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Benzodiazepine overdose
Other namesBenzodiazepine poisoning
US yearly overdose deaths involving benzodiazepines.[1]
SpecialtyToxicology, emergency medicine
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
Benzodiazepine overdose describes the ingestion of one of the drugs in the benzodiazepine class in quantities greater than are recommended or generally practiced. The most common symptoms of overdose include central nervous system (CNS) depression, impaired balance, ataxia, and slurred speech. Severe symptoms include coma and respiratory depression. Supportive care is the mainstay of treatment of benzodiazepine overdose. There is an antidote, flumazenil, but its use is controversial.[2]
Deaths from single-drug benzodiazepine overdoses occur infrequently,[3] particularly after the point of hospital admission.[4] However, combinations of high doses of benzodiazepines with alcohol, barbiturates, opioids or tricyclic antidepressants are particularly dangerous, and may lead to severe complications such as coma or death. In 2013, benzodiazepines were involved in 31% of the estimated 22,767 deaths from prescription drug overdose in the United States.[5] The US Food and Drug Administration (FDA) has subsequently issued a black box warning regarding concurrent use of benzodiazepines and opioids.[6] Benzodiazepines are one of the most highly prescribed classes of drugs,[7] and they are commonly used in self-poisoning.[8][9] Over 10 years in the United Kingdom, 1512 fatal poisonings have been attributed to benzodiazepines with or without alcohol.[10] Temazepam was shown to be more toxic than the majority of benzodiazepines. An Australian (1995) study found oxazepam less toxic and less sedative, and temazepam more toxic and more sedative, than most benzodiazepines in overdose.[11]
## Contents
* 1 Signs and symptoms
* 2 Toxicity
* 2.1 Comparability
* 3 Pathophysiology
* 4 Diagnosis
* 5 Treatment
* 5.1 Supportive measures
* 5.2 Flumazenil
* 6 Epidemiology
* 7 References
* 8 External links
## Signs and symptoms[edit]
Following an acute overdose of a benzodiazepine the onset of symptoms is typically rapid with most developing symptoms within 4 hours.[12] Patients initially present with mild to moderate impairment of central nervous system function. Initial signs and symptoms include intoxication, somnolence, diplopia, impaired balance, impaired motor function, anterograde amnesia, ataxia, and slurred speech. Most patients with pure benzodiazepine overdose will usually only exhibit these mild CNS symptoms.[12][13] Paradoxical reactions such as anxiety, delirium, combativeness, hallucinations, and aggression can also occur following benzodiazepine overdose.[14] Gastrointestinal symptoms such as nausea and vomiting have also been occasionally reported.[13]
Cases of severe overdose have been reported and symptoms displayed might include prolonged deep coma or deep cyclic coma, apnea, respiratory depression, hypoxemia, hypothermia, hypotension, bradycardia, cardiac arrest, and pulmonary aspiration, with the possibility of death.[4][12][15][16][17][18] Severe consequences are rare following overdose of benzodiazepines alone but the severity of overdose is increased significantly if benzodiazepines are taken in overdose in combination with other medications.[18] Significant toxicity may result following recreation drug misuse in conjunction with other CNS depressants such as opioids or alcohol.[19][20][21][22] The duration of symptoms following overdose is usually between 12 and 36 hours in the majority of cases.[13] The majority of drug-related deaths involve misuse of heroin or other opioids in combination with benzodiazepines or other CNS depressant drugs. In most cases of fatal overdose it is likely that lack of opioid tolerance combined with the depressant effects of benzodiazepines is the cause of death.[23]
The symptoms of an overdose such as sleepiness, agitation and ataxia occur much more frequently and severely in children. Hypotonia may also occur in severe cases.[24]
## Toxicity[edit]
The top line represents the number of benzodiazepine deaths that also involved opioids in the US. The bottom line represents benzodiazepine deaths that did not involve opioids.[1]
Benzodiazepines have a wide therapeutic index and taken alone in overdose rarely cause severe complications or fatalities.[13][25] More often than not, a patient who inadvertently takes more than the prescribed dose will simply feel drowsy and fall asleep for a few hours. Benzodiazepines taken in overdose in combination with alcohol, barbiturates, opioids, tricyclic antidepressants, or sedating antipsychotics, anticonvulsants, or antihistamines are particularly dangerous.[26] Additionally, emergency department visits involving benzodiazepines compared to other sedative-hypnotics have much higher odds of hospitalization, patient transfer, or death.[27] In the case of alcohol and barbiturates, not only do they have an additive effect but they also increase the binding affinity of benzodiazepines to the benzodiazepine binding site, which results in a very significant potentiation of the CNS and respiratory depressant effects.[28][29][30][31][32] In addition, the elderly and those with chronic illnesses are much more vulnerable to lethal overdose with benzodiazepines. Fatal overdoses can occur at relatively low doses in these individuals.[13][33][34][35]
### Comparability[edit]
The various benzodiazepines differ in their toxicity since they produce varying levels of sedation in overdose. A 1993 British study of deaths during the 1980s found flurazepam and temazepam more frequently involved in drug-related deaths, causing more deaths per million prescriptions than other benzodiazepines. Flurazepam, now rarely prescribed in the United Kingdom and Australia, had the highest fatal toxicity index of any benzodiazepine (15.0), followed by temazepam (11.9), versus benzodiazepines overall (5.9), taken with or without alcohol.[36] An Australian (1995) study found oxazepam less toxic and less sedative, and temazepam more toxic and more sedative, than most benzodiazepines in overdose.[11] An Australian study (2004) of overdose admissions between 1987 and 2002 found alprazolam, which happens to be the most prescribed benzodiazepine in the U.S. by a large margin, to be more toxic than diazepam and other benzodiazepines. They also cited a review of the Annual Reports of the American Association of Poison Control Centers National Data Collection System, which showed alprazolam was involved in 34 fatal deliberate self-poisonings over 10 years (1992–2001), compared with 30 fatal deliberate self-poisonings involving diazepam.[37] In a New Zealand study (2003) of 200 deaths, Zopiclone, a benzodiazepine receptor agonist, had similar overdose potential as benzodiazepines.[38]
## Pathophysiology[edit]
Benzodiazepines bind to a specific benzodiazepine receptor, thereby enhancing the effect of the neurotransmitter gamma-aminobutyric acid (GABA) and causing CNS depression. In overdose situations this pharmacological effect is extended leading to a more severe CNS depression and potentially coma [13] or cardiac arrest.[15] Benzodiazepine-overdose-related coma may be characterised by an alpha pattern with the central somatosensory conduction time (CCT) after median nerve stimulation being prolonged and the N20 to be dispersed. Brain-stem auditory evoked potentials demonstrate delayed interpeak latencies (IPLs) I-III, III-V and I-V. Toxic overdoses of benzodiazepines therefore cause prolonged CCT and IPLs.[39][40][41]
## Diagnosis[edit]
The diagnosis of benzodiazepine overdose may be difficult, but is usually made based on the clinical presentation of the patient along with a history of overdose.[13][42] Obtaining a laboratory test for benzodiazepine blood concentrations can be useful in patients presenting with CNS depression or coma of unknown origin. Techniques available to measure blood concentrations include thin layer chromatography, gas liquid chromatography with or without a mass spectrometer, and radioimmunoassay.[13] Blood benzodiazepine concentrations, however, do not appear to be related to any toxicological effect or predictive of clinical outcome. Blood concentrations are, therefore, used mainly to confirm the diagnosis rather than being useful for the clinical management of the patient.[13][43]
## Treatment[edit]
Flumazenil is a benzodiazepine antagonist that can reverse the effects of benzodiazepines, although its use following benzodiazepine overdose is controversial.
Medical observation and supportive care are the mainstay of treatment of benzodiazepine overdose.[16] Although benzodiazepines are absorbed by activated charcoal,[44] gastric decontamination with activated charcoal is not beneficial in pure benzodiazepine overdose as the risk of adverse effects would outweigh any potential benefit from the procedure. It is recommended only if benzodiazepines have been taken in combination with other drugs that may benefit from decontamination.[45] Gastric lavage (stomach pumping) or whole bowel irrigation are also not recommended.[45] Enhancing elimination of the drug with hemodialysis, hemoperfusion, or forced diuresis is unlikely to be beneficial as these procedures have little effect on the clearance of benzodiazepines due to their large volume of distribution and lipid solubility.[45]
### Supportive measures[edit]
Supportive measures include observation of vital signs, especially Glasgow Coma Scale and airway patency. IV access with fluid administration and maintenance of the airway with intubation and artificial ventilation may be required if respiratory depression or pulmonary aspiration occurs.[45] Supportive measures should be put in place prior to administration of any benzodiazepine antagonist in order to protect the patient from both the withdrawal effects and possible complications arising from the benzodiazepine. A determination of possible deliberate overdose should be considered with appropriate scrutiny, and precautions taken to prevent any attempt by the patient to commit further bodily harm.[11][46] Hypotension is corrected with fluid replacement, although catecholamines such as norepinephrine or dopamine may be required to increase blood pressure.[13] Bradycardia is treated with atropine or an infusion of norepinephrine to increase coronary blood flow and heart rate.[13]
### Flumazenil[edit]
Flumazenil (Romazicon) is a competitive benzodiazepine receptor antagonist that can be used as an antidote for benzodiazepine overdose. Its use, however, is controversial as it has numerous contraindications.[2][47] It is contraindicated in patients who are on long-term benzodiazepines, those who have ingested a substance that lowers the seizure threshold, or in patients who have tachycardia, widened QRS complex on ECG, anticholinergic signs, or a history of seizures.[48] Due to these contraindications and the possibility of it causing severe adverse effects including seizures, adverse cardiac effects, and death,[49][50] in the majority of cases there is no indication for the use of flumazenil in the management of benzodiazepine overdose as the risks in general outweigh any potential benefit of administration.[2][45] It also has no role in the management of unknown overdoses.[8][47] In addition, if full airway protection has been achieved, a good outcome is expected, and therefore flumazenil administration is unlikely to be required.[51]
Flumazenil is very effective at reversing the CNS depression associated with benzodiazepines but is less effective at reversing respiratory depression.[47] One study found that only 10% of the patient population presenting with a benzodiazepine overdose are suitable candidates for flumazenil.[47] In this select population who are naive to and overdose solely on a benzodiazepine, it can be considered.[52] Due to its short half life, the duration of action of flumazenil is usually less than 1 hour, and multiple doses may be needed.[47] When flumazenil is indicated the risks can be reduced or avoided by slow dose titration of flumazenil.[46] Due to risks and its many contraindications, flumazenil should be administered only after discussion with a medical toxicologist.[52][53]
## Epidemiology[edit]
In a Swedish (2003) study benzodiazepines were implicated in 39% of suicides by drug poisoning in the elderly 1992–1996. Nitrazepam and flunitrazepam accounted for 90% of benzodiazepine implicated suicides. In cases where benzodiazepines contributed to death, but were not the sole cause, drowning, typically in the bath, was a common method used. Benzodiazepines were the predominant drug class in suicides in this review of Swedish death certificates. In 72% of the cases, benzodiazepines were the only drug consumed. Thus, many of deaths associated with benzodiazepine overdoses may not be a direct result of the toxic effects but either due to being combined with other drugs or used as a tool to complete suicide using a different method, e.g. drowning.[54]
In a Swedish retrospective study of deaths of 1987, in 159 of 1587 autopsy cases benzodiazepines were found. In 44 of these cases the cause of death was natural causes or unclear. The remaining 115 deaths were due to accidents (N = 16), suicide (N = 60), drug addiction (N = 29) or alcoholism (N = 10). In a comparison of suicides and natural deaths, the concentrations both of flunitrazepam and nitrazepam (sleeping medications) were significantly higher among the suicides. In four cases benzodiazepines were the sole cause of death.[55]
In Australia, a study of 16 deaths associated with toxic concentrations of benzodiazepines during the period of 5 years leading up to July 1994 found preexisting natural disease as a feature of 11 cases; 14 cases were suicides. Cases where other drugs, including ethanol, had contributed to the death were excluded. In the remaining five cases, death was caused solely by benzodiazepines. Nitrazepam and temazepam were the most prevalent drugs detected, followed by oxazepam and flunitrazepam.[56] A review of self poisonings of 12 months 1976 - 1977 in Auckland, New Zealand, found benzodiazepines implicated in 40% of the cases.[57] A 1993 British study found flurazepam and temazepam to have the highest number of deaths per million prescriptions among medications commonly prescribed in the 1980s. Flurazepam, now rarely prescribed in the United Kingdom and Australia, had the highest fatal toxicity index of any benzodiazepine (15.0) followed by Temazepam (11.9), versus 5.9 for benzodiazepines overall, taken with or without alcohol.[36]
Etizolam overdose deaths are rising - for instance, the National Records of Scotland report on drug-related deaths, implicated 548 deaths from 'street' Etizolam in 2018, almost double the number from 2017 (299) and only six years from the first recorded death (in 2012). The 548 deaths were 45% of all drug-related deaths in Scotland in 2018.[58]
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SUD
* Alcoholism (alcohol use disorder (AUD))
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hypnotic
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* SUD
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* Benzodiazepine dependence
* barbiturate: SID
* Barbiturate overdose
* SUD
* Barbiturate dependence
Stimulants
* SID
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* amphetamine: SUD
* Amphetamine dependence
Volatile
solvent
* SID
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* v
* t
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1 including venoms, toxins, foodborne illnesses.
* Category
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*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
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| Benzodiazepine overdose | c0572933 | 800 | wikipedia | https://en.wikipedia.org/wiki/Benzodiazepine_overdose | 2021-01-18T18:47:08 | {"icd-9": ["969.4"], "icd-10": ["T42.4", "F13"], "wikidata": ["Q4890788"]} |
Acute schizophrenia-like psychotic disorder in which hallucinations and dream-like state are the main clinical features
Oneirophrenia (from the Greek words "ὄνειρος" (oneiros, "dream") and "φρήν" (phrēn, "mind")) is a hallucinatory, dream-like state caused by several conditions such as prolonged sleep deprivation, sensory deprivation, or drugs (such as ibogaine). Oneirophrenia is often confused with an acute case of schizophrenia due to the onset of hallucinations.[1] The severity of this condition can range from derealization to complete hallucinations and delusions. Oneirophrenia was described for the first time in the 1950s but was studied more in the 1960s. Although it is still cited in diagnostic manuals of psychiatry, such as DSM-IV and in the International Statistical Classification of Diseases and Related Health Problems (ICD), oneirophrenia as a separate entity is out of fashion nowadays.[citation needed]
## Contents
* 1 Symptoms
* 2 Causes
* 3 Diagnosis
* 3.1 Differential diagnosis
* 4 Treatments
* 5 History
* 6 References
## Symptoms[edit]
Oneirophrenia is often described as a dream-like state that can lead to hallucinations and confusion. Feelings and emotions are often disturbed but information from the senses is left intact separating it from true schizophrenia.[2]
## Causes[edit]
Oneirophrenia can result from long periods of sleep deprivation or extreme sensory deprivation. The hallucinations in oneirophrenia are increased or derive under decreased sensory input. Psychoanalysts, such as Claudio Naranjo, in the sixties have described the value of ibogaine-induced oneirophrenia for inducing and manipulating free fantasy and dream-like associations in patients under treatment. It can also be caused by drugs such as ibogaine, which has previously been used to induce the dream like state in some forms of treatment.[3]
## Diagnosis[edit]
### Differential diagnosis[edit]
Oneirophrenia and schizophrenia are often confused although there are distinct differences between the conditions. Oneirophrenia has some of the characteristics of schizophrenia, such as a confusional state and clouding of consciousness, but without presenting the dissociative symptoms which are typical of that disorder. Oneiophrenia often begins with the inability to focus on things while schizophrenia frequently starts with a traumatic event. Persons affected by oneirophrenia have a feeling of dream-like derealization which, in its extreme form, may progress to delusions and hallucinations. Therefore, it is considered a schizophrenia-like acute form of psychosis which remits in about 60% of cases within a period of two years. It is estimated that 50% or more of schizophrenic patients present oneirophrenia at least once.[3]
## Treatments[edit]
Oneirophrenic patients are resistant to insulin and when injected with glucose, these patients take 30 to 50% longer to return to normal glycemia. The meaning of this finding is not known, but it has been hypothesized that it may be due to an insulin antagonist present in the blood during psychosis. However, there is currently no known treatment for oneirophrenia.[1]
## History[edit]
Oneirophrenia was studied in the 1950s by the neurologist and psychiatrist Ladislas J. Meduna (1896–1964), also known as the discoverer of one of the forms of shock therapy, using the drug metrazol. Although oneirophrenia was recognized as a specific condition in the 1950s, it was not studied in depth until the 1960s. During its beginning stages oneirophrenia was studied very closely with schizophrenia as an acute form due to the relationship between their symptoms. It wasn't until greater research that oneirophrenia became its own mental disease.[4]
## References[edit]
1. ^ a b Meduna, L. J. (1950). Oneirophrenia; the confused state. Champaign, IL: University of Illinois Press.
2. ^ Meduna, L. J. (1950). Oneirophrenia; the confused state. Champaign, IL: University of Illinois Press.
3. ^ a b Naranjo, C. (1969). "Psychotherapeutic possibilities of new fantasy-enhancing drugs". Clinical Toxicology. 2 (2): 209. doi:10.3109/15563656908990930.
4. ^ Turner, W. J. (1964). "Schizophrenia and oneirophrenia: A clinical and biological note". Transactions of the New York Academy of Sciences. 26: 361–368. doi:10.1111/j.2164-0947.1964.tb01257.x. PMID 14170547.
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*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Oneirophrenia | c0553814 | 801 | wikipedia | https://en.wikipedia.org/wiki/Oneirophrenia | 2021-01-18T18:34:28 | {"umls": ["C0553814"], "icd-9": ["295.4"], "icd-10": ["F23.2"], "wikidata": ["Q1419434"]} |
A number sign (#) is used with this entry because of evidence that pseudo-TORCH syndrome-2 (PTORCH2) is caused by homozygous or compound heterozygous mutation in the USP18 gene (607057) on chromosome 22q11.
Description
Pseudo-TORCH syndrome-2 is an autosomal recessive multisystem disorder characterized by antenatal onset of intracranial hemorrhage, calcification, brain malformations, liver dysfunction, and often thrombocytopenia. Affected individuals tend to have respiratory insufficiency and seizures, and die in infancy. The phenotype resembles the sequelae of intrauterine infection, but there is no evidence of an infectious agent. The disorder results from inappropriate activation of the interferon (IFN) immunologic pathway (summary by Meuwissen et al., 2016).
For a discussion of genetic heterogeneity of PTORCH, see PTORCH1 (251290).
Clinical Features
Knoblauch et al. (2003) described 2 brothers, born to healthy nonconsanguineous parents of German origin, who showed features resembling congenital intrauterine infection-like syndrome. Both showed extensive intra- and extracranial calcifications, thrombocytopenia, a septum pellucidum cyst, 1-sided paresis of the diaphragm, metaphyseal changes on x-ray scans resembling those produced by intrauterine infection, and hepatosplenomegaly. They developed seizures within the first days of life and died from severe cerebral hemorrhage. Postmortem examination of 1 infant showed lack of gyration of the temporal lobes, diminished gyration at the parietal lobes, and pachygyria. One patient also had cerebellar hypoplasia. There was no indication of a metabolic disorder, especially in calcium metabolism. The authors thought that this disorder could be distinguished from Aicardi-Goutieres syndrome (see, e.g., AGS1, 225750). Meuwissen et al. (2016) reported follow-up of the patients reported by Knoblauch et al. (2003), noting that both sibs had thrombocytopenia and that one had dyserythropoiesis on bone marrow aspiration.
Meuwissen et al. (2016) reported 3 sibs, born of consanguineous Turkish parents, with PTORCH2. One patient presented antenatally with microcephaly, cortical destruction, and calcifications in the subcortical regions, basal ganglia, and periventricular regions. This pregnancy was terminated at 23 weeks' gestation. The other 2 sibs were born alive, but died at ages 7 and 17 days. They had severe intracerebral hemorrhages, enlarged lateral ventricles, respiratory failure requiring ventilation, and bradycardia, and they developed liver dysfunction, ascites, and lactic acidosis; one had severe thrombocytopenia with petechiae. Postmortem examination of 1 patient showed microencephaly, polymicrogyria reflecting defective neuronal migration, heterotopic neural cell clusters, necrosis, rarefaction, dystrophic calcifications, and induction of the brain innate immune system with astrocytes, microglia, and activation of the type 1 IFN pathway.
Inheritance
The transmission pattern of PTORCH2 in the families reported by Meuwissen et al. (2016) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 3 sibs, born of consanguineous Turkish parents, with PTORCH2, Meuwissen et al. (2016) identified a homozygous truncating mutation in the USP18 gene (Q218X; 607057.0001). The mutation, which was found by a combination of linkage analysis, whole-exome sequencing, and capillary DNA sequencing, segregated with the disorder in the family. Two German sibs with the disorder, previously reported by Knoblauch et al. (2003), were found to be compound heterozygous for the Q218X mutation and a cryptic 3-prime deletion of the USP18 gene (607057.0002). Haplotype analysis of the region containing the Q218X mutation suggested a common ancestor between the 2 families. Cells from patients in both families showed complete absence of the USP18 protein. Patient fibroblasts showed enhanced induction of IFN-stimulated transcripts after stimulation with alpha-IFN (IFNA1; 147660) compared to controls, and transduction of patient cells with wildtype USP18 rescued these effects at the mRNA and protein level. The findings indicated that the disorder results from an aberrant response to type I IFN, rather than an increase in expression of IFN itself. Accordingly, patient cells had normal IFNB1 (147640) mRNA and protein levels. The results also indicated that USP18-mediated regulation of the IFN response is crucial for normal development of the central nervous system.
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Small head circumference CARDIOVASCULAR Heart \- Patent ductus arteriosus \- Bradycardia RESPIRATORY \- Respiratory insufficiency ABDOMEN External Features \- Ascites Liver \- Hepatomegaly \- Liver dysfunction SKELETAL \- Extracranial calcifications (in some patients) SKIN, NAILS, & HAIR Skin \- Petechiae MUSCLE, SOFT TISSUES \- Hypotonia \- Ascites NEUROLOGIC Central Nervous System \- Seizures (in some patients) \- Lethargy \- Intracerebral hemorrhage \- Intracerebral calcifications \- Dystrophic calcification \- Enlarged ventricles \- Cortical necrosis \- Cortical destruction \- Cerebellar hypoplasia \- Defective neuronal migration \- Polymicrogyria \- Heterotopia \- Increased astrocytes \- Microglia HEMATOLOGY \- Thrombocytopenia IMMUNOLOGY \- Induction of the immune system \- Increased interferon-1 stimulated gene transcription \- Abnormal activation of the immune system without evidence of infection LABORATORY ABNORMALITIES \- Abnormal liver enzymes (in some patients) \- Lactic acidosis (n some patients) MISCELLANEOUS \- Onset in utero \- Death in early infancy \- Two unrelated families have been reported (last curated March 2017) MOLECULAR BASIS \- Caused by mutation in the ubiquitin-specific protease 18 gene (USP18, 607057.0001 ) ▲ Close
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*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
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| PSEUDO-TORCH SYNDROME 2 | c4479376 | 802 | omim | https://www.omim.org/entry/617397 | 2019-09-22T15:45:53 | {"omim": ["617397"], "orphanet": ["481665"], "synonyms": []} |
A rare disorder of the anterior segment of the eye characterized by chronic recurrent epithelial keratitis manifesting with groupings of small, slightly elevated, ovoid, grayish-white intraepithelial opacities, usually located in the central cornea. Patients present with photophobia, tearing, foreign body sensation, and blurred vision. The condition is typically bilateral, takes a relapsing-remitting course, and is mostly self-limiting after a few years.
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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
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| Thygeson superficial punctate keratitis | c4551636 | 803 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=519406 | 2021-01-23T17:34:42 | {"synonyms": ["Thygeson superficial punctate keratopathy"]} |
Charcot-Marie-Tooth disease encompasses a group of disorders called hereditary sensory and motor neuropathies that damage the peripheral nerves. Peripheral nerves connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound. Damage to the peripheral nerves that worsens over time can result in alteration or loss of sensation and wasting (atrophy) of muscles in the feet, legs, and hands.
Charcot-Marie-Tooth disease usually becomes apparent in adolescence or early adulthood, but onset may occur anytime from early childhood through late adulthood. Symptoms of Charcot-Marie-Tooth disease vary in severity and age of onset even among members of the same family. Some people never realize they have the disorder because their symptoms are so mild, but most have a moderate amount of physical disability. A small percentage of people experience severe weakness or other problems which, in very rare cases, can be life-threatening. In most affected individuals, however, Charcot-Marie-Tooth disease does not affect life expectancy.
Typically, the earliest symptoms of Charcot-Marie-Tooth disease result from muscle atrophy in the feet. Affected individuals may have foot abnormalities such as high arches (pes cavus), flat feet (pes planus), or curled toes (hammer toes). They often have difficulty flexing the foot or walking on the heel of the foot. These difficulties may cause a higher than normal step (steppage gait) and increase the risk of ankle injuries and tripping. As the disease worsens, muscles in the lower legs usually weaken, but leg and foot problems rarely require the use of a wheelchair.
Affected individuals may also develop weakness in the hands, causing difficulty with daily activities such as writing, fastening buttons, and turning doorknobs. People with Charcot-Marie-Tooth disease typically experience a decreased sensitivity to touch, heat, and cold in the feet and lower legs, but occasionally feel aching or burning sensations. In rare cases, affected individuals have loss of vision or gradual hearing loss that sometimes leads to deafness.
There are several types of Charcot-Marie-Tooth disease, which are differentiated by their effects on nerve cells and patterns of inheritance. Type 1 (CMT1) is characterized by abnormalities in myelin, the fatty substance that covers nerve cells, protecting them and helping to transmit nerve impulses. These abnormalities slow the transmission of nerve impulses and can affect the health of the nerve fiber. Type 2 (CMT2) is characterized by abnormalities in the fiber, or axon, that extends from a nerve cell body to muscles or to sense organs. These abnormalities reduce the strength of the nerve impulse. In forms of Charcot-Marie-Tooth disease classified as intermediate type, the nerve impulses are both slowed and reduced in strength, probably due to abnormalities in both myelin and axons. Type 4 (CMT4) is distinguished from the other types by its pattern of inheritance; it can affect either the axons or the myelin. Type X Charcot-Marie-Tooth disease (CMTX) is caused by mutations in genes on the X chromosome, one of the two sex chromosomes. Within the various types of Charcot-Marie-Tooth disease, subtypes (such as CMT1A, CMT1B, CMT2A, CMT4A, and CMTX1) indicate different genetic causes.
Sometimes other, historical names are used to refer to particular forms of Charcot-Marie-Tooth disease. For example, Roussy-Levy syndrome is a form of CMT11 with the additional feature of rhythmic shaking (tremors). Dejerine-Sottas syndrome is a term sometimes used to describe a severe, early childhood form of Charcot-Marie-Tooth disease; it is also sometimes called type 3 (CMT3). Depending on the specific gene that is altered, this severe, early-onset form of the disorder may also be classified as CMT1 or CMT4. CMTX5 is also known as Rosenberg-Chutorian syndrome.
## Frequency
Charcot-Marie-Tooth disease is the most common inherited disorder that involves the peripheral nerves, affecting an estimated 150,000 people in the United States. It occurs in populations worldwide with a prevalence of about 1 in 3,300 individuals.
## Causes
Charcot-Marie-Tooth disease can be caused by mutations in many different genes. These genes provide instructions for making proteins that are involved in the function of peripheral nerves in the feet, legs, and hands. The gene mutations that cause Charcot-Marie-Tooth disease affect the function of the proteins in ways that are not fully understood; however, they likely impair axons, which transmit nerve impulses, or affect the specialized cells that produce myelin. In most cases, longer nerves that transmit impulses to the appendages of the body are more likely to be affected. As a result, peripheral nerve cells slowly lose the ability to stimulate the muscles in the feet, legs, and eventually the hands, and to transmit sensory signals from these appendages to the brain. Different mutations within a single gene may cause signs and symptoms of differing severities or lead to different types of Charcot-Marie-Tooth disease.
Between 70 and 80 percent of individuals with CMT1 have mutations affecting the PMP22 gene. Most of these cases occur when there is an extra copy of the gene resulting from a small duplication of genetic material on chromosome 17. Another 10 to 12 percent of individuals with CMT1 have mutations in the MPZ gene. MPZ gene mutations are also occasionally identified in people with other forms of the disorder. The most common cause of CMT2 is mutations in the MFN2 gene, which accounts for about 20 percent of cases. Approximately 90 percent of people with CMTX have GJB1 gene mutations. Mutations in dozens of other genes have been identified in smaller numbers of people with these and the other types. The list of genes associated with Charcot-Marie-Tooth disease continues to grow as researchers study this disorder.
### Learn more about the genes and chromosome associated with Charcot-Marie-Tooth disease
* ATP1A1
* ATP7A
* BSCL2
* DCTN1
* DNM2
* DNMT1
* DYNC1H1
* GARS1
* GJB1
* HINT1
* HSPB1
* HSPB8
* IGHMBP2
* KIF1B
* LMNA
* MFN2
* MPV17
* MPZ
* MT-ATP6
* NAGLU
* PMP22
* PRPS1
* SETX
* SPG11
* SPTLC1
* SURF1
* TRPV4
* VCP
* chromosome 17
Additional Information from NCBI Gene:
* AARS1
* ABHD12
* AIFM1
* ARHGEF10
* BAG3
* CNTNAP1
* COA7
* COX6A1
* DCTN2
* DHTKD1
* DNAJB2
* DRP2
* EGR2
* FGD4
* FIG4
* GDAP1
* GNB4
* HARS1
* HK1
* HSPB3
* INF2
* JPH1
* KARS1
* KIF5A
* LITAF
* LRSAM1
* MARS1
* MCM3AP
* MED25
* MME
* MORC2
* MTMR2
* NDRG1
* NEFH
* NEFL
* PDK3
* PLEKHG5
* PRX
* PTRH2
* RAB7A
* SBF1
* SBF2
* SCO2
* SGPL1
* SH3TC2
* SIGMAR1
* SLC25A46
* TRIM2
* WARS1
* YARS1
## Inheritance Pattern
The pattern of inheritance varies with the type of Charcot-Marie-Tooth disease. CMT1, most cases of CMT2, and most intermediate forms are inherited in an autosomal dominant pattern. This pattern of inheritance means that one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one affected parent. Each of the children of an affected parent has a 50 percent chance of inheriting the disorder.
CMT4, a few CMT2 subtypes, and some intermediate forms are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition. Children of affected individuals are not affected unless the other parent also passes down a mutation in the same gene.
CMTX is inherited in an X-linked dominant pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome. The inheritance is dominant if one copy of the altered gene is sufficient to cause the condition. In most cases, affected males, who have the alteration on their only copy of the X chromosome, experience more severe symptoms of the disorder than affected females, who have the alteration on one of their two X chromosomes. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. All daughters of affected men will have one altered X chromosome, but they may have only mild symptoms of the disorder.
Some cases of autosomal dominant or type X Charcot-Marie-Tooth disease result from a new mutation and occur in people with no history of the disorder in their family.
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*[AA]: Adrenergic agonist
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*[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
| Charcot-Marie-Tooth disease | c3495591 | 804 | medlineplus | https://medlineplus.gov/genetics/condition/charcot-marie-tooth-disease/ | 2021-01-27T08:25:00 | {"gard": ["6034"], "mesh": ["C566136"], "omim": ["118300", "609260", "118210", "600882", "605588", "605589", "601472", "607684", "606595", "607677", "607736", "607831", "608673", "613287", "614228", "614436", "607706", "118220", "118200", "601098", "607678", "607734", "606482", "608323", "607791", "614455", "118230", "608340", "214400", "601382", "604563", "601596", "601455", "609311", "611228", "302800", "310490", "311070", "600361", "606071", "145900", "148360", "605253", "605285", "601152", "616505", "214370", "256855", "180800"], "synonyms": []} |
This article is about aspects of spherocytosis specific to the hereditary form of the disorder. For details that apply generally to this variant as well as others, see Spherocytosis.
Hereditary spherocytosis
Other namesMinkowski–Chauffard syndrome
Peripheral blood smear from patient with hereditary spherocytosis
SpecialtyHematology
Hereditary spherocytosis is an abnormality of red blood cells, or erythrocytes. The disorder is caused by mutations in genes relating to membrane proteins that allow for the erythrocytes to change shape. The abnormal erythrocytes are sphere-shaped (spherocytosis) rather than the normal biconcave disk shaped. Dysfunctional membrane proteins interfere with the cell's ability to be flexible to travel from the arteries to the smaller capillaries. This difference in shape also makes the red blood cells more prone to rupture.[1] Cells with these dysfunctional proteins are degraded in the spleen. This shortage of erythrocytes results in hemolytic anemia.
It was first described in 1871. It is the most common cause of inherited hemolysis in European and North American Caucasian populations, with an incidence of 1 in 5000 births. The clinical severity of HS varies from symptom-free carrier to severe hemolysis because the disorder exhibits incomplete penetrance in its expression.
Symptoms include anemia, jaundice, splenomegaly, and fatigue.[2] Furthermore, the detritus of the broken-down blood cells – unconjugated or indirect bilirubin – accumulates in the gallbladder, and can cause pigmented gallstones to develop. In chronic patients, an infection or other illness can cause an increase in the destruction of red blood cells, resulting in the appearance of acute symptoms, a hemolytic crisis. On a blood smear, Howell-Jolly bodies may be seen within red blood cells. Primary treatment for patients with symptomatic HS has been total splenectomy, which eliminates the hemolytic process, allowing normal hemoglobin, reticulocyte and bilirubin levels. Spherocytosis patients who are heterozygous for a hemochromatosis gene may suffer from iron overload, despite the hemochromatosis genes being recessive.[3][4]
Acute cases can threaten to cause hypoxia through anemia and acute kernicterus through high blood levels of bilirubin, particularly in newborns. Most cases can be detected soon after birth. An adult with this disease should have their children tested, although the presence of the disease in children is usually noticed soon after birth. Occasionally, the disease will go unnoticed until the child is about 4 or 5 years of age. A person may also be a carrier of the disease and show no signs or symptoms of the disease. Other symptoms may include abdominal pain that could lead to the removal of the spleen and/or gallbladder.
## Contents
* 1 Presentation
* 1.1 Complications
* 2 Pathophysiology
* 3 Diagnosis
* 4 Treatment
* 5 Epidemiology
* 6 Research
* 7 See also
* 8 References
* 9 External links
## Presentation[edit]
### Complications[edit]
* Hemolytic crisis, with more pronounced jaundice due to accelerated hemolysis (may be precipitated by infection).
* Aplastic crisis with dramatic fall in hemoglobin level and (reticulocyte count)-decompensation, usually due to maturation arrest and often associated with megaloblastic changes; may be precipitated by infection, such as influenza, notably with parvovirus B19.[5][6][7]
* Folate deficiency caused by increased bone marrow requirement.
* Pigmented gallstones occur in approximately half of untreated patients. Increased hemolysis of red blood cells leads to increased bilirubin levels, because bilirubin is a breakdown product of heme. The high levels of bilirubin must be excreted into the bile by the liver, which may cause the formation of a pigmented gallstone, which is composed of calcium bilirubinate. Since these stones contain high levels of calcium carbonates and phosphate, they are radiopaque and are visible on x-ray.
* Leg ulcer.
* Abnormally low hemoglobin A1C levels.[8] Hemoglobin A1C (glycated hemoglobin) is a test for determining the average blood glucose levels over an extended period of time, and is often used to evaluate glucose control in diabetics. The hemoglobin A1C levels are abnormally low because the life span of the red blood cells is decreased, providing less time for the non-enzymatic glycosylation of hemoglobin. Thus, even with high overall blood sugar, the A1C will be lower than expected.
## Pathophysiology[edit]
Hereditary spherocytosis can be an autosomal recessive or autosomal dominant trait.[9] Hereditary spherocytosis is most commonly (though not exclusively) found in Northern European and Japanese families, although an estimated 25% of cases are due to spontaneous mutations. A patient has a 50% chance of passing the mutation onto each of his/her offspring.
Hereditary spherocytosis is caused by a variety of molecular defects in the genes that code for the red blood cell proteins spectrin (alpha and beta), ankyrin,[10] band 3 protein, protein 4.2,[11] and other red blood cell membrane proteins:[12]
Type OMIM Gene Locus
HS1 182900 ANK1 8p11.2
HS2 182870 SPTB 14q22-q23
HS3 270970 SPTA 1q21
HS4 109270 SLC4A1 17q21-q22
HS5 612690 EPB42 15q15
These proteins are necessary to maintain the normal shape of a red blood cell, which is a biconcave disk. The integrating protein that is most commonly defective is spectrin which is responsible for incorporation and binding of spectrin, thus in its dysfunction cytoskeletal instabilities ensue.
The primary defect in hereditary spherocytosis is a deficiency of membrane surface area. Decreased surface area may be produced by two different mechanisms: 1) Defects of spectrin, ankyrin (most commonly), or protein 4.2 lead to reduced density of the membrane skeleton, destabilizing the overlying lipid bilayer and releasing band 3-containing microvesicles. 2) Defects of band 3 lead to band 3 deficiency and loss of its lipid-stabilizing effect. This results in the loss of band 3-free microvesicles. Both pathways result in membrane loss, decreased surface area, and formation of spherocytes with decreased deformability.
As the spleen normally targets abnormally shaped red cells (which are typically older), it also destroys spherocytes. In the spleen, the passage from the cords of Billroth into the sinusoids may be seen as a bottleneck, where red blood cells need to be flexible in order to pass through. In hereditary spherocytosis, red blood cells fail to pass through and get phagocytosed, causing extravascular hemolysis.[13]
## Diagnosis[edit]
In a peripheral blood smear, the red blood cells will appear abnormally small and lack the central pale area that is present in normal red blood cells. These changes are also seen in non-hereditary spherocytosis, but they are typically more pronounced in hereditary spherocytosis. The number of immature red blood cells (reticulocyte count) will be elevated.[2] An increase in the mean corpuscular hemoglobin concentration is also consistent with hereditary spherocytosis.
Other protein deficiencies cause hereditary elliptocytosis, pyropoikilocytosis or stomatocytosis.
In longstanding cases and in patients who have taken iron supplementation or received numerous blood transfusions, iron overload may be a significant problem. This is a potential cause of heart muscle damage and liver disease. Measuring iron stores is therefore considered part of the diagnostic approach to hereditary spherocytosis.
An osmotic fragility test can aid in the diagnosis.[14] In this test, the spherocytes will rupture in liquid solutions less concentrated than the inside of the red blood cell. This is due to increased permeability of the spherocyte membrane to salt and water, which enters the concentrated inner environment of the RBC and leads to its rupture.[15] Although the osmotic fragility test is widely considered the gold standard for diagnosing hereditary spherocytosis, it misses as many as 25% of cases. Flow cytometric analysis of eosin-5′-maleimide-labeled intact red blood cells and the acidified glycerol lysis test are two additional options to aid diagnosis.[16]
## Treatment[edit]
Although research is ongoing, at this point there is no cure for the genetic defect that causes hereditary spherocytosis.[12] Current management focuses on interventions that limit the severity of the disease. Treatment options include:
* Splenectomy: As in non-hereditary spherocytosis, acute symptoms of anemia and hyperbilirubinemia indicate treatment with blood transfusions or exchanges and chronic symptoms of anemia and an enlarged spleen indicate dietary supplementation of folic acid and splenectomy,[17] the surgical removal of the spleen. Splenectomy is indicated for moderate to severe cases, but not mild cases.[2] To decrease the risk of sepsis, post-splenectomy spherocytosis patients require immunization against the influenza virus, encapsulated bacteria such as Streptococcus pneumoniae and meningococcus, and prophylactic antibiotic treatment. However, the use of prophylactic antibiotics, such as penicillin, remains controversial.[12]
* Partial splenectomy: Since the spleen is important for protecting against encapsulated organisms, sepsis caused by encapsulated organisms is a possible complication of splenectomy.[2] The option of partial splenectomy may be considered in the interest of preserving immune function. Research on outcomes is currently limited,[2] but favorable.[18]
* Surgical removal of the gallbladder may be necessary.[12]
## Epidemiology[edit]
Hereditary spherocytosis is the most common disorder of the red cell membrane and affects 1 in 2,000 people of Northern European ancestry.[19] According to Harrison's Principles of Internal Medicine, the frequency is at least 1 in 5,000.[12]
## Research[edit]
Experimental gene therapy exists to treat hereditary spherocytosis in lab mice; however, this treatment has not yet been tried on humans due to all of the risks involved in human gene therapy.
## See also[edit]
* Spherocytosis
* Anemia
* Hematology
## References[edit]
1. ^ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease. St. Louis, Mo: Elsevier Saunders. p. 625. ISBN 0-7216-0187-1.
2. ^ a b c d e Bolton-Maggs, P. H. B.; Stevens, R. F.; Dodd, N. J.; Lamont, G.; Tittensor, P.; King, M. -J.; General Haematology Task Force of the British Committee for Standards in Haematology (2004). "Guidelines for the diagnosis and management of hereditary spherocytosis". British Journal of Haematology. 126 (4): 455–474. doi:10.1111/j.1365-2141.2004.05052.x. PMID 15287938.
3. ^ J L Rasmussen; D A Odelson; F L Macrina (1987-08-01). "Complete nucleotide sequence of insertion element IS4351 from Bacteroides fragilis. - UKPMC Article - UK PubMed Central". UKPMC Article. Archived from the original on 2012-12-23. Retrieved 2012-07-03.
4. ^ Paula Bolton-Maggs (September 2011). "Guidelines for the Diagnosis and Management of Hereditary Spherocytosis" (PDF). The British Committee for Standards in Haematology. Retrieved 2 July 2012.
5. ^ Fjaerli, H. O.; Vogt, H.; Bruu, A. L. (1991). "Human parvovirus B19 as the cause of aplastic crisis in hereditary spherocytosis". Tidsskrift for den Norske Laegeforening. 111 (22): 2735–2737. PMID 1658972.
6. ^ Beland, S. S.; Daniel, G. K.; Menard, J. C.; Miller, N. M. (1997). "Aplastic crisis associated with parvovirus B19 in an adult with hereditary spherocytosis". The Journal of the Arkansas Medical Society. 94 (4): 163–164. PMID 9308316.
7. ^ Servey, J. T.; Reamy, B. V.; Hodge, J. (2007). "Clinical presentations of parvovirus B19 infection". American Family Physician. 75 (3): 373–376. PMID 17304869.
8. ^ Kutter, D; Thoma, J (2006). "Hereditary spherocytosis and other hemolytic anomalies distort diabetic control by glycated hemoglobin". Clinical Laboratory. 52 (9–10): 477–81. PMID 17078474.
9. ^ Eber S, Lux SE (April 2004). "Hereditary spherocytosis--defects in proteins that connect the membrane skeleton to the lipid bilayer". Semin. Hematol. 41 (2): 118–41. doi:10.1053/j.seminhematol.2004.01.002. PMID 15071790.
10. ^ Gallagher PG, Forget BG (December 1998). "Hematologically important mutations: spectrin and ankyrin variants in hereditary spherocytosis". Blood Cells Mol. Dis. 24 (4): 539–43. doi:10.1006/bcmd.1998.0217. PMID 9887280.
11. ^ Perrotta S, Gallagher PG, Mohandas N (October 2008). "Hereditary spherocytosis". Lancet. 372 (9647): 1411–26. doi:10.1016/S0140-6736(08)61588-3. PMID 18940465.
12. ^ a b c d e Anthony S. Fauci; Eugene Braunwald; Dennis L. Kasper; Stephen L. Hauser; Dan L. Longo; J. Larry Jameson; Joseph Loscalzo (2008). Harrison's principles of internal medicine (17th ed.). New York: McGraw-Hill Medical. pp. Chapter 106. ISBN 978-0071466332.
13. ^ Chapter 12, page 425 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (2007). Robbins Basic Pathology. Philadelphia: Saunders. ISBN 1-4160-2973-7. 8th edition.
14. ^ Won DI, Suh JS (March 2009). "Flow cytometric detection of erythrocyte osmotic fragility". Cytometry Part B. 76 (2): 135–41. doi:10.1002/cyto.b.20448. PMID 18727072.
15. ^ Goljan. Rapid Review Pathology. 2010. Page 213.
16. ^ Bianchi, P.; Fermo, E.; Vercellati, C.; Marcello, A. P.; Porretti, L.; Cortelezzi, A.; Barcellini, W.; Zanella, A. (2011). "Diagnostic power of laboratory tests for hereditary spherocytosis: A comparison study in 150 patients grouped according to molecular and clinical characteristics". Haematologica. 97 (4): 516–523. doi:10.3324/haematol.2011.052845. PMC 3347664. PMID 22058213.
17. ^ Bolton-Maggs PH, Stevens RF, Dodd NJ, Lamont G, Tittensor P, King MJ (August 2004). "Guidelines for the diagnosis and management of hereditary spherocytosis". Br. J. Haematol. 126 (4): 455–74. doi:10.1111/j.1365-2141.2004.05052.x. PMID 15287938.
18. ^ Buesing, K. L.; Tracy, E. T.; Kiernan, C.; Pastor, A. C.; Cassidy, L. D.; Scott, J. P.; Ware, R. E.; Davidoff, A. M.; Rescorla, F. J.; Langer, J. C.; Rice, H. E.; Oldham, K. T. (2011). "Partial splenectomy for hereditary spherocytosis: A multi-institutional review". Journal of Pediatric Surgery. 46 (1): 178–183. doi:10.1016/j.jpedsurg.2010.09.090. PMID 21238662.
19. ^ https://ghr.nlm.nih.gov/condition/hereditary-spherocytosis#genes
## External links[edit]
Classification
D
* ICD-10: D58.0
* ICD-9-CM: 282.0
* OMIM: 182900
* MeSH: D013103
External resources
* MedlinePlus: 000530
* eMedicine: med/2147
* Orphanet: 822
* A short article from WebMD
* A picture of spherocytes from Medline
* v
* t
* e
Diseases of red blood cells
↑
Polycythemia
* Polycythemia vera
↓
Anemia
Nutritional
* Micro-: Iron-deficiency anemia
* Plummer–Vinson syndrome
* Macro-: Megaloblastic anemia
* Pernicious anemia
Hemolytic
(mostly normo-)
Hereditary
* enzymopathy: Glucose-6-phosphate dehydrogenase deficiency
* glycolysis
* pyruvate kinase deficiency
* triosephosphate isomerase deficiency
* hexokinase deficiency
* hemoglobinopathy: Thalassemia
* alpha
* beta
* delta
* Sickle cell disease/trait
* Hereditary persistence of fetal hemoglobin
* membrane: Hereditary spherocytosis
* Minkowski–Chauffard syndrome
* Hereditary elliptocytosis
* Southeast Asian ovalocytosis
* Hereditary stomatocytosis
Acquired
AIHA
* Warm antibody autoimmune hemolytic anemia
* Cold agglutinin disease
* Donath–Landsteiner hemolytic anemia
* Paroxysmal cold hemoglobinuria
* Mixed autoimmune hemolytic anemia
* membrane
* paroxysmal nocturnal hemoglobinuria
* Microangiopathic hemolytic anemia
* Thrombotic microangiopathy
* Hemolytic–uremic syndrome
* Drug-induced autoimmune
* Drug-induced nonautoimmune
* Hemolytic disease of the newborn
Aplastic
(mostly normo-)
* Hereditary: Fanconi anemia
* Diamond–Blackfan anemia
* Acquired: Pure red cell aplasia
* Sideroblastic anemia
* Myelophthisic
Blood tests
* Mean corpuscular volume
* normocytic
* microcytic
* macrocytic
* Mean corpuscular hemoglobin concentration
* normochromic
* hypochromic
Other
* Methemoglobinemia
* Sulfhemoglobinemia
* Reticulocytopenia
* v
* t
* e
Cytoskeletal defects
Microfilaments
Myofilament
Actin
* Hypertrophic cardiomyopathy 11
* Dilated cardiomyopathy 1AA
* DFNA20
* Nemaline myopathy 3
Myosin
* Elejalde syndrome
* Hypertrophic cardiomyopathy 1, 8, 10
* Usher syndrome 1B
* Freeman–Sheldon syndrome
* DFN A3, 4, 11, 17, 22; B2, 30, 37, 48
* May–Hegglin anomaly
Troponin
* Hypertrophic cardiomyopathy 7, 2
* Nemaline myopathy 4, 5
Tropomyosin
* Hypertrophic cardiomyopathy 3
* Nemaline myopathy 1
Titin
* Hypertrophic cardiomyopathy 9
Other
* Fibrillin
* Marfan syndrome
* Weill–Marchesani syndrome
* Filamin
* FG syndrome 2
* Boomerang dysplasia
* Larsen syndrome
* Terminal osseous dysplasia with pigmentary defects
IF
1/2
* Keratinopathy (keratosis, keratoderma, hyperkeratosis): KRT1
* Striate palmoplantar keratoderma 3
* Epidermolytic hyperkeratosis
* IHCM
* KRT2E (Ichthyosis bullosa of Siemens)
* KRT3 (Meesmann juvenile epithelial corneal dystrophy)
* KRT4 (White sponge nevus)
* KRT5 (Epidermolysis bullosa simplex)
* KRT8 (Familial cirrhosis)
* KRT10 (Epidermolytic hyperkeratosis)
* KRT12 (Meesmann juvenile epithelial corneal dystrophy)
* KRT13 (White sponge nevus)
* KRT14 (Epidermolysis bullosa simplex)
* KRT17 (Steatocystoma multiplex)
* KRT18 (Familial cirrhosis)
* KRT81/KRT83/KRT86 (Monilethrix)
* Naegeli–Franceschetti–Jadassohn syndrome
* Reticular pigmented anomaly of the flexures
3
* Desmin: Desmin-related myofibrillar myopathy
* Dilated cardiomyopathy 1I
* GFAP: Alexander disease
* Peripherin: Amyotrophic lateral sclerosis
4
* Neurofilament: Parkinson's disease
* Charcot–Marie–Tooth disease 1F, 2E
* Amyotrophic lateral sclerosis
5
* Laminopathy: LMNA
* Mandibuloacral dysplasia
* Dunnigan Familial partial lipodystrophy
* Emery–Dreifuss muscular dystrophy 2
* Limb-girdle muscular dystrophy 1B
* Charcot–Marie–Tooth disease 2B1
* LMNB
* Barraquer–Simons syndrome
* LEMD3
* Buschke–Ollendorff syndrome
* Osteopoikilosis
* LBR
* Pelger–Huet anomaly
* Hydrops-ectopic calcification-moth-eaten skeletal dysplasia
Microtubules
Kinesin
* Charcot–Marie–Tooth disease 2A
* Hereditary spastic paraplegia 10
Dynein
* Primary ciliary dyskinesia
* Short rib-polydactyly syndrome 3
* Asphyxiating thoracic dysplasia 3
Other
* Tauopathy
* Cavernous venous malformation
Membrane
* Spectrin: Spinocerebellar ataxia 5
* Hereditary spherocytosis 2, 3
* Hereditary elliptocytosis 2, 3
Ankyrin: Long QT syndrome 4
* Hereditary spherocytosis 1
Catenin
* APC
* Gardner's syndrome
* Familial adenomatous polyposis
* plakoglobin (Naxos syndrome)
* GAN (Giant axonal neuropathy)
Other
* desmoplakin: Striate palmoplantar keratoderma 2
* Carvajal syndrome
* Arrhythmogenic right ventricular dysplasia 8
* plectin: Epidermolysis bullosa simplex with muscular dystrophy
* Epidermolysis bullosa simplex of Ogna
* plakophilin: Skin fragility syndrome
* Arrhythmogenic right ventricular dysplasia 9
* centrosome: PCNT (Microcephalic osteodysplastic primordial dwarfism type II)
Related topics: Cytoskeletal proteins
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Hereditary spherocytosis | c0037889 | 805 | wikipedia | https://en.wikipedia.org/wiki/Hereditary_spherocytosis | 2021-01-18T18:45:18 | {"gard": ["6639"], "mesh": ["D013103"], "umls": ["C0037889"], "orphanet": ["822"], "wikidata": ["Q541244"]} |
"LUTS" redirects here. For other uses, see Luts.
Lower urinary tract symptoms
Other namesLUTS, prostatism
SpecialtyUrology
Lower urinary tract symptoms (LUTS) refer to a group of clinical symptoms involving the bladder, urinary sphincter, urethra and, in men, the prostate. Although LUTS is a preferred term for prostatism,[1] and is more commonly applied to men,[2] lower urinary tract symptoms also affect women.[3]
LUTS affect approximately 40% of older men.[4]
## Contents
* 1 Symptoms and signs
* 1.1 [5]Filling (storage) or irritative symptoms
* 1.2 Voiding or obstructive symptoms
* 2 Causes
* 3 Diagnosis
* 4 Treatment
* 4.1 Surgical treatment
* 4.2 Lifestyle changes
* 5 Epidemiology
* 6 References
* 7 External links
## Symptoms and signs[edit]
Symptoms can be categorised into:
### [5]Filling (storage) or irritative symptoms[edit]
* Increased frequency of urination
* Increased urgency of urination
* Urge incontinence
* Excessive passage of urine at night
### Voiding or obstructive symptoms[edit]
* Poor stream (unimproved by straining)[5]
* Hesitancy (worsened if bladder is very full)[5]
* Terminal dribbling[citation needed]
* Incomplete voiding[citation needed]
* Urinary retention[citation needed]
* Overflow incontinence (occurs in chronic retention)[citation needed]
* Episodes of near retention[citation needed]
As the symptoms are common and non-specific, LUTS is not necessarily a reason to suspect prostate cancer.[1][5] Large studies of patients have also failed to show any correlation between lower urinary tract symptoms and a specific diagnosis.[6] Also, recently a report of lower urinary tract symptoms even with malignant features in the prostate failed to be associated with prostate cancer after further laboratory investigation of the biopsy.[5]
## Causes[edit]
* Benign prostatic hyperplasia (BPH)
* Bladder stone
* Cancer of the bladder and prostate
* Detrusor muscle weakness and/or instability
* Diabetes
* Use of ketamine[7]
* Neurological conditions; for example multiple sclerosis, spinal cord injury, cauda equina syndrome
* Prostatitis, including IgG4-related prostatitis[8][9][10]
* Urethral stricture
* Urinary tract infections (UTIs)[5]
## Diagnosis[edit]
The International Prostate Symptom Score (IPSS) can be used to gauge the symptoms, along with physician examination. Other primary and secondary tests are often carried out, such as a PSA (Prostate-specific antigen) test,[5][11] urinalysis, ultrasound, urinary flow studies, imaging, temporary prostatic stent placement, prostate biopsy[5] and/or cystoscopy.
Placement of a temporary prostatic stent as a differential diagnosis test can help identify whether LUTS symptoms are directly related to obstruction of the prostate or to other factors worth investigation.[5]
## Treatment[edit]
Treatment will depend on the cause, if one is found. For example; with a UTI, a course of antibiotics would be given.[5][medical citation needed]
With prostatic causes of LUTS; the first line of treatment is medical, which includes alpha-1 blockade and antiandrogens.[medical citation needed] If medical treatment fails, or is not an option; a number of surgical techniques to destroy part or all of the prostate have been developed.
### Surgical treatment[edit]
Surgical treatment of LUTS can include:
* Ablation procedures - used in treating both bladder tumours[12] and bladder outlet obstruction, such as prostate conditions.[13]
* Bladder-neck incision (BNI)
* Removal of the prostate \- open, robotic, and endoscopic techniques are used.
* Stenting of the prostate[14] and urethra.
* Transurethral removal of the prostate (TURP)
* Transurethral microwave thermotherapy
* Urethral dilatation, a common treatment for strictures.
### Lifestyle changes[edit]
Other treatments include lifestyle advice; for example, avoiding dehydration in recurrent cystitis.
Men with prostatic hypertrophy are advised to sit down whilst urinating.[15] A 2014 meta-analysis found that, for elderly males with LUTS, sitting to urinate meant there was a decrease in post-void residual volume (PVR, ml), increased maximum urinary flow (Qmax, ml/s), which is comparable with pharmacological intervention, and decreased the voiding time (VT, s).[16] The improved urodynamic profile is related to a lower risk of urologic complications, such as cystitis and bladder stones.[16]
## Epidemiology[edit]
* Prevalence increases with age. The prevalence of nocturia in older men is about 78%. Older men have a higher incidence of LUTS than older women.[17]
* Around one third of men will develop urinary tract (outflow) symptoms, of which the principal underlying cause is benign prostatic hyperplasia.[18]
* Once symptoms arise, their progress is variable and unpredictable with about one third of patients improving, one third remaining stable and one third deteriorating.
* It is estimated that the lifetime risk of developing microscopic prostate cancer is about 30%, developing clinical disease 10%, and dying from prostate cancer 3%.
## References[edit]
* Speakman MJ, Kirby RS, Joyce A, Abrams P, Pocock R (May 2004). "Guideline for the primary care management of male lower urinary tract symptoms". BJU Int. 93 (7): 985–90. doi:10.1111/j.1464-410X.2004.04765.x. PMID 15142148.
* Juliao AA, Plata M, Kazzazi A, Bostanci Y, Djavan B (January 2012). "American Urological Association and European Association of Urology guidelines in the management of benign prostatic hypertrophy: revisited". Current Opinion in Urology. 22 (1): 34–9. doi:10.1097/MOU.0b013e32834d8e87. PMID 22123290.
* NHS; Cancer Screening Programmes. Prostate Cancer Risk Management.
1. ^ a b Abrams P (April 1994). "New words for old: lower urinary tract symptoms for "prostatism"". BMJ. 308 (6934): 929–30. doi:10.1136/bmj.308.6934.929. PMC 2539789. PMID 8173393.
2. ^ "Lower Urinary Tract Symptoms in Women | Doctor". patient.info. Retrieved 7 September 2017.
3. ^ Takahashi, Satoru; Takei, Mineo; Nishizawa, Osamu; Yamaguchi, Osamu; Kato, Kumiko; Gotoh, Momokazu; Yoshimura, Yasukuni; Takeyama, Masami; Ozawa, Hideo; Shimada, Makoto; Yamanishi, Tomonori; Yoshida, Masaki; Tomoe, Hikaru; Yokoyama, Osamu; Koyama, Masayasu (1 January 2016). "Clinical Guideline for Female Lower Urinary Tract Symptoms". LUTS: Lower Urinary Tract Symptoms. 8 (1): 5–29. doi:10.1111/luts.12111. ISSN 1757-5672. PMID 26789539.
4. ^ RoehrbornCG and McConnell JD: Etiology, pathophusiology, epidemiology, and natural history of benign prostatic hyperplasia. Campell's Urology. WB Saunders Co 2002; chapt 38, p1309.
5. ^ a b c d e f g h i j Eziyi, Amogu K.; Oluogun, Waheed A.; Adedokun, Kamoru A.; Oyeniyi, Ganiyu A. (2020-01-01). "Prostate tuberculosis: A rare complication of pulmonary tuberculosis with malignant features mimicking prostate cancer". Urological Science. 31 (1): 36. doi:10.4103/UROS.UROS_80_19. ISSN 1879-5226.
6. ^ Clinical Knowledge Summary; Urological cancer — suspected
7. ^ Winstock, Adam R.; Mitcheson, Luke; Gillatt, David A.; Cottrell, Angela M. (2012). "The prevalence and natural history of urinary symptoms among recreational ketamine users". BJU International. 110 (11): 1762–1766. doi:10.1111/j.1464-410X.2012.11028.x. PMID 22416998.
8. ^ Rodolfo Montironi; Marina Scarpelli; Liang Cheng; Antonio Lopez-Beltran; Maurizio Burattini; Ziya Kirkali; Francesco Montorsi (December 2013). "Immunoglobulin G4-related disease in genitourinary organs: an emerging fibroinflammatory entity often misdiagnosed preoperatively as cancer". European Urology. 64 (1): 865–872. doi:10.1016/j.eururo.2012.11.056. PMID 23266239.
9. ^ Yoshimura Y, Takeda S, Ieki Y, Takazakura E, Koizumi H, Takagawa K (1 Sep 2006). "IgG4-associated prostatitis complicating autoimmune pancreatitis". Internal Medicine. 45 (15): 897–901. doi:10.2169/internalmedicine.45.1752. PMID 16946571.
10. ^ Nishimori I, Kohsaki T, Onishi S, Shuin T, Kohsaki S, Ogawa Y, Matsumoto M, Hiroi M, Hamano H, Kawa S (17 Dec 2007). "IgG4-related autoimmune prostatitis: two cases with or without autoimmune pancreatitis". Internal Medicine. 46 (24): 1983–1989. doi:10.2169/internalmedicine.46.0452. PMID 18084121.
11. ^ The Prostate-Specific Antigen (PSA) Test: Q & A — National Cancer Institute
12. ^ Kramer, MW; Wolters, M; Cash, H; Jutzi, S; Imkamp, F; Kuczyk, MA; Merseburger, AS; Herrmann, TR (April 2015). "Current evidence of transurethral Ho:YAG and Tm:YAG treatment of bladder cancer: update 2014". World Journal of Urology. 33 (4): 571–9. doi:10.1007/s00345-014-1337-y. PMID 24935098.
13. ^ Elshal, AM; Elmansy, HM; Elhilali, MM (March 2013). "Transurethral laser surgery for benign prostate hyperplasia in octogenarians: safety and outcomes". Urology. 81 (3): 634–9. doi:10.1016/j.urology.2012.11.042. PMID 23332997.
14. ^ Fitzpatrick JM. Non-surgical treatment of BPH. Edinburgh: Churchill Livingstone, 1992.
15. ^ Y. de Jong; R.M. ten Brinck; J.H.F.M. Pinckaers; A.A.B. Lycklama à Nijeholt. "Influence of voiding posture on urodynamic parameters in men: a literature review" (PDF). Nederlands Tijdschrift voor urologie. Retrieved 2014-07-02.
16. ^ a b de Jong, Y; Pinckaers, JH; Ten Brinck, RM; Lycklama À Nijeholt, AA; Dekkers, OM (2014). "Urinating Standing versus Sitting: Position Is of Influence in Men with Prostate Enlargement. A Systematic Review and Meta-Analysis". PLOS ONE. 9 (7): e101320. Bibcode:2014PLoSO...9j1320D. doi:10.1371/journal.pone.0101320. PMC 4106761. PMID 25051345.
17. ^ Boyle P, Robertson C, Mazzetta C, et al. (September 2003). "The prevalence of lower urinary tract symptoms in men and women in four centres. The UrEpik study". BJU Int. 92 (4): 409–14. doi:10.1046/j.1464-410x.2003.04369.x. PMID 12930430.
18. ^ Enlarged prostate gland —treatment, symptoms and cause
## External links[edit]
Classification
D
* ICD-10: R30, R33, R35, R39
* ICD-9-CM: 600.00 600.01, 600.20, 600.21, 600.90, 600.91
* MeSH: D059411
* LUTS in men \- Patient.info
* LUTS in women \- Patient.info
* v
* t
* e
Symptoms and signs relating to the urinary system
Pain
* Dysuria
* Renal colic
* Costovertebral angle tenderness
* Vesical tenesmus
Control
* Urinary incontinence
* Enuresis
* Diurnal enuresis
* Giggling
* Nocturnal enuresis
* Post-void dribbling
* Stress
* Urge
* Overflow
* Urinary retention
Volume
* Oliguria
* Anuria
* Polyuria
Other
* Lower urinary tract symptoms
* Nocturia
* urgency
* frequency
* Extravasation of urine
* Uremia
Eponymous
* Addis count
* Brewer infarcts
* Lloyd's sign
* Mathe's sign
http://www.e-urol-sci.com/text.asp?2020/31/1/36/278877
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Lower urinary tract symptoms | c0574785 | 806 | wikipedia | https://en.wikipedia.org/wiki/Lower_urinary_tract_symptoms | 2021-01-18T18:52:20 | {"mesh": ["D059411"], "wikidata": ["Q446372"]} |
People with autism who are deemed to be cognitively "higher functioning" (with an IQ of 70 or greater) than other people with autism
High-functioning autism
SpecialtyPsychiatry
SymptomsTrouble with social interaction, impaired communication, restricted interests, repetitive behavior
ComplicationsSocial isolation, employment problems, family stress, bullying, self-harm[1]
Usual onsetBy age two or three[2][3]
DurationLong-term
CausesGenetic and environmental factors
Diagnostic methodBased on behavior and developmental history
Differential diagnosisAsperger syndrome, ADHD, Tourette syndrome, anxiety, bipolar disorder, obsessive–compulsive disorder
TreatmentBehavioral therapy, speech therapy, psychotropic medication[4][5][6]
MedicationAntipsychotics, antidepressants, stimulants (associated symptoms)[7][8][9]
High-functioning autism (HFA) is an autism classification where the patient exhibits no intellectual disability, but may exhibit deficits in communication, emotion recognition and expression, and social interaction.[10][11][12][13] HFA is not included in either the American Psychological Association's DSM-5 or the World Health Organization's ICD-10, neither of which subdivides autism based on intellectual capabilities.
## Contents
* 1 Characterization
* 1.1 Comorbidities
* 1.2 Behavior
* 2 Cause
* 3 Diagnosis
* 4 Treatment
* 4.1 Augmentative and alternative communication
* 4.2 Speech-language therapy
* 4.3 Occupational therapy
* 4.4 Applied behavioral analysis (ABA)
* 4.5 Sensory integration therapy
* 4.6 Medication
* 5 Criticism of functioning labels
* 6 See also
* 7 References
* 8 Further reading
## Characterization
High-functioning autism is characterized by features similar to those of Asperger syndrome. The defining characteristic recognized by psychologists is a significant delay in the development of early speech and language skills, before the age of three years.[11] The diagnostic criteria of Asperger syndrome exclude a general language delay.[14]
Further differences in features between people with high-functioning autism and those with Asperger syndrome include the following:[11][15][16][17]
* People with HFA have a lower verbal reasoning ability
* Better visual/spatial skills (higher performance IQ) than people with Asperger syndrome
* Less deviating locomotion (e.g. clumsiness) than people with Asperger syndrome
* People with HFA more often have problems functioning independently
* Curiosity and interest for many different things, in contrast to people with Asperger syndrome
* People with Asperger syndrome are better at empathizing with another
* The male to female ratio of 4:1 for HFA is much smaller than that of Asperger syndrome
### Comorbidities
Individuals with autism spectrum disorders, including high-functioning autism, risk developing symptoms of anxiety. While anxiety is one of the most commonly occurring mental health symptoms, children and adolescents with high functioning autism are at an even greater risk of developing symptoms.[18]
There are other comorbidities, the presence of one or more disorders in addition to the primary disorder, associated with high-functioning autism. Some of these include bipolar disorder and obsessive compulsive disorder (OCD). In particular the link between HFA and OCD, has been studied; both have abnormalities associated with serotonin.[19]
Observable comorbidities associated with HFA include ADHD and Tourette syndrome. HFA does not cause nor include intellectual disabilities. This characteristic distinguishes HFA from low-functioning autism; between 40 and 55% of individuals with autism also have an intellectual disability.[20]
### Behavior
An association between HFA and criminal behavior is not completely characterized. Several studies have shown that the features associated with HFA may increase the probability of engaging in criminal behavior.[19] While there is still a great deal of research that needs to be done in this area, recent studies on the correlation between HFA and criminal actions suggest that there is a need to understand the attributes of HFA that may lead to violent behavior. There have been several case studies that link the lack of empathy and social naïveté associated with HFA to criminal actions.[21]
## Cause
Main article: Causes of autism
Although little is known about the biological basis of autism, studies have revealed structural abnormalities in specific brain regions. Regions identified in the "social" brain include the amygdala, superior temporal sulcus, fusiform gyrus area and orbitofrontal cortex. Further abnormalities have been observed in the caudate nucleus, believed to be involved in restrictive behaviors, as well as in a significant increase in the amount of cortical grey matter and atypical connectivity between brain regions.[22]
There is a mistaken belief that some vaccinations, such as the MMR (measles, mumps, rubella) vaccine, may cause autism. This was based on a research study published by Andrew Wakefield, which has been determined as fraudulent and retracted. The results of this study caused some parents to take their children off vaccines clinically proven to prevent diseases that can cause intellectual disabilities or death. The claim that some vaccinations cause autism has not been proven; multiple large-scale epidemiological studies conducted in Japan, the United States, and other countries do not support this link.[23][24]
## Diagnosis
HFA is not a recognised diagnosis by the American Psychological Association (DSM-5) or the World Health Organization (ICD-10). HFA is often, however, used in clinical settings to describe a set of symptoms related to an autism spectrum disorder whereby they exhibit standard autism indicators although have an intelligence quotient (IQ) of 70 or greater.[25]
## Treatment
While there exists no single treatment or medicine for people with autism, there exists several strategies to help lessen the symptoms and effects of the condition.
### Augmentative and alternative communication
Augmentative and alternative communication (AAC) is used for autistic patients who cannot communicate orally. Patients who have problems speaking may be taught to use other forms of communication, such as body language, computers, interactive devices, and pictures.[26] The picture exchange communication system (PECS) is a commonly used form of augmentative and alternative communication with children and adults who cannot communicate well orally. Patients are taught how to link pictures and symbols to their feelings, desires and observation, and may be able to link sentences together with the vocabulary that they form.[27]
### Speech-language therapy
Speech-language therapy can help those with autism who need to develop or improve communication skills.[28] According to the organization Autism Speaks, "speech-language therapy is designed to coordinate the mechanics of speech with the meaning and social use of speech".[27] People with autism may have issues with communication, or speaking spoken words. Speech-language Pathologists (SLP) may teach someone how to communicate more effectively with others or work on starting to develop speech patterns.[29] The SLP will create a plan that focuses on what the child needs.
### Occupational therapy
Occupational therapy helps autistic children and adults learn everyday skills that help them with daily tasks, such as personal hygiene and movement. These skills are then integrated into their home, school, and work environments. Therapists will oftentimes help patients learn to adapt their environment to their skill level.[30] This type of therapy could help autistic people become more engaged in their environment.[27] An occupational therapist will create a plan based on the patient's’ needs and desires and work with them to achieve their set goals.
### Applied behavioral analysis (ABA)
Applied behavioral analysis (ABA) is considered the most effective therapy for autism spectrum disorders by the American Academy of Pediatrics.[31] ABA focuses on teaching adaptive behaviors like social skills, play skills, or communication skills[32][33] and diminishing problematic behaviors like eloping or self-injury[34] by creating a specialized plan that uses behavioral therapy techniques, such as positive or negative reinforcement, to encourage or discourage certain behaviors over-time.[35]
### Sensory integration therapy
Sensory integration therapy helps people with autism adapt to different kinds of sensory stimuli. Many with autism can be oversensitive to certain stimuli, such as lights or sounds, causing them to overreact. Others may not react to certain stimuli, such as someone speaking to them.[36] Many types of therapy activities involve a form of play, such as using swings, toys and trampolines to help engage the patients with sensory stimuli.[27] Therapists will create a plan that focuses on the type of stimulation the person needs integration with.
### Medication
There are no medications specifically designed to treat autism. Medication is usually used for symptoms associated with autism, such as depression, anxiety, or behavioral problems.[37] Medicines are usually used after other alternative forms of treatment have failed.[38]
## Criticism of functioning labels
Many autistic rights activists disagree with the categorisation of individuals into "high-functioning autism" and "low-functioning autism", stating that the "low-functioning" label causes people to put low expectations on a child and view them as lesser.[39] Furthermore, critics of functioning labels state that an individual's functioning can fluctuate from day to day, and categories do not take this into consideration.[40] Additionally, individuals with "medium-functioning autism" are typically left out of the discussion entirely, and due to the non-linear nature of the autistic spectrum, individuals can be high-functioning in some areas while at the same time being medium or low functioning in other areas.[citation needed]
## See also
* Asperger syndrome and neuroscience
* Autism-spectrum quotient, a self-administered test for high-functioning autism
* Historical figures sometimes considered autistic
* Low-functioning autism
* Nonverbal learning disorder
* Lorna Wing
## References
1. ^ "Autism spectrum disorder - Symptoms and causes". Mayo Clinic. Archived from the original on 14 July 2019. Retrieved 13 July 2019.
2. ^ "NIMH " Autism Spectrum Disorder". nimh.nih.gov. October 2016. Archived from the original on 21 April 2017. Retrieved 20 April 2017.
3. ^ American Psychiatric Association (2013). "Autism Spectrum Disorder. 299.00 (F84.0)". Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington, VA: American Psychiatric Publishing. pp. 50–59. doi:10.1176/appi.books.9780890425596. hdl:2027.42/138395. ISBN 978-0-89042-559-6.
4. ^ Myers SM, Johnson CP (November 2007). "Management of children with autism spectrum disorders". Pediatrics. 120 (5): 1162–82. doi:10.1542/peds.2007-2362. PMID 17967921. Archived from the original on 2019-03-23. Retrieved 2019-05-24.
5. ^ Sanchack, KE; Thomas, CA (15 December 2016). "Autism Spectrum Disorder: Primary Care Principles". American Family Physician. 94 (12): 972–79. PMID 28075089.
6. ^ Sukhodolsky, DG; Bloch, MH; Panza, KE; Reichow, B (November 2013). "Cognitive-behavioral therapy for anxiety in children with high-functioning autism: a meta-analysis". Pediatrics. 132 (5): e1341–50. doi:10.1542/peds.2013-1193. PMC 3813396. PMID 24167175.
7. ^ Ji N, Findling RL (March 2015). "An update on pharmacotherapy for autism spectrum disorder in children and adolescents". Current Opinion in Psychiatry. 28 (2): 91–101. doi:10.1097/YCO.0000000000000132. PMID 25602248. S2CID 206141453.
8. ^ Oswald DP, Sonenklar NA (June 2007). "Medication use among children with autism spectrum disorders". Journal of Child and Adolescent Psychopharmacology. 17 (3): 348–55. doi:10.1089/cap.2006.17303. PMID 17630868.
9. ^ Jaeggi, S. M.; Buschkuehl, M.; Jonides, J.; Perrig, W. J. (2008). "From the Cover: Improving fluid intelligence with training on working memory". Proceedings of the National Academy of Sciences. 105 (19): 6829–33. Bibcode:2008PNAS..105.6829J. doi:10.1073/pnas.0801268105. PMC 2383929. PMID 18443283.
10. ^ Sanders, James Ladell (2009). "Qualitative or Quantitative Differences Between Asperger's Disorder and Autism? Historical Considerations". Journal of Autism and Developmental Disorders. 39 (11): 1560–1567. doi:10.1007/s10803-009-0798-0. ISSN 0162-3257. PMID 19548078. S2CID 26351778.
11. ^ a b c Carpenter, Laura Arnstein; Soorya, Latha; Halpern, Danielle (2009). "Asperger's Syndrome and High-Functioning Autism". Pediatric Annals. 38 (1): 30–5. doi:10.3928/00904481-20090101-01. PMID 19213291.
12. ^ Sanders, J (2009). "Qualitative or quantitative differences between Asperger's disorder and autism? Historical considerations". Journal of Autism and Developmental Disorders. 39 (11): 1560–1567. doi:10.1007/s10803-009-0798-0. PMID 19548078. S2CID 26351778.
13. ^ Andari, Elissar; Duhamel, Jean-René; Zalla, Tiziana; Herbrecht, Evelyn; Leboyer, Marion; Sirigu, Angela (2 March 2019). "Promoting social behavior with oxytocin in highfunctioning autism spectrum disorders" (PDF). PNAS. 107 (9): 4389–4394. doi:10.1073/pnas.0910249107. PMC 2840168. PMID 20160081.
14. ^ Asperger's Disorder Archived 2013-05-20 at the Wayback Machine – Diagnostic and Statistical Manual of Mental Disorders Fourth edition Text Revision (DSM-IV-TR) American Psychiatric Association (2000)
15. ^ T. Attwood, Is There a Difference Between Asperger's Syndrome and High Functioning Autism? Archived 2007-08-09 at the Wayback Machine[unreliable medical source?]
16. ^ Rinehart, NJ; Bradshaw, JL; Brereton, AV; Tonge, BJ (2002). "Lateralization in individuals with high-functioning autism and Asperger's disorder: A frontostriatal model". Journal of Autism and Developmental Disorders. 32 (4): 321–331. doi:10.1023/A:1016387020095. PMID 12199137. S2CID 23067447.
17. ^ Mazefsky, Carla A.; Oswald, Donald P. (2006). "Emotion Perception in Asperger's Syndrome and High-functioning Autism: The Importance of Diagnostic Criteria and Cue Intensity". Journal of Autism and Developmental Disorders. 37 (6): 1086–95. doi:10.1007/s10803-006-0251-6. PMID 17180461. S2CID 12094187.
18. ^ Reaven, Judy (2011). "The treatment of anxiety symptoms in youth with high-functioning autism spectrum disorders: Developmental considerations for parents". Brain Research. 1380: 255–63. doi:10.1016/j.brainres.2010.09.075. PMID 20875799. S2CID 5226904.
19. ^ a b Mazzone, Luigi; Ruta, Liliana; Reale, Laura (2012). "Psychiatric comorbidities in asperger syndrome and high functioning autism: Diagnostic challenges". Annals of General Psychiatry. 11 (1): 16. doi:10.1186/1744-859X-11-16. PMC 3416662. PMID 22731684.
20. ^ Newschaffer, Craig J.; Croen, Lisa A.; Daniels, Julie; Giarelli, Ellen; Grether, Judith K.; Levy, Susan E.; Mandell, David S.; Miller, Lisa A.; Pinto-Martin, Jennifer; Reaven, Judy; Reynolds, Ann M.; Rice, Catherine E.; Schendel, Diana; Windham, Gayle C. (2007). "The Epidemiology of Autism Spectrum Disorders*". Annual Review of Public Health. 28 (1): 235–258. doi:10.1146/annurev.publhealth.28.021406.144007. ISSN 0163-7525. PMID 17367287.
21. ^ Lerner, Matthew D.; Haque, Omar Sultan; Northrup, Eli C.; Lawer, Lindsay; Bursztajn, Harold J. (2012). "Emerging Perspectives on Adolescents and Young Adults With High-Functioning Autism Spectrum Disorders, Violence, and Criminal Law". Journal of the American Academy of Psychiatry and the Law. 40 (2): 177–90. PMID 22635288.
22. ^ Spencer, Michael; Stanfield, Andrew; Johnstone, Eve (2011). "Brain imaging and the neuroanatomical correlates of autism". In Roth, Ilona; Rezaie, Payam (eds.). Researching the Autism Spectrum. pp. 112–55. doi:10.1017/CBO9780511973918.006. ISBN 978-0-511-97391-8.
23. ^ Klin, Ami (2006). "Autismo e síndrome de Asperger: Uma visão geral" [Autism and Asperger syndrome: an overview]. Revista Brasileira de Psiquiatria (in Portuguese). 28: S3–11. doi:10.1590/S1516-44462006000500002. PMID 16791390.
24. ^ "A mercurial debate over autism". Nature Neuroscience. 8 (9): 1123. September 2005. doi:10.1038/nn0905-1123. ISSN 1546-1726. PMID 16127438.
25. ^ de Giambattista, Concetta (2019). "Subtyping the Autism Spectrum Disorder: Comparison of Children with High Functioning Autism and Asperger Syndrome". Journal of Autism and Developmental Disorders. 49 (1): 138–150. doi:10.1007/s10803-018-3689-4. PMC 6331497. PMID 30043350.
26. ^ "Augmentative and Alternative Communication (AAC)". American Speech-Language-Hearing Association. Archived from the original on 2019-08-15. Retrieved 2019-08-20.
27. ^ a b c d "What Treatments are Available for Speech, Language and Motor Issues?". Autism Speaks. Archived from the original on 2015-12-22. Retrieved 2015-12-16.
28. ^ "What is Autism, Asperger Syndrome, and Pervasive Developmental Disorders?". US Autism and Asperger Association. Archived from the original on 28 December 2015. Retrieved 16 December 2015.
29. ^ for you/parents-and-cares/pc speech and language therapy.aspx "Speech and Language Therapy" Check `|url=` value (help). Autism Education Trust.[permanent dead link]
30. ^ fact sheet.ashx "Occupational Therapy's Role with Autism" Check `|url=` value (help). American Occupational Therapy Association. Archived from the original on 2019-01-03. Retrieved 2019-08-20.
31. ^ Myers, Scott M.; Johnson, Chris Plauché (1 November 2007). "Management of Children With Autism Spectrum Disorders". Pediatrics. 120 (5): 1162–1182. doi:10.1542/peds.2007-2362. ISSN 0031-4005. PMID 17967921. Archived from the original on 9 October 2019. Retrieved 20 August 2019.
