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Butyrylcholinesterase (BChE) deficiency is a metabolic disorder characterised by prolonged apnoea after the use of certain anaesthetic drugs, including the muscle relaxants succinylcholine or mivacurium and other ester local anaesthetics. The duration of the prolonged apnoea varies significantly depending on the extent of the enzyme deficiency.
## Epidemiology
The prevalence of BChE deficiency is highest in the Caucasian population with between 3.4 and 4% of the population displaying a partial enzyme deficiency leading to slightly prolonged apnoea (between 5 minutes and 1 hour) and 1 in 2500 individuals showing a prolongation of more than 1 hour. Individuals with undetectable levels of BChE activity display a severe prolongation lasting more than 8 hours. The prevalence of this severe form is estimated at 1 in 100 000 individuals.
## Etiology
BChE deficiency is a multifactorial disorder. It is caused by mutations in the BChE gene. The BChE gene is located at the E1 locus on chromosome 3 (3q26.1-q26.2) and multiple atypical variants have been identified. However, BChE deficiency and sensitivity to anaesthetic drugs may also occur during pregnancy, in neonates or in association with other pathologies (chronic infections, malnutrition, liver disease, certain cancers etc.).
## Diagnostic methods
Diagnosis can be made by analysis of enzyme activity in plasma samples, combined with dibucaine and fluoride inhibition tests. DNA analysis, although not carried out routinely, can be used to identify heterozygous carriers of atypical alleles.
## Genetic counseling
The hereditary condition is transmitted as an autosomal recessive trait.
## Management and treatment
Affected individuals are asymptomatic unless exposed to neuromuscular blocking agents, however, prolonged respiratory paralysis following anaesthesia makes mechanical ventilation essential until the excess aesthetic agent is metabolised permitting normal neuromuscular function.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Butyrylcholinesterase deficiency | c1283400 | 4,500 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=132 | 2021-01-23T18:27:20 | {"gard": ["7482"], "mesh": ["C537417"], "omim": ["617936"], "umls": ["C1283400"], "synonyms": ["Pseudocholinesterase deficiency"]} |
A number sign (#) is used with this entry because cri-du-chat syndrome is a well-described partial aneusomy resulting from deletion of the short arm of chromosome 5. There is a high probability that deletion of multiple genes is responsible for the phenotype as well as evidence that deletion of the telomerase reverse transcriptase gene (TERT; 187270) is specifically involved in the phenotypic changes of cri-du-chat syndrome.
Description
Cri-du-chat syndrome was first described by Lejeune et al. (1963) as a hereditary congenital syndrome associated with deletion of part of the short arm of chromosome 5. The deletions can vary in size from extremely small and involving only band 5p15.2 to the entire short arm. Although the majority of deletions arise as new mutations, approximately 12% result from unbalanced segregation of translocations or recombination involving a pericentric inversion in one of the parents.
Clinical Features
Cri-du-chat syndrome is characterized in young children by microcephaly, round face, hypertelorism, micrognathia, epicanthal folds, low-set ears, hypotonia, and severe psychomotor and mental retardation. One of the most characteristic features in newborns is a high-pitched cat-like cry that is usually considered diagnostic for the syndrome (see Overhauser et al., 1994); however, the characteristic cat-like cry without the typical dysmorphic and severe developmental features of the syndrome has been found in individuals with a deletion confined to 5p15.3 (see Overhauser et al., 1994 and Gersh et al., 1995).
Kjaer and Niebuhr (1999) studied profile radiographs of the cranial face in 23 patients with cri-du-chat syndrome collected in Denmark in the 1970s. Twenty-two patients had terminal deletions of chromosome 5, and 1 patient had an interstitial deletion. The cranial base angle was in most cases reduced and in no cases increased compared to age-related standards for normal individuals. Malformations in the bony contours of the sella turcica and the clivus occurred in cri-du-chat patients with terminal deletions. They pointed out that this specific cranial base region develops around the notochord at the location from where the rhombencephalic-derived brainstem, pons, and cerebellum develop dorsally, and from where the neurons to the larynx migrate ventrally. They suggested that a cranial developmental field, originating from the notochordal location, is involved in the manifestations of cri-du-chat syndrome.
Van Buggenhout et al. (2000) pointed out that with advancing age the clinical picture of the cri-du-chat syndrome becomes less striking. They presented 7 patients with 5p deletion syndrome, with ages ranging from 16 to 47 years. Some of the clinical characteristics, such as long face, macrostomia, and scoliosis, became more evident. All patients were severely or profoundly mentally retarded except for one who was mildly retarded. Diagnosis was difficult to make in some of the patients who were first seen at an older age. In some of them, the craniofacial appearance resembled that of Angelman syndrome (105830). Most patients had periods of destructive behavior, self mutilation, and aggression.
Fang et al. (2008) reported a 3-generation Chinese Han family in which 5 members had cri-du-chat syndrome. The proband was a 62-year-old woman who presented to a psychiatric ward with temper tantrums, self-injuries, aggressive behavior, and psychotic symptoms, including delusions of persecution, auditory hallucinations, self-talking, and self-laughing. She had a soft, high-pitched, cat-like voice. Her 41-year-old daughter had mental retardation and similar psychotic features, which are rare in cri-du-chat syndrome. She did not have a high-pitched voice. In contrast, the other 3 affected males had mild to moderate mental retardation without psychotic symptoms. All affected individuals were found to have a 10.5-Mb terminal deletion at chromosome 5p15.2, which was confirmed and characterized by karyotyping, FISH, array CGH, and quantitative PCR analyses. The ROPN1L gene (611756) was found to be disrupted by the breakpoint. Although the affected family members apparently shared deletions of the same size, the variation in mental symptoms within this family suggested that other factors besides the size and location of 5p deletions may modify the mental presentation of patients with cri-du-chat syndrome. Fang et al. (2008) noted that familial occurrence of this disorder is rare.
### Clinical Variability
Ladekarl (1968) reported a patient with features of cri-du-chat syndrome and Goldenhar syndrome (164210) associated with a 5q deletion. Choong et al. (2003) reported a male infant, born of nonconsanguineous parents, who had clinical features of cri-du-chat syndrome and Goldenhar syndrome. At birth, he was noted to have dysmorphic facial features, including bilateral preauricular tags, rotated ears, epicanthal folds, a left epibulbar lipodermoid, and an accessory left nipple. He also had hearing loss and feeding difficulties due to esophageal atresia with tracheoesophageal fistula, and horseshoe kidney. In addition, he had a high-pitched, cat-like cry, characteristic of cri-du-chat syndrome. Cytogenetic analysis detected a terminal deletion of chromosome 5p14, consistent with the cri-du-chat locus. The association of Goldenhar syndrome and cri-du-chat syndrome in this patient suggested that the chromosome 5p14 locus may harbor a gene implicated with Goldenhar syndrome.
Population Genetics
The cri-du-chat syndrome appears to be one of the most common human deletion syndromes, with an incidence varying between 1 in 20,000 to 1 in 50,000 births (Niebuhr, 1978). The frequency in populations of profoundly retarded patients (IQ less than 20) is approximately 1% (Niebuhr, 1978).
Molecular Genetics
Overhauser et al. (1994) analyzed the 5p deletion breakpoints in 49 individuals using somatic cell hybrids. They used 5p-specific DNA probes to unambiguously order most of the chromosomal breakpoints present by hybridization to somatic cell hybrid DNA. Comparisons between the deletions present in the patients and their clinical features identified several chromosomal regions that were involved in specific clinical features. A critical chromosomal region involved in the high-pitched cry mapped to proximal 5p15.3 (probe D5S727), while the chromosomal region involved in the remaining features of the syndrome mapped to a small region within central 5p15.2 (probe D5S721). This latter region was estimated to be about 2 Mb in size. Deletions that did not include these 2 chromosomal regions presented varying clinical phenotypes from severe mental retardation and microcephaly to a clinically normal phenotype.
Gersh et al. (1995) studied 4 families in which patients with 5p deletions had only the characteristic cat-like cry, with normal to mildly delayed development. The precise location of the deletion in each family was determined by fluorescence in situ hybridization using lambda phage and cosmid clones. All of the deletion breakpoints mapped distal to a chromosomal region implicated with the facial features and severe mental and developmental delay in the cri-du-chat syndrome. The breakpoints were located distal to the 5p15.2 region and indicated to Gersh et al. (1995) that another genetic component of this contiguous gene syndrome is located in that area.
Simmons et al. (1997) isolated cDNAs from the cri-du-chat critical region by direct sequencing of a chromosome 5-specific cDNA library. A thrombospondin-like gene and 3 other cDNAs were considered candidate genes for the cri-du-chat contiguous gene deletion syndrome.
Cerruti Mainardi et al. (2001) studied 80 patients with cri-du-chat syndrome. Sixty-two had a 5p terminal deletion with breakpoints ranging from p13 to p15.2. Seven patients had a 5p interstitial deletion; 4 had a de novo translocation, and 3 had a familial translocation. Three had a de novo 5p anomaly involving 2 rearranged cell lines, and 1 had a 5p deletion arising from a paternal inversion. Cerruti Mainardi et al. (2001) identified a critical region at p15.2 for dysmorphism and mental retardation and a separate region at p15.3 for the cat-like cry, this region being bounded by the markers at D5S13 and D5S731. They also suggested a separate region at p15.3 for speech delay. The 62 patients were subdivided into 4 groups according to deletion size and a significant trend was identified, with increased severity of dysmorphism and developmental delay corresponding to increased size of deletion.
Medina et al. (2000) determined that the CTNND2 gene (604275) maps to a specific region in chromosome 5p15.2 implicated in the mental retardation phenotype of cri-du-chat syndrome. They characterized the breakpoints in patients with 5p terminal deletions with respect to the severity of mental retardation and the physical location of the CTNND2 gene and found a strong correlation between hemizygous loss of CTNND2 and severe mental retardation. Medina et al. (2000) concluded that these findings, and the properties of CTNND2 as a neuronal-specific protein, expressed early in development and involved in cell motility, supported its role in the mental retardation of cri-du-chat syndrome when present in only 1 copy.
The TERT gene is localized to the distal portion of chromosome 5p (viz., 5p15.33) and is the rate-limiting component for telomerase activity, which is essential for telomere length maintenance and sustained cell proliferation. Zhang et al. (2003) showed that a deletion of the TERT allele had occurred in all 10 patients with cri-du-chat syndrome whom they examined. Induction of TERT mRNA in proliferating lymphocytes derived from 5 of 7 patients was lower than that in unaffected control individuals. The patient lymphocytes exhibited shorter telomeres than age-matched unaffected individuals (P less than 0.0001). A reduction in replicative life span and a high rate of chromosome fusions were observed in cultured patient fibroblasts. Reconstitution of telomerase activity by ectopic expression of TERT extended the telomere length, increased the population doublings, and prevented the end-to-end fusion of chromosomes. Zhang et al. (2003) suggested that haploinsufficiency for telomere maintenance in vivo may be one genetic element contributing to the phenotypic changes in cri-du-chat syndrome.
Perfumo et al. (2000) reported 3 children with mosaic 5p rearrangements, 2 with a partial monosomic cell line and a partial monosomic/trisomic cell line and 1 with 2 different partial monosomic cell lines.
Zhang et al. (2005) used array comparative genomic hybridization to map DNA copy number changes in 94 patients with cri-du-chat syndrome who had been carefully evaluated for the presence of the characteristic cry, speech delay, facial dysmorphology, and level of mental retardation. Most subjects had simple deletions involving 5p; the deletion was terminal in 67 and interstitial in 12. Genotype-phenotype correlations localized the region associated with the cry to 1.5 Mb in distal 5p15.31, between BACs containing markers D5S2054 and D5S676; speech delay to 3.2 Mb in 5p15.33-p15.32, between BACs containing D5S417 and D5S635; and the region associated with facial dysmorphology to 2.4 Mb in 5p15.31-p15.2, between BACs containing D5S208 and D5S2887. Mental retardation depended approximately on the 5p deletion size and location, but there were many cases in which the retardation was disproportionately severe, given the 5p deletion. All 15 of these cases, approximately two-thirds of the severely retarded patients, were found to have copy number aberrations in addition to the 5p deletion. Restriction of consideration to patients with only 5p deletions clarified the effect of such deletions and suggested the presence of 3 regions, referred as MR-I, MR-II, and MR-III, with differing effect on retardation. Deletions including MR-I, a 1.2-Mb region overlapping the previously defined cri-du-chat critical region but not including MR-II and MR-III, produced a moderate level of retardation. Deletions restricted to MR-II, located just proximal to MR-I, produced a milder level of retardation, whereas deletions restricted to the still more proximal MR-III produced no discernible phenotype. However, mental retardation increased as deletions that included MR-I extended progressively into MR-II and MR-III, and mental retardation became profound when all 3 regions were deleted.
South et al. (2006) reported a child with cri-du-chat syndrome and a terminal deletion 5p14.3 which microsatellite analysis confirmed was inherited from the mother. FISH analysis identified a paracentric inversion, inv(5)(p13.3p15.3), in the mother. South et al. (2006) noted that this was an unusual case because paracentric inversion carriers usually do not have liveborn children since recombination is predicted to result in unstable chromosomes that are embryonic lethal. South et al. (2006) proposed a mechanism involving dicentric chromosome formation with subsequent breakage and telomere healing during meiosis to explain the findings in this case.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| CRI-DU-CHAT SYNDROME | c0010314 | 4,501 | omim | https://www.omim.org/entry/123450 | 2019-09-22T16:42:39 | {"doid": ["12580"], "mesh": ["D003410"], "omim": ["123450"], "icd-9": ["758.31"], "icd-10": ["Q93.4"], "orphanet": ["281"], "synonyms": ["Alternative titles", "CAT CRY SYNDROME", "CHROMOSOME 5p DELETION SYNDROME"]} |
Mental disorder involving paranoid delusions and mistrust of others
Not to be confused with paranoid schizophrenia.
Paranoid personality disorder
SpecialtyPsychiatry, clinical psychology
Personality disorders
Cluster A (odd)
* Paranoid
* Schizoid
* Schizotypal
Cluster B (dramatic)
* Antisocial
* Borderline
* Histrionic
* Narcissistic
Cluster C (anxious)
* Avoidant
* Dependent
* Obsessive–compulsive
Not specified
* Depressive
* Haltlose
* Immature
* Passive–aggressive
* Cyclothymic
* Psychopathy
* v
* t
* e
Paranoid personality disorder (PPD) is a mental illness characterized by paranoid delusions, and a pervasive, long-standing suspiciousness and generalized mistrust of others. People with this personality disorder may be hypersensitive, easily insulted, and habitually relate to the world by vigilant scanning of the environment for clues or suggestions that may validate their fears or biases. They are eager observers. They think they are in danger and look for signs and threats of that danger, potentially not appreciating other interpretations or evidence.[1]
They tend to be guarded and suspicious and have quite constricted emotional lives. Their reduced capacity for meaningful emotional involvement and the general pattern of isolated withdrawal often lend a quality of schizoid isolation to their life experience.[2][verification needed] People with PPD may have a tendency to bear grudges, suspiciousness, tendency to interpret others' actions as hostile, persistent tendency to self-reference, or a tenacious sense of personal right.[3] Patients with this disorder can also have significant comorbidity with other personality disorders (such as schizotypal, schizoid, narcissistic, avoidant and borderline).
## Contents
* 1 Causes
* 2 Diagnosis
* 2.1 ICD-10
* 2.2 DSM-5
* 2.3 Other
* 2.4 Differential diagnosis
* 3 Treatment
* 4 Epidemiology
* 5 History
* 6 See also
* 7 References
* 8 External links
## Causes[edit]
A genetic contribution to paranoid traits and a possible genetic link between this personality disorder and schizophrenia exist. A large long-term Norwegian twin study found paranoid personality disorder to be modestly heritable and to share a portion of its genetic and environmental risk factors with the other cluster A personality disorders, schizoid and schizotypal.[4]
Psychosocial theories implicate projection of negative internal feelings and parental modeling.[5] Cognitive theorists believe the disorder to be a result of an underlying belief that other people are unfriendly in combination with a lack of self-awareness.[6]
## Diagnosis[edit]
### ICD-10[edit]
The World Health Organization's ICD-10 lists paranoid personality disorder under (F60.0). It is a requirement of ICD-10 that a diagnosis of any specific personality disorder also satisfies a set of general personality disorder criteria. It is also pointed out that for different cultures it may be necessary to develop specific sets of criteria with regard to social norms, rules and other obligations.[7]
PPD is characterized by at least three of the following symptoms:
1. excessive sensitivity to setbacks and rebuffs;
2. tendency to bear grudges persistently (i.e. refusal to forgive insults and injuries or slights);
3. suspiciousness and a pervasive tendency to distort experience by misconstruing the neutral or friendly actions of others as hostile or contemptuous;
4. a combative and tenacious sense of self-righteousness out of keeping with the actual situation;
5. recurrent suspicions, without justification, regarding sexual fidelity of spouse or sexual partner;
6. tendency to experience excessive self-aggrandizing, manifest in a persistent self-referential attitude;
7. preoccupation with unsubstantiated "conspiratorial" explanations of events both immediate to the patient and in the world at large.
Includes: expansive paranoid, fanatic, querulant and sensitive paranoid personality disorder.
Excludes: delusional disorder and schizophrenia.
### DSM-5[edit]
The American Psychiatric Association's DSM-5 has similar criteria for paranoid personality disorder. They require in general the presence of lasting distrust and suspicion of others, interpreting their motives as malevolent, from an early adult age, occurring in a range of situations. Four of seven specific issues must be present, which include different types of suspicions or doubt (such as of being exploited, or that remarks have a subtle threatening meaning), in some cases regarding others in general or specifically friends or partners, and in some cases referring to a response of holding grudges or reacting angrily.[8]
PPD is characterized by a pervasive distrust and suspiciousness of others such that their motives are interpreted as malevolent, beginning by early adulthood and present in a variety of contexts. To qualify for a diagnosis, the patient must meet at least four out of the following criteria:[8]
1. Suspects, without sufficient basis, that others are exploiting, harming, or deceiving them.
2. Is preoccupied with unjustified doubts about the loyalty or trustworthiness of friends or associates.
3. Is reluctant to confide in others because of unwarranted fear that the information will be used maliciously against them.
4. Reads hidden demeaning or threatening meanings into benign remarks or events.
5. Persistently bears grudges (i.e., is unforgiving of insults, injuries, or slights).
6. Perceives attacks on their character or reputation that are not apparent to others and is quick to react angrily or to counterattack.
7. Has recurrent suspicions, without justification, regarding fidelity of spouse or sexual partner.
The DSM-5 lists paranoid personality disorder essentially unchanged from the DSM-IV-TR[9] version and lists associated features that describe it in a more quotidian way. These features include suspiciousness, intimacy avoidance, hostility and unusual beliefs/experiences.
### Other[edit]
Various researchers and clinicians may propose varieties and subsets or dimensions of personality related to the official diagnoses. Psychologist Theodore Millon has proposed five subtypes of paranoid personality:[10]
Subtype Features
Obdurate paranoid (including compulsive features) Self-assertive, unyielding, stubborn, steely, implacable, unrelenting, dyspeptic, peevish, and cranky stance; legalistic and self-righteous; discharges previously restrained hostility; renounces self-other conflict.
Fanatic paranoid (including narcissistic features) Grandiose delusions are irrational and flimsy; pretentious, expensive supercilious contempt and arrogance toward others; lost pride reestablished with extravagant claims and fantasies.
Querulous paranoid (including negativistic features) Contentious, caviling, fractious, argumentative, faultfinding, unaccommodating, resentful, choleric, jealous, peevish, sullen, endless wrangles, whiny, waspish, snappish.
Insular paranoid (including avoidant features) Reclusive, self-sequestered, hermitical; self-protectively secluded from omnipresent threats and destructive forces; hypervigilant and defensive against imagined dangers.
Malignant paranoid (including sadistic features) Belligerent, cantankerous, intimidating, vengeful, callous, and tyrannical; hostility vented primarily in fantasy; projects own venomous outlook onto others; persecutory delusions.
### Differential diagnosis[edit]
Paranoid personality disorder can involve, in response to stress, very brief psychotic episodes (lasting minutes to hours). The paranoid may also be at greater than average risk of experiencing major depressive disorder, agoraphobia, social anxiety disorder, obsessive-compulsive disorder or alcohol and substance-related disorders. Criteria for other personality disorder diagnoses are commonly also met, such as:[11] schizoid, schizotypal, narcissistic, avoidant, borderline and negativistic personality disorder.
## Treatment[edit]
Because of reduced levels of trust, there can be challenges in treating PPD. However, psychotherapy, antidepressants, antipsychotics and anti-anxiety medications can play a role when a person is receptive to intervention.[12]
## Epidemiology[edit]
PPD occurs in about 0.5–2.5% of the general population.[5][11] It is seen in 2–10% of psychiatric outpatients. It is more common in males.[11]
## History[edit]
See also: History of paranoia
Paranoid personality disorder is listed in DSM-V and was included in all previous versions of the DSM. One of the earliest descriptions of the paranoid personality comes from the French psychiatrist Valentin Magnan who described a "fragile personality" that showed idiosyncratic thinking, hypochondriasis, undue sensitivity, referential thinking and suspiciousness.[13]
Closely related to this description is Emil Kraepelin's description from 1905 of a pseudo-querulous personality who is "always on the alert to find grievance, but without delusions", vain, self-absorbed, sensitive, irritable, litigious, obstinate, and living at strife with the world. In 1921, he renamed the condition paranoid personality and described these people as distrustful, feeling unjustly treated and feeling subjected to hostility, interference and oppression. He also observed a contradiction in these personalities: on the one hand, they stubbornly hold on to their unusual ideas, on the other hand, they often accept every piece of gossip as the truth.[13] Kraepelin also noted that paranoid personalities were often present in people who later developed paranoid psychosis. Subsequent writers also considered traits like suspiciousness and hostility to predispose people to developing delusional illnesses, particularly "late paraphrenias" of old age.[14]
Following Kraepelin, Eugen Bleuler described "contentious psychopathy" or "paranoid constitution" as displaying the characteristic triad of suspiciousness, grandiosity and feelings of persecution. He also emphasized that these people's false assumptions do not attain the form of real delusion.[13]
Ernst Kretschmer emphasized the sensitive inner core of the paranoia-prone personality: they feel shy and inadequate but at the same time they have an attitude of entitlement. They attribute their failures to the machinations of others but secretly to their own inadequacy. They experience constant tension between feelings of self-importance and experiencing the environment as unappreciative and humiliating.[13]
Karl Jaspers, a German phenomenologist, described "self-insecure" personalities who resemble the paranoid personality. According to Jaspers, such people experience inner humiliation, brought about by outside experiences and their interpretations of them. They have an urge to get external confirmation to their self-deprecation and that makes them see insults in the behavior of other people. They suffer from every slight because they seek the real reason for them in themselves. This kind of insecurity leads to overcompensation: compulsive formality, strict social observances and exaggerated displays of assurance.[13]
In 1950, Kurt Schneider described the "fanatic psychopaths" and divided them into two categories: the combative type that is very insistent about his false notions and actively quarrelsome, and the eccentric type that is passive, secretive, vulnerable to esoteric sects but nonetheless suspicious about others.[13]
The descriptions of Leonhard and Sheperd from the sixties describe paranoid people as overvaluing their abilities and attributing their failure to the ill-will of others; they also mention that their interpersonal relations are disturbed and they are in constant conflict with others.[13]
In 1975, Polatin described the paranoid personality as rigid, suspicious, watchful, self-centered and selfish, inwardly hypersensitive but emotionally undemonstrative. However, when there is a difference of opinion, the underlying mistrust, authoritarianism and rage burst through.[13]
In the 1980s, paranoid personality disorder received little attention, and when it did receive it, the focus was on its potential relationship to paranoid schizophrenia. The most significant contribution of this decade comes from Theodore Millon who divided the features of paranoid personality disorder to four categories:[13]
1) behavioral characteristics of vigilance, abrasive irritability and counterattack,
2) complaints indicating oversensitivity, social isolation and mistrust,
3) the dynamics of denying personal insecurities, attributing these to others and self-inflation through grandiose fantasies
4) coping style of detesting dependence and hostile distancing of oneself from others.
## See also[edit]
* Psychology portal
* DSM-IV codes (personality disorders)
* ICD-10 codes (personality disorders)
* Delusional disorder
* Delusions of reference
* Paranoid anxiety
* Paranoid schizophrenia
* Persecutory delusions
* Schizotypal personality disorder
## References[edit]
1. ^ Waldinger, Robert J. (1 August 1997). Psychiatry for Medical Students. American Psychiatric. ISBN 978-0-88048-789-4.
2. ^ Meissner & Kuper, 2008
3. ^ MacManus, Deirdre; Fahy, Tom (August 2008). "Personality disorders". Medicine. 36 (8): 436–441. doi:10.1016/j.mpmed.2008.06.001.
4. ^ Kendler KS, Czajkowski N, Tambs K, et al. (2006). "Dimensional representations of DSM-IV cluster A personality disorders in a population-based sample of Norwegian twins: a multivariate study". Psychological Medicine. 36 (11): 1583–91. doi:10.1017/S0033291706008609. PMID 16893481.
5. ^ a b Personality Disorders at eMedicine
6. ^ Aaron T. Beck, Arthur Freeman (1990). Cognitive Therapy of Personality Disorders (1st ed.). The Guilford Press. ISBN 9780898624342. OCLC 906420553.
7. ^ The Classification of Mental and Behavioural Disorders (ICD-10) by WHO: "Diagnostic guidelines Archived 2014-03-23 at the Wayback Machine, p.158
8. ^ a b "Schizoid Personality Disorder (pp. 652–655)". Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (2013). 2013. ISBN 978-0-89042-555-8.
9. ^ American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision (DSM-IV-TR). Washington, DC: American Psychiatric Association.
10. ^ Millon, Théodore; Grossman, Seth (6 August 2004). Personality disorders in modern life. Wiley. ISBN 978-0-471-23734-1.
11. ^ a b c "Internet Mental Health — paranoid personality disorder". Archived from the original on 2013-01-31. Retrieved 2004-06-01.
12. ^ ""Paranoid Personality Disorder" at Cleveland Clinic". Archived from the original on 2012-03-04. Retrieved 2008-02-13.
13. ^ a b c d e f g h i Salman Akhtar (1990). [https://books.google.de/books?id=bU0eAAAAQBAJ&pg=PA149#v=onepage&q&f=false Paranoid Personality Disorder: A Synthesis of Developmental, Dynamic, and Descriptive Features] Archived 2018-04-01 at the Wayback Machine. American Journal of Psychotherapy, 44, 5–25.
14. ^ Bernstein, D. P., Useda, D., Siever, L. J. (1995). Paranoid Personality Disorder. In: J. W. Livesley (Ed.). The DSM-IV Personality Disorders. (pp. 45-57). New York: Guilford.
## External links[edit]
Classification
D
* ICD-10: F60.0
* ICD-9-CM: 301.0
* MeSH: D010260
* SNOMED CT: 13601005
External resources
* MedlinePlus: 000938
* National Personality Disorder website for England
* Articles about Personality Disorders in Web4health web site
* v
* t
* e
DSM personality disorders
DSM-III-R only
* Sadistic
* Self-defeating (masochistic)
DSM-IV only
Personality disorder not otherwise specified
Appendix B (proposed)
* Depressive
* Negativistic (passive–aggressive)
DSM-5
(Categorical
model)
Cluster A (odd)
* Paranoid
* Schizoid
* Schizotypal
Cluster B (dramatic)
* Antisocial
* Borderline
* Histrionic
* Narcissistic
Cluster C (anxious)
* Avoidant
* Dependent
* Obsessive-compulsive
DSM-5
Alternative hybrid categorical and dimensional model in Section III included to stimulate further research
* v
* t
* e
Personality disorders
Schizotypal
* Schizotypal
Specific
* Anankastic
* Anxious (avoidant)
* Dependent
* Dissocial
* Emotionally unstable
* Histrionic
* Paranoid
* Schizoid
*
Other
* Eccentric
* Haltlose
* Immature
* Narcissistic
* Passive–aggressive
* Psychoneurotic
Organic
* Organic
Unspecified
* Unspecified
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Paranoid personality disorder | c0030477 | 4,502 | wikipedia | https://en.wikipedia.org/wiki/Paranoid_personality_disorder | 2021-01-18T18:38:36 | {"mesh": ["D010260"], "umls": ["C0030477"], "icd-10": ["F60.0"], "wikidata": ["Q747735"]} |
For a phenotypic description and a discussion of genetic heterogeneity of attention deficit-hyperactivity disorder, see 143465.
Mapping
Ogdie et al. (2003) performed linkage analyses on 270 affected sib pairs with ADHD. Multipoint linkage analysis identified suggestive linkage for 17p11 (maximum lod score of 2.98) and for 4 other regions with MLS values greater than 1.0, including 5p13, 6q14, 11q25, and 20q13. The authors noted that 17p11 and the previously identified 16p13 region (608903), as well as 5p13, had been highlighted in genomewide scans for autism.
In an analysis of 308 affected sib pairs, the same group (Ogdie et al., 2004) again found 17p11 as a likely region containing a susceptibility locus for ADHD (MLS of 3.63; empiric P = 0.015).
Among 192 unrelated Korean children with ADHD and 196 age-matched Korean controls, Won et al. (2011) found a significant association between a C-to-T SNP (rs550818) in intron 20 of the GIT1 gene (608434) on chromosome 17p11.2 and ADHD (p = 0.00625 after Bonferroni correction). Although the minor homozygous TT allele was extremely rare (1 in 388), the CT allele was significantly associated with a 2.7-fold increased risk for ADHD compared to the CC allele (p = 0.0056). In vitro functional expression studies showed that the minor T allele was associated with approximately 50% reduced GIT1 expression compared to the major C allele. These results suggested that decreased GIT1 expression may be associated with increased risk for ADHD.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| ATTENTION DEFICIT-HYPERACTIVITY DISORDER, SUSCEPTIBILITY TO, 2 | c1837152 | 4,503 | omim | https://www.omim.org/entry/608904 | 2019-09-22T16:07:05 | {"omim": ["608904"], "synonyms": ["Alternative titles", "ADHD2"]} |
## Description
The International Headache Society (1988) classifies headache associated with sexual activity (HSA) as an idiopathic headache under 'miscellaneous headaches unassociated with structural lesions.' Based on initial descriptions, 3 subtypes are differentiated: type 1 is a dull ache in the head and neck that slowly intensifies as sexual excitement increases, and is believed to be caused by muscle contraction similar to tension-type headache; type 2, also called 'vascular-type,' is a sudden severe, explosive headache occurring at orgasm, which may be due to increased intracranial pressure; type 3, the most uncommon type, is a postural headache resembling that caused by decreased CSF pressure, perhaps due to a meningeal tear during coitus (summary by Frese et al., 2003).
Clinical Features
Johns (1986) reported 4 sisters with the vascular type of benign sexual headache (type 2 HSA). The most severely affected patient was successfully treated with beta-blocker prophylaxis. In a review of the literature, the author found that 28% of those affected had either personal history or family history of migraine (see 157300), suggesting that type 2 HSA is a migraine variant.
Among 51 patients diagnosed with HSA, Frese et al. (2003) found that HSA type 2 was the most common, occurring in 40 patients. Eleven patients had HSA type 1, and no patient had HSA type 3. There was a clear male preponderance (2.9:1). For the whole group, the mean age at onset was 35.2 years, with a first peak between 20 and 24 years and a second peak between 35 and 44 years. Pain was predominantly, but not exclusively, occipital or diffuse, and the duration of pain varied widely from less than 15 minutes to 12 hours. Most patients had longer lasting, milder pain (approximately 4 hours). The usual setting for headache was sexual activity with the usual partner (94%), followed by masturbation (35%). Sixty-one percent of the patients had other headache disorders, including episodic tension-type (in 18), benign exertional (in 15), migraine (in 13), and chronic tension-type (in 5). The only significant difference between types 1 and 2 were time of onset: minutes before orgasm for type 1 and concurrent with orgasm for type 2. Arterial hypertension was not a risk factor.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| HEADACHE ASSOCIATED WITH SEXUAL ACTIVITY | c0393754 | 4,504 | omim | https://www.omim.org/entry/607504 | 2019-09-22T16:09:06 | {"omim": ["607504"], "icd-9": ["339.82"], "icd-10": ["G44.82"], "synonyms": ["Alternative titles", "BENIGN SEXUAL HEADACHE"]} |
Beet vascular necrosis
Scientific classification
Domain:
Bacteria
Phylum:
Proteobacteria
Class:
Gammaproteobacteria
Order:
Enterobacteriales
Family:
Pectobacteriaceae
Genus:
Pectobacterium
Species:
P. carotovorum
Subspecies:
P. c. subsp. betavasculorum
Trinomial name
Pectobacterium carotovorum subsp. betavasculorum
Synonyms
* Erwinia carotovora subsp. betavasculorum
* Pectobacterium betavasculorum
A table beet infected with Pectobacterium carotovorum subsp. betavasculorum. Note the rings of black vascular tissue colonized by the rotting bacteria.
Beet vascular necrosis and rot is a soft rot disease caused by the bacterium Pectobacterium carotovorum subsp. betavasculorum, which has also been known as Pectobacterium betavasculorum and Erwinia carotovora subsp. betavasculorum.[1] It was classified in the genus Erwinia until genetic evidence suggested that it belongs to its own group;[2] however, the name Erwinia is still in use. As such, the disease is sometimes called Erwinia rot today. It is a very destructive disease that has been reported across the United States as well as in Egypt. Symptoms include wilting and black streaks on the leaves and petioles. It is usually not fatal to the plant, but in severe cases the beets will become hollowed and unmarketable. The bacteria is a generalist species which rots beets and other plants by secreting digestive enzymes that break down the cell wall and parenchyma tissues.[3] The bacteria thrive in warm and wet conditions, but cannot survive long in fallow soil.[4][5] However, it is able to persist for long periods of time in the rhizosphere of weeds and non-host crops.[4][6] While it is difficult to eradicate, there are cultural practices that can be used to control the spread of the disease, such as avoiding injury to the plants and reducing or eliminating application of nitrogen fertilizer.
## Contents
* 1 Hosts
* 2 Symptoms
* 3 Disease cycle
* 4 Environment
* 4.1 Agricultural
* 4.2 Laboratory
* 5 Management
* 5.1 Cultural practices
* 5.2 Resistance
* 5.3 Biological control
* 6 Importance
* 7 References
## Hosts[edit]
Fodder beets, sugar beets and fodder-sugar crosses are all susceptible to infection by Pectobacterium carotovorum subsp. betavasculorum.[1] Today most beet cultivars are resistant to the pathogen, however, isolates vary geographically, and some cultivars of beets are only resistant to specific isolates of bacteria. For example, the cultivar USH11 demonstrates resistance to both Montana and California isolates, whereas Beta 4430 is highly susceptible to the Montana isolates but resistant to the California isolate.[7] Other cultivars resistant to California isolates of Pectobacterium caratovorum subsp. betavasculorum include Beta 4776R, Beta 4430R and Beta 4035R, but HH50 has been found to be susceptible.[7]
Breeding for resistance to other diseases such as beet yellows virus without also selecting for vascular necrosis resistance can leave cultivars susceptible to the pathogen. For example, the use of USH9A and H9B in California’s San Joaquin valley is thought to have led to an epiphytotic (severe) outbreak of disease in the early 1970s.[8] This was likely because of the limited gene pool used when selecting strongly for resistance to beet yellows virus. Further information on resistant cultivars can be found in the section Management.
In addition to beets, Pectobacterium carotovara subsp. betavasculorum can also infect tomato, potato, carrots, sweet potato, radish, sunflower, artichokes, squash, cucumber and chrysanthemum.[1][4][6][9] Other subspecies of Pectobacterium carotovora can also be pathogenic to beets. Erwinia carotovara subsp. atroseptica is a bacterial soft rot pathogen that is responsible for the disease Blackleg of Potato (Solanum tuberosum), and variants of this bacterium can cause root rot in sugarbeets,.[10][11] This subspecies also has a wide host-range. Erwinia carotovora var. atroseptica has been detected in the rhizosphere of native vegetation and on weed species such as Lupinus blumerii and Amaranthus palmeri (pigweed).[11] It is thought that the source of inoculums survives on these non-host plants in areas in which it is endemic as well as in the rhizosphere of other crops such as wheat and corn[11]
## Symptoms[edit]
Table beet stem infected with Pectobacterium carotovorum subsp. betavasculorum. Note entry through a wound.
Symptoms can be found on both beet roots and foliage, although foliar symptoms are not always present. If present, foliar symptoms include dark streaking along petioles and viscous froth deposits on the crown which are a by-product of bacterial metabolism.[12] Petioles can also become necrotic and demonstrate vascular necrosis. When roots become severely affected, wilting also occurs.[1] Below ground symptoms include both soft and dry root rot. Affected vascular bundles in roots become necrotic and brown, and tissue adjacent to necrosis becomes pink upon air contact.[1] The plants that do not die completely may have rotted-out, cavernous roots.
Various pathogens can cause root rot in beets; however the black streaking on petioles and necrotic vascular bundles in roots and adjacent pink tissue help to distinguish this disease from others such as Fusarium Yellows. Additionally, sampling from the rhizosphere of infected plants and serological tests can confirm the presence of Erwinia caratovora subs.[11]
## Disease cycle[edit]
Pectobacterium carotovorum subsp. betavasculorum is a gram negative, rod bacteria with peritichous flagella.[4] For it to enter sugar beet, and thus cause infection, it is essential that there is an injury to the leaves, petioles or crown.[4][6] Infection will often start at the crown and then move down into the root, and can occur at any point in the growing season if environmental conditions are favorable.[5] Once the bacteria enters the plant, it will invade the vascular tissue and cause symptoms by producing plant cell wall degrading enzymes, like pectinases, polygalactronases, and celluases.[13] This results in discolored or necrotic vascular tissue in the root, and the tissue bordering the vascular bundles will turn reddish upon contact with air.[5] Following the infection of the vascular tissue, the bacteria reproduce as long as food resources are available, and the root begins to rot.[5] There is significant variability in the type of rot – it can range from a dry rot to soft and wet rot – because of the multitude of additional microorganisms that may colonize the damaged tissue[5]
Upon death of the sugar beet, or harvest of the field, the pathogen appears to survive in select living plant tissue like beet roots,[4] or volunteer beets.[6] However, it does not appear to survive in sugar beet seeds,[4][5][6] or live in the soil after harvest.[4][5] It is also possible for the pathogen to infect injured carrots, potato, sweet potato, tomato, radish, sunflower, artichokes, squash, cucumber and chrysanthemums;[4][6][9] however, since those are often planted in the same season as sugar beets, they are not likely to be overwintering hosts.
## Environment[edit]
Injury to the leaves, petioles or crown is mandatory for the pathogen to gain entry to the host tissue.[4][6] Accordingly, hail damage is correlated with a higher degree of disease outbreak.[4] Young plants (less than eight weeks old) are also considered to be more prone to infection[4][6]
Temperature and availability of moisture are key factors in determining the rate of disease development. Warm temperatures, 25-30 °C, promote rapid disease development.,[4][6][14] and can result in acute symptoms.[4] Symptoms are also reported to appear at temperatures as low as 18 °C, but disease development is slowed;[5] below that temperature, infections do not develop.[4] Excessive water also promotes disease development by providing a more optimal environment for the pathogen,[14] and has been shown to be a key factor in augmenting disease outbreak in fields with sprinkler irrigation[4]
### Agricultural[edit]
The degree of nitrogen fertilization is highly correlated to robust disease development: it has been shown that sugar beets supplied with excessive or adequate nitrogen are more diseased than sugarbeets with sub-optimal nitrogen levels.[4][6][14] This is a paradox for farmers because, while increased nitrogen fertilization does increase sugar yield in non-infected sugarbeets, it also increases the severity of the disease if infection takes place. Thus, depending on the severity of infection, yield may go down with increased fertilizer use.[15]
The spacing between plants also impacts the degree of infection: greater in-row spacing results in more diseased roots.[15] This may be due to the fact that greater spacing promotes faster growth, and hence greater probability of cracks in the crown,[6] or because of the increased amount of nitrogen available per plant.[4]
Since the pathogen has multiple hosts, it is important for farmers to be wary of other plants in the surrounding area. It is possible for the pathogen to survive in weedy hosts, and can infect injured carrots, potato, sweet potato, tomato, radish, squash, and cucumber.[6][9][14] Hence, the presence of these plants may increase the supply of inoculum.
### Laboratory[edit]
If the pathogen is cultured in a lab, it can grow on Miller and Schroth media, can use sucrose to make reducing sugars, and can use either lactose, methyl alpha-glucoside, inulin or raffinose to make acids.[4] It is also capable of surviving in culture medium sodium levels of up to 7–9%,[4] and in temperatures as high as 39 °C.[16]
## Management[edit]
Since the bacteria cannot survive in seeds,[4][6] the best way to prevent the disease is to ensure that vegetatively propagated plant material are clean of infection, such that the bacterium does not enter the soil. However, if the bacteria is already present, there are some methods that can be used to lessen the infection.
### Cultural practices[edit]
Because the bacteria readily enter the plant through wounds, management practices that decrease injury to the plants are important to control the spread of the disease.[17] Cultivation is not recommended, as the machinery can become contaminated and physically spread the bacteria around the soil. Accidental leaf tearing or root scarring can also occur depending on the size of the crop, allowing the bacteria to enter more individual plants. If hilling the beets, great care must be taken to avoid getting soil into the crown,[18] because the pathogen is soil-borne and this could expose the plant to more bacteria, thus increasing the risk of infection.
While most bacteria are motile and can swim, they cannot move very far due to their small size. However, they can be carried along by water, and a significant movement of Pectobacterium can be attributed to being carried downstream from irrigation and rainwater.[3] To control the spread of the disease, limiting irrigation is another strategy. The bacteria also flourishes in wet conditions, so limiting excess water can control both the spread and severity of the disease.
Increased in-row spacing also causes more severe disease. In an infected field, yield decreased linearly when spacing was greater than 15 cm (6 in),[15] so a spacing of 6 inches or less is recommended.
The bacteria can also utilize nitrogen fertilizer to accelerate their growth, thus limiting or eliminating the amount of nitrogen fertilizer applied will lessen the disease severity.[14] For example, when fertilizer was applied to an infected field the infection rate per root increased from 11% (with no added nitrogen) to 36% (with 336 kg nitrogen/hectare), and sugar yields decreased.[15]
Cultivar Resistance Source
H9 No [15]
H10 No
C17 No
546 H3 Moderate
C13 No [19]
E540 No
E538 No
E534 Moderate
E502 Moderate
E506 Yes
E536 Yes
C930-35 Moderate [20]
C927-4 Moderate
C930-19 Yes
C929-62 Yes
### Resistance[edit]
The bacteria can survive in the rhizosphere of other crops such as tomato, carrots, sweet potato, radish, and squash[1][4] as well as weed plants like lupin and pigweed,[11] so it is very hard to get rid of it completely.[3] When it is known that the bacterium is present in the soil, planting resistant varieties can be the best defense against the disease. Many available beet cultivars are resistant to Pectobacterium carotovorum subsp. betavasculorum, and some examples are provided in the corresponding table. A comprehensive list is maintained by the USDA on the Germplasm Resources Information Network.[21] Even though some genes associated with root defense response have been identified, the specific mechanism of resistance is unknown, and it is currently being researched.[22]
### Biological control[edit]
Some bacteriophages, viruses that infect bacteria, have been used as effective controls of bacterial diseases in laboratory experiments. This relatively new technology is a promising control method that is currently being researched. Bacteriophages are extremely host-specific, which makes them environmentally sound as they will not destroy other, beneficial soil microorganisms.[23] Some bacteriophages identified as effective controls of Pectobacterium carotovorum subsp. betavasculorum are the strains ΦEcc2 ΦEcc3 ΦEcc9 ΦEcc14. When mixed with a fertilizer and applied to inoculated calla lily bulbs in a greenhouse, they reduced diseased tissue by 40 to 70%.[24] ΦEcc3 appeared to be the most effective, reducing the percent of diseased plants from 30 to 5% in one trial, to 50 to 15% in a second trial.[24] They have also been used successfully to reduce rotting in lettuce caused by Pectobacterium carotovorum subsp. carotovorum, a different bacterial species closely related to the one that causes beet vascular necrosis.[25]
While it is more difficult to apply bacteriophages in a field setting, it is not impossible, and laboratory and greenhouse trials are showing bacteriophages to potentially be a very effective control mechanism. However, there are a few obstacles to surmount before field trials can begin.[26] A large problem is that they are damaged by UV light, so applying the phage mixture during the evening will help promote its viability. Also, providing the phages with susceptible non-pathogenic bacteria to replicate with can ensure there is adequate persistence until the bacteriophages can spread to the targeted bacteria.[27] The bacteriophages are unable to kill all the bacteria, because they need a dense population of bacteria in order to effectively infect and spread, so while the phages were able to decrease the number of diseased plants by up to 35%, around 2,000 Colony Forming Units per milliliter (an estimate of living bacteria cells) were able to survive the treatment.[24] Lastly, the use of these bacteriophages places strong selection on the host bacteria, which causes a high probability of developing resistance to the attacking bacteriophage. Thus it is recommended that multiple strains of the bacteriophage be used in each application so the bacteria do not have a chance to develop resistance to any one strain.[28]
## Importance[edit]
The disease was first identified in the western states of, California, Washington, Texas, Arizona and Idaho in the 1970s and initially led to substantial yield losses in those areas.[15] Erwinia caratovara subsp betavascularum was not discovered in Montana until 1998. When it first appeared, beet vascular necrosis caused individual farm yield loss ranging from 5–70% in Montana's Bighorn Valley.[7] Today, yield losses from the disease are generally infrequent and patchy as most producers plant resistant varieties. Infection rate is generally low if resistant cultivars are chosen; however, warmer and wetter conditions can lead to higher than normal instance of disease[7]
If infection does occur, bacterial root rots can not only cause economic losses in the field, but also can in storage and processing as well.[12] In processing plants, rotten roots complicate slicing and the bacterially-produced slime can clog filters. This is especially problematic with late-infected beets which are generally harvested and processed along with healthy beets. The disease can also lower sugar-content which greatly reduces the quality[8]
## References[edit]
1. ^ a b c d e f Whitney, E.D, ed. (1986). Compendium of Beet Diseases and Insects (2nd ed.). St. Paul, MN: American Phytopathological Society.
2. ^ Dye, DW (1969). "A taxonomic study of the genus Erwinia. II. The "carotovora" group". New Zealand Journal of Science. 12: 81–97.
3. ^ a b c Perombelon, Michel CM; Kelman, Arthur (1980). "Ecology of the soft rot erwinias". Annual Review of Phytopathology. 18 (1): 361–387. doi:10.1146/annurev.py.18.090180.002045.
4. ^ a b c d e f g h i j k l m n o p q r s t u v Haverson, R.M., ed. (2009). Compendium of Beet Diseases and Pests (2nd ed.). St. Paul, MN: American Phytopathological Society. pp. 58–59.
5. ^ a b c d e f g h Thomson, S.V.; et al. (1977). "Beet Vascular Necrosis and Rot of Sugarbeet: General Description and Etiology" (PDF). Phytopathology. 67 (10): 1183–1189. doi:10.1094/phyto-67-1183. Retrieved 17 October 2013.
6. ^ a b c d e f g h i j k l m "Sugar Beet Production Guide, Chapter 11: Disease Management, pg 138-139" (PDF). University of Nebraska – Lincoln Extension, 2013. Archived from the original (PDF) on 27 June 2010. Retrieved 17 October 2013.
7. ^ a b c d Zidack, Nina; Barry Jacobsen (2001). "First Report and Virulence Evaluation of Erwinia caratovora subs. Betavasculorum on Sugarbeet in Montana". Plant Health Progress. 2: 6. doi:10.1094/PHP-2001-0706-02-RS. Retrieved 18 October 2013.
8. ^ a b Whitney, E.D.; R.T. Lewellen (1977). "Bacterial Vascular Necrosis and Rot of Sugar Beet: Effects on Cultivars and Quality". Phytopathology. 67 (10): 912–916. doi:10.1094/phyto-67-912. S2CID 53705630.
9. ^ a b c Saleh, O.I.; Huang, P.-Y.; J.-S. Huang (1996). "Bacterial Vascular Necrosis and Root Rot Disease of Sugar Beet in Egypt". Journal of Phytopathology. 144 (5): 225–230–1189. doi:10.1111/j.1439-0434.1996.tb01520.x.
10. ^ De Boer, Solke H. (2004). "Blackleg of Potato". The Plant Health Instructor. Retrieved 17 October 2013.
11. ^ a b c d e de Mendonca, Margarida; M.E. Stanghellini (1979). "Endemic and Soilborne Nature of Erwinia Carotovora var. atroseptica, a pathogen of Mature Sugarbeets". Phytopathology. 69 (10): 1093–1099. doi:10.1094/phyto-69-1096.
12. ^ a b Strausbaugh, Carl A.; Anne M. Gillen (2008). "Bacterial and yeast associated with sugar beet root rot at harvest in the Intermountain West". Plant Disease. 92 (3): 357–363. doi:10.1094/pdis-92-3-0357. PMID 30769681.
13. ^ Kim, H.-S.; et al. (2011). "Pectobacterium carotovorum Elicits Plant Cell Death with DspE/F but the P. carotovorum DspE Does Not Suppress Callose or Induce Expression of Plant Genes Early in Plant–Microbe Interactions". Molecular Plant-Microbe Interactions. 24 (7): 773–786. doi:10.1094/mpmi-06-10-0143. PMID 21469936.
14. ^ a b c d e "Sugar Beet (Beta vulgaris)-Bacterial Vascular Necrosis and Rot {Erwinia Root Rot}". pacific northwest plant disease management handbook. Retrieved 17 October 2013.
15. ^ a b c d e f Thomson, S V; Hills, F. J.; Whitney, E. D.; Schroth, M. N. (1981). "Sugar and root yield of sugar beets as affected by bacterial vascular necrosis and rot, nitrogen fertilization, and plant spacing" (PDF). Phytopathology. 71 (6): 605–608. doi:10.1094/phyto-71-605. Retrieved 17 October 2013.
16. ^ Stanghellini, M.E.; et al. (1977). "Serological and Physiological Differences of Erwinia carotovora between Potato and Sugar Beet". Phytopathology. 67 (10): 1178–1182. doi:10.1094/phyto-67-1178. Retrieved 17 October 2013.[permanent dead link]
17. ^ Gallian, John J. "Management of Sugarbeet Root Rots" (PDF). Pacific Northwest Extension. Retrieved 17 October 2013.
18. ^ "UC Pest Management Guidelines". University of California Agriculture and Natural Resources. Retrieved 17 October 2013.
19. ^ Lewellen, R. T.; E. D. Whitney; C. K. Goulas (1978). "Inheritance of resistance to Erwinia root rot in sugarbeet" (PDF). Phytopathology. 68 (6): 947–950. doi:10.1094/phyto-68-947. Retrieved 17 October 2013.
20. ^ Lewellen, R. T. (2004). "Registration of sugarbeet germplasm lines C927-4, C929-62, C930-19, and C930-35 with resistance to rhizomania, virus yellows, and bolting". Crop Science. 44 (1): 359–361. doi:10.2135/cropsci2004.0359. Retrieved 17 October 2013.
21. ^ "Germplasm Resources Information Network". United States Department of Agriculture. Archived from the original on 23 September 2015. Retrieved 28 September 2013.
22. ^ Smigocki, A C. "Molecular Approaches To Pest And Pathogen Resistance in Sugar Beet". united states department of agriculture agricultural research service. Retrieved 17 October 2013.
23. ^ Duffy, B (2006). "Biological control of bacterial diseases in field crops". Symposium on Biological Control of Bacterial Plant Diseases: 93–98. Archived from the original on 5 July 2015. Retrieved 17 October 2013.
24. ^ a b c Ravensdale, M; T. Blom; J. A. Gracia-Garza; R. J. Smith; A. M. Svircev (2007). "Bacteriophages of and the control of Erwinia carotovora subsp. carotovora". Canadian Journal of Plant Pathology. 29 (2): 121–130. doi:10.1080/07060660709507448. S2CID 85123748.
25. ^ Lim, J.A.; Jee S; Lee DH; Roh E; Jung K; Oh C; Heu S. (2013). "Biocontrol of Pectobacterium carotovorum subsp. carotovorum using bacteriophage PP1". Journal of Microbiology and Biotechnology. 23 (8): 1147–1153. doi:10.4014/jmb.1304.04001. PMID 23727798. S2CID 30527360.
26. ^ Frampton, Rebekah A.; Andrew R. Pitman; Peter C. Fineran (2012). "Advances in Bacteriophage-Mediated Control of Plant Pathogens". International Journal of Microbiology. 2012: 1–11. doi:10.1155/2012/326452. PMC 3426239. PMID 22934116.
27. ^ Jones, Jeffrey B.; Gary E. Vallad; Fanny B. Iriarte; Aleksa Obradović; Mine H. Wernsing; Lee E. Jackson; Botond Balogh; Jason C. Hong; M. Timur Momol (2012). "Considerations for using bacteriophages for plant disease control". Bacteriophage. 2 (4): 208–214. doi:10.4161/bact.23857. PMC 3594208. PMID 23531902. Archived from the original on 24 December 2013. Retrieved 17 October 2013.
28. ^ Balogh, B; Jones, Jeffrey B.; Iriarte, F. B.; Momol, M. T. (2010). "Phage Therapy for Plant Disease Control". Current Pharmaceutical Biotechnology. 11 (1): 48–57. doi:10.2174/138920110790725302. PMID 20214607.
Taxon identifiers
* Wikidata: Q16975133
* GBIF: 3221958
* LPSN: pectobacterium.html#carotovorumbetavasculorum
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Beet vascular necrosis | None | 4,505 | wikipedia | https://en.wikipedia.org/wiki/Beet_vascular_necrosis | 2021-01-18T19:10:26 | {"wikidata": ["Q16975133"]} |
A number sign (#) is used with this entry because hypogonadotropic hypogonadism-11 with or without anosmia (HH11) can be caused by homozygous mutation in the TACR3 gene (162332) on chromosome 4q24.
Description
Congenital idiopathic hypogonadotropic hypogonadism (IHH) is a disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. Idiopathic hypogonadotropic hypogonadism can be caused by an isolated defect in gonadotropin-releasing hormone (GNRH; 152760) release, action, or both. Other associated nonreproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss, occur with variable frequency. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism has been called 'Kallmann syndrome (KS),' whereas in the presence of a normal sense of smell, it has been termed 'normosmic idiopathic hypogonadotropic hypogonadism (nIHH)' (summary by Raivio et al., 2007). Because families have been found to segregate both KS and nIHH, the disorder is here referred to as 'hypogonadotropic hypogonadism with or without anosmia (HH).'
For a discussion of genetic heterogeneity of hypogonadotropic hypogonadism with or without anosmia, see 147950.
Molecular Genetics
Topaloglu et al. (2009) performed genomewide SNP analysis in 9 unrelated consanguineous Turkish and Kurdish families with normosmic IHH and identified a region of homozygosity on chromosome 4q that segregated with disease in 1 Turkish and 2 Kurdish families. Analysis of the candidate gene TACR3 revealed homozygosity for 2 missense mutations (162332.0001 and 162332.0002). The mutations were found in heterozygosity in all unaffected parents, and were not found in 100 ethnically matched Turkish or Kurdish controls.
Gianetti et al. (2010) analyzed the TACR3 gene in 345 probands with normosmic IHH and identified 13 distinct variants in 19 of the probands (see, e.g., 162332.0003 and 162332.0004), most of whom were known to be negative for mutation in 7 or 8 other HH-associated genes. In some patients, a mutation was detected on only 1 allele of TACR3. Of 16 males carrying TACR3 variants for whom physical evidence was available, 15 (94%) had microphallus identified either neonatally or later in life. In addition, 10 (83%) of 12 patients who were assessed longitudinally after discontinuation of sex steroid therapy exhibited evidence of spontaneous partial or complete recovery of their reproductive axis, including increases in LH pulsatility, testosterone, testicular volume, presence of withdrawal bleeding, spontaneous menstrual cycles, and/or spontaneous pregnancy. Gianetti et al. (2010) noted that the high prevalence of reversal suggested that the role of the NKB system in GNRH (152760) secretion may be less critical in adult life than during late gestation and the early neonatal period.
INHERITANCE \- Autosomal recessive CHEST Breasts \- Delayed or absent thelarche GENITOURINARY External Genitalia (Male) \- Microphallus Internal Genitalia (Male) \- Small testes \- Cryptorchidism Internal Genitalia (Female) \- Primary amenorrhea ENDOCRINE FEATURES \- Patients have normal pituitary function \- Delayed or absent puberty \- Low testosterone levels in males \- Low estradiol levels in females \- Low or normal serum gonadotropins MISCELLANEOUS \- Neuroendocrine recovery occurs in some patients MOLECULAR BASIS \- Caused by mutation in the tachykinin receptor-3 gene (TAC3R, 162332.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| HYPOGONADOTROPIC HYPOGONADISM 11 WITH OR WITHOUT ANOSMIA | c0162809 | 4,506 | omim | https://www.omim.org/entry/614840 | 2019-09-22T15:54:05 | {"doid": ["0090071"], "mesh": ["D017436"], "omim": ["614840"], "orphanet": ["432", "478"], "synonyms": ["Gonadotropic deficiency", "Isolated congenital gonadotropin deficiency", "Normosmic idiopathic hypogonadotropic hypogonadism", "nIHH"], "genereviews": ["NBK1334"]} |
Hypomyelination with atrophy of basal ganglia and cerebellum (H-ABC) is a disease that affects certain parts of the brain. Symptoms usually begin in infancy or early childhood and worsen over time. Severity of symptoms and rate of progression can vary. Symptoms may include delayed motor development, learning difficulties, upper-motor neuron dysfunction (spasticity, exaggerated reflexes, and Babinski signs), dystonia, rigidity, involuntary movements, and speech and swallowing problems.
H-ABC is caused by a mutation in the TUBB4A gene. Inheritance is autosomal dominant, but most cases are due to a new mutation occurring for the first time in a person with the condition.
Treatment may involve taking medications to ease symptoms, physical therapy, and surgery when dystonia does not improve with medication.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Hypomyelination with atrophy of basal ganglia and cerebellum | c2676244 | 4,507 | gard | https://rarediseases.info.nih.gov/diseases/10917/hypomyelination-with-atrophy-of-basal-ganglia-and-cerebellum | 2021-01-18T17:59:53 | {"mesh": ["C567314"], "omim": ["612438"], "orphanet": ["139441"], "synonyms": ["HABC", "HLD6", "Leukodystrophy, hypomyelinating, 6", "H-ABC", "Leukodystrophy, hypomyelinating, with atrophy of the basal ganglia and cerebellum"]} |
Set of medical signs and symptoms experienced by U.S. and Canadian embassy staff, reported in Cuba and China.
Havana syndrome
The Hotel Nacional in Havana is one of the locations where the syndrome occurred.[1]
SymptomsHearing strange grating noises, headache, hearing loss, memory loss, and nausea
CausesLikely caused by directed microwaves[2]
Havana syndrome is a set of medical signs and symptoms experienced by United States and Canadian embassy staff in Cuba. Beginning in August 2017, reports surfaced that American and Canadian diplomatic personnel in Cuba had suffered a variety of health problems, dating back to late 2016.[3][4]
The U.S. government accused Cuba of perpetrating unspecified attacks causing these symptoms. The U.S. reduced staff at their embassy to a minimum in response.[5] In 2018, U.S. diplomats in China reported problems similar to those reported in Cuba, as well as undercover CIA agents operating in other countries who were negotiating with those countries on ways to counter Russian covert operations around the world.[6][7]
Subsequent studies of the affected diplomats in Cuba, published in the journal JAMA in 2018, found evidence that the diplomats experienced some form of brain injury, but did not determine the cause of the injuries.[8][9] A co-author of the JAMA study considered microwave weapons to be "a main suspect" for the phenomenon.[10]
In December 2020, a study by an expert committee of the U.S. National Academies of Sciences, Engineering, and Medicine, commissioned by the State Department, released its report, concluding that "directed" microwave radiation was the likely cause of illnesses among American diplomats in Cuba and China.[2][11]
## Contents
* 1 Cuba
* 1.1 Events
* 1.2 Impact on American diplomats
* 1.2.1 U.S. government investigations
* 1.3 Impact on Canadian diplomats
* 1.4 Cuban government reactions
* 1.5 Studies regarding injury
* 1.6 Theories regarding cause
* 1.6.1 Microwaves
* 1.6.2 Previously proposed causes
* 1.6.2.1 Ultrasounds
* 1.6.2.2 Psychogenic origin
* 1.6.2.3 Pesticides or infectious agents
* 2 Guangzhou, China
* 3 Theories regarding culprit
* 4 See also
* 5 References
## Cuba[edit]
Cuba
In August 2017, reports began surfacing that American and Canadian[12] diplomatic personnel in Cuba had experienced unusual, unexplained health problems dating back to late 2016.[13][14] The number of American citizens experiencing symptoms was 26 as of June 2018.[15]
### Events[edit]
The health problems typically had a sudden onset: the victim would suddenly begin hearing strange grating noises that they perceived as coming from a specific direction. Some of them experienced it as a pressure or a vibration; or as a sensation comparable to driving a car with the window partly rolled down. The duration of these noises ranged from 20 seconds to 30 minutes, and always happened while the diplomats were either at home or in hotel rooms. Other people nearby, family members and guests in neighboring rooms, did not report hearing anything.[16]
### Impact on American diplomats[edit]
Some U.S. embassy individuals have experienced lasting health effects, including one unidentified diplomat who is said to now need a hearing aid.[17] The State Department declared that the health problems were either the result of an attack, or due to exposure to an as-yet-unknown device,[18] and declared that they were not blaming the Cuban government, but would not say who was to blame.[19] Affected individuals described symptoms such as hearing loss, memory loss, and nausea.[18] Speculation centered around a sonic weapon,[20] with some researchers pointing to infrasound as a possible cause.[21]
In August 2017, the United States expelled two Cuban diplomats in response to the illnesses.[13] In September, the U.S. State Department stated that it was removing non-essential staff from the US embassy, and warned U.S. citizens not to travel to Cuba.[22] In October 2017, U.S. President Donald Trump said that "I do believe Cuba's responsible. I do believe that",[23] going on to say "And it's a very unusual attack, as you know. But I do believe Cuba is responsible."[5]
On March 2, 2018, the U.S. State Department announced it would continue to staff its embassy in Havana at the minimum level required to perform "core diplomatic and consular functions" due to concerns about health attacks on staff. The embassy had been operating under "ordered departure status" since September, but the status was set to expire. This announcement served to extend the staff reductions indefinitely.[24]
#### U.S. government investigations[edit]
In January 2018, the Associated Press reported that a non-public FBI report found no evidence of an intentional sonic attack.[25] A November 2018 report in the New Yorker found that the FBI's investigation into the incidents was stymied by conflict with the CIA and the State Department; the CIA was reluctant to reveal, even to other U.S. government agencies, the identities of affected officers, because of the CIA's concern about possible leaks. Federal rules on the privacy of employee medical records also hindered the investigation.[3]
In January 2018, at the direction of Secretary of State Rex Tillerson, the Department of State convened an Accountability Review Board,[26] which is "an internal State Department mechanism to review security incidents involving diplomatic personnel."[27] Retired United States Ambassador to Libya Peter Bodde was chosen to lead the board.[27]
### Impact on Canadian diplomats[edit]
In March 2018, MRI scans and other tests taken by a chief neurologist in Pittsburgh, on an unspecified number of Canadian diplomats showed evidence of brain damage that mirrored the injuries some of their American counterparts had faced. In spring of 2018, Global Affairs Canada ended family postings to Cuba and withdrew all staff with families. Several of the Canadians who were impacted in 2017 were reported to still be unable to resume their work due to the severity of their ailments. The fact that, as of February 2019[update], there was no knowledge of the cause of “Havana syndrome” had made it challenging for the RCMP to investigate.[28]
In 2019, the government of Canada announced that it was reducing its embassy staff in Havana after a 14th Canadian diplomat reported symptoms of Havana syndrome in late December 2018.[29] In February 2019, several Canadian diplomats sued the Canadian government, arguing that it failed to protect them or promptly address serious health concerns.[30][31] The government has sought to dismiss the suit, arguing in November 2019 that it was not negligent and did not breach its duties to its employees. In court filings, the government acknowledged that several of the 14 plaintiffs in the suit suffered from concussion-like symptoms, but said that no definitive cause or medical diagnosis had been ascertained.[32] In a November 2019 statement, Global Affairs Canada said, "We continue to investigate the potential causes of the unusual health symptoms."[32]
### Cuban government reactions[edit]
After the incident was made public, the Cuban Foreign Minister accused the U.S. of lying about the incident and denied Cuban involvement in the health problems experienced by diplomats or knowledge of their cause.[33][34]
The Cuban government offered to cooperate with the U.S. in an investigation of the incidents.[35] It employed about 2000 scientists and law enforcement officers who interviewed 300 neighbors of diplomats, examined two hotels, and also medically examined non-diplomats who could have been exposed. NBC reported that Cuban officials stated that they analyzed air and soil samples, and considered a range of toxic chemicals. They also examined the possibility that electromagnetic waves were to blame, and even looked into whether insects could be the culprit, but found nothing they could link to the claimed medical symptoms. The FBI and Cuban authorities met to discuss the situation; the Cubans stated that the U.S. neither agreed to share the diplomats' medical records with Cuban authorities nor allowed Cuban investigators access to U.S. diplomats' homes to conduct tests.[36]
### Studies regarding injury[edit]
At the request of the U.S. government, University of Pennsylvania researchers examined 21 affected diplomats, and the preliminary results were published in the Journal of the American Medical Association (JAMA) in March 2018. The report "found no evidence of white matter tract abnormalities" in affected diplomats, beyond what might be seen in a control group of the same age, and described "a new syndrome in the diplomats that resembles persistent concussion."[37][38] While some of those affected recovered swiftly, others had symptoms lasting for months. The study concluded that "the diplomats appear to have sustained injury to widespread brain networks."[37][38] Some experts criticized the study, arguing that there was "no proof that any kind of energy source affected the diplomats, or even that an attack took place."[37] Subsequent study findings by the University of Pennsylvania team, published in July 2019, found that compared to a healthy control group, the diplomats who had reported injury had experienced brain trauma; advanced MRI scans (specifically res-fMRI, multimodal MRI, and diffusion MRI) revealed "differences in whole brain white matter volume, regional gray and white matter volume, cerebellar microstructural integrity, and functional connectivity in the auditory and visuospatial subnetworks" but found no differences in executive functions.[8][9] The study concluded that the U.S. government personnel had been physically injured in a way consistent with the symptoms that they described, but expressed no conclusion on the cause or source of the injury.[8][9] The New York Times reported: "Outside experts were divided on the study's conclusions. Some saw important new evidence; others say it is merely a first step toward an explanation, and difficult to interpret given the small number of patients."[9]
### Theories regarding cause[edit]
#### Microwaves[edit]
In a 2018 interview, Douglas H. Smith, a co-author of the JAMA study, said that microwaves were "considered a main suspect" underlying the phenomenon.[10] A 2018 study published in the journal Neural Computation by Beatrice Alexandra Golomb rejected the idea that a sonic attack was the source of the symptoms, and concluded that the facts were consistent with pulsed radiofrequency/microwave radiation (RF/MW) exposure as the source of injury. Golomb wrote that (1) the nature of the noises reported by the diplomats was consistent with sounds caused by pulsed RF/MW via the Frey effect; (2) the signs and symptoms reported by the diplomats matched symptoms from RF/MW exposure (problems with sleep, cognition, vision, balance, speech; headaches; sensations of pressure or vibration; nosebleeds; brain injury and brain swelling); (3) "oxidative stress provides a documented mechanism of RF/MW injury compatible with reported signs and symptoms"; and (4) in the past, the U.S. embassy in Moscow was subject to a microwave attack.[39] Neuroscientist Allan H. Frey, for whom the Frey effect is named, considered the microwave theory to be viable.[10] Some other scientists, including physicist Peter Zimmerman and bioengineer Kenneth R. Foster, disagreed, considering the microwave hypothesis to be implausible.[40] A 2018 study published in the journal Neural Computation identified pulsed radiofrequency/microwave radiation (RF/MW) exposure via the Frey effect as source of injury, and noted that a microwave attack against the U.S. embassy in Moscow has been historically documented.[39]
In December 2020, a 19-person committee of medical and scientific experts convened by the National Academies of Sciences, Engineering, and Medicine at the request of the State Department published a Consensus Study Report, An Assessment of Illness in U.S. Government Employees and Their Families at Overseas Embassies, based on its review of the incidents and injuries.[11][41] The report concluded that "Overall, directed pulsed RF (radio frequency) energy, especially in those with the distinct early manifestations, appears to be the most plausible mechanism in explaining these cases among those that the committee considered."[41][11]
#### Previously proposed causes[edit]
Prior to 2019, some researchers posited other possible causes for the injuries, including ultrasound via intermodulation distortion caused by malfunctioning or improperly placed Cuban surveillance equipment;[42][43] cricket noises,[44][45] and exposure to neurotoxic pesticides.[46][47] Early speculation of an acoustic or sonic cause was later determined to be unfounded.[39] Some had suggested that the symptoms represented episodes of mass hysteria,[48] but the 2018 JAMA researchers considered a "wholly psychogenic or psychosomatic cause" to be very unlikely, given the physical evidence of brain trauma.[9] The 2020 National Academies report "considered chemical exposures, infectious diseases and psychological issues as potential causes or aggravating factors of the injuries" but determined that these were not the likely cause of the injuries.[41]
##### Ultrasounds[edit]
In March 2018, Kevin Fu and a team of computer scientists at the University of Michigan reported in a study that ultrasound—specifically, intermodulation distortion from multiple inaudible ultrasonic signals—from malfunctioning or improperly placed Cuban surveillance equipment could have been the origin of the reported sounds.[42][43][49]
In January 2019, biologists Alexander L. Stubbs of the University of California, Berkeley and Fernando Montealegre-Z of the University of Lincoln analyzed a recording of a sound made by U.S. personnel in Cuba and released to the Associated Press. Stubbs and Montealegre-Z concluded that the sound was caused by the calling song of the Indies short-tailed cricket (Anurogryllus celerinictus) rather than a technological device. Stubbs and Montealegre-Z matched the song's "pulse repetition rate, power spectrum, pulse rate stability, and oscillations per pulse" to the recording.[50][44] Stubbs and Montealegre wrote that "Although the causes of the health problems reported by embassy personnel are beyond the scope of this paper and called for "more rigorous research into the source of these ailments, including the potential psychogenic effects, as well as possible physiological explanations unrelated to sonic attacks."[44] This conclusion was comparable to a 2017 hypothesis from Cuban scientists that the sound on the same recording is from Jamaican field crickets.[50][51][45][52] Reuters reported that JASON, a group of physicists and scientists who advise the U.S. government, determined that "a rare jungle cricket" was the cause of the sounds in Havana.[53]
##### Psychogenic origin[edit]
In 2017, 2018, and 2019 sociologist Robert Bartholomew[54][55][56] and some neurologists wrote that the attacks represent episodes of mass psychogenic illness.[48][57][58][51] However, the co-lead author of the 2019 study published in JAMA, Ragini Verma of the University of Pennsylvania Perlman School of Medicine, considered a "wholly psychogenic or psychosomatic cause" to be very unlikely, given the researchers' findings,[9] and State Department medical director Dr. Charles Rosenfarb testified that the department had "all but ruled out 'mass hysteria" as a cause.[55][59][60]
##### Pesticides or infectious agents[edit]
A 2019 study commissioned by Global Affairs Canada of 23 exposed Canadian diplomats, completed in May 2019, found "clinical, imaging, and biochemical evidence consistent with the hypothesis" that over-exposure to cholinesterase inhibitors (a class of neurotoxic pesticide) such as pyrethroids and organophosphates (OPs) as a cause of brain injury; the embassies and other places in Cuba had been sprayed frequently as an anti-Zika virus mosquito control measure.[46][47][61] The study concluded that other possible causes could not be ruled out.[46]
The 2020 National Academies study found that that it was unlikely that "acute high-level exposure to OPs and/or pyrethroid contributed" to the illnesses, due to a lack of evidence of exposures to those pesticides or clinical histories consistent with such exposure; however, "the committee could not rule out the possibility, although slight, that exposure to insecticides, particularly OPs, increases susceptibility to the triggering factors that caused the Embassy personnel cases."[11] The 2020 National Academies study also found it "highly unlikely" that an infectious disease (such as Zika virus, which was an epidemic in Cuba in 2016-17) caused the illnesses.[11]
## Guangzhou, China[edit]
In early 2018, accusations similar to those reported by diplomats in Cuba began to be made by U.S. diplomats in China. The first incident reported by an American diplomat in China was in April 2018 at the Guangzhou consulate, the largest U.S. consulate in China. The employee reported that he had been experiencing symptoms since late 2017. Several individuals were taken to the United States for medical examination.[6][62][63] Another incident had previously been reported by a USAID employee at the U.S. Embassy in Tashkent, Uzbekistan, in September 2017; the employee's report was discounted by the U.S. State Department.[64]
Answering questions from the House Foreign Affairs Committee on May 23, 2018, Secretary of State Mike Pompeo confirmed that U.S. diplomatic staff in Guangzhou had reported symptoms "very similar" to, and "entirely consistent" with, those reported from Cuba.[65][66] On June 6, 2018, The New York Times reported that at least two additional U.S. diplomats stationed at the Guangzhou consulate had been evacuated from China, and reported that "it remains unclear whether the illnesses are the result of attacks at all. Other theories have included toxins, listening devices that accidentally emitted harmful sounds, or even mass hysteria."[62] In June 2018, the State Department announced that a task force had been assembled to investigate the reports[67] and expanded their health warning to all of mainland China amid reports some US diplomats outside of Guangzhou had experienced the same symptoms resembling a brain injury.[68] The warning told anyone who experienced "unusual acute auditory or sensory phenomena accompanied by unusual sounds or piercing noises" to "not attempt to locate their source."[69]
## Theories regarding culprit[edit]
Several U.S. State Department employees who consider themselves victims, and some senior CIA Russian analysts, as well as some outside scientists believe Russia is the most likely culprit. Russia has been accused by the U.S. State Department of using directed microwaves in the past. During the Cold War, the U.S. accused Russia of directing a microwave signal at the American embassy in Moscow, and a 2014 NSA report raised suspicions that Russia used an energy weapon to "bathe a target’s living quarters in microwaves", which caused nervous system damage. The purported targets in the 2016-2018 events include undercover CIA agents who were working on ways to counter Russian covert operations. Also, the U.S. diplomats stationed in China and Cuba who reported ailments were working to increase cooperation with those countries. Some CIA analysts suspect Russia was trying to disrupt all those activities.[7]
The New York Times reported in October 2020 that CIA director Gina Haspel and State Department leaders were unconvinced[clarification needed] that Russia is responsible or even whether an attack occurred. However, some believe there is a high-level and deliberate cover-up by the Trump-led State Department after a U.S. Office of Special Counsel investigation "found a substantial likelihood of wrongdoing" by State.[7]
## See also[edit]
* China–United States relations
* Cuba–United States relations
* Russia–United States relations
## References[edit]
1. ^ "Cuba Travel Advisory". Travel.state.gov. Department of State. January 10, 2018. Archived from the original on January 30, 2018. Retrieved June 22, 2018.
2. ^ a b "'Havana syndrome' likely caused by directed microwaves - US report". BBC News. December 6, 2020.
3. ^ a b Entous, Adam; Anderson, Jon Lee (November 19, 2018). "The Mystery of the Havana Syndrome: Unexplained brain injuries afflicted dozens of American diplomats and spies. What happened?". The New Yorker.
4. ^ Payne, Elizabeth (November 30, 2018). "Ottawa doctor treating Canadian diplomats with mysterious 'Havana syndrome'". Ottawa Citizen. "It is being called Havana syndrome and officials in Canada and the United States, where more than 20 diplomats have been affected, are trying to identify the cause of the injuries."
5. ^ a b "Trump says Cuba 'responsible' for alleged sonic attacks, but offers no evidence". The Guardian. October 16, 2017. Retrieved December 7, 2017.
6. ^ a b "China Pledges to Investigate Fears of Sonic Attacks on U.S. Diplomats". The New York Times. June 7, 2018.
7. ^ a b c Ana Swanson (October 19, 2020). "U.S. Diplomats and Spies Battle Trump Administration Over Suspected Attacks". The New York Times. Retrieved October 20, 2020.
8. ^ a b c Ragini Verma; Randel L. Swanson; Drew Parker; et al. (2019). "Neuroimaging Findings in US Government Personnel With Possible Exposure to Directional Phenomena in Havana, Cuba". JAMA. 322 (4): 336–347. doi:10.1001/jama.2019.9269. PMC 6652163. PMID 31334794.
9. ^ a b c d e f Benedict Carey (July 23, 2019). "Were U.S. Diplomats Attacked in Cuba? Brain Study Deepens Mystery". New York Times.
10. ^ a b c Broad, William J. (September 1, 2018). "Microwave Weapons Are Prime Suspect in Ills of U.S. Embassy Workers". New York Times. Retrieved September 2, 2018.
11. ^ a b c d e Consensus Study Report: An Assessment of Illness in U.S. Government Employees and Their Families at Overseas Embassies, Standing Committee to Advise the Department of State on Unexplained Health Effects on U.S. Government Employees and Their Families at Overseas Embassies, of the National Academies of Sciences, Engineering, and Medicine (2020).
12. ^ "Mystery of sonic weapon attacks at US embassy in Cuba deepens". The Guardian. September 14, 2017.
13. ^ a b Neuman, Scott (August 9, 2017). "Cuban Diplomats Expelled After US Embassy Staff 'Incidents' In Havana". NPR. Retrieved October 1, 2017.
14. ^ Connor, Tracy; Murray, Mary; Williams, Abigail (September 17, 2017). "Victim of Cuba embassy 'attacks' frustrated by response". NBC News. Retrieved October 1, 2017.
15. ^ "U.S. says another American suffers illness at its Cuba embassy". Reuters. June 28, 2018. Retrieved July 3, 2018.
16. ^ Hurley, Dan (March 22, 2018). "The Mystery Behind Neurological Symptoms Among US Diplomats in Cuba: Lots of Questions, Few Answers". Neurology Today. 18 (6): 1, 24–26. doi:10.1097/01.NT.0000532085.86007.9b.
17. ^ Zachary Cohen. "New audio adds to mystery of Cuba attacks". CNN. Retrieved October 14, 2017.
18. ^ a b Doubek, James. "At Least 16 U.S. Embassy Staff In Cuba Treated After 'Health Attacks'". NPR.
19. ^ U.S. does not believe Cuba is behind sonic attacks on American diplomats. McClatchy News Service, 26 September 2017
20. ^ Chavez, Nicole. "Using sound to attack: The diverse world of acoustic devices". CNN.
21. ^ Catherine McIntyre (August 24, 2017). "How Canadian diplomats in Cuba are being acoustically attacked". Maclean's.
22. ^ Rich Edson (September 29, 2017). "US stops issuing visas in Cuba, cuts embassy staff, urges no travel to island". Fox News. Retrieved October 1, 2017.
23. ^ Zachary Cohen. "Trump blames Cuba for mysterious attacks on US diplomats". CNN. Retrieved December 7, 2017.
24. ^ Koran, Laura; Oppmann, Patrick (March 2, 2018). "US Embassy in Cuba to reduce staff indefinitely after 'health attacks'". CNN. Retrieved April 22, 2018.
25. ^ Josh Lederman & Matthew Lee, Tillerson tells AP Cuba still risky; FBI doubts sonic attack, Associated Press (January 8, 2018).
26. ^ "Tillerson to order new probe of Havana embassy health "attacks"". Reuters. January 9, 2018. Archived from the original on April 7, 2018. Retrieved April 7, 2018.
27. ^ a b "Retired ambassador to Libya to lead Cuba attacks review". CNN. Retrieved January 10, 2018.
28. ^ "Blood and bureaucracy: Inside Canada's panicked response to 'Havana syndrome'". Retrieved February 7, 2019.
29. ^ "‘Havana Syndrome’ forces Canada to halve its diplomatic presence in Cuba". Radio Canada International, January 30, 2019.
30. ^ "Ailing Canadian diplomats who served in Cuba have 'visible and real' health impacts, Trudeau". The Star. Retrieved February 7, 2019.
31. ^ Dan Bilefsky, Canadian Diplomats Sue Their Government Over Mysterious Cuban Disease, New York Times (February 7, 2019).
32. ^ a b Brian Platt, In court filing, Canadian government argues diplomats exaggerated 'Havana Syndrome' claims behind $28M lawsuit, National Post (November 26, 2019).
33. ^ "Cuba official accuses US of lying about sonic attacks". Associated Press. November 3, 2017. Retrieved December 7, 2017.
34. ^ Gaouette, Nicole (November 2, 2017). "Cuban Minister rejects US sonic attack claims". CNN. Retrieved January 7, 2018.
35. ^ "Statement by the Ministry of Foreign Affairs of Cuba". Minrex.gob.cu. Minrex. August 9, 2017. Archived from the original on April 7, 2018. Retrieved April 7, 2018.
36. ^ Mitchell, Andrea; Murray, Mary (October 24, 2017). "Cubans Forcefully Reject Blame for U.S. Diplomats' Mystery Ailments". NBC News.
37. ^ a b c Sample, Ian (February 24, 2018). "Fresh row over mysterious sickness affecting US diplomats in Cuba". The Guardian.
38. ^ a b Randel L. Swanson II; Stephen Hampton; Judith Green-McKenzie; et al. (2018). "Neurological Manifestations Among US Government Personnel Reporting Directional Audible and Sensory Phenomena in Havana, Cuba". JAMA. 319 (11): 1125–1133. doi:10.1001/jama.2018.1742. PMC 5885885. PMID 29450484.
39. ^ a b c Golomb, Beatrice Alexandra (November 2018). "Diplomats' Mystery Illness and Pulsed Radiofrequency/Microwave Radiation". Neural Computation. 30 (11): 2882–2985. doi:10.1162/neco_a_01133. ISSN 0899-7667. PMID 30183509. S2CID 52162053.
40. ^ Kaplan, Sarah; Achenbach, Joel (September 6, 2018). "Scientists and doctors zap theory that microwave weapon injured Cuba diplomats". Washington Post.
41. ^ a b c Jamie Crawford, 'Sonic attacks' suffered by US diplomats likely caused by microwave energy, government study says, CNN (December 5, 2020).
42. ^ a b "On Cuba, Diplomats, Ultrasound, and Intermodulation Distortion" (PDF). University of Michigan Tech Report CSE-TR-001-18. March 1, 2018.
43. ^ a b Torres, Nora Gámez (March 2, 2018). "Computer scientists may have solved the mystery behind the 'sonic attacks' in Cuba". Miami Herald. Archived from the original on April 22, 2018. Retrieved April 22, 2018.
44. ^ a b c Alexander L. Stubbs & Fernando Montealegre-Z (2019). "Recording of "sonic attacks" on U.S. diplomats in Cuba spectrally matches the echoing call of a Caribbean cricket". doi:10.1101/510834. S2CID 92213135 – via bioRxiv. Cite journal requires `|journal=` (help)
45. ^ a b Stone, Richard (December 8, 2017). "Cuban panel claims stress caused mystery illnesses". Science. AAAS. 358 (6368): 1236–1237. Bibcode:2017Sci...358.1236S. doi:10.1126/science.358.6368.1236. PMID 29217550.
46. ^ a b c Alon Friedman; Cindy Calkin; Chris Bowen (May 24, 2019). Havana Syndrome: Neuroanatomical and Neurofunctional Assessment in Acquired Brain Injury Due to Unknown Etiology (Report). Retrieved September 20, 2019 – via Scribd.
47. ^ a b Luc Chartrand, Martin Movilla and Lisa Ellenwood (September 19, 2019). "Havana syndrome: Exposure to neurotoxin may have been cause, study suggests". Retrieved September 20, 2019.
48. ^ a b Borger, Julian; Jaekl, Philip (October 12, 2017). "Mass hysteria may explain 'sonic attacks' in Cuba, say top neurologists". The Guardian. Retrieved February 27, 2018.
49. ^ McKay, Tom (March 3, 2018). "Study: Malfunctioning Surveillance Gear, Not Sonic Weapons, Could Explain Cuba Embassy 'Attack'". Gizmodo.com. Gizmodo. Archived from the original on April 22, 2018. Retrieved April 22, 2018.
50. ^ a b Zimmer, Carl (January 4, 2019). "The Sounds That Haunted U.S. Diplomats in Cuba? Lovelorn Crickets, Scientists Say". New York Times.
51. ^ a b Stone, Richard (February 15, 2018). "U.S. diplomats in Cuba have unusual brain syndrome, but there's no proof they were attacked, study says". Science. AAAS. doi:10.1126/science.aat3410.
52. ^ Stone, Richard (June 20, 2018). "Sonic attack or mass paranoia? New evidence stokes debate over diplomats' mysterious illness". Science. AAAS. doi:10.1126/science.aau5386 (inactive January 14, 2021). Retrieved July 24, 2019.CS1 maint: DOI inactive as of January 2021 (link)
53. ^ Levinson, Charles (July 30, 2019). "Special Report: Inside a Trump-era purge of military scientists at a legendary think tank". Reuters.
54. ^ Bures, Frank (February 1, 2018). "Cuba's Sonic Attacks Show Us Just How Susceptible Our Brains Are to Mass Hysteria". Slate. Retrieved April 1, 2018.
55. ^ a b Bartholomew, Robert E. (January 10, 2018). "'Sonic Attack' Not Mass Hysteria, Says Top Doc – He's Wrong!". Psychology Today. Archived from the original on April 7, 2018. Retrieved April 7, 2018.
56. ^ Palmer, Robert (February 5, 2019). "Were The 'Sonic Attacks' On American Diplomats Just Sci-Fi?". Skepticalinquirer.org. CFI. Archived from the original on December 8, 2019. Retrieved December 8, 2019. "Any talk of a sonic attack is science fiction … . I have no doubt that the Trump Administration, which has consistently claimed that an attack took place (including Trump himself), now realize that they have made a mistake, but they do not want to admit it … . As for the Senate Foreign Relations Committee hearings chaired by Senator Marco Rubio, it was a sham."
57. ^ Hignett, Katherine. "Mass Hysteria or Microwave Weapon – What's Behind the 'Sonic Attacks' on U.S. Diplomats in Cuba?". Newsweek. Retrieved February 27, 2018.
58. ^ Da Silva, Chantal. "As U.S. Accuses Cuba of Sonic Attacks, Canada Keeps Diplomats in Country Despite Mystery Illnesses". Newsweek. Retrieved February 26, 2018.
59. ^ Bartholomew, Robert E. (January 16, 2018). "Sonic Attack Claims Are Unjustified: Just Follow the Facts". CSI. Archived from the original on April 7, 2018. Retrieved April 7, 2018.
60. ^ Bartholomew, Robert E. "The "Sonic Attack" On U.S. Diplomats in Cuba: Why the State Department's Claims Don't Add Up". Skeptic Magazine. Archived from the original on October 25, 2017. Retrieved April 7, 2018.
61. ^ Frank, Marc (September 19, 2019). "Neurotoxin may have caused diplomats' illness in Cuba: study". Reuters. Retrieved September 19, 2019.
62. ^ a b Steven Lee Myers & Jane Perlez (June 6, 2018). "U.S. Diplomats Evacuated in China as Medical Mystery Grows". The New York Times.
63. ^ "US diplomats evacuated from China amid 'sonic attack' concerns". CNET. June 6, 2018.
64. ^ Dorsey, Steve (November 28, 2017). "Uzbekistan incident raises suspicions of Russian involvement in Cuba attacks". CBS News. Retrieved June 8, 2018.
65. ^ Gardiner Harris, Pompeo Says Mysterious Sickness Among Diplomats in Cuba Has Spread to China, New York Times (May 23, 2018).
66. ^ Steven Jiang, Ben Westcott and Maegan Vazquez (March 23, 2018). "Pompeo says China incident 'entirely consistent' with Cuba 'sonic attacks'". CNN.
67. ^ Kuo, Lily (June 7, 2018). "'Sonic attack' fears as more US diplomats fall ill in China". the Guardian.
68. ^ "U.S. expands China health alert amid illness reports". Reuters. June 7, 2018.
69. ^ Achenbach, Joel (June 8, 2018). "Controversy surrounds research on State Department employees sickened in 'attacks'". The Washington Post. Retrieved June 10, 2018.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Havana syndrome | None | 4,508 | wikipedia | https://en.wikipedia.org/wiki/Havana_syndrome | 2021-01-18T18:45:21 | {"wikidata": ["Q42915945"]} |
A number sign (#) is used with this entry because of evidence that short QT syndrome-1 (SQT1) is caused by heterozygous mutation in the KCNH2 gene (152427) on chromosome 7q36.
Description
Short QT syndrome is a cardiac channelopathy associated with a predisposition to atrial fibrillation and sudden cardiac death. Patients have a structurally normal heart, but electrocardiography (ECG) exhibits abbreviated QTc (Bazett's corrected QT) intervals of less than 360 ms (summary by Moreno et al., 2015).
### Genetic Heterogeneity of Short QT Syndrome
Short QT syndrome-2 (SQT2; 609621) is caused by mutation in the KCNQ1 gene (607542). SQT3 (609622) is caused by mutation in the KCNJ2 gene (600681).
Clinical Features
Gussak et al. (2000) reported a brother, sister, and their mother who had idiopathic persistently short QT interval, which was associated in the 17-year-old sister with several episodes of paroxysmal atrial fibrillation requiring cardioversion. All 3 patients had QT intervals of less than 80% of predicted value (280 ms, 272 ms, and 260 ms in the sister, brother, and mother, respectively). Similar ECG changes (QT interval, 260 ms) in an unrelated 37-year-old female were associated with sudden cardiac death. Hong et al. (2005) reported that in the family originally studied by Gussak et al. (2000) the deceased maternal grandfather also had short QT interval and chronic atrial fibrillation. Programmed electrical stimulation in the mother and 2 sibs revealed a remarkably short atrial and ventricular refractory period and inducibility of atrial and ventricular fibrillation. All 3 affected members of the family received implantable cardioverter defibrillators, and treatment with propafenone maintained them free of atrial fibrillation.
Gaita et al. (2003) described 2 unrelated 5-generation pedigrees with a strong family history of sudden death and an idiopathic persistently and uniformly short QT interval on ECG in the absence of structural heart disease in affected individuals. Symptoms included syncope, palpitations, and cardiac arrest. Sudden death occurred in both males and females over 4 generations with father-to-son transmission in both families, suggesting an autosomal dominant mode of inheritance. Six patients underwent extensive evaluation; all exhibited a QT interval of less than 280 ms on baseline ECG and had short atrial and ventricular refractory periods; increased ventricular vulnerability to fibrillation was demonstrated in 3 of 4 patients.
Molecular Genetics
Using a candidate gene approach in 2 families with short QT syndrome, previously reported by Gaita et al. (2003), Brugada et al. (2004) directly sequenced multiple genes encoding ion channels contributing to repolarization of the ventricular action potential and identified 2 different missense mutations (152427.0017 and 152427.0018, respectively) in the KCNH2 gene, leading to the same asn588-to-lys (N588K) substitution. The mutation was present in all affected family members and in none of the unaffected individuals. The occurrence of sudden cardiac death in the first 12 months of life in 2 patients suggested the possibility of a link between KCNH2 gain-of-function mutations and sudden infant death syndrome (272120).
In a family with short QT syndrome, originally reported by Gussak et al. (2000), Hong et al. (2005) identified an N588K mutation (152427.0017) in the KCNH2 gene. They concluded that codon 588 is a hotspot for this familial form of short QT syndrome. Hong et al. (2005) noted that the disease is clinically heterogeneous, with symptoms varying from atrial to ventricular fibrillation and sudden death in the 3 families with the same mutation.
Schimpf et al. (2005) reviewed the clinical, electrophysiologic, and molecular features of 15 reported cases (Gussak et al., 2000, Gaita et al., 2003, Brugada et al., 2004, Bellocq et al., 2004, and Priori et al., 2005) and 2 unpublished cases of short QT syndrome type 1, 2, and 3.
From a cohort of 2,008 healthy individuals, Gouas et al. (2005) analyzed a group of 200 individuals with the shortest QTc intervals and a group of 198 with the longest QTc intervals, comparing the allele, genotype, and haplotype frequencies of polymorphisms in cardiac ion channel genes (10 SNPs in KCNQ1, 2 in KCNE1 (176261), 4 in SCN5A (600163), and 1 in KCNH2) between the 2 groups. Based on observed differences, Gouas et al. (2005) suggested that genetic determinants located in these genes influence QTc length in healthy individuals and may represent risk factors for arrhythmias or cardiac sudden death in patients with cardiovascular 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
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| SHORT QT SYNDROME 1 | c1865020 | 4,509 | omim | https://www.omim.org/entry/609620 | 2019-09-22T16:05:47 | {"doid": ["0050793"], "mesh": ["C566506"], "omim": ["609620"], "orphanet": ["51083"], "synonyms": ["SQTS"]} |
A rare primary bone dysplasia characterized by Perthes-like pelvic anomalies (premature closure of the capital femoral epiphyses and widened femoral necks with flattened femoral heads), arthralgias of hips and knees, and occurrence of enchondromata and ecchondromata. There have been no further descriptions in the literature since 1971.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Upington disease | c1860596 | 4,510 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3408 | 2021-01-23T17:40:26 | {"gard": ["5421"], "mesh": ["C536472"], "omim": ["191520"], "umls": ["C1860596"], "icd-10": ["M91.8"], "synonyms": ["Hip dysplasia-enchondromata-ecchondroma syndrome"]} |
A number sign (#) is used with this entry because of evidence that methylmalonyl-CoA epimerase deficiency is caused by homozygous mutation in the MCEE gene (608419) on chromosome 2p13.
Clinical Features
Methylmalonic aciduria III, previously thought to be distinct from the other forms and to be due to deficiency of methylmalonyl CoA racemase, is shown not to be distinct by complementation studies. Montgomery et al. (1983) concluded that deficiency of MM-CoA racemase need not result in symptomatic methylmalonic aciduria.
Bikker et al. (2006) presented a 16-year-old female patient with persisting moderate methylmalonic aciduria. She was born to consanguineous Caucasian parents originating from the northwest part of the Netherlands. At the age of 2 years, retarded motor development and signs of spasticity were seen. Selective screening for metabolic disease revealed moderate methylmalonic aciduria. Methylmalonic acid in cerebrospinal fluid was moderately increased. Treatment involved reduction of dietary protein, which resulted in significant lowering of urinary methylmalonic acid; however, no clinical effects were observed and the patient's motor function showed a gradual deterioration leading to dystonia. Analysis of pterins and aromatic neurotransmitter metabolites in cerebrospinal fluid at the age of 14 years suggested a defect in sepiapterin reductase (182125), which was subsequently confirmed (Abeling et al., 2006). Abeling et al. (2006) pointed out a rapid and favorable response on treatment with L-DOPA.
Dobson et al. (2006) reported a 12-year-old Caucasian female with methylmalonyl-CoA epimerase deficiency who had been assigned to the cblA complementation group (251100) on the basis of weak recovery of [(14)C]-propionate incorporation in complementation studies with members of the cblA group. She had failure to thrive and severe gastroesophageal reflux in infancy. At 13.5 months she presented with severe metabolic acidosis, dehydration, and tachypnea, requiring admission to intensive care following a 2-day history of intermittent vomiting and diarrhea. Urine organic acids indicated severe ketonuria and elevated methylmalonic and methylcitric acid, diagnostic of methylmalonic aciduria. Dobson et al. (2006) found that an older sister of the proband was also affected. Other than hydrocephalus diagnosed in the first year of life, she had been completely asymptomatic in terms of methylmalonic aciduria. She successfully self-regulated protein intake. Her growth and development were normal except for macrocephaly due to hydrocephalus.
Molecular Genetics
In a patient with methylmalonic aciduria and retarded development with spasticity, Bikker et al. (2006) found a homozygous mutation in the methylmalonyl-CoA epimerase gene (608419.0001). A mutation in the gene encoding sepiapterin reductase (SPR) was also found (182125.0005); deficiency of this enzyme was shown to result in dystonia as a prominent symptom by Bonafe et al. (2001). The deficiency of methylmalonyl-CoA epimerase in the patient fully explained the in vitro biochemical findings that comprised a decreased propionate incorporation into macromolecules in cultured fibroblasts and a fully normal activity of methylmalonyl-CoA mutase in the same cells. As the patient of Bikker et al. (2006) did not seem to be more severely affected than the patient of Bonafe et al. (2001), Bikker et al. (2006) suggested that isolated methylmalonyl-CoA epimerase deficiency may not have a large clinical impact, or could even be considered a nondisease.
History
Kang et al. (1972) described a single infant with methylmalonic aciduria due to deficiency of methylmalonyl-CoA racemase. Bikker et al. (2006) stated that this was later shown to be a case of mutase deficiency (251000).
INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive ABDOMEN Gastrointestinal \- Gastroesophageal reflux METABOLIC FEATURES \- Metabolic acidosis \- Dehydration \- Self-regulated protein restriction LABORATORY ABNORMALITIES \- Methylmalonic aciduria, mild \- Normal plasma total homocysteine \- Elevated plasma propionylcarnitine \- Ketonuria \- Normal B12 MISCELLANEOUS \- Symptoms vary from asymptomatic patients to patients with metabolic acidosis MOLECULAR BASIS \- Caused by mutation in the methylmalonyl-CoA epimerase gene (MCEE, 608419.0001}) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| METHYLMALONYL-CoA EPIMERASE DEFICIENCY | c1855100 | 4,511 | omim | https://www.omim.org/entry/251120 | 2019-09-22T16:25:13 | {"mesh": ["C565386"], "omim": ["251120"], "orphanet": ["308425"], "synonyms": ["Alternative titles", "METHYLMALONYL-CoA RACEMASE DEFICIENCY", "METHYLMALONIC ACIDURIA III, FORMERLY"], "genereviews": ["NBK1231"]} |
Benzodiazepine dependence
Other namesBenzodiazepine addiction
SpecialtyAddiction Medicine
Benzodiazepine dependence is when one has developed one or more of either tolerance, withdrawal symptoms, drug seeking behaviors, such as continued use despite harmful effects, and maladaptive pattern of substance use, according to the DSM-IV. In the case of benzodiazepine dependence, however, the continued use seems to be associated with the avoidance of unpleasant withdrawal reaction rather than from the pleasurable effects of the drug.[1] Benzodiazepine dependence develops with long-term use, even at low therapeutic doses,[2] without the described dependence behavior.[3][4]
Addiction consists of people misusing or craving the drug not to relieve withdrawal symptoms, but to experience its euphoric or intoxicating effects. It is necessary to distinguish between addiction to and abuse of benzodiazepines and physical dependence on them. The increased GABA inhibition on the neural systems caused by benzodiazepines is counteracted by the body's development of tolerance to the drug's effects; the development of tolerance occurs as a result of neuroadaptations, which result in decreased GABA activity and increased excitability of the glutamate system; these adaptations occur as a result of the body trying to overcome the central nervous system depressant effects of the drug to restore homeostasis. When benzodiazepines are stopped, these neuroadaptations are "unmasked" leading to hyper-excitability of the nervous system and the appearance of withdrawal symptoms.[5]
Therapeutic dose dependence is the largest category of people dependent on benzodiazepines. These individuals typically do not escalate their doses to high levels or abuse their medication. Smaller groups include patients escalating their dosage to higher levels and drug misusers as well. It is unclear exactly how many people illicitly abuse benzodiazepines. Tolerance develops within days or weeks to the anticonvulsant, hypnotic, muscle relaxant and after 4 months there is little evidence that benzodiazepines retain their anxiolytic properties.[6] Some authors, however, disagree and feel that benzodiazepines retain their anxiolytic properties.[7] Long-term benzodiazepine treatment may remain necessary in certain clinical conditions.[8]
Numbers of benzodiazepine prescriptions have been declining, due primarily to concerns of dependence. In the short term, benzodiazepines can be effective drugs for acute anxiety or insomnia. With longer-term use, other therapies, both pharmacological and psychotherapeutic, become more effective. This is in part due to the greater effectiveness over time of other forms of therapy, and also due to the eventual development of pharmacological benzodiazepine tolerance.[9][10]
Benzodiazepines
The core structure of benzodiazepines. "R" labels denote common locations of side chains, which give different benzodiazepines their unique properties.
