyclothymia
* Depression
* Atypical depression
* Dysthymia
* Major depressive disorder
* Melancholic depression
* Seasonal affective disorder
* Mania
Neurological and symptomatic
Autism spectrum
* Autism
* Asperger syndrome
* High-functioning autism
* PDD-NOS
* Savant syndrome
Dementia
* AIDS dementia complex
* Alzheimer's disease
* Creutzfeldt–Jakob disease
* Frontotemporal dementia
* Huntington's disease
* Mild cognitive impairment
* Parkinson's disease
* Pick's disease
* Sundowning
* Vascular dementia
* Wandering
Other
* Delirium
* Organic brain syndrome
* Post-concussion syndrome
Neurotic, stress-related and somatoform
Adjustment
* Adjustment disorder with depressed mood
Anxiety
Phobia
* Agoraphobia
* Social anxiety
* Social phobia
* Anthropophobia
* Specific social phobia
* Specific phobia
* Claustrophobia
Other
* Generalized anxiety disorder
* OCD
* Panic attack
* Panic disorder
* Stress
* Acute stress reaction
* PTSD
Dissociative
* Depersonalization disorder
* Dissociative identity disorder
* Fugue state
* Psychogenic amnesia
Somatic symptom
* Body dysmorphic disorder
* Conversion disorder
* Ganser syndrome
* Globus pharyngis
* Psychogenic non-epileptic seizures
* False pregnancy
* Hypochondriasis
* Mass psychogenic illness
* Nosophobia
* Psychogenic pain
* Somatization disorder
Physiological and physical behavior
Eating
* Anorexia nervosa
* Bulimia nervosa
* Rumination syndrome
* Other specified feeding or eating disorder
Nonorganic sleep
* Hypersomnia
* Insomnia
* Parasomnia
* Night terror
* Nightmare
* REM sleep behavior disorder
Postnatal
* Postpartum depression
* Postpartum psychosis
Sexual dysfunction
Arousal
* Erectile dysfunction
* Female sexual arousal disorder
Desire
* Hypersexuality
* Hypoactive sexual desire disorder
Orgasm
* Anorgasmia
* Delayed ejaculation
* Premature ejaculation
* Sexual anhedonia
Pain
* Nonorganic dyspareunia
* Nonorganic vaginismus
Psychoactive substances, substance abuse and substance-related
* Drug overdose
* Intoxication
* Physical dependence
* Rebound effect
* Stimulant psychosis
* Substance dependence
* Withdrawal
Schizophrenia, schizotypal and delusional
Delusional
* Delusional disorder
* Folie à deux
Psychosis and
schizophrenia-like
* Brief reactive psychosis
* Schizoaffective disorder
* Schizophreniform disorder
Schizophrenia
* Childhood schizophrenia
* Disorganized (hebephrenic) schizophrenia
* Paranoid schizophrenia
* Pseudoneurotic schizophrenia
* Simple-type schizophrenia
Other
* Catatonia
Symptoms and uncategorized
* Impulse control disorder
* Klüver–Bucy syndrome
* Psychomotor agitation
* Stereotypy
* v
* t
* e
Female diseases of the pelvis and genitals
Internal
Adnexa
Ovary
* Endometriosis of ovary
* Female infertility
* Anovulation
* Poor ovarian reserve
* Mittelschmerz
* Oophoritis
* Ovarian apoplexy
* Ovarian cyst
* Corpus luteum cyst
* Follicular cyst of ovary
* Theca lutein cyst
* Ovarian hyperstimulation syndrome
* Ovarian torsion
Fallopian tube
* Female infertility
* Fallopian tube obstruction
* Hematosalpinx
* Hydrosalpinx
* Salpingitis
Uterus
Endometrium
* Asherman's syndrome
* Dysfunctional uterine bleeding
* Endometrial hyperplasia
* Endometrial polyp
* Endometriosis
* Endometritis
Menstruation
* Flow
* Amenorrhoea
* Hypomenorrhea
* Oligomenorrhea
* Pain
* Dysmenorrhea
* PMS
* Timing
* Menometrorrhagia
* Menorrhagia
* Metrorrhagia
* Female infertility
* Recurrent miscarriage
Myometrium
* Adenomyosis
Parametrium
* Parametritis
Cervix
* Cervical dysplasia
* Cervical incompetence
* Cervical polyp
* Cervicitis
* Female infertility
* Cervical stenosis
* Nabothian cyst
General
* Hematometra / Pyometra
* Retroverted uterus
Vagina
* Hematocolpos / Hydrocolpos
* Leukorrhea / Vaginal discharge
* Vaginitis
* Atrophic vaginitis
* Bacterial vaginosis
* Candidal vulvovaginitis
* Hydrocolpos
Sexual dysfunction
* Dyspareunia
* Hypoactive sexual desire disorder
* Sexual arousal disorder
* Vaginismus
* Urogenital fistulas
* Ureterovaginal
* Vesicovaginal
* Obstetric fistula
* Rectovaginal fistula
* Prolapse
* Cystocele
* Enterocele
* Rectocele
* Sigmoidocele
* Urethrocele
* Vaginal bleeding