32. ^ "Applied Behavioral Analysis (ABA): What is ABA?". Autism partnership. Archived from the original on 2019-01-03. Retrieved 2019-08-20.
33. ^ Matson, Johnny; Hattier, Megan; Belva, Brian (January–March 2012). "Treating adaptive living skills of persons with autism using applied behavior analysis: A review". Research in Autism Spectrum Disorders. 6 (1): 271–276. doi:10.1016/j.rasd.2011.05.008.
34. ^ Summers, Jane; Sharami, Ali; Cali, Stefanie; D'Mello, Chantelle; Kako, Milena; Palikucin-Reljin, Andjelka; Savage, Melissa; Shaw, Olivia; Lunsky, Yona (November 2017). "Self-Injury in Autism Spectrum Disorder and Intellectual Disability: Exploring the Role of Reactivity to Pain and Sensory Input". Brain Sci. 7 (11): 140. doi:10.3390/brainsci7110140. PMC 5704147. PMID 29072583.
35. ^ "Applied Behavioral Strategies - Getting to Know ABA". Archived from the original on 2015-10-06. Retrieved 2015-12-16.
36. ^ Smith, M; Segal, J; Hutman, T. "Autism Spectrum Disorders". Cite journal requires `|journal=` (help)
37. ^ National Institute of Mental Health. "Medications for Autism". Psych Central. Archived from the original on 2015-12-13. Retrieved 2015-12-16.
38. ^ Pope, J; Volkmar, F (November 14, 2014). "Medicines for Autism". Cite journal requires `|journal=` (help)
39. ^ "More Problems with Functioning Labels". Ollibean. 2013-09-26. Archived from the original on 2019-04-30. Retrieved 2017-12-29.
40. ^ "Identity-First Autistic". Identity-First Autistic. Archived from the original on 2017-12-30. Retrieved 2017-12-29.
## Further reading
* Robison, John Elder (2007). Look Me in the Eye: My Life with Asperger's. Three Rivers Press. ISBN 9780307395986.
* v
* t
* e
Pervasive developmental disorders and autism spectrum
Main
* Causes
* Comorbid conditions
* Epidemiology
* Heritability
* Societal and cultural aspects
* Medical model
* Therapies
Diagnoses
* Autism spectrum (High-functioning autism
* Classic autism
* Asperger syndrome
* Pervasive developmental disorder not otherwise specified
* Childhood disintegrative disorder
* Rett syndrome)
Related conditions
* Alexithymia
* Attention deficit hyperactivity disorder
* Anxiety disorder (obsessive–compulsive disorder)
* Late talker
* Epilepsy
* Fragile X syndrome
* Hyperlexia
* Savant syndrome
* Sensory processing disorder
* Intellectual disability
* Developmental coordination disorder
* Multiple complex developmental disorder
Controversies
* Autism rights movement
* Autistic enterocolitis
* Facilitated communication
* MMR vaccine
* Rapid prompting method
* Thiomersal (Chelation)
Diagnostic scales
* Gilliam Asperger's disorder scale
* Autism Diagnostic Observation Schedule
* Autism Diagnostic Interview
* Autism-spectrum quotient
* Childhood Autism Rating Scale
Lists
* Autism-related topics
* Fictional characters
* Schools
* v
* t
* e
Autism resources
* Autism
* outline
* spectrum
Awareness
* Autism friendly
* Autism Sunday
* Communication Shutdown
* World Autism Awareness Day
Culture
* Autistic art
* Autism spectrum disorders in the media
* Fictional characters
* Films about autism
* Circle of Friends
* Neurodiversity
* Medical model of autism
* Societal and cultural aspects of autism
Therapies
Psychotropic medication (antipsychotics)
* Aripiprazole
* Risperidone
Behavioral
* Applied behavior analysis (ABA)
* Discrete trial training (Lovaas)
* Picture exchange communication system (PECS)
* Pivotal response treatment
* Positive behavior support
* Cognitive behavior therapy (CBT)
* Social skills training
Developmental
* Early start denver model
* Floortime (The PLAY Project)
Controversial
* Auditory integration training
* Aversive therapy/Electric shocks (Judge Rotenberg Educational Center)
* Chelation of mercury
* Ethical challenges to autism treatment
* Facilitated communication
* Gluten-free casein-free diet
* Hug machine
* Hyperbaric oxygen therapy
* Holding therapy
* Relationship development intervention
* Secretin
* Sensory integration therapy
* Son-Rise
* Vitamin B12
Related
* ADHD medication (Clonidine · Guanfacine · Methylphenidate)
* Melatonin
* Occupational therapy
* Social Stories
* Speech therapy
* SSRI antidepressants (Fluoxetine · Paroxetine · Sertraline)
* Structured teaching (TEACCH)
Centers
Research
United States
* Association for Science in Autism Treatment
* Autism Research Institute
* Autism Science Foundation
* Kennedy Krieger Institute
* National Alliance for Autism Research
* Simons Foundation Autism Research Initiative
* Yale Child Study Center
United Kingdom
* Autism Research Centre (UK)
other / see also
* Conditions and research areas
* Researchers
Therapy
United States
* Center for Autism and Related Disorders (CARD)
* MIND Institute
Schools
* Alpine Learning Group
* Eden II School for Autistic Children
* ELIJA School
* ESPA College (UK)
* Exceptional Minds (USA)
* New England Center for Children
* Pathlight School (Singapore)
* Rebecca School
* Sunfield Children's Home (UK)
* TreeHouse School (UK)
* Western Autistic School (Australia)
* List of schools
Organizations
Americas
United States
* Autism National Committee
* Autism Network International
* Autism Science Foundation
* Autistic Self Advocacy Network
* Autism Society of America
* Autism Speaks
* Centro Ponceño de Autismo
* Daniel Jordan Fiddle Foundation
* Generation Rescue
* Interactive Autism Network
* Interagency Autism Coordinating Committee
* LENA Foundation
* National Alliance for Autism Research
* National Council on Severe Autism
* Talk About Curing Autism
other
* Centro Ann Sullivan (Peru)
* Domus Instituto de Autismo (Mexico)
* Filipino-Canadian Autism Parent Support Group (Canada)
* Geneva Centre for Autism (Canada)
Asia
* Action for Autism (India)
* Autism Resource Centre (Singapore)
Caribbean
* Autistic Society (Trinidad and Tobago)
* Maia Chung Autism and Disabilities Foundation (Jamaica)
Europe
UK
* Autism Anglia
* The Autism Directory
* Autism Awareness Campaign UK
* Autism Cymru
* Autism Plus
* Autistica
* National Autistic Society
* Sacar
other
* Specialisterne (Denmark)
* Aspies For Freedom
* Alliance Autiste
Oceania
* Luke Priddis Foundation (Australia)
International
* Autism rights movement
* Wrong Planet
Literature
Non-fiction
* The Accidental Teacher: Life Lessons from My Silent Son
* Animals in Translation
* Aspergirls: Empowering Females with Asperger's Syndrome
* Autism's False Prophets
* Extreme Love: Autism
* Fall Down 7 Times Get Up 8
* Freaks, Geeks, and Asperger Syndrome: A User Guide to Adolescence
* In a Different Key
* Life Animated
* Like Colour to the Blind
* Look Me in the Eye
* Mother Warriors
* My Autobiography
* NeuroTribes
* Nobody Nowhere
* Overcoming Autism
* The Reason I Jump
* Somebody Somewhere
* Son-Rise: The Miracle Continues
* Strange Son
* Switched On
* Unstrange Minds
Fiction
* The Curious Incident of the Dog in the Night-Time
* Dear John
* House Rules
* Mockingbird
* Saving Max
* Speed of Dark
* The Winter Journey
* With the Light
For younger people
* Everybody Is Different: A Book for Young People Who Have Brothers or Sisters With Autism
* Ian's Walk: A Story about Autism
* Marcelo in the Real World
* Rage: A Love Story
* Rules
Journals
* Autism
* Journal of Autism and Developmental Disorders
* Molecular Autism
* Research in Autism Spectrum Disorders
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| High-functioning autism | c3840214 | 807 | wikipedia | https://en.wikipedia.org/wiki/High-functioning_autism | 2021-01-18T19:07:37 | {"umls": ["C3840214"], "icd-9": [], "icd-10": [], "wikidata": ["Q1788847"]} |
Tibial hemimelia is a rare anomaly characterized by deficiency of the tibia with relatively intact fibula. Jones et al. (1978) classified the anomaly into 4 types according to radiologic criteria. It may present as an isolated anomaly or be associated with a variety of skeletal and extraskeletal malformations. Tibial hemimelia may also constitute a part of a more complicated malformation complex or syndrome, such as the Gollop-Wolfgang complex (228250) and triphalangeal thumb-polysyndactyly syndrome (see 174500 and 188740) (Matsuyama et al., 2003).
Emami-Ahari and Mahloudji (1974) described bilateral absence of the tibia in 3 children, 2 males and 1 female, of phenotypically normal but related parents. No other anomalies were present and intelligence was normal. Jones et al. (1978) reported affected brother and sister. McKay et al. (1984) reported affected sisters. McKay et al. (1984) reviewed syndromes of congenital defects in which tibial hemimelia is a feature. Richieri-Costa et al. (1987) reported on 37 patients belonging to different families who had the tibial hemimelia/split-hand/split-foot syndrome. Quoting others, they suggested that the maximum risk to the offspring of an affected person married to an unaffected person is 8.6% and the maximum risk to a sib of an isolated patient is 12.5%. They suggested that there are 4 well-established and 2 other possible autosomal dominant tibial hemimelia syndromes in addition to 2 types with autosomal recessive inheritance. Richieri-Costa (1987) reported a Brazilian child, born to consanguineous but healthy parents, who had cleft lip/palate in addition to tibial hemimelia.
Stevens and Moore (1999) described a girl with Langer-Giedion syndrome (LGS; 150230), a contiguous gene syndrome caused by deletion in the 8q24.1 region. The patient also showed bilateral tibial hemimelia and unilateral absence of the ulna. Turleau et al. (1982) had described an 8-year-old boy with LGS and bilateral tibial hemimelia. Although no genes involving limb development in the human had been identified in the 8q24.1 region, 2 mouse syndromes with limb abnormalities mapped to the homologous region of 9A1-A4: 'luxoid' (absent toes, radial and tibial hemimelia, preaxial polydactyly, bent tail, and oligospermia) and 'aft' (abnormal feet and tail). Stevens and Moore (1999) suggested that a gene involved in limb development is contiguous with the gene(s) for LGS and that deletion of this gene causes tibial hemimelia.
Matsuyama et al. (2003) reported 2 Japanese brothers, aged 6 and 2 years, with tibial hemimelia, who were born to unrelated, phenotypically normal parents. The type of tibial hemimelia and associated malformations of hands and feet were quite different between the brothers. Findings in the elder brother were compatible with the Gollop-Wolfgang complex, and in the younger brother with tibial aplasia-ectrodactyly syndrome (119100). No mutations were found in 3 candidate genes: Sonic hedgehog (SHH; 600725), HOXD11 (142986), and HOXD12 (142988).
Limbs \- Absent tibia Inheritance \- Autosomal recessive \- also other dominant and recessive tibial hemimelia syndromes ▲ 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
| TIBIAL HEMIMELIA | c0265633 | 808 | omim | https://www.omim.org/entry/275220 | 2019-09-22T16:21:38 | {"mesh": ["C535563"], "omim": ["275220"], "orphanet": ["93322"], "synonyms": ["Alternative titles", "THM", "TIBIA, ABSENCE OF"]} |
Disease of the skin of human fingers
Knuckle pads
SpecialtyRheumatology
Classification
D
* ICD-10: M72.1
* ICD-9-CM: 728.79
* OMIM: 149100
* DiseasesDB: 30724
External resources
* eMedicine: article/1074379
Knuckle pads (also known as "Heloderma", meaning similar to the skin of the Gila monster lizard for which it is named) are circumscribed, keratotic, fibrous growths over the dorsa of the interphalangeal joints.[1] They are described as well-defined, round, plaque-like, fibrous thickening that may develop at any age, and grow to be 10 to 15mm in diameter in the course of a few weeks or months, then go away over time.[2]
Knuckle pads are sometimes associated with Dupuytren's contracture[3] and camptodactyly,[2]:595 and histologically, the lesions are fibromas.[2]:595[4] Knuckle pads are generally non-responsive to treatment, including corticosteroids, and tend to recur after surgery; however, there has been some effectiveness with intralesional fluorouracil.[5]
## Contents
* 1 See also
* 2 References
* 3 Further reading
* 4 External links
## See also[edit]
* Skin lesion
* List of cutaneous conditions
* Garrod's pad
## References[edit]
1. ^ Mackey, SL; Cobb, MW (1994). "Knuckle pads". Cutis. 54 (3): 159–160. PMID 7813233.
2. ^ a b c James, WD; Berger, TG; Elston, DM (2005). Andrews' Diseases of the Skin: Clinical Dermatology (11th ed.). Saunders. p. 595. ISBN 0-7216-2921-0.
3. ^ Mikkelsen, Otto (October 1, 1977). "Knuckle Pads in Dupuytren's Disease". Journal of Hand Surgery. 9 (3): 301–305. doi:10.1016/S0072-968X(77)80121-6. Retrieved 27 October 2020.
4. ^ Meinecke, R; Lagier, R (September 1975). "Pathology of "knuckle pads"". Virchows Archiv. 365: 185–191. doi:10.1007/BF00434037. Retrieved 27 October 2020.
5. ^ Weiss, E; Amini, S (2007). "A Novel Treatment for Knuckle Pads With Intralesional Fluorouracil". Arch Dermatol. 143 (11): 1447–1462. doi:10.1001/archderm.143.11.1458. PMID 18025384.
## Further reading[edit]
* Guberman D; et al. (1996). ""Knuckle pads-a forgotten skin condition " report of a case and review of the literature". Cutis. 57: 241.
* Ly Y; et al. (2003). "A novel mutation of keratin 9 in epidermolytic palmoplantar keratoderma combined with knuckle pads". Am J Med Genet. 120A (3): 345–9. doi:10.1002/ajmg.a.20090. PMID 12838553.
* Peterson CM; et al. (2000). "Knuckle pads: does knuckle cracking play an etiologic role?". Pediatr Dermatol. 17 (6): 450–2. doi:10.1046/j.1525-1470.2000.01819.x. PMID 11123776.
## External links[edit]
* v
* t
* e
Soft tissue disorders
Capsular joint
Synoviopathy
* Synovitis/Tenosynovitis
* Calcific tendinitis
* Stenosing tenosynovitis
* Trigger finger
* De Quervain syndrome
* Transient synovitis
* Ganglion cyst
* osteochondromatosis
* Synovial osteochondromatosis
* Plica syndrome
* villonodular synovitis
* Giant-cell tumor of the tendon sheath
Bursopathy
* Bursitis
* Olecranon
* Prepatellar
* Trochanteric
* Subacromial
* Achilles
* Retrocalcaneal
* Ischial
* Iliopsoas
* Synovial cyst
* Baker's cyst
* Calcific bursitis
Noncapsular joint
Symptoms
* Ligamentous laxity
* Hypermobility
Enthesopathy/Enthesitis/Tendinopathy
upper limb
* Adhesive capsulitis of shoulder
* Impingement syndrome
* Rotator cuff tear
* Golfer's elbow
* Tennis elbow
lower limb
* Iliotibial band syndrome
* Patellar tendinitis
* Achilles tendinitis
* Calcaneal spur
* Metatarsalgia
* Bone spur
other/general:
* Tendinitis/Tendinosis
Nonjoint
Fasciopathy
* Fasciitis: Plantar
* Nodular
* Necrotizing
* Eosinophilic
Fibromatosis/contracture
* Dupuytren's contracture
* Plantar fibromatosis
* Aggressive fibromatosis
* Knuckle pads
This Dermal and subcutaneous growths article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
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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
| Knuckle pads | c0264000 | 809 | wikipedia | https://en.wikipedia.org/wiki/Knuckle_pads | 2021-01-18T18:37:42 | {"umls": ["C0264000"], "icd-9": ["728.79"], "icd-10": ["M72.1"], "wikidata": ["Q6423734"]} |
Cylindromas are non-cancerous (benign) tumors that develop from the skin. They most commonly occur on the head and neck and rarely become cancerous (malignant). An individual can develop one or many cylindromas; if a person develops only one, the cylindroma likely occurred by chance and typically is not inherited. They usually begin to form during mid-adulthood as a slow-growing, rubbery nodule that causes no symptoms. The development of multiple cylindromas can be hereditary and is inherited in an autosomal dominant manner; this condition is called CYLD cutaneous syndrome. Individuals with the inherited form begin to develop many, rounded nodules of various size shortly after puberty. The tumors grow very slowly and increase in number over time.
*[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
| Dermal eccrine cylindroma | c1305968 | 810 | gard | https://rarediseases.info.nih.gov/diseases/10345/dermal-eccrine-cylindroma | 2021-01-18T18:00:54 | {"mesh": ["C536611"], "umls": ["C1305968"], "synonyms": []} |
Mendelian susceptibility to mycobacterial diseases (MSMD) due to partial IRF8 (interferon regulatory factor 8) deficiency is a rare genetic variant of MSMD (see this term) characterized by a selective susceptibility to relatively mild infections with bacillus Calmette-Guérin (BCG)..
## Epidemiology
The prevalence is unknown. Only 2 cases in the world have been described to date.
## Clinical description
The first infections occur after vaccination with BCG and before the age of 2. They are relatively mild with manifestations of fever and lymphadenopathy. No other infectious diseases have been reported.
## Etiology
MSMD due to a partial IRF8 deficiency is caused by heterozygous mutations in the IRF8 gene on chromosome 16q24.1 which encodes IRF8, a protein essential for the development of dendritic cells and the differentiation of macrophages and granulocytes. Mutations in the IRF8 gene impairs IL-12 secretion by monocytes and dendritic cells.
## Genetic counseling
MSMD due to a partial IRF8 deficiency is inherited in an autosomal dominant manner so genetic counseling is possible.
*[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
| Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency | c3808589 | 811 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=319600 | 2021-01-23T17:44:18 | {"omim": ["614893"], "icd-10": ["D84.8"], "synonyms": ["MSMD due to partial IRF8 deficiency", "MSMD due to partial interferon regulatory factor 8 deficiency", "Mendelian susceptibility to mycobacterial diseases due to partial interferon regulatory factor 8 deficiency"]} |
Asparagine synthetase deficiency is a condition that causes neurological problems in affected individuals starting soon after birth. Most people with this condition have an unusually small head size (microcephaly) that worsens over time due to loss (atrophy) of brain tissue. They also have severe developmental delay that affects both mental and motor skills (psychomotor delay). Affected individuals cannot sit, crawl, or walk and are unable to communicate verbally or nonverbally. The few affected children who achieve developmental milestones often lose these skills over time (developmental regression).
Most individuals with asparagine synthetase deficiency have exaggerated reflexes (hyperreflexia) and weak muscle tone (hypotonia). The muscle problems worsen through childhood and lead to muscle stiffness, uncontrolled movements, and ultimately, paralysis of the arms and legs (spastic quadriplegia). Many affected individuals also have recurrent seizures (epilepsy). Not all affected people experience the same type of seizure. The most common types involve a loss of consciousness, muscle rigidity, and convulsions (tonic-clonic); involuntary muscle twitches (myoclonic); or abnormal muscle contraction (tonic). People with asparagine synthetase deficiency may have an exaggerated startle reaction (hyperekplexia) to unexpected stimuli. Some affected individuals have blindness due to impairment of the area of the brain responsible for processing vision, called the occipital cortex (cortical blindness).
People with asparagine synthetase deficiency typically do not survive past childhood.
## Frequency
Asparagine synthetase deficiency is thought to be a rare condition. More than 20 affected individuals have been described in the medical literature.
## Causes
Asparagine synthetase deficiency is caused by mutations in a gene called ASNS. This gene provides instructions for making an enzyme called asparagine synthetase. This enzyme is found in cells throughout the body, where it converts the protein building block (amino acid) aspartic acid to the amino acid asparagine.
In addition to being a component of proteins, asparagine helps to break down toxic ammonia within cells, is important for protein modification, and is needed for making a molecule that transmits signals in the brain (a neurotransmitter). Mutations in the ASNS gene that cause asparagine synthetase deficiency lead to a decrease or loss of functional enzyme. Asparagine from the diet likely makes up for the enzyme's inability to produce the amino acid in most cells. However, asparagine cannot cross the protective barrier that allows only certain substances to pass between blood vessels and the brain (the blood-brain barrier). As a result, brain cells in people with asparagine synthetase deficiency have a shortage (deficiency) of this amino acid. The exact effect of asparagine synthetase deficiency on brain cells is unknown, but because of the severe features of this condition, it is clear that asparagine is necessary for normal brain development.
### Learn more about the gene associated with Asparagine synthetase deficiency
* ASNS
## 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.
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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
| Asparagine synthetase deficiency | c3809971 | 812 | medlineplus | https://medlineplus.gov/genetics/condition/asparagine-synthetase-deficiency/ | 2021-01-27T08:24:55 | {"omim": ["615574"], "synonyms": []} |
Pancreatoblastoma
SpecialtyOncology
Pancreatoblastoma is a rare type of pancreatic cancer.[1]It occurs mainly in childhood[2][3] and has a relatively good prognosis.
## Contents
* 1 Symptoms
* 2 Pathology
* 3 Diagnosis
* 4 Treatment
* 5 See also
* 6 References
* 7 External links
## Symptoms[edit]
Children with pancreatoblastoma rarely present with early-stage disease, instead, most present with locally advanced or metastatic disease. Common presenting symptoms include abdominal pain, emesis, and jaundice. A multidisciplinary approach including good clinical history, state of the art imaging, and careful pathology is often needed to establish the correct diagnosis.[4]
## Pathology[edit]
Resected pancreatoblastomas can be quite large, ranging from 2 centimeters to 20 centimeters in size (1 to 8 inches). They are typically solid, soft masses. Under the microscope, at least two cell types are seen: cells with “acinar” differentiation, and cells forming small “squamoid” nests. The cells with acinar differentiation have some features of the normal acinar cell of the pancreas (the most common cell in the normal pancreas).[5]
## Diagnosis[edit]
This section is empty. You can help by adding to it. (March 2018)
## Treatment[edit]
If the tumor is operable, the first line of therapy should be surgical resection. Then, after surgical resection, adjuvant chemotherapy should be given, even in stage I disease. In patients with inoperable disease, chemotherapy alone should be given.[6] A multi-disciplinary approach to the treatment, including surgeons, oncologists, pathologists, radiologists, and radiation oncologists, is often the best approach to managing these patients.[4]
## See also[edit]
* Grayson Gilbert
## References[edit]
1. ^ "Pancreatoblastoma". Archived from the original on 2004-06-02.
2. ^ Saif MW (2007). "Pancreatoblastoma". JOP. 8 (1): 55–63. PMID 17228135.
3. ^ Naik VR, Jaafar H, Leow VM, Bhavaraju VM (March 2006). "Pancreatoblastoma: a rare tumour accidentally found" (PDF). Singapore Med J. 47 (3): 232–4. PMID 16518559.
4. ^ a b "Pancreatic Cancer Multi-Disciplinary Clinic at Johns Hopkins University".
5. ^ "Pancreatic Cancer Frequently Asked Questions".
6. ^ http://www.orpha.net/data/patho/GB/uk-pancrea.pdf -
## External links[edit]
Classification
D
* ICD-O: M8971/3
* MeSH: C537162 C537162, C537162
* v
* t
* e
Digestive system neoplasia
GI tract
Upper
Esophagus
* Squamous cell carcinoma
* Adenocarcinoma
Stomach
* Gastric carcinoma
* Signet ring cell carcinoma
* Gastric lymphoma
* MALT lymphoma
* Linitis plastica
Lower
Small intestine
* Duodenal cancer
* Adenocarcinoma
Appendix
* Carcinoid
* Pseudomyxoma peritonei
Colon/rectum
* Colorectal polyp: adenoma, hyperplastic, juvenile, sessile serrated adenoma, traditional serrated adenoma, Peutz–Jeghers
Cronkhite–Canada
* Polyposis syndromes: Juvenile
* MUTYH-associated
* Familial adenomatous/Gardner's
* Polymerase proofreading-associated
* Serrated polyposis
* Neoplasm: Adenocarcinoma
* Familial adenomatous polyposis
* Hereditary nonpolyposis colorectal cancer
Anus
* Squamous cell carcinoma
Upper and/or lower
* Gastrointestinal stromal tumor
* Krukenberg tumor (metastatic)
Accessory
Liver
* malignant: Hepatocellular carcinoma
* Fibrolamellar
* Hepatoblastoma
* benign: Hepatocellular adenoma
* Cavernous hemangioma
* hyperplasia: Focal nodular hyperplasia
* Nodular regenerative hyperplasia
Biliary tract
* bile duct: Cholangiocarcinoma
* Klatskin tumor
* gallbladder: Gallbladder cancer
Pancreas
* exocrine pancreas: Adenocarcinoma
* Pancreatic ductal carcinoma
* cystic neoplasms: Serous microcystic adenoma
* Intraductal papillary mucinous neoplasm
* Mucinous cystic neoplasm
* Solid pseudopapillary neoplasm
* Pancreatoblastoma
Peritoneum
* Primary peritoneal carcinoma
* Peritoneal mesothelioma
* Desmoplastic small round cell tumor
* 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
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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
| Pancreatoblastoma | c0334489 | 813 | wikipedia | https://en.wikipedia.org/wiki/Pancreatoblastoma | 2021-01-18T18:38:16 | {"gard": ["4210"], "mesh": ["C537162"], "umls": ["C0334489"], "orphanet": ["677"], "wikidata": ["Q7130423"]} |
A number sign (#) is used with this entry because of evidence that the disorder is caused by duplication of mitochondrial DNA.
Rotig et al. (1992) reported the cases of 2 sisters who presented in the first year of life because of failure to thrive and were found to have a severe proximal tubulopathy with polyuria and loss of potassium, sodium, calcium, and chloride. A mottled pigmentation was present in photoexposed areas (forearms, legs, and cheeks), and episodes of cold-triggered erythrocyanosis of the toes and fingers were noted. The older sister developed fatal diarrhea, vomiting, and dehydration at the age of 5 years. The second sister developed a severe episode of diarrhea and dehydration at the age of 3 years. Although she survived this episode, she subsequently developed extraocular muscle palsy, lid ptosis, pigmentary deposits of the retina, and extinguished electroretinogram. Osteoporosis and rickets were detected as well as liver enlargement. In her fifth year, insulin-dependent diabetes mellitus was found, and she gradually developed cerebellar ataxia and hypotonia with deafness, blindness, myoclonic jerks, and psychomotor regression. Death occurred at the age of 8 years. In this family the mother had gradually developed bilateral extraocular muscle palsy with lid ptosis and micropunctated tapetoretinal degeneration in early adulthood. She also developed myopia, hypoacusis, and muscle weakness after her first pregnancy. The 2 sisters described were her only children. Using polymerase chain reaction (PCR) amplification of lymphocyte DNA, Rotig et al. (1992) detected minute amounts of duplicated mtDNA molecules in the mother. Skeletal muscle and lymphocytes of the younger sister had demonstrated complex III deficiency. Southern blot analysis provided evidence for a heteroplasmic partial duplication of mtDNA (26 kb), involving one full-length and one partly deleted mitochondrial genome and with a single abnormal junction between the genes for ATPase 6 and cytochrome b.
INHERITANCE \- Mitochondrial GROWTH Other \- Failure to thrive HEAD & NECK Ears \- Deafness Eyes \- Extraocular muscle palsy \- Ptosis \- Pigmentary retinal deposits \- Blindness \- Extinguished electroretinogram ABDOMEN Liver \- Hepatomegaly Gastrointestinal \- Diarrhea \- Vomiting GENITOURINARY Kidneys \- Proximal tubulopathy \- Polyuria SKELETAL \- Osteoporosis \- Rickets SKIN, NAILS, & HAIR Skin \- Mottled pigmentation of photoexposed areas \- Episodic cold-triggered erythrocyanosis of toes and fingers NEUROLOGIC Central Nervous System \- Ataxia \- Hypotonia \- Myoclonic jerks \- Psychomotor regression METABOLIC FEATURES \- Dehydration ENDOCRINE FEATURES \- Insulin-dependent diabetes mellitus LABORATORY ABNORMALITIES \- Urinary loss of potassium, sodium, calcium, and chloride \- Heteroplasmic partial duplication of mtDNA MOLECULAR BASIS \- Caused by partial duplication of mtDNA ▲ 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
| RENAL TUBULOPATHY, DIABETES MELLITUS, AND CEREBELLAR ATAXIA | c3151959 | 814 | omim | https://www.omim.org/entry/560000 | 2019-09-22T16:16:46 | {"omim": ["560000"], "orphanet": ["3390"], "synonyms": []} |
Post-traumatic leakage of sperm provoking a granulomatous reaction.
A sperm granuloma is a lump of extravasated sperm that appears along the vasa deferentia or epididymides in vasectomized men. Sperm granulomas are rounded or irregular in shape, one millimeter to one centimeter or more, with a central mass of degenerating sperm surrounded by tissue containing blood vessels and immune system cells.[1] Sperm granulomas can be either asymptomatic or symptomatic (i.e., either not painful or painful, respectively) (see post-vasectomy pain syndrome).
The vast majority of sperm granulomas in vasectomized men are present as a result of the pressure-induced changes of vasectomy.[2]
## References[edit]
1. ^ McDonald S. "Cellular responses to vasectomy." International Review of Cytology. 2000;199:295-339. PMID 10874581
2. ^ Silber S. "Reversal of vasectomy and the treatment of male infertility: role of microsurgery, vasoepididymostomy, and pressure-induced changes of vasectomy." Urologic Clinics of North America. 1981;8:53-62. PMID 7210354
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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
| Sperm granuloma | c0333416 | 815 | wikipedia | https://en.wikipedia.org/wiki/Sperm_granuloma | 2021-01-18T19:01:40 | {"umls": ["C0333416"], "wikidata": ["Q1169972"]} |
Digestive duplication is a rare developmental defect during embryogenesis characterized by cystic, spherical or tubular structures (communicating or not with the lumen), located on a segment of the digestive tract (from the mouth cavity to anus), and constituted of a wall with a double smooth muscle layer and a digestive mucosa. The malformation may be asymptomatic or manifest with various signs including abdominal mass, abdominal pain, transit troubles or subocclusive syndrome. Mild digestive hemorrhage, perforation, pancreatitis and neonatal respiratory distress are possible complications.
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*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Digestive duplication | None | 816 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=238 | 2021-01-23T18:35:24 | {"icd-10": ["Q45.8"]} |
Sommer et al. (1974) reported a brother and sister with this syndrome. The children had congenital glaucoma, telecanthus and frontal bossing as well. The parents were not related. Searches for abnormality in chromosome 11p with 'banding' methods might be worthwhile in light of the deletion found in cases of the WAGR syndrome (194070). The condition (109120) reported by De Hauwere et al. (1973) bore some similarity.
Neuro \- Mental retardation Head \- Frontal bossing GU \- Unilateral renal agenesis Eyes \- Partial aniridia \- Congenital glaucoma \- Telecanthus Inheritance \- Autosomal recessive ▲ Close
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*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| ANIRIDIA, PARTIAL, WITH UNILATERAL RENAL AGENESIS AND PSYCHOMOTOR RETARDATION | c1859782 | 817 | omim | https://www.omim.org/entry/206750 | 2019-09-22T16:30:56 | {"mesh": ["C000598722"], "omim": ["206750"], "orphanet": ["1064"]} |
For a phenotypic description and a discussion of genetic heterogeneity of colorectal cancer, see 114500.
Mapping
In a metaanalysis of 2 previously published genomewide association (GWA) studies (Tomlinson et al., 2008; Tenesa et al., 2008) comprising 13,315 individuals, Houlston et al. (2008) found an association between susceptibility to colorectal cancer and rs961253 on chromosome 20p12.3 within an area bereft of genes (p = 8.9 x 10(-7)). Pooling data from 4 independent case-control series comprising 13,408 individuals with the GWA series yielded a combined p value of 2.0 x 10(-10) for rs961253.
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*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| COLORECTAL CANCER, SUSCEPTIBILITY TO, 11 | c2675480 | 818 | omim | https://www.omim.org/entry/612592 | 2019-09-22T16:01:01 | {"omim": ["612592"], "synonyms": ["Alternative titles", "COLORECTAL CANCER, SUSCEPTIBILITY TO, ON CHROMOSOME 20p"]} |
"Balis" redirects here. It is not to be confused with Barbalissos.
For the surname, see Bališ.
Usog or balis is a topic in psycho-medicine in Filipino Psychology (but considered just as a Filipino superstition in Western Psychology) where an affliction or psychological disorder is attributed to a greeting by a stranger, or an evil eye hex. It usually affects an unsuspecting child, usually an infant or toddler, who has been greeted by a visitor or a stranger.[1]
In some limited areas, it is said that the condition is also caused by the stranger having an evil eye or masamang mata in Tagalog, lurking around. This may have been influenced by the advent of the Spaniards who long believed in the mal de ojo superstition.
Once affected, the child begins to develop fever, and sometimes convulsions. Supposedly, the child can be cured by placing its clothing in hot water and boiling it. In most other places, to counter the effects of the "usog" the stranger or newcomer is asked to put some of his or her saliva on the baby's abdomen, shoulder or forehead before leaving the house. The newcomer then leaves while saying: "Pwera usog... pwera usog..." The saliva is placed on the finger first, before the finger is rubbed on the baby's abdomen or forehead. The stranger is never to lick the child.[2] The practice is that the stranger or visitor is asked to touch his or her finger with saliva to the child's body, arm or foot ("lawayan") to prevent the child from getting overpowered ("upang hindi mausog").
## Possible scientific explanation[edit]
One theory (Kristina Palacio)[3][4] explains usog in terms of child distress that leads to greater susceptibility to illness and diseases. There are observations that a stranger (or a newcomer or even a visiting relative) especially someone with a strong personality (physically big, boisterous, has strong smell, domineering, etc.) may easily distress a child. Thus, the child is said to be "overpowered" or nauusog and thus may feel afraid, develop fever, get sick, etc.[5]
In usog, the child's distress is the consequence of the child's failure to adapt to change. It is, in medical terms, the consequence of the disruption of homeostasis through physical or psychological stimuli brought about by the stranger.[6] Technically, the condition results from the child-environment interaction that leads the child to perceive a painful discrepancy, real or imagined, between the demands of a situation on the one hand and their social, biological, or psychological resources on the other. The stressful stimuli to the child may be mental (stranger is perceived as a threat, malevolent or demanding), physiological (loud and/or high-pitched voice of the stranger that is hurting to the child's eardrum; strong smell of the stranger that irritates the child's nasal nerves), or physical (stranger has heavy hands or is taking up too much space).
The stranger's act of gently placing his finger with his saliva to the child's arm, foot, or any particular part of the child's body, could make him more familiar to the child, and thus, reduce if not remove the stress. As the stranger keeps gently saying, "Pwera usog... pwera usog...," the child is made to feel and assured that he means no harm. The usog is said to be counteracted because the child is prevented from succumbing to an illness since the child is no longer in distress. Children or even adults who are shy or have weak personalities are more susceptible to usog in accordance with observations and theory. Some have observed that at times even praising a shy child by a visiting relative caused an usog.[4][7]
The saliva from the stranger, granted that he or she is healthy and consistent with his or her oral hygiene, is relatively clean[8] and contains enough antimicrobial compounds such as lactoferrin, lactoperoxidase, and secretory immunoglobulin A which can help clear pathogens from the child and benefit the child against infection.[9] Furthermore, human saliva has opiorphin, a newly researched pain-killing substance. Initial research with mice shows the compound has a painkilling effect of up to six times that of morphine. It works by stopping the normal breakdown of natural pain-killing opioids in the spine, called enkephalins. Opiorphin in human saliva is a relatively simple molecule, and the child's immune system may trigger a biochemical cascade (complement system) to produce other stress-reducing compounds.[10][11][12][13]
Usog can also, though less commonly, affect adults, and it may induce vomiting and stomach ache rather than fever. Supposedly, it can be prevented by stopping a stranger or visitor from greeting the person.
Unlike "lihi", however, usog is not yet medically accepted. More than the superstitious folks, researchers dealing with Filipino Psychology say they have observed this phenomenon with regularity and suggest that this be added to the Psychiatric Disorders Handbook DSM-V.[4]
## See also[edit]
* Evil eye
* Lihi
* Albulario
* Saliva
* Opiorphin
## References[edit]
1. ^ PWE-USOG / PWE-BUYAG: Miscellaneous Therapies in Philippine Alternative Medicine
2. ^ http://www.viloria.com/secondthoughts/archives/00000176.html
3. ^ Fadul, J. Public Forum on Witchcraft and Illnesses. Rizal Technological and Polytechnic Institute, Morong, Rizal. July 24, 1988.
4. ^ a b c 100% PINOY (Kapuso Network's cultural program on GMA7 featuring Filipino Culture and Ingenuity to strengthen the Filipino identity.) Aired internationally through GMA Pinoy TV. "Bata, bata, paano ka ginawa?" episode aired August 28, 2008. Pinoy culture, beliefs and practices about "paglilihi, pagbubuntis, panganganak at pag-aalaga sa bata".
5. ^ Cohen S, Janicki-Deverts D, Miller GE (2007). "Psychological stress and disease". JAMA. 298 (14): 1685–7. doi:10.1001/jama.298.14.1685. PMID 17925521. "Stress Contributes To Range Of Chronic Diseases, Review Shows" ScienceDaily.com (Oct. 10, 2007) [1]
6. ^ Tan, Michael (2008). Revisiting Usog, Pasma, Kulam. Quezon City: University of the Philippines Press. p. 178. ISBN 978-971-542-570-4.
7. ^ Youtube Usog
8. ^ http://neurophilosophy.wordpress.com/2006/11/14/lick-your-wounds/ Neurophilosophy: Lick your wounds
9. ^ Discover Magazine, "The Biology of ...Saliva" October 2005
10. ^ Wisner, Anne; Evelyne Dufour; Michaël Messaoudi; Amine Nejdi; Audrey Marcel; Marie-Noelle Ungeheuer; Catherine Rougeot (November 13, 2006). "Human Opiorphin, a natural antinociceptive modulator of opioid-dependent pathways". Proceedings of the National Academy of Sciences. 103 (47): 17979–17984. Bibcode:2006PNAS..10317979W. doi:10.1073/pnas.0605865103. PMC 1693858. PMID 17101991.
11. ^ Andy Coghlan (November 13, 2006). "Natural-born painkiller found in human saliva". New Scientist.
12. ^ "Natural chemical 'beats morphine'". BBC News. November 14, 2006.
13. ^ Mary Beckman (November 13, 2006). "Prolonging Painkillers". ScienceNOW.
* v
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Superstition
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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
| Usog | None | 819 | wikipedia | https://en.wikipedia.org/wiki/Usog | 2021-01-18T18:57:37 | {"wikidata": ["Q7902079"]} |
Dens in dente and deep palatal invaginations (lingual pits) of the secondary maxillary lateral incisors may be inherited as an autosomal dominant. Grahnen et al. (1959) found in a study of 3,000 Swedish children a frequency of about 3%. In 58 families studied, a similar defect was found in over one-third of parents. In the same family some had dens in dente and others had deep lingual pits. Lingual pits offer a favorable setting for development of caries.
Inheritance \- Autosomal dominant Teeth \- Dens in dente \- Lingual pits ▲ Close
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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
| DENS IN DENTE AND PALATAL INVAGINATIONS | c1852250 | 820 | omim | https://www.omim.org/entry/125300 | 2019-09-22T16:42:30 | {"mesh": ["C538211"], "omim": ["125300"]} |
## Clinical Features
Van Lohuizen (1922) described a child with livedo reticularis, telangiectases, and superficial ulceration. Way et al. (1974) found that all reported cases had been sporadic. Andreev and Pramatarov (1979) reported 2 adult sisters with CMTC. Onset was at birth in both. One developed hypertension at age 16 years.
Kurczynski (1982) described the case of a 4-year-old girl whose father and paternal grandmother were said to be identically affected in childhood with improvement by adulthood. Robinow (1985) saw 2 cases of CMTC in seemingly unrelated children of German ancestry living near each other in Ohio.
Shields et al. (1990) described a female child in whom CMTC was associated with congenital bilateral total retinal detachments and secondary neovascular glaucoma. Retinal detachments produced bilateral leukocoria simulating retinoblastoma.
In a report of a patient with CMTC who also had congenital hypothyroidism, Pehr and Moroz (1993) noted that two-thirds of patients with CMTC have other associated anomalies. Lingier et al. (1992) reported 4 cases with prominent phlebectasia. Dutkowsky et al. (1993) reported leg-length discrepancies, and Kennedy et al. (1992) noted that 2 patients had a short leg that was also thinner. They also reported associated tendinitis stenosans (stenosing tendinitis) and bowing of the lower legs.
Toriello et al. (1988) described CMTC in association with Adams-Oliver syndrome (100300).
Ben-Amitai et al. (2001) noted that fewer than 300 cases of CMTC had been reported in the world literature. The first association of CMTC with congenital anomalies, namely, Sturge-Weber syndrome (185300) and patent ductus arteriosus (607411), was described by Petrozzi et al. (1970). Associated malformations are thought to occur in approximately 20 to 40% of affected individuals (Picascia and Esterly, 1989; Devillers et al., 1999; Ben-Amitai et al., 2000). Ben-Amitai et al. (2001) reported the occurrence of hypospadias in 4 patients in a series of 52 Israeli males with CMTC (7.69%), which is more than 13 times the rate of isolated hypospadias in this population. Ben-Amitai et al. (2001) suggested that hypospadias may be an associated noncutaneous feature of CMTC.
Torrelo et al. (2003) reported 2 patients with an unusual association of extensive cutis marmorata telangiectatica congenita and aberrant mongolian spots. They asserted that this association is best explained as a phenomenon of nonallelic twin spotting and suggested that this condition may be a novel variant form of phacomatosis pigmentovascularis.
Hinek et al. (2008) reported a 16-month-old boy with CMTC and generalized vascular abnormalities. At birth, he had multiple bluish-red reticulated bands scattered over the entire skin surface and associated with ulcerations. Dilated veins over the face, scalp, and abdomen were also noted. After 2 to 3 months, the ulcerations had healed well, while the bluish-red reticulated marks and the dilated veins persisted. He had a retinal bleed at age 7 months, and showed developmental delay, seizures, and extensive periventricular white matter calcifications on brain imaging. At 14 months, he was found to have severe pulmonary hypertension with significant tricuspid insufficiency and right heart failure. An open lung biopsy demonstrated marked hyperplasia of medial smooth muscle and small pulmonary arteries. He died at age 20 months from persistent severe hypoxemia. Postmortem examination showed abnormal pulmonary arteries and veins, with irregular thick elastic lamina in the media. Laboratory studies showed increased blood copper levels. Studies of dermal fibroblasts from the patient showed normal tropoelastin (ELN; 130160) synthesis, but decreased deposition of mature elastic fibers that appeared to result from heightened elastolysis. Further studies indicated that the increased elastolysis was due to copper-dependent inactivation of alpha-1-antitrypsin (PI; 107400). The cells also produced more reactive oxygen species. Hinek et al. (2008) suggested that a high level of free copper in this patient was a major triggering factor contributing to the development of the CMTC phenotype.
Molecular Genetics
### Associations Pending Confirmation
For discussion of a possible association between variation in the ARL6IP6 gene and cutis marmorata telangiectatica congenita, see 616495.0001.
Limbs \- Short leg \- Thin leg \- Tendinitis, stenosing \- Bowed legs Inheritance \- Autosomal recessive Misc \- Skin lesions improve with age Eyes \- Congenital retinal detachment \- Neovascular glaucoma \- Leukocoria Skin \- Livedo reticularis \- Telangiectases \- Superficial ulceration \- Phlebectasia Cardiac \- Hypertension ▲ 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
| CUTIS MARMORATA TELANGIECTATICA CONGENITA | c0345419 | 821 | omim | https://www.omim.org/entry/219250 | 2019-09-22T16:29:12 | {"mesh": ["C536226"], "omim": ["219250"], "orphanet": ["1556"]} |
A number sign (#) is used with this entry because myofibrillar myopathy-4 (MFM4) is caused by heterozygous mutation in the ZASP gene (LDB3; 605906) on chromosome 10.
For a phenotypic description and a discussion of genetic heterogeneity of myofibrillar myopathy (MFM), see MFM1 (601419).
Clinical Features
Selcen and Engel (2005) reported 11 unrelated patients with MFM. Age at onset ranged from 44 to 73 years (mean, 54 years). All patients presented with muscle weakness except 1 who presented with palpitations and mildly increased serum creatine kinase. Several patients had family histories consistent with autosomal dominant inheritance. Five patients had more prominent distal weakness than proximal weakness; 1 had only distal weakness, 2 had only proximal weakness, and 3 had both proximal and distal weakness. Three patients had cardiac involvement, and 5 patients had peripheral nerve involvement. EMG showed myopathic changes in 8 patients and both myopathic and neurogenic changes in 2 patients. Ten patients had abnormal electrical irritability. All patients showed MFM on skeletal muscle biopsy, including pleomorphic hyaline, granular, and amorphous deposits on trichrome staining. Ten patients had intensely congophilic hyaline structures, indicating amyloid material. A variable number of fibers had small vacuoles. Immunohistochemistry showed multiple protein deposits, and electron microscopy showed streaming and disintegration of the Z discs, as well as degraded and fragmented filaments in autophagic vacuoles. Selcen and Engel (2005) noted that the clinical and laboratory features of the patients were similar to those in other forms of MFM.
Molecular Genetics
In 11 of 54 unrelated patients with MFM, Selcen and Engel (2005) identified 3 different heterozygous mutations in the ZASP gene (605906.0001-605906.0003).
INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Cardiomyopathy (less common) MUSCLE, SOFT TISSUES \- Muscle weakness, progressive, distal \- Muscle weakness, progressive, proximal \- Patients may have distal or proximal muscle weakness, or both \- EMG shows myopathic changes \- EMG shows fibrillation potentials \- EMG may show neurogenic changes \- Muscle biopsy shows myofibrillar changes \- Muscle biopsy shows pleomorphic hyaline, granular, and amorphous deposits that stain with Gomori trichrome \- Congophilic deposits \- Autophagic vacuoles \- Fiber splitting \- Internal nuclei \- Isolated necrotic fibers \- Z-disk degeneration \- Immunoreactivity for Z-disk proteins NEUROLOGIC Peripheral Nervous System \- Peripheral neuropathy \- Hyporeflexia in lower limbs LABORATORY ABNORMALITIES \- Increased serum creatine kinase \- Serum creatine kinase may be normal MISCELLANEOUS \- Onset in late adulthood (44 to 73 years) MOLECULAR BASIS \- Caused by mutation in the lim domain-binding 3 gene (LDB3, 605906.0001 ) ▲ 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
| MYOPATHY, MYOFIBRILLAR, 4 | c1836155 | 822 | omim | https://www.omim.org/entry/609452 | 2019-09-22T16:06:02 | {"doid": ["0080095"], "mesh": ["C563718"], "omim": ["609452"], "orphanet": ["98912"]} |
A number sign (#) is used with this entry because of evidence that high myopia with cataract and vitreoretinal degeneration (MCVD) is caused by homozygous mutation in the LEPREL1 gene (P3H2; 610341) on chromosome 3q28.
Clinical Features
Mordechai et al. (2011) studied a large consanguineous Israeli Bedouin kindred segregating autosomal recessive nonsyndromic severe myopia with variable expressivity of cataract and vitreoretinal degeneration. The 13 affected family members all presented with poor eyesight in childhood, and all had axial myopia, with increased axial lengths ranging between 25.1 mm and 30.5 mm. Eleven patients developed cataracts that were significant enough to warrant surgery in 1 or both eyes, usually in the first or second decade of life. In 3 patients, subluxated lenses were detected, and were associated with cataract in 2 patients and with lens coloboma in 1 patient. In an additional 5 patients, lens instability due to weak or partially missing lens zonules was found during cataract surgery, resulting in postoperative aphakia in 4 patients because it was impossible to insert the intraocular lens. Peripheral vitreoretinal degenerative changes were observed in 9 of the 13 affected family members, 4 of whom developed retinal tears causing retinal detachment in 1 or both eyes. In 3 patients, surgically unresponsive retinal detachments led to blindness in 1 eye. Examination by a clinical geneticist revealed no apparent dysmorphology in any of the affected individuals.
Guo et al. (2014) reported a consanguineous Chinese family in which 3 sibs had normal vision at birth but presented before 10 years of age with severe myopia (less than -12.00 diopters), followed by early-onset cataract and other ocular abnormalities. Axial lengths ranged between 28.0 mm and 32.2 mm. The proband was a male patient with severely myopic vision in both eyes, who underwent cataract extraction at 45 years of age. Funduscopy showed tigroid fundus and retinal choroid atrophy at the posterior pole. An older affected sister was blind in both eyes following cataract extraction when recruited for study. A younger sister had bilateral vision with high myopia and cataract. On funduscopy, the fundus appeared tigroid, and there was focal atrophy of choroid; in addition, the reflex of the central fovea of the macula was dull. Type B ultrasonography and optical coherence tomography also showed vitreous opacity and macular epiretinal membrane.
Khan et al. (2015) described 4 affected sisters from a consanguineous Saudi family with lens subluxation and juvenile lens opacities. The proband was a 14-year-old girl with long-standing poor vision, in whom examination revealed asymmetric bilateral temporal lens subluxation and crystalline lens opacities that were worse in the right eye. Her 22-year-old sister, who had cataract surgery at age 14 years, developed bilateral retinal breaks postoperatively that were treated with peripheral laser. At age 20, she underwent pars plana vitrectomy and scleral band placement for inferonasal rhegmatogenous detachment in the left eye. The proband's 15-year-old sister had bilateral cataract surgery at age 7 years, and had multiple bilateral rhegmatogenous retinal detachments postoperatively. The youngest sister, aged 10 years, underwent lensectomy and anterior vitrectomy for bilateral temporal lens subluxation at age 8 years. In addition, the proband had bilateral axial lengths of more than 27 mm, and 2 of her sisters had refraction values that were also indicative of long axial lengths.
Mapping
In a large consanguineous Israeli Bedouin kindred segregating autosomal recessive nonsyndromic severe myopia with cataract and vitreoretinal degeneration, Mordechai et al. (2011) performed genomewide linkage analysis followed by fine mapping that indicated a minimal candidate interval of 1.7 Mb (about 4 cM) on chromosome 3q28, with a lod score of 11.5 for marker D3S1314 (theta = 0).
Molecular Genetics
In a large consanguineous Israeli Bedouin kindred with nonsyndromic severe myopia with cataract and vitreoretinal degeneration mapping to chromosome 3q28, Mordechai et al. (2011) analyzed 6 candidate genes and identified homozygosity for a missense mutation in the LEPREL1 gene (G508V; 610341.0001) that segregated fully with disease in the family and was not found in 200 ethnically matched controls.
In 3 affected individuals from a Chinese family with high myopia and early-onset cataract with vitreoretinal degeneration, Guo et al. (2014) identified homozygosity for a nonsense mutation in the LEPREL1 gene (Q5X; 610341.0002). The mutation segregated with disease in the family and was not found in 526 Chinese controls.
In 4 affected sisters from a consanguineous Saudi family with high myopia, juvenile cataract, lens dislocation, and retinal detachment, Khan et al. (2015) sequenced the candidate gene LEPREL1 and identified homozygosity for a 1-bp deletion (610341.0003). Unaffected family members were heterozygous for the mutation. Noting that 2 of the sisters presented with lens subluxation, Khan et al. (2015) stated that LEPREL1-associated ectopia lentis is distinguishable by the presence of juvenile lens opacities and axial myopia; they also noted that there appears to be a predisposition for retinal tears/detachment following intraocular surgery.
INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- High myopia \- Increased axial length of globe \- Cataract \- Lens subluxation (in some patients) \- Lens instability (in some patients) \- Peripheral vitreoretinal degeneration \- Retinal detachment (in some patients) \- Tigroid-appearing fundus (in some patients) \- Choroid atrophy (in some patients) \- Dull-appearing central foveal reflex (rare) MOLECULAR BASIS \- Caused by mutation in leprecan-like-1 gene (LEPREL1, 610341.0001 ) ▲ 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
| MYOPIA, HIGH, WITH CATARACT AND VITREORETINAL DEGENERATION | c0027092 | 823 | omim | https://www.omim.org/entry/614292 | 2019-09-22T15:55:48 | {"mesh": ["D009216"], "omim": ["614292"], "orphanet": ["98619"]} |
Hyperphosphatasia with mental retardation syndrome
Other namesimage_size = 240px
This condition is inherited in an autosomal recessive manner
Hyperphosphatasia with mental retardation syndrome, HPMRS,[1] also known as Mabry syndrome,[2] has been described in patients recruited on four continents world-wide.[3] Mabry syndrome was confirmed[4] to represent an autosomal recessive syndrome characterized by severe mental retardation, considerably elevated serum levels of alkaline phosphatase, hypoplastic terminal phalanges, and distinct facial features that include: hypertelorism, a broad nasal bridge and a rectangular face.
## Contents
* 1 Pathogenesis
* 2 Diagnosis
* 3 Treatment
* 4 References
* 5 External links
## Pathogenesis[edit]
While many cases of HPMRS are caused by mutations in the PIGV gene,[5] there may be genetic heterogeneity in the spectrum of Mabry syndrome as a whole.[6] PIGV is a member of the molecular pathway that synthesizes the glycosylphosphatidylinositol anchor.[7] The loss in PIGV activity results in a reduced anchoring of alkaline phosphatase to the surface membrane and an elevated alkaline phosphatase activity in the serum.[citation needed]
## Diagnosis[edit]
This section is empty. You can help by adding to it. (July 2017)
## Treatment[edit]
This section is empty. You can help by adding to it. (July 2017)
## References[edit]
1. ^ Mabry CC, Bautista A, Kirk RF, Dubilier LD, Braunstein H, Koepke JA (1970). "Familial hyperphosphatasia with mental retardation, seizures, and neurologic deficits". The Journal of Pediatrics.77(1):74-85.
2. ^ Thompson MD, Nezarati MM, Gillessen-Kaesbach G, Meinecke P, Mendoza R, Mornet E, Brun-Heath I, Prost-Squarcioni C, Legeai-Mallet L, Munnich A, Cole DE (2010). "Hyperphosphatasia with seizures, neurologic deficit, and characteristic facial features: Five new patients with Mabry syndrome". American Journal of Medical Genetics. 152A(7):1661-1669.
3. ^ Thompson MD, Killoran A, Percy ME, Nezarati M, Cole DE, Hwang PA (2006). "Hyperphosphatasia with neurologic deficit: a pyridoxine-responsive seizure disorder?". Pediatric Neurology. 34(4):303-7.
4. ^ D Horn; G Schottmann, P Meinecke (2010). "Hyperphosphatasia with mental retardation, brachytelephalangy, and a distinct facial gestalt: Delineation of a recognizable syndrome". European Journal of Medical Genetics. 53(2):85-8.
5. ^ Krawitz PM, Schweiger MR, Rödelsperger C, Marcelis C, Kölsch U, Meisel C, Stephani F, Kinoshita T, Murakami Y, Bauer S, Isau M, Fischer A, Dahl A, Kerick M, Hecht J, Köhler S, Jäger M, Grünhagen J, de Condor BJ, Doelken S, Brunner HG, Meinecke P, Passarge E, Thompson MD, Cole DE, Horn D, Roscioli T, Mundlos S, Robinson PN (2010). "Identity-by-descent filtering of exome sequence data identifies PIGV mutations in hyperphosphatasia mental retardation syndrome". Nature Genetics. 42(10):827-9.
6. ^ Thompson MD, Roscioli T, Nezarati MM, Sweeney E, Meinecke P, Krawitz PM, Mabry CC, Horn D, Mendoza R, van Bokhoven H, Stephani F, Marcelis C, Munnich A, Brunner HB, Cole DE (2010). "Heterogeneity of Mabry syndrome: hyperphosphatasia with seizures, neurologic deficit and characteristic facial features". 60. American Society of Human Genetics. 60:892A. 892.
7. ^ Ji Young Kang; Yeongjin Hong; Hisashi Ashida; Nobue Shishioh; Yoshiko Murakami; Yasu S. Morita; Yusuke Maeda; Taroh Kinoshita (2004). "PIG-V Involved in Transferring the Second Mannose in Glycosylphosphatidylinositol". The Journal of Biological Chemistry. 280(10):9489-9497.
## External links[edit]
Classification
D
* OMIM: 239300
External resources
* Orphanet: 247262
* v
* t
* e
Inborn error of lipid metabolism: Phospholipid metabolism disorders
Tafazzin
* 3-Methylglutaconic aciduria 2 (Barth syndrome)
* CMD3A
Other
* Paroxysmal nocturnal hemoglobinuria
* Hyperphosphatasia with mental retardation syndrome
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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
| Hyperphosphatasia with mental retardation syndrome | c1855923 | 824 | wikipedia | https://en.wikipedia.org/wiki/Hyperphosphatasia_with_mental_retardation_syndrome | 2021-01-18T18:56:51 | {"mesh": ["C565495"], "umls": ["C1855923"], "orphanet": ["247262"], "wikidata": ["Q3144186"]} |
## Summary
### Clinical characteristics.
Laing distal myopathy is characterized by early-onset weakness (usually before age 5 years) that initially involves the dorsiflexors of the ankles and great toes and then the finger extensors, especially those of the third and fourth fingers. Weakness of the neck flexors is seen in most affected individuals and mild facial weakness is often present. After distal weakness has been present for more than ten years, mild proximal weakness may be observed. Life expectancy is normal.
### Diagnosis/testing.
Diagnosis relies on clinical findings and the identification of a heterozygous pathogenic variant in MYH7.
### Management.
Treatment of manifestations: Physiotherapy to prevent or treat tightening of the tendo Achilles is helpful. In more advanced cases, lightweight splinting of the ankle (e.g., with an ankle-foot orthosis) can be useful.
Surveillance: Annual neurologic examination; regular evaluation for scoliosis/kyphoscoliosis (especially during rapid growth); repeat electrocardiogram and echocardiogram if symptoms of cardiac insufficiency occur; respiratory assessment if symptoms suggest sleep apnea / sleep-related respiratory insufficiency.
### Genetic counseling.
Laing distal myopathy is inherited in an autosomal dominant manner. Approximately 65%-70% of affected individuals have an affected parent; de novo mutation of MYH7 accounts for 30%-35% of cases. Each child of an affected individual has a 50% chance of inheriting the pathogenic variant. Prenatal testing for pregnancies at increased risk is possible for families in which the pathogenic variant has been identified.
## Diagnosis
### Suggestive Findings
Laing distal myopathy is suggested in individuals with the following findings [Hedera et al 2003, Lamont et al 2006, Lamont et al 2014]:
* Initial weakness of the great toe and ankle dorsiflexors, eventually leading to a high-stepping gait and secondary tightening of the tendo Achilles. Onset is usually before age five years, but rarely may be later (≤4th decade).
* Subsequent weakness of the finger extensors (onset from months to 3 decades after lower-limb weakness) often accompanied by an action tremor of the hands
* Mild involvement of the facial musculature, particularly of the orbicularis oculi and oris muscles
* Early weakness of neck flexion in most families. Of note, in one family, weakness did not occur until the sixth decade.
* Very slow progression of weakness with gradual involvement of the proximal leg and trunk muscles. Rarely a wheelchair is required for mobility.
* Spinal complications (kyphoscoliosis, spinal rigidity, spinal extensor muscle contractures) in one third of patients
* Cardiac complications (hypertrophic cardiomyopathy with onset from birth to 3rd decade of life, dilated cardiomyopathy with onset from birth to 2nd decade of life) in one third of patients
* Family history consistent with autosomal dominant inheritance. Of note, one third of affected individuals have a de novo pathogenic variant [Lamont et al 2014].
* Serum creatine kinase concentration that is usually normal, but may in rare cases be as high as eight times the upper limit of normal
* Nerve conduction studies normal
* Electromyographic findings that are nonspecific, with occasional fibrillation potentials but no prolonged or large motor unit potentials [Zimprich et al 2000]
### Establishing the Diagnosis
The diagnosis of Laing distal myopathy is established in a proband with a heterozygous pathogenic variant in MYH7, encoding the protein myosin heavy chain, cardiac muscle beta isoform (see Table 1).
Molecular testing approaches can include the following:
* Single-gene testing. Sequence analysis of MYH7 exons 32-39 from genomic DNA should detect the majority of pathogenic variants associated with this phenotype; however, Darin et al [2007] identified the pathogenic variant p.Thr441Met in exon 14 associated with a Laing distal myopathy and cardiomyopathy.
* A multigene panel that includes MYH7 and other genes of interest (see Differential Diagnosis). Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
### Table 1.
Molecular Genetic Testing Used in Laing Distal Myopathy
View in own window
Gene 1MethodProportion of Probands with a Pathogenic Variant Detectable by Method
MYH7Sequence analysis 2~100% 3
Deletion/duplication analysis 4None reported 5
1\.
See Table A. Genes and Databases for chromosome locus and protein. See Molecular Genetics for information on allelic variants detected in this gene.
2\.
Sequence analysis detects variants that are benign, likely benign, of unknown 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.
3\.
Sequence analysis of the exons identifies all pathogenic variants known to date
4\.
Testing that identifies exon or whole-gene deletions/duplications not detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment.
5\.
No gross deletions or deep intronic pathogenic variants have as yet been identified in this gene.
## Clinical Characteristics
### Clinical Description
Laing distal myopathy is characterized by muscle weakness and atrophy beginning in the lower legs [Lamont et al 2006].
Onset is usually before age five years. In a few children onset has been so early as to delay walking. In two families, weakness was not recognized until the teenage years [Zimprich et al 2000, Hedera et al 2003, Lamont et al 2006]. In one family with 20 affected members, onset of lower-limb weakness occurred between early childhood and the fourth decade [Lamont et al 2014].
Weakness follows a typical sequence: initially dorsiflexion of the ankle and great toe is affected and leads to a high-stepping gait, dropped big toe, and secondary tightening of the tendo Achilles (see Figure 1).
#### Figure 1.
Early development of anterior compartment weakness has led to marked tightening of the tendo Achilles bilaterally, with the affected individual unable to place his heels on the ground.
Weakness of finger extensors develops between months and several decades after the onset of leg weakness [Lamont et al 2014]. The third and fourth fingers appear to be more severely affected than the other fingers (see Figure 2), although any of the fingers can be affected. The thumb is spared. Weakness of the finger extensors is often accompanied by a postural and action tremor of the hands.
#### Figure 2.
Individual with Laing distal myopathy attempting to extend her second to fifth fingers. Note marked weakness of third and fourth finger extension.
Mild facial weakness is often present, leading to inability to bury the eyelashes completely when closing the eyes tightly, and inability to keep the lips pursed against resistance. One affected individual has a mild Bell's phenomenon.
Weakness of neck flexion, seen in all affected individuals, is usually early in onset, though weakness of neck flexion did not manifest in one family until the sixth decade. In most affected individuals and sites, the weakness is symmetric.
After distal weakness has been present for more than ten years, mild proximal weakness occurs, with a slight Trendelenburg gait and mild scapular winging (see Figure 3). Axial musculature may be mildly weak as well, manifesting as, for example, inability to do a sit-up.
#### Figure 3.
Mild scapular winging and weakness develops later.
Progression is usually extremely slow; however, in one person the weakness became generalized and a wheelchair was required for mobility by age 15 years [Lamont et al 2014].
Spinal manifestations, which can include kyphoscoliosis and spinal rigidity, occur in one third of patients and can vary within a family.
Cardiac problems are common. In their review of 88 affected individuals from 22 families, Lamont et al [2014] reported cardiac involvement ranging from hypertrophic cardiomyopathy with onset from birth to the third decade of life, to dilated cardiomyopathy with onset from birth to the second decade of life. In an earlier report, a father and son in one family developed a dilated cardiomyopathy for which no other cause was found [Hedera et al 2003].
Pathology. The muscle pathology in Laing distal myopathy is highly variable [Lamont et al 2006, Lamont et al 2014].
The most common myopathic feature is excessive variation in fiber size, with either type 1 or type 2 fibers involved. Fiber type predominance is common. In one large family, ten of 14 muscle biopsies showed abnormally small type 1 fibers with type 1 predominance, fulfilling criteria for congenital fiber-type disproportion [Muelas et al 2010].
Another common finding is core pathology of either central cores or multiminicores [Cullup et al 2012, Lamont et al 2014].
Other findings can include:
* Excessive central nucleation and mild necrosis and regeneration;
* Fatty replacement in "end-stage" muscles.
Of note, in contrast to other distal myopathies, rimmed vacuoles and filamentous inclusions are rarely seen.
Immunohistochemical staining for slow and fast myosin in two individuals revealed co-expression of both isoforms in some muscle fibers, possibly indicating a switch from fiber type 1 to fiber type 2 [Lamont et al 2006].
### Genotype-Phenotype Correlations
No genotype-phenotype correlations for MYH7 have been identified to date.
Laing distal myopathy. Most pathogenic variants known to be associated with Laing distal myopathy occur within exons 32-39. They include missense pathogenic variants to proline, arginine, or valine; deletion of an amino acid; or a charge reversal pathogenic variant from glutamate to lysine in the tail of the encoded protein (myosin heavy chain, cardiac muscle beta isoform protein), including the region of the binding site for M protein and myomesin [Meredith et al 2004, Udd 2009].
The charge reversal pathogenic variants p.Glu1801Lys, p.Glu1856Lys, and p.Glu1914Lys are associated with a Laing distal myopathy phenotype combined with cardiomyopathy [Udd 2009, Lamont et al 2014]. More recently it has been shown that missense pathogenic variants to proline (p.Arg1608Pro) and amino acid deletions (p.Leu1793del, p.Lys1617del) can also be associated with a combined phenotype.
Myosin storage myopathy. The pathogenic variants known to be associated with myosin storage myopathy cluster within exons 37-39.
### Penetrance
Penetrance appears to be at least 85%.
Muelas et al [2010] reported a large Spanish family in which the age of onset ranged from birth to the sixth decade; 15% of family members were reported to be asymptomatic. (Note, however, that individual ages at the time of reporting were not clearly stated.)
In one apparent instance of de novo mutation, the supposedly unaffected father was found to be a somatic mosaic; however, when examined, he did have mild weakness [Lamont et al 2014].
### Nomenclature
The following alternate terms for Laing distal myopathy are no longer in use or are too nonspecific to be used:
* Early-onset chromosome 14-linked distal myopathy (Laing)
* Autosomal dominant distal muscular dystrophy
* Infantile autosomal dominant distal myopathy
* Autosomal dominant distal myopathy (a nonspecific term that could apply to other distal myopathies such as tibial muscular dystrophy)
* Gowers myopathy
### Prevalence
The prevalence of Laing distal myopathy is unknown. It is thought to be the most common distal myopathy worldwide [B Udd, personal communication] and has been reported in most populations [Chai et al 2007, Park et al 2013, Lamont et al 2014]. The frequency of de novo pathogenic variants would also suggest a relatively high prevalence.
Laing distal myopathy does not appear to be more prevalent in any specific populations [Author, personal observation].
## Differential Diagnosis
Mutation of MYH7 accounts for approximately 50% of early-onset distal myopathy [Author, personal observation].
Other disorders to consider in the differential diagnosis of Laing distal myopathy are discussed below.
### Congenital Myopathy
The early onset of Laing distal myopathy means that any of the milder congenital myopathies may be a differential diagnosis. These include central core disease (CCD; OMIM 117000), distal nebulin myopathy (OMIM 256030), or centronuclear myopathy – including X-linked centronuclear myopathy (XLCNM; also known as myotubular myopathy [MTM]), and autosomal dominant centronuclear myopathy (OMIM 160150).
Sometimes clinical manifestations can give a clue. For instance, the weakness in CCD is more proximal than distal, affecting the hip girdle in particular. In centronuclear myopathy, ptosis and restriction of eye movements are common. However, the overlap in phenotype between the milder congenital myopathies and Laing distal myopathy can be considerable. In these situations, muscle biopsy should show characteristic structural changes in the congenital myopathies, such as central cores in CCD, or nemaline bodies in distal nebulin myopathy. The presence of cardiomyopathy points to a MYH7 pathogenic variant being the cause. Use of a multigene panel including MYH7 and the other genes listed in the differential diagnosis in Table 2 is now the most cost-effective method of obtaining a molecular diagnosis of Laing distal myopathy.
### Distal Myopathies
The other major group in the differential diagnosis of Laing distal myopathy is distal myopathy (see Table 2). The distal myopathies most likely to be considered in the differential diagnosis for Laing distal myopathy include Udd distal myopathy (tibial muscular dystrophy), Nonaka distal myopathy, and myofibrillar myopathy [Mastaglia et al 2005]. The major features differentiating Laing distal myopathy from these entities are age of onset and weakness of neck flexion, which – although mild – does present early in most individuals with Laing distal myopathy.
### Table 2.
Distal Myopathies
View in own window
Disease Name 1GeneMode of InheritanceMean Age at OnsetInitial Muscle Group Involved 2Serum CK
Laing distal myopathyMYH7AD<5 yrsAnkle and great toe extensorsUsually normal; rarely 8x normal
Udd distal myopathy (tibial muscular dystrophy)TTNAD>35 yrsAnterior compartment legsNormal
Nonaka/GNE related myopathiesGNEAR>20 yrsAnkle dorsiflexion, toe extension<10x normal
Myofibrillar myopathies (OMIM PS601419)DES
MYOT
LDB3
FLNC
BAG3
CRYABAD or ARMostly adulthood, rarely teensIf presentation is distal, ankle dorsiflexion plantarflexion, +/- finger wrist extensionNormal to 4x normal
Miyoshi myopathyDYS1ARLate teens, early adulthoodCalf muscles20-150x normal
Welander distal myopathy (OMIM 604454)TIA1AD>40 yrsFinger extensorsNormal
Distal anoctaminopathyANO5AR>20 yrsAnkle plantar flexion5x normal
1\.
Listed from most similar to Laing distal myopathy to least similar
2\.
Information on histologic findings is included in the discussion that follows.
Distal myopathies less likely to be considered in the differential diagnosis are Miyoshi distal myopathy (predominantly affecting the posterior compartment of the leg and much more rapidly progressive) and Welander distal myopathy (predominantly affecting the hands).
* Udd distal myopathy (tibial muscular dystrophy) is characterized by weakness of ankle dorsiflexion after age 35 years. Disease progression is slow and muscle weakness remains confined to the anterior tibial muscles. The long-toe extensors become clinically involved after ten to 20 years. Muscle biopsy reveals mild dystrophic or myopathic changes with or without rimmed vacuoles.
* Nonaka early-adult-onset distal myopathy (see GNE-related myopathy) usually begins in the anterior compartment of the legs and in the toe extensors in the second or third decade, progressing to loss of ambulation after 12 to 15 years. Muscle biopsy reveals rimmed vacuoles.
* Myofibrillar myopathies (OMIM PS601419) are a genetically heterogeneous group of disorders with the common finding of disintegration of the sarcomeric Z-discs and the myofibrils, which leads to abnormal ectopic accumulation of multiple proteins involved in the structure of the Z-disc, including desmin, dystrophin, and myotilin. Muscle biopsy reveals hyaline spheroid and granular structures containing numerous deposited proteins. Most myofibrillar myopathies are characterized by onset of proximal weakness, but all can have onset of distal weakness, most often in the legs.
* Miyoshi early-adult-onset myopathy begins in late teenage years or early adulthood and initially affects the calves. It progresses to other distal and proximal muscles. Twenty years after onset it is indistinguishable from its allelic condition, limb-girdle-muscular dystrophy 2B (LGMD2B) (see Dysferlinopathy). The serum CK concentration is 20- to 150-fold normal values – much higher than that in other distal myopathies [Udd 2014]. Muscle biopsy reveals muscular dystrophy and inflammation.
* Welander distal myopathy (OMIM 604454) typically begins in the hand and finger extensors, but may sometimes begin in the anterior compartment muscles of the lower legs [von Tell et al 2002]. Typically, affected individuals experience weakness of the extensor of the index finger after age 40 years, followed by slow progression to the other finger extensors and to the anterior and posterior leg muscles [Hackman et al 2013]. Muscle biopsy reveals rimmed vacuoles.
* Distal anoctaminopathy leads to weakness of ankle plantar flexion, often asymmetrically, after age 20 years. This condition is allelic to limb-girdle-muscular dystrophy 2L (LGMD2L). Muscle biopsy reveals scattered fiber necrosis.
Charcot-Marie-Tooth Hereditary Neuropathy also commonly features foot drop and thus may be considered in the differential diagnosis. Evidence of sensory involvement, namely reduction in pinprick appreciation in the toes, is usually seen in Charcot-Marie-Tooth neuropathy.
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with Laing distal myopathy, the following evaluations are recommended:
* A full neurologic history and examination at presentation, with particular reference to early gross motor milestones. The examination should particularly note tightening of the tendo Achilles (Figure 1) and the pattern of muscle weakness.
* As severe cardiac manifestations are a feature in one third of individuals with Laing distal myopathy, an electrocardiogram and echocardiogram should be performed as a baseline.
* Electromyography/nerve conduction studies
* Consultation with a clinical geneticist and/or genetic counselor
### Treatment of Manifestations
Physiotherapy assessment with particular reference to preventing or treating tightening of the tendo Achilles is very useful. In persons with more advanced disease, lightweight splinting of the ankle (e.g., with an ankle-foot orthosis) may be recommended.
The cardiomyopathy may respond to ACE inhibitors or other medication. Cardiac consultation is recommended.
Kyphoscoliosis may be treated with surgical stabilization of the spine. There is no treatment for spinal rigidity.
### Surveillance
After establishing the diagnosis (see Evaluations Following Initial Diagnosis) and instituting the indicated therapies (see Treatment of Manifestations), annual review is recommended.
Additional recommendations include:
* Spinal review for evidence of scoliosis and/or kyphoscoliosis, especially during the years of rapid growth in adolescence;
* Repeat electrocardiogram and echocardiogram if symptoms of cardiac insufficiency occur;
* Respiratory function and assessment if symptoms suggest either sleep apnea or sleep-related respiratory insufficiency.
### Evaluation of Relatives at Risk
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Therapies Under Investigation
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Laing Distal Myopathy | c4552004 | 825 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1433/ | 2021-01-18T21:15:26 | {"mesh": ["D049310"], "synonyms": ["Laing Early-Onset Distal Myopathy"]} |
A number sign (#) is used with this entry because of evidence that sialuria is caused by heterozygous mutation in the gene encoding uridinediphosphate-N-acetylglucosamine 2-epimerase (UDP-GlcNAc 2-epimerase; 603824) on chromosome 9p13.
Description
Sialuria is a rare inborn error of metabolism in which excessive free sialic acid is synthesized. Clinical features include hepatosplenomegaly, coarse facial features, and varying degrees of developmental delay (summary by Enns et al., 2001).
Clinical Features
Sialuria differs from the sialidoses (256550) in the accumulation and excretion of free sialic acid and normal (or increased) levels of neuraminidase activity. In the disorder originally described by Montreuil et al. (1968) and Fontaine et al. (1968) and characterized by massive excretion of free sialic acid, Kamerling et al. (1979) implicated defective feedback inhibition of one of the enzymes involved in sialic acid synthesis.
Wilcken et al. (1987) described a 2-year-old girl (A.W.) with moderate developmental delay, hepatosplenomegaly, slightly coarse facial features, a large tongue, macrocephaly, and massive urinary excretion of free sialic acid. At age 7 years, she had mild intellectual impairment, with fine-motor difficulty, but attended regular school (Don and Wilcken, 1991). Her growth was at the 10th percentile, and the organomegaly persisted.
Seppala et al. (1989) indicated that only 3 bona fide cases appeared to have been discovered: the French case of Montreuil et al. (1968), the Australian case of Wilcken et al. (1987), and an American case studied by his coauthor Barsh. Seppala et al. (1989) studied the patient reported by Wilcken et al. (1987) and a 3-year-old boy who presented at 3 months of age with hepatosplenomegaly, coarse facies, and massive urinary excretion of free N-acetylneuraminic acid (NANA or NeuAc). Both patients had near normal growth and development, unlike patients with lysosomal storage of NANA. In sialuria fibroblasts, 88% of accumulated NANA was in the cytosolic fraction. From a study of cultured fibroblasts, Seppala et al. (1989) derived evidence that the metabolic defect consists of a loss in sensitivity of the rate-limiting enzyme in NANA synthesis, uridinediphosphate-N-acetylglucosamine 2-epimerase (UDP-GlcNAc 2-epimerase; 603824), to feedback regulation by cytidine monophosphate (CMP)-NANA, as suggested by Thomas et al. (1985). This may be the first instance of a human disease due to defective allosteric inhibition, with apparent preservation of the mutant enzyme's active site.
Thomas et al. (1989) demonstrated striking cellular differences between the original French sialuria patient and patients with infantile sialic acid storage disease (ISSD; 269920). Whereas phase microscopy and immunochemical studies showed abnormal storage within intracellular inclusions in ISSD cells, Thomas et al. (1989) found no morphologic evidence of storage within any subcellular organelle in the French sialuria cells. Moreover, comparative subcellular fractionation studies on gradients of colloidal silica showed the excess sialic acid in ISSD cells to be located within the light (buoyant) lysosomal fraction, whereas the excessive, free sialic acid in the sialuria cells was found in the cytoplasmic fraction with no increased storage within the lysosomal fractions.
In fibroblasts cultured from the 3 known cases of sialuria, Seppala et al. (1991) found 70- to 200-fold increases in soluble sialic acid but normal concentrations of bound sialic acid. They found also that the total cellular content of soluble sialic acid was lowered 14 to 46% by cytidine feeding. They repeated their conclusion that the basic biochemical defect is a failure of CMP-N-acetylneuraminic acid to feedback-inhibit UDP-GlcNAc 2-epimerase. They noted that cells from both parents of 1 sialuria patient contained normal concentrations of free sialic acid, and the parental epimerase activity also responded normally to CMP-NeuAc.
Leroy et al. (2001) reported a patient with sialuria who was heterozygous for a mutation in the epimerase gene (R266Q; 603824.0002). The same heterozygous mutation was detected in the patient's mother, who had similarly increased levels of free N-acetylneuraminic acid, thereby confirming the dominant mode of inheritance of this inborn error. Biochemical diagnosis of the proband was verified by the greatly increased levels of free N-acetylneuraminic acid in his cultured fibroblasts, the distribution of NeuAc mainly, (59%) in the cytoplasm, and by the complete failure of CMP-NeuAc to inhibit 2-epimerase activity in the mutant cells. The findings in this family call for expansion of the phenotype to include adults and for more extensive assaying of free NeuAc in the urine of children with mild developmental delay. The prevalence of sialuria is probably grossly underestimated.
Enns et al. (2001) reported a longitudinal study of 1 of the original sialuria patients (J.C.) to age 11 years. Although he had coarse features and massive hepatomegaly, he showed normal growth and relatively normal development. Pulmonary function testing showed minimal small airway obstruction. At age 11 years, he developed intermittent abdominal pain and transient transaminase elevation above his baseline. Enns et al. (2001) suggested that sialuria should be considered in the differential diagnosis of a patient with a phenotype suggestive of mucopolysaccharidosis or oligosaccharidosis in the absence of developmental regression or prominent dysostosis multiplex.
Population Genetics
Enns et al. (2001) stated that only 5 patients with sialuria had been reported worldwide.
Molecular Genetics
To elucidate the molecular mechanism for defective allosteric regulation of UDP-GlcNAc 2-epimerase in sialuria, Seppala et al. (1999) cloned and sequenced the human cDNA encoding the epimerase and determined the mutations in 3 sialuria patients. They identified 3 heterozygous mutations, arg266 to trp (603824.0001), arg266 to gln (603824.0002), and arg263 to leu (603824.0003), which indicated that the allosteric site of the epimerase resides in the region of codons 263 to 266. The heterozygous nature of the mutant allele in all 3 patients demonstrated dominant inheritance of sialuria, i.e., heterozygosity for a mutation in the allosteric site is sufficient to cause the disorder. One of the 3 patients, A.W., had been described by Wilcken et al. (1987). The other 2 patients were those reported by Weiss et al. (1989) and Gahl et al., 1996 and by Krasnewich et al., 1993.
