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Tricyclic anti-depressant overdose
Other namesTCA poisoning, TCA overdose, TCA toxicity
Chemical structure of the tricyclic antidepressant amitriptyline
SpecialtyEmergency medicine
SymptomsElevated body temperature, large pupils, irregular heart beat, seizures[1]
Usual onsetWithin 6 hours[2]
CausesAccidental or purposeful[2][3]
TreatmentSupportive, sodium bicarbonate, lipid emulsion[2]
FrequencyRelatively common[1][4]
Deaths270 per year (UK)[1]
Tricyclic antidepressant overdose is poisoning caused by excessive medication of the tricyclic antidepressant (TCA) type. Symptoms may include elevated body temperature, blurred vision, dilated pupils, sleepiness, confusion, seizures, rapid heart rate, and cardiac arrest.[1] If symptoms have not occurred within six hours of exposure they are unlikely to occur.[2]
TCA overdose may occur by accident or purposefully in an attempt to cause death.[2] The toxic dose depends on the specific TCA.[2] Most are non-toxic at less than 5 mg/kg except for desipramine, nortriptyline, and trimipramine, which are generally non-toxic at less than 2.5 mg/kg.[5][2] In small children one or two pills can be fatal.[6] An electrocardiogram (ECG) should be included in the assessment when there is concern of an overdose.[2]
In overdose activated charcoal is often recommended.[1] People should not be forced to vomit.[2] In those who have a wide QRS complex (> 100 ms) sodium bicarbonate is recommended.[2] If seizures occur benzodiazepines should be given.[2] In those with low blood pressure intravenous fluids and norepinephrine may be used.[1] The use of intravenous lipid emulsion may also be tried.[3]
In the early 2000s TCAs were one of the most common cause of poisoning.[1] In the United States in 2004 there was more than 12,000 cases.[2] In the United Kingdom they resulted in about 270 deaths a year.[1] An overdose from TCAs was first reported in 1959.[1]
## Contents
* 1 Signs and symptoms
* 2 Cause
* 3 Pathophysiology
* 4 Diagnosis
* 5 Treatment
* 5.1 Decontamination
* 5.2 Medication
* 5.3 Dialysis
* 6 Epidemiology
* 7 References
* 8 External links
## Signs and symptoms[edit]
The peripheral autonomic nervous system, central nervous system and the heart are the main systems that are affected following overdose.[1] Initial or mild symptoms typically develop within 2 hours and include tachycardia, drowsiness, a dry mouth, nausea and vomiting, urinary retention, confusion, agitation, and headache.[7] More severe complications include hypotension, cardiac rhythm disturbances, hallucinations, and seizures. Electrocardiogram (ECG) abnormalities are frequent and a wide variety of cardiac dysrhythmias can occur, the most common being sinus tachycardia and intraventricular conduction delay resulting in prolongation of the QRS complex and the PR/QT intervals.[4] Seizures, cardiac dysrhythmias, and apnea are the most important life-threatening complications.[7]
## Cause[edit]
Tricyclics have a narrow therapeutic index, i.e., the therapeutic dose is close to the toxic dose.[7] Factors that increase the risk of toxicity include advancing age, cardiac status, and concomitant use of other drugs.[8] However, serum drug levels are not useful for evaluating risk of arrhythmia or seizure in tricyclic overdose.[9]
## Pathophysiology[edit]
Most of the toxic effects of TCAs are caused by four major pharmacological effects. TCAs have anticholinergic effects, cause excessive blockade of norepinephrine reuptake at the preganglionic synapse, direct alpha adrenergic blockade, and importantly they block sodium membrane channels with slowing of membrane depolarization, thus having quinidine-like effects on the myocardium.[1]
## Diagnosis[edit]
QRS widening seen in a person who has overdosed on TCAs
A specific blood test to verify toxicity is not typically available.[1] An electrocardiogram (ECG) should be included in the assessment when there is concern of an overdose.[2]
## Treatment[edit]
People with symptoms are usually monitored in an intensive care unit for a minimum of 12 hours, with close attention paid to maintenance of the airways, along with monitoring of blood pressure, arterial pH, and continuous ECG monitoring.[1] Supportive therapy is given if necessary, including respiratory assistance and maintenance of body temperature. Once a person has had a normal ECG for more than 24 hours they are generally medically clear.[1]
### Decontamination[edit]
Initial treatment of an acute overdose includes gastric decontamination. This is achieved by giving activated charcoal, which adsorbs the drug in the gastrointestinal tract either by mouth or via a nasogastric tube. Activated charcoal is most useful if given within 1 to 2 hours of ingestion.[10] Other decontamination methods such as stomach pumps, ipecac induced emesis, or whole bowel irrigation are generally not recommended in TCA poisoning.[11][12] Stomach pumps may be considered within an hour of ingestion but evidence to support the practice is poor.[1][13]
### Medication[edit]
Administration of intravenous sodium bicarbonate as an antidote has been shown to be an effective treatment for resolving the metabolic acidosis and cardiovascular complications of TCA poisoning. If sodium bicarbonate therapy fails to improve cardiac symptoms, conventional antidysrhythmic drugs or magnesium can be used to reverse any cardiac abnormalities. However, no benefit has been shown from Class 1 antiarrhythmic drugs; it appears they worsen the sodium channel blockade, slow conduction velocity, and depress contractility and should be avoided in TCA poisoning.[14] Low blood pressure is initially treated with fluids along with bicarbonate to reverse metabolic acidosis (if present), if the blood pressure remains low despite fluids then further measures such as the administration of epinephrine, norepinephrine, or dopamine can be used to increase blood pressure.[14]
Another potentially severe symptom is seizures: Seizures often resolve without treatment but administration of a benzodiazepine or other anticonvulsive may be required for persistent muscular overactivity. There is no role for physostigmine in the treatment of tricyclic toxicity as it may increase cardiac toxicity and cause seizures.[1] In cases of severe TCA overdose that are refractory to conventional therapy, intravenous lipid emulsion therapy has been reported to improve signs and symptoms in moribund patients suffering from toxicities involving several types of lipophilic substances, therefore lipids may have a role in treating severe cases of refractory TCA overdose.[15]
### Dialysis[edit]
Tricyclic antidepressants are highly protein bound and have a large volume of distribution; therefore removal of these compounds from the blood with hemodialysis, hemoperfusion or other techniques are unlikely to be of any significant benefit.[12]
## Epidemiology[edit]
Studies in the 1990s in Australia and the United Kingdom showed that between 8 and 12% of drug overdoses were following TCA ingestion. TCAs may be involved in up to 33% of all fatal poisonings, second only to analgesics.[16][17] Another study reported 95% of deaths from antidepressants in England and Wales between 1993 and 1997 were associated with tricyclic antidepressants, particularly dothiepin and amitriptyline. It was determined there were 5.3 deaths per 100,000 prescriptions.[18] Sodium channel blockers such as Dilantin should not be used in the treatment of TCA overdose as the Na+ blockade will increase the QTI.
## References[edit]
1. ^ a b c d e f g h i j k l m n o p Kerr G, McGuffie A, Wilkie S (2001). "Tricyclic antidepressant overdose: a review". Emerg Med J. 18 (4): 236–41. doi:10.1136/emj.18.4.236. PMC 1725608. PMID 11435353.
2. ^ a b c d e f g h i j k l m Woolf, Alan D.; Erdman, Andrew R.; Nelson, Lewis S.; Caravati, E. Martin; Cobaugh, Daniel J.; Booze, Lisa L.; Wax, Paul M.; Manoguerra, Anthony S.; Scharman, Elizabeth J.; Olson, Kent R.; Chyka, Peter A.; Christianson, Gwenn; Troutman, William G.; American Association of Poison Control Centers (1 January 2007). "Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management". Clinical Toxicology. 45 (3): 203–233. doi:10.1080/15563650701226192. ISSN 1556-3650. PMID 17453872. S2CID 27172531.
3. ^ a b Cao, Dazhe; Heard, Kennon; Foran, Mark; Koyfman, Alex (1 March 2015). "Intravenous lipid emulsion in the emergency department: a systematic review of recent literature". The Journal of Emergency Medicine. 48 (3): 387–397. doi:10.1016/j.jemermed.2014.10.009. ISSN 0736-4679. PMID 25534900.
4. ^ a b Thanacoody H, Thomas S (2005). "Tricyclic antidepressant poisoning : cardiovascular toxicity". Toxicol Rev. 24 (3): 205–14. doi:10.2165/00139709-200524030-00013. PMID 16390222. S2CID 44532041.
5. ^ Bartram, Tom (1 March 2008). "Best BETs from the Manchester Royal Infirmary. Bet 3. Toxic levels of tricyclic drugs in accidental overdose". Emergency Medicine Journal. 25 (3): 166–167. doi:10.1136/emj.2007.056788. ISSN 1472-0213. PMID 18299371. S2CID 22419961.
6. ^ Rosenbaum T, Kou M (2005). "Are one or two dangerous? Tricyclic antidepressant exposure in toddlers". J Emerg Med. 28 (2): 169–74. doi:10.1016/j.jemermed.2004.08.018. PMID 15707813.
7. ^ a b c Woolf AD, Erdman AR, Nelson LS, Caravati EM, Cobaugh DJ, Booze LL, Wax PM, Manoguerra AS, Scharman EJ, Olson KR, Chyka PA, Christianson G, Troutman WG (2007). "Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management". Clin Toxicol. 45 (3): 203–33. doi:10.1080/15563650701226192. PMID 17453872. S2CID 27172531.
8. ^ Preskorn S, Irwin H (1982). "Toxicity of tricyclic antidepressants--kinetics, mechanism, intervention: a review". J Clin Psychiatry. 43 (4): 151–6. PMID 7068546.
9. ^ Boehnert M, Lovejoy F (1985). "Value of the QRS duration versus the serum drug level in predicting seizures and ventricular arrhythmias after an acute overdose of tricyclic antidepressants". N Engl J Med. 313 (8): 474–9. doi:10.1056/NEJM198508223130804. PMID 4022081.
10. ^ Dart, RC (2004). Medical toxicology. Philadelphia: Williams & Wilkins. pp. 834–43. ISBN 0-7817-2845-2.
11. ^ Teece S, Hogg K (2003). "Gastric lavage in tricyclic antidepressant overdose". Emerg Med J. 20 (1): 64. doi:10.1136/emj.20.1.64. PMC 1726003. PMID 12533375.
12. ^ a b Dargan P, Colbridge M, Jones A (2005). "The management of tricyclic antidepressant poisoning : the role of gut decontamination, extracorporeal procedures and fab antibody fragments". Toxicol Rev. 24 (3): 187–94. doi:10.2165/00139709-200524030-00011. PMID 16390220. S2CID 8482949.
13. ^ Teece, Stewart; Hogg, Kristen (1 January 2003). "Gastric lavage in tricyclic antidepressant overdose". Emergency Medicine Journal. 20 (1): 64. doi:10.1136/emj.20.1.64. ISSN 1472-0205. PMC 1726003. PMID 12533375.
14. ^ a b Bradberry S, Thanacoody H, Watt B, Thomas S, Vale J (2005). "Management of the cardiovascular complications of tricyclic antidepressant poisoning : role of sodium bicarbonate". Toxicol Rev. 24 (3): 195–204. doi:10.2165/00139709-200524030-00012. PMID 16390221. S2CID 7162287.
15. ^ Goldfrank's Toxicological Emergencies 9th Edition
16. ^ Thomas S, Bevan L, Bhattacharyya S, Bramble M, Chew K, Connolly J, Dorani B, Han K, Horner J, Rodgers A, Sen B, Tesfayohannes B, Wynne H, Bateman D (1996). "Presentation of poisoned patients to accident and emergency departments in the north of England". Hum Exp Toxicol. 15 (6): 466–70. doi:10.1177/096032719601500602. PMID 8793528. S2CID 38941654.
17. ^ Buckley N, Whyte I, Dawson A, McManus P, Ferguson N (1995). "Self-poisoning in Newcastle, 1987-1992". Med J Aust. 162 (4): 190–3. doi:10.5694/j.1326-5377.1995.tb126020.x. PMID 7877540. S2CID 7732124.
18. ^ Shah R, Uren Z, Baker A, Majeed A (October 2001). "Deaths from antidepressants in England and Wales 1993-1997: analysis of a new national database". Psychol Med. 31 (7): 1203–10. doi:10.1017/s0033291701004548. PMID 11681546.
## External links[edit]
Classification
D
* ICD-10: T43.0
* ICD-9-CM: 969.0
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* Category
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*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Tricyclic antidepressant overdose | None | 3,000 | wikipedia | https://en.wikipedia.org/wiki/Tricyclic_antidepressant_overdose | 2021-01-18T18:45:36 | {"icd-9": ["969.0"], "icd-10": ["T43.0"], "orphanet": ["43117"], "synonyms": [], "wikidata": ["Q7841334"]} |
Fowler's syndrome
SpecialtyUrologist
Fowler's syndrome (non-neurogenic urinary retention) is a disease characterized by urinary retention with abnormal electromyographic activity in young women in the absence of overt neurological disease.[1]
## Contents
* 1 Presentation
* 2 Cause
* 3 Diagnosis
* 4 Treatment
* 5 History
* 6 References
## Presentation[edit]
This condition affects women, often under the age of 30 years. The predominant complaint is the inability to urinate for a day or more with no urgency to urinate, in spite of a large bladder volume of more than 1 liters. Normally a person feels the need to urinate at a bladder volume of 400-500ml. The person usually has a progressively increasing lower abdominal pain. The condition is commonly seen in women with Polycystic ovary Syndrome and Endometriosis.[2] It is seen in about one third of women having complaints of urinary retention.[3] They will have no neurological or other urological complaints.[citation needed]
Alternatively, women with FS can also present with impairment in urination, like obstructed urination or increased frequency of urination but rarely becoming incontinent.[2]
## Cause[edit]
The exact cause of Fowler's syndrome is not yet known. The probable cause is an abnormality in muscle membrane, possibly due to a hormonally dependent channelopathy.[4] This may cause an excessive excitability of the external urethral sphincter which prevents the adequate relaxation of the muscle necessary for voiding .[5]
## Diagnosis[edit]
Cystometrogram shows large bladder capacity and absence of sensations during the filling phase. The maximum urethral closure pressure (MUCP) is raised.[6] The diagnosis is done by testing the electromyographic (EMG) activity of external striated urethral sphincter. The usual findings are complex repetitive discharges without and with deceleration (decelerating bursts), suggesting an impairment in sphincter muscle relaxation.[7][4]
## Treatment[edit]
Sacral neuro modulation is the commonly practiced treatment for restoration of normal micturition. This technique involves modulation of micturition reflex by stimulating S3 nerve root.[8][9]
## History[edit]
This disease was described first by Fowler et al in 1985.[10]
## References[edit]
1. ^ Wein, Alan J. (2012), "Pathophysiology and Classification of Lower Urinary Tract Dysfunction", Campbell-Walsh Urology, Elsevier, pp. 1834–1846.e1, doi:10.1016/b978-1-4160-6911-9.00061-x, ISBN 978-1-4160-6911-9
2. ^ a b Panicker, Jalesh N; Pakzad, Mahreen; Fowler, Clare J (April 2018). "Fowler's syndrome: a primary disorder of urethral sphincter relaxation" (PDF). The Obstetrician & Gynaecologist. 20 (2): 95–100. doi:10.1111/tog.12448.