* Postcoital bleeding
Other / general
* Pelvic congestion syndrome
* Pelvic inflammatory disease
External
Vulva
* Bartholin's cyst
* Kraurosis vulvae
* Vestibular papillomatosis
* Vulvitis
* Vulvodynia
Clitoral hood or clitoris
* Persistent genital arousal 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 inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| Vaginismus | c2004487 | 2,091 | wikipedia | https://en.wikipedia.org/wiki/Vaginismus | 2021-01-18T18:39:56 | {"mesh": ["D052065"], "umls": ["C2004487"], "icd-9": ["625.1"], "icd-10": ["N94.2"], "wikidata": ["Q1128431"]} |
Johnston et al. (1993) described 2 infant brothers with joint contractures and hyperkeratotic skin changes. Severe hypoplasia of the dorsal roots and posterior columns was found in 1 sib examined at autopsy.
*[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
| ARTHROGRYPOSIS WITH HYPERKERATOSIS | c1859710 | 2,092 | omim | https://www.omim.org/entry/208158 | 2019-09-22T16:30:51 | {"mesh": ["C535883"], "omim": ["208158"], "orphanet": ["1485"]} |
Coffin-Siris syndrome is a genetic condition that causes variable degrees of learning disability, developmental delays, underdeveloped “pinky” toenails or fingernails, and distinct facial features. It can be caused by a change (mutation) in any of several genes including the ARID1A, ARID1B, SMARCA4, SMARCB1, DPF2 or SMARCE1 genes. Coffin-Siris syndrome follows an autosomal dominant pattern of inheritance, however it usually occurs for the first time in a family due to a new mutation. Occupational, physical, and/or speech therapy can help affected individuals reach their full potential.
*[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
| Coffin-Siris syndrome | c0265338 | 2,093 | gard | https://rarediseases.info.nih.gov/diseases/6124/coffin-siris-syndrome | 2021-01-18T18:01:15 | {"mesh": ["C536436"], "omim": ["135900"], "umls": ["C0265338"], "orphanet": ["1465"], "synonyms": ["Fifth digit syndrome", "Intellectual disability with absent fifth fingernail and terminal phalanx"]} |
A number sign (#) is used with this entry because autosomal recessive retinitis pigmentosa-20 (RP20) is caused by homozygous or compound heterozygous mutation in the RPE65 gene (180069) on chromosome 1p31.
Mutations in the RPE65 gene also cause Leber congenital amaurosis (LCA2; 204100).
For a phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa (RP), see 268000.
Clinical Features
Gu et al. (1997) described a 5-generation consanguineous Indian family with 4 members with childhood-onset severe retinal dystrophy (RP20). Onset of severe visual impairment was between 3 and 7 years of age. Night blindness was a typical and early symptom in all patients. Two patients had nystagmus. Ophthalmoscopy revealed attenuated vessels and atrophy of the optic disc. Although bone spicule formation is not a typical feature of the disease, many whitish dots seen on ophthalmoscopy were considered compatible with extensive retinal pigment epithelium (RPE) defects.
In a screen of the RPE65 gene in 147 unrelated patients with autosomal recessive RP and 15 patients with isolated RP, Morimura et al. (1998) identified 3 patients with mutation in RPE65. In one family, from the Dominican Republic, 3 branches of the family had affected children due to homozygosity or compound heterozygosity.
Among 59 probands with RP, 11 with autosomal recessive inheritance, Kondo et al. (2004) identified 1 patient with RP20 (mutation in the RPE65 gene). This 55-year-old Japanese woman, the child of first-cousin parents, had been diagnosed with RP at the age of 40. She had observed the development of night blindness in early childhood and had been free from visual disability until 24 years of age. At the age of 54, she had only basic light-dark perception in both eyes. An examination of the fundus revealed pigmented lesions in the form of clumps or bony spicules involving the posterior retina and associated with a wide area of chorioretinal atrophy, which was prominent in the peripapillary area in both eyes. Electroretinogram showed no recordable rod or cone response in either eye.