INHERITANCE \- Autosomal dominant GROWTH Other \- Normal growth HEAD & NECK Face \- Coarse facial features \- Prominent forehead \- Long, smooth philtrum Ears \- Low-set ears Eyes \- Synophrys \- Epicanthal folds \- Hypertelorism \- Periorbital fullness Nose \- Broad nasal bridge \- High-arched palate \- Thin upper lip RESPIRATORY \- Sleep apnea CHEST External Features \- Small chest Breasts \- Hypoplastic nipples ABDOMEN External Features \- Protuberant abdomen Liver \- Hepatomegaly Spleen \- Splenomegaly GENITOURINARY External Genitalia (Male) \- Inguinal hernias SKELETAL Spine \- Scoliosis Feet \- Large halluces \- 2-3 toe syndactyly SKIN, NAILS, & HAIR Hair \- Low posterior hairline \- Generalized hirsutism NEUROLOGIC Central Nervous System \- Developmental delay \- Seizures \- Attention deficit disorder LABORATORY ABNORMALITIES \- Elevated urinary free sialic acid (N-acetylneuraminic acid) \- Elevated fibroblast free sialic acid MOLECULAR BASIS \- Caused by mutation in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene (GNE, 603824.0001 ) ▲ Close
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*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| SIALURIA | c2931471 | 826 | omim | https://www.omim.org/entry/269921 | 2019-09-22T16:22:27 | {"doid": ["3659"], "mesh": ["C537332"], "omim": ["269921"], "orphanet": ["3166"], "synonyms": ["Alternative titles", "SIALURIA, FRENCH TYPE"]} |
Bile duct adenocarcinoma
Cholangiocarcinoma
Other namesBile duct cancer, cancer of the bile duct[1]
Micrograph of an intrahepatic cholangiocarcinoma (right of image) adjacent to normal liver cells (left of image). H&E stain.
Pronunciation
* koh-LAN-jee-oh-KAR-sih-NOH-muh[2]
SpecialtyOncology
SymptomsAbdominal pain, yellowish skin, weight loss, generalized itching, fever[1]
Usual onset70 years old[3]
TypesIntrahepatic, perihilar, distal[3]
Risk factorsPrimary sclerosing cholangitis, ulcerative colitis, infection with certain liver flukes, some congenital liver malformations[1]
Diagnostic methodConfirmed by examination of the tumor under a microscope[4]
TreatmentSurgical resection, chemotherapy, radiation therapy, stenting procedures, liver transplantation[1]
PrognosisGenerally poor[5]
Frequency1–2 people per 100,000 per year (Western world)[6]
Cholangiocarcinoma, also known as bile duct cancer, is a type of cancer that forms in the bile ducts.[2] Symptoms of cholangiocarcinoma may include abdominal pain, yellowish skin, weight loss, generalized itching, and fever.[1] Light colored stool or dark urine may also occur.[4] Other biliary tract cancers include gallbladder cancer and cancer of the ampulla of Vater.[7]
Risk factors for cholangiocarcinoma include primary sclerosing cholangitis (an inflammatory disease of the bile ducts), ulcerative colitis, cirrhosis, hepatitis C, hepatitis B, infection with certain liver flukes, and some congenital liver malformations.[1][3][8] However, most people have no identifiable risk factors.[3] The diagnosis is suspected based on a combination of blood tests, medical imaging, endoscopy, and sometimes surgical exploration.[4] The disease is confirmed by examination of cells from the tumor under a microscope.[4] It is typically an adenocarcinoma (a cancer that forms glands or secretes mucin).[3]
Cholangiocarcinoma is typically incurable at diagnosis.[1] In these cases palliative treatments may include surgical resection, chemotherapy, radiation therapy, and stenting procedures.[1] In about a third of cases involving the common bile duct and less commonly with other locations the tumor can be completely removed by surgery offering a chance of a cure.[1] Even when surgical removal is successful chemotherapy and radiation therapy are generally recommended.[1] In certain cases surgery may include a liver transplantation.[3] Even when surgery is successful 5-year survival is typically less than 50%.[6]
Cholangiocarcinoma is rare in the Western world, with estimates of it occurring in 0.5–2 people per 100,000 per year.[1][6] Rates are higher in South-East Asia where liver flukes are common.[5] Rates in parts of Thailand are 60 per 100,000 per year.[5] It typically occurs in people in their 70s; however, in those with primary sclerosing cholangitis it often occurs in the 40s.[3] Rates of cholangiocarcinoma within the liver in the Western world have increased.[6]
## Contents
* 1 Signs and symptoms
* 2 Risk factors
* 3 Pathophysiology
* 4 Diagnosis
* 4.1 Blood tests
* 4.2 Abdominal imaging
* 4.3 Imaging of the biliary tree
* 4.4 Surgery
* 4.5 Pathology
* 4.6 Staging
* 5 Treatment
* 5.1 Adjuvant chemotherapy and radiation therapy
* 5.2 Treatment of advanced disease
* 6 Prognosis
* 7 Epidemiology
* 8 Notes
* 9 External links
## Signs and symptoms[edit]
Yellowing of the skin (jaundice) and eyes (scleral icterus).
The most common physical indications of cholangiocarcinoma are abnormal liver function tests, jaundice (yellowing of the eyes and skin occurring when bile ducts are blocked by tumor), abdominal pain (30–50%), generalized itching (66%), weight loss (30–50%), fever (up to 20%), and changes in the color of stool or urine.[9][10] To some extent, the symptoms depend upon the location of the tumor: people with cholangiocarcinoma in the extrahepatic bile ducts (outside the liver) are more likely to have jaundice, while those with tumors of the bile ducts within the liver more often have pain without jaundice.[11]
Blood tests of liver function in people with cholangiocarcinoma often reveal a so-called "obstructive picture", with elevated bilirubin, alkaline phosphatase, and gamma glutamyl transferase levels, and relatively normal transaminase levels. Such laboratory findings suggest obstruction of the bile ducts, rather than inflammation or infection of the liver parenchyma, as the primary cause of the jaundice.[12]
## Risk factors[edit]
Life cycle of Clonorchis sinensis, a liver fluke associated with cholangiocarcinoma
Although most people present without any known risk factors evident, a number of risk factors for the development of cholangiocarcinoma have been described. In the Western world, the most common of these is primary sclerosing cholangitis (PSC), an inflammatory disease of the bile ducts which is closely associated with ulcerative colitis (UC).[13] Epidemiologic studies have suggested that the lifetime risk of developing cholangiocarcinoma for a person with PSC is on the order of 10–15%,[14] although autopsy series have found rates as high as 30% in this population.[15]
Certain parasitic liver diseases may be risk factors as well. Colonization with the liver flukes Opisthorchis viverrini (found in Thailand, Laos PDR, and Vietnam)[16][17][18] or Clonorchis sinensis (found in China, Taiwan, eastern Russia, Korea, and Vietnam)[19][20] has been associated with the development of cholangiocarcinoma. Control programs aimed at discouraging the consumption of raw and undercooked food have been successful at reducing the incidence of cholangiocarcinoma in some countries.[21] People with chronic liver disease, whether in the form of viral hepatitis (e.g. hepatitis B or hepatitis C),[22][23][24] alcoholic liver disease, or cirrhosis of the liver due to other causes, are at significantly increased risk of cholangiocarcinoma.[25][26] HIV infection was also identified in one study as a potential risk factor for cholangiocarcinoma, although it was unclear whether HIV itself or other correlated and confounding factors (e.g. hepatitis C infection) were responsible for the association.[25]
Infection with the bacteria Helicobacter bilis and Helicobacter hepaticus species can cause biliary cancer.[27]
Congenital liver abnormalities, such as Caroli's syndrome (a specific type of five recognized choledochal cysts), have been associated with an approximately 15% lifetime risk of developing cholangiocarcinoma.[28][29] The rare inherited disorders Lynch syndrome II and biliary papillomatosis have also been found to be associated with cholangiocarcinoma.[30][31] The presence of gallstones (cholelithiasis) is not clearly associated with cholangiocarcinoma. However, intrahepatic stones (called hepatolithiasis), which are rare in the West but common in parts of Asia, have been strongly associated with cholangiocarcinoma.[32][33][34] Exposure to Thorotrast, a form of thorium dioxide which was used as a radiologic contrast medium, has been linked to the development of cholangiocarcinoma as late as 30–40 years after exposure; Thorotrast was banned in the United States in the 1950s due to its carcinogenicity.[35][36][37]
## Pathophysiology[edit]
Digestive system diagram showing bile duct location.
Cholangiocarcinoma can affect any area of the bile ducts, either within or outside the liver. Tumors occurring in the bile ducts within the liver are referred to as intrahepatic, those occurring in the ducts outside the liver are extrahepatic, and tumors occurring at the site where the bile ducts exit the liver may be referred to as perihilar. A cholangiocarcinoma occurring at the junction where the left and right hepatic ducts meet to form the common hepatic duct may be referred to eponymously as a Klatskin tumor.[38]
Although cholangiocarcinoma is known to have the histological and molecular features of an adenocarcinoma of epithelial cells lining the biliary tract, the actual cell of origin is unknown. Recent evidence has suggested that the initial transformed cell that generates the primary tumor may arise from a pluripotent hepatic stem cell.[39][40][41] Cholangiocarcinoma is thought to develop through a series of stages – from early hyperplasia and metaplasia, through dysplasia, to the development of frank carcinoma – in a process similar to that seen in the development of colon cancer.[42] Chronic inflammation and obstruction of the bile ducts, and the resulting impaired bile flow, are thought to play a role in this progression.[42][43][44]
Histologically, cholangiocarcinomas may vary from undifferentiated to well-differentiated. They are often surrounded by a brisk fibrotic or desmoplastic tissue response; in the presence of extensive fibrosis, it can be difficult to distinguish well-differentiated cholangiocarcinoma from normal reactive epithelium. There is no entirely specific immunohistochemical stain that can distinguish malignant from benign biliary ductal tissue, although staining for cytokeratins, carcinoembryonic antigen, and mucins may aid in diagnosis.[45] Most tumors (>90%) are adenocarcinomas.[46]
## Diagnosis[edit]
Micrograph of an intrahepatic, i.e. in the liver, cholangiocarcinoma (right of image); benign hepatocytes are seen (left of image). Histologically, this is a cholangiocarcinoma as (1) atypical bile duct-like cells (left of image) extend from the tumor in an interlobular septum (the normal anatomical location of bile ducts), and (2) the tumor has the abundant desmoplastic stroma often seen in cholangiocarcinomas. A portal triad (upper-left of image) has a histologically normal bile duct. H&E stain.
### Blood tests[edit]
There are no specific blood tests that can diagnose cholangiocarcinoma by themselves. Serum levels of carcinoembryonic antigen (CEA) and CA19-9 are often elevated, but are not sensitive or specific enough to be used as a general screening tool. However, they may be useful in conjunction with imaging methods in supporting a suspected diagnosis of cholangiocarcinoma.[47]
### Abdominal imaging[edit]
CT scan showing cholangiocarcinoma
Ultrasound of the liver and biliary tree is often used as the initial imaging modality in people with suspected obstructive jaundice.[48][49] Ultrasound can identify obstruction and ductal dilatation and, in some cases, may be sufficient to diagnose cholangiocarcinoma.[50] Computed tomography (CT) scanning may also play an important role in the diagnosis of cholangiocarcinoma.[51][52][53]
### Imaging of the biliary tree[edit]
ERCP image of cholangiocarcinoma, showing common bile duct stricture and dilation of the proximal common bile duct
While abdominal imaging can be useful in the diagnosis of cholangiocarcinoma, direct imaging of the bile ducts is often necessary. Endoscopic retrograde cholangiopancreatography (ERCP), an endoscopic procedure performed by a gastroenterologist or specially trained surgeon, has been widely used for this purpose. Although ERCP is an invasive procedure with attendant risks, its advantages include the ability to obtain biopsies and to place stents or perform other interventions to relieve biliary obstruction.[12] Endoscopic ultrasound can also be performed at the time of ERCP and may increase the accuracy of the biopsy and yield information on lymph node invasion and operability.[54] As an alternative to ERCP, percutaneous transhepatic cholangiography (PTC) may be utilized. Magnetic resonance cholangiopancreatography (MRCP) is a non-invasive alternative to ERCP.[55][56][57] Some authors have suggested that MRCP should supplant ERCP in the diagnosis of biliary cancers, as it may more accurately define the tumor and avoids the risks of ERCP.[58][59][60]
### Surgery[edit]
Photograph of cholangiocarcinoma in human liver.
Surgical exploration may be necessary to obtain a suitable biopsy and to accurately stage a person with cholangiocarcinoma. Laparoscopy can be used for staging purposes and may avoid the need for a more invasive surgical procedure, such as laparotomy, in some people.[61][62]
### Pathology[edit]
Histologically, cholangiocarcinomas are classically well to moderately differentiated adenocarcinomas. Immunohistochemistry is useful in the diagnosis and may be used to help differentiate a cholangiocarcinoma from hepatocellular carcinoma and metastasis of other gastrointestinal tumors.[63] Cytological scrapings are often nondiagnostic,[64] as these tumors typically have a desmoplastic stroma and, therefore, do not release diagnostic tumor cells with scrapings.
### Staging[edit]
Although there are at least three staging systems for cholangiocarcinoma (e.g. those of Bismuth, Blumgart, and the American Joint Committee on Cancer), none have been shown to be useful in predicting survival.[65] The most important staging issue is whether the tumor can be surgically removed, or whether it is too advanced for surgical treatment to be successful. Often, this determination can only be made at the time of surgery.[12]
General guidelines for operability include:[66][67]
* Absence of lymph node or liver metastases
* Absence of involvement of the portal vein
* Absence of direct invasion of adjacent organs
* Absence of widespread metastatic disease
## Treatment[edit]
Cholangiocarcinoma is considered to be an incurable and rapidly lethal disease unless all the tumors can be fully resected (cut out surgically). Since the operability of the tumor can only be assessed during surgery in most cases,[68] a majority of people undergo exploratory surgery unless there is already a clear indication that the tumor is inoperable.[12] However, the Mayo Clinic has reported significant success treating early bile duct cancer with liver transplantation using a protocolized approach and strict selection criteria.[69]
Adjuvant therapy followed by liver transplantation may have a role in treatment of certain unresectable cases.[70] Locoregional therapies including transarterial chemoembolization (TACE), transarterial radioembolization (TARE) and ablation therapies have a role in intrahepatic variants of cholangiocarcinoma to provide palliation or potential cure in people who are not surgical candidates.[71]
### Adjuvant chemotherapy and radiation therapy[edit]
If the tumor can be removed surgically, people may receive adjuvant chemotherapy or radiation therapy after the operation to improve the chances of cure. If the tissue margins are negative (i.e. the tumor has been totally excised), adjuvant therapy is of uncertain benefit. Both positive[72][73] and negative[11][74][75] results have been reported with adjuvant radiation therapy in this setting, and no prospective randomized controlled trials have been conducted as of March 2007. Adjuvant chemotherapy appears to be ineffective in people with completely resected tumors.[76] The role of combined chemoradiotherapy in this setting is unclear. However, if the tumor tissue margins are positive, indicating that the tumor was not completely removed via surgery, then adjuvant therapy with radiation and possibly chemotherapy is generally recommended based on the available data.[77]
### Treatment of advanced disease[edit]
The majority of cases of cholangiocarcinoma present as inoperable (unresectable) disease[78] in which case people are generally treated with palliative chemotherapy, with or without radiotherapy. Chemotherapy has been shown in a randomized controlled trial to improve quality of life and extend survival in people with inoperable cholangiocarcinoma.[79] There is no single chemotherapy regimen which is universally used, and enrollment in clinical trials is often recommended when possible.[77] Chemotherapy agents used to treat cholangiocarcinoma include 5-fluorouracil with leucovorin,[80] gemcitabine as a single agent,[81] or gemcitabine plus cisplatin,[82] irinotecan,[83] or capecitabine.[84] A small pilot study suggested possible benefit from the tyrosine kinase inhibitor erlotinib in people with advanced cholangiocarcinoma.[85] Radiation therapy appears to prolong survival in people with resected extrahepatic cholangiocarcinoma,[86] and the few reports of its use in unresectable cholangiocarcinoma appear to show improved survival, but numbers are small.[87]
## Prognosis[edit]
Surgical resection offers the only potential chance of cure in cholangiocarcinoma. For non-resectable cases, the 5-year survival rate is 0% where the disease is inoperable because distal lymph nodes show metastases,[88] and less than 5% in general.[89] Overall mean duration of survival is less than 6 months in people with metastatic disease.[90]
For surgical cases, the odds of cure vary depending on the tumor location and whether the tumor can be completely, or only partially, removed. Distal cholangiocarcinomas (those arising from the common bile duct) are generally treated surgically with a Whipple procedure; long-term survival rates range from 15–25%, although one series reported a five-year survival of 54% for people with no involvement of the lymph nodes.[91] Intrahepatic cholangiocarcinomas (those arising from the bile ducts within the liver) are usually treated with partial hepatectomy. Various series have reported survival estimates after surgery ranging from 22–66%; the outcome may depend on involvement of lymph nodes and completeness of the surgery.[92] Perihilar cholangiocarcinomas (those occurring near where the bile ducts exit the liver) are least likely to be operable. When surgery is possible, they are generally treated with an aggressive approach often including removal of the gallbladder and potentially part of the liver. In patients with operable perihilar tumors, reported 5-year survival rates range from 20–50%.[93]
The prognosis may be worse for people with primary sclerosing cholangitis who develop cholangiocarcinoma, likely because the cancer is not detected until it is advanced.[15][94] Some evidence suggests that outcomes may be improving with more aggressive surgical approaches and adjuvant therapy.[95]
## Epidemiology[edit]
Age-standardized mortality rates from intrahepatic (IC) and extrahepatic (EC) cholangiocarcinoma for men and women, by country.[96] Country IC (men/women) EC (men/women)
U.S.A. 0.60/0.43 0.70/0.87
Japan 0.23/0.10 5.87/5.20
Australia 0.70/0.53 0.90/1.23
England/Wales 0.83/0.63 0.43/0.60
Scotland 1.17/1.00 0.60/0.73
France 0.27/0.20 1.20/1.37
Italy 0.13/0.13 2.10/2.60
Liver tumor types by relative incidence in adults in the United States, with cholangiocarcinoma at top right.[97]
Cholangiocarcinoma is a relatively rare form of cancer; each year, approximately 2,000 to 3,000 new cases are diagnosed in the United States, translating into an annual incidence of 1–2 cases per 100,000 people.[98] Autopsy series have reported a prevalence of 0.01% to 0.46%.[78][99] There is a higher prevalence of cholangiocarcinoma in Asia, which has been attributed to endemic chronic parasitic infestation. The incidence of cholangiocarcinoma increases with age, and the disease is slightly more common in men than in women (possibly due to the higher rate of primary sclerosing cholangitis, a major risk factor, in men).[46] The prevalence of cholangiocarcinoma in people with primary sclerosing cholangitis may be as high as 30%, based on autopsy studies.[15]
Multiple studies have documented a steady increase in the incidence of intrahepatic cholangiocarcinoma over the past several decades; increases have been seen in North America, Europe, Asia, and Australia.[100] The reasons for the increasing occurrence of cholangiocarcinoma are unclear; improved diagnostic methods may be partially responsible, but the prevalence of potential risk factors for cholangiocarcinoma, such as HIV infection, has also been increasing during this time frame.[25]
## Notes[edit]
1. ^ a b c d e f g h i j k "Bile Duct Cancer (Cholangiocarcinoma) Treatment (PDQ®)–Health Professional Version". National Cancer Institute. 14 March 2018. Retrieved 21 January 2019.
2. ^ a b "NCI Dictionary of Cancer Terms". National Cancer Institute. 2 February 2011. Retrieved 21 January 2019.
3. ^ a b c d e f g Razumilava N, Gores GJ (June 2014). "Cholangiocarcinoma". Lancet. 383 (9935): 2168–79. doi:10.1016/S0140-6736(13)61903-0. PMC 4069226. PMID 24581682.
4. ^ a b c d "Bile Duct Cancer (Cholangiocarcinoma) Symptoms, Tests, Prognosis, and Stages". National Cancer Institute. 5 July 2018. Retrieved 21 January 2019.
5. ^ a b c Bosman, Frank T. (2014). "Chapter Chapter 5.6: Liver cancer". In Stewart, Bernard W.; Wild, Christopher P (eds.). World Cancer Report. the International Agency for Research on Cancer, World Health Organization. pp. Chapter 5.6. ISBN 978-92-832-0443-5.
6. ^ a b c d Bridgewater JA, Goodman KA, Kalyan A, Mulcahy MF (2016). "Biliary Tract Cancer: Epidemiology, Radiotherapy, and Molecular Profiling". American Society of Clinical Oncology Educational Book. American Society of Clinical Oncology. Annual Meeting. 35 (36): e194-203. doi:10.1200/EDBK_160831. PMID 27249723.
7. ^ Benavides M, Antón A, Gallego J, Gómez MA, Jiménez-Gordo A, La Casta A, et al. (December 2015). "Biliary tract cancers: SEOM clinical guidelines". Clinical & Translational Oncology. 17 (12): 982–7. doi:10.1007/s12094-015-1436-2. PMC 4689747. PMID 26607930.
8. ^ Steele JA, Richter CH, Echaubard P, Saenna P, Stout V, Sithithaworn P, Wilcox BA (May 2018). "Thinking beyond Opisthorchis viverrini for risk of cholangiocarcinoma in the lower Mekong region: a systematic review and meta-analysis". Infectious Diseases of Poverty. 7 (1): 44. doi:10.1186/s40249-018-0434-3. PMC 5956617. PMID 29769113.
9. ^ Nagorney DM, Donohue JH, Farnell MB, Schleck CD, Ilstrup DM (August 1993). "Outcomes after curative resections of cholangiocarcinoma". Archives of Surgery. 128 (8): 871–7, discussion 877–9. doi:10.1001/archsurg.1993.01420200045008. PMID 8393652.
10. ^ Bile duct cancer: cause and treatment
11. ^ a b Nakeeb A, Pitt HA, Sohn TA, Coleman J, Abrams RA, Piantadosi S, Hruban RH, Lillemoe KD, Yeo CJ, Cameron JL (October 1996). "Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors". Annals of Surgery. 224 (4): 463–73, discussion 473–5. doi:10.1097/00000658-199610000-00005. PMC 1235406. PMID 8857851.
12. ^ a b c d Mark Feldman; Lawrence S. Friedman; Lawrence J. Brandt, eds. (21 July 2006). Sleisenger and Fordtran's Gastrointestinal and Liver Disease (8th ed.). Saunders. pp. 1493–6. ISBN 978-1-4160-0245-1.
13. ^ Chapman RW (1999). "Risk factors for biliary tract carcinogenesis". Annals of Oncology. 10 Suppl 4 (Suppl 4): 308–11. doi:10.1023/A:1008313809752. PMID 10436847.
14. ^ Epidemiologic studies which have addressed the incidence of cholangiocarcinoma in people with primary sclerosing cholangitis include the following:
* Bergquist A, Ekbom A, Olsson R, Kornfeldt D, Lööf L, Danielsson A, Hultcrantz R, Lindgren S, Prytz H, Sandberg-Gertzén H, Almer S, Granath F, Broomé U (March 2002). "Hepatic and extrahepatic malignancies in primary sclerosing cholangitis". Journal of Hepatology. 36 (3): 321–7. doi:10.1016/S0168-8278(01)00288-4. PMID 11867174.
* Bergquist A, Glaumann H, Persson B, Broomé U (February 1998). "Risk factors and clinical presentation of hepatobiliary carcinoma in patients with primary sclerosing cholangitis: a case-control study". Hepatology. 27 (2): 311–6. doi:10.1002/hep.510270201. PMID 9462625.
* Burak K, Angulo P, Pasha TM, Egan K, Petz J, Lindor KD (March 2004). "Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis". American Journal of Gastroenterology. 99 (3): 523–6. PMID 15056096.
15. ^ a b c Rosen CB, Nagorney DM, Wiesner RH, Coffey RJ, LaRusso NF (January 1991). "Cholangiocarcinoma complicating primary sclerosing cholangitis". Annals of Surgery. 213 (1): 21–5. doi:10.1097/00000658-199101000-00004. PMC 1358305. PMID 1845927.
16. ^ Watanapa P, Watanapa WB (August 2002). "Liver fluke-associated cholangiocarcinoma". British Journal of Surgery. 89 (8): 962–70. doi:10.1046/j.1365-2168.2002.02143.x. PMID 12153620.
17. ^ Sripa B, Kaewkes S, Sithithaworn P, Mairiang E, Laha T, Smout M, Pairojkul C, Bhudhisawasdi V, Tesana S, Thinkamrop B, Bethony JM, Loukas A, Brindley PJ (July 2007). "Liver fluke induces cholangiocarcinoma". PLOS Medicine. 4 (7): e201. doi:10.1371/journal.pmed.0040201. PMC 1913093. PMID 17622191.
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* Patel AH, Harnois DM, Klee GG, LaRusso NF, Gores GJ (January 2000). "The utility of CA 19-9 in the diagnoses of cholangiocarcinoma in patients without primary sclerosing cholangitis". American Journal of Gastroenterology. 95 (1): 204–7. PMID 10638584.
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91. ^ Studies of surgical outcomes in distal cholangiocarcinoma include:
* Nakeeb A, Pitt HA, Sohn TA, Coleman J, Abrams RA, Piantadosi S, Hruban RH, Lillemoe KD, Yeo CJ, Cameron JL (October 1996). "Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors". Annals of Surgery. 224 (4): 463–73, discussion 473–5. doi:10.1097/00000658-199610000-00005. PMC 1235406. PMID 8857851.
* Jang JY, Kim SW, Park DJ, Ahn YJ, Yoon YS, Choi MG, Suh KS, Lee KU, Park YH (January 2005). "Actual long-term outcome of extrahepatic bile duct cancer after surgical resection". Annals of Surgery. 241 (1): 77–84. doi:10.1097/01.sla.0000150166.94732.88. PMC 1356849. PMID 15621994.
* Bortolasi L, Burgart LJ, Tsiotos GG, Luque-De León E, Sarr MG (2000). "Adenocarcinoma of the distal bile duct. A clinicopathologic outcome analysis after curative resection". Digestive Surgery. 17 (1): 36–41. doi:10.1159/000018798. PMID 10720830.
* Fong Y, Blumgart LH, Lin E, Fortner JG, Brennan MF (December 1996). "Outcome of treatment for distal bile duct cancer". British Journal of Surgery. 83 (12): 1712–5. doi:10.1002/bjs.1800831217. PMID 9038548.
92. ^ Studies of outcome in intrahepatic cholangiocarcinoma include:
* Nakeeb A, Pitt HA, Sohn TA, Coleman J, Abrams RA, Piantadosi S, Hruban RH, Lillemoe KD, Yeo CJ, Cameron JL (October 1996). "Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors". Annals of Surgery. 224 (4): 463–73, discussion 473–5. doi:10.1097/00000658-199610000-00005. PMC 1235406. PMID 8857851.
* Lieser MJ, Barry MK, Rowland C, Ilstrup DM, Nagorney DM (1998). "Surgical management of intrahepatic cholangiocarcinoma: a 31-year experience". Journal of Hepato-Biliary-Pancreatic Surgery. 5 (1): 41–7. doi:10.1007/PL00009949. PMID 9683753.
* Valverde A, Bonhomme N, Farges O, Sauvanet A, Flejou JF, Belghiti J (1999). "Resection of intrahepatic cholangiocarcinoma: a Western experience". Journal of Hepato-Biliary-Pancreatic Surgery. 6 (2): 122–7. doi:10.1007/s005340050094. PMID 10398898.
* Nakagohri T, Asano T, Kinoshita H, Kenmochi T, Urashima T, Miura F, Ochiai T (March 2003). "Aggressive surgical resection for hilar-invasive and peripheral intrahepatic cholangiocarcinoma". World Journal of Surgery. 27 (3): 289–93. doi:10.1007/s00268-002-6696-7. PMID 12607053.
* Weber SM, Jarnagin WR, Klimstra D, DeMatteo RP, Fong Y, Blumgart LH (October 2001). "Intrahepatic cholangiocarcinoma: resectability, recurrence pattern, and outcomes". Journal of the American College of Surgeons. 193 (4): 384–91. doi:10.1016/S1072-7515(01)01016-X. PMID 11584966.
93. ^ Estimates of survival after surgery for perihilar cholangiocarcinoma include:
* Burke EC, Jarnagin WR, Hochwald SN, Pisters PW, Fong Y, Blumgart LH (September 1998). "Hilar Cholangiocarcinoma: patterns of spread, the importance of hepatic resection for curative operation, and a presurgical clinical staging system". Annals of Surgery. 228 (3): 385–94. doi:10.1097/00000658-199809000-00011. PMC 1191497. PMID 9742921.
* Tsao JI, Nimura Y, Kamiya J, Hayakawa N, Kondo S, Nagino M, Miyachi M, Kanai M, Uesaka K, Oda K, Rossi RL, Braasch JW, Dugan JM (August 2000). "Management of hilar cholangiocarcinoma: comparison of an American and a Japanese experience". Annals of Surgery. 232 (2): 166–74. doi:10.1097/00000658-200008000-00003. PMC 1421125. PMID 10903592.
* Chamberlain RS, Blumgart LH (2000). "Hilar cholangiocarcinoma: a review and commentary". Annals of Surgical Oncology. 7 (1): 55–66. doi:10.1007/s10434-000-0055-4. PMID 10674450.
* Washburn WK, Lewis WD, Jenkins RL (March 1995). "Aggressive surgical resection for cholangiocarcinoma". Archives of Surgery. 130 (3): 270–6. doi:10.1001/archsurg.1995.01430030040006. PMID 7534059.
* Nagino M, Nimura Y, Kamiya J, Kanai M, Uesaka K, Hayakawa N, Yamamoto H, Kondo S, Nishio H (1998). "Segmental liver resections for hilar cholangiocarcinoma". Hepato-Gastroenterology. 45 (19): 7–13. PMID 9496478.
* Rea DJ, Munoz-Juarez M, Farnell MB, Donohue JH, Que FG, Crownhart B, Larson D, Nagorney DM (May 2004). "Major hepatic resection for hilar cholangiocarcinoma: analysis of 46 patients". Archives of Surgery. 139 (5): 514–23, discussion 523–5. doi:10.1001/archsurg.139.5.514. PMID 15136352.
* Launois B, Reding R, Lebeau G, Buard JL (2000). "Surgery for hilar cholangiocarcinoma: French experience in a collective survey of 552 extrahepatic bile duct cancers". Journal of Hepato-Biliary-Pancreatic Surgery. 7 (2): 128–34. doi:10.1007/s005340050166. PMID 10982604.
94. ^ Kaya M, de Groen PC, Angulo P, Nagorney DM, Gunderson LL, Gores GJ, Haddock MG, Lindor KD (April 2001). "Treatment of cholangiocarcinoma complicating primary sclerosing cholangitis: the Mayo Clinic experience". American Journal of Gastroenterology. 96 (4): 1164–9. PMID 11316165.
95. ^ Nakeeb A, Tran KQ, Black MJ, Erickson BA, Ritch PS, Quebbeman EJ, Wilson SD, Demeure MJ, Rilling WS, Dua KS, Pitt HA (October 2002). "Improved survival in resected biliary malignancies". Surgery. 132 (4): 555–63, discission 563–4. doi:10.1067/msy.2002.127555. PMID 12407338.
96. ^ Khan SA, Taylor-Robinson SD, Toledano MB, Beck A, Elliott P, Thomas HC (December 2002). "Changing international trends in mortality rates for liver, biliary and pancreatic tumours". Journal of Hepatology. 37 (6): 806–13. doi:10.1016/S0168-8278(02)00297-0. PMID 12445422.
97. ^ Table 37.2 in: Sternberg, Stephen (2012). Sternberg's diagnostic surgical pathology. Place of publication not identified: LWW. ISBN 978-1-4511-5289-0. OCLC 953861627.CS1 maint: ref=harv (link)
98. ^ Landis SH, Murray T, Bolden S, Wingo PA (1998). "Cancer statistics, 1998". Ca. 48 (1): 6–29. doi:10.3322/canjclin.48.1.6. PMID 9449931.
99. ^ Cancer Statistics Home Page — National Cancer Institute
100. ^ Multiple independent studies have documented a steady increase in the worldwide incidence of cholangiocarcinoma. Some relevant journal articles include:
* Patel T (May 2002). "Worldwide trends in mortality from biliary tract malignancies". BMC Cancer. 2: 10. doi:10.1186/1471-2407-2-10. PMC 113759. PMID 11991810.
* Patel T (June 2001). "Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States". Hepatology. 33 (6): 1353–7. doi:10.1053/jhep.2001.25087. PMID 11391522.
* Shaib YH, Davila JA, McGlynn K, El-Serag HB (March 2004). "Rising incidence of intrahepatic cholangiocarcinoma in the United States: a true increase?". Journal of Hepatology. 40 (3): 472–7. doi:10.1016/j.jhep.2003.11.030. PMID 15123362.
* West J, Wood H, Logan RF, Quinn M, Aithal GP (June 2006). "Trends in the incidence of primary liver and biliary tract cancers in England and Wales 1971-2001". British Journal of Cancer. 94 (11): 1751–8. doi:10.1038/sj.bjc.6603127. PMC 2361300. PMID 16736026.
* Khan SA, Taylor-Robinson SD, Toledano MB, Beck A, Elliott P, Thomas HC (December 2002). "Changing international trends in mortality rates for liver, biliary and pancreatic tumours". Journal of Hepatology. 37 (6): 806–13. doi:10.1016/S0168-8278(02)00297-0. PMID 12445422.
* Welzel TM, McGlynn KA, Hsing AW, O'Brien TR, Pfeiffer RM (June 2006). "Impact of classification of hilar cholangiocarcinomas (Klatskin tumors) on the incidence of intra- and extrahepatic cholangiocarcinoma in the United States". Journal of the National Cancer Institute. 98 (12): 873–5. doi:10.1093/jnci/djj234. PMID 16788161.
## External links[edit]
Classification
D
* ICD-10: C22.1
* ICD-9-CM: 155.1, 156.1
* ICD-O: M8160/3
* OMIM: 615619
* MeSH: D018281
* DiseasesDB: 2505
* SNOMED CT: 70179006
External resources
* MedlinePlus: 000291
* eMedicine: med/343 radio/153
* Patient UK: Cholangiocarcinoma
* Orphanet: 70567
Wikimedia Commons has media related to Cholangiocarcinoma.
Scholia has a topic profile for Cholangiocarcinoma.
* American Cancer Society Detailed Guide to Bile Duct Cancer.
* Patient information on extrahepatic bile duct tumors, from the National Cancer Institute.
* Cancer.Net: Bile Duct Cancer
* World Cholangiocarcinoma Day 2018
* v
* t
* e
Digestive system neoplasia
GI tract
Upper
Esophagus
* Squamous cell carcinoma
* Adenocarcinoma
Stomach
* Gastric carcinoma
* Signet ring cell carcinoma
* Gastric lymphoma
* MALT lymphoma
* Linitis plastica
Lower
Small intestine
* Duodenal cancer
* Adenocarcinoma
Appendix
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* benign: Hepatocellular adenoma
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Pancreas
* exocrine pancreas: Adenocarcinoma
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* Intraductal papillary mucinous neoplasm
* Mucinous cystic neoplasm
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* v
* t
* e
Glandular and epithelial cancer
Epithelium
Papilloma/carcinoma
* Small-cell carcinoma
* Combined small-cell carcinoma
* Verrucous carcinoma
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* Basal-cell carcinoma
* Transitional cell carcinoma
* Inverted papilloma
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* Warthin's tumor
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Glands
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adenocarcinomas
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* tract: Linitis plastica
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skin appendage
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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]: 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
| Cholangiocarcinoma | c0206698 | 827 | wikipedia | https://en.wikipedia.org/wiki/Cholangiocarcinoma | 2021-01-18T18:38:21 | {"mesh": ["D018281"], "umls": ["C0206698", "C0280725"], "icd-9": ["156.1", "155.1"], "wikidata": ["Q124292"]} |
Hemihydranencephaly
SpecialtyNeurology
Hemihydranencephaly is a severe cephalic disorder characterized by complete or almost complete absence of the cerebral cortex with preservation of meninges, basal ganglia, pons, medulla, cerebellum, and falx. It is a special type of hydranencephaly.
It is a very rare disease. As it stands, only 7 cases have been reported.
## References[edit]
* Greco F, Finocchiaro M, Pavone P, Trifiletti RR, Parano E. Hemihydranencephaly: case report and literature review. J Child Neurol. 2001;16 :218–221
This article about a medical condition affecting the nervous system is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Hemihydranencephaly | c0751210 | 828 | wikipedia | https://en.wikipedia.org/wiki/Hemihydranencephaly | 2021-01-18T18:42:00 | {"mesh": ["D006832"], "umls": ["C0751210"], "wikidata": ["Q5711633"]} |
Holoprosencephaly-radial heart renal anomalies syndrome is characterised by holoprosencephaly, predominantly radial limb deficiency (absent thumbs, phocomelia), heart defects, kidney malformations and absence of gallbladder.
## Epidemiology
It has been described in two families (with at least seven affected persons).
## Clinical description
Variable manifestations include vertebral anomalies, cleft lip/palate, microphthalmia, absent nose, dysplastic ears, hearing loss, colobomas of the iris and retina and/or bifid uvula.
## Genetic counseling
Inheritance is likely to be autosomal dominant with variable expressivity.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Holoprosencephaly-radial heart renal anomalies syndrome | c1866649 | 829 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3186 | 2021-01-23T17:33:23 | {"gard": ["2727"], "mesh": ["C566655"], "omim": ["184705"], "umls": ["C1866649"], "icd-10": ["Q87.8"], "synonyms": ["Steinfeld syndrome"]} |
Human medical condition
Vitreomacular adhesion
Schematic diagram of the human eye.
Vitreomacular adhesion (VMA) is a human medical condition where the vitreous gel (or simply vitreous, AKA vitreous humour) of the human eye adheres to the retina in an abnormally strong manner. As the eye ages, it is common for the vitreous to separate from the retina. But if this separation is not complete, i.e. there is still an adhesion, this can create pulling forces on the retina that may result in subsequent loss or distortion of vision. The adhesion in of itself is not dangerous, but the resulting pathological vitreomacular traction (VMT) can cause severe ocular damage.
The current standard of care for treating these adhesions is pars plana vitrectomy (PPV), which involves surgically removing the vitreous from the eye. A biological agent for non-invasive treatment of adhesions called ocriplasmin has been approved by the FDA on Oct 17 2012.
## Contents
* 1 Symptom and signs
* 2 Pathology
* 3 Diagnosis
* 4 Treatment
* 5 References
* 6 External links
## Symptom and signs[edit]
Traction caused by VMA is the underlying pathology of an eye disease called symptomatic VMA. There is evidence that symptomatic VMA can contribute to the development of several well-known eye disorders, such as macular hole and macular pucker, that can cause visual impairment, including blindness. It may also be associated with age-related macular degeneration (AMD), diabetic macular edema (DME), retinal vein occlusion, and diabetic retinopathy (DR).
## Pathology[edit]
Over time, it is common for the vitreous within the human eye to liquify and collapse in processes known as syneresis and synchisis respectively. This creates fluid-filled areas that can combine to form pockets of vitreous gel that are mostly liquid with very small concentrations of collagen. If these liquid pockets are close enough to the interface between the vitreous gel and the retina, they can cause complete separation of the vitreous from the retina in a normally occurring process in older humans called posterior vitreous detachment (PVD). PVD in of itself is not dangerous and a natural process.
If the separation of the vitreous from the retina is not complete, areas of focal attachment or adhesions can occur, i.e. a VMA. The pulling forces or traction from this adhesion on the retinal surface can sometimes cause edema within the retina, damage to retinal blood vessels causing bleeding, or damage to the optic nerve causing disruption in the nerve signals sent to the brain for visual processing. It is important to note that while the VMA itself is not dangerous, the resultant pulling on the retina called vitreomacular traction (VMT) causes the above damage. The size and strength of the VMA determine the variety of resulting pathologies or symptoms.[1]
VMA can also lead to the development of VMT/traction-related complications such as macular puckers and macular holes leading to distorted vision or metamorphopsia; epiretinal membrane; tractional macular oedema; myopic macular retinoschisis; visual impairment; blindness. The incidence of VMA is reported as high as 84% for patients with macular hole, 100% for patients with vitreomacular traction syndrome, and 56% in idiopathic epimacular membrane.[2]
## Diagnosis[edit]
Careful eye examination by an ophthalmologist or optometrist is critical for diagnosing symptomatic VMA. Imaging technologies such as optical coherence tomography (OCT) have significantly improved the accuracy of diagnosing symptomatic VMA.
## Treatment[edit]
A new FDA approved drug was released on the market late 2013. Jetrea (Brand name) or Ocriplasmin (Generic name) is the first drug of its kind used to treat vitreomacular adhension. Mechanism of Action: Ocriplasmin is a truncated human plasmin with proteolytic activity against protein components of the vitreous body and vitreretinal interface. It dissolves the protein matrix responsible for the vitreomacular adhesion. Adverse drug reactions: Decreased vision, potential for lens sublaxation, dyschromatopsia (yellow vision), eye pain, floaters, blurred vision. New Drug comparison Rating gave Jetea a 5 indicating an important advance. Previously, no recommended treatment was available for the patient with mild symptomatic VMA. In symptomatic VMA patients with more significant vision loss, the standard of care is pars plana vitrectomy (PPV), which involves surgically removing the vitreous from the eye, thereby surgically releasing the symptomatic VMA. In other words, vitrectomy induces PVD to release the traction/adhesion on the retina. An estimated 850,000 vitrectomy procedures are performed globally on an annual basis with 250,000 in the United States alone.
A standard PPV procedure can lead to serious complications[3][4][5][6] including small-gauge PPV.[7][8][9][10][11] Complications can include retinal detachment, retinal tears, endophthalmitis, and postoperative cataract formation. Additionally, PPV may result in incomplete separation, and it may potentially leave a nidus for vasoactive and vasoproliferative substances, or it may induce development of fibrovascular membranes. As with any invasive surgical procedure, PPV introduces trauma to the vitreous and surrounding tissue.[12][13]
There are data showing that nonsurgical induction of PVD using ocriplasmin (a recombinant protease with activity against fibronectin and laminin)[14] can offer the benefits of successful PVD while eliminating the risks associated with a surgical procedure, i.e. vitrectomy. Pharmacologic vitreolysis is an improvement over invasive surgery as it induces complete separation, creates a more physiologic state of the vitreomacular interface, prevents the development of fibrovascular membranes, is less traumatic to the vitreous, and is potentially prophylactic.[15][16] As of 2012, ThromboGenics is still developing the ocriplasmin biological agent. Ocriplasmin is approved recently under the name Jetrea for use in the United States by the FDA.view.[17]
An experimental test of injections of perfluoropropane (C3F8) on 15 symptomatic eyes of 14 patients showed that vitreomacular traction resolved in 6 eyes within 1 month and resolved in 3 more eyes within 6 months.[18] A systematic review found high-certainty evidence that Ocriplasmin compared to no treatment increases the chance of resolution and improves vision in people with symptomatic VMA. [19] Ocriplasmin probably reduces the need for surgery but there were more adverse events in eyes treated with ocriplasmin compared to control.
## References[edit]
1. ^ Paolo Carpineto, Luca Di Antonio, Agbeanda Aharrh-Gnama, Vincenzo Ciciarelli, Leonardo Mastropasqua. Diagnosing and Treating Vitreomacular Adhesion. European Ophthalmic Review, 2011,5(1):69-73
2. ^ Koerner F, Garweg J. [Diseases of the vitreo-macular interface]. Klin Monbl Augenheilkd. 1999;214(5):305-310.
3. ^ Mojana F, Cheng L, Bartsch DU, et al. The role of abnormal vitreomacular adhesion in age-related macular degeneration: spectral optical coherence tomography and surgical results. Am J Ophthalmol. 2008;146(2):218-227.
4. ^ Doft BH, Wisniewski SR, Kelsey SF, Groer-Fitzgerald S; Endophthalmitis Vitrectomy Study Group. Diabetes and postcataract extraction endophthalmitis. Curr Opin Ophthalmol. 2002;13(3):147-151.
5. ^ Doft BM, Kelsey SF, Wisniewski SR. Retinal detachment in the endophthalmitis vitrectomy study. Arch Ophthalmol. 2000;118(12):1661-1665.
6. ^ Wisniewski SR, Capone A, Kelsey SF, et al. Characteristics after cataract extraction or secondary lens implantation among patients screened for the Endophthalmitis Vitrectomy Study. Ophthalmology. 2000;107(7):1274-1282.
7. ^ Gupta OP, Weichel ED, Regillo CD, et al. Postoperative complications associated with 25-gauge pars plana vitrectomy. Ophthalmic Surg Lasers Imaging. 2007;38(4):270–275.
8. ^ Liu DT, Chan CK, Fan DS, Lam SW, Lam DS, Chan WM. Choroidal folds after 25 gauge transconjunctival sutureless vitrectomy. Eye. 2005;19(7):825–827.
9. ^ Scott IU, Flynn HW Jr, Dev S, et al. Endophthalmitis after 25-gauge and 20-gauge pars plana vitrectomy: incidence and outcomes. Retina. 2008;28(1):138–142.
10. ^ Kunimoto DY, Kaiser RS; Wills Eye Retina Service. Incidence of endophthalmitis after 20- and 25- gauge vitrectomy. Ophthalmology. 2007;114(12):2133–2137.
11. ^ Kaiser RS. Complications of sutureless vitrectomy and the findings of the Micro-Surgical Safety Task Force. Paper presented at: Retina Subspecialty Day, Annual Meeting of the American Academy of Ophthalmology; November 7–8, 2008; Atlanta, GA.
12. ^ de Smet MD, Gandorfer A, Stalmans P, et al. Microplasmin intravitreal administration in patients with vitreomacular traction scheduled for vitrectomy: the MIVI I trial. Ophthalmology. 2009;116(7):1349-1355.
13. ^ Goldenberg DT, Trese MT. Pharmacologic vitreodynamics and molecular flux. Dev Ophthalmol. 2009;44:31-36.
14. ^ Stalmans P, Benz MS, Gandorfer A, Kampik A, Girach A, Pakola S, Haller JA; MIVI-TRUST Study Group. Enzymatic vitreolysis with ocriplasmin for vitreomacular traction and macular holes. N Engl J Med. 2012 Aug 16;367(7):606-15.
15. ^ de Smet MD, Gandorfer A, Stalmans P, et al. Microplasmin intravitreal administration in patients with vitreomacular traction scheduled for vitrectomy: the MIVI I trial. Ophthalmology. 2009;116(7):1349-1355.
16. ^ Goldenberg DT, Trese MT. Pharmacologic vitreodynamics and molecular flux. Dev Ophthalmol. 2009;44:31-36.
17. ^ "Retina Today - May 2012".
18. ^ Rodrigues IA; Stangos AN; McHugh DA; Jackson TL (2013). "Intravitreal injection of expansile perfluoropropane (C3F8) for the treatment of vitreomacular traction". American Journal of Ophthalmology. 155 (2)): 270–276. doi:10.1016/j.ajo.2012.08.018. PMID 23164159.
19. ^ Neffendorf, James E; Kirthi, Varo; Pringle, Edward; Jackson, Timothy L (2017-10-17). "Ocriplasmin for symptomatic vitreomacular adhesion". Cochrane Database of Systematic Reviews. 10: CD011874. doi:10.1002/14651858.cd011874.pub2. ISSN 1465-1858. PMC 6485716. PMID 29040800.
## External links[edit]
Classification
D
* DiseasesDB: 35117
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Vitreomacular adhesion | c2748203 | 830 | wikipedia | https://en.wikipedia.org/wiki/Vitreomacular_adhesion | 2021-01-18T18:35:59 | {"umls": ["C2748203"], "wikidata": ["Q7937230"]} |
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (January 2020)
Axial and sagittal CT views of a vertebral hemangioma
T1, T2, and STIR MRI images of a vertebral hemangioma
A vertebral hemangioma (VH) is a vascular lesion within a vertebral body. Commonly, these are benign lesions that are found incidentally during radiology studies for other indications. Vertebral hemangiomas are a common etiology estimated to be found in 10-12% of humans at autopsy.[1][2][3] They are benign in nature and frequently asymptomatic.[2] Symptoms, if they do occur, are usually related to large hemangiomas, trauma, the hormonal and hemodynamic changes of pregnancy (causing intra-spinal bleeding), or osseous expansion and extra-osseous extension into surround soft tissues or epidural region of the spinal canal.[1][3][4][5][6]
## Contents
* 1 Etiology and epidemiology
* 2 Imaging characteristics
* 3 Differential diagnosis
* 4 Treatment
* 5 References
## Etiology and epidemiology[edit]
Vertebral hemangiomas are hamartomatous lesions, meaning that they arise from dysembryogenetic origin. They are made up of thin-walled vessels infiltrating the medullary cavity between bone trabeculae and are usually confined to the vertebral body.[7] VHs are commonly seen incidentally while obtaining imaging for other indications.[1] Only around 1% of hemangiomas become symptomatic.[3] When symptomatic, they can cause pain and myelopathy by intra-spinal bleeding, bony expansion or extra-osseous extension into surround soft tissue or the posterior neural elements.[1][3][4][5] Highly vascular (cavernous type) hemangiomas can produce neurologic deficits without prominent evidence of spinal cord compression. The deficits in these cases are probably attributable to blood flow disturbances in the spinal cord.[7]
## Imaging characteristics[edit]
On computed tomography (CT) or radiograph, VHs can cause rarefaction with vertical striations (often referred to as corduroy pattern) or a coarse honeycomb appearance. A polka-dot appearance on CT scan represents a cross-section of reinforced trabeculae.[7][8] Baudrez, Galant, and VandeBerg found that MRI appearance is dictated by histology of the tumor—Vascularity, interstitial edema, and interspersed fat.[9] The presence of high or moderate signal intensity on both T1 and T2 images is related to the ration of fat to vessels and edema. For example, a VH with a high concentration of fat and a relatively low make-up of vessels and edema would show a high signal intensity on T1-weighted spin-echo images and intermediate signal intensity on T2-weighted fast spin echo images. Whereas a VH made-up of nearly equal portion of fat and vessels and edema would show intermediate signal intensity on T1-weighted images and high signal intensity on T2-weighted images.[9]
## Differential diagnosis[edit]
The differential diagnosis for lesions with similar radiologic appearance to VH includes but is not limited to hemangioblastoma, lymphangioma, bone metastasis, Ewing Sarcoma, and spinal dural arteriovenous fistula.[7][10][11][12][13][14]
## Treatment[edit]
Symptomatic VHs have been treated with surgery, transarterial embolization, direct ethanol injection, radiotherapy, and vertebroplasty, each with varying degrees of success.[13] Each of these methods can be indicated in specific clinical settings.
## References[edit]
1. ^ a b c d Blecher, R., et al., Management of symptomatic vertebral hemangioma: follow-up of 6 patients. J Spinal Disord Tech, 2011. 24(3): p. 196-201.
2. ^ a b Halpern, C.H. and M.S. Grady, Neurosurgery, in Schwartz's Principles of Surgery, 10e, F.C. Brunicardi, et al., Editors. 2014, McGraw-Hill Education: New York, NY.
3. ^ a b c d Pastushyn, A.I., E.I. Slin'ko, and G.M. Mirzoyeva, Vertebral hemangiomas: diagnosis, management, natural history and clinicopathological correlates in 86 patients. Surg Neurol, 1998. 50(6): p. 535-47.
4. ^ a b Chi, J.H., G.T. Manley, and D. Chou, Pregnancy-related vertebral hemangioma. Case report, review of the literature, and management algorithm. Neurosurg Focus, 2005. 19(3): p. E7.
5. ^ a b Castel, E., et al., Acute spinal cord compression due to intraspinal bleeding from a vertebral hemangioma: two case-reports. Eur Spine J, 1999. 8(3): p. 244-8.
6. ^ Pinto, D.S., et al., Aggressive Vertebral Body Hemangioma Causing Compressive Myelopathy - Two Case Reports. Journal of Orthopaedic Case Reports, 2017. 7(2): p. 7-10.
7. ^ a b c d Rodallec, M.H., et al., Diagnostic imaging of solitary tumors of the spine: what to do and say. Radiographics, 2008. 28(4): p. 1019-41.
8. ^ Slon, V., et al., Vertebral Hemangiomas and Their Correlation With Other Pathologies. Spine (Phila Pa 1976), 2016. 41(8): p. E481-8.
9. ^ a b Baudrez, V., C. Galant, and B.C. Vande Berg, Benign vertebral hemangioma: MR-histological correlation. Skeletal Radiol, 2001. 30(8): p. 442-6.
10. ^ Bemporad, J.A., et al., Pseudohemangioma of the vertebra: an unusual radiographic manifestation of primary Ewing's sarcoma. AJNR Am J Neuroradiol, 1999. 20(10): p. 1809-13.
11. ^ Higgins, J.N., et al., Intraosseous vertebral haemangioblastoma: MRI. Neuroradiology, 1996. 38 Suppl 1: p. S107-10.
12. ^ Mendez, J.A., et al., Radiologic appearance of a rare primary vertebral lymphangioma. AJNR Am J Neuroradiol, 2002. 23(10): p. 1665-8.
13. ^ a b Acosta, F.L., Jr., et al., Current treatment strategies and outcomes in the management of symptomatic vertebral hemangiomas. Neurosurgery, 2006. 58(2): p. 287-95; discussion 287-95.
14. ^ Artigas, C., et al., Vertebral Hemangioma Mimicking Bone Metastasis in 68Ga-PSMA Ligand PET/CT. Clin Nucl Med, 2017. 42(5): p. 368-370.
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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
| Vertebral hemangioma | c3495935 | 831 | wikipedia | https://en.wikipedia.org/wiki/Vertebral_hemangioma | 2021-01-18T18:54:28 | {"umls": ["C3495935"], "wikidata": ["Q65091065"]} |
Shrunken, non-functional eye
Phthisis bulbi
Phthisis bulbi of the right eye due to complication of eye surgery
SpecialtyOphthalmology
SymptomsShrunken eye with little or no function
CausesEye surgery
Risk factorsEye injury, Eye surgery, eye disease
PreventionBy treating the condition before the eye goes to pthisis
TreatmentSurgery
PrognosisUsually permanent blindness in affected eye
Deaths0
Phthisis bulbi is a shrunken,[1] non-functional eye. It may result from severe eye disease, inflammation[2] or injury, or it may represent a complication of eye surgery.[3] Treatment options include insertion of a prosthesis, which may be preceded by enucleation of the eye.[4][5]
## Contents
* 1 Symptoms
* 2 Causes
* 3 Treatment
* 4 References
* 5 External links
## Symptoms[edit]
The affected eye is shrunken, and has little to no vision. The intraocular pressure in the affected eye is very low or nonexistent. The layers in the eye may be fused together, thickened, or edematous. The eyelids may be glued shut. The eye may be soft when palpated.[6] Under a microscope there may be deposits of calcium or bone, and the cornea is often affected by cataracts.[7]
## Causes[edit]
It can be caused by injury, including burns to the eye, or long-term eye disease or inflammation. End-stage glaucoma can cause it. It can often complicate eye surgery.[6] Other common causes include cancer, retinal detachment, vascular lesions, infection, and inflammation.[7]
## Treatment[edit]
Treatment for the affected eye is often futile. Usually, treatment is to end the pain in the affected eye and for cosmetic purposes, not to restore vision.[7] It can be removed, a procedure called enucleation of the eye. Sometimes, though, it is possible to transplant only parts of the eye, and some vision can be restored.[6]
## References[edit]
1. ^ Dornblüth, von Willibald Pschyrembel. Gegr. von Otto (1977). Klinisches Wörterbuch : mit klinischen Syndromen und einem Anhang Nomina Anatomica (253., um einen Anh. 'Nomina anatomica' erw. Aufl. ed.). Berlin [u.a.]: de Gruyter. ISBN 978-3-11-007018-7.
2. ^ Hui JI (September 2010). "Outcomes of orbital implants after evisceration and enucleation in patients with endophthalmitis". Curr Opin Ophthalmol. 21 (5): 375–9. doi:10.1097/ICU.0b013e32833b7a56. PMID 20489621.
3. ^ Apple DJ, Jones GR, Reidy JJ, Loftfield K (1985). "Ocular perforation and phthisis bulbi secondary to strabismus surgery". J Pediatr Ophthalmol Strabismus. 22 (5): 184–7. PMID 4045647.
4. ^ Cote RE, Haddad SE (1990). "Fitting a prosthesis over phthisis bulbi or discolored blind eyes". Adv Ophthalmic Plast Reconstr Surg. 8: 136–45. PMID 2248703.
5. ^ Soares IP, França VP (May 2010). "Evisceration and enucleation". Semin Ophthalmol. 25 (3): 94–7. doi:10.3109/08820538.2010.488575. PMID 20590419.
6. ^ a b c Dohlman CH, D'Amico DJ (January 1999). "Can an eye in phthisis be rehabilitated? A case of improved vision with 1-year follow-up". Arch Ophthalmol. 117 (1): 123–4. doi:10.1001/archopht.117.1.123. PMID 9930175.
7. ^ a b c Tripathy K, Chawla R, Temkar S, Sagar P, Kashyap S, Pushker N, Sharma YR (2018). "Phthisis Bulbi-a Clinicopathological Perspective". Semin Ophthalmol. 33 (6): 788–803. doi:10.1080/08820538.2018.1477966. PMID 29902388.
## External links[edit]
Classification
D
* ICD-10: H44.5
* ICD-9-CM: 360.41
* v
* t
* e
* Diseases of the human eye
Adnexa
Eyelid
Inflammation
* Stye
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* Epiretinal membrane (Macular pucker)
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Other
* Glaucoma / Ocular hypertension / Primary juvenile glaucoma
* Floater
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* Red eye
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* Keratomycosis
* Phthisis bulbi
* Persistent fetal vasculature / Persistent hyperplastic primary vitreous
* Persistent tunica vasculosa lentis
* Familial exudative vitreoretinopathy
Pathways
Optic nerve
Optic disc
* Optic neuritis
* optic papillitis
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Optic neuropathy
* Ischemic
* anterior (AION)
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Strabismus
Extraocular muscles
Binocular vision
Accommodation
Paralytic strabismus
* Ophthalmoparesis
* Chronic progressive external ophthalmoplegia
* Kearns–Sayre syndrome
palsies
* Oculomotor (III)
* Fourth-nerve (IV)
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Other strabismus
* Esotropia / Exotropia
* Hypertropia
* Heterophoria
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* Exophoria
* Cyclotropia
* Brown's syndrome
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Other binocular
* Conjugate gaze palsy
* Convergence insufficiency
* Internuclear ophthalmoplegia
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Refraction
* Refractive error
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* Astigmatism
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Vision disorders
Blindness
* Amblyopia
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* Dichromacy
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* Blindness / Vision loss / Visual impairment
Anopsia
* Hemianopsia
* binasal
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* homonymous
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subjective
* Asthenopia
* Hemeralopia
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* Scintillating scotoma
Pupil
* Anisocoria
* Argyll Robertson pupil
* Marcus Gunn pupil
* Adie syndrome
* Miosis
* Mydriasis
* Cycloplegia
* Parinaud's syndrome
Other
* Nystagmus
* Childhood blindness
Infections
* Trachoma
* Onchocerciasis
This article about a medical condition affecting the nervous system is a stub. You can help Wikipedia by expanding it.
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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
| Phthisis bulbi | c0154788 | 832 | wikipedia | https://en.wikipedia.org/wiki/Phthisis_bulbi | 2021-01-18T18:38:15 | {"umls": ["C0154788"], "icd-10": ["H44.5"], "wikidata": ["Q906264"]} |
Scalp-ear-nipple syndrome, as its name suggests, is a condition characterized by abnormalities of the scalp, ears, and nipples. Less frequently, affected individuals have problems affecting other parts of the body. The features of this disorder can vary even within the same family.
Babies with scalp-ear-nipple syndrome are born with a condition called aplasia cutis congenita, which involves patchy abnormal areas (lesions) on the scalp. These lesions are firm, raised, hairless nodules that resemble open wounds or ulcers at birth, but that heal during childhood.
The external ears of people with scalp-ear-nipple syndrome may be small, cup-shaped, folded over, or otherwise mildly misshapen. Hearing is generally normal. Affected individuals also have nipples that are underdeveloped (hypothelia) or absent (athelia). In some cases the underlying breast tissue is absent as well (amastia).
Other features that can occur in this disorder include malformed and brittle fingernails and toenails (nail dystrophy), dental abnormalities including widely-spaced or missing teeth, fusion of the skin between some of the fingers and toes (cutaneous syndactyly), and kidney defects such as underdevelopment (hypoplasia) of one or both kidneys. Unusual facial features, including narrowed openings of the eyes (narrowed palpebral fissures), an increased distance between the inner corners of the eyes (telecanthus), a flat bridge of the nose, and nostrils that open to the front rather than downward (anteverted nares), can also occur in this disorder.
## Frequency
The prevalence of scalp-ear-nipple syndrome is unknown. Only a small number of affected individuals have been described in the medical literature.
## Causes
Scalp-ear-nipple syndrome is caused by mutations in the KCTD1 gene. This gene provides instructions for making a protein that acts as a transcriptional repressor, which means that it turns off (represses) the activity of certain genes when they are not needed. Specifically, the KCTD1 protein is thought to control (regulate) the activity of genes involved in the development of an embryonic cell layer called the ectoderm. Within the developing embryo, the ectoderm gives rise to several body tissues including the skin, hair, nails, and teeth.
The mutations in the KCTD1 gene that cause scalp-ear-nipple syndrome impair the transcriptional repressor function of the KCTD1 protein. Impairment of this function results in abnormal regulation of genes involved in ectodermal development. The altered gene activity disrupts normal development of the tissues that arise from the ectoderm (ectodermal dysplasia) and leads to the signs and symptoms of scalp-ear-nipple syndrome.
### Learn more about the gene associated with Scalp-ear-nipple syndrome
* KCTD1
## Inheritance Pattern
Scalp-ear-nipple syndrome is considered to be an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases of this condition result from new mutations in the gene and occur in people with no history of the disorder in their family. In other cases, an affected person inherits the mutation from one affected parent.
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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
| Scalp-ear-nipple syndrome | c1867020 | 833 | medlineplus | https://medlineplus.gov/genetics/condition/scalp-ear-nipple-syndrome/ | 2021-01-27T08:24:54 | {"gard": ["159"], "mesh": ["C536623"], "omim": ["181270"], "synonyms": []} |
## Clinical Features
Mehes and Petrovicz (1982) found hypocupremia with normal ceruloplasmin (117700) levels in a 21-month-old boy admitted to hospital because of repeated seizures and failure to thrive. He had blond curly hair, spurring of the femurs and tibias, and mild anemia, but his mental development, electroencephalogram, and hair structure on microscopic examination were normal. His condition improved with supplements of oral copper, but as soon as these were reduced or stopped, hypocupremia and seizures recurred. Photographs showed curly hair and an appearance of the nose and lips reminiscent of that in the infantile hypercalcemia syndrome. The father and 2 brothers were physically and biochemically normal. The mother, aged 28, was notably thin, had always been pale and vulnerable to infections but had no seizures. Her face was seborrheic and her hair so thin that the top of the head was almost bald. Serum copper was low. The mother's brother was also thin and had been frequently ill as a child but had never had seizures. He had had blond, 'extremely curly' hair, but had been bald since age 24 years. His skin was seborrheic and serum copper was low. His 2 sons were healthy with brown, slightly curly hair and normal serum copper levels. Deficient dietary intake of copper and excessive renal loss were excluded. The authors suggested either X-linked or autosomal dominant inheritance and a defect in intestinal absorption of copper. Mehes and Petrovicz (1988-89) provided a 7-year follow-up. Low serum copper levels with marginally low/normal ceruloplasmin values persisted. It was thought that seborrhea improved with copper supplementation.
Hair \- Blond curly hair \- Early balding Growth \- Failure to thrive \- Thin habitus Neuro \- Seizures Skin \- Seborrhea Radiology \- Spurring of femurs and tibias Inheritance \- Autosomal dominant vs. X-linked Lab \- Hypocupremia \- Normal ceruloplasmin levels \- ? Defective intestinal absorption of copper Heme \- Mild anemia ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
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*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| COPPER DEFICIENCY, FAMILIAL BENIGN | c1852576 | 834 | omim | https://www.omim.org/entry/121270 | 2019-09-22T16:43:03 | {"mesh": ["C535468"], "omim": ["121270"], "orphanet": ["1551"]} |
Not to be confused with Trichodysplasia spinulosa.
Trichostasis spinulosa
SpecialtyDermatology
Trichostasis spinulosa is a common but rarely diagnosed disorder of the hair follicles[1] that clinically gives the impression of blackheads, but the follicles are filled with funnel-shaped, horny plugs that are bundles of vellus hairs.[2]:768
## Contents
* 1 Diagnosis
* 2 Treatment
* 3 See also
* 4 References
## Diagnosis[edit]
Standard skin surface biopsy (SSSB) is a noninvasive method used for diagnosis.[1]
## Treatment[edit]
This section is empty. You can help by adding to it. (July 2018)
## See also[edit]
* List of cutaneous conditions
## References[edit]
1. ^ a b Gündüz, Özge; Aytekin, Asli (1 January 2012). "Trichostasis Spinulosa Confirmed by Standard Skin Surface Biopsy". International Journal of Trichology. 4 (4): 273–4. doi:10.4103/0974-7753.111201. PMC 3681110. PMID 23766613.
2. ^ 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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*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Trichostasis spinulosa | c0263487 | 835 | wikipedia | https://en.wikipedia.org/wiki/Trichostasis_spinulosa | 2021-01-18T18:53:45 | {"gard": ["5269"], "mesh": ["C536558"], "umls": ["C0263487"], "wikidata": ["Q7841016"]} |
Slipped capital femoral epiphysis
Other namesSlipped upper femoral epiphysis, coxa vara adolescentium, SCFE, SUFE
X-ray showing a slipped capital femoral epiphysis, before and after surgical fixation.
SpecialtyOrthopedic surgery
SymptomsGroin pain, referred knee and thigh pain, waddling gait, restricted range of motion of leg
Usual onsetAdolescence
Risk factorsObesity, hypothyroidism
Slipped capital femoral epiphysis (SCFE or skiffy, slipped upper femoral epiphysis, SUFE or souffy, coxa vara adolescentium) is a medical term referring to a fracture through the growth plate (physis), which results in slippage of the overlying end of the femur (metaphysis).
Normally, the head of the femur, called the capital, should sit squarely on the femoral neck. Abnormal movement along the growth plate results in the slip. The term slipped capital femoral epiphysis is actually a misnomer, because the epiphysis (end part of a bone) remains in its normal anatomical position in the acetabulum (hip socket) due to the ligamentum teres femoris. It is actually the metaphysis (neck part of a bone) which slips in an anterior direction with external rotation.
SCFE is the most common hip disorder in adolescence. SCFEs usually cause groin pain on the affected side, but sometimes cause knee or thigh pain. One in five cases involves both hips, resulting in pain on both sides of the body. SCFEs occurs slightly more commonly in adolescent males, especially young black males, although it also affects females. Whilst it can occur in any child, the major risk factor is childhood obesity.[1] Symptoms include the gradual, progressive onset of thigh or knee pain with a painful limp. Hip motion will be limited, particularly internal rotation. Running, and other strenuous activity on legs, will also cause the hips to abnormally move due to the condition and can potentially worsen the pain. Stretching is very limited.
## Contents
* 1 Signs and symptoms
* 1.1 Complications
* 2 Cause
* 3 Pathophysiology
* 4 Diagnosis
* 4.1 Classification
* 5 Treatment
* 6 Epidemiology
* 7 See also
* 8 References
* 9 External links
## Signs and symptoms[edit]
Usually, a SCFE causes groin pain, but it may cause pain in only the thigh or knee, because the pain may be referred along the distribution of the obturator nerve.[2] The pain may occur on both sides of the body (bilaterally), as up to 40 percent of cases involve slippage on both sides.[3] In cases of bilateral SCFEs, they typically occur within one year of each other.[4] About 20 percent of all cases include a SCFE on both sides at the time of presentation.[5]
Signs of a SCFE include a waddling gait, decreased range of motion. Often the range of motion in the hip is restricted in internal rotation, abduction, and flexion.[2] A person with a SCFE may prefer to hold their hip in flexion and external rotation.[citation needed]
### Complications[edit]
Failure to treat a SCFE may lead to: death of bone tissue in the femoral head (avascular necrosis), degenerative hip disease (hip osteoarthritis),[6] gait abnormalities and chronic pain. SCFE is associated with a greater risk of arthritis of the hip joint later in life.[6] 17–47 percent of acute cases of SCFE lead to the death of bone tissue (osteonecrosis) effects.[2]
## Cause[edit]
In general, SCFE is caused by increased force applied across the epiphysis, or a decrease in the resistance within the physis to shearing.[4] Obesity is the by far the most significant risk factor. A study in Scotland looked at the weight of 600,000 infants, and followed them up to see who got SCFE.[1] This study identified that obese children had an almost twenty times greater risk than thin children, with a 'dose-response'- so the greater the weight of the child, the greater the risk of SCFE. In 65 percent of cases of SCFE, the person is over the 95th percentile for weight.[2] Endocrine diseases may also contribute (though are far less of a risk than obesity), such as hypothyroidism, hypopituitarism, and renal osteodystrophy.[2][7]
Sometimes no single cause accounts for SCFE, and several factors play a role in the development of a SCFE i.e. both mechanical and endocrine (hormone-related) factors. Skeletal changes may also make someone at risk of SCFE, including femoral or acetabular retroversion,[4] those these may simply be chronic skeletal manifestations of childhood obesity.
## Pathophysiology[edit]
SCFE is a Salter-Harris type 1 fracture through the proximal femoral physis. Stress around the hip causes a shear force to be applied at the growth plate. While trauma has a role in the manifestation of the fracture, an intrinsic weakness in the physeal cartilage also is present. The almost exclusive incidence of SCFE during the adolescent growth spurt indicates a hormonal role. Obesity is another key predisposing factor in the development of SCFE.[citation needed]
The fracture occurs at the hypertrophic zone of the physeal cartilage. Stress on the hip causes the epiphysis to move posteriorly and medially. By convention, position and alignment in SCFE is described by referring to the relationship of the proximal fragment (capital femoral epiphysis) to the normal distal fragment (femoral neck). Because the physis has yet to close, the blood supply to the epiphysis still should be derived from the femoral neck; however, this late in childhood, the supply is tenuous and frequently lost after the fracture occurs. Manipulation of the fracture frequently results in osteonecrosis and the acute loss of articular cartilage (chondrolysis) because of the tenuous nature of the blood supply.[citation needed]
## Diagnosis[edit]
The diagnosis is a combination of clinical suspicion plus radiological investigation. Children with a SCFE experience a decrease in their range of motion, and are often unable to complete hip flexion or fully rotate the hip inward.[8] 20–50% of SCFE are missed or misdiagnosed on their first presentation to a medical facility.[citation needed] SCFEs may be initially overlooked, because the first symptom is knee pain, referred from the hip. The knee is investigated and found to be normal.[7]
The diagnosis requires x-rays of the pelvis, with anteriorposterior (AP) and frog-leg lateral views.[9] The appearance of the head of the femur in relation to the shaft likens that of a "melting ice cream cone", visible with Klein's line. The severity of the disease can be measured using the Southwick angle.[citation needed]
### Classification[edit]
* Atypical/Typical
* Loder classification
* Stable
* Unstable, practically defined as when the patient is unable to ambulate even with crutches[9]
* Temporal
* Acute
* Chronic
* Acute-on-chronic
* Radiological
* Grade I = 0–33% slippage
* Grade II = 34–50% slippage
* Grade III = >50% slippage
## Treatment[edit]
The disease can be treated with external in-situ pinning or open reduction and pinning. Consultation with an orthopaedic surgeon is necessary to repair this problem. Pinning the unaffected side prophylactically is not recommended for most patients, but may be appropriate if a second SCFE is very likely.[9]
Once SCFE is suspected, the patient should be non-weight bearing and remain on strict bed rest. In severe cases, after enough rest the patient may require physical therapy to regain strength and movement back to the leg. A SCFE is an orthopaedic emergency, as further slippage may result in occlusion of the blood supply and avascular necrosis (risk of 25 percent). Almost all cases require surgery, which usually involves the placement of one or two pins into the femoral head to prevent further slippage.[10] The recommended screw placement is in the center of the epiphysis and perpendicular to the physis.[11] Chances of a slippage occurring in the other hip are 20 percent within 18 months of diagnosis of the first slippage and consequently the opposite unaffected femur may also require pinning.[citation needed]
The risk of reducing this fracture includes the disruption of the blood supply to the bone. It has been shown in the past that attempts to correct the slippage by moving the head back into its correct position can cause the bone to die. Therefore the head of the femur is usually pinned 'as is'. A small incision is made in the outer side of the upper thigh and metal pins are placed through the femoral neck and into the head of the femur. A dressing covers the wound.[citation needed]
## Epidemiology[edit]
SCFE affects approximately 1–10 per 100,000 children.[4] The incidence varies by geographic location, season of the year, and ethnicity.[4] In eastern Japan, the incidence is 0.2 per 100,000 and in the northeastern U.S. it is about 10 per 100,000.[2] Africans and Polynesians have higher rates of SCFE.[2]
SCFEs are most common in adolescents 11–15 years of age,[6] and affects boys more frequently than girls (male 2:1 female).[2][4] It is strongly linked to obesity, and weight loss may decrease the risk.[12] Other risk factors include: family history, endocrine disorders, radiation / chemotherapy, and mild trauma.
The left hip is more often affected than the right.[2] Over half of cases may have involvement on both sides (bilateral).[2]
## See also[edit]
* Legg–Calvé–Perthes syndrome – another cause of avascular necrosis of the femoral head, seen in younger children than SCFE
* Hip dysplasia
* Drehmann sign – Clinical test examining for SCFE
## References[edit]
1. ^ a b Perry, Daniel C.; Metcalfe, David; Lane, Steven; Turner, Steven (2018). "Childhood Obesity and Slipped Capital Femoral Epiphysis". Pediatrics. 142 (5): e20181067. doi:10.1542/peds.2018-1067. PMID 30348751.
2. ^ a b c d e f g h i j Kliegman, Robert M. (2011). Nelson textbook of pediatrics (19th ed.). Philadelphia: Saunders. p. 2363. ISBN 9781437707557.
3. ^ Loder, RT (1 May 1998). "Slipped capital femoral epiphysis". American Family Physician. 57 (9): 2135–42, 2148–50. PMID 9606305. Retrieved 30 November 2012.
4. ^ a b c d e f Novais, Eduardo N.; Millis, Michael B. (December 2012). "Slipped Capital Femoral Epiphysis: Prevalence, Pathogenesis, and Natural History". Clinical Orthopaedics and Related Research. 470 (12): 3432–3438. doi:10.1007/s11999-012-2452-y. PMC 3492592. PMID 23054509.
5. ^ Slipped Capital Femoral Epiphysis at eMedicine
6. ^ a b c Kaneshiro, Neil. "Slipped capital femoral epiphysis". U.S. National Library of Medicine. PubMed Health. Retrieved 1 December 2012.
7. ^ a b Perry, Daniel C.; Metcalfe, David; Costa, Matthew L.; Van Staa, Tjeerd (2017). "A nationwide cohort study of slipped capital femoral epiphysis". Archives of Disease in Childhood. 102 (12): 1132–1136. doi:10.1136/archdischild-2016-312328. PMC 5754864. PMID 28663349.
8. ^ Pediatric Orthopaedic Society of North America. "Slipped Capital Femoral Epiphysis". American Academy of Orthopaedic Surgeons. Retrieved 1 December 2012.
9. ^ a b c Peck, David (Aug 1, 2010). "Slipped capital femoral epiphysis: diagnosis and management". American Family Physician. 82 (3): 258–62. PMID 20672790. Retrieved 1 December 2012.
10. ^ Kuzyk, Paul R.; Kim, YJ; Millis, MB (Nov 2011). "Surgical management of healed slipped capital femoral epiphysis". The Journal of the American Academy of Orthopaedic Surgeons. 19 (11): 667–77. doi:10.5435/00124635-201111000-00003. PMID 22052643. S2CID 38580394. Retrieved 1 December 2012.
11. ^ Merz, Michael K.; Amirouche, Farid; Solitro, Giovanni F.; Silverstein, Jeffrey A.; Surma, Tyler; Gourineni, Prasad V. (2014). "Biomechanical Comparison of Perpendicular Versus Oblique in Situ Screw Fixation of Slipped Capital Femoral Epiphysis". Journal of Pediatric Orthopaedics. 35 (8): 816–20. doi:10.1097/BPO.0000000000000379. PMID 25526584. S2CID 11578375.
12. ^ "Slipped Capital Femoral Epiphysis". U.S. National Library of Medicine. National Institute of Health. Retrieved 1 December 2012.
## External links[edit]
Classification
D
* OMIM: 182260
* MeSH: D060048
* DiseasesDB: 12185
* SNOMED CT: 26460006
External resources
* MedlinePlus: 000972
* eMedicine: article/413810
Authority control
* GND: 4152531-0
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Slipped capital femoral epiphysis | c0149887 | 836 | wikipedia | https://en.wikipedia.org/wiki/Slipped_capital_femoral_epiphysis | 2021-01-18T18:54:51 | {"gard": ["11001"], "mesh": ["D060048"], "umls": ["C0149887"], "icd-10": ["M93.0"], "orphanet": ["399329"], "wikidata": ["Q442615"]} |
A type of hereditary congenital cataract, distinguished by bluish and white opacifications in the superficial layers of the fetal lens nucleus and adult lens nucleus, and characterized by reduced visual acuity in childhood, eventually necessitating extraction of the lens.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Cerulean cataract | c0344523 | 837 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98989 | 2021-01-23T18:46:39 | {"gard": ["9508"], "mesh": ["C537955"], "omim": ["115660", "614422"], "umls": ["C0344523"], "icd-10": ["Q12.0"], "synonyms": ["Blue-dot cataract"]} |
Foveal hypoplasia-optic nerve decussation defect-anterior segment dysgenesis syndrome is a rare, genetic, eye disease characterized by foveal hypoplasia, optic nerve misrouting with an increased number of axons decussating at the optic chiasm and innervating the contralateral cortex, and posterior embryotoxon or Axenfeld anomaly (indicating anterior segment dysgenesis), in the absence of albinism. Patients present congenital nystagmus, decreased visual acuity, refractive errors and, ocassionally, strabismus. Microphthalmia and retinochoroidal coloboma may also be associated.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Foveal hypoplasia-optic nerve decussation defect-anterior segment dysgenesis syndrome | c3807873 | 838 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=397618 | 2021-01-23T18:26:00 | {"omim": ["609218"], "icd-10": ["Q15.8"], "synonyms": ["FHONDA syndrome"]} |
Ichthyosis
Other namesIchthyoses
Ichthyosis is characterized by rough, scaly skin.
SpecialtyDermatology
Ichthyosis is a family of genetic skin disorders characterized by dry, thickened, scaly skin.[1] The more than 20 types of ichthyosis range in severity of symptoms, outward appearance, underlying genetic cause and mode of inheritance (e.g., dominant, recessive, autosomal or X-linked).[2] Ichthyosis comes from the Greek ἰχθύς ichthys, literally "fish", since dry, scaly skin is the defining feature of all forms of ichthyosis.[3]
The severity of symptoms can vary enormously, from the mildest, most common, types such as ichthyosis vulgaris, which may be mistaken for normal dry skin, up to life-threatening conditions such as harlequin-type ichthyosis. Ichthyosis vulgaris accounts for more than 95% of cases.[4]
## Contents
* 1 Types
* 1.1 Non-Syndromic Ichthyosis
* 1.2 Syndromic Ichthyosis
* 1.3 Non-genetic ichthyosis
* 2 Diagnosis
* 3 Treatments
* 4 Other animals
* 5 See also
* 6 References
* 7 External links
## Types[edit]
Many types of ichthyoses exist, and an exact diagnosis may be difficult. Types of ichthyoses are classified by their appearance, if they are syndromic or not, and by mode of inheritance.[5] For example, non-syndromic ichthyoses that are inherited recessively come under the umbrella term autosomal recessive congenital ichthyosis (ARCI).