3. ^ Jn, Panicker; X, Game; S, Khan; Tm, Kessler; G, Gonzales; S, Elneil; Cj, Fowler (August 2012). "The Possible Role of Opiates in Women With Chronic Urinary Retention: Observations From a Prospective Clinical Study". The Journal of Urology. 188 (2): 480–4. doi:10.1016/j.juro.2012.04.011. PMID 22704100.
4. ^ a b Tawadros, Cecile; Burnett, Katherine; Derbyshire, Laura F.; Tawadros, Thomas; Clarke, Noel W.; Betts, Christopher D. (September 2015). "External urethral sphincter electromyography in asymptomatic women and the influence of the menstrual cycle". BJU International. 116 (3): 423–431. doi:10.1111/bju.13042. PMID 25600712.
5. ^ K, Jurkat-Rott; H, Lerche; N, Mitrovic; F, Lehmann-Horn (September 1999). "Teaching Course: Ion Channelopathies in Neurology". Journal of Neurology. 246 (9): 758–63. doi:10.1007/s004150050451. PMID 10525971. S2CID 18724264.
6. ^ Wiseman, Oliver J.; Swinn, Michael J.; Brady, Ciaran M.; Fowler, Clare J. (March 2002). "Maximum Urethral Closure Pressure and Sphincter Volume in Women with Urinary Retention". Journal of Urology. 167 (3): 1348–1352. doi:10.1016/S0022-5347(05)65297-4. ISSN 0022-5347. PMID 11832729.
7. ^ Cj, Fowler; Rs, Kirby (February 1985). "Abnormal Electromyographic Activity (Decelerating Burst and Complex Repetitive Discharges) in the Striated Muscle of the Urethral Sphincter in 5 Women With Persisting Urinary Retention". British Journal of Urology. 57 (1): 67–70. doi:10.1111/j.1464-410x.1985.tb08988.x. PMID 4038618.
8. ^ Mj, Swinn; Nd, Kitchen; Rj, Goodwin; Cj, Fowler (October 2000). "Sacral Neuromodulation for Women With Fowler's Syndrome". European Urology. 38 (4): 439–43. doi:10.1159/000020321. PMID 11025383. S2CID 46839550.
9. ^ Jk, Szymański; A, Słabuszewska-Jóźwiak; K, Zaręba; G, Jakiel (December 2019). "Neuromodulation - A Therapeutic Option for Refractory Overactive Bladder. A Recent Literature Review". Videosurgery and Other Miniinvasive Techniques. 14 (4): 476–485. doi:10.5114/wiitm.2019.85352. PMC 6939208. PMID 31908692.
10. ^ Cj, Fowler; Tj, Christmas; Cr, Chapple; Hf, Parkhouse; Rs, Kirby; Hs, Jacobs (1988-12-03). "Abnormal Electromyographic Activity of the Urethral Sphincter, Voiding Dysfunction, and Polycystic Ovaries: A New Syndrome?". BMJ. 297 (6661): 1436–1438. doi:10.1136/bmj.297.6661.1436. PMC 1835186. PMID 3147005.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Fowler's syndrome | c1856972 | 3,001 | wikipedia | https://en.wikipedia.org/wiki/Fowler%27s_syndrome | 2021-01-18T19:07:13 | {"gard": ["2365"], "mesh": ["C565593"], "wikidata": ["Q22965443"]} |
Main article: Alexia (acquired dyslexia)
Pure alexia, also known as agnosic alexia or alexia without agraphia or pure word blindness, is one form of alexia which makes up "the peripheral dyslexia" group.[1] Individuals who have pure alexia have severe reading problems while other language-related skills such as naming, oral repetition, auditory comprehension or writing are typically intact.[2]
Pure alexia is also known as: "alexia without agraphia",[1] "letter-by-letter dyslexia",[3] "spelling dyslexia",[4] or "word-form dyslexia".[5] Another name for it is "Dejerine syndrome", after Joseph Jules Dejerine, who described it in 1892;[6] however, when using this name, it should not be confused with medial medullary syndrome which shares the same eponym.
## Contents
* 1 Classification
* 2 Causes
* 3 Research
* 4 Rehabilitation
* 5 References
## Classification[edit]
Pure alexia results from cerebral lesions in circumscribed brain regions and therefore belongs to the group of acquired reading disorders, alexia,[1] as opposed to developmental dyslexia found in children who have difficulties in learning to read.[7]
## Causes[edit]
Pure alexia almost always involves an infarct to the left posterior cerebral artery (which perfuses the splenium of the corpus callosum and left visual cortex, among other things). The resulting deficit will be pure alexia – i.e., the patient can write but cannot read (even what they have just written). However, because pure alexia affects visual input, not auditory input, patients with pure alexia can recognize words that are spelled out loud to them.[8] This is because the left visual cortex has been damaged, leaving only the right visual cortex (occipital lobe) able to process visual information, but it is unable to send this information to the language areas (Broca's area, Wernicke's area, etc.) in the left brain because of the damage to the splenium of the corpus callosum. Patients with this deficit mostly do have a stroke to the posterior cerebral artery. But they may be susceptible to pure alexia as a consequence of other traumatic brain injuries (TBIs) as well. Anything that stops proper blood flow to the area necessary for normal reading abilities will cause a form of alexia.[9] The posterior cerebral artery is a main local for the cause of this deficit because this artery is not just responsible for itself. It also supplies the anterior temporal branches, the posterior temporal branches, the calcarine branch, and the parieto-occipital branch.[10] What is important about these arteries is their location. All of them supply blood to the back outer parts of the brain.[11] This part of the brain is also referred to as the posterior lateral part of the brain. In cases of pure alexia, locations are found in the section of the brain, specifically the temporo-occipital area.[10] This is the area that is activated when people without any sort of alexia receive activation when undergoing orthographic processing. This area is known as the visual word form area due to this pattern of activation.[9]
[12][13] The patient can still write because the pathways connecting the left-sided language areas to the motor areas are intact.[14] However, many people with pure alexia are able to identify and name individual letters over time as well as recognize sequences of letters as words. These people typically adapt to their disability and are able to use a style of compensatory reading known as letter-by-letter reading.[15] This style of reading takes longer than the conventional style of reading does. As the number of letters in a word increases, the amount of time it takes for the person with pure alexia increases. For each letter that is added, a patient may take up to an additional three seconds to read the word.[16]
Studies have shown that pure alexia may be a result of a disconnection syndrome. Analysis of diffusion images showed that the visual word form area (VWFA) is connected to the occipital lobe via the inferior longitudinal fasciculus (ILF), a projection that runs between the temporal and occipital lobe. functional magnetic resonance imaging (fMRI) and Diffusion Tensor Imaging (DTI) showed that two weeks after surgery in the ILF, the VWFA-Occipital Lobe tract was severely degenerated. The results came from an epileptic patient who showed symptoms of pure alexia after his surgery. Thus, the proposed pathophysiological mechanism is that the ILF lesion interferes with transmission of visual information to the VWFA.[17] There is, however, an alternative view that suggests the "VWFA" is devoted to processing of high acuity foveal input, which is particularly salient for complex visual stimuli like letter strings. Studies have highlighted disrupted processing of non-linguistic visual stimuli after damage to the left pFG, both for familiar and unfamiliar objects [18][19]
Pure alexia exhibits some unexpected residual abilities despite the inability to read words. For instance, one patient had preserved calculation capabilities such as deciding which number was greater, and whether a number was odd or even with greater than chance probability. The study showed that the patient was also able to calculate simple arithmetic tasks such as addition, subtraction, and division, but not multiplication, even though the patient could not read the numbers. For example, the patient would be presented with "8 – 6", and he or she would read it as "five minus four", but still come up with the correct answer "two" with greater than chance accuracy.[20] Pure alexia patients also seem to retain some residual semantic processing. They are able to perform better than chance when forced to make a lexical decision or make a semantic-categorisation decision.[21] These subjects also performed better with nouns than functors, better with words that had high rather than low imageability, and performed poorly with suffixes. However, this may be due to right hemisphere input or residual left hemisphere input.[22]
## Research[edit]
In patients, a common symptom is letter-by-letter reading or LBL. This action is a compensatory strategy which these patients use in order to come up with a semblance of reading.[9] It is essentially looking at the consonants and vowels of the word and sounding them out as they sound. However, this method does not always work, especially for words like 'phone' where the ph sounds like an f, but if sounded out, does not sound like an f. Also, by reading words in the fashion, the rate at which patients read words is much slower compared to people who do not have this disability. Petersen et al. proved that the issue of reading time had more to do with the length of the words than reading ability. The team had 4 patients with right hemisphere damage and 4 patients with left hemisphere damage in the temporo-occipital lobes as well as 26 controls were shown one word at a time on a screen. They were exposed to 20 words of 3 and 5 letters, 12 words of 7 letters. The subjects were asked to read the words as quickly and as accurately as possible. The patients with left hemisphere lesions consistently read the longer words slower than the controls despite the difficulty of the word.[10] It is thought that as the word gets longer, the letters on the outsides of the word go into peripheral vision, making the patient shift their attention thus making the patient take longer to read.
## Rehabilitation[edit]
Though there have been ample attempts to rehabilitate patients with pure alexia, few have proven to be effective on a large scale. Most rehabilitation practices have been specialized to a single patient or small patient group. At the simplest level, patients seeking rehabilitation are asked to practice reading words aloud repeatedly. This is meant to stimulate the damaged system of the brain. This is known as multiple oral re-reading (MOR) treatment. This is a text-based approach that is implemented in order to prevent patients from LBL reading. MOR works by reading aloud the same text repeatedly until certain criteria are reached.[9] The most important criteria for a pure alexic patient is reading at an improved rate. The treatment aims to shift patients away from the LBL reading strategy by strengthening links between visual input and the associated orthographic representations. This repetition supports the idea of using top-down processing initially minimize the effects peripheral processing which were demonstrated in the study above.[9][11] From here, the goal is to increase bottom-up processing. This will hopefully aid in word recognition and promote interactive processing of all available information to support reading. 'The supported reading stimulation from MOR has a rehabilitative effect so that reading rate and accuracy are better for untrained text, and word-form recognition improves as evidenced by a reduced word-length effect.'[10] These tactics have seen quite good success. Another tactic that has been employed is the use of cross modal therapy. In this therapy, patients are asked to trace the words in which they are trying to read aloud. There has been success using cross modal therapy such as kinaesthetic or motor-cross cuing therapy, but tends to be a more feasible approach for those on the slower reading end of the spectrum.[23]
## References[edit]
1. ^ a b c Coslett HB (2000). "Acquired dyslexia". Semin Neurol. 20 (4): 419–26. doi:10.1055/s-2000-13174. PMID 11149697.
2. ^ Behrmann M, Shomstein SS, Black SE, Barton JJ (2001). "The eye movements of pure alexic patients during reading and nonreading tasks". Neuropsychologia. 39 (9): 983–1002. doi:10.1016/S0028-3932(01)00021-5. PMID 11516450.
3. ^ Fiset D, Arguin M, Bub D, Humphreys GW, Riddoch MJ (July 2005). "How to make the word-length effect disappear in letter-by-letter dyslexia: implications for an account of the disorder". Psychol Sci. 16 (7): 535–41. doi:10.1111/j.0956-7976.2005.01571.x. PMID 16008786.
4. ^ Warrington EK, Langdon D (February 1994). "Spelling dyslexia: a deficit of the visual word-form". J. Neurol. Neurosurg. Psychiatry. 57 (2): 211–6. doi:10.1136/jnnp.57.2.211. PMC 1072453. PMID 8126508.
5. ^ Warrington EK, Shallice T (March 1980). "Word-form dyslexia". Brain. 103 (1): 99–112. doi:10.1093/brain/103.1.99. PMID 6244876.
6. ^ Imtiaz KE, Nirodi G, Khaleeli AA (2001). "Alexia without agraphia: a century later". Int. J. Clin. Pract. 55 (3): 225–6. PMID 11351780.
7. ^ Temple CM (August 2006). "Developmental and acquired dyslexias". Cortex. 42 (6): 898–910. doi:10.1016/S0010-9452(08)70434-9. PMID 17131596.
8. ^ Carlson, Neil R. (2013). Physiology of behavior (11th ed.). Boston: Pearson. p. 501. ISBN 978-0-205-23939-9.
9. ^ a b c d e Kim, E. S., Rising, K., Rapcsak, S. Z., & Beeson, P. M. (2015). "Treatment for Alexia With Agraphia Following Left Ventral Occipito-Temporal Damage: Strengthening Orthographic Representations Common to Reading and Spelling". Journal of Speech, Language, and Hearing Research. 58 (5): 1521–1537. doi:10.1044/2015_JSLHR-L-14-0286. PMC 4686312. PMID 26110814.CS1 maint: multiple names: authors list (link)
10. ^ a b c d Petersen, A.; Vangkilde, S.; Fabricius, C.; Iversen, H. K.; Delfi, T. S.; Starrfelt, R. (2016). "Visual attention in posterior stroke and relations to alexia". Neuropsychologia. 92: 79–89. doi:10.1016/j.neuropsychologia.2016.02.029. PMID 26970141.
11. ^ a b "Imaging". 30 March 2015.
12. ^ Sundsten, John W.; Nolte, John (2001). The human brain: an introduction to its functional anatomy. St. Louis: Mosby. p. 552. ISBN 978-0-323-01320-8. OCLC 48416194.
13. ^ "Baylor Neurology Case of the Month". Archived from the original on 2007-05-10. Retrieved 2007-06-07.
14. ^ Nolte, John (2009). The human brain: an introduction to its functional anatomy. St. Louis, Mo: Mosby/Elsevier. p. 571. ISBN 978-0-323-04131-7. OCLC 181903953.
15. ^ "Alexia". Cognitive Neuropsychology Laboratory. Center for Aphasia Research and Rehabilitation. Retrieved 30 March 2015.
16. ^ Montant, Marie; Behrmann, Marlene (2000). "Pure Alexia" (PDF). Neurocase. 6 (4): 265–294. doi:10.1080/13554790008402777. Retrieved 30 March 2015.
17. ^ Epelbaum, S. (2008). "Pure alexia as a disconnection syndrome: New diffusion imaging evidence for an old concept". Cortex. 44 (8): 962–974. doi:10.1016/j.cortex.2008.05.003. PMID 18586235.
18. ^ Roberts, DJ; Woollams, AM; Kim, E; Beeson, PM; Rapcsak, SZ; Lambon Ralph, MA (24 August 2012). "Efficient Visual Object and Word Recognition Relies on High Spatial Frequency Coding in the Left Posterior Fusiform Gyrus: Evidence from a Case-Series of Patients with Ventral Occipito-Temporal Cortex Damage". Cerebral Cortex. 23 (11): 2568–2580. doi:10.1093/cercor/bhs224. PMC 3792736. PMID 22923086.
19. ^ Roberts, DJ; Lambon Ralph, MA; Kim, ES; Tainturier, MJ; Beeson, PM; Rapcsak, SZ; Woollams, AM (November 2015). "Processing deficits for familiar and novel faces in patients with left posterior fusiform lesions". Cortex. 72: 79–96. doi:10.1016/j.cortex.2015.02.003. PMC 4643682. PMID 25837867.