Kondo et al. (2004) summarized the effect of RPE65 mutation. The most common phenotype is severe and early-onset retinal degeneration. In most patients with RPE65 mutation, disease was diagnosed in infancy, with visual impairment associated with nystagmus, night blindness, and a tendency to fixate on light. In contrast, the visual performance of several patients in bright light was sufficient to permit attendance at regular school during the elementary years. At older ages, often during the secondary school years, visual acuity was greatly reduced.
Morimura et al. (1998) summarized the clinical criteria distinguishing RP from Leber congenital amaurosis (LCA). RP is the diagnosis given to patients with photoreceptor degeneration who have good central vision within the first decade of life. The diagnosis of LCA is given to patients who are born blind or who lose vision within a few months after birth. Both diagnostic entities feature attenuated retinal vessels and a variable amount of retinal pigmentation in older patients and a reduced or nondetectable electroretinogram at all ages. There is no universally accepted diagnostic term for those patients with retinal degeneration who lose useful (ambulatory) vision during the first few years of life, with ophthalmologists considering such cases as either LCA or severe RP.
Mapping
Gu et al. (1997) used homozygosity mapping in a consanguineous Indian family with 4 affected individuals to map the RP20 locus to chromosome 1p22-p31.
Molecular Genetics
Gu et al. (1997) identified 5 families with autosomal recessive childhood-onset severe retinal dystrophy and mutations in the RPE65 gene. Five presumed pathogenic RPE65 mutations (e.g., 180069.0003) were found on a total of 9 alleles in 5 probands. Gu et al. (1997) gave the approximate frequency of RPE65-associated autosomal recessive CSRD as 5%, about the same as for other retinal dystrophy genes. The autosomal recessive mode of inheritance and the 4 potentially inactivating mutations suggested that mutations in RPE65 result in complete or partial loss of protein function.
Among 162 unrelated patients with recessive or sporadic RP, Morimura et al. (1998) identified 3 probands with homozygous or compound heterozygous mutation in the RPE65 gene, 2 with recessive RP (e.g., 180069.0004) and 1 with sporadic RP recategorized as recessive (see 180069.0006). Based on their results, Morimura et al. (1998) estimated that mutations in the RPE65 gene account for approximately 2% of cases of recessive RP.
Kondo et al. (2004) identified a homozygous missense mutation in the RPE65 gene (180069.0008) in a 55-year-old Japanese woman with RP. The authors noted that this mutation had previously been found to result in LCA.
INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Nystagmus \- Night blindness \- Severe visual impairment \- Attenuated vessels of optic disc \- Atrophy of optic disc \- Whitish dots on ophthalmoscopy \- Retinitis pigmentosa MISCELLANEOUS \- Early onset (3 to 7 years of age) \- Severe visual impairment by adulthood MOLECULAR BASIS \- Caused by mutation in the retinal pigment epithelium-specific protein, 65-kD (RPE65, 180069.0003 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| RETINITIS PIGMENTOSA 20 | c0035334 | 2,094 | omim | https://www.omim.org/entry/613794 | 2019-09-22T15:57:30 | {"doid": ["0110353"], "mesh": ["D012174"], "omim": ["613794"], "orphanet": ["791"], "genereviews": ["NBK1417"]} |
Ligneous conjunctivitis
Other namesConjunctivitis lignosa[1]
SpecialtyOphthalmology
Ligneous conjunctivitis is a rare form of chronic conjunctivitis characterized by recurrent, fibrin-rich pseudomembranous lesions of wood-like consistency that develop mainly on the underside of the eyelid (tarsal conjunctiva).[2] It is generally a systemic disease which may involve the periodontal tissue, the upper and lower respiratory tract, kidneys, middle ear, and female genitalia.[3] It can be sight-threatening,[3] and death can occasionally occur from pulmonary involvement.[citation needed]
It has been speculated hola ligneous conjunctivitis may be a manifestation of IgG4-related disease (IgG4-RD) involving the conjunctiva.[4]
## Contents
* 1 Pathogenesis
* 2 Diagnosis
* 3 Treatment
* 4 References
* 5 External links
## Pathogenesis[edit]
Histopathological findings from affected humans indicate that wound healing is impaired due to a deficiency in plasmin-mediated extracellular fibrinolysis.[2] Episodes may be triggered by minor trauma, eye surgery, or by systemic events such as infections or antifibrinolytic therapy.[3] Histology shows amorphous subepithelial deposits of eosinophilic material consisting predominantly of fibrin.[clarification needed]
## Diagnosis[edit]
This section is empty. You can help by adding to it. (December 2017)
## Treatment[edit]
Ligneous conjunctivitis may be managed by topical treatments of plasminogen,[2] topical and subconjunctival fresh frozen plasma,[2] and fibrinolytic therapy.[5]
## References[edit]
1. ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Ligneous conjunctivitis". www.orpha.net. Retrieved 26 June 2019.