Ichthyosis caused by mutations in the same gene can vary considerably in severity and symptoms. Some ichthyoses do not appear to fit exactly into any one type while mutations in different genes can produce ichthyoses with similar symptoms. Of note, X-linked ichthyosis is associated with Kallmann syndrome (close to the KAL1 gene). The most common or well-known types are:[5]
### Non-Syndromic Ichthyosis[edit]
Name OMIM Mode Of Inheritance Gene(s)
Ichthyosis Vulgaris 146700 Autosomal semi-dominant FLG
X-linked recessive ichthyosis 308100 X-linked recessive STS
Harlequin ichthyosis 242500 Autosomal recessive ABCA12
Congenital ichthyosiform erythoderma 242100 Autosomal recessive TGMI1, NIPAL4, ALOX12B, ALOXE3, ABCA12, CYP4F22, NIPAL4, LIPN, CERS3, PNPLA1, ST14, CASP14
Lamellar ichthyosis 242300 Autosomal recessive TGMI1, NIPAL4, ALOX12B, ALOXE3, ABCA12, CYP4F22, NIPAL4, LIPN, CERS3, PNPLA1, ST14, CASP14
Self improving congenital ichthyosis 242300 Autosomal recessive TGM1, ALOX12B, ALOXE3
Bathing suit ichthyosis 242300 Autosomal recessive TGMI1
Epidermolytic ichthyosis 113800 Autosomal dominant KRT1, KRT10
Superficial epidermolytic ichthyosis 146800 Autosomal dominant KRT2
Annular epidermolytic ichthyosis 607602 Autosomal dominant KRT1, KRT10
Ichthyosis Curth-Macklin 146590 Autosomal dominant KRT1
Autosomal recessive epidermolytic ichthyosis 113800 Autosomal recessive KRT10
Congenital reticular ichthyosiform erythroderma 609165 Autosomal dominant KRT1, KRT10
Epidermolytic nevi 113800 Postzygotic mosaicism KRT1, KRT10
Loricrin keratoderma 604117 Autosomal dominant LOR
Erythrokeratodermia variabilis 133200 Autosomal dominant GJB3, GJB4
Peeling skin disease 270300 Autosomal recessive CDSN
Keratosis linearis with ichthyosis congenita and sclerosing keratoderma 601952 Autosomal recessive POMP
### Syndromic Ichthyosis[edit]
Name OMIM Mode Of Inheritance Gene(s)
X-linked recessive ichthyosis syndromic forms 308700
300500
300533
X-linked recessive STS
Ichthyosis follicularis with alopecia and photophobia syndrome 308205 X-linked recessive MBTPS2
Conradi-Hunermann-Happle syndrome 302960 X-linked dominant EBP
Netherton syndrome 256500 Autosomal recessive SPINK5
Ichthyosis-hypotrichosis syndrome 610765 Autosomal recessive ST14
Trichothiodystrophy 601675 Autosomal recessive ERCC2, ERCC3, GTF2H5
Trichothiodystrophy (non-congenital forms) 275550
211390
601675
Autosomal recessive C7Orf11, TTDN1
Sjögren-Larsson syndrome 270200 Autosomal recessive ALDH3A2
Refsum's disease 266500 Autosomal recessive PHYH, PEX7
Mental retardation, enteropathy, deafness, neuropathy, ichthyosis, keratoderma syndrome 609528 Autosomal recessive SNAP29
Arthrogryposis, renal dysfunction, cholestasis syndrome 208085 Autosomal recessive VPS33B
Keratitis-ichthosis-deafness syndrome 602450
148210
Autosomal dominant GJB2
Neutral lipid storage disease with ichthyosis 275630 Autosomal recessive ABHD5
Ichthyosis prematurity syndrome 608649 Autosomal recessive SLC27A4
### Non-genetic ichthyosis[edit]
* Ichthyosis acquisita
## Diagnosis[edit]
A physician often can diagnose ichthyosis by looking at the skin. A family history is also useful in determining the mode of inheritance. In some cases, a skin biopsy is done to help to confirm the diagnosis while in others genetic testing may be helpful in making a diagnosis. Diabetes has not been definitively linked to acquired ichthyosis or ichthyosis vulgaris; however, there are case reports associating new onset ichthyosis with diabetes.[6]
Ichthyosis has been found to be more common in Native American, Asian, Mongolian groups[citation needed]. There is no way to prevent ichthyosis.
Ichthyosis is a genetically and phenotypically heterogeneous disease that can be isolated and restricted to the skin manifestations or associated with extracutaneous symptoms. One of which is limb reduction defect known as CHILD syndrome; a rare inborn error of metabolism of cholesterol biosynthesis that is usually restricted to one side of the body. A research done in Egypt proved that it is not a child syndrome and discussed all the case report.[7]
## Treatments[edit]
Treatments for ichthyosis often take the form of topical application of creams and emollient oils, in an attempt to hydrate the skin. Creams containing a high percentage of urea or lactic acid have been shown to work exceptionally well in some cases.[8] Application of propylene glycol is another treatment method. Retinoids are used for some conditions.
Exposure to sunlight may improve[citation needed] or worsen the condition. In some cases, excess dead skin sloughs off much better from wet tanned skin after bathing or a swim, although the dry skin might be preferable to the damaging effects of sun exposure.
There can be ocular manifestations of ichthyosis, such as corneal and ocular surface diseases. Vascularizing keratitis, which is more commonly found in congenital keratitis-ichythosis-deafness (KID), may worsen with isotretinoin therapy.
## Other animals[edit]
Ichthyosis or ichthyosis-like disorders exist for several types of animals, including cattle, chickens, llamas, mice and dogs.[9] Ichthyosis of varying severity is well documented in some popular breeds of domestic dogs. The most common breeds to have ichthyosis are Golden retrievers, American bulldogs, Jack Russell terriers and Cairn terriers.[10]
## See also[edit]
* Skin disease
* Ichthyosis en confetti
* List of cutaneous conditions
* List of cutaneous neoplasms associated with systemic syndromes
## References[edit]
1. ^ "Frequently Asked Questions". Foundation for Ichthyosis & Related Skin Types (FIRST). Retrieved 12 July 2017.
2. ^ thefreedictionary.com/ichthyosis citing: Gale Encyclopedia of Medicine. Copyright 2008
3. ^ "Ichthyosis". Health Information Library. Johns Hopkins Medicine. Archived from the original on 2 February 2009.
4. ^ Okulicz JF, Schwartz RA (2003). "Hereditary and acquired ichthyosis vulgaris". International Journal of Dermatology. 42 (2): 95–8. doi:10.1046/j.1365-4362.2003.01308.x. PMID 12708996. S2CID 20029085.
5. ^ a b Oji, Vinzenz; Preil, Marie-Luise; Kleinow, Barbara; Wehr, Geske; Fischer, Judith; Hennies, Hans Christian; Hausser, Ingrid; Breitkreutz, Dirk; Aufenvenne, Karin; Stieler, Karola; Tantcheva-Poór, Illiana (2017). "S1 guidelines for the diagnosis and treatment of ichthyoses - update" (PDF). JDDG: Journal der Deutschen Dermatologischen Gesellschaft. 15 (10): 1053–1065. doi:10.1111/ddg.13340. PMID 28976107. S2CID 27585177.
6. ^ Scheinfeld, N; Libkind, M; Freilich, S (2001). "New-onset ichthyosis and diabetes in a 14-year-old". Pediatric Dermatology. 18 (6): 501–3. doi:10.1046/j.1525-1470.2001.1862004.x. PMID 11841637. S2CID 22440127.
7. ^ Shawky, R. M., Elsayed, S. M., & Amgad, H. (2016). Autosomal recessive ichthyosis with limb reduction defect: A simple association and not CHILD syndrome. Egyptian Journal of Medical Human Genetics, 17(3), 255-258.
8. ^ Cicely Blair (February 1976). "The action of a urea—lactic acid ointment in ichthyosis". British Journal of Dermatology. 94 (2): 145–153. doi:10.1111/j.1365-2133.1976.tb04363.x. PMID 943169. S2CID 29854858.
9. ^ Sundberg, John P., Handbook of Mouse Mutations with Skin and Hair Abnormalities, Page 333, Published by CRC Press, 1994, ISBN 0-8493-8372-2
10. ^ Gross, Thelma Lee, Veterinary Dermatopathology, Page 174-179, Published by Blackwell Publishing, 2004, ISBN 0-632-06452-8
## External links[edit]
Classification
D
* ICD-10: Q80
* ICD-9-CM: 757.1
* MeSH: D007057
* DiseasesDB: 6646
External resources
* eMedicine: article/1198130
* Orphanet: 79354
Wikimedia Commons has media related to Ichthyosis.
* DermAtlas 1896838546
* Ichthyosis Overview \- US National Institute of Arthritis and Musculoskeletal and Skin Diseases
* 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
Congenital malformations and deformations of integument / skin disease
Genodermatosis
Congenital ichthyosis/
erythrokeratodermia
AD
* Ichthyosis vulgaris
AR
* Congenital ichthyosiform erythroderma: Epidermolytic hyperkeratosis
* Lamellar ichthyosis
* Harlequin-type ichthyosis
* Netherton syndrome
* Zunich–Kaye syndrome
* Sjögren–Larsson syndrome
XR
* X-linked ichthyosis
Ungrouped
* Ichthyosis bullosa of Siemens
* Ichthyosis follicularis
* Ichthyosis prematurity syndrome
* Ichthyosis–sclerosing cholangitis syndrome
* Nonbullous congenital ichthyosiform erythroderma
* Ichthyosis linearis circumflexa
* Ichthyosis hystrix
EB
and related
* EBS
* EBS-K
* EBS-WC
* EBS-DM
* EBS-OG
* EBS-MD
* EBS-MP
* JEB
* JEB-H
* Mitis
* Generalized atrophic
* JEB-PA
* DEB
* DDEB
* RDEB
* related: Costello syndrome
* Kindler syndrome
* Laryngoonychocutaneous syndrome
* Skin fragility syndrome
Ectodermal dysplasia
* Naegeli syndrome/Dermatopathia pigmentosa reticularis
* Hay–Wells syndrome
* Hypohidrotic ectodermal dysplasia
* Focal dermal hypoplasia
* Ellis–van Creveld syndrome
* Rapp–Hodgkin syndrome/Hay–Wells syndrome
Elastic/Connective
* Ehlers–Danlos syndromes
* Cutis laxa (Gerodermia osteodysplastica)
* Popliteal pterygium syndrome
* Pseudoxanthoma elasticum
* Van der Woude syndrome
Hyperkeratosis/
keratinopathy
PPK
* diffuse: Diffuse epidermolytic palmoplantar keratoderma
* Diffuse nonepidermolytic palmoplantar keratoderma
* Palmoplantar keratoderma of Sybert
* Meleda disease
* syndromic
* connexin
* Bart–Pumphrey syndrome
* Clouston's hidrotic ectodermal dysplasia
* Vohwinkel syndrome
* Corneodermatoosseous syndrome
* plakoglobin
* Naxos syndrome
* Scleroatrophic syndrome of Huriez
* Olmsted syndrome
* Cathepsin C
* Papillon–Lefèvre syndrome
* Haim–Munk syndrome
* Camisa disease
* focal: Focal palmoplantar keratoderma with oral mucosal hyperkeratosis
* Focal palmoplantar and gingival keratosis
* Howel–Evans syndrome
* Pachyonychia congenita
* Pachyonychia congenita type I
* Pachyonychia congenita type II
* Striate palmoplantar keratoderma
* Tyrosinemia type II
* punctate: Acrokeratoelastoidosis of Costa
* Focal acral hyperkeratosis
* Keratosis punctata palmaris et plantaris
* Keratosis punctata of the palmar creases
* Schöpf–Schulz–Passarge syndrome
* Porokeratosis plantaris discreta
* Spiny keratoderma
* ungrouped: Palmoplantar keratoderma and spastic paraplegia
* desmoplakin
* Carvajal syndrome
* connexin
* Erythrokeratodermia variabilis
* HID/KID
Other
* Meleda disease
* Keratosis pilaris
* ATP2A2
* Darier's disease
* Dyskeratosis congenita
* Lelis syndrome
* Dyskeratosis congenita
* Keratolytic winter erythema
* Keratosis follicularis spinulosa decalvans
* Keratosis linearis with ichthyosis congenita and sclerosing keratoderma syndrome
* Keratosis pilaris atrophicans faciei
* Keratosis pilaris
Other
* cadherin
* EEM syndrome
* immune system
* Hereditary lymphedema
* Mastocytosis/Urticaria pigmentosa
* Hailey–Hailey
see also Template:Congenital malformations and deformations of skin appendages, Template:Phakomatoses, Template:Pigmentation disorders, Template:DNA replication and repair-deficiency disorder
Developmental
anomalies
Midline
* Dermoid cyst
* Encephalocele
* Nasal glioma
* PHACE association
* Sinus pericranii
Nevus
* Capillary hemangioma
* Port-wine stain
* Nevus flammeus nuchae
Other/ungrouped
* Aplasia cutis congenita
* Amniotic band syndrome
* Branchial cyst
* Cavernous venous malformation
* Accessory nail of the fifth toe
* Bronchogenic cyst
* Congenital cartilaginous rest of the neck
* Congenital hypertrophy of the lateral fold of the hallux
* Congenital lip pit
* Congenital malformations of the dermatoglyphs
* Congenital preauricular fistula
* Congenital smooth muscle hamartoma
* Cystic lymphatic malformation
* Median raphe cyst
* Melanotic neuroectodermal tumor of infancy
* Mongolian spot
* Nasolacrimal duct cyst
* Omphalomesenteric duct cyst
* Poland anomaly
* Rapidly involuting congenital hemangioma
* Rosenthal–Kloepfer syndrome
* Skin dimple
* Superficial lymphatic malformation
* Thyroglossal duct cyst
* Verrucous vascular malformation
* Birthmark
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Ichthyosis | c0020757 | 839 | wikipedia | https://en.wikipedia.org/wiki/Ichthyosis | 2021-01-18T19:07:29 | {"mesh": ["D007057"], "umls": ["C0020757", "C0020758"], "icd-9": ["757.1"], "icd-10": ["Q80"], "orphanet": ["79354"], "wikidata": ["Q523893"]} |
A number sign (#) is used with this entry because of evidence that succinic semialdehyde dehydrogenase deficiency (SSADHD) is caused by homozygous or compound heterozygous mutation in the ALDH5A1 gene (610045) on chromosome 6p22.
Description
Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare autosomal recessive neurologic disorder in which an enzyme defect in the GABA degradation pathway causes a consecutive elevation of gamma-hydroxybutyric acid (GHB) and GABA. The clinical features include developmental delay, hypotonia, mental retardation, ataxia, seizures, hyperkinetic behavior, aggression, and sleep disturbances (summary by Reis et al., 2012).
Clinical Features
Jakobs et al. (1981) reported a patient with neurologic abnormalities and urinary excretion of gamma-hydroxybutyric acid.
Gibson et al. (1983) demonstrated deficiency of the succinic semialdehyde dehydrogenase enzyme in lymphocyte lysates from 2 patients with gamma-hydroxybutyric aciduria. Enzyme activity was 9 to 13% of control values. Gibson et al. (1984) demonstrated levels of SSADH enzyme activity consistent with heterozygosity in both parents of the first reported affected child (Jakobs et al., 1981), who was the offspring of consanguineous Turkish parents. Psychomotor development was mildly retarded but ataxia was severe. He also had marked hypotonia without weakness. Follow-up at age 5 showed no progression or improvement. Increased concentrations of gamma-aminobutyric acid (GABA) were found in the urine and CSF.
Haan et al. (1985) described a 3-year-old boy, born of first-cousin Maltese parents, with SSADH deficiency. Delayed development was the main feature. He did not have ataxia, oculomotor apraxia, or seizures. Roesel et al. (1987) observed this disorder in a brother and sister who also showed increased glycine excretion.
Gibson et al. (1997) described differing clinical presentation of SSADH deficiency in an adolescent brother and sister from Lifu Island, New Caledonia. The 2 affected sibs were from a sibship of 7 whose parents were first cousins. The 15-year-old male had global psychomotor and intellectual retardation, functioning at the developmental level of 4 years. His sight was said to be poor, and growth was subnormal. Genitalia were underdeveloped and there were no secondary sexual characteristics. The younger female sib was more severely affected. As in the case of her brother, her eyesight was thought to be poor. At age 11, she developed tonic/clonic seizures, which were only partially controlled by valproic acid. Treatment with vigabatrin aggravated the convulsive disorder.
Gibson et al. (1997) reported 23 new patients with SSADH deficiency. The most frequent clinical features included developmental delay of motor, mental, and language skills, hypotonia, seizures, hyporeflexia, ataxia, behavioral problems, and EEG abnormalities. Less common features included abnormal eye movements and psychosis in older patients. Approximately 30% of patients had normal early development and there was wide variability in the severity of mental retardation.
Chambliss et al. (1998) stated that SSADH deficiency had been identified in approximately 150 patients. Affected individuals accumulate large quantities of 2 neuroactive compounds in physiologic fluids: GABA and 4-hydroxybutyric acid (GHB).
Gibson et al. (1998) provided a review of succinic semialdehyde dehydrogenase deficiency and contrasted the clinical and biochemical findings in patients with neuropharmacologic data on 4-hydroxybutyric acid accumulation in animals and humans.
Pearl et al. (2003) stated that SSADH deficiency had been diagnosed in approximately 350 patients. They reported 11 additional patients and reviewed the clinical features of 51 previously reported patients. Age at diagnosis ranged from 1 to 21 years. The main clinical features included mild to moderate mental retardation, disproportionate language dysfunction, hypotonia, hyporeflexia, autistic behaviors, seizures, and hallucinations. Brain MRI of 5 patients showed symmetric increased T2 signal in the globus pallidus. Pearl et al. (2003) noted that GHB has neuroactive properties and has been used to manage cataplexy and alcohol- and opiate-withdrawal syndromes.
Blasi et al. (2006) reported a female infant with SSADH deficiency confirmed by genetic analysis (see 610045.0006). She presented at age 9 months with psychomotor delay, strabismus, and generalized hypotonia. Biochemical studies showed severely decreased SSADH enzyme activity.
Leuzzi et al. (2007) reported 2 Italian sibs with SSADH deficiency who developed paroxysmal exercise-induced dystonia at age 16 and 12 years, respectively. Their prior phenotypes were classic for SSADH deficiency. Treatment with vigabatrin improved the paroxysmal dystonia in both patients and also improved gait clumsiness and seizures in 1 patient.
O'Rourke et al. (2010) reported a 9-month-old boy with mild global delay who presented with 'yes-yes' head bobbing. Brain imaging showed abnormal signal hyperintensities in the globus pallidus and white matter on T2-weighted MRI, and brain magnetic resonance spectroscopy (MRS) showed high lactate, consistent with SSADH deficiency. The authors suggested that increased gamma-hydroxybutyrate may affect diencephalic extrapyramidal pathways, resulting in abnormal movement.
Other Features
Using transcranial magnetic stimulation (TMS), Reis et al. (2012) found that patients with SSADH deficiency had GABA-B (see 603540)-ergic cortical motor dysfunction as evidenced by reduced long interval intracortical inhibition and shortened cortical silent period compared to heterozygous parents and controls. This suggested reduced GABAergic inhibition in SSADH-deficient patients. The phenotype was consistent with use-dependent downregulation of postsynaptic GABA-B receptors resulting from chronically elevated GABA and GHB. The results also suggested that patients with SSADH deficiency may have reduced secretion of GABA intro the synaptic cleft by presynaptic GABA-B receptors. These neurotransmitter changes may be responsible for some of the clinical features of the disorder.
Inheritance
Parental consanguinity and intermediate levels of SSADH enzyme in parents of affected children support autosomal recessive inheritance (Gibson et al., 1984).
Diagnosis
Pearl et al. (2003) noted that standard organic acid assays commonly miss increased urinary excretion of 4-hydroxybutyric acid because it is a highly volatile compound. The authors suggested that selective ion monitoring gas chromatography-mass spectrometry for specific compounds yields more accurate results.
### Prenatal Diagnosis
Jakobs et al. (1993) reported prenatal diagnosis of SSADH deficiency by metabolite measurement and enzyme analysis in amniotic fluid and cells.
Molecular Genetics
In 4 patients from 2 unrelated families with SSADH deficiency, Chambliss et al. (1998) identified homozygosity for 2 different splice site mutations in the ALD5A1 gene (610045.0001; 610045.0002). Unaffected parents and sibs were heterozygous for the mutations.
Akaboshi et al. (2003) stated that the underlying mutation in SSADH deficiency had been reported in patients from 6 families worldwide and 8 different mutations were described. They reported the mutational spectrum in 48 additional unrelated patients of different geographic origin. They detected 27 novel mutations in the ALDH5A1 gene (see, e.g., 610045.0003-610045.0005). Almost all the missense mutations reduced the SSADH activity to less than 5% of the normal activity in an in vitro expression system. The findings suggested that residual protein expression is not likely to be an important factor contributing to the very large phenotypic differences observed among different families and even among sibs, suggesting that other modifying factors are of great importance in disease pathology.
INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Abnormal eye movements NEUROLOGIC Central Nervous System \- Delayed development, ranging from mild to severe \- Psychomotor retardation \- Approximately 30% of patients show normal early development \- Delayed motor development \- Delayed language development \- Mental retardation \- Hypotonia \- Hyperkinesis \- Ataxia \- Seizures \- Absence seizures \- Myoclonic seizures \- Generalized tonic-clonic seizures \- Status epilepticus \- EEG abnormalities \- Hyporeflexia \- MRI shows increased T2-weighted signals in the globus pallidi Behavioral Psychiatric Manifestations \- Autism, mild \- Hyperactivity \- Psychosis in older patients \- Aggressiveness \- Anxiety \- Hallucinations \- Self-injurious behaviors LABORATORY ABNORMALITIES \- Increased urinary excretion of 4-hydroxybutyric acid (GHB) \- Increased CSF and plasma GHB \- Increased urinary excretion of gamma-aminobutyric acid (GABA) \- Increased CSF and plasma GABA \- Decreased activity of succinic semialdehyde dehydrogenase (SSADH, ALDH5A1), less than 5% of control values MISCELLANEOUS \- Onset in infancy or early childhood \- Highly variable phenotype MOLECULAR BASIS \- Caused by mutation in the aldehyde dehydrogenase 5 family, member A1 gene (ALDH5A1, 610045.0001 ) ▲ 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
| SUCCINIC SEMIALDEHYDE DEHYDROGENASE DEFICIENCY | c0268631 | 840 | omim | https://www.omim.org/entry/271980 | 2019-09-22T16:22:00 | {"doid": ["0060175"], "mesh": ["C535803"], "omim": ["271980"], "icd-10": ["E72.81"], "orphanet": ["22"], "synonyms": ["Alternative titles", "SSADH DEFICIENCY", "4-HYDROXYBUTYRIC ACIDURIA", "GABA METABOLIC DEFECT", "GAMMA-HYDROXYBUTYRIC ACIDURIA"], "genereviews": ["NBK1195"]} |
A number sign (#) is used with this entry because of evidence that hypomyelinating leukodystrophy-17 (HLD17) is caused by homozygous mutation in the AIMP2 gene (600859) on chromosome 7p22.
Description
Hypomyelinating leukodystrophy-17 is an autosomal recessive neurodevelopmental disorder characterized by poor, if any, development apparent from infancy. Affected individuals never learn to walk or speak, and have early-onset multifocal seizures, spasticity, poor overall growth, and microcephaly (up to -10 SD). Brain imaging shows multiple abnormalities, including cerebral and cerebellar atrophy, thin corpus callosum, abnormal signals in the basal ganglia, and features suggesting hypo- or demyelination. Some patients may die in childhood (summary by Shukla et al., 2018).
For a general phenotypic description and a discussion of genetic heterogeneity of hypomyelinating leukodystrophy, see 312080.
Clinical Features
Shukla et al. (2018) reported 4 children from 2 unrelated consanguineous families of Indian descent with a profound neurodevelopmental disorder apparent from early infancy. The patients were unable to walk or speak, and achieved virtually no development milestones. They had microcephaly (-10 SD), spasticity with hyperreflexia, early-onset multifocal intractable seizures, and feeding difficulties with poor overall growth. Two older patients had kyphoscoliosis and contractures and variable dysmorphic features, including thick vermilion of lips, low hanging columella, gum hypertrophy, prognathism, widely spaced teeth, anteverted nostrils, and hirsutism. EEG showed major abnormalities, including multifocal spike wave discharges and hypsarrhythmia. Brain imaging showed cerebral and cerebellar atrophy, thin corpus callosum, spinal cord atrophy, T2-weighted hypointensities in the basal ganglia, and paucity of white matter, suggestive of demyelination. In the first family, 1 affected sib died at age 6 months due to intractable seizures, and the couple had an additional history of stillbirth, spontaneous abortion, and 3 medically-induced termination of pregnancies. In the second family, 1 of the affected sibs died at age 7 years.
Inheritance
The transmission pattern of HLD17 in the families reported by Shukla et al. (2018) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 4 patients from 2 unrelated consanguineous families of Indian descent with HLD17, Shukla et al. (2018) identified a homozygous nonsense mutation in the AIMP2 gene (Y35X; 600859.0001). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in both families. The variant was in a common region of homozygosity in the families, suggesting a founder effect. Patient cells showed mildly decreased AIMP2 mRNA compared to controls, although the difference was not statistically significant. Additional functional studies were not performed.
Animal Model
Kim et al. (2002) found that mice with a homozygous mutation in the Aimp2 gene showed neonatal lethality, although they were born alive with the normal segregation ratio. Mutant mice had undetectable Aimp2 mRNA levels as well as decreased catalytic activity of complex-forming enzymes of the multi-tRNA synthetase complex (MSC) compared to controls, suggesting that the Aimp2 mutation impaired stability and formation of the complex.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature Other \- Poor overall growth HEAD & NECK Head \- Microcephaly (-10 SD) Face \- Dysmorphic features, variable \- Prognathism Nose \- Low hanging columella \- Anteverted nostrils Mouth \- Thick lip vermilion \- Gum hypertrophy Teeth \- Widely spaced teeth RESPIRATORY \- Breathing difficulties ABDOMEN Gastrointestinal \- Poor feeding SKELETAL \- Contractures Spine \- Kyphoscoliosis SKIN, NAILS, & HAIR Hair \- Hirsutism NEUROLOGIC Central Nervous System \- Lack of developmental milestones \- Intellectual disability, profound \- Inability to walk \- Absent speech \- Seizures, early-onset, intractable \- Multifocal spike wave discharges seen on EEG \- Hypsarrhythmia \- Cerebral atrophy \- Cerebellar atrophy \- Thin corpus callosum \- Spinal cord atrophy \- T2-weighted hypointensities in the basal ganglia \- Hypomyelinating leukodystrophy \- Paucity of white matter MISCELLANEOUS \- Onset in infancy \- Progressive disorder \- Death in childhood may occur \- Two consanguineous families of Indian descent have been reported (last curated June 2018) MOLECULAR BASIS \- Caused by mutation in the aminoacyl tRNA complex-interacting multifunctional protein 2 gene (AIMP2, 600859.0001 ) ▲ Close
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*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| LEUKODYSTROPHY, HYPOMYELINATING, 17 | c4693912 | 841 | omim | https://www.omim.org/entry/618006 | 2019-09-22T15:44:06 | {"omim": ["618006"]} |
A number sign (#) is used with this entry because brittle cornea syndrome-1 (BCS1) is caused by homozygous mutation in the ZNF469 gene (612078) on chromosome 16q24.
Description
Brittle cornea syndrome (BCS) is characterized by blue sclerae, corneal rupture after minor trauma, keratoconus or keratoglobus, hyperelasticity of the skin, and hypermobility of the joints (Al-Hussain et al., 2004). It is classified as a form of Ehlers-Danlos syndrome (Malfait et al., 2017).
### Genetic Heterogeneity of Brittle Cornea Syndrome
Brittle cornea syndrome-2 (BCS2; 614170) is caused by mutation in the PRDM5 gene (614161) on chromosome 4q27.
Nomenclature
The kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VI; 225400) was at one time separated into EDS VIA (with lysyl hydroxylase deficiency) and EDS VIB (with normal lysyl hydroxylase activity). The designation EDS VIB was then thought to include the brittle cornea syndrome. Another entity formerly called EDS VIB is now known as the musculocontractural type of EDS (601776), caused by mutation in the CHST14 gene (608429).
Clinical Features
Bertelsen (1968) described a sister and brother, born of first-cousin parents, with blue sclerae and brittle corneas. The sister was noted to have blue sclerae at birth, and at age 2 years, she presented with a ruptured right cornea after a minor fall. Repair was unsuccessful and the eye was enucleated. One year later, she presented with rupture of the left cornea, again after slight indirect trauma. The wound successfully closed over time, but the eye later became amaurotic, presumably due to retinal detachment; in addition, the corneal diameter of this eye was considerably larger than normal (14 mm). Her younger brother was also noted to have extremely blue sclerae, and ocular examination at 1 month of age showed corneal diameters of 11 mm, deeper than normal anterior chamber, and 10-diopter myopia. At 1 year of age, corneal diameters were 12 mm with normal curvature, and slit-lamp examination under anesthesia showed a very thin cornea that was approximately one-third of normal thickness, with a deeper than normal anterior chamber. Fundi were normal, and there was no evidence of excavated discs. He had sustained a fracture of the distal humerus at birth, but x-ray examination showed normal bone density, and no further fractures occurred. Microscopic examination of the sister's enucleated eye showed that the corneal thinning was localized to the Bowman membrane and substantia propria, which Bertelsen (1968) noted are of mesodermal origin like the sclera; the thickness of the Descemet membrane and endothelium was not affected. Thinning of the cornea and sclera was due in part to a reduced number of lamellae and in part to a reduction in the thickness of individual lamellae, which also contained an excessive amount of reticular fibers. The corneal epithelium had a normal number of cell layers. Bertelsen (1968) concluded that this phenotype represented mesodermal dysgenesis. The parents, 2 sisters, and a brother had normal eyes without myopia. The affected sibs did not present any signs of Marfan syndrome (see 154700) or Ehlers-Danlos syndrome, and there was no family history of bone fragility.
Stein et al. (1968) reported brittle cornea associated with blue sclera in 2 Tunisian Jewish brothers with consanguineous parents, indicating autosomal recessive inheritance. Hyams et al. (1969) reported an affected Tunisian Jewish boy who may have been related to the patients of Stein et al. (1968) because 'the two families come from the same town in Tunisia.' Badtke (1941) reported 2 sisters, born of consanguineous parents, with blue sclerae and keratoconus from south Tyrol. Tucker (1959) reported the disorder in a brother and sister with first-cousin parents, and Arkin (1964) described an affected 17-year-old boy. The features included blue sclerae; large, cloudy, thin, bulging cornea, noted from early in life, and mimicking buphthalmos but accompanied by normal intraocular pressure; fragility of the cornea with repeated rupture; dental abnormalities somewhat like those of osteogenesis imperfecta; abnormal proclivity to fracture of bones; long, slender, hyperextensible fingers; and hernia. The Tunisian cases of Stein et al. (1968) and Hyams et al. (1969) had red hair, a sufficiently unusual finding in this group to suggest to the authors that it was a part of the syndrome. In keratoglobus the thinning of the cornea is generalized or in the periphery, whereas in keratoconus it is mainly central.
Greenfield et al. (1973) reported 2 affected sibs with first-cousin parents.
Judisch et al. (1976) studied 2 brothers with fragilitas oculi and other abnormalities and found normal lysyl hydroxylase activity, thus distinguishing the disorder from EDS VIA. Cadle et al. (1985) studied 3 sisters with EDS VI phenotype but normal lysyl hydroxylase and the additional feature of macrocephaly. On review it was concluded that the 2 sibs reported by Judisch et al. (1976) also had macrocephaly, and Cadle et al. (1985) suggested that macrocephaly and EDS VI phenotype was a recessive entity.
Ticho et al. (1980) described a brother and sister, aged 16 and 8 years, with red hair, blue sclera, uniform keratoglobus, and extremely thin corneae with several leucomata from previous spontaneous perforations. No systemic manifestations were found, and blood examinations were normal. Their 3 sibs and their parents, first cousins of Tunisian Jewish origin, had dark hair and no abnormality of the eyes.
Zlotogora et al. (1990) identified 2 groups of patients with the brittle cornea syndrome. The first group, composed of 5 families of Tunisian Jewish origin, was characterized by red hair in all affected individuals. In the second group, 9 families from various ethnic origins showed a normal distribution of hair color in the affected persons. Zlotogora et al. (1990) suggested that the locus for the gene may be closely linked to the locus for a gene responsible for hair color, with linkage disequilibrium in Tunisian Jews.
Royce et al. (1990) described brittle cornea and blue sclerae in association with red hair in the 4-year-old daughter of healthy, consanguineous Syrian parents. Other features included joint hyperextensibility, soft skin, and dysplastic auricles with unusually soft cartilage. Electron microscopy showed dramatic ultrastructural alterations in the dermis: distributed over its whole thickness were 20-60 micron wide 'holes' or fiber-free spaces, filled with amorphous material.
Al-Hussain et al. (2004) described 23 patients with brittle cornea syndrome from 13 Middle Eastern families (9 from Saudi Arabia, 2 from Syria, 1 from Jordan, and 1 from Yemen). A total of 28 events of corneal rupture were noted in 17 patients; 9 of these patients had bilateral ruptures. By age 4 years, 50% of patients had experienced corneal rupture. Blue sclerae were present in all 22 patients examined, and 20 patients had joint laxity. Most patients also had skin hyperelasticity without excessive fragility. All 19 patients examined biochemically showed normal lysyl hydroxylase activity.
Christensen et al. (2010) restudied a brother and sister with brittle cornea syndrome who were originally reported by Bertelsen (1968) as having 'dysgenesis mesodermalis corneae et sclerae.' Both sibs, born to first-cousin Norwegian parents, had markedly blue sclerae and thin cornea. In the girl, rupture of the cornea occurred in both eyes after slight indirect trauma. Megalocornea, deep anterior chambers, and severe myopia were present. Christensen et al. (2010) examined 8 members in 3 generations of the family. At 42 and 48 years of age, respectively, both affected individuals were blind due to retinal detachment and secondary glaucoma. They had extremely thin and bulging corneas, velvety skin, chestnut colored hair, scoliosis, reduced bone mineral density (BMD), dental anomalies, hearing loss, and minor cardiac defects. Christensen et al. (2010) concluded that BCS is a disorder that affects a variety of connective tissues. The authors noted that reduced BMD and atypical dental crown morphology had not previously been reported in this disorder. The sibs, who were the only members of the family to have red hair, were found to be homozygous for the common red hair variant R151C in the MC1R gene (155555.0004). Christensen et al. (2010) suggested that the association with red hair in some individuals with BCS is likely to occur by chance.
Khan et al. (2010) reported a consanguineous Syrian family in which 2 sibs had brittle cornea syndrome and 1 sib had blue sclerae only. The older affected sib was a 13-year-old boy who had blue sclerae noted at birth and suffered bilateral corneal rupture at 2 years of age due to minor trauma, with multiple corneal operations resulting in phthisis. Examination revealed bilateral phthisical eyes with blue sclerae. His skin was thin and velvety with prominent subcutaneous veins and scattered small scars on all extremities, but there was no abnormal elasticity or joint hypermobility. He also had a slightly arched palate, bilateral valgus foot and hallux valgus, and normal bone density. His 8-year-old sister had blue sclerae and keratoglobus; slit-lamp examination revealed thin corneas and corneal haze in the left eye due to an earlier Descemet membrane detachment. She had thin velvety skin with prominent subcutaneous veins but no abnormal elasticity or scarring, and she had significant joint hypermobility. In addition, she displayed frontal bossing, arched palate, pectus carinatum, lumbar lordosis, and bilateral talipes valgus; radiography confirmed irregular calvaria, exaggerated lumbar lordosis, and bilateral talipes valgus, with normal bone densities. A 4-year-old sister had blue sclerae noted at birth, but ocular examination was normal, and physical examination was unremarkable.
Mapping
Because all but 1 of the reported Tunisian Jewish patients with brittle cornea syndrome had red hair, Abu et al. (2006) genotyped 4 such affected individuals from 3 families, including the 2 sibs reported by Ticho et al. (1980), with markers located close to the melanocortin-1 receptor (MC1R; 155555), a major gene responsible for red hair. All 4 patients had a common haplotype in homozygous state for 16q24 markers; the same haplotype was not found in any of 52 control subjects (p less than 0.00001). The BCS locus was thus mapped to a 4.7-Mb interval between markers D16S3423 and D16S3425. In the 1 reported Tunisian Jewish patient with dark hair, Abu et al. (2006) identified the same ancestral chromosome; however, they also identified a partial chromosome 16 uniparental disomy, which defined a telomeric boundary that excluded MC1R from the linkage interval and accounted for the patient's lack of red hair.
In a highly inbred Palestinian family with brittle cornea syndrome in which linkage to the EDS VI locus on chromosome 1p36.22 had been excluded, Abu et al. (2008) analyzed markers on chromosome 16q24 and obtained a maximum lod score of 4.01 at D16S3420. Haplotype analysis of an unaffected family member indicated that the causative gene must be located telomeric to D16S3422, and combined with data from the Tunisian Jewish patients previously studied by Abu et al. (2006), the disease-gene locus was narrowed to 2.8 Mb between D16S3422 and D16S3425.
Inheritance
The brittle cornea syndrome is an autosomal recessive disorder (Abu et al., 2008).
Molecular Genetics
Abu et al. (2008) analyzed the candidate gene ZNF469 in 4 Tunisian Jewish families, one of which was the family originally reported by Ticho et al. (1980), and 1 Palestinian family with brittle cornea syndrome-1 and identified homozygosity for 2 different 1-bp deletions (612078.0001 and 612078.0002, respectively) that were not found in ethnically matched controls.
In a brother and sister with brittle cornea syndrome who were originally reported by Bertelsen (1968), Christensen et al. (2010) identified a homozygous mutation in the ZNF469 gene that affected the fourth of 5 zinc finger domains (612078.0003).
In affected sibs from a consanguineous Syrian family with brittle cornea syndrome (BCS1), Khan et al. (2010) identified homozygosity for a nonsense mutation in the ZNF469 gene (612078.0004).
Burkitt Wright et al. (2011) noted that the phenotypic spectrum in BCS patients with mutations in either the ZNF469 or PRDM5 (614161) genes is extremely similar if not identical (see BCS2, 614170), suggesting that the 2 genes act within the same developmental pathway. Quantitative PCR of mutant fibroblasts from BCS1 and BCS2 patients showed that mutation in either ZNF469 or PRDM5 causes significant downregulation of genes encoding molecules involved in extracellular matrix development and maintenance compared to controls.
History
Walker et al. (2004) examined cultured fibroblasts from 4 patients with clinical features similar to those of EDS VI but who had normal levels of lysyl hydroxylase-1 (LH1; PLOD1; 153454). Although normal levels of LH1 mRNA were observed in all 4 patients, in 2 patients levels of LH2 (PLOD2; 601865) mRNA were decreased by more 50%, and a similar decrease was observed in LH3 (PLOD3; 603066) mRNA in the other 2 patients. A distinct pattern of collagen crosslinks, indicative of decreased lysyl hydroxylation, could be identified in EDS VIA patients, but there was no clear correlation between collagen crosslink pattern and changes in the individual lysyl hydroxylase mRNAs of EDS VIB patients. An abnormality of tenascin-X (600985) was excluded in these patients. This study suggested that the basis for EDS VIB is genetically heterogeneous, and that alternative pathways in addition to lysine hydroxylation of collagen may be affected.
INHERITANCE \- Autosomal recessive GROWTH Other \- Marfanoid habitus HEAD & NECK Head \- Macrocephaly Ears \- Hearing loss Eyes \- Epicanthal folds \- Blue sclerae \- Vision loss \- Myopia \- Brittle cornea \- Keratoconus \- Keratoglobus Teeth \- Dentinogenesis imperfecta CARDIOVASCULAR Heart \- Mitral valve prolapse SKELETAL \- Joint laxity Spine \- Scoliosis \- Spondylolisthesis Pelvis \- Congenital hip dislocation SKIN, NAILS, & HAIR Skin \- Scarring \- Molluscoid pseudotumor \- Excessive wrinkled skin (palms and soles) Hair \- Red hair LABORATORY ABNORMALITIES \- Normal lysl hydroxylase activity \- Normal dermal hydroxylysine content MOLECULAR BASIS \- Caused by mutation in the zinc finger protein 469 gene (ZNF469, 612078.0001 ) ▲ 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
| BRITTLE CORNEA SYNDROME 1 | c0268344 | 842 | omim | https://www.omim.org/entry/229200 | 2019-09-22T16:27:54 | {"doid": ["14775"], "mesh": ["C536192"], "omim": ["229200"], "orphanet": ["90354"], "synonyms": ["Alternative titles", "FRAGILITAS OCULI WITH JOINT HYPEREXTENSIBILITY", "CORNEAL FRAGILITY, KERATOGLOBUS, BLUE SCLERAE, JOINT HYPEREXTENSIBILITY", "DYSGENESIS MESODERMALIS CORNEAE ET SCLERAE", "EHLERS-DANLOS SYNDROME, TYPE VIB, FORMERLY"]} |
Cancer involving the vulva
Vulvar cancer
Drawing of vulvar cancer
SpecialtyGynecology
SymptomsLump, itchiness, changes in the skin, or bleeding of the vulva[1]
Usual onsetAfter the age of 45[2]
TypesSquamous cell cancer, adenocarcinoma, melanoma, sarcoma, basal cell carcinoma.[3]
Risk factorsVulvar intraepithelial neoplasia (VIN), HPV infection, genital warts, smoking, many sexual partners[1][3]
Diagnostic methodPhysical examination, tissue biopsy[1]
Differential diagnosisLichen sclerosus, hyperplasia[4]
PreventionHPV vaccination[5]
TreatmentSurgery, radiation therapy, chemotherapy, biologic therapy[1]
PrognosisFive-year survival ~ 71% (US 2015)[2]
Frequency44,200 (2018)[6]
Deaths15,200 (2018)[6]
Vulvar cancer is a cancer of the vulva, the outer portion of the female genitals.[1] It most commonly affects the outer vaginal lips.[1] Less often, the inner vaginal lips, clitoris, or vaginal glands.[1] Symptoms include a lump, itchiness, changes in the skin, or bleeding from the vulva.[1]
Risk factors include vulvar intraepithelial neoplasia (VIN), HPV infection, genital warts, smoking, and many sexual partners.[1][3] Most vulvar cancers are squamous cell cancers.[4] Other types include adenocarcinoma, melanoma, sarcoma, and basal cell carcinoma.[3] Diagnosis is suspected based on physical examination and confirmed by tissue biopsy.[1] Routine screening is not recommended.[3]
Prevention may include HPV vaccination.[5] Standard treatments may include surgery, radiation therapy, chemotherapy, and biologic therapy.[1] Vulvar cancer newly affected about 44,200 people and resulted in 15,200 deaths globally in 2018.[6] In the United States, it newly occurred in about 6,070 people with 1,280 deaths a year.[2] Onset is typically after the age of 45.[2] The five-year survival rates for vulvar cancer is around 71% as of 2015.[2] Outcomes, however, are affected by whether spread has occurred to lymph nodes.[4]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 2.1 Risk factors
* 3 Diagnosis
* 3.1 Types
* 3.1.1 Squamous cell carcinoma
* 3.1.2 Basal cell carcinoma
* 3.1.3 Melanoma
* 3.1.4 Bartholin gland carcinoma
* 3.1.5 Other lesions
* 3.2 Staging
* 3.3 Differential diagnosis
* 4 Treatment
* 5 Prognosis
* 6 Epidemiology
* 6.1 United Kingdom
* 6.2 United States
* 7 References
* 8 External links
## Signs and symptoms[edit]
Drawing of cancer of the clitoris with spread to the groin
The signs and symptoms can include:
* Itching, burn, or bleeding on the vulva that does not go away.
* Changes in the color of the skin of the vulva, so that it looks redder or whiter than is normal.
* Skin changes in the vulva, including what looks like a rash or warts.
* Sores, lumps, or ulcers on the vulva that do not go away.
* Pain in the pelvis, especially during urination or sex.[7]
Typically, a lesion presents in the form of a lump or ulcer on the labia majora and may be associated with itching, irritation, local bleeding or discharge, in addition to pain with urination or pain during sexual intercourse.[8] The labia minora, clitoris, perineum and mons are less commonly involved.[9] Due to modesty or embarrassment, people may put off seeing a doctor.[10]
Melanomas tend to display the typical asymmetry, uneven borders and dark discoloration as do melanomas in other parts of the body.
Adenocarcinoma can arise from the Bartholin gland and present with a painful lump.[11]
## Causes[edit]
Two main pathophysiological pathways are currently understood to contribute to development of vulvar cancer—human papillomavirus (HPV) infection and chronic inflammation or autoimmunity affecting the vulvar area.[12][13][14]
HPV DNA can be found in up to 87% of vulvar intraepithelial neoplasia (VIN) and 29% of invasive vulvar cancers; HPV 16 is the most commonly detected subtype in VIN and vulvar cancer, followed by HPV 33 and HPV 18.[15] VIN is a superficial lesion of the skin that has not invaded the basement membrane—or a pre-cancer.[16] VIN may progress to carcinoma-in-situ and, eventually, squamous cell cancer.
Chronic inflammatory conditions of the vulva that may be precursors to vulvar cancer include lichen sclerosus, which can predispose to differentiated VIN.[17][18]
### Risk factors[edit]
Risk factors for vulvar cancer are largely related to the causal pathways above, involving exposure or infection with the HPV virus and/or acquired or innate auto-immunity.[19][20]
* Increasing age
* History of vulvar or cervical intraepithelial neoplasia
* Increased number of male sexual partners
* Prior history pre-invasive or invasive cervical cancer
* History of cigarette smoking
* Infection with human immunodeficiency virus (HIV)
* Vulvar lichen sclerosus
* Immunodeficiency syndromes
* Northern European ancestry
## Diagnosis[edit]
Examination of the vulva is part of the gynecologic evaluation and should include a thorough inspection of the perineum, including areas around the clitoris and urethra, and palpation of the Bartholin's glands.[21] The exam may reveal an ulceration, lump or mass in the vulvar region. Any suspicious lesions need to be sampled, or biopsied. This can generally be done in an office setting under local anesthesia. Small lesions can be removed under local anesthesia as well. Additional evaluation may include a chest X-ray, an intravenous pyelogram, cystoscopy or proctoscopy, as well as blood counts and metabolic assessment.
### Types[edit]
Depending on the cellular origin, different histologic cancer subtypes may arise in vulvar structures.[22][23]
#### Squamous cell carcinoma[edit]
A recent analysis of the Surveillance, Epidemiology and End Results (SEER) registry of the US National Cancer Institute has shown that squamous cell carcinoma accounts for approximately 75% of all vulvar cancers.[22] These lesions originate from epidermal squamous cells, the most common type of skin cell. Carcinoma-in-situ is a precursor lesion of squamous cell cancer that does not invade through the basement membrane. There are two types of precursor lesions:
* Usual-type vulvar intraepithelial neoplasia (uVIN), which is associated with Human papillomavirus (HPV) and often affects younger women. This precursor lesion progresses to basaloid or warty squamous cell carcinoma in approximately 6%.[22]
* Differentiated vulvar intraepithelial neoplasia (dVIN), which is associated with chronic skin conditions including Lichen sclerosus and Lichen planus and typically affects older women. This lesion progresses to keratinizing squamous cell carcinoma in approximately 33%.[22]
Squamous lesions tend to arise in a single site and occur most commonly in the vestibule.[24] They grow by local extension and spread via the local lymph system. The lymphatics of the labia drain to the upper vulva and mons pubis, then to both superficial and deep inguinal and femoral lymph nodes. The last deep femoral node is called the Cloquet’s node.[24] Spread beyond this node reaches the lymph nodes of the pelvis. The tumor may also invade nearby organs such as the vagina, urethra, and rectum and spread via their lymphatics.
A verrucous carcinoma of the vulva is a rare subtype of squamous cell cancer and tends to appear as a slowly growing wart. Verrucous vulvar cancers tend to have a good overall prognosis, as these lesions hardly ever spread to regional lymph nodes or metastasize.[22][25]
#### Basal cell carcinoma[edit]
Basal cell carcinoma account for approximately 8% of all vulvar cancers. It typically affects women in the 7th and 8th decade of life.[22] These tend to be slow-growing lesions on the labia majora but can occur anywhere on the vulva. Their behavior is similar to basal cell cancers in other locations. They often grow locally and have low risk for deep invasion or metastasis.
Treatment involves local excision, but these lesions have a tendency to recur if not completely removed.
#### Melanoma[edit]
Melanoma is the third most common type and accounts for 6% of all vulvar cancers.[22] These lesions arise from melanocytes, the cells that give skin color. The median age at diagnosis is 68 years, however, an analysis of the Surveillance, Epidemiology and End Results (SEER) registry of the US National Cancer Institute has shown that it has been diagnosed in girls as young as 10 years and women up to 107 years.[26][27]
The underlying biology of vulvar melanoma differs significantly from skin melanomas and mutational analyses have shown that fewer harbor a BRAF mutation while KIT mutations are significantly more common in vulvar melanoma.[22] This has a direct impact on the medical treatment of vulvar melanomas: BRAF-inhibitors that are commonly used in the treatment of skin melanomas, play a minor role in vulvar melanomas. However, vulvar melanomas frequently express PD-L1 and Checkpoint inhibitors (including CTLA-4 inhibitors and PD-1 inhibitors) are effective in the treatment of advanced-stage vulvar melanoma.[28] In recurrent melanoma, tyrosine kinase inhibitors may be used in those patients with a KIT mutation.[22]
Based on histology, there are different subtypes of vulvar melanoma: superficial spreading, nodular, acral lentigous and amelanotic melanoma. Vulvar melanomas are unique in that they are staged using the AJCC cancer staging for melanoma instead of the FIGO staging system.[29]
Diagnosis of vulvar melanoma is often delayed and approximately 32% of women already have regional lymph node involvement or distant metastases at the time of diagnosis.[24][29] Lymph node metastases and high mitotic count are indicators of poor outcome.[29] The overall prognosis is poor and significantly worse than in skin melanomas: The median overall survival is 53 months.[29][28]
#### Bartholin gland carcinoma[edit]
Main article: Bartholin gland carcinoma
The Bartholin gland is a rare malignancy and usually occurs in women in their mid-sixties.
#### Other lesions[edit]
Other forms of vulvar cancer include invasive Extramammary Paget's disease, adenocarcinoma (of the Bartholin glands, for example) and sarcoma.[22][30]
### Staging[edit]
Anatomical staging supplemented preclinical staging starting in 1988. FIGO’s revised TNM classification system uses tumor size (T), lymph node involvement (N) and presence or absence of metastasis (M) as criteria for staging. Stages I and II describe the early stages of vulvar cancer that still appear to be confined to the site of origin. Stage III cancers include greater disease extension to neighboring tissues and inguinal lymph nodes on one side. Stage IV indicates metastatic disease to inguinal nodes on both sides or distant metastases.[31]
* Illustrations showing stages of vulvar cancer[32]
* Stage 1A and 1B vulvar cancer
* Stage 2 vulvar cancer
* Stage 3 vulvar cancer
* Stage 4A vulvar cancer
* Stage 4B vulvar cancer
### Differential diagnosis[edit]
Other cancerous lesions in the differential diagnosis include Paget's disease of the vulva and vulvar intraepithelial neoplasia (VIN). Non-cancerous vulvar diseases include lichen sclerosus, squamous cell hyperplasia, and vulvar vestibulitis. A number of diseases cause infectious lesions including herpes genitalis, human papillomavirus, syphilis, chancroid, granuloma inguinale, and lymphogranuloma venereum.
## Treatment[edit]
Diagram of the incisions made in a vulvectomy, a treatment for vulvar cancer
Surgery is a mainstay of therapy depending on anatomical staging and is usually reserved for cancers that have not spread beyond the vulva.[31] Surgery may involve a wide local excision (excision of the tumor with a safety-margin of healthy tissue, that ensures complete removal of the tumor), radical partial vulvectomy, or radical complete vulvectomy with removal of vulvar tissue, inguinal and femoral lymph nodes.[22][27] In cases of early vulvar cancer, the surgery may be less extensive and consist of wide excision or a simple vulvectomy. Surgery is significantly more extensive when the cancer has spread to nearby organs such as the urethra, vagina, or rectum. Complications of surgery include wound infection, sexual dysfunction, edema and thrombosis, as well as lymphedema secondary to dissected lymph nodes.[33]
Sentinel lymph node (SLN) dissection is the identification of the main lymph node(s) draining the tumor, with the aim of removing as few nodes as possible, decreasing the risk of adverse effects. Location of the sentinel node(s) may require the use of technetium(99m)-labeled nano-colloid, or a combination of technetium and 1% isosulfan blue dye, wherein the combination may reduce the number of women with "'missed"' groin node metastases compared with technetium only.[33]
Radiation therapy may be used in more advanced vulvar cancer cases when disease has spread to the lymph nodes and/or pelvis. It may be performed before or after surgery. In early vulvar cancer, primary radiotherapy to the groin results in less morbidity but may be linked with a higher risk of groin recurrence and reduced survival compared to surgery.[34] Chemotherapy is not usually used as primary treatment but may be used in advanced cases with spread to the bones, liver or lungs. It may also be given at a lower dose together with radiation therapy.[35] Checkpoint inhibitors may be given in melanoma of the vulva.[28]
There is no significant difference in overall survival or treatment‐related adverse effects in women with locally advanced vulval cancer when comparing primary chemoradiation or neoadjuvant chemoradiation with primary surgery. There is a need for good quality studies comparing various primary treatments.[36]
Women with vulvar cancer should have routine follow-up and exams with their oncologist, often every 3 months for the first 2–3 years after treatment. They should not have routine surveillance imaging to monitor the cancer unless new symptoms appear or tumor markers begin rising.[37] Imaging without these indications is discouraged because it is unlikely to detect a recurrence or improve survival and is associated with its own side effects and financial costs.[37]
## Prognosis[edit]
Overall, five-year survival rates for vulvar cancer are around 78%[24] but may be affected by individual factors including cancer stage, cancer type, patient age and general medical health. Five-year survival is greater than 90% for patients with stage I lesions but decreases to 20% when pelvic lymph nodes are involved. Lymph node involvement is the most important predictor of prognosis.[38]
Prognosis depends on the stage of cancer, which refers the amount and spread of cancer in the body.[39] The stages are broken into 4 categories. Stage one also called "localized" and is when the cancer is limited to one part of the body.[39] This has the highest survival rate of 59%.[39] When the cancer starts to spread this is referred to "distant" or "regional", this stage usually involves the cancer being spread to the lymph nodes.[39] This survival rate is 29%. The third stage is when the cancer has metastasized and spread throughout the body, this is the lowest survival rate of 6%. When vulvar cancer is caught early that is when the survival rate is at its highest.[39]
## Epidemiology[edit]
Vulvar cancer newly affected about 44,200 people and resulted in 15,200 deaths globally in 2018.[6]
Vulvar cancer can be split up into two types. One starts as an infection by human papillomavirus, which leads to vulvar intraepithelial neoplasia (VIN) and potentially on to vulvar cancer.[40] This is most common in younger women, predominantly under the age of 40.[40] The second type is vulvar non-neoplastic epithelial disorders (VNED). This is most common in older women, due to the increased risk for developing cellular atypia which in turn leads to cancer.[40]
### United Kingdom[edit]
Vulvar cancer causes less than 1% of all cancer cases and deaths but around 6% of all gynecologic cancers diagnosed in the UK. Around 1,200 women were diagnosed with the disease in 2011, and 400 women died in 2012.[41] In the United Kingdom 7 out of 10 vulval cancer patients have major surgical resection as part of their cancer treatment.[42] 22% of patients use radiotherapy and only 7% use chemotherapy as a treatment plan.[42] There are very high survival rates, patients diagnosed with vulvar cancer have an 82% of living more than one year, a 64% chance of living at least 5 years and a 53% chance of living ten or more years.[42] The rate of survival increases dependent on age of patient and the stage the cancer was found in.
### United States[edit]
In the United States, it newly occurred in about 6,070 people with 1,280 deaths a year.[2] It makes up about 0.3% of new cancer cases,[2] and 5% of gynecologic cancers in the United States.[43] Vulvar cancer cases have been rising in the United States at an increase of .6% each year for the past ten years.[39]
## References[edit]
1. ^ a b c d e f g h i j k "Vulvar Cancer Treatment". National Cancer Institute. 9 April 2019. Retrieved 31 May 2019.
2. ^ a b c d e f g "Cancer of the Vulva—Cancer Stat Facts". SEER. Retrieved 30 May 2019.
3. ^ a b c d e Sam A, George J, Mathew B (April 2019). "Less Common Gynecologic Malignancies: An Integrative Review". Seminars in Oncology Nursing. 35 (2): 175–181. doi:10.1016/j.soncn.2019.02.004. PMID 30867101.
4. ^ a b c "Vulvar Cancer Treatment". National Cancer Institute. 1 February 2019. Retrieved 31 May 2019.
5. ^ a b Signorelli C, Odone A, Ciorba V, Cella P, Audisio RA, Lombardi A, et al. (July 2017). "Human papillomavirus 9-valent vaccine for cancer prevention: a systematic review of the available evidence". Epidemiology and Infection. 145 (10): 1962–1982. doi:10.1017/S0950268817000747. PMC 5974698. PMID 28446260.
6. ^ a b c d "Cancer today". IARC. Retrieved 30 May 2019.
7. ^ "What Are the Symptoms of Vaginal and Vulvar Cancers?". CDC. 13 March 2014. Retrieved 2016-03-26.
8. ^ "Vulvar Cancer Treatment". National Cancer Institute. 1980-01-01. Retrieved 2015-04-14.
9. ^ "What is vulvar cancer?". cancer.org. Retrieved 2015-04-14.
10. ^ Zacur H, Genadry R, Woodruff JD (April 1980). "The patient-at-risk for development of vulvar cancer". Gynecologic Oncology. 9 (2): 199–208. doi:10.1016/0090-8258(80)90028-1. PMID 7372192.
11. ^ Copeland LJ, Sneige N, Gershenson DM, McGuffee VB, Abdul-Karim F, Rutledge FN (June 1986). "Bartholin gland carcinoma". Obstetrics and Gynecology. 67 (6): 794–801. doi:10.1097/00006250-198606000-00009. PMID 3010205.
12. ^ de Koning MN, Quint WG, Pirog EC (March 2008). "Prevalence of mucosal and cutaneous human papillomaviruses in different histologic subtypes of vulvar carcinoma". Modern Pathology. 21 (3): 334–44. doi:10.1038/modpathol.3801009. PMID 18192968.
13. ^ Weberpals JI, Lo B, Duciaume MM, Spaans JN, Clancy AA, Dimitroulakos J, et al. (August 2017). "Vulvar Squamous Cell Carcinoma (VSCC) as Two Diseases: HPV Status Identifies Distinct Mutational Profiles Including Oncogenic Fibroblast Growth Factor Receptor 3". Clinical Cancer Research. 23 (15): 4501–4510. doi:10.1158/1078-0432.CCR-16-3230. PMID 28377483.
14. ^ Halec G, Alemany L, Quiros B, Clavero O, Höfler D, Alejo M, et al. (April 2017). "Biological relevance of human papillomaviruses in vulvar cancer". Modern Pathology. 30 (4): 549–562. doi:10.1038/modpathol.2016.197. PMID 28059099.
15. ^ de Sanjosé S, Alemany L, Ordi J, Tous S, Alejo M, Bigby SM, et al. (November 2013). "Worldwide human papillomavirus genotype attribution in over 2000 cases of intraepithelial and invasive lesions of the vulva". European Journal of Cancer. 49 (16): 3450–61. doi:10.1016/j.ejca.2013.06.033. PMID 23886586.
16. ^ "What is Vulvar Cancer?". Society of Gynecologic Oncology. 21 November 2012. Retrieved 19 November 2014.
17. ^ van de Nieuwenhof HP, Bulten J, Hollema H, Dommerholt RG, Massuger LF, van der Zee AG, et al. (February 2011). "Differentiated vulvar intraepithelial neoplasia is often found in lesions, previously diagnosed as lichen sclerosus, which have progressed to vulvar squamous cell carcinoma". Modern Pathology. 24 (2): 297–305. doi:10.1038/modpathol.2010.192. PMID 21057461.
18. ^ Bigby SM, Eva LJ, Fong KL, Jones RW (November 2016). "The Natural History of Vulvar Intraepithelial Neoplasia, Differentiated Type: Evidence for Progression and Diagnostic Challenges". International Journal of Gynecological Pathology. 35 (6): 574–584. doi:10.1097/PGP.0000000000000280. PMID 26974999. S2CID 42163280.
19. ^ Madsen BS, Jensen HL, van den Brule AJ, Wohlfahrt J, Frisch M (June 2008). "Risk factors for invasive squamous cell carcinoma of the vulva and vagina—population-based case-control study in Denmark". International Journal of Cancer. 122 (12): 2827–34. doi:10.1002/ijc.23446. PMID 18348142. S2CID 11542729.
20. ^ Brinton LA, Thistle JE, Liao LM, Trabert B (May 2017). "Epidemiology of vulvar neoplasia in the NIH-AARP Study". Gynecologic Oncology. 145 (2): 298–304. doi:10.1016/j.ygyno.2017.02.030. PMC 5629039. PMID 28236455.
21. ^ "Vulvar Cancer". Gynecologic Neoplasms. Armenian Health Network, Health.am. 2005. Retrieved 2007-11-08.
22. ^ a b c d e f g h i j k Wohlmuth, Christoph; Wohlmuth-Wieser, Iris (December 2019). "Vulvar malignancies: an interdisciplinary perspective". Journal of the German Society of Dermatology. 17 (12): 1257–1276. doi:10.1111/ddg.13995. ISSN 1610-0387. PMC 6972795. PMID 31829526.
23. ^ Hoffman, Barbara (2012). Williams Gynecology (2nd. ed.). New York: McGraw-Hill Medical. pp. 794–806. ISBN 9780071716727.
24. ^ a b c d Hoffman B, Schorge J, Schaffer J, Halvorson L, Bradshaw K, Cunningham G (2012). Williams Gynecology (2nd ed.). The McGraw-Hill Company, Inc. ISBN 978-0-07-171672-7.
25. ^ "American Cancer Society: What is Vulvar Cancer?". www.cancer.org. Retrieved 2014-06-11.
26. ^ Wohlmuth, Christoph; Wohlmuth-Wieser, Iris (December 2019). "Vulvar malignancies: an interdisciplinary perspective". Journal of the German Society of Dermatology. 17 (12): 1257–1276. doi:10.1111/ddg.13995. ISSN 1610-0387. PMC 6972795. PMID 31829526.
27. ^ a b Wohlmuth, Christoph; Wohlmuth-Wieser, Iris; May, Taymaa; Vicus, Danielle; Gien, Lilian T.; Laframboise, Stéphane (April 2020). "Malignant Melanoma of the Vulva and Vagina: A US Population-Based Study of 1863 Patients". American Journal of Clinical Dermatology. 21 (2): 285–295. doi:10.1007/s40257-019-00487-x. ISSN 1179-1888. PMC 7125071. PMID 31784896.
28. ^ a b c Wohlmuth, Christoph; Wohlmuth-Wieser, Iris; Laframboise, Stéphane (2020-11-24). "Clinical Characteristics and Treatment Response With Checkpoint Inhibitors in Malignant Melanoma of the Vulva and Vagina". Journal of Lower Genital Tract Disease. doi:10.1097/LGT.0000000000000583. ISSN 1526-0976. PMID 33252450.
29. ^ a b c d Wohlmuth, Christoph; Wohlmuth-Wieser, Iris; May, Taymaa; Vicus, Danielle; Gien, Lilian T.; Laframboise, Stéphane (April 2020). "Malignant Melanoma of the Vulva and Vagina: A US Population-Based Study of 1863 Patients". American Journal of Clinical Dermatology. 21 (2): 285–295. doi:10.1007/s40257-019-00487-x. ISSN 1179-1888. PMC 7125071. PMID 31784896.
30. ^ Visco AG, Del Priore G (February 1996). "Postmenopausal bartholin gland enlargement: a hospital-based cancer risk assessment". Obstetrics and Gynecology. 87 (2): 286–90. doi:10.1016/0029-7844(95)00404-1. PMID 8559540. S2CID 11159562.
31. ^ a b International Federation of Gynecologists and Obstetricians (FIGO) (2000). "Staging classification and clinical practice guidelines of gynaecologic cancers" (PDF). Archived from the original (PDF) on 2006-04-23. Retrieved 2006-10-13.
32. ^ Staging of vulvar cancer
33. ^ a b Lawrie TA, Patel A, Martin-Hirsch PP, Bryant A, Ratnavelu ND, Naik R, Ralte A (June 2014). "Sentinel node assessment for diagnosis of groin lymph node involvement in vulval cancer". The Cochrane Database of Systematic Reviews (6): CD010409. doi:10.1002/14651858.CD010409.pub2. PMC 6457826. PMID 24970683.
34. ^ van der Velden J, Fons G, Lawrie TA (May 2011). "Primary groin irradiation versus primary groin surgery for early vulvar cancer". The Cochrane Database of Systematic Reviews (5): CD002224. doi:10.1002/14651858.cd002224.pub2. PMC 7154218. PMID 21563133.
35. ^ "What are the treatment options?". Society of Gynecologic Oncology. 21 November 2012. Retrieved 19 November 2014.
36. ^ Shylasree TS, Bryant A, Howells RE (April 2011). "Chemoradiation for advanced primary vulval cancer". The Cochrane Database of Systematic Reviews (4): CD003752. doi:10.1002/14651858.cd003752.pub3. PMC 4164938. PMID 21491387.
37. ^ a b Society of Gynecologic Oncology (February 2014), "Five Things Physicians and Patients Should Question", Choosing Wisely: an initiative of the ABIM Foundation, Society of Gynecologic Oncology, retrieved 19 February 2013
38. ^ Farias-Eisner R, Cirisano FD, Grouse D, Leuchter RS, Karlan BY, Lagasse LD, Berek JS (April 1994). "Conservative and individualized surgery for early squamous carcinoma of the vulva: the treatment of choice for stage I and II (T1-2N0-1M0) disease". Gynecologic Oncology. 53 (1): 55–8. doi:10.1006/gyno.1994.1087. PMID 8175023.
39. ^ a b c d e f "Cancer of the Vulva—Cancer Stat Facts". SEER. Retrieved 2019-12-03.
40. ^ a b c Alkatout I, Schubert M, Garbrecht N, Weigel MT, Jonat W, Mundhenke C, Günther V (March 20, 2015). "Vulvar cancer: epidemiology, clinical presentation, and management options". International Journal of Women's Health. 7: 305–13. doi:10.2147/IJWH.S68979. PMC 4374790. PMID 25848321.
41. ^ "Vulval cancer statistics". Cancer Research UK. Retrieved 28 October 2014.
42. ^ a b c "Vulval cancer statistics". Cancer Research UK. 2015-05-14. Retrieved 2019-12-03.
43. ^ "Vulvar Cancer Treatment". National Cancer Institute. 1980-01-01. Retrieved 12 May 2015.
## External links[edit]
* Vulvar Cancer Treatment (PDQ®)–Health Professional Version—Information from the US National Cancer Institute
* Canavan TP, Cohen D (October 2002). "Vulvar cancer". American Family Physician. 66 (7): 1269–74. PMID 12387439. Review article for general practitioners.
Classification
D
* ICD-10: C51.0 to C51.9
* ICD-9-CM: 4 184. 4
External resources
* NCI: Vulvar cancer
* v
* t
* e
Tumors of the female urogenital system
Adnexa
Ovaries
Glandular and epithelial/
surface epithelial-
stromal tumor
CMS:
* Ovarian serous cystadenoma
* Mucinous cystadenoma
* Cystadenocarcinoma
* Papillary serous cystadenocarcinoma
* Krukenberg tumor
* Endometrioid tumor
* Clear-cell ovarian carcinoma
* Brenner tumour
Sex cord–gonadal stromal
* Leydig cell tumour
* Sertoli cell tumour
* Sertoli–Leydig cell tumour
* Thecoma
* Granulosa cell tumour
* Luteoma
* Sex cord tumour with annular tubules
Germ cell
* Dysgerminoma
* Nongerminomatous
* Embryonal carcinoma
* Endodermal sinus tumor
* Gonadoblastoma
* Teratoma/Struma ovarii
* Choriocarcinoma
Fibroma
* Meigs' syndrome
Fallopian tube
* Adenomatoid tumor
Uterus
Myometrium
* Uterine fibroids/leiomyoma
* Leiomyosarcoma
* Adenomyoma
Endometrium
* Endometrioid tumor
* Uterine papillary serous carcinoma
* Endometrial intraepithelial neoplasia
* Uterine clear-cell carcinoma
Cervix
* Cervical intraepithelial neoplasia
* Clear-cell carcinoma
* SCC
* Glassy cell carcinoma
* Villoglandular adenocarcinoma
Placenta
* Choriocarcinoma
* Gestational trophoblastic disease
General
* Uterine sarcoma
* Mixed Müllerian tumor
Vagina
* Squamous-cell carcinoma of the vagina
* Botryoid rhabdomyosarcoma
* Clear-cell adenocarcinoma of the vagina
* Vaginal intraepithelial neoplasia
* Vaginal cysts
Vulva
* SCC
* Melanoma
* Papillary hidradenoma
* Extramammary Paget's disease
* Vulvar intraepithelial neoplasia
* Bartholin gland carcinoma
* v
* t
* e
Human papillomavirus
Related
diseases
Cancers
* Cervical cancer
* cancers
* Anal
* Vaginal
* Vulvar
* Penile
* Head and neck cancer (HPV-positive oropharyngeal cancer)
Warts
* * genital
* plantar
* flat
* Laryngeal papillomatosis
* Epidermodysplasia verruciformis
* Focal epithelial hyperplasia
* Papilloma
Others
Acrochordon (skin tags)
Vaccine
* HPV vaccines
* Cervarix
* Gardasil
Screening
* Pap test:
* stain
* Bethesda system
* Cytopathology
* Cytotechnology
* Experimental techniques:
* Speculoscopy
* Cervicography
Colposcopy
Biopsy histology
* Cervical intraepithelial neoplasia (CIN)
* Koilocyte
* Vaginal intraepithelial neoplasia (VAIN)
* Vulvar intraepithelial neoplasia (VIN)
Treatment
* Cervical conization
* Loop electrical excision procedure (LEEP)
History
* Georgios Papanikolaou
* Harald zur Hausen
* v
* t
* e
Sexually transmitted infections (STI)
Bacterial
* Chancroid (Haemophilus ducreyi)
* Chlamydia, lymphogranuloma venereum (Chlamydia trachomatis)
* Donovanosis (Klebsiella granulomatis)
* Gonorrhea (Neisseria gonorrhoeae)
* Mycoplasma hominis infection (Mycoplasma hominis)
* Syphilis (Treponema pallidum)
* Ureaplasma infection (Ureaplasma urealyticum)
Protozoal
* Trichomoniasis (Trichomonas vaginalis)
Parasitic
* Crab louse
* Scabies
Viral
* AIDS (HIV-1/HIV-2)
* Cancer
* cervical
* vulvar
* penile
* anal
* Human papillomavirus (HPV)
* Genital warts (condyloma)
* Hepatitis B (Hepatitis B virus)
* Herpes simplex
* HSV-1 & HSV-2
* Molluscum contagiosum (MCV)
General
inflammation
female
Cervicitis
Pelvic inflammatory disease (PID)
male
Epididymitis
Prostatitis
either
Proctitis
Urethritis/Non-gonococcal urethritis (NGU)
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Vulvar cancer | c0375071 | 843 | wikipedia | https://en.wikipedia.org/wiki/Vulvar_cancer | 2021-01-18T18:48:24 | {"gard": ["9349"], "mesh": ["D014846"], "umls": ["C0375071", "C0042995"], "wikidata": ["Q1908194"]} |
Hypervalinemia
Other namesValinemia or Valine transaminase deficiency[1]
Valine
Symptomsloss of apetite, vomiting, hypotonia, dehydration and failure to thrive.
Usual onset1-2 years
Hypervalinemia, is a rare autosomal recessive metabolic disorder in which urinary and serum levels of the branched-chain amino acid valine are elevated, without related elevation of the branched-chain amino acids leucine and isoleucine.[2][3] It is caused by a deficiency of the enzyme valine transaminase.[4]
## Contents
* 1 Presentation
* 2 Genetics
* 3 Diagnosis
* 4 Treatment
* 5 See also
* 6 References
* 7 External links
## Presentation[edit]
Presenting in infancy, symptoms include lack of appetite, vomiting, dehydration, hypotonia and failure to thrive.[5]
## Genetics[edit]
Hypervalinemia has an autosomal recessive pattern of inheritance.
Hypervalinemia is inherited in an autosomal recessive manner.[1] This means the defective gene responsible for the disorder is located on an autosome, and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.[citation needed]
## Diagnosis[edit]
This section is empty. You can help by adding to it. (July 2017)
## Treatment[edit]
This section is empty. You can help by adding to it. (July 2017)
## See also[edit]
* Isovaleric acidemia
* Maple syrup urine disease
* Propionic acidemia
## References[edit]
1. ^ a b Online Mendelian Inheritance in Man (OMIM): 277100
2. ^ Tada K, Wada Y, Arakawa T (1967). "Hypervalinemia. Its metabolic lesion and therapeutic approach". Am. J. Dis. Child. 113 (1): 64–67. doi:10.1001/archpedi.1967.02090160114013. PMID 6066688.
3. ^ Wada Y, Tada K, Minagawa A, Yoshida T, Morikawa T, Okamura T (1963). "Idiopathic hypervalinemia: probably a new entity of inborn error of valine metabolism". Tohoku J. Exp. Med. 81: 46–55. doi:10.1620/tjem.81.46. PMID 14077060.
4. ^ Dancis J, Hutzler J, Tada K, Wada Y, Morikawa T, Arakawa T (1967). "Hypervalinemia. A defect in valine transamination". Pediatrics. 39 (6): 813–817. PMID 6067402.
5. ^ "Valinemia | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2018-04-17.
## External links[edit]
Classification
D
* ICD-9-CM: 270.3
* OMIM: 277100
* MeSH: C536524 C536524, C536524
* v
* t
* e
Inborn error of amino acid metabolism
K→acetyl-CoA
Lysine/straight chain
* Glutaric acidemia type 1
* type 2
* Hyperlysinemia
* Pipecolic acidemia
* Saccharopinuria
Leucine
* 3-hydroxy-3-methylglutaryl-CoA lyase deficiency
* 3-Methylcrotonyl-CoA carboxylase deficiency
* 3-Methylglutaconic aciduria 1
* Isovaleric acidemia
* Maple syrup urine disease
Tryptophan
* Hypertryptophanemia
G
G→pyruvate→citrate
Glycine
* D-Glyceric acidemia
* Glutathione synthetase deficiency
* Sarcosinemia
* Glycine→Creatine: GAMT deficiency
* Glycine encephalopathy
G→glutamate→
α-ketoglutarate
Histidine
* Carnosinemia
* Histidinemia
* Urocanic aciduria
Proline
* Hyperprolinemia
* Prolidase deficiency
Glutamate/glutamine
* SSADHD
G→propionyl-CoA→
succinyl-CoA
Valine
* Hypervalinemia
* Isobutyryl-CoA dehydrogenase deficiency
* Maple syrup urine disease
Isoleucine
* 2-Methylbutyryl-CoA dehydrogenase deficiency
* Beta-ketothiolase deficiency
* Maple syrup urine disease
Methionine
* Cystathioninuria
* Homocystinuria
* Hypermethioninemia
General BC/OA
* Methylmalonic acidemia
* Methylmalonyl-CoA mutase deficiency
* Propionic acidemia
G→fumarate
Phenylalanine/tyrosine
Phenylketonuria
* 6-Pyruvoyltetrahydropterin synthase deficiency
* Tetrahydrobiopterin deficiency
Tyrosinemia
* Alkaptonuria/Ochronosis
* Tyrosinemia type I
* Tyrosinemia type II
* Tyrosinemia type III/Hawkinsinuria
Tyrosine→Melanin
* Albinism: Ocular albinism (1)
* Oculocutaneous albinism (Hermansky–Pudlak syndrome)
* Waardenburg syndrome
Tyrosine→Norepinephrine
* Dopamine beta hydroxylase deficiency
* reverse: Brunner syndrome
G→oxaloacetate
Urea cycle/Hyperammonemia
(arginine
* aspartate)
* Argininemia
* Argininosuccinic aciduria
* Carbamoyl phosphate synthetase I deficiency
* Citrullinemia
* N-Acetylglutamate synthase deficiency
* Ornithine transcarbamylase deficiency/translocase deficiency
Transport/
IE of RTT
* Solute carrier family: Cystinuria
* Hartnup disease
* Iminoglycinuria
* Lysinuric protein intolerance
* Fanconi syndrome: Oculocerebrorenal syndrome
* Cystinosis
Other
* 2-Hydroxyglutaric aciduria
* Aminoacylase 1 deficiency
* Ethylmalonic encephalopathy
* Fumarase deficiency
* Trimethylaminuria
This genetic disorder article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Hypervalinemia | c0268573 | 844 | wikipedia | https://en.wikipedia.org/wiki/Hypervalinemia | 2021-01-18T18:51:52 | {"gard": ["7845"], "mesh": ["C536524"], "umls": ["C0268573"], "icd-9": ["270.3"], "wikidata": ["Q5958808"]} |
Gliosarcoma
Other namesSarcomatous glioblastoma [1]
Micrograph showing a gliosarcoma. Elastic van Gieson's stain.
SpecialtyOncology
Gliosarcoma is a rare type of glioma, a cancer of the brain that comes from glial, or supportive, brain cells, as opposed to the neural brain cells. Gliosarcoma is a malignant cancer, and is defined as a glioblastoma consisting of gliomatous and sarcomatous components.[2]
It is estimated that approximately 2.1% of all glioblastomas are gliosarcomas. Although most gliomas rarely show metastases outside the cerebrum, gliosarcomas have a propensity to do so, most commonly spreading through the blood to the lungs, and also liver and lymph nodes.[3]
Gliosarcomas have an epidemiology similar to that of glioblastomas, with the average age of onset being 54 years, and males being affected twice as often as females. They are most commonly present in the temporal lobe.
## References[edit]
1. ^ "Gliosarcoma | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 13 July 2019.
2. ^ Ayadi L, Charfi S, Khabir A, et al. (March 2010). "[Cerebral gliosarcoma: clinico-pathologic study of 8 cases]". Tunis Med (in French). 88 (3): 142–6. PMID 20415184.
3. ^ Beumont; Kupsky, WJ; Barger, GR; Sloan, AE; et al. (2007). "Gliosarcoma with multiple extracranial metastases: case report and review of the literature". J. Neurooncol. 83 (1): 39–46. doi:10.1007/s11060-006-9295-x. PMID 17171442.
## External links[edit]
Classification
D
* ICD-10: G71.9
* ICD-O: M9442/3
* MeSH: D018316
* SNOMED CT: 35262004
External resources
* Orphanet: 251576
* Gliosarcoma entry in the public domain NCI Dictionary of Cancer Terms
* Gliosarcoma - National Cancer Institute
This article incorporates public domain material from the U.S. National Cancer Institute document: "Dictionary of Cancer Terms".
* v
* t
* e
Tumours of the nervous system
Endocrine
Sellar:
* Craniopharyngioma
* Pituicytoma
Other:
* Pinealoma
CNS
Neuroepithelial
(brain tumors,
spinal tumors)
Glioma
Astrocyte
* Astrocytoma
* Pilocytic astrocytoma
* Pleomorphic xanthoastrocytoma
* Subependymal giant cell astrocytoma
* Fibrillary astrocytoma
* Anaplastic astrocytoma
* Glioblastoma multiforme
Oligodendrocyte
* Oligodendroglioma
* Anaplastic oligodendroglioma
Ependyma
* Ependymoma
* Subependymoma
Choroid plexus
* Choroid plexus tumor
* Choroid plexus papilloma
* Choroid plexus carcinoma
Multiple/unknown
* Oligoastrocytoma
* Gliomatosis cerebri
* Gliosarcoma
Mature
neuron
* Ganglioneuroma: Ganglioglioma
* Retinoblastoma
* Neurocytoma
* Dysembryoplastic neuroepithelial tumour
* Lhermitte–Duclos disease
PNET
* Neuroblastoma
* Esthesioneuroblastoma
* Ganglioneuroblastoma
* Medulloblastoma
* Atypical teratoid rhabdoid tumor
Primitive
* Medulloepithelioma
Meninges
* Meningioma
* Hemangiopericytoma
Hematopoietic
* Primary central nervous system lymphoma
PNS:
* Nerve sheath tumor
* Cranial and paraspinal nerves
* Neurofibroma
* Neurofibromatosis
* Neurilemmoma/Schwannoma
* Acoustic neuroma
* Malignant peripheral nerve sheath tumor
Other
* WHO classification of the tumors of the central nervous system
Note: Not all brain tumors are of nervous tissue, and not all nervous tissue tumors are in the brain (see brain metastasis).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Gliosarcoma | c0206726 | 845 | wikipedia | https://en.wikipedia.org/wiki/Gliosarcoma | 2021-01-18T18:35:11 | {"gard": ["5653"], "mesh": ["D018316"], "umls": ["C0206726"], "orphanet": ["251576"], "wikidata": ["Q609503"]} |
The null syndrome is part of the Pelizaeus-Merzbacher disease (PMD; see this term) spectrum and is characterized by mild PMD features associated with demyelinating peripheral neuropathy.