20. ^ Cohen, L. (2000). "Calculating Without Reading: Unsuspected Residual Abilities In Pure Alexia". Cognitive Neuropsychology. 17 (6): 563–583. doi:10.1080/02643290050110656. PMID 20945195.
21. ^ Roberts, DJ; Lambon Ralph, MA; Woollams, AM (July 2010). "When does less yield more? The impact of severity upon implicit recognition in pure alexia". Neuropsychologia. 48 (9): 2437–2446. doi:10.1016/j.neuropsychologia.2010.04.002. PMID 20406652.
22. ^ Coslett, H.B. (1989). "Evidence For Preserved Reading In 'Pure Alexia'". Brain. 112 (2): 327–359. doi:10.1093/brain/112.2.327. PMID 2706436.
23. ^ Leff, Alexander P.; Schofield, T. M. "Rehabilitation of acquired alexia". International Encyclopedia of Rehabilitation. Center for International Rehabilitation Research Information and Exchange. Retrieved 30 March 2015.
* v
* t
* e
Symptoms, signs and syndromes associated with lesions of the brain and brainstem
Brainstem
Medulla (CN 8, 9, 10, 12)
* Lateral medullary syndrome/Wallenberg
* PICA
* Medial medullary syndrome/Dejerine
* ASA
Pons (CN 5, 6, 7, 8)
* Upper dorsal pontine syndrome/Raymond-Céstan syndrome
* Lateral pontine syndrome (AICA) (lateral)
* Medial pontine syndrome/Millard–Gubler syndrome/Foville's syndrome (basilar)
* Locked-in syndrome
* Internuclear ophthalmoplegia
* One and a half syndrome
Midbrain (CN 3, 4)
* Weber's syndrome
* ventral peduncle, PCA
* Benedikt syndrome
* ventral tegmentum, PCA
* Parinaud's syndrome
* dorsal, tumor
* Claude's syndrome
Other
* Alternating hemiplegia
Cerebellum
* Latearl
* Dysmetria
* Dysdiadochokinesia
* Intention tremor)
* Medial
* Cerebellar ataxia
Basal ganglia
* Chorea
* Dystonia
* Parkinson's disease
Cortex
* ACA syndrome
* MCA syndrome
* PCA syndrome
* Frontal lobe
* Expressive aphasia
* Abulia
* Parietal lobe
* Receptive aphasia
* Hemispatial neglect
* Gerstmann syndrome
* Astereognosis
* Occipital lobe
* Bálint's syndrome
* Cortical blindness
* Pure alexia
* Temporal lobe
* Cortical deafness
* Prosopagnosia
Thalamus
* Thalamic syndrome
Other
* Upper motor neuron lesion
* Aphasia
* v
* t
* e
Dyslexia and related specific developmental disorders
Conditions
Speech, language, and
communication
* Expressive language disorder
* Infantile speech
* Landau–Kleffner syndrome
* Language disorder
* Lisp
* Mixed receptive-expressive language disorder
* Specific language impairment
* Speech and language impairment
* Speech disorder
* Speech error
* Speech sound disorder
* Stuttering
* Tip of the tongue
Learning disability
* Dyslexia
* Dyscalculia
* Dysgraphia
* Disorder of written expression
Motor
* Developmental coordination disorder
* Developmental verbal dyspraxia
Sensory
* Auditory processing disorder
* Sensory processing disorder
Related topics
* Dyslexia research
* Irlen filters
* Learning Ally
* Learning problems in childhood cancer
* Literacy
* Management of dyslexia
* Multisensory integration
* Neuropsychology
* Reading acquisition
* Spelling
* Writing system
Lists
* Dyslexia in fiction
* Languages by Writing System
* People with dyslexia
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Pure alexia | c0751840 | 3,002 | wikipedia | https://en.wikipedia.org/wiki/Pure_alexia | 2021-01-18T18:39:32 | {"mesh": ["D020237"], "wikidata": ["Q7261142"]} |
Rapid, irregular contraction of muscle fibers (typically of the heart)
For the video game, see Fibrillation (video game).
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Fibrillation
Fibrillation is the rapid, irregular, and unsynchronized contraction of muscle fibers. An important occurrence is with regard to the heart.
## Contents
* 1 Cardiology
* 2 Musculoskeletal
* 3 Name
* 4 References
## Cardiology[edit]
There are two major classes of cardiac fibrillation: atrial fibrillation and ventricular fibrillation.
* Atrial fibrillation is an irregular and uncoordinated contraction of the cardiac muscle of atria. It can be a chronic condition, usually treated with anticoagulation and sometimes with conversion to normal sinus rhythm. In this condition the normal electrical pulses coming from the sinoatrial node are overwhelmed by disorganized electrical impulses usually originating in the roots of the pulmonary veins, leading to irregular conduction of impulses to the ventricles which generate the heartbeat.[1][2]
* Ventricular fibrillation is an irregular and uncoordinated contraction of the cardiac muscle of ventricles. It is a common cause of cardiac arrest and is usually fatal if not reversed by defibrillation.[3][4][5][6]
Fibrillation may sometimes be used after heart surgery to stop the heart from beating while any minor leaks are stitched up.
## Musculoskeletal[edit]
Fibrillation also occurs with individual skeletal muscle fibers.[7] This happens when muscle fibers lose contact with their innervating axon producing a spontaneous action potential, "fibrillation potential" that results in the muscle fiber's contraction. These contractions are not visible under the skin and are detectable through needle electromyography (EMG) and ultrasound.[8] Fibrillations can occur in healthy individuals. If the fibrillations have irregular potentials then they don't have pathological significance.[9] In other cases they are a major symptom in acute and severe peripheral nerve disorders, in myopathies in which muscle fibers are split or inflamed, and in lower motor neuron lesions.
They contrast with fasciculations that are visible spontaneous contractions involving small groups of muscle fibers. Fasciculations can be seen in lower motor neuron lesions as well, but they also do not necessarily denote pathology.
## Name[edit]
The word fibrillation (/ˌfɪbrɪlˈeɪʃən/) is related to the word fibril in the sense of muscle fibrils, the proteins that make up each muscle fiber (muscle cell).
## References[edit]
1. ^ Reddy, Vivek; Taha, Wael; Kundumadam, Shanker; Khan, Mazhar (2017-07-05). "Atrial fibrillation and hyperthyroidism: A literature review". Indian Heart Journal. Elsevier BV. 69 (4): 545–550. doi:10.1016/j.ihj.2017.07.004. ISSN 0019-4832. PMC 5560908. PMID 28822529.
2. ^ Dalen, James E.; Alpert, Joseph S. (2017). "Silent Atrial Fibrillation and Cryptogenic Strokes". The American Journal of Medicine. Elsevier BV. 130 (3): 264–267. doi:10.1016/j.amjmed.2016.09.027. ISSN 0002-9343. PMID 27756556.
3. ^ Visser, Marloes; van der Heijden, Jeroen F.; Doevendans, Pieter A.; Loh, Peter; Wilde, Arthur A.; Hassink, Rutger J. (2016). "Idiopathic Ventricular Fibrillation". Circulation: Arrhythmia and Electrophysiology. Ovid Technologies (Wolters Kluwer Health). 9 (5). doi:10.1161/circep.115.003817. ISSN 1941-3149. PMID 27103090.
4. ^ Krummen, David E; Ho, Gordon; Villongco, Christopher T; Hayase, Justin; Schricker, Amir A (2016). "Ventricular fibrillation: triggers, mechanisms and therapies". Future Cardiology. Future Medicine Ltd. 12 (3): 373–390. doi:10.2217/fca-2016-0001. ISSN 1479-6678. PMID 27120223.
5. ^ Luo, Qingzhi; Jin, Qi; Zhang, Ning; Huang, Shangwei; Han, Yanxin; Lin, Changjian; Ling, Tianyou; Chen, Kang; Pan, Wenqi; Wu, Liqun (2017-11-28). "Antifibrillatory effects of renal denervation on ventricular fibrillation in a canine model of pacing-induced heart failure". Experimental Physiology. Wiley. 103 (1): 19–30. doi:10.1113/ep086472. ISSN 0958-0670. PMID 29094471.
6. ^ Ludhwani, Dipesh; Jagtap, Mandar (2018-12-19). "Rhythm, Ventricular Fibrillation". NCBI Bookshelf. PMID 30725805. Retrieved 2019-03-29.
7. ^ "fibrillation" at Dorland's Medical Dictionary
8. ^ Pillen S, Nienhuis M, van Dijk JP, Arts IM, van Alfen N, Zwarts MJ (2009). "Muscles alive: ultrasound detects fibrillations". Clin Neurophysiol. 120 (5): 932–6. doi:10.1016/j.clinph.2009.01.016. PMID 19356976.
9. ^ Stöhr M (1977). "Benign fibrillation potentials in normal muscle and their correlation with endplate and denervation potentials". J. Neurol. Neurosurg. Psychiatry. 40 (8): 765–8. doi:10.1136/jnnp.40.8.765. PMC 492832. PMID 925696.
* v
* t
* e
Cardiovascular disease (heart)
Ischaemic
Coronary disease
* Coronary artery disease (CAD)
* Coronary artery aneurysm
* Spontaneous coronary artery dissection (SCAD)
* Coronary thrombosis
* Coronary vasospasm
* Myocardial bridge
Active ischemia
* Angina pectoris
* Prinzmetal's angina
* Stable angina
* Acute coronary syndrome
* Myocardial infarction
* Unstable angina
Sequelae
* hours
* Hibernating myocardium
* Myocardial stunning
* days
* Myocardial rupture
* weeks
* Aneurysm of heart / Ventricular aneurysm
* Dressler syndrome
Layers
Pericardium
* Pericarditis
* Acute
* Chronic / Constrictive
* Pericardial effusion
* Cardiac tamponade
* Hemopericardium
Myocardium
* Myocarditis
* Chagas disease
* Cardiomyopathy
* Dilated
* Alcoholic
* Hypertrophic
* Tachycardia-induced
* Restrictive
* Loeffler endocarditis
* Cardiac amyloidosis
* Endocardial fibroelastosis
* Arrhythmogenic right ventricular dysplasia
Endocardium /
valves
Endocarditis
* infective endocarditis
* Subacute bacterial endocarditis
* non-infective endocarditis
* Libman–Sacks endocarditis
* Nonbacterial thrombotic endocarditis
Valves
* mitral
* regurgitation
* prolapse
* stenosis
* aortic
* stenosis
* insufficiency
* tricuspid
* stenosis
* insufficiency
* pulmonary
* stenosis
* insufficiency
Conduction /
arrhythmia
Bradycardia
* Sinus bradycardia
* Sick sinus syndrome
* Heart block: Sinoatrial
* AV
* 1°
* 2°
* 3°
* Intraventricular
* Bundle branch block
* Right
* Left
* Left anterior fascicle
* Left posterior fascicle
* Bifascicular
* Trifascicular
* Adams–Stokes syndrome
Tachycardia
(paroxysmal and sinus)
Supraventricular
* Atrial
* Multifocal
* Junctional
* AV nodal reentrant
* Junctional ectopic
Ventricular
* Accelerated idioventricular rhythm
* Catecholaminergic polymorphic
* Torsades de pointes
Premature contraction
* Atrial
* Junctional
* Ventricular
Pre-excitation syndrome
* Lown–Ganong–Levine
* Wolff–Parkinson–White
Flutter / fibrillation
* Atrial flutter
* Ventricular flutter
* Atrial fibrillation
* Familial
* Ventricular fibrillation
Pacemaker
* Ectopic pacemaker / Ectopic beat
* Multifocal atrial tachycardia
* Pacemaker syndrome
* Parasystole
* Wandering atrial pacemaker
Long QT syndrome
* Andersen–Tawil
* Jervell and Lange-Nielsen
* Romano–Ward
Cardiac arrest
* Sudden cardiac death
* Asystole
* Pulseless electrical activity
* Sinoatrial arrest
Other / ungrouped
* hexaxial reference system
* Right axis deviation
* Left axis deviation
* QT
* Short QT syndrome
* T
* T wave alternans
* ST
* Osborn wave
* ST elevation
* ST depression
* Strain pattern
Cardiomegaly
* Ventricular hypertrophy
* Left
* Right / Cor pulmonale
* Atrial enlargement
* Left
* Right
* Athletic heart syndrome
Other
* Cardiac fibrosis
* Heart failure
* Diastolic heart failure
* Cardiac asthma
* Rheumatic fever
* v
* t
* e
Symptoms and signs relating to movement and gait
Gait
* Gait abnormality
* CNS
* Scissor gait
* Cerebellar ataxia
* Festinating gait
* Marche à petit pas
* Propulsive gait
* Stomping gait
* Spastic gait
* Magnetic gait
* Truncal ataxia
* Muscular
* Myopathic gait
* Trendelenburg gait
* Pigeon gait
* Steppage gait
* Antalgic gait
Coordination
* Ataxia
* Cerebellar ataxia
* Dysmetria
* Dysdiadochokinesia
* Pronator drift
* Dyssynergia
* Sensory ataxia
* Asterixis
Abnormal movement
* Athetosis
* Tremor
* Fasciculation
* Fibrillation
Posturing
* Abnormal posturing
* Opisthotonus
* Spasm
* Trismus
* Cramp
* Tetany
* Myokymia
* Joint locking
Paralysis
* Flaccid paralysis
* Spastic paraplegia
* Spastic diplegia
* Spastic paraplegia
* Syndromes
* Monoplegia
* Diplegia / Paraplegia
* Hemiplegia
* Triplegia
* Tetraplegia / Quadruplegia
* General causes
* Upper motor neuron lesion
* Lower motor neuron lesion
Weakness
* Hemiparesis
Other
* Rachitic rosary
* Hyperreflexia
* Clasp-knife response
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Fibrillation | c0232197 | 3,003 | wikipedia | https://en.wikipedia.org/wiki/Fibrillation | 2021-01-18T18:37:50 | {"umls": ["C0232197"], "wikidata": ["Q1001150"]} |
## Description
Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; 608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006).
For a discussion of genetic heterogeneity of autism, see 209850.
Mapping
By fine mapping of markers on chromosome 17q in 56 autism-affected sib pairs from 48 independent families with only affected males, Cantor et al. (2005) found significant linkage to 17q21 (maximum lod score of 4.1 at marker D17S2180). A 1-lod score drop includes a peak from a second scan with a maximum lod score of 3.6 at D17S1299 (approximately 5 cM proximal to D17S2180). Cantor et al. (2005) noted that the ITGB3 gene on 17q21 may be a candidate autism gene because it is involved in serotonin levels, particularly in males, and is a cell adhesion molecule that may play a role in nervous system development.
Molecular Genetics
### Associations Pending Confirmation
Weiss et al. (2006) found a significant (p = 0.00082) association between a common allele in the ITGB3 gene (L33P; 173470.0006) and autism in a combined sample of 730 affected families. There appeared to be a sex difference. Weiss et al. (2006) presented evidence suggesting that genotypes at the ITGB3 and SLC6A4 (182138) genes may interact to affect autism susceptibility.