2. ^ a b c d Schuster, V.; Seregard, S. (2003). "Ligneous conjunctivitis". Survey of Ophthalmology. 48 (4): 369–388. doi:10.1016/s0039-6257(03)00056-0. PMID 12850227.
3. ^ a b c "Ligneous conjunctivitis". Orphanet. Retrieved July 21, 2012.
4. ^ Chiang Wei-Yu; iu Ting-Ting; Huang Wan-Ting; Kuo Ming-Tse (9 September 2016). "Co-existing ligneous conjunctivitis and IgG4-related disease". Indian Journal of Ophthalmology. 64 (7): 532–534. doi:10.4103/0301-4738.190154. PMC 5026081. PMID 27609168.
5. ^ "Ligneous Conjunctivitis". Ocular Pathology. Retrieved July 21, 2012.
## External links[edit]
Classification
D
* ICD-10: H10.4
* OMIM: 217090
* MeSH: C566897
External resources
* Orphanet: 97231
*[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
| Ligneous conjunctivitis | c1274789 | 2,095 | wikipedia | https://en.wikipedia.org/wiki/Ligneous_conjunctivitis | 2021-01-18T19:05:04 | {"gard": ["6187"], "mesh": ["C566897"], "umls": ["C1274789"], "orphanet": ["97231"], "wikidata": ["Q6546687"]} |
Renal papillary necrosis
Other namesRenal medullary necrosis[1]
Frontal section through the kidney
SpecialtyUrology, nephrology
SymptomsBack pain, cloudy urine[1]
CausesDiabetic nephropathy, Kidney infection[1]
Diagnostic methodBlood and urine test[1]
TreatmentDepends on cause[1]
Renal papillary necrosis is a form of nephropathy involving the necrosis of the renal papilla.[1] Lesions that characterize renal papillary necrosis come from an impairment of the blood supply and from subsequent ischemic necrosis that is diffuse.[2]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Pathophysiology
* 4 Diagnosis
* 5 Treatment
* 6 References
* 7 Further reading
* 8 External links
## Signs and symptoms[edit]
Symptoms (and signs) consistent with renal papillary necrosis are:[1]
* Back pain
* Cloudy urine
* Tissue pieces (in urine)
* Fever
* Painful/frequent urination
* Urinary incontinence
## Causes[edit]
In terms of cause, almost any condition that involves ischemia can lead to renal papillary necrosis. A mnemonic for the causes of renal papillary necrosis is POSTCARDS: pyelonephritis, obstruction of the urogenital tract, sickle cell disease, tuberculosis, cirrhosis of the liver, analgesia/alcohol abuse, renal vein thrombosis, diabetes mellitus, and systemic vasculitis.[3] Often, a patient with renal papillary necrosis will have numerous conditions acting synergistically to bring about the disease.[4]
Analgesic nephropathy is a common cause of renal papillary necrosis. The risk is higher for phenacetin (which was withdrawn from market in the United States) and paracetamol (acetaminophen) compared to aspirin and other NSAIDs.[medical citation needed]
## Pathophysiology[edit]
This condition is due to ischemia of the renal papillae, the portion of the kidney that collects urine from the nephron. The papillae are vulnerable to ischemia as they are supplied by small caliber arteries which are liable to obstruction. All of the underlying causes of papillary necrosis cause diminished flow through these arteries, either through direct mechanical obstruction (sickle cell), obstruction secondary to inflammation (vasculitides), or vasoconstriction (NSAIDs).[5] Papillary necrosis is more likely to develop when multiple of these underlying factors are present.[6] Ultimately, necrosis of the papillae results in sloughing into the lumen, causing hematuria. If the degree of necrosis is substantial post-renal failure may occur, though this is uncommon.[7]
## Diagnosis[edit]
Cystoscope
Individuals with renal papillary necrosis due to excess use of analgesic have an elevated risk of epithelial tumors, hence a urine cytology exam is useful.[8] In terms of imaging this condition can be identified by retrograde pyelography (RGP).[9] The diagnosis of renal papillary necrosis is therefore done via:[10]
* Urinalysis
* Blood cell count
* Urine cytology study
* Imaging study (with intravenous contrast)
* Cystoscopy
* Ureteroscopy
## Treatment[edit]
Treatment of renal papillary necrosis is supportive, any obstruction (urethral) can be dealt with via stenting. This condition is not linked to a higher possibility of renal failure.[11] Control of infection is important, thus antimicrobial treatment is begun, so as to avert surgery (should the infection not respond).[12]
## References[edit]
1. ^ a b c d e f g "Renal Papillary Necrosis". Medline. NIH. Retrieved 15 October 2015.