## Epidemiology
Its prevalence is unknown. It predominantly affects males.
## Clinical description
The disease manifests during childhood. Patients may have mild developmental delay, delayed sitting and walking beginning usually in the first 2 to 3 years of life, later associated with mild peripheral neuropathy, mild spastic quadriparesis, hyperreflexia, Babinski signs, ataxia, and/or mild intellectual deficit. Patients do not have nystagmus. Although they usually are ambulatory during childhood and have good speech, patients with the null syndrome tend to decline more rapidly beginning in adolescence or early adulthood compared to patients with other PMD forms.
## Etiology
The syndrome is due to null mutations of the PLP1 gene (on Xq22) that cause hypomyelination of the central nervous system. PLP1 encodes the proteolipid protein (PLP), the most abundant protein of the myelin sheath in the central nervous system, and its alternatively spliced isoform (DM20).
## Genetic counseling
The disease has an X-linked inheritance 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
| Null syndrome | c0205711 | 846 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=280234 | 2021-01-23T17:36:24 | {"mesh": ["D020371"], "omim": ["312080"], "icd-10": ["E75.2"], "synonyms": ["PLP1 null syndrome", "Pelizaeus-Merzbacher disease, null syndrome"]} |
Not to be confused with Haemolytic disease of the newborn.
Vitamin K deficiency bleeding of the newborn
Other namesHaemorrhagic disease of the newborn
Vitamin K1
SpecialtyPediatrics
SymptomsBleeding
Usual onsetBirth to 2 months of age
TypesEarly, Classical, Late
CausesVitamin K deficiency
PreventionVitamin K supplementation after birth
Vitamin K deficiency bleeding (VKDB) of the newborn, previously known as haemorrhagic disease of the newborn,[1] is a rare form of bleeding disorder that affects newborns and young infants due to low stores of vitamin K at birth.[2] It commonly presents with intracranial haemorrhage with the risk of brain damage or death.[3]
Newborn infants have low stores of vitamin K, and human breast milk has low concentrations of the vitamin. This combination can lead to vitamin K deficiency and later onset bleeding. Vitamin K deficiency leads to the risk of blood coagulation problems due to impaired production of clotting factors II, VII, IX, X, protein C and protein S by the liver. More rarely VKDB can be caused by maternal medicines causing vitamin K deficiency in the newborn.[2]
VKDB can largely be prevented by prophylactic supplementation of vitamin K, which is typically given shortly after birth by intramuscular injection. Most national health organisations recommend routine vitamin K supplementation after birth.[2] Widespread use of this has made this a rare disease.
## Contents
* 1 Classification
* 2 Signs and symptoms
* 3 Causes
* 4 Diagnosis
* 5 Prevention
* 5.1 Controversy
* 6 Treatment
* 7 References
* 8 External links
## Classification[edit]
VKDB is classified as early, classical or late depending on when it first starts with each having somewhat different types of bleeding and underlying cause:
Classification of vitamin K deficiency in the newborn (VKDB)[2] Syndrome Time of onset Common sites of bleeding Potential causes
Early First 24 hours Scalp, skin, brain, chest, abdomen Maternal medications
Classical 1-7 days Gut, umbilicus, skin, nose, circumcision Idiopathic, breast feeding
Late After day 8 Brain, skin, gut Idiopathic, breast feeding, cholestasis
## Signs and symptoms[edit]
VKDB presents typically in the first month of life with bleeding which can be from various locations. Late onset VKDB presents with bleeding into the brain (intracranial haemorrhage) in more than half of cases.[2]
## Causes[edit]
Newborns are relatively vitamin K deficient for a variety of reasons: They have low vitamin K stores at birth as vitamin K passes the placenta poorly. Levels of vitamin K in human breast milk are low. Gut flora, that in adults produces vitamin K, has not yet developed.[2] Early VKDB is rare and caused by maternal medications that interact with vitamin K such as warfarin, phenytoin, or rifampicin.[2]Classical VKDB is more common and caused by the relative deficiency at birth with inadequate vitamin K intake. This is often termed idiopathic as no one cause is found[citation needed].Late VKDB presents after day 8 and up to 6 months of age, coinciding with the typical age for exclusive breast feeding due to the low levels of vitamin K in human breast milk. Many of these infants have poor vitamin K absorption due to cholestasis which compounds low intake.[2]
## Diagnosis[edit]
Bleeding in an infant without vitamin K supplementation with elevated prothrombin time (PT) that is corrected by vitamin K administration is typically sufficient to make the diagnosis. Confirmation, or investigation of minor deficiency, can be performed by testing proteins produced in the absence of vitamin K, the most established assay being for PIVKA-II.[2]
## Prevention[edit]
Late onset VKDB is nearly completely prevented by early supplementation of vitamin K which is typically given to newborns shortly after birth.[2][4][5] The most effective method of administration is by intramuscular injection shortly after birth but it can be given orally in three doses over the first month.[2] [6]
It is not possible to reliably distinguish which infants are at high risk of late VKDB and the potential consequences are high, as such most national health organisations recommend routine supplementation in the first 24 hours of life.[2]
### Controversy[edit]
Controversy arose in the early 1990s regarding routine supplementation, when two studies suggested a relationship between parenteral administration of vitamin K and childhood cancer.[7] However, both studies have been discredited on the basis of poor methodology and small sample sizes, and a review of the evidence published in 2000 by Ross and Davies found no link between the two.[8]
## Treatment[edit]
Treatment of established bleeding depends on the location but includes vitamin K1 (phylloquinone; phytomenadione; phytonadione) administration which restores the prothrombin time rapidly. Severe bleeding may require blood products such as fresh frozen plasma (FFP), a prothrombin complex concentrate (PCC).[2]
## References[edit]
1. ^ Sutor, Anton; von Kries, Rüdiger; Cornelissen, Marlies; McNinch, Andrew; Andrew, Maureen (9 December 2017). "Vitamin K Deficiency Bleeding (VKDB) in Infancy". Thrombosis and Haemostasis. 81 (3): 456–461. doi:10.1055/s-0037-1614494.
2. ^ a b c d e f g h i j k l m Shearer, Martin J. (March 2009). "Vitamin K deficiency bleeding (VKDB) in early infancy". Blood Reviews. 23 (2): 49–59. doi:10.1016/j.blre.2008.06.001. PMID 18804903.
3. ^ Volpe, Joseph J (2017-10-06). Volpe's neurology of the newborn (Sixth ed.). ISBN 978-0-323-42876-7. Retrieved 9 March 2020.
4. ^ American Academy of Pediatrics Committee on Fetus Newborn (July 2003). "Controversies concerning vitamin K and the newborn. American Academy of Pediatrics Committee on Fetus and Newborn" (PDF). Pediatrics. 112 (1 Pt 1): 191–2. doi:10.1542/peds.112.1.191. PMID 12837888.
5. ^ Logan S, Gilbert R (1998). "Vitamin K For Newborn Babies" (PDF). Department of Health. Archived from the original (PDF) on 7 January 2013. Retrieved 12 Oct 2014.
6. ^ "Postnatal care up to 8 weeks after birth". www.nice.org.uk. NICE. Retrieved 9 March 2020.
7. ^ Parker L, Cole M, Craft AW, Hey EN (January 1998). "Neonatal vitamin K administration and childhood cancer in the north of England: retrospective case-control study". BMJ. 316 (7126): 189–93. doi:10.1136/bmj.316.7126.189. PMC 2665412. PMID 9468683.
8. ^ McMillan DD, et al. (Canadian Paediatric Society, Fetus and Newborn Committee) (1997). "Routine administration of vitamin K to newborns". Paediatrics & Child Health. 2 (6): 429–431. doi:10.1093/pch/2.6.429. PMC 7745636.
## External links[edit]
Classification
D
* ICD-11: KA8F.0
* ICD-10: P53
* ICD-9-CM: 776.0
* MeSH: D006475
* DiseasesDB: 29544
* SNOMED CT: 12546009
External resources
* MedlinePlus: 007320
* eMedicine: article/974489
* Patient UK: Vitamin K deficiency bleeding
* v
* t
* e
Conditions originating in the perinatal period / fetal disease
Maternal factors
complicating pregnancy,
labour or delivery
placenta
* Placenta praevia
* Placental insufficiency
* Twin-to-twin transfusion syndrome
chorion/amnion
* Chorioamnionitis
umbilical cord
* Umbilical cord prolapse
* Nuchal cord
* Single umbilical artery
presentation
* Breech birth
* Asynclitism
* Shoulder presentation
Growth
* Small for gestational age / Large for gestational age
* Preterm birth / Postterm pregnancy
* Intrauterine growth restriction
Birth trauma
* scalp
* Cephalohematoma
* Chignon
* Caput succedaneum
* Subgaleal hemorrhage
* Brachial plexus injury
* Erb's palsy
* Klumpke paralysis
Affected systems
Respiratory
* Intrauterine hypoxia
* Infant respiratory distress syndrome
* Transient tachypnea of the newborn
* Meconium aspiration syndrome
* Pleural disease
* Pneumothorax
* Pneumomediastinum
* Wilson–Mikity syndrome
* Bronchopulmonary dysplasia
Cardiovascular
* Pneumopericardium
* Persistent fetal circulation
Bleeding and
hematologic disease
* Vitamin K deficiency bleeding
* HDN
* ABO
* Anti-Kell
* Rh c
* Rh D
* Rh E
* Hydrops fetalis
* Hyperbilirubinemia
* Kernicterus
* Neonatal jaundice
* Velamentous cord insertion
* Intraventricular hemorrhage
* Germinal matrix hemorrhage
* Anemia of prematurity
Gastrointestinal
* Ileus
* Necrotizing enterocolitis
* Meconium peritonitis
Integument and
thermoregulation
* Erythema toxicum
* Sclerema neonatorum
Nervous system
* Perinatal asphyxia
* Periventricular leukomalacia
Musculoskeletal
* Gray baby syndrome
* muscle tone
* Congenital hypertonia
* Congenital hypotonia
Infections
* Vertically transmitted infection
* Neonatal infection
* rubella
* herpes simplex
* mycoplasma hominis
* ureaplasma urealyticum
* Omphalitis
* Neonatal sepsis
* Group B streptococcal infection
* Neonatal conjunctivitis
Other
* Miscarriage
* Perinatal mortality
* Stillbirth
* Infant mortality
* Neonatal withdrawal
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Vitamin K deficiency bleeding | c0019088 | 847 | wikipedia | https://en.wikipedia.org/wiki/Vitamin_K_deficiency_bleeding | 2021-01-18T18:41:25 | {"mesh": ["D006475"], "umls": ["C0019088"], "icd-9": ["776.0"], "icd-10": ["P53"], "wikidata": ["Q1671351"]} |
Early-onset generalized dystonia is a neurologic movement disorder that usually begins in childhood or adolescence. This is the most common hereditary form of dystonia. Symptoms start in one part of the body (usually an arm, foot, or leg) and are usually first apparent with actions such as writing or walking. With time, the contractions may spread to other parts of the body, causing the muscles to twist the body into unnatural positions. Symptoms can vary greatly, even among members of the same family. For some, the disorder can cause significant disability, while others may experiences only isolated writer’s cramp. A small deletion in the DYT1 gene is the major cause of early-onset dystonia. The genetic change responsible for early onset generalized dystonia is inherited in an autosomal dominant manner, though not everyone who inherits the genetic change will develop the condition. It is thought that only 30% of individuals who inherit the mutation will develop DYT1 dystonia. This is known as reduced penetrance . Treatments include oral medications such as trihexyphenidyl, baclofen, and clonazepam. Botulinum toxin injections may be used in conjunction with oral medications when symptoms are focused in a certain area. In some cases, deep brain stimulation may be indicated.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| DYT-TOR1A | c1851945 | 848 | gard | https://rarediseases.info.nih.gov/diseases/2027/dyt-tor1a | 2021-01-18T18:00:46 | {"omim": ["128100"], "orphanet": ["256"], "synonyms": ["DYT1", "Early onset torsion dystonia", "EOTD", "Dystonia musculorum deformans 1", "Early-onset primary dystonia", "Oppenheim's dystonia", "Idiopathic dystonia DYT1", "Idiopathic torsion dystonia", "Dystonia 1, torsion, autosomal dominant", "DYT-TOR1A dystonia", "Dystonia 1", "DYT1 Early-Onset Isolated Dystonia", "Early-Onset Torsion Dystonia", "Early-onset generalized dystonia"]} |
Dominant inheritance with reduced penetrance was suggested by Arnoldi (1958). He thought that late menarche is related to varicosity. Varicose veins were about twice as frequent in females as in males and no male-to-male transmission was indicated in his illustrative pedigree. Possible X-linked dominance should be considered. Hauge and Gundersen (1969) presented a family study of 249 probands, with the conclusion that multifactorial inheritance seems 'very probable.' Matousek and Prerovsky (1974) used a multifactorial model and estimated heritability to be about 50%. Varicose veins are frequent in some genetic disorders such as the Marfan syndrome. Osler recognized the heritability of varicose veins: 'Varicose veins are the result of an improper selection of grandparents' (Aphorism 335 in Bean and Bean, 1950).
In a study of 2,060 female twin pairs aged 18 to 80 years who had responded to a self-administered questionnaire regarding varicose veins and hemorrhoids, Ng et al. (2005) found that casewise concordance rates were significantly higher for monozygotic than dizygotic twins for both phenotypes, corresponding to additive genetic heritabilities in liability of 86% for varicose veins and 56 to 61% for hemorrhoids. Varicose veins and hemorrhoids were significantly correlated. In 900 dizygotic female twin pairs, significant linkage for varicose veins was found at marker D16S520, located about 80 kb from FOXC2 (602402), but no association was found. Both linkage and association tests were negative for hemorrhoids and for the combined phenotype of varicose veins and hemorrhoids. Ng et al. (2005) concluded that varicose veins and hemorrhoids are heritable, related conditions, and suggested that FOXC2 is implicated in the development of varicose veins in the general population.
Inheritance \- Multifactorial vs. autosomal or X-linked dominant Misc \- Twice as frequent in females as in males Vascular \- Varicose veins ▲ 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
| VARICOSE VEINS | c0042345 | 849 | omim | https://www.omim.org/entry/192200 | 2019-09-22T16:32:02 | {"doid": ["799"], "mesh": ["D014648"], "omim": ["192200"], "icd-10": ["I83.90"]} |
Localized collection of pus that has built up within the tissue of the body
This article is about the medical condition. For the death metal band, see Abscess (band).
Abscess
Other namesLatin: Abscessus
Five-day-old inflamed epidermal inclusion cyst. The black spot is a keratin plug which connects with the underlying cyst.
SpecialtyGeneral surgery, Infectious disease, dermatology
SymptomsRedness, pain, swelling[1]
Usual onsetRapid
CausesBacterial infection (often MRSA)[1]
Risk factorsIntravenous drug use[2]
Diagnostic methodUltrasound, CT scan[1][3]
Differential diagnosisCellulitis, sebaceous cyst, necrotising fasciitis[3]
TreatmentIncision and drainage, Antibiotics[4]
Frequency~1% per year (United States)[5]
An abscess is a collection of pus that has built up within the tissue of the body.[1] Signs and symptoms of abscesses include redness, pain, warmth, and swelling.[1] The swelling may feel fluid-filled when pressed.[1] The area of redness often extends beyond the swelling.[6] Carbuncles and boils are types of abscess that often involve hair follicles, with carbuncles being larger.[7]
They are usually caused by a bacterial infection.[8] Often many different types of bacteria are involved in a single infection.[6] In the United States and many other areas of the world the most common bacteria present is methicillin-resistant Staphylococcus aureus.[1] Rarely, parasites can cause abscesses; this is more common in the developing world.[3] Diagnosis of a skin abscess is usually made based on what it looks like and is confirmed by cutting it open.[1] Ultrasound imaging may be useful in cases in which the diagnosis is not clear.[1] In abscesses around the anus, computer tomography (CT) may be important to look for deeper infection.[3]
Standard treatment for most skin or soft tissue abscesses is cutting it open and drainage.[4] There appears to be some benefit from also using antibiotics.[9] A small amount of evidence supports not packing the cavity that remains with gauze after drainage.[1] Closing this cavity right after draining it rather than leaving it open may speed healing without increasing the risk of the abscess returning.[10] Sucking out the pus with a needle is often not sufficient.[1]
Skin abscesses are common and have become more common in recent years.[1] Risk factors include intravenous drug use, with rates reported as high as 65% among users.[2] In 2005 in the United States, 3.2 million people went to the emergency department for an abscess.[5] In Australia, around 13,000 people were hospitalized in 2008 with the condition.[11]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 2.1 Perianal abscess
* 2.2 Incisional abscess
* 3 Pathophysiology
* 4 Diagnosis
* 4.1 Classification
* 4.2 IV drug use
* 4.3 Differential
* 5 Treatment
* 5.1 Incision and drainage
* 5.2 Antibiotics
* 5.3 Packing
* 5.4 Loop drainage
* 5.5 Primary closure
* 6 Prognosis
* 7 Epidemiology
* 8 Society and culture
* 8.1 Etymology
* 9 Other types
* 10 References
* 11 External links
## Signs and symptoms[edit]
An abscess.
Abscesses may occur in any kind of tissue but most frequently within the skin surface (where they may be superficial pustules known as boils or deep skin abscesses), in the lungs, brain, teeth, kidneys, and tonsils. Major complications may include spreading of the abscess material to adjacent or remote tissues, and extensive regional tissue death (gangrene).
The main symptoms and signs of a skin abscess are redness, heat, swelling, pain, and loss of function. There may also be high temperature (fever) and chills.[12] If superficial, abscesses may be fluctuant when palpated; this wave-like motion is caused by movement of the pus inside the abscess.[13]
An internal abscess is more difficult to identify, but signs include pain in the affected area, a high temperature, and generally feeling unwell. Internal abscesses rarely heal themselves, so prompt medical attention is indicated if such an abscess is suspected. An abscess can potentially be fatal depending on where it is located.[14][15]
## Causes[edit]
Risk factors for abscess formation include intravenous drug use.[16] Another possible risk factor is a prior history of disc herniation or other spinal abnormality,[17] though this has not been proven.
Abscesses are caused by bacterial infection, parasites, or foreign substances. Bacterial infection is the most common cause.[8] Often many different types of bacteria are involved in a single infection.[6] In the United States and many other areas of the world the most common bacteria present is methicillin-resistant Staphylococcus aureus.[1] Among spinal subdural abscesses, methicillin-sensitive Staphylococcus aureus is the most common organism involved.[17]
Rarely parasites can cause abscesses and this is more common in the developing world.[3] Specific parasites known to do this include dracunculiasis and myiasis.[3]
### Perianal abscess[edit]
See also: Anorectal abscess
Surgery of the anal fistula to drain an abscess treats the fistula and reduces likelihood of its recurrence and the need for repeated surgery.[18] There is no evidence that fecal incontinence is a consequence of this surgery for abscess drainage.[18]
Perianal abscesses can be seen in patients with, for example, inflammatory bowel disease (such as Crohn's disease) or diabetes. Often the abscess will start as an internal wound caused by ulceration, hard stool, or penetrative objects with insufficient lubrication. This wound typically becomes infected as a result of the normal presence of feces in the rectal area, and then develops into an abscess. This often presents itself as a lump of tissue near the anus which grows larger and more painful with time. Like other abscesses, perianal abscesses may require prompt medical treatment, such as an incision and debridement or lancing.
### Incisional abscess[edit]
An incisional abscess is one that develops as a complication secondary to a surgical incision. It presents as redness and warmth at the margins of the incision with purulent drainage from it.[19] If the diagnosis is uncertain, the wound should be aspirated with a needle, with aspiration of pus confirming the diagnosis and availing for Gram stain and bacterial culture.[19]
## Pathophysiology[edit]
An abscess is a defensive reaction of the tissue to prevent the spread of infectious materials to other parts of the body.
The organisms or foreign materials kill the local cells, resulting in the release of cytokines. The cytokines trigger an inflammatory response, which draws large numbers of white blood cells to the area and increases the regional blood flow.
The final structure of the abscess is an abscess wall, or capsule, that is formed by the adjacent healthy cells in an attempt to keep the pus from infecting neighboring structures. However, such encapsulation tends to prevent immune cells from attacking bacteria in the pus, or from reaching the causative organism or foreign object.
* A diagram of an abscess.
* Pyemic abscesses of a kidney.
## Diagnosis[edit]
Play media
Ultrasound showing an abscess of the skin[20]
Ultrasound image of breast abscess, appearing as a mushroom-shaped dark (hypoechoic) area
An abscess is a localized collection of pus (purulent inflammatory tissue) caused by suppuration buried in a tissue, an organ, or a confined space, lined by the pyogenic membrane.[21] Ultrasound imaging in the emergency department can help in a diagnosis.[22]
### Classification[edit]
Abscesses may be classified as either skin abscesses or internal abscesses. Skin abscesses are common; internal abscesses tend to be harder to diagnose, and more serious.[12] Skin abscesses are also called cutaneous or subcutaneous abscesses.[23]
### IV drug use[edit]
For those with a history of intravenous drug use, an X-ray is recommended before treatment to verify that no needle fragments are present.[16] In this population if there is also a fever present, infectious endocarditis should be considered.[16]
### Differential[edit]
Abscesses should be differentiated from empyemas, which are accumulations of pus in a preexisting, rather than a newly formed, anatomical cavity.
Other conditions that can cause similar symptoms include: cellulitis, a sebaceous cyst, and necrotising fasciitis.[3] Cellulitis typically also has an erythematous reaction, but does not confer any purulent drainage.[19]
## Treatment[edit]
The standard treatment for an uncomplicated skin or soft tissue abscess is the act of opening and draining.[4] There does not appear to be any benefit from also using antibiotics in most cases.[1] A small amount of evidence did not find a benefit from packing the abscess with gauze.[1]
### Incision and drainage[edit]
See also: Incision and drainage
Abscess five days after incision and drainage.
Abscess following curettage.
The abscess should be inspected to identify if foreign objects are a cause, which may require their removal. If foreign objects are not the cause, incising and draining the abscess is standard treatment.[4][24]
In critical areas where surgery presents a high risk, it may be delayed or used as a last resort. The drainage of a lung abscess may be performed by positioning the patient in a way that enables the contents to be discharged via the respiratory tract. Warm compresses and elevation of the limb may be beneficial for a skin abscess.
### Antibiotics[edit]
Most people who have an uncomplicated skin abscess should not use antibiotics.[4] Antibiotics in addition to standard incision and drainage is recommended in persons with severe abscesses, many sites of infection, rapid disease progression, the presence of cellulitis, symptoms indicating bacterial illness throughout the body, or a health condition causing immunosuppression.[1] People who are very young or very old may also need antibiotics.[1] If the abscess does not heal only with incision and drainage, or if the abscess is in a place that is difficult to drain such as the face, hands, or genitals, then antibiotics may be indicated.[1]
In those cases of abscess which do require antibiotic treatment, Staphylococcus aureus bacteria is a common cause and an anti-staphylococcus antibiotic such as flucloxacillin or dicloxacillin is used. The Infectious Diseases Society of America advises that the draining of an abscess is not enough to address community-acquired methicillin-resistant Staphylococcus aureus (MRSA), and in those cases, traditional antibiotics may be ineffective.[1] Alternative antibiotics effective against community-acquired MRSA often include clindamycin, doxycycline, minocycline, and trimethoprim-sulfamethoxazole.[1] The American College of Emergency Physicians advises that typical cases of abscess from MRSA get no benefit from having antibiotic treatment in addition to the standard treatment.[4] If the condition is thought to be cellulitis rather than an abscess, consideration should be given to the possibility of the strep species as a cause, that are still sensitive to traditional anti-staphylococcus agents such as dicloxacillin or cephalexin. This would be in the case of patients that are able to tolerate penicillin. Antibiotic therapy alone without surgical drainage of the abscess is seldom effective due to antibiotics often being unable to get into the abscess and their ineffectiveness at low pH levels.
Culturing the wound is not needed if standard follow-up care can be provided after the incision and drainage.[4] Performing a wound culture is unnecessary because it rarely gives information which can be used to guide treatment.[4]
### Packing[edit]
In North America, after drainage, an abscess cavity is often packed, perhaps with cloth, in an attempt to protect the healing wound. However, evidence from emergency medicine literature reports that packing wounds after draining causes pain to the person and does not decrease the rate of recurrence, nor bring faster healing, or fewer physician visits.[25]
### Loop drainage[edit]
More recently, several North American hospitals have opted for less-invasive loop drainage over standard drainage and wound packing. In one study of 143 pediatric outcomes, a failure rate of 1.4% was reported in the loop group versus 10.5% in the packing group (P<.030),[26] while a separate study reported a 5.5% failure rate among loop patients.[27]
### Primary closure[edit]
Closing an abscess immediately after draining it appears to speed healing without increasing the risk of recurrence.[10] This may not apply to anorectal abscesses as while they may heal faster, there may be a higher rate of recurrence than those left open.[28]
## Prognosis[edit]
Even without treatment, skin abscesses rarely result in death, as they will naturally break through the skin.[3] Other types of abscess are more dangerous. Brain abscesses are fatal if untreated. When treated, the mortality rate reduces to 5–10%, but is higher if the abscess ruptures.[29]
## Epidemiology[edit]
Skin abscesses are common and have become more common in recent years.[1] Risk factors include intravenous drug use, with rates reported as high as 65% among users.[2] In 2005 in the United States 3.2 million people went to the emergency department for an abscess.[5] In Australia around 13,000 people were hospitalized in 2008 for the disease.[11]
## Society and culture[edit]
The Latin medical aphorism "ubi pus, ibi evacua" expresses "where there is pus, there evacuate it" and is classical advice in the culture of Western medicine.
Needle exchange programmes often administer or provide referrals for abscess treatment to injection drug users as part of a harm reduction public health strategy.[30][31]
### Etymology[edit]
An abscess is so called "abscess" because there is an abscessus (a going away or departure) of portions of the animal tissue from each other to make room for the suppurated matter lodged between them.[32]
The word carbuncle is believed to have originated from the Latin: carbunculus, originally a small coal; diminutive of carbon-, carbo: charcoal or ember, but also a carbuncle stone, "precious stones of a red or fiery colour", usually garnets.[33]
## Other types[edit]
The following types of abscess are listed in the medical dictionary:[34]
* acute abscess
* alveolar abscess
* amebic abscess
* apical abscess
* appendiceal abscess
* Bartholin abscess
* Bezold abscess
* bicameral abscess
* bone abscess
* brain abscess
* Brodie abscess
* bursal abscess
* caseous abscess
* caseous lymphadenitis
* cheesy abscess
* cholangitic abscess
* chronic abscess
* collar stud abscess
* cold abscess
* crypt abscesses
* dental abscess
* periapical abscess
* periodontal abscess
* apical periodontal abscess
* lateral periodontal abscess
* root abscess
* gingival abscess
* lateral alveolar abscess
* pericoronal abscess
* combined periodontic-endodontic abscess
* diffuse abscess
* Douglas abscess
* dry abscess
* Dubois abscesses
* embolic abscess
* fecal abscess
* follicular abscess
* gas abscess
* gravitation abscess
* gummatous abscess
* hidradenitis suppurativa
* hematogenous abscess
* hot abscess
* hypostatic abscess
* ischiorectal abscess
* mastoid abscess
* metastatic abscess
* migrating abscess
* miliary abscess
* Munro abscess
* orbital abscess
* otitic abscess
* palatal abscess
* pancreatic abscess
* parafrenal abscess
* parametric abscess
* paranephric abscess
* parapharyngeal abscess
* parotid
* Pautrier
* pelvic
* perforating
* periappendiceal
* periarticular
* pericemental
* perinephric
* perirectal
* peritonsillar abscess
* periureteral abscess
* phlegmonous abscess
* Pott abscess
* premammary abscess (including subareolar abscess)
* psoas abscess
* pulp abscess
* pyemic abscess
* radicular abscess
* residual abscess
* retrobulbar abscess
* retrocecal abscess
* retropharyngeal abscess
* ring abscess
* satellite abscess
* septicemic abscess
* stellate abscess
* stercoral abscess
* sterile abscess
* stitch abscess
* subdiaphragmatic abscess
* subepidermal abscess
* subhepatic abscess
* subperiosteal abscess
* subphrenic abscess
* subungual abscess
* sudoriferous abscess
* suture abscess
* thymic abscesses
* Tornwaldt abscess
* tropical abscess
* tubo-ovarian abscess
* verminous abscess
* wandering abscess
* worm abscess
## References[edit]
1. ^ a b c d e f g h i j k l m n o p q r s t u Singer, Adam J.; Talan, David A. (Mar 13, 2014). "Management of skin abscesses in the era of methicillin-resistant Staphylococcus aureus" (PDF). The New England Journal of Medicine. 370 (11): 1039–47. doi:10.1056/NEJMra1212788. PMID 24620867. Archived from the original (PDF) on 2014-10-30. Retrieved 2014-09-24.
2. ^ a b c Langrod, Pedro Ruiz, Eric C. Strain, John G. (2007). The substance abuse handbook. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 373. ISBN 9780781760454. Archived from the original on 2017-09-06.
3. ^ a b c d e f g h Marx, John A. Marx (2014). "Skin and Soft Tissue Infections". Rosen's emergency medicine : concepts and clinical practice (8th ed.). Philadelphia, PA: Elsevier/Saunders. pp. Chapter 137. ISBN 978-1455706051.
4. ^ a b c d e f g h American College of Emergency Physicians, "Five Things Physicians and Patients Should Question", Choosing Wisely: an initiative of the ABIM Foundation, American College of Emergency Physicians, archived from the original on March 7, 2014, retrieved January 24, 2014
5. ^ a b c Taira, BR; Singer, AJ; Thode HC, Jr; Lee, CC (Mar 2009). "National epidemiology of cutaneous abscesses: 1996 to 2005". The American Journal of Emergency Medicine. 27 (3): 289–92. doi:10.1016/j.ajem.2008.02.027. PMID 19328372.
6. ^ a b c Elston, Dirk M. (2009). Infectious Diseases of the Skin. London: Manson Pub. p. 12. ISBN 9781840765144. Archived from the original on 2017-09-06.
7. ^ Marx, John A. Marx (2014). "Dermatologic Presentations". Rosen's emergency medicine : concepts and clinical practice (8th ed.). Philadelphia, PA: Elsevier/Saunders. pp. Chapter 120. ISBN 978-1455706051.
8. ^ a b Cox, Carol Turkington, Jeffrey S. Dover; medical illustrations, Birck (2007). The encyclopedia of skin and skin disorders (3rd ed.). New York, NY: Facts on File. p. 1. ISBN 9780816075096. Archived from the original on 2017-09-06.
9. ^ Vermandere, M; Aertgeerts, B; Agoritsas, T; Liu, C; Burgers, J; Merglen, A; Okwen, PM; Lytvyn, L; Chua, S; Vandvik, PO; Guyatt, GH; Beltran-Arroyave, C; Lavergne, V; Speeckaert, R; Steen, FE; Arteaga, V; Sender, R; McLeod, S; Sun, X; Wang, W; Siemieniuk, RAC (6 February 2018). "Antibiotics after incision and drainage for uncomplicated skin abscesses: a clinical practice guideline". BMJ (Clinical Research Ed.). 360: k243. doi:10.1136/bmj.k243. PMC 5799894. PMID 29437651.
10. ^ a b Singer, Adam J.; Thode, Henry C., Jr; Chale, Stuart; Taira, Breena R.; Lee, Christopher (May 2011). "Primary closure of cutaneous abscesses: a systematic review" (PDF). The American Journal of Emergency Medicine. 29 (4): 361–66. doi:10.1016/j.ajem.2009.10.004. PMID 20825801. Archived from the original (PDF) on 2015-07-22.
11. ^ a b Vaska, VL; Nimmo, GR; Jones, M; Grimwood, K; Paterson, DL (Jan 2012). "Increases in Australian cutaneous abscess hospitalisations: 1999–2008". European Journal of Clinical Microbiology & Infectious Diseases. 31 (1): 93–96. doi:10.1007/s10096-011-1281-3. PMID 21553298. S2CID 20376537.
12. ^ a b United Kingdom National Health Service 'Abscess' Archived 2014-10-30 at the Wayback Machine
13. ^ Churchill Livingstone medical dictionary (16th ed.). Edinburgh: Churchill Livingstone. 2008. ISBN 9780080982458.
14. ^ Ferri, Fred F. (2014). Ferri's Clinical Advisor 2015 E-Book: 5 Books in 1. Elsevier Health Sciences. p. 20. ISBN 9780323084307.
15. ^ Fischer, Josef E.; Bland, Kirby I.; Callery, Mark P. (2006). Mastery of Surgery. Lippincott Williams & Wilkins. p. 1033. ISBN 9780781771658.
16. ^ a b c Khalil, PN; Huber-Wagner, S; Altheim, S; Bürklein, D; Siebeck, M; Hallfeldt, K; Mutschler, W; Kanz, GG (Sep 22, 2008). "Diagnostic and treatment options for skin and soft tissue abscesses in injecting drug users with consideration of the natural history and concomitant risk factors". European Journal of Medical Research. 13 (9): 415–24. PMID 18948233.
17. ^ a b Kraeutler, MJ; Bozzay, JD; Walker, MP; John, K (Oct 24, 2014). "Spinal subdural abscess following epidural steroid injection". J Neurosurg Spine. 22 (1): 90–3. doi:10.3171/2014.9.SPINE14159. PMID 25343407.
18. ^ a b Malik, Ali Irqam; Nelson, Richard L; Tou, Samson; Malik, Ali Irqam (2010). "Incision and drainage of perianal abscess with or without treatment of anal fistula". Reviews (7): CD006827. doi:10.1002/14651858.CD006827.pub2. PMID 20614450.
19. ^ a b c Duff, Patrick (2009). "Diagnosis and Management of Postoperative Infection". The Global Library of Women's Medicine. doi:10.3843/GLOWM.10032. ISSN 1756-2228. Archived from the original on 2014-07-14.
20. ^ "UOTW #66 – Ultrasound of the Week". Ultrasound of the Week. 7 January 2016. Archived from the original on 2 November 2016. Retrieved 27 May 2017.
21. ^ Robins/8th/68
22. ^ Barbic, D; Chenkin, J; Cho, DD; Jelic, T; Scheuermeyer, FX (10 January 2017). "In patients presenting to the emergency department with skin and soft tissue infections what is the diagnostic accuracy of point-of-care ultrasonography for the diagnosis of abscess compared to the current standard of care? A systematic review and meta-analysis". BMJ Open. 7 (1): e013688. doi:10.1136/bmjopen-2016-013688. PMC 5253602. PMID 28073795.
23. ^ Medline Plus 'Abscess' Archived 2016-04-07 at the Wayback Machine
24. ^ Green, James; Saj Wajed (2000). Surgery: Facts and Figures. Cambridge University Press. ISBN 1-900151-96-0.
25. ^ Bergstrom, KG (Jan 2014). "News, views, and reviews. Less may be more for MRSA: the latest on antibiotics, the utility of packing an abscess, and decolonization strategies". Journal of Drugs in Dermatology. 13 (1): 89–92. PMID 24385125.
26. ^ Ladde JG, Baker S, Rodgers CN, Papa L (2015). "The LOOP technique: a novel incision and drainage technique in the treatment of skin abscesses in a pediatric ED". The American Journal of Emergency Medicine. 33 (2): 271–76. doi:10.1016/j.ajem.2014.10.014. PMID 25435407.
27. ^ Tsoraides SS, Pearl RH, Stanfill AB, Wallace LJ, Vegunta RK (2010). "Incision and loop drainage: a minimally invasive technique for subcutaneous abscess management in children". Journal of Pediatric Surgery. 45 (3): 606–09. doi:10.1016/j.jpedsurg.2009.06.013. PMID 20223328.
28. ^ Kronborg O, Olsen H (1984). "Incision and drainage v. incision, curettage and suture under antibiotic cover in anorectal abscess. A randomized study with 4-year follow-up". Acta Chirurgica Scandinavica. 150 (8): 689–92. PMID 6397949.
29. ^ Bokhari, Maria R.; Mesfin, Fassil B. (2019), "Brain Abscess", StatPearls, StatPearls Publishing, PMID 28722871, retrieved 2019-07-28
30. ^ Tomolillo, CM; Crothers, LJ; Aberson, CL (2007). "The damage done: a study of injection drug use, injection related abscesses and needle exchange regulation". Substance Use & Misuse. 42 (10): 1603–11. doi:10.1080/10826080701204763. PMID 17918030. S2CID 20795955.
31. ^ Fink, DS; Lindsay, SP; Slymen, DJ; Kral, AH; Bluthenthal, RN (May 2013). "Abscess and self-treatment among injection drug users at four California syringe exchanges and their surrounding communities". Substance Use & Misuse. 48 (7): 523–31. doi:10.3109/10826084.2013.787094. PMC 4334130. PMID 23581506.
32. ^ Collier's New Encyclopedia, 'Abscess'.
33. ^ OED, "Carbuncle": 1 stone, 3 medical
34. ^ "Abscess". Medical Dictionary – Dictionary of Medicine and Human Biology. Archived from the original on 2013-02-05. Retrieved 2013-01-24.
## External links[edit]
Look up abscess in Wiktionary, the free dictionary.
Wikimedia Commons has media related to Abscesses.
* MedlinePlus Encyclopedia: Abscess
* MedlinePlus Encyclopedia: Skin Abscess
* "Abscess" . Collier's New Encyclopedia. 1921.
* "Abscess" . Encyclopædia Britannica (11th ed.). 1911.
* "Abscess". MedlinePlus. U.S. National Library of Medicine.
Classification
D
* ICD-10: L02
* ICD-9-CM: 682.9, 324.1
* MeSH: D000038
External resources
* MedlinePlus: 001353
* 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
Bacterial skin disease
Gram +ve
Firmicutes
* Staphylococcus
* Staphylococcal scalded skin syndrome
* Impetigo
* Toxic shock syndrome
* Streptococcus
* Impetigo
* Cutaneous group B streptococcal infection
* Streptococcal intertrigo
* Cutaneous Streptococcus iniae infection
* Erysipelas / Chronic recurrent erysipelas
* Scarlet fever
* Corynebacterium
* Erythrasma
* Listeriosis
* Clostridium
* Gas gangrene
* Dermatitis gangrenosa
* Mycoplasma
* Erysipeloid of Rosenbach
Actinobacteria
* Mycobacterium-related: Aquarium granuloma
* Borderline lepromatous leprosy
* Borderline leprosy
* Borderline tuberculoid leprosy
* Buruli ulcer
* Erythema induratum
* Histoid leprosy
* Lepromatous leprosy
* Leprosy
* Lichen scrofulosorum
* Lupus vulgaris
* Miliary tuberculosis
* Mycobacterium avium-intracellulare complex infection
* Mycobacterium haemophilum infection
* Mycobacterium kansasii infection
* Papulonecrotic tuberculid
* Primary inoculation tuberculosis
* Rapid growing mycobacterium infection
* Scrofuloderma
* Tuberculosis cutis orificialis
* Tuberculosis verrucosa cutis
* Tuberculous cellulitis
* Tuberculous gumma
* Tuberculoid leprosy
* Cutaneous actinomycosis
* Nocardiosis
* Cutaneous diphtheria infection
* Arcanobacterium haemolyticum infection
* Group JK corynebacterium sepsis
Gram -ve
Proteobacteria
* α: Endemic typhus
* Epidemic typhus
* Scrub typhus
* North Asian tick typhus
* Queensland tick typhus
* Flying squirrel typhus
* Trench fever
* Bacillary angiomatosis
* African tick bite fever
* American tick bite fever
* Rickettsia aeschlimannii infection
* Rickettsialpox
* Rocky Mountain spotted fever
* Human granulocytotropic anaplasmosis
* Human monocytotropic ehrlichiosis
* Flea-borne spotted fever
* Japanese spotted fever
* Mediterranean spotted fever
* Flinders Island spotted fever
* Verruga peruana
* Brill–Zinsser disease
* Brucellosis
* Cat-scratch disease
* Oroya fever
* Ehrlichiosis ewingii infection
* β: Gonococcemia/Gonorrhea/Primary gonococcal dermatitis
* Melioidosis
* Cutaneous Pasteurella hemolytica infection
* Meningococcemia
* Glanders
* Chromobacteriosis infection
* γ: Pasteurellosis
* Tularemia
* Vibrio vulnificus
* Rhinoscleroma
* Haemophilus influenzae cellulitis
* Pseudomonal pyoderma / Pseudomonas hot-foot syndrome / Hot tub folliculitis / Ecthyma gangrenosum / Green nail syndrome
* Q fever
* Salmonellosis
* Shigellosis
* Plague
* Granuloma inguinale
* Chancroid
* Aeromonas infection
* ε: Helicobacter cellulitis
Other
* Syphilid
* Syphilis
* Chancre
* Yaws
* Pinta
* Bejel
* Chlamydia infection
* Leptospirosis
* Rat-bite fever
* Lyme disease
* Lymphogranuloma venereum
Unspecified
pathogen
* Abscess
* Periapical abscess
* Boil/furuncle
* Hospital furunculosis
* Carbuncle
* Cellulitis
* Paronychia / Pyogenic paronychia
* Perianal cellulitis
* Acute lymphadenitis
* Pilonidal cyst
* Pyoderma
* Folliculitis
* Superficial pustular folliculitis
* Sycosis vulgaris
* Pimple
* Ecthyma
* Pitted keratolysis
* Trichomycosis axillaris
* Necrotizing fascitis
* Gangrene
* Chronic undermining burrowing ulcers
* Fournier gangrene
* Elephantiasis nostras
* Blistering distal dactylitis
* Botryomycosis
* Malakoplakia
* Gram-negative folliculitis
* Gram-negative toe web infection
* Pyomyositis
* Blastomycosis-like pyoderma
* Bullous impetigo
* Chronic lymphangitis
* Recurrent toxin-mediated perineal erythema
* Tick-borne lymphadenopathy
* Tropical ulcer
Authority control
* BNC: 000000029
* BNF: cb120434619 (data)
* GND: 4137515-4
* LCCN: sh85000225
* NDL: 00568732
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Abscess | c0000833 | 850 | wikipedia | https://en.wikipedia.org/wiki/Abscess | 2021-01-18T18:50:13 | {"mesh": ["D000038"], "umls": ["C0000833"], "icd-9": ["682.9", "324.1"], "icd-10": ["L02"], "wikidata": ["Q164655"]} |
A number sign (#) is used with this entry because familial exudative vitreoretinopathy-5 (EVR5) is caused by heterozygous mutations in the TSPAN12 gene (613138) on chromosome 7q31. Severely affected individuals with homozygous or compound heterozygous mutations in TSPAN12 have also been reported.
Description
Familial exudative vitreoretinopathy is an inherited blinding disorder caused by defects in the development of retinal vasculature. There is extensive variation in disease severity among patients, even between members of the same family. Severely affected individuals often are registered as blind during infancy and can present with a phenotype resembling retinal dysplasia. Conversely, mildly affected individuals frequently have few or no visual problems and may have just a small area of avascularity in their peripheral retina, detectable only by fluorescein angiography (summary by Poulter et al., 2012).
For a discussion of genetic heterogeneity of familial exudative vitreoretinopathy (FEVR), see EVR1 (133780).
Clinical Features
Toomes et al. (2005) studied a large 4-generation Mexican family with FEVR. The proband and his paternal grandfather and a paternal great aunt had bilateral tractional retinal detachments in childhood, whereas 10 other family members were more mildly affected and predominantly exhibited retinal exudation: 7 adults, including the proband's father, had clusters of exudates throughout the retina, and 3 young patients had only isolated exudates. An additional 3 patients were of unclear status, 1 due to bilateral cataracts that obscured the view of the retina, as well as 2 young patients who had minimal abnormalities in the far retinal periphery. The proband had hand-motion vision in his right eye and 20/60 vision in his left eye following treatment; his affected grandfather and great aunt were totally blind. All other family members had 20/20 best-corrected vision except for the individual with cataracts. Slit-lamp examination of the proband and his father revealed nasally displaced pupils without well-defined collarettes and some shallowing of the anterior chambers; indocyanine-green angiography failed to demonstrate normal vascularization of the iris; and fluorescein angiography showed the typical exudates of FEVR and termination of the peripheral vessels before reaching the ora serrata in the proband and macular dragging with peripheral retinal atrophic areas in his father.
Nikopoulos et al. (2010) studied 2 large, unrelated Dutch families segregating autosomal dominant exudative vitreoretinopathy. Patients in both families invariably displayed the peripheral avascular area characteristic of FEVR. Visual acuity varied considerably, ranging from normal to light perception only, as a result of secondary defects such as retinal detachment and retinal exudates.
Inheritance
In the large 4-generation Mexican family with familial exudative vitreoretinopathy studied by Toomes et al. (2005), inheritance showed a clear autosomal dominant pattern, with male-to-male transmission excluding an X-linked locus.
Mapping
By performing linkage analysis in a large 4-generation Mexican family with FEVR, Toomes et al. (2005) excluded the 3 known autosomal dominant FEVR loci.
Nikopoulos et al. (2010) performed genomewide linkage analysis in 2 large Dutch families ('A' and 'B') segregating autosomal dominant exudative vitreoretinopathy and obtained a suggestive lod score of 2.34 for a 40.5-Mb genomic region on chromosome 7 in family A and a significant lod score of 3.31 for a 16.7-Mb region on chromosome 7 in family B. SNP and microsatellite alleles in affected individuals defined a 10-Mb shared interval containing many genes. Using array-based sequence capture followed by next-generation sequencing, Nikopoulos et al. (2010) identified variants in 3 candidate genes that were detected in at least 4 nonduplicate reads and had a high score for evolutionary conservation.
Molecular Genetics
Using conventional Sanger sequencing in 2 large Dutch families segregating autosomal dominant exudative vitreoretinopathy mapping to chromosome 7, Nikopoulos et al. (2010) confirmed that a variant detected in the candidate gene TSPAN12 (A237P; 613138.0001) was present in heterozygosity in the probands of both families and in their affected relatives. The variant, which was not found in 140 ethnically matched controls, was also detected in 3 relatives of uncertain clinical status and in 1 healthy individual, suggesting nonpenetrance. Analysis of the TSPAN12 gene in 9 additional Dutch FEVR probands in whom mutations in known FEVR genes had been excluded revealed that the A237P change segregated with the phenotype in 2 of the families, whereas a different missense mutation (G188R; 613138.0002) was found in 2 affected brothers from a third family.
Poulter et al. (2010) screened the TSPAN12 gene in 70 FEVR patients in whom mutations in known FEVR genes had been excluded, and identified 7 heterozygous mutations not present in controls (see, e.g., 613138.0003-613138.0006). The authors stated that there was no correlation between particular mutations or mutation types and phenotypes, and that the variation in eye phenotypes was similar to that reported with other FEVR-causing genes.
Kondo et al. (2011) screened for mutations in the TSPAN12 gene in 90 Japanese probands with FEVR and identified a heterozygous mutation in 3: a previously reported L140X mutation (613136.0004) in 2 and a novel L245P mutation (613136.0007) in 1. The clinical signs and symptoms varied among the patients, but the retinal findings were not different from patients with mutations in other known FEVR-causing genes. Kondo et al. (2011) concluded that mutant TSPAN12 is responsible for approximately 3% of FEVR patients in Japan.
In an affected member of a large 4-generation Mexican family segregating autosomal dominant FEVR, originally studied by Toomes et al. (2005), Poulter et al. (2012) analyzed the TSPAN12 gene and identified a missense mutation (Y138C; 613138.0008). Segregation analysis in the family showed that the 3 most severely affected individuals, the proband, his paternal grandfather, and a paternal great aunt, were homozygous for Y138C, whereas 9 more mildly affected individuals, including the proband's parents, were heterozygous for the missense mutation. Consanguinity was not known in the family, but the parents were from the same village in Mexico and believed that their grandparents might have been distantly related. The proband's 3 sibs, who were asymptomatic and showed no signs of FEVR on indirect ophthalmoscopy, were also heterozygous for Y138C; Poulter et al. (2012) noted that without fluorescein angiography, subtle defects might have been missed, and that the sibs might have been too young to exhibit visible signs of disease such as exudates. In addition, 2 family members previously classified as mildly affected did not carry the mutation; reexamination in their homes showed the presence of retinal exudates but no other features of FEVR. The authors suggested that these individuals represented misdiagnoses or phenocopies, or alternatively, that they might harbor mutations in other FEVR genes. Screening a panel of 10 severely affected FEVR/retinal dysplasia patients without mutations in known FEVR genes revealed a further 3 patients with homozygous or compound heterozygous mutations in TSPAN12 (see, e.g., 613138.0009-613138.0011). Noting the clinical variability seen in FEVR families, Poulter et al. (2012) suggested that patients with severe disease might actually harbor 2 mutant alleles, derived either from the same gene or potentially from other genes encoding components of the norrin (300658)-beta-catenin (116806) signaling pathway.
INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Avascularity of peripheral retina \- Retinal exudates \- Decreased visual acuity (in some patients) \- Tractional retinal detachment (in some patients) \- Shallow anterior chamber (in some patients) \- Nasally displaced pupils (in some patients) \- Abnormal vascularization of the iris on indocyanine green angiography (in some patients) MISCELLANEOUS \- Visual acuity varies considerably, depending on the presence of secondary defects such as retinal exudates or detachment \- Severely affected individuals may carry 2 mutated alleles MOLECULAR BASIS \- Caused by mutation in the tetraspanin-12 gene (TSPAN12, 613138.0001 ) ▲ 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
| EXUDATIVE VITREORETINOPATHY 5 | c0339539 | 851 | omim | https://www.omim.org/entry/613310 | 2019-09-22T15:59:03 | {"doid": ["0050535"], "mesh": ["C580083"], "omim": ["613310"], "orphanet": ["891"], "genereviews": ["NBK1147"]} |
A number sign (#) is used with this entry because of evidence that methemoglobinemia and ambiguous genitalia is caused by homozygous mutation in the microsomal cytochrome b5 gene (CYB5A; 613218) on chromosome 18q22.
Description
Methemoglobinemia and ambiguous genitalia is due to isolated 17,20-lyase deficiency, defined by apparently normal 17-alpha-hydroxylase activity but severely reduced 17,20-lyase activity of the CYP17A1 enzyme (609300), which results in sex steroid deficiency but normal glucocorticoid and mineralocorticoid reserve. The clinical phenotype is characterized by male undermasculinization, with absent or disturbed pubertal development in both 46,XY and 46,XX individuals. Mild to severe methemoglobinemia has been reported in these patients (Idkowiak et al., 2012).
Other autosomal recessive methemoglobinemias include types I and II (see 250800), caused by mutation in the CYB5R3 gene (613213). Isolated 17,20-lyase deficiency can also be caused by mutation in the CYP17A1 gene (609300), and mutation in the POR gene can manifest clinically as isolated 17,20-lyase deficiency (see 124015.0016).
Clinical Features
Hegesh et al. (1986) described the highly instructive case of a female Yemenite Jewish baby who turned blue at 7 days of age and was persistently cyanotic for her 26 years to the time of report. There were no neurologic symptoms. Giordano et al. (1994) reported in full on the findings in this patient, who they stated exhibited female genitalia at birth but was subsequently determined to be a male pseudohermaphrodite. The patient was said to be the only example of 'type IV methemoglobinemia' that had been described. Hegesh et al. (1986) had reported that the parents and 6 sibs had normal methemoglobin levels, whereas those in the patient varied between 12% and 19%. The patient's erythrocyte cytochrome b5 levels were about 25% of those found in other family members. Polyacrylamide gel electrophoresis of cytochrome b5 from the patient and family members demonstrated no differences in mobility. Giordano et al. (1994) suggested that the pseudohermaphroditism was also caused by the cytochrome b5 defect. Androgen deficiencies due to defects in 17-alpha-hydroxylase activity are a known cause of pseudohermaphroditism in males (202110), and cytochrome b5 has been shown to participate in 17-alpha hydroxylation in adrenal steroidogenesis by serving as an electron donor.
Kok et al. (2010) reported a 46,XY infant, born to consanguineous parents, who had ambiguous genitalia at birth. The phallus measured 1.5 cm, and there was a bifid scrotum with bilateral palpable gonads and a scrotal urethral meatus. Ultrasound did not visualize a uterus or vagina. The patient was given a diagnosis of 46,XY disorder of sexual differentiation (DSD) and male gender was assigned. Hormone analysis at age 3 months showed markedly elevated luteinizing hormone (LH; see 152780) with a subnormal rise of testosterone after human chorionic gonadotropin (hCG; see 118860) stimulation. Cortisol levels were normal and rose appropriately after adrenocorticotropic hormone (ACTH) stimulation; 17-hydroxyprogesterone levels were basally elevated and rose significantly with ACTH, whereas levels of androstenedione and dehydroepiandrosterone (DHEA) were normal and did not increase. Plasma ACTH was normal and serum DHEA sulfate was nondetectable. In addition, at age 11 months, the patient had a methemoglobin level that was 4 times the upper limit of normal, but he showed no clinical signs of methemoglobinemia. His unaffected first-cousin parents had normal responses to ACTH stimulation testing. A presumptive diagnosis of isolated 17,20-lyase deficiency was made in the proband.
Idkowiak et al. (2012) studied 3 Pakistani sibs with 46,XY karyotypes and varying degrees of undermasculinization, ranging from clitoral enlargement and intraabdominal testes in an affected sib raised as female, to ambiguous genitalia including micropenis, hypospadias, bifid scrotum, and inguinal testes in 2 affected sibs raised as male. All 3 sibs had elevated methemoglobin levels that were at least 4 times the upper limit of normal, but their methemoglobinemia was clinically inapparent, with no evidence of cyanosis, dyspnea, or respiratory distress. Quantitative gas chromatography/mass spectrometry analysis of urinary steroid metabolites showed low androgen metabolite excretion with increased excretion of the 17-alpha-hydroxypregnenolone metabolite pregnenetriol, suggestive of 17,20-lyase deficiency; concurrently, mineralocorticoid and glucocorticoid metabolite excretion appeared normal, suggesting preserved 17-alpha-hydroxylase activity. In addition, the ratio of corticosterone over cortisol metabolites was normal, whereas the ratio of 17-alpha-hydroxyprogesterone over androgen metabolites was significantly elevated, consistent with isolated 17,20-lyase deficiency.
Biochemical Features
Laboratory studies of the patient reported by Hegesh et al. (1986) showed that adding the cofactor cytochrome b5 restored methemoglobin reductase activity. Cytochrome b5 was very low in the patient's red cells but was normal in the healthy unrelated parents and in the sibs. No abnormality of electrophoresis or heat stability was found. The findings in this patient provided confirmation for the conclusion of Hultquist and Passon (1971) that cytochrome b5 is required for methemoglobin reduction in vivo. The lack of neurologic symptoms in the patient suggested that membrane-bound cytochrome b5 levels in nucleated cells, at least those of the brain, were normal (Charache, 1986).
Molecular Genetics
In a patient with methemoglobinemia and ambiguous genitalia, originally reported by Hegesh et al. (1986), Steggles et al. (1992) identified a homozygous splice site mutation in the CYB5A gene (613218.0001), resulting in premature termination of the protein. Steggles et al. (1992) indicated that whereas more than 300 patients had been reported with hereditary methemoglobinemia types I or II (250800), this patient represented the only reported case of what they designated 'methemoglobinemia type IV.'
In a 46,XY infant with elevated methemoglobin and ambiguous genitalia due to apparent isolated 17,20-lyase deficiency, Kok et al. (2010) sequenced the CYP17A1 and CYB5A genes and identified homozygosity for a nonsense mutation in the CYB5A gene (W27X; 613218.0002) for which his unaffected first-cousin parents were heterozygous.
In 3 Pakistani sibs who were 46,XY and exhibited methemoglobinemia with ambiguous genitalia, Idkowiak et al. (2012) sequenced the CYP17A1, POR, and CYB5A genes, and identified homozygosity for a missense mutation in CYB5A (H44L; 613218.0003) that segregated fully with disease in the family. Functional analysis demonstrated greatly reduced CYP17A1 17,20-lyase activity in the presence of the H44L mutant.
INHERITANCE \- Autosomal recessive GENITOURINARY External Genitalia (Male) \- Ambiguous genitalia \- Micropenis \- Hypospadias \- Bifid scrotum \- Undescended testicles \- Male pseudohermaphroditism SKIN, NAILS, & HAIR Skin \- Cyanosis due to methemoglobinemia ENDOCRINE FEATURES \- Isolated 17,20-lyase deficiency \- Elevated luteinizing hormone levels \- Low testosterone levels \- Subnormal response of testosterone to human chorionic gonadotropin stimulation \- Elevated 17-hydroxyprogesterone levels \- Normal glucocorticoid levels \- Normal mineralocorticoid levels \- Low urinary androgen metabolite excretion \- Increased urinary pregnenetriol excretion \- Increased ratio of 17-alpha-hydroxyprogesterone to androgen metabolites HEMATOLOGY \- Decreased levels of erythrocyte cytochrome B5 LABORATORY ABNORMALITIES \- Methemoglobin concentration 12 to 19% (in 1 patient) \- Methemoglobinemia, mild (in some patients) MISCELLANEOUS \- Onset in infancy \- See the more common methemoglobinemia types I and II ( 250800 ) MOLECULAR BASIS \- Caused by mutation in the cytochrome B5A gene (CYB5A, 613218.0001 ) ▲ 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
| METHEMOGLOBINEMIA AND AMBIGUOUS GENITALIA | c0272087 | 852 | omim | https://www.omim.org/entry/250790 | 2019-09-22T16:25:15 | {"mesh": ["C580280"], "omim": ["250790"], "orphanet": ["621"], "synonyms": ["Alternative titles", "ISOLATED 17,20-LYASE DEFICIENCY, PURE", "METHEMOGLOBINEMIA TYPE IV, FORMERLY", "METHEMOGLOBINEMIA DUE TO DEFICIENCY OF CYTOCHROME b5, FORMERLY"]} |
Pseudohypoparathyroidism type 1A is a type of pseudohypoparathyroidism. Pseudohypoparathyroidism is when your body is unable to respond to parathyroid hormone, which is a hormone that controls the levels of calcium, phosphorous, and vitamin D in the blood. The symptoms are very similar to hypoparathyroidism (when parathyroid hormone levels are too low). The main symptoms are low calcium levels and high phosphate levels in the blood. This results in cataracts, dental problems, seizures, numbness, and tetany (muscle twitches and hand and foot spasms). Symptoms are generally first seen in childhood. People with this disorder are also resistant to other hormones, such as thyroid-stimulating hormone and gonadotropins. Type 1A is also associated with a group of symptoms referred to as Albright's hereditary osteodystrophy, which includes short stature, a round face, obesity, and short hand bones. Pseudohypoparathyroidism type 1A is caused by a spelling mistake (mutation) in the GNAS gene and is inherited in an autosomal dominant manner.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Pseudohypoparathyroidism type 1A | c0033806 | 853 | gard | https://rarediseases.info.nih.gov/diseases/7486/pseudohypoparathyroidism-type-1a | 2021-01-18T17:58:06 | {"mesh": ["D011547"], "omim": ["103580"], "umls": ["C0033806"], "orphanet": ["79443"], "synonyms": ["PHP1A", "Albright hereditary osteodystrophy with multiple hormone resistance"]} |
Gould (1942) described the condition in grandfather, father and son, i.e., males of 3 generations. X-rays were not described. Exostosis of the heel, possibly of the same type, is a manifestation of the Reiter syndrome, a rheumatic disorder that shows a high order of association with a specific HLA type (142800), namely B27 (Brewerton et al., 1973; McClusky et al., 1984; Woodrow et al., 1974). Thus might familial aggregation be accounted for.
Limbs \- Exostosis of heel 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
| EXOSTOSES OF HEEL | c0877431 | 854 | omim | https://www.omim.org/entry/133600 | 2019-09-22T16:41:29 | {"mesh": ["C563167"], "omim": ["133600"]} |
Papillary tumor of the pineal region (PTPR) is a very rare neoplasm of the pineal region that is thought to arise from the specialized ependymocytes of the subcommissural organ and that manifests with visual disturbances, headaches, loss of coordination and balance, nausea and vomiting due to obstructive hydrocephalus.
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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
| Papillary tumor of the pineal region | c2985219 | 855 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=251915 | 2021-01-23T17:59:32 | {"umls": ["C2985219"], "icd-10": ["D44.5"], "synonyms": ["PTPR"]} |
Urrets-Zavalia (1955) observed 2 families with a syndrome consisting of agenesis of the orbital margin, hypoplasia of the palpebral skin and tarsal plates, and variable defects of the lacrimal passages including ectopia and elongation of the lower punctum, shortening or absence of the inferior canaliculi, supernumerary canaliculi, or atresia of the nasolacrimal duct. In some a small coloboma of the inner part of the lower lids and congenital anomalies of the extraocular muscles were present.
Eyes \- Orbital margin hypoplasia \- Lower eyelid coloboma \- Hypoplasia of the palpebral skin and tarsal plates \- Ectopic or elongated lower lacrimal punctum \- Congenital extraocular muscle anomaly Nose \- Variable lacrimal passage defects \- Nasolacrimal duct atresia \- Short or absent inferior canaliculi \- Supernumerary canaliculi 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
| ORBITAL MARGIN, HYPOPLASIA OF | c1833795 | 856 | omim | https://www.omim.org/entry/165600 | 2019-09-22T16:37:05 | {"mesh": ["C563490"], "omim": ["165600"], "orphanet": ["98606"]} |
Complex II deficiency is a mitochondrial disease. Mitochondria are specialized compartments in cells that create more than 90% of the energy needed by the body. In mitochondrial diseases, the mitochondria don't work correctly resulting in less energy in the cell, cell injury and cell death. The signs and symptoms of mitochondrial complex II deficiency can vary greatly from severe life-threatening symptoms in infancy to muscle disease beginning in adulthood. Complex II deficiency can be caused by mutations in the SDHA, SDHB, SDHD, or SDHAF1 genes. In many cases the underlying gene mutations cannot be identified. Complex II deficiency is inherited in an autosomal recessive fashion. Complex II deficiency gene mutation carriers may be at an increased risk for certain cancers.
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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
| Mitochondrial complex II deficiency | c1855008 | 857 | gard | https://rarediseases.info.nih.gov/diseases/5053/mitochondrial-complex-ii-deficiency | 2021-01-18T17:59:03 | {"mesh": ["C565375"], "omim": ["252011"], "umls": ["C1855008"], "orphanet": ["3208"], "synonyms": ["Complex 2 mitochondrial respiratory chain deficiency", "Succinate CoQ reductase deficiency", "Mitochondrial respiratory chain complex II deficiency", " Succinate dehydrogenase deficiency"]} |
Generalized dominant dystrophic epidermolysis bullosa (DDEB-gen) is a subtype of dystrophic epidermolysis bullosa (DEB, see this term), formerly known as DDEB, Pasini and Cockayne-Touraine types, characterized by generalized blistering, milia formation, atrophic scarring, and dystrophic nails.
## Epidemiology
The differential diagnosis includes other forms of EB. In the neonatal period, aplasia cutis congenita, herpes simplex infection, congenital erosive and vesicular dermatosis, epidermolytic ichthyosis, linear IgA bullous dermatosis, bullous pemphigoid, neonatal pemphigus and pemphigoid gestationis, bullous impetigo, and staphylococcal scalded skin syndrome (see these terms) may need to be considered.
## Clinical description
The clinical picture is milder than that of the autosomal recessive generalized EB forms. DDEB-gen manifests usually at birth with the development of blisters, primarily affecting the limbs. Aplasia cutis congenita (congenital absence of the skin) can also be observed, more frequently on the lower part of the legs. Blisters heal by developing numerous milia and atrophic scars, particularly evident on the elbows, knees, and backs of hands. Multiple ivory-white colored papules and plaques, known as albopapuloid lesions, may occur, more frequently on the trunk. Nail dystrophy, always present, can lead to loss of nail plates. Blisters develop in the mucosa, mainly in the oral cavity and, less commonly, the esophagus, where they can cause strictures. Dental caries are relatively frequent. Corneal and genitourinary tract involvement, anemia, and growth delay are rare.
## Etiology
DDEB-gen is caused by mutations within the type VII collagen gene (COL7A1) that lead to an alteration of function or a reduction in the amount of collagen VII. This impairs collagen VII assembly into anchoring fibrils which anchor the basement membrane to the underlying dermis. This in turn causes reduced skin resistance to minor trauma.
## Diagnostic methods
Diagnosis is suspected at clinical examination and is confirmed by immunofluorescence antigen mapping and/or transmission electron microscopy on skin samples showing a cleavage plane located below the lamina densa of the cutaneous basement membrane zone. Genetic testing confirms the diagnosis.
## Differential diagnosis
The differential diagnosis includes other forms of EB. In the neonatal period aplasia cutis congenita, herpes simplex infection, bullous impetigo, incontinentia pigmenti, linear IgA bullous dermatosis, bullous pemphigoid (see these terms) may need to be considered.
## Antenatal diagnosis
DNA-based prenatal diagnosis is possible for at risk pregnancies.
## Genetic counseling
DDEB-gen follows an autosomal dominant pattern of inheritance.
## Management and treatment
Management is preventive: protective padding of the skin and appropriate lifestyle measures reduce blistering, and careful wound care prevents secondary infection and reduces scarring. Oral hygiene is important for the management of caries. When present, esophageal strictures can be treated by balloon dilatation with fluoroscopic guidance. In a minority of patients, a follow-up by a dietitian can be required to evaluate nutritional requirements.
## Prognosis
Life expectancy is normal.
*[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
| Generalized dominant dystrophic epidermolysis bullosa | c0432322 | 858 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=231568 | 2021-01-23T19:03:28 | {"gard": ["2139"], "mesh": ["C535956"], "omim": ["131750"], "umls": ["C0432322"], "icd-10": ["Q81.2"], "synonyms": ["Autosomal dominant dystrophic epidermolysis bullosa, Pasini and Cockayne-Touraine types", "DDEB, Pasini and Cockayne-Touraine types", "DDEB, generalized", "DDEB-gen"]} |
For a general description and a discussion of genetic heterogeneity of inflammatory bowel disease (IBD), including Crohn disease (CD) and ulcerative colitis (UC), see IBD1 (266600).
Mapping
In a panel of 1,182 individuals with Crohn disease and 2,024 controls, Parkes et al. (2007) analyzed 37 SNPs from 31 distinct loci that were associated at p values of less than 10(-5) in the Wellcome Trust Case Control Consortium (2007) dataset and obtained replication on chromosome 18p11 at rs2542151 at the PTPN2 (176887) locus (combined p = 3.16 x 10(-8)).
Using an array custom-made for the Wellcome Trust Case Control Consortium (2007) and a staged experimental design, Fisher et al. (2008) genotyped a total of 3,133 unrelated patients with ulcerative colitis and 4,494 controls but found no association with UC on chromosome 18p11 at rs2542151.
Franke et al. (2008) genotyped 35 SNPs across the PTPN2 region in a German sample of 1,850 CD patients, 1,103 UC patients, and 1,817 controls, and found the strongest association with the previously studied SNP rs2542151: while there was only a weak association with CD (nominal p = 0.01), the association with UC (nominal p = 0.0013; OR = 1.33) remained significant after Bonferroni correction (corrected p = 0.046).
In a metaanalysis of data from 3 studies of Crohn disease involving a total of 3,230 cases and 4,829 controls (Rioux et al., 2007, the Wellcome Trust Case-Control Consortium, 2007, and Libioulle et al., 2007) with replication in 3,664 independent cases, Barrett et al. (2008) confirmed significant association with rs2542151 at 18p11 (combined p = 5.10 x 10(-17); case-control odds ratio, 1.35).
INHERITANCE \- Autosomal dominant ABDOMEN Gastrointestinal \- Crohn disease \- Ulcerative colitis ▲ Close
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*[t]: Discuss this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| INFLAMMATORY BOWEL DISEASE 21 | c2676507 | 859 | omim | https://www.omim.org/entry/612354 | 2019-09-22T16:01:46 | {"mesh": ["C567338"], "omim": ["612354"]} |
## Clinical Features
Robbins and Keene (1964) reported a 19-year-old boy whose teeth showed partial pegging, deep lingual pits, exaggeration of middle labial lobes of the canines, and reduced premolar size. One sib was normal. In 5 generations, 10 persons showed odd shaped teeth; among the children of those affected, 8 were also affected, 4 were unaffected and 5 were of unknown status. Levin (1974) suggested that the disorder in this family is the one some have called lobodontia ('wolf teeth') and the same as the condition reported by Shuff (1972) as 'multiple conical teeth.' The premolar teeth were conical, and the canines trituberculate. The molars had an unusually large number of cusps. Brook and Winder (1979) reported a family.
Inheritance \- Autosomal dominant Teeth \- Partial tooth pegging \- Deep lingual tooth pits \- Exaggerated middle labial lobes of canines \- Reduced premolar size \- Odd shaped teeth \- Large number of molar cusps ▲ 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
| TEETH, ODD SHAPES OF | c1861276 | 860 | omim | https://www.omim.org/entry/187000 | 2019-09-22T16:32:54 | {"mesh": ["C566076"], "omim": ["187000"]} |
A number sign (#) is used with this entry because autosomal recessive cytochrome b-positive chronic granulomatous disease (CGD) type II is caused by homozygous or compound heterozygous mutation in the NCF2 gene (608515), which encodes the p67-phox (phagocyte oxidase) protein, on chromosome 1q25.
A more common form of autosomal cytochrome b-positive chronic granulomatous disease, type I (233700), is caused by mutation in the NCF1 gene (608512), which encodes the p47-phox protein.
For a phenotypic description of chronic granulomatous disease, see the well-established X-linked recessive cytochrome b-negative form (CGD; 306400).
Clinical Features
Nunoi et al. (1995) reported a Japanese patient with p67-deficient CGD confirmed by mutation in the NCF2 gene (608515.0001). He was a 19-year-old man whose first episode of infection was at age 3 when he had perianal abscess, liver abscess, severe lung abscess, pneumonia with Aspergillus infection, and severe spinal Aspergillus osteomyelitis. Recurrent infections occurred at ages 4, 6, 11, 15, and 19 years. His clinical course was worse than that of 4 other patients with p67-phox deficiency found in Japan. CGD was diagnosed by no reduction of nitroblue tetrazolium in neutrophils. Nunoi et al. (1995) stated that only 5 patients with p67-phox deficiency had been reported in the United States and Europe, whereas in Japan, although such CGD patients are also rare, they accounted for 7 of 90 CGD patients.
Patino et al. (1999) reported several girls with p67-phox-deficient CGD confirmed by mutations in the NCF2 gene (608515.0003-608515.0006). In an 8-year-old Hispanic girl, the diagnosis of CGD had been made at age 8 months when the patient presented with a right upper lobe pneumonia caused by Serratia marcescens. A 10-year-old girl, born of first-cousin parents native to Jordan, had recurrent abscesses caused by gram-negative bacteria in the first year of life. At the age of 5 years, she had developed inflammatory bowel disease. The diagnosis of CGD was made on the basis of absent NBT reduction and O2(-) production by her PMA-stimulated neutrophils. Deficiency of p67-phox was demonstrated by Western blot analysis. Her sister, aged 2 years, also showed the genetic defect but had not yet developed serious illness or required hospitalization. In a girl with p67-phox-deficient CGD who was 4 years old at the time of her death in Mexico, the diagnosis of CGD was suspected when she presented with skin abscesses containing Enterobacter and Klebsiella and confirmed by a negative NBT test and absent O2(-) production. In her last year of life she was treated successfully for Aspergillus fumigatus pneumonia; however, a few months later, she presented with a severe respiratory infection characterized by necrotizing granulomas and acid-fast bacteria.
Diagnosis
### Prenatal Diagnosis
Kenney et al. (1993) reported a 9-year-old girl with CGD due to deficiency of p67-phox who was homozygous for a RFLP disease marker in the NCF2 gene. Her phenotypically normal mother was also homozygous for the marker, whereas the father and 2 brothers were heterozygous. A fetus was shown to be heterozygous as well, showing that it had inherited at least 1 normal NCF2 gene from the father, predicting a normal phenotype. Cord blood samples at birth showed normal oxidative function.
Pathogenesis
Volpp et al. (1988) raised a polyclonal antiserum that recognized the 47-kD and 67-kD proteins and showed that the neutrophils from patients with 2 different forms of autosomal CGD lacked either the 47- or the 67-kD protein. A deficiency of the 47-kD protein is more frequent than that of the 67-kD protein.
Clinical Management
Liese et al. (2000) evaluated the effect of antibiotic and antifungal long-term prophylaxis on the prognosis of CGD in 39 patients with different subtypes, both X-linked and autosomal recessive. Antibiotic prophylaxis with TMP-SMX significantly decreased the incidence of severe infections in patients with complete loss of cytochrome b activity but had no significant effect in patients with the other subtypes. Eight of the patients with complete absence of cytochrome b activity were also given itraconazole, and none developed fungal infections over 15.5 patient-years, whereas patients of all subtypes who received only antibiotics showed an increase in severe fungal infections. The different subtypes were also analyzed for age at diagnosis, age at first infection, and long-term survival.
Molecular Genetics
Clark et al. (1989) concluded that the autosomal form of CGD due to deficiency of NCF1 represents about 33% of all cases of CGD; the autosomal form due to deficiency of NCF2 represents about 5% of cases.
In a Japanese patient with p67-deficient CGD, Nunoi et al. (1995) identified a mutation in the NCF2 gene (608515.0001).
INHERITANCE \- Autosomal recessive RESPIRATORY Lung \- Pneumonia due to immunodeficiency ABDOMEN Liver \- Hepatic abscesses due to immunodeficiency \- Hepatomegaly Spleen \- Splenomegaly Gastrointestinal \- Perirectal abscesses due to immunodeficiency SKELETAL \- Osteomyelitis due to immunodeficiency SKIN, NAILS, & HAIR Skin \- Dermatitis, infectious, due to immunodeficiency \- Impetigo \- Eczematoid dermatitis \- Discoid lupus in carriers or adults with mild disease MUSCLE, SOFT TISSUES \- Cellulitis due to immunodeficiency IMMUNOLOGY \- Bacterial infections, recurrent \- Fungal infections, recurrent \- Absence of bactericidal oxidative 'respiratory burst' in phagocytes \- Abscess formation in any organ \- Lymphadenitis \- Lymphadenopathy \- Aspergillus infections \- Klebsiella infections \- Staphylococcus aureus infections \- E. coli infections \- Burkholderia cepacia infections \- Serratia marcescens infections \- Tissue biopsy shows granulomas \- Biopsy shows lipid-laden macrophages LABORATORY ABNORMALITIES \- Presence of cytochrome b(-245) \- Deficiency or absence of p67-phox protein (type II) \- Negative nitroblue tetrazolium (NBT) reduction test \- Decreased activity of NADPH oxidase MISCELLANEOUS \- Onset usually in first decade \- Four types of CGD with basically identical clinical phenotypes \- X-linked recessive cytochrome b-negative CGD ( 306400 ) \- Autosomal recessive cytochrome b-negative CGD ( 233690 ) \- Autosomal recessive cytochrome b-positive CGD, type I ( 233700 ) \- Autosomal recessive cytochrome b-positive CGD, type II MOLECULAR BASIS \- Caused by mutation in the neutrophil cytosolic factor-2 gene, p67-phox (NCF2, 608515.0001 ) ▲ 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
| GRANULOMATOUS DISEASE, CHRONIC, AUTOSOMAL RECESSIVE, CYTOCHROME b-POSITIVE, TYPE II | c0018203 | 861 | omim | https://www.omim.org/entry/233710 | 2019-09-22T16:27:21 | {"doid": ["0070191"], "mesh": ["D006105"], "omim": ["233710"], "orphanet": ["379"], "synonyms": ["Alternative titles", "CGD, AUTOSOMAL RECESSIVE CYTOCHROME b-POSITIVE, TYPE II", "GRANULOMATOUS DISEASE, CHRONIC, DUE TO NCF2 DEFICIENCY", "NEUTROPHIL CYTOSOL FACTOR 2, DEFICIENCY OF", "NCF2, DEFICIENCY OF", "p67-PHOX, DEFICIENCY OF"], "genereviews": ["NBK99496"]} |
Ichthyosis vulgaris
Ichthyosis vulgaris #1 (top-left)
SpecialtyMedical genetics
Ichthyosis vulgaris (also known as "Autosomal dominant ichthyosis,"[1] and "Ichthyosis simplex"[1]) is a skin disorder causing dry, scaly skin. It is the most common form of ichthyosis,[2]:486 affecting around 1 in 250 people.[3] For this reason it is known as common ichthyosis. It is usually an autosomal dominant inherited disease (often associated with filaggrin), although a rare non-heritable version called acquired ichthyosis exists.[4]:560
## Contents
* 1 Presentation
* 1.1 Associated conditions
* 2 Genetics
* 3 Diagnosis
* 4 See also
* 5 References
* 6 External links
## Presentation[edit]
The symptoms of the inherited form of ichthyosis vulgaris are not usually present at birth but generally develop between 3 months and 5 years of age.[5][6] The symptoms will often improve with age, although they may grow more severe again in old age.[7]
The condition is not life-threatening; the impact on the patient, if it is a mild case, is generally restricted to mild itching and the social impact of having skin with an unusual appearance. People with mild cases have symptoms that include scaly patches on the shins, fine white scales on the forearms and upper arms, and rough palms. People with the mildest cases have no symptoms other than faint, tell-tale "mosaic lines" between the Achilles tendons and the calf muscles.
Mild presentation of ichthyosis vulgaris: faint, mosaic lines are visible on the calf.
Severe cases, although rare, do exist. Severe cases entail the buildup of scales everywhere, with areas of the body that have a concentration of sweat glands being least affected. Areas where the skin rubs against each other, such as the armpits, the groin, and the "folded" areas of the elbow and knees, are less affected. When the buildup of scales is bad, the person with a severe case has "prickly itch" when he or she needs to sweat but cannot because of the scales. Various topical treatments are available to "exfoliate" the scales. These include lotions that contain alpha-hydroxy acids.
### Associated conditions[edit]
Many people with severe ichthyosis have problems sweating due to the buildup of scales on the skin. This may lead to problems such as "prickly itch" or problems associated with overheating. The majority of people with vulgaris can sweat at least a little. Paradoxically this means most would be more comfortable living in a hot and humid climate. Sweating helps to shed scales which improves the appearance of the skin and prevents "prickly itch".[citation needed]
The dry skin will crack on digits or extremities and create bloody cuts. Skin is painful when inflamed and/or tight. For children and adolescents: psychological precautions may include inconsistent self-image, mood fluctuates due to cyclical outbreaks, prone to addiction, may socially withdraw and/or separate when skin is noticeably infected, pre-occupation with appearance.[citation needed]
Strong air-conditioning and excessive consumption of alcohol can also increase the buildup of scales.
Over 50% of people with ichthyosis vulgaris have some type of atopic disease such as allergies, eczema, or asthma.[8] Another common condition associated with ichthyosis vulgaris is keratosis pilaris (small bumps mainly appearing on the back of the upper arms).[6]
## Genetics[edit]
Ichthyosis vulgaris is one of the most common genetic disorders caused by a single gene.[5] The disorder is believed to be caused by mutations to the gene encoding profilaggrin (a protein which is converted to filaggrin which plays a vital role in the structure of the skin).[9] Around 10% of the population have some detrimental mutations to the profilaggrin gene that is also linked to atopic dermatitis (another skin disorder that is often present with ichthyosis vulgaris).[6] The exact mutation is only known for some cases of ichthyosis vulgaris.[5]
It is generally considered to be an autosomal dominant condition, i.e., a single genetic mutation causes the disease and an affected person has a 50% chance of passing the condition on to their child. There is some research indicating it may be semi-dominant. This means that a single mutation would cause a mild case of ichthyosis vulgaris and mutations to both copies of the gene would produce a more severe case.[9]
## Diagnosis[edit]
This section is empty. You can help by adding to it. (February 2018)
## See also[edit]
* Harlequin-type ichthyosis
* List of cutaneous conditions
* List of cutaneous conditions caused by mutations in keratins
## References[edit]
1. ^ a b Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
2. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0.