* Pronunciation: /ˌbɛnzoʊdaɪˈæzəpiːn/
* Benzodiazepine
* List of benzodiazepines
* Benzodiazepine overdose
* Benzodiazepine dependence
* Benzodiazepine misuse
* Benzodiazepine withdrawal syndrome
* Effects of long-term benzodiazepine use
* v
* t
* e
## Contents
* 1 Signs and symptoms
* 1.1 Elderly
* 2 Cause
* 2.1 Risk factors
* 3 Mechanism
* 3.1 Tolerance and physical dependence
* 3.2 Cross tolerance
* 3.3 Physiology of withdrawal
* 3.4 Withdrawal
* 4 Diagnosis
* 4.1 Definition
* 5 Prevention
* 5.1 The Committee on the Review of Medicines (UK)
* 6 Treatment
* 6.1 Cognitive behavioral therapy
* 6.2 Letter to patients
* 6.3 Flumazenil
* 7 Epidemiology
* 8 History
* 9 Society and culture
* 9.1 Misuse and addiction
* 10 See also
* 11 References
* 12 External links
## Signs and symptoms[edit]
See also: Benzodiazepine withdrawal syndrome § Signs and symptoms
The signs and symptoms of benzodiazepine dependence include feeling unable to cope without the drug, unsuccessful attempts to cut down or stop benzodiazepine use, tolerance to the effects of benzodiazepines, and withdrawal symptoms when not taking the drug. Some withdrawal symptoms that may appear include anxiety, depressed mood, depersonalisation, derealisation, sleep disturbance, hypersensitivity to touch and pain, tremor, shakiness, muscular aches, pains, twitches, and headache.[11] Benzodiazepine dependence and withdrawal have been associated with suicide and self-harming behaviors, especially in young people. The Department of Health substance misuse guidelines recommend monitoring for mood disorder in those dependent on or withdrawing from benzodiazepines.[12]
Benzodiazepine dependence is a frequent complication for those prescribed for or using for longer than four weeks, with physical dependence and withdrawal symptoms being the most common problem, but also occasionally drug-seeking behavior. Withdrawal symptoms include anxiety, perceptual disturbances, distortion of all the senses, dysphoria, and, in rare cases, psychosis and epileptic seizures.[13]
### Elderly[edit]
See also: Benzodiazepine withdrawal syndrome § Elderly
Long-term use and benzodiazepine dependence is a serious problem in the elderly. Failure to treat benzodiazepine dependence in the elderly can cause serious medical complications.[14] The elderly have less cognitive reserve and are more sensitive to the short (e.g., in between dose withdrawal) and protracted withdrawal effects of benzodiazepines, as well as the side-effects both from short-term and long-term use. This can lead to excessive contact with their doctor. Research has found that withdrawing elderly people from benzodiazepines leads to a significant reduction in doctor visits per year, it is presumed, due to an elimination of drug side-effects and withdrawal effects.[10]
Tobacco and alcohol are the most common substances that elderly people get a dependence on or misuse. The next-most-common substance that elderly people develop a drug dependence to or misuse is benzodiazepines. Drug-induced cognitive problems can have serious consequences for elderly people and can lead to confusional states and "pseudo-dementia". About 10% of elderly patients referred to memory clinics actually have a drug-induced cause that most often is benzodiazepines. Benzodiazepines have also been linked to an increased risk of road traffic accidents and falls in the elderly. The long-term effects of benzodiazepines are still not fully understood in the elderly or any age group. Long-term benzodiazepine use is associated with attentional and visuospatial functional impairments. Withdrawal from benzodiazepines can lead to improved alertness and decreased forgetfulness in the elderly. Withdrawal led to statistical significant improvements in memory function and performance related skills in those having withdrawn successfully from benzodiazepines, whereas those having remained on benzodiazepines experienced worsening symptoms. People having withdrawn from benzodiazepines also felt their sleep was more refreshing, making statements such as "I feel sharper when I wake up" or "I feel better, more awake", or "It used to take me an hour to fully wake up." This suggests that benzodiazepines may actually make insomnia worse in the elderly.[15]
## Cause[edit]
Tolerance occurs to the muscle-relaxant, anticonvulsant, and sleep-inducing effects of benzodiazepines, and upon cessation a benzodiazepine withdrawal syndrome occurs. This can lead to benzodiazepines being taken for longer than originally intended, as people continue to take the drugs over a long period of time to suppress withdrawal symptoms. Some people abuse benzodiazepines at very high doses and devote a lot of time to doing so, satisfying the diagnostic criteria in DSM IV for substance abuse and dependence. Another group of people include those on low to moderate therapeutic doses of benzodiazepines who do not abuse their benzodiazepines but develop a tolerance and benzodiazepine dependence.[5] A considerable number of individuals using benzodiazepines for insomnia escalate their dosage, sometimes above therapeutically-prescribed dose levels. Tolerance to the anxiolytic effect of benzodiazepines has been clearly demonstrated in rats. In humans, there is little evidence that benzodiazepines retain their anti-anxiety effects beyond four months of continuous treatment; there is evidence that suggests that long-term use of benzodiazepines may actually worsen anxiety, which in turn may lead to dosage escalation, with one study finding 25% of patients escalated their dosage. Some authors, however, consider benzodiazepines to be effective long-term; however, it is more likely that the drugs are acting to prevent rebound anxiety withdrawal effects which can be mistaken as continued drug efficacy. Tolerance to the anticonvulsant and muscle-relaxing effects of benzodiazepines occurs within a few weeks in most patients.[7][16]
### Risk factors[edit]
The risk factors for benzodiazepine dependence are long-term use beyond four weeks, use of high doses, use of potent short-acting benzodiazepines, dependent personalities, and proclivity for drug abuse.[13] Use of short-acting benzodiazepines leads to repeated withdrawal effects that are alleviated by the next dose, which reinforce in the individual the dependence.[11] A physical dependence develops more quickly with higher potency benzodiazepines such as alprazolam (Xanax) than with lower potency benzodiazepines such as chlordiazepoxide (Librium).[10]
Symptom severity is worse with the use of high doses, or with benzodiazepines of high potency or short half-life. Other cross-tolerant sedative hypnotics, such as barbiturates or alcohol, increase the risk of benzodiazepine dependence.[17] Similar to opioids' use for pain, therapeutic use of benzodiazepines rarely leads to substance abuse.[18]
## Mechanism[edit]
### Tolerance and physical dependence[edit]
See also: Kindling (sedative–hypnotic withdrawal)
Tolerance develops rapidly to the sleep-inducing effects of benzodiazepines. The anticonvulsant and muscle-relaxant effects last for a few weeks before tolerance develops in most individuals. Tolerance results in a desensitization of GABA receptors and an increased sensitization of the excitatory neurotransmitter system, such as NMDA glutamate receptors. These changes occur as a result of the body trying to overcome the drug's effects. Other changes that occur are the reduction of the number of GABA receptors (downregulation) as well as possibly long-term changes in gene transcription coding of brain cells. The differing speed at which tolerance occurs to the therapeutic effects of benzodiazepines can be explained by the speed of changes in the range of neurotransmitter systems and subsystems that are altered by chronic benzodiazepine use. The various neurotransmitter systems and subsystems may reverse tolerance at different speeds, thus explaining the prolonged nature of some withdrawal symptoms. As a result of a physical dependence that develops due to tolerance, a characteristic benzodiazepine withdrawal syndrome often occurs after removal of the drug or a reduction in dosage.[19] Changes in the expression of neuropeptides such as corticotropin-releasing hormone and neuropeptide Y may play a role in benzodiazepine dependence.[20] Individuals taking daily benzodiazepine drugs have a reduced sensitivity to further additional doses of benzodiazepines.[21] Tolerance to benzodiazepines can be demonstrated by injecting diazepam into long-term users. In normal subjects, increases in growth hormone occurs, whereas, in benzodiazepine-tolerant individuals, this effect is blunted.[22]
Animal studies have shown that repeated withdrawal from benzodiazepines leads to increasingly severe withdrawal symptoms, including an increased risk of seizures; this phenomenon is known as kindling. Kindling phenomena are well established for repeated ethanol (alcohol) withdrawal; alcohol has a very similar mechanism of tolerance and withdrawal to benzodiazepines, involving the GABAA, NMDA, and AMPA receptors.[5]
The shift of benzodiazepine receptors to an inverse agonist state after chronic treatment leads the brain to be more sensitive to excitatory drugs or stimuli. Excessive glutamate activity can result in excitotoxicity, which may result in neurodegeneration. The glutamate receptor subtype NMDA is well known for its role in causing excito-neurotoxicity. The glutamate receptor subtype AMPA is believed to play an important role in neuronal kindling as well as excitotoxicity during withdrawal from alcohol as well as benzodiazepines. It is highly possible that NMDA receptors are involved in the tolerance to some effects of benzodiazepines.[5]
Animal studies have found that glutamergic changes as a result of benzodiazepine use are responsible for a delayed withdrawal syndrome, which in mice peaks 3 days after cessation of benzodiazepines. This was demonstrated by the ability to avoid the withdrawal syndrome by the administration of AMPA antagonists. It is believed that different glutamate subreceptors, e.g., NMDA and AMPA, are responsible for different stages/time points of the withdrawal syndrome. NMDA receptors are upregulated in the brain as a result of benzodiazepine tolerance. AMPA receptors are also involved in benzodiazepine tolerance and withdrawal.[5][23] A decrease in benzodiazepine binding sites in the brain may also occur as part of benzodiazepine tolerance.[24]
### Cross tolerance[edit]
Benzodiazepines share a similar mechanism of action with various sedative compounds that act by enhancing the GABAA receptor. Cross tolerance means that one drug will alleviate the withdrawal effects of another. It also means that tolerance of one drug will result in tolerance of another similarly-acting drug. Benzodiazepines are often used for this reason to detoxify alcohol-dependent patients and can have life-saving properties in preventing or treating severe life-threatening withdrawal syndromes from alcohol, such as delirium tremens. However, although benzodiazepines can be very useful in the acute detoxification of alcoholics, benzodiazepines in themselves act as positive reinforcers in alcoholics, by increasing the desire for alcohol. Low doses of benzodiazepines were found to significantly increase the level of alcohol consumed in alcoholics.[25] Alcoholics dependent on benzodiazepines should not be abruptly withdrawn but be very slowly withdrawn from benzodiazepines, as over-rapid withdrawal is likely to produce severe anxiety or panic, which is well known for being a relapse risk factor in recovering alcoholics.[26]
There is cross tolerance between alcohol, the benzodiazepines, the barbiturates, the nonbenzodiazepine drugs, and corticosteroids, which all act by enhancing the GABAA receptor's function via modulating the chloride ion channel function of the GABAA receptor.[27][28][29][30][31]
Neuroactive steroids, e.g., progesterone and its active metabolite allopregnanolone, are positive modulators of the GABAA receptor and are cross tolerant with benzodiazepines.[32] The active metabolite of progesterone has been found to enhance the binding of benzodiazepines to the benzodiazepine binding sites on the GABAA receptor.[33] The cross-tolerance between GABAA receptor positive modulators, including benzodiazepines, occurs because of the similar mechanism of action and the subunit changes that occur from chronic use from one or more of these compounds in expressed receptor isoforms. Abrupt withdrawal from any of these compounds, e.g., barbiturates, benzodiazepines, alcohol, corticosteroids, neuroactive steroids, and nonbenzodiazepines, precipitate similar withdrawal effects characterized by central nervous system hyper-excitability, resulting in symptoms such as increased seizure susceptibility and anxiety.[34] While many of the neuroactive steroids do not produce full tolerance to their therapeutic effects, cross-tolerance to benzodiazepines still occurs as had been demonstrated between the neuroactive steroid ganaxolone and diazepam. Alterations of levels of neuroactive steroids in the body during the menstrual cycle, menopause, pregnancy, and stressful circumstances can lead to a reduction in the effectiveness of benzodiazepines and a reduced therapeutic effect. During withdrawal of neuroactive steroids, benzodiazepines become less effective.[35]
### Physiology of withdrawal[edit]
Withdrawal symptoms are a normal response in individuals having chronically used benzodiazepines, and an adverse effect and result of drug tolerance. Symptoms typically emerge when dosage of the drug is reduced. GABA is the second-most-common neurotransmitter in the central nervous system (the most common being glutamate[36][37][38]) and by far the most abundant inhibitory neurotransmitter; roughly one-quarter to one-third of synapses use GABA.[39] The use of benzodiazepines has a profound effect on almost every aspect of brain and body function, either directly or indirectly.[40]
Benzodiazepines cause a decrease in norepinephrine (noradrenaline), serotonin, acetylcholine, and dopamine[citation needed]. These neurotransmitters are needed for normal memory, mood, muscle tone and coordination, emotional responses, endocrine gland secretions, heart rate, and blood pressure control. With chronic benzodiazepine use, tolerance develops rapidly to most of its effects, so that, when benzodiazepines are withdrawn, various neurotransmitter systems go into overdrive due to the lack of inhibitory GABA-ergic activity. Withdrawal symptoms then emerge as a result, and persist until the nervous system physically reverses the adaptions (physical dependence) that have occurred in the CNS.[40]
Withdrawal symptoms typically consist of a mirror image of the drug's effects: Sedative effects and suppression of REM and SWS stages of sleep can be replaced by insomnia, nightmares, and hypnogogic hallucinations; its antianxiety effects are replaced with anxiety and panic; muscle-relaxant effects are replaced with muscular spasms or cramps; and anticonvulsant effects are replaced with seizures, especially in cold turkey or overly-rapid withdrawal.[40]
Benzodiazepine withdrawal represents in part excitotoxicity to brain neurons.[41] Rebound activity of the hypothalamic-pituitary-adrenocortical axis also plays an important role in the severity of benzodiazepine withdrawal.[42] Tolerance and the resultant withdrawal syndrome may be due to alterations in gene expression, which results in long-term changes in the function of the GABAergic neuronal system.[43][44]
During withdrawal from full or partial agonists, changes occur in benzodiazepine receptor with upregulation of some receptor subtypes and downregulation of other receptor subtypes.[45]
### Withdrawal[edit]
See also: Benzodiazepine withdrawal syndrome
Long-term use of benzodiazepines leads to increasing physical and mental health problems, and as a result, discontinuation is recommended for many long-term users. The withdrawal syndrome from benzodiazepines can range from a mild and short-lasting syndrome to a prolonged and severe syndrome. Withdrawal symptoms can lead to continued use of benzodiazepines for many years, long after the original reason for taking benzodiazepines has passed. Many patients know that the benzodiazepines no longer work for them but are unable to discontinue benzodiazepines because of withdrawal symptoms.[40]
Withdrawal symptoms can emerge despite slow reduction but can be reduced by a slower rate of withdrawal. As a result, withdrawal rates have been recommended to be customized to each individual patient. The time needed to withdrawal can vary from a couple of months to a year or more and often depends on length of use, dosage taken, lifestyle, health, and social and environmental stress factors.[40]
Diazepam is often recommended due to its long elimination half-life and also because of its availability in low potency doses. The non-benzodiazepine Z drugs such as zolpidem, zaleplon, and zopiclone should not be used as a replacement for benzodiazepines, as they have a similar mechanism of action and can induce a similar dependence. The pharmacological mechanism of benzodiazepine tolerance and dependence is the internalization (removal) of receptor site in the brain and changes in gene transcription codes in the brain.[40]
With long-term use and during withdrawal of benzodiazepines, treatment-emergent depression and[7] emotional blunting may emerge and sometimes also suicidal ideation. There is evidence that the higher the dose used the more likely it is benzodiazepine use will induce these feelings. Reducing the dose or discontinuing benzodiazepines may be indicated in such cases. Withdrawal symptoms can persist for quite some time after discontinuing benzodiazepines. Some common protracted withdrawal symptoms include anxiety, depression, insomnia, and physical symptoms such as gastrointestinal, neurologic, and musculoskeletal effects. The protracted withdrawal state may still occur despite slow titration of dosage. It is believed that the protracted withdrawal effects are due to persisting neuroadaptations.[10]
## Diagnosis[edit]
For a diagnosis of benzodiazepine dependence to be made, the ICD-10 requires that at least 3 of the below criteria are met and that they have been present for at least a month, or, if less than a month, that they appeared repeatedly during a 12-month period.[46][47]
* Behavioral, cognitive, and physiological phenomena that are associated with the repeated use and that typically include a strong desire to take the drug.
* Difficulty controlling use
* Continued use despite harmful consequences
* Preference given to drug use rather than to other activities and obligations
* Increased tolerance to effects of the drug and sometimes a physical withdrawal state.
These diagnostic criteria are good for research purposes, but, in everyday clinical practice, they should be interpreted according to clinical judgement. In clinical practice, benzodiazepine dependence should be suspected in those having used benzodiazepines for longer than a month, in particular, if they are from a high-risk group. The main factors associated with an increased incidence of benzodiazepine dependence include:[46]
* Dose
* Duration
* Concomitant use of antidepressants
Benzodiazepine dependence should be suspected also in individuals having substance use disorders including alcohol, and should be suspected in individuals obtaining their own supplies of benzodiazepines. Benzodiazepine dependence is almost certain in individuals who are members of a tranquilizer self-help group.[46]
Research has found that about 40 percent of people with a diagnosis of benzodiazepine dependence are not aware that they are dependent on benzodiazepines, whereas about 11 percent of people judged not to be dependent believe that they are. When assessing a person for benzodiazepine dependence, asking specific questions rather than questions based on concepts is recommended by experts as the best approach of getting a more accurate diagnosis. For example, asking persons if they "think about the medication at times of the day other than when they take the drug" would provide a more meaningful answer than asking "do you think you are psychologically dependent?".[46] The Benzodiazepine Dependence Self Report Questionnaire is one questionnaire used to assess and diagnose benzodiazepine dependence.[46]
### Definition[edit]
Benzodiazepine dependence is the condition resulting from repeated use of benzodiazepine drugs. It can include both a physical dependence as well as a psychological dependence and is typified by a withdrawal syndrome upon a fall in blood plasma levels of benzodiazepines, e.g., during dose reduction or abrupt withdrawal.[48]
## Prevention[edit]
Due to the risk of developing tolerance, dependence, and adverse health effects,[49] such as cognitive impairment,[20] benzodiazepines are indicated for short-term use only - a few weeks, followed by a gradual dose reduction.[50]
### The Committee on the Review of Medicines (UK)[edit]
The Committee on the Review of Medicines carried out a review into benzodiazepines due to significant concerns of tolerance, drug dependence, benzodiazepine withdrawal problems, and other adverse effects and published the results in the British Medical Journal in March 1980. The committee found that benzodiazepines do not have any antidepressant or analgesic properties and are, therefore, unsuitable treatments for conditions such as depression, tension headaches, and dysmenorrhea. Benzodiazepines are also not beneficial in the treatment of psychosis. The committee also recommended against benzodiazepines for use in the treatment of anxiety or insomnia in children.[6]
The committee was in agreement with the Institute of Medicine (USA) and the conclusions of a study carried out by the White House Office of Drug Policy and the National Institute on Drug Abuse (USA) that there is little evidence that long-term use of benzodiazepine hypnotics are beneficial in the treatment of insomnia due to the development of tolerance. Benzodiazepines tend to lose their sleep-promoting properties within 3–14 days of continuous use, and, in the treatment of anxiety, the committee found that there was little convincing evidence that benzodiazepines retains efficacy in the treatment of anxiety after 4 months of continuous use due to the development of tolerance.[6]
The committee found that the regular use of benzodiazepines causes the development of dependence characterized by tolerance to the therapeutic effects of benzodiazepines and the development of the benzodiazepine withdrawal syndrome including symptoms such as anxiety, apprehension, tremors, insomnia, nausea, and vomiting upon cessation of benzodiazepine use. Withdrawal symptoms tend to develop within 24 hours upon cessation of short-acting benzodiazepines, and 3–10 days after cessation of longer-acting benzodiazepines. Withdrawal effects could even occur after treatment lasting only 2 weeks at therapeutic dose levels; however, withdrawal effects tend to occur with habitual use beyond 2 weeks and are more likely the higher the dose. The withdrawal symptoms may appear to be similar to the original condition.[6]
The committee recommended that all benzodiazepine treatment be withdrawn gradually and recommended that benzodiazepine treatment be used only in carefully selected patients and that therapy be limited to short-term use only. It was noted in the review that alcohol can potentiate the central nervous system-depressant effects of benzodiazepines and should be avoided. The central nervous system-depressant effects of benzodiazepines may make driving or operating machinery dangerous, and the elderly are more prone to these adverse effects. High single doses or repeated low doses have been reported to produce hypotonia, poor sucking, and hypothermia in the neonate, and irregularities in the fetal heart. The committee recommended that benzodiazepines be avoided in lactation.[6]
The committee recommended that withdrawal from benzodiazepines be gradual, as abrupt withdrawal from high doses of benzodiazepines may cause confusion, toxic psychosis, convulsions, or a condition resembling delirium tremens. Abrupt withdrawal from lower doses may cause depression, nervousness, rebound insomnia, irritability, sweating, and diarrhea.[6]
The committee also made a mistake[citation needed] concluding:[6]
> on the present available evidence, the true addiction potential of benzodiazepines was low. The number dependent on the benzodiazepines in the UK from 1960 to 1977 has been estimated to be 28 persons. This is equivalent to a dependence rate of 5-10 cases per million patient months.
## Treatment[edit]
Benzodiazepines are regarded as a highly addictive drug class.[51] A psychological and physical dependence can develop in as short as a few weeks but may take years to develop in other individuals. Patients wanting to withdraw from benzodiazepines typically receive little advice or support, and such withdrawal should be by small increments over a period of months.[52]
Benzodiazepines are usually prescribed only short-term, as there is little justification for their prescribing long-term.[53] Some doctors however, disagree and believe long-term use beyond 4 weeks is sometimes justified, although there is little data to support this viewpoint.[9] Such viewpoints are a minority in the medical literature.[54]
There is no evidence that "drug holidays" or periods of abstinence reduced the risk of dependence; there is evidence from animal studies that such an approach does not prevent dependence from happening. Use of short-acting benzodiazepines is associated with interdose withdrawal symptoms. Kindling has clinical relevance with regard to benzodiazepines; for example, there is an increasing shift to use of benzodiazepines with a shorter half-life and intermittent use, which can result in interdose withdrawal and rebound effects.[5]
### Cognitive behavioral therapy[edit]
Cognitive behavioral therapy has been found to be more effective for the long-term management of insomnia than sedative hypnotic drugs. No formal withdrawal programs for benzodiazepines exists with local providers in the UK. Meta-analysis of published data on psychological treatments for insomnia show a success rate between 70 and 80%.[citation needed] A large-scale trial utilizing cognitive behavioral therapy in chronic users of sedative hypnotics including nitrazepam, temazepam, and zopiclone found CBT to be a significantly more effective long-term treatment for chronic insomnia than sedative hypnotic drugs. Persisting improvements in sleep quality, sleep onset latency, increased total sleep, improvements in sleep efficiency, significant improvements in vitality, physical and mental health at 3-, 6-, and 12-month follow-ups were found in those receiving CBT. A marked reduction in total sedative hypnotic drug use was found in those receiving CBT, with 33% reporting zero hypnotic drug use. Age has been found not to be a barrier to successful outcome of CBT. It was concluded that CBT for the management of chronic insomnia is a flexible, practical, and cost-effective treatment, and it was also concluded that CBT leads to a reduction of benzodiazepine drug intake in a significant number of patients.[55]
Chronic use of hypnotic medications is not recommended due to their adverse effects on health and the risk of dependence. A gradual taper is usual clinical course in getting people off of benzodiazepines, but, even with gradual reduction, a large proportion of people fail to stop taking benzodiazepines. The elderly are particularly sensitive to the adverse effects of hypnotic medications. A clinical trial in elderly people dependent on benzodiazepine hypnotics showed that the addition of CBT to a gradual benzodiazepine reduction program increased the success rate of discontinuing benzodiazepine hypnotic drugs from 38% to 77% and at the 12-month follow-up from 24% to 70%. The paper concluded that CBT is an effective tool for reducing hypnotic use in the elderly and reducing the adverse health effects that are associated with hypnotics such as drug dependence, cognitive impairments, and increased road traffic accidents.[56]
A study of patients undergoing benzodiazepine withdrawal who had a diagnosis of generalized anxiety disorder showed that those having received CBT had a very high success rate of discontinuing benzodiazepines compared to those not having receive CBT. This success rate was maintained at the 12-month follow-up. Furthermore, it was found that, in patients having discontinued benzodiazepines, they no longer met the diagnosis of general anxiety disorder, and that the number of patients no longer meeting the diagnosis of general anxiety disorder was higher in the group having received CBT. Thus, CBT can be an effective tool to add to a gradual benzodiazepine dosage reduction program leading to improved and sustained mental health benefits (Disputed).[57]
### Letter to patients[edit]
Sending a letter to patients warning of the adverse effects of long-term use of benzodiazepines and recommending dosage reduction has been found to be successful and a cost-effective strategy in reducing benzodiazepine consumption in general practice. Within a year of the letter's going out, there was found to be a 17% fall in the number of benzodiazepines being prescribed, with 5% of patients having totally discontinued benzodiazepines.[58][59] A study in the Netherlands reported a higher success rate by sending a letter to patients who are benzodiazepine-dependent. The results of the Dutch study reported 11.3% of patients discontinuing benzodiazepines completely within a year.[60]
### Flumazenil[edit]
Flumazenil delivered via slow subcutaneous infusion represents a safe procedure for those withdrawing from long-term, high dose benzodiazepine dependency.[61] It has a low risk of seizures even amongst those who have experienced convulsions when previously attempting benzodiazepine withdrawal.[62]
## Epidemiology[edit]
Research studies have come to different conclusions on the number of therapeutic dose users who develop a physical dependence and withdrawal syndrome. Researches estimate 20-100% of patients, taking benzodiazepines at therapeutic dosages for the long term, are physically dependent and will experience withdrawal symptoms.[63]
Benzodiazepines can be addictive and induce dependence even at low doses, with 23% becoming addicted within 3 months of use. Benzodiazepine addiction is considered a public health problem. Approximately 68.5% of prescriptions of benzodiazepines originate from local health centers, with psychiatry and general hospitals accounting for 10% each. A survey of general practitioners reported that the reason for initiating benzodiazepines was due to an empathy for the patients suffering and a lack of other therapeutic options rather than patients demanding them. However, long-term use was more commonly at the insistence of the patient, it is presumed, because physical dependence or addiction had developed.[64][65][66]
Approximately twice as many women as men are prescribed benzodiazepines. It is believed that this is largely because men typically turned to alcohol to cope with stress and women to prescription drugs. Biased perception of women by male doctors may also play a role in increased prescribing rates to women; however, increased anxiety features in women does not account for the wide gap alone between men and women.[22]
Based on findings in the US from the Treatment Episode Data Set (TEDS), an annual compilation of patient characteristics in substance abuse treatment facilities in the United States, admissions due to "primary tranquilizer" (including, but not limited to, benzodiazepine-type) drug use increased 79% from 1992 to 2002.[67]
A study published in the British Journal of General Practice in July 2017 found that in a sample taken from a survey conducted in 2014–2015 in Bradford a mean of 0.69% of registered patients had been prescribed benzodiazepines for more than a year. This would suggest that there were around 300,000 long-term users of diazepine in the UK.[68]
## History[edit]
Previously, physical dependence on benzodiazepines was largely thought to occur only in people on high-therapeutic-dose ranges. Low- or normal-dose dependence was not suspected until the 1970s, and it was not until the early 1980s that it was confirmed.[69][70] Low-dose dependence has now been clearly demonstrated in both animal studies and human studies,[71][72] and is a recognized clinical disadvantage of benzodiazepines. Severe withdrawal syndromes can occur from these low doses of benzodiazepines even after gradual dose reduction.[73][74] An estimated 30–45% of chronic low-dose benzodiazepine users are dependent and it has been recommended that benzodiazepines even at low dosage be prescribed for a maximum of 7–14 days to avoid dependence.[75] As a result, the global trend is toward strict regulations for the prescription of benzodiazepines due to this risk of low-dose dependence.[76]
Some controversy remains, however, in the medical literature as to the exact nature of low-dose dependence and the difficulty in getting patients to discontinue their benzodiazepines, with some papers attributing the problem to predominantly drug-seeking behavior and drug craving, whereas other papers having found the opposite, attributing the problem to a problem of physical dependence with drug-seeking and craving not being typical of low-dose benzodiazepine users.[77][78]
## Society and culture[edit]
### Misuse and addiction[edit]
Lorazepam (Ativan) tablets.
See also: Benzodiazepine use disorder
Benzodiazepines are one of the largest classes of abused drugs; they are classed as schedule IV controlled drugs because of their recognized medical uses.[79] Across the world the most frequently diverted and abused benzodiazepines include temazepam, diazepam, nimetazepam, nitrazepam, triazolam, flunitrazepam, midazolam, and in the United States alprazolam, clonazepam, and lorazepam.
Benzodiazepines can cause serious addiction problems. A survey of doctors in Senegal found that many doctors feel that their training and knowledge of benzodiazepines is, in general, poor; a study in Dakar found that almost one-fifth of doctors ignored prescribing guidelines regarding short-term use of benzodiazepines, and almost three-quarters of doctors regarded their training and knowledge of benzodiazepines to be inadequate. More training regarding benzodiazepines has been recommended for doctors.[80] Due to the serious concerns of addiction, national governments were recommended to urgently seek to raise knowledge via training about the addictive nature of benzodiazepines and appropriate prescribing of benzodiazepines.[81]
A six-year study on 51 Vietnam veterans who were drug abusers of either mainly stimulants (11 people), mainly opiates (26 people), or mainly benzodiazepines (14 people) was carried out to assess psychiatric symptoms related to the specific drugs of abuse. After six years, opiate abusers had little change in psychiatric symptomatology; five of the stimulant users had developed psychosis, and eight of the benzodiazepine users had developed depression. Therefore, long-term benzodiazepine abuse and dependence seems to carry a negative effect on mental health, with a significant risk of causing depression.[82] Benzodiazepines are also sometimes abused intra-nasally.[83]
In the elderly, alcohol and benzodiazepines are the most commonly abused substances, and the elderly population is more susceptible to benzodiazepine withdrawal syndrome and delirium than are younger patients.[84]
## See also[edit]
* Long-term effects of benzodiazepines
* Alcohol withdrawal syndrome
* Long-term effects of alcohol consumption
* SSRI discontinuation syndrome
* Drug related crime
## References[edit]
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> ...the committee concluded that, on the present available evidence, the true addiction potential of benzodiazepines was low. The number dependent on the benzodiazepines in the UK from 1960 to 1977 has been estimated to be 28 persons. This is equivalent to a dependence rate of 5-10 cases per million patient months.
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28. ^ World Health Organisation - Assessment of Zopiclone
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## External links[edit]
Classification
D
* ICD-10: F13.2
* ICD-9-CM: 304.1
* DiseasesDB: 29548
External resources
* MedlinePlus: 003578
* eMedicine: Bztox/813255
* Benzodiazepine dependence at Curlie
* 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
* t
* e
Reinforcement disorders: Addiction and Dependence
Addiction
Drug
* Alcohol
* Amphetamine
* Cocaine
* Methamphetamine
* Methylphenidate
* Nicotine
* Opioid
Behavioral
* Financial
* Gambling
* Shopping
* Palatable food
* Sex-related
* Intercourse
* Pornography
* Internet-related
* Internet addiction disorder
* Internet sex addiction
* Video game addiction
* Digital media addictions
Cellular
mechanisms
* Transcriptional
* ΔFosB
* c-Fos
* Cdk5
* CREB
* GluR2
* NF-κB
* Epigenetic
* G9a
* G9a-like protein
* HDAC1
* HDAC2
* HDAC3
* HDAC4
* HDAC5
* HDAC9
* HDAC10
* SIRT1
* SIRT2
* ...
Dependence
Concepts
* Physical dependence
* Psychological dependence
* Withdrawal
Disorders
* Drugs
* Alcoholism
* Amphetamine
* Barbiturate
* Benzodiazepine
* Caffeine
* Cannabis
* Cocaine
* Nicotine
* Opioid
* Non-drug stimuli
* Tanning dependence
Treatment and management
Detoxification
* Alcohol detoxification
* Drug detoxification
Behavioral therapies
* Cognitive behavioral therapy
* Relapse prevention
* Contingency management
* Community reinforcement approach and family training
* Motivational enhancement therapy
* Motivational interviewing
* Motivational therapy
* Physical exercise
Treatment programs
* Drug rehab
* Residential treatment center
* Heroin-assisted treatment
* Intensive outpatient program
* Methadone maintenance
* Smoking cessation
* Nicotine replacement therapy
* Tobacco cessation clinics in India
* Twelve-step program
Support groups
* Addiction recovery groups
* List of twelve-step groups
Harm reduction
* Category:Harm reduction
* Drug checking
* Reagent testing
* Low-threshold treatment programs
* Managed alcohol program
* Moderation Management
* Needle exchange program
* Responsible drug use
* Stimulant maintenance
* Supervised injection site
* Tobacco harm reduction
See also
* Addiction medicine
* Allen Carr
* Category:Addiction
* Discrimination against drug addicts
* Dopamine dysregulation syndrome
* Cognitive control
* Inhibitory control
* Motivational salience
* Incentive salience
* Sober companion
* Category
* v
* t
* e
Treatment of drug dependence (N07B)
Nicotine dependence
* Bupropion
* Cytisine
* Lobeline
* Mecamylamine
* Varenicline
* AA (Clonidine)
Alcohol dependence
* AD inhibitor (Disulfiram
* Calcium carbimide
* Hydrogen cyanamide)
* Acamprosate
* Opioid antagonists
* Naltrexone
* Nalmefene)
* κ-Opioid receptor antagonists
* Aticaprant
* Topiramate
* AA (Clonidine)
* Baclofen
* Phenibut
Opioid dependence
* AA (Clonidine
* Lofexidine)
* Ibogaine
* Opioids
* Buprenorphine (+naloxone)
* Levacetylmethadol
* Methadone
* Dihydrocodeine
* Dihydroetorphine
* Hydromorphone (extended-release)
* Morphine (extended-release)
* Opioid antagonists (Naltrexone
* Nalmefene)
Benzodiazepine dependence
* AA (Clonidine)
* Benzodiazepines (Diazepam
* Lorazepam
* Chlordiazepoxide
* Oxazepam)
* Barbiturates (Phenobarbital)
Research
Salvia divinorum
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Benzodiazepine dependence | c0338768 | 4,512 | wikipedia | https://en.wikipedia.org/wiki/Benzodiazepine_dependence | 2021-01-18T18:31:54 | {"icd-9": ["304.1"], "icd-10": ["F13"], "wikidata": ["Q380409"]} |
Presence of blood in ejaculation
Hematospermia
The ejaculatory output of a man with severe hematospermia.
SpecialtyUrology
Hematospermia (also known as haematospermia, hemospermia, or haemospermia) is the presence of blood in ejaculation. It is most often a benign symptom.[1] Among men age 40 or older, hematospermia is a slight predictor of cancer, typically prostate cancer.[2] No specific cause is found in up to 70% of cases.[3]
## Contents
* 1 Cause
* 1.1 Infection and inflammation
* 1.2 Neoplasm
* 1.3 Prostate
* 1.4 Other
* 1.5 Unknown
* 2 Diagnosis
* 3 Epidemiology
* 4 History
* 5 References
* 6 External links
## Cause[edit]
Though haematospermia may cause considerable distress to patients, it is often a benign and self-limiting condition caused by infections, particularly in younger patients. An isolated episode is usually considered benign and not likely to be associated with malignancy. Recurrent haematospermia may indicate a more serious underlying pathology particularly in patients over 40 years of age.[4]
### Infection and inflammation[edit]
Infection or inflammation is considered the most common cause of the condition. Implicated pathogens include; Gram-negative bacteria (often E. coli), gonococci, T. pallidum, C. trachomatis, N. gonorrhoeae, echinococcus (rarely), HSV type 1 or 2, and HPV. The condition may also rarely be caused by some chronic systemic infections like tuberculosis or schistosomiasis. Additionally, testicular, prostate, and epididymal inflammation in general may present with haematospermia as feature.[1][4][5]
### Neoplasm[edit]
Some neoplasms of the genitourinary system may present with haematospermia. Malignant causes of haematospermia include; prostate cancer, testicular or epididymal tumours, seminal vesicle carcinoma (rarely), and urethral tumour.[4] Lymphomas and leukaemias may also feature haematospermia as symptom.[5]
### Prostate[edit]
Various prostate pathologies (including prostatitis, calculi (stones), cysts, benign prostatic hyperplasia, bacterial infection, etc.) may result in blood occurring in the ejaculate.[4][5]
### Other[edit]
Systemic conditions like malignant hypertension, liver dysfunction, or bleeding disorders, and amyloidosis may sometimes present with haematospermia as symptom. Trauma to the region may also cause the condition.[4] Additionally, structural anomalies of genitourinary anatomy (e.g. vascular anomalies, polyps, urethral malformations, etc.) may result in haematospermia as symptom.[1][5]
Excessive sex or masturbation, prolonged sexual abstinence, interrupted sex, and certain sexual behaviours may also result in (mostly isolated events of) haematospermia.[1]
### Unknown[edit]
The exact cause cannot be determined in up to 70% of patients.[4]
## Diagnosis[edit]
The main focus of an evaluation should be to determine its cause (if possible) and rule out infection and malignancy. It is important to rule out pseudo-haematospermia where blood originates from the partner during intercourse.[4]
## Epidemiology[edit]
Though the exact incidence is unknown, haematospermia has been reported in one per 5,000 patients in initial examinations at urological out-patient clinics. Most patients are between 30–40 years of age.[4] It is thought to make up ~1% of all urological symptoms.[5]
## History[edit]
Traditionally, the condition was thought to be a clinically insignificant consequence of prolonged sexual abstinence or intense sexual experiences.[4]
## References[edit]
1. ^ a b c d Stefanovic KB, Gregg PC, Soung M (December 2009). "Evaluation and treatment of hematospermia". American Family Physician. 80 (12): 1421–7. PMID 20000304.
2. ^ "Blood in semen: Causes". Mayo Clinlic.
3. ^ Akhter W, Khan F, Chinegwundoh F (April 2013). "Should every patient with hematospermia be investigated? A critical review". Central European Journal of Urology. 66 (1): 79–82. doi:10.5173/ceju.2013.01.art25. PMC 3921834. PMID 24578999.
4. ^ a b c d e f g h i Akhter W, Khan F, Chinegwundoh F (2013). "Should every patient with hematospermia be investigated? A critical review". Central European Journal of Urology. 66 (1): 79–82. doi:10.5173/ceju.2013.01.art25. PMC 3921834. PMID 24578999.
5. ^ a b c d e Mathers MJ, Degener S, Sperling H, Roth S (March 2017). "Hematospermia-a Symptom With Many Possible Causes". Deutsches Ärzteblatt International. 114 (11): 186–191. doi:10.3238/arztebl.2017.0186. PMC 5387851. PMID 28382905.
## External links[edit]
Classification
D
* ICD-10: N50.1
* ICD-9-CM: 608.82
* MeSH: D051516
* DiseasesDB: 31879
External resources
* eMedicine: med/3466
* Patient UK: Hematospermia
* v
* t
* e
Male diseases of the pelvis and genitals
Internal
Testicular
* Orchitis
* Hydrocele testis
* Testicular cancer
* Testicular torsion
* Male infertility
* Aspermia
* Asthenozoospermia
* Azoospermia
* Hyperspermia
* Hypospermia
* Oligospermia
* Necrospermia
* Teratospermia
Epididymis
* Epididymitis
* Spermatocele
* Hematocele
Prostate
* Prostatitis
* Acute prostatitis
* Chronic bacterial prostatitis
* Chronic prostatitis/chronic pelvic pain syndrome
* Asymptomatic inflammatory prostatitis
* Benign prostatic hyperplasia
* Prostate cancer
Seminal vesicle
* Seminal vesiculitis
External
Penis
* Balanoposthitis / Balanitis
* Balanitis plasmacellularis
* Pseudoepitheliomatous keratotic and micaceous balanitis
* Phimosis
* Paraphimosis
* Priapism
* Sexual dysfunction
* Erectile dysfunction
* Peyronie's disease
* Penile cancer
* Penile fracture
* Balanitis xerotica obliterans
Other
* Hematospermia
* Retrograde ejaculation
* Postorgasmic illness syndrome
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Hematospermia | c0149707 | 4,513 | wikipedia | https://en.wikipedia.org/wiki/Hematospermia | 2021-01-18T19:00:05 | {"mesh": ["D051516"], "icd-9": ["608.82"], "icd-10": ["N50.1"], "wikidata": ["Q2077117"]} |
A number sign (#) is used with this entry because this form of peroxisome biogenesis disorder (PBD2B) is caused by homozygous mutation in the PEX5 gene (600414) on chromosome 12p13.3. Mutations in the PEX5 gene also cause Zellweger syndrome (PBD2A; 214110).
Description
The overlapping phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD) represent the milder manifestations of the Zellweger syndrome spectrum (ZSS) of peroxisome biogenesis disorders. The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy, and visual impairment. Children with the NALD presentation may reach their teens, and those with the IRD presentation may reach adulthood (summary by Waterham and Ebberink, 2012).
For a complete phenotypic description and a discussion of genetic heterogeneity of PBD(NALD/IRD), see 601539.
Individuals with mutations in the PEX5 gene have cells of complementation group 2 (CG2). For information on the history of PBD complementation groups, see 214100.
Molecular Genetics
Dodt et al. (1995) reported a homozygous mutation in the PEX5 gene in a cell line from a patient with NALD (600414.0001).
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Dolichocephaly \- Prominent forehead \- High forehead Face \- Peculiar facies Ears \- Low-set ears Eyes \- Cataracts, neonatal polar \- Esotropia \- Epicanthal folds Nose \- Nasal bridge broad \- Anteverted nostrils Mouth \- Palate high-arched NEUROLOGIC Central Nervous System \- Mental retardation \- Seizures ENDOCRINE FEATURES \- Adrenal insufficiency LABORATORY ABNORMALITIES \- Elevated long chain fatty acids Caused by mutation in the peroxisome biogenesis factor 5 gene (PEX5, 600414.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| PEROXISOME BIOGENESIS DISORDER 2B | c0282527 | 4,514 | omim | https://www.omim.org/entry/202370 | 2019-09-22T16:31:25 | {"mesh": ["D052919"], "omim": ["202370"], "orphanet": ["772", "44"], "genereviews": ["NBK1448"]} |
A rare genetic multiple congenital anomalies/dysmorphic syndrome without intellectual disability characterized by unilateral or bilateral cleft lip and palate and craniofacial dysmorphism (including frontal bossing, hypertelorism, broad flat nasal bridge, cupped ears/thickened helices, and micrognathia). Additional manifestations are variable congenital cardiac anomalies, pectus excavatum, abnormalities of the hands and feet, ocular abnormalities (myopia, cataract, staphyloma), and conductive or sensorineural hearing loss.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Cleft lip and palate-craniofacial dysmorphism-congenital heart defect-hearing loss syndrome | None | 4,515 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=508476 | 2021-01-23T17:35:36 | {"synonyms": ["Cleft lip and palate-craniofacial dysmorphism-congenital heart defect-deafness syndrome", "Hyaluronidase 2 deficiency"]} |
A number sign (#) is used with this entry because of evidence that Gitelman syndrome (GTLMNS) is caused by homozygous or compound heterozygous mutation in the (SLC12A3; 600968) on chromosome 16q13.
Description
Gitelman syndrome is an autosomal recessive renal tubular salt-wasting disorder characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria. It is the most common renal tubular disorder among Caucasians (prevalence of 1 in 40,000). Most patients have onset of symptoms as adults, but some can present in childhood. Clinical features include transient periods of muscle weakness and tetany, abdominal pains, and chondrocalcinosis (summary by Glaudemans et al., 2012). Gitelman syndrome is sometimes referred to as a mild variant of classic Bartter syndrome (607364).
For a discussion of genetic heterogeneity of Bartter syndrome, see 607364.
Clinical Features
It has been proposed that Bartter syndrome, defined generically as an autosomal recessive disorder featuring hypokalemic metabolic alkalosis with salt wasting, is a heterogeneous entity with at least 2 subsets, Gitelman syndrome and 'true Bartter syndrome.' Simon et al. (1996) stated that Gitelman syndrome refers to the numerically predominant subset of patients with hypokalemic alkalosis in conjunction with hypocalciuria and hypomagnesemia, whereas true Bartter syndrome refers to patients with normal or hypercalciuria and typically normal magnesium levels. True Bartter patients usually present under the age of 5 years with signs of intravascular volume depletion, whereas Gitelman syndrome patients typically present at older ages without overt hypovolemia. Nevertheless, the overlapping features of these disorders has resulted in considerable confusion and controversy regarding their classification, with many patients with features of Gitelman syndrome being labeled as having Bartter syndrome.
Gitelman et al. (1966) reported 2 affected sisters who were the offspring of parents related as half first cousins once removed. They had experienced occasional mild episodes of muscle weakness and had suffered for many years from a chronic dermatitis characterized by thickening with a purple-red hue. Erythema of the skin is a feature of experimental magnesium depletion in the rat. Spencer and Voyce (1976) reported 3 affected sibs. Symptoms were precipitated by nonspecific illness and consisted mainly of tetany. A depressed creatinine clearance in the oldest sib (aged 19 years) suggested renal damage from hypokalemia. Long-term correction of the potassium deficiency is warranted.
Zarraga Larrondo et al. (1992) described a 33-year-old woman who presented with hypokalemia-hypomagnesemia associated with renal potassium and magnesium wasting. Her mean 24-hr urinary calcium excretion was strikingly low despite normocalcemia, normal creatinine clearance, and normal serum parathyroid hormone and calcitriol. In response to intravenous furosemide, the patient showed significant increments in sodium, chloride and magnesium excretion as well as abolition of hypocalciuria. The dissociation of renal calcium transport from magnesium transport together with exaggerated natriuresis after furosemide suggested the presence of a defect in the distal tubule rather than in the loop of Henle. The patient's symptoms included paresthesia and carpopedal spasms. She had been hospitalized at the age of 23 for tetanic convulsions which were interpreted as periodic hypokalemia. She often felt tired and had muscle cramps provoked by physical exertion. She had not been treated with diuretics, antirheumatics or hormones, and denied laxative abuse or diarrhea.
Hisakawa et al. (1998) identified 25 cases of an association between Bartter syndrome and chondrocalcinosis (118600) that were reported between 1978 and 1998. Hypomagnesemia had been associated with chondrocalcinosis. Because all of the reports of an association with Bartter syndrome referred to hypomagnesemia and hypocalciuria, Hisakawa et al. (1998) suggested that these might be cases of Gitelman syndrome, not 'true' Bartter syndrome. Hisakawa et al. (1998) described a 45-year-old Japanese woman, treated for Bartter syndrome for 14 years, who presented with numbness of her extremities and polyarthralgia. It was concluded that she had Gitelman syndrome with chondrocalcinosis, and treatment with spironolactone and magnesium supplementation was effective. Previously reported cases of 'Bartter syndrome' with chondrocalcinosis were tabulated.
Gitelman syndrome is widely described as a benign or milder variant of Bartter syndrome. However, Pachulski et al. (2005) described a patient with this disorder who presented with presyncope coincident with long runs of ventricular tachycardia. The otherwise well 39-year-old woman took no medications. Serum potassium and magnesium levels were very low. An electrophysiologic study was negative for inducible, sustained ventricular tachycardia; however, the patient continued to have ventricular tachycardia with presyncope despite aggressive potassium and magnesium supplementation. The patient was managed with amiodarone and an implanted defibrillator to guard against a potential breakthrough of sustained ventricular arrhythmia. Pachulski et al. (2005) pointed to reports suggesting that about half the patients with Gitelman syndrome have QTc prolongation. Although Gitelman syndrome is described as an asymptomatic or benign disorder with characteristic electrolyte abnormalities, most reports of clinical series document presyncope, vertigo, ataxia, and blurred vision. Patients, particularly those with prolonged QTc, should be investigated for ventricular arrhythmia.
Ng et al. (2006) reported a 22-year-old Chinese man with Gitelman syndrome. He reported periodic paralysis since age 11 years. The episodes usually developed after strenuous exercise and lasted 2 to 3 days with spontaneous resolution. Laboratory studies showed decreased serum potassium, decreased serum magnesium, and low calcium excretion. Genetic analysis identified compound heterozygosity for mutations in the SLC12A3 gene (600968.0013; 600968.0014). His unaffected parents were heterozygous for each of the mutations. The patient's sister, who had the same genotype, had decreased serum potassium and decreased calcium excretion, but did not have any clinical symptoms. Ng et al. (2006) noted the intrafamilial variability and suggested a gender effect.
### Heterozygous Mutation Carriers
Among relatives of patients with Gitelman syndrome, Fava et al. (2008) identified 35 individuals who were heterozygous carriers of mutations in the SLC12A3 gene. Compared to unrelated matched controls, the heterozygous carriers had markedly lower blood pressure (systolic 103.3 vs 123.2 mm Hg; diastolic 62.5 vs 73.1 mm Hg; p less than 0.001). Although there were no significant differences between the groups in plasma concentration or urinary excretion rate of electrolytes, heterozygous mutation carriers had slightly higher fasting plasma glucose concentrations. Overall, the phenotype of heterozygous mutation carriers was similar to patients being treated with low-dose thiazide diuretics, suggesting that they are partially protected from hypertension through partial genetic loss of function of the SLC12A3 transporter.
Mapping
An attractive candidate gene for one form of Bartter syndrome is the thiazide-sensitive Na-Cl cotransporter of the distal convoluted tubule (SLC12A3; 600968), which is believed to be the principal mediator of sodium and chloride reabsorption in this segment of the nephron, accounting for a significant fraction of net renal sodium reabsorption. This cotransporter is the target of thiazide diuretics, one of the major classes of agents used in the treatment of hypertension. Simon et al. (1996) demonstrated complete linkage of Gitelman syndrome to the thiazide-sensitive Na-Cl cotransporter gene on 16q13.
Molecular Genetics
In patients with Gitelman syndrome, Simon et al. (1996) identified a wide variety of nonconservative mutations in the SLC12A3 gene consistent with loss-of-function alleles (600968.0001). Many of their patients were genetic compounds and this, together with the finding of independent mutant alleles in different branches of kindreds, suggested to the authors that mutant alleles are not rare in the population. Moreover, the same conclusion was suggested by the finding that consanguineous marriage is not prominent in Gitelman syndrome kindreds. The prevalence of heterozygotes may be at least 1% in Swedish and Italian populations. A puzzling finding was the high proportion of affected offspring of heterozygous parents. After excluding index cases, they found that 22 of 33 offspring of heterozygous parents had Gitelman syndrome, far more than the expected 8 affected subjects. Whether this was the result of ascertainment bias or segregation distortion remained to be determined. Simon et al. (1996) speculated that these mutant alleles lead to reduced sodium chloride reabsorption in the heterozygotes, potentially protecting against development of hypertension. They noted that identification of specific mutations causing Gitelman syndrome permits testing of these hypotheses by identifying cohorts of heterozygous carriers and comparing their blood pressures and responses to pharmacologic intervention to those of their homozygous wildtype sibs or other controls. Subjects with unexplained hypokalemia or hypokalemia complicating drug therapy may be carrying Gitelman mutations. The potential for DNA diagnosis of this disorder is indicated by the fact that at initial presentation some patients with this disease are incorrectly believed to be diuretic abusers or to have bulimia (607499). Indeed, one of the patients of Simon et al. (1996) was committed to a locked psychiatric ward and it was only when her hypokalemia persisted for 2 weeks in this setting that a proper diagnosis was made.
Jeck et al. (2000) described 3 unrelated patients presenting with the typical laboratory findings of Gitelman syndrome. Mutation analysis in these 3 patients revealed no abnormality in the SLC12A3 gene. Instead, all patients were found to carry previously described mutations in the CLCNKB (602023) gene: 2 were homozygous for complete deletion of the gene (602023.0006) and 1 was homozygous for an A-G substitution at the splice acceptor site of intron 7 (602023.0007). Review of the medical histories revealed manifestation of the disease within the first year of life in all cases. Clinical presentation included episodes of dehydration, weakness, and failure to thrive, much more suggestive of classic Bartter syndrome type 3 (607364) than of Gitelman syndrome. The coexistence of hypomagnesemia and hypocalciuria was not present from the beginning. In the follow-up, a drop of both parameters below normal range was a consistent finding reflecting a transition from classic Bartter syndrome to Gitelman syndrome phenotype. Jeck et al. (2000) suggested that the phenotypic overlap may indicate a physiologic cooperation of the apical thiazide-sensitive Na-Cl cotransporter and the basolateral chloride channel for salt reabsorption in the distal convoluted tubule.
Animal Model
Yang et al. (2010) found that mice with a homozygous truncating mutation in the Slc12a3 gene (S707X) showed features of Gitelman syndrome, including relative hypotension with increased plasma renin activity, increased aldosterone levels, hypokalemia, hypomagnesemia, hypocalciuria, and metabolic alkalosis. There was markedly reduced Slc12a3 mRNA and protein expression in the kidneys, which was primarily due to nonsense-mediated mRNA decay. The later distal convoluted tubules of mutant mice showed increased cell volume, but cell structure was similar to wildtype. The distal and cortical collecting tubules had increased expression of the epithelial sodium channel Scnn1b (600760), calcium channels Trpv5 (606679) and Trpv6 (606680), and potassium channels Romk1 (KCNJ1; 600359) and Kcnma1 (600150), which was also observed in a renal biopsy from a human patient with GS. These changes indicated adaptive changes in channel expression, which may contribute to electrolyte imbalances observed in the disorder.
INHERITANCE \- Autosomal recessive ABDOMEN \- Abdominal pain (in some patients) GENITOURINARY Kidneys \- Polyuria \- Renal potassium wasting \- Renal magnesium wasting SKELETAL \- Chondrocalcinosis MUSCLE, SOFT TISSUES \- Generalized muscle weakness \- Muscle cramps \- Tetany NEUROLOGIC Central Nervous System \- Seizures \- Paresthesias \- Paralysis, episodic, after strenuous exercise METABOLIC FEATURES \- Hypokalemic alkalosis \- Polydipsia ENDOCRINE FEATURES \- Increased plasma renin LABORATORY ABNORMALITIES \- Hypokalemia \- Hypomagnesemia \- Hypocalciuria MISCELLANEOUS \- Onset in childhood (later than in antenatal Bartter syndrome 241200 ) \- Prevalence of 19 in 1,000,000 in Sweden \- Prevalence of 1 in 40,000 among Caucasians \- Heterozygous carriers have decreased blood pressure compared to the general population MOLECULAR BASIS \- Caused by mutation in the thiazide-sensitive Na-Cl cotransporter (SLC12A3, 600968.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| GITELMAN SYNDROME | c0268450 | 4,516 | omim | https://www.omim.org/entry/263800 | 2019-09-22T16:23:17 | {"doid": ["0050450"], "mesh": ["D053579"], "omim": ["263800"], "orphanet": ["358"], "synonyms": ["Alternative titles", "HYPOMAGNESEMIA-HYPOKALEMIA, PRIMARY RENOTUBULAR, WITH HYPOCALCIURIA", "POTASSIUM AND MAGNESIUM DEPLETION"]} |
A number sign (#) is used with this entry because of evidence that mirror movements-2 (MRMV2) is caused by heterozygous mutation in the RAD51 gene (179617) on chromosome 15q15.
Description
Mirror movements are involuntary movements of a side of the body that mirror intentional movements on the opposite side. Mild mirror movements are physiologic in young children and gradually disappear within the first decade of life, likely due to maturation of the motor network. Mirror movements that persist beyond age 10 years represent a rare disorder usually showing autosomal dominant inheritance with incomplete penetrance (summary by Depienne et al., 2012).
For a discussion of genetic heterogeneity of mirror movements, see MRMV1 (157600).
Clinical Features
Depienne et al. (2011) and Depienne et al. (2012) reported a large 4-generation French family in which 8 individuals had congenital mirror movements. Affected individuals had involuntary mirror movements affecting the hands and forearms, resulting in functional disability in fine manual activities, and in pain and cramping during sustained manual activities, including writing. The disorder showed a stable course, and none required treatment. There were no associated disorders. An unrelated German family with 2 affected individuals had a similar phenotype.
Franz et al. (2015) reported a family (family A) in which at least 11 individuals spanning 3 generations had mirror movements. Eight patients had visually confirmed mirror movements, 2 were reportedly affected according to family history, and 1 patient (patient IV.6, aged 30) did not have visually apparent mirroring, but did show subtle mirror movements detected by an accelerometer glove. In this family, those with visually apparent mirror movements had 'actual' mirroring, in which the non-volitional hand and fingers virtually mirrored the volitional hand precisely in all movements.
Trouillard et al. (2016) reported a multigenerational family from Norway in which 8 individuals had congenital mirror movements. Four mutation carriers had obvious mirror movements in the hands that disturbed activities of daily living, whereas the other 4 mutation carriers had no complaints despite mild mirror movements, indicating intrafamilial variability.
Inheritance
The transmission pattern of MRMV2 in the families reported by Depienne et al. (2012) was consistent with autosomal dominant inheritance with incomplete penetrance (50% in 1 family).
Molecular Genetics
By exome sequencing of a large French family with mirror movements reported by Depienne et al. (2011), Depienne et al. (2012) identified a heterozygous truncating mutation in the RAD51 gene (R254X; 179617.0003). The mutation was found in 8 affected individuals and in 8 unaffected individuals, indicating incomplete penetrance. A second truncating mutation in the RAD51 gene (179617.0004) was identified in a German family with the disorder. The authors concluded that haploinsufficiency was the pathogenic mechanism. Rad1 expression was found in the developing mouse cortex, and specifically in a subpopulation of corticospinal axons at the pyramidal decussation. The mechanism linking RAD1 deficiency to the disorder was unclear: insufficient RAD51-related DNA repair during early corticogenesis might lead to excessive apoptosis and altered central nervous system development; however, RAD51 may have a direct or indirect role in axonal guidance.
Trouillard et al. (2016) identified a heterozygous R254X mutation in the RAD51 gene in 8 members of a Norwegian family with MRMV2. The mutation, which was found by direct sequencing of the RAD51 gene, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed.
In 2 unrelated patients with sporadic MRMV2 (female probands from families 3 and 16), Meneret et al. (2014) identified heterozygous missense variants in the RAD51 gene (H47R and I137F) by direct Sanger sequencing. Both variants were inherited from the patients' unaffected mothers, and 1 of them (H47R) was also present in an unaffected brother. Functional studies and studies of patient cells were not performed. The patients were ascertained from a cohort of 6 familial and 20 simplex cases of congenital mirror movements who were specifically screened for mutations in the DCC (120470) and RAD51 genes.
In 9 individuals spanning 2 generations of a family (family A) with MRMV2, Franz et al. (2015) identified a heterozygous missense mutation in the RAD51 gene (R250Q; 179617.0006). The variant, which was found by a combination of linkage analysis and exome sequencing, segregated with the disorder in the family. Functional studies of the RAD51 variant and studies of patient cells were not performed. One variant carrier (patient IV.6) did not have overt mirror movements, but did show subtle mirror movements detected by an accelerometer glove.
INHERITANCE \- Autosomal dominant MUSCLE, SOFT TISSUES \- Pain or cramping during sustained manual activity NEUROLOGIC Central Nervous System \- Mirror movements, involuntary, usually of the upper limb and hand \- Difficulties in fine bimanual activities \- Writing fatigability \- Abnormal corticospinal tract decussation MISCELLANEOUS \- Onset in infancy or early childhood \- Disorder usually remains stable over time \- Incomplete penetrance (50%) MOLECULAR BASIS \- Caused by mutation in the homolog of S. cerevisiae RAD51 gene (RAD51, 179617.0003 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| MIRROR MOVEMENTS 2 | c3281089 | 4,517 | omim | https://www.omim.org/entry/614508 | 2019-09-22T15:55:02 | {"omim": ["614508"], "orphanet": ["238722"], "synonyms": ["Familial congenital controlateral synkinesia", "Hereditary congenital controlateral synkinesia", "Hereditary congenital mirror movements", "Isolated congenital controlateral synkinesia", "Isolated congenital mirror movements"], "genereviews": ["NBK279760"]} |
Fuchs heterochromic iridocyclitis (FHI) is an ocular disease of unknown etiology occurring in a very small percentage (0.5-6.2%) of uvietis cases, characterized by diffuse iris heterochromia or atrophy, keratic precipitates in the absence of synechiae, and in some cases evolving to glaucoma and vitreous opacities.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Fuchs heterochromic iridocyclitis | c0016782 | 4,518 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=263479 | 2021-01-23T18:26:21 | {"gard": ["6791"], "umls": ["C0016782"], "icd-10": ["H20.8"], "synonyms": ["FHI"]} |
Saito et al. (1989) described 2 sibs, a male and female born of a nonconsanguineous, relatively young couple, with a lethal acrorenal developmental complex. Both died of respiratory failure in the neonatal period. Radiologic features were symmetric mesomelic shortness of the limbs, fibular agenesis, oligosyndactyly, micrognathia, and hypoplastic ulna. The ears were abnormally formed, and the kidneys were cystic or hypoplastic. Some of the features, such as malformed ears and respiratory failure, are consistent with Potter sequence; however, the disorder appeared to be different from previously described forms of fibular aplasia/hypoplasia (Lewin and Opitz, 1986). Autopsy in the brother showed truncus arteriosus and ventricular septal defect. In the second pregnancy, that of the male, ultrasound detected 2 gestational sacs early in the pregnancy; one contained a fetus and the other regressed and disappeared by 15 weeks' gestation.
GU \- Cystic kidneys \- Hypoplastic kidneys Radiology \- Symmetric mesomelic limb shortness \- Fibular agenesis \- Oligosyndactyly \- Hypoplastic ulna Inheritance \- Autosomal recessive Resp \- Respiratory failure Growth \- Neonatal death Cardiac \- Truncus arteriosus \- Ventricular septal defect HEENT \- Micrognathia \- Malformed ears ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| FIBULOULNAR APLASIA OR HYPOPLASIA WITH RENAL ABNORMALITIES | c1856727 | 4,519 | omim | https://www.omim.org/entry/228940 | 2019-09-22T16:27:50 | {"mesh": ["C537226"], "omim": ["228940"], "orphanet": ["2256"]} |
Fear of submerged man-made objects
Submechanophobia
SpecialtyPsychology
Submechanophobia (from Latin sub 'under'; from English mechano; and from Ancient Greek φόβος (phóbos) 'fear') is a fear of submerged man-made objects, either partially or entirely underwater.[1][2]
## See also[edit]
Look up submechanophobia in Wiktionary, the free dictionary.
* List of phobias
* Thalassophobia – fear of the sea
## References[edit]
1. ^ Roane, Henry S.; Ringdahl, Joel E.; Falcomata, Terry S., eds. (2015). Clinical and Organizational Applications of Applied Behavior Analysis. Academic Press. p. 461. ISBN 978-0-12-420249-8.
2. ^ Linder, Courtney (November 29, 2019). "The 25 Coolest Shipwrecks In the World". Popular Mechanics. Retrieved July 7, 2020.
### Further reading[edit]
* Alexander, David E. (December 2019). "The strange case of the Richard Montgomery: on the evolution of intractable risk". Safety Science. 120: 575–582. doi:10.1016/j.ssci.2019.08.010. Retrieved July 7, 2020.
* Bryan, Meredith (May 19, 2016). "Can Virtual Reality Cure My (Really Weird) Phobia?". Elle. Retrieved July 7, 2020.
This psychology-related article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Submechanophobia | None | 4,520 | wikipedia | https://en.wikipedia.org/wiki/Submechanophobia | 2021-01-18T19:01:25 | {"wikidata": ["Q97173234"]} |
## Clinical Features
Mendoza-Londono et al. (2005) described the clinical characterization, molecular analysis, and genetic mapping of a distinct genetic disorder, designated by the acronym CDAGS, which summarizes its most prominent features: 'C' stands for craniosynostosis and clavicular hypoplasia; 'D' stands for delayed closure of the fontanel, cranial defects, and, in some patients, deafness; 'A' stands for anal anomalies, including anterior placement of the anus and imperforate anus; 'G' stands for genitourinary malformations; and 'S' stands for skin eruption, which, in some patients, had been classified as porokeratosis. They identified the CDAGS phenotype in 4 families from different geographic regions and ethnic backgrounds. The families displayed an autosomal recessive pattern of inheritance. The craniofacial component of CDAGS overlapped with some of the features seen in cleidocranial dysplasia (CCD; 119600), an autosomal dominant disorder characterized by hypoplastic or absent clavicles, delayed closure of the cranial sutures and fontanels, dental anomalies, and delayed skeletal development.
One of the families studied by Mendoza-Londono et al. (2005) had been described by Flanagan et al. (1998), who reported coronal craniosynostosis, anal anomalies, and porokeratosis in 2 male sibs. One of the brothers had anterior imperforate anus, and the other had anterior placement of the anus. A third male sib and the parents were phenotypically normal. Flanagan et al. (1998) used the acronym CAP to designate the constellation of findings and suggested autosomal recessive inheritance, although X-linked inheritance or gonadal mosaicism could not be excluded.
Mapping
Mendoza-Londono et al. (2005) isolated DNA from all affected individuals and first-degree relatives and performed a genomewide screen with 400 markers. Analysis of the genotype data yielded a maximum estimated lod score of 2.38 for markers D22S283 and D22S274 on 22q12-q13. Haplotype analysis narrowed the region of interest to a 34-cM interval between D22S1163 and D22S1170.
Molecular Genetics
In affected members of the family originally reported by them, Flanagan et al. (1998) analyzed the FGFR1 (136350), FGFR2 (176943), FGFR3 (134934), and TWIST1 (601622) genes for mutations associated with craniosynostosis; no abnormalities were found.
To identify the molecular basis of the CDAGS phenotype, Mendoza-Londono et al. (2005) initially undertook a candidate gene approach. Because CDAGS shares multiple features with CCD, the authors considered RUNX2 (600211) and its coactivator CBFB (121360) as attractive candidates. They examined these and several other candidate genes, screening for mutations by direct sequencing of the coding regions and for microdeletions by fluorescence in situ hybridization, with negative results. Mendoza-Londono et al. (2005) hypothesized that the gene defect in CDAGS causes novel context-dependent dysregulation of multiple signaling pathways, including that of RUNX2, during osteoblast differentiation and craniofacial morphogenesis.
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Delayed closure of fontanels \- Large anterior and posterior fontanels \- Brachycephaly Face \- Frontal bossing \- Midface hypoplasia Ears \- Sensorineural hearing loss Eyes \- Sparse eyelashes \- Sparse eyebrows \- Ptosis \- Ectropion Mouth \- Cleft palate CHEST Ribs Sternum Clavicles & Scapulae \- Clavicular hypoplasia \- Short ribs ABDOMEN Gastrointestinal \- Imperforate anus \- Anal atresia GENITOURINARY External Genitalia (Male) \- Hypospadias \- Urethrorectal fistula Internal Genitalia (Female) \- Rectovaginal fistula SKELETAL Skull \- Craniosynostosis (coronal, lambdoid, sagittal) \- Bilateral parietal foramina Spine \- Kyphosis SKIN, NAILS, & HAIR Skin \- Hyperkeratotic plaques (face, elbow, knees) \- Porokeratosis Hair \- Sparse eyelashes \- Sparse eyebrows \- Sparse scalp hair NEUROLOGIC Central Nervous System \- Developmental delay MISCELLANEOUS \- CDAGS is an acronym - Craniosynostosis and Clavicular hypoplasia, Delayed closure of fontanel, Anal anomalies, Genitourinary malformations, and Skin eruption ▲ Close
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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
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| CDAGS SYNDROME | c1864186 | 4,521 | omim | https://www.omim.org/entry/603116 | 2019-09-22T16:13:20 | {"mesh": ["C536789"], "omim": ["603116"], "orphanet": ["85199"], "synonyms": ["Alternative titles", "CRANIOSYNOSTOSIS, ANAL ANOMALIES, AND POROKERATOSIS", "CAP SYNDROME"]} |
A number sign (#) is used with this entry because perinatal lethal Gaucher disease is caused by homozygous or compound heterozygous mutation in the glucocerebrosidase gene (GBA; 606463) on chromosome 1q22.
Description
Perinatal lethal Gaucher disease is considered to be a distinct form of type II Gaucher disease (230900) (Mignot et al., 2003).
Clinical Features
Drukker et al. (1970) reported a Sephardic-Jewish infant with the infantile form of Gaucher disease. Intracranial hemorrhage led to death at age 48 hours. Owada et al. (1977) described 2 Japanese infants with Gaucher disease. Fractions from the liver showed no glucocerebroside activity.
Lui et al. (1988) reported 2 Lebanese sibs with acute infantile cerebral Gaucher disease with prominent collodion skin. Generalized thick skin, hepatosplenomegaly, and hypotonia were noted at birth. The infants showed respiratory distress, convulsions, and thrombocytopenia; 1 had joint contractures. In both, the tight collodion ichthyotic skin began to peel in large sheets. Both died as infants. Postmortem examination of 1 sib showed Gaucher cells in lymph nodes, thymus, liver, spleen, adrenals, and bone marrow. Keratinocytes showed normal maturation with hyperkeratosis and reduced granular layer. No abnormal storage products were identified in the skin. Lui et al. (1988) postulated that the skin abnormalities in these children may have resulted from disturbed composition of lipid in the stratum corneum.
Sidransky et al. (1992) described 2 cases of neonatal Gaucher disease: one, of Greek ancestry, died at age 2 months; the second, of African American ethnicity, died at age 7 days. The second baby required mechanical ventilation throughout life and had stiff, thick, shiny collodion skin. Biopsy demonstrated lamellar exfoliated ichthyosis. In a review of 15 additional patients with neonatal Gaucher disease from 11 unrelated families, they noted that 6 infants in 4 families had Coombs-negative hydrops. They pointed out that the phenotype in these infants is analogous to the Gaucher mouse created by targeted disruption in the mouse glucocerebroside gene.
Fujimoto et al. (1995) described male and female sibs of Mexican extraction who presented with ichthyotic skin at birth and subsequently developed neurologic manifestations of type II Gaucher disease. The authors suggested that Gaucher disease should be considered in the differential diagnosis of congenital ichthyosis, even if the scaling resolves spontaneously.
Sidransky et al. (1996) reported 2 conceptuses from an Afghan family with perinatal lethal Gaucher disease. The first was shown to have severe hydrops fetalis with bilateral hydrothorax and fetal hypokinesia with multiple joint contractures. Fetal blood sampling indicated thrombocytopenia and abnormal liver enzymes. Delivery was induced at 33 weeks' gestation. Other features included joint contractures, hepatosplenomegaly, pulmonary hypoplasia, muscular atrophy, flattened nose with small nares, malformed ears, and tight and shiny skin. The infant died less than an hour after delivery. In the next pregnancy a prenatal diagnosis of Gaucher disease was made by enzyme assay on cultured amniocytes obtained at week 15. Neither hydrops nor joint contractures was found in the fetus aborted at 23 weeks' gestation. The findings were comparable to those in the 'knockout' Gaucher mouse in which absence of enzyme is incompatible with long survival (Sidransky et al., 1992; Tybulewicz et al., 1992).
Stone et al. (1999) reported 2 female sibs and an unrelated male infant with perinatal lethal Gaucher disease. The female sibs were born of a consanguineous couple from Cape Verde. The older sib was hydropic and delivered dead at 31 weeks' gestation. The second infant was hydropic and delivered alive at 30 weeks' gestation but died shortly after birth. The male infant was delivered at 36 weeks' gestation weighing 1900 grams with dysmorphic features including triangular face, small malformed ears, a small thorax, joint contractures, and severe microstomia, hepatosplenomegaly, and collodion-like skin. The infant was immobile except upon painful stimuli and was hypertonic with an absent Moro reflex. GBA enzyme activity was severely decreased in leukocytes from the patient. The patient's father was from Surinam and his mother was Dutch.
Stone et al. (2000) reported a male infant born to consanguineous Lebanese parents with perinatal lethal Gaucher disease. Ultrasound scanning demonstrated reduced fetal movement, neck hyperextension, and hepatomegaly. He was born at 34 weeks' gestation and died shortly thereafter. Autopsy findings included thick collodion-like skin, ectropia, joint contractures, hepatosplenomegaly, and facial dysmorphism. Gaucher cells were seen in many tissues. The diagnosis of Gaucher disease was confirmed enzymatically.
Finn et al. (2000) reported a case of type II Gaucher disease in a female Mexican infant who was born at 34 weeks' gestation and died at 2 days of age with arthrogryposis, collodion membrane, minimal neurologic reflexes and few spontaneous movements, hepatosplenomegaly, and other malformations. 'Gaucher cells' were present in the spleen, lymph nodes, bone marrow, brain, spinal cord, and other sites. There was extensive destruction, apoptosis, and loss of neurons in the brain and the spinal cord. Glucocerebroside accumulated in neurons and microglia of the brain. Beta-glucocerebrosidase activity was absent in all tissues tested. The patient was homozygous for a rare null allele, RecNciI.
Mignot et al. (2003) reported a series of perinatal lethal Gaucher disease cases highlighting the specificity of this phenotype. They retrospectively studied 8 cases of proven Gaucher disease with fetal onset. Nonimmune hydrops fetalis was present in all cases but one, and associated with hepatosplenomegaly, ichthyosis, arthrogryposis, and facial dysmorphism. The similarities between these cases and 33 previously described cases allowed a better delineation of the perinatal lethal Gaucher disease phenotype. When hydrops is absent, neurologic involvement begins in the first week and leads to death within 3 months. Hepatosplenomegaly is a major sign, and is associated with ichthyosis, arthrogryposis, and facial dysmorphism in 35 to 43% of cases.
Biochemical Features
Orvisky et al. (2000) found increased levels of glucosylsphingosine (Glc-sph), a cytotoxic compound, in mice with a severe form of Gaucher disease created with a null Gba allele. Compared with unaffected littermates, affected mice had approximately a 100-fold elevation of Glc-sph in brain, as well as elevated levels in other tissues. This accumulation was detected in utero by embryonic day 13 and increased progressively throughout gestation. Similarly, elevated Glc-sph levels were seen in 2 human fetuses with perinatal lethal Gaucher disease, indicating that therapy initiated after birth may be too late to prevent sequelae of progressive neurologic damage that begins early in gestation. The findings suggested that the accumulation of Glc-sph may be responsible for the rapid demise of Gba-null mice and the devastating clinical course seen in patients with perinatal lethal Gaucher disease.
Molecular Genetics
Sidransky et al. (1996) described homozygosity for a triply mutant recombinant GBA allele (606463.0009) in 2 conceptuses from an Afghan family with lethal perinatal Gaucher disease. Stone et al. (2000) found that a male infant with perinatal lethal Gaucher disease, born to consanguineous Lebanese parents, was homozygous for the triply mutant recombinant allele.
In 2 female sibs with perinatal lethal Gaucher disease, Stone et al. (1999) identified a homozygous mutation in the GBA gene (H311R; 606463.0037).
Stone et al. (2000) reported 6 children who presented at birth with collodion-type skin changes and hepatosplenomegaly and were found to be beta-glucocerebrosidase-deficient. All died shortly after birth or in the first year of life from respiratory insufficiency or progressive neurologic disease. Three of the cases were homozygous for GBA mutations (see 606463.0009 and 606463.0042) and the others were compound heterozygotes.
In a premature infant with the perinatal lethal form of Gaucher disease, Felderhoff-Mueser et al. (2004) identified compound heterozygosity for 2 mutations in the GBA gene (606463.0004 and 606463.0046).
INHERITANCE \- Autosomal recessive GROWTH Other \- Intrauterine growth retardation (IUGR) HEAD & NECK Head \- Microcephaly Face \- Dysmorphic facies (30%) \- Triangular face \- Retrognathia \- Micrognathia Ears \- Small ears \- Low-set ears \- Malformed ears Eyes \- Strabismus \- Hypertelorism Nose \- Flat nasal bridge \- Anteverted nares \- Small nose Mouth \- Microstomia \- Everted lips \- Open mouth CARDIOVASCULAR Heart \- Cardiomegaly RESPIRATORY \- Respiratory distress \- Apnea Lung \- Lung hypoplasia with fetal hydrops CHEST External Features \- Small thorax ABDOMEN External Features \- Ascites Liver \- Hepatomegaly \- Liver failure Spleen \- Splenomegaly Gastrointestinal \- Dysphagia SKELETAL \- Arthrogryposis SKIN, NAILS, & HAIR Skin \- Collodion skin \- Shiny, taut, erythematous skin \- Ichthyosis \- Desquamation of skin soon after birth \- Petechiae \- Purpura Skin Histology \- Hyperkeratosis NEUROLOGIC Central Nervous System \- Progressive neurologic deterioration \- Seizures \- Apathy \- Decreased spontaneous movements at birth \- Hypokinesia \- Akinesia \- Opisthotonos \- Secondary hypertonia \- Loss of primary reflexes \- Enlarged cerebral ventricles \- Loss of neurons HEMATOLOGY \- Thrombocytopenia \- Anemia PRENATAL MANIFESTATIONS \- Intrauterine growth retardation Movement \- Decreased fetal movements Amniotic Fluid \- Hydrops fetalis, nonimmune \- Polyhydramnios Delivery \- Premature birth LABORATORY ABNORMALITIES \- Decreased beta-glucocerebrosidase protein and activity \- Gaucher cells, diffuse, in spleen, liver, lymph nodes, bone marrow, central nervous system MISCELLANEOUS \- Death in utero (30%) \- Hydrops fetalis is associated with death in utero (90%) or within 2 days of birth \- In the absence of hydrops, death occurs within 3 months \- Most severe form of Gaucher disease \- Considered to be a severe form of Gaucher disease type II ( 230900 ) MOLECULAR BASIS \- Caused by mutation in the acid beta-glucosidase gene (GBA, 606463.0004 ) ▲ 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
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| GAUCHER DISEASE, PERINATAL LETHAL | c1842704 | 4,522 | omim | https://www.omim.org/entry/608013 | 2019-09-22T16:08:29 | {"doid": ["0110960"], "mesh": ["C564306"], "omim": ["608013"], "orphanet": ["85212", "355"], "synonyms": ["Alternative titles", "GAUCHER DISEASE, COLLODION TYPE"], "genereviews": ["NBK1269"]} |
## Summary
### Clinical characteristics.
ANKRD26-related thrombocytopenia is characterized by lifelong mild-to-moderate thrombocytopenia with a normal platelet size and no syndromic associations. Most individuals have normal hemostasis or a mild bleeding phenotype and do not develop severe spontaneous bleeding. Some individuals may have concomitant erythrocytosis and leukocytosis. The risk for myeloid malignancies (including myelodysplastic syndrome, acute myelogenous leukemia, and chronic myelogenous leukemia) is increased in individuals with ANKRD26 pathogenic variants.
### Diagnosis/testing.
The diagnosis of ANKRD26-related thrombocytopenia is established in a proband by the presence of lifelong thrombocytopenia and identification of a heterozygous pathogenic variant in ANKRD26 on molecular genetic testing.
### Management.
Treatment of manifestations: Adjunct hemostatic agents (e.g., antifibrinolytics, desmopressin) for bleeding or a major surgical procedure; platelet transfusions are reserved for severe bleeding or procedures with a high bleeding risk.
Prevention of secondary complications: For individuals with a myeloid neoplasm, careful consideration of stem cell transplant eligibility and pre-transplant therapies undertaken through a large academic institution with experience in the management of individuals with germline predisposition syndromes.
Surveillance: Surveillance for early detection of myeloid neoplasms should include an annual complete blood count with bone marrow examination if abnormalities are noted.
Evaluation of relatives at risk: It is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk relatives of an affected individual by evaluation of the platelet count and molecular genetic testing of the ANKRD26 pathogenic variant in the family in order to identify as early as possible those who may benefit from surveillance.
### Genetic counseling.
ANKRD26-related thrombocytopenia is inherited in an autosomal dominant manner. All individuals reported to date have an affected parent. Each child of an individual with ANKRD26-related thrombocytopenia has a 50% chance of inheriting the ANKRD26 pathogenic variant. Once the ANKRD26 pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible; however, phenotypic variability (due to variable expressivity) within families is observed.
## Diagnosis
ANKRD26-related thrombocytopenia is a nonsyndromic congenital thrombocytopenia disorder lacking pathognomonic features and thus requiring molecular confirmation of a heterozygous ANKRD26 pathogenic variant to establish a diagnosis. Formal diagnostic criteria have not been published.
### Suggestive Findings
ANKRD26-related thrombocytopenia should be suspected in individuals with the following:
* Lifelong mild-to-moderate thrombocytopenia (<150 x 109/L, confirmed with repeat examination)
* Normal platelet size (mean platelet volume [fL] per reference interval of automated instrument)
* Absent or minimal bleeding tendency
* Family history of thrombocytopenia with an autosomal dominant pattern of inheritance
* Personal or family history of myeloid neoplasms at a young age
* Previous or suspected diagnosis of immune thrombocytopenia (ITP) without improvement on immunosuppressive treatment
* Absence of features suggesting syndromic association
### Establishing the Diagnosis
The diagnosis of ANKRD26-related thrombocytopenia is established in a proband by the presence of lifelong thrombocytopenia and identification of a heterozygous pathogenic variant in ANKRD26 on molecular genetic testing (see Table 1).
Molecular genetic testing approaches can include single-gene testing and use of a multigene panel:
* Single-gene testing. Sequence analysis of ANKRD26 should include the 5' untranslated region (5'UTR) to detect known regulatory pathogenic variants. Of note, all individuals diagnosed with ANKRD26-related thrombocytopenia to date have had pathogenic variants identified by ANKRD26 sequence analysis, primarily of the 5'UTR; therefore, the utility of ANKRD26 deletion/duplication analysis is unclear.
* A multigene panel that includes ANKRD26 and other genes of interest (see Differential Diagnosis) may be considered. Note: (1) The genes included and the sensitivity of multigene panels 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 unknown significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include custom laboratory-designed panels and/or custom phenotype-focused exome analysis. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests (5) The multigene panel should include sequence analysis of ANKRD26 5'UTR.
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 ANKRD26-Related Thrombocytopenia
View in own window
Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method
ANKRD26Sequence analysis 3, 442 of 42 reported probands 5
Gene-targeted deletion/duplication analysis 6Unknown 7
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
See Molecular Genetics for information on allelic variants detected in this gene.
3\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. 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\.
Must include sequencing of 5'UTR, which has a significant number of the known pathogenic variants
5\.
Al Daama et al [2013], Noris et al [2013], Marquez et al [2014], Ouchi-Uchiyama et al [2015], Perez Botero et al [2015], Averina et al [2017], Ferrari et al [2017], Marconi et al [2017]
6\.
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.
7\.
No data on detection rate of gene-targeted deletion/duplication analysis are available.
## Clinical Characteristics
### Clinical Description
Individuals with ANKRD26-related thrombocytopenia usually present with lifelong mild-to-moderate thrombocytopenia with a normal platelet size and no syndromic associations. Incidental presentation following routine complete blood count is not uncommon. Some individuals are identified after developing a myeloid neoplasm such as acute myeloid leukemia or myelodysplastic syndrome.
Bleeding history. Most individuals have normal hemostasis or a mild bleeding phenotype and do not develop severe spontaneous bleeding.
Complete blood counts
* Mild to moderate thrombocytopenia (50 to 150 x 109/L) is usually observed. Some individuals can have platelets as low as <10 x 109/L while others have transient correction of thrombocytopenia to >150 x109/L during infectious episodes.
* Platelet size is normal by automated method (mean platelet volume) or microscopic analysis.
* Platelets have normal granularity on light microscopy.
* Individuals can have erythrocytosis, with some presenting with hemoglobin as high as 18.5 g/dL.
* Some individuals have presented with leukocytosis.
Platelet structure and function studies. While abnormal platelet aggregation studies, decreased expression of platelet glycoprotein Ia (GPIa), decreased alpha granules, and increased canalicular network on platelet transmission electron microscopy have been reported, no consistent or definitive structural or functional alterations have been established.
Bone marrow biopsy. On bone marrow biopsy, megakaryocytes are increased in number but small and hypolobated [Noris et al 2011, Perez Botero et al 2015].
Predisposition to myeloid malignancies. The incidence of myeloid malignancies, including myelodysplastic syndrome (MDS), acute myelogenous leukemia (AML), and chronic myelogenous leukemia, is increased in families with pathogenic variants in ANKRD26, with one series showing an estimated 24-fold increased risk of AML compared to the general population [Noris et al 2013]. Prevalence of AML or MDS among individuals with ANKRD26-related thrombocytopenia is about 8% (see Molecular Genetics, Cancer predisposition).
### Genotype-Phenotype Correlations
No consistent genotype-phenotype correlations are known.
### Penetrance
Penetrance for thrombocytopenia is complete in individuals with an ANKRD26 pathogenic variant. The risk of transformation to a myeloid malignancy is variable [Noris et al 2013].
### Prevalence
The prevalence for this rare disorder is unknown. Fewer than 200 affected individuals have been reported. However, in one large cohort, ANKRD26 5'UTR pathogenic variants appeared to be one of the most frequent causes of inherited thrombocytopenia [Noris et al 2011]. Due to the recent description of this entity and difficulties in diagnosis, the number of affected individuals may be higher.
## Differential Diagnosis
Due to the clinical and genetic heterogeneity and low incidence of inherited platelet disorders, the diagnosis is challenging, and sometimes inherited platelet disorders are misdiagnosed as idiopathic thrombocytopenic purpura (immune thrombocytopenia; ITP). Complex diagnostic algorithms have been proposed [Balduini et al 2013a].
### Table 2.
Disorders to Consider in the Differential Diagnosis of ANKRD26-Related Thrombocytopenia
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DisorderGene(s)MOIClinical Features
OverlappingDistinguishing
Familial platelet disorder w/predisposition to acute myelogenous leukemia (FPD/AML; OMIM 151385)RUNX1ADNonsyndromic thrombocytopenia w/normal platelet size & predisposition to myeloid neoplasmsFPD/AML:
* Can have normal platelet counts
* More bleeding due to platelet storage pool disorder (dense granule deficiency)
ETV6-related thrombocytopenia (thrombocytopenia-5, ETV6-RT)ETV6ADNonsyndromic thrombocytopenia w/normal platelet size & predisposition to myeloid neoplasmsETV6-RT:
* Can have red cell macrocytosis & neutropenia
* Predisposes to lymphoid malignancy
CYCS-related thrombocytopenia (thrombocytopenia-4, CYCS-RT; OMIM 616216)CYCSADNonsyndromic thrombocytopenia w/normal platelet sizeCYCS-RT: Does not predispose to neoplasms
Immune thrombocytopenia (ITP)NANAThrombocytopenia w/normal (or mildly elevated) platelet size, minimal bleeding unless thrombocytopenia is severeITP:
* Sporadic
* Family history negative
* Prior platelet count normal
* Responds to immunosuppressive treatments
* Does not predispose to malignancy
AD = autosomal dominant; MOI = mode of inheritance; NA = not applicable; RT = related thrombocytopenia
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with ANKRD26-related thrombocytopenia, the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended:
* Clinical evaluation by a hematologist and a complete blood count including peripheral smear review for early detection of myeloid neoplasms
* Consideration of bone marrow aspirate and biopsy at initial evaluation to exclude hematologic malignancies if there are other cytopenias, or abnormalities in:
* Mean corpuscular volume
* Cell morphology
* Leukocyte differential
* Consultation with a clinical geneticist and/or genetic counselor
### Treatment of Manifestations
Most individuals are asymptomatic and undergo observation and surveillance.
When bleeding is present or a major surgical procedure is required, adjunct hemostatic agents such as antifibrinolytics or desmopressin can be given. Platelet transfusions are reserved for severe bleeding or procedures with a high bleeding risk [Balduini et al 2013b].
Thrombopoietin analogs have been used selectively for short periods of time (preoperative). The long-term safety has not been established [Pecci 2013, Fiore et al 2016].
### Prevention of Secondary Complications
Once a myeloid neoplasm has been diagnosed, careful consideration of stem cell transplant eligibility and pre-transplant therapies should be undertaken. This is best accomplished at a large academic institution with experience in the management of individuals with germline predisposition syndromes [Babushok et al 2016].
### Surveillance
Surveillance for early detection of myeloid neoplasms is indicated in all individuals with ANKRD26-related thrombocytopenia. Guidelines have not been published on the type of testing or frequency of surveillance. A complete blood count on an annual basis with bone marrow examination if abnormalities are noted is commonly recommended.
### Agents/Circumstances to Avoid
If a myeloid neoplasm that requires allogeneic stem cell transplantation develops and a related donor is being considered, a donor who does not have the ANKRD26 pathogenic variant present in the family should be used [Godley 2014].
### Evaluation of Relatives at Risk
It is appropriate to consider clarifying the genetic status of apparently asymptomatic older and younger at-risk relatives of an affected individual by evaluation of the platelet count and molecular genetic testing of the ANKRD26 pathogenic variant in the family in order to identify those who may benefit from surveillance.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Pregnancy Management
Platelet counts and bleeding complications should be monitored during pregnancy. While the thrombocytopenia itself (particularly if mild) is unlikely to affect the pregnancy, low platelet counts can limit the ability to receive epidural analgesia or neuroaxial anesthesia. Strategies to increase platelet count (transfusion) can be considered on an individual basis in consultation with the anesthesiologist.
### Therapies Under Investigation
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| ANKRD26-Related Thrombocytopenia | None | 4,523 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK507664/ | 2021-01-18T21:45:20 | {"synonyms": ["Thrombocytopenia 2 (THC2)"]} |
## Clinical Features
Shprintzen and Goldberg (1979) described a 'new' autosomal dominant malformation syndrome characterized by mildly dysmorphic facies, omphalocele, scoliosis, learning disabilities, and pharyngeal and laryngeal hypoplasia. A father and 3 daughters were affected; one of the daughters died in infancy, probably of airway narrowing. The father had had omphalocele repair, had a high pitched voice, and by fiberoptic endoscopy was discovered to have severe constriction of the glottic and subglottic airway. The larynx was short in the anteroposterior dimension, the epiglottis was omega-shaped, and the pharyngeal lumen was about half normal in diameter. He had poor muscle tone and had been a poor student. One daughter was noted to have a single umbilical artery and had prolonged respiratory problems in the neonatal period, remaining in intensive hospital care for a month. She repeated the first grade. An unusual eyebrow pattern was described in the father and the 2 living daughters. The older daughter has a full scale IQ was 87. Both daughters had scoliosis. The columella was short, producing flaring of the nostrils. Epicanthus was striking in the daughters. (Shprintzen's name is also associated with the velocardiofacial syndrome (192430), which he first described, and with the Shprintzen-Goldberg craniosynostosis syndrome (182212).)
Zelante et al. (2006) reported a 6-year-old boy born with omphalocele and imperforate anus who developed scoliosis at age 4 and had a facial appearance similar to that of the patients originally described by Shprintzen and Goldberg (1979). The boy also had abnormal esophageal motility, narrow shoulders, webbed neck, and unilateral ectopic testis. Laryngeal hypoplasia was diagnosed at 2 years of age because of a high-pitched voice, but did not cause respiratory problems. Zelante et al. (2006) concluded that this patient represented a second observation of the syndrome described by Shprintzen and Goldberg (1979).
INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature (<25% centile) Weight \- Low weight (<25% centile) HEAD & NECK Face \- Mildly dysmorphic facies Eyes \- Epicanthus \- Unusual eyebrow pattern \- S-shaped eyelids Nose \- Short columella \- Flared nostrils \- Broad nasal bridge Mouth \- Thin lips \- Downturned oral commissures Neck \- Webbed neck (1 patient) RESPIRATORY \- Neonatal respiratory distress Nasopharynx \- Pharyngeal hypoplasia \- Constricted glottic and subglottic airway Larynx \- Anteroposteriorly shortened larynx \- Laryngeal hypoplasia CHEST External Features \- Narrow shoulders (1 patient) ABDOMEN External Features \- Omphalocele Gastrointestinal \- Imperforate anus (1 patient) SKELETAL Spine \- Scoliosis \- Kyphosis \- Lumbar lordosis MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Learning disability VOICE \- High pitched voice PRENATAL MANIFESTATIONS Placenta & Umbilical Cord \- Single umbilical artery ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| SHPRINTZEN OMPHALOCELE SYNDROME | c1866958 | 4,524 | omim | https://www.omim.org/entry/182210 | 2019-09-22T16:34:51 | {"mesh": ["C537329"], "omim": ["182210"], "orphanet": ["3164"], "synonyms": ["Alternative titles", "OMPHALOCELE WITH HYPOPLASIA OF PHARYNX AND LARYNX, LEARNING DISABILITY, DYSMORPHIC FACIES, AND SCOLIOSIS", "PHARYNX AND LARYNX HYPOPLASIA WITH OMPHALOCELE"]} |
## Cloning and Expression
Nagayama et al. (1989) isolated a TSHR cDNA from a human thyroid cDNA library. The deduced 764-amino acid protein has a molecular mass of 86.8 kD and contains a signal peptide, 7 transmembrane regions, 5 potential glycosylation sites, and a short intracytoplasmic region. The TSHR cDNA encoded a functional receptor that activated adenylate cyclase in response to TSH.
Libert et al. (1989) used a dog Tshr cDNA to isolate a human TSHR cDNA from a thyroid cDNA library. The cDNA encodes a deduced 744-amino acid protein with 90.3% homology to the dog protein. Two major 4.6- and 4.4-kb mRNA transcripts were identified, suggesting alternative splicing.
By analyzing several TSHR cDNA clones, Misrahi et al. (1990) determined that the mature TSHR polypeptide contains 743 amino acids with a calculated molecular mass of 84.5 kD. The putative TSH receptor has a 394-residue extracellular domain, a 266-residue transmembrane domain, and an 83-residue intracellular domain. The authors observed a high degree of homology with the luteinizing hormone/choriogonadotropin receptor (LHCGR; 152790).
Kakinuma and Nagayama (2002) found that the TSHR gene can express at least 5 alternatively spliced forms.
Gene Function
The TSH receptor differs from the LHCG receptor by the presence of 2 unique insertions of 8 and 50 amino acids in the extracellular domain. Wadsworth et al. (1990) showed that the 8-amino acid tract near the amino terminus of the TSH receptor is an important site of interaction with both TSH and autoantibodies against the TSH receptor (thyroid-stimulating immunoglobulins, TSI). Either deletion or substitution of this region abolished the interaction, whereas a deletion of the 50-amino acid tract had no effect.
Contiguous to the 5-prime end of the thyroid transcription factor-1 (TTF1; 600635) element upstream and within the TSHR promoter is an element on the noncoding strand with single-strand binding activity that is important for regulation of TSHR expression. Ohmori et al. (1996) identified a cDNA encoding a single-strand binding protein (SSBP), referred to as SSBP1, that forms a specific complex with this element on the noncoding strand of TSHR. SSBP1 is a ubiquitous transcription factor that contributes to TSHR maximal expression, and mutation analyses showed that a GXXXXG motif is important for the binding and enhancer function of SSBP1. The authors concluded that the common transcription factors regulate TSHR and major histocompatibility gene expression. They also concluded that SSBP1 is a member of a family of SSBPs that interact with RNA and with the promoter of retroviruses, and are important in RNA processing. Members of this family also can interact with c-myc (190080), a gene linked to growth and DNA replication.
Biochemical Features
The high sequence homology with the LHCG receptor, which is composed of a single polypeptide chain, led many to suppose a similar structure for the TSH receptor. However, Loosfelt et al. (1992) presented evidence for a heterodimeric structure of TSHR. The extracellular (hormone-binding) alpha subunit had an apparent molecular mass of 53 kD, whereas the membrane-spanning beta subunit seemed heterogeneous and had an apparent molecular mass of 33 to 42 kD. Human thyroid membranes contained 2.5 to 3 times as many beta subunits as alpha subunits; however, the 2 subunits probably derive from a single gene since a single reading frame was demonstrated by cDNA cloning and sequencing. The exact site of cleavage that results in the 2 subunits was difficult to define.
The TSH receptor is the antigen targeted by autoantibodies in Graves disease (275000). By PCR amplification of specific cDNA, Feliciello et al. (1993) demonstrated that mature TSH receptor mRNA is expressed in the retroorbital tissue of both healthy subjects and patients with Graves disease. Of other tissues and cells tested, only thyroid tissue expressed the TSHR mRNA. The findings provided a link between orbital involvement and thyroid disease in Graves disease.
Graves et al. (1999) used epitope-mapped monoclonal and polyclonal antibodies to TSHR as immunoblot probes to detect and characterize the molecular species of the receptor present in normal human thyroid tissue. In reduced membrane fractions, both full-length (uncleaved) holoreceptor and cleavage-derived subunits of the holoreceptor were detected. Uncleaved holoreceptor species included a nonglycosylated form of apparent molecular mass 85 kD and 2 glycosylated forms of approximately 110 and 120 kD. The membranes also contained several forms of cleavage-derived TSHR alpha and beta subunits. Alpha subunits were detected by antibodies to epitopes localized within the N-terminal end of the TSHR ectodomain and migrated diffusely between 45 and 55 kD, reflecting a differentially glycosylated status. Several species of beta subunit were present, the most abundant having apparent molecular masses of 50, 40, and 30 kD. The authors concluded that posttranslational processing of the TSHR occurs in human thyroid tissue and involves multiple cleavage sites.
Lazar et al. (1999) studied the expression of 4 thyroid-specific genes (sodium-iodide symporter (NIS, or SLC5A5; 601843), thyroid peroxidase (TPO; 274500), thyroglobulin (TG; 188450), and TSHR) as well as the gene encoding glucose transporter-1 (GLUT1, or SLC2A1; 138140) in 90 human thyroid tissues. Messenger RNAs were extracted from 43 thyroid carcinomas (38 papillary and 5 follicular), 24 cold adenomas, 5 Graves thyroid tissues, 8 toxic adenomas, and 5 hyperplastic thyroid tissues; 5 normal thyroid tissues were used as reference. A kinetic quantitative PCR method, based on the fluorescent TaqMan methodology and real-time measurement of fluorescence, was used. NIS expression was decreased in 40 of 43 (93%) thyroid carcinomas and in 20 of 24 (83%) cold adenomas; it was increased in toxic adenomas and Graves thyroid tissues. TPO expression was decreased in thyroid carcinomas but was normal in cold adenomas; it was increased in toxic adenomas and Graves thyroid tissues. TG expression was decreased in thyroid carcinomas but was normal in the other tissues. TSHR expression was normal in most tissues studied and was decreased in only some thyroid carcinomas. In thyroid cancer tissues, a positive relationship was found between the individual levels of expression of NIS, TPO, TG, and TSHR. No relationship was found with the age of the patient. Higher tumor stages (stages greater than I vs stage I) were associated with lower expression of NIS and TPO. Expression of the GLUT1 gene was increased in 1 of 24 (4%) adenomas and in 8 of 43 (19%) thyroid carcinomas. In 6 thyroid carcinoma patients, 131-I uptake was studied in vivo. NIS expression was low in all samples, and 3 patients with normal GLUT1 expression had 131-I uptake in metastases, whereas the other 3 patients with increased GLUT1 gene expression had no detectable 131-I uptake. The authors concluded that (1) reduced NIS gene expression occurs in most hypofunctioning benign and malignant thyroid tumors; (2) there is differential regulation of the expression of thyroid-specific genes; and (3) an increased expression of GLUT1 in some malignant tumors may suggest a role for glucose-derivative tracers to detect in vivo thyroid cancer metastases by positron-emission tomography scanning.
Chia et al. (2007) studied the diagnostic value of circulating TSHR mRNA for preoperative detection of differentiated thyroid cancer (DTC) in patients with thyroid nodules. Based on cytology/pathology, 88 patients had DTC and 119 had benign thyroid disease. The TSHR mRNA levels in cancer patients were significantly higher than in benign disease (P less than 0.0001). At a cutoff value of 1.02 ng/g total RNA, the TSHR mRNA correctly classified 78.7% of patients preoperatively (sensitivity = 72.0%; specificity = 82.5%). Chia et al. (2007) concluded that TSHR mRNA measured with fine needle aspirations enhances the preoperative detection of cancer in patients with thyroid nodules, reducing unnecessary surgeries, and immediate postoperative levels can predict residual/metastatic disease.
Gene Structure
Kakinuma and Nagayama (2002) determined that the TSHR gene contains 13 exons.
Mapping
Akamizu et al. (1990) mapped the TSHR gene to human chromosome 14 by study of somatic cell hybrid DNAs. By in situ hybridization, Rousseau-Merck et al. (1990) and Libert et al. (1990) regionalized the gene to 14q31.
Akamizu et al. (1990) mapped the mouse Tshr gene to chromosome 12 using linkage studies in interspecies backcross mice. Wilkie et al. (1993) also localized the mouse Tshr gene to chromosome 12.
Molecular Genetics
### Nonautoimmune Hyperthyroidism
Duprez et al. (1994) demonstrated heterozygous constitutively activating germline mutations in the TSHR gene (603372.0019; 603372.0020) in patients with hereditary nonautoimmune hyperthyroidism (609152). The functional in vitro characteristics of these 2 mutations were similar to those already described previously for autonomously functioning thyroid adenomas (Van Sande et al., 1995), and thus explained the development of thyroid hyperplasia and hyperthyroidism in the affected patients.
Paschke and Ludgate (1997) found reports of 4 infants with sporadic congenital hyperthyroidism occurring from a de novo germline mutation. In all cases, both parents were euthyroid. The authors noted that a number of gain-of-function mutations had been observed as somatic mutations in hyperfunctioning thyroid adenomas and in familial autosomal dominant hyperthyroidism. In their Figure 1, Paschke and Ludgate (1997) outlined the constitutively activating and inactivating mutations of the TSHR gene, as well as the location of somatic mutations found in thyroid carcinomas. At some locations, several different amino acid substitutions had been described. Most gain-of-function mutations were in exon 10.
### Hypothyroidism, Congenital, Nongoitrous, 1
Alberti et al. (2002) sequenced the entire TSHR gene in a series of 10 unrelated patients with slight (6.6-14.9 mU/liter) to moderate (24-46 mU/liter) elevations of serum TSH, associated with normal free thyroid hormone concentrations, consistent with a diagnosis of thyrotropin resistance (CHNG1; 275200). Thyroid volume was normal in all patients, except 2 with modest hypoplasia. Autoimmune thyroid disease was excluded in all patients on the basis of clinical and biochemical parameters. Eight patients had at least 1 first-degree relative bearing the same biochemical picture. TSHR mutations were detected in 4 of 10 (40%) cases by analyzing DNA from peripheral leukocytes (see, e.g., 603372.0006; 603372.0029; 603372.0030; 603372.0031; 603372.0013). The authors concluded that partial resistance to TSH action is a frequent finding among patients with slight hyperthyrotropinemia of nonautoimmune origin, and that heterozygous germline mutations of TSHR may be associated with serum TSH values fluctuating above the upper limit of the normal range.
Calebiro et al. (2005) cotransfected COS-7 cells with wildtype TSHR and mutant receptors (C41S, 603372.0013; C600R, 603372.0029; L467P, 603372.0030) found in patients with autosomal dominant partial TSH resistance. Variable impairment of cAMP response to bovine TSH stimulation was observed, suggesting that inactive TSHR mutants may exert a dominant-negative effect on wildtype TSHR. By using chimeric constructs of wildtype or inactive TSHR mutants fused to different reporters, the authors documented an intracellular entrapment, mainly in the endoplasmic reticulum, and reduced maturation of wildtype TSHR in the presence of inactive TSHR mutants. Fluorescence resonance energy transfer and coimmunoprecipitation experiments supported the presence of oligomers formed by wildtype and mutant receptors in the endoplasmic reticulum. Calebiro et al. (2005) concluded that their findings provide an explanation for the dominant transmission of partial TSH resistance.
### Familial Gestational Hyperthyroidism
Rodien et al. (1998) described a gain-of-function mutation of the TSHR gene (603372.0024) as the cause of familial gestational hyperthyroidism (603373). The mutation rendered the thyrotropin receptor hypersensitive to chorionic gonadotropin.
### Hyperfunctioning Thyroid Adenoma and Thyroid Carcinoma with Thyrotoxicosis, Somatic
In 3 of 11 hyperfunctioning thyroid adenomas, Parma et al. (1993) identified somatic mutations in the TSHR gene (603372.0002; 603372.0003). These mutations were restricted to tumor tissue.
By direct sequencing, Fuhrer et al. (1997) screened a consecutive series of 31 toxic thyroid nodules (TTNs) for mutations in exons 9 and 10 of the TSHR gene and in exons 7 to 10 of the Gs-alpha protein gene (GNAS1; 139320). Somatic TSHR mutations were identified in 15 of the 31 (48%) TTNs. The TSHR mutations were localized in the third intracellular loop (asp619 to gly, 603372.0002; ala623 to val; and a 27-bp deletion resulting in deletion of 9 amino acids at codons 613 to 621), the sixth transmembrane segment (phe631 to leu, 603372.0004; thr632 to ile; and asp633 to glu), the second extracellular loop (ile568 to thr), and the third extracellular loop (val656 to phe). One mutation, ser281 to asn, was found in the part of the extracellular domain encoded by exon 9. All of the identified TSHR mutations resulted in constitutive activity. No mutations were found in exons 7 to 10 of GNAS1. The authors concluded that constitutively activating TSHR mutations occur in 48% of TTNs, representing the most frequent molecular mechanism known to cause TTNs.
Parma et al. (1997) investigated 33 different, autonomous hot nodules from 31 patients for the presence of somatic mutations in the TSHR and Gs-alpha genes. Twenty-seven mutations (82%) were found in the TSHR gene, affecting a total of 12 different residues or locations. All but 2 of the mutations studied had previously been identified as activating mutations. The authors identified the 2 novel mutations as a point mutation causing a leu629-to-phe substitution (L629F; 603372.0022), a deletion of 12 bases removing residues 658-661 (asn-ser-lys-ile) at the C-terminal portion of exoloop 3 (del658-661). Only 2 mutations (6%) were found in Gs-alpha genes. In 4 nodules, no mutation was detected. Five residues (ser281, ile486, ile568, phe631, and asp633) were found to be mutated in 3 or 4 different nodules, making them hotspots for activating mutations. The authors concluded that in a cohort of patients from a moderately iodine-deficient area, somatic mutations increasing the constitutive activity of TSHR are the major cause of autonomous thyroid adenomas.
### Possible Association with Toxic Multinodular Goiter
Toxic multinodular goiter (TMNG) represents a frequent cause of endogenous hyperthyroidism, affecting 5 to 15% of such patients. To search for alterations of TSHR in autonomously functioning thyroid nodules (AFTN) and TMNG, Gabriel et al. (1999) used bidirectional, dye primer automated fluorescent DNA sequencing of the entire transmembrane domain and cytoplasmic tail of TSHR using DNA extracted from nodular regions of 24 patients with TMNG and 7 patients with AFTN. Eight of the 24 (33.3%) patients with TMNG were heterozygous for an asp727-to-glu polymorphism (D727E) in the cytoplasmic tail of TSHR. Three of the 24 (12.5%) patients with TMNG were heterozygous for a missense mutation, and 1 patient had multiple heterozygous mutations. Two patients had silent polymorphism of codons 460 and 618. The authors found no mutations in the transmembrane domain and cytoplasmic tail of TSHR in the 7 patients with AFTN, except for a silent polymorphism of codon 460 in 1. DNA fingerprinting of codon 727 using restriction enzyme NlaIII and genomic DNA confirmed the sequencing results in all cases, indicating that the sequence alterations were not somatic in nature. This technique was also used to examine peripheral blood genomic DNA from 52 normal individuals and 49 patients with Graves disease; 33.3% of TMNG (P of 0.019 vs normal subjects), 16.3% of Graves disease patients (p of 0.10 vs normal subjects), and 9.6% of normal individuals were heterozygous for the D727E polymorphism. Expression of the D727E variant in eukaryotic cells resulted in an exaggerated cAMP response to TSH stimulation compared with that of the wildtype TSHR. The authors concluded that the germline polymorphism D727E is associated with TMNG, and suggested that its presence is an important predisposing genetic factor in TMNG pathogenesis.
Muhlberg et al. (2000) compared the D727E frequencies of 128 European Caucasian patients with toxic nonautoimmune thyroid disease (83 with toxic adenoma, 31 with toxic multinodular goiter, and 14 with disseminated autonomy) with those of 99 healthy controls and 108 patients with Graves disease. They found no significant differences in codon 727 polymorphism frequencies between patients with autonomously functioning thyroid disorders (13.3%) and the healthy control group (16.2%). Moreover, the subtypes of toxic nonautoimmune thyroid disease were not related to significant differences in codon 727 polymorphism frequencies compared with the healthy control group. There was no significant difference between the polymorphism frequency among patients with Graves disease (21.3%) and that of healthy controls. The authors concluded that there was no association between the D727E polymorphism of the TSHR and toxic thyroid adenomas or toxic multinodular goiter in their study population.
Tonacchera et al. (2000) searched for inactivating TSHR or Gs-alpha mutations in areas of toxic or functionally autonomous multinodular goiters that appeared hyperfunctioning at thyroid scintiscan but did not clearly correspond to definite nodules at physical or ultrasonographic examination. Activating TSHR mutations were detected in 14 of these 20 hyperfunctioning areas, whereas no mutation was identified in nonfunctioning nodules or areas contained in the same gland. No Gs-alpha mutation was found. The authors concluded that activating TSHR mutations are present in the majority of nonadenomatous hyperfunctioning nodules scattered throughout the gland in patients with toxic or functionally autonomous multinodular goiter.