2. ^ Jung, Dae Chul; Kim, Seung Hyup; Jung, Sung Il; Hwang, Sung Il; Kim, Sun Ho (November 2006). "Renal Papillary Necrosis: Review and Comparison of Findings at Multi–Detector Row CT and Intravenous Urography1". RadioGraphics. 26 (6): 1827–1836. doi:10.1148/rg.266065039. PMID 17102053.
3. ^ Kim, Seung Hyup (2011-11-19). Radiology Illustrated: Uroradiology. Springer Science & Business Media. p. 471. ISBN 9783642053221.
4. ^ Powell, Christopher. "Papillary Necrosis". Medscape Reference. Retrieved 10 Nov 2011.
5. ^ "Analgesic Nephropathy. Chronic kidney disease information. Patient | Patient". Patient. Retrieved 2015-10-15.
6. ^ Greenberg, Arthur; Cheung, Alfred K. (2005-01-01). Primer on Kidney Diseases. Elsevier Health Sciences. p. 387. ISBN 978-1416023128.
7. ^ Powell, Christopher (Jan 12, 2017). "Papillary Necrosis". Medscape.
8. ^ Wein, Alan J.; Kavoussi, Louis R.; Novick, Andrew C.; Partin, Alan W.; Peters, Craig A. (2011-09-28). Campbell-Walsh Urology. Elsevier Health Sciences. p. 269. ISBN 978-1455722983.
9. ^ Kim, Seung Hyup (2011-11-19). Radiology Illustrated: Uroradiology. Springer Science & Business Media. p. 472. ISBN 9783642053221.
10. ^ "Papillary Necrosis Workup: Laboratory Studies, Imaging Studies, Diagnostic Procedures". emedicine.medscape.com. Retrieved 2015-10-15.
11. ^ Schrier, Robert W. (2007-01-01). Diseases of the Kidney and Urinary Tract. Lippincott Williams & Wilkins. p. 2008. ISBN 9780781793070.
12. ^ Schlossberg, David (2015-04-23). Clinical Infectious Disease. Cambridge University Press. p. 438. ISBN 9781107038912.
## Further reading[edit]
* Steinberg, Martin H.; Forget, Bernard G.; Higgs, Douglas R. (2009-08-17). Disorders of Hemoglobin: Genetics, Pathophysiology, and Clinical Management. Cambridge University Press. ISBN 9780521875196.
* Stern, Adam W.; Ritchey, Jerry W.; Hall, Brittany; Ketz-Riley, Cornelia J.; Genova, Suzanne G. (2010-05-01). "Nonsteroidal Anti-Inflammatory Drug—Associated Renal Papillary Necrosis in a White-Tailed Deer (Odocoileus Virginianus)". Journal of Veterinary Diagnostic Investigation. 22 (3): 476–478. doi:10.1177/104063871002200328. ISSN 1040-6387. PMID 20453233.
## External links[edit]
Classification
D
* ICD-10: N17.2
* ICD-9-CM: 584.7
* MeSH: D007681
* DiseasesDB: 9572
External resources
* MedlinePlus: 000488
* eMedicine: med/2839 radio/523
Scholia has a topic profile for Renal papillary necrosis.