3. ^ www.ichthyosis.com
4. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
5. ^ a b c Ichthyosis vulgaris, OMIM (Online Mendelian Inheritance in Man), Johns Hopkins University
6. ^ a b c Ichthyosis vulgaris, eMedicine.com
7. ^ "Ichthyosis vulgaris", MedlinePlus Medical Encyclopedia.
8. ^ Ichthyosis vulgaris, Foundation for Ichthyosis and Related Skin Types (F.I.R.S.T.)
9. ^ a b Ichthyosis Research (2006), Foundation for Ichthyosis & Related Skin Types (F.I.R.S.T)
## External links[edit]
* DermAtlas 28
* Photographs from Ichthyosis Information
Classification
D
* ICD-10: Q80.0
* ICD-9-CM: 757.1
* OMIM: 146700
* MeSH: D016112
* DiseasesDB: 6647
* SNOMED CT: 254157005
External resources
* MedlinePlus: 001451
* eMedicine: derm/678
* v
* t
* e
Congenital malformations and deformations of integument / skin disease
Genodermatosis
Congenital ichthyosis/
erythrokeratodermia
AD
* Ichthyosis vulgaris
AR
* Congenital ichthyosiform erythroderma: Epidermolytic hyperkeratosis
* Lamellar ichthyosis
* Harlequin-type ichthyosis
* Netherton syndrome
* Zunich–Kaye syndrome
* Sjögren–Larsson syndrome
XR
* X-linked ichthyosis
Ungrouped
* Ichthyosis bullosa of Siemens
* Ichthyosis follicularis
* Ichthyosis prematurity syndrome
* Ichthyosis–sclerosing cholangitis syndrome
* Nonbullous congenital ichthyosiform erythroderma
* Ichthyosis linearis circumflexa
* Ichthyosis hystrix
EB
and related
* EBS
* EBS-K
* EBS-WC
* EBS-DM
* EBS-OG
* EBS-MD
* EBS-MP
* JEB
* JEB-H
* Mitis
* Generalized atrophic
* JEB-PA
* DEB
* DDEB
* RDEB
* related: Costello syndrome
* Kindler syndrome
* Laryngoonychocutaneous syndrome
* Skin fragility syndrome
Ectodermal dysplasia
* Naegeli syndrome/Dermatopathia pigmentosa reticularis
* Hay–Wells syndrome
* Hypohidrotic ectodermal dysplasia
* Focal dermal hypoplasia
* Ellis–van Creveld syndrome
* Rapp–Hodgkin syndrome/Hay–Wells syndrome
Elastic/Connective
* Ehlers–Danlos syndromes
* Cutis laxa (Gerodermia osteodysplastica)
* Popliteal pterygium syndrome
* Pseudoxanthoma elasticum
* Van der Woude syndrome
Hyperkeratosis/
keratinopathy
PPK
* diffuse: Diffuse epidermolytic palmoplantar keratoderma
* Diffuse nonepidermolytic palmoplantar keratoderma
* Palmoplantar keratoderma of Sybert
* Meleda disease
* syndromic
* connexin
* Bart–Pumphrey syndrome
* Clouston's hidrotic ectodermal dysplasia
* Vohwinkel syndrome
* Corneodermatoosseous syndrome
* plakoglobin
* Naxos syndrome
* Scleroatrophic syndrome of Huriez
* Olmsted syndrome
* Cathepsin C
* Papillon–Lefèvre syndrome
* Haim–Munk syndrome
* Camisa disease
* focal: Focal palmoplantar keratoderma with oral mucosal hyperkeratosis
* Focal palmoplantar and gingival keratosis
* Howel–Evans syndrome
* Pachyonychia congenita
* Pachyonychia congenita type I
* Pachyonychia congenita type II
* Striate palmoplantar keratoderma
* Tyrosinemia type II
* punctate: Acrokeratoelastoidosis of Costa
* Focal acral hyperkeratosis
* Keratosis punctata palmaris et plantaris
* Keratosis punctata of the palmar creases
* Schöpf–Schulz–Passarge syndrome
* Porokeratosis plantaris discreta
* Spiny keratoderma
* ungrouped: Palmoplantar keratoderma and spastic paraplegia
* desmoplakin
* Carvajal syndrome
* connexin
* Erythrokeratodermia variabilis
* HID/KID
Other
* Meleda disease
* Keratosis pilaris
* ATP2A2
* Darier's disease
* Dyskeratosis congenita
* Lelis syndrome
* Dyskeratosis congenita
* Keratolytic winter erythema
* Keratosis follicularis spinulosa decalvans
* Keratosis linearis with ichthyosis congenita and sclerosing keratoderma syndrome
* Keratosis pilaris atrophicans faciei
* Keratosis pilaris
Other
* cadherin
* EEM syndrome
* immune system
* Hereditary lymphedema
* Mastocytosis/Urticaria pigmentosa
* Hailey–Hailey
see also Template:Congenital malformations and deformations of skin appendages, Template:Phakomatoses, Template:Pigmentation disorders, Template:DNA replication and repair-deficiency disorder
Developmental
anomalies
Midline
* Dermoid cyst
* Encephalocele
* Nasal glioma
* PHACE association
* Sinus pericranii
Nevus
* Capillary hemangioma
* Port-wine stain
* Nevus flammeus nuchae
Other/ungrouped
* Aplasia cutis congenita
* Amniotic band syndrome
* Branchial cyst
* Cavernous venous malformation
* Accessory nail of the fifth toe
* Bronchogenic cyst
* Congenital cartilaginous rest of the neck
* Congenital hypertrophy of the lateral fold of the hallux
* Congenital lip pit
* Congenital malformations of the dermatoglyphs
* Congenital preauricular fistula
* Congenital smooth muscle hamartoma
* Cystic lymphatic malformation
* Median raphe cyst
* Melanotic neuroectodermal tumor of infancy
* Mongolian spot
* Nasolacrimal duct cyst
* Omphalomesenteric duct cyst
* Poland anomaly
* Rapidly involuting congenital hemangioma
* Rosenthal–Kloepfer syndrome
* Skin dimple
* Superficial lymphatic malformation
* Thyroglossal duct cyst
* Verrucous vascular malformation
* Birthmark
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Ichthyosis vulgaris | c0079584 | 862 | wikipedia | https://en.wikipedia.org/wiki/Ichthyosis_vulgaris | 2021-01-18T18:45:45 | {"gard": ["6752"], "mesh": ["D016112"], "umls": ["C0079584"], "icd-9": ["757.1"], "orphanet": ["462"], "wikidata": ["Q3765145"]} |
A cardiac disorder characterized on electrocardiogram (ECG) by ST segment elevation with a coved aspect on the right precordial leads, and a clinical susceptibility to ventricular tachyarrhythmias and sudden death occurring in the absence of overt myocardial abnormalities.
## Epidemiology
Given that the ECG pattern diagnostic for Brugada Syndrome is fluctuant, unlike other inherited arrhythmogenic syndromes, the data regarding the prevalence of the disease are controversial. According to a recent metanalysis, the worldwide prevalence of Brugada syndrome is estimated at 1/2,000, but it varies according to region and ethnicity. Brugada syndrome is rare in Hispanic and Caucasian populations and non-rare in Asian populations. By region, the prevalence is estimated at 1/20,000 in North America and 1/10,000 in Europe. Prevalence is higher in Asia and Middle East where estimates range between 1/270-625. The disease is observed more frequently in men than in women (8:1) and it is extremely rare in children.
## Clinical description
Symptoms usually manifest in the third-fourth decade of life. Syncope, typically occurring at rest, is a common presentation. In some cases, tachycardia does not terminate spontaneously and leads to sudden death. Most frequently, the disease occurs in a normal heart, but subtle structural abnormalities of the right ventricle have been described in a subset of patients. Triggers for the onset of arrhythmias may include fever, abundant meals, some drugs (including antiarrhythmics and antidepressants). On ECG, three different patterns may be observed. Type 1, which is the only diagnostic pattern, is defined as a coved-type ST-segment elevation (0.2 mV) followed by a negative T wave. In type 2, ST-segment elevation has a saddleback appearance with a high-takeoff ST-segment elevation (0.2 mV), a trough (0.1mV) displaying ST elevation, and then either a positive or biphasic T wave. Type 3 has either a saddleback appearance or a coved-type ST-segment elevation (maximum 0.1mV). It is important to underline that only Type 1 ECG is diagnostic for the syndrome.
## Etiology
The gene SCN5A (3p22.2) is responsible for 30% of cases with a gene variant implicated. Other identified genes include CACNA1C (12p13.33), SCNN1A (12p13), SLMAP (3p14.3), SEMA3A (7q21.11), SCN2B (11q23.3). However, in nearly 70% of affected families the genetic cause is unknown.
## Diagnostic methods
The diagnosis is based on clinical examination and detection of type 1 ECG pattern using a 12-lead Holter ECG. In some cases, the ECG manifestations are not obvious or non-diagnostic (type 2, 3 and S ECG patterns). In such instances, a provocative test with the administration of class IC antiarrhythmic drugs (ajmaline, flecainide or procainamide) may be used to confirm/exclude diagnosis. Genetic testing is available after a clinical diagnosis has been established.
## Differential diagnosis
Disorders that could present the typical Brugada ECG pattern include isolated right bundle branch block, pectus excavatum, arrhythmogenic right ventricular cardiomyopathy, acute pericarditis, acute myocardial ischemia or infarction, and early repolarization.
## Genetic counseling
Both sporadic and familial cases have been reported and pedigree analysis suggests an autosomal dominant pattern of inheritance.
## Management and treatment
Implantable cardioverter defibrillator (ICD) is the only therapeutic option of proven efficacy for primary and secondary prophylaxis of cardiac arrest. Thus, correct risk stratification is a major goal for management. Quinidine may be regarded as an adjunctive therapy for patients at higher risk and may reduce the number of cases of ICD shock in patients at risk of recurrence. Recently, epicardial ablation of the right ventricular outflow tract has emerged as a therapeutic option in patients at higher risk.
## Prognosis
The majority of patients remain asymptomatic, 20-30% experience syncope and 8-12% experience at least one cardiac arrest (potentially leading to sudden death). Risk factors for cardiac arrest and sudden death are a spontaneously diagnostic ECG pattern and a history of syncope.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Brugada syndrome | c1142166 | 863 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=130 | 2021-01-23T18:33:08 | {"gard": ["1030"], "mesh": ["D053840"], "omim": ["601144", "611777", "611875", "611876", "612838", "613119", "613120", "613123", "616399"], "umls": ["C1142166", "C1955837"], "icd-10": ["I49.8"], "synonyms": ["Idiopathic ventricular fibrillation, Brugada type"]} |
Condition that affects the arteries that supply the brain
"Cerebrovascular diseases" redirects here. For the medical journal, see Cerebrovascular Diseases (journal).
Cerebrovascular disease
Cerebral angiogram of a carotid-cavernous fistula
SpecialtyNeurology
SymptomsWeakness on one side of body[1]
TypesStroke, vascular dementia, TIA, subarachnoid haemorrhage[2]
Diagnostic methodNeurological exam, physical exam[3]
TreatmentBlood thinners, anti-hypertensives[4]
Cerebrovascular disease includes a variety of medical conditions that affect the blood vessels of the brain and the cerebral circulation. Arteries supplying oxygen and nutrients to the brain are often damaged or deformed in these disorders.[2] The most common presentation of cerebrovascular disease is an ischemic stroke or mini-stroke and sometimes a hemorrhagic stroke.[2] Hypertension (high blood pressure) is the most important contributing risk factor for stroke and cerebrovascular diseases as it can change the structure of blood vessels and result in atherosclerosis.[5] Atherosclerosis narrows blood vessels in the brain, resulting in decreased cerebral perfusion. Other risk factors that contribute to stroke include smoking and diabetes.[6] Narrowed cerebral arteries can lead to ischemic stroke, but continually elevated blood pressure can also cause tearing of vessels, leading to a hemorrhagic stroke.[4]
A stroke usually presents with an abrupt onset of a neurologic deficit – such as hemiplegia (one-sided weakness), numbness, aphasia (language impairment), or ataxia (loss of coordination) – attributable to a focal vascular lesion.[7] The neurologic symptoms manifest within seconds because neurons need a continual supply of nutrients, including glucose and oxygen, that are provided by the blood. Therefore if blood supply to the brain is impeded, injury and energy failure is rapid.[8]
Besides hypertension, there are also many less common causes of cerebrovascular disease, including those that are congenital or idiopathic and include CADASIL, aneurysms, amyloid angiopathy, arteriovenous malformations, fistulas, and arterial dissections.[9] Many of these diseases can be asymptomatic until an acute event, such as a stroke, occurs.[9] Cerebrovascular diseases can also present less commonly with headache or seizures.[10] Any of these diseases can result in vascular dementia due to ischemic damage to the brain.[11][12]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 2.1 Congenital
* 2.2 Acquired
* 2.3 Idiopathic
* 3 Pathophysiology
* 3.1 Mechanism of brain cell death
* 3.2 Types of stroke
* 3.2.1 Ischemic
* 3.2.2 Hemorrhagic
* 4 Diagnosis
* 5 Treatment
* 6 Prognosis
* 7 Epidemiology
* 8 References
* 9 Further reading
* 10 External links
## Signs and symptoms[edit]
Types of brain herniation
The most common presentation of cerebrovascular diseases is an acute stroke, which occurs when blood supply to the brain is compromised.[13] Symptoms of stroke are usually rapid in onset, and may include weakness of one side of the face or body, numbness on one side of the face or body, inability to produce or understand speech, vision changes, and balance difficulties.[1] Hemorrhagic strokes can present with a very severe, sudden headache associated with vomiting, neck stiffness, and decreased consciousness.[13] Symptoms vary depending on the location and the size of the area of involvement of the stroke. Edema, or swelling, of the brain may occur which increases intracranial pressure and may result in brain herniation. A stroke may result in coma or death if it involves key areas of the brain.[14]
Other symptoms of cerebrovascular disease include migraines, seizures, epilepsy, or cognitive decline. However, cerebrovascular disease may go undetected for years until an acute stroke occurs. In addition, patients with some rare congenital cerebrovascular diseases may begin to have these symptoms in childhood.[15]
## Causes[edit]
### Congenital[edit]
Congenital diseases are medical conditions that are present at birth that may be associated with or inherited through genes.[16] Examples of congenital cerebrovascular diseases include arteriovenous malformations, germinal matrix hemorrhage, and CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy).[9] Arteriovenous malformations are abnormal tangles of blood vessels. Usually, a capillary bed separates arteries from veins, which protects the veins from the higher blood pressures that occur in arteries. In arteriovenous malformations, arteries are directly connected to veins, which increases the risk of venous rupture and hemorrhage. Arteriovenous malformations in the brain have a 2–4% chance of rupture each year. However, many arteriovenous malformations go unnoticed and are asymptomatic throughout a person's lifetime.[17]
MRI demonstrating white matter changes in the brain of patients with CADASIL
A germinal matrix hemorrhage is bleeding into the brain of premature infants caused by the rupture of fragile blood vessels within the germinal matrix of premature babies.[18] The germinal matrix is a highly vascularized area within an unborn infant's brain from which brain cells, including neurons and glial cells, originate. Infants are at most risk to germinal matrix hemorrhages when they are born prematurely, before 32 weeks.[18] The stresses exposed after birth, along with the fragile blood vessels, increase risk of hemorrhage. Signs and symptoms include flaccid weakness, seizures, abnormal posturing, or irregular respiration.[18]
CADASIL is an inherited disorder caused by mutations in the Notch 3 gene located on chromosome 19.[19] The Notch 3 gene codes for a transmembrane protein whose function is not well-known. However, the mutation causes accumulation of this protein within small to medium-sized blood vessels.[19] This disease often presents in early adulthood with migraines, stroke, mood disturbances, and cognitive deterioration. MRI shows white matter changes in the brain and also signs of repeated strokes. The diagnosis can be confirmed by gene testing.[20]
### Acquired[edit]
Acquired cerebrovascular diseases are those that are obtained throughout a person's life that may be preventable by controlling risk factors. The incidence of cerebrovascular disease increases as an individual ages.[21] Causes of acquired cerebrovascular disease include atherosclerosis, embolism, aneurysms, and arterial dissections.[9] Atherosclerosis leads to narrowing of blood vessels and less perfusion to the brain, and it also increases the risk of thrombosis, or a blockage of an artery, within the brain. Major modifiable risk factors for atherosclerosis include:[22]
* Hypertension
* Smoking
* Obesity
* Diabetes[23][24]
Illustration of a cerebral aneurysm, demonstrating the bulge in an artery in the brain
Controlling these risk factors can reduce the incidence of atherosclerosis and stroke.[25] Atrial fibrillation is also a major risk factor for strokes. Atrial fibrillation causes blood clots to form within the heart, which may travel to the arteries within the brain and cause an embolism. The embolism prevents blood flow to the brain, which leads to a stroke.[citation needed]
An aneurysm is an abnormal bulging of small sections of arteries, which increases the risk of artery rupture. Intracranial aneurysms are a leading cause of subarachnoid hemorrhage, or bleeding around the brain within the subarachnoid space. There are various hereditary disorders associated with intracranial aneurysms, such as Ehlers-Danlos syndrome, autosomal dominant polycystic kidney disease, and familial hyperaldosteronism type I.[26][27][28] However, individuals without these disorders may also obtain aneurysms. The American Heart Association and American Stroke Association recommend controlling modifiable risk factors including smoking and hypertension.[29]
Arterial dissections are tears of the internal lining of arteries, often associated with trauma.[30] Dissections within the carotid arteries or vertebral arteries may compromise blood flow to the brain due to thrombosis, and dissections increase the risk of vessel rupture.[31]
### Idiopathic[edit]
Idiopathic diseases are those that occur spontaneously without a known cause.[32] Moyamoya is an example of an idiopathic cerebrovascular disorder that results in narrowing and occlusion of intracranial blood vessels.[9] The most common presentation is stroke or transient ischemic attack, but cognitive decline within children may also be a presenting symptom.[9][13] The disease may begin to show symptoms beginning in adolescence, but some may not have symptoms until adulthood.[13]
## Pathophysiology[edit]
### Mechanism of brain cell death[edit]
When a reduction in blood flow lasting seconds occurs, the brain tissue suffers ischemia, or inadequate blood supply.[33][34] If the interruption of blood flow is not restored in minutes, the tissue suffers infarction followed by tissue death.[35] When the low cerebral blood flow persists for a longer duration, this may develop into an infarction in the border zones (areas of poor blood flow between the major cerebral artery distributions). In more severe instances, global hypoxia-ischemia causes widespread brain injury leading to a severe cognitive sequelae called hypoxic-ischemic encephalopathy.[36]
An ischemic cascade occurs where an energetic molecular problem arises due to lack of oxygen and nutrients. The cascade results in decreased production of adenosine triphosphate (ATP), which is a high-energy molecule needed for cells in the brain to function.[37] Consumption of ATP continues in spite of insufficient production, this causes total levels of ATP to decrease and lactate acidosis to become established (ionic homeostasis in neurons is lost). The downstream mechanisms of the ischemic cascade thus begins. Ion pumps no longer transport Ca2+ out of cell, this triggers release of glutamate, which in turn allows calcium into cell walls. In the end the apoptosis pathway is initiated and cell death occurs.[38]
There are several arteries that supply oxygen to different areas of the brain, and damage or occlusion of any of them can result in stroke.[39] The carotid arteries cover the majority of the cerebrum. The common carotid artery divides into the internal and the external carotid arteries. The internal carotid artery becomes the anterior cerebral artery and the middle central artery. The ACA transmits blood to the frontal parietal. From the basilar artery are two posterior cerebral arteries. Branches of the basilar and PCA supply the occipital lobe, brain stem, and the cerebellum.[40] Ischemia is the loss of blood flow to the focal region of the brain. This produces heterogeneous areas of ischemia at the affected vascular region, furthermore, blood flow is limited to a residual flow. Regions with blood flow of less than 10 mL/100 g of tissue/min are core regions (cells here die within minutes of a stroke). The ischemic penumbra with a blood flow of <25 ml/100g tissue/min, remain usable for more time (hours).[41]
### Types of stroke[edit]
There are two main divisions of strokes: ischemic and hemorrhagic. Ischemic stroke involves decreased blood supply to regions of the brain, while hemorrhagic stroke is bleeding into or around the brain.[42]
#### Ischemic[edit]
* Ischemic stroke, the most common is caused by a blockage of a blood vessel in the brain, usually caused by thrombosis or emboli from a proximal arterial source or the heart, that leads to the brain being starved of oxygen.[43] The neurologic signs and symptoms must last longer than 24 hours or the brain infarction is demonstrated, mainly by imaging techniques.[44]
* Transient ischemic attack (TIA) also called a mini-stroke. This is a condition in which the blood flow to a region of the brain is blocked, but blood flow is quickly restored and the brain tissue can fully recover. The symptoms are only transient, leaving no sequelae, or long-term deficits.[45] In order to diagnose this entity, all neurologic signs and symptoms must have been resolved within 24 hrs without evidence of brain infarction on brain imaging.[46]
#### Hemorrhagic[edit]
* Subarachnoid haemorrhage occurs when blood leaks out of damaged vessels into the cerebrospinal fluid in the subarachnoid space around the brain.[2] The most common cause of a subarachnoid hemorrhage is an aneurysm rupture due to the weakened blood vessel walls and increased wall stress.[47] The neurologic symptoms are produced by the blood mass effect on neural structures, from the toxic effects of blood on the brain tissue, or by the increasing of intracranial pressure.[48]
* Intracerebral haemorrhage is bleeding directly into the brain rather than around the brain.[42] Causes and risk factors include hypertension, blood thinning medications, trauma, and arteriovenous malformations.[49]
Brain infarct
## Diagnosis[edit]
Diagnoses of cerebrovascular disease may include:[3]
* medical history
* physical exam
* neurological examination.
* acute stroke imaging is generally performed in significant symptoms of new onset.
It is important to differentiate the symptoms caused by a stroke from those caused by syncope (fainting) which is also a reduction in cerebral blood flow, almost always generalized, but they are usually caused by systemic hypotension of various origins: cardiac arrhythmias, myocardial infarction, hemorrhagic shock, among others.[50]
## Treatment[edit]
Treatment for cerebrovascular disease may include medication, lifestyle changes, and surgery, depending on the cause.[4]
Examples of medications are:
* antiplatelets (aspirin, clopidogrel)
* blood thinners (heparin, warfarin)
* antihypertensives:
* ACE inhibitors
* beta blockers
* calcium channel blockers \- in particular Nimodipine reduces the incidence and severity of ischemic deficits in patients with subarachnoid hemorrhage (SAH)[51]
* anti-diabetic medications.
Surgical procedures include:
* endovascular surgery and vascular surgery (for future stroke prevention).
## Prognosis[edit]
Prognostics factors: Lower Glasgow Coma Scale score, higher pulse rate, higher respiratory rate and lower arterial oxygen saturation level is prognostic features of in-hospital mortality rate in acute ischemic stroke.[52]
## Epidemiology[edit]
Disability-adjusted life year for cerebrovascular disease per 100,000 inhabitants in 2004.[53]
less than 250
250–425
425–600
600–775
775–950
950–1125
1125–1300
1300–1475
1475–1650
1650–1825
1825–2000
more than 2000
Worldwide, it is estimated there are 31 million stroke survivors, though about 6 million deaths were due to cerebrovascular disease (2nd most common cause of death in the world and 6th most common cause of disability).[54]
Cerebrovascular disease primarily occurs with advanced age; the risk for developing it goes up significantly after 65 years of age. CVD tends to occur earlier than Alzheimer's Disease (which is rare before the age of 80). In some countries such as Japan, CVD is more common than AD.[medical citation needed]
In 2012 6.4 million US individuals (adults) had a stroke, which corresponds to 2.7% in the U.S. With approximately 129,000 deaths in 2013 (U.S.)[55]
Geographically, a "stroke belt" in the US has long been known, similar to the "diabetes belt" which includes all of Mississippi and parts of Alabama, Arkansas, Florida, Georgia, Kentucky, Louisiana, North Carolina, Ohio, Pennsylvania, South Carolina, Tennessee, Texas, Virginia, and West Virginia.[56]
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46. ^ Easton, J. Donald; Saver, Jeffrey L.; Albers, Gregory W.; Alberts, Mark J.; Chaturvedi, Seemant; Feldmann, Edward; Hatsukami, Thomas S.; Higashida, Randall T.; Johnston, S. Claiborne; Kidwell, Chelsea S.; Lutsep, Helmi L.; Miller, Elaine; Sacco, Ralph L. (2009). "Definition and evaluation of transient ischemic attack: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists". Stroke. 40 (6): 2276–2293. doi:10.1161/STROKEAHA.108.192218. ISSN 1524-4628. PMID 19423857.
47. ^ Van Gijn, Jan; Kerr, Richard S; Rinkel, Gabriel JE (2007). "Subarachnoid haemorrhage". The Lancet. 369 (9558): 306–318. doi:10.1016/S0140-6736(07)60153-6. PMID 17258671. S2CID 29126514.
48. ^ Xi, Guohua; Keep, Richard F; Hoff, Julian T (2006). "Mechanisms of brain injury after intracerebral haemorrhage". The Lancet Neurology. 5 (1): 53–63. doi:10.1016/S1474-4422(05)70283-0. PMID 16361023. S2CID 30474999.
49. ^ Meretoja, A; Strbian, D; Putaala, J; Curtze, S; Haapaniemi, E; Mustanoja, S; Sairanen, T; Satopaa, J; Silvennoinen, H; Niemela, M; Kaste, M; Tatlisumak, T (2012). "SMASH-U: A Proposal for Etiologic Classification of Intracerebral Hemorrhage". Stroke. 43 (10): 2592–2597. doi:10.1161/STROKEAHA.112.661603. PMID 22858729.
50. ^ Bonanno, Fabriziogiuseppe (2011). "Clinical pathology of the shock syndromes". Journal of Emergencies, Trauma, and Shock. 4 (2): 233–43. doi:10.4103/0974-2700.82211. PMC 3132364. PMID 21769211.
51. ^ Research, Center for Drug Evaluation and (2018-11-03). "Postmarket Drug and Biologic Safety Evaluations Completed from July 2016 – September 2016". FDA.
52. ^ Shah, Bhupendra; Bartaula, Bijay; Adhikari, Janak; Neupane, Harishankar; Shah, Birendraprasad; Poudel, Gunaraj (2017). "Predictors of in-hospital mortality of acute ischemic stroke in adult population". Journal of Neurosciences in Rural Practice. 8 (4): 591–594. doi:10.4103/jnrp.jnrp_265_17. PMC 5709883. PMID 29204020.
53. ^ "WHO Disease and injury country estimates". World Health Organization. 2009. Retrieved Nov 11, 2009.
54. ^ Ward, Helen; Toledano, Mireille B.; Shaddick, Gavin; Davies, Bethan; Elliott, Paul (2012-05-24). Oxford Handbook of Epidemiology for Clinicians. OUP Oxford. p. 310. ISBN 9780191654787.
55. ^ "FastStats". www.cdc.gov. Retrieved 2015-09-01.
56. ^ BORHANI NO (1965). "Changes and Geographic Distribution of Mortality from Cerebrovascular Disease". American Journal of Public Health and the Nation's Health. 55 (5): 673–81. doi:10.2105/AJPH.55.5.673. PMC 1256296. PMID 14287837.
## Further reading[edit]
* Chan, Pak H. (2002-03-28). Cerebrovascular Disease: 22nd Princeton Conference. Cambridge University Press. ISBN 9781139439657.
* Mark, S. D; Wang, W; Fraumeni, J. F; Li, J.-Y; Taylor, P. R; Wang, G.-Q; Guo, W; Dawsey, S. M; Li, B; Blot, W. J (1996). "Lowered Risks of Hypertension and Cerebrovascular Disease after Vitamin/Mineral Supplementation: The Linxian Nutrition Intervention Trial". American Journal of Epidemiology. 143 (7): 658–664. doi:10.1093/oxfordjournals.aje.a008798. PMID 8651227.
* Ning, Mingming; Lopez, Mary; Cao, Jing; Buonanno, Ferdinando S; Lo, Eng H (2012). "Application of proteomics to cerebrovascular disease". Electrophoresis. 33 (24): 3582–3597. doi:10.1002/elps.201200481. PMC 3712851. PMID 23161401.
## External links[edit]
Classification
D
* ICD-10: I60-I69
* MeSH: D002561
Scholia has a topic profile for Cerebrovascular disease.
Wikimedia Commons has media related to Cerebrovascular diseases.
* v
* t
* e
Cerebrovascular diseases including stroke
Ischaemic stroke
Brain
* Anterior cerebral artery syndrome
* Middle cerebral artery syndrome
* Posterior cerebral artery syndrome
* Amaurosis fugax
* Moyamoya disease
* Dejerine–Roussy syndrome
* Watershed stroke
* Lacunar stroke
Brain stem
* Brainstem stroke syndrome
* Medulla
* Medial medullary syndrome
* Lateral medullary syndrome
* Pons
* Medial pontine syndrome / Foville's
* Lateral pontine syndrome / Millard-Gubler
* Midbrain
* Weber's syndrome
* Benedikt syndrome
* Claude's syndrome
Cerebellum
* Cerebellar stroke syndrome
Extracranial arteries
* Carotid artery stenosis
* precerebral
* Anterior spinal artery syndrome
* Vertebrobasilar insufficiency
* Subclavian steal syndrome
Classification
* Brain ischemia
* Cerebral infarction
* Classification
* Transient ischemic attack
* Total anterior circulation infarct
* Partial anterior circulation infarct
Other
* CADASIL
* Binswanger's disease
* Transient global amnesia
Haemorrhagic stroke
Extra-axial
* Epidural
* Subdural
* Subarachnoid
Cerebral/Intra-axial
* Intraventricular
Brainstem
* Duret haemorrhages
General
* Intracranial hemorrhage
Aneurysm
* Intracranial aneurysm
* Charcot–Bouchard aneurysm
Other
* Cerebral vasculitis
* Cerebral venous sinus thrombosis
* v
* t
* e
Diseases of the nervous system, primarily CNS
Inflammation
Brain
* Encephalitis
* Viral encephalitis
* Herpesviral encephalitis
* Limbic encephalitis
* Encephalitis lethargica
* Cavernous sinus thrombosis
* Brain abscess
* Amoebic
Brain and spinal cord
* Encephalomyelitis
* Acute disseminated
* Meningitis
* Meningoencephalitis
Brain/
encephalopathy
Degenerative
Extrapyramidal and
movement disorders
* Basal ganglia disease
* Parkinsonism
* PD
* Postencephalitic
* NMS
* PKAN
* Tauopathy
* PSP
* Striatonigral degeneration
* Hemiballismus
* HD
* OA
* Dyskinesia
* Dystonia
* Status dystonicus
* Spasmodic torticollis
* Meige's
* Blepharospasm
* Athetosis
* Chorea
* Choreoathetosis
* Myoclonus
* Myoclonic epilepsy
* Akathisia
* Tremor
* Essential tremor
* Intention tremor
* Restless legs
* Stiff-person
Dementia
* Tauopathy
* Alzheimer's
* Early-onset
* Primary progressive aphasia
* Frontotemporal dementia/Frontotemporal lobar degeneration
* Pick's
* Dementia with Lewy bodies
* Posterior cortical atrophy
* Vascular dementia
Mitochondrial disease
* Leigh syndrome
Demyelinating
* Autoimmune
* Inflammatory
* Multiple sclerosis
* For more detailed coverage, see Template:Demyelinating diseases of CNS
Episodic/
paroxysmal
Seizures and epilepsy
* Focal
* Generalised
* Status epilepticus
* For more detailed coverage, see Template:Epilepsy
Headache
* Migraine
* Cluster
* Tension
* For more detailed coverage, see Template:Headache
Cerebrovascular
* TIA
* Stroke
* For more detailed coverage, see Template:Cerebrovascular diseases
Other
* Sleep disorders
* For more detailed coverage, see Template:Sleep
CSF
* Intracranial hypertension
* Hydrocephalus
* Normal pressure hydrocephalus
* Choroid plexus papilloma
* Idiopathic intracranial hypertension
* Cerebral edema
* Intracranial hypotension
Other
* Brain herniation
* Reye syndrome
* Hepatic encephalopathy
* Toxic encephalopathy
* Hashimoto's encephalopathy
Both/either
Degenerative
SA
* Friedreich's ataxia
* Ataxia–telangiectasia
MND
* UMN only:
* Primary lateral sclerosis
* Pseudobulbar palsy
* Hereditary spastic paraplegia
* LMN only:
* Distal hereditary motor neuronopathies
* Spinal muscular atrophies
* SMA
* SMAX1
* SMAX2
* DSMA1
* Congenital DSMA
* Spinal muscular atrophy with lower extremity predominance (SMALED)
* SMALED1
* SMALED2A
* SMALED2B
* SMA-PCH
* SMA-PME
* Progressive muscular atrophy
* Progressive bulbar palsy
* Fazio–Londe
* Infantile progressive bulbar palsy
* both:
* Amyotrophic lateral sclerosis
Authority control
* NDL: 00568663
*[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
| Cerebrovascular disease | c0038454 | 864 | wikipedia | https://en.wikipedia.org/wiki/Cerebrovascular_disease | 2021-01-18T18:56:36 | {"mesh": ["D020521", "D002561"], "umls": ["C0038454", "C0007820"], "icd-10": ["I60", "I69"], "wikidata": ["Q3010352"]} |
Cornelia de Lange syndrome (CdLS) is a developmental disorder that affects many parts of the body. The severity of the condition and the associated signs and symptoms can vary widely, but may include distinctive facial characteristics, growth delays, intellectual disability and limb defects. Approximately 60% of people affected by CdLS have a disease-causing variation (mutation) in the NIPBL gene, and about 10% of cases are caused by mutations in one of four known genes: SMC1A, SMC3, HDAC8 and RAD21. In the remaining 30% of cases, the underlying genetic cause of the condition is unknown. CdLS can be inherited in an autosomal dominant (NIPBL, SMC2, or RAD21) or X-linked (SMC1A or HDAC8) manner. However, most cases result from new (de novo) mutations and occur in people with no family history of the condition. Treatment is based on the signs and symptoms present in each person.
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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
| Cornelia de Lange syndrome | c0270972 | 865 | gard | https://rarediseases.info.nih.gov/diseases/10109/cornelia-de-lange-syndrome | 2021-01-18T18:01:05 | {"mesh": ["D003635"], "omim": ["122470"], "umls": ["C0270972"], "orphanet": ["199"], "synonyms": ["Brachmann de Lange syndrome", "CDLS", "De Lange syndrome", "Typus degenerativus amstelodamensis"]} |
A number sign (#) is used with this entry because of evidence that congenital nongoitrous hypothyroidism-4 (CHNG4) is caused by homozygous mutation in the TSHB gene (188540) on chromosome 1p13.
For a general phenotypic description and a discussion of genetic heterogeneity of congenital nongoitrous hypothyroidism, see 275200.
Clinical Features
The first familial incidence of isolated thyrotropin deficiency was reported by Miyai et al. (1971), who observed 2 affected sisters. Synthetic thyrotropin-releasing hormone (TRH) resulted in no rise in serum TSH levels. (Thyrotropin is more generally known as TSH (thyroid-stimulating hormone).) The parents were second cousins. A male sib, who died at age 3 years, may also have been affected.
TSH deficiency has been described (Zisman et al., 1969) in patients with pseudohypoparathyroidism (see 103580), but the defect resides in the receptor or response mechanism. The use of TRH produced by the hypothalamus reveals the existence of isolated hypothalamic hypothyroidism (275120) otherwise indistinguishable from TSH deficiency (Pittman et al., 1971).
Kohno et al. (1980) reported a family in which 2 sisters had pituitary hypothyroidism. Similarities to the cases of Miyai et al. (1971) included Japanese race, female sex, second-cousin parentage, and severe hypothyroidism in the neonatal period. Serum TSH did not increase with administration of TRH.
Nygren and Rojdmark (1982) described a patient with isolated thyrotropin deficiency unresponsive to prolonged treatment with thyrotropin-releasing hormone. The patient had narcolepsy. They granted that the defect might be in the responsiveness of pituitary cells rather than in the production of TSH.
Molecular Genetics
In 2 sisters with isolated TSH deficiency, born of consanguineous parents, Hayashizaki et al. (1989) found homozygosity for a missense mutation (G29R; 188540.0001) in the TSHB gene.
In affected members of 2 related Greek families with congenital TSH-deficient hypothyroidism, Dacou-Voutetakis et al. (1990) demonstrated homozygosity for a nonsense mutation (E12X; 188540.0002) in the TSHB gene. The 4 parents and 2 unaffected children were heterozygous for the mutation.
Medeiros-Neto et al. (1996) described 2 related consanguineous Brazilian sibships in which 4 children had congenital nongoitrous hypothyroidism due to homozygosity for a 1-bp deletion (313delT; 188540.0003) in the TSHB gene, resulting in a circulating form of biologically inactive TSH. Five unaffected family members were heterozygous for the deletion.
In a 5-month-old female infant with severe congenital nongoitrous hypothyroidism and undetectable TSH levels, born of unrelated parents of German ancestry, Doeker et al. (1998) identified homozygosity for the 313delT mutation in the TSHB gene.
Brumm et al. (2002) stated that the most frequent mutation in the TSHB gene, 313delT, had been described in 6 apparently unrelated families. To investigate the frequency and possible monophyletic origin of 313delT alleles, they performed haplotype analysis in 3 German families with the mutation; their results suggested a monophyletic origin of the mutation from a common ancestor, with no significant population prevalence.
In an Egyptian girl with congenital hypothyroidism and a hypoplastic thyroid, who was born of first-cousin parents, Bonomi et al. (2001) identified homozygosity for a nonsense mutation (Q49X; 188540.0004) in the TSHB gene. The patient had a hyperplastic-appearing pituitary gland on MRI in infancy, but a CT scan at age 7 showed complete normalization. The authors noted that in this patient TSH values were highly variable depending on the measurement method used, because although the mutant Q49X TSHB is completely devoid of bioactivity, it forms with the alpha-subunit a heterodimer with preserved immunoreactivity in some TSH measurement methods. Bonomi et al. (2001) concluded that high circulating free glycoprotein alpha-subunit levels, variable TSH levels, and possibly hyperplastic pituitary gland are hallmarks of isolated central hypothyroidism due to mutations of the TSHB gene.
Vuissoz et al. (2001) reported a brother and sister from a consanguineous Turkish kindred with congenital nongoitrous hypothyroidism who were homozygous for the Q49X mutation in the TSHB gene.
In a 4-month-old girl with congenital nongoitrous hypothyroidism, born of consanguineous parents, Pohlenz et al. (2002) identified homozygosity for a splice site mutation (IVS2+5G-A; 188540.0005) in the TSHB gene. Her parents and an unaffected older brother were heterozygous for the mutation.
Borck et al. (2004) identified homozygosity for the IVS2+5G-A splice site mutation in 4 children with congenital hypothyroidism from 2 consanguineous Turkish families. By genotyping members of their 2 families and the family reported by Pohlenz et al. (2002) for polymorphic markers at the TSHB locus, Borck et al. (2004) demonstrated that the mutation arose on a common ancestral haplotype in these 3 unrelated Turkish families, indicating a founder mutation.
INHERITANCE \- Autosomal recessive GROWTH Other \- Growth retardation, severe (if untreated) HEAD & NECK Nose \- Depressed nasal bridge Mouth \- Macroglossia ABDOMEN External Features \- Umbilical hernia \- Omphalocele (rare) SKELETAL Skull \- Large anterior fontanelle \- Open posterior fontanelle MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Mental retardation, severe (if untreated) VOICE \- Hoarse cry ENDOCRINE FEATURES \- Hypothyroidism, nongoitrous LABORATORY ABNORMALITIES \- Low to normal TSH (values may vary depending on the measurement methods used) MOLECULAR BASIS \- Caused by mutation in the thyroid-stimulating hormone, beta polypeptide gene (TSHB, 188540.0001 ) ▲ 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
| HYPOTHYROIDISM, CONGENITAL, NONGOITROUS, 4 | c1848794 | 866 | omim | https://www.omim.org/entry/275100 | 2019-09-22T16:21:38 | {"doid": ["0070123"], "mesh": ["C564765"], "omim": ["275100"], "orphanet": ["90674"], "synonyms": ["Alternative titles", "Isolated thyrotropin deficiency", "THYROTROPIN DEFICIENCY, ISOLATED", "Isolated TSH deficiency", "PITUITARY CRETINISM", "THYROID-STIMULATING HORMONE DEFICIENCY", "TSH DEFICIENCY"]} |
A rare congenital cardiac malformation that is a variant of an atrioventricular septal defect (AVSD) with an interatrial communication (ostium primum defect) just above the common atrioventricular (AV) valve, no interventricular communication just below the atrioventricular valve, a common atrioventricular junction but separate right and left atrioventricular valvar orifices, and a three-leaflet, left-sided component of the common atrioventricular valve (''cleft''). Shunting is restricted to the atrial level because of fusion of the leaflets of the common AV valve with the crest of the ventricular septum.
## Epidemiology
Partial atrioventricular septum defect (PAVSD) accounts for 1-2% of all congenital heart malformations and its prevalence is estimated to be 1/5,000-1/2,500.
## Clinical description
Most patients with PAVSD are asymptomatic until late in life. The clinical presentation depends on the degree of mitral regurgitation and on the associated cardiac defects. The two most common clinical manifestations are impaired exercise capacity and exertional dyspnea. Rarely, cardiac failure may occur in infancy. Additional features in adults include palpitations, presyncope or syncope, and sustained atrial arrhythmias. The ventricles may be equal or nearly equal in size (balanced) or one of the ventricles may be significantly larger than the other (unbalanced). Unbalanced ventricles are associated with hypoplasia of the arterial valve above and aortic coarctation if the left ventricle is hypoplastic.
## Etiology
CRELD1 (3p25.3), GATA4 (8p23.1-p22), GATA6 (18q11-q12) and NR2F2 (15q26) have been associated with a small fraction of PAVC cases. These genes encode developmental transcription factors that are critical for normal cardiac morphogenesis.
## Diagnostic methods
Diagnosis of PAVC is established by means of 2D-echocardiography. Transesophageal echocardiography or cardiac catheterization can be useful in adults (to assess pulmonary vascular resistance and status of the left AV valve and, in patients > 40 years, to exclude coexisting coronary arterial disease). An elevated pulmonary arterial pressure and moderate to severe left atrioventricular valve regurgitation may be observed. First-degree AV block, right bundle branch block, and a superior QRS axis may be noted on electrocardiogram.
## Differential diagnosis
Differential diagnosis includes the complete and intermediate forms of atrioventricular septal defects. Intermediate (transitional) atrioventricular septal defect is a variant of complete atrioventricular septal defect with a restrictive ventricular component due to multiple attachments of the bridging leaflets on the crest of the ventricular septum. PAVSD may be associated with syndromes including the RASopathies (particularly Noonan syndrome caused by mutations in PTPN11 and RAF1), Ellis Van Creveld and Down, and CHARGE syndrome.
## Antenatal diagnosis
PAVSD may be detectable prenatally by 4-chamber view screening during obstetric ultrasonography.
## Management and treatment
The early diagnosis of PAVSD requires cardiology follow-up and elective complete repair between 3 and 5 years of age, which involves closure of a primum atrial septal defect with an appropriately shaped patch through right atriotomy, and partial suture of the ''cleft'' of the left component of the common atrioventricular valve. A pacemaker insertion may be required for complete AV block, which may spontaneously develop after repair. A continuous lifelong follow-up is recommended to avoid late complications. Symptom free patients may be referred for PAVSD repair because of a substantial left-to right atrial shunt (pulmonary to systemic flow ratio 1.8:1) and echocardiographic evidence of right heart volume overload.
## Prognosis
Long-term survival after repair of partial AVSD is the rule. The elective age for repair is 3-5 years, but some patients will not present until later in life. The later the repair is made, the greater the loss of ventricular function that occurs. High morbidity and need for reoperation, often related to residual problems of the systemic AV valve or LAVV regurgitation, may be observed. Furthermore, the prognosis can be severely impaired if the left ventricle and left component of the common atrioventricular valve are hypoplastic or severely malformed. Norwood-type intervention in infancy can be required, as well as prosthetic replacement of the left AV valve.
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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
| Partial atrioventricular septal defect | c0344735 | 867 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1330 | 2021-01-23T17:54:52 | {"gard": ["4229"], "mesh": ["C536112"], "umls": ["C0344735"], "icd-10": ["Q21.2"], "synonyms": ["PAVC", "Partial AVSD", "Partial atrioventricular canal defect"]} |
Yellow nail syndrome is a very rare disorder characterized by three features: yellow nail discoloration, respiratory problems, and lower limb swelling (lymphedema). It usually occurs in people over age 50, but can occur in younger people. In addition to being yellow, nails may lack a cuticle, grow very slowly, and become detached (onycholysis). Respiratory problems may include chronic cough, bronchiectasis, and pleural effusion. Chronic sinusitis may also occur. The cause of yellow nail syndrome remains unknown. It usually occurs on its own, but is sometimes associated with autoimmune disease, lymphatic diseases, or cancers. Some researchers have hypothesized that titanium may play a role in the development of yellow nail syndrome (for example, in dental or joint implants or other environmental exposures). Treatment addresses each symptom present. In some cases, yellow nail syndrome goes away on its own.
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*[AA]: Adrenergic agonist
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*[Ki]: Inhibitor constant
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*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Yellow nail syndrome | c0221348 | 868 | gard | https://rarediseases.info.nih.gov/diseases/184/yellow-nail-syndrome | 2021-01-18T17:57:01 | {"mesh": ["D056684"], "omim": ["153300"], "umls": ["C0221348"], "orphanet": ["662"], "synonyms": ["Lymphedema with yellow nails", "YNS"]} |
Fibrochondrogenesis is a rare, neonatally lethal, rhizomelic chondrodysplasia. Eleven cases have been reported. The face is distinctive and characterized by protuberant eyes, flat midface, flat small nose with anteverted nares and a small mouth with long upper lip. Cleft palate, micrognathia and bifid tongue can occur. The limbs show marked shortness of all segments with relatively normal hands and feet. No internal anomalies other than omphalocele have been reported. Transmission is probably autosomal recessive. Recurrence in a consanguineous family (affecting both sexes) and concordance of affected male twins have been reported.
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*[AA]: Adrenergic agonist
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*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Fibrochondrogenesis | c0265282 | 869 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2021 | 2021-01-23T18:20:57 | {"gard": ["2321"], "mesh": ["C562524"], "omim": ["228520", "614524"], "umls": ["C0265282"], "icd-10": ["Q77.7"]} |
Glycogen storage disease type 6 (GSD6) is a genetic disease in which the liver cannot process sugar properly. The liver is responsible for breaking down a substance called glycogen. Glycogen is the stored form of sugar that is made by breaking down carbohydrates. When the liver cannot break down glycogen properly it causes a buildup that is damaging to the body. Symptoms of the disease usually begin in infancy or childhood and include low blood sugar (hypoglycemia), an enlarged liver (hepatomegaly), and an increase in the amount of lactic acid in the blood (lactic acidosis). These symptoms are especially likely to occur when an individual does not eat for a long time. Symptoms tend to improve as people with this disease get older. The disease is especially common in the Mennonite population.
GSD6 is caused by mutations (changes) in the PYGL gene. The disease is inherited in an autosomal recessive manner. The diagnosis is made based on genetic testing of the PYGL gene. A liver biopsy that tests the function of liver glycogen phosphorylase may be necessary if the results of the genetic testing are inconclusive. Treatment may include eating frequent meals that are high in carbohydrates.
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*[AA]: Adrenergic agonist
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*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Glycogen storage disease type 6 | c0017925 | 870 | gard | https://rarediseases.info.nih.gov/diseases/6529/glycogen-storage-disease-type-6 | 2021-01-18T18:00:15 | {"mesh": ["D006013"], "omim": ["232700"], "umls": ["C0017925"], "orphanet": ["369"], "synonyms": ["GSD6", "Glycogen storage disease 6", "Hers disease", "Phosphorylase deficiency glycogen-storage disease of liver"]} |
A rare ciliopathy characterized by congenital moderate-to-severe deafness, retinitis pigmentosa developing in the first or second decade, and normal vestibular function. Congenital bilateral sensorineural hearing loss is mild to moderate in the low frequencies and severe to profound in the higher frequencies. Additional manifestations include night blindness, constricted visual field (tunnel vision), and later on decreased visual acuity sometimes ending with bare light perception.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Usher syndrome type 2 | c1568249 | 871 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=231178 | 2021-01-23T17:37:54 | {"gard": ["5440"], "mesh": ["D052245"], "omim": ["276901", "605472", "611383"], "umls": ["C0339534", "C1568249"], "icd-10": ["H35.5"], "synonyms": ["USH2"]} |
## Description
Myopia, or nearsightedness, is a refractive error of the eye. Light rays from a distant object are focused in front of the retina and those from a near object are focused in the retina; therefore distant objects are blurry and near objects are clear (summary by Kaiser et al., 2004).
For a discussion of genetic heterogeneity of susceptibility to myopia, see 160700.
Mapping
Nallasamy et al. (2007) reported a large Hutterite family from South Dakota segregating nonsyndromic high-grade myopia. The average refractive error of affected individuals was -7.04 diopters. Nallasamy et al. (2007) excluded linkage of myopia in this family to previously identified myopia loci and found linkage of the disorder to microsatellite marker D10S1643, with a maximum multipoint lod score of 3.22 under an autosomal dominant model. Fine-point mapping and haplotype analysis defined a critical region of 2.67 cM on chromosome 10q21.1. Haplotype analysis demonstrated 2 distinct haplotypes segregating with the disorder, indicative of 2 distinct mutations occurring in the same gene.
INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Myopia, high-grade (average refractive error -7.04 diopters) MISCELLANEOUS \- Reported in a large Hutterite family ▲ 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
| MYOPIA 15, AUTOSOMAL DOMINANT | c2675180 | 872 | omim | https://www.omim.org/entry/612717 | 2019-09-22T16:00:43 | {"mesh": ["C567193"], "omim": ["612717"]} |
Squamous cell skin cancer
Other namesCutaneous squamous cell carcinoma (cSCC), epidermoid carcinoma, squamous cell epithelioma
SCC of the skin tends to arise from pre-malignant lesions, actinic keratoses; surface is usually scaly and often ulcerates (as shown here).
SpecialtyDermatology, plastic surgery, otorhinolaryngology
SymptomsHard lump with a scaly top or ulceration.[1]
Risk factorsUltraviolet radiation, actinic keratosis, lighter skin, arsenic exposure, radiation therapy, poor immune system function, HPV infection[2]
Diagnostic methodTissue biopsy[2][3]
Differential diagnosisKeratoacanthoma, actinic keratosis, melanoma, warts, basal cell cancer[4]
PreventionDecreased UV radiation exposure, sunscreen[5][6]
TreatmentSurgical removal, radiation therapy, chemotherapy, immunotherapy[2][7]
PrognosisUsually good[5]
Frequency2.2 million (2015)[8]
Deaths51,900 (2015)[9]
Squamous-cell skin cancer, also known as cutaneous squamous-cell carcinoma (cSCC), is one of the main types of skin cancer along with basal cell cancer, and melanoma.[10] It usually presents as a hard lump with a scaly top but can also form an ulcer.[1] Onset is often over months.[4] Squamous-cell skin cancer is more likely to spread to distant areas than basal cell cancer.[11] When confined to the outermost layer of the skin, a precancerous or in situ form of cSCC is known as Bowen's disease.[12][13]
The greatest risk factor is high total exposure to ultraviolet radiation from the Sun.[2] Other risks include prior scars, chronic wounds, actinic keratosis, lighter skin, Bowen's disease, arsenic exposure, radiation therapy, poor immune system function, previous basal cell carcinoma, and HPV infection.[2][14] Risk from UV radiation is related to total exposure, rather than early exposure.[15] Tanning beds are becoming another common source of ultraviolet radiation.[15] Risk is also elevated in certain genetic skin disorders, such as xeroderma pigmentosum[16] and certain forms of epidermolysis bullosa.[17] It begins from squamous cells found within the skin.[18] Diagnosis is often based on skin examination and confirmed by tissue biopsy.[2][3]
New in vivo and in vitro studies have proven that the upregulation of FGFR2, a subset of the Fibroblast growth factor receptor (FGFR) immunoglobin family, has a critical role to play in the progression of cSCC cells.[19] Mutation in the Tpl2 gene causes the overexpression of FGFR2, which activates mTORC1 and AKT pathways in both primary and metastatic cSCC cell lines. Only by using FGFR pan-inhibitor, AZD4547, could cell migration and cell proliferation on cSCC be attenuated[19]
Decreasing exposure to ultraviolet radiation and the use of sunscreen appear to be effective methods of preventing squamous-cell skin cancer.[5][6] Treatment is typically by surgical removal.[2] This can be by simple excision if the cancer is small otherwise Mohs surgery is generally recommended.[2] Other options may include application of cold and radiation therapy.[7] In the cases in which distant spread has occurred chemotherapy or biologic therapy may be used.[7]
As of 2015, about 2.2 million people have cSCC at any given time.[8] It makes up about 20% of all skin cancer cases.[20] About 12% of males and 7% of females in the United States developed cSCC at some point in time.[2] While prognosis is usually good, if distant spread occurs five-year survival is ~34%.[4][5] In 2015 it resulted in about 51,900 deaths globally.[9] The usual age at diagnosis is around 66.[4] Following the successful treatment of one case of cSCC people are at high risk of developing further cases.[2]
## Contents
* 1 Signs and symptoms
* 1.1 Spread
* 2 Causes
* 2.1 Immunosuppression
* 3 Diagnosis
* 3.1 Characteristics
* 3.2 In situ disease
* 3.3 Invasive disease
* 3.4 Degree of differentiation
* 4 Prevention
* 5 Management
* 6 Prognosis
* 7 Epidemiology
* 8 Additional images
* 9 See also
* 10 References
* 11 External links
## Signs and symptoms[edit]
Squamous cell carcinoma
SCC of the skin begins as a small nodule and as it enlarges the center becomes necrotic and sloughs and the nodule turns into an ulcer.[citation needed]
* The lesion caused by SCC is often asymptomatic
* Ulcer or reddish skin plaque that is slow growing
* Intermittent bleeding from the tumor, especially on the lip
* The clinical appearance is highly variable
* Usually the tumor presents as an ulcerated lesion with hard, raised edges
* The tumor may be in the form of a hard plaque or a papule, often with an opalescent quality, with tiny blood vessels
* The tumor can lie below the level of the surrounding skin, and eventually ulcerates and invades the underlying tissue
* The tumor commonly presents on sun-exposed areas (e.g. back of the hand, scalp, lip, and superior surface of pinna)
* On the lip, the tumor forms a small ulcer, which fails to heal and bleeds intermittently
* Evidence of chronic skin photodamage, such as multiple actinic keratoses (solar keratoses)
* The tumor grows relatively slowly
### Spread[edit]
* Unlike basal-cell carcinoma (BCC), squamous cell carcinoma (SCC) has a higher risk of metastasis.
* Risk of metastasis is higher in SCC arising in scars, on the lower lips or mucosa, and occurring in immunosuppressed patients.
## Causes[edit]
Squamous cell carcinoma is the second-most common cancer of the skin (after basal-cell carcinoma but more common than melanoma). It usually occurs in areas exposed to the sun. Sunlight exposure and immunosuppression are risk factors for SCC of the skin, with chronic sun exposure being the strongest environmental risk factor.[21] There is a risk of metastasis starting more than 10 years[citation needed] after diagnosable appearance of squamous cell carcinoma, but the risk is low,[specify] though much[specify] higher than with basal-cell carcinoma. Squamous cell cancers of the lip and ears have high rates of local recurrence and distant metastasis.[22] In a recent study, it has also been shown that the deletion or severe down-regulation of a gene titled Tpl2 (tumor progression locus 2) may be involved in the progression of normal keratinocytes into becoming squamous cell carcinoma.[23]
SCCs represent about 20% of the non-melanoma skin cancers, but due to their more obvious nature and growth rates, they represent 90% of all head and neck cancers that are initially presented.[24]
The vast majority of SCCs are those of the skin, and are often the result of ultraviolet exposure. SCCs usually occur on portions of the body commonly exposed to the Sun; the face, ears, neck, hands, or arm. The main symptom is a growing bump that may have a rough, scaly surface and flat reddish patches. Unlike basal-cell carcinomas, SCCs carry a higher risk of metastasis, and may spread to the regional lymph nodes,[25]
Erythroplasia of Queyrat (SCC in situ of the glans or prepuce in males,[26] M[27]:733[28]:656[29] or the vulvae in females.[30]) may be induced by human papilloma virus.[31] It is reported to occur in the corneoscleral limbus.[32] Erythroplasia of Queyrat may also occur on the anal mucosa or the oral mucosa.[33] Some sources state that this condition is synonymous with Bowen's disease,[30] however generally speaking Bowen's disease refers to carcinoma in situ of any location on the skin such as the lower leg.
### Immunosuppression[edit]
People who have received solid organ transplants are at a significantly increased risk of developing squamous cell carcinoma due to the use of chronic immunosuppressive medication. While the risk of developing all skin cancers increases with these medications, this effect is particularly severe for SCC, with hazard ratios as high as 250 being reported, versus 40 for basal cell carcinoma.[34] The incidence of SCC development increases with time posttransplant.[35] Heart and lung transplant recipients are at the highest risk of developing SCC due to more intensive immunosuppressive medications used.[citation needed]
Squamous cell cancers of the skin in individuals on immunotherapy or suffering from lymphoproliferative disorders (i.e. leukemia) tend to be much more aggressive, regardless of their location.[36] The risk of SCC, and non-melanoma skin cancers generally, varies with the immunosuppressive drug regimen chosen. The risk is greatest with calcineurin inhibitors like cyclosporine and tacrolimus, and least with mTOR inhibitors, such as sirolimus and everolimus. The antimetabolites azathioprine and mycophenolic acid have an intermediate risk profile.[37]
## Diagnosis[edit]
Diagnosis is confirmed via biopsy of the tissue(s) suspected to be affected by SCC. For the skin, look under skin biopsy.
The pathological appearance of a squamous cell cancer varies with the depth of the biopsy. For that reason, a biopsy including the subcutaneous tissue and basilar epithelium, to the surface is necessary for correct diagnosis. The performance of a shave biopsy (see skin biopsy) might not acquire enough information for a diagnosis. An inadequate biopsy might be read as actinic keratosis with follicular involvement. A deeper biopsy down to the dermis or subcutaneous tissue might reveal the true cancer. An excision biopsy is ideal, but not practical in most cases. An incisional or punch biopsy is preferred. A shave biopsy is least ideal, especially if only the superficial portion is acquired.[citation needed]
### Characteristics[edit]
Histopathologically, the epidermis in SCC in situ (Bowen’s disease) will show hyperkeratosis and parakeratosis. There will also be marked acanthosis with elongation and thickening of the rete ridges. These changes will overly keratinocytic cells which are often highly atypical and may in fact have a more unusual appearance than invasive SCC. The atypia spans the full thickness of the epidermis, with the keratinocytes demonstrating intense mitotic activity, pleomorphism, and greatly enlarged nuclei. They will also show a loss of maturity and polarity, giving the epidermis a disordered or “windblown” appearance.[citation needed]
Two types of multinucleated cells may be seen: the first will present as a multinucleated giant cell, and the second will appear as a dyskeratotic cell engulfed in the cytoplasm of a keratinocyte. Occasionally, cells of the upper epidermis will undergo vacuolization, demonstrating an abundant and strongly eosinophilic cytoplasm. There may be a mild to moderate lymphohistiocytic infiltrate detected in the upper dermis.[12]
* Histopathology of squamous cell carcinoma in situ (black arrow), compared to normal skin, showing marked atypia.
* Squamous cell carcinoma in situ, showing prominent dyskeratosis and aberrant mitoses at all levels of the epidermis, along with marked parakeratosis.[12]
### In situ disease[edit]
Bowen's disease is essentially equivalent to and used interchangeably with SCC in situ, when not having invaded through the basement membrane.[12] Depending on source, it is classified as precancerous[13] or SCC in situ (technically cancerous but non-invasive).[38][39] In SCC in situ (Bowen's disease), atypical squamous cells proliferate through the whole thickness of the epidermis.[12] The entire tumor is confined to the epidermis and does not invade into the dermis.[12] The cells are often highly atypical under the microscope, and may in fact look more unusual than the cells of some invasive squamous cell carcinomas.[12]
* SCC in situ, high magnification, demonstrating an intact basement membrane.[12]
* SCC in situ
* SCC in situ
* SCC in situ
* SCC in situ
Erythroplasia of Queyrat is a particular type of Bowen's disease that can arise on the glans or prepuce in males,[26][27]:733[28]:656[29] and the vulvae in females.[30] It mainly occurs in uncircumcised males,[30][40] over the age of 40.[33] It is named for French dermatologist Louis Queyrat (1856–1933),[41][42][43] who was head of the dermatology service of l'Hôpital Ricord, a venereal hospital in Paris, now Hôpital Cochin.[44]
### Invasive disease[edit]
In invasive SCC, tumor cells infiltrate through the basement membrane. The infiltrate can be somewhat difficult to detect in the early stages of invasion: however, additional indicators such as full thickness epidermal atypia and the involvement of hair follicles can be used to facilitate the diagnosis. Later stages of invasion are characterized by the formation of nests of atypical tumor cells in the dermis, often with a corresponding inflammatory infiltrate.[12]
* Gross slice of a squamous cell carcinoma of the skin.
* Superficially invasive squamous cell carcinoma (SCCSI). These lesions often do not show the marked pleomorphism and atypical nuclei of SCC in situ, but demonstrate early keratinocyte invasion of the dermis.[12]
* High magnification demonstrates the pleomorphism of the invading keratinocytes.[12]
* Invasive nests with characteristic large celled centers. Ulceration (at left) is common in invasive SCC.
### Degree of differentiation[edit]
* Well-differentiated (and yet invasive) SCC, showing prominent keratinization and may form “pearllike” structures where dermal nests of keratinocytes attempt to mature in a layered fashion. Well-differentiated SCC has slightly enlarged, hyperchromatic nuclei with abundant amounts of cytoplasm. Intercellular bridges will frequently be visible.[12]
* Moderately differentiated lesions of invasive SCC show much less organization and maturation with significantly less keratin formation.[12]
* Poorly differentiated, where attempts at keratinization are often no longer evident. This is a clear-cell squamous cell carcinoma. The dysplastic cells here infiltrate in cords through the dermis. Poorly differentiated SCC has greatly enlarged, pleomorphic nuclei demonstrating a high degree of atypia and frequent mitoses.[12]
* Poorly differentiated clear-cell squamous cell carcinoma. For this type of SCC, immunostains will likely be required to classify it unless other areas of the tumor show obvious squamous cell features such as seen here (arrow).
## Prevention[edit]
Appropriate sun-protective clothing, use of broad-spectrum (UVA/UVB) sunscreen with at least SPF 50, and avoidance of intense sun exposure may prevent skin cancer.[45] A 2016 review of sunscreen for preventing squamous cell skin cancer found insufficient evidence to demonstrate whether it was effective.[46]
## Management[edit]
Most squamous cell carcinomas are removed with surgery. A few selected cases are treated with topical medication. Surgical excision with a free margin of healthy tissue is a frequent treatment modality. Radiotherapy, given as external beam radiotherapy or as brachytherapy (internal radiotherapy), can also be used to treat squamous cell carcinomas. There is little evidence comparing the effectiveness of different treatments for non-metastatic SCC of the skin.[47]
Mohs surgery is frequently utilized; considered the treatment of choice for squamous cell carcinoma of the skin, physicians have also utilized the method for the treatment of squamous cell carcinoma of the mouth, throat, and neck.[48] An equivalent method of the CCPDMA standards can be utilized by a pathologist in the absence of a Mohs-trained physician. Radiation therapy is often used afterward in high risk cancer or patient types.[citation needed] Radiation or radiotherapy can also be a standalone option in treating SCCs. As a non invasive option brachytherapy serves a painless possibility to treat in particular but not only difficult to operate areas like the earlobes or genitals. A Example for this kind of therapy ist the High dose brachytherapy Rhenium-SCT which makes use of the beta rays emitting property of Rhenium-188. The radiation source is enclosed in an compund which is applied to a thin protection foile directly over the lesion. This way the radiation source can be aplied to complexe locations and minimize radiation to healthy tissue.[49]
After removal of the cancer, closure of the skin for patients with a decreased amount of skin laxity involves a split-thickness skin graft. A donor site is chosen and enough skin is removed so that the donor site can heal on its own. Only the epidermis and a partial amount of dermis is taken from the donor site which allows the donor site to heal. Skin can be harvested using either a mechanical dermatome or Humby knife.[50]
Electrodessication and curettage or EDC can be done on selected squamous cell carcinoma of the skin. In areas where SCC's are known to be non-aggressive, and where the patient is not immunosuppressed, EDC[clarification needed] can be performed with good to adequate cure rate.
Treatment options for SCC in situ (Bowen's disease) include photodynamic therapy with 5-aminolevulinic acid, cryotherapy, topical 5-fluorouracil or imiquimod, and excision. A meta-analysis showed evidence that PDT is more effective than cryotherapy and has better cosmetic outcomes. There is generally a lack of evidence comparing the effectiveness of all treatment options.[51]
High-risk squamous cell carcinoma, as defined by those occurring around the eye, ear, or nose, is of large size, is poorly differentiated, and grows rapidly, requires more aggressive, multidisciplinary management.
Nodal spread:
1. Surgical block dissection if palpable nodes or in cases of Marjolin's ulcers but the benefit of prophylactic block lymph node dissection with Marjolin's ulcers is not proven.
2. Radiotherapy
3. Adjuvant therapy may be considered in those with high-risk SCC even in the absence of evidence for local mestastasis. Imiquimod (Aldara) has been used with success for squamous cell carcinoma in situ of the skin and the penis, but the morbidity and discomfort of the treatment is severe. An advantage is the cosmetic result: after treatment, the skin resembles normal skin without the usual scarring and morbidity associated with standard excision. Imiquimod is not FDA-approved for any squamous cell carcinoma.
In general, squamous cell carcinomas have a high risk of local recurrence, and up to 50% do recur.[52] Frequent skin exams with a dermatologist is recommended after treatment.
## Prognosis[edit]
The long-term outcome of squamous cell carcinomas is dependent upon several factors: the sub-type of the carcinoma, available treatments, location(s) and severity, and various patient health-related variables (accompanying diseases, age, etc.). Generally, the long-term outcome is positive, as less than 4% of Squamous cell carcinoma cases are at risk of metastasis.[53][54] When it does metastasize, the most common involved organs are the lungs, brain, bone and other skin locations.[55]
One study found squamous cell carcinoma of the penis had a much greater rate of mortality than some other forms of squamous cell carcinoma, that is, about 23%,[56] although this relatively high mortality rate may be associated with possibly latent diagnosis of the disease due to patients avoiding genital exams until the symptoms are debilitating, or refusal to submit to a possibly scarring operation upon the genitalia. Squamous cell carcinoma occurring in the organ transplant population is also associated with a higher risk of mortality.[57]
## Epidemiology[edit]
Age-standardized death from melanoma and other skin cancers per 100,000 inhabitants in 2004.[58]
no data
less than 0.7
0.7–1.4
1.4–2.1
2.1–2.8
2.8–3.5
3.5–4.2
4.2–4.9
4.9–5.6
5.6–6.3
6.3–7
7–7.7
more than 7.7
The incidence of squamous cell carcinoma continues to rise around the world. A recent study estimated that there are between 180,000 and 400,000 cases of SCC in the United States in 2013.[59] Risk factors for squamous cell carcinoma varies with age, gender, race, geography, and genetics. The incidence of SCC increases with age and the peak incidence is usually around 60 years old. Males are affected with SCC at a ratio of 2:1 in comparison to females. Caucasians are more likely to be affected, especially those with fair skin or those chronically exposed to UV radiation.[citation needed]
Squamous cell carcinoma of the skin can be found on all areas of the body but is most common on frequently sun-exposed areas, such as the face, legs and arms.[60] Solid organ transplant recipients (heart, lung, liver, pancreas, among others) are also at a heightened risk of developing aggressive, high-risk SCC. There are also a few rare congenital diseases predisposed to cutaneous malignancy. In certain geographic locations, exposure to arsenic in well water or from industrial sources may significantly increase the risk of SCC.[21]
## Additional images[edit]
* Biopsy-proven squamous cell carcinoma
* Squamous carcinoma of dorsum of hand
* SCC in situ (Bowen's disease).
* Squamous Cell Carcinoma, Right Upper Cheek; Lesion outlined in blue marker with a dashed line prior to biopsy
## See also[edit]
* List of cutaneous conditions associated with increased risk of nonmelanoma skin cancer
## References[edit]
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20. ^ Stratigos, A; Garbe, C; Lebbe, C; Malvehy, J; del Marmol, V; Pehamberger, H; Peris, K; Becker, JC; Zalaudek, I; Saiag, P; Middleton, MR; Bastholt, L; Testori, A; Grob, JJ; European Dermatology Forum, (EDF).; European Association of Dermato-Oncology, (EADO).; European Organization for Research and Treatment of Cancer, (EORTC). (September 2015). "Diagnosis and treatment of invasive squamous cell carcinoma of the skin: European consensus-based interdisciplinary guideline". European Journal of Cancer. 51 (14): 1989–2007. doi:10.1016/j.ejca.2015.06.110. PMID 26219687.
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26. ^ a b Marks, James G; Miller, Jeffery (2006). Lookingbill and Marks' Principles of Dermatology (4th ed.). Elsevier Inc. Page 63. ISBN 1-4160-3185-5.
27. ^ a b Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0.
28. ^ a b James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.
29. ^ a b Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 1050. ISBN 978-1-4160-2999-1.
30. ^ a b c d Zenilman JM, Shahmanesh M, eds. (2012). Sexually transmitted infections diagnosis, management, and treatment. Sudbury, Mass.: Jones & Bartlett Learning. p. 109. ISBN 9781449619848.
31. ^ J Invest Dermatol 2000 Sep;115(3):396–401
32. ^ Syed Imtiaz Ali Shah, Saeed Ahmed Sangi, Seraj Ahmed Abbasi: Bowen’s Disease: Pak J Ophthalmol 1998 Vol. 14, No. 1, pp. 37–38.
33. ^ a b Katsambas AD, Lotti TM, eds. (2003). European handbook of dermatological treatments (2nd ed.). Berlin [u.a.]: Springer. p. 169. ISBN 9783540008781.
34. ^ Tessari, G.; Girolomoni, G. (2012). "Nonmelanoma skin cancer in solid organ transplant recipients: update on epidemiology, risk factors, and management". Dermatol. Surg. 38 (10): 1622–30. doi:10.1111/j.1524-4725.2012.02520.x. PMID 22805312. S2CID 40490951.
35. ^ Zwald, FO (2011). "Skin cancer in solid organ transplant recipients: advances in therapy and management: part I. Epidemiology of skin cancer in solid organ transplant recipients". Journal of the American Academy of Dermatology. 65 (2): 253–61, quiz 262. doi:10.1016/j.jaad.2010.11.062. PMID 21763561.
36. ^ "Squamous Cell Carcinoma: What it Looks Like". Archived from the original on 2008-12-21.
37. ^ Kuschal, C.; Thoms, K. M.; Schubert, S.; et al. (2012). "Skin cancer in organ transplant recipients: effects of immunosuppressive medications on DNA repair". Exp. Dermatol. 21 (1): 2–6. doi:10.1111/j.1600-0625.2011.01413.x. PMID 22151386. S2CID 25776283.
38. ^ Janine Khalyl-Mawad. "Pathology of Cutaneous Squamous Cell Carcinoma and Bowen Disease". Medscape. Updated: Jun 11, 2019
39. ^ "Bowen's disease". National Health Service. Page last reviewed: 21 May 2019
40. ^ Berkow, Robert (1997). The Merck manual of medical information. Whitehouse Station, N.J: Merck Research Laboratories. p. 1057. ISBN 0911910875.
41. ^ synd/3373 at Who Named It?
42. ^ A. Queyrat. Érythroplasie du gland. Bulletin de la Société française de dermatologie et de syphiligraphie, Paris, 1911, 22: 378–382.
43. ^ Steffen C (2007). "Squamous cell carcinoma in situ: a historical note". Skinmed. 6 (1): 7–10. doi:10.1111/j.1540-9740.2007.06033.x. PMID 17215613.
44. ^ Fonds d'archives, Lieu de conservation Archived 2013-10-23 at the Wayback Machine : Institut Pasteur, Service des Archives.
45. ^ Gallagher, RP; Lee, TK; Bajdik, CD; Borugian, M (2010). "Ultraviolet radiation". Chronic Diseases in Canada. 29 (Suppl 1): 51–68. doi:10.24095/hpcdp.29.S1.04. PMID 21199599.
46. ^ Sánchez, Guillermo; Nova, John; Rodriguez-Hernandez, Andrea Esperanza; Medina, Roger David; Solorzano-Restrepo, Carolina; Gonzalez, Jenny; Olmos, Miguel; Godfrey, Kathie; Arevalo-Rodriguez, Ingrid (25 July 2016). "Sun protection for preventing basal cell and squamous cell skin cancers". Cochrane Database of Systematic Reviews. 7: CD011161. doi:10.1002/14651858.CD011161.pub2. PMC 6457780. PMID 27455163.
47. ^ Lansbury, Louise; Leonardi-Bee, Jo; Perkins, William; Goodacre, Timothy; Tweed, John A; Bath-Hextall, Fiona J (2010-04-14). "Interventions for non-metastatic squamous cell carcinoma of the skin". Cochrane Database of Systematic Reviews (4): CD007869. doi:10.1002/14651858.CD007869.pub2. ISSN 1465-1858. PMID 20393962.
48. ^ Gross, K.G.; et al. (1999). Mohs Surgery, Fundamentals and Techniques. Mosby.
49. ^ Castellucci, Paolo; Savoia, F.; Farina, A.; Lima, G. M.; Patrizi, A.; Baraldi, C.; Zagni, F.; Vichi, S.; Pettinato, C.; Morganti, A. G.; Strigari, L. (2020-11-02). "High dose brachytherapy with non sealed 188Re (rhenium) resin in patients with non-melanoma skin cancers (NMSCs): single center preliminary results". European Journal of Nuclear Medicine and Molecular Imaging. doi:10.1007/s00259-020-05088-z. ISSN 1619-7089. PMID 33140131. S2CID 226231693.
50. ^ [1], Hallock G. Squamous Cell Carcinoma Excision from Right Forearm with Split-Thickness Skin Graft from the Thigh. J Med Ins. 2020;2020(290.16) doi:https://jomi.com/article/290.16
51. ^ Bath-Hextall, Fiona J; Matin, Rubeta N; Wilkinson, David; Leonardi-Bee, Jo (2013-06-24). "Interventions for cutaneous Bowen's disease". Cochrane Database of Systematic Reviews (6): CD007281. doi:10.1002/14651858.CD007281.pub2. ISSN 1465-1858. PMC 6464151. PMID 23794286.
52. ^ Jennings, C (2010). "Management of High-Risk Cutaneous Squamous Cell Carcinoma". Journal of Clinical and Aesthetic Dermatology. 61 (3): 282–5. doi:10.1016/0022-3913(89)90128-5. PMID 2921745.
53. ^ Chollet A, Hohl D, Perrier P (April 2012). "[Risk of cutaneous squamous cell carcinomas: the role of clinical and pathological reports]". Rev Med Suisse. 8 (335): 743–6. PMID 22545495.
54. ^ Brantsch Kay D; Meisner Christoph; Schönfisch Birgitt; Trilling Birgit; Wehner-Caroli Jörg; Röcken Martin; Breuninger Helmut (2008). "Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: A prospective study". The Lancet Oncology. 9 (8): 713–720. doi:10.1016/S1470-2045(08)70178-5. PMID 18617440.
55. ^ Major, Ajay; Anderson, Mel (2017). "Not Just Skin Deep: Distant Metastases from Cutaneous Squamous Cell Carcinoma". The American Journal of Medicine. 130 (8): e327–e328. doi:10.1016/j.amjmed.2017.02.031. ISSN 0002-9343. PMID 28344135.
56. ^ Bethune, G; Campbell, J; Rocker, A; Bell, D; Rendon, R; Merrimen, J (2012). "Clinical and pathologic factors of prognostic significance in penile squamous cell carcinoma in a North American population". Urology. 79 (5): 1092–7. doi:10.1016/j.urology.2011.12.048. PMID 22386252.
57. ^ Chapman, JR (2013). "Cancer in the Transplant Recipient". Cold Spring Harbor Perspectives in Medicine. 3 (7): a015677. doi:10.1101/cshperspect.a015677. PMC 3685882. PMID 23818517.
58. ^ "WHO Disease and injury country estimates". World Health Organization. 2009. Archived from the original on 2009-11-11. Retrieved Nov 11, 2009.
59. ^ Kari, PS (2012). "Cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012". Journal of the American Academy of Dermatology. 68 (6): 957–66. doi:10.1016/j.jaad.2012.11.037. PMID 23375456.
60. ^ "Squamous Cell Carcinoma". Skin Cancer.Org. 2018. Retrieved Dec 12, 2018.
## External links[edit]
Classification
D
* ICD-10: C44
* ICD-9-CM: 199
* ICD-O: M8070/3
* MeSH: D002294
External resources
* MedlinePlus: 000829
* eMedicine: derm/401
Wikimedia Commons has media related to Squamous-cell carcinoma of the skin.