### Possible Association with Susceptibility to Graves Disease
Although Heldin et al. (1991) and Bahn et al. (1994) suggested that substitutions in the TSHR gene (D36H; 603372.0001 and pro52-to-thr; P52T) were associated with Graves disease (275000) and Graves ophthalmopathy, respectively, Simanainen et al. (1999) reported that the D36H and P52T substitutions were polymorphic variants with a frequency of approximately 5% and 7.3%, respectively. Simanainen et al. (1999) found no association between these 2 polymorphisms and Graves disease. Similarly, Kotsa et al. (1997) found no association between the TSHR P52T polymorphism and Graves disease among 180 patients with Graves disease. The variant allele was present in 8.3% of patients and 7.3% of controls.
For additional discussion of a possible association between variation in the TSHR gene and Graves disease, see 275000.
### Reviews
Vassart et al. (1991) reviewed the molecular genetics of the thyrotropin receptor.
### TSHR Mutation Database
Trulzsch et al. (1999) described a database of TSHR mutations. The desirability of such a database came from the growing number of mutations identified and the variety of clinical phenotypes associated with the different mutations: somatic constitutively activating mutations in toxic thyroid nodules (e.g., 603372.0002); constitutively activating germline mutations as the cause of sporadic (e.g., 603372.0004) and familial (e.g., 603372.0019) nonautoimmune autosomal dominant hyperthyroidism (609152); and inactivating mutations associated with inherited TSH resistance (275200) (e.g., 603372.0005).
Animal Model
Using an adenovirus-mediated mouse model of Graves disease, Chen et al. (2003) demonstrated that goiter and hyperthyroidism occurred to a significantly greater extent when the adenovirus expressed the free alpha subunit as opposed to a genetically modified TSHR that cleaves minimally into subunits (p less than 0.005). Chen et al. (2003) concluded that shed alpha subunits induce or amplify the immune response leading to hyperthyroidism in Graves disease.
Abe et al. (2003) generated Tshr-null mice by replacing exon 1 of Tshr with a GFP cassette. They detected intense GFP fluorescence in thyroid follicles. Western blot analysis showed a 50% decrease in Tshr expression in heterozygotes and no expression in Tshr-null mice. Tshr-null mice were runted and hypothyroid, and they died by age 10 weeks with severe osteoporosis and significant reduction of calvarial thickness. Profound osteoporosis and focal osteosclerosis were observed in heterozygotes. Confocal microscopy demonstrated expression of Tshr in bone cells. They found 3-fold increased expression of Tnf (191160) in the bone marrow of Tshr-null mice. Neutralizing anti-Tnf antibody inhibited enhanced osteoclastogenesis in Tshr-null bone marrow cell cultures, suggesting that TNF is a proosteoclastic signal mediating the effects of TSHR deletion. Abe et al. (2003) found that TSH activation of Tshr resulted in attenuated osteoclast formation by inhibiting Jnk (see 601158) and Nfkb (see 164011) signaling, resorption, and survival. They showed that TSH regulated osteoblast differentiation through a Runx2 (600211)- and osterix (SP7; 606633)-independent mechanism that involved downregulation of the prodifferentiation factors Lrp5 (603506) and Flk1 (KDR; 191306). Abe et al. (2003) concluded that TSH acts as a single molecular switch in the independent control of both bone formation and resorption. Hase et al. (2006) found that the increased osteoclastogenesis in homozygous and heterozygous Tshr-null mice was rescued with graded reductions in the dosage of the Tnf gene.
Rubin et al. (2010) described the use of massively parallel sequencing to identify selective sweeps of favorable alleles and candidate mutations that have had a prominent role in the domestication of chickens and their subsequent specialization into broiler (meat-producing) and layer (egg-producing) chickens. Rubin et al. (2010) generated 44.5-fold coverage of the chicken genome using pools of genomic DNA representing 8 different populations of domestic chickens as well as red jungle fowl (Gallus gallus), the major wild ancestor. Rubin et al. (2010) reported more than 7,000,000 SNPs, almost 1,300 deletions, and a number of putative selective sweeps. One of the most striking selective sweeps found in all domestic chickens occurred at the locus for thyroid-stimulating hormone receptor (TSHR), which has a pivotal role in metabolic regulation and photoperiod control of reproduction in vertebrates. Several of the selective sweeps detected in broilers overlapped genes associated with growth, including growth hormone receptor (600946), appetite, and metabolic regulation. Rubin et al. (2010) found little evidence that selection for loss-of-function mutations had a prominent role in chicken domestication, but they detected 2 deletions in coding sequences, including one in SH3RF2 (613377), that the authors considered functionally important.
*[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
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*[NET]: Norepinephrine transporter
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*[ND]: No data
*[NOP]: Nociceptin receptor
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*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
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| THYROID-STIMULATING HORMONE RECEPTOR | c1863961 | 4,525 | omim | https://www.omim.org/entry/603372 | 2019-09-22T16:13:06 | {"mesh": ["C566386"], "omim": ["603372"], "synonyms": ["Alternative titles", "THYROTROPIN RECEPTOR", "LGR3"]} |
Abortion in Pennsylvania is legal. 51% of adults said in a poll by the Pew Research Center that abortion should be legal in all or most cases.
The number of abortion clinics in Pennsylvania has declined over the years, with 114 in 1982, 81 in 1992 and twenty in 2014. There were 32,126 legal abortions in 2014, and 31,818 in 2015.
## Contents
* 1 Terminology
* 2 Context
* 3 History
* 3.1 Legislative history
* 3.2 Judicial history
* 3.3 Clinic history
* 4 Statistics
* 5 Abortion rights views and activities
* 5.1 Protests
* 6 Anti-abortion views and activities
* 7 Footnotes
* 8 References
## Terminology[edit]
Main article: Abortion
The abortion debate most commonly relates to the "induced abortion" of an embryo or fetus at some point in a pregnancy, which is also how the term is used in a legal sense.[note 1] Some also use the term "elective abortion", which is used in relation to a claim to an unrestricted right of a woman to an abortion, whether or not she chooses to have one. The term elective abortion or voluntary abortion describes the interruption of pregnancy before viability at the request of the woman, but not for medical reasons.[1]
Anti-abortion advocates tend to use terms such as "unborn baby", "unborn child", or "pre-born child",[2][3] and see the medical terms "embryo", "zygote", and "fetus" as dehumanizing.[4][5] Both "pro-choice" and "pro-life" are examples of terms labeled as political framing: they are terms which purposely try to define their philosophies in the best possible light, while by definition attempting to describe their opposition in the worst possible light. "Pro-choice" implies that the alternative viewpoint is "anti-choice", while "pro-life" implies the alternative viewpoint is "pro-death" or "anti-life".[6] The Associated Press encourages journalists to use the terms "abortion rights" and "anti-abortion".[7]
## Context[edit]
See also: Abortion in the United States
Free birth control correlates to teenage girls having a fewer pregnancies and fewer abortions. A 2014 New England Journal of Medicine study found such a link. At the same time, a 2011 study by Center for Reproductive Rights and Ibis Reproductive Health also found that states with more abortion restrictions have higher rates of maternal death, higher rates of uninsured pregnant women, higher rates of infant and child deaths, higher rates of teen drug and alcohol abuse, and lower rates of cancer screening.[8]
According to a 2017 report from the Center for Reproductive Rights and Ibis Reproductive Health, states that tried to pass additional constraints on a women's ability to access legal abortions had fewer policies supporting women's health, maternal health and children's health. These states also tended to resist expanding Medicaid, family leave, medical leave, and sex education in public schools.[9] According to Megan Donovan, a senior policy manager at the Guttmacher Institute, states have legislation seeking to protect a woman's right to access abortion services have the lowest rates of infant mortality in the United States.[9]
Poor women in the United States had problems paying for menstrual pads and tampons in 2018 and 2019. Almost two-thirds of American women could not pay for them. These were not available through the federal Women, Infants, and Children Program (WIC).[10] Lack of menstrual supplies has an economic impact on poor women. A study in St. Louis found that 36% had to miss days of work because they lacked adequate menstrual hygiene supplies during their period. This was on top of the fact that many had other menstrual issues including bleeding, cramps and other menstrual induced health issues.[10] Connecticut, Florida, Illinois, Maryland, Massachusetts, Minnesota, New Jersey, New York, Nevada, and Pennsylvania all had exemptions for essential hygiene products like tampons and menstrual pads as of November 2018.[11][12][13][14]
## History[edit]
In 2011, Kermit Gosnell, a licensed doctor who provided abortion services in the American state of Pennsylvania, was indicted by a grand jury on murder charges after a woman died in his clinic. The grand jury found that the conditions in Gosnell's clinic were not only unsanitary and that Gosnell staffed his clinic with unlicensed individuals, he had also commonly conducted the lesser known practice of severing the spinal cords of newly born babies.[15]
### Legislative history[edit]
By the end of the 1800s, all states in the Union except Louisiana had therapeutic exceptions in their legislative bans on abortions.[16] In the 19th century, bans by state legislatures on abortion were about protecting the life of the mother given the number of deaths caused by abortions; state governments saw themselves as looking out for the lives of their citizens.[16] The Abortion Control Act was passed by the Pennsylvania government in 1982. The law required women seeking abortions wait 24 hours before getting an abortion, and required informed consent of parents for minor children and husbands for married women.[17][18] It was principally written by Rep. Stephen F. Freind.[18]
The state was one of 23 states in 2007 to have a detailed abortion-specific informed consent requirement.[19] From 2011, the crimes of Kermit Gosnell, a physician who ran an abortion clinic in Philadelphia, spurred federal and state bills to more strictly regulate abortion facilities. Opponents of the restrictions questioned whether stricter regulations would have deterred Gosnell, who was alleged to be knowingly in violation of existing regulations.[20] In 2013, state Targeted Regulation of Abortion Providers (TRAP) law applied to private doctor offices in addition to abortion clinics.[21]
A fetal heartbeat bill (HB 2315) was introduced in the Pennsylvania House of Representatives on May 2, 2018, primarily sponsored by Rep Rick Saccone.[22] The bill was referred to the Judiciary Committee where it died.[23] The state legislature was one of ten states nationwide that tried to unsuccessfully pass a fetal heartbeat bill in 2018. Only Iowa successfully passed such a bill, but it was struck down by the courts.[24] As of May 14, 2019, the state prohibited abortions after the fetus was viable, considered to be week 24 in state law. This period uses a standard defined by the US Supreme Court in 1973 with the Roe v. Wade ruling.[25][26]
### Judicial history[edit]
See also: Planned Parenthood v. Casey
The US Supreme Court's decision in 1973's Roe v. Wade ruling meant the state could no longer regulate abortion in the first trimester.[16] In Planned Parenthood of Southeastern Pennsylvania v. Casey, the Court of Appeals for the Third Circuit affirmed in part and reversed in part, upholding all of the regulations except for the husband notification requirement.[27] The Third Circuit concluded that the husband notification was unduly burdensome because it potentially exposed married women to spousal abuse, violence, and economic duress at the hands of their husbands.[28]
In the 1992 United States Supreme Court ruling on Planned Parenthood of Southeastern Pennsylvania v. Casey, the court upheld Pennsylvania's law requiring pre-abortion counseling with a caveat that materials provided to women in this counseling needed to be "truthful and nonmisleading."[29][17] At the conference of the Justices two days after oral argument, Justice David Souter defied expectations, joining Justices Sandra Day O'Connor, John Paul Stevens, and Harry Blackmun, who had all dissented three years earlier in Webster v. Reproductive Health Services with regard to that plurality's suggested reconsideration and narrowing of Roe. This resulted in a precarious five Justice majority consisting of Chief Justice William Rehnquist, Byron White, Antonin Scalia, Anthony Kennedy, and Clarence Thomas that favored upholding all five contested abortion restrictions. However, Justice Kennedy changed his mind shortly thereafter and joined with fellow Reagan-Bush justices Sandra Day O'Connor and David Souter to write a plurality opinion that would reaffirm Roe.[30]
Although upholding the "essential holding" in Roe, and recognizing that women have some constitutional liberty to terminate their pregnancies, the O'Connor–Kennedy–Souter plurality overturned the Roe trimester framework in favor of a viability analysis. The Roe trimester framework completely forbade states from regulating abortion during the first trimester of pregnancy, permitted regulations designed to protect a woman's health in the second trimester, and permitted prohibitions on abortion during the third trimester (when the fetus becomes viable) under the justification of fetal protection, and so long as the life or health of the mother was not at risk.[31] The plurality found that continuing advancements in medical technology had proven that a fetus could be considered viable at 23 or 24 weeks rather than at the 28 weeks previously understood by the Court in Roe.[32] The plurality thus redrew the line of increasing state interest at viability because of increasing medical accuracy about when fetus viability takes place. Likewise, the authors of the plurality opinion felt that fetus viability was "more workable" than the trimester framework.[33]
Under this new fetus viability framework, the plurality held that at the point of viability and subsequent to viability, the state could promote its interest in the "potentiality of human life" by regulating, or possibly proscribing, abortion "except where it is necessary, in appropriate medical judgment, for the preservation of the life or health of the mother."[34] Prior to fetus viability, the plurality held, the State can show concern for fetal development, but it cannot pose an undue burden on a woman's fundamental right to abortion.[35] The plurality reasoned that the new pre- and post-viability line would still uphold the essential holding of Roe, which recognized both the woman's constitutionally protected liberty, and the State's "important and legitimate interest in potential life."[36]
In replacing the trimester framework with the viability framework, the plurality also replaced the strict scrutiny analysis under Roe, with the "undue burden" standard previously developed by O'Connor in her dissent in Akron v. Akron Center for Reproductive Health.[37] A legal restriction posing an undue burden is one that has "the purpose or effect of placing a substantial obstacle in the path of a woman seeking an abortion of a nonviable fetus."[38] An undue burden is found even where a statute purports to further the interest of potential life or another valid state interest, if it places a substantial obstacle in the path of a woman's fundamental right to choice.[38] The Supreme Court in the 2016 case Whole Woman's Health v. Hellerstedt clarified exactly what the 'undue burden' test requires: "Casey requires courts to consider the burdens a law imposes on abortion access together with the benefits those laws confer."[39][40] In this case the court described the undue burden standard in its overall context with these words:
In applying the new undue burden standard, the plurality overruled City of Akron v. Akron Center for Reproductive Health, 462 U.S. 416 (1983) and Thornburgh v. American College of Obstetricians and Gynecologists, 476 U.S. 747 (1986),[41] each of which applied "strict scrutiny" to abortion restrictions.[42]
Applying this new standard to the challenged Pennsylvania Act, the plurality struck down the spousal notice requirement, finding that for many women, the statutory provision would impose a substantial obstacle in their path to receive an abortion.[43] The plurality recognized that the provision gave too much power to husbands over their wives ("a spousal notice requirement enables the husband to wield an effective veto over his wife's decision"), and could worsen situations of spousal and child abuse.[44] In finding the provision unconstitutional, the authors of the plurality opinion clarified that the focus of the undue burden test is on the group "for whom the law is a restriction, not the group for whom the law is irrelevant."[45] Otherwise stated, courts should not focus on what portion of the population is affected by the legislation, but rather on the population the law would restrict.[46] The plurality upheld the remaining contested regulations – the State's informed consent and 24-hour waiting period, parental consent requirements, reporting requirements, and the "medical emergencies" definition – holding that none constituted an undue burden.[47]
### Clinic history[edit]
Number of abortion clinics in Pennsylvania by year.
See also: Abortion clinic
Madame Restell opened a business that performed abortions in the 1830s in New York City. Her business remained open for around 35 years and openly advertised its services, including in newspaper advertisements. She had branches in several other cities including Boston and Philadelphia, as well as having traveling agents working for the company who sold her "Female Monthly Pills."[48][49]
Between 1982 and 1992, the number of abortion clinics in the state decreased by 33, going from 114 in 1982 to 81 in 1992.[50] In the period between 1992 and 1996, the state ranked fourth in the loss of number of abortion clinics, losing 20 to have a total of 61 in 1996.[51] In 2014, there were twenty abortion clinics in the state.[52] That year, 85% of the counties in the state did not have an abortion clinic. That year, 48% of women in the state aged 15 – 44 lived in a county without an abortion clinic.[53]
In March 2016, there were 35 Planned Parenthood clinics in the state.[54] In 2017, there were 32 Planned Parenthood clinics in a state with a population of 2,825,578 women aged 15 – 49 of which eleven offered abortion services.[55]
## Statistics[edit]
In the period between 1972 and 1974, the state had an illegal abortion mortality rate per million women aged 15 – 44 of between 0.1 and 0.9.[56] In 1990, 1,480,000 women in the state faced the risk of an unintended pregnancy.[50] In 2010, the state had seven publicly funded abortions, of which were zero federally funded and seven were state funded.[57] In 2014, 51% of adults said in a poll by the Pew Research Center that abortion should be legal in all or most cases.[58] In 2017, the state had an infant mortality rate of 6.1 deaths per 1,000 live births.[9]
Number of reported abortions, abortion rate and percentage change in rate by geographic region and state in 1992, 1995 and 1996[51] Census division and state Number Rate % change 1992–1996
1992 1995 1996 1992 1995 1996
Middle Atlantic 300,450 278,310 270,220 34.6 32.7 32 –8
New Jersey 55,320 61,130 63,100 31 34.5 35.8 16
New York 195,390 176,420 167,600 46.2 42.8 41.1 –11
Pennsylvania 49,740 40,760 39,520 18.6 15.5 15.2 –18
Number, rate, and ratio of reported abortions, by reporting area of residence and occurrence and by percentage of abortions obtained by out-of-state residents, US CDC estimates Location Residence Occurrence % obtained by
out-of-state residents
Year Ref
No. Rate^ Ratio^^ No. Rate^ Ratio^^
Pennsylvania 32,683 13.6 230 32,126 13.3 226 4.2 2014 [59]
Pennsylvania 32,025 13.3 227 31,818 13.3 226 5 2015 [60]
Pennsylvania 30,954 13.0 222 30,881 13.0 222 5.4 2016 [61]
^number of abortions per 1,000 women aged 15–44; ^^number of abortions per 1,000 live births
## Abortion rights views and activities[edit]
### Protests[edit]
Women from the state participated in marches supporting abortion rights as part of a #StoptheBans movement in May 2019.[62][63] One #StoptheBans took place in Philadelphia outside the state legislature building on May 21, 2019.[63]
## Anti-abortion views and activities[edit]
The Democrats for Life of America are a group of anti-abortion Democrats on the political left who advocate for an anti-abortion plank in the Democratic Party's platform and for anti-abortion Democratic candidates. Former vice-presidential candidate Sargent Shriver, the late Robert Casey, a former two-term governor of Pennsylvania, and former Rep. Bart Stupak (D-Mich), a former leader of the bipartisan anti-abortion caucus in the United States House of Representatives, have been among the most well-known anti-abortion Democrats.[64]
## Footnotes[edit]
1. ^ According to the Supreme Court's decision in Roe v. Wade:
> (a) For the stage prior to approximately the end of the first trimester, the abortion decision and its effectuation must be left to the medical judgement of the pregnant woman's attending physician. (b) For the stage subsequent to approximately the end of the first trimester, the State, in promoting its interest in the health of the mother, may, if it chooses, regulate the abortion procedure in ways that are reasonably related to maternal health. (c) For the stage subsequent to viability, the State in promoting its interest in the potentiality of human life may, if it chooses, regulate, and even proscribe, abortion except where it is necessary, in appropriate medical judgement, for the preservation of the life or health of the mother.
Likewise, Black's Law Dictionary defines abortion as "knowing destruction" or "intentional expulsion or removal".
## References[edit]
1. ^ Watson, Katie (20 Dec 2019). "Why We Should Stop Using the Term "Elective Abortion"". AMA Journal of Ethics. 20: E1175-1180. doi:10.1001/amajethics.2018.1175. PMID 30585581. Retrieved 17 May 2019.
2. ^ Chamberlain, Pam; Hardisty, Jean (2007). "The Importance of the Political 'Framing' of Abortion". The Public Eye Magazine. 14 (1).
3. ^ "The Roberts Court Takes on Abortion". New York Times. November 5, 2006. Retrieved January 18, 2008.
4. ^ Brennan 'Dehumanizing the vulnerable' 2000
5. ^ Getek, Kathryn; Cunningham, Mark (February 1996). "A Sheep in Wolf's Clothing – Language and the Abortion Debate". Princeton Progressive Review.
6. ^ "Example of "anti-life" terminology" (PDF). Archived from the original (PDF) on 2011-07-27. Retrieved 2011-11-16.
7. ^ Goldstein, Norm, ed. The Associated Press Stylebook. Philadelphia: Basic Books, 2007.
8. ^ Castillo, Stephanie (2014-10-03). "States With More Abortion Restrictions Hurt Women's Health, Increase Risk For Maternal Death". Medical Daily. Retrieved 2019-05-27.
9. ^ a b c "States pushing abortion bans have highest infant mortality rates". NBC News. Retrieved May 25, 2019.
10. ^ a b Mundell, E.J. (January 16, 2019). "Two-Thirds of Poor U.S. Women Can't Afford Menstrual Pads, Tampons: Study". US News & World Report. Retrieved May 26, 2019.
11. ^ Larimer, Sarah (January 8, 2016). "The 'tampon tax,' explained". The Washington Post. Archived from the original on December 11, 2016. Retrieved December 10, 2016.
12. ^ Bowerman, Mary (July 25, 2016). "The 'tampon tax' and what it means for you". USA Today. Archived from the original on December 11, 2016. Retrieved December 10, 2016.
13. ^ Hillin, Taryn. "These are the U.S. states that tax women for having periods". Splinter. Retrieved 2017-12-15.
14. ^ "Election Results 2018: Nevada Ballot Questions 1-6". KNTV. Retrieved 2018-11-07.
15. ^ "Investigation of the Women's Medical Society Grand Jury Report". Phila.gov. Retrieved 7 December 2017.
16. ^ a b c Buell, Samuel (1991-01-01). "Criminal Abortion Revisited". New York University Law Review. 66: 1774–1831.
17. ^ a b Larson, Jordan. "Timeline: The 200-Year Fight for Abortion Access". The Cut. Retrieved May 25, 2019.
18. ^ a b deCourcy Hind, Michael (1992-02-21). "The 1992 Campaign: Pennsylvania; Trouble Shadows Specter in Senate Race". The New York Times. Retrieved 2009-08-15.
19. ^ "State Policy On Informed Consent for Abortion" (PDF). Guttmacher Policy Review. Fall 2007. Retrieved May 22, 2019.
20. ^ Caplan-Bricker, Nora (May 1, 2013). "The Kermit Gosnell Effect". The New Republic.
21. ^ "TRAP Laws Gain Political Traction While Abortion Clinics—and the Women They Serve—Pay the Price". Guttmacher Institute. 2013-06-27. Retrieved 2019-05-27.
22. ^ "Regular Session 2017–2018 - House Bill 2315". legis.state.pa.us. Pennsylvania General Assembly. Retrieved February 16, 2019. "Referred to Judiciary, May 2, 2018 [House]"
23. ^ "PA HB2315 | 2017–2018 | Regular Session". legiscan.com. Legi Scan. Retrieved February 16, 2019. "Status: Introduced on May 2, 2018 - 25% progression, died in committee Action: 2018-05-02 - Referred to Judiciary"
24. ^ Lai, K. K. Rebecca (2019-05-15). "Abortion Bans: 8 States Have Passed Bills to Limit the Procedure This Year". The New York Times. ISSN 0362-4331. Retrieved 2019-05-24.
25. ^ Lai, K. K. Rebecca (2019-05-15). "Abortion Bans: 8 States Have Passed Bills to Limit the Procedure This Year". The New York Times. ISSN 0362-4331. Retrieved 2019-05-24.
26. ^ Tavernise, Sabrina (2019-05-15). "'The Time Is Now': States Are Rushing to Restrict Abortion, or to Protect It". The New York Times. ISSN 0362-4331. Retrieved 2019-05-24.
27. ^ Planned Parenthood v. Casey, 947 F.2d 682 (3d Cir. 1991).
28. ^ Constitutional Law and Politics: Civil Rights and Civil Liberties, Eighth Edition, Norton & Company, 2011
29. ^ "Misinformed Consent: The Medical Accuracy of State-Developed Abortion Counseling Materials". Guttmacher Institute. 2006-10-25. Retrieved 2019-05-23.
30. ^ Lane, Charles. "All Eyes on Kennedy in Court Debate On Abortion". The Washington Post. Retrieved May 22, 2010.
31. ^ Casey, 505 U.S. at 872; Roe v. Wade, 410 U.S. 113, 163–66 (1973).
32. ^ Casey, 505 U.S. at 860.
33. ^ Casey, 505 U.S. at 870.
34. ^ Casey, 505 U.S. at 879.
35. ^ Casey, 505 U.S. at 873, 876-78.
36. ^ Casey, 505 U.S. at 871 ("[t]o protect the central right recognized by Roe v. Wade while at the same time accommodating the State's profound interest in potential life, we will employ the undue burden analysis as explained in this opinion.").
37. ^ City of Akron v. Akron Center for Reproductive Health, 462 U.S. 416 (1983).
38. ^ a b Casey, 505 U.S. at 877.
39. ^ Whole Woman's Health v. Hellerstedt, 579 U.S. ___ (2016), [1] Archived 2017-06-23 at the Wayback Machine, Opinion of the Court, page 19-20.
40. ^ David H. Gans (June 27, 2015). "Symposium: No more rubber-stamping state regulation of abortion". SCOTUSblog. Retrieved June 29, 2016. "[T]he majority held that the 'undue burden' standard announced in Planned Parenthood v. Casey 'requires that courts consider the burdens a law imposes on abortion access together with the benefits those laws confer.'"
41. ^ Thornburgh v. American College of Obstetricians and Gynecologists, 476 U.S. 747 (1986).
42. ^ Dorf, Michael C. (1996). "Incidental Burdens on Fundamental Rights". Harv. L. Rev. 109 (6): 1175–1251. doi:10.2307/1342214. JSTOR 1342214. "The undue burden standard is binding on lower courts, see Marks v. United States, 430 U.S. 188, 193 (1977) (defining the holding of a divided Court as the view of the members of the Court who concurred on the narrowest grounds), although for stare decisis purposes, only the portion of the three-Justice opinion that garnered five votes counts as a full-fledged precedent in the Supreme Court itself." [at Note 197]
43. ^ Casey, 505 U.S. at 893–94.
44. ^ See 897, 892–94 (noting that women may not inform their husbands because of "justifiable fears of physical abuse" or fear that notification will "provoke further instances of child abuse," and women may also fear reporting past abuse to the State because of the other consequences that can come from that).
45. ^ Casey, 505 U.S. at 894.
46. ^ Casey, 505 U.S. at 894 ("The proper focus of constitutional inquiry is the group for whom the law is a restriction, not the group for whom the law is irrelevant.").
47. ^ Casey, 505 U.S. at 880 (medical emergency), 887 (informed consent and 24-hour waiting period), 899 (parental consent), and 900 (finding that recordkeeping and reporting requirements are constitutional, except those related to spousal notice).
48. ^ "When Abortion Was a Crime". www.theatlantic.com. Retrieved 2019-05-22.
49. ^ Jessica Ravitz. "The surprising history of abortion in the U.S." CNN. Retrieved 2019-05-23.
50. ^ a b Arndorfer, Elizabeth; Michael, Jodi; Moskowitz, Laura; Grant, Juli A.; Siebel, Liza (December 1998). A State-By-State Review of Abortion and Reproductive Rights. Diane Publishing. ISBN 9780788174810.
51. ^ a b "Abortion Incidence and Services in the United States, 1995-1996". Guttmacher Institute. 2005-06-15. Retrieved 2019-06-02.
52. ^ Gould, Rebecca Harrington, Skye. "The number of abortion clinics in the US has plunged in the last decade — here's how many are in each state". Business Insider. Retrieved 2019-05-23.
53. ^ businessinsider (2018-08-04). "This is what could happen if Roe v. Wade fell". Business Insider (in Spanish). Retrieved 2019-05-24.
54. ^ Bohatch, Emily. "27 states with the most Planned Parenthood clinics". thestate. Retrieved 2019-05-24.
55. ^ "Here's Where Women Have Less Access to Planned Parenthood". Retrieved 2019-05-23.
56. ^ Cates, Willard; Rochat, Roger (March 1976). "Illegal Abortions in the United States: 1972–1974". Family Planning Perspectives. 8 (2): 86. doi:10.2307/2133995. JSTOR 2133995. PMID 1269687.
57. ^ "Guttmacher Data Center". data.guttmacher.org. Retrieved 2019-05-24.
58. ^ "Views about abortion by state - Religion in America: U.S. Religious Data, Demographics and Statistics". Pew Research Center. Retrieved May 23, 2019.
59. ^ Jatlaoui, Tara C. (2017). "Abortion Surveillance — United States, 2014". MMWR. Surveillance Summaries. 66 (24): 1–48. doi:10.15585/mmwr.ss6624a1. ISSN 1546-0738. PMID 29166366.
60. ^ Jatlaoui, Tara C. (2018). "Abortion Surveillance — United States, 2015". MMWR. Surveillance Summaries. 67 (13): 1–45. doi:10.15585/mmwr.ss6713a1. ISSN 1546-0738. PMC 6289084. PMID 30462632.
61. ^ Jatlaoui, Tara C. (2019). "Abortion Surveillance — United States, 2016". MMWR. Surveillance Summaries. 68. doi:10.15585/mmwr.ss6811a1. ISSN 1546-0738.
62. ^ Bacon, John. "Abortion rights supporters' voices thunder at #StopTheBans rallies across the nation". USA Today. Retrieved May 25, 2019.
63. ^ a b "Would overturning abortion rights turn back clock to 1973?". The Public's Radio. 2019-05-26. Retrieved 2019-05-26.
64. ^ Patrick O'Connor (21 March 2010). "Historic win close after Bart Stupak deal". Politico.com. Retrieved 2011-11-16.
Abortion in the United States by state
States
* Alabama
* Alaska
* Arizona
* Arkansas
* California
* Colorado
* Connecticut
* Delaware
* Florida
* Georgia
* Hawaii
* Idaho
* Illinois
* Indiana
* Iowa
* Kansas
* Kentucky
* Louisiana
* Maine
* Maryland
* Massachusetts
* Michigan
* Minnesota
* Mississippi
* Missouri
* Montana
* Nebraska
* Nevada
* New Hampshire
* New Jersey
* New Mexico
* New York
* North Carolina
* North Dakota
* Ohio
* Oklahoma
* Oregon
* Pennsylvania
* Rhode Island
* South Carolina
* South Dakota
* Tennessee
* Texas
* Utah
* Vermont
* Virginia
* Washington
* West Virginia
* Wisconsin
* Wyoming
Federal district
Washington, D.C.
Insular areas
* American Samoa
* Guam
* Northern Mariana Islands
* Puerto Rico
* U.S. Virgin Islands
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Abortion in Pennsylvania | None | 4,526 | wikipedia | https://en.wikipedia.org/wiki/Abortion_in_Pennsylvania | 2021-01-18T18:43:53 | {"wikidata": ["Q64876950"]} |
A number sign (#) is used with this entry because the disorder is associated with mutations in the PRNP gene (176640).
Clinical Features
Nitrini et al. (1997) studied a Brazilian family in which 9 members had clinically demonstrated prion disease characterized by autosomal dominant presenile dementia with a rapidly progressive and protracted clinical course. The mean age at onset was 44.8 +/- 3.8 years, and the mean duration of symptoms was 4.2 +/- 2.4 years. The dementia was characterized clinically by frontotemporal features, including early personality changes. Four patients had memory loss, several showed aggressiveness, hyperorality and verbal stereotypy, and 6 had parkinsonian symptoms. No periodic activity was seen in electroencephalograms in 7 patients. Pathologic evaluation of 3 patients showed severe spongiform change, neuronal loss, and minimal gliosis in the most severely affected areas. PRNP immunostaining was restricted to cerebellum and putamen.
Samaia et al. (1997) reported a family in which several members had prion encephalopathy with neuropsychiatric features. The proband had persecutory delusions, auditory hallucinations, severe depression, and had a history of suicide attempts and violent behavior over a 10-year period. Neurologic symptoms such as ataxia or dementia, typical of known prion diseases, were absent. Of the other members of the patient's family identified as mutation carriers, the patient's mother had dementia and urinary incontinence and a 35-year history of similar psychiatric symptoms. The patient's uncle presented 7 years previously with abnormal behavior, including apathy, social withdrawal, mutism, and occasional violence, and subsequently developed urinary and fecal incontinence, walking difficulty, and dementia. Two sibs with the mutation had a psychiatric history of alternating severe depression and aggressiveness and 1 of them also had persecutory delusions and auditory hallucinations, whereas the third sib carrying the mutation was symptom-free. No neuropathologic findings were reported.
Hall et al. (2005) reported a family with early-onset dementia (range 20 to 44 years), cerebellar signs, and extrapyramidal signs. Four patients developed neuropsychiatric symptoms in childhood or adolescence, including kleptomania, pyromania, and impulsivity. Neuropathologic examination of 4 patients showed moderate to severe cerebral atrophy, without other distinctive features. All affected individuals had a mutation in the PRNP gene (176640.0024).
Rogaeva et al. (2006) reported 3 affected members of a family of East Indian origin with a rapidly progressive neurodegenerative disorder characterized by dementia, motor decline, and ataxia, resulting from a PRNP mutation. The proband showed anxiety and paranoia at age 13, developing dysarthria, gait difficulties, and trouble with self-care soon after onset. At the time of examination at age 15 years, the proband was anarthric, dysphagic, made few purposeful movements, and required total care. The proband's affected mother and affected maternal uncle had rapidly progressive dementia and motor dysfunction, but lacked psychiatric disturbance. Family history indicated at least 3 additional members with disease and a mean age at onset of 36 years (range 13 to 41).
Molecular Genetics
In a Brazilian family with spongiform encephalopathy with neuropsychiatric features, Nitrini et al. (1997) identified a mutation in the PRNP gene (176640.0022) in the proband and his affected mother.
In affected members of a family with prion encephalopathy with neuropsychiatric features, Samaia et al. (1997) identified a mutation in the PRNP gene (176640.0018). The mutant allele also had the val129 (176640.0005) polymorphism. The same genotype was found in 5 of 11 living relatives of the patient; only 1 mutation carrier was asymptomatic.
In 3 affected members of a family of East Indian origin with a rapidly progressive neurodegenerative disorder characterized by personality changes, dementia, and motor decline, Rogaeva et al. (2006) identified heterozygosity for a mutation in the PRNP gene (176640.0025). The mother and uncle both were homozygous for 129met (176640.0005), whereas the proband was heterozygous for 129met/val.
INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Dementia, rapidly progressive \- Personality changes \- Parkinsonian symptoms \- Spongiform changes \- No amyloid plaques \- No neurofibrillary tangles \- Minimal gliosis \- Prp immunoreactivity limited to cerebellum and putamen MISCELLANEOUS \- Mean duration of symptoms 4.2 plus or minus 2.4 years MOLECULAR BASIS \- Caused by mutations in the prion protein gene (PRNP, 176640.0018 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| SPONGIFORM ENCEPHALOPATHY WITH NEUROPSYCHIATRIC FEATURES | c1847650 | 4,527 | omim | https://www.omim.org/entry/606688 | 2019-09-22T16:10:17 | {"mesh": ["C564678"], "omim": ["606688"]} |
Leiomyoma
Other namesleiomyomas, leiomyomata
Uterine lipoleiomyoma, a type of leiomyoma. H&E stain.
SpecialtyOncology
A leiomyoma, also known as fibroids, is a benign smooth muscle tumor that very rarely becomes cancer (0.1%). They can occur in any organ, but the most common forms occur in the uterus, small bowel, and the esophagus. Polycythemia may occur due to increased erythropoietin production as part of a paraneoplastic syndrome.
The word is from leio- \+ myo- \+ -oma, "smooth-muscle tumor". The plural form can be either the English leiomyomas or the classical leiomyomata.
## Contents
* 1 Uterus
* 2 Gallbladder
* 3 Skin
* 4 Esophagus, stomach and small intestines
* 5 Other locations, metastatic leiomyoma
* 6 Familial leiomyoma
* 7 See also
* 8 References
* 9 External links
## Uterus[edit]
Main article: Uterine fibroids
Leiomyoma enucleated from a uterus. External surface on left; cut surface on right
Micrograph of a small, well-circumscribed colonic leiomyoma arising from the muscularis mucosae and showing fascicles of spindle cells with eosinophilic cytoplasm and elongated, cigar-shaped nuclei.
Uterine fibroids are leiomyomata of the uterine smooth muscle. As other leiomyomata, they are benign, but may lead to excessive menstrual bleeding (menorrhagia), often cause anemia and may lead to infertility.
A rare form of these tumors is uterine lipoleiomyoma—benign tumors consisting of a mixture of adipocytes and smooth muscle cells. Uterine lipoleiomyomata have been observed together with ovarian and other pathologies and some of them may develop into liposarcoma.[1][2] These tumors are monoclonal, and non-random chromosomal abnormalities have been seen in 40% of the tumors.
## Gallbladder[edit]
Mesenchymal neoplasms of the gallbladder are rare and in particular leiomyomas of the gallbladder have been rarely reported, all of them in patients with immune system disorders. Although, recently, a case was reported in absence of associated immunodeficiency at Monash Hospital in Melbourne Australia in a healthy 39-year-old woman with no symptoms.[3]
## Skin[edit]
Leiomyomas of the skin are generally (1) acquired, and (2) divided into several categories:[4][5]
* Solitary cutaneous leiomyoma
* Multiple cutaneous (or pilar) leiomyomas arising from the arrectores pilorum muscles
* Angioleiomyomas (Vascular leiomyomas) that are thought to arise from vascular smooth muscle
* Dartoic (or genital) leiomyomas originating in the dartos muscles of the genitalia, areola, and nipple
* Angiolipoleiomyoma
## Esophagus, stomach and small intestines[edit]
Leiomyoma is the most common benign mesenchymal tumor of esophagus and second most common benign tumor of the small bowel (with gastrointestinal stromal tumor as most common).[6] Although leiomyoma is the most common benign esophageal tumor, malignant carcinoma is still 50 times more likely.[7] Approximately 50% of cases are found in the jejunum, followed by the ileum in 31% of cases. Almost one half of all lesions are less than 5 centimeters.[8]
## Other locations, metastatic leiomyoma[edit]
* Metastatic leiomyoma are an extremely rare complication after surgery to remove the uterus for uterine fibroids. The most frequent sites of occurrence are the lungs and pelvis. The lesions are hormonally responsive.[9][10][11]
* Fibromyoma of the breast is an extremely rare benign breast neoplasm. Most reports in literature mention a history of hysterectomy for uterine fibroids, although the question of whether these fibromyomas are possibly metastases of the uterine fibroids has not been investigated. An alternative hypothesis is an origin from the smooth muscle of the nipple.
* Leiomyoma may spontaneously occur in any muscle. Depending on the location of the tumor, identification may not be timely until overall mass becomes undeniably noticeable. The symptoms for a 30 year old male with a 10 cm leiomyoma included "dead leg" pains. Tumor was intertwined with quadricep muscles, making identification and excision difficult. Tumor was successfully excised with only minor rehabilitation required.[citation needed]
## Familial leiomyoma[edit]
* Associated with papillary variant of renal cell carcinoma and multiple cutaneous leiomyoma. Defect is in the fumarate hydratase gene in the long arm of chromosome 1.
## See also[edit]
* Leiomyosarcoma
* Elagolix/estradiol/norethindrone acetate
## References[edit]
1. ^ Pedeutour, F.; Quade, B. J.; Sornberger, K.; Tallini, G.; Ligon, A. H.; Weremowicz, S.; Morton, C. C. (2000). "Dysregulation ofHMGIC in a uterine lipoleiomyoma with a complex rearrangement including chromosomes 7, 12, and 14". Genes, Chromosomes and Cancer. 27 (2): 209–215. doi:10.1002/(SICI)1098-2264(200002)27:2<209::AID-GCC14>3.0.CO;2-U. PMID 10612811.
2. ^ McDonald, A. G.; Cin, P. D.; Ganguly, A.; Campbell, S.; Imai, Y.; Rosenberg, A. E.; Oliva, E. (2011). "Liposarcoma Arising in Uterine Lipoleiomyoma". The American Journal of Surgical Pathology. 35 (2): 221–227. doi:10.1097/PAS.0b013e31820414f7. PMID 21263242.
3. ^ Segura-Sampedro, J. J.; Alamo-Martínez, J. M.; Cañete-Gómez, J.; Suárez-Artacho, G.; González-Cantón, J. R.; Gómez-Bravo, M. Á.; Padillo-Ruiz, F. J. (2012). "Gallbladder leiomyoma in absence of immune system disorders: An unusual diagn". Revista espanola de enfermedades digestivas. 104 (7): 382–384. doi:10.4321/S1130-01082012000700009. PMID 22849501.
4. ^ Freedberg, Irwin M.; Fitzpatrick, Thomas B. (2003). Fitzpatrick's dermatology in general medicine (6th ed.). New York: McGraw-Hill, Medical Pub. Division. p. 1033. ISBN 0-07-138076-0.
5. ^ Odom, Richard B.; Davidsohn, Israel; James, William D.; Henry, John Bernard; Berger, Timothy G.; Dirk M. Elston (2006). Andrews' diseases of the skin: clinical dermatology (10th ed.). Saunders Elsevier. p. 627. ISBN 0-7216-2921-0.
6. ^ Radiologic Pathology Archives: Esophageal Neoplasms: Radiologic-Pathologic Correlation Rachel B. Lewis, Anupamjit K. Mehrotra, Pablo Rodriguez, and Marc S. Levine. RadioGraphics 2013 33:4, 1083-1108. Accessed 2017-07-08
7. ^ Radiologic Pathology Archives: Esophageal Neoplasms: Radiologic-Pathologic Correlation Rachel B. Lewis, Anupamjit K. Mehrotra, Pablo Rodriguez, and Marc S. Levine. RadioGraphics 2013 33:4, 1083-1108. Accessed 2017-07-08
8. ^ Michael P. Buetow, M.D. "Leiomyoma of Jejunum". Applied Radiology Online. Archived from the original on 2007-09-27. Retrieved 2007-03-21.
9. ^ Patton, K.; Cheng, L.; Papavero, V.; Blum, M.; Yeldandi, A.; Adley, B.; Luan, C.; Diaz, L.; Hui, P.; Yang, X. J. (2006). "Benign metastasizing leiomyoma: clonality, telomere length and clinicopathologic analysis". Modern Pathology. 19 (1): 130–140. doi:10.1038/modpathol.3800504. PMID 16357844.
10. ^ Beck, M. M.; Biswas, B.; d'Souza, A.; Kumar, R. (2012). "Benign metastasising leiomyoma after hysterectomy and bilateral salpingo-oophorectomy". Hong Kong medical [Xianggang yi xue za zhi / Hong Kong Academy of Medicine]. 18 (2): 153–155. PMID 22477740.
11. ^ Rivera, J. A.; Christopoulos, S.; Small, D.; Trifiro, M. (2004). "Hormonal Manipulation of Benign Metastasizing Leiomyomas: Report of Two Cases and Review of the Literature". Journal of Clinical Endocrinology & Metabolism. 89 (7): 3183–3188. doi:10.1210/jc.2003-032021. PMID 15240591.
## External links[edit]
Classification
D
* ICD-10: D21, D25 (ILDS D21.M40)
* ICD-9-CM: 218
* ICD-O: M8890/0-8894
* MeSH: D007889
External resources
* MedlinePlus: dostinex
* Esophageal Leiomyoma at eMedicine
* 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
Connective/soft tissue tumors and sarcomas
Not otherwise specified
* Soft-tissue sarcoma
* Desmoplastic small-round-cell tumor
Connective tissue neoplasm
Fibromatous
Fibroma/fibrosarcoma:
* Dermatofibrosarcoma protuberans
* Desmoplastic fibroma
Fibroma/fibromatosis:
* Aggressive infantile fibromatosis
* Aponeurotic fibroma
* Collagenous fibroma
* Diffuse infantile fibromatosis
* Familial myxovascular fibromas
* Fibroma of tendon sheath
* Fibromatosis colli
* Infantile digital fibromatosis
* Juvenile hyaline fibromatosis
* Plantar fibromatosis
* Pleomorphic fibroma
* Oral submucous fibrosis
Histiocytoma/histiocytic sarcoma:
* Benign fibrous histiocytoma
* Malignant fibrous histiocytoma
* Atypical fibroxanthoma
* Solitary fibrous tumor
Myxomatous
* Myxoma/myxosarcoma
* Cutaneous myxoma
* Superficial acral fibromyxoma
* Angiomyxoma
* Ossifying fibromyxoid tumour
Fibroepithelial
* Brenner tumour
* Fibroadenoma
* Phyllodes tumor
Synovial-like
* Synovial sarcoma
* Clear-cell sarcoma
Lipomatous
* Lipoma/liposarcoma
* Myelolipoma
* Myxoid liposarcoma
* PEComa
* Angiomyolipoma
* Chondroid lipoma
* Intradermal spindle cell lipoma
* Pleomorphic lipoma
* Lipoblastomatosis
* Spindle cell lipoma
* Hibernoma
Myomatous
general:
* Myoma/myosarcoma
smooth muscle:
* Leiomyoma/leiomyosarcoma
skeletal muscle:
* Rhabdomyoma/rhabdomyosarcoma: Embryonal rhabdomyosarcoma
* Sarcoma botryoides
* Alveolar rhabdomyosarcoma
* Leiomyoma
* Angioleiomyoma
* Angiolipoleiomyoma
* Genital leiomyoma
* Leiomyosarcoma
* Multiple cutaneous and uterine leiomyomatosis syndrome
* Multiple cutaneous leiomyoma
* Neural fibrolipoma
* Solitary cutaneous leiomyoma
* STUMP
Complex mixed and stromal
* Adenomyoma
* Pleomorphic adenoma
* Mixed Müllerian tumor
* Mesoblastic nephroma
* Wilms' tumor
* Malignant rhabdoid tumour
* Clear-cell sarcoma of the kidney
* Hepatoblastoma
* Pancreatoblastoma
* Carcinosarcoma
Mesothelial
* Mesothelioma
* Adenomatoid tumor
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Leiomyoma | c0023267 | 4,528 | wikipedia | https://en.wikipedia.org/wiki/Leiomyoma | 2021-01-18T18:56:37 | {"mesh": ["D007889"], "umls": ["C0023267"], "icd-9": ["218"], "icd-10": ["D21", "D25"], "wikidata": ["Q4667534"]} |
A number sign (#) is used with this entry because of evidence that preaxial polydactyly I (PPD1) is caused by homozygous mutation in the GLI1 gene (165220) on chromosome 12q13. One such family has been reported.
Homozygous mutation in the GLI1 gene has also been reported to cause postaxial polydactyly type A8 (PAPA8; 618123).
Description
Preaxial polydactyly, i.e., polydactyly on the radial side of the hand, is a heterogeneous category. Four types are: (1) thumb polydactyly, (2) polydactyly of triphalangeal thumb, (3) polydactyly of index finger, and (4) polysyndactyly. Preaxial polydactyly I, 'thumb polydactyly,' involves duplication of 1 or more of the skeletal components of a biphalangeal thumb. Severity varies from mere broadening of the distal phalanx with slight bifurcation at the tip to full duplication of the thumb including the metacarpals. This type is the most frequent form of polydactyly in many populations (Handforth, 1950).
Clinical Features
Digby (1645) reported preaxial polydactyly, presumably of this type, in females in 5 generations. Pott (1884) observed 10 affected (6 females and 4 males) in 3 generations. Sinha (1918) found irregular segregation in a family with affected persons in 3 generations. In 1 generation, only 1 of 13 persons at risk were affected. Sobbota and De Marinis (1957) observed a girl with bilateral thumb polydactyly whose mother had radial deviation of the terminal phalanx (a feature that Pott also considered a manifestation of the same trait). No male-to-male transmission seems to have been documented.
Bingle and Niswander (1975) found that polydactyly is about twice as frequent in the American Indian as in Caucasians. Preaxial polydactyly type I was 3 to 4 times more frequent than in Caucasians or Blacks. More females than males were affected. It showed a strong predilection for the hands and was always unilateral, whereas postaxial polydactyly type B was bilateral in more than half of affected persons. Although the evidence suggests that polydactyly is in large part genetically determined, it was difficult to choose between a single autosomal dominant gene with reduced penetrance and a multigenic threshold model involving a few major genes.
Kelly (1982) observed a family in which symmetric duplication of the thumbs and great toes was observed over 5 or 6 generations with frequent examples of male-to-male transmission.
Graham and Hoefnagel (1982) and Graham et al. (1985, 1987) suggested that a minor expression of thumb polydactyly is aplasia or hypoplasia of the thumb musculature and that this trait may more often be autosomal dominant than one would realize from a study of polydactyly alone. They referred to this minor change as Fromont anomaly, after the French anatomist who described it (Fromont, 1895); see Haller (1977).
Ray (1987) reported a family in Andhra Pradesh, India with preaxial polydactyly in 15 males and 5 females in 6 generations. Bilateral duplication of the big toe showed reduced penetrance and variable expressivity. Duplication of the thumb was a less consistent feature.
Castilla et al. (1997) concluded from epidemiologic studies that hand postaxial polydactyly differs from foot postaxial polydactyly. This prompted Orioli and Castilla (1999) to test whether thumb and hallux duplication also had different clinical and epidemiologic characteristics, depending on the limb involved. They studied 920 newborns with first digit duplication, ascertained among 3,444,374 births by the Latin-American Collaborative Study of Congenital Malformations, from 1967 to 1995. Since biphalangeal thumb duplication or hallux duplication can occur in families with triphalangeal thumb or polysyndactyly propositi, these groups were also analyzed. The 715 isolated (nonsyndromal) cases (prevalence 2.08 per 10,000) were subdivided into 5 groups: (1) thumb duplication (n = 568; prevalence = 1.65/10,000); (2) hallux duplication (n = 82; prevalence = 0.24); (3) thumb and/or hallux duplication plus syndactyly (polysyndactyly) (n = 37; prevalence = 0.11); (4) triphalangeal thumb (n = 24; prevalence = 0.07); and (5) thumb duplication plus hallux duplication (n = 4; prevalence = 0.01). Both the thumb and hallux duplication groups showed a significant excess of males, and right-sidedness was also more frequent in both forms though without statistical significance for hallux duplication. Thumb duplication was more often unilateral (94.7% vs. 81.5% for hallux duplication), and its prevalence was higher in Bolivia (3.37/10,000) than in the other 10 Latin-American countries included in this study (1.62/10,000).
Ullah et al. (2019) reported a consanguineous Pakistani family in which 2 cousins exhibited bilateral preaxial polydactyly of the hands. The authors stated that x-ray showed duplication of the distal phalanx of the thumb (Figure 1 appears to show bifid distal phalanx of the thumb).
Mapping
By genotyping highly polymorphic microsatellite markers in a consanguineous Pakistani family in which 2 cousins exhibited bilateral preaxial polydactyly of the hands, Ullah et al. (2019) established linkage to the GLI1 locus on chromosome 12q13.3.
Molecular Genetics
In a consanguineous Pakistani family in which 2 cousins exhibited bilateral preaxial polydactyly mapping to chromosome 12q13.3, Ullah et al. (2019) identified homozygosity for a missense mutation in the GLI1 gene (L506Q; 165220.0004) that segregated fully with disease in the family and was not found in 70 unrelated Pakistani controls.
### Associations Pending Confirmation
For discussion of a possible association between preaxial polydactyly and mutation in the STKLD1 gene, see 618530.0001.
INHERITANCE \- Autosomal recessive SKELETAL Hands \- Duplication of distal phalanx of thumbs \- Bifid thumb MISCELLANEOUS \- Based on report of 2 cousins from a consanguineous Pakistani family (last curated April 2019) MOLECULAR BASIS \- Caused by mutation in the glioma-associated oncogene homolog (GLI1, 165220.0004 ) ▲ Close
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*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| POLYDACTYLY, PREAXIAL I | c1395852 | 4,529 | omim | https://www.omim.org/entry/174400 | 2019-09-22T16:36:03 | {"mesh": ["C536332"], "omim": ["174400"], "icd-10": ["Q69.1"], "orphanet": ["93339"], "synonyms": ["Alternative titles", "POLYDACTYLY, PREAXIAL", "THUMB POLYDACTYLY"]} |
## Clinical Features
In the son and daughter of consanguineous Arab parents, Lubani et al. (1991) observed cystic fibrosis and gastritis associated with Helicobacter pylori, folate deficiency, megaloblastic anemia, and subnormal mentality. Warren and Marshall (1983) first identified Helicobacter pylori (previously known as Campylobacter pylori) in patients with chronic active gastritis. Although the association of findings in these sibs may have been coincidental, the possibility of a distinct autosomal recessive disorder associated with facies different from the rest of the family (including a broad nasal bridge and prominent ear lobules) led Lubani et al. (1991) to favor a new recessive syndrome.
INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Long face \- Frontal bossing Ears \- Prominent ear lobule Eyes \- Telecanthus \- Small, deep-set eyes Mouth \- Micrognathia, mild RESPIRATORY \- Recurrent bronchopulmonary infections ABDOMEN Gastrointestinal \- Helicobacter pylori gastritis \- Diarrhea GENITOURINARY External Genitalia (Male) \- Shawl scrotum \- Glanular hypospadias SKIN, NAILS, & HAIR Skin \- High sweat electrolyte NEUROLOGIC Central Nervous System \- Mental retardation (IQ 50-60 combined Griffiths and Stanford-Binet scale) HEMATOLOGY \- Megaloblastic anemia LABORATORY ABNORMALITIES \- Folate deficiency \- High sweat electrolyte MISCELLANEOUS \- Reported in 2 sibs (February 1991) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| CYSTIC FIBROSIS WITH HELICOBACTER PYLORI GASTRITIS, MEGALOBLASTIC ANEMIA, AND MENTAL RETARDATION | c2931402 | 4,530 | omim | https://www.omim.org/entry/219721 | 2019-09-22T16:29:01 | {"mesh": ["C537039"], "omim": ["219721"], "orphanet": ["2575"]} |
Irvine–Gass Syndrome
Other namesPseudophakic cystoid macular edema, Postcataract CME
SpecialtyOphthalmology
Irvine–Gass syndrome, pseudophakic cystoid macular edema or postcataract CME is one of the most common causes of visual loss after cataract surgery.[1][2] The syndrome is named in honor of S. Rodman Irvine[3][4] and J. Donald M. Gass.[5]
The incidence is more common in older types of cataract surgery, where postcataract CME could occur in 20–60% of patients,[6] but with modern cataract surgery, incidence of Irvine–Gass syndrome have reduced significantly.[7]
Replacement of the lens as treatment for cataract can cause pseudophakic macular edema. (‘pseudophakia’ means ‘replacement lens’) this could occur as the surgery involved sometimes irritates the retina (and other parts of the eye) causing the capillaries in the retina to dilate and leak fluid into the retina. This is less common today with modern lens replacement techniques.[8]
## References[edit]
1. ^ Flach, A J (1998). "The incidence, pathogenesis and treatment of cystoid macular edema following cataract surgery". Trans Am Ophthalmol Soc. 96: 557–634. PMC 1298410. PMID 10360304.
2. ^ Kiernan, Daniel F.; Hariprasad, Seenu M. (1 November 2013). "Controversies in the management of Irvine–Gass syndrome". Ophthalmic Surgery, Lasers and Imaging Retina. 44 (6): 522–527. doi:10.3928/23258160-20131105-01. PMID 24221459.
3. ^ Straatsma, Bradley R. (2000). "S. Rodman Irvine, MD". Transactions of the American Ophthalmological Society. 98: 9–10. PMC 1298207.
4. ^ Irvine, Alexander (2000). "S. Rodman Irvine, MD (1906–1999". Archives of Ophthalmology. 118 (6): 863. doi:10.1001/archopht.118.6.863.
5. ^ Flynn, Harry W.; Curtin, Victor T. (2005). "J. Donald M. Gass, MD (1928–2005)". Archives of Ophthalmology. 123 (7): 1023. doi:10.1001/archopht.123.7.1023.
6. ^ Telander, David G; Cessna, Christopher T (2019-10-20). "Pseudophakic (Irvine–Gass) Macular Edema". Medscape.
7. ^ Bélair, Marie-Lyne; Kim, Stephen J.; Thorne, Jennifer E.; Dunn, James P.; Kedhar, Sanjay R.; Brown, Diane M.; Jabs, Douglas A. (July 2009). "Incidence of Cystoid Macular Edema after Cataract Surgery in Patients with and without Uveitis Using Optical Coherence Tomography". American Journal of Ophthalmology. 148 (1): 128–135.e2. doi:10.1016/j.ajo.2009.02.029. PMC 2722753. PMID 19403110.
8. ^ Boston, David R. Lally, MD, and Chirag P. Shah, MD, MPH. "Pseudophakic Cystoid Macular Edema". Retrieved 2017-12-13.
## External links[edit]
Classification
D
External resources
* eMedicine: article/1224224
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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
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*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Irvine–Gass syndrome | c0271178 | 4,531 | wikipedia | https://en.wikipedia.org/wiki/Irvine%E2%80%93Gass_syndrome | 2021-01-18T18:33:30 | {"mesh": ["D008269"], "umls": ["C0271178"], "wikidata": ["Q19597605"]} |
Metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome is characterized by metaphyseal dysplasia associated with short stature and facial dysmorphism (a beaked nose, short philtrum, thin lips, maxillary hypoplasia, dystrophic yellowish teeth) and acral anomalies (short fifth metacarpals and/or short middle phalanges of fingers two and five). It has been described in several members spanning four generations of a French-Canadian family. The syndrome is likely to be transmitted as an autosomal dominant trait.
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*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
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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
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*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome | c3549874 | 4,532 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2504 | 2021-01-23T17:36:13 | {"gard": ["3568"], "omim": ["156510"], "icd-10": ["Q77.8"]} |
Microdamage in bone can be caused by the various loads to which bones are subjected during normal daily activity. It occurs in two different types mainly depending on the load: diffuse damage and microcracks.
## References[edit]
* Burr, D.B.; Allen, M.R. (2013). Basic and Applied Bone Biology. Elsevier Science. pp. 23–24. ISBN 978-0-12-391459-0.
This human musculoskeletal system article is a stub. You can help Wikipedia by expanding it.
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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
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*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
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*[MSNs]: medium spiny neurons
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*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
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| Microdamage in bone | None | 4,533 | wikipedia | https://en.wikipedia.org/wiki/Microdamage_in_bone | 2021-01-18T18:36:29 | {"wikidata": ["Q6839441"]} |
Essex-Lopresti fracture
SpecialtyOrthopaedics
SymptomsDislocation of the forearm
ComplicationsMal-Union
TreatmentOpen reduction and internal fixation with plates
PrognosisGood if treated early
DeathsRare
The Essex-Lopresti fracture is a fracture of the radial head with concomitant dislocation of the distal radio-ulnar joint and disruption of the interosseous membrane.[1] The injury is named after Peter Essex-Lopresti who described it in 1951.[2]
Descriptive image link
## Contents
* 1 Cause
* 2 Diagnosis
* 3 Management
* 4 References
* 5 External links
## Cause[edit]
This fracture occurs in patients who have fallen from a height.[citation needed]
## Diagnosis[edit]
The injury can be difficult to diagnose initially as the attention is focused on the injury to the radial head, leading to the distal radio-ulnar injury being overlooked. The examination finding of tenderness of the distal radio-ulnar joint suggests an Essex-Lopresti injury in patients who have sustained high energy forearm trauma. Plain radiography shows the radial head fracture, with dorsal subluxation of the ulna often seen on lateral view of the pronated wrist.[1]
## Management[edit]
The radial head fracture is usually managed by open reduction internal fixation; if the fracture is too comminuted, a radial head implant can be used. Excision of the radial head should be avoided, as the radius will migrate proximally leading to wrist pain and loss of pronation and supination of the wrist. Delayed treatment of the radial head fracture will also lead to proximal migration of the radius.[3]
The distal radio-ulnar joint dislocation can be reduced by supination of the forearm, and may be pinned in place for 6 weeks to allow healing of the interosseous membrane.[1]
## References[edit]
1. ^ a b c Essex Lopresti fracture at Wheeless' Textbook of Orthopaedics online
2. ^ Essex-Lopresti, P (May 1951). "Fractures of the radial head with distal radio-ulnar dislocation: report of two cases". J Bone Joint Surg Br. 33B (2): 244–7. PMID 14832324.
3. ^ Edwards, GS Jr.; Jupiter JB (Sep 1988). "Radial head fractures with acute radioulnar dislocation. Essex-Lopresti revisited". Clin Orthop Relat Res (234): 61–9. PMID 3409602.
## External links[edit]
Classification
D
* ICD-10: S52.1
* MeSH: 68011885
External resources
* AO Foundation: 21-A2.2
* v
* t
* e
Fractures and cartilage damage
General
* Avulsion fracture
* Chalkstick fracture
* Greenstick fracture
* Open fracture
* Pathologic fracture
* Spiral fracture
Head
* Basilar skull fracture
* Blowout fracture
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* Le Fort fracture of skull
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Ribs
* Rib fracture
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* Clavicle
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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
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* Duverney fracture
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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
*[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
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Essex-Lopresti fracture | c2711658 | 4,534 | wikipedia | https://en.wikipedia.org/wiki/Essex-Lopresti_fracture | 2021-01-18T18:57:23 | {"umls": ["C2711658"], "wikidata": ["Q1368814"]} |
This syndrome is characterized by hypergonadotropic hypogonadism, intellectual deficit, congenital skeletal anomalies involving the cervical spine and superior ribs, and diabetes mellitus.
## Epidemiology
It has been described in two brothers.
## Clinical description
Testicular biopsy revealed germinal aplasia and complete seminiferous tubular fibrosis.
*[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
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Male hypergonadotropic hypogonadism-intellectual disability-skeletal anomalies syndrome | c2931285 | 4,535 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2234 | 2021-01-23T18:22:31 | {"gard": ["4899"], "mesh": ["C536679"], "omim": ["307500"], "umls": ["C2931285"], "icd-10": ["Q87.8"], "synonyms": ["Sohval-Soffer syndrome"]} |
Bowen–Conradi syndrome
Other namesBCS[1] or BWCNS[2]
Bowen–Conradi syndrome is a disease in humans that can affect children.[2] The disease is due to an autosomal recessive abnormality of the EMG1 gene, which plays a role in small ribosomal subunit (SSU) assembly.[1][3] The preponderance of diagnoses has been in North American Hutterite children, but BWCNS can affect other population groups.[2][4]
BWCNS is a ribosomopathy.[1][5] A D86G mutation of EMG1 destroys an EcoRV restriction endonuclease site in the most highly conserved region of the protein.[3]
Skeletal dysmorphology is seen[2][4] and severe prenatal and postnatal growth failure usually leads to death by one year of age.[6]
## References[edit]
1. ^ a b c Sondalle SB, Baserga SJ (2014). "Human diseases of the SSU processome". Biochim. Biophys. Acta. 1842 (6): 758–64. doi:10.1016/j.bbadis.2013.11.004. PMC 4058823. PMID 24240090.CS1 maint: uses authors parameter (link)
2. ^ a b c d Online Mendelian Inheritance in Man (OMIM): 211180
3. ^ a b Online Mendelian Inheritance in Man (OMIM): 611531
4. ^ a b Armistead J, Khatkar S, Meyer B, Mark BL, Patel N, Coghlan G, Lamont RE, Liu S, Wiechert J, Cattini PA, Koetter P, Wrogemann K, Greenberg CR, Entian KD, Zelinski T, Triggs-Raine B (2009). "Mutation of a gene essential for ribosome biogenesis, EMG1, causes Bowen-Conradi syndrome". Am. J. Hum. Genet. 84 (6): 728–39. doi:10.1016/j.ajhg.2009.04.017. PMC 2694972. PMID 19463982.CS1 maint: uses authors parameter (link)
5. ^ De Souza RA (2010). "Mystery behind Bowen-Conradi syndrome solved: a novel ribosome biogenesis defect". Clin. Genet. 77 (2): 116–8. doi:10.1111/j.1399-0004.2009.01304.x. PMID 20096068.CS1 maint: uses authors parameter (link)
6. ^ Armistead J, Patel N, Wu X, et al. (2015). "Growth arrest in the ribosomopathy, Bowen-Conradi syndrome, is due to dramatically reduced cell proliferation and a defect in mitotic progression". Biochim. Biophys. Acta. 1852 (5): 1029–37. doi:10.1016/j.bbadis.2015.02.007. PMID 25708872.
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*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Bowen–Conradi syndrome | c1859405 | 4,536 | wikipedia | https://en.wikipedia.org/wiki/Bowen%E2%80%93Conradi_syndrome | 2021-01-18T18:30:59 | {"gard": ["5950"], "mesh": ["C537081"], "umls": ["C1859405"], "orphanet": ["1270"], "wikidata": ["Q18553398"]} |
A number sign (#) is used with this entry because the Finkel type of late-onset autosomal dominant spinal muscular atrophy (SMAFK) is caused by heterozygous mutation in the gene encoding vesicle-associated membrane protein-associated protein B (VAPB; 605704) on chromosome 20q13.
Description
Spinal muscular atrophy is characterized by degeneration of the anterior horn cells in the spinal cord, leading to symmetric muscle weakness and wasting.
See also autosomal recessive adult-onset proximal spinal muscular atrophy (SMA4; 271150), caused by defect in the SMN1 gene (600354), and autosomal dominant childhood-onset proximal SMA (158600).
Clinical Features
Pearn (1978) reported 13 patients from 6 kindreds with autosomal dominant proximal spinal muscular atrophy. Median age at disease onset was 37 years. The authors estimated that 30% of adult onset cases of SMA are due to an autosomal dominant gene. Pearn (1978) suggested that a separate gene was responsible for autosomal dominant SMA with childhood onset (birth to 8 years).
Richieri-Costa et al. (1981) studied 2 kindreds in which 80 members were affected with an autosomal dominant, slowly progressive spinal muscular atrophy of late onset (average 48.8 years). One of the 2 kindreds was first described by Finkel (1962); the second was a black family living in the same region. The neurogenic nature of the disorder was established by electromyography and muscle biopsy. Unusual findings in this disorder were slow loss of muscle strength and progressive proximal atrophy, which started in the legs and later involved the arms; hypoactive or absent deep tendon reflexes; and generalized fasciculations. Adult spinal muscular atrophy usually begins after the third decade of life, and survival for several decades is typical. Emery (1971) cited cases by Tsukagoshi et al. (1965) and Peters et al. (1968).
In a study on the classification and genetics of proximal SMA, Zerres (1989) documented the clinical course of 6 families including 20 patients suffering from an autosomal dominant form. Three families were classified as having the adult-onset form (after age 20 years). The patients showed a benign course, most of them remaining ambulatory 10 to 40 years after clinical onset (Rietschel et al., 1992). Three patients of the other 3 families suffered from the childhood-onset form, with first symptoms before the age of 12 years and walking difficulties throughout life, whereas other members of these families would have been classified as the adult-onset form. The latter had an onset between ages 17 and 28 years and were only moderately handicapped when examined at ages 38 to 60 years. Rietschel et al. (1992) suggested that the great intrafamilial variability in at least some of the families with autosomal dominant SMA is not compatible with the distinction of 2 clinically defined genetic entities.
Mapping
Kausch et al. (1991) performed linkage studies in 4 families with the autosomal dominant form of proximal spinal muscular atrophy. Three of the families met the criteria proposed by Pearn (1978). In a fourth family, affected individuals presented with an unusually mild SMA with muscle cramps (Ricker and Moxley, 1990); see 158400. For the first 3 families taken together and the fourth family taken alone, close linkage to D5S6, where the SMN1 gene is located, was excluded. The authors concluded that autosomal dominant and autosomal recessive forms of SMA are distinct genetic entities.
Molecular Genetics
In 3 families with the Finkel type of late-onset spinal muscular atrophy, Nishimura et al. (2004) found a missense mutation in the VAPB gene (605704.0001). They identified the same mutation in another 3 families with ALS8 (608627) and in 1 family in which some patients had typical, and others atypical, ALS. Although it was not possible to link all these families genealogically, haplotype analysis suggested founder effect. Members of the vesicle-associated proteins are intracellular membrane proteins that can associate with microtubules and that have a function in membrane transport. The data suggested that clinically variable motor neuron diseases may be caused by a dysfunction in intracellular membrane trafficking.
INHERITANCE \- Autosomal dominant MUSCLE, SOFT TISSUES \- Muscle weakness, proximal, due to neuronopathy, begins in the lower limbs and then progresses to upper limbs NEUROLOGIC Central Nervous System \- Muscle weakness, proximal, due to neuronopathy begins in the lower limbs and then progresses to upper limbs \- Fasciculations \- Hyporeflexia \- EMG shows neurogenic abnormalities MISCELLANEOUS \- Onset after third decade MOLECULAR BASIS \- Caused by mutation in the vesicle-associated membrane protein-associated protein B gene (VAPB, 605704.0001 ) ▲ Close
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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
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| SPINAL MUSCULAR ATROPHY, LATE-ONSET, FINKEL TYPE | c1866777 | 4,537 | omim | https://www.omim.org/entry/182980 | 2019-09-22T16:34:34 | {"doid": ["0111194"], "mesh": ["C566672"], "omim": ["182980"], "orphanet": ["209335"], "synonyms": ["Alternative titles", "FINKEL LATE-ADULT TYPE SMA", "SPINAL MUSCULAR ATROPHY, PROXIMAL, ADULT, AUTOSOMAL DOMINANT"]} |
Epilepsy-microcephaly-skeletal dysplasia syndrome is characterized by the association of moderate to severe intellectual deficit, microcephaly, epilepsy, coarse face, hirsutism and skeletal abnormalities (scoliosis and retarded bone development). It has been described only once, in two sibs (one male and one female). This syndrome is likely to be an autosomal recessive condition and thus parents should be informed of a 25% risk of recurrence for other children.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Epilepsy-microcephaly-skeletal dysplasia syndrome | c2931579 | 4,538 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1948 | 2021-01-23T19:07:30 | {"gard": ["836"], "mesh": ["C537662"], "omim": ["601352"], "umls": ["C2931579"], "icd-10": ["Q87.8"], "synonyms": ["Battaglia-Neri syndrome"]} |
Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) is a condition that mainly affects development of the eyelids. People with this condition have a narrowing of the eye opening (blepharophimosis), droopy eyelids (ptosis), and an upward fold of the skin of the lower eyelid near the inner corner of the eye (epicanthus inversus). In addition, there is an increased distance between the inner corners of the eyes (telecanthus). Because of these eyelid abnormalities, the eyelids cannot open fully, and vision may be limited.
Other structures in the eyes and face may be mildly affected by BPES. Affected individuals are at an increased risk of developing vision problems such as nearsightedness (myopia) or farsightedness (hyperopia) beginning in childhood. They may also have eyes that do not point in the same direction (strabismus) or "lazy eye" (amblyopia) affecting one or both eyes. People with BPES may also have distinctive facial features including a broad nasal bridge, low-set ears, or a shortened distance between the nose and upper lip (a short philtrum).
There are two types of BPES, which are distinguished by their signs and symptoms. Both types I and II include the eyelid malformations and other facial features. Type I is also associated with an early loss of ovarian function (primary ovarian insufficiency) in women, which causes their menstrual periods to become less frequent and eventually stop before age 40. Primary ovarian insufficiency can lead to difficulty conceiving a child (subfertility) or a complete inability to conceive (infertility).
## Frequency
The prevalence of BPES is unknown.
## Causes
Mutations in the FOXL2 gene cause BPES types I and II. The FOXL2 gene provides instructions for making a protein that is active in the eyelids and ovaries. The FOXL2 protein is likely involved in the development of muscles in the eyelids. Before birth and in adulthood, the protein regulates the growth and development of certain ovarian cells and the breakdown of specific molecules.
It is difficult to predict the type of BPES that will result from the many FOXL2 gene mutations. However, mutations that result in a partial loss of FOXL2 protein function generally cause BPES type II. These mutations probably impair regulation of normal development of muscles in the eyelids, resulting in malformed eyelids that cannot open fully. Mutations that lead to a complete loss of FOXL2 protein function often cause BPES type I. These mutations impair the regulation of eyelid development as well as various activities in the ovaries, resulting in eyelid malformation and abnormally accelerated maturation of certain ovarian cells and the premature death of egg cells.
### Learn more about the gene associated with Blepharophimosis, ptosis, and epicanthus inversus syndrome
* FOXL2
## Inheritance Pattern
This condition is typically 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.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Blepharophimosis, ptosis, and epicanthus inversus syndrome | c1862263 | 4,539 | medlineplus | https://medlineplus.gov/genetics/condition/blepharophimosis-ptosis-and-epicanthus-inversus-syndrome/ | 2021-01-27T08:25:18 | {"gard": ["23"], "mesh": ["C566222"], "omim": ["110100"], "synonyms": []} |
A rare, lethal perinatal bone dysplasia characterized by limb shortening, normal sized skull with cleft palate, hitchhiker thumbs, distinctive facial dysmorphism and radiographic skeletal features, caused by mutations in the diastrophic dysplasia sulfate transporter gene.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Atelosteogenesis type II | c1850554 | 4,540 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=56304 | 2021-01-23T18:51:33 | {"gard": ["8329"], "mesh": ["C535395"], "omim": ["256050"], "umls": ["C0432203", "C1850554", "C1850555"], "icd-10": ["Q77.5"], "synonyms": ["AO2", "AOII", "Atelosteogenesis type 2", "De la Chapelle dysplasia", "Neonatal osseous dysplasia type 1"]} |
This article needs more links to other articles to help integrate it into the encyclopedia. Please help improve this article by adding links that are relevant to the context within the existing text. (April 2014) (Learn how and when to remove this template message)
MURCS association
Other namesMüllerian duct aplasia-renal dysplasia-cervical somite anomalies syndrome
This condition can be inherited in an autosomal dominant manner(though not always)[1]
SpecialtyMedical genetics
MURCS association (a variant of Mayer-Rokitansky-Küster-Hauser syndrome) is a very rare developmental disorder[2] that primarily affects the reproductive and urinary systems involving MUllerian agenesis, Renal agenesis, Cervicothoracic Somite abnormalities.[3] It affects only females.
## Contents
* 1 Genetics
* 2 Diagnosis
* 3 Treatment
* 4 Notes
* 5 References
* 6 External links
## Genetics[edit]
Genetic heterogeneity is observed in MURCS association.[4]
## Diagnosis[edit]
This section is empty. You can help by adding to it. (August 2017)
## Treatment[edit]
This section is empty. You can help by adding to it. (August 2017)
## Notes[edit]
1. ^ RESERVED, INSERM US14 -- ALL RIGHTS. of diseases=Mayer-Rokitansky-Kuster-Hauser-syndrome-type-2&title=Mayer-Rokitansky-Kuster-Hauser-syndrome-type-2&search=Disease_Search_Simple "Orphanet: Mayer Rokitansky Kuster Hauser syndrome type 2" Check `|url=` value (help). www.orpha.net. Retrieved 1 August 2017.
2. ^ "MURCS association". Genetic and Rare Diseases Information Center (GARD). Retrieved 1 November 2013.
3. ^ Mahajan, P; Kher, A; Khungar, A; Bhat, M; Sanklecha, M; Bharucha, BA (Jul–Sep 1992). "MURCS association--a review of 7 cases". Journal of Postgraduate Medicine. 38 (3): 109–11. PMID 1303407.
4. ^ Hofstetter, G; Concin, N; Marth, C; Rinne, T; Erdel, M; Janecke, A (2008). "Genetic analyses in a variant of Mayer-Rokitansky-Kuster-Hauser syndrome (MURCS association)". Wiener klinische Wochenschrift. 120 (13–14): 435–9. doi:10.1007/s00508-008-0995-4. PMID 18726671. S2CID 9454103.
## References[edit]
* "MURCS Association". National Organization for Rare Disorders, Inc. Archived from the original on 2013-11-03.
* Duncan, PA; Shapiro, LR; Stangel, JJ; Klein, RM; Addonizio, JC (September 1979). "The MURCS association: Müllerian duct aplasia, renal aplasia, and cervicothoracic somite dysplasia". The Journal of Pediatrics. 95 (3): 399–402. doi:10.1016/s0022-3476(79)80514-4. PMID 469663.
* Greene, RA; Bloch, MJ; Huff, DS; Iozzo, RV (January 1986). "MURCS association with additional congenital anomalies". Human Pathology. 17 (1): 88–91. doi:10.1016/s0046-8177(86)80160-5. PMID 3510965.
## External links[edit]
Classification
D
* ICD-10: Q87.8
* OMIM: 601076
External resources
* Orphanet: 2578
*[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
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| MURCS association | c1832817 | 4,541 | wikipedia | https://en.wikipedia.org/wiki/MURCS_association | 2021-01-18T19:04:02 | {"gard": ["5513"], "mesh": ["C537371"], "umls": ["C1832817"], "icd-10": ["Q87.8"], "orphanet": ["2578"], "wikidata": ["Q9161215"]} |
Hutchinson-Gilford progeria syndrome is a genetic condition characterized by the dramatic, rapid appearance of aging beginning in childhood. Affected children typically look normal at birth and in early infancy, but then grow more slowly than other children and do not gain weight at the expected rate (failure to thrive). They develop a characteristic facial appearance including prominent eyes, a thin nose with a beaked tip, thin lips, a small chin, and protruding ears. Hutchinson-Gilford progeria syndrome also causes hair loss (alopecia), aged-looking skin, joint abnormalities, and a loss of fat under the skin (subcutaneous fat). This condition does not affect intellectual development or the development of motor skills such as sitting, standing, and walking.
People with Hutchinson-Gilford progeria syndrome experience severe hardening of the arteries (arteriosclerosis) beginning in childhood. This condition greatly increases the chances of having a heart attack or stroke at a young age. These serious complications can worsen over time and are life-threatening for affected individuals.
## Frequency
This condition is very rare; it is reported to occur in 1 in 4 million newborns worldwide. More than 130 cases have been reported in the scientific literature since the condition was first described in 1886.
## Causes
Mutations in the LMNA gene cause Hutchinson-Gilford progeria syndrome. The LMNA gene provides instructions for making a protein called lamin A. This protein plays an important role in determining the shape of the nucleus within cells. It is an essential scaffolding (supporting) component of the nuclear envelope, which is the membrane that surrounds the nucleus. Mutations that cause Hutchinson-Gilford progeria syndrome result in the production of an abnormal version of the lamin A protein. The altered protein makes the nuclear envelope unstable and progressively damages the nucleus, making cells more likely to die prematurely. Researchers are working to determine how these changes lead to the characteristic features of Hutchinson-Gilford progeria syndrome.
### Learn more about the gene associated with Hutchinson-Gilford progeria syndrome
* LMNA
## Inheritance Pattern
Hutchinson-Gilford progeria syndrome is considered an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. The condition results from new mutations in the LMNA gene, and almost always occurs in people with no history of the disorder in their family.
*[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
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Hutchinson-Gilford progeria syndrome | c0033300 | 4,542 | medlineplus | https://medlineplus.gov/genetics/condition/hutchinson-gilford-progeria-syndrome/ | 2021-01-27T08:24:49 | {"gard": ["7467"], "mesh": ["D011371"], "omim": ["176670"], "synonyms": []} |
Sign of a few neurodegenerative disorders
Rosenthal fibers.
H&E staining showing these elongated eosinophilic structures in a case of pilocytic astrocytoma. Magnification 400x
A Rosenthal fiber is a thick, elongated, worm-like or "corkscrew" eosinophilic (pink) bundle that is found on staining of brain tissue in the presence of long-standing gliosis, occasional tumors, and some metabolic disorders.
## Contents
* 1 Associated conditions
* 2 Composition
* 3 References
* 4 External links
## Associated conditions[edit]
Its presence is associated with either pilocytic astrocytoma[1] (more common) or Alexander's disease (a rare leukodystrophy). They are also seen in the context of fucosidosis.
Pilocytic astrocytoma is the most common primitive tumor found in pediatrics.
## Composition[edit]
The fibers are found in astrocytic processes and are thought to be clumped intermediate filament proteins, primarily glial fibrillary acidic protein.[2] Other reported constituents include alphaB crystallin, heat shock protein 27, protein beta-1), ubiquitin, vimentin, plectin, c-Jun, the 20 S proteasome, and synemin.[3]
## References[edit]
1. ^ Wippold FJ, Perry A, Lennerz J (May 2006). "Neuropathology for the neuroradiologist: Rosenthal fibers". AJNR Am J Neuroradiol. 27 (5): 958–61. PMID 16687524.
2. ^ Tanaka KF, Ochi N, Hayashi T, Ikeda E, Ikenaka K (October 2006). "Fluoro-Jade: new fluorescent marker of Rosenthal fibers". Neurosci. Lett. 407 (2): 127–30. doi:10.1016/j.neulet.2006.08.014. PMID 16949206.
3. ^ Heaven, MR; Flint, D; Randall, SM; et al. (1 July 2016). "Composition of Rosenthal Fibers, the Protein Aggregate Hallmark of Alexander Disease". Journal of proteome research. 15 (7): 2265–82. doi:10.1021/acs.jproteome.6b00316. PMC 5036859. PMID 27193225.
## External links[edit]
* Neuropathology Mini-Course. Chapter 9 - Tumors of the Nervous System
* Doctor's Doctor - Brain and Spinal Cord
* Isolation of a major protein component of Rosenthal fibers
This article related to pathology 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
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*[NOP]: Nociceptin receptor
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*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Rosenthal fiber | None | 4,543 | wikipedia | https://en.wikipedia.org/wiki/Rosenthal_fiber | 2021-01-18T18:37:34 | {"umls": ["C0333731"], "wikidata": ["Q1541620"]} |
Neuronal ceroid lipofuscinosis 3 (CLN3-NCL) is a rare condition that affects the nervous system. Signs and symptoms generally develop between age 4 and 8 years, although later onset cases have been reported. Affected people may experience rapidly progressive vision loss, developmental regression (loss of acquired milestones), cognitive decline, heart problems, seizures, speech disturbances, behavioral problems (including aggression), and movement abnormalities. Life expectancy generally ranges from the late teens to the 30's. CLN3-NCL is caused by changes (mutations) in the CLN3 gene and is inherited in an autosomal recessive manner. Treatment options are limited to therapies that can help relieve some of the symptoms.
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*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Neuronal ceroid lipofuscinosis 3 | c0751383 | 4,544 | gard | https://rarediseases.info.nih.gov/diseases/5897/neuronal-ceroid-lipofuscinosis-3 | 2021-01-18T17:58:44 | {"mesh": ["D009472"], "omim": ["204200"], "orphanet": ["79264"], "synonyms": ["Juvenile neuronal ceroid lipofuscinosis", "Vogt Spielmeyer disease", "Spielmeyer Sjogren disease", "CLN3 disease, juvenile "]} |
A number sign (#) is used with this entry because of evidence that achondrogenesis type IA (ACG1A) is caused by homozygous or compound heterozygous mutation in the TRIP11 gene (604505) on chromosome 14q32.
Description
The term achondrogenesis has been used to characterize the most severe forms of chondrodysplasia in humans, invariably lethal before or shortly after birth. Achondrogenesis type I is a severe chondrodystrophy characterized radiographically by deficient ossification in the lumbar vertebrae and absent ossification in the sacral, pubic and ischial bones and clinically by stillbirth or early death (Maroteaux and Lamy, 1968; Langer et al., 1969). In addition to severe micromelia, there is a disproportionately large cranium due to marked edema of soft tissues.
### Classification of Achondrogenesis
Achondrogenesis was traditionally divided into 2 types: type I (Parenti-Fraccaro) and type II (Langer-Saldino). Borochowitz et al. (1988) suggested that achondrogenesis type I of Parenti-Fraccaro should be classified into 2 distinct disorders: type IA, corresponding to the cases originally published by Houston et al. (1972) and Harris et al. (1972), and type IB (600972), corresponding to the case originally published by Fraccaro (1952). Analysis of the case reported by Parenti (1936) by Borochowitz et al. (1988) suggested the diagnosis of achondrogenesis type II, i.e., the Langer-Saldino type (200610). Type IA would be classified as lethal achondrogenesis, Houston-Harris type; type IB, lethal achondrogenesis, Fraccaro type; and type II, lethal achondrogenesis-hypochondrogenesis, Langer-Saldino type. Superti-Furga (1996) suggested that hypochondrogenesis should be considered separately from achondrogenesis type II because the phenotype can be much milder.
### Genetic Heterogeneity of Achondrogenesis
Achondrogenesis type IB (ACG1B; 600972) is caused by mutation in the DTDST gene (606718), and achondrogenesis type II (ACG2; 200610) is caused by mutation in the COL2A1 gene (120140).
Clinical Features
Houston et al. (1972) described a family from Saskatchewan, Canada, in which 4 of 10 sibs were diagnosed with achondrogenesis. Two were stillborn and 2 died shortly after birth. No osseous tissue or hemopoietic bone marrow was found in the cartilaginous sternum or vertebral bodies.
Wiedemann et al. (1974) pointed out the importance of distinguishing achondrogenesis from hypophosphatasia (241500).
Smith et al. (1981) reported 3 affected sibs, with in utero diagnosis of the third.
Borochowitz et al. (1988) studied the clinical, radiologic, and morphologic features of 17 cases previously diagnosed with achondrogenesis type I. On radiographic analysis, 2 distinct groups of patients were defined based on the presence or absence of rib fractures and ossification of the vertebral pedicles, ischium, and fibula. Microscopic studies of the chondroosseous morphology showed 2 distinct patterns that correlated directly with the radiographic grouping: one group had round, vacuolated chondrocytes with inclusion bodies, and the other had collagenous rings around the chondrocytes.
Vanegas et al. (2018) reported a male infant, born of nonconsanguineous Colombian parents, who was diagnosed with ACG1A at 28 weeks' gestation and died shortly after birth. Postmortem findings included turricephaly, cerebral gyrus flattening, a hypoplastic nasal bridge, short neck and trunk, short and bowed extremities, clubfoot, and hypoplastic lungs. Radiography showed deficient mineralization of the calvaria and vertebral bodies, unossified sacrum, hypoplastic thorax, and markedly short and beaded ribs with flared and spurred ends. Examination of the sternum and femur tissue demonstrated hypercellularity of bone and myxoid cartilage matrix; cytoplasmic inclusions were described as 'vacuolated chondrocytes.'
Molecular Genetics
Smits et al. (2010) noted similarities between the skeletal and cellular phenotypes of Trip11 (604505)-null mice and patients with ACG1A, including absence of vertebral-body and skull ossification on radiography, lack of organized columnar zones of proliferating chondrocytes on histologic analysis, reduced expression of COL10A1 (120110) on immunohistochemical analysis, and expanded endoplasmic reticulum cisternae in chondrocytes on electron microscopy. Smits et al. (2010) analyzed the TRIP11 gene in 10 unrelated patients with ACG1A and identified homozygous or compound heterozygous loss-of-function mutations in all 10 patients (see, e.g., 604505.0001-604505.0004).
In a male infant, born of nonconsanguineous Colombian parents, with ACG1A, Vanegas et al. (2018) identified compound heterozygous frameshift mutations in the TRIP11 gene (604505.0010 and 604505.0013). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the phenotype.
History
Several distinct disorders have been called achondrogenesis, 2 of which are the severe disorder of the limbs described by Grebe (1952), which is now called Grebe dysplasia (200700), and a lethal neonatal chondrodysplasia which had been found to be made up of at least 2 distinct disorders. In the past OMIM referred to Grebe dysplasia as type II achondrogenesis and to the lethal neonatal chondrodysplasias as types IA and IB (200610). Spranger et al. (1974) referred to the lethal neonatal chondrodysplasias as types 'I' and 'II (200600)' a nomenclature which has become widely accepted and is therefore used here.
INHERITANCE \- Autosomal recessive GROWTH Height \- Dwarfism, marked micromelic Other \- Short trunk HEAD & NECK Nose \- Flat nasal bridge \- Short nose \- Anteverted nares Neck \- Short neck CHEST External Features \- Barrel-shaped chest Ribs Sternum Clavicles & Scapulae \- Short, fractured ribs \- Beaded ribs \- Short, wide clavicles \- Hypoplastic scapulae ABDOMEN External Features \- Protuberant abdomen SKELETAL Skull \- Poorly ossified skull Spine \- Unossified vertebral bodies \- Cervical and upper thoracic pedicles ossified Pelvis \- Pubic bones ossified \- Arched ilium \- Hypoplastic ischium Limbs \- Micromelia \- Wedged-shape femur with proximal metaphyseal spike \- Short broad tibia \- Short radius Hands \- Unossified hands Feet \- Unossified feet PRENATAL MANIFESTATIONS \- Hydrops Amniotic Fluid \- Polyhydramnios Delivery \- Stillborn MISCELLANEOUS \- Infants are stillborn or die shortly after birth MOLECULAR BASIS \- Caused by mutation in the thyroid hormone receptor interactor 11 gene (TRIP11, 604505.0001 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| ACHONDROGENESIS, TYPE IA | c0001079 | 4,545 | omim | https://www.omim.org/entry/200600 | 2019-09-22T16:31:40 | {"doid": ["0080054"], "mesh": ["C579878"], "omim": ["200600"], "orphanet": ["932", "93299"], "synonyms": ["Alternative titles", "ACHONDROGENESIS, HOUSTON-HARRIS TYPE"]} |
This article includes a list of general references, but it remains largely unverified because it lacks sufficient corresponding inline citations. Please help to improve this article by introducing more precise citations. (August 2014) (Learn how and when to remove this template message)
Congenital amputation is birth without a limb or limbs, or without a part of a limb or limbs.
It is known to be caused by blood clots forming in the fetus while in utero (vascular insult) and from amniotic band syndrome: fibrous bands of the amnion that constrict foetal limbs to such an extent that they fail to form or actually fall off due to missing blood supply. Congenital amputation can also occur due to maternal exposure to teratogens during pregnancy.
## Contents
* 1 Causes
* 2 Diagnosis
* 3 Treatment
* 4 See also
* 5 References
* 6 Further reading
* 7 External links
## Causes[edit]
The exact cause of congenital amputation is unknown and can result from a number of causes. However, most cases show that the first three months in a pregnancy are when most birth defects occur because that is when the organs of the fetus are beginning to form. One common cause is amniotic band syndrome, which occurs when the inner fetal membrane (amnion) ruptures without injury to the outer membrane (chorion). Fibrous bands from the ruptured amnion float in the amniotic fluid and can get entangled with the fetus, thus reducing blood supply to the developing limbs to such an extent that the limbs can become strangulated; the tissues die and are absorbed into the amniotic fluid. A baby with congenital amputation can be missing a portion of a limb or the entire limb, which results in the complete absence of a limb beyond a certain point where only a stump is left is known as transverse deficiency or amelia. When a specific part is missing, it is referred to as longitudinal deficiency. Finally, phocomelia occurs when only a mid-portion of a limb is missing; for example when the hands or feet are directly attached to the trunk of the body. Amnion ruptures can be caused by:[citation needed]
* teratogenic drugs (e.g. thalidomide, which causes phocomelia), or environmental chemicals
* ionizing radiation (atomic weapons, radioiodine, radiation therapy)
* infections
* metabolic imbalance
* trauma
Congenital amputation is the least common reason for amputation, but it a study published in BMC Musculoskeletal Disorders found that 21.1 in 10,000 babies were born with a missing or deformed limb between 1981 and 2010 in the Netherlands,[1] and the CDC estimates that 4 in 10,000 babies are born in the United States with upper limb reductions and 2 in 10,000 with lower limb reductions.[2] During certain periods in history, an increase in congenital amputations has been documented. One example includes the thalidomide tragedy that occurred in the 1960s when pregnant mothers were given a tranquilizer that contained the harmful drug, which produced an increase in children born without limbs.[citation needed]
## Diagnosis[edit]
For most cases the diagnosis for congenital amputation is not made until the infant is born. One procedure that is helpful in determining this condition in an infant is an ultrasound examination of a fetus when still in the mother's abdomen as it can reveal the absence of a limb. However, since ultrasounds are routine they may not pick up all the signs of some of the more subtle birth defects.[citation needed]
## Treatment[edit]
The most popular method of treatment for congenital amputation is having the child be fit for a prosthesis which can lead to normal development, so the muscles don't atrophy. If there is congenital amputation of the fingers, plastic surgery can be performed by using the big toe or second toes in place of the missing fingers of the hand.[citation needed] In rare cases of amniotic banding syndrome, if diagnosed in utero, fetal surgery may be considered to save a limb which is in danger of amputation.[citation needed]
## See also[edit]
* congenital absence
* Tetra-amelia syndrome
## References[edit]
1. ^ Vasluian E, van der Sluis CK, van Essen AJ, Bergman JE, Dijkstra PU, Reinders-Messelink HA, de Walle HE (November 2013). "Birth prevalence for congenital limb defects in the northern Netherlands: a 30-year population-based study". BMC Musculoskeletal Disorders. 14: 323. doi:10.1186/1471-2474-14-323. PMC 3840683. PMID 24237863.
2. ^ "Upper and Lower Limb Reduction Defects". Centers for Disease Control and Prevention. 2018-04-20. Retrieved 2018-09-12.
## Further reading[edit]
* Gabos PG (May 2006). "Modified technique for the surgical treatment of congenital constriction bands of the arms and legs of infants and children". Orthopedics. 29 (5): 401–4. PMID 16729738.
* Walter JH, Goss LR, Lazzara AT (July–August 1998). "Amniotic band syndrome". The Journal of Foot and Ankle Surgery. 37 (4): 325–33. doi:10.1016/s1067-2516(98)80070-7. PMID 9710786.
* Light TR, Ogden JA (May–June 1993). "Congenital constriction band syndrome. Pathophysiology and treatment". The Yale Journal of Biology and Medicine. 66 (3): 143–55. PMC 2588858. PMID 8209551.
## External links[edit]
* "Congenital amputation". The Free Dictionary.
* v
* t
* e
Congenital malformations and deformations of musculoskeletal system / musculoskeletal abnormality
Appendicular
limb / dysmelia
Arms
clavicle / shoulder
* Cleidocranial dysostosis
* Sprengel's deformity
* Wallis–Zieff–Goldblatt syndrome
hand deformity
* Madelung's deformity
* Clinodactyly
* Oligodactyly
* Polydactyly
Leg
hip
* Hip dislocation / Hip dysplasia
* Upington disease
* Coxa valga
* Coxa vara
knee
* Genu valgum
* Genu varum
* Genu recurvatum
* Discoid meniscus
* Congenital patellar dislocation
* Congenital knee dislocation
foot deformity
* varus
* Club foot
* Pigeon toe
* valgus
* Flat feet
* Pes cavus
* Rocker bottom foot
* Hammer toe
Either / both
fingers and toes
* Polydactyly / Syndactyly
* Webbed toes
* Arachnodactyly
* Cenani–Lenz syndactylism
* Ectrodactyly
* Brachydactyly
* Stub thumb
reduction deficits / limb
* Acheiropodia
* Ectromelia
* Phocomelia
* Amelia
* Hemimelia
multiple joints
* Arthrogryposis
* Larsen syndrome
* RAPADILINO syndrome
Axial
Skull and face
Craniosynostosis
* Scaphocephaly
* Oxycephaly
* Trigonocephaly
Craniofacial dysostosis
* Crouzon syndrome
* Hypertelorism
* Hallermann–Streiff syndrome
* Treacher Collins syndrome
other
* Macrocephaly
* Platybasia
* Craniodiaphyseal dysplasia
* Dolichocephaly
* Greig cephalopolysyndactyly syndrome
* Plagiocephaly
* Saddle nose
Vertebral column
* Spinal curvature
* Scoliosis
* Klippel–Feil syndrome
* Spondylolisthesis
* Spina bifida occulta
* Sacralization
Thoracic skeleton
ribs:
* Cervical
* Bifid
sternum:
* Pectus excavatum
* Pectus carinatum
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Congenital amputation | c1857583 | 4,546 | wikipedia | https://en.wikipedia.org/wiki/Congenital_amputation | 2021-01-18T18:37:31 | {"gard": ["3254", "1471"], "mesh": ["C565682"], "umls": ["C1857583"], "wikidata": ["Q5160408"]} |
This article needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed.
Find sources: "Facial weakness" – news · newspapers · books · scholar · JSTOR (August 2019)
Facial weakness
SpecialtyNeurology
Facial weakness is a medical sign associated with a variety of medical conditions.
Some specific conditions associated with facial weakness include:
* Stroke
* Neurofibromatosis
* Bell's palsy
* Ramsay Hunt syndrome
* Spontaneous cerebrospinal fluid leak
* Myasthenia gravis
## See also[edit]
* Acute facial nerve paralysis
* Facioscapulohumeral muscular dystrophy
## References[edit]
## External links[edit]
Classification
D
* ICD-9-CM: 781.94, 438.83
* Differential diagnosis
* Diagram of appearance in stroke
* v
* t
* e
Cerebrovascular diseases including stroke
Ischaemic stroke
Brain
* Anterior cerebral artery syndrome
* Middle cerebral artery syndrome
* Posterior cerebral artery syndrome
* Amaurosis fugax
* Moyamoya disease
* Dejerine–Roussy syndrome
* Watershed stroke
* Lacunar stroke
Brain stem
* Brainstem stroke syndrome
* Medulla
* Medial medullary syndrome
* Lateral medullary syndrome
* Pons
* Medial pontine syndrome / Foville's
* Lateral pontine syndrome / Millard-Gubler
* Midbrain
* Weber's syndrome
* Benedikt syndrome
* Claude's syndrome
Cerebellum
* Cerebellar stroke syndrome
Extracranial arteries
* Carotid artery stenosis
* precerebral
* Anterior spinal artery syndrome
* Vertebrobasilar insufficiency
* Subclavian steal syndrome
Classification
* Brain ischemia
* Cerebral infarction
* Classification
* Transient ischemic attack
* Total anterior circulation infarct
* Partial anterior circulation infarct
Other
* CADASIL
* Binswanger's disease
* Transient global amnesia
Haemorrhagic stroke
Extra-axial
* Epidural
* Subdural
* Subarachnoid
Cerebral/Intra-axial
* Intraventricular
Brainstem
* Duret haemorrhages
General
* Intracranial hemorrhage
Aneurysm
* Intracranial aneurysm
* Charcot–Bouchard aneurysm
Other
* Cerebral vasculitis
* Cerebral venous sinus thrombosis
This medical sign article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Facial weakness | c0427055 | 4,547 | wikipedia | https://en.wikipedia.org/wiki/Facial_weakness | 2021-01-18T18:55:11 | {"mesh": ["D005158"], "umls": ["C0427055"], "wikidata": ["Q5428572"]} |
Intellectual disability-seizures-macrocephaly-obesity syndrome is a rare syndromic obesity due to complex chromosomal rearrangement characterized by development delay and intellectual disability, childhood-onset obesity, seizures, poor coordination and broad-based gait, macrocephaly and mild dysmorphic features (such as narrow palpebral fissures, malar hypoplasia and thin upper lips), eczema, ocular abnormalities and a social personality.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Intellectual disability-seizures-macrocephaly-obesity syndrome | None | 4,548 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=369950 | 2021-01-23T18:47:34 | {"icd-10": ["Q87.8"], "synonyms": ["Der(8)t(8;12)"]} |
Disease caused by Nipah virus
Nipah virus infection
Structure of a Henipavirus
SpecialtyInfectious disease
SymptomsNone, fever, cough, headache, confusion[1]
ComplicationsInflammation of the brain, seizures[2]
Usual onset5 to 14 days after exposure[1]
CausesNipah virus (spread by direct contact)[3]
Diagnostic methodBased on symptoms, confirmed by laboratory testing[4]
PreventionAvoiding exposure to bats and to sick pigs and people.
TreatmentSupportive care only[2]
Frequency~701 human cases (1998 to May 2018)[5][6]
Deaths~50 to 75% risk of death[5][7]
A Nipah virus infection is a viral infection caused by the Nipah virus.[2] Symptoms from infection vary from none to fever, cough, headache, shortness of breath, and confusion.[1][2] This may worsen into a coma over a day or two,[1] and 50% to 75% of those infected die. Complications can include inflammation of the brain and seizures following recovery.[2]
The Nipah virus (NiV) is a type of RNA virus in the genus Henipavirus.[2] The virus normally circulates among specific types of fruit bats.[2] It can both spread between people and from other animals to people.[2] Spread typically requires direct contact with an infected source.[3] Diagnosis is based on symptoms and confirmed by laboratory testing.[4]
Management is restricted to supportive care;[2] as of 2020[update] there is neither vaccine nor specific treatment.[2] Preventive measures include avoiding exposure to bats and sick pigs, and not drinking raw date palm sap.[8] As of May 2018 about 700 human cases of Nipah virus were estimated to have occurred, and 50 to 75 percent of those infected died.[5][7][6] In May 2018, an outbreak of the disease caused 17 deaths in the Indian state of Kerala.[9][10][11]
The disease was first identified in 1998 by a team of researchers at the Faculty of Medicine, University of Malaya during an outbreak in Malaysia. The majority of the patients in Malaysia diagnosed with the disease were referred to and treated at the University of Malaya Medical Centre. The virus was isolated and identified in 1999.[2][12] The disease is named after a village in Malaysia, Sungai Nipah.[12] Pigs may also be infected, and millions were killed by Malaysian authorities in 1999 to stop the spread of disease, a measure which proved to be successful.[2][12]
## Contents
* 1 Signs and symptoms
* 2 Risks
* 3 Laboratory diagnosis
* 4 Prevention
* 5 Treatment
* 6 Outbreaks
* 7 Research
* 7.1 Medication
* 7.2 Immunization
* 8 Popular culture
* 9 See also
* 10 References
## Signs and symptoms[edit]
The symptoms start to appear 5 to 14 days after exposure.[12] Initial symptoms are fever, headache, and drowsiness, followed by disorientation and mental confusion. Respiratory issues can also be present during the early stages.[12] Coma may ensue within 24 to 48 hours. Encephalitis, inflammation of the brain, is a potentially fatal complication of Nipah virus infection. Nipah patients who have breathing difficulty are more likely than those without respiratory illness to transmit the virus,[13] as are those who are more than 45 years of age.[14] The disease is suspected in symptomatic individuals in the context of an epidemic outbreak.
## Risks[edit]
The risk of exposure is high for hospital workers and caretakers of those infected with the virus. In Malaysia and Singapore, Nipah virus infected people with close contact to infected pigs. In Bangladesh and India, the disease has been linked to consumption of raw date palm sap (toddy), eating of fruits partially consumed by bats, and using water from wells inhabited by bats.[15][16]
* How the Nipah virus spreads[17]
* Fruit bats are the natural reservoirs of Nipah virus
## Laboratory diagnosis[edit]
Transmission electron micrograph (TEM) depicted a number of Nipah virus virions from a person's cerebrospinal fluid (CSF).
During acute and convalescent stages of the disease, RNA can be detected using reverse transcriptase polymerase chain reaction (RT-PCR) from throat swabs, cerebrospinal fluid, urine and blood analysis.[12]
After recovery, IgG and IgM antibody detection can confirm a prior Nipah virus infection. Immunohistochemistry on tissues collected during autopsy also confirms the disease.[12]
## Prevention[edit]
There is no effective treatment for Nipah disease; prevention is the only protection. The likelihood of infection through animal transmission can be reduced by avoiding exposure to sick pigs, and to bats where the disease is endemic. Bats harbour a significantly higher proportion of zoonotic viruses than all other mammalian orders,[18] and are known not to be affected by the many viruses they carry, apparently due to their developing special immune systems to deal with the stress of flying.[19] Infection via bats can be caused by drinking raw palm sap (palm toddy) contaminated by bat excreta,[20] eating fruits partially consumed by bats, and using water from wells infested by bats.[21] Bats are known to drink toddy that is collected in open containers, and occasionally urinate in it, which contaminates it with the virus;[20] switching to closed-top containers prevents transmission via this route. Outbreaks can be reduced by surveillance and awareness. The association of this disease with the reproductive cycle of bats is not well studied.
Standard infection control practices can protect against human-to-human nosocomial infections.
A subunit vaccine using the Hendra G protein was found to produce cross-protective antibodies against both henipavirus and nipavirus; this has been used in monkeys to protect against Hendra virus, although its potential for use in humans has not been studied.[22]
## Treatment[edit]
As of 2020[update] there is no specific treatment for Nipah virus infection.[23] The mainstay of treatment is supportive care.[24][23] Standard infection control practices and proper barrier nursing techniques are recommended to avoid the spread of the infection from person to person.[24] All suspected cases of Nipah virus infection should be isolated.[25] While tentative evidence supports the use of ribavirin, it has not yet been studied in people with the disease.[24] Specific antibodies have also been studied in an animal model with potential benefit.[24] Acyclovir, favipiravir,[23] and remdesivir[26] have been assessed as potential antivirals against Nipah virus.