* v
* t
* e
Kidney disease
Glomerular disease
* See Template:Glomerular disease
Tubules
* Renal tubular acidosis
* proximal
* distal
* Acute tubular necrosis
* Genetic
* Fanconi syndrome
* Bartter syndrome
* Gitelman syndrome
* Liddle's syndrome
Interstitium
* Interstitial nephritis
* Pyelonephritis
* Balkan endemic nephropathy
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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
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| Renal papillary necrosis | c0022667 | 2,096 | wikipedia | https://en.wikipedia.org/wiki/Renal_papillary_necrosis | 2021-01-18T18:37:03 | {"mesh": ["D007681"], "umls": ["C0022667"], "icd-9": ["584.7"], "icd-10": ["N17.2"], "wikidata": ["Q7312498"]} |
Developmental and speech delay due to SOX5 deficiency is a rare genetic syndromic intellectual disability characterized by mild to severe global developmental delay, intellectual disability and behavioral abnormalities, hypotonia, strabismus, optic nerve hypoplasia and mild facial dysmorphic features (down slanting palpebral fissures, frontal bossing, crowded teeth, auricular abnormalities and prominent philtral ridges). Other associated clinical features may include seizures and skeletal anomalies (kyphosis/scoliosis, pectus deformities).
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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
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*[NOP]: Nociceptin receptor
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*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
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*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
| Developmental and speech delay due to SOX5 deficiency | c4225202 | 2,097 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=313892 | 2021-01-23T18:44:33 | {"omim": ["616803"]} |
A number sign (#) is used with this entry because of evidence that ablepharon-macrostomia syndrome (AMS) is caused by heterozygous mutation in the TWIST2 gene (607556) on chromosome 2q37.
Description
Ablepharon-macrostomia syndrome is a congenital ectodermal dysplasia characterized by absent eyelids, macrostomia, microtia, redundant skin, sparse hair, dysmorphic nose and ears, variable abnormalities of the nipples, genitalia, fingers, and hands, largely normal intellectual and motor development, and poor growth (summary by Marchegiani et al., 2015).
Clinical Features
McCarthy and West (1977) reported 2 unrelated male children with absent eyelids, eyebrows, and eyelashes; fusion defects of the mouth; rudimentary external ears; ambiguous genitalia; absent or rudimentary nipples; coarse, dry skin with redundant skin folds; and delayed development of expressive language. Jackson et al. (1988) provided follow-up at age 12 years on the second case of McCarthy and West (1977). They pointed out another feature of the disorder, namely, absence of the zygomatic arches.
Hornblass and Reifler (1985) described a 10-day-old infant with total absence of the upper and lower eyelids, failure of lip fusion resulting in an enlarged, fish-like mouth, abnormally shaped ears and nose, absence of lanugo, ventral hernia, and ambiguous genitalia. They reconstructed the eyelids in a 3-stage procedure and later the child underwent successful reconstruction of the mouth. Hornblass and Reifler (1985) drew attention to the presence of vestigial eyelid structures, suggesting that the true nature of the eyelid deformity in this syndrome may be severe microblepharon rather than ablepharon.
Price et al. (1991) reported a male infant who was born with shallow orbits with inadequate eyelids, hypertelorism, large square mouth, protrusion of maxilla, and malformed, low-set ears. Skin was wrinkled and hairless, and eyelashes and eyebrows were absent. Genitalia were ambiguous. Periorbital skin biopsies taken during reconstructive surgery showed no specific abnormality, and collagen studies were normal. His parents were nonconsanguineous, and there was no family history of congenital anomalies.
Ferraz et al. (2000) described an infant with ablepharon-macrostomia syndrome, the sister of a previously reported affected female (Cruz et al., 1995). Manifestations of the syndrome included severe shortness of the eyelids, low nasal bridge with hypoplastic and anteverted nostrils, macrostomia, small ears, absence of nipples, and absence of lanugo. The father had more mild abnormalities of the eyelids, eyebrows, and ears. The authors suggested that this family supports autosomal dominant inheritance with variable expression.
Stevens and Sargent (2002) reported 3 new cases, gave a 10-year follow-up of a newborn reported in an abstract by Markouizos et al. (1990), and reviewed the findings in the 4 other reported cases. All of the patients had absent hair, brows, and lashes, absent or short eyelids, macrostomia, ear anomalies, redundant skin, and abnormal genitalia. Many had persistent visual problems, often related to early corneal exposure. Hearing loss, poor hair growth, finger contractures, and growth retardation were also chronic problems. Developmental impairment was present in two-thirds of patients but was usually mild. Their series included the first reported adult patient, a 27-year-old woman. She had no scalp hair, eyelids, eyebrows, or eyelashes at birth. She had macrostomia and tiny 'rosebud' ears. There was camptodactyly and mild syndactyly of fingers 2 to 5 bilaterally and ambiguous genitalia.
Because of distinctive clinical manifestations that are shared in common by AMS and Barber-Say syndrome (209885), some have suggested that they may represent defects in the same gene (Mazzanti et al., 1998).