* Information on Squamous Cell Carcinoma from The Skin Cancer Foundation
* DermNet NZ: Squamous cell carcinoma
* v
* t
* e
Diseases of the skin and appendages by morphology
Growths
Epidermal
* Wart
* Callus
* Seborrheic keratosis
* Acrochordon
* Molluscum contagiosum
* Actinic keratosis
* Squamous-cell carcinoma
* Basal-cell carcinoma
* Merkel-cell carcinoma
* Nevus sebaceous
* Trichoepithelioma
Pigmented
* Freckles
* Lentigo
* Melasma
* Nevus
* Melanoma
Dermal and
subcutaneous
* Epidermal inclusion cyst
* Hemangioma
* Dermatofibroma (benign fibrous histiocytoma)
* Keloid
* Lipoma
* Neurofibroma
* Xanthoma
* Kaposi's sarcoma
* Infantile digital fibromatosis
* Granular cell tumor
* Leiomyoma
* Lymphangioma circumscriptum
* Myxoid cyst
Rashes
With
epidermal
involvement
Eczematous
* Contact dermatitis
* Atopic dermatitis
* Seborrheic dermatitis
* Stasis dermatitis
* Lichen simplex chronicus
* Darier's disease
* Glucagonoma syndrome
* Langerhans cell histiocytosis
* Lichen sclerosus
* Pemphigus foliaceus
* Wiskott–Aldrich syndrome
* Zinc deficiency
Scaling
* Psoriasis
* Tinea (Corporis
* Cruris
* Pedis
* Manuum
* Faciei)
* Pityriasis rosea
* Secondary syphilis
* Mycosis fungoides
* Systemic lupus erythematosus
* Pityriasis rubra pilaris
* Parapsoriasis
* Ichthyosis
Blistering
* Herpes simplex
* Herpes zoster
* Varicella
* Bullous impetigo
* Acute contact dermatitis
* Pemphigus vulgaris
* Bullous pemphigoid
* Dermatitis herpetiformis
* Porphyria cutanea tarda
* Epidermolysis bullosa simplex
Papular
* Scabies
* Insect bite reactions
* Lichen planus
* Miliaria
* Keratosis pilaris
* Lichen spinulosus
* Transient acantholytic dermatosis
* Lichen nitidus
* Pityriasis lichenoides et varioliformis acuta
Pustular
* Acne vulgaris
* Acne rosacea
* Folliculitis
* Impetigo
* Candidiasis
* Gonococcemia
* Dermatophyte
* Coccidioidomycosis
* Subcorneal pustular dermatosis
Hypopigmented
* Tinea versicolor
* Vitiligo
* Pityriasis alba
* Postinflammatory hyperpigmentation
* Tuberous sclerosis
* Idiopathic guttate hypomelanosis
* Leprosy
* Hypopigmented mycosis fungoides
Without
epidermal
involvement
Red
Blanchable
Erythema
Generalized
* Drug eruptions
* Viral exanthems
* Toxic erythema
* Systemic lupus erythematosus
Localized
* Cellulitis
* Abscess
* Boil
* Erythema nodosum
* Carcinoid syndrome
* Fixed drug eruption
Specialized
* Urticaria
* Erythema (Multiforme
* Migrans
* Gyratum repens
* Annulare centrifugum
* Ab igne)
Nonblanchable
Purpura
Macular
* Thrombocytopenic purpura
* Actinic/solar purpura
Papular
* Disseminated intravascular coagulation
* Vasculitis
Indurated
* Scleroderma/morphea
* Granuloma annulare
* Lichen sclerosis et atrophicus
* Necrobiosis lipoidica
Miscellaneous
disorders
Ulcers
*
Hair
* Telogen effluvium
* Androgenic alopecia
* Alopecia areata
* Systemic lupus erythematosus
* Tinea capitis
* Loose anagen syndrome
* Lichen planopilaris
* Folliculitis decalvans
* Acne keloidalis nuchae
Nail
* Onychomycosis
* Psoriasis
* Paronychia
* Ingrown nail
Mucous
membrane
* Aphthous stomatitis
* Oral candidiasis
* Lichen planus
* Leukoplakia
* Pemphigus vulgaris
* Mucous membrane pemphigoid
* Cicatricial pemphigoid
* Herpesvirus
* Coxsackievirus
* Syphilis
* Systemic histoplasmosis
* Squamous-cell carcinoma
* v
* t
* e
Skin cancer of nevi and melanomas
Melanoma
* Mucosal melanoma
* Superficial spreading melanoma
* Nodular melanoma
* lentigo
* Lentigo maligna/Lentigo maligna melanoma
* Acral lentiginous melanoma
* Amelanotic melanoma
* Desmoplastic melanoma
* Melanoma with features of a Spitz nevus
* Melanoma with small nevus-like cells
* Polypoid melanoma
* Nevoid melanoma
* Melanocytic tumors of uncertain malignant potential
Nevus/
melanocytic nevus
* Nevus of Ito/Nevus of Ota
* Spitz nevus
* Pigmented spindle cell nevus
* Halo nevus
* Pseudomelanoma
* Blue nevus
* of Jadassohn–Tièche
* Cellular
* Epithelioid
* Deep penetrating
* Amelanotic
* Malignant
* Congenital melanocytic nevus (Giant
* Medium-sized
* Small-sized)
* Balloon cell nevus
* Dysplastic nevus/Dysplastic nevus syndrome
* Acral nevus
* Becker's nevus
* Benign melanocytic nevus
* Nevus spilus
* 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
Skin cancer of the epidermis
Tumor
Carcinoma
BCC
* Forms
* Aberrant
* Cicatricial
* Cystic
* Fibroepithelioma of Pinkus
* Infltrative
* Micronodular
* Nodular
* Pigmented
* Polypoid
* Pore-like
* Rodent ulcer
* Superficial
* Nevoid basal cell carcinoma syndrome
SCC
* Forms
* Adenoid
* Basaloid
* Clear cell
* Signet-ring-cell
* Spindle-cell
* Marjolin's ulcer
* Bowen's disease
* Bowenoid papulosis
* Erythroplasia of Queyrat
* Actinic keratosis
Adenocarcinoma
* Aggressive digital papillary adenocarcinoma
* Extramammary Paget's disease
Ungrouped
* Merkel cell carcinoma
* Microcystic adnexal carcinoma
* Mucinous carcinoma
* Primary cutaneous adenoid cystic carcinoma
* Verrucous carcinoma
* Malignant mixed tumor
Benign
tumors
Acanthoma
* Forms
* Large cell
* Fissuring
* Clear cell
* Epidermolytic
* Melanoacanthoma
* Pilar sheath acanthoma
* Seboacanthoma
* Seborrheic keratosis
* Warty dyskeratoma
Keratoacanthoma
* Generalized eruptive
* Keratoacanthoma centrifugum marginatum
* Multiple
* Solitary
Wart
* Verruca vulgaris
* Verruca plana
* Plantar wart
* Periungual wart
Other
Epidermal nevus
* Syndromes
* Epidermal nevus syndrome
* Schimmelpenning syndrome
* Nevus comedonicus syndrome
* Nevus comedonicus
* Inflammatory linear verrucous epidermal nevus
* Linear verrucous epidermal nevus
* Pigmented hairy epidermal nevus syndrome
* Systematized epidermal nevus
* Phakomatosis pigmentokeratotica
Other nevus
* Nevus unius lateris
* Patch blue nevus
* Unilateral palmoplantar verrucous nevus
* Zosteriform speckled lentiginous nevus
Ungrouped
* Cutaneous horn
* v
* t
* e
Cancer involving the respiratory tract
Upper RT
Nasal cavity
Esthesioneuroblastoma
Nasopharynx
Nasopharyngeal carcinoma
Nasopharyngeal angiofibroma
Larynx
Laryngeal cancer
Laryngeal papillomatosis
Lower RT
Trachea
* Tracheal tumor
Lung
Non-small-cell lung carcinoma
* Squamous-cell carcinoma
* Adenocarcinoma (Mucinous cystadenocarcinoma)
* Large-cell lung carcinoma
* Rhabdoid carcinoma
* Sarcomatoid carcinoma
* Carcinoid
* Salivary gland–like carcinoma
* Adenosquamous carcinoma
* Papillary adenocarcinoma
* Giant-cell carcinoma
Small-cell carcinoma
* Combined small-cell carcinoma
Non-carcinoma
* Sarcoma
* Lymphoma
* Immature teratoma
* Melanoma
By location
* Pancoast tumor
* Solitary pulmonary nodule
* Central lung
* Peripheral lung
* Bronchial leiomyoma
Pleura
* Mesothelioma
* Malignant solitary fibrous tumor
* v
* t
* e
Tumors of the female urogenital system
Adnexa
Ovaries
Glandular and epithelial/
surface epithelial-
stromal tumor
CMS:
* Ovarian serous cystadenoma
* Mucinous cystadenoma
* Cystadenocarcinoma
* Papillary serous cystadenocarcinoma
* Krukenberg tumor
* Endometrioid tumor
* Clear-cell ovarian carcinoma
* Brenner tumour
Sex cord–gonadal stromal
* Leydig cell tumour
* Sertoli cell tumour
* Sertoli–Leydig cell tumour
* Thecoma
* Granulosa cell tumour
* Luteoma
* Sex cord tumour with annular tubules
Germ cell
* Dysgerminoma
* Nongerminomatous
* Embryonal carcinoma
* Endodermal sinus tumor
* Gonadoblastoma
* Teratoma/Struma ovarii
* Choriocarcinoma
Fibroma
* Meigs' syndrome
Fallopian tube
* Adenomatoid tumor
Uterus
Myometrium
* Uterine fibroids/leiomyoma
* Leiomyosarcoma
* Adenomyoma
Endometrium
* Endometrioid tumor
* Uterine papillary serous carcinoma
* Endometrial intraepithelial neoplasia
* Uterine clear-cell carcinoma
Cervix
* Cervical intraepithelial neoplasia
* Clear-cell carcinoma
* SCC
* Glassy cell carcinoma
* Villoglandular adenocarcinoma
Placenta
* Choriocarcinoma
* Gestational trophoblastic disease
General
* Uterine sarcoma
* Mixed Müllerian tumor
Vagina
* Squamous-cell carcinoma of the vagina
* Botryoid rhabdomyosarcoma
* Clear-cell adenocarcinoma of the vagina
* Vaginal intraepithelial neoplasia
* Vaginal cysts
Vulva
* SCC
* Melanoma
* Papillary hidradenoma
* Extramammary Paget's disease
* Vulvar intraepithelial neoplasia
* Bartholin gland carcinoma
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Squamous cell skin cancer | c0553723 | 873 | wikipedia | https://en.wikipedia.org/wiki/Squamous_cell_skin_cancer | 2021-01-18T18:59:18 | {"umls": ["C0553723"], "wikidata": ["Q5749018"]} |
Cerebral arteriovenous malformation (AVM) is a congenital malformative communication between the veins and the arteries in the brain in the form of a nidus, an anatomical structure composed of dilated and tangled supplying arterioles and drainage veins with no intervening capillary bed, that can be asymptomatic or cause, depending on the location and the size of the AVM, headaches of varying severity, generalized or focal seizures, focalneurological defects (weakness, numbness, speech difficulties, vision loss) or potentially fatal intracranial hemorrhage in case the AVM ruptures.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Cerebral arteriovenous malformation | c0007772 | 874 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=46724 | 2021-01-23T18:21:38 | {"gard": ["3020"], "mesh": ["D002538"], "omim": ["108010"], "umls": ["C0007772", "C0917804"], "icd-10": ["Q28.2"], "synonyms": ["Intracranial arteriovenous malformation"]} |
A number sign (#) is used with this entry because 3M syndrome-3 (3M3) can be caused by homozygous mutation in the CCDC8 gene (614145) on chromosome 19q13.
Description
The 3M syndrome is characterized by poor postnatal growth and distinctive facial features, including triangular facies, frontal bossing, fleshy tipped nose, and fleshy lips. Other features may include skeletal anomalies and prominent heels (summary by Hanson et al., 2011).
For a general phenotypic description and a discussion of genetic heterogeneity of 3M syndrome, see 3M1 (273750).
Clinical Features
Hanson et al. (2011) described 5 unrelated probands, all born of consanguineous Asian parents, with 3M syndrome. All had poor growth, fleshy tipped nose, short thorax, and prominent heels. More variable, but common features included anteverted nares, triangular face, dolichocephaly, frontal bossing, midface hypoplasia, long philtrum, pointed chin, prominent ears, short neck, and square shoulders. Less common features included tall vertebral bodies, slender long bones, clinodactyly, hyperlordosis, transverse chest groove, and hip dysplasia.
Molecular Genetics
By autozygosity mapping followed by exome sequencing of 3 Asian patients with 3M syndrome-3, Hanson et al. (2011) identified 2 different homozygous 1-bp duplications in the CCDC8 gene (614145.0001 and 614145.0002). Both mutations were predicted to result in truncation, consistent with a loss of function. The findings supported the hypothesis that the 3M syndrome results from defects in a pathway controlling human growth.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature Weight \- Low birth weight \- Low weight Other \- Poor growth HEAD & NECK Head \- Dolichocephaly Face \- Frontal bossing \- Triangular facies \- Midface hypoplasia \- Pointed chin Ears \- Prominent ears Nose \- Fleshy tipped nose \- Anteverted nares Mouth \- Fleshy lips Neck \- Short neck CHEST External Features \- Short thorax \- Square shoulders \- Transverse chest groove SKELETAL Spine \- Hyperlordosis \- Tall vertebral bodies Pelvis \- Hip dysplasia Limbs \- Slender long bones Feet \- Prominent heels MISCELLANEOUS \- Five patients have been reported (as of 8/2011) MOLECULAR BASIS \- Caused by mutation in the coiled-coil domain-containing protein 8 gene (CCDC8, 614145.0001 ) ▲ 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
| THREE M SYNDROME 3 | c1851996 | 875 | omim | https://www.omim.org/entry/614205 | 2019-09-22T15:56:07 | {"doid": ["0060241"], "mesh": ["C535725"], "omim": ["614205"], "orphanet": ["2616"], "synonyms": ["Alternative titles", "3M SYNDROME 3"], "genereviews": ["NBK1481"]} |
Isolated autosomal dominant hypomagnesemia, Glaudemans type (IADHG) is a form of familial primary hypomagnesemia (FPH, see this term), characterized by low serum magnesium (Mg) values but normal urinary Mg values. The typical clinical features are recurrent muscle cramps, episodes of tetany, tremor, and muscle weakness, especially in distal limbs. The disease is potentially fatal.
## Epidemiology
IADHG has only been described in one large Brazilian kindred with 46 family members, of whom 21 were affected.
## Clinical description
Onset of IADHG is typically in infancy. Clinical manifestations consist of recurrent and severe muscle cramps, episodes of tetany, tremor, and muscle weakness, especially in distal limbs. Additional features include facial myokymia, arythmias, severe muscle spasms and muscular pain.
## Etiology
IADHG is caused by a N255D mutation in the KCNA1 gene (12p13), which encodes the voltage-gated potassium channel Kv1.1 (expressed in the kidney, where it colocalized with TRPM6 in apical membrane of distal convoluted tubule). Mutations in KCNA1 result in a nonfunctional channel protein, with a dominant negative effect on wild-type Kv1.1 channel function, which is involved in the maintenance of membrane voltage and optimal function of the TRPM6 channel.
## Diagnostic methods
Diagnosis relies on laboratory findings showing low serum Mg levels, while serum potassium (K) and calcium (Ca) levels and urinary Ca excretion are not affected. Diagnosis is confirmed by genetic screening of KCNA1.
## Differential diagnosis
Differential diagnosis includes the other forms of FPH and episodic ataxia type 1 (see these terms).
## Genetic counseling
Transmission is autosomal dominant. Genetic counseling may be proposed and the recurrence risk is 50%.
## Management and treatment
Management is mainly symptomatic and involves a daily dose of magnesium chloride. During manifestations, intravenous or intramuscular administration of magnesium sulfate is preferred.
## Prognosis
Prognosis highly depends on rapidity of diagnosis and treatment, as the disease can be fatal following tetany attacks.
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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
| Isolated autosomal dominant hypomagnesemia, Glaudemans type | None | 876 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=199326 | 2021-01-23T17:27:41 | {"icd-10": ["E83.4"]} |
## Description
Segmental spinal muscular atrophy is a form of anterior horn cell disease that affects predominantly the hand muscles (Kamholz et al., 1988). The disease is usually sporadic and nonprogressive.
Cytogenetics
Kamholz et al. (1988) found typical features of segmental spinal muscular atrophy in a woman who also had a deletion of part of the long arm of chromosome 18; the q21.3-qter segment was missing. She had normal intelligence, although she had had some learning difficulties, and did not have the dysmorphic features usually associated with the 18q- syndrome. By molecular methods, Kamholz et al. (1988) demonstrated that the deletion included the myelin basic protein gene (159430) but did not include the transthyretin gene (176300).
Misc \- Usually sporadic and nonprogressive Muscle \- Segmental spinal muscular atrophy \- Hand muscle atrophy Neuro \- Anterior horn cell disease Inheritance \- ? Autosomal dominant ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| SPINAL MUSCULAR ATROPHY, SEGMENTAL | c1866774 | 877 | omim | https://www.omim.org/entry/183020 | 2019-09-22T16:34:33 | {"mesh": ["C566670"], "omim": ["183020"]} |
## Summary
### Clinical characteristics.
Noonan syndrome with multiple lentigines (NSML) is a condition in which the cardinal features consist of lentigines, hypertrophic cardiomyopathy, short stature, pectus deformity, and dysmorphic facial features, including widely spaced eyes and ptosis. Multiple lentigines present as dispersed flat, black-brown macules, mostly on the face, neck and upper part of the trunk with sparing of the mucosa. In general, lentigines do not appear until age four to five years but then increase to the thousands by puberty. Some individuals with NSML do not exhibit lentigines. Approximately 85% of affected individuals have heart defects, including hypertrophic cardiomyopathy (HCM) (typically appearing during infancy and sometimes progressive) and pulmonary valve stenosis. Postnatal growth retardation resulting in short stature occurs in fewer than 50% of affected persons, although most affected individuals have a height that is less than the 25th percentile for age. Sensorineural hearing deficits, present in approximately 20%, are poorly characterized. Intellectual disability, typically mild, is observed in approximately 30% of persons with NSML.
### Diagnosis/testing.
The diagnosis of NSML is established either by clinical findings or, if clinical findings are insufficient, by identification of a heterozygous pathogenic variant in one of four genes (PTPN11, RAF1, BRAF, and MAP2K1) by molecular genetic testing. At least one additional gene in which mutation is causative is likely to exist.
### Management.
Treatment of manifestations: Treatment of cardiovascular anomalies and cryptorchidism is the same as in the general population. Treatment of hearing loss includes hearing aids, enrollment in an educational program for the hearing impaired, and consideration of cochlear implantation. Developmental disability is managed by early intervention programs and individualized education strategies.
Prevention of secondary complications: For individuals with hypertrophic cardiomyopathy, certain physical activities may be curtailed in order to reduce the risk of sudden cardiac death.
Surveillance: Periodic follow up and often lifelong monitoring may be necessary for any abnormality, especially a cardiovascular abnormality. For hearing loss, twice-yearly examination by a physician familiar with hereditary hearing impairment and repeat audiometry to confirm the stability of the hearing loss are recommended. Routine monitoring of developmental progress and linear growth in childhood and adolescence.
Agents/circumstances to avoid: For individuals with hypertrophic cardiomyopathy, treatment with growth hormone must be undertaken with great caution, if at all, to avoid exacerbating a cardiac condition.
Pregnancy management: Affected women with hypertrophic cardiomyopathy or valve dysfunction may be at risk for development or exacerbation of heart failure during pregnancy; cardiac status in these women should be monitored, especially during the second and third trimesters of pregnancy.
### Genetic counseling.
NSML is inherited in an autosomal dominant manner. A proband with NSML may have the disorder as the result of a de novo pathogenic variant; the proportion of cases caused by de novo pathogenic variants is unknown. Each child of an individual with NSML has a 50% chance of inheriting the pathogenic variant. Prenatal diagnosis for pregnancies at increased risk is possible if the pathogenic variant in an affected family member is known.
## Diagnosis
### Suggestive Findings
Noonan syndrome with multiple lentigines (NSML) should be suspected in individuals with one or more of the following cardinal features:
* Lentigines
* Cardiac abnormalities, particularly hypertrophic cardiomyopathy
* Poor linear growth/short stature
* Pectus deformity
* Dysmorphic facial features, including widely spaced eyes and ptosis
Additional features occurring frequently in NSML:
* Variable degree of cognitive deficits
* Sensorineural hearing loss
* Cryptorchidism
* Skeletal anomalies
* Café au lait macules
### Establishing the Diagnosis
The diagnosis of Noonan syndrome with multiple lentigines is established either clinically in a proband with the following clinical findings or, if clinical findings are insufficient, by identification of a heterozygous pathogenic variant in one of four genes (PTPN11, RAF1, BRAF, and MAP2K1) by molecular genetic testing (see Table 1).
Clinical findings
* Multiple lentigines plus two of the other cardinal features; OR
* In the absence of lentigines, three of the other cardinal features plus a first-degree relative with NSML [Sarkozy et al 2008]
Molecular genetic testing approaches can include single-gene testing and use of a multigene panel:
* A multigene panel that includes PTPN11, RAF1, BRAF, MAP2K1, and other genes of interest (see Differential Diagnosis(1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
* Serial single-gene testing of PTPN11, RAF1, BRAF, and MAP2K1 based on the order in which a pathogenic variant is most likely to be identified. Although gene-targeted deletion/duplication analysis could be considered, the variant detection frequency is unknown and expected to be extremely low.
### Table 1.
Summary of Molecular Genetic Testing Used in Noonan Syndrome with Multiple Lentigines
View in own window
Gene 1Proportion of NSML Attributed to Mutation of This GeneProportion of Variants Detected by Test Method
Sequence analysis 2Gene-targeted deletion/duplication analysis 3
PTPN1190%Nearly 100% 4Unknown, none reported 5
RAF1<5%Nearly 100% 6Unknown, none reported 5
BRAF2 individualsSee footnote 7Unknown, none reported 5
MAP2K11 individualSee footnote 8Unknown, none reported 5
Unknown 9~5%NA
1\.
See Table A. Genes and Databases for chromosome locus and protein. See Molecular Genetics for information on allelic variants detected in this gene.
2\.
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.
3\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods that may be used can 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.
4\.
Most pathogenic variants causing NSML are identified in exons 7, 12, and 13 [Digilio et al 2002, Legius et al 2002, Sarkozy et al 2009].
5\.
No exon or whole-gene deletion or duplication involving PTPN11or RAF1 has been reported as causative of NSML. Based on the molecular mechanisms implicated in disease pathogenesis, exon or whole-gene deletions or duplications are not expected to cause NSML.
6\.
Sequence analysis of coding exons 6, 13, and 16 detects all reported pathogenic missense variants [Pandit et al 2007].
7\.
Sequence analysis of all coding exons detected pathogenic missense variants in two individuals with clinical features of NSML [Sarkozy et al 2009, Koudova et al 2009].
8\.
Sequence analysis of all coding exons detected pathogenic missense variants in one individual with clinical features of NSML [Nishi et al 2015].
9\.
It is likely that one or more additional, as-yet undefined genes, possibly related to RAS signal transduction, are associated with the ~5% of individuals with NSML in whom no pathogenic variant has been identified in PTPN11, RAF1, or BRAF.
## Clinical Characteristics
### Clinical Description
Males are more likely than females to be affected with Noonan syndrome with multiple lentigines (NSML) [Voron et al 1976], either as a result of bias of ascertainment or preferential survival of affected male fetuses, as proposed for Noonan syndrome (NS) [Tartaglia et al 2004a].
Dermatologic. Multiple lentigines present as dispersed flat, black-brown macules, mostly on the face, neck, and upper part of the trunk with sparing of the mucosa. In general, lentigines do not appear until age four to five years but then increase into the thousands by puberty [Coppin & Temple 1997]. Some individuals with NSML do not exhibit lentigines.
Café au lait macules are also observed in up to 70%-80% of affected individuals [Digilio et al 2006], usually preceding the appearance of lentigines.
Skin hyperelasticity has also been described.
Cardiovascular. Approximately 85% of affected individuals have heart defects, which are similar to those observed in NS but with different frequencies [Limongelli et al 2007].
Hypertrophic cardiomyopathy is detected in up to 70% of individuals with heart defects (compared to 25% in NS). It most commonly appears during infancy and can be progressive.
Pulmonary valve stenosis is noted in approximately 25% of affected individuals. Abnormalities of the aortic and mitral valves are also observed in a minority of persons with NSML.
ECG abnormalities, aside from those typically associated with hypertrophic cardiomyopathy, include conduction defects (23%).
Facial features. Dysmorphic facial features are similar to those seen in Noonan syndrome, although usually milder [Digilio et al 2006]. Features include inverted triangular-shaped face, downslanted palpebral fissures, low-set posteriorly rotated ears with thickened helices, and widely spaced eyes. The neck can be short with excess nuchal skin and a low posterior hairline.
Hearing. Sensorineural hearing deficits are present in approximately 20% of persons with NSML. Minimal information is available about the progression of deafness in those with milder degrees of hearing impairment.
Growth. Birth weight is usually normal but may be above the 97th percentile. Postnatal growth retardation resulting in short stature is noted in fewer than 50% of affected individuals, although most have a height that is less than the 25th percentile for age. Issues such as adult height and response to growth hormone therapy have not been studied in this disorder.
Psychomotor development. Intellectual disability, typically mild, is observed in approximately 30% of persons with NSML. Specific information concerning the deficits typically found in these children is not available.
Genitourinary. Cryptorchidism, unilateral or bilateral, is present in approximately one third of affected males. Other abnormalities including hypospadias, urinary tract defects, and ovarian abnormalities are observed infrequently.
### Genotype-Phenotype Correlations
No clear-cut genotype-phenotype correlations have been observed among the PTPN11 pathogenic variants causing NSML.
The two RAF1 pathogenic variants observed in NSML (see Table 3) reside in mutational hot spots strongly associated with hypertrophic cardiomyopathy [Pandit et al 2007]. Of note, the p.Ser257Leu pathogenic variant was associated with both NS and NSML [Pandit et al 2007].
In addition to NSML in two persons, one third of persons with NS and a RAF1 pathogenic variant had other findings including multiple nevi, lentigines, and/or café au lait spots, suggesting a predisposition to hyperpigmented cutaneous lesions associated with these pathogenic variants.
Koudova et al [2009] reported a person with NSML and normal intelligence who had a novel sequence change in BRAF, further illustrating that the phenotypic spectrum caused by BRAF pathogenic variants is broader than previously assumed and does not always include intellectual disability.
### Nomenclature
Noonan syndrome with multiple lentigines (NSML) was referred to as cardiomyopathic lentiginosis in the older medical literature.
Until recently, NSML was referred to as LEOPARD syndrome but this name is being phased out due to objections from some families with affected children who found the term offensive.
### Penetrance
Penetrance of NSML is difficult to determine because of ascertainment bias and variable expressivity, frequently with subtlety of phenotypic features. Affected adults may be diagnosed only after the birth of a more obviously affected infant.
### Prevalence
The population prevalence of NSML is not known.
## Differential Diagnosis
Turner syndrome, found only in females, is distinguished from Noonan syndrome with multiple lentigines (NSML) by demonstration of an X-chromosome abnormality on cytogenetic studies. The characteristic facial features are also distinct, and in Turner syndrome renal anomalies are more common, developmental delay is much less frequently found, and left-sided heart defects are the rule.
The Watson syndrome (OMIM 193520) phenotype also overlaps with that of neurofibromatosis type 1 and the two are now known to be allelic. Variably present in both Watson syndrome and NSML are short stature, pulmonary valve stenosis, variable intellectual development, and skin pigment changes including café au lait macules. Lentigines are not described in Watson syndrome. Heterozygous pathogenic variants in NF1 are causative.
Costello syndrome (CS) shares features with NSML, NS, and CFCS. Two series of individuals with CS have been studied molecularly and no PTPN11 has been identified [Tartaglia et al 2003a, Tröger et al 2003]. Germline pathogenic variants predominantly in the first and third coding exons of the HRAS proto-oncogene have been shown to cause CS [Aoki et al 2005].
Other. NSML should be distinguished from other syndromes with developmental delay, short stature, congenital heart defects, and distinctive facies, especially Williams syndrome.
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with Noonan syndrome with multiple lentigines (NSML), the following evaluations are recommended:
* Complete physical and neurologic examination
* Plotting of growth parameters on Noonan syndrome growth charts by Witt et al [1986] (Specific growth charts for NSML are not available.)
* Cardiac evaluation with echocardiography and electrocardiography
* Ophthalmologic evaluation
* Hearing evaluation including complete assessment of auditory acuity using age-appropriate tests (e.g., ABR testing, auditory steady-state response [ASSR] testing, pure tone audiometry)
* Renal ultrasound examination; urinalysis if urinary tract abnormalities are identified
* Clinical and radiographic assessment of spine and rib cage
* Brain and cervical spine MRI if neurologic symptoms are present
* Multidisciplinary developmental evaluation
* Consultation with a clinical geneticist and/or genetic counselor
### Treatment of Manifestations
Treatment of cardiovascular anomalies and cryptorchidism is usually the same as in the general population.
Treatment of hearing loss may include the following:
* Fitting with appropriate hearing aids
* Enrollment in an appropriate educational program for the hearing impaired
* Consideration for cochlear implantation, a promising habilitation option for persons with profound deafness
* Recognition that, as distinct from many clinical conditions, the management and treatment of severe-to-profound congenital deafness involves primarily the social welfare and educational systems rather than the medical care system [Smith et al 2005]
Any developmental disability should be addressed by early intervention programs and individualized education strategies.
Treatment of cryptorchidism in males is usually the same as in the general population.
### Prevention of Secondary Complications
For individuals with hypertrophic cardiomyopathy, certain physical activities may be curtailed in order to reduce the risk of sudden cardiac death.
For individuals diagnosed in infancy, early intervention may limit the extent of intellectual and developmental disabilities.
### Surveillance
If anomalies are found in any system, periodic follow up should be planned and lifelong monitoring may be necessary, especially of cardiovascular abnormalities.
For hearing loss, twice-yearly examination by a physician familiar with hereditary hearing impairment and repeat audiometry to confirm the stability of the hearing loss is recommended.
Surveillance for intellectual and developmental disabilities as per routine pediatric care is of particular importance due to the higher prevalence of these issues in individuals with NSML.
Surveillance for growth delay as per routine pediatric care is important due to the higher prevalence of poor linear growth in affected children.
### Agents/Circumstances to Avoid
For individuals with hypertrophic cardiomyopathy, treatment with growth hormone must be undertaken with great caution, if at all, to avoid exacerbating a cardiac condition.
### Evaluation of Relatives at Risk
It is appropriate to evaluate relatives at risk in order to identify as early as possible those who would benefit from initiation of treatment and preventive measures.
* If the PTPN11, RAF1, BRAF, or MAP2K1 pathogenic variant in the family is known, molecular genetic testing can be used to clarify the genetic status of at-risk relatives.
* If the pathogenic variant in the family is not known, a thorough physical examination with particular attention to the features of NSML may clarify the disease status of at-risk relatives.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Pregnancy Management
For affected women, cardiac status should be monitored during pregnancy. Those with hypertrophic cardiomyopathy or valve dysfunction may be at risk for the development or exacerbation of heart failure during pregnancy, especially during the second and third trimesters.
### Therapies Under Investigation
Search Clinical Trials.gov in the US and www.ClinicalTrialsRegister.eu in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Noonan Syndrome with Multiple Lentigines | c0175704 | 878 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1383/ | 2021-01-18T21:07:28 | {"mesh": ["D044542"], "synonyms": ["LEOPARD Syndrome", "Multiple Lentigines Syndrome"]} |
A very rare surgically-correctable form of primary aldosteronism (PA) due to an aldosterone-secreting adrenal malignancy.
## Epidemiology
The prevalence of adrenocortical carcinoma with pure aldosterone hypersecretion is unknown.
## Clinical description
Pure APAC is characterized by renin suppression, unilateral aldosterone hypersecretion and moderate to severe hypertension that may be associated with hypokalemia, and the presence of a large adrenal tumor. Hypokalemia may be symptomatic and present as muscular weakness, cramps, paresthesia or palpitations with or without atrial fibrillation.
## Etiology
Etiology is unknown.
## Diagnostic methods
The diagnosis of carcinoma is suggested by CT scan, showing a tumor exceeding 4 cm in diameter, and possible metastases and/or invasion of the inferior vena cava.
## Management and treatment
Open laparotomy enables resection of the tumor and possible metastases or adjacent organs. Unless unresectable tumor or metastases are present, adrenalectomy abolishes aldosterone hypersecretion and hypokalemia in most patients. Adjuvant mitotane therapy may be indicated based on tumor scoring using the Weiss score or ENS@T score.
## Prognosis
The prognosis of pure APAC is the same as for others adrenocortical carcinomas: 5-year survival is 15% in patients with metastatic adrenocortical carcinomas.
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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
| Adrenocortical carcinoma with pure aldosterone hypersecretion | None | 879 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=231625 | 2021-01-23T18:21:06 | {"icd-10": ["C74.0"], "synonyms": ["Pure APAC", "Pure aldosterone-producing adrenocortical carcinoma", "Pure aldosterone-secreting adrenocortical carcinoma"]} |
A number sign (#) is used with this entry because of evidence that the Penttinen type of premature aging syndrome (PENTT) is caused by heterozygous mutation in the PDGFRB gene (173410) on chromosome 5q32.
Description
Penttinen syndrome is characterized by a prematurely aged appearance involving lipoatrophy and epidermal and dermal atrophy, as well as hypertrophic lesions that resemble scars, thin hair, proptosis, underdeveloped cheekbones, and marked acroosteolysis (Johnston et al., 2015).
Clinical Features
Penttinen et al. (1997) reported a 10-year-old Finnish boy with a prematurely aged appearance, delayed bone maturation and dental development, pronounced acroosteolysis with brachydactyly, and distinctive cutaneous findings including hard, confluent skin lesions with some clinical and histologic resemblance to those of juvenile hyaline fibromatosis (228600). He also had hyperopia, sensorineural hearing loss, and elevated thyroid stimulating hormone (188540) levels. Linear growth and intellectual functions were normal.
Zufferey et al. (2013) reported 2 unrelated patients, a 15-year-old girl of North Vietnamese and Chinese ancestry and a 20-year-old French man, who exhibited a progeroid syndrome of the Penttinen type. Although they lacked the classic progeroid facial gestalt, the patients presented a prematurely aged appearance, with premaxillary and maxillary retraction, pseudoprognathism, proptosis, and a flat occiput Their thumbs and halluces were large, broad, and spatulate. Their hair was sparse but without alopecia. Their permanent teeth were normal, despite retention of deciduous teeth. They exhibited ocular pterygia, diffuse keloid-like skin lesions, and acroosteolysis. Linear growth was increased, despite stature limitations due to kyphoscoliosis. Skin retraction and joint contractures developed during adolescence, and the French patient died at age 20 years due to restrictive respiratory insufficiency and cachexia.
Johnston et al. (2015) provided follow-up on the Finnish boy originally described by Penttinen et al. (1997) and reported 2 additional similarly affected individuals. The Finnish patient, who was reexamined at 29 years of age, reported experiencing multiple fractures, scoliosis requiring surgical treatment, and osteoporosis. His anterior and posterior fontanels were still open, each measuring approximately 5 cm by 3 cm. He had sparse hair, bitemporal prominences, closely spaced eyes, long nose with convex ridge, extremely narrow philtrum and palate, partial eruption of 4 maxillary teeth, and retrognathia. He displayed severe contractures and shortening of his fingers and toes, with small, broad, and thick toenails. Ophthalmologic examination showed bilateral temporal and nasal corneal edema, occludable anterior segment angles, simple microphthalmia (nanophthalmos), and retinal striae with shallow orbits. The previously observed nodules and scarlike lesions had resolved, although he had thin skin with prominent venous patterning and hyperkeratotic palms and soles, with significant callous formation on the soles. Johnston et al. (2015) also studied a boy of Indonesian and Chinese ancestry and a girl of Pakistani descent, who both initially presented in early childhood due to star-shaped scar-like skin lesions. Biopsy of a new nodule in the boy showed epidermal atrophy, hyperkeratosis, and dermal fibrosis. Both patients exhibited proptosis; the boy had widely spaced eyes whereas the girl had closely spaced eyes. Skin was thin with marked vascular patterning on the face, trunk, and limbs. Skeletal survey showed small maxilla and thin long bones, as well as acroosteolysis of all distal phalanges and delayed bone age. At age 14 years, the Pakistani girl had severe contractures of fingers and toes, progressive acroosteolysis, hyperkeratotic plaques on her soles that limited her walking, and a swollen appearance of the elbows and knees due to progression of scarring and loss of subcutaneous tissue in the extremities. Her facial features had become more striking, with proptosis, loss of subcutaneous tissue, and thinning of her hair. Intelligence was reported to be normal in the Finnish man and the Pakistani girl, whereas the boy was functioning below grade level.
Molecular Genetics
In a boy of Indonesian and Chinese ancestry with a premature aging syndrome of the Penttinen type, Johnston et al. (2015) performed exome sequencing and identified heterozygosity for a de novo missense mutation in the PDGFRB gene (V665A; 173410.0006). Sequencing PDGFRB in 3 more affected individuals, including the Finnish patient originally described by Penttinen et al. (1997) and a girl of North Vietnamese and Chinese ancestry previously reported by Zufferey et al. (2013), revealed heterozygosity for the same V665A mutation in all 3 patients. The mutation was confirmed to have arisen de novo in a Pakistani girl; parental DNA was not available for the other 2 patients.
### Exclusion Studies
In a 20-year-old French man with a progeroid syndrome of the Penttinen type, Zufferey et al. (2013) excluded mutation in the FGFR1 (136350), FGFR2 (176943), TWIST (601622), LMNA (150330), and BANF1 (603811) genes. In a similarly affected 15-year-old girl of North Vietnamese and Chinese ancestry, mutations in the COL3A1 (120180), ZMPSTE24 (606480), and LMNA genes were excluded, and 2 homozygous variants detected in the 3-prime UTR of the BANF1 gene could not be further assessed due to early growth arrest of patient fibroblasts.
INHERITANCE \- Autosomal dominant GROWTH Height \- Normal or increased HEAD & NECK Face \- Midface hypoplasia Ears \- Sensorineural hearing loss (rare) Eyes \- Proptosis \- Recurrent pterygia (in some patients) Nose \- Narrow nose \- Convex nasal bridge Mouth \- Thin lips Teeth \- Delayed tooth eruption SKELETAL \- Delayed bone maturation \- Osteopenia Skull \- Delayed closure of fontanels \- Thin calvarium \- Wormian bones (in some patients) \- Zygomatic arch hypoplasia \- Maxillary hypoplasia \- Mandibular hypoplasia Spine \- Scoliosis (in some patients) Limbs \- Contractures of joints \- Thin long bones Hands \- Acroosteolysis \- Brachydactyly \- Contractures of fingers Feet \- Acroosteolysis \- Brachydactyly (in some patients) \- Contractures of toes SKIN, NAILS, & HAIR Skin \- Progressive cutaneous atrophy \- Thin translucent skin with prominent venous patterning \- Hypertrophic keloid-like lesions \- Skin retraction Skin Histology \- Epidermal atrophy \- Hyperkeratosis \- Dermal fibrosis \- Nonspecific mononuclear inflammation \- Lack of elastic fibers in reticular dermis Hair \- Sparse hair MUSCLE, SOFT TISSUES \- Lipoatrophy NEUROLOGIC Central Nervous System \- Normal intellect MOLECULAR BASIS \- Caused by mutation in the platelet-derived growth factor receptor, beta polypeptide gene (PDGFRB, 173410.0006 ) ▲ 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
| PREMATURE AGING SYNDROME, PENTTINEN TYPE | c1866182 | 880 | omim | https://www.omim.org/entry/601812 | 2019-09-22T16:14:17 | {"mesh": ["C536653"], "omim": ["601812"], "orphanet": ["363665"]} |
Pilomatrixoma is a rare and benign hair cell-derived tumor occurring mostly in young adults (usually under the age of 20) and characterized as a 3-30 mm solitary, painless, firm, mobile, deep dermal or subcutaneous tumor, most commonly found in the head, neck or upper extremities. When superficial, the tumors tint the skin blue-red. Multiple pilomatrixomas are seen in myotonic dystrophy, Gardner syndrome, Rubinstein-Taybi syndrome, and Turner syndrome (see these terms).
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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
| Pilomatrixoma | c0206711 | 881 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=91414 | 2021-01-23T18:40:51 | {"gard": ["9452"], "mesh": ["D018296"], "omim": ["132600"], "umls": ["C0206711"], "icd-10": ["D23.3", "D23.4", "D23.6"], "synonyms": ["Epithelioma calcificans of Malherbe", "Pilomatricoma"]} |
Gallin (1988) observed an apparently autosomal dominant cytochrome-b-positive form of chronic granulomatous disease of childhood.
Immunology \- Chronic granulomatous disease of childhood Lab \- Cytochrome-b-positive Inheritance \- Autosomal dominant form ▲ 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
| GRANULOMATOUS DISEASE, CHRONIC, AUTOSOMAL DOMINANT TYPE | c1841825 | 882 | omim | https://www.omim.org/entry/138990 | 2019-09-22T16:40:35 | {"mesh": ["C564210"], "omim": ["138990"]} |
Juxtaglomerular cell tumor
Other namesReninoma
SpecialtyNephrology/oncology
Juxtaglomerular cell tumor (JCT, JGCT, also reninoma) is an extremely rare kidney tumour of the juxtaglomerular cells, with less than 100 cases reported in literature. This tumor typically secretes renin, hence the former name of reninoma. It often causes severe hypertension that is difficult to control, in adults and children, although among causes of secondary hypertension it is rare. It develops most commonly in young adults, but can be diagnosed much later in life. It is generally considered benign, but its malignant potential is uncertain.[1]
## Contents
* 1 Pathophysiology
* 2 Histopathology
* 3 Diagnosis
* 4 Prognosis
* 5 History
* 6 References
## Pathophysiology[edit]
By hypersecretion of renin, JCT causes hypertension, often severe and usually sustained but occasionally paroxysmal,[2] and secondary hyperaldosteronism inducing hypokalemia, though the later can be mild despite high renin.[3] Both of these conditions may be corrected by surgical removal of the tumor.[4] Asymptomatic cases have been reported.[5]
## Histopathology[edit]
JCT is morphologically characterized by multiple foci malignant mesenchymal epithelioid cells with, often with admixed necrosis, and a perivascular growth pattern. The immunophenotype is rather characteristic, as the neoplastic cells express renin, CD34, smooth muscle actin, CD138, vimentin, collagen IV and is negative for cytokeratins as well as for S100, c-Kit and desmin.[6]
## Diagnosis[edit]
Clinically, hypertension, especially when severe or poorly controlled, combined with evidence of a kidney tumor via imaging or gross examination suggest a JCT. However, other kidney tumors can cause hypertension by secreting renin. JCTs have a variable appearance and have often being misdiagnosed as renal cell carcinomas; dynamic computed tomography is helpful in the differential diagnosis.[7]
Post-operatively, the presence of renin granules in pathology specimens as well as immunohistochemical analyses could help differentiating this tumor from other primary renal tumors such as hemangiopericytoma, glomus tumor, metanephric adenoma, epithelioid angiomyolipoma, Wilms tumor, solitary fibrous tumor, and some epithelial neoplasms.[6][8]
## Prognosis[edit]
JCT often is described as benign, however one case of metastasis has been reported, so its malignant potential is uncertain.[1] In most cases the tumor is encapsulated.[9]
## History[edit]
Juxtaglomerular cell tumor was first described in 1967 in a paper by Robertson et al., and first named by Kihara et al. in 1968. Since then, approximately 100 case reports have been published.[5] Karyotyping of a small number of these tumors revealed a common loss of chromosomes 9 and 11.[1]
## References[edit]
1. ^ a b c Capovilla M, Couturier J, Molinié V, Amsellem-Ouazana D, Priollet P, Baumert H, Bruneval P, Vieillefond A (March 2008). "Loss of chromosomes 9 and 11 may be recurrent chromosome imbalances in juxtaglomerular cell tumors". Hum. Pathol. 39 (3): 459–62. doi:10.1016/j.humpath.2007.08.010. PMID 18261631.
2. ^ W. Hanna; et al. (April 2, 1979). "Juxtaglomerular cell tumour (reninoma) with paroxysmal hypertension". Can Med Assoc J. 120 (8): 957–9. PMC 1819229. PMID 436071.
3. ^ Beaudoin, J.; Périgny M; Têtu B; Lebel M. (2008). "A Patient With A Juxtaglomerular Cell Tumor With Histological Vascular Invasion". Nature Clinical Practice Nephrology. 4 (8): 458–62. doi:10.1038/ncpneph0890. PMID 18654602.
4. ^ Wong L, Hsu TH, Perlroth MG, Hofmann LV, Haynes CM, Katznelson L (February 2008). "Reninoma: case report and literature review". J. Hypertens. 26 (2): 368–73. doi:10.1097/HJH.0b013e3282f283f3. PMID 18192852.
5. ^ a b Naoto Kuroda; et al. (2011). "Review of juxtaglomerular cell tumor with focus on pathobiological aspect". Diagnostic Pathology. 6: 80. doi:10.1186/1746-1596-6-80. PMC 3173291. PMID 21871063.
6. ^ a b Cucchiari D, Bertuzzi A, Colombo P, De Sanctis R, Faucher E, Fusco N, Pellegrinelli A, Arosio P, Angelini C (May 2013). "Juxtaglomerular cell tumor: multicentric synchronous disease associated with paraneoplastic syndrome". J Clin Oncol. 31 (14): e240–2. doi:10.1200/JCO.2012.43.5545. PMID 23547072.
7. ^ Tanabe; et al. (July 2001). "Dynamic computer tomography is useful in the differential diagnosis of juxtaglomerular cell tumor and renal cell carcinoma.Tanab". Hypertens. Res. 24 (4): 331–6. doi:10.1291/hypres.24.331. PMID 11510743.
8. ^ Martin SA, Mynderse LA, Lager DJ, Cheville JC; Martin; Lager; Cheville (December 2001). "Juxtaglomerular cell tumor: a clinicopathologic study of four cases and review of the literature". Am. J. Clin. Pathol. 116 (6): 854–63. doi:10.1309/B10J-FKQ5-J7P8-WKU4. PMID 11764074.CS1 maint: multiple names: authors list (link)
9. ^ Abbi RK, McVicar M, Teichberg S, Fish L, Kahn E (1993). "Pathologic characterization of a renin-secreting juxtaglomerular cell tumor in a child and review of the pediatric literature". Pediatr Pathol. 13 (4): 443–51. doi:10.3109/15513819309048234. PMID 8372029.
* v
* t
* e
Tumors of the urinary and genital systems
Kidney
Glandular and epithelial neoplasm
* Renal cell carcinoma
* Renal oncocytoma
Mixed tumor
* Wilms' tumor
* Mesoblastic nephroma
* Clear-cell sarcoma of the kidney
* Angiomyolipoma
* Cystic nephroma
* Metanephric adenoma
by location
* Renal medullary carcinoma
* Juxtaglomerular cell tumor
* Renal medullary fibroma
Ureter
* Ureteral neoplasm
Bladder
* Transitional cell carcinoma
* Squamous-cell carcinoma
* Inverted papilloma
Urethra
* Transitional cell carcinoma
* Squamous-cell carcinoma
* Adenocarcinoma
* Melanoma
Other
* Malignant fibrous histiocytoma
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Juxtaglomerular cell tumor | c0334331 | 883 | wikipedia | https://en.wikipedia.org/wiki/Juxtaglomerular_cell_tumor | 2021-01-18T19:06:29 | {"umls": ["C0334331"], "wikidata": ["Q6319133"]} |
A number sign (#) is used with this entry because an autosomal dominant form of fundus albipunctatus can be caused by mutation in the RDS gene (PRPH2; 179605) and an autosomal recessive form can be caused by mutation in the RDH5 gene (601617). Furthermore, this fundus picture also occurs in Bietti crystalline corneoretinopathy (210370), an autosomal recessive. See also 180380.0012, which describes an association between this disorder and a mutation in the rhodopsin gene segregating with the APOE epsilon-4 allele (107741) (Souied et al., 1996). Mutation in the RLBP1 gene (180090) has been shown to cause fundus albipunctatus and retinitis punctata albescens.
Description
This form of fleck retina disease (see 228980) is characterized by discrete uniform white dots over the entire fundus with greatest density in the midperiphery and no macular involvement. Night blindness occurs. Both autosomal dominant and autosomal recessive inheritance had been suggested (Krill and Folk, 1962; Krill, 1977).
Clinical Features
Pearce et al. (1984) described retinitis punctata albescens in association with Bardet-Biedl syndrome (see 209900) in an isolated community in northern Canada.
Fishman et al. (2004) described autosomal recessive retinitis punctata albescens in 5 patients from 3 families. The 3 probands had similar clinical findings: a history of poor night vision, the presence of punctate white deposits in the retina, and substantially reduced or absent rod responses on electroretinogram (ERG) testing.
Niwa et al. (2005) investigated the frequency of cone and rod dysfunction in patients with fundus albipunctatus due to RDH5 mutation. Cone electroretinography showed considerable variability in b-wave amplitudes, and 6 (38%) of 16 patients had b-wave amplitudes smaller than that seen in controls, suggesting extensive cone dysfunction. Cone dysfunction was more severe in older patients. In patients with reduced standard cone ERGs, cone a-wave analysis showed significantly smaller maximal response amplitudes, and rod ERGs were also reduced. Niwa et al. (2005) concluded that reduced full-field cone ERGs were mainly due to loss of cone photoreceptors and the rod system was also affected.
Molecular Genetics
Yamamoto et al. (1999) and Gonzalez-Fernandez et al. (1999) identified mutations in the RDH5 gene in patients with fundus albipunctatus (see 601617.0001-601617.0004).
Nakamura and Miyake (2002) reported fundus albipunctatus and a novel macular dystrophy in a 9-year-old boy who was a compound heterozygote for mutations in the RDH5 gene (601617.0006-601617.0007). The authors described the patient's macular findings, visual acuity, and electrophysiologic responses. They concluded that the macular dystrophy was caused by the RDH5 mutations as a phenotype variation of fundus albipunctatus.
Fishman et al. (2004) evaluated the molecular genetic defects associated with autosomal recessive retinitis punctata albescens in 5 patients from 3 families. One of the probands was compound heterozygous for mutations in the RLBP1 gene; her parents manifested round white deposits in the retina. The other 2 probands had no detected pathogenic mutations in the RLBP1 gene or in 3 other genes evaluated: RDH5, RBP3 (180290), and RDH8 (608575).
In a proband with fundus albipunctatus, Cideciyan et al. (2000) found a novel arg157-to-trp (R157W) mutation in the RDH5 gene (601617.0008). Three-dimensional structure modeling and in vitro experiments suggested that this mutation destabilized proper folding and would inactivate the enzyme. Studies using RPE membranes indicated the existence of an alternative oxidizing system for the production of 11-cis-retinal in fundus albipunctatus. The authors concluded that pathways in addition to 11-cis-RDH likely provide 11-cis-retinal to rods and cones and can maintain normal kinetics of visual recovery, but only under certain constraints and less efficiently for cone than for rod function.
INHERITANCE \- Autosomal dominant \- Autosomal recessive HEAD & NECK Eyes \- Fleck retina disease \- Discrete uniform white dots over entire fundus \- Cone dysfunction seen on ERG (in some patients) \- Macular involvement (in some patients) \- Absent rod responses seen on ERG (in some patients) \- Night blindness MOLECULAR BASIS \- Caused by mutation in the retinaldehyde-binding protein-1, cellular gene (RLBP1, 180090.0001 ) \- Caused by mutation in the retinol dehydrogenase-5 gene (RDH5, 601617.0001 ) \- Caused by mutation in the peripherin 2 gene (PRPH2, 179605.0005 ) ▲ 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
| FUNDUS ALBIPUNCTATUS | c0311338 | 884 | omim | https://www.omim.org/entry/136880 | 2019-09-22T16:40:55 | {"doid": ["11105"], "mesh": ["C562733"], "omim": ["136880"], "orphanet": ["52427", "227796"]} |
"Zika" redirects here. For other uses, see Zika (disambiguation).
Infectious disease caused by the Zika virus
Zika fever
Other namesZika virus disease, Zika, Zika virus infection
Rash during Zika fever infection
Pronunciation
* Zika /ˈziːkə/
SpecialtyInfectious disease
SymptomsFever, red eyes, joint pain, headache, maculopapular rash, Sometimes none[1][2][3]
ComplicationsGuillain–Barré syndrome, during pregnancy can cause microcephaly in the baby[4][5][6]
DurationShort-term[2]
CausesZika virus mainly spread by mosquitoes, can also be sexually transmitted[2]
Diagnostic methodTesting blood, urine, or saliva for viral RNA or blood for antibodies[1][2]
Differential diagnosisChikungunya, malaria, dengue, leptospirosis, measles[7]
PreventionDecreasing mosquito bites, condoms[2][8]
TreatmentSupportive care, Generally not needed in mild cases[2]
DeathsNone during initial infection[4]
Zika fever, also known as Zika virus disease or simply Zika, is an infectious disease caused by the Zika virus.[1] Most cases have no symptoms, but when present they are usually mild and can resemble dengue fever.[1][4] Symptoms may include fever, red eyes, joint pain, headache, and a maculopapular rash.[1][2][3] Symptoms generally last less than seven days.[2] It has not caused any reported deaths during the initial infection.[4] Mother-to-child transmission during pregnancy can cause microcephaly and other brain malformations in some babies.[5][6] Infections in adults have been linked to Guillain–Barré syndrome (GBS).[4]
Zika fever is mainly spread via the bite of mosquitoes of the Aedes type.[2] It can also be sexually transmitted and potentially spread by blood transfusions.[2][8] Infections in pregnant women can spread to the baby.[5][6][9] Diagnosis is by testing the blood, urine, or saliva for the presence of the virus's RNA when the person is sick, or the blood for antibodies after symptoms are present more than a week.[1][2]
Prevention involves decreasing mosquito bites in areas where the disease occurs and proper use of condoms.[2][8] Efforts to prevent bites include the use of insect repellent, covering much of the body with clothing, mosquito nets, and getting rid of standing water where mosquitoes reproduce.[1] There is no effective vaccine.[2] Health officials recommended that women in areas affected by the 2015–16 Zika outbreak consider putting off pregnancy and that pregnant women not travel to these areas.[2][10] While there is no specific treatment, paracetamol (acetaminophen) may help with the symptoms.[2] Admission to hospital is rarely necessary.[4]
The virus that causes the disease was first isolated in Africa in 1947.[11] The first documented outbreak among people occurred in 2007 in the Federated States of Micronesia.[2] An outbreak started in Brazil in 2015, and spread to the Americas, Pacific, Asia, and Africa.[12] This led to the World Health Organization declared it a Public Health Emergency of International Concern in February 2016.[12] The emergency was lifted in November 2016, but 84 countries still reported cases as of March 2017.[13] The last proven case of Zika spread in the Continental United States was in 2017.[14]
## Contents
* 1 Signs and symptoms
* 1.1 Guillain–Barré syndrome
* 1.2 Pregnancy
* 2 Cause
* 2.1 Reservoir
* 2.2 Transmission
* 3 Pathophysiology
* 4 Diagnosis
* 4.1 Screening in pregnancy
* 4.2 Infant testing
* 5 Prevention
* 5.1 CDC travel alert
* 5.2 WHO response
* 5.3 Vaccine
* 5.4 Mosquito control
* 6 Treatment
* 7 Outcomes
* 8 Epidemiology
* 8.1 Yap Islands
* 8.2 Oceania
* 8.3 Americas
* 8.4 Asia
* 9 History
* 9.1 Origin of the name
* 9.2 Microcephaly and other infant disorders
* 9.3 Guillain–Barré syndrome
* 10 Research
* 10.1 Mechanism
* 10.2 Mosquito control
* 11 References
* 12 External links
## Signs and symptoms[edit]
Rash on an arm due to Zika fever
Most people who are infected have no or few symptoms.[15] Otherwise the most common signs and symptoms of Zika fever are fever, rash, conjunctivitis (red eyes), muscle and joint pain, and headache, which are similar to signs and symptoms of dengue and chikungunya fever.[16] The time from a mosquito bite to developing symptoms is not yet known, but is probably a few days to a week.[17] The disease lasts for several days to a week and is usually mild enough that people do not have to go to a hospital.[1][18]
Due to being in the same family as dengue, there has been concern that it could cause similar bleeding disorders. However that has only been documented in one case, with blood seen in semen, also known as hematospermia.[19]
### Guillain–Barré syndrome[edit]
Zika virus infections have been strongly associated with Guillain–Barré syndrome (GBS), which is a rapid onset of muscle weakness caused by the immune system damaging the peripheral nervous system, and which can progress to paralysis.[20] While both GBS and Zika infection can simultaneously occur in the same individual, it is difficult to definitively identify Zika virus as the cause of GBS.[21] Though Zika virus has been shown to infect human Schwann cells.[22] Several countries affected by Zika outbreaks have reported increases in the rate of new cases of GBS. During the 2013–2014 outbreak in French Polynesia there were 42 reported cases of GBS over a 3-month period, compared to between 3 and 10 annually prior to the outbreak.[23]
### Pregnancy[edit]
Microcephaly
See also: § Microcephaly
The disease spreads from mother to child in the womb and can cause multiple problems, most notably microcephaly, in the baby. The full range of birth defects caused by infection during pregnancy is not known, but they appear to be common, with large scale abnormalities seen in up to 42% of live births.[24][25] The most common observed associations have been abnormalities with brain and eye development such as microcephaly and chorioretinal scarring.[26] Less commonly there have been systemic abnormalities such as hydrops fetalis, where there is abnormal accumulation of fluid in the fetus.[27][28] These abnormalities can lead to intellectual problems, seizures, vision problems, hearing problems, problems feeding and slow development.[29]
Whether the stage of pregnancy at which the mother becomes infected affects the risk to the fetus is not well understood, nor is whether other risk factors affect outcomes.[5][6][9] One group has estimated the risk of a baby developing microcephaly at about 1% when the mother is infected during the first trimester, with the risk of developing microcephaly becoming uncertain beyond the first trimester.[30] Affected babies might appear normal but actually have brain abnormalities; infection in newborns could also lead to brain damage.[31]
## Cause[edit]
### Reservoir[edit]
Zika virus is a mosquito-borne flavivirus closely related to the dengue and yellow fever viruses. While mosquitoes are the vector, the main reservoir species remains unknown, though serological evidence has been found in both West African monkeys and rodents.[32][33]
### Transmission[edit]
Transmission is via the bite of mosquitoes from the genus Aedes, primarily Aedes aegypti in tropical regions. It has also been isolated from Ae. africanus, Ae. apicoargenteus, Ae. luteocephalus,[34] Ae. Albopictus,[35][36] Ae. vittatus and Ae. furcifer.[32] During the 2007 outbreak on Yap Island in the South Pacific, Aedes hensilli was the vector, while Aedes polynesiensis spread the virus in French Polynesia in 2013.[37]
Zika virus can also spread by sexual transmission from infected men to their partners.[38][39][40] Zika virus has been isolated from semen samples, with one person having 100,000 times more virus in semen than blood or urine, two weeks after being infected.[41] It is unclear why levels in semen can be higher than other body fluids, and it is also unclear how long infectious virus can remain in semen. There have also been cases of men with no symptoms of Zika virus infection transmitting the disease.[42] The CDC has recommended that all men who have travelled to affected areas should wait at least 6 months before trying to attempt conception, regardless of if they were ill.[43] To date there have been no reported sexual transmissions from women to their sexual partners.[40] Oral, anal or vaginal sex can spread the disease.[44][45]
Cases of vertical perinatal transmission have been reported.[46] The CDC recommends that women with Zika fever should wait at least 8 weeks after they start having symptoms of disease before attempting to conceive.[47] There have been no reported cases of transmission from breastfeeding, but infectious virus has been found in breast milk.[48]
Like other flaviviruses it could potentially be transmitted by blood transfusion and several affected countries have developed strategies to screen blood donors.[18][49] The U.S. FDA has recommended universal screening of blood products for Zika.[50] The virus is detected in 3% of asymptomatic blood donors in French Polynesia.[51]
## Pathophysiology[edit]
In fruit flies microcephaly appears to be caused by the flavivirid virus protein NS4A, which can disrupt brain growth by hijacking a pathway which regulates growth of new neurons.[52]
## Diagnosis[edit]
It is difficult to diagnose Zika virus infection based on clinical signs and symptoms alone due to overlaps with other arboviruses that are endemic to similar areas.[18][53] The US Centers for Disease Control and Prevention (CDC) advises that "based on the typical clinical features, the differential diagnosis for Zika virus infection is broad. In addition to dengue, other considerations include leptospirosis, malaria, rickettsia, group A streptococcus, rubella, measles, and parvovirus, enterovirus, adenovirus, and alphavirus infections (e.g., chikungunya, Mayaro, Ross River, Barmah Forest, O'nyong'nyong, and Sindbis viruses)."[54]
In small case series, routine chemistry and complete blood counts have been normal in most patients. A few have been reported to have mild leukopenia, thrombocytopenia, and elevated liver transaminases.[55]
Zika virus can be identified by reverse transcriptase PCR (RT-PCR) in acutely ill patients. However, the period of viremia can be short[4] and the World Health Organization (WHO) recommends RT-PCR testing be done on serum collected within 1 to 3 days of symptom onset or on saliva samples collected during the first 3 to 5 days.[37] When evaluating paired samples, Zika virus was detected more frequently in saliva than serum.[55] Urine samples can be collected and tested up to 14 days after the onset of symptoms, as the virus has been seen to survive longer in the urine than either saliva or serum.[56] The longest period of detectable virus has been 11 days and Zika virus does not appear to establish latency.[32]
Later on, serology for the detection of specific IgM and IgG antibodies to Zika virus can be used. IgM antibodies can be detectable within 3 days of the onset of illness.[32] Serological cross-reactions with closely related flaviviruses such as dengue and West Nile virus as well as vaccines to flaviviruses are possible.[4][57][58] As of 2019, the FDA has authorized two tests to detect Zika virus antibodies.[59]
### Screening in pregnancy[edit]
The CDC recommends screening some pregnant women even if they do not have symptoms of infection. Pregnant women who have traveled to affected areas should be tested between two and twelve weeks after their return from travel.[60] Due to the difficulties with ordering and interpreting tests for Zika virus, the CDC also recommends that healthcare providers contact their local health department for assistance.[60] For women living in affected areas, the CDC has recommended testing at the first prenatal visit with a doctor as well as in the mid-second trimester, though this may be adjusted based on local resources and the local burden of Zika virus.[60] Additional testing should be done if there are any signs of Zika virus disease. Women with positive test results for Zika virus infection should have their fetus monitored by ultrasound every three to four weeks to monitor fetal anatomy and growth.[60]
### Infant testing[edit]
For infants with suspected congenital Zika virus disease, the CDC recommends testing with both serologic and molecular assays such as RT-PCR, IgM ELISA and plaque reduction neutralization test (PRNT).[61] RT-PCR of the infants serum and urine should be performed in the first two days of life.[61] Newborns with a mother who was potentially exposed and who have positive blood tests, microcephaly or intracranial calcifications should have further testing including a thorough physical investigation for neurologic abnormalities, dysmorphic features, splenomegaly, hepatomegaly, and rash or other skin lesions.[61] Other recommended tests are cranial ultrasound, hearing evaluation,[62] and eye examination.[61] Testing should be done for any abnormalities encountered as well as for other congenital infections such as syphilis, toxoplasmosis, rubella, cytomegalovirus infection, lymphocytic choriomeningitis virus infection, and herpes simplex virus.[61] Some tests should be repeated up to 6 months later as there can be delayed effects, particularly with hearing.[61]
## Prevention[edit]
The virus is spread by mosquitoes, making mosquito avoidance an important element to disease control. The CDC recommends that individuals:[63]
* Cover exposed skin by wearing long-sleeved shirts and long pants treated with permethrin.[64]
* Use an insect repellent containing DEET,[65] picaridin, oil of lemon eucalyptus (OLE), or ethyl butylacetylaminopropionate (IR3535)
* Always follow product directions and reapply as directed
* If you are also using sunscreen, apply sunscreen first, let it dry, then apply insect repellent
* Follow package directions when applying repellent on children. Avoid applying repellent to their hands, eyes, or mouth
* Stay and sleep in screened-in or air-conditioned rooms
* Use a bed net if the area where you are sleeping is exposed to the outdoors
* Cover cribs, strollers and carriers with mosquito netting for babies under 2 months old.
The CDC also recommends strategies for controlling mosquitoes such as eliminating standing water, repairing septic tanks and using screens on doors and windows.[66][67] Spraying insecticide is used to kill flying mosquitoes and larvicide can be used in water containers.[1]
Because Zika virus can be sexually transmitted, men who have gone to an area where Zika fever is occurring should be counseled to either abstain from sex or use condoms for 6 months after travel if their partner is pregnant or could potentially become pregnant.[18][38][47] Breastfeeding is still recommended by the WHO, even by women who have had Zika fever. There have been no recorded cases of Zika transmission to infants through breastfeeding, though the replicative virus has been detected in breast milk.[48][68]
When returning from travel, with or without symptoms, it is suggested that prevention of mosquito bites continue for 3 weeks in order reduce the risk of virus transmission to uninfected mosquitos.[63]
### CDC travel alert[edit]
This section needs to be updated. Please update this article to reflect recent events or newly available information. (May 2020)
Because of the "growing evidence of a link between Zika and microcephaly", in January 2016, the CDC issued a travel alert advising pregnant women to consider postponing travel to countries and territories with ongoing local transmission of Zika virus.[69] Later, the advice was updated to caution pregnant women to avoid these areas entirely if possible and, if travel is unavoidable, to protect themselves from mosquito bites.[70] Male partners of pregnant women and couples contemplating pregnancy who must travel to areas where Zika is active are advised to use condoms or abstain from sex entirely.[70] The agency also suggested that women thinking about becoming pregnant should consult with their physicians before traveling.[69][71]
As of September 2016, the CDC travel advisories include:[72]
* Cape Verde
* Many parts of the Caribbean: Anguilla, Antigua and Barbuda, Aruba, The Bahamas, Barbados, Bonaire, British Virgin Islands, Cayman Islands, Cuba, Curaçao, Dominica, Dominican Republic, Grenada, Guadeloupe, Haiti, Jamaica, Martinique, Puerto Rico, Saba, Saint Saint Barthélemy, Saint Lucia, Saint Martin, Saint Vincent and the Grenadines, Sint Eustatius, Sint Maarten, Trinidad and Tobago, and the U.S. Virgin Islands
* Central America: Belize, Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua, and Panama
* Mexico
* Most of South America: Argentina, Bolivia, Brazil, Colombia, Ecuador, French Guiana, Guyana, Paraguay, Peru, Suriname, and Venezuela
* Several Pacific Islands: American Samoa, Fiji, Marshall Islands, Micronesia, New Caledonia, Papua New Guinea, Samoa, and Tonga
* In Asia: Singapore, Malaysia, Brunei
### WHO response[edit]
Both the regional Pan American Health Organization (PAHO) as well as the WHO have issued statements of concern about the widespread public health impact of the Zika virus and its links to GBS and microcephaly.[73][74] The WHO Director-General, Margaret Chan, issued a statement in February 2016 "declaring that the recent cluster of microcephaly cases and other neurological disorders reported in Brazil, following a similar cluster in French Polynesia in 2014, constitutes a Public Health Emergency of International Concern."[12] The declaration allowed the WHO to coordinate international response to the virus as well as gave its guidance the force of international law under the International Health Regulations.[75][76] The declaration was ended in November 2016.[77]
### Vaccine[edit]
Main article: Zika virus vaccine
As of 2016 there was no available vaccine. Development was a priority of the US National Institutes of Health (NIH), but officials stated that development of a vaccine could take years.[4][18][53][78] To speed new drug development regulatory strategies were proposed by the WHO and NIH.[79][80] Animal and early human studies were underway as of September 2016.[81][82] As of December 2019, there were several vaccine candidates in various stages of development.[83]
### Mosquito control[edit]
Disease control in the affected countries currently centres around mosquito control. Several approaches are available for the management of Aedes aegypti mosquito populations, including the destruction of larval breeding sites (the aquatic pools in which eggs are laid and larvae hatch prior to mosquito development into flying adults); and, insecticides targeting either the larval stages, adult mosquitoes or both. Additionally, a whole host of novel technologies are under current development for mosquito control and the World Health Organization has recently lent its support for the accelerated development of modern methods for mosquito control such as the use of Wolbachia bacteria to render mosquitoes resistant to the virus, and, the release of sterilized male mosquitoes that breed with wild female mosquitoes to give rise to non-viable offspring (offspring that do not survive to the biting, adult stage).[84]
Oxitec’s genetically modified OX513A mosquito was approved by Brazil's National Biosecurity Technical Commission (CTNBio) in April 2014[85] and it was being used to try to combat mosquitoes carrying the Zika virus in the town of Piracicaba, São Paulo in 2016.[86]
In the 1940s and 1950s, the Aedes aegypti mosquito was eradicated on some Caribbean islands and in at least eighteen Latin American countries. Decreasing political will and presumably available money, mosquito resistance to insecticide, and a pace of urbanization which exceeded eradication efforts led to this mosquito's comeback.[87]
## Treatment[edit]
There is currently no specific treatment for Zika virus infection. Care is supportive with treatment of pain, fever, and itching.[37] Some authorities have recommended against using aspirin and other NSAIDs as these have been associated with hemorrhagic syndrome when used for other flaviviruses.[4][18] Additionally, aspirin use is generally avoided in children when possible due to the risk of Reye syndrome.[88]
Zika virus had been relatively little studied until the major outbreak in 2015, and no specific antiviral treatments are available as yet.[18] Advice to pregnant women is to avoid any risk of infection so far as possible, as once infected there is little that can be done beyond supportive treatment.[89]
## Outcomes[edit]
Most of the time, Zika fever resolves on its own in 2 to 7 days, but rarely, some people develop Guillain–Barré syndrome.[4][90] The fetus of a pregnant woman who has Zika fever may die or be born with congenital central nervous system malformations, like microcephaly.[4]
## Epidemiology[edit]
Countries with active Zika virus transmission as of September 2016.
In April 1947, as part of studies sponsored by the Rockefeller Foundation into yellow fever, 6 caged rhesus monkeys were placed in the canopy of the Zika Forest of Uganda.[91] On April 18 one of the monkeys (no. 776) developed a fever and blood samples revealed the first known case of Zika fever.[32][91] Population surveys at the time in Uganda found 6.1% of individuals to be seropositive for Zika.[46] The first human cases were reported in Nigeria in 1954.[92] A few outbreaks have been reported in tropical Africa and in some areas in Southeast Asia.[93] There have been no documented cases of Zika virus in the Indian subcontinent. Surveys have found antibodies to Zika in healthy people in India which could indicate past exposure, though it could also be due to cross-reaction with other flaviviruses.[94]
By using phylogenetic analysis of Asian strains, it was estimated that Zika virus had moved to Southeast Asia by 1945.[46] In 1977–1978, Zika virus infection was described as a cause of fever in Indonesia.[95] Before 2007, there were only 13 reported natural infections with Zika virus, all with a mild, self-limited febrile illness.[32][96]
### Yap Islands[edit]
Main article: 2007 Yap Islands Zika virus outbreak
The first major outbreak, with 185 confirmed cases, was reported in 2007 in the Yap Islands of the Federated States of Micronesia.[97] A total of 108 cases were confirmed by PCR or serology and 72 additional cases were suspected. The most common symptoms were rash, fever, arthralgia, and conjunctivitis, and no deaths were reported. The mosquito Aedes hensilli, which was the predominant species identified in Yap during the outbreak, was probably the main vector of transmission. While the way of introduction of the virus on Yap Island remains uncertain, it is likely to have happened through introduction of infected mosquitoes or a human infected with a strain related to those in Southeast Asia.[46][97] This was also the first time Zika fever had been reported outside Africa and Asia.[3] Before the Yap Island outbreak, only 14 human cases had ever been reported.[98]
### Oceania[edit]
Main article: 2013–2014 Zika virus outbreaks in Oceania
In 2013–2014, several outbreaks of Zika were reported in French Polynesia, New Caledonia, Easter Island and the Cook Islands. The source of the virus was thought to be an independent introduction of the virus from Southeast Asia, unrelated to the Yap Islands outbreak.[46]
### Americas[edit]
Further information: 2015–16 Zika virus epidemic
Areas of active Zika virus transmission, April 2016
Genetic analyses of Zika virus strains suggest that Zika first entered the Americas between May and December 2013.[99] It was first detected in the Western Hemisphere in February 2014, and rapidly spread throughout South and Central America, reaching Mexico in November 2015.[18][46][100] In 2016 it established local transmission in Florida and Texas.[101][102] The first death in the United States due to Zika occurred in February 2016.[103]
In May 2015, Brazil officially reported its first 16 cases of the illness.[104] Although, a case of illness was reported in March 2015 in a returning traveller.[105] According to the Brazilian Health Ministry, as of November 2015 there was no official count of the number of people infected with the virus in Brazil, since the disease is not subject to compulsory notification. Even so, cases were reported in 14 states of the country. Mosquito-borne Zika virus is suspected to be the cause of 2,400 possible cases of microcephaly and 29 infant deaths in Brazil in 2015 (of the 2400 or so notified cases in 2015, 2165 were under investigation in December 2015, 134 were confirmed and 102 were ruled out for microcephaly).[106]
The Brazilian Health Ministry has reported at least 2,400 suspected cases of microcephaly in the country in 2015 as of 12 December, and 29 fatalities.[106][107][108][109] Before the Zika outbreak, only an average of 150 to 200 cases per year were reported in Brazil.[110] In the state of Pernambuco the reported rates of microcephaly in 2015 are 77 times higher than in the previous 5 years.[110] A model using data from a Zika outbreak in French Polynesia estimated the risk of microcephaly in children born to mothers who acquired Zika virus in the first trimester to be 1%.[111]
On 24 January 2016, the WHO warned that the virus is likely to spread to nearly all countries of the Americas, since its vector, the mosquito Aedes aegypti, is found in all countries in the region, except for Canada and continental Chile.[112][113] The mosquito and dengue fever have been detected in Chile's Easter Island, some 3,500 km (2,200 mi) away from its closest point in mainland Chile, since 2002.[114]
In February 2016, WHO declared the outbreak a Public Health Emergency of International Concern as evidence grew that Zika is a cause of birth defects and neurological problems.[18][115][116][117] In April 2016, WHO stated there is a scientific consensus, based on preliminary evidence, that Zika is a cause of microcephaly in infants and Guillain–Barré syndrome in adults.[9] Studies of this and prior outbreaks have found Zika infection during pregnancy to be associated with early pregnancy loss and other pregnancy problems.[118][119]
### Asia[edit]
In 2016 imported or locally transmitted Zika was reported in all the countries of Asia except Brunei, Hong Kong, Myanmar and Nepal.[120] Serological surveys have indicated that Zika virus is endemic in most areas of Asia, though at a low level.[120] While there was a sharp rise in the number of cases of Zika detected in Singapore after the 2016 Summer Olympics in Brazil, genetic analysis revealed that the strains were more closely related to strains from Thailand than from those causing the epidemic in the Americas.[121][122][123]
## History[edit]
### Origin of the name[edit]
It is named after the Zika Forest near Entebbe, Uganda, where the Zika virus was first identified.[124]
### Microcephaly and other infant disorders[edit]
Zika virus was first identified in the late 1940s in Kampala, Uganda, Africa but was first confirmed in Brazil. Since it was first identified, Zika has been found in more than 27 countries and territories.[125] Following the initial Zika outbreak in Northeastern Brazil in May 2015, physicians observed a very large surge of reports of infants born with microcephaly, with 20 times the number of expected cases.[126][127] Many of these cases have since been confirmed, leading WHO officials to project that approximately 2,500 infants will be found to have born in Brazil with Zika-related microcephaly.[128][129]
Proving that Zika causes these effects was difficult and complex for several reasons.[130][131] For example, the effects on an infant might not be seen until months after the mother's initial infection, long after the time when Zika is easily detected in the body.[130] In addition, research was needed to determine the mechanism by which Zika produced these effects.[132]
Since the initial outbreak, studies that use several different methods found evidence of a link, leading public health officials to conclude that it appears increasingly likely the virus is linked to microcephaly and miscarriage.[132][133] On 1 February 2016, the World Health Organization declared recently reported clusters of microcephaly and other neurological disorders a Public Health Emergency of International Concern (PHEIC).[134] On 8 March 2016, the WHO Committee reconfirmed that the association between Zika and neurological disorders is of global concern.[132]
The Zika virus was first linked with newborn microcephaly during the Brazil Zika virus outbreak. In 2015, there were 2,782 suspected cases of microcephaly compared with 147 in 2014 and 167 in 2013.[126] Confirmation of many of the recent cases is pending,[135] and it is difficult to estimate how many cases went unreported before the recent awareness of the risk of virus infections.[136]
Brazilian President Dilma Rousseff in a videoconference about the Zika virus at the National Center for Disaster Management.
In November 2015, the Zika virus was isolated in a newborn baby from the northeastern state of Ceará, Brazil, with microcephaly and other congenital disorders. The Lancet medical journal reported in January 2016 that the Brazilian Ministry of Health had confirmed 134 cases of microcephaly "believed to be associated with Zika virus infection" with an additional 2,165 cases in 549 counties in 20 states remaining under investigation.[18][137] An analysis of 574 cases of microcephaly in Brazil during 2015 and the first week of 2016, reported in March 2016, found an association with maternal illness involving rash and fever during the first trimester of pregnancy.[138] During this period, 12 Brazilian states reported increases of at least 3 standard deviations (SDs) in cases of microcephaly compared with 2000–14, with the northeastern states of Bahia, Paraíba and Pernambuco reporting increases of more than 20 SDs.[138]
In January 2016, a baby in Oahu, Hawaii, was born with microcephaly, the first case in the United States of brain damage linked to the virus. The baby and mother tested positive for a past Zika virus infection. The mother, who had probably acquired the virus while traveling in Brazil in May 2015 during the early stages of her pregnancy, had reported her bout of Zika. She recovered before relocating to Hawaii. Her pregnancy had progressed normally, and the baby's condition was not known until birth.[139]
In February 2016, ocular disorders in newborns have been linked to Zika virus infection.[140] In one study in Pernambuco state in Brazil, about 40 percent of babies with Zika-related microcephaly also had scarring of the retina with spots, or pigment alteration.[141] On 20 February 2016, Brazilian scientists announced that they had successfully sequenced the Zika virus genome and expressed hope that this would help in both developing a vaccine and in determining the nature of any link to birth defects.[142]
Also in February 2016, rumors that microcephaly is caused by the use of the larvicide pyriproxyfen in drinking water were refuted by scientists.[143][144][145] "It's important to state that some localities that do not use pyriproxyfen also had reported cases of microcephaly", read a Brazilian government statement.[146] The Brazilian government also refuted conspiracy theories that chickenpox and rubella vaccinations or genetically modified mosquitoes were causing increases in microcephaly.[145]
Researchers also suspected that Zika virus could be transmitted by a pregnant woman to her babies ("vertical transmission"). This remained unproven until February 2016, when a paper by Calvet et al. was published, showing not only was the Zika virus genome found in the amniotic fluid but also IgM antibodies against the virus.[147] This means that not only can the virus cross the placental barrier, but also the antibodies produced by the mother can reach the fetus, which suggests that vertical transmission is plausible in these cases. One other study published in March 2016 by Mlakar and colleagues analyzed autopsy tissues from a fetus with microcephaly that was probably related to Zika virus; researchers found ZIKV in the brain tissue and suggested that the brain injuries were probably associated with the virus, which also shed a light on the vertical transmission theory.[148] Also in March 2016, first solid evidence was reported on how the virus affects the development of the brain, indicating that it appears to preferentially kill developing brain cells.[149]
The first cases of birth defects linked to Zika in Colombia[150] and in Panama were reported in March 2016.[151] In the same month, researchers published a prospective cohort study that found profound impacts in 29 percent of infants of mothers infected with Zika, some of whom were infected late in pregnancy.[24] This study did not suffer from some of the difficulties of studying Zika: the study followed women who presented to a Rio de Janeiro clinic with fever and rash within the last five days. The women were then tested for Zika using PCR, then the progress of the pregnancies were followed using ultrasound.[24][152]
### Guillain–Barré syndrome[edit]
A high rate of the autoimmune disease Guillain–Barré syndrome (GBS), noted in the French Polynesia outbreak, has also been found in the outbreak that began in Brazil.[137] Laboratory analysis found Zika infections in some patients with GBS in Brazil, El Salvador, Suriname and Venezuela,[153] and the WHO declared on 22 March 2016 that Zika appeared to be "implicated" in GBS infection and that if the pattern was confirmed it would represent a global public health crisis.[154]
## Research[edit]
### Mechanism[edit]
Research has been ongoing to better understand how Zika virus causes microcephaly and other neurological disorders.[155]
It may involve infection of the primary neural stem cells of the fetal brain, known as neural progenitor cells.[156][28] The main roles of brain stem cells are to proliferate until the correct number is achieved, and then to produce neurons through the process of neurogenesis.[157] Zika proteins NS4A and NS4B have also been shown to directly suppress neurogenesis.[28] Infection of brain stem cells can cause cell death, which reduces the production of future neurons and leads to a smaller brain.[156] Zika also appears to have an equal tropism for cells of the developing eye, leading to high rates of eye abnormalities as well.[28]
In addition to inducing cell death, infection of neural progenitor cells may alter the process of cell proliferation, causing a depletion in the pool of progenitor cells.[158] A large number of cases of microcephaly have been associated with inherited gene mutations, and specifically with mutations that lead to dysfunction of the mitotic spindle. There is some evidence that Zika virus may directly or indirectly interfere with mitotic function, this may play a role in altering cell proliferation.[159]
Another line of research considers that Zika, unlike other flaviviruses, may target developing brain cells after it crosses the placenta, and considers the resulting damage likely to be the result of inflammation as a byproduct of the immune response to the infection of those cells.[160]
### Mosquito control[edit]
Some experimental methods of prevention include breeding and releasing mosquitoes that have been genetically modified to prevent them from transmitting pathogens, or have been infected with the Wolbachia bacterium, believed to inhibit the spread of viruses.[18][161] A strain of Wolbachia helped to reduce the vector competence of the Zika virus in infected Aedes aegypti released in Medellin, Colombia.[162] Gene drive is a technique for changing wild populations, for instance to combat insects so they cannot transmit diseases (in particular mosquitoes in the cases of malaria and Zika).[163] Another method which been researched aims to render male mosquitoes infertile by nuclear radiation in the hope to reduce populations; this is done with a cobalt-60 gamma cell irradiator.[164] In 2016 the World Health Organization encouraged field trials of transgenic male Aedes aegypti mosquitoes developed by Oxitec to try to halt the spread of the Zika virus.[165]
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158. ^ Merfeld, Emily; Ben-Avi, Lily; Kennon, Mason; Cerveny, Kara L. (1 July 2017). "Potential mechanisms of Zika-linked microcephaly". Wiley Interdisciplinary Reviews: Developmental Biology. 6 (4): n/a. doi:10.1002/wdev.273. ISSN 1759-7692. PMC 5516183. PMID 28383800.
159. ^ Bullerdiek, J; Dotzauer, A; Bauer, I (2016). "The mitotic spindle: linking teratogenic effects of Zika virus with human genetics?". Molecular Cytogenetics. 9: 32. doi:10.1186/s13039-016-0240-1. PMC 4837584. PMID 27099632.