In a family-based association study of 281 simplex and 12 multiplex Caucasian families with autism, Napolioni et al. (2011) reported an association between autism and certain ITGB3 haplotypes. Haplotype H3 was largely overtransmitted to the affected offspring and doubled the risk of an ASD diagnosis (odds ratio (OR) of 2.0; p = 0.005), whereas haplotype H1 was undertransmitted (OR of 0.725; p = 0.018). These 2 common haplotypes differ only at rs12603582 in intron 11, located toward the 3-prime end of the ITGB3 gene. In contrast, rs2317385, located at the 5-prime end of the gene, was significantly associated with 5-HT (see 607478) blood levels. The SNP rs12603582 was strongly associated with preterm delivery in the autism patients (p = 0.008). No gene-gene interaction between ITGB3 and SLC6A4 was detected.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| AUTISM, SUSCEPTIBILITY TO, 7 | c1970807 | 3,004 | omim | https://www.omim.org/entry/610676 | 2019-09-22T16:04:13 | {"omim": ["610676"]} |
A parapharyngeal abscess is a deep neck space abscess of the parapharyngeal space (or pharyngomaxillary space), which is lateral to the superior pharyngeal constrictor muscle and medial to the masseter muscle. [1] This space is divided by the styloid process into anterior and posterior compartments. The posterior compartment contains the carotid artery, internal jugular vein, and many nerves.[2]
## Contents
* 1 Signs and symptoms
* 2 Cause
* 3 Epidemiology
* 4 References
## Signs and symptoms[edit]
Symptoms include fever, sore throat, painful swallowing, and swelling in the neck.[2] An anterior space abscess can cause lockjaw (spasm of jaw muscle), and hard mass formation along the angle of the mandible, with medial bulging of the tonsil and lateral pharyngeal wall. A posterior space abscess causes swelling in the posterior pharyngeal wall, and lockjaw is minimal. Other structures within the carotid sheath may be involved, causing rigors, high fever, bacteremia, neurologic deficit, or a massive haemorrhage caused by carotid artery rupture.[2]
## Cause[edit]
Infection can occur from:
* Pharynx: acute and chronic infection of tonsil and adenoids
* Teeth: dental infection occurs from lower last molar tooth
* Ear: Bezold's abscess and petrositis
* Other space: infection of parotid retropharyngeal space
* External trauma: penetrating injuries of neck, injection of local anaesthetic[3]
## Epidemiology[edit]
Both genders are equally affected.[citation needed] Any age group can develop a parapharyngeal abscess but it is most commonly seen in children and adolescents.[4] Adults who are immunocompromised are also at high risk.[5]
## References[edit]
1. ^ Cuete, David; et al. "Radiology Reference Article: Parapharyngeal abscess". Radiopaedia.org. Retrieved 28 February 2017.
2. ^ a b c Sasaki, Clarence T. (October 2016). "Ear, Nose, and Throat Disorders: Parapharyngeal Abscess". MSD Manual Professional Edition. Merck Sharp & Dohme Corp. Retrieved 28 February 2017.
3. ^ Dhingra, PL (2014). Diseases of Ear, Nose and Throat & Head and Neck Surgeries (6th ed.). Elsiver. ISBN 978-81-312-3431-0.[page needed]
4. ^ Croche Santander, B.; Prieto Del Prado, A.; Madrid Castillo, M.D.; Neth, O.; Obando Santaella, I. (2011). "Abscesos retrofaríngeo y parafaríngeo: Experiencia en hospital terciario de Sevilla durante la última década" [Retropharyngeal and parapharyngeal abscess: experience in a tertiary-care center in Seville during the last decade]. Anales de Pediatría. 75 (4): 266–72. doi:10.1016/j.anpedi.2011.03.010. PMID 21531183.
5. ^ Alaani, A.; Griffiths, H.; Minhas, S. S.; Olliff, J.; Drake Lee, A. B. (2004). "Parapharyngeal abscess: Diagnosis, complications and management in adults". European Archives of Oto-Rhino-Laryngology. 262 (4): 345–50. doi:10.1007/s00405-004-0800-6. PMID 15235797.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Parapharyngeal abscess | c0155842 | 3,005 | wikipedia | https://en.wikipedia.org/wiki/Parapharyngeal_abscess | 2021-01-18T19:06:40 | {"umls": ["C0155842"], "icd-10": ["J39.0"], "wikidata": ["Q16682714"]} |
Traboulsi et al. (1988) described a brother and sister, born to parents related as third cousins, who had pigmentary retinopathy in a pericentral distribution. The retinopathy was noted in infancy when the sibs were examined for strabismus. The optic discs, maculae, and retinal vessels were normal. Both sibs had moderate hyperopic astigmatism and esotropia. The fundus and visual acuity remained unchanged for 9 and 13 years in the brother and sister, respectively. Results of eye examinations in the father, mother, and older sister were normal. The stability of the retinal findings in visual acuity suggested a long-term favorable prognosis. Traboulsi et al. (1988) found 18 well-documented cases of pericentral pigmentary retinopathy in the literature. Although recessive inheritance had been suggested, it had never been substantiated in any of the reports. Disorders that have been labeled as central pigmentary retinopathy or inverse retinitis pigmentosa include cone-rod dystrophy (120970), Stargardt disease (248200), and Best disease (153700).
Sandberg et al. (2005) studied 18 patients, aged 32 to 65 years, with pericentral retinitis pigmentosa with follow-up for 3 to 26 years. Estimated mean annual rates of decline of remaining ocular function were 1.2% for visual acuity, 1.9% for visual field area, and 2.9% for electroretinogram amplitude for 30 Hz flashes. Sandberg et al. (2005) noted that these rates were generally slower than those previously reported for patients with typical forms of retinitis pigmentosa. Their patient sample included 2 pairs of affected sibs with normal parents and otherwise isolated cases.
See 180210 for a possible autosomal dominant form of pericentral pigmentary retinopathy.
Eyes \- Pericentral pigmentary retinopathy \- Strabismus \- Hyperopia \- Astigmatism Inheritance \- Autosomal recessive ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| RETINOPATHY, PERICENTRAL PIGMENTARY, AUTOSOMAL RECESSIVE | c0035334 | 3,006 | omim | https://www.omim.org/entry/268060 | 2019-09-22T16:22:40 | {"doid": ["0110422"], "mesh": ["D012174"], "omim": ["268060"], "orphanet": ["791"], "synonyms": ["Alternative titles", "RETINITIS PIGMENTOSA, PERICENTRAL"]} |
Disease of mental health where symptoms are deliberately produced, feigned or exaggerated
This article needs attention from an expert in psychology. See the talk page for details. WikiProject Psychology may be able to help recruit an expert. (April 2012)
Factitious disorder
SpecialtyPsychiatry, psychology
A factitious disorder is a condition in which a person, without a malingering motive, acts as if they have an illness by deliberately producing, feigning, or exaggerating symptoms, purely to attain (for themselves or for another) a patient's role. People with a factitious disorder may produce symptoms by contaminating urine samples, taking hallucinogens, injecting fecal material to produce abscesses, and similar behaviour.
Factitious disorder imposed on self (also called Munchausen syndrome) was for some time the umbrella term for all such disorders.[1] Factitious disorder imposed on another (also called Munchausen syndrome by proxy, Munchausen by proxy, or factitious disorder by proxy) is a condition in which a person deliberately produces, feigns, or exaggerates the symptoms of someone in their care. In either case, the perpetrator's motive is to perpetrate factitious disorders, either as a patient or by proxy as a caregiver, in order to attain (for themselves or for another) a patient's role. Malingering differs fundamentally from factitious disorders in that the malingerer simulates illness intending to obtain a material benefit or avoid an obligation or responsibility. Somatic symptom disorders, though also diagnoses of exclusion, are characterized by physical complaints that are not produced intentionally.[2]
## Contents
* 1 Causes
* 2 Diagnosis
* 2.1 Factitious disorder imposed on self
* 2.2 Factitious disorder imposed on another
* 2.3 Ganser syndrome
* 2.4 Differential diagnosis
* 3 Treatment
* 4 Prognosis
* 5 History
* 6 See also
* 7 References
* 8 External links
## Causes[edit]
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The causes are mostly unknown. One possible cause is trauma but the rest is still going through a testing process. It is also been suspected that it might be hereditary, like depression. There are still many possible causes for this disorder which haven't been defined yet.
These individuals may be trying to reenact unresolved issues with their parents. A history of frequent illnesses may also contribute to the development of this disorder. In some cases, individuals afflicted with factitious disorder are accustomed to actually being sick, and thus return to their previous state to recapture what they once considered the "norm". Another cause is a history of close contact with someone (a friend or family member) who had a severe or chronic condition. The patients found themselves subconsciously envious of the attention said relation received, and felt that they themselves faded into the background. Thus medical attention makes them feel glamorous and special.
## Diagnosis[edit]
Criteria for diagnosis includes intentionally fabricating to produce physical or psychological signs or symptoms and the absence of any other mental disorder. Motivation for their behavior must be to assume the "sick" role, and they do not act sick for personal gain as in the case of malingering sentiments. When the individual applies this pretended sickness to a dependent, for example a child, it is often referred to as "factitious disorder by proxy".[citation needed]
The DSM-5 differentiates among two types:
* Factitious disorder imposed on self (Munchausen syndrome)
* Factitious disorder imposed on another (Munchausen syndrome by proxy),[3] defined as: When an individual falsifies illness in another, whether that be a child, pet, or older adult.[4]
### Factitious disorder imposed on self[edit]
Factitious disorder imposed on self, previously called Munchausen syndrome, or factitious disorder with predominantly physical signs and symptoms,[5][6] has specified symptoms. Factitious disorder symptoms may seem exaggerated; individuals undergo major surgery repeatedly, and they "hospital jump" or migrate to avoid detection.
### Factitious disorder imposed on another[edit]
Main article: Factitious disorder imposed on another
Factitious disorder imposed on another, previously Munchausen syndrome by proxy, is the involuntary use of another individual to play the patient role. For example, false symptoms are produced in children by the caregivers or parents, to produce the appearance of illness, or they may give misleading medical histories about their children. The parent may falsify the child's medical history or tamper with laboratory tests to make the child appear sick. Occasionally, in Munchausen by proxy, the caregiver actually injures the child or makes them sick to ensure that the child is treated. For instance, a father whose son has celiac disease might knowingly introduce gluten into the diet. Such parents may be validated by the attention that they receive from having a sick child. The word "proxy" means "substitute".
### Ganser syndrome[edit]
Ganser syndrome was once considered a separate factitious disorder, but is now considered a dissociative disorder. It is a disorder of extreme stress or an organic condition. The patient suffers from approximation or giving absurd answers to simple questions. The syndrome is sometimes diagnosed as merely malingering—however, it is more often defined as a factitious disorder. This has been seen in prisoners following solitary confinement, and the symptoms are consistent in different prisons, though the patients do not know one another.
Symptoms include a clouding of consciousness, somatic conversion symptoms, confusion, stress, loss of personal identity, echolalia, and echopraxia. Individuals also give approximate answers to simple questions such as, "How many legs on a cat?" "Three"; "What's the day after Wednesday?" "Friday"; and so on. The disorder is extraordinarily rare with fewer than 100 recorded cases. While individuals of all backgrounds have been reported with the disorder, there is a higher inclination towards males (75% or more). The average age of those with Ganser syndrome is 32, though it stretches from ages 15–62 years old.
### Differential diagnosis[edit]
Factitious disorder should be distinguished from somatic symptom disorder (formerly called somatization disorder), in which the patient is truly experiencing the symptoms and has no intention to deceive. In conversion disorder (previously called hysteria), a neurological deficit appears with no organic cause. The patient, again, is truly experiencing the symptoms and signs and has no intention to deceive. The differential also includes body dysmorphic disorder and pain disorder.
## Treatment[edit]
No true psychiatric medications are prescribed for factitious disorder.[7] However, selective serotonin reuptake inhibitors (SSRIs) can help manage underlying problems. Medicines such as SSRIs that are used to treat mood disorders can be used to treat factitious disorder, as a mood disorder may be the underlying cause of factitious disorder. Some authors (such as Prior and Gordon 1997) also report good responses to antipsychotic drugs such as Pimozide. Family therapy can also help. In such therapy, families are helped to better understand patients (the individual in the family with factitious disorder) and that person's need for attention.
In this therapeutic setting, the family is urged not to condone or reward the factitious disorder individual's behavior. This form of treatment can be unsuccessful if the family is uncooperative or displays signs of denial and/or antisocial disorder. Psychotherapy is another method used to treat the disorder. These sessions should focus on the psychiatrist's establishing and maintaining a relationship with the patient. Such a relationship may help to contain symptoms of factitious disorder. Monitoring is also a form that may be indicated for the factitious disorder patient's own good; factitious disorder (especially proxy) can be detrimental to an individual's health—if they are, in fact, causing true physiological illnesses. Even faked illnesses and injuries can be dangerous, and might be monitored for fear that unnecessary surgery may subsequently be performed.
## Prognosis[edit]
Some individuals experience only a few outbreaks of the disorder. However, in most cases, factitious disorder is a chronic long-term condition that is difficult to treat. There are relatively few positive outcomes for this disorder; in fact, treatment provided a lower percentage of positive outcomes than did treatment of individuals with obvious psychotic symptoms such as people with schizophrenia. In addition, many individuals with factitious disorder do not present for treatment, often insisting their symptoms are genuine. Some degree of recovery, however, is possible. The passage of time seems to help the disorder greatly. There are many possible explanations for this occurrence, although none are currently considered definitive. It may be that a factitious disorder individual has mastered the art of feigning sickness over so many years of practice that the disorder can no longer be discerned. Another hypothesis is that many times a factitious disorder individual is placed in a home, or experiences health issues that are not self-induced or feigned. In this way, the problem with obtaining the "patient" status is resolved because symptoms arise without any effort on the part of the individual.
## History[edit]
Previously, the DSM-IV differentiated among three types:
* Factitious disorders with predominantly psychological signs and symptoms: if psychological signs and symptoms predominate in the clinical presentation
* Factitious disorders with predominantly physical signs and symptoms: if physical signs and symptoms predominate in the clinical presentation
* Factitious disorders with combined psychological and physical signs and symptoms: if both psychological and physical signs and symptoms are present and neither predominates in the clinical presentation[8]
## See also[edit]
* Attention seeking
* Somatic symptom disorder
* Victim playing
## References[edit]
1. ^ Factitious Disorder Imposed on Self at eMedicine
2. ^ Somatoform Disorders Archived 2007-10-24 at the Wayback Machine
3. ^ "Factitious Disorders". Cleveland Clinic. Archived from the original on 4 April 2015. Retrieved 1 April 2015. Reference for the two as described 1 April 2015
4. ^ Nolan- Hoeksema, Susan. (2014). Abnormal Psychology. McGraw Hill Publishing; 6th int ed. p. 159
5. ^ Jerald Kay and Allan Tasman (2006). Essentials of psychiatry. John Wiley & Sons, Ltd. pp. 680. ISBN 0-470-01854-2.
6. ^ Sadock, Benjamin J.; Sadock, Virginia A., eds. (January 15, 2000). Kaplan & Sadock's Comprehensive Textbook of Psychiatry (2 Volume Set) (7th ed.). Lippincott Williams & Wilkins Publishers. p. 1747. ISBN 0683301284.
7. ^ "Factitious Disorder". Mayo Clinic.