## Outbreaks[edit]
Map showing locations of outbreaks of Nipah and Hendra virus as well as the range of Pteropus bats as of 2014
Nipah virus outbreaks have been reported in Malaysia, Singapore, Bangladesh and India. The highest mortality due to Nipah virus infection was found in Bangladesh,[citation needed] where outbreaks are typically seen in winter.[27] Nipah virus was first seen in 1998 in peninsular Malaysia in pigs and pig farmers. By mid-1999, more than 265 human cases of encephalitis, including 105 deaths, had been reported in Malaysia, and 11 cases of either encephalitis or respiratory illness with one fatality were reported in Singapore.[28] In 2001, Nipah virus was reported from Meherpur District, Bangladesh[29][30] and Siliguri, India.[29] The outbreak again appeared in 2003, 2004 and 2005 in Naogaon District, Manikganj District, Rajbari District, Faridpur District and Tangail District.[30] In Bangladesh there were further outbreaks in subsequent years.[31][7]
* September 1998 - May 1999: in the states of Perak, Negeri Sembilan and Selangor in Malaysia. A total of 265 cases of acute encephalitis with 105 deaths caused by the virus were reported in the three states throughout the outbreak.[32] The Malaysian health authorities at first thought Japanese encephalitis (JE) was the cause of infection which hampered the deployment of effective measures to prevent the spread of Nipah virus.[33]
* 2001: 31 January–23 February, Siliguri, India: 66 cases with a 74% mortality rate.[34] 75% of patients were either hospital staff or had visited one of the other patients in hospital, indicating person-to-person transmission.
* 2001: April – May, Meherpur District, Bangladesh: 13 cases with nine fatalities (69% mortality).[35]
* 2003: January, Naogaon District, Bangladesh: 12 cases with eight fatalities (67% mortality).[35]
* 2004: January – February, Manikganj and Rajbari districts, Bangladesh: 42 cases with 14 fatalities (33% mortality).
* 2004: 19 February – 16 April, Faridpur District, Bangladesh: 36 cases with 27 fatalities (75% mortality). 92% of cases involved close contact with at least one other person infected with Nipah virus. Two cases involved a single short exposure to an ill patient, including a rickshaw driver who transported a patient to hospital. In addition, at least six cases involved acute respiratory distress syndrome, which has not been reported previously for Nipah virus illness in humans.
* 2005: January, Tangail District, Bangladesh: 12 cases with 11 fatalities (92% mortality). The virus was probably contracted from drinking date palm juice contaminated by fruit bat droppings or saliva.[36]
* 2007: February – May, Nadia District, India: up to 50 suspected cases with 3–5 fatalities. The outbreak site borders the Bangladesh district of Kushtia where eight cases of Nipah virus encephalitis with five fatalities occurred during March and April 2007. This was preceded by an outbreak in Thakurgaon during January and February affecting seven people with three deaths.[37] All three outbreaks showed evidence of person-to-person transmission.
* 2008: February – March, Manikganj and Rajbari districts, Bangladesh: Nine cases with eight fatalities.[38]
* 2010: January, Bhanga subdistrict, Faridpur, Bangladesh: Eight cases with seven fatalities. During March, one physician of the Faridpur Medical College Hospital caring for confirmed Nipah cases died.[39]
* 2011: February: An outbreak of Nipah Virus occurred at Hatibandha, Lalmonirhat, Bangladesh. The deaths of 21 schoolchildren due to Nipah virus infection were recorded on 4 February 2011. IEDCR confirmed the infection was due to this virus.[40] Local schools were closed for one week to prevent the spread of the virus. People were also requested to avoid consumption of uncooked fruits and fruit products. Such foods, contaminated with urine or saliva from infected fruit bats, were the most likely source of this outbreak.[41]
* 2018: May: Deaths of seventeen[42] people in Perambra near Calicut, Kerala, India were confirmed to be due to the virus. Treatment using antivirals such as Ribavirin was initiated.[43][44]
* 2019: June: A 23-year-old student was admitted into hospital with Nipah virus infection at Kochi in Kerala.[45] Health Minister of Kerala, K. K. Shailaja said that 86 people who had had recent interactions with the patient were under observation. This included two nurses who treated the patient, and had fever and sore throat. The situation was monitored and precautionary steps were taken to control the spread of virus by the Central[46] and State Government.[45] 338 people were kept under observation, 17 of them in isolation, by the Health Department of Kerala. After undergoing treatment for 54 days at a private hospital, the 23-year-old student was discharged. On 23 July, the Kerala government declared Ernakulam district to be Nipah-free.[47]
## Research[edit]
Ribavirin, m102.4 monoclonal antibody and favipiravir were being studied as treatments as of 2019.[48]
### Medication[edit]
Ribavirin has been studied in a small number of people. As of 2011[update] it was unclear whether it was useful, although a few people had returned to normal life after treatment.[49] In vitro studies and animal studies have shown conflicting results in the efficacy of ribavirin against NiV and Hendra, with some studies showing effective inhibition of viral replication in cell lines,[50][51] whereas some studies in animal models showed that ribavirin treatment only delayed but did not prevent death after NiV or Hendra virus infection.[52][53]
In 2013 the anti-malarial drug chloroquine was shown to block the critical functions needed for maturation of Nipah virus, although no clinical benefit was observed.[54]
### Immunization[edit]
Passive immunization using a human monoclonal antibody, m102.4, that targets the ephrin-B2 and ephrin-B3 receptor-binding domain of the henipavirus Nipah G glycoprotein was evaluated in the ferret model as post-exposure prophylaxis.[5][12] m102.4, has been used in people on a compassionate use basis in Australia, and was in pre-clinical development in 2013.[5]
## Popular culture[edit]
A Malayalam movie Virus was released in 2019, based on the 2018 Kerala (India) outbreak of Nipah virus.[55][56]
The fictional MEV-1 virus featured in the 2011 film Contagion was based on a combination of the Nipah and the measles viruses.[57]
## See also[edit]
* Coalition for Epidemic Preparedness Innovations
## References[edit]
1. ^ a b c d "Signs and Symptoms Nipah Virus (NiV)". CDC. Retrieved 24 May 2018.
2. ^ a b c d e f g h i j k l "Nipah Virus (NiV) Infection". World Health Organization (WHO). Archived from the original on 26 September 2020. Retrieved 14 October 2020.
3. ^ a b "Transmission Nipah Virus (NiV)". CDC. 20 March 2014. Retrieved 24 May 2018.
4. ^ a b "Diagnosis Nipah Virus (NiV)". CDC. 20 March 2014. Retrieved 24 May 2018.
5. ^ a b c d e Broder CC, Xu K, Nikolov DB, Zhu Z, Dimitrov DS, Middleton D, et al. (October 2013). "A treatment for and vaccine against the deadly Hendra and Nipah viruses". Antiviral Research. 100 (1): 8–13. doi:10.1016/j.antiviral.2013.06.012. PMC 4418552. PMID 23838047.
6. ^ a b "Morbidity and mortality due to Nipah or Nipah-like virus encephalitis in WHO South-East Asia Region, 2001-2018" (PDF). SEAR. Archived from the original (PDF) on 13 June 2018. Retrieved 2 June 2018. "112 cases since Oct 2013"
7. ^ a b c "Nipah virus outbreaks in the WHO South-East Asia Region". South-East Asia Regional Office. WHO. Archived from the original on 23 May 2018. Retrieved 23 May 2018.
8. ^ "Prevention Nipah Virus (NiV)". CDC. 20 March 2014. Retrieved 24 May 2018.
9. ^ CNN, Manveena Suri (22 May 2018). "10 confirmed dead from Nipah virus outbreak in India". CNN. Retrieved 25 May 2018.
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11. ^ "After the outbreak". Frontline. Retrieved 10 July 2018.
12. ^ a b c d e f g h "Nipah Virus (NiV) CDC". www.cdc.gov. CDC. Archived from the original on 16 December 2017. Retrieved 21 May 2018.
13. ^ Luby SP, Hossain MJ, Gurley ES, Ahmed BN, Banu S, Khan SU, et al. (August 2009). "Recurrent zoonotic transmission of Nipah virus into humans, Bangladesh, 2001-2007". Emerging Infectious Diseases. 15 (8): 1229–35. doi:10.3201/eid1508.081237. PMC 2815955. PMID 19751584. Archived from the original on 22 May 2018.
14. ^ Nikolay B, Salje H, Hossain MJ, Khan AK, Sazzad HM, Rahman M, et al. (May 2019). "Transmission of Nipah Virus - 14 Years of Investigations in Bangladesh". The New England Journal of Medicine. 380 (19): 1804–1814. doi:10.1056/NEJMoa1805376. PMC 6547369. PMID 31067370.
15. ^ Luby SP, Gurley ES, Hossain MJ (2012). Transmission of Human Infection with Nipah Virus. National Academies Press (US). Archived from the original on 22 May 2018. Retrieved 21 May 2018.
16. ^ Balan, Sarita (21 May 2018). "6 Nipah virus deaths in Kerala: Bat-infested house well of first victims sealed". The News Minute. Archived from the original on 22 May 2018. Retrieved 21 May 2018.
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18. ^ Olival, Kevin J.; Hosseini, Parviez R.; Zambrana-Torrelio, Carlos; Ross, Noam; Bogich, Tiffany L.; Daszak, Peter (2017). "Host and viral traits predict zoonotic spillover from mammals". Nature. 546 (7660): 646–650. doi:10.1038/nature22975. ISSN 0028-0836. PMC 5570460.
19. ^ Huang, Pien (9 February 2020). "Bats Carry Many Viruses. So Why Don't They Get Sick?". National Public Radio (npr).
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21. ^ Balan, Sarita (21 May 2018). "6 Nipah virus deaths in Kerala: Bat-infested house well of first victims sealed". The News Minute. Archived from the original on 22 May 2018. Retrieved 21 May 2018.
22. ^ Bossart KN, Rockx B, Feldmann F, Brining D, Scott D, LaCasse R, et al. (August 2012). "A Hendra virus G glycoprotein subunit vaccine protects African green monkeys from Nipah virus challenge". Science Translational Medicine. 4 (146): 146ra107. doi:10.1126/scitranslmed.3004241. PMC 3516289. PMID 22875827.
23. ^ a b c Sharma, V; Kaushik, S; Kumar, R; Yadav, JP; Kaushik, S (January 2019). "Emerging trends of Nipah virus: A review". Reviews in Medical Virology. 29 (1): e2010. doi:10.1002/rmv.2010. PMID 30251294.
24. ^ a b c d "Nipah Virus (NiV) - Treatment". Centers for Disease Control and Prevention (CDC). 20 March 2014.
25. ^ "Nipah yet to be confirmed, 86 under observation: Shailaja". OnManorama. Retrieved 4 June 2019.
26. ^ Lo, Michael K.; Feldmann, Friederike; Gary, Joy M.; Jordan, Robert; Bannister, Roy; Cronin, Jacqueline; Patel, Nishi R.; Klena, John D.; Nichol, Stuart T.; Cihlar, Tomas; Zaki, Sherif R. (29 May 2019). "Remdesivir (GS-5734) protects African green monkeys from Nipah virus challenge". Science Translational Medicine. 11 (494): eaau9242. doi:10.1126/scitranslmed.aau9242. ISSN 1946-6234. PMC 6732787. PMID 31142680.
27. ^ Chadha MS, Comer JA, Lowe L, Rota PA, Rollin PE, Bellini WJ, et al. (February 2006). "Nipah virus-associated encephalitis outbreak, Siliguri, India". Emerging Infectious Diseases. 12 (2): 235–40. doi:10.3201/eid1202.051247. PMC 3373078. PMID 16494748.
28. ^ Eaton BT, Broder CC, Middleton D, Wang LF (January 2006). "Hendra and Nipah viruses: different and dangerous". Nature Reviews. Microbiology. 4 (1): 23–35. doi:10.1038/nrmicro1323. PMC 7097447. PMID 16357858.
29. ^ a b Chadha MS, Comer JA, Lowe L, Rota PA, Rollin PE, Bellini WJ, et al. (February 2006). "Nipah virus-associated encephalitis outbreak, Siliguri, India". Emerging Infectious Diseases. 12 (2): 235–40. doi:10.3201/eid1202.051247. PMC 3373078. PMID 16494748.
30. ^ a b Hsu VP, Hossain MJ, Parashar UD, Ali MM, Ksiazek TG, Kuzmin I, et al. (December 2004). "Nipah virus encephalitis reemergence, Bangladesh". Emerging Infectious Diseases. 10 (12): 2082–7. doi:10.3201/eid1012.040701. PMC 3323384. PMID 15663842.
31. ^ "Basic preventive measures can reduce Nipah virus attack". The Daily Star (Bangladesh). 8 March 2008.
32. ^ Looi, Lai-Meng; Chua, Kaw-Bing (2007). "Lessons from the Nipah virus outbreak in Malaysia" (PDF). The Malaysian Journal of Pathology. Department of Pathology, University of Malaya and National Public Health Laboratory of the Ministry of Health, Malaysia. 29 (2): 63–67. Archived (PDF) from the original on 30 August 2019.
33. ^ Looi, Lai-Meng; Chua, Kaw-Bing (2007). "Lessons from the Nipah virus outbreak in Malaysia" (PDF). The Malaysian Journal of Pathology. Department of Pathology, University of Malaya and National Public Health Laboratory of the Ministry of Health, Malaysia. 29 (2): 63–67. Archived (PDF) from the original on 30 August 2019.
34. ^ Chadha MS, Comer JA, Lowe L (2006). "Nipah virus-associated encephalitis outbreak, Siliguri, India". Emerging Infectious Diseases. 12 (2): 235–40. doi:10.3201/eid1202.051247. PMC 3373078. PMID 16494748.
35. ^ a b Hsu VP, Hossain MJ, Parashar UD (2004). "Nipah virus encephalitis reemergence, Bangladesh". Emerging Infectious Diseases. 10 (12): 2082–7. doi:10.3201/eid1012.040701. PMC 3323384. PMID 15663842.
36. ^ ICDDR,B (December 2005). "Nipah virus outbreak from date palm juice" (PDF). Centre for Population Research - Health and Science Bulletin. 3 (4): 1–5. ISSN 1729-343X.
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38. ^ ICDDR,B (2008). "Outbreaks of Nipah virus in Rajbari and Manikgonj". Health and Science Bulletin. 6 (1): 12–3. Archived from the original on 3 February 2009.
39. ^ ICDDR,B (2010). "Nipah outbreak in Faridpur District, Bangladesh, 2010". Health and Science Bulletin. 8 (2): 6–11. Archived from the original on 28 September 2011.
40. ^ "Arguments in Bahodderhat murder case begin". The Daily Star. 18 March 2008. Retrieved 21 May 2014.
41. ^ তাহেরকে ফাঁসি দেওয়ার সিদ্ধান্ত নেন জিয়া. prothom-alo.com. 4 February 2011
42. ^ "Nipah virus outbreak: Death toll rises to 14 in Kerala, two more cases confirmed". indianexpress.com. 27 May 2018. Retrieved 29 May 2018.
43. ^ "Kozhikode on high alert as three deaths attributed to Nipah virus". The Indian Express. 20 May 2018. Retrieved 20 May 2018.
44. ^ "Deadly Nipah virus claims victims in India". BBC News. 21 May 2018. Retrieved 11 December 2018 – via www.bbc.com.
45. ^ a b "Kerala Govt Confirms Nipah Virus, 86 Under Observation". New Delhi. 4 June 2019. Archived from the original on 14 July 2019. Retrieved 15 July 2019.
46. ^ Sharma, Neetu Chandra (4 June 2019). "Centre gears up to contain re-emergence of Nipah virus in Kerala". Mint. Retrieved 7 June 2019.
47. ^ "Ernakulam district declared Nipah virus free, says Kerala health minister". India Today. Press Trust of India. 23 July 2019.
48. ^ Banerjee, S; Gupta, N; Kodan, P; Mittal, A; Ray, Y; Nischal, N; Soneja, M; Biswas, A; Wig, N (February 2019). "Nipah virus disease: A rare and intractable disease". Intractable & Rare Diseases Research. 8 (1): 1–8. doi:10.5582/irdr.2018.01130. PMC 6409114. PMID 30881850.
49. ^ Vigant F, Lee B (June 2011). "Hendra and nipah infection: pathology, models and potential therapies". Infectious Disorders Drug Targets. 11 (3): 315–36. doi:10.2174/187152611795768097. PMC 3253017. PMID 21488828.
50. ^ Wright PJ, Crameri G, Eaton BT (March 2005). "RNA synthesis during infection by Hendra virus: an examination by quantitative real-time PCR of RNA accumulation, the effect of ribavirin and the attenuation of transcription". Archives of Virology. 150 (3): 521–32. doi:10.1007/s00705-004-0417-5. PMID 15526144.
51. ^ Aljofan M, Saubern S, Meyer AG, Marsh G, Meers J, Mungall BA (June 2009). "Characteristics of Nipah virus and Hendra virus replication in different cell lines and their suitability for antiviral screening". Virus Research. 142 (1–2): 92–9. doi:10.1016/j.virusres.2009.01.014. PMC 2744099. PMID 19428741.
52. ^ Georges-Courbot MC, Contamin H, Faure C, Loth P, Baize S, Leyssen P, et al. (May 2006). "Poly(I)-poly(C12U) but not ribavirin prevents death in a hamster model of Nipah virus infection". Antimicrobial Agents and Chemotherapy. 50 (5): 1768–72. doi:10.1128/AAC.50.5.1768-1772.2006. PMC 1472238. PMID 16641448.
53. ^ Freiberg AN, Worthy MN, Lee B, Holbrook MR (March 2010). "Combined chloroquine and ribavirin treatment does not prevent death in a hamster model of Nipah and Hendra virus infection". The Journal of General Virology. 91 (Pt 3): 765–72. doi:10.1099/vir.0.017269-0. PMC 2888097. PMID 19889926.
54. ^ Broder CC, Xu K, Nikolov DB, Zhu Z, Dimitrov DS, Middleton D, et al. (October 2013). "A treatment for and vaccine against the deadly Hendra and Nipah viruses". Antiviral Research. 100 (1): 8–13. doi:10.1016/j.antiviral.2013.06.012. PMC 4418552. PMID 23838047.
55. ^ Virus, retrieved 1 September 2019
56. ^ Virus Movie Review {3.5/5}: A well-crafted multi-starrer, fictional documentation on the Nipah virus attack, retrieved 1 September 2019
57. ^ "Nipah virus inspired "Contagion." We're testing a vaccine". www.path.org. Retrieved 17 May 2020.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Nipah virus infection | c1535917 | 4,549 | wikipedia | https://en.wikipedia.org/wiki/Nipah_virus_infection | 2021-01-18T19:10:46 | {"mesh": ["D045464"], "orphanet": ["99825"], "synonyms": ["Nipah encephalitis", "Nipah fever"], "wikidata": ["Q53926008"]} |
Colobomatous microphthalmia-rhizomelic dysplasia syndrome is a rare, genetic developmental defect during embryogenesis characterized by a range of developmental eye anomalies (including anophthalmia, microphthalmia, colobomas, microcornea, corectopia, cataract) and symmetric limb rhizomelia with short stature and contractures of large joints. Intellectual disability with autistic features, macrocephaly, dysmorphic features, urogenital anomalies (hypospadia, cryptorchidism), cutaneous syndactyly and precocious puberty may also be present.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Colobomatous microphthalmia-rhizomelic dysplasia syndrome | c4014540 | 4,550 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=424099 | 2021-01-23T17:26:28 | {"omim": ["615877"], "icd-10": ["Q87.5"], "synonyms": ["Microphthalmia-coloboma-rhizomelic skeletal dysplasia"]} |
A number sign (#) is used with this entry because generalized epilepsy with febrile seizures plus, type 7 (GEFSP7) and familial febrile seizures-3B (FEB3B) are both caused by heterozygous mutation in the SCN9A gene (603415) on chromosome 2q24.
See also GEFS+, type 2 and FEB3A (604403), which are both caused by mutation in the SCN1A gene (182389) on chromosome 2q24.
Description
Mutations in the SCN9A gene cause a spectrum of seizure disorders, ranging from early-onset isolated febrile seizures to generalized epilepsy with febrile seizures plus, type 7, which represents a more severe phenotype. Patients with isolated febrile seizures usually have onset between ages 5 months to 4 years and show spontaneous remission by age 6 years (summary by Singh et al., 2009), whereas patients with GEFS+ continue to have various types of febrile and afebrile seizures later in life (summary by Singh et al., 1999).
Mutations in certain genes can cause a phenotypic spectrum of overlap between the isolated febrile phenotype and the GEFS+ phenotype. For a general phenotypic description and a discussion of genetic heterogeneity of GEFS+, see 604233.
For a phenotypic description and a discussion of genetic heterogeneity of familial febrile seizures, see 121210.
Clinical Features
Singh et al. (2009) studied a large Utah family with autosomal dominant GEFS+. The family was originally reported by Peiffer et al. (1999) as having predominantly febrile seizures, which was mapped to a locus on chromosome 2q24 designated 'FEB3.' However, Moulard et al. (2000) and Scheffer et al. (2000) both concluded that the phenotype reported in the family by Peiffer et al. (1999) was most consistent with GEFS+, since afebrile seizures continued beyond childhood in several affected individuals. The follow-up report by Singh et al. (2009) stated that this family showed a broad spectrum of seizure manifestations. Eleven individuals experienced only febrile seizures before age 6 years, whereas 10 additional individuals developed later afebrile seizures. In 8 of the 10, seizures remitted by age 16 years. The remaining 2 affected individuals developed intractable epilepsy: 1 had complex-partial seizures associated with left mesial temporal sclerosis, and the other had afebrile generalized convulsive seizures requiring the placement of a vagal nerve stimulator. This phenotype is designated GEFS+, type 7.
Singh et al. (2009) also reported 2 unrelated patients with simple febrile seizures and 2 different heterozygous mutations in the SCN9A gene (I62V; 603415.0020 and P149Q; 603415.0021, respectively). This phenotype is designated FEB3B.
Mapping
Peiffer et al. (1999) first mapped this locus, which they designated FEB3, to chromosome 2q23-q24 by linkage analysis of a large Utah family with febrile seizures (lod score of 8.08 at D2S2330). Haplotype analysis identified a critical 10-cM interval between D2S141 and D2S2345.
Molecular Genetics
In affected members of a large Utah family with generalized epilepsy with febrile seizures plus, type 7, originally reported by (Peiffer et al., 1999), Singh et al. (2009) identified a heterozygous mutation in the SCN9A gene (N641Y; 603415.0018) on 2q24.
In 2 unrelated probands with isolated febrile seizures (FEB3B), Singh et al. (2009) identified 2 different heterozygous mutations in the SCN9A gene (I62V, 603415.0020 and P149Q, 603415.0021, respectively).
Nomenclature
Two different genes, SCN1A (182389) and SCN9A (603415), map to the FEB3 locus on chromosome 2q24, first identified by Peiffer et al. (1999) in a large Utah family with febrile seizures. This family was later found to have GEFS+7 caused by mutation in the SCN9A gene by Singh et al. (2009).
In an Italian family with isolated febrile seizures, Mantegazza et al. (2005) found linkage to the FEB3 locus and identified a pathogenic mutation in the SCN1A gene (182389); this form of febrile seizures is designated FEB3A.
In 2 unrelated probands with isolated febrile seizures, Singh et al. (2009) identified pathogenic mutations in the SCN9A gene on chromosome 2q24; this form of febrile seizures is designated FEB3B.
INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Seizures, generalized, associated with fever \- Generalized tonic-clonic seizures \- Febrile seizures \- Afebrile seizures \- Absence seizures \- Partial seizures \- Atonic seizures MISCELLANEOUS \- Variable severity \- Onset of febrile seizures typically between 6 months and 6 years of age \- Simple febrile seizures usually remit by age 6 years \- Some patients have a more severe phenotype and have febrile and afebrile seizures after childhood (GEFS+) MOLECULAR BASIS \- Caused by mutation in the sodium channel, voltage-gated, type IX, alpha subunit gene (SCN9A, 603415.0018 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| GENERALIZED EPILEPSY WITH FEBRILE SEIZURES PLUS, TYPE 7 | c3502809 | 4,551 | omim | https://www.omim.org/entry/613863 | 2019-09-22T15:57:09 | {"doid": ["0060170", "0111295"], "mesh": ["C565808"], "omim": ["613863"], "orphanet": ["36387"], "synonyms": ["Alternative titles", "GEFS+, TYPE 7"]} |
X-linked sideroblastic anemia is an inherited disorder that prevents developing red blood cells (erythroblasts) from making enough hemoglobin. People with X-linked sideroblastic anemia have mature red blood cells that are smaller than normal (microcytic) and appear pale (hypochromic) because of the shortage of hemoglobin. This disorder also leads to an abnormal accumulation of iron in red blood cells. The iron-loaded erythroblasts, which are present in bone marrow, are called ring sideroblasts. These abnormal cells give the condition its name. The signs and symptoms of X-linked sideroblastic anemia result from a combination of reduced hemoglobin and an overload of iron. They range from mild to severe and most often appear in young adulthood. Common features include fatigue, dizziness, a rapid heartbeat, pale skin, and an enlarged liver and spleen (hepatosplenomegaly). Over time, severe medical problems such as heart disease and liver damage (cirrhosis) can result from the buildup of excess iron in these organs. X-linked sideroblastic anemia is caused by mutation in the ALAS2 gene. In rare cases, mutations are found in both the HFE gene and the ALAS2 gene, resulting in a more severe form of X-linked sideroblastic anemia. X-linked sideroblastic anemia is inherited in an X-linked recessive pattern.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| X-linked sideroblastic anemia | c0221018 | 4,552 | gard | https://rarediseases.info.nih.gov/diseases/9456/x-linked-sideroblastic-anemia | 2021-01-18T17:57:02 | {"omim": ["300751"], "umls": ["C0221018"], "orphanet": ["75563"], "synonyms": ["Sideroblastic anemia X-linked", "XLSA", "Anemia sex-linked hypochromic sideroblastic", "ANH1", "Congenital sideroblastic anemia", "Erythroid 5-aminolevulinate synthase deficiency", "Hereditary iron-loading anemia", "X chromosome-linked sideroblastic anemia", "Anemia hereditary sideroblastic"]} |
Visual disorder where eyes work independently
For the similar condition, where the eyes deviate inward (rather than outward), see esotropia.
Exotropia
Other namesDivergent squint, wall eyes
Exotropia of the right eye
SpecialtyOphthalmology
Exotropia is a form of strabismus where the eyes are deviated outward. It is the opposite of esotropia and usually involves more severe axis deviation than exophoria. People with exotropia often experience crossed diplopia. Intermittent exotropia is a fairly common condition. "Sensory exotropia" occurs in the presence of poor vision. Infantile exotropia (sometimes called "congenital exotropia") is seen during the first year of life, and is less common than "essential exotropia" which usually becomes apparent several years later.
The brain's ability to see three-dimensional objects depends on proper alignment of the eyes. When both eyes are properly aligned and aimed at the same target, the visual portion of the brain fuses the forms into a single image. When one eye turns inward, outward, upward, or downward, two different pictures are sent to the brain. This causes loss of depth perception and binocular vision. The term is from Greek exo meaning "outward" and trope meaning "a turning".[1]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Treatment
* 4 References
* 5 External links
## Signs and symptoms[edit]
The earliest sign of exotropia is usually a noticeable outward deviation of the eye. This sign may at first be intermittent, occurring when a child is daydreaming, not feeling well, or tired. It may also be more noticeable when the child looks at something in the distance. Squinting or frequent rubbing of the eyes is also common with exotropia. The child probably will not mention seeing double, i.e., double vision. However, he or she may close one eye to compensate for the problem.
Generally, exotropia progresses in frequency and duration. As the disorder progresses, the eyes start to turn out when looking at close objects as well as those in the distance. If left untreated, the eye may turn out continually, causing a loss of binocular vision.
In young children with any form of strabismus, the brain may learn to ignore the misaligned eye's image and see only the image from the best-seeing eye. This is called amblyopia, or lazy eye, and results in a loss of binocular vision, impairing depth perception. In adults who develop strabismus, double vision sometimes occurs because the brain has already been trained to receive images from both eyes and cannot ignore the image from the turned eye.
Additionally in adults who have had exotropia since childhood, the brain may adapt to using a "blind-spot", whereby it receives images from both eyes, but no full image from the deviating eye, thus avoiding double vision, and in fact, increasing peripheral vision on the side of the deviating eye.
## Causes[edit]
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The causes of exotropia are not fully understood. Six muscles control eye movement, four that move the eye up and down and two that move it left and right. All these muscles must be coordinated and working properly for the brain to see a single image. When one or more of these muscles does not work properly, some form of strabismus may occur. Strabismus is more common in children with disorders that affect the brain such as cerebral palsy, Down syndrome, hydrocephalus, and brain tumors. One study has found that children with exotropia are three times more likely to develop a psychiatric disorder in comparison with the general population.[2][3][4]
## Treatment[edit]
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See also: Strabismus § Management
A comprehensive eye examination including an ocular motility (i.e., eye movement) evaluation and an evaluation of the internal ocular structures allows an eye doctor to accurately diagnose exotropia. Although glasses and/or patching therapy, exercises, or prisms may reduce or help control the outward-turning eye in some children, surgery is often required.
A common form of exotropia is known as "convergence insufficiency" that responds well to orthoptic vision therapy including exercises. This disorder is characterized by an inability of the eyes to work together when used for near viewing, such as reading. Instead of the eyes focusing together on the near object, one deviates outward.
Consecutive exotropia arises after an initial esotropia. Most often it results from surgical overcorrection of the initial esotropia. It can be addressed with further surgery or with vision therapy; vision therapy has shown promising results if the consecutive exotropia is intermittent, alternating, and of small magnitude.[5] (Consecutive exotropia may however also spontaneously develop from esotropia, without surgery or botulinum toxin treatment.[6])
Because of the risks of surgery, and because about 35% of people require at least one more surgery, many people try vision therapy first. This consists of visual exercises. Although vision therapy is generally not covered by American health insurance companies, many large insurers such as Aetna[7] have recently begun offering full or partial coverage in response to recent studies.
Strabismus surgery is sometimes recommended if the exotropia is present for more than half of each day or if the frequency is increasing over time. It is also indicated if a child has significant exotropia when reading or viewing near objects or if evidence shows that the eyes are losing their ability to work as a single unit (binocular vision). If none of these criteria is met, surgery may be postponed pending simple observation with or without some form of eyeglass and/or patching therapy. In very mild cases, a chance exists that the exotropia will diminish with time. The long-term success of surgical treatment for conditions such as intermittent exotropia is not well proven, and surgery can often result in a worsening of symptoms due to overcorrection. Evidence from the available literature suggests that unilateral surgery was more effective than bilateral surgery for individuals affected with intermittent exotropia.[8]
The surgical procedure for the correction of exotropia involves making a small incision in the tissue covering the eye to reach the eye muscles. The appropriate muscles are then repositioned to allow the eye to move properly. The procedure is usually done under general anesthesia. Recovery time is rapid, and most people are able to resume normal activities within a few days. Following surgery, corrective eyeglasses may be needed, and in many cases, further surgery is required later to keep the eyes straight.
When a child requires surgery, the procedure is usually performed before the child attains school age. This is easier for the child and gives the eyes a better chance to work together. As with all surgery, some risks occur. However, strabismus surgery is usually a safe and effective treatment.
## References[edit]
1. ^ "Exotropia Origin". dictionary.com. Retrieved 21 July 2015.
2. ^ Mohney BG, McKenzie JA, Capo JA, Nusz KJ, Mrazek D, Diehl NN (November 2008). "Mental illness in young adults who had strabismus as children". Pediatrics. 122 (5): 1033–8. doi:10.1542/peds.2007-3484. PMC 2762944. PMID 18977984.
3. ^ Mayo Clinic. "Eye Divergence In Children Triples Risk Of Mental Illness." ScienceDaily 28 November 2008. 30 November 2008
4. ^ McKenzie J, et al "Prevalence and sex differences of psychiatric disorders in young adults who had intermittent exotropia as children" Arch Ophthalmol 2009; 127:743-47.[1]
5. ^ B. Chorn; A. Steiner. "Optometric Vision Therapy in the Management of Consecutive Intermittent Exotropia with Dissociated Vertical Deviation and Anomalous Correspondence - A Case Study". Journal of Behavioral Optometry (JBO). 18 (6). (abstract, full text)
6. ^ J.D. Senior; A. Chandna; A.R. O'Connor (2009). "Spontaneous consecutive exotropia in childhood". Strabismus. 17 (1): 33–6. doi:10.1080/09273970802678818. PMID 19301191.
7. ^ Clinical policy bulletins: Vision therapy, Number 0489, 4 June 2013, for review 13 June 2013 (downloaded 21 July 2013)
8. ^ Hatt SR, Gnanaraj L (2013). "Interventions for intermittent exotropia" (PDF). Cochrane Database Syst Rev. 5 (5): CD003737. doi:10.1002/14651858.CD003737.pub3. PMC 4307390. PMID 23728647.
## External links[edit]
Classification
D
* ICD-10: H50.1, H50.3
* ICD-9-CM: 378.1
* MeSH: D005099
* DiseasesDB: 33268
* eMedicine on congenital exotropia
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*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Exotropia | c0015310 | 4,553 | wikipedia | https://en.wikipedia.org/wiki/Exotropia | 2021-01-18T18:32:13 | {"mesh": ["D005099"], "umls": ["C0015310"], "wikidata": ["Q2556242"]} |
This article is about the precancerous change in cells and tissues. For the clinical condition affecting the hip joint, see Hip dysplasia.
Not to be confused with Dyscrasia.
Normal squamous cells
Dysplastic cells
Dysplasia is any of various types of abnormal growth or development of cells (microscopic scale) and/or organs (macroscopic scale), and/or the abnormal histology or anatomical structure presumably resulting from such growth.[1] Dysplasias on a mainly microscopic scale include epithelial dysplasia and fibrous dysplasia of bone. Dysplasias on a mainly macroscopic scale include hip dysplasia, myelodysplastic syndrome, and multicystic dysplastic kidney. In one of the modern histopathologic senses of the term, dysplasia is sometimes differentiated from other categories of tissue change including hyperplasia, metaplasia, and neoplasia, and dysplasias are thus generally not neoplastic (not cancerous). An exception is that the myelodysplasias include a range of benign, precancerous, and cancerous forms. Various other dysplasias tend to be precancerous. The word's meanings thus span across a spectrum of histopathologic variations.
## Contents
* 1 Mainly microscopic scale
* 1.1 Epithelial dysplasia
* 1.2 Myelodysplastic syndrome
* 1.3 Fibrous dysplasia of bone
* 2 Mainly macroscopic scale
* 2.1 Hip dysplasia
* 2.2 Multicystic dysplastic kidney
* 3 Etymology
* 4 See also
* 5 References
* 6 Further reading
## Mainly microscopic scale[edit]
### Epithelial dysplasia[edit]
Main article: Epithelial dysplasia
-plasia and -trophy
* Anaplasia (structural differentiation loss within a cell or group of cells).
* Aplasia (organ or part of organ missing)
* Desmoplasia (connective tissue growth)
* Dysplasia (change in cell or tissue phenotype)
* Hyperplasia (proliferation of cells)
* Hypoplasia (congenital below-average number of cells, especially when inadequate)
* Metaplasia (conversion in cell type)
* Neoplasia (abnormal proliferation)
* Prosoplasia (development of new cell function)
* Abiotrophy (loss in vitality of organ or tissue)
* Atrophy (reduced functionality of an organ, with decrease in the number or volume of cells)
* Hypertrophy (increase in the volume of cells or tissues)
* Hypotrophy (decrease in the volume of cells or tissues)
* Dystrophy (any degenerative disorder resulting from improper or faulty nutrition)
* v
* t
* e
Epithelial dysplasia consists of an expansion of immature cells (such as cells of the ectoderm), with a corresponding decrease in the number and location of mature cells. Dysplasia is often indicative of an early neoplastic process. The term dysplasia is typically used when the cellular abnormality is restricted to the originating tissue, as in the case of an early, in-situ neoplasm.
Dysplasia, in which cell maturation and differentiation are delayed, can be contrasted with metaplasia, in which cells of one mature, differentiated type are replaced by cells of another mature, differentiated type.
### Myelodysplastic syndrome[edit]
Main article: Myelodysplastic syndrome
Myelodysplastic syndromes (MDS) are a group of cancers in which immature blood cells in the bone marrow do not mature and therefore do not become healthy blood cells.[2] Problems with blood cell formation result in some combination of low red blood cells, low platelets, and low white blood cells.[2] Some types have an increase in immature blood cells, called blasts, in the bone marrow or blood.[2]
### Fibrous dysplasia of bone[edit]
Main article: Fibrous dysplasia of bone
Fibrous dysplasia of bone is a disorder where normal bone and marrow is replaced with fibrous tissue, resulting in formation of bone that is weak and prone to expansion. As a result, most complications result from fracture, deformity, functional impairment and pain.[3]
## Mainly macroscopic scale[edit]
### Hip dysplasia[edit]
Main article: Hip dysplasia
Hip dysplasia is an abnormality of the hip joint where the socket portion does not fully cover the ball portion, resulting in an increased risk for joint dislocation.[4] Hip dysplasia may occur at birth or develop in early life.[4] Regardless, it does not typically produce symptoms in babies less than a year old.[5] Occasionally one leg may be shorter than the other.[4] The left hip is more often affected than the right.[5] Complications without treatment can include arthritis, limping, and low back pain.[5]
### Multicystic dysplastic kidney[edit]
Main article: Multicystic dysplastic kidney
Multicystic dysplastic kidney (MCDK) is a condition that results from the malformation of the kidney during fetal development. The kidney consists of irregular cysts of varying sizes. Multicystic dysplastic kidney is a common type of renal cystic disease, and it is a cause of an abdominal mass in infants.[6]
## Etymology[edit]
From Ancient Greek δυσ- dys-, "bad" or "difficult" and πλάσις plasis, "formation". The equivalent surface analysis, in parallel with classical compounds, is dys- \+ -plasia.
## See also[edit]
* Pleomorphism
* List of biological development disorders
## References[edit]
1. ^ "Definition of dysplasia". Merriam-Webster dictionary. Retrieved 2019-09-09.
2. ^ a b c "Myelodysplastic Syndromes Treatment (PDQ®)–Patient Version". NCI. 12 August 2015. Archived from the original on 5 October 2016. Retrieved 27 October 2016.
3. ^ Boyce, Alison M.; Collins, Michael T. (1993-01-01). Pagon, Roberta A.; Adam, Margaret P.; Ardinger, Holly H.; Wallace, Stephanie E.; Amemiya, Anne; Bean, Lora JH; Bird, Thomas D.; Fong, Chin-To; Mefford, Heather C. (eds.). Fibrous Dysplasia/McCune-Albright Syndrome. Seattle (WA): University of Washington, Seattle. PMID 25719192.
4. ^ a b c "Your Orthopaedic Connection: Developmental Dysplasia of the Hip". October 2013.
5. ^ a b c Shaw, BA; Segal, LS; SECTION ON, ORTHOPAEDICS. (December 2016). "Evaluation and Referral for Developmental Dysplasia of the Hip in Infants". Pediatrics. 138 (6): e20163107. doi:10.1542/peds.2016-3107. PMID 27940740.
6. ^ Multicystic Dysplastic Kidney Imaging at eMedicine
## Further reading[edit]
* Noel Weidner (editor), Richard Cote, Saul Suster, Lawrence Weiss (2003). Modern Surgical Pathology. London: W.B. Saunders. ISBN 978-0-7216-7253-3. OCLC 50244347.CS1 maint: multiple names: authors list (link)
* Ramzi S. Cotran, Vinay Kumar, Tucker Collins (Editor) (1999). Robbins Pathologic Basis of Disease (6th ed.). London: W.B. Saunders. ISBN 978-0-7216-7335-6. OCLC 39465455.CS1 maint: multiple names: authors list (link) CS1 maint: extra text: authors list (link)
* v
* t
* e
Overview of tumors, cancer and oncology
Conditions
Benign tumors
* Hyperplasia
* Cyst
* Pseudocyst
* Hamartoma
Malignant progression
* Dysplasia
* Carcinoma in situ
* Cancer
* Metastasis
* Primary tumor
* Sentinel lymph node
Topography
* Head and neck (oral, nasopharyngeal)
* Digestive system
* Respiratory system
* Bone
* Skin
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* Urogenital
* Nervous system
* Endocrine system
Histology
* Carcinoma
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*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Dysplasia | c0334044 | 4,554 | wikipedia | https://en.wikipedia.org/wiki/Dysplasia | 2021-01-18T18:44:44 | {"mesh": ["D002471"], "umls": ["C0334044"], "wikidata": ["Q1128996"]} |
Pure autonomic failure (PAF) is a neurodegenerative disease of the autonomic nervous system, which regulates involuntary body processes such as blood pressure and breathing rate. PAF affects only the peripheral autonomic nervous system, which means it does not involve the brain and spinal cord (the central nervous system). It usually begins in midlife, although it can begin earlier. The main symptom of PAF is orthostatic hypotension, a sudden drop in blood pressure upon standing. This causes a person to feel dizzy and lightheaded, requiring them to sit or lie down to prevent fainting. People with PAF also have an abnormal blood pressure response to other common daily activities or exposures, as well as additional symptoms affecting various body systems.
The reason that PAF develops is not known. It is not known to be inherited. The symptoms are caused by abnormal accumulations of protein, called Lewy bodies, in the cells of autonomic nerves. The Lewy bodies restrict the production and release of norepinephrine from nerve cells, which in turn causes hypotension. Diagnosing PAF may involve tilt table testing, 24-hour blood pressure monitoring, hyperventilation testing, and a norepinephrine blood test. Treatment options do not stop disease progression but help to control symptoms. Options may include avoiding triggers of symptoms, increasing fluid and salt intake, using compressive garments, and/or various medications. PAF usually has a slowly progressive course and may result in a person being restricted to a reclined position in their home.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Pure autonomic failure | c0393911 | 4,555 | gard | https://rarediseases.info.nih.gov/diseases/10428/pure-autonomic-failure | 2021-01-18T17:58:03 | {"mesh": ["D054970"], "umls": ["C0393911"], "orphanet": ["441"], "synonyms": ["Bradbury Eggleston syndrome", "Bradbury-Eggleston syndrome", "Orthostatic hypotension (a symptom)", "Idiopathic orthostatic hypotension (a symptom)"]} |
PAPA syndrome
Other namesPyogenic arthritis-pyoderma gangrenosum-acne syndrome[1]
PAPA syndrome is inherited in an autosomal dominant pattern.
PAPA syndrome is an acronym for pyogenic arthritis, pyoderma gangrenosum and acne. It is a rare genetic disorder characterised by its effects on skin and joints.[2][3]
## Contents
* 1 Signs and symptoms
* 2 Genetics
* 3 Diagnosis
* 4 Treatment
* 5 See also
* 6 References
* 7 External links
## Signs and symptoms[edit]
PAPA syndrome usually begins with arthritis at a young age, with the skin changes more prominent from the time of puberty.
The arthritis is the predominant feature, noted by its juvenile onset and destructive course. Individuals often recall episodes of arthritis precipitated by a traumatic event. With repeated episodes the joints become damaged with multiple joint replacements required. Hopefully, with improved treatment options, the damage will be limited in new cases.
Pyoderma gangrenosum is variably expressed, which means that it is not always present in all individuals with the disease. It presents as poorly healing ulcers with undermined edges. Pathergy is an important feature (this term refers to the tendency of ulcers to arise at points of injury). There are reports of lesions developing at the site of a joint replacement wound, central venous line and intravenous drip insertion.
Acne affects most individuals with PAPA syndrome but to a variable degree. It is usually of a severe nodulocystic type which if untreated results in scarring.[citation needed]
## Genetics[edit]
PAPA syndrome is inherited in an autosomal dominant fashion, which means that if one parent is affected, there is a 100% chance that a child will inherit the disease from a homozygous affected parent and a 50% chance that a child will inherit the disease from an affected heterozygous parent.
Recently the responsible gene has been identified on Chromosome 15.[4][5][6] Two mutations have been found in a protein called CD2 binding protein 1 (CD2BP1).[7] This protein is part of an inflammatory pathway associated with other autoinflammatory diseases such as familial Mediterranean fever, Hyperimmunoglobulinemia D with recurrent fever, Muckle–Wells syndrome, neonatal onset multisystem inflammatory disease, and familial cold urticaria.[8]
## Diagnosis[edit]
Clinical features along with the familial tendency may be enough to make a diagnosis. Genetic testing may also be used.[citation needed]
## Treatment[edit]
Acne treatment may require oral tetracycline antibiotics or isotretinoin. Treatments directed at tumor necrosis factor (TNF) (infliximab, etanercept) and interleukin-1 (anakinra) have shown a good response in resistant arthritis and pyoderma gangrenosum.[9][10][11] Other traditional immunosuppressant treatments for arthritis or pyoderma gangrenosum may also be used.
## See also[edit]
* SAPHO syndrome
* Psoriatic arthritis
* List of cutaneous conditions
## References[edit]
1. ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Pyogenic arthritis pyoderma gangrenosum acne syndrome". www.orpha.net. Retrieved 27 April 2019.
2. ^ Lindor NM, Arsenault TM, Solomon H, Seidman CE, McEvoy MT. A new autosomal dominant disorder of pyogenic sterile arthritis, pyoderma gangrenosum, and acne: PAPA Syndrome. Mayo Clin Proc 1997; 72:611-5.
3. ^ McDermott MF, Aksentijevich I. The Autoinflammatory syndromes. Curr Opin Allergy Clin Immunol 2002; 2(6): 511-516.
4. ^ Yeon HB, Lindor HM, Seidman JG, Seidman CE et al.Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Syndrome Maps to Chromosome 15q. Am J Hum Genet 2000; 66:1443-8.
5. ^ Lindor NM, Arsenault TM, Solomon H, Seidman CE, McEvoy MT. A new autosomal dominant disorder of pyogenic sterile arthritis, pyoderma gangrenosum, and acne: PAPA Syndrome. Mayo Clin Proc 1997; 72:611-5.
6. ^ Wise CA, Bennett LB, Pascual V, Gillum JD, Bowcock AM. Localization of a gene for familial recurrent arthritis. Arthritis Rheum. 2000 Sep; 43(9):2041-5.
7. ^ Wise CA, Gillum JD, Seidman CE, Lindor NM, Veile R, Bashiardes S, Lovett M. Mutations in CD2BP1 disrupt binding to PTP PEST and are responsible for PAPA syndrome, an autoinflammatory disorder. Hum Mol Genet. 2002 Apr 15; 11(8): 961-9
8. ^ Shoham NG, Centola M, Mansfield E, Hull KM, Wood G, Wise CA, Kastner DL. Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway. Proc Natl Acad Sci USA. 2003 Nov 11; 100(23): 13501-6.
9. ^ Stichweh DS, Punaro M, Pascual V. Dramatic improvement of pyoderma gangrenosum with infliximab in a patient with PAPA Syndrome. 2005 May-Jun; 22(3): 262-5.
10. ^ Cortis E, De Benedetti F, Insalaco A, Cioschi S, Muratori F, D’Urbano LE, Ugazio AG. Abnormal production of the tumor necrosis factor alpha and clinical efficacy of the TNF Inhibitor Etanercept in a patient with PAPA syndrome. J Pediatr. 2004 Dec; 145 (6): 851-5. Erratum in: J Pediatr. 2005 Feb; 146(2):193.
11. ^ Dierselhuis MP, Frenkel J, Wulffraat NM, Boelens JJ. Anakinra for flares of pyogenic arthritis in PAPA syndrome. Rheumatology (Oxford). 2005 Jan 5;(Epub ahead of print)
## External links[edit]
Classification
D
* OMIM: 604416
* MeSH: C536253
* DiseasesDB: 32724
* SNOMED CT: 724015007
External resources
* Orphanet: 69126
*[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
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| PAPA syndrome | c1858361 | 4,556 | wikipedia | https://en.wikipedia.org/wiki/PAPA_syndrome | 2021-01-18T19:04:17 | {"gard": ["9176"], "mesh": ["C536253"], "umls": ["C1858361"], "orphanet": ["69126"], "wikidata": ["Q7118181"]} |
Leukoencephalopathy (leukodystrophy-like diseases) is all of the brain white matter diseases, whether their molecular cause is known or not.[1] It can refer specifically to any of these diseases:
* Progressive multifocal leukoencephalopathy
* Toxic leukoencephalopathy
* Leukoencephalopathy with vanishing white matter
* Leukoencephalopathy with neuroaxonal spheroids
* Reversible posterior leukoencephalopathy syndrome
* Megalencephalic leukoencephalopathy with subcortical cysts. It can also refer to gene MLC1 or Megalencephalic leukoencephalopathy with subcortical cysts 1, a human gene related to the former disease.
* Hypertensive leukoencephalopathy
The classification of leukoencephalopathies is a matter of debate. Some authors divide leukoencephalopathies into hereditary disorders and acquired disorders. The hereditary demyelinating disorders are then classified according to the localization of the underlying metabolic defect, and they include the leukodystrophies when myelin growth is the underlying problem.
The acquired demyelinating disorders are classified according to their underlying causes into five groups: noninfectious–inflammatory, infectious–inflammatory, toxic–metabolic, hypoxic–ischemic (vascular problems like Binswanger's disease), and traumatic.[2]
This classification is diffuse sometimes. For example CADASIL is at the same time hereditary and hypoxic.
## References[edit]
1. ^ Lyon, G.; Fattal-Valevski, A.; Kolodny, E. H. (2006). "Leukodystrophies". Topics in Magnetic Resonance Imaging. 17 (4): 219–242. doi:10.1097/RMR.0b013e31804c99d4. PMID 17414998.
2. ^ Marjo S. van der Knaap and Jaap Valk, eds. New York: Springer; 2005, Magnetic Resonance of Myelination and Myelin Disorders, 3rd ed.
*[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
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Leukoencephalopathy | c0270612 | 4,557 | wikipedia | https://en.wikipedia.org/wiki/Leukoencephalopathy | 2021-01-18T18:48:16 | {"mesh": ["D056784"], "umls": ["C0270612"], "wikidata": ["Q3237081"]} |
SOST-related sclerosing bone dysplasia is a disorder of bone development characterized by excessive bone formation (hyperostosis). As a result of hyperostosis, bones throughout the body are denser and wider than normal, particularly the bones of the skull. Affected individuals typically have an enlarged jaw with misaligned teeth. People with this condition may also have a sunken appearance of the middle of the face (midface hypoplasia), bulging eyes with shallow eye sockets (ocular proptosis), and a prominent forehead. People with this condition often experience headaches because increased thickness of the skull bones increases pressure on the brain. The excessive bone formation seen in this condition seems to occur throughout a person's life, so the skeletal features become more pronounced over time. However, the excessive bone growth may only occur in certain areas.
Abnormal bone growth can pinch (compress) the cranial nerves, which emerge from the brain and extend to various areas of the head and neck. Compression of the cranial nerves can lead to paralyzed facial muscles (facial nerve palsy), hearing loss, vision loss, and a sense of smell that is diminished (hyposmia) or completely absent (anosmia). Abnormal bone growth can cause life-threatening complications if it compresses the part of the brain that is connected to the spinal cord (the brainstem).
There are two forms of SOST-related sclerosing bone dysplasia: sclerosteosis and van Buchem disease. The two forms are distinguished by the severity of their symptoms.
Sclerosteosis is the more severe form of the disorder. People with sclerosteosis are often tall and have webbed or fused fingers (syndactyly), most often involving the second and third fingers. The syndactyly is present from birth, while the skeletal features typically appear in early childhood. People with sclerosteosis may also have absent or malformed nails.
Van Buchem disease represents the milder form of the disorder. People with van Buchem disease are typically of average height and do not have syndactyly or nail abnormalities. Affected individuals tend to have less severe cranial nerve compression, resulting in milder neurological features. In people with van Buchem disease, the skeletal features typically appear in childhood or adolescence.
## Frequency
SOST-related sclerosing bone dysplasia is a rare condition; its exact prevalence is unknown.
Approximately 100 individuals with sclerosteosis have been reported in the scientific literature. Sclerosteosis is most common in the Afrikaner population of South Africa.
Van Buchem disease has been reported in approximately 30 people. Most people with van Buchem disease are of Dutch ancestry.
## Causes
SOST-related sclerosing bone dysplasia is caused by mutations in or near the SOST gene. The SOST gene provides instructions for making the protein sclerostin. Sclerostin is produced in osteocytes, which are a type of bone cell. The main function of sclerostin is to stop (inhibit) bone formation.
Mutations in the SOST gene that cause sclerosteosis prevent the production of any functional sclerostin. A lack of sclerostin disrupts the inhibitory role it plays during bone formation, causing excessive bone growth.
SOST mutations that cause van Buchem disease result in a shortage of functional sclerostin. This shortage reduces the protein's ability to inhibit bone formation, causing the excessive bone growth seen in people with van Buchem disease.
### Learn more about the gene associated with SOST-related sclerosing bone dysplasia
* SOST
## Inheritance Pattern
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| SOST-related sclerosing bone dysplasia | c4551483 | 4,558 | medlineplus | https://medlineplus.gov/genetics/condition/sost-related-sclerosing-bone-dysplasia/ | 2021-01-27T08:24:44 | {"gard": ["2833", "4771"], "omim": ["269500", "239100"], "synonyms": []} |
A number sign (#) is used with this entry because susceptibility to this form of renal disease, referred to here as focal segmental glomerulosclerosis-4 (FSGS4), is conferred by variation in the APOL1 gene (603743) on chromosome 22q12. These APOL1 variants confer protection against infection with T. b. rhodesiense, a human-specific Trypanosoma subspecies. Susceptibility to this form of FSGS is prevalent in populations of African ancestry.
Description
Focal segmental glomerulosclerosis (FSGS) is a pathologic entity associated clinically with proteinuria, the nephrotic syndrome (NPHS), and progressive loss of renal function. It is a common cause of end-stage renal disease (ESRD) (Meyrier, 2005).
For a general phenotypic description and a discussion of genetic heterogeneity of focal segmental glomerulosclerosis and nephrotic syndrome, see FSGS1 (603278).
Mapping
To identify genetic variants predisposing to idiopathic and HIV-1-associated focal segmental glomerulosclerosis (FSGS), Kopp et al. (2008) carried out an admixture mapping linkage disequilibrium genome scan in 190 African American individuals with FSGS and 222 controls. They identified a chromosome 22q12 region with a genomewide lod score of 9.2 and a peak lod of 12.4 centered on MYH9 (160775), a functional candidate gene expressed in kidney podocytes. Multiple MYH9 SNPs and haplotypes were recessively associated with FSGS, most strongly in haplotypes spanning exons 14 through 23 (odds ratio = 5.0, 95% confidence interval = 3.5-7.1; P = 4 x 10(-23), n = 852). Kopp et al. (2008) found that their association extended to hypertensive end-stage renal disease (ESRD) (odds ratio = 2.2, 95% confidence interval = 1.5-3.4; n = 433), but not type 2 diabetic ESRD (n = 476). Kopp et al. (2008) concluded that genetic variation at the MYH9 locus substantially explains the increased burden of FSGS and hypertensive ESRD among African Americans. For 3 MYH9 intron 23 SNPs in strong linkage disequilibrium (rs4821480, rs2032487, and rs4821481), 79 to 83% of the association was attributable to the SNPs alone, with the remaining fraction attributable to chromosomal ancestry. The single strongest risk allele within MYH9 was at rs2032487, which had a P value for idiopathic FSGS of 7 x 10(-12) and a P value for HIV-1-associated FSGS of 8 x 10(-8).
Kao et al. (2008) independently performed a genomewide admixture scan in 1,372 end-stage renal disease (ESRD) cases and 806 controls and found a highly significant association between excess African ancestry and nondiabetic ESRD (lod score = 5.70) but not diabetic ESRD (lod = 0.47) on chromosome 22q12. Each copy of the European ancestral allele conferred a relative risk of 0.50 (95% confidence interval = 0.39-0.63) compared to African ancestry. Multiple common SNPs (allele frequencies ranging from 0.02 to 0.06) in MYH9, the gene encoding nonmuscle myosin heavy chain type II isoform A, were associated with 2 to 4 times greater risk of nondiabetic ESRD and accounted for a large proportion of the excess risk of ESRD observed in African compared to European Americans. This risk was associated with all nondiabetes ESRD with a lod score of 4.55 and also with hypertensive ESRD at 1.79, FSGS at 2.47, and HIV-related ESRD at 2.09. Kao et al. (2008) showed that any of the 3 SNPs, rs4821480, rs2032487, and rs4821481, in strong linkage disequilibrium is sufficient to account for all of the association between the excess African ancestry observed on chromosome 22q12 and nondiabetic ESRD.
Molecular Genetics
Although genetic variation in or near the MYH9 gene on chromosome 22 was associated with increased risk of FSGS, causal mutations in MHY9 had not been identified. Genomewide analyses showed a strong signal of natural selection in the region containing the MHY9 and APOL1 (603743) genes. The longer patterns of linkage disequilibrium (LD) associated with variants undergoing natural selection suggested to Genovese et al. (2010) that a positively selected risk variant could be in a larger interval containing the APOL genes rather than be confined to MYH9. In an association analysis comparing 205 African Americans with biopsy-proven FSGS and no family history of FSGS with 180 African American controls, Genovese et al. (2010) identified association of kidney disease with 2 independent sequence variants in the last exon of the APOL1 gene (FSGS odds ratio = 10.5, 95% confidence interval 6.0 to 18.4; ESRD odds ratio = 7.3, 95% confidence interval 5.6 to 9.5). Association with renal disease was confirmed in a larger cohort of 1,030 African American cases with ESRD and 1,025 geographically matched African American controls. The 2 APOL1 variants, which Genovese et al. (2010) referred to as G1 (603743.0001) and G2 (603743.0002), are common in African chromosomes but absent in European chromosomes, and both reside within haplotypes that harbor signatures of positive selection. APOL1 is a serum factor that lyses trypanosomes. In vitro assays revealed that only the kidney disease-associated APOL1 variants lysed Trypanosoma brucei rhodesiense. Association of renal disease with MYH9 sequence variants disappeared after controlling for the APOL1 risk variants. Comparing participants with zero or 1 risk allele of APOL1 to participants with 2 risk alleles provided an odds ratio for FSGS of 10.5 (confidence interval 6.0 to 18.4). This analysis supported a completely recessive pattern of inheritance. Genovese et al. (2010) speculated that evolution of a critical survival factor in Africa may have contributed to the high rates of renal disease in African Americans.
Parsa et al. (2013) performed 2 studies examining the effects of variants in the APOL1 gene on the progression of chronic kidney disease. In the African American Study of Kidney Disease and Hypertension (AASK), 693 black patients with chronic kidney disease attributed to hypertension were examined for a primary outcome of composite end-stage renal disease or doubling of the serum creatinine level. A total of 160 (23%) individuals carried 2 copies of APOL1 risk variants G1 (603743.0001) and/or G2 (603743.0002). Of these individuals in the high-risk group, the primary outcome occurred in 58%; in the APOL1 low-risk group (all other genotypes), the primary outcome occurred in 37% (hazard ratio in the high-risk group, 1.88; p less than 0.001). In the Chronic Renal Insufficiency Cohort (CRIC), Parsa et al. (2013) evaluated 2,955 white patients and black patients with chronic kidney disease (46% of whom had diabetes) for the primary outcomes of the slope of the estimated glomerular filtration rate (eGFR) and the composite of end-stage renal disease, or a reduction of 50% in the eGFR from baseline. Black patients were genotyped for the G1 and G2 risk alleles. In the CRIC study, black patients in the APOL1 high-risk group (270 of 1,411 total black patients) had a more rapid decline in the eGFR and a higher risk of the composite renal outcome than did white patients, with or without diabetes as a complication (p less than 0.001 for all comparisons).
Nomenclature
In the literature, the clinical term 'nephrotic syndrome' (NPHS) and the pathologic term 'focal segmental glomerulosclerosis' (FSGS) have often been used to refer to the same disease entity. In OMIM, these disorders are designated as NPHS or FSGS according to how they were first described in the literature.
*[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
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| FOCAL SEGMENTAL GLOMERULOSCLEROSIS 4, SUSCEPTIBILITY TO | c2675525 | 4,559 | omim | https://www.omim.org/entry/612551 | 2019-09-22T16:01:15 | {"omim": ["612551"], "orphanet": ["84271"], "synonyms": ["Alternative titles", "END-STAGE RENAL DISEASE, NONDIABETIC, SUSCEPTIBILITY TO, INCLUDED", "Sporadic idiopathic nephrosis"]} |
A number sign (#) is used with this entry because hypermanganesemia with dystonia-1 (HMNDYT1) is caused by homozygous mutation in the SLC30A10 gene (611146) on chromosome 1q41.
Description
Hypermanganesemia with dystonia-1 is an autosomal recessive metabolic disorder characterized by increased serum manganese, motor neurodegeneration with extrapyramidal features, polycythemia, and hepatic dysfunction, which leads to cirrhosis in some cases. Intellectual function is preserved (summary by Tuschl et al., 2012 and Quadri et al., 2012).
### Genetic Heterogeneity of Hypermanganesemia With Dystonia
See also HMNDYT2 (617013), caused by mutation in the SLC39A14 gene (608736) on chromosome 8p21.
Clinical Features
Tuschl et al. (2008) reported an Arabic girl with a constellation of clinical features consisting of hypermanganesemia, liver cirrhosis, an extrapyramidal motor disorder, and polycythemia. She was born to healthy first-cousin parents. The pregnancy, delivery, and neonatal period were uneventful, and her development was normal until the age of 2 years, when difficulty with walking became apparent. This corrected itself until she presented again with walking difficulties at age 11. Her motor problems affected both her gait and fine movements of her hands. Apart from the movement disorder, her general physical health and development were normal for age. At 12 years of age her height and weight were at the 50th percentile, but her head circumference was 50.1 cm (2nd percentile). She showed mild icterus but no stigmata of chronic liver disease; liver and spleen were normal. Neurologic exam showed toe walking, increased tone of all 4 extremities, and dysdiadochokinesis. There was no dysmetria. Ocular exam was normal with no evidence of Kayser-Fleischer rings. She had polycythemia with a hemoglobin of 18 g/dl, unconjugated hyperbilirubinemia, and increased blood manganese concentrations (3,285 nmol/L, normal less than 320 nmol/L). Total iron binding capacity was increased. Plasma copper and zinc levels were normal. Prothrombin time and activated partial thromboplastin time were somewhat prolonged. Liver biopsy showed bridging fibrosis and cirrhosis with patchy moderate to severe portal and periportal chronic inflammatory cell infiltrate. Abdominal ultrasound showed an enlarged liver with coarse echotexture and a mildly enlarged spleen suggestive of cirrhosis and early portal hypertension. Hepatic manganese content was elevated (3.4 microg/g wet weight, normal 1-2 microg/g). Muscle biopsy was microscopically normal, but manganese content was elevated 3-fold. Copper was borderline high in both liver and muscle but not in the range of Wilson disease (277900). MRI of the brain showed hyperintense signal from the anterior pituitary, caudate, lentiform, and dentate nuclei and cerebellar white matter in the T1 sequence but normal T2 sequence consistent with manganese deposition in these regions. MRI of the spine was unremarkable. The patient had 4 healthy brothers and 3 healthy sisters; 1 older brother died at the age of 18 years from gastrointestinal hemorrhage secondary to cirrhosis. His clinical course was very similar to that of his sister, including microcephaly and MRI showing manganese deposition in the basal ganglia. Tuschl et al. (2008) excluded mutation in the ATP2C2 (613082) and ATP2A3 (601929) genes as the cause of the disorder in their patient.
Gospe et al. (2000) reported a 14-year-old white male, the product of a nonconsanguineous union, who presented with stiffness of gait and progressive leg weakness. He had spastic paraparesis of the lower extremities. MRI of the spinal cord was normal but MRI of the brain showed high signal in the lenticular and dentate nuclei, brain stem, and pituitary, consistent with deposition of manganese. Brain stem atrophy was also present. Whole-blood manganese measured 3.48 micromol/l. There was no evidence of environmental exposure. His liver biopsy showed evidence of micronodular cirrhosis with no evidence of steatosis or of increased iron storage. There was no indication of hepatic copper deposition. Liver manganese concentration was approximately 3 times normal. During 11 years of clinical observation, the patient had progressive spastic weakness of the legs leading to loss of ambulation and painful extensor spasms. Whole-blood magnesium ranged from 2.93 to 3.66 micromol/l. The patient had persistent polycythemia, requiring phlebotomy twice weekly. Lechpammer et al. (2014) reported postmortem examination results on this patient, who died of pneumonia at age 38 years. The liver showed hepatomegaly with micronodular cirrhosis with portal hypertension manifest by congestive splenomegaly and esophageal varices. Many hepatocytes contained a finely granular brown-orange pigment. Western blot analysis showed decreased levels of SLC30A10. Hypertrophic cardiomyopathy was also observed, with granular rhodanine-positive accumulates in rare myocytes. The basal ganglia showed severe neuronal loss in the globus pallidus, and there was deposition of rhodanine-positive brown pigment in residual neurons and astrocytes. Other findings included reactive astrocytosis, myelin loss, and spongiosis. Similar features were observed in the putamen, caudate nucleus, thalamus, and cerebellum. There was diffuse reactive gliosis throughout the white matter with axonal loss in the corticospinal tracts, and the brainstem showed poorly pigmented neurons in the substantia nigra. There were increased levels of Mn and decreased amounts of SLC30A10 in various brain regions. Lechpammer et al. (2014) noted that this patient had the unusual feature of spastic paraparesis rather than extrapyramidal signs, which may have reflected the corticospinal tract pathology. The findings indicated that SLC30A10 mutations result in chronic, cumulative brain injury, and Lechpammer et al. (2014) suggested that early chelation therapy may prevent symptom progression.
Sahni et al. (2007) and Brna et al. (2011) reported a Canadian girl who presented at age 5 years with pica, emotional lability, decreased speech output, echolalia, and social withdrawal. Her motor coordination had deteriorated, and she had lost fine motor skills and was unable to walk independently. Neurologic examination shoed a narrow-based, high stepping gait, mild truncal ataxia, and action tremor. Brain MRI showed hyperintensities in the basal ganglia, and laboratory studies showed increased serum manganese, low iron, and polycythemia. Liver biopsy was normal, but showed increased manganese. Results of extensive environmental studies did not explain the toxicity, suggesting a metabolic disorder. Chelation therapy resulted in some neurologic improvement, as well as improvement of brain lesions. At age 10 years, she had a stable neurologic status and was able to walk short distances, but preferred using a wheelchair. Cognition was unimpaired and she functioned at an appropriate level in school.
Tuschl et al. (2012) reported 15 individuals from 8 families with HMDPC, including 4 patients from 3 families previously reported by Gospe et al. (2000), Tuschl et al. (2008), Sahni et al. (2007), and Brna et al. (2011). The patients presented between 2 and 15 years of age with gait disturbances and hypertonia, with some becoming wheelchair-bound. Most had a pure 4-limb dystonia, with a high stepping gait and fine motor impairment, sometimes with dysarthria, fine tremor, and bradykinesia; 1 had pure spastic paraparesis without extrapyramidal features. Intellectual development was normal. All had pathognomonic MRI brain scans with hyperintensities of the globus pallidus, putamen, caudate, subthalamic and dentate nucleus and sparing of the thalamus and ventral pons on T1-weighted images. Those with more extensive disease showed white matter and anterior pituitary involvement. Most patients had liver impairment with raised transaminases and unconjugated hyperbilirubinemia; 2 died of cirrhosis. Other features included polycythemia associated with high erythropoietin levels, decreased iron stores, and increased total iron binding capacity. Liver tissue and blood showed significantly increased Mn content, and parental blood Mn levels were mildly increased in 3 families, consistent with a carrier status. Chelation therapy in some patients resulted in improvement of the neurologic symptoms.
Quadri et al. (2012) reported 2 consanguineous families, of Italian and Dutch descent, respectively, in which a total of 5 patients had hypermanganesemia associated with degenerative motor symptoms. The patients were adults at the time of the report, ranging in age from 46 to 65 years. In the Italian family, 2 brothers presented at age 47 and 57 years, respectively, with parkinsonism, including gait disturbances, bradykinesia, hypomimia, rigidity, and postural instability. Both also had polycythemia, hepatomegaly, and brain MRI lesions in the basal ganglia, midbrain, thalamus, cerebellum, and corticospinal tract. One patient had a sensorimotor axonal polyneuropathy. Laboratory studies showed markedly increased manganese, increased transferrin, and decreased ferritin. Chelation therapy resulted in clinical improvement. There were 3 affected sibs in the Dutch family. All developed polycythemia in early childhood. Neurologic symptoms appeared at ages 2, 14, and 10 years, respectively, but the features were variable between patients. The oldest brother developed walking difficulties and limb spasms at age 14. This progressed and he developed generalized dystonia and became wheelchair-bound. Brain MRI showed no gross abnormalities. His younger brother developed walking difficulties at age 2 years. He had progressive dystonia and was wheelchair-bound at age 34. Both had increased serum manganese and increased total iron binding capacity, but normal iron. Brain MRI of the older brother was normal, but that of the younger brother showed hyperintense lesions of the globus pallidus. Neither had liver involvement. However, their younger sister died at age 46 of liver cirrhosis, portal hypertension, splenomegaly, and hepatic encephalopathy. She developed gait difficulties at the age of about 10, but there was no clear documentation of dystonia. Manganese levels were never determined, and neuroimaging was never performed.
Inheritance
Tuschl et al. (2008) considered autosomal recessive inheritance likely in their patient because the family was consanguineous and the patient and 1 brother were affected.
Clinical Management
The patient of Tuschl et al. (2008) was treated with co-careldopa with good effect on the dystonia. D-Penicillamine had only modest effect on urinary manganese excretion. However, a 5-day course of disodium calcium edetate at a dose of 1 gram twice daily (20 mg/kg per dose) resulted in a marked increase in 24-hour urinary manganese excretion and a decrease in blood manganese levels to 1,790 by day 4. The patient was started on monthly 5-day courses of chelation therapy, which were well tolerated and led to significant improvement in her dystonia. After 4 years of chelation, the patient's handwriting, tremor, and stiffness were much better; she suffered no obvious progression of her liver disease, although unconjugated hyperbilirubinemia was still present. Repeat liver biopsy showed that chelation therapy had normalized the liver manganese content and there was less inflammation and fibrosis. Blood manganese level was still very high at 2,322 nmol/L. Since manganese intake is virtually impossible to restrict, oral iron therapy was started to act as a competitive inhibitor of manganese absorption. This led to further improvement in patient's motor symptoms and a rapid fall of blood manganese to 171 nmol/L within 1 month.
Molecular Genetics
By homozygosity mapping followed by candidate gene analysis of 2 consanguineous families with HMDPC, Tuschl et al. (2012) identified a deletion in the SLC30A10 gene (611146.0001) in the family reported by Tuschl et al. (2008). The other family had a large deletion encompassing exons 3 and 4 of the SLC30A10 gene. Subsequent mutation analysis in 6 additional families with the disorder identified homozygous mutations in all patients (see, e.g., 611146.0002-611146.0003). Some of the patients had previously been reported (Gospe et al., 2000; Sahni et al., 2007; Brna et al., 2011). When DNA from parents was available, they were found to be heterozygous carriers. In vitro functional expression studies of 2 of the mutant proteins in a yeast strain lacking a manganese transporter demonstrated that both mutant proteins were nonfunctional.
INHERITANCE \- Autosomal recessive ABDOMEN Liver \- Hepatomegaly \- Liver dysfunction \- Cirrhosis NEUROLOGIC Central Nervous System \- Dystonia \- Hypertonia of the limbs \- High-steppage gait \- Fine motor impairment \- Dysarthria \- Extrapyramidal signs \- Parkinsonism \- Tremor \- Bradykinesia \- Rigidity \- Postural instability \- Spastic paraparesis (1 patient) \- Brain MRI shows hyperintensities in the basal ganglia \- Lesions in the white matter \- Lesions in the anterior pituitary (less common) Peripheral Nervous System \- Sensorimotor neuropathy (1 patient) HEMATOLOGY \- Polycythemia LABORATORY ABNORMALITIES \- Increased serum manganese \- Hyperbilirubinemia, unconjugated \- Increased liver enzymes \- Increased erythropoietin \- Low ferritin \- Low iron \- Increased total iron binding capacity MISCELLANEOUS \- Onset usually in first decade \- Adult onset of neurologic symptoms has been reported in 1 family \- Variable severity \- Chelation therapy can result in clinical improvement MOLECULAR BASIS \- Caused by mutation in the solute carrier family 30 (zinc transporter), member 10 gene (SLC30A10, 611146.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| HYPERMANGANESEMIA WITH DYSTONIA 1 | c2750442 | 4,560 | omim | https://www.omim.org/entry/613280 | 2019-09-22T15:59:07 | {"doid": ["0080536"], "mesh": ["C548016"], "omim": ["613280"], "orphanet": ["309854"], "synonyms": ["Alternative titles", "HYPERMANGANESEMIA WITH DYSTONIA, POLYCYTHEMIA, AND CIRRHOSIS"], "genereviews": ["NBK100241"]} |
Fungal infection of the skin
"Ringworm" redirects here. For the band, see Ringworm (band).
"Tinea" redirects here. For the moth genus, see Tinea (moth).
Not to be confused with Ringed worm or Taenia (cestode).
Dermatophytosis
Other namesRingworm, tinea
Ringworm on a human leg
SpecialtyDermatology
SymptomsRed, itchy, scaly, circular skin rash[1]
CausesFungal infection[2]
Risk factorsUsing public showers, contact sports, excessive sweating, contact with animals, obesity, poor immune function[3][4]
Diagnostic methodBased on symptoms, microbial culture, microscopic examination[5]
Differential diagnosisDermatitis, psoriasis, pityriasis rosea, tinea versicolor[6]
PreventionKeep the skin dry, no walking barefoot in public, not sharing personal items[3]
TreatmentAntifungal creams (clotrimazole, miconazole)[7]
Frequency20% of the population[8]
Dermatophytosis, also known as ringworm, is a fungal infection of the skin.[2] Typically it results in a red, itchy, scaly, circular rash.[1] Hair loss may occur in the area affected.[1] Symptoms begin four to fourteen days after exposure.[1] Multiple areas can be affected at a given time.[4]
About 40 types of fungi can cause ringworm.[2] They are typically of the Trichophyton, Microsporum, or Epidermophyton type.[2] Risk factors include using public showers, contact sports such as wrestling, excessive sweating, contact with animals, obesity, and poor immune function.[3][4] Ringworm can spread from other animals or between people.[3] Diagnosis is often based on the appearance and symptoms.[5] It may be confirmed by either culturing or looking at a skin scraping under a microscope.[5]
Prevention is by keeping the skin dry, not walking barefoot in public, and not sharing personal items.[3] Treatment is typically with antifungal creams such as clotrimazole or miconazole.[7] If the scalp is involved, antifungals by mouth such as fluconazole may be needed.[7]
Globally, up to 20% of the population may be infected by ringworm at any given time.[8] Infections of the groin are more common in males, while infections of the scalp and body occur equally in both sexes.[4] Infections of the scalp are most common in children while infections of the groin are most common in the elderly.[4] Descriptions of ringworm date back to ancient history.[9]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Diagnosis
* 3.1 Classification
* 4 Prevention
* 4.1 Vaccination
* 5 Treatment
* 6 History
* 7 Terminology
* 8 Other animals
* 8.1 Diagnosis
* 8.2 Treatment
* 8.2.1 Pet animals
* 8.2.2 Cattle
* 9 See also
* 10 References
* 11 Further reading
* 12 External links
## Signs and symptoms
Infections on the body may give rise to typical enlarging raised red rings of ringworm. Infection on the skin of the feet may cause athlete's foot and in the groin, jock itch. Involvement of the nails is termed onychomycosis, and they may thicken, discolour, and finally crumble and fall off. They are common in most adult people, with up to 20% of the population having one of these infections at any given moment.[citation needed]
Animals including dogs and cats can also be affected by ringworm, and the disease can be transmitted between animals and humans, making it a zoonotic disease.
Specific signs can be:
* red, scaly, itchy or raised patches
* patches may be redder on outside edges or resemble a ring
* patches that begin to ooze or develop a blister
* bald patches may develop when the scalp is affected
* nails may thicken, discolour or begin to crack[10]
## Causes
Fungi thrive in moist, warm areas, such as locker rooms, tanning beds, swimming pools, and skin folds; accordingly, those that cause dermatophytosis may be spread by using exercise machines that have not been disinfected after use, or by sharing towels, clothing, footwear, or hairbrushes.
## Diagnosis
### Classification
Main article: List of types of tinea
A number of different species of fungi are involved in dermatophytosis. Dermatophytes of the genera Trichophyton and Microsporum are the most common causative agents. These fungi attack various parts of the body and lead to the conditions listed below. The Latin names are for the conditions (disease patterns), not the agents that cause them. The disease patterns below identify the type of fungus that causes them only in the cases listed:
* Dermatophytosis
* Tinea pedis (athlete's foot): fungal infection of the feet
* Tinea unguium: fungal infection of the fingernails and toenails, and the nail bed
* Tinea corporis: fungal infection of the arms, legs, and trunk
* Tinea cruris (jock itch): fungal infection of the groin area
* Tinea manuum: fungal infection of the hands and palm area
* Tinea capitis: fungal infection of the scalp and hair
* Tinea faciei (face fungus): fungal infection of the face
* Tinea barbae: fungal infestation of facial hair
* Other superficial mycoses (not classic ringworm, since not caused by dermatophytes)
* Tinea versicolor: caused by Malassezia furfur
* Tinea nigra: caused by Hortaea werneckii
## Prevention
Advice often given includes:
* Avoid sharing clothing, sports equipment, towels, or sheets.
* Wash clothes in hot water with fungicidal soap after suspected exposure to ringworm.
* Avoid walking barefoot; instead wear appropriate protective shoes in locker rooms and sandals at the beach.[11][12][13]
* Avoid touching pets with bald spots, as they are often carriers of the fungus.
### Vaccination
As of 2016,[update] no approved human vaccine exist against Dermatophytosis. For horses, dogs and cats there is available an approved inactivated vaccine called Insol Dermatophyton (Boehringer Ingelheim) which provides time-limited protection against several trichophyton and microsporum fungal strains.[14] With cattle, systemic vaccination has achieved effective control of ringworm. Since 1979 a Russian live vaccine (LFT 130) and later on a Czechoslovakian live vaccine against bovine ringworm has been used. In Scandinavian countries vaccination programmes against ringworm are used as a preventive measure to improve the hide quality. In Russia, fur-bearing animals (silver fox, foxes, polar foxes) and rabbits have also been treated with vaccines.[15]
## Treatment
Antifungal treatments include topical agents such as miconazole, terbinafine, clotrimazole, ketoconazole, or tolnaftate applied twice daily until symptoms resolve — usually within one or two weeks.[16] Topical treatments should then be continued for a further 7 days after resolution of visible symptoms to prevent recurrence.[16][17] The total duration of treatment is therefore generally two weeks,[18][19] but may be as long as three.[20]
In more severe cases or scalp ringworm, systemic treatment with oral medications may be given.[21]
To prevent spreading the infection, lesions should not be touched, and good hygiene maintained with washing of hands and the body.[22]
Misdiagnosis and treatment of ringworm with a topical steroid, a standard treatment of the superficially similar pityriasis rosea, can result in tinea incognito, a condition where ringworm fungus grows without typical features, such as a distinctive raised border.
## History
Dermatophytosis has been prevalent since before 1906, at which time ringworm was treated with compounds of mercury or sometimes sulfur or iodine. Hairy areas of skin were considered too difficult to treat, so the scalp was treated with X-rays and followed up with antifungal medication.[23] Another treatment from around the same time was application of Araroba powder.[24]
## Terminology
The most common term for the infection, "ringworm", is a misnomer, since the condition is caused by fungi of several different species and not by parasitic worms.
## Other animals
Ringworm caused by Trichophyton verrucosum is a frequent clinical condition in cattle. Young animals are more frequently affected. The lesions are located on the head, neck, tail, and perineum.[25] The typical lesion is a round, whitish crust. Multiple lesions may coalesce in "map-like" appearance.
* Multiple lesions, head
* Around the eyes and on ears
* On cheeks: crusted lesion (right)
* Old lesions, with regrowing hair
* On neck and withers
* On perineum
Clinical dermatophytosis is also diagnosed in sheep, dogs, cats, and horses. Causative agents, besides Trichophyton verrucosum, are T. mentagrophytes, T. equinum, Microsporum gypseum, M. canis, and M. nanum.[26]
Dermatophytosis may also be present in the holotype of the Cretaceous eutriconodont mammal Spinolestes, suggesting a Mesozoic origin for this disease.
### Diagnosis
Ringworm in pets may often be asymptomatic, resulting in a carrier condition which infects other pets. In some cases, the disease only appears when the animal develops an immunodeficiency condition. Circular bare patches on the skin suggest the diagnosis, but no lesion is truly specific to the fungus. Similar patches may result from allergies, sarcoptic mange, and other conditions. Three species of fungi cause 95% of dermatophytosis in pets:[citation needed] these are Microsporum canis, Microsporum gypseum, and Trichophyton mentagrophytes.
Veterinarians have several tests to identify ringworm infection and identify the fungal species that cause it:
Woods test: This is an ultraviolet light with a magnifying lens. Only 50% of M. canis will show up as an apple-green fluorescence on hair shafts, under the UV light. The other fungi do not show. The fluorescent material is not the fungus itself (which does not fluoresce), but rather an excretory product of the fungus which sticks to hairs. Infected skin does not fluoresce.
Microscopic test: The veterinarian takes hairs from around the infected area and places them in a staining solution to view under the microscope. Fungal spores may be viewed directly on hair shafts. This technique identifies a fungal infection in about 40%–70% of the infections, but cannot identify the species of dermatophyte.
Culture test: This is the most effective, but also the most time-consuming, way to determine if ringworm is on a pet. In this test, the veterinarian collects hairs from the pet, or else collects fungal spores from the pet's hair with a toothbrush, or other instrument, and inoculates fungal media for culture. These cultures can be brushed with transparent tape and then read by the veterinarian using a microscope, or can be sent to a pathological lab. The three common types of fungi which commonly cause pet ringworm can be identified by their characteristic spores. These are different-appearing macroconidia in the two common species of Microspora, and typical microconidia in Trichophyton infections.[26]
Identifying the species of fungi involved in pet infections can be helpful in controlling the source of infection. M. canis, despite its name, occurs more commonly in domestic cats, and 98% of cat infections are with this organism.[citation needed] It can also infect dogs and humans, however. T. mentagrophytes has a major reservoir in rodents, but can also infect pet rabbits, dogs, and horses. M. gypseum is a soil organism and is often contracted from gardens and other such places. Besides humans, it may infect rodents, dogs, cats, horses, cattle, and swine.[27]
### Treatment
#### Pet animals
Treatment requires both systemic oral treatment with most of the same drugs used in humans—terbinafine, fluconazole, or itraconazole—as well as a topical "dip" therapy.[28]
Because of the usually longer hair shafts in pets compared to those of humans, the area of infection and possibly all of the longer hair of the pet must be clipped to decrease the load of fungal spores clinging to the pet's hair shafts. However, close shaving is usually not done because nicking the skin facilitates further skin infection.
Twice-weekly bathing of the pet with diluted lime sulfur dip solution is effective in eradicating fungal spores. This must continue for 3 to 8 weeks.[29]
Washing of household hard surfaces with 1:10 household sodium hypochlorite bleach solution is effective in killing spores, but it is too irritating to be used directly on hair and skin.
Pet hair must be rigorously removed from all household surfaces, and then the vacuum cleaner bag, and perhaps even the vacuum cleaner itself, discarded when this has been done repeatedly. Removal of all hair is important, since spores may survive 12 months or even as long as two years on hair clinging to surfaces.[30]
#### Cattle
In bovines, an infestation is difficult to cure, as systemic treatment is uneconomical. Local treatment with iodine compounds is time-consuming, as it needs scraping of crusty lesions. Moreover, it must be carefully conducted using gloves, lest the worker become infested.
## See also
* Mycobiota
## References
1. ^ a b c d "Symptoms of Ringworm Infections". CDC. December 6, 2015. Archived from the original on 20 January 2016. Retrieved 5 September 2016.
2. ^ a b c d "Definition of Ringworm". CDC. December 6, 2015. Archived from the original on 5 September 2016. Retrieved 5 September 2016.
3. ^ a b c d e "Ringworm Risk & Prevention". CDC. December 6, 2015. Archived from the original on 7 September 2016. Retrieved 5 September 2016.
4. ^ a b c d e Domino, Frank J.; Baldor, Robert A.; Golding, Jeremy (2013). The 5-Minute Clinical Consult 2014. Lippincott Williams & Wilkins. p. 1226. ISBN 9781451188509. Archived from the original on 2016-09-15.
5. ^ a b c "Diagnosis of Ringworm". CDC. December 6, 2015. Archived from the original on 8 August 2016. Retrieved 5 September 2016.
6. ^ Teitelbaum, Jonathan E. (2007). In a Page: Pediatrics. Lippincott Williams & Wilkins. p. 274. ISBN 9780781770453. Archived from the original on 2017-04-26.
7. ^ a b c "Treatment for Ringworm". CDC. December 6, 2015. Archived from the original on 3 September 2016. Retrieved 5 September 2016.
8. ^ a b Mahmoud A. Ghannoum; John R. Perfect (24 November 2009). Antifungal Therapy. CRC Press. p. 258. ISBN 978-0-8493-8786-9. Archived from the original on 8 September 2017.
9. ^ Bolognia, Jean L.; Jorizzo, Joseph L.; Schaffer, Julie V. (2012). Dermatology (3 ed.). Elsevier Health Sciences. p. 1255. ISBN 978-0702051821. Archived from the original on 2016-09-15.
10. ^ "recognizing Ringworm". Healthline. Archived from the original on 2015-10-22.
11. ^ Klemm, Lori (2 April 2008). "Keeping footloose on trips". The Herald News. Archived from the original on 18 February 2009.
12. ^ Fort Dodge Animal Health: Milestones from Wyeth.com. Retrieved April 28, 2008.
13. ^ "Ringworm In Your Dog, Cat And Other Pets". Vetspace. Retrieved 14 November 2020.
14. ^ "Insol Dermatophyton 5x2 ml". GROVET - The veterinary warehouse. Archived from the original on 2016-08-17. Retrieved 2016-02-01.
15. ^ F. Rochette; M. Engelen; H. Vanden Bossche (2003), "Antifungal agents of use in animal health - practical applications", Journal of Veterinary Pharmacology and Therapeutics, 26 (1): 31–53, doi:10.1046/j.1365-2885.2003.00457.x, PMID 12603775
16. ^ a b Kyle AA, Dahl MV (2004). "Topical therapy for fungal infections". Am J Clin Dermatol. 5 (6): 443–51. doi:10.2165/00128071-200405060-00009. PMID 15663341. S2CID 37500893.
17. ^ McClellan KJ, Wiseman LR, Markham A (July 1999). "Terbinafine. An update of its use in superficial mycoses". Drugs. 58 (1): 179–202. doi:10.2165/00003495-199958010-00018. PMID 10439936.
18. ^ Tinea~treatment at eMedicine
19. ^ Tinea Corporis~treatment at eMedicine
20. ^ "Antifungal agents for common paediatric infections". Can J Infect Dis Med Microbiol. 19 (1): 15–8. January 2008. doi:10.1155/2008/186345. PMC 2610275. PMID 19145261.
21. ^ Gupta AK, Cooper EA (2008). "Update in antifungal therapy of dermatophytosis". Mycopathologia. 166 (5–6): 353–67. doi:10.1007/s11046-008-9109-0. PMID 18478357. S2CID 24116721.
22. ^ "Ringworm on Body Treatment" at eMedicineHealth
23. ^ Sequeira, J.H. (1906). "The Varieties of Ringworm and Their Treatment" (PDF). British Medical Journal. 2 (2378): 193–196. doi:10.1136/bmj.2.2378.193. PMC 2381801. PMID 20762800. Archived (PDF) from the original on 2009-11-22.
24. ^ Mrs. M. Grieve. A Modern Herbal. Archived from the original on 2015-03-25.
25. ^ Scott, David W. (2007). Colour Atlas of Animal Dermatology. Blackwell. ISBN 978-0-8138-0516-0.
26. ^ a b "Ringworm in Dogs Diagnosis". Dogclassonline.com. Archived from the original on 2011-05-15. Retrieved 2011-01-10.
27. ^ "General ringworm information". Ringworm.com.au. Archived from the original on 2010-12-21. Retrieved 2011-01-10.
28. ^ "Facts About Ringworm". Archived from the original on 2011-10-06. Retrieved 2011-10-03. Detailed veterinary discussion of animal treatment
29. ^ "Veterinary treatment site page". Marvistavet.com. Archived from the original on 2013-01-04. Retrieved 2011-01-10.
30. ^ "Persistence of spores". Ringworm.com.au. Archived from the original on 2010-12-21. Retrieved 2011-01-10.
## Further reading
* Weitzman I, Summerbell RC (1995). "The dermatophytes". Clinical Microbiology Reviews. 8 (2): 240–259. doi:10.1128/cmr.8.2.240. PMC 172857. PMID 7621400.
## External links
Classification
D
* ICD-10: B35.0-B36
* ICD-9-CM: 110.9
* MeSH: D003881
* DiseasesDB: 17492
External resources
* MedlinePlus: 001439
* eMedicine: emerg/592
* Patient UK: Dermatophytosis
* Tinea photo library at Dermnet
* v
* t
* e
Fungal infection and mesomycetozoea
Superficial and
cutaneous
(dermatomycosis):
Tinea = skin;
Piedra (exothrix/
endothrix) = hair
Ascomycota
Dermatophyte
(Dermatophytosis)
By location
* Tinea barbae/tinea capitis
* Kerion
* Tinea corporis
* Ringworm
* Dermatophytids
* Tinea cruris
* Tinea manuum
* Tinea pedis (athlete's foot)
* Tinea unguium/onychomycosis
* White superficial onychomycosis
* Distal subungual onychomycosis
* Proximal subungual onychomycosis
* Tinea corporis gladiatorum
* Tinea faciei
* Tinea imbricata
* Tinea incognito
* Favus
By organism
* Epidermophyton floccosum
* Microsporum canis
* Microsporum audouinii
* Trichophyton interdigitale/mentagrophytes
* Trichophyton tonsurans
* Trichophyton schoenleini
* Trichophyton rubrum
* Trichophyton verrucosum
Other
* Hortaea werneckii
* Tinea nigra
* Piedraia hortae
* Black piedra
Basidiomycota
* Malassezia furfur
* Tinea versicolor
* Pityrosporum folliculitis
* Trichosporon
* White piedra
Subcutaneous,
systemic,
and opportunistic
Ascomycota
Dimorphic
(yeast+mold)
Onygenales
* Coccidioides immitis/Coccidioides posadasii
* Coccidioidomycosis
* Disseminated coccidioidomycosis
* Primary cutaneous coccidioidomycosis. Primary pulmonary coccidioidomycosis
* Histoplasma capsulatum
* Histoplasmosis
* Primary cutaneous histoplasmosis
* Primary pulmonary histoplasmosis
* Progressive disseminated histoplasmosis
* Histoplasma duboisii
* African histoplasmosis
* Lacazia loboi
* Lobomycosis
* Paracoccidioides brasiliensis
* Paracoccidioidomycosis
Other
* Blastomyces dermatitidis
* Blastomycosis
* North American blastomycosis
* South American blastomycosis
* Sporothrix schenckii
* Sporotrichosis
* Talaromyces marneffei
* Talaromycosis
Yeast-like
* Candida albicans
* Candidiasis
* Oral
* Esophageal
* Vulvovaginal
* Chronic mucocutaneous
* Antibiotic candidiasis
* Candidal intertrigo
* Candidal onychomycosis
* Candidal paronychia
* Candidid
* Diaper candidiasis
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* Perianal candidiasis
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* Erosio interdigitalis blastomycetica
* C. auris
* C. glabrata
* C. lusitaniae
* C. tropicalis
* Pneumocystis jirovecii
* Pneumocystosis
* Pneumocystis pneumonia
Mold-like
* Aspergillus
* Aspergillosis
* Aspergilloma
* Allergic bronchopulmonary aspergillosis
* Primary cutaneous aspergillosis
* Exophiala jeanselmei
* Eumycetoma
* Fonsecaea pedrosoi/Fonsecaea compacta/Phialophora verrucosa
* Chromoblastomycosis
* Geotrichum candidum
* Geotrichosis
* Pseudallescheria boydii
* Allescheriasis
Basidiomycota
* Cryptococcus neoformans
* Cryptococcosis
* Trichosporon spp
* Trichosporonosis
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(Zygomycosis)
Mucorales
(Mucormycosis)
* Rhizopus oryzae
* Mucor indicus
* Lichtheimia corymbifera
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* Apophysomyces variabilis
Entomophthorales
(Entomophthoramycosis)
* Basidiobolus ranarum
* Basidiobolomycosis
* Conidiobolus coronatus/Conidiobolus incongruus
* Conidiobolomycosis
Microsporidia
(Microsporidiosis)
* Enterocytozoon bieneusi/Encephalitozoon intestinalis
Mesomycetozoea
* Rhinosporidium seeberi
* Rhinosporidiosis
Ungrouped
* Alternariosis
* Fungal folliculitis
* Fusarium
* Fusariosis
* Granuloma gluteale infantum
* Hyalohyphomycosis
* Otomycosis
* Phaeohyphomycosis
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Dermatophytosis | c0011636 | 4,561 | wikipedia | https://en.wikipedia.org/wiki/Dermatophytosis | 2021-01-18T18:44:45 | {"umls": ["C0011636"], "wikidata": ["Q1909343"]} |
Soft, non-cancerous growth resulting from the tertiary stage of syphilis
Gumma (pathology)
Gumma of nose due to a long-standing tertiary syphilitic infection.
SpecialtyInfectious disease
Hepatic gumma
Moulage of a gumma in syphilis for training students. University of Tübingen.
A gumma (plural gummata or gummas) is a soft, non-cancerous growth resulting from the tertiary stage of syphilis (and yaws[1]). It is a form of granuloma. Gummas are most commonly found in the liver (gumma hepatis), but can also be found in brain, heart, skin, bone, testis, and other tissues, leading to a variety of potential problems including neurological disorders or heart valve disease.
## Contents
* 1 Presentation
* 2 Pathology
* 3 Epidemiology
* 4 References
* 5 External links
## Presentation[edit]
Gummas have a firm, necrotic center surrounded by inflamed tissue, which forms an amorphous proteinaceous mass. The center may become partly hyalinized. These central regions begin to die through coagulative necrosis, though they also retain some of the structural characteristics of previously normal tissues, enabling a distinction from the granulomas of tuberculosis where caseous necrosis obliterates preexisting structures. Other histological features of gummas include an intervening zone containing epithelioid cells with indistinct borders and multinucleated giant cells, and a peripheral zone of fibroblasts and capillaries. Infiltration of lymphocytes and plasma cells can be seen in the peripheral zone as well. With time, gummas eventually undergo fibrous degeneration, leaving behind an irregular scar or a round fibrous nodule.
It is restricted to necrosis involving spirochaetal infections that cause syphilis. Growths that have the appearance of gummas are described as gummatous.
## Pathology[edit]
In syphilis, the gumma is caused by reaction to spirochaete bacteria in the tissue. It appears to be the human body's way to slow down the action of this bacteria; it is a unique immune response that develops in humans after the immune system fails to kill off syphilis.
## Epidemiology[edit]
The formation of gummata is rare in developed countries, but common in areas that lack adequate medical treatment.
Syphilitic gummas are found in most but not all cases of tertiary syphilis, and can occur either singly or in groups. Gummatous lesions are usually associated with long-term syphilitic infection; however, such lesions can also be a symptom of benign late syphilis.
## References[edit]
1. ^ Marks, Michael (29 August 2018). "Advances in the Treatment of Yaws". Tropical Medicine and Infectious Disease. 3 (3): 92. doi:10.3390/tropicalmed3030092. ISSN 2414-6366. PMC 6161241. PMID 30274488.
## External links[edit]
Classification
D
* ICD-10: A52.3 A52.7
* ICD-9-CM: 090.5 094.9 095 102.6
* DiseasesDB: 30601
External resources
* MedlinePlus: 000859
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Gumma (pathology) | None | 4,562 | wikipedia | https://en.wikipedia.org/wiki/Gumma_(pathology) | 2021-01-18T18:41:52 | {"icd-9": ["090.5", "102.6", "094.9", "095"], "icd-10": ["A52.3", "A52.7"], "wikidata": ["Q2466723"]} |
A number sign (#) is used with this entry because autosomal recessive Charcot-Marie-Tooth disease type 4F (CMT4F) is caused by homozygous or compound heterozygous mutation in the periaxin gene (PRX; 605725) on chromosome 19q13.
Description
Charcot-Marie-Tooth disease type 4F is an autosomal recessive demyelinating neuropathy characterized by distal sensory impairment and distal muscle weakness and atrophy affecting the lower more than the upper limbs. Nerve conduction velocities are decreased and sural nerve biopsy shows loss of myelinated fibers. The age at onset is variable and can range from childhood to adult years. When the onset is in infancy, the phenotype is characterized as Dejerine-Sottas syndrome (DSS; 145900).
For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive demyelinating Charcot-Marie-Tooth disease, see CMT4A (214400).
Clinical Features
Delague et al. (2000) reported a large inbred Lebanese family affected with autosomal recessive demyelinating Charcot-Marie-Tooth disease in which they excluded linkage to the previously known CMT4 loci. Clinical features and results of histopathologic studies confirmed that the disease in this family represented a demyelinating autosomal recessive CMT subtype, which the authors referred to as CMT4F. Histopathologic and immunohistochemical analysis of a sural nerve biopsy of 1 patient revealed common features with the periaxin-null mouse and the absence of L-periaxin from the myelin sheath. These data confirmed the importance of the periaxin proteins to normal Schwann cell function.
Takashima et al. (2002) reported 2 sibs with CMT4F. Both had much worse sensory than motor impairment. Despite early onset of disease, these sibs had a relatively slow disease progression and adult motor impairment typical for classic demyelinating Charcot-Marie-Tooth neuropathy. Neuropathology showed demyelination, onion bulb and occasional tomacula formation with focal myelin thickening, abnormalities of the paranodal myelin loops, and focal absence of paranodal septate-like junctions between the terminal loops and axon.
Kijima et al. (2004) reported 3 unrelated Japanese patients with CMT4F. They presented with early-onset and slowly progressive distal motor and sensory neuropathy. All 3 patients were born of healthy, consanguineous parents. Two of the patients also had an affected sib. On sural nerve biopsy, 1 patient had atypical onion bulb formation, the second had more typical onion bulb formation, and the third had onion bulb and tomacula formation.
Kabzinska et al. (2006) reported an 8-year-old boy with severe CMT4F. He began to walk with a clumsy gait at age 2 years and showed foot drop at age 5. He had weak distal muscle weakness of the upper and lower extremities which was more pronounced in the lower limbs, absent reflexes, sensory ataxia, distal sensory impairment, and pes cavus. Electrophysiologic studies showed severely prolonged or absent motor conduction velocities. EMG was consistent with mild stable chronic reinnervation. Sural nerve biopsy showed severe loss of myelinated axons of all diameters, onion bulb formation, and some areas of focally folded myelin.
Marchesi et al. (2010) reported 4 adult patients, including 2 sibs, with CMT4F due to homozygous or compound heterozygous truncating mutations in the PRX gene. The patients were between 34 and 45 years of age at the time of the report. All had onset in early childhood with delayed motor development, and achieved walking with an unsteady gait by 2 or 3 years of age. All developed pes cavus and scoliosis of varying severity. There was variable distal muscle weakness and atrophy affecting both the upper and lower limbs and associated with distal sensory impairment; deep tendon reflexes were absent. The patients tended to walk with a steppage gait and some showed sensory ataxia. Nerve conduction velocities were severely decreased, between 3 and 13.3 m/s in the median nerve. Sensory nerve action potentials were undetectable. Sural nerve biopsy of 2 patients showed severe demyelination and complex onion bulb formation and occasional myelin foldings. In a review of previously reported patients with PRX mutations, Marchesi et al. (2010) concluded that the disorder was phenotypically homogeneous with mild variability in severity, and was slowly progressive, despite the early age at onset.
Tokunaga et al. (2012) reported 2 unrelated Japanese patients with adult-onset CMT4F due to a homozygous R1070X mutation (605725.0008). One patient developed mild distal muscle wasting and sensory disturbance in all limbs at age 50 years. The disorder was slowly progressive, and she could still walk independently at age 63 despite having pes cavus. Sural nerve biopsy showed moderate demyelination and complex onion bulb formation. The other patient developed lower limb weakness at age 37 years. At age 47, he could walk with a walking vehicle. Other features included scoliosis and areflexia. Sural nerve biopsy showed myelin thinning and onion bulbs. Motor nerve conduction velocities in the median nerve were 20 m/s in both patients. Tokunaga et al. (2012) reported another Japanese woman with adult-onset CMT4F. Although she had delayed independent ambulation due to nonspecific infantile paralysis at age 18 months, she developed mild distal muscle weakness and sensory impairment in the lower limbs at age 30 years. Upper limb wasting was observed at age 44 years, and she had vocal cord paralysis. Other features included pes cavus, scoliosis, and areflexia. The disorder was slowly progressive. At age 65, she had to use leg braces and a wheelchair. Nerve conduction velocities were not recordable and sural nerve biopsy showed significant demyelination. Tokunaga et al. (2012) emphasized the late onset and relatively mild phenotype in these 3 patients.
Inheritance
The transmission pattern of demyelinating CMT in the family reported by Delague et al. (2000) was consistent with autosomal recessive inheritance.
Mapping
In a Lebanese family, Delague et al. (2000) found linkage of a severe autosomal recessive demyelinating neuropathy, which they called Charcot-Marie-Tooth disease type 4F, to chromosome 19q13.1-q13.3 with a maximum pairwise lod score of 5.37 for D19S420.
Molecular Genetics
In affected members of a Lebanese family with CMT4F studied by Delague et al. (2000), Guilbot et al. (2001) identified a homozygous truncating mutation in the PRX gene (R196X; 605725.0005).
In 2 sibs with CMT4F, Takashima et al. (2002) identified a homozygous mutation in the PRX gene (C715X; 605725.0006).
In 3 unrelated Japanese patients with Charcot-Marie-Tooth disease type 4F, Kijima et al. (2004) identified a homozygous mutation in the PRX gene (R1070X; 605725.0008).
In a Japanese woman with adult-onset CMT4F, Tokunaga et al. (2012) identified a homozygous missense mutation in the PRX gene (D651N; 605725.0011). The mutation was not found in 292 control chromosomes, but was found in 1 of 2,188 exomes. Her 3 unaffected brothers were all heterozygous for the mutation. Functional analysis was not performed. This was the first reported missense mutation in this gene.
INHERITANCE \- Autosomal recessive SKELETAL Spine \- Scoliosis Feet \- Pes cavus NEUROLOGIC Central Nervous System \- Delayed motor development \- Sensory ataxia (less common) Peripheral Nervous System \- Distal lower limb muscle weakness due to peripheral neuropathy \- Distal lower limb muscle atrophy due to peripheral neuropathy \- Difficulty walking \- Distal upper limb involvement may occur later \- Proximal lower limb involvement \- Distal sensory impairment \- Areflexia \- Decreased motor nerve conduction velocity (NCV) (less than 38 m/s) \- Sural nerve biopsy shows demyelination \- Basal lamina 'onion bulb' formations on nerve biopsy \- Focal myelin thickening \- Focally folded myelin \- Loss of large myelinated fibers VOICE \- Vocal cord paresis (reported in 1 patient) MISCELLANEOUS \- Variable age at onset (range from early childhood to mid-adult) \- Slowly progressive MOLECULAR BASIS \- Caused by mutation in the periaxin gene (PRX, 605725.0005 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 4F | c3540453 | 4,563 | omim | https://www.omim.org/entry/614895 | 2019-09-22T15:53:48 | {"doid": ["0110193"], "omim": ["614895"], "orphanet": ["99952"], "synonyms": ["CMT4F"]} |
Fiddler's neck
Other namesViolin hickey, viola love bite
SpecialtyOccupational health
Fiddler's neck is an occupational disease that affects violin and viola players.[1]
It is a cutaneous condition usually characterized by redness, thickening, and inflammation on the left side of the neck below the angle of the jaw where the instrument is held.[1] Acne-like lesions and cysts may form at the site due to foreign body reactions, and infections may also occur due to poor hygiene.[1] The primary causes of fiddler's neck are constant friction and local pressure.[2] It is well known among professional orchestra musicians but is "not well recognized by dermatologists",[2] and a red mark on the left side of the neck under the jaw "functions as an identifying sign" of a violinist or violist "in public without seeing the instrument".[3]
Although the presence of fiddler's neck is sometimes used as an indicator of a violinist's skill, or 'battle scars' from constant practice, many violinists never develop fiddler's neck, due to differences in skin sensitivity, playing habits, and the materials used in the construction of the instrument. An accomplished professional player could practice hard their whole life and never develop fiddler's neck.