Stevens and Sargent (2002) suggested that their experience provided evidence that AMS is distinct from Barber-Say syndrome. Common features of the 2 syndromes are macrostomia, abnormal ears and nose, hypoplastic nipples, sparse eyebrows and eyelashes, and redundant skin. Distinguishing features include ablepharon in AMS versus ectropion in Barber-Say syndrome and marked hypertrichosis in Barber-Say syndrome. Genital abnormalities are much more severe in AMS.
Brancati et al. (2004) contributed to the characterization of the AMS phenotype in adulthood. They reported an Italian woman in whom the diagnosis was made at the age of 46 years. At birth, absent eyelashes and eyebrows, with slight and asymmetric vertical shortening of upper and lower eyelids, and abnormal ears with rudimentary cartilage were described. At the age of 14 years, when surgical repair of the eyelids was performed, alae nasi and malar hypoplasia, absent zygomatic arches, macrostomia, and small chin were noted. At 22 years of age, chin and breast hypoplasia were treated by plastic surgery, and hypoplasia of the zygomatic arches was remodeled some months later, by implantation of subcutaneous prostheses. At 31 years of age, surgical reconstruction of external ears was attempted. On evaluation at age 46 years, the findings included partial cutaneous syndactyly with camptodactyly of the fifth fingers, particularly on the left. Other finger bone anomalies included short left third, fourth, and fifth and right fourth and fifth metacarpal bones. Audiograms showed bilateral high frequency hearing loss. Developmental milestones were considered normal as well as intelligence at the time of examination. Menarche occurred at 12 years of age. The findings were compared to those in 13 other patients: 11 aged newborn to 12 years, one aged 25 years (Ferraz et al., 2000), and one aged 27 years (Stevens and Sargent, 2002).
Kallish et al. (2011) described a female infant, noted to have micrognathia, abnormalities of the fingers, and clubfoot prenatally, who at birth showed deficient skin of eyelids and lips, macrostomia, absent nipples, and hypoplastic labia. Additional findings on examination at 7 months of age included a small head (less than fifth percentile for age) with palpable metopic ridge, small nose with deficient lateral alae nasi, short upper lip and deficient lateral lower lip bilaterally, unfused labial commissures, absent upper and lower gingiva, and small mandible. She also displayed an inferiorly placed umbilicus and sacral dimple. Extremities were remarkable for a small left thumb that was syndactylous with the second digit, small right thumb with proximal syndactyly of the first and second digits, and bilateral syndactyly of the second through fifth toes with partial syndactyly of the great toes, and medially rotated feet. Kallish et al. (2011) stated that in addition to the classic features of AMS, this patient exhibited more significant hand and foot anomalies than previously reported.
Marchegiani et al. (2015) restudied the AMS family originally reported by Rohena et al. (2011). Extensive craniofacial phenotyping of the affected daughter revealed harlequin-shaped eyebrows with absence of the distal third, hypoplastic nasal dorsum with no projection of the nasal tip, absent columella, hypoplastic ala nasi, macrostomia, CL II malocclusion with 50% overbite, Brodie bite, conical teeth, and long uvula. The macrostomia was characterized by deficient lateral development of the vermilion border and an inability to raise the oral commissures on smiling, suggesting discontinuity of the orbicularis oris muscle. Electron microscopy of skin biopsies from the affected father and daughter showed thin, disrupted elastic fibers with areas of amorphous deposits along abnormally oriented collagen fibers and adjacent areas of microfibrillar proliferation. Masson-trichrome staining revealed abnormal reticulodermal collagen patterns in both patients, whereas elastic fiber staining was within normal limits.
Inheritance
Rohena et al. (2011) reported AMS in a newborn female and her 22-year-old father and suggested autosomal dominant inheritance of the disorder. Marchegiani et al. (2015) confirmed autosomal dominant inheritance of the AMS in this family.
Possible autosomal recessive inheritance was proposed because of a postulated relationship to the disorder in monozygotic twins from a consanguineous marriage: one twin had bilateral cryptophthalmos and the other had cryptophthalmos on the left and ablepharon on the right (Azevedo et al., 1973).
Cytogenetics
Pellegrino et al. (1996) described a male infant with ablepheron-macrostomia syndrome and a complex rearrangement and partial deletion of chromosome 18; the final karyotype, based on molecular cytogenetic analysis, was 46,XY,-18,+[del(18)(q21.3q23),inv(18)(q12.3q21.2)]. The authors stated that this was the first AMS patient to be reported with an abnormal karyotype, and that he lacked the typical features of the 18q deletion syndrome (601808). Pellegrino et al. (1996) suggested that the gene(s) for ablepharon-macrostomia syndrome might lie on chromosome 18 in the region of this patient's deletion or inversion breakpoints.