8. ^ Jerald Kay and Allan Tasman (2006). Essentials of psychiatry. John Wiley & Sons, Ltd. pp. 680. ISBN 0-470-01854-2. Reference for the three types as described 20 January 2013
## External links[edit]
Classification
D
* ICD-10: F68.1
* ICD-10-CM: F68.10, F68.11, F68.12, F68.13
* ICD-9-CM: 300.16, 300.19, 301.51
* MeSH: D005162
* v
* t
* e
Mental and behavioral disorders
Adult personality and behavior
Gender dysphoria
* Ego-dystonic sexual orientation
* Paraphilia
* Fetishism
* Voyeurism
* Sexual maturation disorder
* Sexual relationship disorder
Other
* Factitious disorder
* Munchausen syndrome
* Intermittent explosive disorder
* Dermatillomania
* Kleptomania
* Pyromania
* Trichotillomania
* Personality disorder
Childhood and learning
Emotional and behavioral
* ADHD
* Conduct disorder
* ODD
* Emotional and behavioral disorders
* Separation anxiety disorder
* Movement disorders
* Stereotypic
* Social functioning
* DAD
* RAD
* Selective mutism
* Speech
* Stuttering
* Cluttering
* Tic disorder
* Tourette syndrome
Intellectual disability
* X-linked intellectual disability
* Lujan–Fryns syndrome
Psychological development
(developmental disabilities)
* Pervasive
* Specific
Mood (affective)
* Bipolar
* Bipolar I
* Bipolar II
* Bipolar NOS
* Cyclothymia
* Depression
* Atypical depression
* Dysthymia
* Major depressive disorder
* Melancholic depression
* Seasonal affective disorder
* Mania
Neurological and symptomatic
Autism spectrum
* Autism
* Asperger syndrome
* High-functioning autism
* PDD-NOS
* Savant syndrome
Dementia
* AIDS dementia complex
* Alzheimer's disease
* Creutzfeldt–Jakob disease
* Frontotemporal dementia
* Huntington's disease
* Mild cognitive impairment
* Parkinson's disease
* Pick's disease
* Sundowning
* Vascular dementia
* Wandering
Other
* Delirium
* Organic brain syndrome
* Post-concussion syndrome
Neurotic, stress-related and somatoform
Adjustment
* Adjustment disorder with depressed mood
Anxiety
Phobia
* Agoraphobia
* Social anxiety
* Social phobia
* Anthropophobia
* Specific social phobia
* Specific phobia
* Claustrophobia
Other
* Generalized anxiety disorder
* OCD
* Panic attack
* Panic disorder
* Stress
* Acute stress reaction
* PTSD
Dissociative
* Depersonalization disorder
* Dissociative identity disorder
* Fugue state
* Psychogenic amnesia
Somatic symptom
* Body dysmorphic disorder
* Conversion disorder
* Ganser syndrome
* Globus pharyngis
* Psychogenic non-epileptic seizures
* False pregnancy
* Hypochondriasis
* Mass psychogenic illness
* Nosophobia
* Psychogenic pain
* Somatization disorder
Physiological and physical behavior
Eating
* Anorexia nervosa
* Bulimia nervosa
* Rumination syndrome
* Other specified feeding or eating disorder
Nonorganic sleep
* Hypersomnia
* Insomnia
* Parasomnia
* Night terror
* Nightmare
* REM sleep behavior disorder
Postnatal
* Postpartum depression
* Postpartum psychosis
Sexual dysfunction
Arousal
* Erectile dysfunction
* Female sexual arousal disorder
Desire
* Hypersexuality
* Hypoactive sexual desire disorder
Orgasm
* Anorgasmia
* Delayed ejaculation
* Premature ejaculation
* Sexual anhedonia
Pain
* Nonorganic dyspareunia
* Nonorganic vaginismus
Psychoactive substances, substance abuse and substance-related
* Drug overdose
* Intoxication
* Physical dependence
* Rebound effect
* Stimulant psychosis
* Substance dependence
* Withdrawal
Schizophrenia, schizotypal and delusional
Delusional
* Delusional disorder
* Folie à deux
Psychosis and
schizophrenia-like
* Brief reactive psychosis
* Schizoaffective disorder
* Schizophreniform disorder
Schizophrenia
* Childhood schizophrenia
* Disorganized (hebephrenic) schizophrenia
* Paranoid schizophrenia
* Pseudoneurotic schizophrenia
* Simple-type schizophrenia
Other
* Catatonia
Symptoms and uncategorized
* Impulse control disorder
* Klüver–Bucy syndrome
* Psychomotor agitation
* Stereotypy
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Factitious disorder | c0233752 | 3,007 | wikipedia | https://en.wikipedia.org/wiki/Factitious_disorder | 2021-01-18T18:28:15 | {"mesh": ["D005162"], "umls": ["C0233752", "C0015481"], "wikidata": ["Q2686385"]} |
Nevoid hypertrichosis
SpecialtyDermatology
Nevoid hypertrichosis is a cutaneous condition characterized by the growth of terminal hairs in a circumscribed area.[1]
## See also[edit]
* Onychauxis
* List of cutaneous conditions
## References[edit]
1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
This dermatology article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Nevoid hypertrichosis | c0018508 | 3,008 | wikipedia | https://en.wikipedia.org/wiki/Nevoid_hypertrichosis | 2021-01-18T18:33:24 | {"wikidata": ["Q7004995"]} |
Kindler syndrome
Other namesCongenital poikiloderma with blisters and keratoses,[1] Congenital poikiloderma with bullae and progressive cutaneous atrophy,[1] Hereditary acrokeratotic poikiloderma,[1] Hyperkeratosis–hyperpigmentation syndrome,[2]:511 Acrokeratotic poikiloderma, Weary–Kindler syndrome[3]:558
Kindler syndrome has an autosomal recessive pattern of inheritance.
SpecialtyMedical genetics
Kindler syndrome (also known as "bullous acrokeratotic poikiloderma of Kindler and Weary",[1]) is a rare congenital disease of the skin caused by a mutation in the KIND1 gene.
## Contents
* 1 Symptoms and signs
* 2 Genetics
* 3 Diagnosis
* 4 Management
* 5 See also
* 6 References
* 7 External links
## Symptoms and signs[edit]
Infants and young children with Kindler syndrome have a tendency to blister with minor trauma and are prone to sunburns. As individuals with Kindler syndrome age, they tend to have fewer problems with blistering and photosensitivity. However, pigment changes and thinning of the skin become more prominent.[4] Kindler syndrome can affect various mucous tissues such as the mouth and eyes, which can lead to other health problems.[5]
## Genetics[edit]
Kindler syndrome is an autosomal recessive genodermatosis. The KIND1 gene mutated in Kindler syndrome codes for the protein kindlin-1, which is thought to be active in the interactions between actin and the extracellular matrix (focal adhesion plaques).[6] Kindler syndrome was first described in 1954 by Theresa Kindler.[7]
## Diagnosis[edit]
Clinical and genetic tests are used to confirm diagnosis.[5]
## Management[edit]
Treatment may involve several different types of practitioner to address the various manifestations that may occur. This multidisciplinary team will also be involved in preventing secondary complications.[8]
## See also[edit]
* Rothmund–Thomson syndrome
* List of cutaneous conditions
## References[edit]
1. ^ a b c d 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. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
4. ^ Bardhan, Ajoy; Bruckner-Tuderman, Leena; Chapple, Iain L. C.; Fine, Jo-David; Harper, Natasha; Has, Cristina; Magin, Thomas M.; Marinkovich, M. Peter; Marshall, John F.; McGrath, John A.; Mellerio, Jemima E. (2020-09-24). "Epidermolysis bullosa". Nature Reviews Disease Primers. 6 (1): 78. doi:10.1038/s41572-020-0210-0. ISSN 2056-676X. PMID 32973163. S2CID 221861310.
5. ^ a b "Kindler syndrome". Genetics Home Reference. NIH. Retrieved November 18, 2018.
6. ^ Siegel DH, Ashton GH, Penagos HG, Lee JV, Feiler HS, Wilhelmsen KC, et al. (July 2003). "Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes Kindler syndrome". Am. J. Hum. Genet. 73 (1): 174–87. doi:10.1086/376609. PMC 1180579. PMID 12789646.
7. ^ Kindler T (March 1954). "Congenital poikiloderma with traumatic bulla formation and progressive cutaneous atrophy". Br. J. Dermatol. 66 (3): 104–11. doi:10.1111/j.1365-2133.1954.tb12598.x. PMID 13149722. S2CID 22888894.
8. ^ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LH, Stephens K, Amemiya A, Youssefian L, Vahidnezhad H, Uitto J (December 2016). "Kindler Syndrome - Synonym: Congenital Bullous Poikiloderma". GeneReviews. PMID 26937547.
## External links[edit]
Classification
D
* ICD-10: Q82.8
* OMIM: 173650
* MeSH: C536321
* DiseasesDB: 32778
External resources
* eMedicine: derm/943
* Orphanet: 2908
* 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
* t
* e
Cell membrane protein disorders (other than Cell surface receptor, enzymes, and cytoskeleton)
Arrestin
* Oguchi disease 1
Myelin
* Pelizaeus–Merzbacher disease
* Dejerine–Sottas disease
* Charcot–Marie–Tooth disease 1B, 2J
Pulmonary surfactant
* Surfactant metabolism dysfunction 1, 2
Cell adhesion molecule
IgSF CAM:
* OFC7
Cadherin:
* DSG1
* Striate palmoplantar keratoderma 1
* DSG2
* Arrhythmogenic right ventricular dysplasia 10
* DSG4
* LAH1
* DSC2
* Arrhythmogenic right ventricular dysplasia 11
Integrin:
* cell surface receptor deficiencies
Tetraspanin
* TSPAN7
* X-Linked mental retardation 58
* TSPAN12
* Familial exudative vitreoretinopathy 5
Other
* KIND1
* Kindler syndrome
* HFE
* HFE hereditary haemochromatosis
* DYSF
* Distal muscular dystrophy
* Limb-girdle muscular dystrophy 2B
See also other cell membrane proteins
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*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Kindler syndrome | c0406557 | 3,009 | wikipedia | https://en.wikipedia.org/wiki/Kindler_syndrome | 2021-01-18T18:44:37 | {"gard": ["4391"], "mesh": ["C536321"], "icd-10": ["Q82.8"], "orphanet": ["306539"], "wikidata": ["Q1741965"]} |
Aggressive infantile fibromatosis is a locally recurring, non-metastasizing lesion, presenting with a single or multiple fast-growing masses that are present at birth or occur within the first year of life.[1]:607[2]
## See also[edit]
* Infantile digital fibromatosis
* Skin lesion
## References[edit]
1. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
2. ^ Yesudian, DP; Krishnan, SG; Jayaraman, M; Janaki, VR; Raj, BJ (1995). "Aggressive infantile fibromatosis". Indian Journal of Dermatology, Venereology and Leprology. 62 (5): 327–8. PMID 20948107.
This Dermal and subcutaneous growths article is a stub. You can help Wikipedia by expanding it.
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* 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
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Aggressive infantile fibromatosis | c0406580 | 3,010 | wikipedia | https://en.wikipedia.org/wiki/Aggressive_infantile_fibromatosis | 2021-01-18T19:01:51 | {"wikidata": ["Q4692278"]} |
Osteofibrous dysplasia is a rare, non-cancerous (benign) tumor that affects the long bones. It usually develops in children and adolescents. The most common location is the middle part of the tibia (shin), although the fibula (a smaller bone in the calf) and the long bones in the arm (humerus, radius, or ulna) may also be affected. In many cases, there are no symptoms and the condition is discovered when an x-ray is done for another reason (incidental finding). When symptoms are present, they most often include swelling and/or pain at the site of the tumor, a break in the bone (fracture) where it is weakened by the tumor, and/or bowing of the leg. The cause of osteofibrous dysplasia is unknown. Treatment is usually conservative, involving observation until the bone stops growing (skeletal maturity). Bracing may help prevent bowing of the limb and fractures. Surgery may be recommended once bone growth is complete.
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*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Osteofibrous dysplasia | c4085248 | 3,011 | gard | https://rarediseases.info.nih.gov/diseases/10887/osteofibrous-dysplasia | 2021-01-18T17:58:33 | {"omim": ["607278", "137575"], "orphanet": ["435329"], "synonyms": ["Intracortical fibrous dysplasia", "Multiple ossifying fibroma", "Ossifying fibroma", "Jaffe-Campanacci syndrome"]} |
Tangential speech or tangentiality is a communication disorder in which the train of thought of the speaker wanders and shows a lack of focus, never returning to the initial topic of the conversation.[1] It tends to occur in situations where a person is experiencing high anxiety, as a manifestation of the psychosis known as schizophrenia, in dementia or in states of delirium.[2] It is less severe than logorrhea and may be associated with the middle stage in dementia.[1] It is, however, more severe than circumstantial speech in which the speaker wanders, but eventually returns to the topic.[3]
Some adults with right hemisphere brain damage may exhibit behavior that includes tangential speech.[4] Those who exhibit these behaviors may also have related symptoms such as seemingly inappropriate or self-centered social responses, and a deterioration in pragmatic abilities (including appropriate eye contact as well as topic maintenance).[5]
## Contents
* 1 Definition
* 2 History
* 3 Other
* 4 See also
* 5 References
## Definition[edit]
The term refers simplistically to a thought disorder shown from speech with a lack of observance to the main subject of discourse, such that a person whilst speaking on a topic deviates from the topic. Further definition is of speech that deviates from an answer to a question that is relevant in the first instance but deviates from the relevancy to related subjects not involved in a direct answering of the question.[6][7][8] In the context of a conversation or discussion the communication is a response that is ineffective in that the form is inappropriate for adequate understanding.[9] The person's speech seems to indicate that their attention to their own speech has perhaps in some way been overcome during the occurrence of cognition whilst speaking, causing the vocalized content to follow thought that is apparently without reference to the original idea or question; or the person's speech is considered evasive in that the person has decided to provide an answer to a question that is an avoidance of a direct answer.[2]
## History[edit]
The earlier phenomenological description (Schneider 1930;et al.) allowed for further definition on the basis of formal characteristic rather than content, producing later practice relying upon clinical assessment (Andreasen 1979).[10] The term has undergone a re-definition to refer only to a persons speech in response to a question, and to provide the definition separation from the similar symptoms loosening of association and derailment (Andreasen 1979).[6][11]
## Other[edit]
According to the St. Louis system for the diagnosis of schizophrenia,[12] tangentiality is significantly associated with a low IQ prior to diagnosis (AU Parnas et al 2007).[13]
## See also[edit]
* Aphasia
* Theories of communication
* Circumstantial speech
* Harold Lasswell
## References[edit]
1. ^ a b Forensic Aspects of Communication Sciences and Disorders by Dennis C. Tanner 2003 ISBN 1-930056-31-1 page 289
2. ^ a b G. David Elkin (1999). Introduction to clinical psychiatry. McGraw-Hill Professional - 1999. ISBN 9780838543337. Retrieved 2012-01-17.