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Diagnosis
* 3.1 Differential diagnoses
* 4 Treatment
* 5 Prevalence
* 6 References
* 7 External links
## Signs and symptoms[edit]
Fiddler's neck usually involves highly localized lichenification, mild hyperpigmentation, and erythema where the chin rest or instrument body presses against the skin of the neck.[2] Other signs and symptoms include scale buildup, cyst and scar formation, papules and pustules related to local infection, and focal edema.[1] In Blum & Ritter's study in West Germany (1990), they found that 27% of their population had only minor issues, 72% had a palpable mass at the site, and 23% reported pain and other signs of inflammation such as hyperthermia, pulsation, and cystic, pustular, or papular lesions.[3] Size of masses were an average of 2 cm in diameter ranging up to 4 cm, some being associated with purulent drainage, continuous discharge, and crusting. Dystrophic calcinosis cutis has also been reported.[4] Other serious sequelae include sialolithiasis of the submandibular gland and adenolymphoma of the parotid gland.[3]
The histopathology of fiddler's neck frequently shows hyperkeratosis and acanthosis, along with plugging of follicles.[2] Histiocytic infiltration with granulomas to foreign body and follicular cysts are also common.[3] Foreign body granulomas are thought to derive from abrasion of the wooden surface of the chin rest and its absorption into the superficial dermis.[3] The location and complex mechanism of causation for fiddler's neck give rise to a wider spectrum of skin changes when compared to contact dermatitis from more common irritants.[1] Fiddler's neck can be differentiated from rosacea and sarcoid reaction with granulomas.[1]
## Causes[edit]
The proximal causes of fiddler's neck are friction and pressure, but both repetitive shearing stress and occlusion with consequent trapping of sweat give rise to progressive damage.[1] This damage along with poor hygiene predisposes the area to local infection, and such infection can progress to scarring and other long-term effects.[1] Hot weather is reported to exacerbate fiddler's neck, as are tiredness, playing emotional music, and playing in smaller groups where individual stress is higher.[2] Type I hypersensitivity reactions may also be involved, particularly to rosewood and ebony in the chinrest and tailpiece, as well as to varnish of the instrument body when chinrests are not used and to rosin deposits on the instrument and on chin cloths.[3] Nickel or other metal allergies are common causes if the chin rest has a metal clip that comes into constant contact with the skin. Rosin exposure in particular may lead to abietic acid dermatitis.[3]
## Diagnosis[edit]
### Differential diagnoses[edit]
The differential diagnoses of fiddler's neck include branchial cleft cyst, disease of the salivary glands, tumors of the parotid gland, psoriasis, lichen planus, contact dermatitis, herpes simplex and similar infections, and insect bites and stings especially from fleas.[1][3]
## Treatment[edit]
Treatment for fiddler's neck is unnecessary if it is painless and shows minimal swelling,[3] particularly since minor cases are taken as a mark of pride. But fiddler's neck may lead to worse disorders. The primary methods of treatment involve adjustments to playing of the instrument:[3][5]
* good hygiene for the affected area and for the instrument
* use of a clean cotton cloth that is changed frequently
* use of a comfortable pad to absorb sweat and reduce friction between the instrument and skin
* use of a shoulder rest to reduce pressure below the jaw
* a suitable chin rest, especially one carved or molded for the individual
* Covering or changing potentially allergenic materials on the instrument.
* shifting the chin rest to the center of the body over the tailpiece
* smoothing coarse surfaces to reduce abrasion
* for males, growing a beard to avoid folliculitis
Surgery is necessary for sialolithiasis, parotid tumors, and cysts.[3] Cervical lymph nodes that are larger than 1 cm must be biopsied.[3] Connective tissue can be removed by excision when a non-inflamed mass is large, and there is generally little recurrence.[3] Infections should be treated conservatively, and causative species should be identified through smear and culture for appropriate antibiotic selection.[3] Reduction of playing time may be helpful for cases without inflammation, but in 30% of cases this did not improve the symptoms.[3]
## Prevalence[edit]
Fiddler's neck does not usually form unless the musician is practicing or playing for more than a few hours each day, and only seems to develop after a few years of serious playing.[2] Thus, when not infected or otherwise problematic, fiddler's neck may be known as a benign practice mark and may be worn proudly as an indication of long hours of practice.[3] Blum & Ritter (1990) found that 62% of 523 professional violinists and violists in West Germany experienced fiddler's neck, with the percentage among violists being higher (67%) than among violinists (59%).[3] Viola players are believed to be more predisposed to developing fiddler's neck than violinists because the viola is larger and heavier, but this has not been empirically confirmed.[2]
The development of fiddler's neck does not depend on preexisting skin problems, and Blum & Ritter find that only 23% of men and 14% of women in their study reported cutaneous disorders in other parts of the face (mainly acne and eczema) that were independent of playing the violin or viola.[3] Fiddler's neck may exacerbate existing acne, but acne may also be limited solely to the lesion and not appear elsewhere.[2] Nonetheless, musicians with underlying dermatologic diseases like acne and eczema are more endangered by fiddler's neck than others.[3] Males may develop folliculitis or boils due to involvement of beard hair.[3]
## References[edit]
1. ^ a b c d e f g h i Gambichler, T.; Boms, S.; Freitag, M. (2004). "Contact dermatitis and other skin conditions in instrumental musicians". BMC Dermatology. 4: 3. doi:10.1186/1471-5945-4-3. PMC 416484. PMID 15090069.
2. ^ a b c d e f g h Peachey, R. D.; Matthews, C. N. (1978). "'Fiddler's neck'". The British Journal of Dermatology. 98 (6): 669–674. doi:10.1111/j.1365-2133.1978.tb03586.x. PMID 150281.
3. ^ a b c d e f g h i j k l m n o p q r s t Blum, Jochen; Ritter, G. (December 1990). "Violinists and violists with masses under the left side angle of the jaw known as "fiddler's neck"". Medical Problems of Performing Artists. 5 (4): 155–160. ISSN 0885-1158.
4. ^ Oga, A.; Kadowaki, T.; Hamanaka, S.; Sasaki, K. (1998). "Dystrophic calcinosis cutis in the skin below the mandible of a violinist". The British Journal of Dermatology. 139 (5): 940–941. doi:10.1046/j.1365-2133.1998.02544.x. PMID 9892983.
5. ^ Myint, Calvin W.; Rutt, Amy L.; Sataloff, Robert T. (February 2017). "Fiddler's Neck: A Review". Ear, Nose & Throat Journal. 96 (2): 76–79. doi:10.1177/014556131709600210. ISSN 0145-5613.
## External links[edit]
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D
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* European Agency for Safety and Health at Work
* UK Health and Safety Executive
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* US Occupational Safety and Health Administration
* National Institute for Safety and Health at Work (Spain)
* World Health Organization
Standards
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* Environment, health and safety
* Environmental toxicology
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* National Day of Mourning (Canadian observance)
* Process safety management
* Public health
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* Category
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*[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
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Fiddler's neck | c0406180 | 4,564 | wikipedia | https://en.wikipedia.org/wiki/Fiddler%27s_neck | 2021-01-18T18:37:29 | {"wikidata": ["Q9352582"]} |
Synchysis scintillans
Human eye (vitreous humor in the middle)
SpecialtyOphthalmology
Synchysis scintillans is a degenerative condition of the eye resulting in liquefied vitreous humor and the accumulation of cholesterol crystals within the vitreous. It is also known as cholesterolosis bulbi. The vitreous liquifies in a process known as syneresis. Synchysis scintillans appears as small white floaters that freely move in the posterior part of the eye, giving a snow globe effect. It is most commonly seen in eyes that have suffered from a degenerative disease and are end-stage.[1]
In humans as well, the condition is seen rarely. Associated with the advanced stages of diabetic retinopathy, but the exact pathogenesis is unknown.
The condition is symptomless and untreatable. It appears as a beautiful shower of golden rain in ophthalmoscopic examination.
## References[edit]
1. ^ Gelatt, Kirk N. (ed.) (1999). Veterinary Ophthalmology (3rd ed.). Lippincott, Williams & Wilkins. ISBN 0-683-30076-8.CS1 maint: extra text: authors list (link)
This article about the eye is a stub. You can help Wikipedia by expanding it.
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*[v]: View this template
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*[AA]: Adrenergic agonist
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*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
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*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
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| Synchysis scintillans | c0271407 | 4,565 | wikipedia | https://en.wikipedia.org/wiki/Synchysis_scintillans | 2021-01-18T18:45:38 | {"umls": ["C0271407"], "icd-10": ["H43.8"], "wikidata": ["Q9081129"]} |
For a discussion of genetic heterogeneity of multiple sclerosis (MS), see MS1 (126200).
Mapping
In a multistage genomewide association study involving a total of 1,540 MS family trios, 2,322 case subjects, and 5,418 control subjects, the International Multiple Sclerosis Genetics Consortium (2007) identified 2 SNPs within intron 1 of the IL2RA gene (147730) on chromosome 10p15.1, rs12722489 and rs2104286, that were strongly associated with MS (p = 2.96 x 10(-8) and p = 2.16 x 10(-7), respectively). The 2 SNPs were in strong linkage disequilibrium.
D'Netto et al. (2009) found associations between MS and rs12722489 (OR, 1.06; p = 0.016) and rs2104286 (OR, 1.1; p = 0.0274) in 211 patients and 521 unaffected relatives from 43 multiplex MS families. However, significant associations were not found with these SNPs in a case-control study of the 211 patients and 182 unrelated controls.
By longitudinal analysis of soluble IL2RA (sIL2RA) levels in serum, Maier et al. (2009) showed that the 2 variants, SNPs rs12722489 and rs2104286, associated with MS account for 15% and 18%, respectively, of the total variance in sIL2RA concentrations in control subjects but only 2% and 5% in subjects with MS. Levels of sIL2RA were a stable phenotype in both healthy controls and untreated MS patients, but a difference was observed between benign and malignant MS. Maier et al. (2009) proposed that, in addition to allelic variants in IL2RA, immunologic perturbations associated with aggressive forms of MS can influence sIL2RA levels.
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*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| MULTIPLE SCLEROSIS, SUSCEPTIBILITY TO, 2 | c2675478 | 4,566 | omim | https://www.omim.org/entry/612594 | 2019-09-22T16:01:01 | {"omim": ["612594"]} |
Influenza caused by viruses adapted to birds
For the H5N1 subtype of Avian influenza, see Influenza A virus subtype H5N1.
Influenza (Flu)
Types
* Avian
* A/H5N1 subtype
* Canine
* Equine
* Swine
* A/H1N1 subtype
Vaccines
* 2009 pandemic
* Pandemrix
* Live attenuated
* Seasonal flu vaccine brands
Treatment
* Amantadine
* Baloxavir marboxil
* Laninamivir
* Oseltamivir
* Peramivir
* Rimantadine
* Umifenovir
* Zanamivir
Pandemics
* 1918 Spanish flu
* 1957 Asian flu
* 1968–1969 Hong Kong flu
* 2009 swine flu
Outbreaks
* 1976 swine flu
* 2006 H5N1 India
* 2007 Australian equine
* 2007 Bernard Matthews H5N1
* 2008 West Bengal
* 2015 United States H5N2 outbreak
See also
* Flu season
* Influenza evolution
* Influenza research
* Influenza-like illness
* Vaccine reformulations
* v
* t
* e
Avian influenza, known informally as avian flu or bird flu, is a variety of influenza caused by viruses adapted to birds.[1][2][3][4][5][6][7] The type with the greatest risk is highly pathogenic avian influenza (HPAI). Bird flu is similar to swine flu, dog flu, horse flu and human flu as an illness caused by strains of influenza viruses that have adapted to a specific host. Out of the three types of influenza viruses (A, B, and C), influenza A virus is a zoonotic infection with a natural reservoir almost entirely in birds.[8] Avian influenza, for most purposes, refers to the influenza A virus.
Though influenza A is adapted to birds, it can also stably adapt and sustain person-to-person transmission.[8] Recent influenza research into the genes of the Spanish flu virus shows it to have genes adapted from both human and avian strains. Pigs can also be infected with human, avian, and swine influenza viruses, allowing for mixtures of genes (reassortment) to create a new virus, which can cause an antigenic shift to a new influenza A virus subtype which most people have little to no immune protection against.[8]
Avian influenza strains are divided into two types based on their pathogenicity: high pathogenicity (HP) or low pathogenicity (LP).[9] The most well-known HPAI strain, H5N1, was first isolated from a farmed goose in Guangdong Province, China in 1996, and also has low pathogenic strains found in North America.[9][10] Companion birds in captivity are unlikely to contract the virus and there has been no report of a companion bird with avian influenza since 2003. Pigeons can contract avian strains, but rarely become ill and are incapable of transmitting the virus efficiently to humans or other animals.[11]
Between early 2013 and early 2017, 916 lab-confirmed human cases of H7N9 were reported to the World Health Organization (WHO).[12] On 9 January 2017, the National Health and Family Planning Commission of China reported to WHO 106 cases of H7N9 which occurred from late November through late December, including 35 deaths, 2 potential cases of human-to-human transmission, and 80 of these 106 persons stating that they have visited live poultry markets. The cases are reported from Jiangsu (52), Zhejiang (21), Anhui (14), Guangdong (14), Shanghai (2), Fujian (2) and Hunan (1). Similar sudden increases in the number of human cases of H7N9 have occurred in previous years during December and January.[12]
## Contents
* 1 History
* 2 Genetics
* 3 Subtypes
* 4 Mode of transmission
* 4.1 Village poultry
* 5 H5N1
* 5.1 Controversial research
* 6 H7N9
* 7 Domestic animals
* 7.1 Birds
* 7.2 Cats
* 8 Global impact
* 8.1 Bird Flu in 2020
* 8.2 Stigma
* 8.3 Indonesia
* 8.4 Economic
* 9 Prevention
* 9.1 For village poultry farmers
* 9.2 Culling
* 9.3 People-poultry relations
* 10 See also
* 11 References
* 12 Sources
* 13 External links
## History[edit]
The most widely quoted date for the beginning of recorded history of avian influenza (initially known as fowl plague) was in 1878 when it was differentiated from other diseases that caused high mortality rates in birds.[13] Fowl plague, however, also included Newcastle disease until as recently as the 1950s. Between 1959 and 1995, there were 15 recorded occasions of the emergence of HPAI viruses in poultry, but losses were minimal. Between 1996 and 2008 however, HPAI outbreaks in poultry have occurred at least 11 times and 4 of these outbreaks have involved millions of birds.[13]
In the 1990s, the world's poultry population grew 76% in developing countries and 23% in developed countries, contributing to the increased prevalence of avian influenza.[14] Before the 1990s, HPAI caused high mortality in poultry, but infections were sporadic and contained. Outbreaks have become more common due to the high density and frequent movement of flocks from intensive poultry production.
Influenza A/H5N1 was first isolated from a goose in China in 1996. Human infections were first reported in 1997 in Hong Kong.[10] Since 2003, more than 700 human cases of Asian HPAI H5N1 have been reported to the WHO, primarily from 15 countries in Asia, Africa, the Pacific, Europe, and the Middle East, though over 60 countries have been affected.[10][13]
## Genetics[edit]
Genetic factors in distinguishing between "human flu viruses" and "avian flu viruses" include:
PB2: (RNA polymerase): Amino acid (or residue) position 627 in the PB2 protein encoded by the PB2 RNA gene. Until H5N1, all known avian influenza viruses had a Glu at position 627, while all human influenza viruses had a Lys.[15]
HA: (hemagglutinin): Avian influenza HA viruses bind alpha 2-3 sialic acid receptors, while human influenza HA viruses bind alpha 2-6 sialic acid receptors. Swine influenza viruses have the ability to bind both types of sialic acid receptors. Hemagglutinin is the major antigen of the virus against which neutralizing antibodies are produced, and influenza virus epidemics are associated with changes in its antigenic structure. This was originally derived from pigs, and should technically be referred to as "pig flu".[16]
The evolution of avian influenza virus has been influenced by genetic variation in the virus population due to genome segment reassortment and mutation. Also homologous recombination occurs in viral genes, suggesting that genetic variation generated by homologous recombination has also played a role in driving the evolution of the virus and potentially has affected virulence and host range.[17]
## Subtypes[edit]
There are many subtypes of avian influenza viruses, but only some strains of five subtypes have been known to infect humans: H5N1, H7N3, H7N7, H7N9, and H9N2.[18] At least one person, an elderly woman in Jiangxi Province, China, died of pneumonia in December 2013 from the H10N8 strain, the first human fatality confirmed to be caused by that strain.[19]
Most human cases of the avian flu are a result of either handling dead infected birds or from contact with infected fluids. It can also be spread through contaminated surfaces and droppings. While most wild birds have only a mild form of the H5N1 strain, once domesticated birds such as chickens or turkeys are infected, H5N1 can potentially become much more deadly because the birds are often in close contact. H5N1 is a large threat in Asia with infected poultry due to low hygiene conditions and close quarters. Although it is easy for humans to contract the infection from birds, human-to-human transmission is more difficult without prolonged contact. However, public health officials are concerned that strains of avian flu may mutate to become easily transmissible between humans.[20]
Spreading of H5N1 from Asia to Europe is much more likely caused by both legal and illegal poultry trades than dispersing through wild bird migrations, being that in recent studies, there were no secondary rises in infection in Asia when wild birds migrate south again from their breeding grounds. Instead, the infection patterns followed transportation such as railroads, roads, and country borders, suggesting poultry trade as being much more likely. While there have been strains of avian flu to exist in the United States, they have been extinguished and have not been known to infect humans.
Examples of avian influenza A virus strains:[21]
HA subtype
designation NA subtype
designation Avian influenza A viruses
H1 N1 A/duck/Alberta/35/76(H1N1)
H1 N8 A/duck/Alberta/97/77(H1N8)
H2 N9 A/duck/Germany/1/72(H2N9)
H3 N8 A/duck/Ukraine/63(H3N8)
H3 N8 A/duck/England/62(H3N8)
H3 N2 A/turkey/England/69(H3N2)
H4 N6 A/duck/Czechoslovakia/56(H4N6)
H4 N3 A/duck/Alberta/300/77(H4N3)
H5 N3 A/tern/South Africa/300/77(H4N3)
H5 N4 A/Ethiopia/300/77(H6N6)
H5 N8 H5N8
H5 N9 A/turkey/Ontario/7732/66(H5N9)
H5 N1 A/chick/Scotland/59(H5N1)
H6 N2 A/turkey/Massachusetts/3740/65(H6N2)
H6 N8 A/turkey/Canada/63(H6N8)
H6 N5 A/shearwater/Australia/72(H6N5)
H6 N1 A/duck/Germany/1868/68(H6N1)
H7 N7 A/fowl plague virus/Dutch/27(H7N7)
H7 N1 A/chick/Brescia/1902(H7N1)
H7 N9 A/chick/China/2013(H7N9)
H7 N3 A/turkey/England/639H7N3)
H7 N1 A/fowl plague virus/Rostock/34(H7N1)
H8 N4 A/turkey/Ontario/6118/68(H8N4)
H9 N2 A/turkey/Wisconsin/1/66(H9N2)
H9 N6 A/duck/Hong Kong/147/77(H9N6)
H9 N6 A/duck/Hong Kong/147/77(H9N6)
H9 N7 A/turkey/Scotland/70(H9N7)
H10 N8 A/quail/Italy/1117/65(H10N8)
H11 N6 A/duck/England/56(H11N6)
H11 N9 A/duck/Memphis/546/74(H11N9)
H12 N5 A/duck/Alberta/60/76/(H12N5)
H13 N6 A/gull/Maryland/704/77(H13N6)
H14 N4 A/duck/Gurjev/263/83(H14N4)
H15 N9 A/shearwater/Australia/2576/83(H15N9)
## Mode of transmission[edit]
Birds that have died of avian influenza. The virus is spread by contact between healthy and unhealthy birds.
Avian influenza is most often spread by contact between infected and healthy birds, though can also be spread indirectly through contaminated equipment.[22] The virus is found in secretions from the nostrils, mouth, and eyes of infected birds as well as their droppings. HPAI infection is spread to people often through direct contact with infected poultry, such as during slaughter or plucking.[22] Though the virus can spread through airborne secretions, the disease itself is not an airborne disease. Highly pathogenic strains spread quickly among flocks and can destroy a flock within 28 hours; the less pathogenic strains may affect egg production but are much less deadly.[citation needed]
Although it is possible for humans to contract the avian influenza virus from birds, human-to-human contact is much more difficult without prolonged contact. However, public health officials are concerned that strains of avian flu may mutate to become easily transmissible between humans.[20] Some strains of avian influenza are present in the intestinal tract of large numbers of shore birds and water birds, but these strains rarely cause human infection.[23]
Five manmade ecosystems have contributed to modern avian influenza virus ecology: integrated indoor commercial poultry, range-raised commercial poultry, live poultry markets, backyard and hobby flocks, and bird collection and trading systems including cockfighting. Indoor commercial poultry has had the largest impact on the spread of HPAI, with the increase in HPAI outbreaks largely the result of increased commercial production since the 1990s.[14]
### Village poultry[edit]
In the early days of the HPAI H5N1 pandemic, village poultry and their owners were frequently implicated in disease transmission.[14] Village poultry, also known as backyard and hobby flocks, are small flocks raised under extensive conditions and often allowed free range between multiple households. However, research has shown that these flocks pose less of a threat than intensively raised commercial poultry with homogenous genetic stock and poor biosecurity.[14] Backyard and village poultry also do not travel great distances compared to transport of intensively raised poultry and contribute less to the spread of HPAI.[24] This initial implication of Asian poultry farmers as one broad category presented challenges to prevention recommendations as commercial strategies did not necessarily apply to backyard poultry flocks.
## H5N1[edit]
H5N1
* Influenza A virus
* subtype H5N1
* Genetic structure
* Infection
* Human mortality
* Global spread
* in 2004
* in 2005
* in 2006
* in 2007
* Social impact
* Pandemic
* Vaccine
* v
* t
* e
Further information: Influenza A virus subtype H5N1 and Transmission and infection of H5N1
The highly pathogenic influenza A virus subtype H5N1 is an emerging avian influenza virus that is causing global concern as a potential pandemic threat. It is often referred to simply as "bird flu" or "avian influenza", even though it is only one of many subtypes.
H5N1 has killed millions of poultry in a growing number of countries throughout Asia, Europe, and Africa. Health experts are concerned that the coexistence of human flu viruses and avian flu viruses (especially H5N1) will provide an opportunity for genetic material to be exchanged between species-specific viruses, possibly creating a new virulent influenza strain that is easily transmissible and lethal to humans. The mortality rate for humans with H5N1 is 60%.[citation needed]
Since the first human H5N1 outbreak occurred in 1997, there has been an increasing number of HPAI H5N1 bird-to-human transmissions, leading to clinically severe and fatal human infections. Because a significant species barrier exists between birds and humans, the virus does not easily spread to humans, however some cases of infection are being researched to discern whether human-to-human transmission is occurring.[25] More research is necessary to understand the pathogenesis and epidemiology of the H5N1 virus in humans. Exposure routes and other disease transmission characteristics, such as genetic and immunological factors that may increase the likelihood of infection, are not clearly understood.[26]
The first known transmission of H5N1 to a human occurred in Hong Kong in 1997, when there was an outbreak of 18 human cases; 6 deaths were confirmed. None of the infected people worked with poultry. After culling all of the poultry in the area, no more cases were diagnosed.[23] In 2006, the first human-to-human transmission likely occurred when 7 members of a family in Sumatra became infected after contact with a family member who had worked with infected poultry.[27]
Although millions of birds have become infected with the virus since its discovery, 359 people have died from H5N1 in twelve countries according to World Health Organization reports as of August 10, 2012.[28]
The H5N1 outbreak in Thailand caused massive economic losses, especially among poultry workers. Infected birds were culled and slaughtered. The public lost confidence with the poultry products, thus decreasing the consumption of chicken products. This also elicited a ban from importing countries. There were, however, factors which aggravated the spread of the virus, including bird migration, cool temperature (increases virus survival) and several festivals at that time.[29]
A mutation in the virus was discovered in two Guangdong patients in February 2017 which rendered it more deadly to chickens, inasmuch as it could infect every organ; the risk to humans was not increased, however.[30]
### Controversial research[edit]
A study published in 2012 in Science Magazine reported on research findings that allowed for the airborne transmission of H5N1 in laboratory ferrets. The study identified the 5 mutations necessary for the virus to become airborne and immediately sparked controversy over the ethical implications of making such potentially dangerous information available to the general public. The study was allowed to remain available in its entirety, though it remains a controversial topic within the scientific community.
The study in question, however, created airborne H5N1 via amino acid substitutions that largely mitigated the devastating effects of the disease. This fact was underscored by the 0% fatality rate among the ferrets infected via airborne transmission, as well as the fundamental biology underlying the substitutions. Flu viruses attach to host cells via the hemagluttinin proteins on their envelope. These hemagluttinin proteins bind to sialic acid receptors on host cells, which can fall into two categories. The sialic acid receptors can be either 2,3 or 2,6-linked, with the species of origin largely deciding receptor preference. In influenzas of avian origin 2,3-linkage is preferred, vs. influenzas of human origin in which 2,6-linkage is preferable. 2,3-linked SA receptors in humans are found predominantly in the lower respiratory tract, a fact that is the primary foundation for the deadliness of avian influenzas in humans, and also the key to their lack of airborne transmission. In the study that created an airborne avian influenza among ferrets it was necessary to switch the receptor preference of the host cells to those of 2,6-linkage, found predominantly in humans' upper respiratory tract, in order to create an infection that could shed aerosolized virus particles. Such an infection, however, must occur in the upper respiratory tract of humans, thus fundamentally undercutting the fatal trajectory of the disease.[31]
## H7N9[edit]
Further information: Influenza A virus subtype H7N9
Influenza A virus subtype H7N9 is a novel avian influenza virus first reported to have infected humans in 2013 in China.[32] Most of the reported cases of human infection have resulted in severe respiratory illness.[33] In the month following the report of the first case, more than 100 people had been infected, an unusually high rate for a new infection; a fifth of those patients had died, a fifth had recovered, and the rest remained critically ill.[34] The World Health Organization (WHO) has identified H7N9 as "...an unusually dangerous virus for humans."[35] As of June 30, 133 cases have been reported, resulting in the deaths of 43.
Research regarding background and transmission is ongoing.[36] It has been established that many of the human cases of H7N9 appear to have a link to live bird markets.[37] As of July 2013, there had been no evidence of sustained human-to-human transmission, however a study group headed by one of the world's leading experts on avian flu reported that several instances of human-to-human infection were suspected.[38] It has been reported that H7N9 virus does not kill poultry, which will make surveillance much more difficult. Researchers have commented on the unusual prevalence of older males among H7N9-infected patients.[39] While several environmental, behavioral, and biological explanations for this pattern have been proposed,[40] as yet, the reason is unknown.[41] Currently no vaccine exists, but the use of influenza antiviral drugs known as neuraminidase inhibitors in cases of early infection may be effective.[42]
The number of cases detected after April fell abruptly. The decrease in the number of new human H7N9 cases may have resulted from containment measures taken by Chinese authorities, including closing live bird markets, or from a change in seasons, or possibly a combination of both factors. Studies indicate that avian influenza viruses have a seasonal pattern, thus it is thought that infections may pick up again when the weather turns cooler in China.[43]
In the four years from early 2013 to early 2017, 916 lab-confirmed human cases of H7N9 were reported to WHO.[12]
On 9 January 2017, the National Health and Family Planning Commission of China reported to WHO 106 cases which occurred from late November through December. 29, 2016. The cases are reported from Jiangsu (52), Zhejiang (21), Anhui (14), Guangdong (14), Shanghai (2), Fujian (2) and Hunan (1). 80 of these 106 persons have visited live poultry markets. Of these cases, there have been 35 deaths. In two of the 106 cases, human-to-human transmission could not be ruled out.[12]
Affected prefectures in Jiangsu province closed live poultry markets in late December 2016, whereas Zhejiang, Guangdong and Anhui provinces went the route of strengthening live poultry market regulations. Travellers to affected regions are recommended to avoid poultry farms, live bird markets, and surfaces which appear to be contaminated with poultry feces. Similar sudden increases in the number of human cases of H7N9 have occurred in previous years during December and January.[12]
## Domestic animals[edit]
A chicken being tested for flu
Several domestic species have been infected with and shown symptoms of H5N1 viral infection, including cats, dogs, ferrets, pigs, and birds.[44]
### Birds[edit]
Attempts are made in the United States to minimize the presence of HPAI in poultry through routine surveillance of poultry flocks in commercial poultry operations. Detection of a HPAI virus may result in immediate culling of the flock. Less pathogenic viruses are controlled by vaccination, which is done primarily in turkey flocks (ATCvet codes: QI01AA23 (WHO) for the inactivated fowl vaccine, QI01CL01 (WHO) for the inactivated turkey combination vaccine).[45]
### Cats[edit]
Avian influenza in cats can show a variety of symptoms and usually lead to death. Cats are able to get infected by either consuming an infected bird or by contracting the virus from another infected cat.
## Global impact[edit]
In 2005, the formation of the International Partnership on Avian and Pandemic Influenza was announced in order to elevate the importance of avian flu, coordinate efforts, and improve disease reporting and surveillance in order to better respond to future pandemics. New networks of laboratories have emerged to detect and respond to avian flu, such as the Crisis Management Center for Animal Health, the Global Avian Influenza Network for Surveillance, OFFLU, and the Global Early Warning System for major animal diseases. After the 2003 outbreak, WHO member states have also recognized the need for more transparent and equitable sharing of vaccines and other benefits from these networks.[46] Cooperative measures created in response to HPAI have served as a basis for programs related to other emerging and re-emerging infectious diseases.
HPAI control has also been used for political ends. In Indonesia, negotiations with global response networks were used to recentralize power and funding to the Ministry of Health.[47] In Vietnam policymakers, with the support of the Food and Agriculture Organization of the United Nations (FAO), used HPAI control to accelerate the industrialization of livestock production for export by proposing to increase the portion of large-scale commercial farms and reducing the number of poultry keepers from 8 to 2 million by 2010.[48]
### Bird Flu in 2020[edit]
By the end of 2020 several outbreaks of Avian flu of various varieties were reported in Europe. Since mid-October several European countries, including Belgium, Denmark, France, Germany, Ireland, the Netherlands, Sweden, and the United Kingdom have reported outbreaks of highly pathogenic avian influenza (HPAI) viruses, mostly in wild birds. Positive tests were also among poultry and captive birds. According to a report by the European Centre for Disease Prevention and Control (ECDC), three varieties of HPAI viruses were found, A(H5N8), A(H5N5) and A(H5N1), with H5N8 being the most commonly found.[49] In Germany 29,000 chickens were killed to halt the spread of H5N8.[50] In Belgium H5N5 was found on a poultry farm according to the World Organization for Animal Health (OIE). The outbreak was reported in Menen, near the border with France, and killed 600 birds and the culling of an additional 151,000 chickens from the flock.[51]
### Stigma[edit]
Backyard poultry production was viewed as "traditional Asian" agricultural practices that contrasted with modern commercial poultry production and seen as a threat to biosecurity. Backyard production appeared to hold greater risk than commercial production due to lack of biosecurity and close contact with humans, though HPAI spread in intensively raised flocks was greater due to high density rearing and genetic homogeneity.[14][52] Asian culture itself was blamed as the reason why certain interventions, such as those that only looked at placed-based interventions, would fail without looking for a multifaceted solutions.[48]
### Indonesia[edit]
Press accounts of avian flu in Indonesia were seen by poultry farmers as conflating suspected cases while the public did see the accounts as informative, though many became de-sensitized to the idea of impending danger or only temporarily changed their poultry-related behavior.[53] Rumors also circulated in Java in 2006. These tended to focus on bird flu being linked to big businesses in order to drive small farmers out of the market by exaggerating the danger of avian influenza, avian flu being introduced by foreigners to force Indonesians to purchase imported chicken and keep Indonesian chicken off the world market, and the government using avian flu as a ploy to attract funds from wealthy countries. Such rumors reflected concerns about big businesses, globalization, and a distrust of the national government in a country where "the amount of decentralization here is breathtaking" according to Steven Bjorge, a WHO epidemiologist in Jakarta in 2006.[53]
In the context a decentralized national government that the public did not completely trust, Indonesian Health Minister Siti Fadilah Supari announced in December 2006 that her government would no longer be sharing samples of H5N1 collected from Indonesian patients. This decision came as a shock to the international community as it disrupted the Global Influenza Surveillance Network (GISN) coordinated by the WHO for managing seasonal and pandemic influenza. GISN is based on countries sharing virus specimens freely with the WHO which assesses and eventually sends these samples to pharmaceutical companies in order to produce vaccines that are sold back to these countries.[47] Though this was initially seen as an attempt to protect national sovereignty at all costs, it was instead used for a domestic political struggle. Prior to Indonesia's dispute with the GISN, the Ministry of Health, already weak due to the decentralized nature the government, was experiencing further leakage of funding to state and non-state agencies due to global health interventions. By reasserting control over public health issues and funding by setting itself up as the sole Indonesian representative to the WHO, the Ministry of Health made itself a key player in the management of future international funds relating vaccine production and renegotiated benefits from global surveillance networks.
### Economic[edit]
Approximately 20% of the protein consumed in developing countries come from poultry.[14] In the wake of the H5N1 pandemic, millions of poultry were killed. In Vietnam alone, over 50 million domestic birds were killed due to HPAI infection and control attempts.[54] A 2005 report by the FAO totaled economic losses in South East Asia around US$10 billion.[54] This had the greatest impact on small scale commercial and backyard producers relative to total assets compared to industrial chains which primarily experience temporary decreases in exports and loss of consumer confidence. Some governments did provide compensation for culled poultry, it was often far below market value (close to 30% of market value in Vietnam), while others such as Cambodia provide no compensation to farmers at all.
As poultry serves as a source of food security and liquid assets, the most vulnerable populations were poor small scale farmers.[48] The loss of birds due to HPAI and culling in Vietnam led to an average loss of 2.3 months of production and US$69–108 for households where many have an income of $2 a day or less.[54] The loss of food security for vulnerable households can be seen in the stunting of children under 5 in Egypt.[14] Women are another population at risk as in most regions of the world, small flocks are tended to by women.[55] Widespread culling also resulted in the decreased enrollment of girls in school in Turkey.[14]
## Prevention[edit]
People who do not regularly come into contact with birds are not at high risk for contracting avian influenza. Those at high risk include poultry farm workers, animal control workers, wildlife biologists, and ornithologists who handle live birds.[20] Organizations with high-risk workers should have an avian influenza response plan in place before any cases have been discovered. Biosecurity of poultry flocks is also important for prevention. Flocks should be isolated from outside birds, especially wild birds, and their waste; vehicles used around the flock should be regularly disinfected and not shared between farms; and birds from slaughter channels should not be returned to the farm.[56]
With proper infection control and use of personal protective equipment (PPE), the chance for infection is low. Protecting the eyes, nose, mouth, and hands is important for prevention because these are the most common ways for the virus to enter the body. Appropriate personal protective equipment includes aprons or coveralls, gloves, boots or boot covers, and a head cover or hair cover. Disposable PPE is recommended. An N-95 respirator and unvented/indirectly vented safety goggles are also part of appropriate PPE. A powered air purifying respirator (PAPR) with hood or helmet and face shield is also an option.[23]
Proper reporting of an isolated case can help to prevent spread. The Centers for Disease Control and Prevention (US) recommendation is that if a worker develops symptoms within 10 days of working with infected poultry or potentially contaminated materials, they should seek care and notify their employer, who should notify public health officials.[23]
For future avian influenza threats, the WHO suggests a 3 phase, 5 part plan.[57]
* Phase: Pre-pandemic
* Reduce opportunities for human infection
* Strengthen the early warning system
* Phase: Emergence of a pandemic virus
* Contain or delay spread at the source
* Phase: Pandemic declared and spreading internationally
* Reduce morbidity, mortality, and social disruption
* Conduct research to guide response measures
Vaccines for poultry have been formulated against several of the avian H5N1 influenza varieties. Control measures for HPAI encourage mass vaccinations of poultry though The World Health Organization has compiled a list of known clinical trials of pandemic influenza prototype vaccines, including those against H5N1.[58] In some countries still at high risk for HPAI spread, there is compulsory strategic vaccination though vaccine supply shortages remain a problem.[14]
### For village poultry farmers[edit]
During the initial response to H5N1, a one size fits all recommendation was used for all poultry production systems, though measures for intensively raised birds were not necessarily appropriate for extensively raised birds. When looking at village-raised poultry, it was first assumed that the household was the unit and that flocks did not make contact with other flocks, though more effective measures came into use when the epidemiological unit was the village.[14]
Recommendations involve restructuring commercial markets to improve biosecurity against avian influenza. Poultry production zoning is used to limit poultry farming to specific areas outside of urban environments while live poultry markets improve biosecurity by limiting the number of traders holding licenses and subjecting producers and traders to more stringent inspections. These recommendations in combination with requirements to fence and house all poultry, and to limit free ranging flocks, will eventually lead to fewer small commercial producers and backyard producers, costing livelihoods as they are unable to meet the conditions needed to participate.[48]
A summary of reports to the World Organisation for Animal Health in 2005 and 2010 suggest that surveillance and under-reporting in developed and developing countries is still a challenge.[14] Often, donor support can focus on HPAI control alone, while similar diseases such as Newcastle disease, acute fowl cholera, infectious laryngotracheitis, and infectious bursal disease still affect poultry populations. When HPAI tests come back negative, a lack of funded testing for differential diagnoses can leave farmers wondering what killed their birds.
Since traditional production systems require little investment and serve as a safety net for lower income households, prevention and treatment can be seen as less cost-effective than letting poultry die.[48][54] Effective control not only requires prior agreements to be made with relevant government agencies, such as seen with Indonesia, they must also not unduly threaten food security.[47]
### Culling[edit]
The interior of a barn showing infected birds who have been killed by suffocation with foam.
Culling is used in order to decrease the threat of avian influenza transmission by killing potentially infected birds. The FAO manual on HPAI control recommends a zoning strategy which begins with the identification of an infected area (IA) where sick or dead birds have tested positive. All poultry in this zone are culled while the area 1 to 5 km from the outer boundary of the IA is considered the restricted area (RA) placed under strict surveillance. 2 to 10 km from the RA is the control area (CA) that serves as a buffer zone in case of spread. Culling is not recommended beyond the IA unless there is evidence of spread.[24] The manual, however, also provides examples of how control was carried out between 2004 and 2005 to contain H5N1 where all poultry was to be stamped out in a 3 km radius beyond the infected point and beyond that a 5 km radius where all fowl was to be vaccinated. This culling method was indiscriminate as a large proportion of the poultry inside these areas were small backyard flocks which did not travel great enough distances to carry infection to adjacent villages without human effort and may have not been infected at all.[24] Between 2004 and 2005, over 100 million chickens were culled in Asia to contain H5N1.[59]
The risk of mass culling of birds and the resulting economic impact led to farmers who were reluctant to report sick poultry. The culls often preempted actual lab testing for H5N1 as avian flu policy justified sacrificing poultry as a safeguard against HPAI spread.[52] In response to these policies, farmers in Vietnam between 2003 and 2004 became more and more unwilling to surrender apparently healthy birds to authorities and stole poultry destined for culls as it stripped poultry of their biosocial and economic worth. By the end of 2005, the government implemented a new policy that targeted high-risk flock in the immediate vicinity of infected farms and instituted voluntary culling with compensation in the case of a local outbreak.[52]
Not only did culling result in severe economic impacts especially for small scale farmers, culling itself may be an ineffective preventative measure. In the short-term, mass culling achieves its goals of limiting the immediate spread of HPAI, it has been found to impede the evolution of host resistance which is important for the long-term success of HPAI control. Mass culling also selects for elevated influenza virulence and results in the greater mortality of birds overall.[59] Effective culling strategies must be selective as well as considerate of economic impacts to optimize epidemiological control and minimize economic and agricultural destruction.
### People-poultry relations[edit]
Prevention and control programs must take into account local understandings of people-poultry relations. In the past, programs that have focused on singular, place-based understandings of disease transmission have been ineffective. In the case of Northern Vietnam, health workers saw poultry as commodities with an environment that was under the control of people. Poultry existed in the context of farms, markets, slaughterhouses, and roads while humans were indirectly the primary transmitters of avian flu, placing the burden of disease control on people. However, farmers saw their free ranging poultry in an environment dominated by nonhuman forces that they could not exert control over. There were a host of nonhuman actors such as wild birds and weather patterns whose relationships with the poultry fostered the disease and absolved farmers of complete responsibility for disease control.[48]
Attempts at singular, place-based controls sought to teach farmers to identify areas where their behavior could change without looking at poultry behaviors. Behavior recommendations by Vietnam's National Steering Committee for Avian Influenza Control and Prevention (NSCAI) were drawn from the FAO Principles of Biosecurity.[48] These included restrictions from entering areas where poultry are kept by erecting barriers to segregate poultry from non-human contact, limits on human movement of poultry and poultry-related products ideally to transporters, and recommendations for farmers to wash hands and footwear before and after contact with poultry.[48][60] Farmers, pointed to wind and environmental pollution as reasons poultry would get sick. NSCAI recommendations also would disrupt longstanding livestock production practices as gates impede sales by restricting assessment of birds by appearance and offend customers by limiting outside human contact. Instead of incorporating local knowledge into recommendations, cultural barriers were used as scapegoats for failed interventions. Prevention and control methods have been more effective when also considering the social, political, and ecological agents in play.[48]
## See also[edit]
* H7N9
* Global spread of H5N1
* H5N1
* Health crisis
* Influenza
* Influenzavirus A
* Influenza pandemic
* Influenza Genome Sequencing Project
* Influenza research
* Influenza vaccine
* International Partnership on Avian and Pandemic Influenza
* OIE/FAO Network of Expertise on Avian Influenza
* Pandemic Preparedness and Response Act
* Subtypes of Influenza A virus
* Transmission and infection of H5N1
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## Sources[edit]
* Orent, Wendy (2006) The Science of Avian Flu, Answers to Nine Frequently Asked Questions (Discover Magazine. Health & Medicine. February 20, 2006. 59–61)
* Haugan, Salomon (2012) Avian Influenza: Etiology, Pathogenesis and Interventions (Nova Science Publishers, Inc.) ISBN 978-1607418467
## External links[edit]
Wikimedia Commons has media related to Avian influenza.
Wikinews has related news:
* Six-year-old Egyptian boy contracts bird flu
Wikinews has related news:
* Category:Avian Flu
International
United Nations System Coordinator for Avian and Human Influenza (UNSIC)
* Avian Influenza and the Pandemic Threat
World Health Organisation (WHO)
* WHO Avian influenza resource
* The United Nation's World Health Organization's Avian Flu Facts Sheet for 2006
* In-depth analysis of bird flu Symptoms & in-depth analysis on avian flu
Food and Agriculture Organization of the UN (FAO)
* FAO Avian Influenza portal Information resources, animations, videos, photos
* FAO Bird Flu disease card
World Organisation for Animal Health (OIE)
* Current status of HPAI worldwide at OIE. WAHID Interface – OIE World Animal Health Information Database
* Disease card
* Avian influenza resource By Dr. Nati Elkin – Atlases, vaccines and information.
United States
* PandemicFlu.Gov U.S. Government avian and pandemic flu information
* CIDRAP Avian Flu Overview "Avian Influenza (Bird Flu): Agricultural and Wildlife Considerations"
* US Avian Influenza Response U.S. Agency for International Development (USAID)
* Avian influenza research and recommendations National Institute for Occupational Safety and Health
* Influenza Research Database Database of influenza sequences and related information.
* Species Profile- Avian Influenza (Orthomyxoviridae Influenza Type A, subtype H5N1), National Invasive Species Information Center, United States National Agricultural Library. Lists general information and resources for Avian Influenza.
* Strategic Health Communication for Avian and Pandemic Influenza Prevention Johns Hopkins Bloomberg School of Public Health Center for Communication Programs Global Program on Avian and Pandemic Influenza.
* Avian Influenza: Critical Program Issues Global Health Technical Brief on Avian Influenza.
* NIOSH Alert: Protecting Poultry Workers from Avian Influenza (Bird Flu) CDC/NIOSH recommendations for poultry workers
Europe
* European Commission Avian Influenza control measures
* Avian Influenza: Prevention and Control Proceedings of the Frontis workshop on Avian Influenza: Prevention and Control, Wageningen, The Netherlands
* Avian Influenza: Questions & Answers European Centre for Disease Prevention and Control – Official website
* FluTrop: Avian Influenza Research in Tropical Countries French Agricultural Research Center for Developing Countries (CIRAD), Avian Influenza website
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A syndrome marked by sensory neuropathy induced from acute overdose, or chronic supplementation, of vitamin b6
Megavitamin-B6 syndrome
Other namesVitamin B6 Excess, Hypervitaminosis B6, Vitamin B6 Toxicity[1][2]
SpecialtyNeurology, toxicology
SymptomsPeripheral sensory neuropathy
Usual onsetGradual onset with slow progression, in the usual case of chronic vitamin B6 supplementation.[3]
DurationUsually, but not always, resolves within 6 months from cessasation of vitamin B6.[4]
CausesChronic vitamin B6 supplementation, or acute parenteral or oral over‐dosages of vitamin B6.[5][4][6][7][8]
Risk factorsImpaired kidney function, parenteral nutrition[9]
Diagnostic methodSerum testing for elevated levels of vitamin B6, testing of tendon reflexes, nerve conduction studies and electrodiagnostic testing.[10][11]
Differential diagnosisProgressive mixed sensory or sensorimotor polyneuropathy of undetermined etiology.[12][13]
TreatmentCessation of vitamin B6 supplementation.[14]
PrognosisSymptom progression for 2-6 weeks following cessation of vitamin B6, followed by gradual improvement.[14][4][15][16]
Megavitamin-B6 syndrome is a collection of symptoms that can result from chronic supplementation, or acute overdose, of vitamin B6.[4][6][5] While it is also known as hypervitaminosis B6, vitamin B6 toxicity and vitamin B6 excess, megavitamin-b6 syndrome is the name used in the ICD-10.[17][1][2][a]
## Contents
* 1 Signs and symptoms
* 2 Cause
* 2.1 Potential mechanisms
* 3 Tolerable upper limits
* 3.1 Exceptions
* 4 Diagnosis
* 4.1 Classification
* 5 Treatment
* 6 Prognosis
* 7 See also
* 8 Notes
* 9 References
* 10 Further reading
* 11 External links
## Signs and symptoms[edit]
The predominant symptom is peripheral sensory neuropathy[23][4][6][24] that is experienced as numbness, pins-and-needles and burning sensations (paresthesia) in a patient's limbs on both sides of their body.[14][4][13][15] Patients may experience unsteadiness of gait, incoordination (ataxia),[15][25][4][26] involuntary muscle movements (choreoathetosis)[10] the sensation of an electric zap in their bodies (Lhermitte's sign),[15] a heightened sensitivity to sense stimuli including photosensitivity (hyperesthesia),[4][25] impaired skin sensation (hypoesthesia),[27][14] numbness around the mouth,[27][3] and gastrointestinal symptoms such as nausea and heartburn.[25][28] The ability to sense vibrations and to sense one's position are diminished to a greater degree than pain or temperature.[27][3] Skin lesions have also been reported.[25][26][29][28] Megavitamin-B6 syndrome may also contribute to burning mouth syndrome.[30][31] Potential psychiatric symptoms range from anxiety, depression, agitation, and cognitive deficits to psychosis.[32]
Symptom severity appears to be dose-dependent (higher doses cause more severe symptoms)[25] and the duration of supplementation with vitamin B6 before onset of systems appears to be inversely proportional to the amount taken daily (the smaller the daily dosage, the longer it will take for symptoms to develop).[15][4][10][12][7] It is also possible that some individuals are more susceptible to the toxic effects of vitamin B6 than others.[4] Megavitamin-B6 syndrome has been reported in doses as low as 24 mg/day.[33]
Symptoms may also be dependent on the form of vitamin B6 taken in supplements.[24][34] It has been proposed that vitamin B6 in supplements should be in pyridoxal or pyridoxal phosphate form rather than pyridoxine as these are thought to reduce the likelihood of toxicity.[24][35] A tissue culture study, however, showed that all B6 vitamers that could be converted into active coenzymes (pyridoxal, pyridoxine and pyridoxamine) were neurotoxic at similar concentrations.[19][36] Consuming high amounts of vitamin B6 from food has not been reported to cause adverse effects.[25][29][37]
Early diagnosis and cessation of vitamin B6 supplementation can reduce the morbidity of the syndrome.[25][12]
## Cause[edit]
There is a longstanding common misconception that because vitamin B6 is water-soluble it is therefore harmless.[19][38][27] While vitamin B6 is water-soluble, it has a half-life of 25–33 days and accumulates in the body where it is stored in muscle, plasma, the liver, red blood cells and bound to proteins in tissues.[38][37][39]
### Potential mechanisms[edit]
The common supplemental form of vitamin B6, pyridoxine, is similar to pyridine which can be neurotoxic. Pyridoxine has limited transport across the blood–brain barrier explaining why the central nervous system is spared. Cell bodies of motor fibers are located within the spinal cord that is also restricted by the blood-brain barrier explaining why motor impairment is rare. The dorsal root ganglia, however, are located outside of the blood-brain barrier making them more susceptible.[27]
Pyridoxine is converted to pyridoxal phosphate via two enzymes, pyridoxal kinase and pyridoxine 5′-phosphate oxidase. High levels of pyridoxine can inhibit these enzymes. As pyridoxal phosphate is the active form of vitamin B6, this saturation of pyridoxine could mimic a deficiency of vitamin B6.[27][24] In 2017, this was demonstrated in an in vitro study of human cells.[38]
## Tolerable upper limits[edit]
Several government agencies have reviewed the data on vitamin B6 supplementation and produced upper limits on intake with the desired goal to prevent sensory neuropathy from excessive amounts. Each agency developed their own criteria for usable studies in relation to tolerable upper limits, and as such the recommendations vary by agency. Between agencies, current tolerable upper limit guidelines vary from 10 mg per day to 100 mg per day.[37]
Daily vitamin B6 tolerable upper limits for adults as established by agency Agency Upper limit Notes Reference
National Health Service (NHS) United Kingdom 10 mg/day [40]
Norwegian Scientific Committee for Food and Environment (VKM) 25 mg/day In 2017 VKM proposed to raise this to 25 mg/day, it was previously 4.2 mg/day. [37]
Netherlands Food and Consumer Product Safety Authority [nl] (NVWA) 25 mg/day Supplements may only contain dosages of 21 mg/day. [41]
European Food Safety Authority 25 mg/day [42]
National Health and Medical Research Council (NHMRC) Australia 50 mg/day [43]
U.S. Institute of Medicine \- Food and Nutrition Board 100 mg/day [25]
Reviews of vitamin B6 related neuropathy cautioned that supplementation at doses greater than 50 mg per day for extend periods of time may be harmful and should be discouraged.[44][45] In 2008, the Australian Complementary Medicines Evaluation Committee recommended warning statements appear on products containing daily doses of 50 mg or more vitamin B6 to avoid toxicity.[46]
The relationship between amount of vitamin B6 consumed and serum concentrations is not known, some people may have high serum concentrations without symptoms of neuropathy.[13][47][48] It is also not known if inhalation of vitamin B6 while, for example, working with animal feed containing vitamin B6 is safe.[49]
### Exceptions[edit]
High parenteral doses of vitamin B6 are used to treat isoniazid overdose with no adverse effects found,[4] although a preservative in parenteral vitamin B6 may cause transient worsening of metabolic acidosis.[4] High doses of vitamin B6 are used to treat gyromitra mushroom (false morel) poisoning, hydrazine exposure and homocystinuria[8][50] Doses of 50 mg to 100 mg per day may also be used to treat pyridoxine deficient seizures and where patients are taking medications that reduce vitamin B6.[14] Daily doses of 10 mg to 50 mg are recommended for patients undergoing hemodialysis.[14] High doses of vitamin B6 may be effective at suppressing lactation.[29]
Outside of rare medical conditions, placebo-controlled studies have generally failed to show benefits of high doses of vitamin B6.[28] Reviews of supplementing with vitamin B6 have not found it to be effective at reducing swelling, reducing stress, producing energy, preventing neurotoxicity, or treating asthma.[27]
## Diagnosis[edit]
The clinical hallmark of megavitamin-B6 syndrome is ataxia due to sensory polyneuropathy. Blood tests are performed to rule out other causes and to confirm an elevated level of vitamin B6 with an absence of hypophosphatasia.[14][11][12][51][52] Examination does not typically show signs of a motor deficit, dysfunction of the autonomic nervous system or impairment of the central nervous system,[4][3] although in severe cases motor and autonomic imparement can occur.[14][12][53] When examined, patients typically have diminished reflexes (hyporeflexia), such as a diminished response when performing an ankle jerk reflex test.[14][23][3] Nerve conduction studies typically show normal motor conduction but decrease in large sensory wave amplitude in the arms and legs.[23][10][14][13][3] Needle electromyography studies generally reveal no signs of denervation.[15]
### Classification[edit]
Megavitamin-B6 syndrome is characterized mainly by degeneration of dorsal root ganglion axons and cell bodies,[54][19][27][12][10][21] although it also affects the trigeminal ganglia[27][3] it is classified as a sensory ganglionopathy due to involvement of these ganglia.[55][b] In electrodiagnostic testing, it has characteristic non-length-dependent abnormalities of sensory action potentials that occur globally, rather than distally decreasing of sensory nerve action potential amplitudes.[51] Megavitamin-B6 syndrome is predominately a large fiber neuropathy characterized by sensory loss of joint position, vibration and ataxia.[19] Although it has characteristics of small fiber neuropathy in severe cases where there is impairment of pain, temperature, and autonomic functions.[56][57][14][12][53][58][18]
## Treatment[edit]
The primary treatment for megavitamin-B6 syndrome is to stop taking supplemental vitamin B6.[14] Physical therapy, including vestibular rehabilitation, has been used in attempts to improve recovery following cessation of vitamin B6 supplementation.[46][11] Medications such as amitriptyline have been used to help with neuropathic pain.[20]
In experimental tests using animal subjects, neurotrophic factors, specifically neurotrophin-3, were shown to potentially reverse the neuropathy caused from the vitamin B6 toxicity.[4][19] With rats and mice, improvement has also been seen with 4-methylcatechol, a specific chicory extract, coffee and trigonelline.[59][60][61]
## Prognosis[edit]
Other than with extremely high doses of vitamin B6, neurologic dysfunction improves following cessation of vitamin B6 supplementation and usually, but not always, resolves within six months.[3][4] In cases of acute high doses, for example in people receiving daily doses of 2 grams of vitamin B6 per kilogram of body weight, symptoms may be irreversible and may additionally cause pseudoathetosis.[3][15][20][16][6][8]
In the immediate 2–6 weeks following discontinuation of vitamin B6, patients may experience a symptom progression before gradual improvement begins. This is known as coasting and is encountered in other toxic neuropathies.[14][4][15][16] A vitamin B6 substance dependency may exist in daily dosages of 200 mg or more, making a drug withdrawal effect possible when discontinued.[27]
## See also[edit]
* B vitamins
* Dietary Reference Intake
* Dietary supplement
* Hypervitaminosis
* Hypervitaminosis A
* Hypervitaminosis D
* Megavitamin therapy
* Overnutrition
* Peripheral nervous system
* Regulation of alternative medicine
## Notes[edit]
1. ^ While megavitamin-B6 syndrome, hypervitaminosis B6, vitamin B6 toxicity and vitamin B6 excess are officially recognized, terms for this in literate vary. Often vitamin B6 and its most common supplemental vitamer, pyridoxine, are used interchangeably. Some other terms include vitamin B6 overdose,[18] pyridoxine abuse,[19][20] pyridoxine megavitamosis,[12] pyridoxine poisoning,[21] and pyridoxine neuropathy.[22]
2. ^ The terms sensory ganglionopathy and sensory neuronopathy are interchangable.[55]
## References[edit]
1. ^ a b Bell, Daniel J. "Vitamin B6 excess". Radiopaedia. Archived from the original on 2019-10-24. Retrieved 2019-12-01.
2. ^ a b "Hypervitaminosis B6 (Concept Id: C0238176) - MedGen - NCBI". MedGen. National Center for Biotechnology Information (NCBI). Archived from the original on 2019-11-05. Retrieved 2019-12-02.
3. ^ a b c d e f g h i Koontz, Daniel W; Maddux, Brian; Katirji, Bashar (2004). "Evaluation of a Patient Presenting With Rapidly Progressive Sensory Ataxia". Journal of Clinical Neuromuscular Disease. 6 (1): 40–47. doi:10.1097/01.cnd.0000133065.28161.00. ISSN 1522-0443. PMID 19078751. S2CID 26316070.
4. ^ a b c d e f g h i j k l m n o p Lheureux, P.; Penaloza, A.; Gris, M. (2005). "Pyridoxine in clinical toxicology: A review". European Journal of Emergency Medicine. 12 (2): 78–85. doi:10.1097/00063110-200504000-00007. PMID 15756083. S2CID 39197646.
5. ^ a b Silva, C D; D'Cruz, D P (2006). "Pyridoxine toxicity courtesy of your local health food store". Annals of the Rheumatic Diseases. 65 (12): 1666–1667. doi:10.1136/ard.2006.054213. ISSN 0003-4967. PMC 1798481. PMID 17105856.
6. ^ a b c d James W. Albers; Stanley Berent (15 August 2005). Neurobehavioral Toxicology: Neurological and Neuropsychological Perspectives, Volume II: Peripheral Nervous System. Taylor & Francis. pp. 2–. ISBN 978-1-135-42106-9.
7. ^ a b Kennedy, Ashleigh; Schaeffer, Tammi (2016). "Pyridoxine". Critical Care Toxicology. pp. 1–4. doi:10.1007/978-3-319-20790-2_174-1. ISBN 978-3-319-20790-2.
8. ^ a b c London, Zachary; Albers, James W. (2007). "Toxic Neuropathies Associated with Pharmaceutic and Industrial Agents". Neurologic Clinics. 25 (1): 257–276. doi:10.1016/j.ncl.2006.10.001. ISSN 0733-8619. PMID 17324727.
9. ^ Mikalunas, Vida; Fitzgerald, Kathleen; Rubin, Halina; McCarthy, Roberta; Craig, Robert M. (2001). "Abnormal Vitamin Levels in Patients Receiving Home Total Parenteral Nutrition". Journal of Clinical Gastroenterology. 33 (5): 393–396. doi:10.1097/00004836-200111000-00010. ISSN 0192-0790. PMID 11606856. S2CID 12384721.
10. ^ a b c d e Donofrio, Peter D. (2005). "Evaluating the Patient With Peripheral Neuropathy" (PDF). Numbness, Tingling, Pain, and Weakness: A Basic Course in Electrodiagnostic Medicine. Monterey, California: AANEM 52nd Annual Scientific Meeting.
11. ^ a b c Rohitha Moudgal, Shahla Hosseini, Patricia Colapietro, Oluwole Awosika (2018-04-25). "Vitamin B6 Toxicity Revisited: A Case of Reversible Pyridoxine-associated Neuropathy and Disequilibrium. (P4.021)". Neurology. 90 (15 Supplement).CS1 maint: uses authors parameter (link)
12. ^ a b c d e f g h Ahmed, Aiesha; Velazquez-Rodriguez, Yadira; Kaur, Divpreet (2014-04-08). "When Expected Turns Unexpected: A Case of Subacute Progressive Weakness and Paresthesias of the Distal Lower Extremities Following a Brief Diarrheal Episode. (P6.111)". Neurology. 82 (10 Supplement): P6.111.
13. ^ a b c d Scott, K.; Zeris, S.; Kothari, M. J. (2008). "Elevated B6 levels and peripheral neuropathies". Electromyography and Clinical Neurophysiology. 48 (5): 219–23. PMID 18754531.
14. ^ a b c d e f g h i j k l m Hammond, N.; Wang, Y.; Dimachkie, M.; Barohn, R. (2013). "Nutritional Neuropathies". Neurologic Clinics. 31 (2): 477–489. doi:10.1016/j.ncl.2013.02.002. PMC 4199287. PMID 23642720.
15. ^ a b c d e f g h Bromberg, Mark B. (2000). "Peripheral Neurotoxic Disorders". Neurologic Clinics. 18 (3): 681–694. doi:10.1016/S0733-8619(05)70218-8. ISSN 0733-8619. PMID 10873238.
16. ^ a b c Saleh, Firas G. MD; Seidman, Roberta J. MD (2003-12-01). "Drug-Induced Myopathy and Neuropathy". Journal of Clinical Neuromuscular Disease. 5 (2): 81–91. doi:10.1097/00131402-200312000-00003. PMID 19078725. S2CID 31440274.CS1 maint: uses authors parameter (link)
17. ^ de Onis, Mercedes; Zeitlhuber, Julia; Martínez-Costa, Cecilia (2016). "Nutritional disorders in the proposed 11th revision of the International Classification of Diseases: feedback from a survey of stakeholders". Public Health Nutrition. 19 (17): 3135–3141. doi:10.1017/S1368980016001427. ISSN 1368-9800. PMC 5217466. PMID 27293047.
18. ^ a b Sène, Damien (2018). "Small fiber neuropathy: Diagnosis, causes, and treatment". Joint Bone Spine. 85 (5): 553–559. doi:10.1016/j.jbspin.2017.11.002. ISSN 1297-319X. PMID 29154979.
19. ^ a b c d e f Hlubocky, Ales; Smith, Benn E. (2014). "Dorsal Root Ganglion Disorders". Neuromuscular Disorders in Clinical Practice. pp. 467–491. doi:10.1007/978-1-4614-6567-6_23. ISBN 978-1-4614-6566-9.
20. ^ a b c Lacerna, Rhodora A.; Chien, Chloe; Yeh, Shing-Shing (2003). "Paresthesias Developing in an Elderly Patient after Chronic Usage of Nitrofurantoin and Vitamin B6". Journal of the American Geriatrics Society. 51 (12): 1822–1823. doi:10.1046/j.1532-5415.2003.51572_8.x. PMID 14687374. S2CID 26337220.
21. ^ a b Donofrio, Peter Daniel (2000). "Electrophysiological Evaluations". Neurologic Clinics. 18 (3): 601–613. doi:10.1016/S0733-8619(05)70213-9. ISSN 0733-8619. PMID 10873233.
22. ^ Schaeppi, U.; Krinke, G. (1982). "Pyridoxine neuropathy: Correlation of functional tests and neuropathology in beagle dogs treated with large doses of vitamin B6". Agents and Actions. 12 (4): 575–582. doi:10.1007/BF01965944. ISSN 0065-4299. PMID 7180742. S2CID 30742144.
23. ^ a b c Callizot, Noëlle; Poindron, Philippe (2008). "Pyridoxine-Induced Peripheral Neuropathy". New Animal Models of Human Neurological Diseases. Biovalley Monographs. pp. 66–80. doi:10.1159/000117724. ISBN 978-3-8055-8405-0.
24. ^ a b c d Wilmshurst, Jo M.; Ouvrier, Robert A.; Ryan, Monique M. (2019). "Peripheral nerve disease secondary to systemic conditions in children". Therapeutic Advances in Neurological Disorders. 12: 175628641986636. doi:10.1177/1756286419866367. PMC 6691669. PMID 31447934.
25. ^ a b c d e f g h "Vitamin B6 — Health Professional Fact Sheet". National Institutes of Health Office Dietary Supplements. U.S. Department of Health and Human Services. Archived from the original on 2019-11-25. Retrieved 2019-12-02.
26. ^ a b Stover, Patrick J; Field, Martha S (2015). "Vitamin B-6". Advances in Nutrition. 6 (1): 132–133. doi:10.3945/an.113.005207. ISSN 2161-8313. PMC 4288272. PMID 25593152.
27. ^ a b c d e f g h i j Gangsaas, Ingvild (1995). "Dispelling the Myths of Vitamin B6" (PDF). Nutrition Bytes. 1 (1). ISSN 1548-4327.
28. ^ a b c Chawla, Jasvinder; Kvarnberg, David (2014). "Hydrosoluble vitamins". Neurologic Aspects of Systemic Disease Part II. Handbook of Clinical Neurology. 120. pp. 891–914. doi:10.1016/B978-0-7020-4087-0.00059-0. ISBN 9780702040870. ISSN 0072-9752. PMID 24365359.
29. ^ a b c Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline (1998). "Vitamin B6". Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington (DC): National Academies Press (US).CS1 maint: multiple names: authors list (link)
30. ^ Dieb, Wisam; Boucher, Yves (2017). "Burning Mouth Syndome and Vitamin B6". Pain Medicine. 18 (8): 1593–1594. doi:10.1093/pm/pnw345. ISSN 1526-2375. PMID 28371806.
31. ^ Dieb, Wisam; Moreau, Nathan; Rochefort, Juliette; Boucher, Yves (2016). "Role of vitamin B6 in idiopathic burning mouth syndrome: some clinical observations" (PDF). Médecine Buccale Chirurgie Buccale. 23 (2): 77–83. doi:10.1051/mbcb/2016038. ISSN 1273-2761.
32. ^ Hani R. Khouzam; Doris Tiu Tan; Tirath S. Gill (9 March 2007). Handbook of Emergency Psychiatry E-Book. Elsevier Health Sciences. pp. 65–. ISBN 978-0-323-07661-6.
33. ^ De Kruijk, J. R.; Notermans, N. C. (2005). "Sensory disturbances caused by multivitamin preparations". Nederlands Tijdschrift voor Geneeskunde. 149 (46): 2541–4. PMID 16320661.
34. ^ Levine, Seymour; Saltzman, Arthur (2004). "Pyridoxine (vitamin B6) neurotoxicity: enhancement by protein-defcient diet". Journal of Applied Toxicology. 24 (6): 497–500. doi:10.1002/jat.1007. ISSN 0260-437X. PMID 15558839. S2CID 8280774.
35. ^ Vrolijk, M. F.; Opperhuizen, A.; Jansen EHJM; Hageman, G. J.; Bast, A.; Haenen GRMM (2017). "The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function". Toxicology in Vitro. 44: 206–212. doi:10.1016/j.tiv.2017.07.009. PMID 28716455.
36. ^ Windebank, Anthony J. (1985). "Neurotoxicity of pyridoxine analogs is related to coenzyme structure". Neurochemical Pathology. 3 (3): 159–167. doi:10.1007/BF02834268. ISSN 0734-600X. PMID 4094726.
37. ^ a b c d Assessment of vitamin B6 intake in relation to tolerable upper intake levels. Opinion of the Panel on Nutrition, Dietetic Products, Novel Food and Allergy of the Norwegian Scientific Committee for Food Safety (PDF). Oslo, Norway. ISBN 978-82-8259-260-4. Archived from the original (PDF) on 2019-11-17. Retrieved 2019-12-07.
38. ^ a b c Reeds, Karen (2019-03-04). "Vitamin B Complexities". H-Nutrition. Lay summary.
39. ^ Institute of Medicine (29 September 2006). Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. National Academies Press. pp. 184–. ISBN 978-0-309-15742-1.
40. ^ "Vitamins and minerals - B vitamins and folic acid - NHS". National Health Service. 3 March 2017. Archived from the original on 2019-10-21. Retrieved 2019-11-01.
41. ^ "Advies van BuRO over vitamine B6 uit voedingssupplementen". Netherlands Food and Consumer Product Safety Authority (in Dutch). 2016-12-16. Retrieved 2019-12-07.
42. ^ "Opinion of the Scientific Committee on Food on the Tolerable Upper Intake Level of Vitamin B6" (PDF). Tolerable upper intake levels for vitamins and minerals. European Food Safety Authority (EFSA). 2006. pp. 29–44. ISBN 978-92-9199-014-6. Archived from the original (PDF) on 2019-04-12.
43. ^ "Vitamin B6". Nutrient Reference Values for Australia and New Zealand. National Health and Medication Research Council (NHMRC). 2014-03-17. Archived from the original on 2019-03-04. Retrieved 2019-12-02.
44. ^ Ghavanini, A. A.; Kimpinski, K. (2014). "Revisiting the evidence for neuropathy caused by pyridoxine deficiency and excess". Journal of Clinical Neuromuscular Disease. 16 (1): 25–31. doi:10.1097/CND.0000000000000049. PMID 25137514. S2CID 205557831.
45. ^ Bender, David A. (1997). "Vitamin B6". Nutrition & Food Science. 97 (4): 128–133. doi:10.1108/00346659710179642. ISSN 0034-6659.
46. ^ a b Adverse Drug Reactions Advisory Committee (ADRAC) and the Office of Medicine Safety Monitoring (OMSM) of the TGA. (2008-08-01). "High-dose vitamin B6 may cause peripheral neuropathy". Australian Adverse Drug Reactions Bulletin. 27 (4). Archived from the original on 2017-09-23.
47. ^ Van Hunsel, Florence; Van De Koppel, Sonja; Van Puijenbroek, Eugène; Kant, Agnes (2018). "Vitamin B6 in Health Supplements and Neuropathy: Case Series Assessment of Spontaneously Reported Cases". Drug Safety. 41 (9): 859–869. doi:10.1007/s40264-018-0664-0. PMID 29737502. S2CID 13685351.
48. ^ Critcher, Matt S.; Sobczynska-Malefora, Agata (2015-09-15). "Vitamin B6: low and very high concentrations in hospital patients" (PDF). Cite journal requires `|journal=` (help)
49. ^ "Scientific Opinion on the safety and efficacy of vitamin B6(pyridoxine hydrochloride) as a feed additive for all animal species". EFSA Journal. 9 (5): 2171. 2011. doi:10.2903/j.efsa.2011.2171. ISSN 1831-4732.
50. ^ Echaniz-Laguna, Andoni; Mourot-Cottet, Rachel; Noel, Esther; Chanson, Jean-Baptiste (2018). "Regressive pyridoxine-induced sensory neuronopathy in a patient with homocystinuria". BMJ Case Reports. 2018: bcr–2018–225059. doi:10.1136/bcr-2018-225059. ISSN 1757-790X. PMC 6040505. PMID 29954767.
51. ^ a b Gdynia, Hans-Jürgen; Müller, Timo; Sperfeld, Anne-Dorte; Kühnlein, Peter; Otto, Markus; Kassubek, Jan; Ludolph, Albert C. (2008). "Severe sensorimotor neuropathy after intake of highest dosages of vitamin B6". Neuromuscular Disorders. 18 (2): 156–158. doi:10.1016/j.nmd.2007.09.009. ISSN 0960-8966. PMID 18060778. S2CID 7370460.
52. ^ Whyte, M P; Mahuren, J D; Vrabel, L A; Coburn, S P (1985). "Markedly increased circulating pyridoxal-5'-phosphate levels in hypophosphatasia. Alkaline phosphatase acts in vitamin B6 metabolism". Journal of Clinical Investigation. 76 (2): 752–756. doi:10.1172/JCI112031. ISSN 0021-9738. PMC 423894. PMID 4031070.
53. ^ a b Bacharach, Rae; Lowden, Max; Ahmed, Aiesha (2017). "Pyridoxine Toxicity Small Fiber Neuropathy With Dysautonomia". Journal of Clinical Neuromuscular Disease. 19 (1): 43–46. doi:10.1097/CND.0000000000000172. ISSN 1522-0443. PMID 28827489.
54. ^ Bashar Katirji; Henry J. Kaminski; Robert L. Ruff (11 October 2013). Neuromuscular Disorders in Clinical Practice. Springer Science & Business Media. pp. 468–. ISBN 978-1-4614-6567-6.
55. ^ a b Sheikh, S. I.; Amato, A. A. (2010). "The dorsal root ganglion under attack: the acquired sensory ganglionopathies". Practical Neurology. 10 (6): 326–334. doi:10.1136/jnnp.2010.230532. ISSN 1474-7758. PMID 21097829. S2CID 38755244.
56. ^ Perry, Tracy Ann; Weerasuriya, Ananda; Mouton, Peter R.; Holloway, Harold W.; Greig, Nigel H. (2004). "Pyridoxine-induced toxicity in rats: A stereological quantification of the sensory neuropathy". Experimental Neurology. 190 (1): 133–. doi:10.1016/j.expneurol.2004.07.013. PMID 15473987. S2CID 25543353.
57. ^ Misra, UshaKant; Kalita, Jayantee; Nair, PradeepP (2008). "Diagnostic approach to peripheral neuropathy". Annals of Indian Academy of Neurology. 11 (2): 89–97. doi:10.4103/0972-2327.41875. ISSN 0972-2327. PMC 2771953. PMID 19893645.
58. ^ Bakkers, Mayienne (2015). Small fibers, big troubles : diagnosis and implications of small fiber neuropathy (PDF). Datawyse / Universitaire Pers Maastricht.
59. ^ Hasannejad, Farkhonde; Ansar, Malek Moein; Rostampour, Mohammad; Mahdavi Fikijivar, Edris; Khakpour Taleghani, Behrooz (2019). "Improvement of pyridoxine-induced peripheral neuropathy by Cichorium intybus hydroalcoholic extract through GABAergic system". The Journal of Physiological Sciences. 69 (3): 465–476. doi:10.1007/s12576-019-00659-8. ISSN 1880-6546. PMID 30712095. S2CID 59541162.
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61. ^ Hong, Bin Na; Yi, Tae Hoo; Kim, Sun Yeou; Kang, Tong Ho (2009). "High-Dosage Pyridoxine-Induced Auditory Neuropathy and Protection with Coffee in Mice". Biological & Pharmaceutical Bulletin. 32 (4): 597–603. doi:10.1248/bpb.32.597. ISSN 0918-6158. PMID 19336890.
## Further reading[edit]
* A chapter with a story about a woman experiencing a severe case of Megavitamin-B6 syndrome titled "The Disembodied Lady" appears in Chapter 3 of The Man Who Mistook His Wife for a Hat: Oliver Sacks; Oliver W. Sacks (1998). "Chapter 3: The Disembodied Lady". The Man Who Mistook His Wife For A Hat: And Other Clinical Tales. Simon and Schuster. pp. 43–52. ISBN 978-0-684-85394-9.
* An ethnographic study of an online support group for megavitamin B6 syndrome appears in: Laura D. Russell (16 December 2019). "Chapter 9: Making Collective Sense of Uncertainty: How Online Social Support Communities Negotiate Meaning for Contested Illnesses". In Nichole Egbert; Kevin B Wright (eds.). Social Support and Health in the Digital Age. Rowman & Littlefield. pp. 171–191. ISBN 978-1-4985-9535-3.
## External links[edit]
* StatPearls - Vitamin B6 Toxicity
Classification
D
* ICD-10: E67.2
* ICD-10-CM: E67.2
* ICD-9-CM: 278.8
* SNOMED CT: 238146000
External resources
* Patient UK: Megavitamin-B6 syndrome
* Radiopedia: vitamin-b6excess
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*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Megavitamin-B6 syndrome | c0238176 | 4,568 | wikipedia | https://en.wikipedia.org/wiki/Megavitamin-B6_syndrome | 2021-01-18T19:08:38 | {"icd-10": ["E67.2"], "wikidata": ["Q82684153"]} |
Spondyloperipheral dysplasia is a disorder that impairs bone growth. This condition is characterized by flattened bones of the spine (platyspondyly) and unusually short fingers and toes (brachydactyly), with the exception of the first (big) toes. Other skeletal abnormalities associated with spondyloperipheral dysplasia include short stature, shortened long bones of the arms and legs, exaggerated curvature of the lower back (lordosis), and an inward- and upward-turning foot (clubfoot). Additionally, some affected individuals have nearsightedness (myopia), hearing loss, and intellectual disability.
## Frequency
This condition is rare; only a few affected individuals have been reported worldwide.
## Causes
Spondyloperipheral dysplasia is one of a spectrum of skeletal disorders caused by mutations in the COL2A1 gene. This gene provides instructions for making a protein that forms type II collagen. This type of collagen is found mostly in the clear gel that fills the eyeball (the vitreous) and in cartilage. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Type II collagen is essential for the normal development of bones and other connective tissues that form the body's supportive framework.
Mutations in the COL2A1 gene interfere with the assembly of type II collagen molecules, reducing the amount of this type of collagen in the body. Instead of forming collagen molecules, the abnormal COL2A1 protein builds up in cartilage cells (chondrocytes). These changes disrupt the normal development of bones and other connective tissues, leading to the signs and symptoms of spondyloperipheral dysplasia.
### Learn more about the gene associated with Spondyloperipheral dysplasia
* COL2A1
## Inheritance Pattern
This condition is probably inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Spondyloperipheral dysplasia | c0796173 | 4,569 | medlineplus | https://medlineplus.gov/genetics/condition/spondyloperipheral-dysplasia/ | 2021-01-27T08:24:34 | {"gard": ["4994"], "mesh": ["C535799"], "omim": ["271700"], "synonyms": []} |
An aggressive and life-threatening form of thrombotic microangiopathy (TMA) characterized by profound peripheral thrombocytopenia, microangiopathic hemolytic anemia (MAHA) and organ failure of variable severity and is comprised of a congenital (cTTP) and acquired, immune-mediated (iTTP) form.
## Clinical description
iTTP generally occurs in adulthood, whereas cTTP usually in the neonatal period, during childhood or in the setting of pregnancy. Onset is usually acute but early symptoms may include fatigue, purpura or ecchymoses, abdominal pain, arthralgia and myalgia, resembling a flu-like episode. Disseminated microvascular thrombosis leads to consumptive peripheral thrombocytopenia, MAHA and widespread organ injury associated with cerebral (headache, confusion, altered consciousness, coma, seizures, hemiparesis and visual disturbances), cardiac (arrhythmia, infarction, congestive heart failure and cardiac arrest) and gastrointestinal (nausea, vomiting, abdominal pain and diarrhea) manifestations. Purpura and petechiae are the most common bleeding manifestations. Renal involvement is usually mild. Fever occurs in less than 50% of patients. Patients with iTTP may suffer from only one episode, but relapses can occur in 30 to 40% of cases in the absence of preemptive therapies. A chronic and frequently relapsing disease course is more typical in those with cTTP, without prophylactic treatment.
## Etiology
TTP is caused by a severely decreased activity (< 10%) of ADAMTS13, a metalloprotease involved in the cleavage of ultra-large von Willebrand factor multimers. In cTTP, ADAMTS13 deficiency is caused by homozygous or compound heterozygous mutations ADAMTS13 (9q34), whereas it is associated with the presence of anti-ADAMTS13 immunoglobulin G (IgG) antibodies in iTTP.
## Diagnostic methods
First, the diagnosis of TMA must be evoked in a patient with MAHA and a negative direct antiglobulin test, associated with a peripheral thrombocytopenia, especially if there is an associated organ failure (cerebral, renal or cardiac involvement, abdominal pain). Once the diagnosis of TMA is made, TTP must be recognized. The diagnosis can be strongly suspected in a patient with TMA when thrombocytopenia is profound (platelet count < 30 G/L) and when renal involvement is only mild (serum creatinine level < 2.27 mg/dL). However, the diagnosis of TTP can only be ascertained by an undetectable ADAMTS13 activity (activity < 10%). cTTP is characterized by a persistently severe ADAMTS13 deficiency with no identifiable anti-ADAMTS13 antibodies. The sequencing of ADAMTS13 gene then identifies bi-allelic mutations. Acquired, iTTP is associated with anti-ADAMTS13 antibodies in serum. In 20% of cases, antibodies may not be detectable, but ADAMTS13 activity normalizes after the acute phase.
## Differential diagnosis
Differential diagnosis includes other TMAs (hemolytic uremic syndrome, TMA secondary to transplantation, chemotherapy, drug, HIV/AIDS, as well as HELLP syndrome) and other diseases including catastrophic antiphospholipid syndrome, severe sepsis, vitamin B12 deficiency, malignant hypertension and severe disseminated intravascular coagulopathy.
## Genetic counseling
cTTP is inherited autosomal recessively and genetic counseling is suggested. The risk of inheriting the disease is 25% where both parents are unaffected carriers.
## Management and treatment
Given the severity of the disease and the risk of sudden organ failure, management in intensive care units until platelet count recovery is recommended. The current standard of care consists of plasma exchange replenishing active ADAMTS13 from donors' plasma (and to a lesser extend removing anti-ADAMTS13 antibodies and pro-aggregant substances), immunosuppressive therapies (e.g. glucocorticoids and rituximab) to prevent ADAMTS13 antibody production, and caplacizumab. Caplacizumab is a nanobody that targets von Willebrand factor (VWF) and accelerates platelet count recovery and prevents worse outcomes. After recovery, patients benefit from long-term follow-up with regular assessment of ADAMTS13 activity. Where decreased ADAMTS13 activity is observed, a preemptive infusion of rituximab should be proposed.
## Prognosis
With a rapid diagnosis and the current standard of treatment, the prognosis of the disease is usually excellent with a complete recovery in more than 95% of cases. However, in a substantial number of cases patients suffer neurocognitive disorders including chronic fatigue, problems of memory and concentration, as well as depression. These troubles still have no clear explanation, and significantly impact quality of life.
* European Reference Network
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Thrombotic thrombocytopenic purpura | c0034155 | 4,570 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=54057 | 2021-01-23T17:35:04 | {"mesh": ["D011697"], "omim": ["274150"], "umls": ["C0034155"], "icd-10": ["M31.1"], "synonyms": ["Moschcowitz disease", "TTP"]} |
Immunodeficiency due to MASP-2 deficiency is a rare, genetic immunodeficiency due to a complement cascade protein anomaly characterized by low serum levels of MASP-2 and a variable susceptibility to bacterial infections (e.g. pulmonary tuberculosis, pneumococcal pneumonia, skin abscesses and sepsis), and autoimmune diseases (e.g. inflammatory lung disease, cystic fibrosis, systemic lupus erythematosus). In many cases it remains asymptomatic.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Immunodeficiency due to MASP-2 deficiency | c3151085 | 4,571 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=331187 | 2021-01-23T17:59:02 | {"mesh": ["C565360"], "omim": ["613791"], "umls": ["C3151085"], "icd-10": ["D84.1"]} |
A number sign (#) is used with this entry because severe congenital neutropenia-2 (SCN2) is caused by heterozygous mutation in the GFI1 gene (600871) on chromosome 1p22.
For a phenotypic description and a discussion of genetic heterogeneity of severe congenital neutropenia, see SCN1 (202700).
Clinical Features
Person et al. (2003) identified a heterozygous mutation in the GFI1 gene (600871.0001; see MOLECULAR GENETICS) in a 4-month-old boy with SCN2 who had a neutrophil count of zero and marked monocytosis. The mutation segregated with his 3-year-old paternal half brother, who was identically affected, and with their father, who had recurrent pneumonia and pyogenic abscesses abating during childhood. The father's childhood blood counts were not available, but at age 27 his neutrophil count was low and monocytes high. His peripheral blood showed a population of myeloid cells that appeared immature. The myeloid, but not erythroid, colony formation potential of his cultured peripheral blood was lower than normal; nonerythroid colonies had intact differentiation to monocytes or macrophages but had an excess of myeloid precursors with no mature neutrophils. The absolute cell number of CD4 T lymphocytes was reduced. Moreover, B lymphocytes were also reduced. Peripheral blood lymphocytes from both the father and the older son showed similar trends, and both had poor uptake of 3H-thymidine after stimulation with phytohemagglutinin, alloantigen, and Candida albicans compared with normal individuals. Nonetheless, the child had adequate circulating titers to immunizations, and all immunoglobulin isotypes were present in his serum, indicating that, though reduced in number and activation potential, the T and B lymphocyte populations were functional.
Mapping
SCN2 results from mutation in the GFI1 gene, which was mapped to chromosome 1p22 by Bell et al. (1995).
Molecular Genetics
Person et al. (2003) screened GFI1 as a candidate for association with neutropenia in individuals without mutations in ELA2 (130130), the most common cause of autosomal dominant severe congenital neutropenia (SCN1; 202700). They identified a dominant-negative zinc finger mutation (600871.0003) in individuals with SCN2 that disabled transcriptional repressor activity. They showed by chromatin immunoprecipitation, gel shift, reporter assays, and elevated expression of ELA2 in vivo in neutropenic individuals that GFI1 represses ELA2, thus linking these 2 genes in a common pathway involved in myeloid differentiation.
Animal Model
Karsunky et al. (2002) found that Gfi1 is expressed outside the lymphoid system in granulocytes and activated macrophages, cells that mediate innate immunity (i.e., nonspecific immunity). They generated Gfi1-deficient mice (Gfi1 -/-) and showed that these animals are severely neutropenic and accumulate immature monocytic cells in blood and bone marrow. Their myeloid precursor cells were unable to differentiate into granulocytes upon stimulation with granulocyte colony-stimulating factor (138970) but could develop into mature macrophages. They found that macrophages of the Gfi1-null animals produced enhanced levels of inflammatory cytokines, such as tumor necrosis factor (191160), interleukin-10 (124092), and interleukin-1-beta (147720), when stimulated with bacterial lipopolysaccharide, and that Gfi1-null mice succumb to low doses of this endotoxin that were tolerated by wildtype mice. They concluded that Gfi1 influences the differentiation of myeloid precursors into granulocytes or monocytes and acts in limiting the inflammatory immune response.
See 600871 for further information on studies involving Gfi1 deficiency in animals.
INHERITANCE \- Autosomal dominant IMMUNOLOGY \- Low neutrophil number \- Elevated monocytes \- Immature neutrophils \- Immature monocytes \- Reduced absolute cell number of CD4 T lymphocytes \- Reduced B lymphocytes \- Recurrent pneumonia during childhood (some patients) \- Pyogenic abscesses during childhood (some patients) MOLECULAR BASIS \- Caused by mutation in the growth factor-independent 1 gene (GFI1, 600871.0001 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| NEUTROPENIA, SEVERE CONGENITAL, 2, AUTOSOMAL DOMINANT | c2751288 | 4,572 | omim | https://www.omim.org/entry/613107 | 2019-09-22T15:59:38 | {"mesh": ["C567748"], "omim": ["613107", "202700"], "orphanet": ["486"], "synonyms": []} |
Hinman syndrome (HS) or non-neurogenic neurogenic bladder is a voiding dysfunction of the bladder of neuropsychological origin that is characterized by functional bladder outlet obstruction in the absence of neurologic deficits.
## Epidemiology
Prevalence is not known.
## Clinical description
The syndrome typically occurs in early to late childhood but some adult cases have been observed. It typically manifests at some point after toilet training in early to late childhood. Patients present with enuresis, urgent voiding with incontinence, infrequent voiding, intermittency, straining, urinary tract infections and diffuse abdominal pain.
## Etiology
The syndrome is probably caused by acquired behavioral and psychological disorders manifested by bladder dysfunction mimicking neurologic disease. The dysfunction is associated with abnormal family dynamics in 50% of cases. Individuals under psychosocial pressure try to inhibit enuresis by voluntarily contracting the external sphincter. These voluntary contractions lead to an obstruction of the urinary tract, characterized by an intermittent stream, increased residual urine and increased intravesicular pressure. The resultant destruction of the urinary tract simulates true neurogenic bladder.
## Diagnostic methods
Diagnosis is based on the presence of the clinical and radiographic manifestations of neurogenic bladder in the absence of an underlying neurogenic abnormality. The diagnosis of HS should be considered at uroradiography in any child with unexplained bladder trabeculations, residual urine, incontinence or posterior urethral distention. The observation of posterior urethral distention following voluntary contraction of the external sphincter using a voiding cystourethrogram is suggestive of the condition.
## Differential diagnosis
Differential diagnoses include neurogenic bladder, enuresis and urinary tract infection. HS can be differentiated from neurogenic bladder by five criteria: a) intact perineal sensation and anal tone, b) normal anatomy and function of the lower extremities, c) absence of skin lesions overlying the sacrum, d) normal lumbosacral spine at plain radiography, and e) normal spinal cord and magnetic resonance imaging (MRI). It is important to distinguish between true neurogenic bladder and HS because true neurogenic bladder requires surgery.
## Management and treatment
Treatment for HS focuses on helping the child void normally through alleviating psychosocial pressures which are likely to be causing the problem with voiding through suggestion therapy including hypnosis, bladder retraining and timed voiding. Catheterization may be used if the bladder does not empty completely and if the bladder has uninhibited contractions. Antispasmodic drugs may be of benefit. Occasionally external sphincterotomy is required.
## Prognosis
HS can result in trabeculated bladder, ureterovesical obstruction, dilation of the upper tracts and renal damage and is often associated with urinary tract infections. However, improvements in patients with HS have been seen with bladder retraining and suggestion therapy.
*[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
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Hinman syndrome | c1997362 | 4,573 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=84085 | 2021-01-23T18:30:43 | {"icd-10": ["N32.8"], "synonyms": ["HAS", "HS", "Hinman-Allen syndrome", "Non-neurogenic neurogenic bladder", "Occult neuropathic bladder"]} |
A number sign (#) is used with this entry because some cases of megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) have been found to have somatic mutations in the PIK3CA gene (171834) on chromosome 3q26.
Description
Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) is characterized by a spectrum of anomalies including primary megalencephaly, prenatal overgrowth, brain and body asymmetry, cutaneous vascular malformations, digital anomalies consisting of syndactyly with or without postaxial polydactyly, connective tissue dysplasia involving the skin, subcutaneous tissue, and joints, and cortical brain malformations, most distinctively polymicrogyria (summary by Mirzaa et al., 2012). This disorder is also known as the macrocephaly-capillary malformation (MCM) syndrome (Conway et al., 2007). Mirzaa et al. (2012) suggested use of the term MCAP rather than MCM to reflect the very large brain size, rather than simply large head size, that characterizes this syndrome, and the importance and high frequency of perisylvian polymicrogyria.
Clinical Features
Moore et al. (1997) described 13 unrelated children with abnormalities of somatic growth, face, brain, and connective tissue including vasculature. They proposed that these children had a distinct disorder, megalencephaly-cutis marmorata telangiectatica congenita (MCMTC), with the features of cutis marmorata, nevus flammeus, cavernous hemangiomas, asymmetric growth pattern, central nervous system malformations, and neurologic abnormalities. See 219250 for a discussion of cutis marmorata telangiectatica congenita (CMTC) without report of the other major findings.
Clayton-Smith et al. (1997) described 9 additional patients and recognized the macrocephaly-CMTC syndrome as a distinct entity.
Carcao et al. (1998) described a child, with nonconsanguineous parents of Guyanese ancestry, with cherry red macules, megalencephaly with hemifacial and segmental overgrowth, macrosomia, cutis marmorata telangiectatica congenita of the trunk, and visceral and subcutaneous cavernous hemangiomas. The megalencephaly was accompanied by MRI findings of CNS dysgenesis with protrusion of the cerebellar tonsils through the foramen magnum (Chiari type I; 118420), lumbar syrinx, and hydrops of the optic nerves. The findings in the patient suggest that a visceral hemangioma and cherry red macules in the eye may be findings of MCMTC. The cases reported by Moore et al. (1997) and Carcao et al. (1998) supported the concept of CNS and vascular dysgenesis in MCMTC.
Vogels et al. (1998) reviewed 4 children with the same association of macrocephaly-body asymmetry-cutis marmorata telangiectatica and cutaneous hemangiomas observed over a period of 20 years. They commented on a distinct craniofacial appearance with macrocephaly and full lips.
Yano and Watanabe (2001) described 3 cases with features of macrocephaly-cutis marmorata telangiectatica congenita with poor clinical outcomes. All cases showed severe growth failure resulting in a weight below the second percentile before a year of age, 2 cases died suddenly of unknown cause at 33 and 19 months, and a third developed atrial flutter, leading to hypotensive shock during a viral illness at age 13 months. The authors suggested that a distinct clinical subtype of MCMTC may exist, and recommended that patients with this condition presenting with severe failure to thrive be closely monitored for arrhythmia and life-threatening episodes.
Lapunzina et al. (2004) reported 6 additional patients with MCMTC and reviewed 69 previously reported patients. Based on their findings, they listed the very frequent (observed in more than 75%), frequent (25 to 75%), and less frequent (less than 25%) components of the syndrome. Mode of inheritance was not clear from this analysis. There was a slight preponderance of males (male:female ratio, 41:33). No affected parents or sibs were observed. Increased paternal age was noted in several cases and parental consanguinity in some.
Giuliano et al. (2004) described 7 patients with MCMTC, including 2 with unusual cerebral manifestations and severe outcomes. One had a complex congenital heart defect and died in the neonatal period; brain MRI revealed generalized cortical dysplasia. The other had an ischemic stroke at age 14; cerebral arteriography showed an abnormal vascular pattern.
Garavelli et al. (2005) reported 10 patients with MCMTC, all of whom had some structural cerebral abnormalities on MRI, including asymmetric hemimegalencephaly, Chiari type I malformation (70%), enlargement of the lateral ventricles, and an abnormally increased signal of periventricular white matter.
Conway et al. (2007) reported a longitudinal analysis of neuroimaging findings in 17 patients with macrocephaly-capillary malformation. More than half the patients had cerebellar tonsillar herniation associated with rapid brain growth and progressive crowding of the posterior fossa during infancy. Concurrent findings included ventriculomegaly and dilated dural venous sinuses, reflecting a dynamic process of mechanical compromise in the posterior fossa. The malformation was considered to be distinct from Chiari malformation type I as it appeared to be acquired in at least 4 patients. There was also evidence of abnormal cortical morphogenesis, including focal cortical dysplasia, polymicrogyria, and cerebral and/or cerebellar asymmetric overgrowth. Other findings included a high frequency of cavum septum pellucidum or vergae, thickened corpus callosum, prominent optic nerve sheaths and a single case of venous sinus thrombosis. One patient was found to have a frontal perifalcine mass resembling a meningioma at age 5 years.
Canham and Holder (2008) described a 14-year-old girl with mild MCMTC who was noted to have 'mottled skin' in infancy that had faded by the time of presentation at 3.5 years of age, at which examination she was noted to have macrocephaly, capillary hemangioma over the upper eyelids, nasal bridge, upper lip, and philtrum, and a faint pigmented area over the lower back. In early childhood, she had been diagnosed with a semantic pragmatic language disorder, although she subsequently entered mainstream school without a statement of special educational needs. At 14 years of age, she developed marked varicose veins around her left knee and was found to have incompetence of the long saphenous vein on Duplex scan, with no evidence of other structural anomalies. Her facial hemangioma had almost entirely resolved. Growth had ceased at menarche 3 years earlier, and although her height and head circumference were above the 99.6th centile, the authors noted that those parameters would likely be within the normal range in adulthood. Her secondary dentition had come in earlier than usual, and her teeth were very large, such that several had to be removed. Canham and Holder (2008) concluded that it is possible to have this condition and function within the normal range or with only minor problems, particularly for children with no structural brain anomaly.
Gripp et al. (2009) presented 3 unrelated patients with a phenotype consistent with MCM. In the first patient, brain MRI showed striking megalencephaly and polymicrogyria, along with very large ventricles and cerebellar tonsillar herniation filling the cisterna magna. She had a nevus flammeus extending over the forehead, nose, and philtrum, as well as a capillary malformation resembling cutis marmorata over the trunk and extremities. She had mild coarse dysmorphic features, such as low nasal bridge, wide lips, and low-set ears. Other features included ventricular septal defect and a vascular ring formed by a right aortic arch and aberrant left subclavian artery, as well as vesicoureteral reflux. The second child had megalencephaly with mild ventriculomegaly and diffuse bilateral polymicrogyria. Other features included postaxial polysyndactyly of 1 foot, frontal bossing, depressed nasal bridge, hypertelorism, low-set ears, and mild hemihyperplasia of the right face. Skin findings included a large hemangioma over the left elbow, a facial nevus flammeus that extended from the upper lip to the forehead, and generalized cutis marmorata. The third child had increasing macrocephaly from birth. Brain MRI at 6 weeks showed showed large brain size, extensive asymmetric bilateral polymicrogyria, and mildly enlarged lateral ventricles. Repeat brain MRI at 5 months demonstrated progressive ventricular enlargement and cerebellar tonsillar herniation filling the cisterna magna and crowding the back of the brainstem and upper cervical spinal cord. There was frontal bossing, mildly deep-set eyes, and thickened soft tissue of the cheeks, philtrum and lips. Although there was no syndactyly, polydactyly, or visible capillary malformation, he had mild cutis marmorata, and abdominal ultrasound reportedly showed a vascular anomaly beneath the umbilicus. All children were born premature at 30, 34, and 38 weeks' gestation, respectively. All were less than 12 months of age at the time of the report, and all showed hypotonia with delayed development. None of the parents were related, and there was no family history in any case. Gripp et al. (2009) noted that 2 of the patients had an initial diagnosis of megalencephaly, polymicrogyria-polydactyly hydrocephalus syndrome (MPPH; 603387), a similar syndrome with overlapping features. Gripp et al. (2009) suggested that the 2 disorders may be related or on the same phenotypic spectrum; they proposed the term MPPH-CM to refer to this phenotypic spectrum.
Diagnosis
Franceschini et al. (2000) reported 2 patients with features consistent with a diagnosis of MCMTC, only one of whom had typical cutis marmorata when examined at age 4 months. Based on these cases and their review of the literature, the authors suggested that macrocephaly and at least 2 of the main reported findings (i.e., overgrowth, cutis marmorata, angiomata, polydactyly/syndactyly, asymmetry) are necessary for the diagnosis of MCMTC. They also noted the increased risk for development of nonobstructive hydrocephalus in this syndrome.
Martinez-Glez et al. (2010) reported 13 Spanish patients with MCM and proposed diagnostic criteria. Among their patients, the most frequent features were neuroimaging alterations (100%), macrocephaly (92%), overgrowth (92%), capillary malformations (85%), developmental delay (85%), and asymmetry (62%). Less common features included capillary malformation of the nose, lip and/or philtrum (54%), hydrocephalus (46%), hypotonia (46%), joint laxity (38%), tonsillar herniation/Chiari I (31%), syndactyly of the toes (31%), hemimegalencephaly (31%), polymicrogyria (31%), and frontal bossing (25%). The proposed diagnostic criteria included 3 of 4 major criteria and 2 of 7 minor criteria. Major criteria included macrocephaly, capillary malformation, overgrowth/asymmetry, and neuroimaging alterations. Minor criteria included developmental delay, midline facial capillary malformation, neonatal hypotonia, syndactyly/polydactyly, frontal bossing, connective tissue abnormalities, and hydrocephalus. Genomewide SNP array analysis did not identify any altered gene or region common to all patients.
Mirzaa et al. (2012) reviewed the phenotypic features of 42 patients with a megalencephalic syndrome in an attempt to clarify and simplify the categorization and diagnosis of these disorders. Statistical analysis of particular features yielded 2 main groups: 21 patients with a vascular malformation consistent with MCAP and 19 with no vascular malformation consistent with MPPH; 2 patients were in an overlap group. Vascular malformations were significantly associated with syndactyly and somatic overgrowth at birth, and lack of vascular malformations was associated with polydactyly. The various features were assigned to 5 major classes of developmental abnormalities. Both MCAP and MPPH had (1) megalencephaly and variable somatic overgrowth (particularly in MCAP); (2) distal limb malformations, syndactyly being more associated with MCAP and polydactyly with MPPH; and (3) similar cortical brain malformations (mainly polymicrogyria). In addition, MCAP included (4) developmental vascular abnormalities and (5) occasional connective tissue dysplasia, such as hyperelasticity or thick skin. MPPH lacks vascular malformations, connective tissue dysplasia, and heterotopia. Based on these findings, Mirzaa et al. (2012) proposed diagnostic criteria for the MCAP and MPPH syndromes, and postulated that the 2 disorders represent different, although overlapping, syndromes that may be caused by different genes involved in the same biologic pathway.
Cytogenetics
Stoll (2003) reported a patient with MCMTC who carried a de novo translocation t(2;17)(p11;p13). At birth the patient had widespread erythematous violaceous reticulate cutaneous marking, nevus flammeus of the philtrum, syndactyly of third and fourth fingers of the right hand, prominent forehead, upslanting palpebral fissures, flat nasal bridge, and hypotonia. Transfontanellar ultrasound showed mild ventriculomegaly. Motor development was delayed. At 18 months of age CT scan showed cerebral asymmetry and dilated cerebral ventricles; a ventriculoperitoneal shunt was inserted. Right upper and lower limbs were larger than those on the left. Knees, ankles, and small joints of the hands were hypermobile. The patient died suddenly at 8 years of age.
Molecular Genetics
Riviere et al. (2012) conducted exome sequencing in an individual with MCAP and his parents and performed an analysis of de novo mutations in this trio by including the raw variants that did not meet their initial hard-filtering criteria. Using this approach, they identified a missense change in the PIK3CA gene (G914R; 171834.0011), which encodes the p110-catalytic subunit of class IA PI3K. This mutation was supported by 20 of 177 reads (11%) in the exome sequencing data and was confirmed to be de novo and mosaic by Sanger sequencing and a custom restriction enzyme assay. Riviere et al. (2012) then sequenced the coding exons of PIK3CA in 29 individuals with megalencephaly with no mutations in the AKT3 (611223) or PIK3R2 (603157) genes and identified 14 additional PIK3CA mutations, with mutant allele frequencies ranging from 10 to 50%. Standard variant calling in exomes from 7 additional subjects with MCAP identified a mutation of the PIK3CA gene (C378Y; 171834.0012) that was supported by 68 of 250 reads (27%) in another individual. This mutation showed variable levels of mosaicism depending on the tissue tested. Manual inspection of the Sequence Alignment/Map (SAM) files of the remaining 6 subjects with MCAP of unknown cause using the Integrative Genomics Viewer revealed other candidate mosaic mutations in the PIK3CA gene in all of the 6 affected individuals, with mutations represented by 2 to 15% of the total reads. Sanger sequencing, a custom restriction enzyme assay, or both, confirmed all 6 mutations. Riviere et al. (2012) next performed targeted ultra-deep sequencing (coverage of more than 10,000 reads) of 5 mutation sites in 15 mutation-negative affected individuals, as well as in known mutation carriers and control individuals. This experiment confirmed all previously identified mutations and detected 2 additional low-level mosaic mutations missed by Sanger sequencing. Both were confirmed by a second deep-sequencing experiment and showed mutant allele frequencies ranging from 1 to 8%. Riviere et al. (2012) identified a total of 24 affected individuals with PIK3CA mutations, and all but 3 (LR06-220, LR11-153, and LR11-230) showed evidence of postzygotic mosaicism. In 13 individuals with MCAP, no mutation was found in the PIK3CA gene, the PTEN gene (601728), or 4 other genes encoding subunits of class IA PI3K.
Lee et al. (2012) performed whole-exome sequencing on brain and peripheral blood DNA from 5 HME cases and identified 3 missense mutations: one in the PIK3CA gene (E545K; 171834.0003), one in the AKT3 gene (E17K; 611223.0003), and one in the MTOR gene (C1483Y; see 616638). The individual with the MTOR gene mutation also carried a diagnosis of hypomelanosis of Ito (300337). Lee et al. (2012) then used a modified single base-extension protocol followed by mass spectrometry analysis to detect somatic mutations at a frequency as low as 3% in genetically heterogeneous samples. Reanalysis of the same DNA samples used for whole-exome sequencing again showed the absence of the mutant allele in blood but its presence in the brain, with similar mutation burden as that detected with Illumina sequencing. These somatic mutations were detected at a frequency of 36.6%, 40.4%, and 8.1% in each brain sample. Using the same technology, Lee et al. (2012) screened for these mutations in 15 other HME cases and identified 3 additional cases carrying the PIK3CA E545K variant, each with a mutation burden of about 30%. One of these individuals had hypertrophic regions in the right hand and foot.
Nomenclature
Toriello and Mulliken (2007) suggested that the name MCMTC should be changed to MCM, for 'macrocephaly-capillary malformation.' The authors argued that the vascular lesions in this disorder are neither cutis marmorata nor cutis marmorata telangiectatica congenita, but are rather a type of capillary malformation in a patchy reticular pattern. Mirzaa et al. (2012) suggested use of the term MCAP rather than MCM to reflect the very large brain size, rather than simply large head size, that characterizes this syndrome, and the importance and high frequency of perisylvian polymicrogyria.