160. ^ Wang, A; Thurmond, S; Islas, L; Hui, K; Hai, R (22 March 2017). "Zika virus genome biology and molecular pathogenesis". Emerging Microbes & Infections. 6 (3): e13. doi:10.1038/emi.2016.141. PMC 5378920. PMID 28325921. Archived from the original on 4 April 2017.
161. ^ Gale, Jason (4 February 2016). "The Best Weapon for Fighting Zika? More Mosquitoes". Bloomberg. Archived from the original on 6 April 2017.
162. ^ Aliota, Matthew T.; Peinado, Stephen A.; Velez, Ivan Dario; Osorio, Jorge E. (2016). "The w Mel strain of Wolbachia Reduces Transmission of Zika virus by Aedes aegypti". Scientific Reports. 6: 28792. Bibcode:2016NatSR...628792A. doi:10.1038/srep28792. PMC 4929456. PMID 27364935. The wMel strain of Wolbachia Reduces Transmission of Zika virus by Aedes aegypti
163. ^ Flam, Faye (4 February 2016). "Fighting Zika Virus With Genetic Engineering". Bloomberg. Archived from the original on 6 June 2016.
164. ^ Viegas, Luciana (23 February 2016). "IAEA Helps Brazil Step up the Fight Against 'Zika' Mosquitoes". International Atomic Energy Agency. Archived from the original on 29 June 2016.
165. ^ Kelland, Kate (18 March 2016). "WHO backs trials of genetically modified mosquitoes to fight Zika". The Globe and Mail. Archived from the original on 18 March 2016. Retrieved 19 March 2016.
## External links[edit]
Classification
D
* ICD-10: U06
* ICD-9-CM: 066.3
* DiseasesDB: 36480
External resources
* MedlinePlus: 007666
* Scholia: Q8071861
* Managing Zika in babies (CDC)
* Species Profile - Zika Virus Disease, National Invasive Species Information Center, United States National Agricultural Library. Lists general information and resources for White-Nose Syndrome.
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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
| Zika fever | c0276289 | 885 | wikipedia | https://en.wikipedia.org/wiki/Zika_fever | 2021-01-18T18:45:21 | {"mesh": ["D000071243"], "umls": ["C0276289"], "icd-10": ["U06"], "orphanet": ["448237"], "wikidata": ["Q8071861"]} |
Netherton syndrome (NS) is a skin disorder characterized by congenital ichthyosiform erythroderma (CIE), a distinctive hair shaft defect (trichorrhexis invaginata; TI) and atopic manifestations.
## Epidemiology
Incidence is estimated at 1/200,000 births.
## Clinical description
Patients generally present at birth with generalized erythroderma and scaling, and failure to thrive. Frequent complications include hypernatremic dehydration, recurrent infections, and diarrhea and intestinal malabsorption. The disease course is heterogeneous: the generalized erythroderma may persist in some patients, but more frequently it evolves during childhood into ichthyosis linearis circumflexa (ILC). ILC is a milder and highly characteristic skin disorder marked by migratory erythematous plaques with a double-edged scale. Hair anomalies usually become apparent after infancy, with sparse and brittle hair caused by TI (bamboo hair viewed by light microscopy) and other hair shaft anomalies (pili torti and/or trichorrhexis nodosa). Eyebrows and eyelashes are also affected. The large majority of NS patients develop atopic manifestations including asthma, atopic dermatitis, food allergies, urticaria, angioedema, and elevated IgE levels. Other clinical findings are delayed growth and development, short stature, and, rarely, intermittent aminoaciduria. Intellectual deficit has been associated in some cases.
## Etiology
NS is caused by mutations in the SPINK5 gene (5q31-q32) encoding the serine protease inhibitor LEKTI. LEKTI deficiency results in an increase in trypsin-like hydrolytic activity in the stratum corneum (SC) leading to SC premature desquamation and a severe skin barrier defect.
## Diagnostic methods
Early diagnosis may be problematic as the most distinctive findings (TI and ILC) do not generally become apparent until childhood. Immunohistochemistry of skin biopsies revealing LEKTI deficiency has been proposed as a useful diagnostic test for NS, but identification of the disease-causing mutation allows molecular confirmation of the diagnosis.
## Differential diagnosis
Differential diagnoses include other infantile erythrodermas, particularly nonbullous congenital ichthyosiform erythroderma (see this term) and erythrodermic psoriasis. Atopic dermatitis, lamellar ichthyosis (see this term), primary immunodeficiency syndromes, seborrheic dermatitis, and acrodermatitis enteropathica (see this term) should also be excluded.
## Antenatal diagnosis
Molecular prenatal diagnosis is feasible.
## Genetic counseling
NS is an autosomal recessive disorder and genetic counseling should be proposed for affected families.
## Management and treatment
Treatment is symptomatic and requires prompt management of the neonatal complications and long-term use of emollients for treatment of the skin disorder. Use of topical steroids and topical immunomodulators (tacrolimus and pimecrolimus) has been described as beneficial in some cases, but these agents are not indicated for long-term use or treatment of large surface areas as the skin barrier defect allows increased systemic drug absorption.
## Prognosis
The prognosis may be severe in neonates with life-threatening complications and postnatal lethality is high. The skin manifestations and hair anomalies persist throughout life, but the disease usually improves with age and most patients begin to thrive during the second year of life.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Netherton syndrome | c0265962 | 886 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=634 | 2021-01-23T19:08:45 | {"gard": ["7182"], "mesh": ["D056770"], "omim": ["256500"], "umls": ["C0265962"], "icd-10": ["Q80.8"], "synonyms": ["Bamboo hair syndrome", "Comèl-Netherton syndrome", "NS"]} |
Diffuse infiltrative lymphocytosis syndrome
SpecialtyImmunology
Diffuse infiltrative lymphocytosis syndrome occurs in HIV positive patients with low CD4 counts.[1][2]
It is similar to Sjögren's syndrome,[3] with painless parotid and submandibular swelling, and sicca symptoms.
The syndrome typically improves with HAART.[citation needed]
## References[edit]
1. ^ Snow, James Byron; Ballenger, John Jacob (2009). Ballenger's Otorhinolaryngology: Head and Neck Surgery. PMPH-USA. p. 1132. ISBN 9781550093377.
2. ^ Kimura, Jun (2006). Peripheral Nerve Diseases. Elsevier Health Sciences. p. 87. ISBN 978-0444513588.
3. ^ Shin J. Oh (2002). Color atlas of nerve biopsy pathology. CRC Press. pp. 161–. ISBN 978-0-8493-1676-0. Retrieved 1 July 2010.
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This article about a disease, disorder, or medical condition is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Diffuse infiltrative lymphocytosis syndrome | c1333292 | 887 | wikipedia | https://en.wikipedia.org/wiki/Diffuse_infiltrative_lymphocytosis_syndrome | 2021-01-18T19:09:51 | {"umls": ["C1333292"], "wikidata": ["Q5275415"]} |
This article may need to be rewritten to comply with Wikipedia's quality standards. You can help. The talk page may contain suggestions. (June 2020)
Abortion in Missouri is legal.
In 1900, Missouri criminalized abortion[citation needed]. It was legalized after the Roe v. Wade decision in 1973. Peaking at 29 abortion clinics in 1982, the number began to decline, going from twelve in 1992 to one in 2014, down to zero for a time in 2016, but back to one from 2017 to May 2019 when the last remaining clinic announced it would likely lose its license. However, the clinic remains open as of 2020.
A parental consent law came into effect in 1990[citation needed]. Informed consent laws existed by 2007[citation needed].
According to Guttmacher Institute, in 2017, there were 4,710 abortions in Missouri, and that there was an eight percent decline in the abortion rate in Missouri between 2014 and 2017, from 4.4 to 4.0 abortions per 1,000 women of reproductive age. Abortions in Missouri represent 0.5 percent of all abortions in the United States[citation needed].
In 2017, about 33 percent of abortions were medicated abortions[citation needed].
The state saw anti-abortion rights violence in 2000 in Marion County[citation needed].
## Contents
* 1 Terminology
* 2 Context
* 3 History
* 3.1 Legislative history
* 3.2 Judicial history
* 3.3 Clinic history
* 4 Statistics
* 5 Women's abortion experiences
* 6 Abortion rights views and activities
* 6.1 Views
* 6.2 Protests
* 7 Anti-abortion views and activities
* 7.1 Views
* 8 Footnotes
* 9 References
## Terminology[edit]
Main article: Abortion
See also: Definitions of 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
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.[8] In 2017, Georgia, Ohio, Missouri, Louisiana, Alabama and Mississippi have among the highest rates of infant mortality in the United States.[8] In 2017, Missouri had an infant mortality rate of 6.2 infant deaths per 1,000 live births.[8] Medicaid expansion under the Affordable Care Act was rejected by Alabama, Georgia, Mississippi and Missouri. Consequently, poor women in the typical age range to become mothers had a gap in coverage for prenatal care. According to Georgetown University Center for Children and Families research professor Adam Searing, "The uninsured rate for women of childbearing age is nearly twice as high in states that have not expanded Medicaid. [...] That means a lot more women who don't have health coverage before they get pregnant or after they have their children. [...] If states would expand Medicaid coverage, they would improve the health of mothers and babies and save lives."[8] According to the 2018 Premature Birth Report Cards, Louisiana, Mississippi and Alabama were all given an F.[8] According to the 2018 America's Health Rankings produced by United Health Foundation, Missouri ranked 42nd among US states for maternal mortality.[8]
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).[9] 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.[9] This state was one of a majority that taxed essential hygiene products like tampons and menstrual pads as of November 2018.[10][11][12][13]
## History[edit]
### Legislative history[edit]
Fetal heartbeat bills by state, including time limit without exceptions marked:
Heartbeat bill passed (to go into effect)
Law partially passed by state legislature
Law blocked by court order
By the end of the 1800s, all states in the Union except Louisiana had therapeutic exceptions in their legislative bans on abortions.[14] 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.[14]
Missouri passed a parental consent law in the early 1990s. This law impacted when minors sought abortions, resulting in an increase of 19% to 22% for abortions sought after 12 weeks.[15][16] The state was one of 10 states in 2007 to have a customary informed consent provision for abortions.[17]
In 2015, the state was one of five where the legislature introduced a bill that would have banned abortion in almost all cases. It did not pass. They tried and failed again in 2017 and 2018.[18] The 2018 bill was introduced in the legislature to ban abortion after 15 weeks.[19] Around 2016, the state legislature passed a law that said facilities providing abortions needed to be licensed ambulatory surgical centers and to have hospital admitting privileges.[20] The state legislature was one of eight states nationwide that tried, and failed, to pass a fetal heartbeat bill in 2017. They tried and failed again in 2018.[18]
Nationally, 2019 was one of the most active years for state legislatures in terms of trying to pass abortion rights restrictions. These state governments generally saw this as a positive sign that new moves to restrict abortion rights would less likely face resistance by the courts.[18] In mid-2019, the state legislature passed a law that would make abortion illegal in almost cases after 8 weeks. It was one of several states passing such laws in May 2019 alongside Georgia, Louisiana and Alabama. The law was a "fetal heartbeat" bill.[21][22][18]
Dates of when heartbeat laws come into effect (as of May 25, 2019)
Two fetal heartbeat bills have been filed in Missouri on January 9, 2019.[23] SB 139 was filed in the Missouri Senate by Sen. Andrew Koenig; the bill is pending in the Health and Pensions Committee.[24] HB 126 was filed in the Missouri House of Representatives by Rep. Nick Schroer.[25] On January 30, 2019, HB 126 was referred to the Children and Families Committee, and on February 12, 2019, a public hearing on the bill was completed.[26] On February 21, 2018, HB 126 was voted out of committee to the full House with the recommendation that it "do pass."[27][28] On February 27, 2019, HB 126 was passed out of the Missouri House and was sent to the state Senate.[29] Missouri's House Speaker Elijah Haahr has said he supports the “heartbeat bill” calling it a top priority for the 2019 session.[30][31] When asked if he would sign a fetal heartbeat bill, Governor Mike Parson said, "I’ve been pro-life my entire career, and I support that all the time."[32] At the time the bill passed, only 25% of the state legislators were female.[33]
In March 2019, Missouri Family Health Council was the state's only Title X administrator. The Council distributed approximately 34% of its funding to Planned Parenthood clinics.[34] In 2019, women in Missouri were eligible for pregnancy accommodation and pregnancy related disability as a result of legal abortion or miscarriage, and women claim such disability could not be treated differently than any other employee claiming disability.[35][36]
### Judicial history[edit]
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.[14] In 1979, a court found that the part of Missouri law dealing with women having abortions after the first trimester needing to have it performed in a hospital was unconstitutional.[37] Webster v. Reproductive Health Services was before the US Supreme Court in 1989. The Court ruled in a case over a Missouri law that banned abortions being performed in public buildings unless there was a need to save the life of the mother, required physicians to determine if a fetus was past 20 weeks and was viable in addition to other restrictions on a woman's ability to get an abortion. The US Supreme Court largely ruled in favor of the law, but made clear that this was not an overruling of Roe v. Wade.[38]
In 2019, a judge blocked a state law which would have banned abortion after eight weeks.[39]
### Clinic history[edit]
Number of abortion clinics in Missouri by year.
See also: Abortion clinic
Following the Roe v. Wade ruling, a number of abortion clinics quickly set up in the state. These included private suppliers, many of which remained in the state during the 1980s.[20] Reproductive Health Services was a non-profit that provided abortion services in the state operating during that time.[20] Between 1982 and 1992, the number of abortion clinics in the state decreased by 17, going from 29 in 1982 to 12 in 1992.[40]
Planned Parenthood in St. Louis took over operations of Reproductive Health Services on May 1, 1996. Prior to this, while Planned Parenthood had operated in the state, they had not provided abortion services.[20] In 1998, they moved three blocks to a new building.[20] After TRAP laws came into effect in Missouri and Texas, women had to travel even greater distances to be able to visit an abortion clinic.[41]
In 2014, there was only one abortion clinic in the state.[42] In 2014, 99% of the counties in the state did not have an abortion clinic. That year, 94% of women in the state aged 15–44 lived in a county without an abortion clinic.[41] In March 2016, there were 13 Planned Parenthood clinics in the state.[43] In 2016, Planned Parenthood's clinic that provided abortions in Colombia had to stop doing so while they faced a court injunction they were challenging over the legal need to be a licensed ambulatory surgical centers and to have hospital admitting privileges.[20]
In 2017, there were 12 Planned Parenthood clinics in a state with a population of 1,365,575 women aged 15–49 of which 1 offered abortion services.[44][20] Reproductive Health Services of Planned Parenthood St. Louis Region was the only licensed abortion service provider in the state in 2017, providing reproductive services primarily to women from Missouri and Illinois but also 10 other states. Only about 10% of their operations were related to abortion services.[20] On May 28, 2019, the sole remaining abortion clinic in Missouri announced it would likely be shutting down by the end of the week as the state pulled its operating license. They were seeking an injunction to prevent that from happening.[45] They succeeded when Missouri Circuit Court Judge Michael Stelzer granted a temporary injunction, saying in giving the order that the clinic "demonstrated that immediate and irreparable injury will result" and also saying that doing so "is necessary to preserve the status quo and prevent irreparable injury."[46] He then set a hearing date for June 4, 2019.[46]
## Statistics[edit]
In the period between 1972 and 1974, there were zero recorded illegal abortion death in the state.[47] In 1990, 597,000 women in the state faced the risk of an unintended pregnancy.[40] In 2010, the state had zero publicly funded abortions.[48] In 2013, among white women aged 15–19, there were abortions 670, 440 abortions for black women aged 15–19, 80 abortions for Hispanic women aged 15–19, and 80 abortions for women of all other races.[49] In 2014, 45% of adults said in a poll by the Pew Research Center that abortion should be legal in all or most cases.[50] According to a 2014 Public Religion Research Institute (PRRI) study, 51% of white women in the state believed that abortion be legal in all or most cases.[51] In 2017, about 33% of abortions were performed using drug induced abortions. The percentage had been increasing every year for several years.[20]
Number of reported abortions, abortion rate and percentage change in rate by geographic region and state in 1992, 1995 and 1996[52] Census division and state Number Rate % change 1992–1996
1992 1995 1996 1992 1995 1996
West North Central 57,340 48,530 48,660 14.3 11.9 11.9 –16
Iowa 6,970 6,040 5,780 11.4 9.8 9.4 –17
Kansas 12,570 10,310 10,630 22.4 18.3 18.9 –16
Minnesota 16,180 14,910 14,660 15.6 14.2 13.9 –11
Missouri 13,510 10,540 10,810 11.6 8.9 9.1 –21
Nebraska 5,580 4,360 4,460 15.7 12.1 12.3 –22
North Dakota 1,490 1,330 1,290 10.7 9.6 9.4 –13
South Dakota 1,040 1,040 1,030 6.8 6.6 6.5 –4
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^^
Missouri 13,510 11.6 1992 [52]
Missouri 10,540 8.9 1995 [52]
Missouri 10,810 9.1 1996 [52]
Missouri 8,935 7.6 119 5,060 4.3 67 8.8 2014 [53]
Missouri 8,636 7.3 115 4,765 4 63 9.5 2015 [54]
Missouri 9,036 7.7 121 4,562 3.9 61 9.0 2016 [55]
^number of abortions per 1,000 women aged 15–44; ^^number of abortions per 1,000 live births
## Women's abortion experiences[edit]
This section may stray from the topic of the article. Please help improve this section or discuss this issue on the talk page. (June 2020)
Janice Mac Avoy, a lawyer with Fried, Frank, Harris, Shriver & Jacobson, had an abortion when she was an 18-year-old in high school. She was on track to become the first person in her family to graduate from high school and go to college, for which she had a scholarship, and then hopefully on to law school. She decided to have an abortion because she saw becoming a mother as not compatible with her goals.[56]
Then 36-year-old Robin Utz of St. Louis had an abortion in November 2016 in week 21 of her pregnancy. The reason she got an abortion was she was told by her doctors that her daughter had a fatal kidney disease and could not survive outside the womb. Submitting testimony to the Missouri legislature in early 2018, she said, "A 20-week abortion ban sounds OK, but if that gets passed, what's next — 18 weeks, 15 weeks? At what point does it make abortion truly illegal? It's terrifying and it's willfully ignorant."[19]
30-year-old Missouri resident Lexi Moore got a medicated abortion at a Planned Parenthood clinic in September 2018. She said, "It's safe and comfortable. [...] You get to sit in the comfort of your home instead of doing it in a clinic or in a back alley. ... You will have cramps, like a heavy period. But it's worth it in the end, and you have control over that."[57]
## Abortion rights views and activities[edit]
Women's March on St. Louis 1-21-17
Women's March on St. Louis 1-21-17
### Views[edit]
In talking about the granting of a temporary restraining order allowing the state's last remaining abortion clinic to remain open, President and CEO of Planned Parenthood Leana Wen said, "This is a victory for women across Missouri, but this fight is far from over. We have seen just how vulnerable access to abortion care is in Missouri — and in the rest of the country."
### Protests[edit]
Women from the state participated in marches supporting abortion rights as part of a #StoptheBans movement in May 2019.[58]
## Anti-abortion views and activities[edit]
### Views[edit]
In talking about the granting of a temporary restraining order allowing the state's last remaining abortion clinic to remain open, Students for Life of America President Kristan Hawkins said, "Planned Parenthood caused this artificial crisis when they ignored the law and refused to comply with the state of Missouri's very reasonable requests." [46]
## 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 (12): 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. ^ a b c d e f "States pushing abortion bans have highest infant mortality rates". NBC News. Retrieved 2019-05-25.
9. ^ 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.
10. ^ Larimer, Sarah (January 8, 2016). "The 'tampon tax,' explained". The Washington Post. Archived from the original on December 11, 2016. Retrieved December 10, 2016.
11. ^ 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.
12. ^ Hillin, Taryn. "These are the U.S. states that tax women for having periods". Splinter. Retrieved 2017-12-15.
13. ^ "Election Results 2018: Nevada Ballot Questions 1-6". KNTV. Retrieved 2018-11-07.
14. ^ a b c Buell, Samuel (1991-01-01). "Criminal Abortion Revisited". New York University Law Review. 66 (6): 1774–1831. PMID 11652642.
15. ^ Adolescence, Committee On (2017-02-01). "The Adolescent's Right to Confidential Care When Considering Abortion". Pediatrics. 139 (2): e20163861. doi:10.1542/peds.2016-3861. ISSN 0031-4005. PMID 28115537.
16. ^ Pierson, Vicky Howell; Features Submission, Haworth Continuing (1995-04-04). "Missouri's Parental Consent Law and Teen Pregnancy Outcomes". Women & Health. 22 (3): 47–58. doi:10.1300/j013v22n03_04. ISSN 0363-0242. PMID 7638977.
17. ^ "State Policy On Informed Consent for Abortion" (PDF). Guttmacher Policy Review. Fall 2007. Retrieved May 22, 2019.
18. ^ a b c d 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.
19. ^ a b "State legislatures see flurry of activity on abortion bills". PBS NewsHour. 2018-02-03. Retrieved 2019-05-26.
20. ^ a b c d e f g h i McCann, Allison (May 23, 2017). "Seven states have only one remaining abortion clinic. We talked to the people keeping them open". Vice News. Retrieved 2019-05-23.
21. ^ Lartey, Jamiles (2019-05-22). "Louisiana senate passes anti-abortion bill in latest attack on women's rights". The Guardian. ISSN 0261-3077. Retrieved 2019-05-22.
22. ^ "National Debate Over Abortion Laws Comes To Rhode Island". www.wbur.org. Retrieved 2019-05-23.
23. ^ "MO HB126 - 2019 - Regular Session". LegiScan.
24. ^ "MO SB139 - 2019 - Regular Session". LegiScan.
25. ^ "100th General Assembly, 1st Regular Session - HB126". Missouri House of Representatives. Retrieved February 9, 2019.
26. ^ "MO HB126 - 2019 - Regular Session". LegiScan.com. History. Retrieved February 16, 2019. "2019-01-30 House Referred: Children and Families; 2019-02-12 House Public Hearing Completed"
27. ^ "House and Senate Joint Bill Tracking - 2019 Regular Session - HB126". house.mo.gov. Missouri House of Representatives. Retrieved February 26, 2019. "Date/Last Action: 2/21/2019 - Reported Do Pass (H)"
28. ^ Cole, Ashley (February 21, 2019). "Bill to ban fetal heartbeat abortion in Missouri goes to House next". KSDK-TV. NBC 5. Retrieved February 26, 2019. "The bill to ban fetal heartbeat abortion will go to the Missouri House next. The rules committee met Thursday morning."
29. ^ Associated Press (February 28, 2019). "MO House passes fetal heartbeat bill; legislation moves to the Senate". ABC 7 - KHQA. Retrieved February 28, 2019.
30. ^ Ballentine, Summer (February 14, 2019). "Abortion bill could cost Missouri $7B in Medicaid funding". apnews.com. Associated Press. Retrieved February 16, 2019. "Republican House Speaker Elijah Haahr on Thursday called a bill to ban most abortions after a fetal heartbeat is detected a priority"
31. ^ McKinley, Edward; Woodall, Hunter (February 12, 2019). "With eye on Supreme Court, Missouri Republicans file flurry of anti-abortion bills". The Kansas City Star. Retrieved February 16, 2019. "Haahr said he supports the “heartbeat bill” and that some form of anti-abortion legislation will definitely pass the House this year."
32. ^ McKinley, Edward; Woodall, Hunter (February 12, 2019). "With eye on Supreme Court, Missouri Republicans file flurry of anti-abortion bills". The Kansas City Star. Retrieved February 16, 2019. "Gov. Mike Parson, asked if he would sign such legislation, said: “I’ve been pro-life my entire career, and I support that all the time… I’m going to support pro-life.”"
33. ^ "Yes, you can blame the patriarchy for these horrible abortion laws. We did the math". Mother Jones. Retrieved 2019-05-26.
34. ^ Mir, Alice; Ollstein, A.; Roubein, Rachel. "States struggle to replace Planned Parenthood as Trump rules loom". POLITICO. Retrieved 2019-05-23.
35. ^ "U.S. Department of Labor - Employment Protection For Workers Who Are Pregnant Or Nursing". www.dol.gov. Retrieved 2019-05-29.
36. ^ "Employment Protections For Workers Who Are Pregnant or Nursing". www.dol.gov. Retrieved 2019-05-29.
37. ^ Tribune, Chicago. "Timeline of abortion laws and events". chicagotribune.com. Retrieved 2019-05-23.
38. ^ "Timeline of Important Reproductive Freedom Cases Decided by the Supreme Court". American Civil Liberties Union. Retrieved 2019-05-25.
39. ^ Kelly, Caroline; Kupperman, Tammy (August 27, 2019). "Judge blocks Missouri 8-week abortion ban". CNN. Retrieved August 27, 2019.
40. ^ 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.
41. ^ a b businessinsider (2018-08-04). "This is what could happen if Roe v. Wade fell". Business Insider (in Spanish). Retrieved 2019-05-24.
42. ^ 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.
43. ^ Bohatch, Emily. "27 states with the most Planned Parenthood clinics". thestate. Retrieved 2019-05-24.
44. ^ "Here's Where Women Have Less Access to Planned Parenthood". Retrieved 2019-05-23.
45. ^ "Missouri's last abortion clinic says it may lose its license this week". www.cbsnews.com. Retrieved 2019-05-28.
46. ^ a b c "Text-Only NPR.org: Missouri's Last Abortion Provider Wins Reprieve, As Judge Rules Against State". text.npr.org. Retrieved 2019-06-02.
47. ^ Cates, Willard; Rochat, Roger (March 1976). "Illegal Abortions in the United States: 1972–1974". Family Planning Perspectives. 8 (2): 86–92. doi:10.2307/2133995. JSTOR 2133995. PMID 1269687.
48. ^ "Guttmacher Data Center". data.guttmacher.org. Retrieved 2019-05-24.
49. ^ "No. of abortions among women aged 15–19, by state of residence, 2013 by racial group". Guttmacher Data Center. Retrieved 2019-05-24.
50. ^ "Views about abortion by state - Religion in America: U.S. Religious Data, Demographics and Statistics". Pew Research Center. Retrieved 2019-05-23.
51. ^ Brownstein, Ronald (2019-05-23). "White Women Are Helping States Pass Abortion Restrictions". The Atlantic. Retrieved 2019-05-26.
52. ^ a b c d "Abortion Incidence and Services in the United States, 1995-1996". Guttmacher Institute. 2005-06-15. Retrieved 2019-06-02.
53. ^ 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.
54. ^ 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.
55. ^ Jatlaoui, Tara C. (2019). "Abortion Surveillance — United States, 2016". MMWR. Surveillance Summaries. 68 (11): 1–41. doi:10.15585/mmwr.ss6811a1. ISSN 1546-0738. PMID 31774741.
56. ^ Liptak, Adam (2016-02-29). "Eyes on Kennedy, Women Tell Supreme Court Why Abortion Was Right for Them". The New York Times. ISSN 0362-4331. Retrieved 2019-06-02.
57. ^ "Would overturning abortion rights turn back clock to 1973?". The Public's Radio. 2019-05-26. Retrieved 2019-05-26.
58. ^ Bacon, John. "Abortion rights supporters' voices thunder at #StopTheBans rallies across the nation". USA Today. Retrieved 2019-05-25.
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
| Abortion in Missouri | None | 888 | wikipedia | https://en.wikipedia.org/wiki/Abortion_in_Missouri | 2021-01-18T18:30:59 | {"wikidata": ["Q64876932"]} |
A rare, genetic dysostosis with predominant craniofacial involvement characterized by bilateral external ear malformations, mandibular condyle hypoplasia, microstomia, micrognathia, microglossia and facial asymmetry. Additional manifestations include hypotonia, ptosis, cleft palate, full cheeks, developmental delay, hearing impairment and respiratory distress. Significant intra- and interfamilial phenotypic variation has been reported.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Auriculocondylar syndrome | c1865295 | 889 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=137888 | 2021-01-23T18:09:52 | {"gard": ["9798"], "mesh": ["C538270"], "omim": ["602483", "612798", "614669", "615706"], "umls": ["C1865295"], "icd-10": ["Q75.8"], "synonyms": ["Question mark ear syndrome"]} |
Ataxia with oculomotor apraxia is a condition characterized by problems with movement that worsen over time. The hallmark of this condition is poor coordination and balance (ataxia), which is often the first symptom. Most affected people also have oculomotor apraxia, which makes it difficult to move their eyes side-to-side. People with oculomotor apraxia have to turn their head to see things in their side (peripheral) vision.
There are several types of ataxia with oculomotor apraxia, the most common of which are types 1, 2, and 4. The types are very similar but are caused by mutations in different genes.
Type 1 begins around age 4. In addition to ataxia and oculomotor apraxia, affected individuals can have involuntary jerking movements (chorea) or muscle twitches (myoclonus); these movement problems tend to disappear over time. Individuals with this type may also develop muscle wasting in their hands and feet, which further impairs movement. As in all forms of ataxia with oculomotor apraxia, nearly all people with type 1 develop nerve abnormalities (neuropathy). Neuropathy impairs reflexes and leads to limb weakness and an inability to sense vibrations. Many individuals with ataxia with oculomotor apraxia require wheelchair assistance, typically 10 to 15 years after the start of movement problems.
People with some types of ataxia with oculomotor apraxia may have characteristic blood abnormalities. Individuals with type 1 tend to have reduced amounts of a protein called albumin, which transports molecules in the blood. The shortage of albumin likely results in elevated levels of cholesterol circulating in the bloodstream. Increased cholesterol levels raise a person's risk of developing heart disease.
Ataxia with oculomotor apraxia type 2 usually begins around age 15. As in type 1, affected individuals may have chorea or myoclonus, although these movement problems persist throughout life in type 2. Neuropathy is also common in this type.
A key feature of ataxia with oculomotor apraxia type 2 is high amounts of a protein called alpha-fetoprotein (AFP) in the blood. (Raised levels of this protein are normally seen in the bloodstream of pregnant women.) Individuals with type 2 may also have high amounts of a protein called creatine phosphokinase (CPK) in their blood. This protein is normally found primarily in muscle tissue. The effect of abnormally high levels of AFP or CPK in people with ataxia with oculomotor apraxia type 2 is unknown. Although individuals with type 2 usually have normal albumin levels, cholesterol may be elevated.
Ataxia with oculomotor apraxia type 4 begins around age 4. In addition to ataxia and oculomotor apraxia, individuals with this type typically develop dystonia, which is involuntary, sustained muscle tensing that causes unusual positioning of body parts. Dystonia can be the first feature of the condition, and it tends to disappear gradually over time. Muscle wasting in the hands and feet and neuropathy are also common in individuals with type 4.
In ataxia with oculomotor apraxia type 4, albumin levels can be low, and cholesterol or AFP can be elevated. However, the amounts of these molecules are normal in many affected individuals.
Intelligence is usually not affected by ataxia with oculomotor apraxia, but some people with the condition have intellectual disability.
## Frequency
Ataxia with oculomotor apraxia is a rare condition. Types 1 and 4 are most frequent in Portugal, and type 1 is also found in Japan. Type 2 is estimated to occur in 1 in 900,000 individuals worldwide. Type 3 has been found in only one family.
## Causes
Mutations in the APTX, SETX, or PNKP gene cause ataxia with oculomotor apraxia types 1, 2, or 4, respectively. Mutations in another gene cause ataxia with oculomotor apraxia type 3.
The APTX, SETX, and PNKP genes provide instructions for making proteins that are involved in repairing damaged DNA. Mutations in any of these genes reduce the amount of functional protein produced from that gene. This shortage prevents the efficient repair of DNA damage, which leads to the accumulation of broken DNA strands. DNA breaks may be caused by potentially harmful molecules (called reactive oxygen species) produced during normal cellular functions, natural and medical radiation, or other environmental exposures. They may also occur when chromosomes exchange genetic material in preparation for cell division. DNA damage that is not repaired makes the cell unstable and can lead to cell death. It is thought that cell death has a particularly severe effect in the brain because the nervous system does not replace nerve cells that have been lost. The part of the brain involved in coordinating movements (the cerebellum) is especially at risk. It is thought that the loss of brain cells in the cerebellum causes the movement problems characteristic of ataxia with oculomotor apraxia.
### Learn more about the genes associated with Ataxia with oculomotor apraxia
* APTX
* PNKP
* SETX
Additional Information from NCBI Gene:
* PIK3R5
* XRCC1
## Inheritance Pattern
All types of this condition are 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
| Ataxia with oculomotor apraxia | c1859598 | 890 | medlineplus | https://medlineplus.gov/genetics/condition/ataxia-with-oculomotor-apraxia/ | 2021-01-27T08:25:54 | {"gard": ["9283", "12860", "13112", "13111"], "mesh": ["C538013"], "omim": ["208920", "615217", "616267", "606002"], "synonyms": []} |
Subacute lymphocytic thyroiditis
Other namesSilent thyroiditis or Painless thyroiditis
SpecialtyEndocrinology
Subacute lymphocytic thyroiditis is a form of thyroiditis. Subacute lymphocytic thyroiditis may occur at any age and is more common in females.
A variant of subacute lymphocytic thyroiditis occurs postpartum: postpartum thyroiditis. Both of these entities can be considered subtypes of Hashimoto's thyroiditis and have an autoimmune basis. Anti-thyroid antibodies are common in all three and the underlying histology is similar. [1][2] This disorder should not be confused with de Quervain's thyroiditis which is another form of subacute thyroiditis.
## Contents
* 1 Symptoms and signs
* 2 Diagnosis
* 3 Treatment
* 4 References
## Symptoms and signs[edit]
Subacute lymphocytic thyroiditis features a small goiter without tenderness. This condition tends to have a phase of hyperthyroidism followed by a return to a euthyroid state, and then a phase of hypothyroidism, followed again by a return to the euthyroid state. The time span of each phase can vary; however, each phase usually lasts 2–3 months.[1]
## Diagnosis[edit]
Subacute lymphocytic thyroiditis can only be diagnosed correctly by taking a radioactive iodine uptake test (RAIU) test.[1][3] During both the hyperthyroid and hypothyroid phases, radioiodine uptake is decreased.[4] This situation contrasts greatly with the elevated iodine uptake found in patients with Graves' disease.[1]
## Treatment[edit]
Treatment is based on symptoms. Beta-blockers relieve rapid heart rate and excessive sweating during the hyperthyroid phase.[4]
## References[edit]
1. ^ a b c d Thyroiditis: Differential Diagnosis and Management, American Family Physician, February 15, 2000
2. ^ "Subacute lymphocytic thyroiditis" at Dorland's Medical Dictionary
3. ^ Description of Radioactive Iodine Uptake Test, WebMD.com, August 14, 2008
4. ^ a b NIH Medline Plus
* v
* t
* e
Thyroid disease
Hypothyroidism
* Iodine deficiency
* Cretinism
* Congenital hypothyroidism
* Myxedema
* Myxedema coma
* Euthyroid sick syndrome
* Signs and symptoms
* Queen Anne's sign
* Woltman sign
* Thyroid dyshormonogenesis
* Pickardt syndrome
Hyperthyroidism
* Hyperthyroxinemia
* Thyroid hormone resistance
* Familial dysalbuminemic hyperthyroxinemia
* Hashitoxicosis
* Thyrotoxicosis factitia
* Thyroid storm
Graves' disease
* Signs and symptoms
* Abadie's sign of exophthalmic goiter
* Boston's sign
* Dalrymple's sign
* Stellwag's sign
* lid lag
* Griffith's sign
* Möbius sign
* Pretibial myxedema
* Graves' ophthalmopathy
Thyroiditis
* Acute infectious
* Subacute
* De Quervain's
* Subacute lymphocytic
* Palpation
* Autoimmune/chronic
* Hashimoto's
* Postpartum
* Riedel's
Enlargement
* Goitre
* Endemic goitre
* Toxic nodular goitre
* Toxic multinodular goiter
* Thyroid nodule
* Colloid nodule
*[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
| Subacute lymphocytic thyroiditis | c1306804 | 891 | wikipedia | https://en.wikipedia.org/wiki/Subacute_lymphocytic_thyroiditis | 2021-01-18T18:57:30 | {"umls": ["C1306804"], "wikidata": ["Q4368172"]} |
Seizures-intellectual disability due to hydroxylysinuria syndrome is characterised by hydroxylysinuria, myoclonic and motor seizures and intellectual deficit. It has been described in a brother and sister born to consanguineous parents and in one unrelated patient.
*[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
| Seizures-intellectual disability due to hydroxylysinuria syndrome | c1855986 | 892 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79156 | 2021-01-23T17:14:59 | {"mesh": ["C565502"], "omim": ["236900"], "icd-10": ["E72.3"]} |
A rare neoplastic gastroenterologic disease most often found in children, which usually presents with the non-specific symptoms of a palpable mass, vomiting, abdominal pain, jaundice, and weight loss/failure to thrive. Histologically, this malignant epithelial pancreatic neoplasm of the exocrine cells is characterized by multiple lines of differentiation (acinar, ductal, mesenchymal, neuroendocrine) and the presence of squamoid nests.
## Epidemiology
The incidence is less than 1/1,000,000 in Europe. Pancreatoblastoma accounts for 0.5% of all pancreatic exocrine tumors and occurs equally in females and males. It is the most common malignant pancreatic tumor in young children and has a mean age of diagnosis of 5 years.
## Clinical description
Pancreatoblastoma most often presents in children under the age of 10 (mean of 5 years). Onset in adulthood (third/fourth decade) is extremely rare, and patients are more likely to develop metastases. Symptoms are often non-specific and include a large abdominal mass, abdominal distension/pain, failure to thrive, diarrhea, vomiting and jaundice. Tumors in the head of the pancreas can lead to mechanical obstruction of the upper duodenum and gastric outlet, as well as gastrointestinal bleeding. Local invasion and metastasis to the liver (most commonly), lungs and/or regional lymph nodes can often be discovered at diagnosis. Pancreatoblastoma can sometimes be associated with Beckwith-Wiedemann syndrome and familial adenomatous polyposis (FAP).
## Etiology
The etiology is unknown but pancreatoblastoma can occur in any part of the pancreas. It is a malignant embryonal tumor that seems to recapitulate the embryogenesis of the pancreas, presumably because it originates from the pluripotent pancreatic stem cells during foregut development. Sporadic and FAP-associated pancreatoblastomas have frequent alterations in the adenomatous polyposis coli (APC)/beta-catenin pathway, and allelic loss in chromosome 11p.
## Diagnostic methods
Diagnosis is based on histological characteristics. Pancreatoblastoma is usually a large (2 to 20 cm), encapsulated mass with a histological picture of multiple squamoid nests composed of whorls of spindle-shaped cells that are diagnostic of this tumor. It shows significant acinar cell differentiation but also ductal, mesenchymal and neuroendocrine differentiation. The tumor marker alpha-fetoprotein (AFP) is raised in 68% of cases, regardless of age. Full staging needs to be performed, including ultrasound and computed tomography (CT) or magnetic resonance imaging (MRI) scans of the primary tumor, as well as CT scans of the chest to detect any metastasis.
## Differential diagnosis
Differential diagnoses include poorly differentiated adenocarcinomas, solid pseudopapillary tumors, pancreatic carcinoma, pancreatic neuroendocrine tumors and autoimmune pancreatitis.
## Management and treatment
Treatment involves complete surgical resection of the tumor. Procedures include a distal pancreatectomy with or without splenectomy (for tumors in the body and tail of pancreas) and pancreaticoduodenectomy (for those in the head of the pancreas). Chemotherapy (usually cisplatin and doxorubicin) and radiotherapy are used in cases of unresectable, recurrent or metastatic tumors with variable results. In adults, 5-fluorouracil/doxorubicin/mitomycin and doxorubicin/carboplatin have been given as adjuvant therapy.
## Prognosis
The prognosis for pediatric cases is usually good if the tumor is resectable, but recurrences still occur. If unresectable and in the presence of metastasis, pancreatoblastoma has an aggressive course and prognosis is poor. Adult cases usually have a poorer prognosis, with a median survival time of 15 months.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| Pancreatoblastoma | c0334489 | 893 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=677 | 2021-01-23T17:59:45 | {"gard": ["4210"], "mesh": ["C537162"], "umls": ["C0334489"], "icd-10": ["C25.1"]} |
HCV infections in children and pregnancy are less understood than in adults. Worldwide, the prevalence of hepatitis C virus infection in pregnant women and children has been estimated to 1-8% and 0.05-5% respectively.[1] The vertical transmission rate has been estimated to be 3-5% and there is a high rate of spontaneous clearance (25-50%) in the children. Higher rates have been reported for both vertical transmission (18%, 6-36% and 41%).[2][3] and prevalence in children (15%).[4]
In developed countries, transmission around the time of birth is now the leading cause of HCV infection. In the absence of virus in the mother's blood, transmission seems to be rare.[3] Factors associated with an increased rate of infection include membrane rupture of longer than 6 hours before delivery and procedures exposing the infant to maternal blood.[5] Cesarean sections are not recommended. Breastfeeding is considered safe if the nipples are not damaged. Infection around the time of birth in one child does not increase the risk in a subsequent pregnancy. All genotypes appear to have the same risk of transmission.
HCV infection is frequently found in children who have previously been presumed to have non-A, non-B hepatitis and cryptogenic liver disease.[6] The presentation in childhood may be asymptomatic or with elevated liver function tests.[7] While infection is commonly asymptomatic both cirrhosis with liver failure and hepatocellular carcinoma may occur in childhood.
## Diagnosis[edit]
Guidelines for the investigation of babies born to hepatitis C positive mothers have been published.[8]
In children born to hepatitis C virus antibody positive but hepatitis C virus RNA negative mothers, the alanine aminotransferase and hepatitis C virus antibodies should be investigated at 18-24 months of life. If both the alanine aminotransferase value is normal and hepatitis C virus antibody is not found, follow up should be interrupted.
In children born to hepatitis C virus RNA positive mothers, alanine aminotransferase and hepatitis C virus RNA should be investigated at 3 months of age. Of these
(1) hepatitis C virus RNA positive children should be considered infected if viremia is confirmed by a second assay performed by the 12th month of age
(2) hepatitis C virus RNA negative children with abnormal alanine aminotransferase should be tested again for viremia at 6-12 months and for antibodies to the hepatitis C virus at 18 months
(3) hepatitis C virus RNA negative children with normal alanine aminotransferase should be tested for antibodies to the hepatitis C virus and have their alanine aminotransferase reestimated at 18-24 months. They should be considered non infected if both the alanine aminotransferase is normal and the antibody levels to the hepatitis C virus are undetectable.
The presence of anti hepatitis C virus antibody beyond the 18th month of age in a never viremic child with normal alanine aminotransferase is likely consistent with past hepatitis C virus infection.
## Treatment[edit]
Treatment of children has been with interferon and ribavirin.[9] The response to treatment is similar to that in adults.[10] It shows a similar dependence on the genotype. Recurrence after transplant is universal and the outcomes after transplant are usually poor.[11]
In children treatment should be initiated within 12 weeks of the detection of the viral RNA if viral clearance has not occurred within this time.[12] Given the difficulties with establishing a diagnosis of hepatitis C infection in infancy, this recommendation does not apply to infants.
Both pegylated interferon and ribavirin are unsuitable for use in pregnancy and infancy: newer methods of treatment are urgently required.
## References[edit]
1. ^ Arshad M, El-Kamary SS, Jhaveri R (2011). "Hepatitis C virus infection during pregnancy and the newborn period--are they opportunities for treatment?". J Viral Hepat. 18 (4): 229–236. doi:10.1111/j.1365-2893.2010.01413.x. PMID 21392169.
2. ^ Hunt CM, Carson KL, Sharara AI (1997). "Hepatitis C in pregnancy". Obstet Gynecol. 89 (5 Pt 2): 883–890.
3. ^ a b Thomas SL, Newell ML, Peckham CS, Ades AE, Hall AJ (1998). "A review of hepatitis C virus (HCV) vertical transmission: risks of transmission to infants born to mothers with and without HCV viraemia or human immunodeficiency virus infection". Int J Epidemiol. 27 (1): 108–117. doi:10.1093/ije/27.1.108. PMID 9563703.
4. ^ Fischler B (2007). "Hepatitis C virus infection". Semin Fetal Neonatal Med. 12 (3): 168–173. doi:10.1016/j.siny.2007.01.008. PMID 17320495.
5. ^ Indolfi G, Resti M (2009). "Perinatal transmission of hepatitis C virus infection". J Med Virol. 81 (5): 836–843. doi:10.1002/jmv.21437. PMID 19319981.
6. ^ González-Peralta RP (1997). "Hepatitis C virus infection in pediatric patients". Clin Liver Dis. 1 (3): 691–705. doi:10.1016/s1089-3261(05)70329-9. PMID 15560066.
7. ^ Suskind DL, Rosenthal P. "Chronic viral hepatitis". Adolesc Med Clin. 15 (1): 145–58, x–xi. doi:10.1016/j.admecli.2003.11.001. PMID 15272262.
8. ^ Resti M, Bortolotti F, Vajro P, Maggiore G, Committee of Hepatology of the Italian Society of Pediatric Gastroenterology and Hepatology (2003). "Guidelines for the screening and follow-up of infants born to anti-HCV positive mothers". Dig Liver Dis. 35 (7): 453–457. doi:10.1016/s1590-8658(03)00217-2.CS1 maint: multiple names: authors list (link)
9. ^ Hu J, Doucette K, Hartling L, Tjosvold L, Robinson J (Jul 13, 2010). "Treatment of hepatitis C in children: a systematic review". PLoS ONE. 5 (7): e11542. doi:10.1371/journal.pone.0011542. PMC 2903479.
10. ^ Serranti D, Buonsenso D, Ceccarelli M, Gargiullo L, Ranno O, Valentini P (2011). "Pediatric hepatitis C infection: to treat or not to treat...what's the best for the child?". Eur Rev Med Pharmacol Sci. 15 (9): 1057–1067.
11. ^ Rumbo C, Fawaz RL, Emre SH, Suchy FJ, Kerkar N, Morotti RA, Shneider BL (2006). "Hepatitis C in children: a quaternary referral center perspective". J Pediatr Gastroenterol Nutr. 43 (2): 209–216. doi:10.1097/01.mpg.0000228117.52229.32.
12. ^ Lagging M, Duberg AS, Wejstål R, Weiland O, Lindh M, Aleman S, Josephson F, Swedish Consensus Group (2012). "Treatment of hepatitis C virus infection in adults and children: updated Swedish consensus recommendations". Scand J Infect Dis. 44 (7): 502–521. doi:10.3109/00365548.2012.669045. PMC 4732459.
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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
| HCV in children and pregnancy | None | 894 | wikipedia | https://en.wikipedia.org/wiki/HCV_in_children_and_pregnancy | 2021-01-18T18:58:39 | {"wikidata": ["Q17082305"]} |
Judging by the family of a colleague, McKusick (1986) suggested that space between the great toe and the second toe may be inherited as an irregular autosomal dominant.
Limbs \- Space between great toe and second toe 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
| TOES, SPACE BETWEEN FIRST AND SECOND | c1861058 | 895 | omim | https://www.omim.org/entry/189230 | 2019-09-22T16:32:29 | {"omim": ["189230"]} |
SCN2A related disorders are a group of epilepsy and neurodevelopmental disorders, each caused by changes (mutations) in a gene called SCN2A. These disorders range from mild to severe and primarily include:
* Infantile epileptic encephalopathy (IEE) - characterized by seizures beginning in infancy (before 12 months of age) followed by developmental delay.
* Benign (familial) infantile seizures (BISs) - characterized by seizures beginning in infancy that stop by 2 years of age, without major long-term effects.
* Autism spectrum disorder/intellectual disability (ASD/ID) - characterized by global developmental delay (particularly of social and language skills). Up to a third of children with ASD/ID may also develop seizures in childhood, around of after 12 months of age.
Signs and symptoms depend on the specific condition and severity in each person. Some children with an SCN2A related disorder do not fit directly into one of these major forms. Most children with SCN2A mutations will have seizures that start in the first few weeks of life. Other symptoms of an SCN2A related disorder may include feeding or gastrointestinal problems, developmental delay, movement disorders, and/or poor muscle tone (hypotonia).
SCN2A mutations may be inherited from a parent or may occur for the first time in a child with an SCN2A related disorder (a de novo mutation). Treatment depends on symptoms and severity, but often includes antiepileptic drugs (AEDs). Unfortunately, in many cases, seizures associated with SCN2A related disorders cannot be controlled, even with the use of multiple AEDs. However, for infants who begin to have seizures within 3 months of birth, nonselective sodium channel blockers (such as phenytoin and carbamazepine) are more effective. Treatment for global developmental delay, ASD, and other associated signs and symptoms follow standard management recommendations.
*[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
| SCN2A related disorders | None | 896 | gard | https://rarediseases.info.nih.gov/diseases/13355/scn2a-related-disorders | 2021-01-18T17:57:47 | {"synonyms": ["SCN2A-related disorders", "SCN2A related conditions", "SCN2A-related epilepsy", "SCN2A disorders", "SCN2a mutations", "SCN2A mutation"]} |
Peters anomaly is a disorder of the eye which involves thinning and clouding of the cornea and attachment of the iris to the cornea, which causes blurred vision. It may also be associated with clouding of the lens of the eye (cataracts) or other lens abnormalities. The cause of Peters anomaly is unknown; it may be caused by genetic factors (including alterations of several genes, like the FOXC1, PAX6, PITX2, or CYP1B1 genes, environmental factors, or both. The critical event must occur in the first trimester of pregnancy during the formation of the anterior chamber. Most cases of Peters anomaly are sporadic or inherited in an autosomal recessive pattern. Some few cases might be inherited in an autosomal dominant pattern. Peters anomaly may occur as an isolated ocular abnormality or in association with other ocular defects. Peters anomaly is a feature of the Krause-Kivlin syndrome and the Peters-plus syndrome. Treatment depends on the problems that the patient has and may include glaucoma treatment or surgery to correct the cataracts or other lens abnormalities.
*[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
| Peters anomaly | c0344559 | 897 | gard | https://rarediseases.info.nih.gov/diseases/7377/peters-anomaly | 2021-01-18T17:58:21 | {"mesh": ["C537884"], "omim": ["604229"], "umls": ["C0344559"], "orphanet": ["708"], "synonyms": []} |
## Summary
### Clinical characteristics.
X-linked protoporphyria (XLP) is characterized in affected males by cutaneous photosensitivity (usually beginning in infancy or childhood) that results in tingling, burning, pain, and itching within minutes of sun/light exposure and may be accompanied by swelling and redness. Blistering lesions are uncommon. Pain, which may seem out of proportion to the visible skin lesions, may persist for hours or days after the initial phototoxic reaction. Photosensitivity is lifelong. Multiple episodes of acute photosensitivity may lead to chronic changes of sun-exposed skin (lichenification, leathery pseudovesicles, grooving around the lips) and loss of lunulae of the nails. An unknown proportion of individuals with XLP develop liver disease. Except for those with advanced liver disease, life expectancy is not reduced. The phenotype in heterozygous females ranges from asymptomatic to as severe as in affected males.
### Diagnosis/testing.
The diagnosis of XLP is established in a male proband with markedly increased free erythrocyte protoporphyrin and zinc-chelated erythrocyte protoporphyrin by identification of a hemizygous pathogenic gain-of-function variant in ALAS2 on molecular genetic testing.
The diagnosis of XLP is established in a female proband with increased free erythrocyte protoporphyrin and zinc-chelated erythrocyte protoporphyrin by identification of a heterozygous pathogenic gain-of-function variant in ALAS2 on molecular genetic testing.
### Management.
Treatment of manifestations: The phototoxicity and subsequent pain can be reduced by the administration of afamelanotide, an α-melanocyte-stimulating hormone analog. Otherwise, the only effective treatment is prevention of the painful attacks by avoidance of sun/light (including the long-wave ultraviolet light that passes through window glass) through use of protective clothing (e.g., long sleeves, gloves, wide-brimmed hats, protective tinted glass for cars and windows). Although topical sunscreens are typically not useful, some tanning products containing creams that cause increased pigmentation may be helpful. Oral Lumitene™ (β-carotene) has been used to improve tolerance to sunlight by causing mild skin discoloration due to carotenemia; however, a systematic review of treatment options showed no evidence of efficacy. Vitamin D supplementation is recommended to prevent vitamin D insufficiency due to sun avoidance.
Severe liver complications are difficult to treat: cholestyramine and other porphyrin absorbents (to interrupt the enterohepatic circulation of protoporphyrin and promote its fecal excretion) and plasmapheresis and intravenous hemin are sometimes beneficial. Liver transplantation can be a lifesaving measure in individuals with severe protoporphyric liver disease; combined bone marrow and liver transplantation is indicated in those with liver failure to prevent future damage to the allografts.
Surveillance: Monitoring of: hepatic function every 6-12 months and hepatic imaging if cholelithiasis is suspected; erythrocyte protoporphyrin levels (free and zinc-chelated), hematologic indices, and iron profile annually; vitamin D 25-OH levels.
Agents/circumstances to avoid: Sunlight and UV light; for those with hepatic dysfunction, drugs that may induce cholestasis (e.g., estrogens). For those with cholestatic liver failure, protective filters should be used for the operating room lights for liver transplant surgery to avoid phototoxic damage.
Evaluation of relatives at risk: If the ALAS2 pathogenic variant has been identified in an affected family member, at-risk relatives can be tested as newborns or infants so that those with the pathogenic variant can benefit from early intervention (sun protection) and future monitoring for signs of liver dysfunction.
### Genetic counseling.
By definition, XLP is inherited in an X-linked manner. Affected males transmit the pathogenic variant to all of their daughters and none of their sons. Women with an ALAS2 pathogenic variant have a 50% chance of transmitting the variant to each child. Once the ALAS2 pathogenic variant has been identified in an affected family member, heterozygote testing for at-risk female relatives, prenatal testing for pregnancies at increased risk, and preimplantation genetic testing are possible.
## Diagnosis
There are no established guidelines or diagnostic algorithms.
### Suggestive Findings
X-linked protoporphyria (XLP) should be suspected in individuals with the following clinical findings and initial laboratory findings.
Clinical findings
* Cutaneous photosensitivity, usually beginning in childhood
* Burning, tingling, pain, and itching of the skin (the most common findings); may occur within minutes of sun/light exposure, followed later by erythema and swelling
* Painful symptoms; may occur without obvious skin damage
* Absent or sparse blisters and bullae
Note: The absence of skin damage (e.g., scarring), vesicles, and bullae often make it difficult to suspect the diagnosis.
* Hepatic complications, particularly cholestatic liver disease, may develop in fewer than 5% of patients.
Initial laboratory findings. Detection of markedly increased free erythrocyte protoporphyrin and zinc-chelated erythrocyte protoporphyrin is the most sensitive biochemical diagnostic test for XLP (Table 1).
Note: It is essential to use an assay for erythrocyte protoporphyrin that distinguishes between free protoporphyrin and zinc-chelated protoporphyrin to differentiate XLP from erythropoietic protoporphyria (EPP-AR) and several other conditions that may lead to elevation of erythrocyte protoporphyrins (see Table 1, footnotes 3 and 4).
### Table 1.
Biochemical Characteristics of X-Linked Protoporphyria (XLP)
View in own window
Enzyme
DefectEnzyme
ActivityErythrocytesUrineStoolOther
Erythroid-specific 5-aminolevulinate synthase 2 (ALAS2)>100% of normal 1Free protoporphyrin/
zinc-chelated protoporphyrin ratio 90:10 to 50:50 2, 3, 4Protoporphyrins not detectableProtoporphyrin normal or ↑Plasma porphyrins ↑ 5
1\.
Increased enzyme activity is due to ALAS2 pathogenic gain-of-function variants in exon 11. Note: Lymphocyte ferrochelatase activity is normal.
2\.
Many assays for erythrocyte protoporphyrin or "free erythrocyte protoporphyrin" measure both zinc-chelated protoporphyrin and free protoporphyrin. Free protoporphyrin is distinguished from zinc-chelated protoporphyrin by ethanol extraction or HPLC.
3\.
Protoporphyrins (usually zinc-chelated protoporphyrin) are also increased in lead poisoning, iron deficiency, anemia of chronic disease, and various hemolytic disorders, as well as in those porphyrias caused by biallelic pathogenic variants (e.g., harderoporphyria).
4\.
In erythropoietic protoporphyria, free protoporphyrin levels are elevated significantly as compared to zinc-chelated protoporphyrin (see Differential Diagnosis).
5\.
Plasma total porphyrins are increased in porphyrias with cutaneous manifestations including XLP. If plasma porphyrins are increased, the fluorescence emission spectrum of plasma porphyrins at neutral pH can be characteristic and can distinguish XLP and EPP-AR from other porphyrias. The emission maximum in XLP and EPP-AR occurs at 634 nm.
### Establishing the Diagnosis
Male proband. The diagnosis of X-linked protoporphyria (XLP) is established in a male proband with markedly increased free erythrocyte protoporphyrin and zinc-chelated erythrocyte protoporphyrin by identification of a hemizygous pathogenic gain-of-function variant in ALAS2 (encoding erythroid specific 5-aminolevulinate synthase 2) on molecular genetic testing (see Table 2).
Female proband. The diagnosis of X-linked protoporphyria (XLP) is established in a female proband with increased free erythrocyte protoporphyrin and zinc-chelated erythrocyte protoporphyrin by identification of a heterozygous pathogenic gain-of-function variant in ALAS2 on molecular genetic testing (see Table 2).
#### Molecular Genetic Testing
Molecular genetic testing approaches include gene-targeted testing (single-gene testing).
Single-gene testing. Sequence analysis of ALAS2 detects small intragenic deletions/insertions and missense, nonsense, and splice site variants.
Note: All ALAS2 pathogenic variants associated with XLP reported to date are gain-of-function missense, nonsense, or deletion variants in the last exon (exon 11; see Molecular Genetics). Therefore, sequence analysis of all other exons, as well as testing for haploinsufficiency or duplication (overexpression) is not indicated based on current knowledge.
### Table 2.
Molecular Genetic Testing Used in X-Linked Protoporphyria
View in own window
Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method
ALAS2Sequence analysis 3All variants reported to date 4
Gene-targeted deletion/duplication analysis 5See footnote 6.
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\.
Balwani [2019]
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\.
All ALAS2 pathogenic variants reported to date are gain-of-function missense variants; thus, testing for deletion (haploinsufficiency) or duplication (overexpression) is not indicated.
## Clinical Characteristics
### Clinical Description
The natural history of X-linked protoporphyria (XLP) is not as well characterized as that of the autosomal recessive type of erythropoietic protoporphyria (EPP-AR) (see Differential Diagnosis). A natural history study from the US described 22 individuals with XLP from seven unrelated families [Balwani et al 2017].
#### XLP in Males
While the cutaneous manifestations in males with XLP are similar to those of EPP, Balwani et al [2017] suggest that males with XLP have significantly higher protoporphyrin levels and increased risk of liver dysfunction.
Photosensitivity. Onset of photosensitivity is typically in infancy or childhood (with the first exposure to sun); in most individuals with XLP the photosensitivity is lifelong.
Most males with XLP develop acute cutaneous photosensitivity within five to 30 minutes following exposure to sun or ultraviolet light. Photosensitivity symptoms are provoked mainly by visible blue-violet light in the Soret band, to a lesser degree in the long-wave UV region.
The initial symptoms reported are tingling, burning, and/or itching that may be accompanied by swelling and redness. Symptoms vary based on the intensity and duration of sun exposure; pain may be severe and refractory to narcotic analgesics, persisting for hours or days after the initial phototoxic reaction. Symptoms may seem out of proportion to the visible skin lesions. Blistering lesions are uncommon.
Affected males are also sensitive to sunlight that passes through window glass, which does not block long-wave UVA or visible light.
Cutaneous manifestations. Multiple episodes of acute photosensitivity may lead to chronic changes of sun-exposed skin (lichenification, leathery pseudovesicles, grooving around the lips) and loss of lunulae of the nails. The dorsum of the hands is most notably affected.
Severe scarring is rare, as are hyper- or hypopigmentation, skin friability, and hirsutism.
Unlike in other cutaneous porphyrias, blistering and scarring rarely occur.
Hepatobiliary manifestations. Protoporphyrin is not excreted in the urine by the kidneys, but is taken up by the liver and excreted in the bile. Accumulated protoporphyrin in the bile can form stones, reduce bile flow, and damage the liver. Protoporphyric liver disease may cause back pain and severe abdominal pain (especially in the right upper quadrant).
The information on XLP and liver disease is limited. The risk for liver dysfunction in XLP (observed in 5/31 affected individuals) is higher than the risk in EPP-AR [Whatley et al 2008]. A natural history study in the US showed that 40% of males with XLP had a history of abnormal liver enzymes compared to 33% of persons with EPP-AR. Gallstones were seen in 40% of males with XLP and 33.3% of females with XLP compared to 22.1% of individuals with EPP-AR.
Note that the information on liver involvement presented below is based on experience with liver disease in autosomal recessive EPP. Gallstones composed in part of protoporphyrin may be symptomatic in individuals with XLP and need to be excluded as a cause of biliary obstruction in persons with hepatic decompensation.
Life-threatening hepatic complications are preceded by increased levels of plasma and erythrocyte protoporphyrins, worsening hepatic function tests, increased photosensitivity, and increased deposition of protoporphyrins in hepatic cells and bile canaliculi. End-stage liver disease may be accompanied by motor neuropathy, similar to that seen in acute porphyrias. Comorbid conditions, such as viral hepatitis, alcohol abuse, and use of oral contraceptives, which may impair hepatic function or protoporphyrin metabolism, may contribute to hepatic disease in some [McGuire et al 2005].
Hematologic. Anemia and abnormal iron metabolism can occur in XLP. Mild anemia with microcytosis and hypochromia or occasionally reticulocytosis can be seen; however, hemolysis is absent or mild. In a recent series, 30% of males with XLP and 75% of females with XLP were anemic [Balwani et al 2017]
Vitamin D deficiency. Persons with XLP who avoid sun/light are at risk for vitamin D deficiency [Holme et al 2008, Spelt et al 2010, Wahlin et al 2011a].
Precipitating factors. Unlike the precipitating factors for acute hepatic porphyrias, the only known precipitating factor for XLP is sunlight.
#### XLP in Females
The phenotype of XLP in heterozygous females, the consequence of random X-chromosome inactivation, ranges from as severe as in affected males to asymptomatic. The median age of symptom onset for females with XLP was 11 years. Following sun exposure, symptom onset ranged from within ten minutes to none [Balwani et al 2017].
### Pathophysiology
Bone marrow reticulocytes are thought to be the primary source of the accumulated protoporphyrin that is excreted in bile and feces. Most of the excess protoporphyrin in circulating erythrocytes is found in a small percentage of cells, and the rate of protoporphyrin leakage from these cells is proportional to their protoporphyrin content.
The skin of persons with XLP is maximally sensitive to visible blue-violet light near 400 nm, which corresponds to the so-called "Soret band" (the narrow peak absorption maximum that is characteristic for protoporphyrin and other porphyrins). When porphyrins absorb light they enter an excited energy state. This energy is presumably released as fluorescence and by formation of singlet oxygen and other oxygen radicals that can produce tissue and vessel damage. This may involve lipid peroxidation, oxidation of amino acids, and cross-linking of proteins in cell membranes.
Photoactivation of the complement system and release of histamine, kinins, and chemotactic factors may mediate skin damage. Histologic changes occur predominantly in the upper dermis and include deposition of amorphous material containing immunoglobulin, complement components, glycoproteins, glycosaminoglycans, and lipids around blood vessels. Damage to capillary endothelial cells in the upper dermis has been demonstrated immediately after light exposure in this disease [Schneider-Yin et al 2000].
Long-term observations of patients with protoporphyria generally show little change in protoporphyrin levels in erythrocytes, plasma, and feces [Gou et al 2018]. In contrast, severe hepatic complications, when they occur, often follow increasing accumulation of protoporphyrin in erythrocytes, plasma, and liver. Iron deficiency and factors that impair liver function sometimes contribute. Enterohepatic circulation of protoporphyrin may favor its return and retention in the liver, especially when liver function is impaired. Liver damage probably results at least in part from protoporphyrin accumulation itself. As this porphyrin is insoluble, it tends to form crystalline structures in liver cells, can impair mitochondrial functions in liver cells, and can decrease hepatic bile formation and flow [Anderson et al 2001].
### Genotype-Phenotype Correlations
Because of the limited number of families known to have XLP, no genotype-phenotype correlations have been identified.
### Penetrance
XLP appears to be 100% penetrant in males.
In heterozygous females, clinical variability is attributed to random X-chromosome inactivation. Symptomatic females have been reported [Whatley et al 2008, Di Pierro et al 2009].
### Nomenclature
Although sometimes considered a synonym for XLP, the term "erythropoietic protoporphyria, X-linked dominant" is incorrect and should not be used: in all X-linked metabolic disorders the phenotype in heterozygous females can range from asymptomatic to as severe as that seen in affected male relatives.
### Prevalence
The prevalence of XLP is unknown.
* Based on studies from the UK, XLP appears to account for about 2% of individuals with the erythropoietic protoporphyria phenotype [Whatley et al 2010].
* In the US, XLP accounts for about 10% of individuals with the erythropoietic protoporphyria phenotype [Balwani et al 2017].
## Differential Diagnosis
Other causes of the X-linked protoporphyria (XLP) phenotype include the following:
* Polymorphous light eruption
* Solar urticaria
* Drug-induced photosensitivity
The phenotype of acquired late-onset cutaneous photosensitivity and elevated erythrocyte protoporphyrins, observed on occasion in myelodysplastic syndrome, is caused by somatic pathogenic variant(s) or chromosome 18 deletions that decrease ferrochelatase activity, presumably resulting from the genomic instability associated with this syndrome [Aplin et al 2001, Sarkany et al 2006, Blagojevic et al 2010].
Late-onset XLP with photosensitivity and elevated protoporphyrin levels has been reported in an instance of emerging myelodysplastic syndrome with somatic mosaicism of a nonsense ALAS2 variant in the bone marrow [Livideanu et al 2013].
Erythropoietic protoporphyria, autosomal recessive (EPP-AR) is caused by biallelic pathogenic variants in FECH (encoding ferrochelatase). The photosensitivity and cutaneous manifestations are clinically indistinguishable from those seen in males with XLP. The only significant phenotypic difference is that only about 20%-30% of individuals with EPP-AR have some degree of liver dysfunction, which is typically mild with slight elevations of the liver enzymes; however, up to 5% may develop more advanced liver disease.
In EPP-AR free protoporphyrin levels are elevated significantly as compared to zinc-chelated protoporphyrin (Table 3).
### Table 3.
Biochemical Characteristics of Autosomal Recessive Erythropoietic Protoporphyria (EPP-AR)
View in own window
Deficient
EnzymeEnzyme ActivityErythrocytesUrineStoolOther
Ferro-
chelatase~10%-30% of normalFree protoporphyrin ↑: >90% free, <10% zinc-chelatedProtoporphyrins normalProtoporphyrin normal or ↑Plasma porphyrins ↑
Possible additional genetic loci. It is presumed that additional loci may be responsible for the EPP phenotype (i.e., cutaneous photosensitivity and elevated erythrocyte protoporphyrins). Molecular epidemiology studies in the UK have identified biallelic FECH pathogenic variants or an ALAS2 pathogenic variant in only 94% of individuals with the EPP phenotype [Whatley et al 2010]. Studies in the North American population showed that 4% of persons with the EPP phenotype and elevated protoporphyrin levels did not have a detectable FECH or ALAS2 pathogenic variant.
Recently a heterozygous pathogenic variant was identified in CLPX, a heme biosynthesis modulator, in a family with elevated protoporphyrin levels and the EPP phenotype inherited in an autosomal dominant manner [Yien et al 2017].
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs of an individual diagnosed with X-linked protoporphyria (XLP), the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended [Balwani 2019]:
* Comprehensive medical history including history of phototoxicity
* Complete physical examination, including thorough skin examination
* Assessment of erythrocyte protoporphyrin levels (free and zinc-chelated), complete blood count with indices to evaluate for anemia, and iron profile (including ferritin) to monitor iron stores
* Assessment for liver disease:
* Hepatic function panel (including serum aminotransferases)
* Imaging studies such as abdominal ultrasound examination if cholelithiasis is suspected
* Newer imaging modalities such as Fibroscan® may be useful in evaluating liver fibrosis; however, this has not been validated in erythropoietic protoporphyria, autosomal recessive (EPP-AR) or XLP.
* A liver biopsy may be indicated to evaluate for protoporphyric liver disease.
* Vitamin D studies to evaluate for deficiency as affected individuals are predisposed to vitamin D insufficiency due to sun avoidance
* Consultation with a clinical geneticist and/or genetic counselor
### Treatment of Manifestations
Acute photosensitivity. Although several treatments have been proposed, most have been tried only in a single individual or a small number of patients.
* Use of protective clothing including long sleeves, gloves, and wide-brimmed hats is indicated.
* Protective tinted glass for cars and windows prevents exposure to UV light. Gray or smoke-colored filters provide only partial protection.
* Topical sunscreens are typically not useful; however, some tanning products containing creams that cause increased pigmentation may be helpful. Sun creams containing a physical reflecting agent (e.g., zinc oxide) are often effective but are not cosmetically acceptable to all.
* Oral Lumitene™ (β-carotene) (120–180 mg/dL) has been used to improve tolerance to sunlight if the dose is adjusted to maintain serum carotene levels in the range of 10-15 μmol/L (600–800 μg/dL), causing mild skin discoloration due to carotenemia. The beneficial effects of β-carotene may involve quenching of singlet oxygen or free radicals. However, a systematic review of about 25 studies showed that the available data are unable to prove efficacy of treatments including beta-carotene, N-acetyl cysteine, and vitamin C [Minder et al 2009].
* Afamelanotide (Scenesse®), a controlled-release, long-acting, α-melanocyte-stimulating hormone analogue, increases eumelanin by binding to the melanocortin-1 receptor and provides photoprotection by increasing pigmentation and antioxidant properties [Harms et al 2009, Minder 2010].
Afamelanotide showed positive results in Phase III clinical trials in the US and Europe [Langendonk et al 2015]. Long-term studies in Europe show good compliance, clinical effectiveness, and improved quality of life [Biolcati et al 2015]. It was approved for patients with the EPP phenotype by the European Medicines Agency in 2014, and by the FDA in October 2019.
Hepatic disease. Treatment of hepatic complications, which may be accompanied by motor neuropathy, is difficult.
* Cholestyramine and other porphyrin absorbents, such as activated charcoal, may interrupt the enterohepatic circulation of protoporphyrin and promote its fecal excretion, leading to some improvement [McCullough et al 1988].
* Plasmapheresis and intravenous hemin are sometimes beneficial [Do et al 2002].
* Liver transplantation has been performed as a lifesaving measure in individuals with severe protoporphyric liver disease [McGuire et al 2005, Wahlin et al 2011b]. However, many transplant recipients experience a recurrence of the protoporphyric liver disease in the transplanted liver. Combined bone marrow and liver transplantation is indicated in patients with liver failure to prevent future damage to the allografts [Rand et al 2006], and sequential liver and bone marrow transplantation has been successful in curing protoporphyric liver disease [Wahlin & Harper 2010].
* Bone marrow transplantation has also been attempted without liver transplantation in some instances. A child age two years with XLP and stage IV hepatic fibrosis was treated with a hematopoietic progenitor cell transplantation that stabilized his liver disease, thus avoiding liver transplantation [Butler et al 2015].
Other
* Vitamin D supplementation is advised as patients are predisposed to vitamin D insufficiency due to sun avoidance.
* Immunization for hepatitis A and B is recommended.
* Iron supplementation may be attempted in persons with XLP who have anemia and low ferritin levels.
Whatley et al [2008] reported some evidence of diminished iron stores in males with XLP; in one patient with iron deficiency, iron repletion decreased protoporphyrin accumulation and corrected the anemia. Subsequent reports indicate that iron supplementation can improve protoporphyrin levels, liver damage, and anemia in XLP [Landefeld et al 2016]. A pilot study using oral iron supplementation in persons with XLP showed a reduction in protoporphyrin levels [Balwani 2019].
### Surveillance
### Table 4.
Recommended Surveillance for Individuals with X-Linked Protoporphyria
View in own window
System/ConcernEvaluationFrequency
Erythrocyte
protoporphyrin levels &
plasma total porphyrinsBoth free & zinc-chelatedYearly
AnemiaComplete blood count w/indicesYearly
Iron store depletionSerum ferritin levelsYearly
Hepatic involvementHepatic function (liver transaminases)Yearly
US examination (if cholelithiasis is suspected)As indicated
Fibroscan® to evaluate for hepatic fibrosisAs indicated
Vitamin D deficiencyVitamin D 25-OH levels whether or not receiving supplementsYearly
US = ultrasound
### Agents/Circumstances to Avoid
The following are appropriate:
* Avoidance of sunlight and UV light
* In patients with hepatic dysfunction, avoidance of alcohol and drugs that may induce cholestasis (e.g., estrogens)
* In patients with cholestatic liver failure, use of protective filters for artificial lights in the operating room to prevent phototoxic damage during procedures such as endoscopy and surgery [Wahlin et al 2008]
### Evaluation of Relatives at Risk
It is appropriate to clarify the genetic status of at-risk newborn or infant family members in order to identify as early as possible those who would benefit from early intervention (sun protection) and routine monitoring (Table 4).
Evaluations include:
* Targeted molecular genetic testing if the ALAS2 pathogenic variant has been identified in an affected family member;
* Detection of markedly elevated erythrocyte protoporphyrin levels with a predominance of metal-free protoporphyrin if the pathogenic variant in the family is not known.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Pregnancy Management
There is no information on pregnancy management in XLP. Based on experience with autosomal recessive EPP, pregnancy is unlikely to be complicated by XLP [Poh-Fitzpatrick 1997].
### Therapies Under Investigation
A Phase II clinical trial with MT-7117, an oral small molecule that works as a melanocortin 1 receptor agonist and increases skin pigmentation, has been completed. A Phase III clinical trial for adults and children is planned for MT-7117.
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions.
*[v]: View this template
*[t]: Discuss this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
| X-Linked Protoporphyria | None | 898 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK121284/ | 2021-01-18T20:48:12 | {"synonyms": []} |
A number sign (#) is used with this entry because of evidence that spermatogenic failure-4 (SPGF4) and recurrent pregnancy loss (RPRGL4) are caused by heterozygous mutation in the SYCP3 gene (604759) on chromosome 12q23.
Description
Azoospermia, a condition in which there are no sperm present in the ejaculate, has historically been divided into 2 broad categories, obstructive (e.g., 277180) and nonobstructive. Among the genetically based, inherited nonobstructive causes are defects of spermatogenesis, which may interrupt the development of the sperm at various stages, either before (e.g., 415000) or during meiosis. SPGF4 is a form of azoospermia due to perturbations of meiosis.
For a discussion of phenotypic and genetic heterogeneity of spermatogenic failure, see SPGF1 (258150).
### Recurrent Pregnancy Loss
Miscarriage, the commonest complication of pregnancy, is the spontaneous loss of a pregnancy before the fetus has reached viability. The term therefore includes all pregnancy losses from the time of conception until 24 weeks' gestation. Recurrent miscarriage, defined as 3 or more consecutive pregnancy losses, affects about 1% of couples; when defined as 2 or more losses, the scale of the problem increases to 5% of all couples trying to conceive (summary by Rai and Regan, 2006).
Pregnancy losses have traditionally been designated 'spontaneous abortions' if they occur before 20 weeks' gestation and 'stillbirths' if they occur after 20 weeks. Subtypes of spontaneous abortions can be further distinguished on the basis of embryonic development and include anembryonic loss in the first 5 weeks after conception (so-called 'blighted ovum'), embryonic loss from 6 to 9 weeks' gestation, and fetal loss from 10 weeks' gestation through the remainder of the pregnancy. These distinctions are important because the causes of pregnancy loss vary over gestational ages, with anembryonic losses being more likely to be associated with chromosomal abnormalities, for example. Possible etiologies for recurrent pregnancy loss include uterine anatomic abnormalities, cytogenetic abnormalities in the parents or fetus, single gene disorders, thrombophilic conditions, and immunologic or endocrine factors as well as environmental or infectious agents (summary by Warren and Silver, 2008).
For a discussion of genetic heterogeneity of recurrent pregnancy loss, see RPRGL1 (614389).
Clinical Features
Chaganti and German (1979) reported a family in which infertility due to azoospermia or oligospermia affected 3 men related through their mothers. Testicular tissue obtained from the 46,XY phenotypically male but azoospermic propositus exhibited normal zygotene and pachytene pairing but premature desynapsis, with a reduced chiasma frequency and degeneration of spermatocytes during the first meiotic division. They postulated that a gene for meiotic disturbance, spermatogenic arrest, and azoospermia was segregating in this family, inherited in either an X-linked recessive or sex-limited autosomal dominant fashion.
Soderstrom and Suominen (1980) examined testicular biopsy specimens from 147 men with the clinical diagnosis of azoospermia or oligospermia. Meiotic arrest was found in 27 cases; closer scrutiny of 7 of the specimens showed that the pattern of meiotic arrest commonly varied in the same specimen, with coexisting areas of normal spermatogenesis and meiotic arrest. Because the timing of the arrest was consistently in the late pachytene stage, with condensation of chromatin along the synaptonemal complex, Soderstrom and Suominen (1980) concluded that there might be a genetic cause for the meiotic arrest.
Chaganti et al. (1980) reported 2 nearly azoospermic sibs of a consanguineous marriage; meiotic cells from a testicular biopsy of the 46,XY phenotypically male proband exhibited asynapsis, defective synaptonemal complex formation, chiasma failure, and degeneration of prophase spermatocytes with asynapsis. The meiotic abnormalities and infertility in this family appeared to comprise an autosomal recessive trait.
Cantu et al. (1981) studied three 46,XY phenotypically male, azoospermic brothers in a sibship of 13 from a consanguineous marriage and found a unique pattern of testicular histology with arrest of spermatogenesis at the pachytene stage of primary spermatocytes.
### Recurrent Pregnancy Loss 4
Bolor et al. (2009) studied 2 Japanese women, aged 39 and 29 years, with recurrent pregnancy loss. Each had experienced 3 miscarriages between 6 and 10 weeks of gestation, with no liveborns.
Molecular Genetics
Miyamoto et al. (2003) screened for mutations in the SYCP3 (604759) gene in DNA from 19 unrelated azoospermic patients with maturation arrest and 75 normal pregnancy-proven fertile men. In 2 patients they identified a heterozygous 1-bp deletion (643delA; 604759.0001) that resulted in truncation of the C-terminal, coiled-coil-forming region of the protein. The mutant protein showed greatly reduced interaction with the wildtype protein in vitro and interfered with SYCP3 fiber formation in cultured cells. The results suggested that SYCP3 has an essential meiotic function in human spermatogenesis that is compromised by the mutant protein by dominant-negative interference.
### Susceptibility to Recurrent Pregnancy Loss
Bolor et al. (2009) analyzed the SYCP3 gene in 26 Japanese women with recurrent pregnancy loss (RPRGL) and identified heterozygosity for a deletion and a point mutation in 2 of the women (604759.0002 and 604759.0003, respectively) that were not found in 150 fertile women. Both mutant proteins were shown to inhibit normal fiber formation of SYCP3 when coexpressed in a heterologous system. This suggested that the heterozygous mutations are likely to form aberrant lateral elements in the synaptonemal complex in a dominant-negative manner, possibly leading to abnormal chromosomal behavior in meiosis I during oogenesis. Bolor et al. (2009) noted that the SYCP3-related phenotype in humans, in which affected males are infertile whereas affected females have recurrent pregnancy loss, is similar to that seen in Scyp3-deficient mice (Yuan et al., 2000; Yuan et al., 2002).
INHERITANCE \- Autosomal dominant GENITOURINARY Internal Genitalia (Male) \- Azoospermia \- Testicular histology shows arrest of spermatogenesis at the pachytene stage of primary spermatocytes Internal Genitalia (Female) \- Spontaneous abortion, recurrent \- Fetal loss after 6 to 10 weeks of gestation MISCELLANEOUS \- Affected males are infertile, whereas affected females have recurrent pregnancy loss MOLECULAR BASIS \- Caused by mutation in the synaptonemal complex protein-3 gene (SYCP3, 604759.0001 ) ▲ 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
| SPERMATOGENIC FAILURE 4 | c0232981 | 899 | omim | https://www.omim.org/entry/270960 | 2019-09-22T16:22:13 | {"doid": ["0070176"], "mesh": ["C536875"], "omim": ["270960"], "orphanet": ["399805"], "synonyms": ["AZOOSPERMIA DUE TO PERTURBATIONS OF MEIOSIS", "Alternative titles", "SPERMATOGENESIS ARREST", "AZOOSPERMIA WITH MATURATION ARREST"]} |
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