3. ^ Crash Course: Psychiatry by Julius Bourke, Matthew Castle, Alasdair D. Cameron 2008 ISBN 0-7234-3476-X page 255
4. ^ Introduction to Neurogenic Communication Disorders by Robert H. Brookshire 1997 ISBN 0-323-04531-6 page 393
5. ^ Perspectives on Treatment for Communication Deficits Associated With Right Hemisphere Brain Damage by Margaret Lehman Blake 2007 ISSN 1058-0360 page 333
6. ^ a b P. J. McKenna, Tomasina M. Oh Schizophrenic speech: making sense of bathroots and ponds that fall in doorways - 210 pages. Cambridge University Press, 2005. 2005-02-17. ISBN 9780521810753. Retrieved 2012-01-12. ISBN 0-521-81075-2
7. ^ Tali Ditman & Gina R. Kuperberg Building coherence : A framework for exploring the breakdown of links across clause boundaries in schizophrenia. Martinos Center for Biomedical Imaging. Retrieved 2012-01-17.
8. ^ Howard H. Goldman 2000 - Review of general psychiatry \- 583 pages A Lange medical book McGraw-Hill Professional, Retrieved 2012-01-17 ISBN 0-8385-8434-9
9. ^ Jeffrey A. Lieberman, T. Scott Stroup, M.D., Diana O. Perkins, M.D. 2011 Essentials of Schizophrenia \- 268 pages American Psychiatric Pub, 2 Jun 2011 Retrieved 2012-01-12 ISBN 1-58562-401-2
10. ^ S.J.Wood, N.B.Allen & C.Pantelis (Editors) 2009 - The Neuropsychology of Mental Illness Cambridge University Press Archived 2016-03-04 at the Wayback Machine Retrieved 2012-01-17 ISBN 978-0-521-86289-9
11. ^ Branca Telles Ribeiro 23 Jun 1994 - Coherence in psychotic discourse \- 320 pages Oxford studies in sociolinguistics Oxford University Press, Retrieved 2012-01-17 ISBN 0-19-506615-4
12. ^ Stephens, J. H.; Astrup, C.; Carpenter Jr, W. T.; Shaffer, J. W.; Goldberg, J. (1982). "A comparison of nine systems to diagnose schizophrenia". Psychiatry Research. 6 (2): 127–43. doi:10.1016/0165-1781(82)90001-4. PMID 6953455. S2CID 9781596.
13. ^ Urfer Parnas, A.; Jansson, L.; Handest, P.; Nielsen, J.; Sæbye, D.; Parnas, J. (2007). "Premorbid IQ varies across different definitions of schizophrenia". World Psychiatry. 6 (1): 38–41. PMC 1805734. PMID 17342225.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Tangential speech | None | 3,012 | wikipedia | https://en.wikipedia.org/wiki/Tangential_speech | 2021-01-18T18:59:33 | {"wikidata": ["Q7682883"]} |
## Summary
### Clinical characteristics.
Branchiootorenal spectrum disorder (BORSD) is characterized by malformations of the outer, middle, and inner ear associated with conductive, sensorineural, or mixed hearing impairment, branchial fistulae and cysts, and renal malformations ranging from mild renal hypoplasia to bilateral renal agenesis. Some individuals progress to end-stage renal disease (ESRD) later in life.
Extreme variability can be observed in the presence, severity, and type of branchial arch, otologic, audiologic, and renal abnormality from right side to left side in an affected individual and also among individuals in the same family.
### Diagnosis/testing.
The diagnosis of branchiootorenal spectrum disorder is based on clinical criteria. The diagnosis is established in a proband with the clinical features and/or heterozygous pathogenic variants in EYA1, SIX1, or SIX5 identified on molecular genetic testing.
### Management.
Treatment of manifestations: Excision of branchial cleft cysts/fistulae, fitting with appropriate aural habilitation, and enrollment in appropriate educational programs for the hearing impaired are appropriate. A canaloplasty should be considered to correct an atretic external auditory canal. Medical and surgical treatment for vesicoureteral reflux may prevent progression to end-stage renal disease (ESRD). ESRD may require renal transplantation.
Surveillance: Semiannual examination for hearing impairment and annual audiometry to assess progression of hearing loss; monitoring of renal function to prevent progression to ESRD; semiannual/annual examination by a nephrologist and/or urologist, as indicated.
Agents/circumstances to avoid: Nephrotoxic medications.
Evaluation of relatives at risk: At-risk relatives should be screened for hearing loss and renal involvement to allow for early diagnosis and treatment.
### Genetic counseling.
BORSD is inherited in an autosomal dominant manner. The offspring of an affected individual are at a 50% risk of inheriting the pathogenic variant. Once the pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.
## Diagnosis
Branchiootorenal spectrum disorder comprises branchiootorenal (BOR) syndrome and branchiootic syndrome (BOS), two phenotypes that differ only by the presence or absence of renal abnormality. Many affected persons in families with diagnosis confirmed by molecular genetic testing have clinical findings consistent with the diagnosis of BOR syndrome; however, some affected persons in these same families have clinical findings consistent with BOS [Orten et al 2008]. For this reason, these syndromes are best considered as one disorder known as branchiootorenal spectrum disorder.
### Suggestive Findings
Branchiootorenal spectrum disorder (BORSD) should be suspected in individuals with the following characteristics. See Table 1.
### Table 1.
Major and Minor Diagnostic Criteria for Branchiootorenal Spectrum Disorder
View in own window
Major CriteriaMinor Criteria
* Second branchial arch anomalies
* Deafness
* Preauricular pits
* Auricular malformation
* Renal anomalies
* External auditory canal anomalies
* Middle ear anomalies
* Inner ear anomalies
* Preauricular tags
* Other: facial asymmetry, palate abnormalities
In the absence of a family history, three or more major criteria OR two major and two minor criteria (Table 1) must be present to make the clinical diagnosis of BORSD [Chang et al 2004].
Second branchial arch anomalies
* Branchial cleft sinus tract appearing as a pinpoint opening anterior to the sternocleidomastoid muscle, usually in the lower third of the neck
* Branchial cleft cyst appearing as a palpable mass under the sternocleidomastoid muscle, usually above the level of the hyoid bone
Otologic findings
* Deafness: mild to profound in degree; conductive, sensorineural, or mixed in type (see Deafness and Hereditary Hearing Loss Overview)
* Preauricular pits
* Auricular malformation (lop ear, cupped ear)
* Preauricular tags
* Abnormalities of the external auditory canal: atresia or stenosis
* Middle ear abnormalities: malformation, malposition, dislocation, or fixation of the ossicles; reduction in size or malformation of the middle ear space
* Inner ear abnormalities: cochlear hypoplasia; enlargement of the cochlear and vestibular aqueducts; hypoplasia of the lateral semicircular canal [Ceruti et al 2002, Kemperman et al 2002]
Renal anomalies
* Renal agenesis, hypoplasia, dysplasia
* Uretero-pelvic junction (UPJ) obstruction
* Calyceal cyst/diverticulum
* Calyectasis, pelviectasis, hydronephrosis, and vesicoureteral reflux
Note: Individuals with an affected family member need only one major criterion to make the diagnosis of BORSD [Chang et al 2004].
### Establishing the Diagnosis
The diagnosis of a branchiootorenal spectrum disorder is established in a proband with the clinical features listed in Suggestive Findings and/or by identification of a heterozygous pathogenic variant in one of the genes listed in Table 2.
Molecular genetic testing approaches can include a combination of gene-targeted testing (multigene panel) and comprehensive genomic testing (chromosomal microarray analysis, exome sequencing, exome array, genome sequencing) depending on the phenotype.
Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of branchiootorenal spectrum disorder is broad, individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those with atypical features in whom the diagnosis of branchiootorenal spectrum disorder has not been considered are more likely to be diagnosed using genomic testing (see Option 2).
#### Option 1
When the phenotypic and laboratory findings suggest the diagnosis of branchiootorenal spectrum disorder the use of a multigene panel is recommended.
A multigene panel including EYA1, SIX1, SIX5, and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
For this disorder a multigene panel that also includes deletion/duplication analysis is recommended (see Table 1).
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
#### Option 2
When the diagnosis of branchiootorenal spectrum disorder is not considered because an individual has atypical phenotypic features, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is the best option. Exome sequencing is most commonly used; genome sequencing is also possible.
Exome array (when clinically available) may be considered if exome sequencing is not diagnostic.
For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
### Table 2.
Molecular Genetic Testing Used in Branchiootorenal Spectrum Disorder (BORSD)
View in own window
Gene 1, 2Proportion of BORSD Attributed to Pathogenic Variants in GeneProportion of Pathogenic Variants 3 Detectable by Method
Sequence analysis 4Gene-targeted deletion/duplication analysis 5
EYA140% 680% 620% 6
SIX12% 7100% 7Unknown 8
SIX52.5% 9100% 9Unknown 8
Unknown 10>50%NA
1\.
Genes are listed in alphabetic order.
2\.
See Table A. Genes and Databases for chromosome locus and protein.
3\.
See Molecular Genetics for information on allelic variants detected in this gene.
4\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
5\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.
6\.
Chang et al [2004], Krug et al [2011]
7\.
Heterozygous pathogenic variants were identified in 10 (4.0%) of 247 unrelated individuals with BORSD syndrome in whom an EYA1 or SIX5 pathogenic variant was not identified [Kochhar et al 2008]. This prevalence implies that SIX1 pathogenic variants account for approximately 2% of cases of BORSD.
8\.
No data on detection rate of gene-targeted deletion/duplication analysis are available.
9\.
Heterozygous pathogenic variants were identified in 5 (5.2%) of 95 unrelated individuals with BORSD in whom an EYA1 or SIX1 pathogenic variant was not identified [Hoskins et al 2007]; these data imply a SIX5 mutation rate of fewer than 2.5% of persons with BORSD syndrome.
10\.
Brophy et al [2013], Morisada et al [2014]
## Clinical Characteristics
### Clinical Description
The presence, severity, and type of branchial arch, otologic, audiologic, and renal abnormality in branchiootorenal spectrum disorder (BORSD) may differ from right side to left side in an affected individual and among individuals in the same family.
Second branchial arch anomalies include branchial cleft cyst or sinus tract (cervical fistulae) (50%). Cysts can become infected and sinus tracts can drain.
Otologic findings, found in more than 90% of individuals with BORSD [Chang et al 2004], include:
* Hearing loss (>90%) [Stinckens et al 2001]
* Type: mixed (52%), conductive (33%), sensorineural (29%)
* Severity: mild (27%), moderate (22%), severe (33%), profound (16%)
* Non-progressive (~70%), progressive (~30%, correlates with presence of a dilated vestibular aqueduct on computed tomography) [Kemperman et al 2004]
* Abnormalities of the pinnae
* Preauricular pits (82%)
* Lop ear malformation (36%)
* Preauricular tags (13%)
* Abnormalities of the external auditory canal. Atresia or stenosis (29%)
* Middle ear abnormalities. Malformation, malposition, dislocation, or fixation of the ossicles; reduction in size or malformation of the middle ear space
* Inner ear abnormalities. Variably present:
* Cochlear hypoplasia
* Enlargement of the cochlear and vestibular aqueducts
* Hypoplasia of the lateral semicircular canal [Ceruti et al 2002, Kemperman et al 2002]
Renal anomalies. Renal malformations can be unilateral or bilateral and can occur in any combination. The most severe malformations result in pregnancy loss (since bilateral renal agenesis can end in miscarriage) or neonatal death; ESRD later in life may necessitate dialysis or transplantation.
Although renal anomalies are common, the true prevalence is difficult to establish because not all affected individuals undergo intravenous pyelography or renal ultrasonography. In a study in which 21 affected individuals had one of these two tests, renal anomalies were noted in 67% [Chang et al 2004] and included the following:
* Renal agenesis (29%), hypoplasia (19%), dysplasia (14%)
* Uretero-pelvic junction (UPJ) obstruction (10%)
* Calyceal cyst/diverticulum (10%)
* Calyectasis, pelviectasis, hydronephrosis, and vesicoureteral reflux (5% each)
Other findings [Chang et al 2004]
* Lacrimal duct aplasia
* Short or cleft palate
* Retrognathia
* Euthyroid goiter
* Facial nerve paralysis
* Gustatory lacrimation
### Genotype-Phenotype Correlations
A genotype-phenotype correlation has not been defined for BORSD. In fact, families have been identified segregating SIX1 pathogenic variants and exhibiting broad intrafamilial phenotypic variability. For example, in one large family all 18 persons with hearing loss carried the p.Tyr129Cys variant in SIX1, although six persons also had ear pits, three others had branchial cysts, and two developed a renal carcinoma [Ruf et al 2004]. In a small Tunisian family [Mosrati et al 2011], five persons with moderate-to-profound mixed or sensorineural hearing loss had the SIX1 p.Glu125Lys variant. Preauricular pits were present in four persons, but none had other branchial, renal, or temporal bone anomalies. These reports suggest that genetic background and stochastic factors influence intrafamilial phenotypic variability and preclude making genotypic-phenotypic correlations.
### Penetrance
Based on careful clinical studies of large pedigrees, branchiootorenal spectrum disorder appears to have 100% penetrance, although expressivity is highly variable [Chang et al 2004].
### Nomenclature
BOR syndrome was originally known eponymously as Melnick-Fraser syndrome. While phenotypic descriptions are applied to BOR, BOS, and even branchiootoureteral (BOU) syndrome, these clinical distinctions must be considered in light of the associated molecular genetics. Affected individuals within a single family may have findings of any of the phenotypes. Thus, the term "branchiootorenal spectrum disorder" has replaced the older descriptive phenotype designations.
### Prevalence
The prevalence of branchiootorenal spectrum disorder is not known. In 1976, GR Fraser surveyed 3,640 children with profound hearing impairment and found only five (0.15%) with a family history of branchial fistulae and preauricular pits (1:700,000) [Fraser 1976]. Four years later, FC Fraser et al [1980] surveyed 421 children attending schools for the deaf in Montreal for preauricular pits and branchial fistulae, and identified 19 children with preauricular pits; two also had branchial fistulae. The parents of nine children agreed to participate in further investigation, which included audiograms and intravenous pyelograms, and confirmed BORSD segregating in four families, leading the authors to estimate the prevalence of BORSD at 1:40,000, or roughly 2% of profoundly deaf children. Interestingly, Morisada et al [2014] reported that only 250 patients with BORSD (95% confidence interval, 170-320) were identified in clinics in Japan in 2009-2010, suggesting that there are ethnic differences in the prevalence. In the authors' experience at the Molecular Otolaryngology and Renal Research Laboratories (MORL), of 3,379 persons screened for genetic causes of hearing loss (no exclusionary criteria), the diagnostic rate was 42.4% (1,434 persons had an identified genetic cause of hearing loss); 25 of the 1,434 persons (1.7%) had BORSD [Smith, unpublished data].
## Differential Diagnosis
More than 400 genetic syndromes that include hearing loss have been described [Toriello & Smith 2013, Korver et al 2017]. Although the branchiootorenal spectrum disorder has a distinctive phenotype that is readily appreciated when segregating in large families, the diagnosis can be difficult to establish in small families. See Hereditary Hearing Loss and Deafness Overview.
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with branchiootorenal spectrum disorder the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended:
* Second branchial arch anomalies. Cervical examination for fistulae; computed tomography of the neck if a mass is palpable under the sternocleidomastoid muscle above the level of the hyoid bone
* Otologic findings
* A complete assessment of auditory acuity using ABR, emission testing, and pure tone audiometry (see Hereditary Hearing Loss and Deafness Overview)
* Computed tomography of the temporal bones, especially if the hearing impairment fluctuates or is progressive
* Renal anomalies. Renal ultrasound examination and/or excretory urography (intravenous pyelography); tests of renal function: BUN and creatinine; urinanalysis
* Other. Consultation with a clinical geneticist and/or genetic counselor
### Treatment of Manifestations
Recommended treatment:
* Second branchial arch anomalies. Excise branchial cleft cysts/fistulae.