Molecular Genetics
Using DNA from a father and daughter with AMS, originally reported by Rohena et al. (2011), Marchegiani et al. (2015) performed exome sequencing and identified heterozygosity for a missense mutation in the TWIST2 gene (E75K; 607556.0004) that was not found in an in-house exome cohort or in public variant databases. Targeted sequencing revealed heterozygosity for the same E75K mutation in 8 more individuals with AMS from 6 unrelated, previously reported families (Price et al., 1991; Cruz et al., 1995; Ferraz et al., 2000; Stevens and Sargent, 2002; Brancati et al., 2004). Analysis of TWIST2 in individuals with Barber-Say syndrome (BSS; 209885), the features of which closely overlap those of AMS, revealed heterozygosity for 2 different missense mutations also involving codon 75, E75Q (607556.0005) and E75A (607556.0006), as well as a 6-bp duplication at codons 77 and 78 (607556.0007). All 4 mutations are located in the basic domain of the protein, and molecular analyses suggested that the mutations alter the DNA-binding activity of TWIST2, leading to both dominant-negative and gain-of-function effects. Analysis of affected and unaffected skin from 3 mildly affected AMS patients with variable skin pigmentation (Ferraz et al., 2000; Brancati et al., 2004; Rohena et al., 2011) revealed mosaicism for the TWIST2 E75K mutation.
### Exclusion Studies
In a female infant with AMS who displayed similarities to an infant with Fraser syndrome (219000) reported by Cavalcanti et al. (2007), Kallish et al. (2011) analyzed the FRAS1 (607830) and FREM2 (608945) genes but found no mutations.
INHERITANCE \- Autosomal dominant HEAD & NECK Face \- Zygomatic arches absent Ears \- External ears rudimentary Eyes \- Ablepharon (absent eyelids) \- Cryptophthalmos \- Microblepharon \- Eyebrows absent \- Eyelashes absent \- Hypertelorism Nose \- Shape abnormal \- Deficiency of lateral alae nasi (in some patient) Mouth \- Macrostomia \- Short upper lip (in some patients) \- Bilateral deficiency of lateral lower lip (in some patients) \- Unfused labial commissures (in some patients) \- Absent gingiva (in some patients) CHEST Breasts \- Nipples absent or rudimentary ABDOMEN External Features \- Ventral hernia GENITOURINARY External Genitalia (Male) \- Ambiguous genitalia External Genitalia (Female) \- Ambiguous genitalia SKELETAL Hands \- Syndactyly of fingers, variable (in some patients) \- Shortening of metacarpals, variable (in some patients) \- Fifth-finger camptodactyly (in some patients) Feet \- Syndactyly of toes, variable (in some patients) \- Clubfeet (in some patients) SKIN, NAILS, & HAIR Skin \- Coarse skin \- Dry skin \- Redundant folds Hair \- Lanugo absent NEUROLOGIC Central Nervous System \- Language delayed MISCELLANEOUS \- Overlapping features with Barber-Say syndrome ( 209885 ) MOLECULAR BASIS \- Caused by mutation in the homolog of Drosophila TWIST-2 gene (TWIST2, 607556.0004 ) ▲ 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
| ABLEPHARON-MACROSTOMIA SYNDROME | c1860224 | 2,098 | omim | https://www.omim.org/entry/200110 | 2019-09-22T16:31:44 | {"doid": ["0060550"], "mesh": ["C535557"], "omim": ["200110"], "orphanet": ["920"]} |
Hereditary thrombophilia due to congenital histidine-rich (poly-L) glycoprotein deficiency is a rare, genetic, coagulation disorder characterized by a tendency to develop thrombosis, resulting from decreased histidine-rich glycoprotein (HRG) plasma levels. Manifestations are variable depending on location of thrombosis, but may include headaches, diplopia, progressive pain, limb swelling, itching or ulceration, and brownish skin discoloration, among others.
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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
| Hereditary thrombophilia due to congenital histidine-rich (poly-L) glycoprotein deficiency | c2751090 | 2,099 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=217467 | 2021-01-23T17:45:13 | {"mesh": ["C567737"], "omim": ["613116"], "icd-10": ["D68.5"], "synonyms": ["Hereditary thrombophilia due to congenital HRG deficiency"]} |
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