INHERITANCE \- Somatic mutation GROWTH Height \- Increased birth length Weight \- Increased birth weight Other \- Somatic overgrowth, asymmetric \- Hemihyperplasia HEAD & NECK Head \- Megalencephaly \- Macrocephaly, progressive in infancy Face \- Broad forehead \- Smooth philtrum Ears \- Fleshy earlobes Eyes \- Epicanthus \- Hypertelorism \- Downslanting palpebral fissures \- Unilateral microphthalmia Nose \- Flattened nasal bridge Mouth \- Narrow arched palate CARDIOVASCULAR Heart \- Ventricular septal defect SKELETAL \- Joint laxity Hands \- Syndactyly \- Polydactyly Feet \- Syndactyly \- Polydactyly SKIN, NAILS, & HAIR Skin \- Thick, loose, doughy skin \- Cutaneous vascular malformations \- Patchy, reticular stains \- Cutis marmorata MUSCLE, SOFT TISSUES \- Thickened subcutaneous tissue NEUROLOGIC Central Nervous System \- Developmental delay \- Mental retardation \- Hypotonia \- Seizures \- MRI shows brain asymmetry \- Ventriculomegaly \- Hydrocephalus \- Large cerebellum, progressive \- Cerebellar tonsil herniation \- Crowding of the posterior fossa \- Cavum septum pellucidum \- Cavum vergae \- Polymicrogyria \- Cortical dysgenesis \- Thickened corpus callosum \- Thickened optic nerve sheath \- Dilated venous sinuses \- White matter signal abnormalities in the deep white matter and periventricular regions NEOPLASIA \- Increased risk of meningioma \- Increased risk of Wilms tumor \- Increased risk of leukemia MOLECULAR BASIS \- Caused by somatic mutation in the phosphatidylinositol 3-kinase, catalytic, alpha polypeptide gene (PIK3CA, 171834.0003 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| MEGALENCEPHALY-CAPILLARY MALFORMATION-POLYMICROGYRIA SYNDROME | c1865285 | 4,574 | omim | https://www.omim.org/entry/602501 | 2019-09-22T16:13:38 | {"mesh": ["C536142"], "omim": ["602501"], "orphanet": ["60040"], "synonyms": ["Alternative titles", "MACROCEPHALY-CAPILLARY MALFORMATION", "MEGALENCEPHALY-CAPILLARY MALFORMATION SYNDROME", "MACROCEPHALY-CUTIS MARMORATA TELANGIECTATICA CONGENITA", "MEGALENCEPHALY-CUTIS MARMORATA TELANGIECTATICA CONGENITA"], "genereviews": ["NBK153722"]} |
Epidermolysis bullosa simplex (EBS), generalized is a form of epidermolysis bullosa, a group of genetic conditions that cause the skin to be fragile and blister easily. This disorder usually presents at birth or during infancy and results in widespread blisters over the body's surface. Though it is not a common feature of this type, scarring may occur. There may also be mild involvement of mucous membranes, fingernails and toenails, and localized thickening of the skin on the soles of the feet and the palms of the hands that increases with age. There are two major subtypes of this condition and 17 minor subtypes. The four most common types of epidermolysis bullosa simplex are EBS localized, EBS generalized intermediate, EBS with mottled pigmentation and EBS generalized severe. These four common types are caused by mutations in the EXPH5, KRT5, KRT14, and TGM5 genes. This condition is usually inherited in an autosomal dominant or autosomal recessive fashion.. These conditions are diagnosed based on the symptoms and by genetic testing. Treatment is focused on managing the symptoms. The symptoms of EBS tend to get better with age. The long-term outlook for people with EBS depends on how well the skin symptoms can be managed.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Epidermolysis bullosa simplex, generalized | c0079299 | 4,575 | gard | https://rarediseases.info.nih.gov/diseases/2147/epidermolysis-bullosa-simplex-generalized | 2021-01-18T18:00:41 | {"mesh": ["D016110"], "omim": ["131900"], "umls": ["C0079299"], "synonyms": ["EBS, generalized", "Generalized EBS", "Epidermolysis bullosa simplex, Koebner type", "EBS-K", "Epidermolysis bullosa simplex, generalized non-Dowling-Meara"]} |
A number sign (#) is used with this entry because of evidence that susceptibility to accelerated tumor formation is associated with variation in the MDM2 gene (164785) on chromosome 12q15.
Mapping
Susceptibility to accelerated tumor formation was associated by Bond et al. (2004) with a polymorphism in the MDM2 gene, which Mitchell et al. (1995) had mapped to chromosome 12q14.3-q15.
Molecular Genetics
By screening 50 healthy volunteers, Bond et al. (2004) identified a SNP in the MDM2 promoter, -410T-G (164785.0001), which they called SNP309 (rs2279744) because of its position at the 309th nucleotide of intron 1. SNP309 was present at a relatively high frequency in both the heterozygous state (T/G, 40%) and the homozygous state (G/G, 12%). Bond et al. (2004) showed that SNP309 increased the affinity of the transcriptional activator Sp1 (189906), resulting in higher levels of MDM2 RNA and protein and subsequent attenuation of the p53 (191170) pathway. They demonstrated that SNP309 was associated with accelerated tumor formation in both hereditary and sporadic cancers in humans. Bond et al. (2004) studied 88 individuals who were members of Li-Fraumeni syndrome (LFS1; 151623) families and had germline mutations in 1 allele of p53. The frequency of SNP309 in these individuals was similar to that found in the 50 normal volunteers. Of the 88 individuals in the Li-Fraumeni cohort, 66 were diagnosed with at least 1 cancer at a median age of 22 years old. Those either heterozygous or homozygous for SNP309 developed tumors on average 7 years earlier than those lacking SNP309. To determine whether SNP309 acted upon sporadic tumors as well as genetically altered individuals with a p53 defect, Bond et al. (2004) studied a group of patients who developed sporadic adult soft tissue sarcomas and had no known hereditary cancer predisposition and no known germline p53 mutation. Individuals homozygous for SNP309 were diagnosed on average 12 years earlier than those without SNP309, and the frequency of the SNP309 G allele was greatly increased in those who developed soft tissue sarcomas at a young age. These data demonstrated that SNP309 does not require the presence of an inactivating germline p53 mutation to associate with earlier soft tissue sarcoma formation.
Bougeard et al. (2006) studied the effect of the SNP309 polymorphism and the arg72-to-pro polymorphism of the p53 gene (191170.0005) on cancer risk in 61 French carriers of the p53 germline mutation. The mean age of tumor onset in MDM2 SNP309 G allele carriers (19.6 years) was significantly different from that observed in patients homozygous for the T allele (29.9 years, p less than 0.05). For the p53 codon 72 polymorphism, the mean age of tumor onset in arg allele carriers (21.8 years) was also different from that of pro/pro patients (34.4 years, p less than 0.05). Bougeard et al. (2006) also observed a cumulative effect of both polymorphisms because the mean ages of tumor onset in carriers of MDM2 G and p53 arg alleles (16.9 years) and those with the MDM2 T/T and p53 pro/pro genotypes (43 years) were clearly different (p less than 0.02). Therefore, the results confirmed the impact of the MDM2 SNP309 G allele on the age of tumor onset in germline p53 mutation carriers, and suggested that this effect may be amplified by the p53 arg72 allele. Polymorphisms affecting p53 degradation therefore represent one of the few examples of modifier genetic factors identified to that time in mendelian predispositions to cancer.
In 25 Dutch and 11 Finnish p53 mutation carriers, Ruijs et al. (2007) observed a significantly earlier age of tumor onset in SNP309 G allele carriers versus those homozygous for the T allele (mean difference, 16 years earlier; p = 0.005), confirming previously reported results. In 72 Dutch p53-negative LFS and LFS-related patients, no difference was seen in the age of tumor onset, but there was a significantly higher percentage of SNP309 G/G homozygotes than in the general population (p = 0.02). Ruijs et al. (2007) suggested that the MDM2 SNP309 G allele contributes to cancer susceptibility in LFS and LFS-related families.
INHERITANCE \- Autosomal dominant NEOPLASIA \- Accelerated tumor formation MOLECULAR BASIS \- Susceptibility conferred by mutation in the MDM2 protooncogene (MDM2, 164785.0001 ) ▲ Close
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| ACCELERATED TUMOR FORMATION, SUSCEPTIBILITY TO | c3280690 | 4,576 | omim | https://www.omim.org/entry/614401 | 2019-09-22T15:55:24 | {"omim": ["614401"]} |
A rare partial autosomal trisomy/tetrasomy characterized by obesity, global developmental delay and intellectual disability, facial dysmorphism (synophrys, high-arched eyebrows, large posteriorly rotated ears, upturned nose, long smooth philtrum, overbite and high palate), large hands and limb hypotonia. Additional features include seizures and behavioral abnormalities.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| 11p15.4 microduplication syndrome | None | 4,577 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=300305 | 2021-01-23T19:10:33 | {"icd-10": ["Q92.3"], "synonyms": ["Dup(11)p(15.4)", "Trisomy 11p15.4"]} |
Hypomyelination with brain stem and spinal cord involvement and leg spasticity is a rare, genetic, leukodystrophy disorder characterized by diffuse hypomyelination in the supratentorial brain white matter, brain stem and spinal cord. Patients usually present nystagmus, lower limb spasticity, hypotonia, and motor developmental delay, as well as MRI signal abnormalities involving the corpus callosum, anterior brainstem, pyramidal tracts, superior and inferior cerebellar peduncles, dorsal columns and/or lateral corticospinal tracts.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Hypomyelination with brain stem and spinal cord involvement and leg spasticity | c3809008 | 4,578 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=363412 | 2021-01-23T18:30:20 | {"omim": ["615281"], "icd-10": ["E75.2"], "synonyms": ["HBSL"]} |
Congenital erosive and vesicular dermatosis
SpecialtyDermatology
Congenital erosive and vesicular dermatosis is a cutaneous condition characterized by generalized erosions, vesicles, crusting and ‘scalded skin-like’ erythematous areas affecting up to 75% of the body surface area.[1]
## See also[edit]
* Melanotic neuroectodermal tumor of infancy
* 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.
This dermatology article is a stub. You can help Wikipedia by expanding it.
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* e
*[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
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Congenital erosive and vesicular dermatosis | None | 4,579 | wikipedia | https://en.wikipedia.org/wiki/Congenital_erosive_and_vesicular_dermatosis | 2021-01-18T18:52:39 | {"umls": ["CL942357"], "wikidata": ["Q5160429"]} |
Chromosome 1q deletion is a chromosome abnormality that occurs when there is a missing copy of the genetic material located on the long arm (q) of chromosome 1. The severity of the condition and the signs and symptoms depend on the size and location of the deletion and which genes are involved. Features that often occur in people with chromosome 1q deletion include developmental delay, intellectual disability, behavioral problems, and distinctive facial features. Most cases are not inherited, but people can pass the deletion on to their children. 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
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Chromosome 1q deletion | c0795799 | 4,580 | gard | https://rarediseases.info.nih.gov/diseases/8669/chromosome-1q-deletion | 2021-01-18T18:01:23 | {"synonyms": ["Deletion 1q", "Monosomy 1q", "1q deletion", "1q monosomy", "Partial monosomy 1q"]} |
A number sign (#) is used with this entry because of evidence that Kaiser-type neurogenic scapuloperoneal syndrome (SCPNK) is caused by heterozygous mutation in the DES gene (125660) on chromosome 2q35.
Clinical Features
Peroneal atrophy is accompanied by bilateral foot drop and talipes equinovarus. Following atrophy of the lower legs, the shoulder girdle is involved. Bulbar involvement is late. Autopsy shows muscular atrophy and involvement of caudal cranial nuclei. Palmer (1932) described a family with 8 persons affected, the earliest having onset about 1800. Davidenkow (1939) suggested that cases reported by Wohlfart (see juvenile muscular atrophy, 253400 and 158600) were the same as those he designated scapuloperoneal amyotrophy.
Kaeser (1965) reported a kindred (kindred F) in which 12 members in 5 generations had neurogenic scapuloperoneal syndrome in an autosomal dominant pattern of inheritance. Age at onset was between 30 and 50 years and followed a slowly progressive course. In the first 3 generations, weakness and atrophy started in the legs and spread to the thighs and pelvic girdle, resulting in paraplegia. In the fifth generation, the atrophies extended to the shoulder girdle, upper arms, neck, face, pharynx, and external eye muscles. Histologic examination at autopsy in 1 patient showed that the atrophies were neurogenic in origin, similar to those in Wohlfart-Kugelberg-Welander muscular atrophy. Kindred F, however, demonstrated significant differences from the cases reported by Davidenkow (1939) and from Wohlfart-Kugelberg-Welander juvenile muscular atrophy. Kaeser (1965) concluded that the scapuloperoneal syndrome is a descriptive term comprising various myopathies, peroneal muscular atrophies, and spinal muscular atrophies.
Emery et al. (1968) and Schuchmann (1970) reported sporadic childhood cases with electromyographic and biopsy evidence of neurogenic disease; motor nerve conduction velocities were borderline or normal, suggesting anterior horn cell pathology. Kazakov et al. (1976) provided a follow-up on the kindred reported by Davidenkow (1939). The disorder in many ways resembled Landouzy-Dejerine facioscapulohumeral muscular dystrophy (158900). There are both myopathic (see 181430) and neurogenic dominant forms of the scapuloperoneal syndrome. Emery (1981) described a large kindred in the West of Scotland. Ferguson-Smith and McKusick (1981) saw a brother and sister who clearly had this disorder. The sister had been diagnosed as having Charcot-Marie-Tooth disease and the brother muscular dystrophy. Their disease was neurogenic scapuloperoneal syndrome.
Tawil et al. (1995) described a 3-generation kindred in which 7 members were affected with neurogenic scapuloperoneal syndrome in which nerve conduction velocities showed evidence of a mild demyelinating polyneuropathy and electromyography demonstrated acute and chronic denervation in both proximal and distal muscles. The proband fulfilled the diagnostic criteria for facioscapulohumeral dystrophy (158900), but none of the other affected members had facial weakness. Linkage to markers on 4q35 was excluded, demonstrating this to be a genetically distinct disorder.
Walter et al. (2007) studied the large, multigenerational kindred first described by Kaeser (1964, 1965) with a peculiar scapuloperoneal distribution of weakness and atrophy, inherited in an autosomal dominant fashion, named scapuloperoneal syndrome type Kaeser. A large clinical variability was recognized, even within the same family, ranging from scapuloperoneal (n = 2, 12%), limb-girdle (n = 10, 60%), and distal phenotypes (n = 3, 18%) with variable cardiac (n = 7, 41%) or respiratory involvement (n = 7, 41%). Facial weakness, dysphagia, and gynecomastia were frequent additional symptoms. Affected men seemingly carried a higher risk of sudden, cardiac death as compared to affected women. Histologic and immunohistochemical examination of muscle biopsy specimens revealed a wide spectrum of findings ranging from near normal or unspecific pathology to typical, mild fibrillar changes with accumulation of desmin.
Molecular Genetics
By genetic analysis of the original kindred described by Kaeser (1964), Walter et al. (2007) found possible linkage to the gene encoding desmin and identified a heterozygous missense mutation of the desmin gene (R350P; 125660.0016) cosegregating with the disorder. Moreover, Walter et al. (2007) found the R350P mutation in 4 unrelated German families, which allowed for genotype-phenotype correlations in a total of 15 patients carrying the same mutation. This study suggested that the clinical and pathologic variability generally observed in desminopathies may not be attributed to the nature of the DES mutation alone, but may be influenced by additional genetic and epigenetic factors such as gender. Walter et al. (2007) suggested that mutations of the desmin gene should be considered early in the diagnostic workup of any adult-onset, autosomal dominant myopathy, even if specific myofibrillar pathology is absent.
Limbs \- Talipes equinovarus Muscle \- Peroneal atrophy \- Shoulder girdle atrophy Neuro \- Neurogenic scapuloperoneal syndrome \- Bilateral foot drop \- Late bulbar involvement Inheritance \- Autosomal dominant ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| SCAPULOPERONEAL SYNDROME, NEUROGENIC, KAESER TYPE | c1867005 | 4,581 | omim | https://www.omim.org/entry/181400 | 2019-09-22T16:34:59 | {"mesh": ["C566695"], "omim": ["181400"], "orphanet": ["85146"], "synonyms": ["Alternative titles", "KAESER SYNDROME", "STARK-KAESER SYNDROME", "SCAPULOPERONEAL SYNDROME, NEUROGENIC TYPE, OF KAESER"]} |
Onychophosis is a localized or diffuse hyperkeratotic tissue that develops on the lateral or proximal nailfolds, within the space between the nailfolds and the nail plate, and is a common finding in the elderly.[1]:784 Onychophosis may involve the subungual area, as a direct result of repeated minor trauma, and most frequently affects the first and fifth toes.[1]:784
## References[edit]
1. ^ a b James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
This condition of the skin appendages 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
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Onychophosis | c0423812 | 4,582 | wikipedia | https://en.wikipedia.org/wiki/Onychophosis | 2021-01-18T19:05:47 | {"umls": ["CL548940"], "wikidata": ["Q7095156"]} |
A number sign (#) is used with this entry because of evidence that familial hypertrophic cardiomyopathy-16 (CMH16) is caused by heterozygous mutation in the MYOZ2 gene (605602) on chromosome 4q26.
For a phenotypic description and a discussion of genetic heterogeneity of familial hypertrophic cardiomyopathy, see CMH1 (192600).
Clinical Features
Osio et al. (2007) studied a black family in which 6 individuals over 3 generations, including a pair of dizygotic twins, had hypertrophic cardiomyopathy. The index case presented at 12 years of age with symptoms of diastolic heart failure and episodes of syncope. She had severe left ventricular hypertrophy (LVH) with a septal thickness of 3.2 cm, atrial fibrillation, and runs of ventricular tachycardia. At 36 years of age, she had left bundle branch block and had undergone implantation of a permanent pacemaker and an automatic internal cardioverter-defibrillator. Her 62-year-old mother had borderline LVH with normal sinus rhythm, and her 27-year-old sister and 42-year-old twin male cousins had LVH and normal sinus rhythm with repolarization abnormalities. The dizygotic twin brothers also exhibited different degrees of asymmetric septal hypertrophy, which the authors suggested might reflect the effects of modifier genes and environmental factors. Osio et al. (2007) noted that affected family members had normal skeletal muscle strength on physical examination, but that subclinical abnormalities might exist.
Mapping
In 6 affected individuals from a 3-generation black family segregating autosomal dominant hypertrophic cardiomyopathy, in whom mutation in 4 common CMH genes had been excluded by direct sequencing and 4 additional CMH genes had been excluded by locus-specific haplotyping, Osio et al. (2007) identified a common haplotype on chromosome 4q26-q27 that was not shared by 4 clinically normal family members. A maximum lod score of 2.03 was obtained at D4S2303 and D4S1573, the closest markers to the candidate gene MYOZ2 (605602).
Molecular Genetics
In 6 affected individuals from a 3-generation black family segregating autosomal dominant CMH mapping to chromosome 4q26-q27, Osio et al. (2007) identified heterozygosity for a missense mutation in the candidate gene MYOZ2 (S48P; 605602.0001). The mutation was not found in 4 clinically normal family members or in 658 controls who were asymptomatic and had normal electrocardiograms and echocardiograms, including 253 black individuals. Analysis of MYOZ2 in 516 additional CMH probands revealed another heterozygous missense mutation (I246M; 605602.0002) in a white proband who had 2 deceased sibs with CMH; this mutation was not found in 517 controls, including 405 white individuals.
Animal Model
Ruggiero et al. (2013) generated transgenic mice carrying the Myoz2 S48P or I246M mutations and observed the development of cardiac hypertrophy with preserved systolic function; histologic examination revealed cardiac myocyte hypertrophy and interstitial fibrosis. Immunofluorescence staining showed colocalization of wildtype and mutant Myoz2 proteins with alpha-actinin (see 102573) at the Z discs, and electron microscopy revealed disrupted and malaligned Z discs in the mutant mice. Cardiac calcineurin (see 114105) activity was unchanged in the mutant mice compared to wildtype; however, levels of phospho-Erk1 (601795)/Erk2 (176948) were increased and levels of Jnk54/46 were reduced in transgenic mice compared to controls. Ruggiero et al. (2013) proposed that the CMH phenotype caused by MYOZ2 mutations might be independent of calcineurin activity in the heart.
INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Left ventricular hypertrophy \- Repolarization abnormalities \- Asymmetric septal hypertrophy (in some patients) \- Atrial fibrillation (in some patients) \- Ventricular tachycardia (in some patients) \- Left bundle branch block (in some patients) MOLECULAR BASIS \- Caused by mutation in the myozenin 2 gene (MYOZ2, 605602.0001 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 16 | c3151204 | 4,583 | omim | https://www.omim.org/entry/613838 | 2019-09-22T15:57:16 | {"omim": ["613838"], "genereviews": ["NBK1768"]} |
## Summary
### Clinical characteristics.
SOST-related sclerosing bone dysplasias include sclerosteosis and van Buchem disease, both disorders of progressive bone overgrowth due to increased bone formation.
The major clinical features of sclerosteosis are progressive skeletal overgrowth, most pronounced in the skull and mandible, and variable syndactyly, usually of the second (index) and third (middle) fingers. Affected individuals appear normal at birth except for syndactyly. Facial distortion due to bossing of the forehead and mandibular overgrowth is seen in nearly all individuals and becomes apparent in early childhood with progression into adulthood. Hyperostosis of the skull results in narrowing of the foramina, causing entrapment of the seventh cranial nerve (leading to facial palsy) with other, less common nerve entrapment syndromes including visual loss (2nd cranial nerve), neuralgia or anosmia (5th cranial nerve), and sensory hearing loss (8th cranial nerve). In sclerosteosis, hyperostosis of the calvarium reduces intracranial volume, increasing the risk for potentially lethal elevation of intracranial pressure. Survival of individuals with sclerosteosis into old age is unusual, but not unprecedented.
The manifestations of van Buchem disease are generally milder than sclerosteosis and syndactyly is absent; life span appears to be normal.
### Diagnosis/testing.
The diagnosis of SOST-related sclerosing bone dysplasia is established in a proband with typical clinical and radiographic findings and identification of biallelic pathogenic variants in SOST (for sclerosteosis) or the presence of a biallelic 52-kb deletion downstream of SOST (for van Buchem disease) on molecular genetic testing.
### Management.
No specific treatment is currently available, and management aims at relieving symptoms and preventing complications.
Treatment of manifestations: Surgical correction of syndactyly; surgical decompression of entrapped cranial nerves, notably the facial nerve; craniectomy and ventriculo-peritoneal drain for increased intracranial pressure; surgical reduction of mandibular overgrowth; hearing aids with middle ear surgery or cochlear implant depending on nature of hearing loss; spinal cord decompression for radiculopathy; orbital decompression for proptosis or glaucoma.
Surveillance: At least annual assessments from infancy for bone mass, evidence of cranial nerve entrapment and of increased intracranial pressure, vision issues, hearing loss, and tooth malalignment/malocclusion.
Agents to avoid: Agents known to suppress bone resorption (e.g., bisphosphonates, denosumab, selective estrogen receptor modulators) and agents known to stimulate bone formation (e.g., teriparatide, abaloparatide, romozosumab).
### Genetic counseling.
SOST-related sclerosing bone dysplasia is inherited in an autosomal recessive manner. Each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Prenatal diagnosis for pregnancies at increased risk and preimplantation diagnosis for SOST-related sclerosing bone dysplasias are possible if the pathogenic variants in the family have been identified. Ultrasound examination may detect syndactyly in fetuses at risk for sclerosteosis, but its absence on ultrasound examination does not rule out an affected fetus.
## Diagnosis
Sclerosteosis and van Buchem disease are both disorders of progressive bone overgrowth due to increased bone formation; they are clinically and radiographically similar disorders that are caused by pathogenic variants in SOST [Balemans et al 2001, Brunkow et al 2001, Balemans et al 2002, Staehling-Hampton et al 2002]. The two disorders differ in severity and in type of molecular genetic variants.
### Suggestive Findings
SOST-related sclerosing bone dysplasias should be suspected in individuals with the following findings.
Clinical findings
* Generalized progressive skeletal overgrowth, most pronounced in the skull and mandible, leading to:
* Potentially lethal elevation of intracranial pressure in childhood or early adulthood as a result of calvarial overgrowth
* Entrapment of the seventh cranial nerve leading to recurrent facial palsy that is initially intermittent and eventually constant, resulting in impaired facial movements in adulthood
* Conductive hearing loss in childhood followed by additional entrapment of the eighth cranial nerve and closure of the oval and round windows, leading to sensorineural hearing loss in adulthood
* Distortion of the face with asymmetric mandibular hypertrophy, frontal bossing, midface hypoplasia, or proptosis
* Tall stature with accelerated bone growth beginning in childhood
* Variable cutaneous or bony syndactyly of fingers two (index) and three (middle), and occasionally fingers three and other fingers. The syndactyly is usually bilateral but not necessarily symmetric. (Note: Syndactyly is not found in van Buchem disease.)
* Radial deviation of the terminal phalanges
* Dysplastic or absent nails
Radiographic findings
* Widening (hyperostosis) and increased density (sclerosis) of the calvarium, the base of the skull, and the shafts of the tubular bones
* Undermodeling of the shafts of the tubular bones of the metacarpals and phalanges
* Broad and dense clavicles and ribs
* Sclerosis of the scapulae and pelvis without an increase in size
* High bone mineral density (Z-score >5) measured by dual energy x-ray absorptiometry (DXA) [van Lierop et al 2017]
Ethnicity and neonatal findings. The majority of persons affected with sclerosteosis are members of the Afrikaner (Dutch ancestry) population of South Africa. Within this population the diagnosis should be suspected in any neonate with syndactyly, or in the presence of fluctuating facial palsy.
Van Buchem disease is almost exclusively found within the Netherlands. There are no specific neonatal findings in patients with van Buchem disease, although facial palsy can already be present at birth [van Egmond et al 2012].
### Establishing the Diagnosis
The diagnosis of SOST-related sclerosing bone dysplasia is established in a proband with typical clinical and radiographic findings and biallelic pathogenic variants involving SOST identified on molecular genetic testing (see Table 1).
Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, multigene panel) and comprehensive genomic testing (chromosomal microarray analysis, exome sequencing, exome array, genome sequencing) depending on the phenotype.
Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of SOST-related sclerosing bone dysplasia is broad, individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those with atypical findings in whom the diagnosis of SOST-related sclerosing bone dysplasia has not been considered are more likely to be diagnosed using genomic testing (see Option 2).
#### Option 1
When the phenotypic and laboratory findings suggest the diagnosis of SOST-related sclerosing bone dysplasia, molecular genetic testing approaches can include single-gene testing or use of a multigene panel:
* Single-gene testing. Sequence analysis of SOST detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected.
Perform sequence analysis first. If only one or no pathogenic variant is found, perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications.
* A multigene panel that includes SOST and other genes of interest (see Differential Diagnosis) 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. 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. (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 this disorder a multigene panel that also includes deletion/duplication analysis is recommended (see Table 1).
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
Note: A homozygous 52-kb deletion downstream of SOST, which does not overlap the coding region, has been described in all individuals with van Buchem disease [Balemans et al 2002, Staehling-Hampton et al 2002]. This defect will not be found with single-gene testing or in a multigene panel. However, because van Buchem disease is almost exclusively found in the Netherlands, it is recommended to test for this genetic defect in non-Dutch individuals only if no genetic defects were found in a multigene panel.
#### Option 2
When the diagnosis of SOST-related sclerosing bone dysplasia is not considered because an individual has atypical phenotypic features, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is the best option. Exome sequencing is most commonly used; genome sequencing is also possible.
If exome sequencing is not diagnostic, exome array (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis.
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 SOST-related Sclerosing Bone Dysplasia
View in own window
Gene 1MethodProportion of Pathogenic Variants 2 Detectable by This Method
SOSTSequence analysis 3All reported 4
Gene-targeted deletion/duplication analysis 5See footnotes 6 and 7
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
See Molecular Genetics for information on allelic variants detected in this gene.
3\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
4\.
All pathogenic variants associated with SOST-related sclerosteosis in 94/96 cases are detectable by sequencing [van Lierop et al 2017]. Note that 66/96 reported cases are homozygous for the c.69C>T (p.Gln24Ter) South African founder variant. See footnote 6 regarding the pathogenic variant associated with van Buchem disease.
5\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.
6\.
A homozygous 52-kb deletion downstream of SOST, which does not overlap the coding region, has been described in all Dutch individuals with van Buchem disease [Balemans et al 2002, Staehling-Hampton et al 2002].
7\.
No additional data on detection rate of gene-targeted deletion/duplication analysis are available.
## Clinical Characteristics
### Clinical Description
Hypothesized to be allelic disorders [Beighton et al 1984], sclerosteosis and van Buchem disease were confirmed to be caused by pathogenic variants in the same gene in 2002 [Balemans et al 2002, Staehling-Hampton et al 2002]. The two disorders have very similar phenotypes caused by genetic deficiency of sclerostin; however, the manifestations of van Buchem disease are generally milder than those in sclerosteosis and syndactyly is absent (Table 2) [Beighton 1995]. Taken together, these two disorders are known as SOST-related sclerosing bone dysplasias.
#### Clinical Features of Sclerosteosis
Syndactyly, ranging from soft-tissue webbing to bony union of the phalanges, is found at birth in 66% of individuals. It most often affects the second and third fingers, although other fingers or toes can be affected as well.
More subtle deformity of the digits can also be seen, such as radial deviation of the phalanges or nail aplasia [Itin et al 2001].
Facial distortion due to bossing of the forehead and mandibular overgrowth is seen in 90% of individuals, with proptosis, hypertelorism, or midfacial hypoplasia found in some. These facial findings become apparent in early childhood and progress into adulthood [Hamersma et al 2003, van Lierop et al 2017].
Tall stature appears at school age. Longitudinal growth arrests at puberty, by which time individuals can reach heights exceeding two meters (6.5 feet).
Recurrent facial palsies are hallmark complications in sclerosteosis, affecting 93% of individuals. The first episodes develop in early childhood and in some cases within the first months of life. The palsies are caused by narrowing of the neural foramina due to bone overgrowth of the skull.
Other, less common nerve entrapment syndromes in sclerosteosis are visual loss (2nd cranial nerve), neuralgia or anosmia (5th cranial nerve), and sensory hearing loss (8th cranial nerve) [van Lierop et al 2017].
Hearing loss is also highly prevalent, affecting 94% of individuals. It starts as conductive hearing loss in childhood, but often progresses into mixed conductive, sensorineural hearing loss later in life [Hamersma et al 2003, van Lierop et al 2017].
Increased intracranial pressure can develop due to narrowing of the intracranial cavity by the thickening of calvaria. It often starts in late adolescence. In a recent study, it was reported in 71% of individuals with sclerosteosis, and was considered the cause of death in 12 out of 33 deceased individuals of Afrikaner background, while six additional individuals died due to perioperative complications [van Lierop et al 2017].
Clinical course of the disease. While syndactyly is the only symptom of sclerosteosis present at birth, other symptoms develop early in childhood. The disease progresses into adulthood but appears to stabilize in the third decade in the majority of those with sclerosteosis [van Lierop et al 2011, van Lierop et al 2013].
#### Clinical Features of van Buchem Disease
All of the above features can be found, except for syndactyly.
Overall there is a milder phenotype than observed in sclerosteosis. For example, increased intracranial pressure is rare in individuals with van Buchem disease [van Lierop et al 2010, van Lierop et al 2013].
Van Buchem disease also tends to stabilize in adulthood [van Lierop et al 2013].
### Table 2.
Distinguishing Features of Sclerosteosis and van Buchem Disease
View in own window
Sclerosteosisvan Buchem Disease
Reported cases9631
PrognosisPotentially lethalComparatively benign
HabitusGigantismNormal stature
FaciesGross distortionProminent mandible
TeethMalaligned, w/malocclusionNormal
Cranial nerve palsyVery commonCommon
Intracranial pressureRaisedInconsistent elevation
SyndactylyFrequentAbsent
Nail hypoplasiaFrequentAbsent
Cranial hyperostosisGrossModerate
Distortion of tubular bones of hands & feetMarkedMild
Modified from Beighton [1995], p 234
#### Laboratory Tests
Sclerostin. Serum levels of sclerostin are undetectable in sclerosteosis [van Lierop et al 2011], but low levels can be detected in patients with van Buchem disease [van Lierop et al 2013].
Bone formation markers. Levels of bone formation markers, such as procollagen type 1 aminoterminal propeptide (P1NP), alkaline phosphatase, or osteocalcin, are elevated in both sclerosteosis and van Buchem disease. Levels decline with age but remain elevated above the upper limit of normal in the majority of individuals [Wergedal et al 2003, van Lierop et al 2011, van Lierop et al 2013].
Bone resorption markers. Levels of the bone resorption marker serum collagen type 1 cross-linked C-telopeptide (sCTX) are increased in childhood, but levels decrease with age toward the lower end of the reference range in adulthood [van Lierop et al 2011, van Lierop et al 2013]. Urinary cross-linker N-telopeptide (uNTX) was elevated in six individuals with van Buchem disease [Wergedal et al 2003].
Normal findings. Serum concentrations of calcium and phosphorus and levels of parathyroid hormone are normal [Epstein et al 1979, van Lierop et al 2011].
#### Bone Findings
Bone mineral density measured by DXA is greatly increased with Z-scores ranging from +7.7 to +14.4 at the spine and +7.8 to +11.5 at the hip in individuals with sclerosteosis [Balemans et al 2005, Piters et al 2010, Power et al 2010, van Lierop et al 2011], and from +5.4 to +12.3 at the spine and +5.2 to +12.1 at the hip, in individuals with van Buchem disease [van Lierop et al 2013].
Histologic examination of bone reveals increased bone volume and thickness of cortex and trabeculae, increased osteoblastic bone formation with normal or decreased osteoclastic bone resorption, and no abnormal mineralization of bone tissue [Stein et al 1983, van Lierop et al 2017, Hassler et al 2014].
The high bone density in sclerosteosis is not associated with increased mineralization [Hassler et al 2014], as is seen in osteopetrosis, but there is an increased biomechanical competence of the bone and resistance to fractures [van Lierop et al 2017].
The risk for fractures, osteomyelitis, or bone marrow failure is not increased.
#### Life Expectancy
Survival into old age is unusual in sclerosteosis but not unprecedented [Barnard et al 1980, van Lierop et al 2011, van Lierop et al 2013]. Life expectancy is reduced because of sudden deaths due to herniation of the brain stem, or perioperative complications from surgery to correct increased intracranial pressure. Mean age of death is 33 years [Hamersma et al 2003], but with increasing use of early craniectomy, longer-term survival is likely. The natural history of sclerosteosis has been reviewed in Beighton [1988], Beighton [1995], Hamersma et al [2003], and van Lierop et al [2017].
Life expectancy in van Buchem disease appears to be normal and individuals have had no significant comorbidities. Sudden death due to herniation of the brain stem has never been reported in patients with van Buchem disease. The oldest individual to be studied was 81 years old with type 2 diabetes mellitus, mild heart failure, and non-metastasized prostate cancer, comorbidities frequent in elderly populations [van Lierop et al 2017].
### Genotype-Phenotype Correlations
There is no apparent difference in phenotype associated with any of the known SOST pathogenic variants. The phenotype of van Buchem disease, which is not caused by pathogenic variants in SOST itself but by a 52-kb deletion downstream of SOST, is milder than that of sclerosteosis.
### Nomenclature
In the past, sclerosteosis and van Buchem disease have been grouped with other dense bone disorders under nonspecific general terms including "marble bones," "osteopetrosis," and "Albers-Schönberg disease." Diagnostic precision and syndromic delineation followed, and the term "sclerosteosis" became established. Similarly, van Buchem and his colleagues employed the designation "hyperostosis corticalis generalisata familiaris" for the condition that is now known as "van Buchem disease."
In the nosology of the dense bone disorders, sclerosteosis and van Buchem disease have been categorized as "craniotubular hyperostoses." With the elucidation of the molecular basis of these conditions, they are now classified together as SOST-related sclerosing bone dysplasias.
### Prevalence
Sclerosteosis is primarily found among the Afrikaner (Dutch ancestry) community of South Africa, where the carrier rate is estimated at 1:100 and prevalence at 1: 60.000 [Beighton & Hamersma 1979]. However, cases outside the Afrikaner population have been reported [van Lierop et al 2017]. With 96 cases reported worldwide up to 2017, of which 66 were from South Africa, sclerosteosis is an extremely rare disease outside South Africa.
There have been only 31 reported cases of van Buchem disease, of which 29 were from the Netherlands and two were from Germany [van Lierop et al 2017].
## Differential Diagnosis
SOST-related sclerosing bone dysplasia is included in the category of craniotubular hyperostoses, which need to be distinguished from other sclerosing bone dysplasias. These include:
* The osteoscleroses, notably osteopetrosis, characterized by increased bone density with no bone overgrowth and little or no disturbance of the contours of the bones; and
* The craniotubular dysplasias, characterized by abnormal modeling of the skeleton and moderate sclerosis of the calvarium and base of the skull.
The predominant feature of the craniotubular hyperostoses is overgrowth of bone, which leads to alterations of contours and increase in radiologic density of the skeleton. The bones are often very resistant to trauma. In addition to SOST-related sclerosing bone dysplasia, this group of disorders includes the conditions summarized in Table 3.
### Table 3.
Other Craniotubular Hyperostoses to Consider in the Differential Diagnosis of SOST-Related Sclerosing Bone Dysplasias
View in own window
DisorderGene(s)MOIClinical Features
Overlapping w/SOST-related sclerosing bone dysplasiasDistinguishing from SOST-related sclerosing bone dysplasias
Endosteal hyperostosis, Worth form (OMIM 144750)LRP5AD
* Hyperostosis of long bones & skull
* Cranial nerve impingement & hearing loss
* Enlargement of the mandible
* Smooth or bony swellings may be on the palate (taurus palatinum).
* Milder phenotype
* Normal height
* No syndactyly
Camurati-Engelmann disease (CED; progressive diaphyseal dysplasia)TGFB1 1AD
* Hyperostosis of long bones, skull may be affected
* Frontal bossing, enlargement of mandible & proptosis, & cranial nerve impingement resulting in facial palsy seen in severe cases later in life
* Proximal muscle weakness
* Severe limb pain
* Joint contractures
* No syndactyly
Craniodiaphyseal dysplasia (CDD)
(OMIM 122860)Footnote 2AD
* Hyperostosis of skull
* Facial deformity w/hypertelorism
* Cranial nerve impingement & hearing loss
* Severe progressive sclerosing bone dysplasia w/maximal involvement of the craniofacial skeleton
Long bones, ribs, & pelvis less affected
* Short stature
* No syndactyly
Sclerosteosis-like phenotype (sclerosteosis 2)
(OMIM 614305)LRP4AD
AR
* Hyperostosis of long bones & skull
* Facial deformity
* Cranial nerve impingement & hearing loss
* Tall stature
Normal or increased serum sclerostin levels
AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance; XL = X-linked
1\.
Diagnosis of CED is based on physical examination and radiographic findings and can be confirmed by molecular genetic testing. Bone and muscle histology are nonspecific. TGFB1 is the only gene in which mutation is known to cause CED. Sequence analysis identifies pathogenic variants in TGFB1 in about 90% of affected individuals.
2\.
CDD is possibly heterogeneous. Heterozygous pathogenic variants in SOST have been demonstrated in two unrelated affected children [Kim et al 2011] (see Genetically Related Disorders).
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease in an individual diagnosed with a SOST-related sclerosing bone dysplasia, the evaluations summarized in Table 4 (if not performed as part of the evaluation that led to the diagnosis) are recommended:
### Table 4.
Recommended Evaluations Following Initial Diagnosis in Individuals with SOST-Related Sclerosing Bone Dysplasia
View in own window
System/ConcernEvaluation
Skeletal
* Radiographic & imaging studies incl bone densitometry
* Assessment of necessity for surgical correction of syndactyly when present
NeurologicNeurologic evaluation for consequences of cranial nerve entrapment
OphthalmologicOphthalmologic evaluation for evidence of increased intracranial pressure &/or proptosis
HearingFormal audiologic evaluation
OtherConsultation w/clinical geneticist &/or genetic counselor
### Treatment of Manifestations
No specific treatment for sclerosteosis or van Buchem disease is currently available, and management aims at relieving symptoms and preventing complications. Treatment of these disorders therefore mainly consists of surgical intervention to ameliorate complications.
In one adult case of severe van Buchem disease, treatment with glucocorticoids was successful in suppressing bone formation and disease progression [van Lierop et al 2010], although the individual still needed repeated surgery [Datema et al 2015]. In two children with van Buchem disease short courses of prednisolone were given during exacerbations of facial palsies. While biochemical bone turnover markers decreased during therapy, there was no clinical improvement of steroid treatment in these cases [van Egmond et al 2012] The long-term benefits of this treatment in sclerosteosis or van Buchem disease have not been studied.
Important note: The bones in sclerosteosis are thick and dense; surgical intervention may be difficult and prolonged. Standard neurosurgical instruments may not be sufficient (i.e., drill bits may be too short and power tools may be damaged by the dense bone) [du Plessis 1993]. In addition, bone regrowth occurs and may cause recurrence of symptoms.
### Table 5.
Treatment of Manifestations in Individuals with SOST-Related Sclerosing Bone Dysplasia
View in own window
Manifestation/ConcernTreatmentConsiderations/Other
SyndactylySurgical correctionMay be necessary in early childhood to improve function & cosmetic appearance
Entrapped cranial nerves that can cause recurrent facial paralysis similar to Bell's palsy or facial painSurgical decompressionFrom age 2 yrs onwards
Elevated intracranial pressure
* Craniectomy
* Ventriculo-peritoneal drain
* From age 5 yrs onwards but usually in young adulthood
* In South Africa this procedure is undertaken at an increasingly young age.
Mandibular overgrowthSurgical reduction
* May be performed for cosmetic reasons or if mouth closure is impaired due to mandible overgrowth
* Tooth extraction may be difficult.
* Management by an orthodontic or craniofacial team is recommended.
Hearing loss
* Hearing aids
* Middle-ear surgery for conductive loss
* Cochlear implant if obliteration of the internal auricular canal & damage to auditory nerve
RadiculopathySpinal cord decompressionIn adulthood
Proptosis & glaucomaOrbital decompressionIn adulthood
### Surveillance
### Table 6.
Recommended Surveillance for Individuals with SOST-Related Sclerosing Bone Dysplasia
View in own window
System/ConcernEvaluationFrequency 1
Bone massBone mineral density measurement & biochemical markers of bone turnoverAnnually at pediatric age, biennially at adult age
NeurologicExamination for consequences of cranial nerve entrapmentEvery 6 mos at pediatric age, annually at adult age
OphthalmologicProptosis, eye pressure, & evaluation of the optic nerve papillaAnnually
HearingAudiologic assessmentAnnually
TeethDental & orthodontic evaluation of tooth malalignment & malocclusionAnnually at pediatric age, routine dental care at adult age
1\.
Note: Since no published guidelines are available, all suggested intervals are at the discretion of the treating physician.
### Agents/Circumstances to Avoid
Agents known to suppress bone resorption:
* Bisphosphonates
* Denosumab
* Selective estrogen receptor modulators (SERMS)
Agents known to stimulate bone formation:
* Teriparatide
* Abaloparatide
* Romozosumab
### 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 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
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| SOST-Related Sclerosing Bone Dysplasias | None | 4,584 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1228/ | 2021-01-18T20:58:36 | {"synonyms": []} |
Lupus vasculitis is a complication of Systemic Lupus Erythematosus in which the autoimmune response causes the deposition of immune complexes, such as rheumatoid factor, within the blood vessels. It may manifest in as high as 56% of lupus patients throughout their life, in contrast to antiphospholipid syndrome which has a prevalence of 15%. Vasculitis more often affects younger men.[1]
## References[edit]
1. ^ Pyrpasopoulou, Athina; Chatzimichailidou, Sofia; Aslanidis, Spyros (2012). "Vascular Disease in Systemic Lupus Erythematosus". Autoimmune Diseases. 2012: 876456. doi:10.1155/2012/876456. PMC 3432322. PMID 22957213.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Lupus vasculitis | c0343205 | 4,585 | wikipedia | https://en.wikipedia.org/wiki/Lupus_vasculitis | 2021-01-18T18:51:03 | {"umls": ["C0343205"], "wikidata": ["Q25339307"]} |
A limited form of Stevens-Johnson syndrome/toxic epidermal necrolysis spectrum characterized by destruction and detachment of the skin epithelium and mucous membranes involving less than 10% of the body surface area.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Stevens-Johnson syndrome | c0038325 | 4,586 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=36426 | 2021-01-23T18:44:42 | {"gard": ["7700"], "mesh": ["D013262"], "omim": ["608579"], "umls": ["C0038325"], "icd-10": ["L51.1"], "synonyms": ["Dermatostomatitis, Stevens Johnson type"]} |
Fibrochondrogenesis is a very severe disorder of bone growth. Affected infants have a very narrow chest, which prevents the lungs from developing normally. Most infants with this condition are stillborn or die shortly after birth from respiratory failure. However, some affected individuals have lived into childhood.
Fibrochondrogenesis is characterized by short stature (dwarfism) and other skeletal abnormalities. Affected individuals have shortened long bones in the arms and legs that are unusually wide at the ends (described as dumbbell-shaped). People with this condition also have a narrow chest with short, wide ribs and a round and prominent abdomen. The bones of the spine (vertebrae) are flattened (platyspondyly) and have a characteristic pinched or pear shape that is noticeable on x-rays. Other skeletal abnormalities associated with fibrochondrogenesis include abnormal curvature of the spine and underdeveloped hip (pelvic) bones.
People with fibrochondrogenesis also have distinctive facial features. These include prominent eyes, low-set ears, a small mouth with a long upper lip, and a small chin (micrognathia). Affected individuals have a relatively flat-appearing midface, particularly a small nose with a flat nasal bridge and nostrils that open to the front rather than downward (anteverted nares). Vision problems, including severe nearsightedness (high myopia) and clouding of the lens of the eye (cataract), are common in those who survive infancy. Most affected individuals also have sensorineural hearing loss, which is caused by abnormalities of the inner ear.
## Frequency
Fibrochondrogenesis appears to be a rare disorder. About 20 affected individuals have been described in the medical literature.
## Causes
Fibrochondrogenesis can result from mutations in the COL11A1 or COL11A2 gene. When the condition is caused by COL11A1 gene mutations, it is designated as type 1; when it is caused by COL11A2 gene mutations, it is designated as type 2. Both of these genes provide instructions for making components of type XI collagen, which is a complex molecule that gives structure and strength to the connective tissues that support the body's joints and organs. Specifically, type XI collagen is found in cartilage, a tough but flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Type XI collagen is also part of the inner ear; the vitreous, which is the clear gel that fills the eyeball; and the nucleus pulposus, which is the center portion of the discs between vertebrae.
Mutations in the COL11A1 or COL11A2 gene impair the assembly of type XI collagen, in most cases leading to the production of abnormal collagen molecules. The defective collagen weakens connective tissues, impairing the formation of bones throughout the skeleton and causing changes in the eye and inner ear that lead to vision and hearing problems.
### Learn more about the genes associated with Fibrochondrogenesis
* COL11A1
* COL11A2
## Inheritance Pattern
Fibrochondrogenesis is generally 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 usually do not show signs and symptoms of the condition. In a few reported cases, parents of children with fibrochondrogenesis have had mild features that may be related to the condition, including slightly short stature, myopia, cataracts, joint pain, and hearing loss.
In at least one case of fibrochondrogenesis caused by a COL11A2 gene mutation, the condition was inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In this case, the condition resulted from a new (de novo) mutation in the gene that occurred during the formation of reproductive cells (eggs or sperm) in one of the affected individual's parents. There was no history of the disorder in the family.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Fibrochondrogenesis | c3278138 | 4,587 | medlineplus | https://medlineplus.gov/genetics/condition/fibrochondrogenesis/ | 2021-01-27T08:24:56 | {"gard": ["2321"], "omim": ["228520", "614524"], "synonyms": []} |
Mosaic variegated aneuploidy (MVA) syndrome is a rare disorder in which some cells in the body have an abnormal number of chromosomes instead of the usual 46 chromosomes, a situation known as aneuploidy. Most commonly, cells have an extra chromosome, which is called trisomy, or are missing a chromosome, which is known as monosomy. In MVA syndrome, some cells are aneuploid and others have the normal number of chromosomes, which is a phenomenon known as mosaicism. Typically, at least one-quarter of cells in affected individuals have an abnormal number of chromosomes. Because the additional or missing chromosomes vary among the abnormal cells, the aneuploidy is described as variegated.
In MVA syndrome, growth before birth is slow (intrauterine growth restriction). After birth, affected individuals continue to grow at a slow rate and are shorter than average. In addition, they typically have an unusually small head size (microcephaly). Another common feature of MVA syndrome is an increased risk of developing cancer in childhood. Cancers that occur most frequently in affected individuals include a cancer of muscle tissue called rhabdomyosarcoma, a form of kidney cancer known as Wilms tumor, and a cancer of the blood-forming tissue known as leukemia.
Less commonly, people with MVA syndrome have eye abnormalities or distinctive facial features, such as a broad nasal bridge and low-set ears. Some affected individuals have brain abnormalities, the most common of which is called Dandy-Walker malformation. Intellectual disability, seizures, and other health problems can also occur in people with MVA syndrome.
There are at least three types of MVA syndrome, each with a different genetic cause. Type 1 is the most common and displays the classic signs and symptoms described above. Type 2 appears to have slightly different signs and symptoms than type 1, although the small number of affected individuals makes it difficult to define its characteristic features. Individuals with MVA syndrome type 2 grow slowly before and after birth; however, their head size is typically normal. Some people with MVA syndrome type 2 have unusually short arms. Individuals with MVA syndrome type 2 do not seem to have an increased risk of cancer. Another form of MVA syndrome is characterized by a high risk of developing Wilms tumor. Individuals with this form may also have other signs and symptoms typical of MVA syndrome type 1.
## Frequency
MVA syndrome is a rare condition. Its prevalence is unknown.
## Causes
BUB1B gene mutations cause MVA syndrome type 1, CEP57 gene mutations cause MVA syndrome type 2, and TRIP13 gene mutations cause the other form of MVA syndrome. Some people with MVA syndrome do not have mutations in any of these genes. Other genes that have not been identified are likely also involved in the condition.
The proteins produced from the BUB1B, CEP57, and TRIP13 genes have roles in the proper separation of chromosomes during cell division. Before cells divide, they copy all of their chromosomes. To aid in the equal sorting of chromosomes to the two new cells, structures called spindle microtubules attach to the chromosomes and pull one copy of each to opposite sides of the cell. Then the cell divides such that each new cell has a full set of chromosomes. The CEP57 protein helps organize and stabilize the spindle microtubules. The BUBR1 protein, produced from the BUB1B gene, and the TRIP13 proteins help ensure that each copy of the duplicated chromosomes is attached to a spindle microtubule, and they prevent cell division if any remain unattached.
The BUB1B gene mutations reduce the amount of functional BUBR1 protein, and TRIP13 gene mutations lead to an absence of TRIP13 protein in cells. Without BUBR1 or TRIP13, cell division can proceed, even if not all the chromosomes are attached to spindle microtubules. The resulting errors in the sorting of chromosomes typically leads to the aneuploidy that occurs in MVA syndrome. (Some people with TRIP13 gene mutations have chromosome abnormalities that indicate problems with chromosome sorting but do not develop aneuploidy. These individuals do have the other signs and symptoms of MVA syndrome.) Research suggests that impairment of the process that delays cell division until the correct time underlies the increased risk of cancer in MVA syndrome, although the mechanism is not completely understood. It is also unclear how BUB1B or TRIP13 gene mutations or aneuploidy is involved in the other features of the condition.
CEP57 gene mutations are thought to reduce the amount of functional CEP57 protein in cells. The resulting problems with spindle microtubule organization may prevent the normal separation of chromosomes during cell division, leading to aneuploidy, although the mechanism is unknown. Researchers are working to understand how these genetic changes lead to the other features of MVA syndrome type 2 and why individuals with this form of the condition do not seem to have an increased risk of cancer.
### Learn more about the genes associated with Mosaic variegated aneuploidy syndrome
* BUB1B
* CEP57
* TRIP13
## Inheritance Pattern
All types of MVA syndrome are inherited in an autosomal recessive pattern, which means both copies of the BUB1B, CEP57, or TRIP13 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.
Parents of individuals with MVA syndrome type 1, who have a mutation in one copy of the BUB1B gene, can have a related problem with their chromosomes called premature chromatid separation trait. Although these individuals have chromosome abnormalities that indicate trouble with normal chromosome separation during cell division, affected individuals usually have no health problems related to the trait.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Mosaic variegated aneuploidy syndrome | c1850343 | 4,588 | medlineplus | https://medlineplus.gov/genetics/condition/mosaic-variegated-aneuploidy-syndrome/ | 2021-01-27T08:24:39 | {"gard": ["3007"], "mesh": ["C536987"], "omim": ["257300", "614114"], "synonyms": []} |
"PTSD" redirects here. For other uses, see PTSD (disambiguation).
"Post traumatic" redirects here. For the album, see Post Traumatic.
mental disorder that can develop after experiencing or witnessing a terrifying or life-threatening event
Post-traumatic stress disorder
Art therapy project created by a U.S. Marine with post-traumatic stress disorder
SpecialtyPsychiatry, clinical psychology
SymptomsDisturbing thoughts, feelings, or dreams related to the event; mental or physical distress to trauma-related cues; efforts to avoid trauma-related situations; increased fight-or-flight response[1]
ComplicationsSelf-harm, suicide[2]
Duration> 1 month[1]
CausesExposure to a traumatic event[1]
Diagnostic methodBased on symptoms[2]
TreatmentCounseling, medication[3]
MedicationSelective serotonin reuptake inhibitor[4]
Frequency8.7% (lifetime risk); 3.5% (12-month risk) (US)[5]
Post-traumatic stress disorder (PTSD)[note 1] is a mental disorder that can develop after a person is exposed to a traumatic event, such as sexual assault, warfare, traffic collisions, child abuse, or other threats on a person's life.[1][6] Symptoms may include disturbing thoughts, feelings, or dreams related to the events, mental or physical distress to trauma-related cues, attempts to avoid trauma-related cues, alterations in how a person thinks and feels, and an increase in the fight-or-flight response.[1][3] These symptoms last for more than a month after the event.[1] Young children are less likely to show distress, but instead may express their memories through play.[1] A person with PTSD is at a higher risk of suicide and intentional self-harm.[2][7]
Most people who experience traumatic events do not develop PTSD.[2] People who experience interpersonal trauma such as rape or child abuse are more likely to develop PTSD as compared to people who experience non-assault based trauma, such as accidents and natural disasters.[8] About half of people develop PTSD following rape.[2][9][disputed – discuss] Children are less likely than adults to develop PTSD after trauma, especially if they are under 10 years of age.[10] Diagnosis is based on the presence of specific symptoms following a traumatic event.[2]
Prevention may be possible when counselling is targeted at those with early symptoms but is not effective when provided to all trauma-exposed individuals whether or not symptoms are present.[2] The main treatments for people with PTSD are counselling (psychotherapy) and medication.[3][11] Antidepressants of the selective serotonin reuptake inhibitor type are the first-line medications used for PTSD and are beneficial for about half of people.[4] Benefits from medication are less than those seen with counselling.[2] It is not known whether using medications and counselling together has greater benefit than either method separately.[2][12] Medications, other than SSRIs, do not have enough evidence to support their use and, in the case of benzodiazepines, may worsen outcomes.[13][14]
In the United States, about 3.5% of adults have PTSD in a given year, and 9% of people develop it at some point in their life.[1] In much of the rest of the world, rates during a given year are between 0.5% and 1%.[1] Higher rates may occur in regions of armed conflict.[2] It is more common in women than men.[3] Symptoms of trauma-related mental disorders have been documented since at least the time of the ancient Greeks.[15] During the world wars, the condition was known under various terms including "shell shock" and "combat neurosis".[16] The term "post-traumatic stress disorder" came into use in the 1970s in large part due to the diagnoses of U.S. military veterans of the Vietnam War.[17] It was officially recognized by the American Psychiatric Association in 1980 in the third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III).[18]
## Contents
* 1 Symptoms
* 1.1 Associated medical conditions
* 2 Risk factors
* 2.1 Trauma
* 2.1.1 Intimate partner violence
* 2.1.2 War-related trauma
* 2.1.3 Unexpected death of a loved one
* 2.1.4 Life-threatening illness
* 2.1.5 Pregnancy-related trauma
* 2.2 Genetics
* 3 Pathophysiology
* 3.1 Neuroendocrinology
* 3.2 Neuroanatomy
* 4 Diagnosis
* 4.1 Screening
* 4.2 Assessment
* 4.3 Diagnostic and statistical manual
* 4.4 International classification of diseases
* 4.5 Differential diagnosis
* 5 Prevention
* 5.1 Psychological debriefing
* 5.2 Risk-targeted interventions
* 6 Management
* 6.1 Counselling
* 6.1.1 Cognitive behavioral therapy
* 6.1.2 Eye movement desensitization and reprocessing
* 6.1.3 Interpersonal psychotherapy
* 6.2 Medication
* 6.2.1 Antidepressants
* 6.2.2 Benzodiazepines
* 6.2.3 Prazosin
* 6.2.4 Glucocorticoids
* 6.2.5 Cannabinoids
* 6.3 Other
* 6.3.1 Exercise, sport and physical activity
* 6.3.2 Play therapy for children
* 6.3.3 Military programs
* 6.3.4 Nightmares
* 7 Epidemiology
* 7.1 United States
* 7.1.1 Military combat
* 7.1.2 Man-made disasters
* 8 Veterans
* 8.1 United States
* 8.2 Iraq
* 8.3 United Kingdom
* 8.4 Canada
* 9 History
* 10 Terminology
* 11 Research
* 11.1 Psychotherapy
* 12 Notes
* 13 References
* 14 External links
## Symptoms
Service members use art to relieve PTSD symptoms.
See also: Psychological stress and sleep
Symptoms of PTSD generally begin within the first three months after the inciting traumatic event, but may not begin until years later.[1][3] In the typical case, the individual with PTSD persistently avoids either trauma-related thoughts and emotions or discussion of the traumatic event, and may even have amnesia of the event.[1] However, the event is commonly relived by the individual through intrusive, recurrent recollections, dissociative episodes of reliving the trauma ("flashbacks"), and nightmares.[19] While it is common to have symptoms after any traumatic event, these must persist to a sufficient degree (i.e., causing dysfunction in life or clinical levels of distress) for longer than one month after the trauma to be classified as PTSD (clinically significant dysfunction or distress for less than one month after the trauma may be acute stress disorder).[1][20][21][22] Some following a traumatic event experience post-traumatic growth.[23]
### Associated medical conditions
Trauma survivors often develop depression, anxiety disorders, and mood disorders in addition to PTSD.[24]
Drug abuse and alcohol abuse commonly co-occur with PTSD.[25] Recovery from post-traumatic stress disorder or other anxiety disorders may be hindered, or the condition worsened, when substance use disorders are comorbid with PTSD. Resolving these problems can bring about improvement in an individual's mental health status and anxiety levels.[26][27]
In children and adolescents, there is a strong association between emotional regulation difficulties (e.g. mood swings, anger outbursts, temper tantrums) and post-traumatic stress symptoms, independent of age, gender, or type of trauma.[28]
## Risk factors
No quieren (They do not want to) by Francisco Goya (1746–1828) depicts an elderly woman wielding a knife in defense of a girl being assaulted by a soldier.[29]
Persons considered at risk include combat military personnel, victims of natural disasters, concentration camp survivors, and victims of violent crime. Persons employed in occupations that expose them to violence (such as soldiers) or disasters (such as emergency service workers) are also at risk.[30] Other occupations that are at higher risk include police officers, firefighters, ambulance personnel, health care professionals, train drivers, divers, journalists, and sailors, in addition to people who work at banks, post offices or in stores.[31]
### Trauma
Main article: Psychological trauma
See also: Psychological resilience
PTSD has been associated with a wide range of traumatic events. The risk of developing PTSD after a traumatic event varies by trauma type[32][33] and is highest following exposure to sexual violence (11.4%), particularly rape (19.0%).[34] Men are more likely to experience a traumatic event (of any type), but women are more likely to experience the kind of high-impact traumatic event that can lead to PTSD, such as interpersonal violence and sexual assault.[35]
Motor vehicle collision survivors, both children and adults, are at an increased risk of PTSD.[36][37] Globally, about 2.6% of adults are diagnosed with PTSD following a non-life threatening traffic accident, and a similar proportion of children develop PTSD.[34] Risk of PTSD almost doubles to 4.6% for life-threatening auto accidents.[34] Females were more likely to be diagnosed with PTSD following a road traffic accident, whether the accident occurred during childhood or adulthood.[36][37]
Post-traumatic stress reactions have been studied in children and adolescents.[38] The rate of PTSD may be lower in children than adults, but in the absence of therapy, symptoms may continue for decades.[10] One estimate suggests that the proportion of children and adolescents having PTSD in a non-wartorn population in a developed country may be 1% compared to 1.5% to 3% of adults, and much lower below the age of 10 years.[10] On average, 16% of children exposed to a traumatic event develop PTSD, varying according to type of exposure and gender.[39] Similar to the adult population, risk factors for PTSD in children include: female gender, exposure to disasters (natural or manmade), negative coping behaviours, and/or lacking proper social support systems.[40]
Predictor models have consistently found that childhood trauma, chronic adversity, neurobiological differences, and familial stressors are associated with risk for PTSD after a traumatic event in adulthood.[41][42][43] It has been difficult to find consistently aspects of the events that predict, but peritraumatic dissociation has been a fairly consistent predictive indicator of the development of PTSD.[44] Proximity to, duration of, and severity of the trauma make an impact. It has been speculated that interpersonal traumas cause more problems than impersonal ones,[45] but this is controversial.[46] The risk of developing PTSD is increased in individuals who are exposed to physical abuse, physical assault, or kidnapping.[47][48] Women who experience physical violence are more likely to develop PTSD than men.[47]
#### Intimate partner violence
See also: Rape trauma syndrome
An individual that has been exposed to domestic violence is predisposed to the development of PTSD. However, being exposed to a traumatic experience does not automatically indicate that an individual will develop PTSD.[49] There is a strong association between the development of PTSD in mothers that experienced domestic violence during the perinatal period of their pregnancy.[50]
Those who have experienced sexual assault or rape may develop symptoms of PTSD.[51][52] PTSD symptoms include re-experiencing the assault, avoiding things associated with the assault, numbness, and increased anxiety and an increased startle response. The likelihood of sustained symptoms of PTSD is higher if the rapist confined or restrained the person, if the person being raped believed the rapist would kill them, the person who was raped was very young or very old, and if the rapist was someone they knew. The likelihood of sustained severe symptoms is also higher if people around the survivor ignore (or are ignorant of) the rape or blame the rape survivor.[53]
#### War-related trauma
See also: Veteran and Refugee health
Military service is a risk factor for developing PTSD.[54] Around 78% of people exposed to combat do not develop PTSD; in about 25% of military personnel who develop PTSD, its appearance is delayed.[54]
Refugees are also at an increased risk for PTSD due to their exposure to war, hardships, and traumatic events. The rates for PTSD within refugee populations range from 4% to 86%.[55] While the stresses of war affect everyone involved, displaced persons have been shown to be more so than others.[56]
Challenges related to the overall psychosocial well-being of refugees are complex and individually nuanced. Refugees have reduced levels of well-being and a high rates of mental distress due to past and ongoing trauma. Groups that are particularly affected and whose needs often remain unmet are women, older people and unaccompanied minors.[57] Post-traumatic stress and depression in refugee populations also tend to affect their educational success.[57]
#### Unexpected death of a loved one
Sudden, unexpected death of a loved one is the most common traumatic event type reported in cross-national studies.[34][58] However, the majority of people who experience this type of event will not develop PTSD. An analysis from the WHO World Mental Health Surveys found a 5.2% risk of developing PTSD after learning of the unexpected death of a loved one.[58] Because of the high prevalence of this type of traumatic event, unexpected death of a loved one accounts for approximately 20% of PTSD cases worldwide.[34]
#### Life-threatening illness
Medical conditions associated with an increased risk of PTSD include cancer,[59][60][61] heart attack,[62] and stroke.[63] 22% of cancer survivors present with lifelong PTSD like symptoms.[64] Intensive-care unit (ICU) hospitalization is also a risk factor for PTSD.[65] Some women experience PTSD from their experiences related to breast cancer and mastectomy.[66][67][59] Loved ones of those who experience life-threatening illnesses are also at risk for developing PTSD, such as parents of child with chronic illnesses.[68]
#### Pregnancy-related trauma
Main article: Childbirth-related post-traumatic stress disorder
Women who experience miscarriage are at risk of PTSD.[69][70][71] Those who experience subsequent miscarriages have an increased risk of PTSD compared to those experiencing only one.[69] PTSD can also occur after childbirth and the risk increases if a woman has experienced trauma prior to the pregnancy.[72][73] Prevalence of PTSD following normal childbirth (that is, excluding stillbirth or major complications) is estimated to be between 2.8 and 5.6% at 6 weeks postpartum,[74] with rates dropping to 1.5% at 6 months postpartum.[74][75] Symptoms of PTSD are common following childbirth, with prevalence of 24-30.1%[74] at 6 weeks, dropping to 13.6% at 6 months.[76] Emergency childbirth is also associated with PTSD.[77]
### Genetics
Main article: Genetics of post-traumatic stress disorder
There is evidence that susceptibility to PTSD is hereditary. Approximately 30% of the variance in PTSD is caused from genetics alone.[44] For twin pairs exposed to combat in Vietnam, having a monozygotic (identical) twin with PTSD was associated with an increased risk of the co-twin's having PTSD compared to twins that were dizygotic (non-identical twins).[78] Women with a smaller hippocampus might be more likely to develop PTSD following a traumatic event based on preliminary findings.[79] Research has also found that PTSD shares many genetic influences common to other psychiatric disorders. Panic and generalized anxiety disorders and PTSD share 60% of the same genetic variance. Alcohol, nicotine, and drug dependence share greater than 40% genetic similarities.[44]
Several biological indicators have been identified that are related to later PTSD development. Heightened startle responses and, with only preliminary results, a smaller hippocampal volume have been identified as possible biomarkers for heightened risk of developing PTSD.[80] Additionally, one study found that soldiers whose leukocytes had greater numbers of glucocorticoid receptors were more prone to developing PTSD after experiencing trauma.[81]
## Pathophysiology
### Neuroendocrinology
PTSD symptoms may result when a traumatic event causes an over-reactive adrenaline response, which creates deep neurological patterns in the brain. These patterns can persist long after the event that triggered the fear, making an individual hyper-responsive to future fearful situations.[20][82] During traumatic experiences, the high levels of stress hormones secreted suppress hypothalamic activity that may be a major factor toward the development of PTSD.[83]
PTSD causes biochemical changes in the brain and body, that differ from other psychiatric disorders such as major depression. Individuals diagnosed with PTSD respond more strongly to a dexamethasone suppression test than individuals diagnosed with clinical depression.[84][85]
Most people with PTSD show a low secretion of cortisol and high secretion of catecholamines in urine,[86] with a norepinephrine/cortisol ratio consequently higher than comparable non-diagnosed individuals.[87] This is in contrast to the normative fight-or-flight response, in which both catecholamine and cortisol levels are elevated after exposure to a stressor.[88]
Brain catecholamine levels are high,[89] and corticotropin-releasing factor (CRF) concentrations are high.[90][91] Together, these findings suggest abnormality in the hypothalamic-pituitary-adrenal (HPA) axis.
The maintenance of fear has been shown to include the HPA axis, the locus coeruleus-noradrenergic systems, and the connections between the limbic system and frontal cortex. The HPA axis that coordinates the hormonal response to stress,[92] which activates the LC-noradrenergic system, is implicated in the over-consolidation of memories that occurs in the aftermath of trauma.[93] This over-consolidation increases the likelihood of one's developing PTSD. The amygdala is responsible for threat detection and the conditioned and unconditioned fear responses that are carried out as a response to a threat.[44]
The HPA axis is responsible for coordinating the hormonal response to stress.[44] Given the strong cortisol suppression to dexamethasone in PTSD, HPA axis abnormalities are likely predicated on strong negative feedback inhibition of cortisol, itself likely due to an increased sensitivity of glucocorticoid receptors.[94] PTSD has been hypothesized to be a maladaptive learning pathway to fear response through a hypersensitive, hyperreactive, and hyperresponsive HPA axis.[95]
Low cortisol levels may predispose individuals to PTSD: Following war trauma, Swedish soldiers serving in Bosnia and Herzegovina with low pre-service salivary cortisol levels had a higher risk of reacting with PTSD symptoms, following war trauma, than soldiers with normal pre-service levels.[96] Because cortisol is normally important in restoring homeostasis after the stress response, it is thought that trauma survivors with low cortisol experience a poorly contained—that is, longer and more distressing—response, setting the stage for PTSD.
It is thought that the locus coeruleus-noradrenergic system mediates the over-consolidation of fear memory. High levels of cortisol reduce noradrenergic activity, and because people with PTSD tend to have reduced levels of cortisol, it has been proposed that individuals with PTSD cannot regulate the increased noradrenergic response to traumatic stress.[83] Intrusive memories and conditioned fear responses are thought to be a result of the response to associated triggers. Neuropeptide Y has been reported to reduce the release of norepinephrine and has been demonstrated to have anxiolytic properties in animal models. Studies have shown people with PTSD demonstrate reduced levels of NPY, possibly indicating their increased anxiety levels.[44]
Other studies indicate that people that suffer from PTSD have chronically low levels of serotonin, which contributes to the commonly associated behavioral symptoms such as anxiety, ruminations, irritability, aggression, suicidality, and impulsivity.[97] Serotonin also contributes to the stabilization of glucocorticoid production.
Dopamine levels in a person with PTSD can contribute to symptoms: low levels can contribute to anhedonia, apathy, impaired attention, and motor deficits; high levels can contribute to psychosis, agitation, and restlessness.[97]
Several studies described elevated concentrations of the thyroid hormone triiodothyronine in PTSD.[98] This kind of type 2 allostatic adaptation may contribute to increased sensitivity to catecholamines and other stress mediators.
Hyperresponsiveness in the norepinephrine system can also be caused by continued exposure to high stress. Overactivation of norepinephrine receptors in the prefrontal cortex can be connected to the flashbacks and nightmares frequently experienced by those with PTSD. A decrease in other norepinephrine functions (awareness of the current environment) prevents the memory mechanisms in the brain from processing the experience, and emotions the person is experiencing during a flashback are not associated with the current environment.[97]
There is considerable controversy within the medical community regarding the neurobiology of PTSD. A 2012 review showed no clear relationship between cortisol levels and PTSD. The majority of reports indicate people with PTSD have elevated levels of corticotropin-releasing hormone, lower basal cortisol levels, and enhanced negative feedback suppression of the HPA axis by dexamethasone.[44][99]
### Neuroanatomy
Regions of the brain associated with stress and post-traumatic stress disorder[100]
A meta-analysis of structural MRI studies found an association with reduced total brain volume, intracranial volume, and volumes of the hippocampus, insula cortex, and anterior cingulate.[101] Much of this research stems from PTSD in those exposed to the Vietnam War.[102][103]
People with PTSD have decreased brain activity in the dorsal and rostral anterior cingulate cortices and the ventromedial prefrontal cortex, areas linked to the experience and regulation of emotion.[104]
The amygdala is strongly involved in forming emotional memories, especially fear-related memories. During high stress, the hippocampus, which is associated with placing memories in the correct context of space and time and memory recall, is suppressed. According to one theory this suppression may be the cause of the flashbacks that can affect people with PTSD. When someone with PTSD undergoes stimuli similar to the traumatic event, the body perceives the event as occurring again because the memory was never properly recorded in the person's memory.[44][105]
The amygdalocentric model of PTSD proposes that the amygdala is very much aroused and insufficiently controlled by the medial prefrontal cortex and the hippocampus, in particular during extinction.[106] This is consistent with an interpretation of PTSD as a syndrome of deficient extinction ability.[106][107]
The basolateral nucleus (BLA) of the amygdala is responsible for the comparison and development of associations between unconditioned and conditioned responses to stimuli, which results in the fear conditioning present in PTSD. The BLA activates the central nucleus (CeA) of the amygdala, which elaborates the fear response, (including behavioral response to threat and elevated startle response). Descending inhibitory inputs from the medial prefrontal cortex (mPFC) regulate the transmission from the BLA to the CeA, which is hypothesized to play a role in the extinction of conditioned fear responses.[44] While as a whole, amygdala hyperactivity is reported by meta analysis of functional neuroimaging in PTSD, there is a large degree of heterogeniety, more so than in social anxiety disorder or phobic disorder. Comparing dorsal(roughly the CeA) and ventral(roughly the BLA) clusters, hyperactivity is more robust in the ventral cluster, while hypoactivity is evident in the dorsal cluster. The distinction may explain the blunted emotions in PTSD(via desensitization in the CeA) as well as the fear related component.[108]
In a 2007 study Vietnam War combat veterans with PTSD showed a 20% reduction in the volume of their hippocampus compared with veterans having suffered no such symptoms.[109] This finding was not replicated in chronic PTSD patients traumatized at an air show plane crash in 1988 (Ramstein, Germany).[110]
Evidence suggests that endogenous cannabinoid levels are reduced in PTSD, particularly anandamide, and that cannabinoid receptors (CB1) are increased in order to compensate.[111] There appears to be a link between increased CB1 receptor availability in the amygdala and abnormal threat processing and hyperarousal, but not dysphoria, in trauma survivors.
A 2020 study found no evidence for conclusions from prior research that suggested low IQ is a risk factor for developing PTSD.[112]
## Diagnosis
PTSD can be difficult to diagnose, because of:
* the subjective nature of most of the diagnostic criteria (although this is true for many mental disorders);
* the potential for over-reporting, e.g., while seeking disability benefits, or when PTSD could be a mitigating factor at criminal sentencing;[citation needed]
* the potential for under-reporting, e.g., stigma, pride, fear that a PTSD diagnosis might preclude certain employment opportunities;
* symptom overlap with other mental disorders such as obsessive compulsive disorder and generalized anxiety disorder;[113]
* association with other mental disorders such as major depressive disorder and generalized anxiety disorder;
* substance use disorders, which often produce some of the same signs and symptoms as PTSD; and
* substance use disorders can increase vulnerability to PTSD or exacerbate PTSD symptoms or both; and
* PTSD increases the risk for developing substance abuse disorders.
* the differential expression of symptoms culturally (specifically with respect to avoidance and numbing symptoms, distressing dreams, and somatic symptoms)[114]
### Screening
There are a number of PTSD screening instruments for adults, such as the PTSD Checklist for DSM-5 (PCL-5)[115][116] and the Primary Care PTSD Screen for DSM-5 (PC-PTSD-5).[117]
There are also several screening and assessment instruments for use with children and adolescents. These include the Child PTSD Symptom Scale (CPSS),[118][119] Child Trauma Screening Questionnaire,[120][121] and UCLA Post-traumatic Stress Disorder Reaction Index for DSM-IV.[122][123]
In addition, there are also screening and assessment instruments for caregivers of very young children (six years of age and younger). These include the Young Child PTSD Screen,[124] the Young Child PTSD Checklist,[124] and the Diagnostic Infant and Preschool Assessment.[125]
### Assessment
Evidence-based assessment principles, including a multimethod assessment approach, form the foundation of PTSD assessment.[126][127][128]
### Diagnostic and statistical manual
PTSD was classified as an anxiety disorder in the DSM-IV, but has since been reclassified as a "trauma- and stressor-related disorder" in the DSM-5.[1] The DSM-5 diagnostic criteria for PTSD include four symptom clusters: re-experiencing, avoidance, negative alterations in cognition/mood, and alterations in arousal and reactivity.[1][3]
### International classification of diseases
The International Classification of Diseases and Related Health Problems 10 (ICD-10) classifies PTSD under "Reaction to severe stress, and adjustment disorders."[129] The ICD-10 criteria for PTSD include re-experiencing, avoidance, and either increased reactivity or inability to recall certain details related to the event.[129]
The ICD-11 diagnostic description for PTSD contains three components or symptom groups (1) re-experiencing, (2) avoidance, and (3) heightened sense of threat.[130][131] ICD-11 no longer includes verbal thoughts about the traumatic event as a symptom.[131] There is a predicted lower rate of diagnosed PTSD using ICD-11 compared to ICD10 or DSM-5.[131] ICD-11 also proposes identifying a distinct group with complex post-traumatic stress disorder (CPTSD), who have more often experienced several or sustained traumas and have greater functional impairment than those with PTSD.[131]
### Differential diagnosis
A diagnosis of PTSD requires that the person has been exposed to an extreme, life-threatening stressor. Any stressor can result in a diagnosis of adjustment disorder and it is an appropriate diagnosis for a stressor and a symptom pattern that does not meet the criteria for PTSD.
The symptom pattern for acute stress disorder must occur and be resolved within four weeks of the trauma. If it lasts longer, and the symptom pattern fits that characteristic of PTSD, the diagnosis may be changed.[19]
Obsessive compulsive disorder may be diagnosed for intrusive thoughts that are recurring but not related to a specific traumatic event.[19]
In extreme cases of prolonged, repeated traumatization where there is no viable chance of escape, survivors may develop complex post-traumatic stress disorder.[132] This occurs as a result of layers of trauma rather than a single traumatic event, and includes additional symptomatology, such as the loss of a coherent sense of self.[133]
## Prevention
See also: Traumatic memories
Modest benefits have been seen from early access to cognitive behavioral therapy. Critical incident stress management has been suggested as a means of preventing PTSD, but subsequent studies suggest the likelihood of its producing negative outcomes.[134][135] A 2019 Cochrane review did not find any evidence to support the use of an intervention offered to everyone", and that "...multiple session interventions may result in worse outcome than no intervention for some individuals."[136] The World Health Organization recommends against the use of benzodiazepines and antidepressants in for acute stress (symptoms lasting less than one month).[137] Some evidence supports the use of hydrocortisone for prevention in adults, although there is limited or no evidence supporting propranolol, escitalopram, temazepam, or gabapentin.[138]
### Psychological debriefing
See also: Debriefing § Crisis intervention
Trauma-exposed individuals often receive treatment called psychological debriefing in an effort to prevent PTSD, which consists of interviews that are meant to allow individuals to directly confront the event and share their feelings with the counselor and to help structure their memories of the event.[139] However, several meta-analyses find that psychological debriefing is unhelpful and is potentially harmful.[139][140][141] This is true for both single-session debriefing and multiple session interventions.[136] As of 2017 The American Psychological Association assessed psychological debriefing as No Research Support/Treatment is Potentially Harmful.[142]
### Risk-targeted interventions
For one such method, see trauma risk management.
Risk-targeted interventions are those that attempt to mitigate specific formative information or events. It can target modeling normal behaviors, instruction on a task, or giving information on the event.[143][144]
## Management
Further information: Treatments for PTSD
Reviews of studies have found that combination therapy (psychological and pharmacotherapy) is no more effective than psychological therapy alone.[12]
### Counselling
The approaches with the strongest evidence include behavioral and cognitive-behavioral therapies such as prolonged exposure therapy,[145] cognitive processing therapy, and eye movement desensitization and reprocessing (EMDR).[146][147][148] In addition, brief eclectic psychotherapy (BEP), narrative exposure therapy (NET), and written narrative exposure therapies also have a evidence.[149]
A 2019 Cochrane review evaluated couples and family therapies compared to no care and individual and group therapies for the treatment of PTSD.[150] There were to few studies on couples therapies to determine if substantive benefits were derived but preliminary RCTs suggested that couples therapies may be beneficial for reducing PTSD symptoms.[150]
A meta-analytic comparison of EMDR and cognitive behavioral therapy (CBT) found both protocols indistinguishable in terms of effectiveness in treating PTSD; however, "the contribution of the eye movement component in EMDR to treatment outcome" is unclear.[151] A meta-analysis in children and adolescents also found that EMDR was as efficacious as cognitive behavioral therapy.[152]
Children with PTSD are far more likely to pursue treatment at school (because of its proximity and ease) than at a free clinic.[153]
#### Cognitive behavioral therapy
The diagram depicts how emotions, thoughts, and behaviors all influence each other. The triangle in the middle represents CBT's tenet that all humans' core beliefs can be summed up in three categories: self, others, future.
CBT seeks to change the way a person feels and acts by changing the patterns of thinking or behavior, or both, responsible for negative emotions. Results from a 2018 systematic review found high strength of evidence that supports CBT-exposure therapy efficacious for a reduction in PTSD and depression symptoms, as well as the loss of PTSD diagnosis.[154] CBT has been proven to be an effective treatment for PTSD and is currently considered the standard of care for PTSD by the United States Department of Defense.[155][156] In CBT, individuals learn to identify thoughts that make them feel afraid or upset and replace them with less distressing thoughts. The goal is to understand how certain thoughts about events cause PTSD-related stress.[157][158] The provision of CBT in an Internet-based format has also been studied in a 2018 Cochrane review. This review did find similar beneficial effects for Internet-based settings as in face-to-face but the quality of the evidence was low due to the small number of trials reviewed.[159]
Exposure therapy is a type of cognitive behavioral therapy[160] that involves assisting trauma survivors to re-experience distressing trauma-related memories and reminders in order to facilitate habituation and successful emotional processing of the trauma memory. Most exposure therapy programs include both imaginal confrontation with the traumatic memories and real-life exposure to trauma reminders; this therapy modality is well supported by clinical evidence.[citation needed] The success of exposure-based therapies has raised the question of whether exposure is a necessary ingredient in the treatment of PTSD.[161] Some organizations[which?] have endorsed the need for exposure.[162][163] The U.S. Department of Veterans Affairs has been actively training mental health treatment staff in prolonged exposure therapy[164] and Cognitive Processing Therapy[165] in an effort to better treat U.S. veterans with PTSD.
Recent research on contextually based third-generation behavior therapies suggests that they may produce results comparable to some of the better validated therapies.[166] Many of these therapy methods have a significant element of exposure[167] and have demonstrated success in treating the primary problems of PTSD and co-occurring depressive symptoms.[168]
#### Eye movement desensitization and reprocessing
Main article: Eye movement desensitization and reprocessing
Eye movement desensitization and reprocessing (EMDR) is a form of psychotherapy developed and studied by Francine Shapiro.[169] She had noticed that, when she was thinking about disturbing memories herself, her eyes were moving rapidly. When she brought her eye movements under control while thinking, the thoughts were less distressing.[169]
In 2002, Shapiro and Maxfield published a theory of why this might work, called adaptive information processing.[170] This theory proposes that eye movement can be used to facilitate emotional processing of memories, changing the person's memory to attend to more adaptive information.[171] The therapist initiates voluntary rapid eye movements while the person focuses on memories, feelings or thoughts about a particular trauma.[10][172] The therapists uses hand movements to get the person to move their eyes backward and forward, but hand-tapping or tones can also be used.[10] EMDR closely resembles cognitive behavior therapy as it combines exposure (re-visiting the traumatic event), working on cognitive processes and relaxation/self-monitoring.[10] However, exposure by way of being asked to think about the experience rather than talk about it has been highlighted as one of the more important distinguishing elements of EMDR.[173]
There have been several small controlled trials of four to eight weeks of EMDR in adults[174] as well as children and adolescents.[172] There is moderate strength of evidence to support the efficacy of EMDR "for reduction in PTSD symptoms, loss of diagnosis, and reduction in depressive symptoms" according to a 2018 systematic review update.[154] EMDR reduced PTSD symptoms enough in the short term that one in two adults no longer met the criteria for PTSD, but the number of people involved in these trials was small and thus results should be interpreted with caution pending further research.[174] There was not enough evidence to know whether or not EMDR could eliminate PTSD in adults.[174] In children and adolescents, a recent meta-analysis of randomized controlled trials using MetaNSUE to avoid biases related to missing information found that EMDR was at least as efficacious as CBT, and superior to waitlist or placebo.[152] There was some evidence that EMDR might prevent depression.[174] There were no studies comparing EMDR to other psychological treatments or to medication.[174] Adverse effects were largely unstudied.[174] The benefits were greater for women with a history of sexual assault compared with people who had experienced other types of traumatizing events (such as accidents, physical assaults and war). There is a small amount of evidence that EMDR may improve re-experiencing symptoms in children and adolescents, but EMDR has not been shown to improve other PTSD symptoms, anxiety, or depression.[172]
The eye movement component of the therapy may not be critical for benefit.[10][171] As there has been no major, high quality randomized trial of EMDR with eye movements versus EMDR without eye movements, the controversy over effectiveness is likely to continue.[173] Authors of a meta-analysis published in 2013 stated, "We found that people treated with eye movement therapy had greater improvement in their symptoms of post-traumatic stress disorder than people given therapy without eye movements....Secondly we found that that in laboratory studies the evidence concludes that thinking of upsetting memories and simultaneously doing a task that facilitates eye movements reduces the vividness and distress associated with the upsetting memories."[147]
#### Interpersonal psychotherapy
Other approaches, in particular involving social supports,[175][176] may also be important. An open trial of interpersonal psychotherapy[177] reported high rates of remission from PTSD symptoms without using exposure.[178] A current, NIMH-funded trial in New York City is now (and into 2013) comparing interpersonal psychotherapy, prolonged exposure therapy, and relaxation therapy.[179][full citation needed][180][181]
### Medication
While many medications do not have enough evidence to support their use, three (fluoxetine, paroxetine, and venlafaxine) have been shown to have a small to modest benefit over placebo.[14] With many medications, residual PTSD symptoms following treatment is the rule rather than the exception.[182]
#### Antidepressants
Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) may have some benefit for PTSD symptoms.[14][183][184] Tricyclic antidepressants are equally effective but are less well tolerated.[185] Evidence provides support for a small or modest improvement with sertraline, fluoxetine, paroxetine, and venlafaxine.[14][186] Thus, these four medications are considered to be first-line medications for PTSD.[183][4]
#### Benzodiazepines
Benzodiazepines are not recommended for the treatment of PTSD due to a lack of evidence of benefit and risk of worsening PTSD symptoms.[187] Some authors believe that the use of benzodiazepines is contraindicated for acute stress, as this group of drugs can cause dissociation.[188] Nevertheless, some use benzodiazepines with caution for short-term anxiety and insomnia.[189][190][191] While benzodiazepines can alleviate acute anxiety, there is no consistent evidence that they can stop the development of PTSD and may actually increase the risk of developing PTSD 2–5 times.[13] Additionally, benzodiazepines may reduce the effectiveness of psychotherapeutic interventions, and there is some evidence that benzodiazepines may actually contribute to the development and chronification of PTSD. For those who already have PTSD, benzodiazepines may worsen and prolong the course of illness, by worsening psychotherapy outcomes, and causing or exacerbating aggression, depression (including suicidality), and substance use.[13] Drawbacks include the risk of developing a benzodiazepine dependence, tolerance (i.e., short-term benefits wearing off with time), and withdrawal syndrome; additionally, individuals with PTSD (even those without a history of alcohol or drug misuse) are at an increased risk of abusing benzodiazepines.[4][192] Due to a number of other treatments with greater efficacy for PTSD and less risks (e.g., prolonged exposure, cognitive processing therapy, eye movement desensitization and reprocessing, cognitive restructuring therapy, trauma-focused cognitive behavioral therapy, brief eclectic psychotherapy, narrative therapy, stress inoculation training, serotonergic antidepressants, adrenergic inhibitors, antipsychotics, and even anticonvulsants), benzodiazepines should be considered relatively contraindicated until all other treatment options are exhausted.[11][193] For those who argue that benzodiazepines should be used sooner in the most severe cases, the adverse risk of disinhibition (associated with suicidality, aggression and crimes) and clinical risks of delaying or inhibiting definitive efficacious treatments, make other alternative treatments preferable (e.g., inpatient, residential, partial hospitalization, intensive outpatient, dialectic behavior therapy; and other fast-acting sedating medications such as trazodone, mirtazapine, amitripytline, doxepin, prazosin, propranolol, guanfacine, clonidine, quetiapine, olanzapine, valproate, gabapentin).[4][193][194]
#### Prazosin
Prazosin, an alpha-1 adrenergic antagonist, has been used in veterans with PTSD to reduce nightmares. Studies show variability in the symptom improvement, appropriate dosages, and efficacy in this population.[195][196][197]
#### Glucocorticoids
Glucocorticoids may be useful for short-term therapy to protect against neurodegeneration caused by the extended stress response that characterizes PTSD, but long-term use may actually promote neurodegeneration.[198]
#### Cannabinoids
As of 2019 cannabis is specifically not recommended as a treatment.[199][200] However, use of cannabis or derived products is widespread among U.S. veterans with PTSD.[201]
The cannabinoid nabilone is sometimes used for nightmares in PTSD. Although some short-term benefit was shown, adverse effects are common and it has not been adequately studied to determine efficacy.[202] Currently, a handful of states permit the use of medical cannabis for the treatment of PTSD.[203]
### Other
#### Exercise, sport and physical activity
Physical activity can influence people's psychological[204] and physical health.[205] The U.S. National Center for PTSD recommends moderate exercise as a way to distract from disturbing emotions, build self-esteem and increase feelings of being in control again. They recommend a discussion with a doctor before starting an exercise program.[206]
#### Play therapy for children
Play is thought to help children link their inner thoughts with their outer world, connecting real experiences with abstract thought.[207] Repetitive play can also be one way a child relives traumatic events, and that can be a symptom of trauma in a child or young person.[208] Although it is commonly used, there have not been enough studies comparing outcomes in groups of children receiving and not receiving play therapy, so the effects of play therapy are not yet understood.[10][207]
#### Military programs
Many veterans of the wars in Iraq and Afghanistan have faced significant physical, emotional, and relational disruptions. In response, the United States Marine Corps has instituted programs to assist them in re-adjusting to civilian life, especially in their relationships with spouses and loved ones, to help them communicate better and understand what the other has gone through.[209] Walter Reed Army Institute of Research (WRAIR) developed the Battlemind program to assist service members avoid or ameliorate PTSD and related problems. Wounded Warrior Project partnered with the US Department of Veterans Affairs to create Warrior Care Network, a national health system of PTSD treatment centers.[210][211]
#### Nightmares
In 2020, the United States Food and Drug Administration granted marketing approval for an Apple Watch app call NightWare. The app aims to improve sleep for people suffering from PTSD-related nightmares, by vibrating when it detects a nightmare in progress based on monitoring heart rate and body movement.[212]
## Epidemiology
Disability-adjusted life year rates for post-traumatic stress disorder per 100,000 inhabitants in 2004.[213]
no data
< 43.5
43.5–45
45–46.5
46.5–48
48–49.5
49.5–51
51–52.5
52.5–54
54–55.5
55.5–57
57–58.5
> 58.5
There is debate over the rates of PTSD found in populations, but, despite changes in diagnosis and the criteria used to define PTSD between 1997 and 2013, epidemiological rates have not changed significantly.[214][215] Most of the current reliable data regarding the epidemiology of PTSD is based on DSM-IV criteria, as the DSM-5 was not introduced until 2013.
The United Nations' World Health Organization publishes estimates of PTSD impact for each of its member states; the latest data available are for 2004. Considering only the 25 most populated countries ranked by overall age-standardized Disability-Adjusted Life Year (DALY) rate, the top half of the ranked list is dominated by Asian/Pacific countries, the US, and Egypt.[216] Ranking the countries by the male-only or female-only rates produces much the same result, but with less meaningfulness, as the score range in the single-sex rankings is much-reduced (4 for women, 3 for men, as compared with 14 for the overall score range), suggesting that the differences between female and male rates, within each country, is what drives the distinctions between the countries.[217][218]
As of 2017, the cross-national lifetime prevalence of PTSD was 3.9%, based on a survey were 5.6% had been exposed to trauma.[219] The primary factor impacting treatment-seeking behavior, which can help to mitigate PTSD development after trauma was income, while being younger, female, and having less social status (less education, lower individual income, and being unemployed) were all factors associated with less treatment-seeking behaviour.[219]
Age-standardized Disability-adjusted life year (DALY) rates for PTSD, per 100,000 inhabitants, in 25 most populous countries, ranked by overall rate (2004) Region Country PTSD DALY rate,
overall[216] PTSD DALY rate,
females[217] PTSD DALY rate,
males[218]
Asia / Pacific Thailand 59 86 30
Asia / Pacific Indonesia 58 86 30
Asia / Pacific Philippines 58 86 30
Americas USA 58 86 30
Asia / Pacific Bangladesh 57 85 29
Africa Egypt 56 83 30
Asia / Pacific India 56 85 29
Asia / Pacific Iran 56 83 30
Asia / Pacific Pakistan 56 85 29
Asia / Pacific Japan 55 80 31
Asia / Pacific Myanmar 55 81 30
Europe Turkey 55 81 30
Asia / Pacific Vietnam 55 80 30
Europe France 54 80 28
Europe Germany 54 80 28
Europe Italy 54 80 28
Asia / Pacific Russian Federation 54 78 30
Europe United Kingdom 54 80 28
Africa Nigeria 53 76 29
Africa Dem. Republ. of Congo 52 76 28
Africa Ethiopia 52 76 28
Africa South Africa 52 76 28
Asia / Pacific China 51 76 28
Americas Mexico 46 60 30
Americas Brazil 45 60 30
### United States
The National Comorbidity Survey Replication has estimated that the lifetime prevalence of PTSD among adult Americans is 6.8%, with women (9.7%) more than twice as likely as men[97] (3.6%) to have PTSD at some point in their lives.[47] More than 60% of men and more than 60% of women experience at least one traumatic event in their life. The most frequently reported traumatic events by men are rape, combat, and childhood neglect or physical abuse. Women most frequently report instances of rape, sexual molestation, physical attack, being threatened with a weapon and childhood physical abuse.[97] 88% of men and 79% of women with lifetime PTSD have at least one comorbid psychiatric disorder. Major depressive disorder, 48% of men and 49% of women, and lifetime alcohol abuse or dependence, 51.9% of men and 27.9% of women, are the most common comorbid disorders.[220]
#### Military combat
The United States Department of Veterans Affairs estimates that 830,000 Vietnam War veterans suffered symptoms of PTSD.[221] The National Vietnam Veterans' Readjustment Study (NVVRS) found 15% of male and 9% of female Vietnam veterans had PTSD at the time of the study. Life-time prevalence of PTSD was 31% for males and 27% for females. In a reanalysis of the NVVRS data, along with analysis of the data from the Matsunaga Vietnam Veterans Project, Schnurr, Lunney, Sengupta, and Waelde found that, contrary to the initial analysis of the NVVRS data, a large majority of Vietnam veterans suffered from PTSD symptoms (but not the disorder itself). Four out of five reported recent symptoms when interviewed 20–25 years after Vietnam.[222]
A 2011 study from Georgia State University and San Diego State University found that rates of PTSD diagnosis increased significantly when troops were stationed in combat zones, had tours of longer than a year, experienced combat, or were injured. Military personnel serving in combat zones were 12.1 percentage points more likely to receive a PTSD diagnosis than their active-duty counterparts in non-combat zones. Those serving more than 12 months in a combat zone were 14.3 percentage points more likely to be diagnosed with PTSD than those having served less than one year. Experiencing an enemy firefight was associated with an 18.3 percentage point increase in the probability of PTSD, while being wounded or injured in combat was associated with a 23.9 percentage point increase in the likelihood of a PTSD diagnosis. For the 2.16 million U.S. troops deployed in combat zones between 2001 and 2010, the total estimated two-year costs of treatment for combat-related PTSD are between $1.54 billion and $2.69 billion.[223]
As of 2013, rates of PTSD have been estimated at up to 20% for veterans returning from Iraq and Afghanistan.[224] As of 2013 13% of veterans returning from Iraq were unemployed.[225]
#### Man-made disasters
The September 11 attacks took the lives of nearly 3,000 people, leaving 6,000 injured.[226] First responders (police and firefighters), emergency medical services, sanitation workers, and volunteers were all involved in the recovery efforts. The prevalence of probable PTSD in these highly exposed populations was estimated across several studies using in-person, telephone, and online interviews and questionnaires.[226][227][228] Overall prevalence of PTSD was highest immediately following the attacks and decreased over time. However, disparities were found among the different types of recovery workers.[226][227] The rate of probable PTSD for first responders was lowest directly after the attacks and increased from ranges of 4.8-7.8% to 7.4-16.5% between the 5-6 year follow-up and a later assessment.[226] When comparing traditional responders to non-traditional responders (volunteers), the probable PTSD prevalence 2.5 years after the initial visit was greater in volunteers with estimates of 11.7% and 17.2% respectively.[226] Volunteer participation in tasks atypical to the defined occupational role was a significant risk factor for PTSD.[227] Other risk factors included exposure intensity, earlier start date, duration of time spent on site, and constant, negative reminders of the trauma.[226][227] Additional research has been performed to understand the social consequences of the September 11 attacks. Alcohol consumption was assessed in a cohort of World Trade Center workers using the cut-annoyed-guilty-eye (CAGE) questionnaire for alcohol abuse. Almost 50% of World Trade Center workers who self-identified as alcohol users reported drinking more during the rescue efforts.[228] Nearly a quarter of these individuals reported drinking more following the recovery.[228] If determined to have probable PTSD status, the risk of developing an alcohol problem was double compared to those without psychological morbidity.[228] Social disability was also studied in this cohort as a social consequence of the September 11 attacks. Defined by the disruption of family, work, and social life, the risk of developing social disability increased 17-fold when categorized as having probable PTSD.[228]
## Veterans
Vietnam Veterans Memorial, Washington, D.C.
### United States
See also: Benefits for US Veterans with PTSD
The United States provides a range of benefits for veterans that the VA has determined have PTSD, which developed during, or as a result of, their military service. These benefits may include tax-free cash payments,[229] free or low-cost mental health treatment and other healthcare,[230] vocational rehabilitation services,[231] employment assistance,[232] and independent living support.[233][234]
### Iraq
Young Iraqis have high rates of post-traumatic stress disorder due to the 2003 invasion of Iraq.[235]
### United Kingdom
In the UK, there are various charities and service organisations dedicated to aiding veterans in readjusting to civilian life. The Royal British Legion and the more recently established Help for Heroes are two of Britain's more high-profile veterans' organisations which have actively advocated for veterans over the years. There has been some controversy that the NHS has not done enough in tackling mental health issues and is instead "dumping" veterans on charities such as Combat Stress.[236][237]
### Canada
Veterans Affairs Canada offers a new program that includes rehabilitation, financial benefits, job placement, health benefits program, disability awards, peer support[238][239][240] and family support.[241]
## History
The 1952 edition of the DSM-I includes a diagnosis of "gross stress reaction", which has similarities to the modern definition and understanding of PTSD.[242] Gross stress reaction is defined as a normal personality using established patterns of reaction to deal with overwhelming fear as a response to conditions of great stress.[243] The diagnosis includes language which relates the condition to combat as well as to "civilian catastrophe".[243]
A USAF study carried out in 1979 focused on individuals (civilian and military) who had worked to recover or identify the remains of those who died in Jonestown. The bodies had been dead for several days, and a third of them had been children. The study used the term "dysphoria" to describe PTSD-like symptoms.[244]
Early in 1978, the diagnosis term "post-traumatic stress disorder" was first recommended in a working group finding presented to the Committee of Reactive Disorders.[245] The condition was described in the DSM-III (1980) as posttraumatic stress disorder.[242][245] In the DSM-IV, the spelling "posttraumatic stress disorder" is used, while in the ICD-10, the spelling is "post-traumatic stress disorder".[246]
The addition of the term to the DSM-III was greatly influenced by the experiences and conditions of U.S. military veterans of the Vietnam War.[247] Owing to its association with the war in Vietnam, PTSD has become synonymous with many historical war-time diagnoses such as railway spine, stress syndrome, nostalgia, soldier's heart, shell shock, battle fatigue, combat stress reaction, or traumatic war neurosis.[248][249] Some of these terms date back to the 19th century, which is indicative of the universal nature of the condition. In a similar vein, psychiatrist Jonathan Shay has proposed that Lady Percy's soliloquy in the William Shakespeare play Henry IV, Part 1 (act 2, scene 3, lines 40–62[250]), written around 1597, represents an unusually accurate description of the symptom constellation of PTSD.[251]
Statue, Three Servicemen, Vietnam Veterans Memorial
The correlations between combat and PTSD are undeniable; according to Stéphane Audoin-Rouzeau and Annette Becker, "One-tenth of mobilized American men were hospitalized for mental disturbances between 1942 and 1945, and, after thirty-five days of uninterrupted combat, 98% of them manifested psychiatric disturbances in varying degrees."[252] In fact, much of the available published research regarding PTSD is based on studies done on veterans of the war in Vietnam. A study based on personal letters from soldiers of the 18th-century Prussian Army concludes that combatants may have had PTSD.[253] Aspects of PTSD in soldiers of ancient Assyria have been identified using written sources from 1300–600 BCE. These Assyrian soldiers would undergo a three-year rotation of combat before being allowed to return home, and were reported to have faced immense challenges in reconciling their past actions in war with their civilian lives.[254] Connections between the actions of Viking berserkers and the hyperarousal of post-traumatic stress disorder have also been drawn.[255]
The researchers from the Grady Trauma Project highlight the tendency people have to focus on the combat side of PTSD: "less public awareness has focused on civilian PTSD, which results from trauma exposure that is not combat related... " and "much of the research on civilian PTSD has focused on the sequelae of a single, disastrous event, such as the Oklahoma City bombing, September 11th attacks, and Hurricane Katrina".[256] Disparity in the focus of PTSD research affects the already popular perception of the exclusive interconnectedness of combat and PTSD. This is misleading when it comes to understanding the implications and extent of PTSD as a neurological disorder. Dating back to the definition of Gross stress reaction in the DSM-I, civilian experience of catastrophic or high stress events is included as a cause of PTSD in medical literature. The 2014 National Comorbidity Survey reports that "the traumas most commonly associated with PTSD are combat exposure and witnessing among men and rape and sexual molestation among women."[47] Because of the initial overt focus on PTSD as a combat related disorder when it was first fleshed out in the years following the war in Vietnam, in 1975 Ann Wolbert Burgess and Lynda Lytle Holmstrom defined Rape trauma syndrome, RTS, in order to draw attention to the striking similarities between the experiences of soldiers returning from war and of rape victims.[257] This paved the way for a more comprehensive understanding of causes of PTSD.
After PTSD became an official psychiatric diagnosis with the publication of DSM-III (1980), the number of personal injury lawsuits (tort claims) asserting the plaintiff suffered from PTSD increased rapidly. However, triers of fact (judges and juries) often regarded the PTSD diagnostic criteria as imprecise, a view shared by legal scholars, trauma specialists, forensic psychologists, and forensic psychiatrists. Professional discussions and debates in academic journals, at conferences, and between thought leaders, led to a more clearly-defined set of diagnostic criteria in DSM-IV, particularly the definition of a "traumatic event".[258]
The DSM-IV classified PTSD under anxiety disorders, but the DSM-5 created a new category called "trauma and stressor-related disorders," in which PTSD is now classified.[1]
## Terminology
The Diagnostic and Statistical Manual of Mental Disorders does not hyphenate 'post' and 'traumatic', thus, the DSM-5 lists the disorder as posttraumatic stress disorder. However, many scientific journal articles and other scholarly publications do hyphenate the name of the disorder, viz., post-traumatic stress disorder.[259] Dictionaries also differ with regard to the preferred spelling of the disorder with the Collins English Dictionary – Complete and Unabridged using the hyphenated spelling, and the American Heritage Dictionary of the English Language, Fifth Edition and the Random House Kernerman Webster's College Dictionary giving the non-hyphenated spelling.[260]
Some, particularly current or former U.S. Department of Defense officials, have used the terminology "PTSS" (syndrome instead of disorder, to avoid connotation of stigma), or just "PTS".[261]
The comedian George Carlin criticized the euphemism treadmill which led to progressive change of the way PTSD was referred to over the course of the 20th century, from "shell shock" in the First World War to the "battle fatigue" in the Second World War, to "operational exhaustion" in the Korean War, to the current "post-traumatic stress disorder", coined during the Vietnam War, which "added a hyphen" and which, he commented, "completely burie[s] [the pain] under jargon". He also stated that the name given to the condition has had a direct effect on the way veteran soldiers with PTSD were treated and perceived by civilian populations over time.[262]
## Research
Most knowledge regarding PTSD comes from studies in high-income countries.[263]
To recapitulate some of the neurological and neurobehavioral symptoms experienced by the veteran population of recent conflicts in Iraq and Afghanistan, researchers at the Roskamp Institute and the James A Haley Veteran's Hospital (Tampa) have developed an animal model to study the consequences of mild traumatic brain injury (mTBI) and PTSD.[264] In the laboratory, the researchers exposed mice to a repeated session of unpredictable stressor (i.e. predator odor while restrained), and physical trauma in the form of inescapable foot-shock, and this was also combined with a mTBI. In this study, PTSD animals demonstrated recall of traumatic memories, anxiety, and an impaired social behavior, while animals subject to both mTBI and PTSD had a pattern of disinhibitory-like behavior. mTBI abrogated both contextual fear and impairments in social behavior seen in PTSD animals. In comparison with other animal studies,[264][265] examination of neuroendocrine and neuroimmune responses in plasma revealed a trend toward increase in corticosterone in PTSD and combination groups.
Stellate ganglion block is an experimental procedure for the treatment of PTSD.[266]
Researchers are investigating a number of experimental FAAH and MAGL-inhibiting drugs of hopes of finding a better treatment for anxiety and stress-related illnesses.[267] In 2016, the FAAH-inhibitor drug BIA 10-2474 was withdrawn from human trials in France due to adverse effects.[268]
### Psychotherapy
Trauma-focused psychotherapies for PTSD (also known as "exposure-based" or "exposure" psychotherapies), such as prolonged exposure therapy (PE), eye movement desensitization and reprocessing (EMDR), and cognitive-reprocessing therapy (CPT) have the most evidence for efficacy and are recommended as first-line treatment for PTSD by almost all clinical practice guidelines.[269][270][271] Exposure-based psychotherapies demonstrate efficacy for PTSD caused by different trauma "types", such as combat, sexual-assault, or natural disasters.[269] At the same time, many trauma-focused psychotherapies evince high drop-out rates.[272]
Most systematic reviews and clinical guidelines indicate that psychotherapies for PTSD, most of which are trauma-focused therapies, are more effective than pharmacotherapy (medication),[273] although there are reviews that suggest exposure-based psychotherapies for PTSD and pharmacotherapy are equally effective.[274] Interpersonal psychotherapy shows preliminary evidence of probable efficacy, but more research is needed to reach definitive conclusions.[275]
Researchers are exploring the possibility that MDMA might be an effective adjunctive treatment with psychotherapy.[276][277] Researchers are also investigating using D-cycloserine, hydrocortisone, and propranolol as an adjunctive treatment to evidence-based exposure therapies, although there is not any evidence that such add-on treatments are more effective than trauma-focused psychotherapies.[278]
## Notes
1. ^ Acceptable variants of this term exist; see the Terminology section in this article.