* Otologic anomalies
* Fit with appropriate aural habilitation as indicated.
* Enroll in an appropriate educational program for the hearing impaired.
* Consider canaloplasty to correct an atretic canal; however, in individuals with BORSD, associated middle ear anomalies (e.g., a facial nerve overriding the oval window) can preclude a successful result. Evaluate the status of the middle ear preoperatively by obtaining thin-cut CT images of the temporal bones in both the axial and coronal planes.
* Renal anomalies
* Treat urologic and renal abnormalities in the standard manner.
* If renal anomalies (e.g., vesicoureteral reflux) are present, medical and surgical treatment may prevent progression to end-stage renal disease (ESRD).
* If ESRD develops, consider renal transplantation.
### Surveillance
Surveillance for otologic and renal anomalies should be offered as described below.
Otologic anomalies. Serial audiometry to survey for progression of hearing loss:
* Annual examination by a physician who is familiar with hereditary hearing impairment
* Semiannual examination for hearing impairment and annual audiometry to assess stability of hearing loss (more frequent if fluctuation or progression is described by the affected individual)
Renal anomalies. Semiannual/annual examination by a nephrologist and/or urologist may be indicated based on level of renal function and type of renal and/or collecting system malformation.
### Agents/Circumstances to Avoid
Individuals with renal abnormalities should use appropriate caution when taking medications (i.e., antibiotics and analgesics) that can impair renal function or require normal renal physiology for clearance.
### Evaluation of Relatives at Risk
It is appropriate to evaluate apparently asymptomatic relatives at risk for BORSD to determine if a treatable and/or possibly progressive otologic and/or renal abnormality is present. Evaluations can include:
* Molecular genetic testing if the pathogenic variant in the family is known;
* Comprehensive physical examination (to include hearing evaluation and renal imaging and function studies) 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.
### Therapies Under Investigation
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Branchiootorenal Spectrum Disorder | None | 3,013 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1380/ | 2021-01-18T21:39:01 | {"synonyms": []} |
Acute myelomonocytic leukemia (AMML) is a cancer that typically develops in the bone marrow and blood of older individuals. AMML is one type of acute myeloid leukemia, a group of blood cancers that occur when the amount of white blood cells increases rapidly. Symptoms of AMML often include fatigue (due to anemia) or easy bruising or bleeding (due to thrombocytopenia). The cause of AMML is currently unknown. Treatment typically consists of chemotherapy.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22) | c0023479 | 3,014 | gard | https://rarediseases.info.nih.gov/diseases/536/acute-myeloid-leukemia-with-abnormal-bone-marrow-eosinophils-inv16p13q22-or-t1616p13q22 | 2021-01-18T18:02:18 | {"mesh": ["D015479"], "umls": ["C0023479"], "orphanet": ["98829"], "synonyms": ["AML with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22)", "AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22)", "CBFB-MYH11", "Acute myelomonocytic leukemia "]} |
Finnish upper limb-onset distal myopathy is a rare, genetic distal myopathy characterized by slowly progressive distal to proximal limb muscle weakness and atrophy, with characteristic early involvement of thenar and hypothenar muscles. Patients present with clumsiness of the hands and stumbling in the fourth to fifth decade of life, and later develop steppage gait and contractures of the hands. Progressive fatty degeneration affects intrinsic muscles of the hands, gluteus medium and both anterior and posterior compartment muscles of the distal lower extremities, with later involvement of forearm muscles, triceps, infraspinatus and the proximal lower limb muscles. Asymmetry of muscle involvement is common.
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Finnish upper limb-onset distal myopathy | c1864706 | 3,015 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=399086 | 2021-01-23T18:20:33 | {"mesh": ["C566445"], "omim": ["610099"], "umls": ["C1864706"], "icd-10": ["G71.0"], "synonyms": ["Distal myopathy type 3", "MPD3"]} |
Functional constipation
Other namesChronic idiopathic constipation
Functional constipation, known as chronic idiopathic constipation (CIC), is constipation that does not have a physical (anatomical) or physiological (hormonal or other body chemistry) cause. It may have a neurological, psychological or psychosomatic cause. A person with functional constipation may be healthy, yet has difficulty defecating.
## Contents
* 1 Symptoms and diagnosis
* 2 Treatment
* 3 Research
* 4 See also
* 5 References
## Symptoms and diagnosis[edit]
Chronic idiopathic constipation is similar to constipation-predominant irritable bowel syndrome (IBS-C); however, people with CIC do not have other symptoms of IBS, such as abdominal pain.[1] Diagnosing CIC can be difficult as other syndromes must be ruled out as there is no physiological cause for CIC. Doctors will typically look for other symptoms, such as blood in stool, weight loss, low blood count, or other symptoms.
To be considered functional constipation, symptoms must be present at least a fourth of the time.[1] Possible causes are:
* Anismus
* Descending perineum syndrome
* Other inability or unwillingness to control the external anal sphincter, which normally is under voluntary control
* A poor diet
* An unwillingness to defecate
* Nervous reactions, including prolonged and/or chronic stress and anxiety, that close the internal anal sphincter, a muscle that is not under voluntary control
* Deeper psychosomatic disorders which sometimes affect digestion and the absorption of water in the colon
There is also possibility of presentation with other comorbid symptoms such as headache, especially in children.[2]
## Treatment[edit]
Treatment options appear similar and include prucalopride, lubiprostone, linaclotide, tegaserod, velusetrag, elobixibat, bisacodyl, sodium picosulphate,[3] and most recently, plecanatide.
## Research[edit]
A 2014 meta-analysis of three small trials evaluating probiotics showed a slight improvement in management of chronic idiopathic constipation, but well-designed studies are necessary to know the true efficacy of probiotics in treating this condition.[4]
Children with functional constipation often claim to lack the sensation of the urge to defecate, and may be conditioned to avoid doing so due to a previous painful experience.[5] One retrospective study showed that these children did indeed have the urge to defecate using colonic manometry, and suggested behavioral modification as a treatment for functional constipation.[6]
## See also[edit]
* Functional symptom
* Sacral nerve stimulation
## References[edit]
1. ^ a b Americal College of Gastroenterology: Fuinctional Bowel Disorders
2. ^ Inaloo S, Dehghani SM, Hashemi SM, Heydari M, Heydari ST (2014). "Comorbidity of headache and functional constipation in children: a cross-sectional survey". Turk J Gastroenterol. 25 (5): 508–11. doi:10.5152/tjg.2014.6183. PMID 25417610.
3. ^ Nelson, AD; Camilleri, M; Chirapongsathorn, S; Vijayvargiya, P; Valentin, N; Shin, A; Erwin, PJ; Wang, Z; Murad, MH (September 2017). "Comparison of efficacy of pharmacological treatments for chronic idiopathic constipation: a systematic review and network meta-analysis". Gut. 66 (9): 1611–1622. doi:10.1136/gutjnl-2016-311835. hdl:1805/12164. PMID 27287486.
4. ^ Ford, Alexander C; Quigley, Eamonn M M; Lacy, Brian E; Lembo, Anthony J; Saito, Yuri A; Schiller, Lawrence R; Soffer, Edy E; Spiegel, Brennan M R; Moayyedi, Paul (2014). "Efficacy of Prebiotics, Probiotics, and Synbiotics in Irritable Bowel Syndrome and Chronic Idiopathic Constipation: Systematic Review and Meta-analysis". The American Journal of Gastroenterology. 109 (10): 1547–1561. doi:10.1038/ajg.2014.202. ISSN 0002-9270. PMID 25070051.
5. ^ Fleisher, DR (November 1976). "Diagnosis and treatment of disorders of defecation in children". Pediatric Annals. 5 (11): 71–101. PMID 980548.
6. ^ Firestone Baum, C; John A; Srinivasan K; Harrison P; Kolomensky A; Monagas J; Cocjin J; Hyman PE (January 2013). "Colon manometry proves that perception of the urge to defecate is present in children with functional constipation who deny sensation". Journal of Pediatric Gastroenterology and Nutrition. 56 (1): 19–22. doi:10.1097/MPG.0b013e31826f2740. PMID 22922371.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Functional constipation | c0401146 | 3,016 | wikipedia | https://en.wikipedia.org/wiki/Functional_constipation | 2021-01-18T18:35:02 | {"wikidata": ["Q5508805"]} |
UV-sensitive syndrome
Other namesUVSS
This condition is inherited in an autosomal recessive manner.
SpecialtyDermatology
UV-sensitive syndrome is a cutaneous condition inherited in an autosomal recessive fashion, characterized by photosensitivity and solar lentigines.[1] Recent research identified that mutations of the KIAA1530 (UVSSA) gene as cause for the development of UV-sensitive syndrome.[2] Furthermore, this protein was identified as a new player in the Transcription-coupled repair (TC-NER).[2]
## Contents
* 1 See also
* 2 References
* 3 Further reading
* 4 External links
## See also[edit]
* Solar urticaria
* List of cutaneous conditions
* Cockayne syndrome
* Xeroderma pigmentosum
* Nucleotide excision repair
## References[edit]
1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 1342. ISBN 978-1-4160-2999-1.
2. ^ a b Schwertman P., Marteijn JA.; Lagarou A; Dekkers DH; Raams A; van der Hoek AC; Laffeber C; Hoeijmakers JH; Demmers JA; Fousteri M; Vermeulen W (May 2012). "UV-sensitive syndrome protein UVSSA recruits USP7 to regulate transcription-coupled repair". Nat. Genet. 44 (5): 598–602. doi:10.1038/ng.2230. PMID 22466611. S2CID 5486230.
## Further reading[edit]
* "UV sensitive syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 6 November 2018.
## External links[edit]
Classification
D
* OMIM: 600630
* MeSH: 563466
External resources
* Orphanet: 178338
This dermatology article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| UV-sensitive syndrome | c3551173 | 3,017 | wikipedia | https://en.wikipedia.org/wiki/UV-sensitive_syndrome | 2021-01-18T18:53:21 | {"gard": ["10947"], "mesh": ["563466"], "umls": ["C3551173"], "orphanet": ["178338"], "wikidata": ["Q7876086"]} |
Not to be confused with bronchitis, bronchiolitis obliterans, or bronchiolitis obliterans organizing pneumonia.
Blockage of the small airways in the lungs due to a viral infection
Bronchiolitis
An X-ray of a child with RSV showing the typical bilateral perihilar fullness of bronchiolitis.
SpecialtyEmergency medicine, pediatrics
SymptomsFever, cough, runny nose, wheezing, breathing problems[1]
ComplicationsRespiratory distress, dehydration[1]
Usual onsetLess than 2 years old[2]
CausesViral infection (respiratory syncytial virus, human rhinovirus)[2]
Diagnostic methodBased on symptoms[1]
Differential diagnosisAsthma, pneumonia, heart failure, allergic reaction, cystic fibrosis[1]
TreatmentSupportive care (oxygen, support with feeding, intravenous fluids)[3]
Frequency~20% (children less than 2)[2][1]
Deaths1% (among those hospitalized)[4]
Bronchiolitis is blockage of the small airways in the lungs due to a viral infection.[1] It usually only occurs in children less than two years of age.[2] Symptoms may include fever, cough, runny nose, wheezing, and breathing problems.[1] More severe cases may be associated with nasal flaring, grunting, or the skin between the ribs pulling in with breathing.[1] If the child has not been able to feed properly, signs of dehydration may be present.[1]
Bronchiolitis is usually the result of infection by respiratory syncytial virus (72% of cases) or human rhinovirus (26% of cases).[2] Diagnosis is generally based on symptoms.[1] Tests such as a chest X-ray or viral testing are not routinely needed.[2]
There is no specific treatment.[3][5] Supportive care at home is generally sufficient.[1] Occasionally hospital admission for oxygen, support with feeding, or intravenous fluids is required.[1] Tentative evidence supports nebulized hypertonic saline.[6] Evidence for antibiotics, antivirals, bronchodilators, or nebulized epinephrine is either unclear or not supportive.[7]
About 10% to 30% of children under the age of two years are affected by bronchiolitis at some point in time.[1][2] It more commonly occurs in the winter in the Northern hemisphere.[1] It is the leading cause of hospitalizations in those less than one year of age in the United States.[8][5] The risk of death among those who are admitted to hospital is about 1%.[4] Outbreaks of the condition were first described in the 1940s.[9]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 2.1 Risk factors
* 3 Diagnosis
* 3.1 Differential diagnosis
* 4 Prevention
* 5 Management
* 5.1 Diet
* 5.2 Oxygen
* 5.3 Hypertonic saline
* 5.4 Bronchodilators
* 5.5 Epinephrine
* 5.6 Unclear evidence
* 5.7 Non-effective treatments
* 6 Epidemiology
* 7 References
* 8 External links
## Signs and symptoms[edit]
Play media
Video explanation
Bronchiolitis typically presents in children under two years old and is characterized by a constellation of respiratory symptoms that consists of fever, rhinorrhea, cough, wheeze, tachypnea and increased work of breathing such as nasal flaring or grunting that develops over one to three days.[8] Crackles or wheeze are typical findings on listening to the chest with a stethoscope. The child may also experience apnea, or brief pauses in breathing. After the acute illness, it is common for the airways to remain sensitive for several weeks, leading to recurrent cough and wheeze.
Some signs of severe disease include:[10]
* poor feeding (less than half of usual fluid intake in preceding 24 hours)
* significantly decreased activity
* history of stopping breathing
* respiratory rate >70/min
* presence of nasal flaring and/or grunting
* severe chest wall recession (Hoover's sign)
* bluish skin
## Causes[edit]
Acute inflammatory exudate occluding the lumen of the bronchiole and acute inflammation of part of the wall of the bronchiole
The term usually refers to acute viral bronchiolitis, a common disease in infancy. This is most commonly caused by respiratory syncytial virus[11] (RSV, also known as human pneumovirus). Other agents that cause this illness include human metapneumovirus, influenza, parainfluenza, coronavirus, adenovirus, rhinovirus and mycoplasma.[12][13]
### Risk factors[edit]
Children are at an increased risk for progression to severe respiratory disease if they have any of the following additional factors:[5][8][13][14]
* Preterm infant (gestational age less than 37 weeks)
* Younger age at onset of illness (less than 3 months of age)
* Congenital heart disease
* Immunodeficiency
* Chronic lung disease
* Neurological disorders
* Tobacco smoke exposure
## Diagnosis[edit]
Wheezing
Wheezing heard in the lungs of an adult using a stethoscope. Similar sounds might be heard in a child with bronchiolitis.
* * *
Problems playing this file? See media help.