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## External links
Wikiquote has quotations related to: Post-traumatic stress disorder
Wikimedia Commons has media related to Posttraumatic stress disorder.
* Post-traumatic stress disorder at Curlie
* Post traumatic stress disorder information from The National Child Traumatic Stress Network
* Information resources from The University of Queensland School of Medicine
* APA practice parameters for assessment and treatment for PTSD (Updated 2017)
* Resources for professionals from the VA National PTSD Center
* Psychiatry portal
Classification
D
* ICD-10: F43.1
* ICD-9-CM: 309.81
* MeSH: D013313
* DiseasesDB: 33846
* SNOMED CT: 47505003
External resources
* MedlinePlus: 000925
* eMedicine: med/1900
* Patient UK: Post-traumatic stress disorder
* 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
Trauma
Principles
* Polytrauma
* Major trauma
* Traumatology
* Triage
* Resuscitation
* Trauma triad of death
Assessment
Clinical prediction rules
* Revised Trauma Score
* Injury Severity Score
* Abbreviated Injury Scale
* NACA score
Investigations
* Diagnostic peritoneal lavage
* Focused assessment with sonography for trauma
Management
Principles
* Advanced trauma life support
* Trauma surgery
* Trauma center
* Trauma team
* Damage control surgery
* Early appropriate care
Procedures
* Resuscitative thoracotomy
Pathophysiology
Injury
* MSK
* Bone fracture
* Joint dislocation
* Degloving
* Soft tissue injury
* Resp
* Flail chest
* Pneumothorax
* Hemothorax
* Diaphragmatic rupture
* Pulmonary contusion
* Cardio
* Internal bleeding
* Thoracic aorta injury
* Cardiac tamponade
* GI
* Blunt kidney trauma
* Ruptured spleen
* Neuro
* Penetrating head injury
* Traumatic brain injury
* Intracranial hemorrhage
Mechanism
* Blast injury
* Blunt trauma
* Burn
* Penetrating trauma
* Crush injury
* Stab wound
* Ballistic trauma
* Electrocution
Region
* Abdominal trauma
* Chest trauma
* Facial trauma
* Head injury
* Spinal cord injury
Demographic
* Geriatric trauma
* Pediatric trauma
Complications
* Posttraumatic stress disorder
* Wound healing
* Acute lung injury
* Crush syndrome
* Rhabdomyolysis
* Compartment syndrome
* Contracture
* Volkmann's contracture
* Embolism
* air
* fat
* Chronic traumatic encephalopathy
* Subcutaneous emphysema
Authority control
* GND: 4361388-3
* LCCN: sh85105424
* NARA: 10675626
* NDL: 01000003
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Post-traumatic stress disorder | c0038436 | 4,589 | wikipedia | https://en.wikipedia.org/wiki/Post-traumatic_stress_disorder | 2021-01-18T18:47:02 | {"mesh": ["D013313"], "umls": ["C0038436"], "wikidata": ["Q202387"]} |
Granulomatous mastitis
SpecialtyGynecology
Granulomatous mastitis can be divided into idiopathic granulomatous mastitis (also known as granular lobular mastitis[1]) and granulomatous mastitis occurring as a rare secondary complication of a great variety of other conditions such as tuberculosis and other infections, sarcoidosis and granulomatosis with polyangiitis. Special forms of granulomatous mastitis occur as complication of diabetes. Some cases are due to silicone injection (Silicone-induced granulomatous inflammation) or other foreign body reactions.[2][3]
Idiopathic granulomatous mastitis (IGM) is defined as granulomatous mastitis without any other attributable cause such as those above mentioned. It occurs on average two years and almost exclusively up to six years after pregnancy, usual age range is 17 to 42 years. Some cases have been reported that were related to drug induced hyperprolactinemia.[4][5] Exceptionally rarely it has been diagnosed during pregnancy and in men.[6][7]
Primary presentation of any of these conditions as mastitis is very rare and in many cases probably predisposed by other breast or systemic conditions. Although granulomatous mastitis is easily confused with cancer it is a completely benign (non-cancerous) condition. Treatment is radically different for idiopathic granulomatous mastitis and other granulomatous lesions of the breast, so the precise diagnosis is therefore very important.
## Contents
* 1 Symptoms
* 2 Diagnosis
* 3 Causes of idiopathic granulomatous mastitis
* 3.1 Microbiology
* 4 Treatment
* 5 References
* 6 External links
## Symptoms[edit]
Patients mostly present with a hard lump in one breast without any sign of a systemic disease. Other possible symptoms include nipple retraction, pain, inflammation of the overlying skin, nipple discharge, fistula, enlarged lymph nodes, in rare case peau d'orange-like changes. Presentation is mostly unilateral although a significant share of cases is bilateral, also in many cases contralateral or bilateral recurrences were documented. Several cases occurring together with fever, polyarthralgia and erythema nodosum were documented.[citation needed]
## Diagnosis[edit]
Characteristic for idiopathic granulomatous mastitis are multinucleated giant cells and epithelioid histiocytes forming non-caseating granulomas around lobules. Often minor ductal and periductal inflammation is present. The lesion is in some cases very difficult to distinguish from breast cancer and other causes such as infections (tuberculosis, syphilis, corynebacterial infection, mycotic infection), autoimmune diseases (sarcoidosis, granulomatosis with polyangiitis), foreign body reaction and granulomatous reaction in a carcinoma must be excluded.[4][8]
The condition is diagnosed very rarely. As the diagnosis is a lengthy differential diagnosis of exclusion there is considerable uncertainty about incidence. It has been suspected that some cases diagnosed as IGM in developing countries may have other explanations. On the other hand, IGM is usually diagnosed only after complications and referral to a secondary breast care center so light cases may resolve spontaneously or after symptomatic treatment and thus never be diagnosed as IGM. As a completely pathogen free breast will be exceedingly rare even in completely healthy population there is also uncertainty when to consider pathogens as causative or as mere coincidental finding.[citation needed]
## Causes of idiopathic granulomatous mastitis[edit]
Causes are not known. The histology is suggestive of an autoimmune reaction. The high rate of relapses as well as relatively high proportion of bilateral cases is highly suggestive of a systemic predisposition. Presently most evidence points towards an important role of elevated prolactin levels or overt hyperprolactinemia with additional triggers such as local trauma or irritation. Alpha 1-antitrypsin deficiency was documented in one case, interferon-alpha therapy in another case. Similar cases of granulomatous mastitis were reported in IgG4-related disease though the exact relationship to IGM remains to be elucidated. Other contributing factors of IGM were investigated such as oral contraceptives usage. Many cases were reported after use of prolactin elevating medications such as antipsychotics.[4][5][9][10][11]
Elevated prolactin levels have the direct effects of increasing secretory activity of breast lobules, maintaining tight junctions of the ductal epithelium, preventing involution of the breast gland after weaning and are known to stimulate the immune system, contributing to both physiological and pathological granulomatous lesions and non-caseating granulomas.[4] PRL is also secreted locally in the breast and local secretion by lymphocytes may be enhanced during inflammatory reactions.[12] Autoimmune reaction to extravasated fat and protein rich luminal fluid (denaturized milk) resulting from the secretory activity is assumed to be one of the triggers of IGM.[4][13] Several other hormones can contribute to PRL signaling in the breast gland, high levels of insulin caused for example by peripheral insulin resistance (resulting from pregnancy, gestational diabetes or developing diabetes mellitus type 2) will enhance the galactogenic and antiapoptotic effects of PRL and growth hormone by acting synergistically with IGF-1.
### Microbiology[edit]
The presence of Corynebacterium in granulomatous mastitis was first reported in 1996.[14] Since then multiple reports have confirmed the presence of this genus in granulomatous mastitis.[15][16][17] The most commonly isolated species is Corynebacterium kroppenstedtii. A selective medium for the isolation of this species has been described.[18] This organism, first isolated from human sputum in 1998, requires lipids for its growth which may help to explain its association with this condition.
## Treatment[edit]
Treatment protocols are not well established. Some sources report that approximately half of the patients will fully recover after 2–24 months management.[19]
One review recommended complete resection or corticosteroid therapy, stating also that long-term follow-up was indicated due to a high rate of recurrence.[20] Treatment with steroids usually requires about 6 months. While some source report very good success with steroids,[21] most report a considerable risk of recurrence after a treatment with steroids alone. Steroids are known to cause elevation of prolactin levels and increase risk of several conditions such as diabetes, and other endocrinopathies which in turn increase the risk of IGM. For surgical treatment, recurrence rates of 5-50% have been reported.[4]
Treatment with a combination of glucocorticoids and prolactin lowering medications such as bromocriptine or cabergoline was used with good success in Germany.[22] Prolactin-lowering medication has also been reported to reduce the risk of recurrence.[23] In cases of drug-induced hyperprolactinemia (such as antipsychotics) prolactin-sparing medication can be tried.[4]
Methotrexate alone or in combination with steroids has been used with good success. Its principal mechanism of action is immunomodulating activity, with a side effect profile that is more favorable for treating IGM.[24]
Colchicine, azathioprine, and NSAIDs have also been used.[25][26]
## References[edit]
1. ^ Garcia-Rodiguez JA, Pattullo A (2013). "Idiopathic granulomatous mastitis: a mimicking disease in a pregnant woman: a case report". BMC Research Notes. 6 (95). doi:10.1186/1756-0500-6-95. PMC 3606122. PMID 23497626.
2. ^ El-Charnoubi, W. A.; Foged Henriksen, T; Joergen Elberg, J (2011). "Cutaneous silicone granuloma mimicking breast cancer after ruptured breast implant". Case Reports in Dermatological Medicine. 2011: 129138. doi:10.1155/2011/129138. PMC 3505939. PMID 23198167.
3. ^ Symmers, W. S. (1968). "Silicone mastitis in "topless" waitresses and some other varieties of foreign-body mastitis". British Medical Journal. 3 (5609): 19–22. doi:10.1136/bmj.3.5609.8-a. PMC 1989508. PMID 5690841.
4. ^ a b c d e f g Lin CH, Hsu CW, Tsao TY, Chou J (2012). "Idiopathic granulomatous mastitis associated with risperidone-induced hyperprolactinemia". Diagnostic Pathology. 7 (1): 2. doi:10.1186/1746-1596-7-2. PMC 3261802. PMID 22221904.
5. ^ a b Bellavia, M.; Damiano, G.; Palumbo, V. D.; Spinelli, G.; Tomasello, G.; Marrazzo, A.; Ficarella, S.; Bruno, A.; Sammartano, A.; Fiorentini, T.; Scio, A.; Maione, C.; Lo Monte, A. I. (2012). "Granulomatous Mastitis during Chronic Antidepressant Therapy: Is It Possible a Conservative Therapeutic Approach?". Journal of Breast Cancer. 15 (3): 371–372. doi:10.4048/jbc.2012.15.3.371. PMC 3468794. PMID 23091553.
6. ^ Reddy KM, Meyer CE, Nakdjevani A, Shrotria S (2005). "Idiopathic Granulomatous Mastitis in the Male Breast". The Breast Journal. 11 (1): 73. doi:10.1111/j.1075-122X.2005.21404.x. PMID 15647084.
7. ^ Goldberg, J.; Baute, L.; Storey, L.; Park, P. (2000). "Granulomatous mastitis in pregnancy". Obstetrics and gynecology. 96 (5 Pt 2): 813–815. doi:10.1016/S0029-7844(00)01051-6. PMID 11094217.
8. ^ Seo HR, Na KY, Yim HE, Kim TH, et al. (2012). "Differential Diagnosis in Idiopathic Granulomatous Mastitis and Tuberculous Mastitis". Journal of Breast Cancer. 15 (1): 111–118. doi:10.4048/jbc.2012.15.1.111. PMC 3318162. PMID 22493637.
9. ^ Schelfout, K.; Tjalma, W. A.; Cooremans, I. D.; Coeman, D. C.; Colpaert, C. G.; Buytaert, P. M. (2001). "Observations of an idiopathic granulomatous mastitis". European Journal of Obstetrics, Gynecology, and Reproductive Biology. 97 (2): 260–262. doi:10.1016/s0301-2115(00)00546-7. PMID 11451563.
10. ^ Shaaban, H.; Slim, J.; Choo, H. (2012). "Idiopathic granulomatous mastitis as a complication of interferon-alpha therapy". North American Journal of Medical Sciences. 4 (9): 424–426. doi:10.4103/1947-2714.101005. PMC 3456487. PMID 23050257.
11. ^ Ogura, K.; Matsumoto, T.; Aoki, Y.; Kitabatake, T.; Fujisawa, M.; Kojima, K. (2010). "IgG4-related tumour-forming mastitis with histological appearances of granulomatous lobular mastitis: Comparison with other types of tumour-forming mastitis". Histopathology. 57 (1): 39–45. doi:10.1111/j.1365-2559.2010.03581.x. PMID 20653779.
12. ^ Shelly, S.; Boaz, M.; Orbach, H. (2012). "Prolactin and autoimmunity". Autoimmunity Reviews. 11 (6–7): A465–A470. doi:10.1016/j.autrev.2011.11.009. PMID 22155203.
13. ^ Bässler, R. (1997). "Mastitis. Classification, histopathology and clinical aspects". Der Pathologe. 18 (1): 27–36. doi:10.1007/s002920050193. PMID 9157401.
14. ^ Binelli C, Lorimier G, Bertrand G, Parvery F, Bertrand AF, Verriele V (1996). "Granulomatous mastitis and corynebacteria infection. Two case reports". J Gynecol Obstet Biol Reprod (Paris). 25 (1): 27–32.CS1 maint: multiple names: authors list (link)
15. ^ Mathelin C, Riegel P, Chenard MP, Tomasetto C, Brettes JP (2005). "Granulomatous mastitis and corynebacteria: clinical and pathologic correlations". Breast J. 11 (5): 357. doi:10.1111/j.1075-122x.2005.21562.x.CS1 maint: multiple names: authors list (link)
16. ^ Mathelin C, Riegel P, Chenard MP, Brettes JP (2005). "Association of corynebacteria with granulomatous mastitis". Eur J Obstet Gynecol Reprod Biol. 119 (2): 260–261. doi:10.1016/j.ejogrb.2004.08.003.CS1 maint: multiple names: authors list (link)
17. ^ Tauch A, Fernández-Natal I, Soriano F (2016). "A microbiological and clinical review on Corynebacterium kroppenstedtii". Int J Infect Dis. 48: 33–39. doi:10.1016/j.ijid.2016.04.023.CS1 maint: multiple names: authors list (link)
18. ^ Wong SC, Poon RW, Foo CH, Ngan AH, Tse H, Lam VC, Leung TH, Wong CP, Cheng VC, Chen JH, Yuen KY (2018). "Novel selective medium for the isolation of corynebacterium kroppenstedtii from heavily colonised clinical specimens". J. Clin. Pathol. 71 (9): 781–786. doi:10.1136/jclinpath-2017-204834. PMID 29593062.
19. ^ Lai, E. C. H.; Chan, W. C.; Ma, T. K. F.; Tang, A. P. Y.; Poon, C. S. P.; Leong, H. T. (2005). "The Role of Conservative Treatment in Idiopathic Granulomatous Mastitis". The Breast Journal. 11 (6): 454–456. doi:10.1111/j.1075-122X.2005.00127.x. PMID 16297091.
20. ^ Imoto S, Kitaya T, Kodama T, Hasebe T, Mukai K (1997). "Idiopathic granulomatous mastitis: case report and review of the literature". Japanese Journal of Clinical Oncology (review). 27 (4): 274–277. doi:10.1093/jjco/27.4.274. PMID 9379518.
21. ^ Aldaqal, SM (2004). "Idiopathic granulomatous mastitis. Clinical presentation, radiological features and treatment". Saudi medical journal. 25 (12): 1884–1887. PMID 15711659.
22. ^ Krause, A.; Gerber, B.; Rhode, E. (1994). "Puerperal and non-puerperal mastitis". Zentralblatt für Gynäkologie. 116 (8): 488–491. PMID 7941820.
23. ^ Erhan, Y.; Veral, A.; Kara, E.; Ozdemir, N.; Kapkac, M.; Ozdedeli, E.; Yilmaz, R.; Koyuncu, A.; Erhan, Y.; Ozbal, O. (2000). "A clinicopthologic study of a rare clinical entity mimicking breast carcinoma: Idiopathic granulomatous mastitis". The Breast. 9 (1): 52–56. doi:10.1054/brst.1999.0072. PMID 14731585.
24. ^ Akbulut, S.; Arikanoglu, Z.; Senol, A.; Sogutcu, N.; Basbug, M.; Yeniaras, E.; Yagmur, Y. (2011). "Is methotrexate an acceptable treatment in the management of idiopathic granulomatous mastitis?". Archives of Gynecology and Obstetrics. 284 (5): 1189–1195. doi:10.1007/s00404-010-1825-2. PMID 21207047.
25. ^ Ayeva-Derman, M.; Perrotin, F.; Lefrancq, T.; Roy, F.; Lansac, J.; Body, G. (1999). "Idiopathic granulomatous mastitis. Review of the literature illustrated by 4 cases". Journal de gynécologie, obstétrique et biologie de la reproduction. 28 (8): 800–807. PMID 10635482.
26. ^ Vingerhoedt, N. M.; Janssen, S.; Mravunac, M.; Wauters, C. A.; Strobbe, L. J. (2008). "Granulomatous lobular mastitis: A benign abnormality that mimics malignancy". Nederlands tijdschrift voor geneeskunde. 152 (18): 1052–1056. PMID 18547028.
## External links[edit]
Classification
D
* MeSH: D058890
* SNOMED CT: 237444008
External resources
* Orphanet: 64722
* v
* t
* e
Breast disease
Inflammation
* Mastitis
* Nonpuerperal mastitis
* Subareolar abscess
* Granulomatous mastitis
Physiological changes
and conditions
* Benign mammary dysplasia
* Duct ectasia of breast
* Chronic cystic mastitis
* Mammoplasia
* Gynecomastia
* Adipomastia (lipomastia, pseudogynecomastia)
* Breast hypertrophy
* Breast atrophy
* Micromastia
* Amastia
* Anisomastia
* Breast engorgement
Nipple
* Nipple discharge
* Galactorrhea
* Inverted nipple
* Cracked nipples
* Nipple pigmentation
Masses
* Galactocele
* Breast cyst
* Breast hematoma
* Breast lump
* Pseudoangiomatous stromal hyperplasia
Other
* Pain
* Tension
* Ptosis
* Fat necrosis
* Amazia
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Granulomatous mastitis | c0405469 | 4,590 | wikipedia | https://en.wikipedia.org/wiki/Granulomatous_mastitis | 2021-01-18T18:42:57 | {"mesh": ["D058890"], "umls": ["C0405469"], "orphanet": ["64722"], "wikidata": ["Q5596838"]} |
"Skipped beat" redirects here. For other uses, see Skipped beat (disambiguation).
Premature atrial contraction
Other namesSupraventricular extra systole (SVES)
Two PACs as seen on a rhythm strip
SpecialtyCardiology
Premature atrial contractions (PACs), also known as atrial premature complexes (APC) or atrial premature beats (APB), are a common cardiac dysrhythmia characterized by premature heartbeats originating in the atria. While the sinoatrial node typically regulates the heartbeat during normal sinus rhythm, PACs occur when another region of the atria depolarizes before the sinoatrial node and thus triggers a premature heartbeat.[1] The exact cause of PACs is unclear; while several predisposing conditions exist, PACs commonly occur in healthy young and elderly people. Elderly people that get PACs usually don't need any further attention besides follow ups due to unclear evidence.[2][3] PACs are often completely asymptomatic and may be noted only with Holter monitoring, but occasionally they can be perceived as a skipped beat or a jolt in the chest. In most cases, no treatment other than reassurance is needed for PACs, although medications such as beta blockers can reduce the frequency of symptomatic PACs.[4]
## Contents
* 1 Risk factors
* 2 Diagnosis
* 2.1 Electrocardiogram
* 3 Treatment
* 4 Prognosis
* 5 Supraventricular extrasystole
* 6 See also
* 7 References
* 8 External links
## Risk factors[edit]
Hypertension, or abnormally high blood pressure, often signifies an elevated level of both psychological and physiological stress. Often, hypertension goes hand in hand with various atrial fibrillations including premature atrial contractions (PACs).[5] Additional factors that may contribute to spontaneous premature atrial contractions could be:[4]
* Increased age
* Abnormal body height
* History of cardiovascular disease (CV)
* Abnormal ANP levels
* Elevated cholesterol
## Diagnosis[edit]
Premature atrial contractions are typically diagnosed with an electrocardiogram, Holter monitor, or cardiac event monitor.
### Electrocardiogram[edit]
On an electrocardiogram (ECG), PACs are characterized by an abnormally shaped P wave. Since the premature beat initiates outside the sinoatrial node, the associated P wave appears different from those seen in normal sinus rhythm. Typically, the atrial impulse propagates normally through the atrioventricular node and into the cardiac ventricles, resulting in a normal, narrow QRS complex. However, if the atrial beat is premature enough, it may reach the atrioventricular node during its refractory period, in which case it will not be conducted to the ventricle and there will be no QRS complex following the P wave.
## Treatment[edit]
Premature atrial contractions are often benign, requiring no treatment. Occasionally, the patient having the PAC will find these symptoms bothersome, in which case the doctor may treat the PACs. Sometimes the PACs can indicate heart disease or an increased risk for other cardiac arrhythmias. In this case the underlying cause is treated. Often a beta blocker will be prescribed for symptomatic PACs.[6]
## Prognosis[edit]
In otherwise healthy patients, occasional premature atrial contractions are a common and normal finding and do not indicate any particular health risk. Rarely, in patients with other underlying structural heart problems, PACs can trigger a more serious arrhythmia such as atrial flutter or atrial fibrillation.[7] In otherwise healthy people, PACs usually disappear with adolescence.
## Supraventricular extrasystole[edit]
A supraventricular extrasystole (SVES) is an extrasystole or premature electrical impulse in the heart, generated above the level of the ventricle. This can be either a premature atrial contraction or a premature impulse from the atrioventricular node. SVES should be viewed in contrast to a premature ventricular contraction that has a ventricular origin and the associated QRS change. Instead of the electrical impulse beginning in the sinoatrial (SA) node and propagating to the atrioventricular (AV) node, the signal is conducted both to the ventricle and back to the SA node where the signal began.[8]
## See also[edit]
* Premature junctional contraction
* Premature ventricular contraction
## References[edit]
1. ^ [1], Nickolls, Peter; Richard M. T. Lu & Kenneth A. Collins, "Apparatus and method for antitachycardia pacing using a virtual electrode"
2. ^ Brodsky M, Wu D, Denes P, Kanakis C, Rosen KM (March 1977). "Arrhythmias documented by 24 hour continuous electrocardiographic monitoring in 50 male medical students without apparent heart disease". Am. J. Cardiol. 39 (3): 390–5. doi:10.1016/S0002-9149(77)80094-5. PMID 65912.
3. ^ Folarin VA, Fitzsimmons PJ, Kruyer WB (September 2001). "Holter monitor findings in asymptomatic male military aviators without structural heart disease". Aviat Space Environ Med. 72 (9): 836–8. PMID 11565820.
4. ^ a b Lin, Chin-Yu; Lin, Yenn-Jiang; Chen, Yun-Yu; Chang, Shih-Lin; Lo, Li-Wei; Chao, Tze-Fan; Chung, Fa-Po; Hu, Yu-Feng; Chong, Eric (2015-08-27). "Prognostic Significance of Premature Atrial Complexes Burden in Prediction of Long-Term Outcome". Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease. 4 (9): e002192. doi:10.1161/JAHA.115.002192. ISSN 2047-9980. PMC 4599506. PMID 26316525.
5. ^ Healy, Jeff (2003). "Atrial fibrillation: hypertension as a causative agent, risk factor for complications, and potential therapeutic target". The American Journal of Cardiology. 91 (10): 9–14. doi:10.1016/S0002-9149(03)00227-3.
6. ^ Hueston, Kesh A. Hebbar|William J. (2002-06-15). "Management of Common Arrhythmias: Part I. Supraventricular Arrhythmias". American Family Physician. 65 (12): 2479–86. PMID 12086237. Retrieved 2017-03-29.
7. ^ Jensen, Thomas J.; Haarbo, Jens; Pehrson, Steen M.; Thomsen, Bloch (2004-04-01). "Impact of premature atrial contractions in atrial fibrillation". Pacing and Clinical Electrophysiology: PACE. 27 (4): 447–452. doi:10.1111/j.1540-8159.2004.00462.x. ISSN 0147-8389. PMID 15078396.
8. ^ Ernst., Mutschler (1995-01-01). Drug actions : basic principles and theraputic aspects. Medpharm Scientific Publishers. ISBN 978-0849377747. OCLC 28854659.
## External links[edit]
Classification
D
* ICD-10: I49.1
* ICD-9-CM: 427.61
* MeSH: D018880
* v
* t
* e
Cardiovascular disease (heart)
Ischaemic
Coronary disease
* Coronary artery disease (CAD)
* Coronary artery aneurysm
* Spontaneous coronary artery dissection (SCAD)
* Coronary thrombosis
* Coronary vasospasm
* Myocardial bridge
Active ischemia
* Angina pectoris
* Prinzmetal's angina
* Stable angina
* Acute coronary syndrome
* Myocardial infarction
* Unstable angina
Sequelae
* hours
* Hibernating myocardium
* Myocardial stunning
* days
* Myocardial rupture
* weeks
* Aneurysm of heart / Ventricular aneurysm
* Dressler syndrome
Layers
Pericardium
* Pericarditis
* Acute
* Chronic / Constrictive
* Pericardial effusion
* Cardiac tamponade
* Hemopericardium
Myocardium
* Myocarditis
* Chagas disease
* Cardiomyopathy
* Dilated
* Alcoholic
* Hypertrophic
* Tachycardia-induced
* Restrictive
* Loeffler endocarditis
* Cardiac amyloidosis
* Endocardial fibroelastosis
* Arrhythmogenic right ventricular dysplasia
Endocardium /
valves
Endocarditis
* infective endocarditis
* Subacute bacterial endocarditis
* non-infective endocarditis
* Libman–Sacks endocarditis
* Nonbacterial thrombotic endocarditis
Valves
* mitral
* regurgitation
* prolapse
* stenosis
* aortic
* stenosis
* insufficiency
* tricuspid
* stenosis
* insufficiency
* pulmonary
* stenosis
* insufficiency
Conduction /
arrhythmia
Bradycardia
* Sinus bradycardia
* Sick sinus syndrome
* Heart block: Sinoatrial
* AV
* 1°
* 2°
* 3°
* Intraventricular
* Bundle branch block
* Right
* Left
* Left anterior fascicle
* Left posterior fascicle
* Bifascicular
* Trifascicular
* Adams–Stokes syndrome
Tachycardia
(paroxysmal and sinus)
Supraventricular
* Atrial
* Multifocal
* Junctional
* AV nodal reentrant
* Junctional ectopic
Ventricular
* Accelerated idioventricular rhythm
* Catecholaminergic polymorphic
* Torsades de pointes
Premature contraction
* Atrial
* Junctional
* Ventricular
Pre-excitation syndrome
* Lown–Ganong–Levine
* Wolff–Parkinson–White
Flutter / fibrillation
* Atrial flutter
* Ventricular flutter
* Atrial fibrillation
* Familial
* Ventricular fibrillation
Pacemaker
* Ectopic pacemaker / Ectopic beat
* Multifocal atrial tachycardia
* Pacemaker syndrome
* Parasystole
* Wandering atrial pacemaker
Long QT syndrome
* Andersen–Tawil
* Jervell and Lange-Nielsen
* Romano–Ward
Cardiac arrest
* Sudden cardiac death
* Asystole
* Pulseless electrical activity
* Sinoatrial arrest
Other / ungrouped
* hexaxial reference system
* Right axis deviation
* Left axis deviation
* QT
* Short QT syndrome
* T
* T wave alternans
* ST
* Osborn wave
* ST elevation
* ST depression
* Strain pattern
Cardiomegaly
* Ventricular hypertrophy
* Left
* Right / Cor pulmonale
* Atrial enlargement
* Left
* Right
* Athletic heart syndrome
Other
* Cardiac fibrosis
* Heart failure
* Diastolic heart failure
* Cardiac asthma
* Rheumatic fever
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Premature atrial contraction | c0033036 | 4,591 | wikipedia | https://en.wikipedia.org/wiki/Premature_atrial_contraction | 2021-01-18T18:39:58 | {"mesh": ["D018880"], "umls": ["C0033036"], "icd-9": ["427.61"], "icd-10": ["I49.1"], "wikidata": ["Q7240236"]} |
Fraser syndrome is a rare disorder that affects development starting before birth. Characteristic features of this condition include eyes that are completely covered by skin and usually malformed (cryptophthalmos), fusion of the skin between the fingers and toes (cutaneous syndactyly), and abnormalities of the genitalia and the urinary tract (genitourinary anomalies). Other tissues and organs can also be affected. Depending on the severity of the signs and symptoms, Fraser syndrome can be fatal before or shortly after birth; less severely affected individuals can live into childhood or adulthood.
Cryptophthalmos is the most common abnormality in people with Fraser syndrome. Both eyes are usually completely covered by skin, but in some cases, only one eye is covered or one or both eyes are partially covered. In cryptophthalmos, the eyes can also be malformed; for example, the eyeballs may be fused to the skin covering them, or they may be small (microphthalmia) or missing (anophthalmia). Eye abnormalities typically lead to impairment or loss of vision in people with Fraser syndrome. Affected individuals can have other problems related to abnormal eye development, including missing eyebrows or eyelashes or a patch of hair extending from the side hairline to the eyebrow.
Cutaneous syndactyly typically occurs in both the hands and the feet in Fraser syndrome. In most people with this feature, the skin between the middle three fingers and toes are fused, but the other digits can also be involved. Other abnormalities of the hands and feet can occur in people with Fraser syndrome.
Individuals with Fraser syndrome can have abnormalities of the genitalia, such as an enlarged clitoris in females or undescended testes (cryptorchidism) in males. Some affected individuals have external genitalia that do not appear clearly female or male (ambiguous genitalia).
The most common urinary tract abnormality in Fraser syndrome is the absence of one or both kidneys (renal agenesis). Affected individuals can have other kidney problems or abnormalities of the bladder and other parts of the urinary tract.
A variety of other signs and symptoms can be involved in Fraser syndrome, including heart malformations or abnormalities of the voicebox (larynx) or other parts of the respiratory tract. Some affected individuals have facial abnormalities, including ear or nose abnormalities or an opening in the upper lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate).
## Frequency
Fraser syndrome affects an estimated 1 in 200,000 newborns. The condition occurs in approximately 1 in 10,000 fetuses that do not survive to birth.
## Causes
Mutations in the FRAS1, FREM2, or GRIP1 gene can cause Fraser syndrome. FRAS1 gene mutations are the most common cause, accounting for about half of cases of Fraser syndrome. FREM2 and GRIP1 gene mutations are each found in a small percentage of cases.
The FRAS1 and FREM2 proteins (produced from the FRAS1 and FREM2 genes, respectively) are part of a group of proteins called the FRAS/FREM complex. The GRIP1 protein (produced from the GRIP1 gene) ensures that FRAS1 and FREM2 get to the correct location of the cell to form the FRAS/FREM complex.
The FRAS/FREM complex is found in basement membranes, which are thin, sheet-like structures that separate and support cells in many tissues. This complex is particularly important during development before birth. One of the complex's roles is to anchor the top layer of skin by connecting its basement membrane to the layer of skin below. The FRAS/FREM complex is also involved in the proper development of other organs and tissues, including the kidneys, although the mechanism is unclear.
Mutations in any of these genes prevent formation of the FRAS/FREM complex. Lack of this complex in the basement membrane of the skin leads to detachment of the top layer of skin, causing blisters to form during development. These blisters likely impair the proper formation of certain structures before birth, leading to cryptophthalmos and cutaneous syndactyly. It is unknown how lack of the FRAS/FREM complex leads to kidney and genital abnormalities and other problems in Fraser syndrome.
### Learn more about the genes associated with Fraser syndrome
* FRAS1
* FREM2
* GRIP1
## Inheritance Pattern
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Fraser syndrome | c0265233 | 4,592 | medlineplus | https://medlineplus.gov/genetics/condition/fraser-syndrome/ | 2021-01-27T08:24:46 | {"gard": ["6465"], "mesh": ["D058497"], "omim": ["219000"], "synonyms": []} |
Pharynx cancer that is located in the oropharynx
Oropharyngeal cancer
3D medical illustration showing the cancer formation in the tissues of the oropharynx
SpecialtyOncology, head and neck surgery
SymptomsSore or blister in back of mouth, difficulty with speech, swallowing or breathing, swelling in neck, loss of appetite, loss of weight, and weakness
CausesHuman papilloma virus, tobacco use, alcohol use
Diagnostic methodEndoscopy, biopsy, staining for p16, CT scan
PreventionVaccination
TreatmentSurgery, radiation, chemotherapy
Oropharyngeal cancer (OPC) also known as tonsil cancer, is a disease in which abnormal cells with the potential to both grow locally and spread to other parts of the body are found in the tissue of the part of the throat (oropharynx) that includes the base of the tongue, the tonsils, the soft palate, and the walls of the pharynx.[1] The two types of oropharyngeal cancers are HPV-positive oropharyngeal cancer, which is caused by an oral human papillomavirus infection; and HPV-negative oropharyngeal cancer, which is linked to use of alcohol, tobacco, or both.[2]
OPC is diagnosed by biopsy of observed abnormal tissue in the throat. OPC is staged according to the appearance of the abnormal cells on the biopsy coupled with the dimensions and the extent of the abnormal cells found. Treatment is with surgery, chemotherapy, or radiation therapy; or some combination of those treatments.
## Contents
* 1 Signs and symptoms
* 2 Risk factors
* 2.1 Major
* 2.2 Minor
* 2.3 Precancerous lesions
* 2.3.1 High-risk
* 2.3.2 Medium-risk
* 2.3.3 Low-risk
* 3 Pathophysiology
* 4 Diagnosis
* 4.1 Stages
* 4.1.1 Stage 0 (carcinoma in situ)
* 4.1.2 Stage 1
* 4.1.3 Stage 2
* 4.1.4 Stage 3
* 4.1.5 Stage 4A
* 4.1.6 Stage 4B
* 4.1.7 Stage 4C
* 5 Prognosis
* 6 Society and culture
* 7 See also
* 8 References
* 9 External links
## Signs and symptoms[edit]
The signs and symptoms of oropharyngeal cancer may include:[1][3][4]
* A sore throat that persists for over 2 weeks
* Throat pain or difficulty swallowing
* Unexplained rapid weight loss
* Voice changes (more hoarse)
* Ear pain
* A lump in the back of the throat or mouth
* A lump in the neck
* A dull pain behind the sternum
* Persistent Cough
* Breathing problems
* Hoarseness or other changes in the voice
## Risk factors[edit]
The risk factors that can increase the risk of developing oropharyngeal cancer are:[3]
### Major[edit]
* Performing oral/mouth-genital sex on a person(s) with a human papillomavirus (HPV) genital infection.[5]
* Smoking and chewing tobacco
* Heavy alcohol use
### Minor[edit]
* A diet low in fruits and vegetables
* Chewing betel quid, a stimulant commonly used in parts of Asia
* Plummer–Vinson syndrome
* Poor nutrition
* Asbestos exposure
* Certain genetic changes including: P53 mutation and CDKN2A (p16) mutations.[6]
### Precancerous lesions[edit]
#### High-risk[edit]
* Erythroplakia
* Speckled erythroplakia
* Chronic hyperplastic candidiasis
#### Medium-risk[edit]
* Oral submucosal fibrosis
* Syphilitic glossitis
* Sideropenic dysphagia (Paterson-Kelly-Brown syndrome)
#### Low-risk[edit]
* Oral lichen planus[7]
* Discoid lupus erythematosus
* Discoid keratosis congenita
## Pathophysiology[edit]
The cancer can spread three ways:[3]
* Cancer invades the surrounding normal tissues.
* Cancer invades the lymph system and travels through the lymph vessels to other places in the body.
* Cancer invades the veins and capillaries and travels through the blood to other places in the body.
## Diagnosis[edit]
Oropharyngeal cancer (from right tonsil, HPV-negative), T4a N2c, 48 year old man.
Diagnosis is by biopsy of observed abnormal tissue in the oropharynx.
### Stages[edit]
The National Cancer Institute (2016) provides the following definition:[8]
#### Stage 0 (carcinoma in situ)[edit]
Abnormal cells are found in the lining of the oropharynx. These may become cancer and spread into nearby normal tissue.
#### Stage 1[edit]
Cancer has formed and is 20 mm or smaller and has not spread outside the oropharynx.
#### Stage 2[edit]
Cancer has formed and is larger than 20 mm, but not larger than 40 mm. Also, it has not yet spread outside the oropharynx.
#### Stage 3[edit]
* Cancer is larger than 40 mm and has not spread outside the oropharynx.
* Any size and has spread to only one lymph node on the same side of the neck as the cancer. The lymph node with cancer is 30 mm or smaller.
#### Stage 4A[edit]
* Cancer has spread to tissues near the oropharynx, including the larynx (voice box), roof of the mouth, lower jaw, muscle of the tongue, or central muscles of the jaw, and may have spread to one or more nearby lymph nodes; none is larger than 60 mm.
* Cancer is any size and has spread to one lymph node that is larger than 30 mm, but not larger than 60 mm on the same side of the neck as the cancer or to more than one lymph node, none larger than 60 mm, on one of both sides of the neck.
#### Stage 4B[edit]
* Cancer surrounds the main artery in the neck or has spread to bones in the jaw or skull, to muscle in the side of the jaw, or to the upper part of the throat behind the nose, and may have spread to nearby lymph nodes.
* Cancer has spread to a lymph node that is larger than 60 mm and may have spread to tissues around the oropharynx.
#### Stage 4C[edit]
Cancer has spread to other parts of the body; the tumor may be any size and may have spread to lymph nodes.
## Prognosis[edit]
People with HPV-positive oropharyngeal cancer tend to have higher survival rates.[2] The prognosis for people with oropharyngeal cancer depends on the age and health of the person and the stage of the disease. It is important for people with oropharyngeal cancer to have follow-up exams for the rest of their lives, as cancer can occur in nearby areas. In addition, it is important to eliminate risk factors such as smoking and drinking alcohol, which increase the risk for second cancers.[1]
## Society and culture[edit]
* In 1989, Monty Python member Graham Chapman died of oropharyngeal cancer, on the eve of Monty Python's 20th anniversary.
* In 1995, actress Lana Turner died from oropharyngeal cancer three years after diagnosis.[9][10]
* In 2010, American actor Michael Douglas reported that he was diagnosed with oropharyngeal cancer.[11]
* In 2014, Japanese musician and composer Ryuichi Sakamoto released a statement indicating that he had been diagnosed with oropharyngeal cancer in late June of the same year.[12]
* In 2014, American musician and rhythm guitar player of Green Day, Jason White, was diagnosed with oropharyngeal cancer on December 3.[13][14]
* In 2015, British musician Bruce Dickinson was diagnosed, and took a one-year break from Iron Maiden while undergoing treatment.
* In 2017, Rob Derhak, bassist of the jam band moe, was diagnosed, prompting the band to go on indefinite hiatus.[15]
## See also[edit]
* Head and neck cancer
* Cancer of the larynx
* Thyroid cancer
## References[edit]
1. ^ a b c "Oropharyngeal Cancer Overview". Cleveland Clinic. 2007-09-07. Retrieved 2011-04-18.
2. ^ a b Nordqvist C (October 4, 2011). "HPV Linked Oropharyngeal Cancer Rates Rise Dramatically". Medical News Today.
3. ^ a b c "Oropharyngeal Cancer Treatment (PDQ®)". National Cancer Institute. Retrieved 2011-04-18.
4. ^ "Throat Cancer". MD Anderson Cancer Center. Retrieved 2019-02-12.
5. ^ Isayeva T, Li Y, Maswahu D, Brandwein-Gensler M (July 2012). "Human papillomavirus in non-oropharyngeal head and neck cancers: a systematic literature review". Head and Neck Pathology. 6 Suppl 1: S104-20. doi:10.1007/s12105-012-0368-1. PMC 3394168. PMID 22782230.
6. ^ Helgadottir H, Höiom V, Jönsson G, Tuominen R, Ingvar C, Borg A, et al. (August 2014). "High risk of tobacco-related cancers in CDKN2A mutation-positive melanoma families". Journal of Medical Genetics. 51 (8): 545–52. doi:10.1136/jmedgenet-2014-102320. PMC 4112445. PMID 24935963.
7. ^ Idrees, M; Kujan, O; Shearston, K; Farah, CS (25 January 2020). "Oral lichen planus has a very low malignant transformation rate: A systematic review and meta-analysis using strict diagnostic and inclusion criteria". Journal of Oral Pathology & Medicine. doi:10.1111/jop.12996. PMID 31981238.
8. ^ "Oropharyngeal Cancer Treatment". Head and neck Cancer - Patient version. National Institutes of Health - National Cancer Institute. December 2016. Retrieved 12 June 2017.
9. ^ "Movie star Lana Turner part of Hollywood lore". Milwaukee Journal Sentinel. June 30, 1995. p. 6B.
10. ^ "Lana Turner reveals she has throat cancer". The Union Democrat. May 26, 1992. p. 5A. Retrieved June 25, 2017 – via Google News.
11. ^ DeNoon DJ (September 1, 2010). "Michael Douglas and Throat Cancer FAQ". WebMD Health News. WebMD. Retrieved 2011-04-18.
12. ^ Sakamoto R (July 10, 2014). "Announcement from commons". WebMD Health News. Retrieved 2014-08-06.
13. ^ "The Big Cats — Timeline Photos". www.facebook.com. The Big Cats. 3 December 2014. Retrieved 6 December 2014.
14. ^ White J. "Jason White has been diagnosed with cancer". www.greendayauthority.com. Green Day Authority. Retrieved 6 December 2014.
15. ^ "moe. Announces Indefinite Hiatus Following Rob Derhak Cancer Diagnosis". JamBase. 2017-07-17. Retrieved 2017-07-18.
## External links[edit]
Classification
D
* ICD-10: C01, C02.4, C05.1, C09, C10
* v
* t
* e
Tumors of lip, oral cavity and pharynx / head and neck cancer
Oral cancer
Salivary gland
malignant epithelial tumors
* Acinic cell carcinoma
* Mucoepidermoid carcinoma
* Adenoid cystic carcinoma
* Salivary duct carcinoma
* Epithelial-myoepithelial carcinoma
* Polymorphous low-grade adenocarcinoma
* Hyalinizing clear cell carcinoma
benign epithelial tumors
* Pleomorphic adenoma
* Warthin's tumor
ungrouped:
* Oncocytoma
Tongue
* Leukoplakia
* Rhabdomyoma
* Oropharynx
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Oropharyngeal cancer | c0153388 | 4,593 | wikipedia | https://en.wikipedia.org/wiki/Oropharyngeal_cancer | 2021-01-18T18:43:19 | {"umls": ["C0153388", "C0153389", "C0153390", "C0153382"], "wikidata": ["Q2031424"]} |
Congenital adrenal hyperplasia (CAH) due to 11-beta-hydroxylase deficiency is one of a group of disorders (collectively called congenital adrenal hyperplasia) that affect the adrenal glands. In this condition, the adrenal glands produce excess androgens (male sex hormones). This condition is caused by mutations in the CYP11B1 gene and is inherited in an autosomal recessive pattern. There are two types, the classic form and the non-classic form. Females with the classic form have ambiguous external genitalia with normal internal reproductive organs. Males and females with the classic form have early development of their secondary sexual characteristics (precocious puberty). The early growth spurt can prevent growth later in adolescence and lead to short stature in adulthood. About two-thirds of individuals with the classic form have high blood pressure which develops in the first year of life.
Females with the non-classic form of 11-beta-hydroxylase deficiency have normal female genitalia. As affected females get older, they may develop excessive body hair growth and irregular menstruation. Males with the non-classic form do not typically have any signs or symptoms except for short stature. High blood pressure is not a feature of the non-classic form.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| 11-beta-hydroxylase deficiency | c0268292 | 4,594 | gard | https://rarediseases.info.nih.gov/diseases/5658/11-beta-hydroxylase-deficiency | 2021-01-18T18:02:28 | {"mesh": ["C535978"], "omim": ["202010"], "umls": ["C0268292"], "orphanet": ["90795"], "synonyms": ["Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency", "Adrenal hyperplasia IV", "Adrenal hyperplasia 4", "Steroid 11-beta-hydroxylase deficiency", "Adrenal hyperplasia hypertensive form", "P450c11b1 deficiency", "CAH due to 11-beta-hydroxylase deficiency", "CYP11B1 deficiency"]} |
Cracked tooth syndrome
Other namesCracked cusp syndrome,[1] split tooth syndrome,[1] incomplete fracture of posterior teeth[1]
Cross-section of a posterior tooth.
SpecialtyDentistry
Cracked tooth syndrome (CTS)[2] is where a tooth has incompletely cracked but no part of the tooth has yet broken off. Sometimes it is described as a greenstick fracture.[1] The symptoms are very variable, making it a notoriously difficult condition to diagnose.
## Contents
* 1 Classification and definition
* 2 Signs and symptoms
* 3 Pathophysiology
* 4 Diagnosis
* 4.1 Clinical examination
* 4.2 Gentian Violet or Methylene Blue Stains
* 4.3 Transillumination
* 4.4 Radiographs
* 4.5 Bite Test
* 5 Epidemiology
* 6 Treatments
* 7 History
* 8 References
* 9 External links
## Classification and definition[edit]
Cracked tooth syndrome could be considered a type of dental trauma and also one of the possible causes of dental pain. One definition of cracked tooth syndrome is "a fracture plane of unknown depth and direction passing through tooth structure that, if not already involving, may progress to communicate with the pulp and/or periodontal ligament."[1]
## Signs and symptoms[edit]
Tooth crack in the upper first molar tooth in a patient who suffers from bruxism.
The reported symptoms are very variable,[2] and frequently have been present for many months before the condition is diagnosed.[1] Reported symptoms may include some of the following:
* Sharp pain[1] when biting on a certain tooth,[2] which may get worse if the applied biting force is increased.[1] Sometimes the pain on biting occurs when the food being chewed is soft with harder elements, e.g. seeded bread.[2]
* "Rebound pain" i.e. sharp, fleeting pain occurring when the biting force is released from the tooth,[1] which may occur when eating fibrous foods.
* Pain on biting[3]
* Pain when grinding the teeth backward and forward and side to side.[1]
* Sharp pain when drinking cold beverages or eating cold foods, lack of pain with heat stimuli.[1]
* Pain when eating or drinking sugary substances.[1]
* Sometimes the pain is well localized, and the individual is able to determine the exact tooth from which the symptoms are originating, but not always.[1]
If the crack propagates into the pulp, irreversible pulpitis, pulpal necrosis and periapical periodontitis may develop, with the respective associated symptoms.[1]
## Pathophysiology[edit]
Crack (vertical fracture) of tooth and root #1.4 (green arrows) splitting it in two even pieces which has caused a lateral periodontal abscess (blue arrows).
CTS is typically characterized by pain when releasing biting pressure on an object. This is because when biting down the segments are usually moving apart and thereby reducing the pressure in the nerves in the dentin of the tooth. When the bite is released the "segments" snap back together sharply increasing the pressure in the intradentin nerves causing pain. The pain is often inconsistent, and frequently hard to reproduce. Pain associated with CTS has been reported to occur more commonly on biting, rather than on release of pressure after biting. If untreated, CTS can lead to severe pain, possible pulpal death, abscess, and even the loss of the tooth.
If the fracture propagates into the pulp, this is termed a complete fracture, and pulpitis and pulp death may occur. If the crack propagates further into the root, a periodontal defect may develop, or even a vertical root fracture.[1]
According to one theory, the pain on biting is caused by the 2 fractured sections of the tooth moving independently of each other, triggering sudden movement of fluid within the dentinal tubules.[1] This activates A-type nociceptors in the dentin-pulp complex, reported by the pulp-dentin complex as pain. Another theory is that the pain upon cold stimuli results from leak of noxious substances via the crack, irritating the pulp.[1]
## Diagnosis[edit]
Cracked tooth syndrome (CTS) was defined as 'an incomplete fracture of a vital posterior tooth that involves the dentine and occasionally extends to the pulp' by Cameron in 1964 and more recently has included 'a fracture plane of unknown depth and direction passing through tooth structure that, if not already involving, may progress to communicate with the pulp and/or periodontal ligament'.[4] The diagnosis of cracked tooth syndrome is notoriously difficult even for experienced clinicians.[2] The features are highly variable and may mimic sinusitis, temporomandibular disorders, headaches, ear pain, or atypical facial pain/atypical odontalgia (persistent idiopathic facial pain).[2] When diagnosing cracked tooth syndrome, a dentist takes many factors into consideration. Effective management and good prognosis of cracked teeth is linked to prompt diagnosis. A detailed history may reveal pain on release of pressure when eating or sharp pain when consuming cold food and drink. There are a variety of habits which predispose patients to CTS including chewing ice, pens and hard sweets etc. Recurrent occlusal adjustment of restorations due to discomfort may also be indicative of CTS, alongside a history of extensive dental treatment. Below different techniques used for diagnosing CTS are discussed.
### Clinical examination[edit]
Cracks are difficult to see during a clinical exam which may limit diagnosis. However other clinical signs which may lead to the diagnosis of CTS includes wear faceting indicating excessive forces perhaps from clenching or grinding or the presence of an isolated deep periodontal pocket which may symbolise a split tooth. Removing restorations may help to visualise fracture lines but should only be carried out after gaining informed consent from the patient, as removing a restoration may prove to be of little diagnostic benefit. Tactile examination with a sharp probe may also aid diagnosis.
### Gentian Violet or Methylene Blue Stains[edit]
Dyes may be used to aid visualisation of fractures. The technique requires 2–5 days to be effective and a temporary restoration may be required. The structural integrity can be weakened by this method, leading to crack propagation.
### Transillumination[edit]
Transillumination of tooth 2.1 showing vertical fracture (blue arrows) and inflammation in marginal gingiva at fracture site (green arrow)
Transillumination is best performed by placing a fibre optic light source directly onto the tooth and optimal results can be achieved with the aid of magnification. Cracks involving dentine interrupt the light transmission. However, transillumination may cause cracks to appear enlarged as well as causing colour changes to become invisible.
### Radiographs[edit]
Radiographs offer little benefit in visualising cracks. This is due to the fact that cracks propagate in a direction which is parallel to the plane of the film (Mesiodistal) however radiographs can be useful when examining the periodontal and pulpal status.
### Bite Test[edit]
Different tools can be used when carrying out a bite test which produce symptoms associated with cracked tooth syndrome. Patients bite down followed by sudden release of pressure. CTS diagnosis is confirmed by pain on release of pressure. The involved cusp can be determined by biting on individual cusps separately. Tooth Slooth II (Professional Results Inc., Laguna Niguel, CA, USA) and Fractfinder (Denbur, Oak Brook, IL, USA) are commercially available tools.
## Epidemiology[edit]
[5] Aetiology of CTS is multifactorial, the causative factors include:
* previous restorative procedures.
* occlusal factors; patients who suffer from bruxism, or clenching are prone to have cracked teeth.
* developmental conditions/anatomical considerations.
* trauma
* others, e.g., aging dentition or presence of lingual tongue studs.
Most commonly involved teeth are mandibular molars followed by maxillary premolars, maxillary molars and maxillary premolars. in a recent audit, mandibular first molar thought to be most affected by CTS possibly due to the wedging effect of opposing pointy, protruding maxillary mesio-palatal cusp onto the mandibular molar central fissure. Studies have also found signs of cracked teeth following the cementation of porcelain inlays; it is suggested that the debonding of intracoronal restorations may be caused by unrecognized cracks in the tooth.[6]
## Treatments[edit]
Fractured tooth (blue arrows) viewed in the mouth (left) and after extraction (right).
There is no universally accepted treatment strategy, but, generally, treatments aim to prevent movement of the segments of the involved tooth so they do not move or flex independently during biting and grinding (stabilisation of the crack) to prevent propagation of the crack.[7] Provisionally, a band may be placed around the tooth or a direct composite splint can be placed in supra-occlusion to minimize flexing. Definitive options include:[8]
* Bonded intra-coronal restoration
* Onlay restoration, either direct or indirectly placed (currently the recommended technique)
* Crown restoration (though this is associated with a high incidence of loss of vitality in teeth with CTS)
Teeth originally presenting with CTS may subsequently require Root Canal therapy (if pain persists after above) or Extraction
## History[edit]
The term "cuspal fracture odontalgia" was suggested in 1954 by Gibbs.[1] Subsequently, the term "cracked tooth syndrome" was coined in 1964 by Cameron,[2] who defined the condition as "an incomplete fracture of a vital posterior tooth that involves the dentin and occasionally extends into the pulp."[1]
## References[edit]
1. ^ a b c d e f g h i j k l m n o p q r s Banerji, S; Mehta, SB; Millar, BJ (May 22, 2010). "Cracked tooth syndrome. Part 1: aetiology and diagnosis". British Dental Journal. 208 (10): 459–63. doi:10.1038/sj.bdj.2010.449. PMID 20489766.
2. ^ a b c d e f g Mathew, S; Thangavel, B; Mathew, CA; Kailasam, S; Kumaravadivel, K; Das, A (Aug 2012). "Diagnosis of cracked tooth syndrome". Journal of Pharmacy & Bioallied Sciences. 4 (Suppl 2): S242–4. doi:10.4103/0975-7406.100219. PMC 3467890. PMID 23066261.
3. ^ Bailey, O; Whitworth, J (2020). "Cracked tooth syndrome diagnosis part 1: integrating the old with the new". Dental Update. 47 (6): 494–499. doi:10.12968/denu.2020.47.6.494.
4. ^ Millar, B. J.; Mehta, S. B.; Banerji, S. (May 2010). "Cracked tooth syndrome. Part 1: aetiology and diagnosis". British Dental Journal. 208 (10): 459–463. doi:10.1038/sj.bdj.2010.449. ISSN 1476-5373. PMID 20489766.
5. ^ Banerji, S. (May 2017). "Programme Director, MSc Aesthetic Dentistry, Senior Clinical Teache" (PDF). British Dental Journal. 222 (9): 659–666. doi:10.1038/sj.bdj.2017.398. PMID 28496251.
6. ^ Mathew, Sebeena; Thangavel, Boopathi; Mathew, Chalakuzhiyil Abraham; Kailasam, SivaKumar; Kumaravadivel, Karthick; Das, Arjun (August 2012). "Diagnosis of cracked tooth syndrome". Journal of Pharmacy & Bioallied Sciences. 4 (Suppl 2): S242–S244. doi:10.4103/0975-7406.100219. ISSN 0976-4879. PMC 3467890. PMID 23066261.
7. ^ Banerji, S.; Mehta, S. B.; Millar, B. J. (12 June 2010). "Cracked tooth syndrome. Part 2: restorative options for the management of cracked tooth syndrome". BDJ. 208 (11): 503–514. doi:10.1038/sj.bdj.2010.496. PMID 20543791.
8. ^ Bailey, O (2020). "Cracked tooth syndrome management part 2: integrating the old with the new". Dental Update. 47 (7): 570–582. doi:10.12968/denu.2020.47.7.570.
## External links[edit]
Classification
D
* ICD-9-CM: 521.81
* MeSH: D003387
* v
* t
* e
Acquired tooth disease
Hard tissues
* Caries (tooth decay)
* Attrition
* Abrasion
* Erosion
* Hypercementosis
* tooth resorption (External resorption, Internal resorption, Root resorption)
Pulp/periapical (Endodontal)
Pulpal
* External resorption
* Internal resorption
* Irreversible pulpitis
* Reversible pulpitis
* Pulp necrosis
* Pink tooth of Mummery
Periapical
* Acute apical periodontitis
* Chronic apical periodontitis
* Combined periodontic-endodontic lesions
* Fistula
* Periapical abscess
* Phoenix abscess
* Vertical root fracture
Ungrouped
* Pulpitis
* Radicular cyst
* Periapical abscess
Gingiva/periodontal
(Periodontal)
* Gingivitis
* Periodontitis (Chronic periodontitis)
* Periodontal disease
Bone cyst
* Dentigerous cyst
* Calcifying odontogenic cyst
* Glandular odontogenic cyst
Other
* Cracked tooth syndrome
To be grouped
from periodontology
Diagnoses
* Chronic periodontitis
* Localized aggressive periodontitis
* Generalized aggressive periodontitis
* Periodontitis as a manifestation of systemic disease
* Necrotizing periodontal diseases
* Abscesses of the periodontium
* Combined periodontic-endodontic lesions
Pathogenesis
* A. actinomycetemcomitans
* Capnocytophaga sp.
* F. nucleatum
* P. gingivalis
* P. intermedia
* T. forsythia
* T. denticola
Pathologic entities
* Calculus
* Edentulism
* Fremitus
* Furcation defect
* Gingival enlargement
* Gingival pocket
* Gingivitis
* Horizontal bony defect
* Linear gingival erythema
* Occlusal trauma
* Periodontal pocket
* Periodontal disease
* Periodontitis
* Plaque
* Recession
* Vertical bony defect
* v
* t
* e
Oral and maxillofacial pathology
Lips
* Cheilitis
* Actinic
* Angular
* Plasma cell
* Cleft lip
* Congenital lip pit
* Eclabium
* Herpes labialis
* Macrocheilia
* Microcheilia
* Nasolabial cyst
* Sun poisoning
* Trumpeter's wart
Tongue
* Ankyloglossia
* Black hairy tongue
* Caviar tongue
* Crenated tongue
* Cunnilingus tongue
* Fissured tongue
* Foliate papillitis
* Glossitis
* Geographic tongue
* Median rhomboid glossitis
* Transient lingual papillitis
* Glossoptosis
* Hypoglossia
* Lingual thyroid
* Macroglossia
* Microglossia
* Rhabdomyoma
Palate
* Bednar's aphthae
* Cleft palate
* High-arched palate
* Palatal cysts of the newborn
* Inflammatory papillary hyperplasia
* Stomatitis nicotina
* Torus palatinus
Oral mucosa – Lining of mouth
* Amalgam tattoo
* Angina bullosa haemorrhagica
* Behçet's disease
* Bohn's nodules
* Burning mouth syndrome
* Candidiasis
* Condyloma acuminatum
* Darier's disease
* Epulis fissuratum
* Erythema multiforme
* Erythroplakia
* Fibroma
* Giant-cell
* Focal epithelial hyperplasia
* Fordyce spots
* Hairy leukoplakia
* Hand, foot and mouth disease
* Hereditary benign intraepithelial dyskeratosis
* Herpangina
* Herpes zoster
* Intraoral dental sinus
* Leukoedema
* Leukoplakia
* Lichen planus
* Linea alba
* Lupus erythematosus
* Melanocytic nevus
* Melanocytic oral lesion
* Molluscum contagiosum
* Morsicatio buccarum
* Oral cancer
* Benign: Squamous cell papilloma
* Keratoacanthoma
* Malignant: Adenosquamous carcinoma
* Basaloid squamous carcinoma
* Mucosal melanoma
* Spindle cell carcinoma
* Squamous cell carcinoma
* Verrucous carcinoma
* Oral florid papillomatosis
* Oral melanosis
* Smoker's melanosis
* Pemphigoid
* Benign mucous membrane
* Pemphigus
* Plasmoacanthoma
* Stomatitis
* Aphthous
* Denture-related
* Herpetic
* Smokeless tobacco keratosis
* Submucous fibrosis
* Ulceration
* Riga–Fede disease
* Verruca vulgaris
* Verruciform xanthoma
* White sponge nevus
Teeth (pulp, dentin, enamel)
* Amelogenesis imperfecta
* Ankylosis
* Anodontia
* Caries
* Early childhood caries
* Concrescence
* Failure of eruption of teeth
* Dens evaginatus
* Talon cusp
* Dentin dysplasia
* Dentin hypersensitivity
* Dentinogenesis imperfecta
* Dilaceration
* Discoloration
* Ectopic enamel
* Enamel hypocalcification
* Enamel hypoplasia
* Turner's hypoplasia
* Enamel pearl
* Fluorosis
* Fusion
* Gemination
* Hyperdontia
* Hypodontia
* Maxillary lateral incisor agenesis
* Impaction
* Wisdom tooth impaction
* Macrodontia
* Meth mouth
* Microdontia
* Odontogenic tumors
* Keratocystic odontogenic tumour
* Odontoma
* Dens in dente
* Open contact
* Premature eruption
* Neonatal teeth
* Pulp calcification
* Pulp stone
* Pulp canal obliteration
* Pulp necrosis
* Pulp polyp
* Pulpitis
* Regional odontodysplasia
* Resorption
* Shovel-shaped incisors
* Supernumerary root
* Taurodontism
* Trauma
* Avulsion
* Cracked tooth syndrome
* Vertical root fracture
* Occlusal
* Tooth loss
* Edentulism
* Tooth wear
* Abrasion
* Abfraction
* Acid erosion
* Attrition
Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures
* Cementicle
* Cementoblastoma
* Gigantiform
* Cementoma
* Eruption cyst
* Epulis
* Pyogenic granuloma
* Congenital epulis
* Gingival enlargement
* Gingival cyst of the adult
* Gingival cyst of the newborn
* Gingivitis
* Desquamative
* Granulomatous
* Plasma cell
* Hereditary gingival fibromatosis
* Hypercementosis
* Hypocementosis
* Linear gingival erythema
* Necrotizing periodontal diseases
* Acute necrotizing ulcerative gingivitis
* Pericoronitis
* Peri-implantitis
* Periodontal abscess
* Periodontal trauma
* Periodontitis
* Aggressive
* As a manifestation of systemic disease
* Chronic
* Perio-endo lesion
* Teething
Periapical, mandibular and maxillary hard tissues – Bones of jaws
* Agnathia
* Alveolar osteitis
* Buccal exostosis
* Cherubism
* Idiopathic osteosclerosis
* Mandibular fracture
* Microgenia
* Micrognathia
* Intraosseous cysts
* Odontogenic: periapical
* Dentigerous
* Buccal bifurcation
* Lateral periodontal
* Globulomaxillary
* Calcifying odontogenic
* Glandular odontogenic
* Non-odontogenic: Nasopalatine duct
* Median mandibular
* Median palatal
* Traumatic bone
* Osteoma
* Osteomyelitis
* Osteonecrosis
* Bisphosphonate-associated
* Neuralgia-inducing cavitational osteonecrosis
* Osteoradionecrosis
* Osteoporotic bone marrow defect
* Paget's disease of bone
* Periapical abscess
* Phoenix abscess
* Periapical periodontitis
* Stafne defect
* Torus mandibularis
Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities
* Bruxism
* Condylar resorption
* Mandibular dislocation
* Malocclusion
* Crossbite
* Open bite
* Overbite
* Overeruption
* Overjet
* Prognathia
* Retrognathia
* Scissor bite
* Maxillary hypoplasia
* Temporomandibular joint dysfunction
Salivary glands
* Benign lymphoepithelial lesion
* Ectopic salivary gland tissue
* Frey's syndrome
* HIV salivary gland disease
* Necrotizing sialometaplasia
* Mucocele
* Ranula
* Pneumoparotitis
* Salivary duct stricture
* Salivary gland aplasia
* Salivary gland atresia
* Salivary gland diverticulum
* Salivary gland fistula
* Salivary gland hyperplasia
* Salivary gland hypoplasia
* Salivary gland neoplasms
* Benign: Basal cell adenoma
* Canalicular adenoma
* Ductal papilloma
* Monomorphic adenoma
* Myoepithelioma
* Oncocytoma
* Papillary cystadenoma lymphomatosum
* Pleomorphic adenoma
* Sebaceous adenoma
* Malignant: Acinic cell carcinoma
* Adenocarcinoma
* Adenoid cystic carcinoma
* Carcinoma ex pleomorphic adenoma
* Lymphoma
* Mucoepidermoid carcinoma
* Sclerosing polycystic adenosis
* Sialadenitis
* Parotitis
* Chronic sclerosing sialadenitis
* Sialectasis
* Sialocele
* Sialodochitis
* Sialosis
* Sialolithiasis
* Sjögren's syndrome
Orofacial soft tissues – Soft tissues around the mouth
* Actinomycosis
* Angioedema
* Basal cell carcinoma
* Cutaneous sinus of dental origin
* Cystic hygroma
* Gnathophyma
* Ludwig's angina
* Macrostomia
* Melkersson–Rosenthal syndrome
* Microstomia
* Noma
* Oral Crohn's disease
* Orofacial granulomatosis
* Perioral dermatitis
* Pyostomatitis vegetans
Other
* Eagle syndrome
* Hemifacial hypertrophy
* Facial hemiatrophy
* Oral manifestations of systemic disease
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Cracked tooth syndrome | c0010261 | 4,595 | wikipedia | https://en.wikipedia.org/wiki/Cracked_tooth_syndrome | 2021-01-18T18:34:59 | {"mesh": ["D003387"], "umls": ["C0010261"], "icd-9": ["521.81"], "wikidata": ["Q497584"]} |
Fibroepithelial neoplasms
Fibroepithelial neoplasm (Phyllodes tumor).
SpecialtyOncology
A fibroepithelial neoplasm (or tumor) is a biphasic tumor. They consist of epithelial tissue, and stromal or mesenchymal tissue. They may be benign or malignant.[1]
Examples include:
* Brenner tumor of the ovary
* Fibroadenoma of the breast
* Phyllodes tumor of the breast
## References[edit]
1. ^ Tavassoli, F.A., Devilee, P. (Eds). 2003. World Health Organization Classification of Tumours: Pathology & Genetics: Tumours of the breast and female genital organs. IARC Press: Lyon. ISBN 92-832-2412-4
## External links[edit]
Classification
D
* ICD-O: 9000-9030
* MeSH: D018225
* derm/346 at eMedicine \- "Premalignant Fibroepithelial Tumor"
* v
* t
* e
Glandular and epithelial cancer
Epithelium
Papilloma/carcinoma
* Small-cell carcinoma
* Combined small-cell carcinoma
* Verrucous carcinoma
* Squamous cell carcinoma
* Basal-cell carcinoma
* Transitional cell carcinoma
* Inverted papilloma
Complex epithelial
* Warthin's tumor
* Thymoma
* Bartholin gland carcinoma
Glands
Adenomas/
adenocarcinomas
Gastrointestinal
* tract: Linitis plastica
* Familial adenomatous polyposis
* pancreas
* Insulinoma
* Glucagonoma
* Gastrinoma
* VIPoma
* Somatostatinoma
* Cholangiocarcinoma
* Klatskin tumor
* Hepatocellular adenoma/Hepatocellular carcinoma
Urogenital
* Renal cell carcinoma
* Endometrioid tumor
* Renal oncocytoma
Endocrine
* Prolactinoma
* Multiple endocrine neoplasia
* Adrenocortical adenoma/Adrenocortical carcinoma
* Hürthle cell
Other/multiple
* Neuroendocrine tumor
* Carcinoid
* Adenoid cystic carcinoma
* Oncocytoma
* Clear-cell adenocarcinoma
* Apudoma
* Cylindroma
* Papillary hidradenoma
Adnexal and
skin appendage
* sweat gland
* Hidrocystoma
* Syringoma
* Syringocystadenoma papilliferum
Cystic, mucinous,
and serous
Cystic general
* Cystadenoma/Cystadenocarcinoma
Mucinous
* Signet ring cell carcinoma
* Krukenberg tumor
* Mucinous cystadenoma / Mucinous cystadenocarcinoma
* Pseudomyxoma peritonei
* Mucoepidermoid carcinoma
Serous
* Ovarian serous cystadenoma / Pancreatic serous cystadenoma / Serous cystadenocarcinoma / Papillary serous cystadenocarcinoma
Ductal, lobular,
and medullary
Ductal carcinoma
* Mammary ductal carcinoma
* Pancreatic ductal carcinoma
* Comedocarcinoma
* Paget's disease of the breast / Extramammary Paget's disease
Lobular carcinoma
* Lobular carcinoma in situ
* Invasive lobular carcinoma
Medullary carcinoma
* Medullary carcinoma of the breast
* Medullary thyroid cancer
Acinar cell
* Acinic cell carcinoma
* v
* t
* e
Connective/soft tissue tumors and sarcomas
Not otherwise specified
* Soft-tissue sarcoma
* Desmoplastic small-round-cell tumor
Connective tissue neoplasm
Fibromatous
Fibroma/fibrosarcoma:
* Dermatofibrosarcoma protuberans
* Desmoplastic fibroma
Fibroma/fibromatosis:
* Aggressive infantile fibromatosis
* Aponeurotic fibroma
* Collagenous fibroma
* Diffuse infantile fibromatosis
* Familial myxovascular fibromas
* Fibroma of tendon sheath
* Fibromatosis colli
* Infantile digital fibromatosis
* Juvenile hyaline fibromatosis
* Plantar fibromatosis
* Pleomorphic fibroma
* Oral submucous fibrosis
Histiocytoma/histiocytic sarcoma:
* Benign fibrous histiocytoma
* Malignant fibrous histiocytoma
* Atypical fibroxanthoma
* Solitary fibrous tumor
Myxomatous
* Myxoma/myxosarcoma
* Cutaneous myxoma
* Superficial acral fibromyxoma
* Angiomyxoma
* Ossifying fibromyxoid tumour
Fibroepithelial
* Brenner tumour
* Fibroadenoma
* Phyllodes tumor
Synovial-like
* Synovial sarcoma
* Clear-cell sarcoma
Lipomatous
* Lipoma/liposarcoma
* Myelolipoma
* Myxoid liposarcoma
* PEComa
* Angiomyolipoma
* Chondroid lipoma
* Intradermal spindle cell lipoma
* Pleomorphic lipoma
* Lipoblastomatosis
* Spindle cell lipoma
* Hibernoma
Myomatous
general:
* Myoma/myosarcoma
smooth muscle:
* Leiomyoma/leiomyosarcoma
skeletal muscle:
* Rhabdomyoma/rhabdomyosarcoma: Embryonal rhabdomyosarcoma
* Sarcoma botryoides
* Alveolar rhabdomyosarcoma
* Leiomyoma
* Angioleiomyoma
* Angiolipoleiomyoma
* Genital leiomyoma
* Leiomyosarcoma
* Multiple cutaneous and uterine leiomyomatosis syndrome
* Multiple cutaneous leiomyoma
* Neural fibrolipoma
* Solitary cutaneous leiomyoma
* STUMP
Complex mixed and stromal
* Adenomyoma
* Pleomorphic adenoma
* Mixed Müllerian tumor
* Mesoblastic nephroma
* Wilms' tumor
* Malignant rhabdoid tumour
* Clear-cell sarcoma of the kidney
* Hepatoblastoma
* Pancreatoblastoma
* Carcinosarcoma
Mesothelial
* Mesothelioma
* Adenomatoid tumor
This article about a neoplasm is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
This article related to pathology is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
This oncology article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Fibroepithelial neoplasm | c0206649 | 4,596 | wikipedia | https://en.wikipedia.org/wiki/Fibroepithelial_neoplasm | 2021-01-18T18:32:40 | {"mesh": ["D018225"], "umls": ["C0206649"], "wikidata": ["Q5446462"]} |
Chromosome 7q duplication is a chromosome abnormality that occurs when there is an extra copy of genetic material on the long arm (q) of chromosome 7. The severity of the condition and the signs and symptoms depend on the size and location of the duplication and which genes are involved. Features that often occur in people with chromosome 7q duplication include developmental delay, intellectual disability, behavioral problems and distinctive facial features. Most cases are not inherited, but people can pass the duplication on to their children. Treatment is based on the signs and symptoms present in each person.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Chromosome 7q duplication | c0795821 | 4,597 | gard | https://rarediseases.info.nih.gov/diseases/5357/chromosome-7q-duplication | 2021-01-18T18:01:20 | {"mesh": ["C537821"], "umls": ["C0795821"], "synonyms": ["Duplication 7q", "Trisomy 7q", "7q duplication", "7q trisomy", "Partial trisomy 7q"]} |
Primary lateral sclerosis (PLS) is a rare neuromuscular disease that affects the nerve cells that control the voluntary muscles. Problems in the legs (such as weakness, stiffness, spasticity, and balance problems) are often observed first, but hand clumsiness and changes in speech can be early symptoms, as well. The condition is progressive (gradually becomes worse over time); however, affected people have a normal life expectancy. The underlying cause of adult PLS is currently unknown. In most cases, it occurs sporadically in people with no family history of the condition. A subtype of PLS, called juvenile PLS, is caused by changes (mutations) in the ALS2 gene and is inherited in an autosomal recessive manner. Treatment is based on the signs and symptoms present in each person.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Primary lateral sclerosis | c0154682 | 4,598 | gard | https://rarediseases.info.nih.gov/diseases/10684/primary-lateral-sclerosis | 2021-01-18T17:58:11 | {"mesh": ["D016472"], "omim": ["611637"], "umls": ["C0154682"], "orphanet": ["35689"], "synonyms": ["Adult-onset PLS", "Adult-onset primary lateral sclerosis"]} |
This article needs to be updated. Please update this article to reflect recent events or newly available information. (December 2020)
Ongoing COVID-19 viral pandemic in Sweden
COVID-19 pandemic in Sweden
Map of confirmed cases in Sweden
(per 100,000 residents)[1]
Map of confirmed cases in Sweden
(absolute numbers)[1]
(left-to-right, from top)
* Sahlgrenska University Hospital in Mölndal
* Signs on the floor at the checkout in Coop, Åmål, to facilitate social distancing
* People queuing with 1.5-meter distance outside Systembolaget
* State epidemiologist Anders Tegnell
* An empty Drottninggatan, a usually busy pedestrian street in Stockholm
DiseaseCOVID-19
Virus strainSARS-CoV-2
LocationSweden
First outbreakWuhan, Hubei, China
Index caseJönköping
Arrival date24 January 2020
(11 months, 3 weeks and 4 days)
Date14 January 2021 CET
Confirmed cases523,486[1]
Severe cases4,518 ICU hospitalisations (total)[1]
Deaths
10,323[1][note 1]
Government website
Swedish Public Health Agency Covid-19
(in Swedish)
The COVID-19 pandemic in Sweden is part of the pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus was confirmed to have reached Sweden on 31 January 2020, when a woman returning from Wuhan tested positive. On 26 February, following outbreaks in Italy and in Iran, multiple travel-related clusters appeared in Sweden. Community transmission was confirmed on 9 March in the Stockholm region. Since then, individuals in every län (county) have tested positive for COVID-19. The first death was reported on 11 March in Stockholm, a case of community transmission. However, it is believed that the virus could have reached Sweden as early as December 2019, when several individuals sought care for respiratory illness in Falun after contact with an individual with recent travel history to Wuhan.
Sweden has not imposed a lockdown, unlike many other countries, and kept large parts of its society open. The Swedish Constitution legally protects the freedom of movement for the people, thus preventing a lockdown in peace time. The Swedish public is expected to follow a series of non-voluntary recommendations[note 2] from the government agency responsible for this area, in this case the Public Health Agency of Sweden (Folkhälsomyndigheten). The Swedish Constitution prohibits ministerial rule – politicians overruling the advice from its agencies is extremely unusual in Sweden – and mandates that the relevant government body, in this case an expert agency – the Public Health Agency – must initiate all actions to prevent the virus in accordance with Swedish law, rendering state epidemiologist Anders Tegnell a central figure in the crisis.
The Swedish government's approach has received considerable criticism. Some Swedish scientists had called for stricter preventative measures throughout the pandemic,[6] and an independent commission (Coronakommissionen) found that Sweden failed to protect care home residents due to the overall spread of the virus in society.[7] In December 2020 both King Carl XVI Gustaf and Prime Minister Stefan Löfven admitted they felt that Sweden's COVID-19 strategy had been a failure due to the large number of deaths.[8]
Following agency advice, the government has passed legislation limiting freedom of assembly by temporarily banning gatherings of over 50 individuals, banning people from visiting nursing homes, and physically closing secondary schools and universities. Primary schools have remained open, in part to avoid healthcare workers staying home with their children.
The Public Health Agency issued recommendations to: if possible, work from home; avoid unnecessary travel within the country; engage in social distancing; and for people above 70 to stay at home, as much as possible. Those with even minimal symptoms that could be caused by COVID-19 are recommended to stay home. The karensdag, or initial day without paid sick-leave, has been removed by the government and the length of time one can stay home with pay without a doctor's note has been raised from 7 to 21 days.
The pandemic has put the Swedish healthcare system under severe strain, with tens of thousands of operations being postponed throughout the year, and only emergency and COVID-related care being available during a surge in the winter. Initially, Swedish hospitals and other facilities reported a shortage of personal protective equipment. Swedish hospitals were able to increase their intensive care capacity during the earlier stages of the pandemic, but Stockholm's health system still became seriously overwhelmed during the winter surge, with intensive care bed occupancy reaching 99% by December 18 and the city experiences healthcare staff shortages.[9]
As of 23 December 2020[update], there have been 396,048 confirmed cases and 8,279 confirmed deaths[note 1] related to COVID-19 in Sweden, with Stockholm County being the most affected.[1] Sweden has several times the number of confirmed cases and deaths of all neighboring Scandinavian countries. Close to half of those who died had been living at nursing homes,[10][11][12] which is similar to other European countries.[13]
## Contents
* 1 Background
* 1.1 Outbreak of a novel coronavirus disease
* 1.2 Planning
* 1.3 Preparedness
* 2 Timeline
* 2.1 Early cases (December 2019 – February 2020)
* 2.2 Community spread (March–)
* 2.3 Winter surge
* 3 Response from the authorities
* 3.1 Government
* 3.1.1 Legislation
* 3.1.2 Advice against travel abroad
* 3.2 Strategy
* 3.3 Measures
* 3.3.1 Social distancing
* 3.3.2 Ban on gatherings
* 3.3.3 Travel
* 3.4 Communication and information
* 4 Monitoring and modelling
* 5 Public healthcare system
* 5.1 Testing
* 5.2 Capacity
* 5.3 Equipment
* 5.4 Staffing
* 6 Social impact
* 6.1 Finance and the economy
* 6.2 Transportation
* 6.3 Politics
* 6.4 Royal family
* 6.5 Education
* 6.6 Defence
* 6.7 Arts and entertainment
* 6.7.1 Television
* 6.8 Sports
* 6.9 Notable Swedes who have died of Covid-19
* 7 Statistics
* 7.1 Cases
* 7.1.1 Total cases
* 7.1.2 Cases per day
* 7.2 Intensive care
* 7.2.1 Total hospitalisations
* 7.2.2 Hospitalisations per day
* 7.3 Deaths
* 7.3.1 Total deaths
* 7.3.2 Deaths per day
* 7.3.3 Nursing homes
* 7.3.4 Age and gender
* 7.3.5 Excess mortality
* 7.4 Additional data, charts and tables
* 8 Timeline of responses
* 8.1 Economic policy
* 9 See also
* 10 Notes
* 11 References
* 12 External links
## Background[edit]
### Outbreak of a novel coronavirus disease[edit]
Further information: COVID-19 pandemic § History
On 12 January, the World Health Organization (WHO) confirmed that a novel coronavirus (nCoV) was the cause of a respiratory illness in a cluster of people in Wuhan, in Hubei, China, who had initially come to the WHO's attention on 31 December 2019. This cluster was initially linked to the Huanan Seafood Wholesale Market in Wuhan City.[14][15] A few days later, on 16 January, the Public Health Agency of Sweden issued a press release highlighting the discovery of the novel coronavirus, and the agency monitoring the situation. The risk of spread to Sweden was described as "very low" as there was yet no evidence that the virus could spread between humans, but they recommended that individuals developing cough or fever after visiting Wuhan should seek medical care, and asked for healthcare professionals to be observant.[16]
After the World Health Organization classified the novel Coronavirus as a Public Health Emergency of International Concern on 30 January and demanded that all member states should cooperate to prevent further spread of the virus, the Agency requested for the Swedish government to classify the novel disease as a notifiable infectious disease in the Swedish Communicable Diseases Act as both dangerous to public health (allmänfarlig) and dangerous to society (samhällsfarlig), where contact tracing is required,[17][18][19] giving the disease the same legislative status as Ebola, SARS and smallpox.[20] The agency also announced that they have analysing methods that can diagnose a case of the novel disease ‘within hours’ after testing, and that such tests had already been carried out, but that all had turned out negative.[17]
### Planning[edit]
Following the 2005 outbreak of the H5N1 avian flu, Sweden drafted their first national pandemic plan which since then had undergone several revisions. Since a 2008 revision to prepare for the 2009 swine flu pandemic, the plan includes the formation of a National Pandemic Group (NPG) in the event of a possible pandemic. The group involves several Swedish government agencies and defines each agency's role.[21][22]
The Public Health Agency
The plan states that the Public Health Agency of Sweden will be the expert agency responsible for monitoring diseases with a pandemic potential, and with the mandate to assemble the National Pandemic Group to coordinate pandemic preparations and strategies on a national level between the relevant agencies. The pandemic group includes four additional Swedish government agencies: the Swedish Civil Contingencies Agency, the Swedish Medical Products Agency, the Swedish National Board of Health and Welfare and the Swedish Work Environment Authority, as well as the county administrative boards of Sweden and the employer's organisation Swedish Association of Local Authorities and Regions.[23][22]
Swedish crisis management is built on a principle of responsibility which means that the organisation who is responsible for an area of activity under normal circumstances is also responsible for that area of activity during a crisis. As the Public Health Agency of Sweden, headed by director general Johan Carlson, is the agency responsible of monitoring and preventing the spread of infectious diseases, the agency had a central role in the Swedish response to the pandemic. The Public Health Agency also tasked with having a coordinating role for the national response to a pandemic according to the National Pandemic Plan, together with the Swedish Civil Contingencies Agency headed by Dan Eliasson and the Swedish National Board of Health and Welfare headed by Olivia Wigzell.[24][25]
### Preparedness[edit]
In risk and impact assessments by the Swedish Civil Contingencies Agency, the Swedish expert agency on crisis management, the risk of Sweden in the future being affected by a severe pandemic was assessed as "high" with a "catastrophic" impact on human health and economics. They believed that a future pandemic would be inevitable within 5–50 years.[26][27]
In the 2019 Global Health Security Index of the ‘most prepared’ countries in the world for an epidemic or a pandemic published by the Johns Hopkins Center for Health Security, Sweden was ranked 7th overall. Sweden received high rankings regarding prevention of the emergence of a new pathogen, early detection and reporting of an epidemic of international concern and having a low risk environment. However, the Swedish healthcare system received a lower score, questioning if it was sufficient and robust enough to treat the sick and protect health workers.[28] [note 3] In 2013, the Swedish Civil Contingencies Agency investigated Sweden's ability to cope with a pandemic through a simulation where a severe avian influenza infects a third of the population, out of which 190,000 gets severely ill, and up to 10,000 die from the disease. They concluded that Sweden was generally well prepared, with pandemic plans on both national and regional level, but that the health-care system would be the weak link. They noted that Swedish hospitals were already under heavy burden, and would not have the capacity to treat everyone who become sick, even when alternative facilities (like schools and sports centres) were used as hospitals. They also pointed out that issues concerning prioritising, including triage, would become central during the crisis, and that they believed this subject needed to be addressed.[26][27] Before the outbreak of the new coronavirus, Sweden had a relatively low number of hospital beds per capita, with 2.2 beds per 1000 people (2017),[30] and intensive care unit (ICU) beds per capita of 5.8 per 100.000 people (2012).[31] Both numbers were lower than most countries' in the EU. The total number of ICU beds in Swedish hospitals was 526.[32]
By the time of the Fall of the Berlin Wall, the Swedish Defence Forces was equipped with a total of 35 field hospitals, with what some considered to be the most modern battlefield medicine in the world, with the Swedish Navy having an additional 15 hospitals. The field hospitals had a combined capacity of treating 10.000 patients and performing 1000 surgeries every 24 hours, as well as stockpiles with drugs, medical supplies and personal protective equipment to treat 150.000 war casualties. Additionally, the Swedish state had several preparedness hospitals and Swedish schools were constructed to be converted into hospital units in case of a military conflict and with a total capacity of treating 125.000 patients, supported by a network of preparedness storages containing medicine and medical equipment. From 1990 and onwards, the system was gradually dismantled to eventually disappear altogether, with the equipment, including more than 600 new ventilators, being either given away or disposed of. At the start of the 2020 COVID-19 pandemic, the Swedish Defence Forces owned 2 medical units with a total of 96 beds, out of which 16 were ICU beds, and there were no civil preparedness storages for medical equipment left in Sweden.[33][34] Until 2009, the Swedish state-run pharmacy chain Apoteket had the responsibility to ensure drug supply in case of emergency.[35][36][37] Following a controversial[38] privatisation, the responsibility was handed over to the private sector. However, a lack of regulations meant that the companies had no incentive to keep a bigger stock than necessary[citation needed], effectively leaving Sweden without an entity responsible for medicine preparedness. At the start of the pandemic, the Swedish healthcare system were instead relying on a "just-in-time" deliveries of medication and medical equipment, and Sweden had no medicine manufacturing of its own, which was considered to make the country's drug supply vulnerable as it relied on global trade and long supply lines. The Swedish healthcare system was already experiencing a growing number of backordered drugs in the years leading up to the pandemic. The lack of medicine preparedness had been strongly criticised in several inquiries and reports since 2013 by a number of Swedish governmental agencies, including the Swedish National Audit Office, the Swedish Defence Research Agency and the Swedish Civil Contingencies Agency. The latter had regarded disturbances in the drug supply as one of their biggest concerns in their annual risk assessments.[37][36][35]
## Timeline[edit]
Main article: Timeline of the COVID-19 pandemic in Sweden
COVID-19 cases in Sweden (
* v
* t
* e
)
Deaths Active cases
2020202020212021
FebFebMarMarAprAprMayMayJunJunJulJulAugAugSepSepOctOctNovNovDecDec
JanJan
Last 15 daysLast 15 days
Date
# of cases
# of deaths
2020-02-04 1(n.a.)
2020-02-05 1(=)
2020-02-06 1(=)
2020-02-07 1(=)
2020-02-08 1(=)
2020-02-09 1(=)
2020-02-10 1(=)
2020-02-11 1(=)
2020-02-12 1(=)
2020-02-13 1(=)
2020-02-14 1(=)
2020-02-15 1(=)
2020-02-16 1(=)
2020-02-17 1(=)
2020-02-18 1(=)
2020-02-19 1(=)
2020-02-20 1(=)
2020-02-21 1(=)
2020-02-22 1(=)
2020-02-23 1(=)
2020-02-24 1(=)
2020-02-25 1(=)
2020-02-26 2(+100%)
2020-02-27 3(+50%)
2020-02-28
11(+267%)
2020-02-29
14(+27%)
2020-03-01
14(=)
2020-03-02
19(+36%)
2020-03-03
32(+68%)
2020-03-04
62(+94%)
2020-03-05
87(+40%)
2020-03-06
146(+68%)
2020-03-07
179(+23%)
2020-03-08
225(+26%)
2020-03-09
326(+45%)
2020-03-10
424(+30%)
2020-03-11
620(+46%) 2(n.a.)
2020-03-12
771(+24%) 2(=)
2020-03-13
923(+20%) 3(+50%)
2020-03-14
994(+7.7%) 4(+33%)
2020-03-15
1,063(+6.9%) 6(+50%)
2020-03-16
1,146(+7.8%) 8(+33%)
2020-03-17
1,265(+10%) 9(+12%)
2020-03-18
1,410(+11%) 15(+67%)
2020-03-19
1,553(+10%) 22(+47%)
2020-03-20
1,733(+12%) 31(+41%)
2020-03-21
1,869(+7.8%) 39(+26%)
2020-03-22
1,987(+6.3%) 50(+28%)
2020-03-23
2,169(+9.2%) 61(+22%)
2020-03-24
2,399(+11%) 82(+34%)
2020-03-25
2,713(+13%) 104(+27%)
2020-03-26
2,999(+11%) 135(+30%)
2020-03-27
3,364(+12%) 167(+24%)
2020-03-28
3,664(+8.9%) 202(+21%)
2020-03-29
3,944(+7.6%) 240(+19%)
2020-03-30
4,360(+11%) 285(+19%)
2020-03-31
4,835(+11%) 333(+17%)
2020-04-01
5,321(+10%) 386(+16%)
2020-04-02
5,875(+10%) 456(+18%)
2020-04-03
6,476(+10%) 536(+18%)
2020-04-04
6,833(+5.5%) 606(+13%)
2020-04-05
7,173(+5%) 691(+14%)
2020-04-06
7,562(+5.4%) 781(+13%)
2020-04-07
8,300(+9.8%) 865(+11%)
2020-04-08
8,954(+7.9%) 980(+13%)
2020-04-09
9,599(+7.2%) 1,066(+8.8%)
2020-04-10
10,053(+4.7%) 1,156(+8.4%)
2020-04-11
10,448(+3.9%) 1,258(+8.8%)
2020-04-12
10,912(+4.4%) 1,355(+7.7%)
2020-04-13
11,349(+4%) 1,439(+6.2%)
2020-04-14
11,828(+4.2%) 1,531(+6.4%)
2020-04-15
12,432(+5.1%) 1,646(+7.5%)
2020-04-16
13,055(+5%) 1,757(+6.7%)
2020-04-17
13,743(+5.3%) 1,840(+4.7%)
2020-04-18
14,275(+3.9%) 1,926(+4.7%)
2020-04-19
14,663(+2.7%) 2,013(+4.5%)
2020-04-20
15,124(+3.1%) 2,098(+4.2%)
2020-04-21
15,831(+4.7%) 2,160(+3%)
2020-04-22
16,553(+4.6%) 2,237(+3.6%)
2020-04-23
17,311(+4.6%) 2,323(+3.8%)
2020-04-24
18,091(+4.5%) 2,412(+3.8%)
2020-04-25
18,564(+2.6%) 2,485(+3%)
2020-04-26
18,864(+1.6%) 2,559(+3%)
2020-04-27
19,427(+3%) 2,633(+2.9%)
2020-04-28
20,169(+3.8%) 2,716(+3.2%)
2020-04-29
20,968(+4%) 2,799(+3.1%)
2020-04-30
21,604(+3%) 2,877(+2.8%)
2020-05-01
22,136(+2.5%) 2,955(+2.7%)
2020-05-02
22,435(+1.4%) 3,028(+2.5%)
2020-05-03
22,696(+1.2%) 3,103(+2.5%)
2020-05-04
23,173(+2.1%) 3,187(+2.7%)
2020-05-05
23,830(+2.8%) 3,259(+2.3%)
2020-05-06
24,575(+3.1%) 3,332(+2.2%)
2020-05-07
25,359(+3.2%) 3,412(+2.4%)
2020-05-08
26,060(+2.8%) 3,472(+1.8%)
2020-05-09
26,569(+2%) 3,540(+2%)
2020-05-10
26,848(+1.1%) 3,613(+2.1%)
2020-05-11
27,303(+1.7%) 3,678(+1.8%)
2020-05-12
28,057(+2.8%) 3,739(+1.7%)
2020-05-13
28,755(+2.5%) 3,789(+1.3%)
2020-05-14
29,412(+2.3%) 3,835(+1.2%)
2020-05-15
30,100(+2.3%) 3,893(+1.5%)
2020-05-16
30,458(+1.2%) 3,941(+1.2%)
2020-05-17
30,717(+0.85%) 3,994(+1.3%)
2020-05-18
31,147(+1.4%) 4,053(+1.5%)
2020-05-19
31,813(+2.1%) 4,094(+1%)
2020-05-20
32,621(+2.5%) 4,146(+1.3%)
2020-05-21
33,231(+1.9%) 4,199(+1.3%)
2020-05-22
33,763(+1.6%) 4,255(+1.3%)
2020-05-23
34,166(+1.2%) 4,310(+1.3%)
2020-05-24
34,376(+0.61%) 4,354(+1%)
2020-05-25
34,867(+1.4%) 4,396(+0.96%)
2020-05-26
35,613(+2.1%) 4,424(+0.64%)
2020-05-27
36,413(+2.2%) 4,462(+0.86%)
2020-05-28
37,187(+2.1%) 4,502(+0.9%)
2020-05-29
37,960(+2.1%) 4,543(+0.91%)
2020-05-30
38,392(+1.1%) 4,582(+0.86%)
2020-05-31
38,657(+0.69%) 4,628(+1%)
2020-06-01
39,305(+1.7%) 4,667(+0.84%)
2020-06-02
40,205(+2.3%) 4,703(+0.77%)
2020-06-03
41,251(+2.6%) 4,731(+0.6%)
2020-06-04
42,290(+2.5%) 4,774(+0.91%)
2020-06-05
43,436(+2.7%) 4,811(+0.78%)
2020-06-06
44,216(+1.8%) 4,840(+0.6%)
2020-06-07
44,678(+1%) 4,873(+0.68%)
2020-06-08
45,355(+1.5%) 4,911(+0.78%)
2020-06-09
46,292(+2.1%) 4,944(+0.67%)
2020-06-10
47,729(+3.1%) 4,984(+0.81%)
2020-06-11
49,022(+2.7%) 5,019(+0.7%)
2020-06-12
50,351(+2.7%) 5,048(+0.58%)
2020-06-13
51,383(+2%) 5,081(+0.65%)
2020-06-14
51,801(+0.81%) 5,108(+0.53%)
2020-06-15
52,486(+1.3%) 5,138(+0.59%)
2020-06-16
53,695(+2.3%) 5,166(+0.54%)
2020-06-17
55,152(+2.7%) 5,198(+0.62%)
2020-06-18
56,646(+2.7%) 5,227(+0.56%)
2020-06-19
57,855(+2.1%) 5,257(+0.57%)
2020-06-20
58,553(+1.2%) 5,286(+0.55%)
2020-06-21
58,874(+0.55%) 5,308(+0.42%)
2020-06-22
59,674(+1.4%) 5,328(+0.38%)
2020-06-23
60,983(+2.2%) 5,353(+0.47%)
2020-06-24
62,681(+2.8%) 5,375(+0.41%)
2020-06-25
63,959(+2%) 5,398(+0.43%)
2020-06-26
65,163(+1.9%) 5,409(+0.2%)
2020-06-27
65,918(+1.2%) 5,423(+0.26%)
2020-06-28
66,333(+0.63%) 5,446(+0.42%)
2020-06-29
67,060(+1.1%) 5,462(+0.29%)
2020-06-30
67,864(+1.2%) 5,482(+0.37%)
2020-07-01
68,549(+1%) 5,497(+0.27%)
2020-07-02
69,236(+1%) 5,512(+0.27%)
2020-07-03
69,930(+1%) 5,520(+0.15%)
2020-07-04
70,294(+0.52%) 5,535(+0.27%)
2020-07-05
70,609(+0.45%) 5,544(+0.16%)
2020-07-06
70,860(+0.36%) 5,559(+0.27%)
2020-07-07
71,138(+0.39%) 5,571(+0.22%)
2020-07-08
71,671(+0.75%) 5,582(+0.2%)
2020-07-09
72,005(+0.47%) 5,597(+0.27%)
2020-07-10
72,374(+0.51%) 5,611(+0.25%)
2020-07-11
72,682(+0.43%) 5,621(+0.18%)
2020-07-12
72,788(+0.15%) 5,629(+0.14%)
2020-07-13
72,958(+0.23%) 5,641(+0.21%)
2020-07-14
73,270(+0.43%) 5,649(+0.14%)
2020-07-15
73,557(+0.39%) 5,655(+0.11%)
2020-07-16
73,825(+0.36%) 5,661(+0.11%)
2020-07-17
74,109(+0.38%) 5,668(+0.12%)
2020-07-18
74,300(+0.26%) 5,679(+0.19%)
2020-07-19
74,410(+0.15%) 5,686(+0.12%)
2020-07-20
74,541(+0.18%) 5,692(+0.11%)
2020-07-21
74,767(+0.3%) 5,699(+0.12%)
2020-07-22
75,064(+0.4%) 5,705(+0.11%)
2020-07-23
75,284(+0.29%) 5,710(+0.09%)
2020-07-24
75,546(+0.35%) 5,713(+0.05%)
2020-07-25
75,684(+0.18%) 5,714(+0.02%)
2020-07-26
75,726(+0.06%) 5,716(+0.04%)
2020-07-27
75,797(+0.09%) 5,722(+0.1%)
2020-07-28
76,080(+0.37%) 5,726(+0.07%)
2020-07-29
76,381(+0.4%) 5,727(+0.02%)
2020-07-30
76,683(+0.4%) 5,727(=)
2020-07-31
76,941(+0.34%) 5,729(+0.03%)
2020-08-01
77,244(+0.39%) 5,731(+0.03%)
2020-08-02
77,282(+0.05%) 5,734(+0.05%)
2020-08-03
77,447(+0.21%) 5,738(+0.07%)
2020-08-04
77,780(+0.43%) 5,740(+0.03%)
2020-08-05
78,205(+0.55%) 5,741(+0.02%)
2020-08-06
78,583(+0.48%) 5,745(+0.07%)
2020-08-07
78,963(+0.48%) 5,747(+0.03%)
2020-08-08
79,223(+0.33%) 5,748(+0.02%)
2020-08-09
79,296(+0.09%) 5,752(+0.07%)
2020-08-10
79,492(+0.25%) 5,754(+0.03%)
2020-08-11
79,909(+0.52%) 5,758(+0.07%)
2020-08-12
80,352(+0.55%) 5,761(+0.05%)
2020-08-13
80,715(+0.45%) 5,766(+0.09%)
2020-08-14
81,059(+0.43%) 5,767(+0.02%)
2020-08-15
81,285(+0.28%) 5,768(+0.02%)
2020-08-16
81,348(+0.08%) 5,768(=)
2020-08-17
81,522(+0.21%) 5,771(+0.05%)
2020-08-18
81,836(+0.39%) 5,775(+0.07%)
2020-08-19
82,187(+0.43%) 5,776(+0.02%)
2020-08-20
82,520(+0.41%) 5,778(+0.03%)
2020-08-21
82,818(+0.36%) 5,783(+0.09%)
2020-08-22
82,978(+0.19%) 5,784(+0.02%)
2020-08-23
83,035(+0.07%) 5,787(+0.05%)
2020-08-24
83,209(+0.21%) 5,788(+0.02%)
2020-08-25
83,431(+0.27%) 5,789(+0.02%)
2020-08-26
83,675(+0.29%) 5,791(+0.03%)
2020-08-27
83,877(+0.24%) 5,792(+0.02%)
2020-08-28
84,056(+0.21%) 5,793(+0.02%)
2020-08-29
84,187(+0.16%) 5,794(+0.02%)
2020-08-30
84,235(+0.06%) 5,797(+0.05%)
2020-08-31
84,397(+0.19%) 5,799(+0.03%)
2020-09-01
84,568(+0.2%) 5,802(+0.05%)
2020-09-02
84,781(+0.25%) 5,804(+0.03%)
2020-09-03
85,067(+0.34%) 5,806(+0.03%)
2020-09-04
85,329(+0.31%) 5,806(=)
2020-09-05
85,500(+0.2%) 5,806(=)
2020-09-06
85,567(+0.08%) 5,809(+0.05%)
2020-09-07
85,752(+0.22%) 5,810(+0.02%)
2020-09-08
85,988(+0.28%) 5,811(+0.02%)
2020-09-09
86,302(+0.37%) 5,813(+0.03%)
2020-09-10
86,556(+0.29%) 5,815(+0.03%)
2020-09-11
86,847(+0.34%) 5,819(+0.07%)
2020-09-12
87,053(+0.24%) 5,820(+0.02%)
2020-09-13
87,159(+0.12%) 5,822(+0.03%)
2020-09-14
87,379(+0.25%) 5,824(+0.03%)
2020-09-15
87,671(+0.33%) 5,825(+0.02%)
2020-09-16
88,001(+0.38%) 5,827(+0.03%)
2020-09-17
88,390(+0.44%) 5,828(+0.02%)
2020-09-18
88,827(+0.49%) 5,829(+0.02%)
2020-09-19
89,106(+0.31%) 5,830(+0.02%)
2020-09-20
89,239(+0.15%) 5,834(+0.07%)
2020-09-21
89,505(+0.3%) 5,836(+0.03%)
2020-09-22
89,943(+0.49%) 5,837(+0.02%)
2020-09-23
90,496(+0.61%) 5,837(=)
2020-09-24
91,036(+0.6%) 5,838(+0.02%)
2020-09-25
91,666(+0.69%) 5,842(+0.07%)
2020-09-26
91,991(+0.35%) 5,844(+0.03%)
2020-09-27
92,158(+0.18%) 5,845(+0.02%)
2020-09-28
92,536(+0.41%) 5,846(+0.02%)
2020-09-29
93,149(+0.66%) 5,848(+0.03%)
2020-09-30
93,838(+0.74%) 5,852(+0.07%)
2020-10-01
94,471(+0.67%) 5,853(+0.02%)
2020-10-02
95,183(+0.75%) 5,856(+0.05%)
2020-10-03
95,644(+0.48%) 5,859(+0.05%)
2020-10-04
95,800(+0.16%) 5,862(+0.05%)
2020-10-05
96,174(+0.39%) 5,864(+0.03%)
2020-10-06
96,960(+0.82%) 5,868(+0.07%)
2020-10-07
97,791(+0.86%) 5,871(+0.05%)
2020-10-08
98,625(+0.85%) 5,872(+0.02%)
2020-10-09
99,408(+0.79%) 5,877(+0.09%)
2020-10-10
99,917(+0.51%) 5,882(+0.09%)
2020-10-11
100,078(+0.16%) 5,884(+0.03%)
2020-10-12
100,715(+0.64%) 5,887(+0.05%)
2020-10-13
101,631(+0.91%) 5,888(+0.02%)
2020-10-14
102,599(+0.95%) 5,890(+0.03%)
2020-10-15
103,501(+0.88%) 5,893(+0.05%)
2020-10-16
104,680(+1.1%) 5,895(+0.03%)
2020-10-17
105,377(+0.67%) 5,899(+0.07%)
2020-10-18
105,698(+0.3%) 5,900(+0.02%)
2020-10-19
106,469(+0.73%) 5,904(+0.07%)
2020-10-20
107,759(+1.2%) 5,908(+0.07%)
2020-10-21
109,330(+1.5%) 5,911(+0.05%)
2020-10-22
110,996(+1.5%) 5,920(+0.15%)
2020-10-23
112,864(+1.7%) 5,927(+0.12%)
2020-10-24
114,341(+1.3%) 5,935(+0.13%)
2020-10-25
114,855(+0.45%) 5,943(+0.13%)
2020-10-26
115,924(+0.93%) 5,954(+0.19%)
2020-10-27
118,338(+2.1%) 5,963(+0.15%)
2020-10-28
121,728(+2.9%) 5,972(+0.15%)
2020-10-29
124,990(+2.7%) 5,981(+0.15%)
2020-10-30
129,046(+3.2%) 5,990(+0.15%)
2020-10-31
132,033(+2.3%) 6,003(+0.22%)
2020-11-01
133,330(+0.98%) 6,025(+0.37%)
2020-11-02
134,899(+1.2%) 6,045(+0.33%)
2020-11-03
138,507(+2.7%) 6,064(+0.31%)
2020-11-04
142,989(+3.2%) 6,085(+0.35%)
2020-11-05
147,733(+3.3%) 6,107(+0.36%)
2020-11-06
152,187(+3%) 6,132(+0.41%)
2020-11-07
156,638(+2.9%) 6,159(+0.44%)
2020-11-08
158,735(+1.3%) 6,181(+0.36%)
2020-11-09
162,460(+2.3%) 6,216(+0.57%)
2020-11-10
166,957(+2.8%) 6,251(+0.56%)
2020-11-11
172,667(+3.4%) 6,278(+0.43%)
2020-11-12
178,233(+3.2%) 6,306(+0.45%)
2020-11-13
184,963(+3.8%) 6,339(+0.52%)
2020-11-14
188,476(+1.9%) 6,377(+0.6%)
2020-11-15
190,057(+0.84%) 6,416(+0.61%)
2020-11-16
192,602(+1.3%) 6,453(+0.58%)
2020-11-17
197,061(+2.3%) 6,495(+0.65%)
2020-11-18
202,023(+2.5%) 6,546(+0.79%)
2020-11-19
209,639(+3.8%) 6,591(+0.69%)
2020-11-20
215,099(+2.6%) 6,636(+0.68%)
2020-11-21
219,592(+2.1%) 6,687(+0.77%)
2020-11-22
222,014(+1.1%) 6,746(+0.88%)
2020-11-23
225,890(+1.7%) 6,801(+0.82%)
2020-11-24
231,565(+2.5%) 6,868(+0.99%)
2020-11-25
237,631(+2.6%) 6,938(+1%)
2020-11-26
244,534(+2.9%) 6,997(+0.85%)
2020-11-27
250,996(+2.6%) 7,061(+0.91%)
2020-11-28
254,821(+1.5%) 7,111(+0.71%)
2020-11-29
257,575(+1.1%) 7,162(+0.72%)
2020-11-30
261,057(+1.4%) 7,228(+0.92%)
2020-12-01
266,877(+2.2%) 7,296(+0.94%)
2020-12-02
273,424(+2.5%) 7,367(+0.97%)
2020-12-03
280,410(+2.6%) 7,443(+1%)
2020-12-04
287,748(+2.6%) 7,513(+0.94%)
2020-12-05
292,613(+1.7%) 7,556(+0.57%)
2020-12-06
294,416(+0.62%) 7,636(+1.1%)
2020-12-07
298,198(+1.3%) 7,694(+0.76%)
2020-12-08
305,644(+2.5%) 7,748(+0.7%)
2020-12-09
314,040(+2.7%) 7,823(+0.97%)
2020-12-10
320,732(+2.1%) 7,909(+1.1%)
2020-12-11
328,451(+2.4%) 7,994(+1.1%)
2020-12-12
334,989(+2%) 8,063(+0.86%)
2020-12-13
338,046(+0.91%) 8,131(+0.84%)
2020-12-14
341,583(+1%) 8,224(+1.1%)
2020-12-15
348,587(+2.1%) 8,309(+1%)
2020-12-16
357,412(+2.5%) 8,410(+1.2%)
2020-12-17
367,053(+2.7%) 8,528(+1.4%)
2020-12-18
374,971(+2.2%) 8,599(+0.83%)
2020-12-19
380,481(+1.5%) 8,679(+0.93%)
2020-12-20
384,233(+0.99%) 8,770(+1%)
2020-12-21
389,395(+1.3%) 8,842(+0.82%)
2020-12-22
395,992(+1.7%) 8,928(+0.97%)
2020-12-23
407,370(+2.9%) 9,011(+0.93%)
2020-12-24
412,406(+1.2%) 9,096(+0.94%)
2020-12-25
415,200(+0.68%) 9,198(+1.1%)
2020-12-26
418,167(+0.71%) 9,290(+1%)
2020-12-27
421,377(+0.77%) 9,384(+1%)
2020-12-28
428,472(+1.7%) 9,500(+1.2%)
2020-12-29
437,348(+2.1%) 9,570(+0.74%)
2020-12-30
447,806(+2.4%) 9,645(+0.78%)
2020-12-31
454,807(+1.6%) 9,738(+0.96%)
2021-01-01
457,425(+0.58%) 9,804(+0.68%)
2021-01-02
459,958(+0.55%) 9,884(+0.82%)
2021-01-03
462,714(+0.6%) 9,953(+0.7%)
2021-01-04
469,695(+1.5%) 10,008(+0.55%)
2021-01-05
477,239(+1.6%) 10,046(+0.38%)
2021-01-06
482,271(+1.1%) 10,078(+0.32%)
2021-01-07
489,423(+1.5%) 10,122(+0.44%)
2021-01-08
495,124(+1.2%) 10,160(+0.38%)
2021-01-09
499,861(+0.96%) 10,194(+0.33%)
2021-01-10
502,179(+0.46%) 10,232(+0.37%)
2021-01-11
506,830(+0.93%) 10,254(+0.22%)
2021-01-12
512,172(+1.1%) 10,277(+0.22%)
2021-01-13
518,779(+1.3%) 10,286(+0.09%)
2021-01-14
523,486(+0.91%) 10,289(+0.03%)
Source: Public Health Agency of Sweden – Folkhälsomyndigheten[a][b][c]
Notes:
1. ^ Data on cases and deaths is compiled by Folkhälsomyndigheten on weekdays (except Mondays) at 14:00 (CET). Swedish authorities do not publish data on recoveries. Reports of new cases and deaths to Folkhälsomyndigheten might be delayed by up to several days, possibly introducing delays in reported number of cases for the last few days of data. Reports include deaths with a confirmed Covid-19 diagnosis where the cause of death isn't attributed to Covid-19. As of data from the National Board of Health and Welfare from 21 April 2020, this number amounted to 4.5% of cases confirmed in a laboratory. Data includes confirmed cases (ICD-10 U07.1) but excludes non-confirmed cases (ICD-10 U07.2). As this only include cases confirmed in a laboratory, the actual number is believed to be higher due to the number of laboratory-confirmed cases only amounting to 70% (as of 3 May 2020) of an excess mortality observed in Sweden since late March, according to an statistical analysis by the Public Health Agency based on data from the Swedish Tax Agency and the European mortality monitoring activity (EuroMOMO). By late April, there had been approximately 2,800 excess deaths in Sweden.[2][39][40]
2. ^ As of 14 January 2020 CET, 34 deaths have been registered with an unknown date. These deaths have not been included in this table. The total number of deaths (including dated and undated deaths) is 10,323.
3. ^ On 27 August 2020, Folkhälsomyndigheten announced that the use of faulty test kits made by BGI Biotechnology (Wuhan) Co. Ltd. had led to about 3,700 tests wrongly attributed as positive. As a result, they were removed from the cumulative number of cases. On 2 September 2020, an additional 200 cases were removed for the same reason.[41]
### Early cases (December 2019 – February 2020)[edit]
On 31 January, the first Swedish case was confirmed in a woman in Jönköping who had travelled to Sweden from Wuhan, China, on 24 January directly from Wuhan. The case was fully isolated and there are no reports of further spread.[42][43] It is believed that the virus could have reached Sweden as early as December 2019 when several individuals sought care at a primary care clinic in Svärdsjö, Falun Municipality, with signs of respiratory disease, as all of them had been in contact with an individual with a recent travel history to Wuhan, and later tested positive for antibodies against the disease. There is however no evidence of further spread in connection with those early cases.[44]
The second confirmed case was diagnosed at Sahlgrenska University Hospital, Gothenburg, on 26 February, after a man who had recently returned from northern Italy following the COVID-19 outbreak in Italy had developed symptoms.[45][42] With five additional cases confirmed on 27 February,[46] the Public Health Agency put out a statement that these cases were all related to travel to high-risk zones and that there was no evidence of community transmission.[47] Disease control measures, including extensive contact tracing, turned up over 200 travel-related cases in the following weeks, all with connection to confirmed cases or travel to high risk regions.[48] Many of those who tested positive for the virus during this early stage of the outbreak in Sweden had been infected while on vacation in Italy during the one-week spring break in late February.[49]
During the four-week period from February to March in which the spring break takes place in different areas of Sweden, around one million Swedes (about one tenth of the total population) had travelled abroad.[50] Testing was initially primarily done on individuals who had developed symptoms after travelling from the areas hardest hit by the outbreak, such as China, Iran, northern Italy, Tyrol and South Korea, or those with pneumonia of unknown cause. Subsequent whole genome sequencing studies carried out by the Public Health Agency proved that disease control measures including isolation and contact tracing had been largely successful in preventing the infection to spread from Italy.
The studies also revealed that early assumptions that Swedes returning from Northern Italy and Tyrol were the main drivers of the outbreak in Sweden was incorrect, as the virus had likely been brought to Sweden by "hundreds" of different people from a range of countries, as the outbreak by that time had "gone under the radar" in many other parts of the world and that other countries already had a large spread.[51][52][50]
Analysis of early Swedish cases suggested that several early cases had carried the virus from the United Kingdom and the United States, and also from France and the Netherlands.[53][50] From the start of the outbreak in Sweden, Stockholm County saw a significantly higher number of cases in the Stockholm region compared to other counties of Sweden, including the densely populated regions Skåne and Västra Götaland. According to Johan Carlson, director-general at the Public Health Agency, one reason was believed to be that the Stockholm spring break took place later than in other regions.[54]
On 27 February, Uppsala County confirmed its first case in a woman with a travel history to Germany, where she had met with an Italian colleague, and had been admitted to Uppsala University Hospital[55] after seeking medical attention with flu-like symptoms.
In June, it was discovered that a number of persons in Svärdsjö, Dalarna County, had antibodies against SARS-CoV-2. These persons had been in contact with a person visiting from Wuhan, China, in December 2019 and sought medical attention after experiencing respiratory symptoms. It is since believed that SARS-CoV-2 came to Sweden as early as December 2019.[56]
### Community spread (March–)[edit]
On 9 March, an infection and a suspected infection were diagnosed in two patients, with no connection between them, who had sought care at S:t Göran Hospital, Stockholm, on 6 March. They were assumed to have been infected through community transmission.[57][58] The following day, Jämtland and Västernorrland also confirmed initial cases.[59][60]
Responding to indications of local transmission in the Stockholm area and Västra Götaland, the Public Health Agency on 10 March raised the risk assessment of community spread from moderate to very high, which is the highest level.[61][62][63] The first death was reported on 11 March, the same day as the COVID-19 outbreak was declared a pandemic by the WHO, when a person in their 70s from the Stockholm region died in the intensive care unit of Karolinska University Hospital. The person was reported to have acquired the virus through community transmission, believed to have occurred about one week before death. The person also belonged to a risk group.[64][65] After the first case in Västmanland County was confirmed on 13 March, the disease had reached all of the 21 regions in Sweden.[1]
The Public Health Agency of Sweden declared on 13 March that stopping the spread of COVID-19 had entered a "new phase" which required "other efforts". The continued focus was now to delay spread among the population and to protect the elderly and most vulnerable against the disease.[66] Contact tracing would no longer be part of the strategy, and testing would instead focus on people already in hospital or those considered to belong to be of a bigger risk of a more severe disease.[67][68]
The health agency believed that 5–10% of the population in Stockholm County was carrying the virus on 9 April.[69] In mid-April, it was reported that out of the approximately 1,300 people who had died after having caught the virus, one third had been living at nursing homes. The figure differed between the regions. In Stockholm, the city most affected by the pandemic, half of the deaths had been residents in one of its many nursing homes.[70] The situation led to the Health and Social Care Inspectorate to begin carrying out controls at the homes.[70]
According to estimations by the Health Agency in early May, the R value had dropped below 1.0 for the first time on 21 April.[71] In June, the Health Agency declared that several regions had entered a "late pandemic phase" with a decrease in the number of new cases, and called for those regions to return to the strategy of stopping the disease through increased testing and detailed contact tracing.[72][73]
### Winter surge[edit]
Like much of Europe, Sweden experienced a dramatic increase in COVID-19 cases and deaths from October to December 2020. Alcohol sales were banned after 10pm, gatherings were limited to a maximum of eight people and some schools switched to online learning in response.[74]
On December 7, schools in Stockholm were switched to distance learning and the government began recommending face masks on public transport for the first time, having previously been one of the few countries not to recommend them.[75] The health system in Stockholm became particularly overwhelmed, with 99% of intensive care beds full, and private sector staff called to stand in due to staff shortages.[9]
An independent commission released a report in December which criticized Sweden's approach for failing to protect care home residents by allowing the virus to become widespread.[76][77] King Carl XVI Gustaf and Stefan Löfven both characterized Sweden's approach as a 'failure' in December 2020 due to the high number of deaths. Löfven suggested that many experts had failed to predict and prepare for the severity of the increase during the winter.[8] Public approval for Tegnell and the Swedish health authorities also fell to the lowest level since the start of the pandemic, 59%, in response to the surge.[78]
Neighboring Finland and Norway criticized Sweden's approach for potentially undermining their own preventative measures.[8]
## Response from the authorities[edit]
### Government[edit]
Main article: Swedish government response to the COVID-19 pandemic
The Swedish government considered its overall objective in the Swedish response to the pandemic was to limit the spread of infection in the country to not exceed the capacity of the Swedish health system. They also aimed to ensure that the municipalities and regions responsible for the health care would have the necessary resources to handle the pandemic.[79]
The government has tried to focus efforts on encouraging the right behaviour and creating social norms rather than mandatory restrictions. Government officials including Swedish prime minister Stefan Löfven has encouraged each individual to take responsibility for their own health and the health of others, and to follow the recommendations from the Public Health Agency of Sweden,[80] as the agency responsible for monitoring a pandemic and coordinating the response.
The Swedish Constitution mandates that government agencies should work independently from the government and that the relevant expert agencies must issue advice prior to any government actions within the agency's area, in this case aiming to prevent the spread of the virus, with a strong mandate that the expert agencies should initiate actions, avoiding rule by ministers.[81] Having its public health agency almost completely controlling the strategy without the involvement of politicians set Sweden apart from most, perhaps all, other countries.[82] However, the agencies do not have the power to pass laws. Instead, they give out recommendations on how someone can or should act to meet a binding regulation within the agency's area of activity (in this case The Swedish Communicable Diseases Act). Although there is no legal framework for a governmental agency to impose sanctions on someone for going against its recommendations, it is not optional as the recommendations work as guidelines on how to act to follow a regulation (in this case an obligation to help halting the spread of an infectious disease).[83][84] The independence of Swedish agencies and the choice of 'recommendations' instead of legislation has received much coverage in international media.[85]
Swedish foreign minister Ann Linde described Sweden as having ‘rather small ministries, but rather big authorities’ (with the Public Health Agency being one such authority), and this going back 300–400 years, and Sweden being characterised by a very high level of trust in its authorities from both the people and the politicians, and that Swedes had a very strong urge to following recommendations from authorities, thus making legislation largely unnecessary. When asked if Sweden would consider tougher restrictions, Löfven and Linde both made clear that the Swedish government would not hesitate to do so if deemed necessary and on advice from the expert agencies, but that such measures needed to be taken at the right time, and they believe it is hard to make people adhere to lockdowns for an extended period. Deputy Prime Minister of Sweden Isabella Lövin referred to the pandemic being "not a sprint, but a marathon".[86][87][88]
#### Legislation[edit]
Main article: Swedish government response to the COVID-19 pandemic
#### Advice against travel abroad[edit]
Main article: Swedish government response to the COVID-19 pandemic
### Strategy[edit]
According to the Swedish Public Health Agency, the Swedish strategy aimed to protect their senior and vulnerable citizens, and to slow down the spread of the virus, to keep the healthcare system from getting overwhelmed.[89][90][91][92] They are also mandated by law to make their response based on scientific evidence.[93] The Swedish state epidemiologist Anders Tegnell has questioned the scientific basis of some of the "stricter" measures taken by other governments, including lockdowns and border closures.[94]
"Closedown, lockdown, closing borders – nothing has a historical scientific basis, in my view. We have looked at a number of European Union countries to see whether they have published any analysis of the effects of these measures before they were started and we saw almost none."
-Anders Tegnell, current state epidemiologist of Sweden, in a Nature interview, April 2020
While many countries imposed nationwide lockdowns and curfews, such measures were prohibited by the Swedish constitution as it is considered to be a violation of people's freedom of movement,[95] and Swedish laws on communicable diseases (Smittskyddslagen) only allow for quarantining individuals and small areas such as buildings, not for entire geographical areas. Instead, it is based mostly around individual responsibility.[96][94] Although the government was later granted more authority for imposing restrictions on transport following a temporary amendment in April,[97] the Swedish authorities considered lockdowns to be unnecessary, as they believed that voluntary measures could be just as effective as bans.[95] Although many thought this to be a 'relaxed' approach, it was defended by the authorities and government officials. Among them is the Prime Minister of Sweden, Stefan Löfvén, who said, it is more sustainable, as unlike lockdowns, it could be in place for "months, even years" as it was not assumed to be likely that the disease could be stopped until a vaccine was produced.[98][99][94] Therefore, the Swedish response only included measures where an exit strategy was not needed.[100]
Unlike many European countries, including neighbouring Denmark and Norway, Sweden did not close its preschools or elementary schools as a preventive measure. This was met with criticism within Sweden.[101][102][103] According to the Health Agency, the main reasons for not closing schools was that as a preventive measure, it lacked support by research or scientific literature, and because of its adverse effects on society. They argued that many parents, including healthcare professionals, would have no choice but to stay home from work to care for their children if schools were closed. There was also a concern for a situation where older people babysit their grandchildren, as they face a more significant risk of severe symptoms in case of infection. According to the agency's estimations, closures of elementary schools and preschool could result in the absence of up to 43,000 healthcare professionals, including doctors, nurses and nurse's assistants, equalling 10 per cent of the total workforce in the sector.[104][105]
Additionally, there was concern of school closures having negative consequences for disadvantaged and vulnerable children.[106] According to the agency yet no evidence of children playing a major role in the spread of the virus, nor of a high infection rate among children or preschool teachers, and that children who become infected showed mild symptoms.[107] In May, Tegnell said that the decision was right, as the healthcare system would not have managed the situation the past months if Swedish authorities had chosen to close elementary schools.[108] He later said that the decision to close secondary schools might have been unnecessary because it possibly had little effect in slowing the spread of the disease.[109]
After the Danish government went against the advice of the Danish Health Authority and closed their national borders in March, Tegnell remarked that there were currently no scientific studies supporting border closures to be a useful measure against a pandemic, and that "history has proven it to be completely meaningless measure", and argued that it could, at best, delay the outbreak for one week, and also pointed out that border closures went against the recommendations from the WHO. He later said closures would be "ridiculous" in a situation where the disease had spread across all of Europe, saying that movements within the country were of more concern.[110][111][94]
The government's response to the pandemic has been the subject of criticism from numerous sources, including the Vetenskapsforum COVID-19, a group of scientists and their supporters.[112]
State epidemiologist Anders Tegnell, the architect of the Swedish strategy
Representatives of the Swedish government, as well as its agencies, have denied that pursuing herd immunity is part of the Swedish strategy.[85][113][92] According to state epidemiologist Anders Tegnell, herd immunity had not been calculated in the strategy, and if it had been the goal, "we would have done nothing and let coronavirus run rampant". But in April 2020, he said that Sweden would benefit from herd immunity in the long run,[113] and reasoned that all countries would eventually have to achieve it to beat the virus.[114] In an email from Tegnell to his Finnish counterpart Mika Salminen in March 15, he expressed that keeping schools open would achieve herd immunity quicker.[115] In May 2020 he said that he believed it was unlikely that Sweden, or any other country, would ever reach full herd immunity, and also that it would be a mistake to base a strategy on a hypothetical vaccine, as it would likely be years until there is a vaccine that can be distributed to an entire population. Instead, he believed COVID-19 was something "we're going to have to live with for a very long time".[99] Herd immunity has also not been achieved, with an estimated 7.1% of the population having acquired antibodies according to a September 2020 study, far below the 20% that the authorities had predicted.[115]
As the health experts built the strategy at the Public Health Agency without any influence from the government, it was built solely on a public health perspective, without any political considerations to the economy. The agency did, however, regard the economy as part of its broader public health considerations, due to unemployment and a weakening economy typically leading to poorer public health.[116]
Although Sweden was regarded to have succeeded with making sure the hospitals would keep at pace, it admitted to have failed with protecting its elderly, as three-fourths of its deaths had occurred among nursing home residents or those receiving home care.[116] The Health Agency saw the spread at the homes as their biggest concern, but "not as a failure of our overall strategy, but as a failure of our way to protect the elderly".[117][118] In an interview with Sveriges Radio in early June, Tegnell was asked if he would have done things differently if he could ‘back the tape’, to which he replied that Sweden should have done more earlier during the outbreak. This received extensive coverage in national as well as international media and was interpreted as he was distancing himself from the Swedish strategy. Tegnell however denied this being the case, and said they still believed the strategy being good, but that "you can always improve things, especially in hindsight". When asked to give examples, he said that it would have been much better if they had been more prepared at nursing homes and that it would have been better if the testing capacity had been increased earlier on during the outbreak.[119][120] He also said that the closure of secondary schools might have been unnecessary.[121]
### Measures[edit]
On 10 March 2020, responding to indications of community transmission, the Public Health Agency advised everyone with respiratory infections, even mild cases, to refrain from social contacts where there is a risk of spreading the virus, in private as well as working life. They also ask health care staff working with risk groups, including nursing homes, not work if they have any symptoms of respiratory infection. Relatives of elderly should also avoid unnecessary visits at hospitals and in facilities for elderly, and never visit if there are any respiratory symptoms.[122][123]
#### Social distancing[edit]
On 16 March 2020, the agency recommended that people over 70 should limit close contact with other people, and avoid crowded areas such as stores, public transport and public spaces.[124] At the end of March, 93% of those older than 70 said that they were following the recommendations from the health service to some extent, with the majority having decreased their contacts with friends and family.[125] In May, the agency looked at easening the recommendations for the 'young elderly' of good health, but ultimately decided against it. They did however encourage those over 70 not to isolate completely in their homes, but to go outside for walks while still following the recommendations.[126] On 16 March 2020, they also recommended that employers should recommend their employees work from home.[124] One month later, statistics showed that roughly half the Swedish workforce was working from home.[127] The following day, the agency recommended that secondary schools and universities use distance learning,[128] with schools following suit all over the country.[129] The decision to recommend distance education for secondary and tertiary education, but not for elementary schools, was that studies at secondary schools and universities to a higher extent require commuting and travelling, and that students would not depend on parental care while not in schools, and school closings therefore did not risk interrupting society.[130][131] In May, it was announced that the Health Agency were to lift the recommendations on 15 June, and thereby allowing secondary schools and universities to open up as normal after the summer holidays.[132]
In April, many of the organisations running the public transport systems for the Swedish counties had reported a 50% drop in public transport usage, including Kalmar Länstrafik in Kalmar County, Skånetrafiken in Skåne County, Stockholm Public Transit in Stockholm County, and Västtrafik in Västra Götaland County.[133][134][127][135] In Stockholm, the streets grew increasingly emptier, with a 30% drop in the number of cars,[136] and 70% fewer pedestrians.[127]
In mid-May, and on the request of the Public Health Agency, the Swedish Transport Agency temporarily suspended the regulations that allowed for passenger transport on lorries or trailers pulled by tractors, trucks or engineering vehicles at graduations and carnivals. The new rules were to be in place between 15 May and 31 December.[137][138]
These social distancing recommendations have been effective in part because Swedes tend to have a "disposition to social distancing anyway."[139]
#### Ban on gatherings[edit]
The same day as the first Swedish death to COVID-19, 11 March, the Swedish government passed a new law at the request of the Public Health Agency, limiting freedom of assembly by banning all gatherings larger than 500 people, with threat of fine and prison.[140] The ban would apply until further notice.[141] According to the Health Agency, the reasoning behind drawing the line at 500 was to limit long-distance travel within the nation's borders, as bigger events are more likely to attract visitors from all over the country.[142] Although freedom of assembly is protected by the Swedish constitution in the Fundamental Law on Freedom of Expression, the constitution allows for a government to restrict the freedom, if needed to limit the spread of an epidemic.[143][144] On 27 March the government announced that the ban on public gatherings would be lowered to include all gatherings of more than 50 people, to further decrease the spread of the infection, again at the request of the Public Health Agency.[145][146] The ban would apply to arts and entertainment events including theatre, cinema and concerts, religious meetings, demonstrations, lectures, competitive sports, amusement parks, fairs and markets. The ban did not include gatherings in schools, workplaces, public transport, grocery stores or shopping malls, health clubs or private events.[147][148] The agency also recommended that plans for events and gatherings of fewer than 50 people should be preceded by a risk assessment and, if necessary, followed by mitigation measures. Additionally, they recommend that digital meetings should be considered.[149] The ban on large gatherings had no end-date, and as of late April, the Health Agency was reported as having no plans for when the ban should be lifted.[150] Starting from 24 November gatherings have been limited to up to eight persons.[151][152]
#### Travel[edit]
On 18 March, the Health Agency recommended that everyone should avoid travelling within the country. This came after signs of ongoing community transmission in parts of the country, due to concern that a rapid spread over the country would make redistribution of healthcare resources more difficult. They also called for the public to reconsider any planned holidays during the upcoming Easter weekend.[153][154] The calls to avoid travelling and social interactions during the Easter weekend were repeated several times by agency and government officials, among them Prime Minister Stefan Löfvén and King, Carl XVI Gustaf.[155][156][157] Telia, a Swedish multinational mobile network operator, did an analysis of mobile network data during the week of Easter, and found that most Swedes had followed the agency's recommendations to avoid unnecessary travels during the Easter holidays. Overall, travel from the Stockholm region had decreased by 80–90%, and the number of citizens of Stockholm travelling to popular holiday destinations like Gotland and the ski resorts in Åre had fallen with more than 90%. Travel between other regions in Sweden had fallen as well.[158][159] Ferry-line operator Destination Gotland, who previously had called on their customers to rethink their planned trips for Easter, reported that 85% of all bookings had been rescheduled.[160]
The restrictions on domestic travel were somewhat softened on 13 May, allowing for travels equalling one to two hours from home by car would be allowed under some circumstances to which Löfvén referred to as ‘common sense’, such as not risking to burden healthcare in other regions, keeping contact with others low and not travelling to visit new social contacts, the elderly or those at risk of severe disease.[161] On 4 June, the government announced that the restrictions on domestic travel were to be lifted on 13 June, allowing everyone to freely travel in the country if they were without symptoms and rules on social distancing were followed. However, they cautioned that new restrictions could be introduced if the situation were to worsen, and that the County administrative boards of Sweden were tasked to monitor the situation.[162][163]
### Communication and information[edit]
State epidemiologist Anders Tegnell during a press conference outside the Karolinska Institute in Stockholm, Sweden, in 2020
Beginning in March, press conferences were held daily to at 14:00 local time, with representatives from the three government agencies responsible for coordinating Sweden's response to the pandemic; the Public Health Agency, usually represented by state epidemiologist Tegnell or deputy state epidemiologist Anders Wallensten, the National Board of Health and Welfare and the Swedish Civil Contingencies Agency.[164] According to the latter, close to one million people followed each press conference on the TV or the radio. The ratings excluded other types of media.[165][166]
In response to COVID-19, the Public Health Agency of Sweden issued a series of infographics in different languages describing how to protect oneself and others from infection.
For official information on the disease and the situation in Sweden, the authorities referred the public to the website krisinformation.se, which compiles official emergency information from Swedish authorities. The website is operated by the Civil Contingencies Agency, as the agency responsible for emergency information to the public during emergencies.[167] The agency reported a big increase in the number of people visiting the website during the beginning of the pandemic, with 4.5 million views between January and April 2020, compared to 200,000 during the same period in 2019.[165][166]
In March, the Civil Contingencies Agency received 75 million SEK from the government for public service announcements to inform the public about the virus, and how to reduce the spread of the disease to slow down the spread of the virus.[168]
## Monitoring and modelling[edit]
In early March, the Health Agency expanded the sentinel surveillance system in use for monitoring the influenza season, so that samples from patients with flu-like symptoms would also be tested for SARS-CoV-2 along with the influenza viruses.[169] In early May, approximately 1500 samples had been analysed within the sentinel system.[170]
Between 27 March and 3 April, the health agency tested approximately 800 randomly selected individuals in Stockholm County, to seek knowledge of the then current infection rate.[171] As it was estimated that Stockholm County by then had the highest infection rate in Sweden, the agency choose to focus on that region.[172] According to the results, 2.5% of the local population were carrying the virus in the upper respiratory tract during the surveyed period.[171] Based on the study and a doubling time of 6–7 days, the agency concluded that 5–10% of the population in the region were carrying the virus on 9 April.[69] This was followed by a similar study on national level. In the study, approximately 4000 people would be tested for an active infection.[173] It was followed by a second national study on 4000 individuals in late April,[174] and a similar national study where "thousands" would be tested for antibodies.[175]
In an April study by researchers at the KTH Royal Institute of Technology and the Science for Life Laboratory, home sample kits were mailed to 1,000 randomly selected individuals in Stockholm to be tested for the presence of antibodies against the SARS-CoV-2 virus which causes the COVID-19 disease. After analysing 440 out of the 550 blood samples returned, the scientists concluded that 10% of the donors were infected during or prior to late March. A follow-up study was carried out later that month with an additional 1,000 tests to determine how much the spread has increased during the weeks between the two studies.[176][177] The same month, a study was carried out by researchers at the KTH Royal Institute of Technology and Danderyd Hospital where staff at the hospitals were tested for antibodies. After analysing 527 samples, the researchers reported that approximately 20% of the staff had developed antibodies against the virus. After testing the entire staff a total of 19.1% of the staff had developed IgG antibodies at the end of May / early June. The researchers intended to continue testing to carry out several follow-up tests during the following 12 months to learn how long the antibodies will stay in the body.[178][179][180] In late April, approximately 11,000 out of the staff at Karolinska University Hospital were tested for the virus in either PCR based or serological tests. The tested individuals included both those with clinical medical and non-clinical medical jobs, as well as staff with non-medical jobs. When 5,500 PCR tests and 3,200 serological tests had been analysed, a total of 15% samples came back positive (7% of PCR tests, 10% of serology tests, with 2% being positive in both tests). Only people without symptoms were tested.[181][175]
## Public healthcare system[edit]
### Testing[edit]
Number of analyzed samples per week Week Date Tests Positive Positive %
4–8 25 January – 23 February 180 1 0.6%
9 24 February – 1 March 752 13 1.7%
10 2–8 March 4,302 211 4.9%
11 9–15 March 8,990 835 9.3%
12 16–22 March 10,404 911 8.8%
13 23–29 March 12,349 1,943 15.7%
14 30 March – 5 April 17,776 3,211 18.1%
15 6–12 April 19,880 3,711 18.7%
16 13–19 April 20,233 3,741 18.5%
17[182] 20–26 April 24,560 4,181 17.0%
18[183] 27 April – 3 May 28,802 3,906 13.6%
19[184] 4–10 May 29,129 4,215 14.5%
20[185] 11–17 May 33,003 4,004 12.1%
21[186] 18–24 May 28,986 3,713 12.8%
22[187] 25–31 May 36,466 4,300 11.8%
23[188] 1–7 June 49,162 6,060 12.3%
24[189] 8–14 June 59,861 7,229 12.1%
25[190] 15–21 June 61,803 7,462 12.1%
26[191] 22–28 June 75,171 7,645 10.2%
27[192] 29 June – 5 July 77,642 4,935 6.4%
28[193] 6–13 July 81,801 2,789 3.4%
29[194] 14–19 July 69,393 2,274 3.2%
30[195] 20–26 July 59,143 1,376 2.3%
31[196] 27 July – 2 August 52,959 1,598 3.0%
32[197] 3–9 August 53,721 2,016 3.8%
33[198] 10–16 August 56,487 2,058 3.6%
34[199] 17–23 August 65,546 1,687 2.6%
35[200] 24–30 August 85,060 1,361 1.6%
36[201] 31 August – 6 September 126,219 1,515 1.2%
37[202] 7–13 September 142,673 1,598 1.1%
38[203] 14–20 September 139,471 2,084 1.5%
39[204] 21–27 September 128,852 2,926 2.3%
40[205] 28 September – 4 October 127,844 3,641 2.8%
41[206] 5–11 October 136,883 4,282 3.1%
42[207] 12–18 October 148,267 5,624 3.8%
43[208] 19 – 25 October 164,742 9,165 5.6%
44[209] 26 October – 1 November 189,301 18,489 9.8%
45[210] 2–8 November 228,023 25,483 11.2%
46[211] 9–15 November 260,673 31,405 12.0%
47[212] 16–22 November 260,710 31,975 12.3%
48[213] 23–29 November 275,712 35,552 13.3%
Total — 3,452,931 261,495 —
The first tests were carried out in January, and according to the Swedish Public Health Agency, ‘around twenty tests’ had already been carried out before the first positive case was confirmed on 30 January.[17] The agency considered that all individuals who developed any symptoms of disease in the respiratory tract after visiting Wuhan should be tested, even those with less severe symptoms.[214] The Public Health Agency expanded testing for COVID-19 on 4 March beyond only those who have been in risk areas abroad, to also test cases of pneumonia without known cause.[215] Initially, all tests were carried out at the agency's high-containment laboratory in Solna. But in mid-February, to increase testing capacity and allow for faster test results, testing also began at the clinical medical laboratories in Göteborg, Halmstad, Lund, Skövde, Stockholm, Umeå and Uppsala.[216] The Public Health agency considered testing and contact tracing to be more important in the early and late pandemic phases, to stop the spread of the disease and find every case, as "it isn't possible to test millions of individuals in the country" during the pandemic phase.[72]
At the end of March, the number of tests carried out each week numbered 10,000.[217] In mid-April, the number of weekly tests had doubled to approximately 20,000.[218] In early April, the government instructed for the testing capacity to be vastly increased to be able to analyse 100.000 samples every week. This was mainly to make it possible to test people with jobs considered crucial to society, for instance policemen and those working in rescue service or with electric power supply, while still having enough capacity to handle all tests needed for the health-care sector.[219][220] In mid-May, the number of tests carried out were still far from the goal, with approximately 30.000 tests carried out weekly, and according to a representative for Swedish municipalities and regions it would likely be 'weeks' until goals were met.[221][218] On 4 June, the government announced that due to several regions in Sweden having entered a late phase of the pandemic, coronavirus testing and contact tracing were to be broadened so that everyone with suspected COVID-19 symptoms could be tested free of cost.[222] On 31 May, a total of 275,819 samples had been tested since the start of the Swedish outbreak.[223]
### Capacity[edit]
This section needs to be updated. Please update this article to reflect recent events or newly available information. (December 2020)
The Stockholm International Fairs, Stockholmsmässan, are being converted into a field hospital with the help of the Swedish Defence Force. The field hospital will be able to house 600 seriously and critically sick patients.[224] The Swedish Defence Forces will provide equipment for 30 of the 600 beds and the Stockholm Regional Council will provide the remaining 570.[224] The facilities were initially used for treating less severe cases, as opposed to those needing intensive care.[225] In late April, it was reported that the Defence Force had provided 50 intensive care beds as part of the two field hospitals.[226] Field hospitals were also erected in Gothenburg,[227][228] and Helsingborg.[229] The field hospital in Älvsjö were never needed to be taken into use, and were dismantled in early June.[230] The Gothenburg hospital was used for intensive care during a short time span, but was soon taken out of use following massive criticism from health-care workers who voiced concern for patient safety, increased risks of infection and working conditions.[231][232]
An army-constructed field hospital outside Östra Sjukhuset in Gothenburg on 23 March 2020. The tents contain temporary intensive care units for COVID-19 patients.
Medical tent set up outside Visby Hospital, 14 March 2020.
Medical tent set up outside Enköping Hospital
Streetsigns outside Sahlgrenska hospital from late February telling those with potential symptoms of COVID-19 to wait outside the hospital.
The increasing number of cases in March resulted in the cancellation or postponement of close to 50% of planned surgeries, including cancer-related surgeries, in all of Sweden, and up to 90% in large areas such as Stockholm and Uppsala.[233] By May, 44,000 planned surgeries had been postponed in Sweden, increasing the total number of Swedes in line for a surgery to over 150,000.[234] Several regions also chose to cancel many, or all, planned non-acute dentistry as a measure to redistribute healthcare equipment like disposable gloves and masks.[235]
Before the pandemic, the Swedish healthcare system had the capacity to treat approximately 500 persons in Intensive Care Units (ICU). The relatively low number of beds had stayed a source of concern as the crisis evolved, and even though the number had increased to 800 at the beginning of April, healthcare professionals continued to express worry that their hospitals would eventually run out of beds. According to the calculations of the Swedish health agency, up to 1300 ICU beds would be needed when Sweden reached the top of the pandemic.[236][237] Sweden was eventually able to double the number of intensive care beds in a few weeks,[219] and on 13 April, the National Board of Health and Welfare reported that the total number of ICU beds had risen to 1039, with an occupancy of 80%.[238][239]
### Equipment[edit]
On 13 March, media reported that there is a shortage in personal protective equipment (PPE) for health care staff, and hospitals in Stockholm have been forced to reuse disposable PPEs after sanitation. The regional Health Care Director warned about this scenario in early March and government agencies have temporarily waived the public procurement law to hastily procure more supplies.[240] The National Board of Health and Welfare ('Socialstyrelsen') confirmed that there is no preparedness storage and nothing to distribute to the health care sector.[241][242] In early April, several counties expressed concern that they might run out of some vital drugs used in intensive care.[243][244] Later that month, Stockholm County reported of an acute shortage of the anaesthetic propofol.[245]
As one of the main tasks of the Swedish Defence Force is to support the civil community in case of disasters, their resources were used to lessen equipment shortages in the health-care system. The material supplied by the military included crucial medical equipment; X-ray generators, electrocardiographic machines, 154 ventilators and 154 intensive care monitors. The military also supplied personal protective equipment, including 60,000 gas masks and 40,000 protective suits.[226]
### Staffing[edit]
On 25 March 2020, Björn Eriksson, the Director of Healthcare in Stockholm, appealed to anyone in the Stockholm region who had experience in healthcare to volunteer. As of the 26 March 2020, 5100 people with healthcare experience had registered as volunteers.[246]
The increasing number of cases in large areas such as Stockholm and Uppsala has resulted in the cancellation or postponement of up to 90% of planned surgeries, including cancer related surgeries.[233]
When it became clear that the civil society would face difficulties managing the emergent crisis, the Swedish Defence Force were called in to assist the civilian society with manpower, equipment, and logistics. The preparations began in February and the first servicemen were deployed in March. By early April the total military deployed in civilian society numbered 400 servicemen, among them a number of officers to support the National Board of Health and Welfare with crisis management and laboratory technicians to support the Public Health Agency of Sweden. Tasks for the military personnel also including collecting and transporting samples. A number of military ambulances were also taken in use within the civilian health system.[226][247]
## Social impact[edit]
### Finance and the economy[edit]
In March, Swedish Minister for Finance Magdalena Andersson said that the government believed that the Swedish economy would be heavily hit by the pandemic, with a 4% downturn in gross domestic product (GDP), similar to the levels seen following the 2008 financial crisis. Andersson also warned that they also expected unemployment to increase up to 9% during the year.[248] In a forecast by the Swedish National Institute of Economic Research published in late April, the Swedish GDP was expected to fall with 7% during 2020 due to the impact of the ongoing pandemic. The European Commission predicted that the Swedish economy would contract -6.1%, a level similar to that of the eurozone (-7.7%). In June, the Swedish central bank Sveriges Riksbank forecasted a fall of 10%. This was mainly due to the Swedish economy being heavily reliant on exports (which attributes to around half of the Swedish GDP) with the shrinking global economy being predicted to decrease international demand of Swedish goods and services. The Economy were also affected by problems with global supply lines, which had forced some of the biggest manufacturing companies in Sweden, including Scania and Volvo Cars, to halt their production in March, as well as a decrease in consumption.[249][116] The National Institute of Economic Research also expected that unemployment in Sweden would rise to 11% during 2020, and the Swedish Pensions Agency calculated a 1.5% drop in pensions for 2021, as Swedish pensions are attached to GDP and income.[249][250] While some predicted a rebound already in the second half of 2020, Magdalena Andersson warned that things "could get worse before they get better."[116] In mid-June, Andersson said it was possible that Sweden had reached the bottom of the downturn, as the government had revised their forecast to a -6% GDP downturn in GDP and an unemployment level of 9.3% (down from -7% and 11% respectively in their previous forecast) although they expected unemployment to further increase in 2021 to 10.3%. However, she cautioned that there was still a big uncertainty regarding the numbers. Similarly, the National Institute of Economic Research also revised their forecast downwards, to a -5.5% fall in GDP and for unemployment to increase to 8.5% during 2020, with a further increase up to 10% in 2021.[251]
In mid-March, the government proposed a 300 billion SEK (€27bn) emergency package to reduce the economic impact of the crisis. The proposal included a system with a reduction in work hours where the government will pay half to salary, aiming to help businesses stay afloat without having to do layoffs. Further, the government would pay the employer's expenses for any sick leaves, which is normally shared between the employer and the state.[252] The normal costs of employer contributions have also been temporarily discontinued for small business owners. This will save small businesses approximately 5000 SEK per employee each month but will result in a loss of tax revenue of 33 billion SEK.[253] The budget emergency package proposed by the government in mid-March to lessen the economic impact of the crisis was supported across the political spectrum, including all parties in opposition in the Riksdag. It was also welcomed by trade unions as well as the private and business sectors. However, some union representatives[who?] stressed that "it won't be enough", a view shared by the biggest employer's organisation, the Confederation of Swedish Enterprise.[254]
On 2 April, the Financial Supervisory Authority ('Finansinspektionen') decided that Swedish banks temporarily can allow exemptions for housing mortgage lenders regarding amortising of loans.[255]
### Transportation[edit]
Air transportation in Sweden is primarily run by public and private companies – principally Scandinavian Airlines System (SAS) and Norwegian Air Shuttle – and has been severely impacted by the pandemic and greatly reduced. Like airlines around the world, Sweden's carriers have reduced the frequency of their flights, reduced their work force and asked the local government for financial assistance. On 15 March, SAS announced that they would temporarily reduce their workforce by 10,000 people, which constitutes about 90% of their workforce.[256] Soon almost all domestic flights were cancelled. Swedish authorities advised against all non-essential travel inside and out of Sweden. SAS Group decided to fly only four domestic departures and four domestic arrivals from Arlanda from 6 April 2020, plus some international flights,[257] while Norwegian cancelled all domestic flights in Sweden.[258] Several airports closed temporarily.[citation needed]
Rail transport in Sweden, which is principally run by the public operator SJ AB, has continued to operate throughout the pandemic, albeit with a slightly reduced schedule so that additional carriages can be added to trains, which in conjunction with fewer tickets being made available for sale, aims to ensure social distancing of those passengers that continue to travel.[259] The decrease in travel had a big impact on the public transport sector due to a loss of revenue in ticket sales, which led to trade association Swedish Public Transport Association (Svensk kollektivtrafik) asking the government for financial aid.[260]
### Politics[edit]
In mid-March, the parliamentary leaders from the parties in the Riksdag agreed on using pairing for the upcoming weeks, to make it possible to decrease the number of members of parliament present during voting sessions, from the usual 349 to 55. This decision was taken both as a measure to lower the risk of spread of the infection (social distancing), and to make sure the daily work in the parliament could proceed even if a big number of MPs would become sick.[261][262] Similar decisions were taken in many of Swedish municipal councils.[263][264] Several regional assemblies also decreased the number of politicians present each session, including Västerbotten County who did it as a measure to decrease long-distance travelling, and Skåne County.[265][266][267]
On 25 March, The Swedish Social Democratic Party together with the Swedish Trade Union Confederation decided to cancel their traditional May Day demonstrations. They will instead hold an event on a digital platform, which will include speeches by the Swedish prime minister and leader of the Social Democrats, Stefan Löfven, as well as union confederation leader Karl-Petter Thorwaldsson.[268] The Left Party also cancelled their nationwide demonstrations, and announced that there would instead be a digital celebration, including a speech by party leader Jonas Sjöstedt.[269] The Almedalen Week, considered to be the biggest and most important forum in Sweden for seminars, debates and political speeches on current social issues, held in Visby every summer,[270] was cancelled as a result of the ban on large gatherings. The decision was taken on 1 April by the organiser after consultation with the major political parties.[271] Prime Minister Stefan Löfvén had already announced that he had cancelled his planned participation in the upcoming event.[272] A similar event in Stockholm, 'Järvaveckan', was also cancelled, and will not be held until 2021.[273] The annual LGBT festival West Pride in Gothenburg was also cancelled as a result of the pandemic. Instead, the organisers proclaimed 25 May to 7 June a 'flag period', encouraging organisations and individuals to hoist the rainbow flag.[274]
### Royal family[edit]
Following the recommendation from the Swedish authorities that those over the age of 70 should self-isolate, the Swedish King and Queen, Carl XVI Gustaf and Queen Silvia, aged 74 and 76, both chose to leave the palace to work from distance in the estate Stenhammar in Sörmland.[275][276]
On 5 April, at the first day of the Holy week, King Carl XVI Gustaf addressed the nation in a televised speech. In his speech, he stressed that all Swedes had an obligation to the country to "act responsibly and selflessly". He also stressed that many who otherwise would travel, spend time with friends and family or go to church would need to make sacrifices during the upcoming Easter holiday. In his speech, he specifically addressed those working or volunteering in the health-care sector, saying "This is a huge task. It requires courage. And it will require endurance. To all of you involved in this vital work, I offer my heartfelt thanks", as well as other people doing vital work in society, to ensure Swedes "can buy food, that public transport continues to operate, and everything else we so easily take for granted – my warmest thanks to you all". He finished saying that all would embrace the message "The journey is long and arduous. But in the end, light triumphs over darkness, and we will be able to feel hope again", ending his speech wishing everyone a happy Easter.[157][277]
On December 17, King Carl Gustaf admitted he felt that Sweden's COVID-19 strategy "[has] failed. We have a large number who have died and that is terrible".[8]
### Education[edit]
On 13 March 2020, the spring Swedish Scholastic Aptitude Test (′Högskoleprovet′) was cancelled affecting approximately 70,000 prospective students who had registered themselves. This was the first time the Swedish Scholastic Aptitude Test has been cancelled since it was established in 1977.[278] On 23 March 2020 the Swedish National Agency for Education ('Skolverket'), cancelled the national tests to give teachers in Sweden more time to prepare for the possibility of distance education.[279]
### Defence[edit]
The Swedish Armed Forces cancelled the international military exercise Aurora 20 which was scheduled to be held between May and June. Austria and Canada had previously announced their cancellation of their planned participation.[280]
### Arts and entertainment[edit]
The ban of public gatherings with more than 500 people, later revised down to 50, led to concerts and other events being cancelled or postponed. Concerts cancelled due to the ban on large crowds included four sold-out concerts with Håkan Hellström at the Nya Ullevi Arena, Gothenburg, scheduled for June and August. As the total number of tickets sold to the concerts numbered 300,000,[281][282] it was believed to be a significant blow to Gothenburg's tourism industry, with a potential loss of 900 million SEK (€84 million) if all concerts scheduled at the arena were to be cancelled.[283] The organiser of the music festival Summerburst had previously announced cancelling their scheduled event at Nya Ullevi.[284] The rock festival Sweden Rock, held every year since 1992 in Blekinge and scheduled for June, was cancelled due to the ongoing pandemic.[285] Theatre and opera were affected, with major venues such as Gothenburg opera house, Malmö Opera, Royal Dramatic Theatre and Royal Swedish Opera all closing their venues and cancel upcoming events.[286][287][288] Cinema were affected as well, and Sweden's largest cinema chain, Filmstaden, decided to close all their cinemas on 17 March until further notice.[49] In April, the Swedish amusement parks Gröna Lund in Stockholm and Liseberg in Gothenburg announced that they were to cancel or reschedule all concerts scheduled before midsummer.[289] The former had already postponed the season opening indefinitely, while the latter were still hoping to open the park as planned in mid-May. As the amusement parks mostly rely on seasonal workers, closures would result in thousands of cancelled employment contracts.[290]
Starting 30 March 2020 the public library in Gävle will start with a book delivery service for people aged 70 or older. The library will also start a take-away service where you can pre-loan books and pick them in a take-away bag.[291]
#### Television[edit]
On 6 March, Swedish National Broadcaster SVT held a crisis meeting to consider broadcasting the live finals of Melodifestivalen 2020 on 7 March without an audience, as a response to the growing outbreak. The Danish equivalent had recently decided to broadcast their version of the finals without an audience. Ultimately, SVT decided to allow the audience to enter the arena, although they advised people who felt sick to stay at home.[292]
The popular TV show Antikrundan, broadcast by public broadcaster SVT, where a number of antiques appraisers visits different locations in Sweden to appraise antiques brought there by local people, cancelled their planned tour for the recording of the 2020 winter season. According to the producers, they were instead working on an 'alternative' show.[293] The sing-along show Lotta på Liseberg, which is televised live by TV4 from the amusement park Liseberg in Gothenburg, announced that the 2020 season would not be cancelled, but would be recorded without an audience due to the ban of gatherings.[294] SVT had previously announced similar plans for their live sing-along show Allsång på Skansen, which is broadcast live from the amusement park Skansen in Stockholm.[295]
### Sports[edit]
In athletics, all 2020 Diamond League events scheduled to be held in May were postponed, which included the meet in Stockholm.[296] The world's largest half marathon in Gothenburg, Göteborgsvarvet, was postponed until later in 2020 and then cancelled completely on 27 March.[297] The annual recreational bicycle race Vätternrundan, scheduled to be held in June, was also cancelled as a result of the pandemic. The organisers made the decision public on 2 April.[298][299] The professional bicycle race Postnord UCI WWT Vårgårda West Sweden, part of the UCI Women's World Tour and scheduled for August, was also cancelled.[300]
On 19 March, the governing body for association football in Sweden formally announced that the premiere of the 2020 season for the first and second division leagues, men's Allsvenskan and Superettan as well as women's Damallsvenskan and Elitettan, will be postponed to late May or early June. The decision will not affect the leagues below the second level.[301] Two days later it was announced that the 2020 edition of the association football award ceremony Fotbollsgalan was cancelled.[302] Many of the professional teams in the highest division warned that the loss of income following the postponement of the season would have a severe impact on their economy.[303] After consultations with the Public Health Agency, the organisation behind youth football tournament Gothia Cup, in Gothenburg, decided to cancel the 2020 event. According to the organisers, the tournament will return in 2021.[304] The youth handball tournament Partille Cup was also cancelled.[305] Professional handball was affected as well, with the last rounds and the finals in the highest men's and women's leagues, Handbollsligan and Svensk handbollselit, being cancelled.[306] Similarly, the Swedish Basketball Federation choose to stop all games until May, effectively stopping the highest divisions SBL and SBL Dam mid-season.[307] In Speedway, the start of Elitserien, the highest league in the Swedish league system, was rescheduled to 2 June. To manage a tighter schedule, the sport's governing body Swedish Motorcycle and Snowmobile Federation also decided to cancel the quarterfinals.[308]
Swedish Minister for Sports Amanda Lind announced on 29 May that some recommendations were to be lifted starting from 14 June, when sports events would be allowed under the condition that they're practised outdoors. And as the ban on crowds and the recommendations against travel were still in place, all games had to be played on virtually empty arenas and athletes would not be allowed to travel longer than two miles to participate in sports events. However, professional athletes would be exempt from the recommendations, and allowed to travel nationwide if needed for competitive events.[309]
Rally Sweden, which was scheduled for 11 February–14 February 2021, was cancelled on 15 December due to rising virus cases in its country.[310]
### Notable Swedes who have died of Covid-19[edit]
Radio presenter Kerstin Behrendtz died on 28 March from COVID-19. She had been diagnosed with the disease on 23 March, and had been ill since about a week before that with cold symptoms. She spent a week in intensive care receiving respiratory care. She was 69 when she died.[311][312]
Photographer Tomas Oneborg died on 29 March from COVID-19. Oneborg had developed cold symptoms in early March and died in his home at the age of 62. He had worked for the Swedish newspaper Svenska Dagbladet for 34 years, and was the first press photographer in place after the terrorist attacks on Drottninggatan in Stockholm in 2017.[313][314]
Television and radio host Adam Alsing died on 15 April 2020 from COVID-19 after having suffered from the disease for several weeks. He was 51, and his death raised awareness in Sweden of the dangers of the disease, since he was comparatively young and had no known risk factors.[315]
## Statistics[edit]
This section needs to be updated. Please update this article to reflect recent events or newly available information. (October 2020)
### Cases[edit]
As of 26 April, 18,670 people had tested positive for COVID-19 in Sweden.[1] As of mid-April, Södermanland County was the region most affected by the pandemic (in cases per capita), followed by Stockholm County and Östergötland County.[316]
#### Total cases[edit]
source: Public Health Agency of Sweden[1]
Total confirmed cases
Note: Data on new cases is compiled by the Public Health Agency of Sweden at 11:30 CEST (UTC+02:00) each day (but from 18 June 2020 not on weekends). Reports of new cases to the Public Health Agency might be delayed by up to several days, especially around weekends, possibly introducing delays in reported number of cases for the last few days.[2] The jump in cases in early June is due to increased primary care testing in several counties.[317]
#### Cases per day[edit]
source: Public Health Agency of Sweden[1]
Cases per day
Note: Data on new cases is compiled by the Public Health Agency of Sweden at 11:30 CEST (UTC+02:00) each day. Reports of new cases to the Public Health Agency might be delayed by up to several days, especially around weekends, possibly introducing delays in reported number of cases for the last few days.[2] The jump in cases in early June is due to increased primary care testing in several counties.[317]
### Intensive care[edit]
Swedish hospitals saw a sharp rise in the number of COVID-19 patients receiving intensive care during March. The number of new patients somewhat stabilised during the first two weeks of April, with between 30 and 45 patients per day, averaging 39. The number of new patients admitted to ICU decreased slightly during the third week of April, averaging 35. The mean age of the patients who underwent intensive care was 59 years old, three out of four (74%) were men, and the average time between diagnosis and admission to an intensive care unit was 10 days. The majority (68%) of those who received intensive care had one or more underlying condition considered as one of the risk groups, with the most prevalent being hypertension (37%), diabetes (25%), chronic pulmonary heart disease (24%), chronic respiratory disease (14%) and chronic cardiovascular disease (11%). The share of patients not belonging to a risk group was significantly higher among younger patients. Among those younger than 60 years, 39% did not have any of those underlying conditions.[318] As of 26 April, 1,315 with a confirmed COVID-19 infection had received intensive care in Sweden.[1]
#### Total hospitalisations[edit]
source: Public Health Agency of Sweden[1]
Total intensive care hospitalisations
Note: Data on new intensive care hospitalisations is compiled by the Public Health Agency of Sweden at 11:30 CEST (UTC+02:00) each day, and is based on reports to the Swedish Intensive Care Registry (SIR). Data includes all intensive care cases with a COVID-19 diagnosis (U07.1), but excludes non-confirmed cases (U07.2).[2]
#### Hospitalisations per day[edit]
source: Public Health Agency of Sweden[1]
intensive care hospitalisations per day
Note: Data on new intensive care hospitalisations is compiled by the Public Health Agency of Sweden at 11:30 CEST (UTC+02:00) each day, and is based on reports to the Swedish Intensive Care Registry (SIR). Data includes all intensive care cases with a COVID-19 diagnosis (U07.1), but excludes non-confirmed cases (U07.2).[2]
### Deaths[edit]
A large majority (93%) of the deaths belonged to at least one risk group, with chronic cardiovascular disease being the most prevalent (53%), followed by diabetes (26%), chronic respiratory disease (18%) and chronic renal failure (16%).[319] More than half of the deaths have been in Stockholm County.[320] As of early May, the mean age among those who had died with confirmed COVID-19 disease was 82,[3] and the majority (54%) of those who had died with the disease were men.[321]
#### Total deaths[edit]
source: Public Health Agency of Sweden[1]
Total deaths with confirmed COVID-19
Note: Data on new deaths is compiled by the Public Health Agency of Sweden at 11:30 CEST (UTC+02:00) each day from the communicable disease surveillance system SmiNet. Reports of new deaths to the Public Health Agency might be delayed by up to several days, especially around weekends, possibly introducing delays in reported number of cases for the last few days. In mid-April, approximately 30% of the cases were reported within 24 hours, 50% within 48 hours, and 90% within one week. Data from the Health Agency includes all deaths where a COVID-19 diagnosis (U07.1) had been confirmed during the past 30 days, including cases where the cause of death was not attributed to COVID-19 (as of data from the National Board of Health and Welfare from 21 April, this number amounted to 4.5% of cases confirmed in a laboratory), but excludes non-confirmed cases (U07.2).
#### Deaths per day[edit]
source: Public Health Agency of Sweden[1]
Deaths with confirmed COVID-19 per day
Note: Data on new deaths is compiled by the Public Health Agency of Sweden at 11:30 CEST (UTC+02:00) each day from the communicable disease surveillance system SmiNet. Reports of new deaths to the Public Health Agency might be delayed by up to several days, especially around weekends, possibly introducing delays in reported number of cases for the last few days. In mid-April, approximately 30% of the cases were reported within 24 hours, 50% within 48 hours, and 90% within one week. Data from the Health Agency includes all deaths where a COVID-19 diagnosis (U07.1) had been confirmed during the past 30 days, including cases where the cause of death was not attributed to COVID-19 (as of data from the National Board of Health and Welfare from 21 April, this number amounted to 4.5% of cases confirmed in a laboratory), but excludes non-confirmed cases (U07.2).
#### Nursing homes[edit]
Out of the people who died of the disease in Sweden, many were residents in nursing homes. In early May, more than 500 nursing homes had reported cases of COVID-19.[322] Among people aged 70 or older, half (50%) of those who died had been living at a nursing home, while another 26% had received home care.[11][323] A 30% excess mortality was observed at Swedish nursing homes during the pandemic.[12] The figure differed between regions, with the figures being highest in Stockholm County where the excess mortality at nursing homes reached approximately 100%, according to research by SVT.[324][325]
source: Socialstyrelsen[326]
COVID-19 deaths of 70+ years old inhabitants by place of death and county (11-Jan-2021)
According to Socialstyrelsen 108 523 individuals were living in Swedish care homes during 2019, and 244 174 individuals received home care.[327] According to Eurostat in 2018 Sweden had 140 979 long-term care beds in nursing and residential care facilities,[328] and on 1 January 2019 Sweden had 2 035 711 inhabitants in age group 65 years or over.[329]
#### Age and gender[edit]
source: National Board of Health and Welfare[321]
COVID-19 deaths by gender and age (11-Jan-2021)
Note: Data is compiled by the National Board of Health and Welfare and is based on death certificates. Data includes both confirmed cases (U07.1) and non-confirmed cases (U07.2)
According to Eurostat median age of Swedish population is 40.5 years[330] and life expectancy at birth is 80.9 years.[331]
#### Excess mortality[edit]
During the pandemic, an excess mortality was observed in Sweden from late March and onwards.[note 4] As the number of deaths with a laboratory-confirmed COVID-19 diagnosis only amounted to 75% of this number, the actual number of deaths related to COVID-19 was believed to be higher.[332] The excess mortality reached a peak during the first half of April, but the mortality rate was still considered to be above normal levels in mid-May. As of 17 May, there had been approximately 4000 excess deaths in Sweden since late March.[333][334] As of 31 May, there had been approximately 4,800 excess deaths in Sweden.[2][4][5] According to SCB preliminary statistics in week 15, the number of deaths registered was 2 564[335] (on average 366 per day). This is 200 deaths more than the second highest number of deaths in a week, which was 2 364 deaths in the first week of 2000.[336] A total of 10,458 people died in April 2020, which almost reaches the level of December 1993 – then 11,057 people died. In total, 97,008 people died in 1993 which was the highest number of deaths in one year since 1918 during the peak of the Spanish flu.[337][338]
source: Statistics Sweden[339] smoothed by applying 7-day moving average
All-cause daily deaths 2015–2020
source: Statistics Sweden[340]
All-cause deaths per standardized month per 100 000 inhabitants 2015–2020
Similar weekly information available at Socialstyrelsen.[341]
### Additional data, charts and tables[edit]
All-cause deaths in Sweden in Oct–May, calculated from SCB, for 1990–2020:[342][343]
Above, each year on the x-axis is the year of Jan–May data, while Oct–Dec data are for the previous year.[clarification needed] Beware that the above is not adjusted for population, which was growing during the shown period.
All-cause deaths in Sweden in Oct–May, calculated from SCB, for 1900–2020:[342][343]
Above, each year on the x-axis is the year of Jan–May data, while Oct–Dec data are for the previous year. Beware that the above is not adjusted for population.
All-cause weekly deaths in Sweden in 2016–2020, from FOHM:[344]
New weekly cases as percentage of tests for Sweden from FOHM:[345][346][347]
Weekly all-cause deaths in Sweden for 2015–2020 for three major counties,[348] calculated from Socialstyrelsen[349] (Smoothened by 4-weeks moving average)
Weekly all-cause deaths per 100 000 inhabitants in Sweden for 2015–2020 for entire Sweden and three major counties, calculated from Socialstyrelsen[350] (Smoothened by 4-weeks moving average)
At an early point, it was reported that a disproportionate number of those that had died by then in Stockholm County were Somali Swedes (6 out of 15)[351]
New COVID-19 cases in Sweden by county (
* v
* t
* e
) Source: FOHM[352][a] County Cases[b] Deaths[b] ICU admissions Analysed samples[354]
Date
Blekinge
Dalarna
Gotland
Gävleborg
Halland
Jämtland
Jönköping
Kalmar
Kronoberg
Norrbotten
Skåne
Stockholm
Södermanland
Uppsala
Värmland
Västerbotten
Västernorrland
Västmanland
Västra Götaland
Örebro
Östergötland
New Total Diff 7d avg New Total Diff 7d avg New Total Diff 7d avg New Total Week
11 11 4
26 37 5
2020-02-04 1 1 1 78 115 6
1 38 153 7
1 27 180 8
2020-02-26 1 1 2 +100% 752 781 9
2020-02-27 1 1 3 +50%
2020-02-28 1 2 2 3 8 11 +267% 1
2020-02-29 1 2 3 14 +27% 2
2020-03-01 14 2
2020-03-02 1 1 3 5 19 +36% 2 4302 5083 10
2020-03-03 1 10 2 13 32 +68% 4
2020-03-04 7 21 1 1 30 62 +94% 8
2020-03-05 22 2 1 25 87 +40% 11
2020-03-06 2 8 36 1 11 1 59 146 +68% 17 1 1 1
2020-03-07 5 21 1 5 1 33 179 +23% 21 1 2 +100% 1
2020-03-08 1 2 29 1 11 2 46 225 +26% 26 1 3 +50% 1
2020-03-09 4 6 1 3 64 1 7 15 101 326 +45% 38 0 3 1 8990 14073 11
2020-03-10 1 1 1 1 34 26 4 3 8 6 13 98 424 +30% 49 2 5 +67% 1
2020-03-11 6 1 2 1 16 3 16 2 7 4 37 32 6 4 2 57 196 620 +46% 70 1 1 1 1 6 +20% 1
2020-03-12 2 3 2 9 5 7 2 2 32 42 3 11 4 1 3 19 3 1 151 771 +24% 86 1 1 6 1
2020-03-13 1 1 9 3 4 3 1 42 31 6 10 3 2 5 19 2 10 152 923 +20% 97 1 2 +100% 1 2 8 +33% 1
2020-03-14 1 3 2 1 25 18 1 4 1 3 5 7 71 994 +7.7% 102 1 3 +50% 1 6 14 +75% 2
2020-03-15 1 2 7 4 1 4 17 4 1 1 18 9 69 1063 +6.9% 105 2 5 +67% 1 5 19 +36% 2
2020-03-16 2 1 1 2 3 34 12 2 2 2 1 7 6 8 83 1146 +7.8% 103 2 7 +40% 1 5 24 +26% 3 10404 24477 12
2020-03-17 1 3 1 4 3 1 1 1 6 35 5 5 1 3 1 6 13 16 13 119 1265 +10% 105 1 8 +14% 1 3 27 +13% 3
2020-03-18 1 2 1 2 2 4 2 1 1 8 58 17 1 3 1 10 3 28 145 1410 +11% 99 6 14 +75% 2 15 42 +56% 5
2020-03-19 2 1 2 1 2 1 1 1 2 66 5 5 2 1 14 9 28 143 1553 +10% 98 7 21 +50% 3 8 50 +19% 6
2020-03-20 5 5 5 3 3 1 5 5 84 4 1 2 5 2 23 5 22 180 1733 +12% 101 9 30 +43% 4 17 67 +34% 7
2020-03-21 4 3 16 4 1 3 5 71 6 2 1 8 12 136 1869 +7.8% 109 8 38 +27% 4 13 80 +19% 8
2020-03-22 5 1 9 1 1 4 3 59 11 5 1 1 4 13 118 1987 +6.3% 116 11 49 +29% 6 27 107 +34% 11
2020-03-23 9 3 4 2 3 5 7 99 2 8 2 2 3 9 6 18 182 2169 +9.2% 128 11 60 +22% 7 37 144 +35% 15 12349 36826 13
2020-03-24 9 5 4 5 1 2 6 5 105 14 11 3 3 2 4 10 11 30 230 2399 +11% 142 21 81 +35% 9 32 176 +22% 19
2020-03-25 3 13 1 7 7 2 7 2 1 5 13 154 37 15 4 2 3 19 8 11 314 2713 +13% 163 22 103 +27% 11 31 207 +18% 21
2020-03-26 8 4 5 9 7 9 6 2 3 7 132 16 12 3 3 5 20 6 29 286 2999 +11% 181 31 134 +30% 14 40 247 +19% 25
2020-03-27 2 15 1 9 3 3 15 5 4 4 9 176 26 20 1 2 2 11 18 6 33 365 3364 +12% 204 32 166 +24% 17 29 276 +12% 26
2020-03-28 6 12 6 8 10 1 2 4 2 147 8 7 3 5 2 3 25 8 41 300 3664 +8.9% 224 35 201 +21% 20 28 304 +10% 28
2020-03-29 4 10 11 2 2 8 1 4 2 3 149 4 11 1 1 9 15 3 40 280 3944 +7.6% 245 38 239 +19% 24 41 345 +13% 30
2020-03-30 9 10 5 2 15 3 1 5 5 172 60 21 1 7 6 23 27 17 27 416 4360 +11% 274 45 284 +19% 28 29 374 +8.4% 29 17783 54609 14
2020-03-31 1 23 1 14 7 1 17 2 5 6 7 209 49 15 8 13 10 29 11 47 475 4835 +11% 305 48 332 +17% 31 34 408 +9.1% 29
2020-04-01 5 19 30 4 13 5 1 5 8 205 49 25 2 5 2 11 29 5 63 486 5321 +10% 326 53 385 +16% 35 48 456 +12% 31
2020-04-02 3 6 1 17 9 4 32 5 7 8 8 216 34 28 12 1 18 47 28 70 554 5875 +10% 360 70 455 +18% 40 47 503 +10% 32
2020-04-03 1 20 1 16 12 2 29 2 2 6 24 245 59 38 1 17 3 27 48 20 28 601 6476 +10% 389 80 535 +18% 46 38 541 +7.6% 33
2020-04-04 4 18 12 2 2 15 1 2 3 12 129 17 11 1 17 6 14 30 3 58 357 6833 +5.5% 396 70 605 +13% 51 36 577 +6.7% 34
2020-04-05 1 7 7 3 12 3 2 2 6 172 27 9 1 8 2 7 30 41 340 7173 +5.0% 404 85 690 +14% 56 45 622 +7.8% 35
2020-04-06 16 12 10 4 10 6 3 10 6 131 18 31 2 4 4 18 53 12 39 389 7562 +5.4% 400 90 780 +13% 62 42 664 +6.8% 36 19880 74489 15
2020-04-07 1 28 16 13 6 23 4 14 17 24 243 42 37 7 13 10 46 64 73 57 738 8300 +9.8% 433 84 864 +11% 67 45 709 +6.8% 38
2020-04-08 2 28 1 17 9 8 18 2 7 12 15 271 33 29 1 12 5 23 68 37 56 654 8954 +7.9% 454 115 979 +13% 74 48 757 +6.8% 38
2020-04-09 1 30 1 18 12 8 21 1 5 5 11 240 38 29 4 12 4 25 116 10 54 645 9599 +7.2% 466 86 1065 +8.8% 76 36 793 +4.8% 36
2020-04-10 1 17 18 4 8 19 1 4 6 23 148 41 4 3 15 8 27 69 7 31 454 10053 +4.7% 447 90 1155 +8.5% 78 36 829 +4.5% 36
2020-04-11 9 10 2 2 5 3 10 2 6 200 22 15 2 2 33 32 13 27 395 10448 +3.9% 452 103 1258 +8.9% 82 45 874 +5.4% 37
2020-04-12 1 31 17 3 6 9 2 4 2 14 182 14 13 4 5 18 42 75 22 464 10912 +4.4% 467 97 1355 +7.7% 83 36 910 +4.1% 36
2020-04-13 12 11 3 6 5 6 3 17 9 200 20 13 3 5 6 18 48 21 31 437 11349 +4.0% 473 85 1440 +6.3% 83 43 953 +4.7% 36 20233 94722 16
2020-04-14 1 12 11 6 14 11 5 6 4 12 179 16 39 2 5 5 12 63 53 23 479 11828 +4.2% 441 91 1531 +6.3% 83 41 994 +4.3% 36
2020-04-15 28 2 17 6 15 28 2 12 3 19 215 42 32 3 14 5 30 70 30 31 604 12432 +5.1% 435 115 1646 +7.5% 83 32 1026 +3.2% 34
2020-04-16 25 1 21 15 12 23 4 10 13 17 221 47 37 7 3 3 31 84 30 19 623 13055 +5.0% 432 111 1757 +6.7% 87 33 1059 +3.2% 33
2020-04-17 26 24 9 19 36 5 12 15 21 221 64 44 3 19 5 27 77 32 29 688 13743 +5.3% 461 82 1839 +4.7% 86 39 1098 +3.7% 34
2020-04-18 27 29 7 9 35 2 21 1 17 180 8 18 3 3 2 18 48 52 52 532 14275 +3.9% 478 86 1925 +4.7% 83 29 1127 +2.6% 32
2020-04-19 8 8 6 6 15 4 11 2 5 192 13 17 4 7 8 29 31 6 16 388 14663 +2.7% 469 88 2013 +4.6% 82 33 1160 +2.9% 31
2020-04-20 1 10 1 4 10 1 8 6 9 8 9 211 13 32 7 4 2 28 50 23 24 461 15124 +3.1% 472 84 2097 +4.2% 82 28 1188 +2.4% 29 24560 119282 17
2020-04-21 4 35 22 17 13 49 11 14 3 7 163 53 32 7 5 12 38 123 64 35 707 15831 +4.7% 500 62 2159 +3.0% 79 34 1222 +2.9% 29
2020-04-22 6 33 3 22 19 17 31 11 13 5 20 288 50 32 5 9 4 19 79 27 29 722 16553 +4.6% 515 77 2236 +3.6% 74 49 1271 +4.0% 31
2020-04-23 2 41 2 13 18 8 46 11 25 15 22 291 26 41 3 12 17 26 72 38 29 758 17311 +4.6% 532 86 2322 +3.8% 71 27 1298 +2.1% 30
2020-04-24 7 29 1 19 17 10 24 1 2 8 38 227 53 55 4 12 16 36 147 41 33 780 18091 +4.5% 544 89 2411 +3.8% 72 46 1344 +3.5% 31
2020-04-25 45 2 23 2 13 19 1 21 12 138 8 12 5 6 5 94 37 30 473 18564 +2.6% 536 73 2484 +3.0% 70 28 1372 +2.1% 31
2020-04-26 1 5 3 6 5 1 5 2 4 2 23 110 8 8 2 11 11 24 46 17 6 300 18864 +1.6% 525 75 2559 +3.0% 68 26 1398 +1.9% 30
2020-04-27 8 4 11 18 6 23 7 7 10 34 213 10 35 8 4 11 24 99 18 13 563 19427 +3.0% 538 73 2632 +2.9% 67 28 1426 +2.0% 30 28802 148084 18
2020-04-28 3 35 4 16 10 11 18 5 21 1 33 240 57 52 17 3 4 21 83 74 34 742 20169 +3.8% 542 82 2714 +3.1% 69 32 1458 +2.2% 30
2020-04-29 6 52 7 21 10 18 43 11 14 7 37 247 34 22 14 18 11 24 149 34 19 798 20967 +4.0% 552 84 2798 +3.1% 70 25 1483 +1.7% 27
2020-04-30 14 3 21 8 20 28 7 12 9 30 215 23 43 9 5 19 14 94 44 17 635 21602 +3.0% 536 78 2876 +2.8% 69 33 1516 +2.2% 27
2020-05-01 2 1 21 2 7 23 7 15 7 12 141 55 13 13 2 9 20 123 34 25 532 22134 +2.5% 505 78 2954 +2.7% 68 15 1531 1.0% 23
2020-05-02 1 1 2 14 8 13 18 2 12 1 28 81 7 12 6 3 7 13 33 20 17 299 22433 +1.4% 484 73 3027 +2.5% 68 28 1559 +1.8% 23
2020-05-03 3 1 8 2 6 7 1 10 1 6 127 1 11 3 6 4 42 14 8 261 22694 +1.2% 479 75 3102 +2.5% 68 27 1586 +1.7% 24
2020-05-04 64 6 23 10 2 16 14 4 4 38 148 2 21 6 1 4 8 75 17 13 476 23170 +2.1% 468 84 3186 +2.7% 69 25 1611 +1.6% 23 29129 177213 19
2020-05-05 3 28 14 21 22 22 5 34 7 20 169 39 52 17 3 4 17 110 49 21 657 23827 +2.8% 457 72 3258 +2.3% 68 20 1631 +1.2% 22
2020-05-06 1 22 23 23 9 24 3 22 8 41 206 34 37 14 8 17 19 177 35 22 745 24572 +3.1% 451 73 3331 +2.2% 67 26 1657 +1.6% 22
2020-05-07 2 19 2 36 15 18 28 8 34 5 13 266 20 42 9 8 25 17 164 37 16 784 25356 +3.2% 469 80 3411 +2.4% 67 28 1685 +1.7% 21
2020-05-08 4 16 1 23 15 10 27 5 26 4 52 222 23 43 8 5 10 21 129 35 21 700 26056 +2.8% 490 60 3471 +1.8% 65 26 1711 +1.5% 23
2020-05-09 1 11 1 51 5 19 33 4 21 17 115 7 41 7 9 7 109 29 22 509 26565 +2.0% 517 69 3540 +2.0% 64 14 1725 +0.8% 21
2020-05-10 4 6 4 6 4 6 2 19 78 6 12 3 1 10 1 86 16 15 279 26844 +1.1% 519 74 3614 +2.1% 64 17 1742 1.0% 20
2020-05-11 3 12 10 14 11 6 6 11 21 210 1 19 3 1 4 32 54 27 10 455 27299 +1.7% 516 64 3678 +1.8% 62 15 1757 +0.9% 18 33003 210216 20
2020-05-12 4 18 2 27 13 13 29 6 28 3 34 234 33 30 15 10 19 10 150 46 30 754 28053 +2.8% 528 61 3739 +1.7% 60 16 1773 +0.9% 18
2020-05-13 3 21 30 7 15 34 1 31 12 30 236 14 27 6 7 15 27 133 30 19 698 28751 +2.5% 522 50 3789 +1.3% 57 19 1792 +1.1% 17
2020-05-14 2 15 40 13 30 14 5 18 6 39 148 11 37 14 14 14 31 151 24 31 657 29408 +2.3% 507 46 3835 +1.2% 53 15 1807 +0.8% 15
2020-05-15 6 10 30 22 15 35 7 23 2 42 184 19 37 8 14 25 14 154 26 15 688 30096 +2.3% 505 58 3893 +1.5% 53 21 1828 +1.2% 15
2020-05-16 2 1 1 24 8 7 21 3 16 3 21 64 5 24 7 3 18 97 20 13 358 30454 +1.2% 486 49 3942 +1.3% 50 18 1846 +1.0% 15
2020-05-17 1 17 7 4 8 24 2 7 1 11 59 6 3 3 2 89 3 12 259 30713 +0.9% 484 53 3995 +1.3% 48 20 1866 +1.1% 16
2020-05-18 9 15 19 15 5 7 8 3 23 150 6 31 8 6 7 36 40 11 31 430 31143 +1.4% 481 61 4056 +1.5% 47 23 1889 +1.2% 17 28986 239202 21
2020-05-19 6 2 1 34 14 9 41 2 27 2 63 177 20 35 15 14 38 22 105 22 17 666 31809 +2.1% 470 41 4097 +1.0% 45 13 1902 +0.7% 16
2020-05-20 23 31 2 25 42 18 32 3 20 7 44 174 24 53 16 4 27 21 162 54 26 808 32617 +2.5% 483 53 4150 +1.3% 45 14 1916 +0.7% 16
2020-05-21 17 25 10 22 28 1 18 6 23 120 6 17 20 9 16 25 168 38 41 610 33227 +1.9% 477 54 4204 +1.3% 46 13 1929 +0.7% 15
2020-05-22 10 5 23 8 8 12 11 13 3 44 144 15 27 2 7 21 11 146 10 12 532 33759 +1.6% 458 56 4260 +1.3% 46 15 1944 +0.8% 15
2020-05-23 2 13 1 22 6 23 27 18 1 27 78 2 19 19 6 24 84 8 23 403 34162 +1.2% 464 56 4316 +1.3% 47 16 1960 +0.8% 14
2020-05-24 3 7 1 8 2 2 17 11 9 59 1 13 3 3 10 27 29 5 210 34372 +0.6% 457 44 4360 +1.0% 46 17 1977 +0.9% 14
2020-05-25 3 3 18 8 2 24 16 8 9 29 160 21 30 2 3 28 107 11 9 491 34863 +1.4% 465 42 4402 +1.0% 43 28 2005 +1.4% 15 36466 275668 22
2020-05-26 12 18 22 21 15 35 17 12 7 51 197 18 48 23 2 41 35 119 28 25 746 35609 +2.1% 475 28 4430 +0.6% 42 14 2019 +0.7% 15
2020-05-27 19 16 30 34 18 45 14 32 10 37 206 23 35 27 14 33 40 106 31 30 800 36409 +2.2% 474 39 4469 +0.9% 40 15 2034 +0.7%
2020-05-28 11 16 2 27 27 17 38 18 20 6 49 278 19 39 26 3 23 22 102 31 774 37183 +2.1% 495 40 4509 +0.9% 38 19 2053 +0.9% 16
2020-05-29 10 10 1 30 17 11 28 4 11 21 46 210 7 41 30 6 29 19 223 18 1 773 37956 +2.1% 525 40 4549 +0.9% 36 13 2066 +0.6% 15
2020-05-30 6 15 8 26 11 24 36 1 12 3 34 73 2 38 16 8 2 117 432 38388 +1.1% 528 39 4588 +0.9% 34 19 2085 +0.9% 16
2020-05-31 7 5 12 7 7 18 3 10 8 67 14 2 2 4 99 265 38653 +0.7% 535 45 4633 +1.0% 34 14 2099 +0.7% 15
2020-06-01 3 7 9 22 2 11 10 6 21 27 160 16 31 6 30 53 91 51 92 648 39301 +1.7% 555 40 4673 +0.9% 34 20 2119 +1.0% 14 47080 322748 23
2020-06-02 18 23 5 46 31 11 35 5 18 9 71 153 20 62 21 8 16 35 264 18 32 901 40202 +2.3% 574 37 4710 +0.8% 35 15 2134 +0.7% 14
2020-06-03 18 14 1 31 11 11 41 9 12 15 39 234 15 50 14 5 30 33 409 24 30 1046 41248 +2.6% 605 26 4736 +0.6% 33 18 2152 +0.8% 15
2020-06-04 10 13 1 44 22 15 26 14 11 19 42 207 26 58 21 5 27 33 400 8 37 1039 42287 +2.5% 638 45 4781 +1.0% 34 16 2168 +0.7% 14
2020-06-05 10 20 1 43 23 13 42 14 20 16 37 227 17 37 12 5 24 19 478 46 42 1146 43433 +2.7% 685 38 4819 +0.8% 34 20 2188 +0.9% 15
2020-06-06 5 16 2 37 19 22 40 1 3 7 23 177 1 56 24 8 7 268 19 45 780 44213 +1.8% 728 31 4850 +0.6% 33 20 2208 +0.9% 15
2020-06-07 18 6 21 8 7 23 3 11 12 47 3 14 11 4 20 230 15 9 462 44675 +1.0% 753 33 4883 +0.7% 31 14 2222 +0.6% 15
2020-06-08 10 9 15 17 1 13 13 5 30 33 243 29 15 15 4 24 67 123 7 4 677 45352 +1.5% 756 38 4921 +0.8% 31 16 2238 +0.7% 15 60296 383044 24
2020-06-09 9 17 5 12 28 17 63 11 15 11 45 239 3 59 21 6 20 33 248 26 48 936 46288 +2.1% 761 33 4954 +0.7% 31 16 2254 +0.7% 15
2020-06-10 1 17 4 66 26 15 155 11 11 12 63 263 6 44 26 8 29 62 539 27 52 1437 47725 +3.1% 810 40 4994 +0.8% 32 9 2263 +0.4% 14
2020-06-11 26 9 5 52 29 11 131 10 13 12 55 207 8 40 20 5 13 69 491 36 51 1293 49018 +2.7% 841 36 5030 +0.7% 31 12 2275 +0.5% 13
2020-06-12 14 13 6 56 24 19 137 14 12 41 59 186 23 46 15 8 28 51 496 12 69 1329 50347 +2.7% 864 30 5060 +0.6% 30 12 2287 +0.5% 12
2020-06-13 12 6 1 44 24 5 121 9 15 32 40 165 53 38 14 6 3 385 14 45 1032 51379 +2.0% 896 33 5093 +0.7% 30 14 2301 +0.6% 12
2020-06-14 10 4 35 4 6 16 3 2 41 8 75 19 5 4 3 1 161 11 10 418 51797 +0.8% 890 27 5120 +0.5% 30 12 2313 +0.5% 11
2020-06-15 3 3 5 23 9 20 11 11 1 48 38 116 6 13 10 1 37 80 222 8 20 685 52482 +1.3% 891 31 5151 +0.6% 29 13 2326 +0.6% 11 61842 444886 25
2020-06-16 7 7 38 47 21 143 9 12 56 93 214 3 56 22 8 29 35 306 54 49 1209 53691 +2.3% 925 28 5179 +0.5% 28 9 2335 +0.4% 10
2020-06-17 13 6 5 41 25 23 206 14 4 66 98 361 25 62 12 6 28 71 310 19 62 1457 55148 +2.7% 928 33 5212 +0.6% 27 13 2348 +0.6% 11
2020-06-18 6 16 2 65 23 12 169 22 8 65 88 380 62 84 12 15 54 34 283 21 73 1494 56642 +2.7% 953 29 5241 +0.6% 26 13 2361 +0.6% 11
2020-06-19 5 20 1 30 9 10 224 11 5 19 65 371 5 33 16 10 1 48 245 10 71 1209 57851 +2.1% 938 29 5270 +0.6% 26 8 2369 +0.3% 10
2020-06-20 4 5 3 31 6 1 7 2 3 2 13 198 60 7 11 2 323 1 19 698 58549 +1.2% 896 29 5299 +0.6% 26 6 2375 +0.3% 9
2020-06-21 4 4 12 2 1 7 2 1 17 92 9 5 3 139 5 18 321 58870 +0.6% 884 21 5320 +0.4% 25 12 2387 +0.5% 9
2020-06-22 11 4 9 10 5 9 2 51 23 219 57 21 6 5 41 38 262 8 19 800 59670 +1.4% 899 21 5341 +0.5% 24 15 2402 +0.6% 10 75151 520037 26
2020-06-23 8 29 8 52 86 12 170 15 6 103 73 217 25 100 17 10 14 24 261 19 61 1310 60980 +2.2% 911 25 5366 +0.5% 23 7 2409 +0.3% 9
2020-06-24 5 30 3 136 17 8 229 7 2 55 86 284 41 92 27 15 47 81 447 8 78 1698 62678 +2.8% 941 22 5388 +0.4% 22 6 2415 +0.3% 8
2020-06-25 6 29 1 86 24 9 159 13 6 63 52 228 8 71 17 12 17 40 354 27 57 1279 63957 +2.0% 914 24 5412 +0.5% 21 10 2425 +0.4% 8
2020-06-26 3 34 10 84 70 12 110 19 5 67 54 225 40 52 14 11 29 28 284 16 37 1204 65161 +1.9% 914 11 5423 +0.2% 19 5 2430 +0.2% 8
2020-06-27 3 31 1 2 32 5 100 7 2 2 17 248 50 11 4 9 176 6 49 755 65916 +1.2% 921 14 5437 +0.2% 17 5 2435 +0.2% 8
2020-06-28 2 3 5 1 3 10 1 4 5 191 1 15 1 4 151 4 14 415 66331 +0.6% 933 22 5459 +0.4% 17 8 2443 +0.3% 7
2020-06-29 3 2 27 54 8 7 6 53 28 239 23 6 13 49 43 137 3 26 727 67058 +1.1% 924 18 5477 +0.3% 17 4 2447 +0.2% 6 79811 599848 27
2020-06-30 3 33 2 7 52 4 90 20 3 4 25 170 17 68 7 8 17 21 200 14 38 803 67861 +1.2% 860 21 5498 +0.4% 17 5 2452 +0.2% 5
2020-07-01 2 32 56 3 2 91 22 2 7 17 172 2 44 4 8 30 29 105 8 48 684 68545 +1.0% 733 17 5515 +0.3% 16 6 2458 +0.2% 5
2020-07-02 3 46 7 36 10 48 26 4 14 27 169 21 22 14 7 7 24 163 19 20 687 69232 +1.0% 659 15 5530 +0.3% 15 10 2468 +0.4% 5
2020-07-03 8 25 69 17 11 53 9 1 30 27 176 8 26 6 5 36 34 135 6 12 694 69926 +1.0% 596 8 5538 +0.1% 14 3 2471 +0.1% 5
2020-07-04 14 2 13 1 48 2 2 96 18 1 3 17 105 16 26 364 70290 +0.5% 547 15 5553 +0.3% 15 1 2472 +0.0% 5
2020-07-05 25 7 49 2 2 2 1 108 3 6 27 69 14 315 70605 +0.5% 534 9 5562 +0.2% 13 5 2477 +0.2% 4
2020-07-06 2 2 3 19 1 2 8 2 38 28 53 9 2 4 26 25 17 7 3 251 70856 +0.4% 475 16 5578 +0.3% 13 2 2479 +0.1% 4 81801 681649 28
2020-07-07 3 9 13 28 2 49 5 10 9 46 12 11 3 6 6 11 38 7 10 278 71134 +0.4% 409 12 5590 +0.2% 12 2 2481 +0.1% 4
2020-07-08 2 22 4 51 6 2 42 9 5 14 27 123 18 16 7 1 26 19 115 11 13 533 71667 +0.8% 390 11 5601 +0.2% 11 1 2482 +0.0% 3
2020-07-09 3 13 3 25 4 8 26 4 3 13 27 85 13 7 2 5 14 63 6 10 334 72001 +0.5% 346 15 5616 +0.3% 11 2 2484 +0.1% 2
2020-07-10 6 1 33 14 6 31 5 4 22 29 73 10 15 4 3 27 15 49 11 11 369 72370 +0.5% 306 14 5630 +0.3% 12 2 2486 +0.1% 2
2020-07-11 1 5 1 86 3 2 24 2 4 4 3 73 5 9 3 9 63 3 8 308 72678 +0.4% 299 10 5640 +0.2% 11 2 2488 +0.1% 2
2020-07-12 2 6 1 3 1 1 1 28 1 19 16 20 2 5 106 72784 +0.2% 272 9 5649 +0.2% 11 3 2491 +0.1% 2
2020-07-13 2 12 1 21 4 4 3 1 1 3 31 31 1 2 2 1 13 23 7 7 170 72954 +0.2% 262 14 5663 +0.3% 11 3 2494 +0.1% 2 69393 751042 29
2020-07-14 2 11 1 8 5 3 22 1 5 13 15 88 23 19 1 5 21 15 44 2 8 312 73266 +0.4% 267 8 5671 +0.1% 10 2 2496 +0.1% 2
2020-07-15 1 1 20 8 2 31 3 4 8 35 64 13 1 1 9 8 58 9 11 287 73553 +0.4% 236 6 5677 +0.1% 10 0 2496 +0.0% 2
2020-07-16 2 9 7 10 5 7 9 5 1 11 30 86 4 16 2 4 6 7 35 5 7 268 73821 +0.4% 228 7 5684 +0.1% 9 4 2500 +0.2% 2
2020-07-17 5 4 10 12 3 16 2 8 10 36 78 3 8 2 8 12 3 56 2 6 284 74105 +0.4% 217 7 5691 +0.1% 8 3 2503 +0.1% 2
2020-07-18 1 9 5 15 15 1 7 5 30 11 2 5 4 69 3 9 191 74296 +0.3% 202 11 5702 +0.2% 8 0 2503 +0.0% 2
2020-07-19 5 1 6 1 2 9 1 1 2 18 3 1 1 17 4 35 3 110 74406 +0.2% 203 8 5710 +0.1% 8 2 2505 +0.1% 2
2020-07-20 1 1 8 4 2 5 8 35 23 1 14 7 14 2 6 131 74537 +0.2% 198 7 5717 +0.1% 7 4 2509 +0.2% 2 59143 810185 30
2020-07-21 11 4 13 7 3 19 6 2 7 26 78 5 1 2 2 4 30 2 4 226 74763 +0.3% 187 7 5724 +0.1% 7 5 2514 +0.2% 2
2020-07-22 1 4 7 11 5 18 2 6 5 34 69 14 7 3 1 9 10 86 3 2 297 75060 +0.4% 188 6 5730 +0.1% 7 1 2515 +0.0% 2
2020-07-23 4 2 23 4 2 6 8 6 19 56 4 1 1 14 4 58 7 1 220 75280 +0.3% 182 5 5735 +0.1% 6 1 2516 +0.0% 2
2020-07-24 1 8 4 9 5 6 9 2 2 8 24 60 4 2 2 3 15 5 84 4 5 262 75542 +0.4% 180 3 5738 +0.1% 6 1 2517 +0.0% 2
2020-07-25 1 2 2 7 1 3 6 2 1 5 2 21 2 6 1 5 5 56 4 6 138 75680 +0.2% 173 1 5739 +0.0% 5 0 2517 +0.0% 2
2020-07-26 5 1 1 1 21 2 1 8 2 42 75722 +0.1% 165 2 5741 +0.0% 4 1 2518 +0.0% 2
2020-07-27 1 1 1 7 1 1 1 28 9 1 1 3 10 3 3 71 75793 +0.1% 157 6 5747 +0.1% 4 0 2518 +0.0% 1 52959 863144 31
2020-07-28 4 3 4 6 5 15 1 4 10 8 78 3 6 4 11 5 101 10 5 283 76076 +0.4% 164 6 5753 +0.1% 4 1 2519 +0.0% 1
2020-07-29 1 3 8 5 15 1 11 5 8 6 44 46 1 10 3 3 12 111 8 301 76377 +0.4% 165 2 5755 +0.0% 3 2 2521 +0.1% 1
2020-07-30 2 4 11 3 16 4 14 4 4 4 32 49 2 8 3 2 13 4 108 7 8 302 76679 +0.4% 175 0 5755 +0.0% 3 0 2521 +0.0% 1
2020-07-31 2 11 1 4 14 10 4 8 3 38 43 13 2 1 8 9 66 17 4 258 76937 +0.3% 174 3 5758 +0.1% 3 1 2522 +0.0% 1
2020-08-01 1 4 5 1 9 1 2 1 64 2 5 11 2 6 177 3 9 303 77240 +0.4% 195 3 5761 +0.1% 3 3 2525 +0.1% 1
2020-08-02 1 1 1 3 2 1 4 6 2 1 10 6 38 77278 +0.0% 195 2 5763 +0.0% 3 4 2529 +0.2% 1
2020-08-03 1 14 12 2 2 2 4 40 22 5 2 2 7 19 6 25 165 77443 +0.2% 206 4 5767 +0.1% 3 1 2530 +0.0% 2 53721 916865 32
2020-08-04 9 8 5 4 7 1 21 7 7 10 92 2 14 3 7 14 108 8 6 333 77776 +0.4% 213 2 5769 +0.0% 2 1 2531 +0.0% 2
2020-08-05 2 15 12 2 30 2 16 3 5 2 54 59 8 15 11 4 163 7 15 425 78201 +0.6% 228 3 5772 +0.1% 2 3 2534 +0.1% 2
2020-08-06 7 9 2 9 19 4 12 1 20 3 26 67 3 5 12 1 7 7 138 15 11 378 78579 +0.5% 238 4 5776 +0.1% 3 2 2536 +0.1% 2
2020-08-07 9 4 5 1 25 15 4 17 8 46 49 3 19 13 4 4 5 134 7 8 380 78959 +0.5% 253 3 5779 +0.1% 3 2 2538 +0.1% 2
2020-08-08 4 6 19 2 9 2 10 7 51 4 1 13 9 2 102 8 11 260 79219 +0.3% 247 1 5780 +0.0% 2 5 2543 +0.2% 2
2020-08-09 1 6 10 2 6 2 1 1 24 2 6 12 73 79292 +0.1% 252 4 5784 +0.1% 3 2 2545 +0.1% 2
2020-08-10 7 4 2 21 4 2 11 4 46 37 4 2 1 10 29 3 9 196 79488 +0.3% 256 2 5786 +0.0% 2 1 2546 +0.0% 2 56627 973492 33
2020-08-11 11 5 3 14 33 1 19 1 21 5 34 102 6 6 3 11 2 8 108 14 10 417 79905 +0.5% 266 4 5790 +0.1% 3 3 2549 +0.1% 2
2020-08-12 10 6 3 10 11 2 13 9 24 4 68 81 4 13 13 5 6 6 140 10 6 444 80349 +0.6% 269 3 5793 +0.1% 3 2 2551 +0.1% 2
2020-08-13 9 10 4 8 12 11 7 10 3 46 55 1 12 11 10 8 4 128 5 9 363 80712 +0.5% 267 6 5799 +0.1% 3 4 2555 +0.2% 2
2020-08-14 4 8 4 10 12 6 9 3 16 5 40 81 1 7 5 13 8 86 8 18 344 81056 +0.4% 262 2 5801 +0.0% 3 0 2555 +0.0% 2
2020-08-15 4 2 6 3 1 3 15 2 5 3 11 55 4 9 11 3 4 5 57 4 19 226 81282 +0.3% 258 1 5802 +0.0% 3 2 2557 +0.1% 2
2020-08-16 1 1 1 2 1 2 3 3 5 1 32 1 10 63 81345 +0.1% 257 0 5802 +0.0% 2 1 2558 +0.0% 2
2020-08-17 1 5 1 5 12 2 3 3 1 75 35 1 4 1 1 3 6 8 7 174 81519 +0.2% 254 3 5805 +0.1% 2 1 2559 +0.0% 2 65546 1039038 34
2020-08-18 2 8 2 3 39 18 12 7 4 46 71 4 10 2 8 1 6 58 5 8 314 81833 +0.4% 241 5 5810 +0.1% 3 1 2560 +0.0% 1
2020-08-19 11 7 1 4 4 11 2 10 1 53 73 1 15 5 14 14 105 12 8 351 82184 +0.4% 229 1 5811 +0.0% 2 2 2562 +0.1% 1
2020-08-20 3 5 1 8 10 2 14 8 14 55 65 2 5 6 2 2 4 112 4 11 333 82517 +0.4% 226 2 5813 +0.0% 2 1 2563 +0.0% 1
2020-08-21 3 9 2 5 29 8 9 3 1 63 59 7 5 4 7 6 67 3 8 298 82815 +0.4% 220 5 5818 +0.1% 2 0 2563 +0.0% 1
2020-08-22 2 4 8 2 7 5 7 5 49 1 22 8 2 3 27 8 160 82975 +0.2% 212 1 5819 +0.0% 2 1 2564 +0.0% 1
2020-08-23 4 1 1 3 2 2 2 2 1 1 22 16 57 83032 +0.1% 211 3 5822 +0.1% 3 1 2565 +0.0% 1
2020-08-24 5 21 2 2 90 30 1 2 13 3 5 174 83206 +0.2% 211 1 5823 +0.0% 2 3 2568 +0.1% 1 85060 1124098 35
2020-08-25 2 10 3 20 5 2 15 1 48 49 10 1 5 1 6 32 5 8 223 83429 +0.3% 200 1 5824 +0.0% 2 1 2569 +0.0% 1
2020-08-26 4 8 16 16 2 5 8 7 53 47 3 6 7 2 5 5 40 2 8 244 83673 +0.3% 186 2 5826 +0.0% 2 1 2570 +0.0% 1
2020-08-27 1 11 3 1 10 1 5 1 4 6 49 35 1 6 1 1 1 5 54 3 3 202 83875 +0.2% 170 1 5827 +0.0% 2 1 2571 +0.0% 1
2020-08-28 6 7 4 1 1 11 3 13 1 40 39 4 7 3 2 2 31 4 179 84054 +0.2% 155 1 5828 +0.0% 1 0 2571 +0.0% 1
2020-08-29 2 11 1 4 7 6 8 4 4 26 2 6 2 2 1 45 131 84185 +0.1% 151 1 5829 +0.0% 1 0 2571 +0.0% 1
2020-08-30 4 3 4 1 3 14 1 18 48 84233 +0.1% 150 3 5832 +0.1% 1 1 2572 +0.0% 1
2020-08-31 6 1 28 1 1 1 1 66 20 2 1 4 11 19 162 84395 +0.12% 149 2 5834 +0.0% 1 0 2572 +0.0% 1 126219 1250317 36
2020-09-01 1 13 2 19 1 9 7 2 8 31 7 5 1 6 27 30 3 172 84567 +0.2% 142 3 5837 +0.1% 2 1 2573 +0.0% 1
2020-09-02 13 9 6 14 2 8 2 41 38 5 3 1 53 14 4 213 84780 +0.3% 138 3 5840 +0.1% 2 2 2575 +0.1% 1
2020-09-03 10 7 27 15 13 2 8 34 59 1 11 1 4 3 9 55 16 11 286 85066 +0.3% 149 2 5842 +0.0% 2 3 2578 +0.1% 1
2020-09-04 1 6 1 2 8 23 2 6 1 43 53 4 4 1 2 7 75 14 9 262 85328 +0.3% 159 0 5842 +0.0% 2 0 2578 +0.0% 1
2020-09-05 5 3 3 5 17 2 8 6 42 1 5 8 1 1 5 39 9 11 171 85499 +0.2% 164 0 5842 +0.0% 2 1 2579 +0.0% 1
2020-09-06 1 3 2 1 1 11 5 35 3 5 67 85566 +0.1% 167 2 5844 +0.0% 2 0 2579 +0.0% 1
2020-09-07 4 9 16 1 3 1 5 62 11 5 1 3 1 13 34 9 7 185 85751 +0.2% 170 1 5845 +0.0% 1 0 2579 +0.0% 1 37
2020-09-08 3 11 7 16 2 20 2 13 3 17 39 6 14 9 5 1 11 33 11 16 239 85990 +0.3% 178 1 5846 +0.0% 1 1 2580 +0.0% 1
2020-09-09 1 16 1 8 18 5 37 1 14 48 44 2 12 3 1 4 5 66 15 13 314 86304 +0.34% 191 0 5846 +0.0% 1 0 2580 +0.0% 1
2020-09-10 15 2 3 9 13 1 11 46 50 3 5 2 3 7 66 9 12 257 86561 +0.3% 187 1 5847 +0.% 1 0 2580 +0.0% 0
2020-09-11 9 14 1 30 2 10 3 44 65 3 22 2 6 2 3 57 8 11 292 86853 +0.3% 191 0 5847 +0.0% 1 1 2581 +0.0% 0
2020-09-12 16 7 1 28 5 78 2 16 1 8 2 20 15 7 206 87059 +0.2% 195 0 5847 +0.0% 1 4 2585 +0.2% 1
2020-09-13 8 8 5 1 1 2 1 2 18 1 1 2 5 8 29 9 5 106 87165 +0.1% 200 0 5847 +0.0% 0 1 2586 +0.0% 1
2020-09-14 1 13 1 3 13 3 84 15 3 3 1 1 19 16 2 2 180 87345 +0.2% 199 0 5847
(+4)
+0.0% 0 0 2586 +0.0% 1 38
County Total cases[b] Total deaths[b][c] Total ICU admissions Total analysed samples
Total cases[b] 624 2365 324 3285 2356 1222 5224 911 1548 1685 5366 23739 2460 3919 1241 905 1881 2854 19514 2860 3954 87,345
(863 per 100k pop)
5,851
(57.8 per 100k pop)
2586
(25.6 per 100K pop)
1,250,317
(12,354 per 100k pop)
Cases per 100k 391 821 543 1143 706 934 1437 371 768 674 389 999 827 1021 439 333 767 1035 1131 938 849
Total deaths[b] 17 174 6 167 83 64 181 64 116 88 276 2400 254 243 73 31 136 183 860 172 277
Deaths per 100k 11 60 10 58 25 49 50 26 58 35 20 101 85 63 26 11 55 66 50 56 60 Currently in ICU-care for COVID-19: 17[355]
Total ICU-care 9 67 7 72 40 20 96 31 25 60 121 931 133 158 33 34 51 55 456 84 108
Notes
1. ^ Data is compiled by Folkhälsomyndigheten at 11:30 (UTC+02:00) each day. Reports of new cases and deaths to Folkhälsomyndigheten might be delayed by up to several days, especially around weekends, possibly introducing delays in reported number of cases for the last few days.[353]
2. ^ a b c d e f Reported, confirmed cases. Actual case numbers may be higher.
3. ^ Cases in brackets have unknown or not yet reported date of death.
Distribution
Confirmed cases Deaths ICU admissions Category
Amount Percent Amount Percent Rate Amount Percent Rate
37595 43% 3198 55% 8.5% 1884 73% 5.0% Male Sex
49743 57% 2653 45% 5.3% 702 27% 1.4% Female
7 0.0% 0 0% 0% 0 0% 0% Unspecified
656 0.8% 1 0.0% 0.2% 8 0.3% 1.2% 0-9 Age
4225 4.8% 0 0% 0% 18 0.7% 0.4% 10-19
14279 16% 10 0.2% 0.1% 95 3.7% 0.7% 20-29
13473 15% 17 0.3% 0.1% 119 4.6% 0.9% 30-39
14253 16% 45 0.8% 0.3% 288 11% 2.0% 40-49
15285 17% 163 2.8% 1.1% 659 25% 4.3% 50-59
8734 10.0% 405 6.9% 4.6% 772 30% 8.8% 60-69
6083 7.0% 1261 22% 21% 513 20% 8.4% 70-79
6717 7.7% 2427 41% 36% 110 4.3% 1.6% 80-89
3620 4.1% 1522 26% 42% 4 0.2% 0.1% 90+
20 0.0% 0 0% 0% 0 0% 0% Unspecified
## Timeline of responses[edit]
### Economic policy[edit]
Local governments, such as the municipal government in Gävle, have applied measures to businesses delaying the payment of invoices until 1 September 2020 at the earliest and deferring rent payments.[356]
## See also[edit]
* COVID-19 pandemic
* COVID-19 pandemic by country and territory
* COVID-19 pandemic in Europe
* COVID-19 pandemic in the European Union
* Healthcare in Sweden
## Notes[edit]
1. ^ a b Data on new deaths is compiled by the Public Health Agency of Sweden at 11:30 CEST (UTC+02:00) each day from the communicable disease surveillance system SmiNet. Reports of new deaths to the Public Health Agency might be delayed by up to several days, especially around weekends, possibly introducing delays in reported number of cases for the last few days. In mid-April, approximately 30% of the cases were reported within 24 hours, 50% within 48 hours, and 90% within one week. Data from the Health Agency includes all deaths where a COVID-19 diagnosis had been confirmed (U07.1) during the past 30 days, including cases where the cause of death was not attributed to COVID-19 (as of data from the National Board of Health and Welfare from 21 April, this number amounted to 4.5% of cases confirmed in a laboratory), but excludes non-confirmed cases (U07.2). On 12 May 87% of the deaths attributed to COVID-19 were not confirmed in a laboratory. As this only includes cases confirmed in a laboratory, the actual number is believed to be higher due to the number of laboratory-confirmed cases only amounting to 83% (as of 31 May) of an excess mortality observed in Sweden since late March, according to a statistical analysis by the Public Health Agency based on data from the Swedish Tax Agency and the European mortality monitoring activity (EuroMOMO). By late May, there had been approximately 4,800 excess deaths in Sweden.[2][3][4][5]
2. ^ A Swedish government agency is an independent body without the power to pass laws. Instead, they give out recommendations on how someone can or should act to meet a binding regulation within the agency's area of activity (in this case The Swedish Communicable Diseases Act). Although there is not a legal framework for a governmental agency to impose sanctions on someone for going against its recommendations, they are not optional as they work as guidelines on how to act to follow a regulation (in this case an obligation to help halting the spread of an infectious disease).
3. ^ The index is based on 140 questions, grouped into 85 subindicators, 34 indicators and 6 categories, with countries being ranked overall and for each category; Prevention: Prevention of the emergence or release of pathogens (Sweden ranked 2nd), Detection and Reporting: Early detection and reporting for epidemics of potential international concern (7th), Rapid Response: Rapid response to and mitigation of the spread of an epidemic (14th), Health System: Sufficient and robust health system to treat the sick and protect health workers (20th), Compliance with International Norms: Commitments to improving national capacity, financing plans to address gaps, and adhering to global norms (11th), and Risk Environment: Overall risk environment and country vulnerability to biological threats (6th)[29]
4. ^ Excess mortality according to a published statistical analysis by the Public Health Agency based on data from the Swedish Tax Agency and the European mortality monitoring activity (EuroMOMO)
## References[edit]
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## External links[edit]
Wikimedia Commons has media related to COVID-19 pandemic in Sweden.
* Emergency Information from Swedish Authorities: Official information on the novel corona Virus from the Swedish Civil Contingencies Agency – Myndigheten för samhällsskydd och beredskap.
* Information om Coronavirus covid-19 from The Public Health Agency of Sweden – Folkhälsomyndigheten (In Swedish).
* FAQ about COVID-19 on The Public Health Agency of Sweden – Folkhälsomyndigheten.
* Covid-19 – coronavirus from Vårdguiden 1177 (In Swedish).
#invoke:Navbox with collapsible groups
* COVID-19 portal
* Sweden portal
* Medicine portal
* Viruses portal
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
| COVID-19 pandemic in Sweden | None | 4,599 | wikipedia | https://en.wikipedia.org/wiki/COVID-19_pandemic_in_Sweden | 2021-01-18T18:37:56 | {"wikidata": ["Q84081576"]} |
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