The diagnosis is typically made by clinical examination. Chest X-ray is sometimes useful to exclude bacterial pneumonia, but not indicated in routine cases.[15] Chest x-ray may also be useful in people with impending respiratory failure.[16] Additional testing such as blood cultures, complete blood count, and electrolyte analyses are not recommended for routine use although may be useful in children with multiple comorbidities or signs of sepsis or pneumonia.[5][16]
Testing for the specific viral cause can be done but has little effect on management and thus is not routinely recommended.[15] RSV testing by direct immunofluorescence testing on nasopharyngeal aspirate had a sensitivity of 61% and specificity of 89%.[13][16] Identification of those who are RSV-positive can help for disease surveillance, grouping ("cohorting") people together in hospital wards to prevent cross infection, predicting whether the disease course has peaked yet, and reducing the need for other diagnostic procedures (by providing confidence that a cause has been identified).[5] Identification of the virus may help reduce the use of antibiotics.[16]
Infants with bronchiolitis between the age of two and three months have a second infection by bacteria (usually a urinary tract infection) less than 6% of the time.[17] When further evaluated with a urinalysis, infants with bronchiolitis had a concomitant UTI 0.8% of the time.[18] Preliminary studies have suggested that elevated procalcitonin levels may assist clinicians in determining the presence of bacterial co-infection, which could prevent unnecessary antibiotic use and costs.[19]
### Differential diagnosis[edit]
There are many childhood illnesses that can present with respiratory symptoms, particularly persistent cough and wheezing.[8][20] Bronchiolitis may be differentiated from some of these by the characteristic pattern of preceding febrile upper respiratory tract symptoms lasting for 1 to 3 days followed by the persistent cough, tachypnea, and wheezing.[20] However, some infants may present without fever (30% of cases) or may present with apnea without other signs or with poor weight gain prior to onset of symptoms.[20] In such cases, additional laboratory testing and radiographic imaging may be useful.[8][20] The following are some other diagnoses to consider in an infant presenting with signs of bronchiolitis:[citation needed]
* Asthma and reactive airway disease
* Bacterial pneumonia
* Congenital heart disease
* Heart failure
* Whooping cough
* Allergic reaction
* Cystic fibrosis
* Chronic pulmonary disease
* Foreign body aspiration
* Vascular ring
## Prevention[edit]
Prevention of bronchiolitis relies strongly on measures to reduce the spread of the viruses that cause respiratory infections (that is, handwashing, and avoiding exposure to those symptomatic with respiratory infections).[5][8] Guidelines are mixed on the use of gloves, aprons, or personal protective equipment.[5] In addition to good hygiene, an improved immune system is a great tool for prevention.[citation needed]
One way to improve the immune system is to feed the infant with breast milk, especially during the first month of life.[14][21] Respiratory infections were shown to be significantly less common among breastfed infants and fully breastfed RSV-positive hospitalized infants had shorter hospital stays than non or partially breastfed infants.[8] Guidelines recommend exclusive breastfeeding for infants for the first 6 months of life.[8]
Palivizumab, a monoclonal antibody against RSV, can be administered to prevent bronchiolitis to infants less than one year of age that were born very prematurely or that have underlying heart disease or chronic lung disease of prematurity.[8] Passive immunization therapy requires monthly injections during winter.[8] Otherwise healthy premature infants that were born after a gestational age of 29 weeks should not be administered palivizumab as the harms outweigh the benefits.[8] Passive protection through the administration of other novel monoclonal antibodies is also under evaluation.[16]
The development of immunizations for RSV are being developed but there are none available currently.[16][22]
Tobacco smoke exposure has been shown to increase both the rates of lower respiratory disease in infants as well as the risk and severity of bronchiolitis.[8] Tobacco smoke lingers in the environment for prolonged periods and on clothing even when smoking outside the home.[8] Guidelines recommend that parents be fully educated on the risks of tobacco smoke exposure on children with bronchiolitis.[8][20]
## Management[edit]
Treatment of bronchiolitis is usually focused on the hydration and symptoms instead of the infection itself since the infection will run its course and complications are typically from the symptoms themselves.[23] Without active treatment, half of cases will go away in 13 days and 90% in three weeks.[24] Children with severe symptoms, especially poor feeding or dehydration, may be considered for hospital admission.[5] Oxygen saturation under 90%-92% as measured with pulse oximetry is also frequently used as an indicator of need for hospitalization.[5] High-risk infants, apnea, cyanosis, malnutrition, and diagnostic uncertainty are additional indications for hospitalization.[5]
Most guidelines recommend sufficient fluids and nutritional support for affected children.[5] Measures for which the recommendations were mixed include nebulized hypertonic saline, nebulized epinephrine, and nasal suctioning.[1][5][25][26] Treatments which the evidence does not support include salbutamol, steroids, antibiotics, antivirals, heliox, continuous positive airway pressure (CPAP), chest physiotherapy, and cool mist or steam inhalation.[1][27][28][29][30]
### Diet[edit]
Maintaining hydration is an important part of management of bronchiolitis.[8][16][31] Infants with mild pulmonary symptoms may require only observation if feeding is unaffected.[8] However, oral intake may be affected by nasal secretions and increased work of breathing.[8] Poor feeding or dehydration, defined as less than 50% of usual intake, is often cited as an indication for hospital admission.[5] Guidelines recommend the use of nasogastric or intravenous fluids in children with bronchiolitis who cannot maintain usual oral intake.[8][20][16] The risk of health care caused hyponatremia and fluid retention are minimal with the use of isotonic fluids such as normal saline, breast milk, or formula.[8]
### Oxygen[edit]
A newborn wearing a nasal CPAP device.
Inadequate oxygen supply to the tissue is one of the main concerns during severe bronchiolitis and oxygen saturation is often closely associated with both the need for hospitalization and continued length of hospital stay in children with bronchiolitis.[16] However, oxygen saturation is a poor predictor of respiratory distress.[8] Accuracy of pulse oximetry is limited in the 76% to 90% range and there is weak correlation between oxygen saturation and respiratory distress as brief hypoxemia is common in healthy infants.[8][16] Additionally, pulse oximetry is associated with frequent false alarms and parental stress and fatigue.[8] Clinicians may choose not to given additional oxygen to children with bronchiolitis if their oxygen saturation is above 90%.[8][20][16] Additionally, clinicians may choose not to use continuous pulse oximetry in these people.[8]
When choosing to use oxygen therapy for a child with bronchiolitis, there is evidence that home oxygen may reduce hospitalization rate and length of stay although readmission rates and follow-up visits are increased.[8] Also, the use of humidified, heated, high-flow nasal cannula may be a safe initial therapy to decrease work of breathing and need for intubation.[8][32] However, evidence is lacking regarding the use of high-flow nasal cannula compared to standard oxygen therapy or continuous positive airway pressure.[16][32][33] These practices may still be used in severe cases prior to intubation.[20][34][35]
Blood gas testing is not recommended for people hospitalized with the disease and is not useful in the routine management of bronchiolitis.[16][20] People with severe worsening respiratory distress or impending respiratory failure may be considered for capillary blood gas testing.[20]
### Hypertonic saline[edit]
Guidelines recommend against the use of nebulized hypertonic saline in the emergency department for children with bronchiolitis but it may be given to children who are hospitalized.[8][16]
Nebulized hypertonic saline (3%) has limited evidence of benefit and previous studies lack consistency and standardization.[6][7][36][37] A 2017 review found tentative evidence that it reduces the risk of hospitalization, duration of hospital stay, and improved the severity of symptoms.[6][38] The majority of evidence suggests that hypertonic saline is safe and effective at improving respiratory symptoms of mild to moderate bronchiolitis after 24 hours of use.[39] However, it does not appear effective in reducing the rate of hospitalization when used in the emergency room or other outpatient settings in which length of therapy is brief.[8] Side effects were mild and resolved spontaneously.[6]
### Bronchodilators[edit]
Guidelines recommend against the use of bronchodilators in children with bronchiolitis as evidence does not support a change in outcomes with such use.[8][20][40][41] Additionally, there are adverse effects to the use of bronchodilators in children such as tachycardia and tremors as well as adding increased financial expenses.[42][43]
Several studies have shown that bronchodilation with β-adrenergic agents such as salbutamol may improve symptoms briefly but do not affect the overall course of the illness or reduce the need for hospitalization.[8] However, there are conflicting recommendations about the use of a trial of a bronchodilator, especially in those with history of previous wheezing, due to the difficulty with assessing an objective improvement in symptoms.[5][8][16] Bronchiolitis-associated wheezing is likely not effectively alleviated by bronchodilators anyway as it is caused by airway obstruction and plugging of the small airway diameters by luminal debris, not bronchospasm as in asthma-associated wheezing that bronchodilators usually treat well.[43]
Anticholinergic inhalers, such as ipratropium bromide, have a modest short term effect at best and are not recommended for treatment.[20][44][45]
### Epinephrine[edit]
The current state of evidence suggests that nebulized epinephrine is not indicated for children with bronchiolitis except as a trial of rescue therapy for severe cases.[8][20]
Epinephrine is an α and β adrenergic agonist that has been used to treat other upper respiratory tract illnesses, such as croup, as a nebulized solution.[46] A Cochrane meta-analysis in 2011 found no benefit to the use of epinephrine in the inpatient setting and suggested that there may be utility in the outpatient setting in reducing the rate of hospitalization.[47][26] However, current guidelines do not support the outpatient use of epinephrine given the lack of substantial sustained benefit.[8]
A 2017 review found inhaled epinephrine with corticosteroids did not change the need for hospitalization or the time spent in hospital.[48] Other studies suggest a synergistic effect of epinephrine with corticosteroids but have not consistently demonstrated benefits in clinical trials.[8] Guidelines recommend against its use currently.[8][5]
### Unclear evidence[edit]
Currently other medications do not yet have evidence to support their use, although they have been studied for use in bronchiolitis.[8][49] Experimental trials with novel antiviral medications in adults are promising but it remains unclear if the same benefit will be present.[16]
* Surfactant had favorable effects for severely critical infants on duration of mechanical ventilation and ICU stay however studies were few and small.[50][12]
* Chest physiotherapy, such as vibration or percussion, to promote airway clearance may slightly reduce duration of oxygen therapy but there is a lack of evidence that demonstrates any other benefits.[8][51] People with difficulty clearing secretions due to underlying disorders such as spinal muscle atrophy or severe tracheomalacia may be considered for chest physiotherapy.[20]
* Suctioning of the nares may provide temporarily relief of nasal congestion but deep suctioning of the nasopharynx has been shown prolong length of hospital stay in infants.[8][20] Upper airway suctioning may be considered in people with respiratory distress, feeding difficulties, or infants presenting with apnea.[20]
* Heliox, a mixture of oxygen and the inert gas helium, may be beneficial in infants with severe acute RSV bronchiolitis who require CPAP but overall evidence is lacking.[52]
* DNAse has not been found to be effective but might play a role in severe bronchiolitis complicated by atelectasis.[53]
* There are no systematic reviews or controlled trials on the effectiveness of nasal decongestants, such as xylometazoline, for the treatment of bronchiolitits.[12]
* Overall evidence is insufficient to support the use of alternative medicine.[54] There is tentative evidence for Chinese herbal medicine, vitamin D, N-acetylcysteine, and magnesium but this is insufficient to recommend their use.[54]
### Non-effective treatments[edit]
* Ribavirin is an antiviral drug which does not appear to be effective for bronchiolitis.[55]
* Antibiotics are often given in case of a bacterial infection complicating bronchiolitis, but have no effect on the underlying viral infection and their benefit is not clear.[55][56][57][58] The risks of bronchiolitis with a concomitant serious bacterial infection among hospitalized febrile infants is minimal and work-up and antibiotics are not justified.[8][18] Azithromycin adjuvant therapy may reduce the duration of wheezing and coughing in children with bronchiolitis but has not effect on length of hospital stay or duration of oxygen therapy.[59]
* Corticosteroids, although useful in other respiratory disease such as asthma and croup, have no proven benefit in bronchiolitis treatment and are not advised.[8][5][55][60][61] Additionally, corticosteroid therapy in children with bronchiolitis may prolong viral shedding and transmissibility.[8] The overall safety of corticosteroids is questionable.[62]
* Leukotriene inhibitors, such as montelukast, have not been found to be beneficial and may increase adverse effects.[5][63][64][65]
* Immunoglobulins are of unclear benefit.[66]
## Epidemiology[edit]
Bronchiolitis typically affects infants and children younger than two years, principally during the autumn and winter.[16] It is the leading cause of hospital admission for respiratory disease among infants in the United States and accounts for one out of every 13 primary care visits.[5] Bronchiolitis accounts for 3% of emergency department visits for children under 2 years old.[12] Bronchiolitis is the most frequent lower respiratory tract infection and hospitalization in infants worldwide.[16]
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64. ^ Peng, Wan-Sheng; Chen, Xin; Yang, Xiao-Yun; Liu, En-Mei (March 2014). "Systematic review of montelukast's efficacy for preventing post-bronchiolitis wheezing". Pediatric Allergy and Immunology. 25 (2): 143–150. doi:10.1111/pai.12124. ISSN 1399-3038. PMID 24118637. S2CID 27539127.
65. ^ Liu, Fang; Ouyang, Jing; Sharma, Atul N; Liu, Songqing; Yang, Bo; Xiong, Wei; Xu, Rufu (16 March 2015). "Leukotriene inhibitors for bronchiolitis in infants and young children". Cochrane Database of Systematic Reviews (3): CD010636. doi:10.1002/14651858.CD010636.pub2. PMID 25773054.
66. ^ Sanders, Sharon L; Agwan, Sushil; Hassan, Mohamed; van Driel, Mieke L; Del Mar, Chris B (26 August 2019). "Immunoglobulin treatment for hospitalised infants and young children with respiratory syncytial virus infection". Cochrane Database of Systematic Reviews. 8: CD009417. doi:10.1002/14651858.CD009417.pub2. PMC 6708604. PMID 31446622.
## External links[edit]
* Bronchiolitis. Patient information from NHS Choices
* "Bronchiolitis in children – A national clinical guideline" (PDF). Archived from the original (PDF) on 4 March 2016. Retrieved 6 December 2007. (1.74 MB) from the Scottish Intercollegiate Guidelines Network
* Ralston, SL; Lieberthal, AS; Meissner, HC; Alverson, BK; Baley, JE; Gadomski, AM; Johnson, DW; Light, MJ; Maraqa, NF; Mendonca, EA; Phelan, KJ; Zorc, JJ; Stanko-Lopp, D; Brown, MA; Nathanson, I; Rosenblum, E; Sayles S, 3rd; Hernandez-Cancio, S (27 October 2014). "Clinical Practice Guideline: The Diagnosis, Management, and Prevention of Bronchiolitis". Pediatrics. 134 (5): e1474–502. doi:10.1542/peds.2014-2742. PMID 25349312.
Classification
D
* ICD-10: J21
* ICD-9-CM: 466.1
* MeSH: D001988
* DiseasesDB: 1701
External resources
* MedlinePlus: 000975
* eMedicine: emerg/365
* Patient UK: Bronchiolitis
Look up bronchiolitis in Wiktionary, the free dictionary.
* v
* t
* e
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(including URTIs,
common cold)
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sinuses
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nose
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unspecified
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* v
* t
* e
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* Adenovirus
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Drugs
* Antiviral drugs
* Pleconaril (experimental)
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Bronchiolitis | c0006271 | 3,018 | wikipedia | https://en.wikipedia.org/wiki/Bronchiolitis | 2021-01-18T18:32:52 | {"mesh": ["D001988"], "umls": ["C0006271"], "icd-9": ["466.1"], "icd-10": ["J21"], "wikidata": ["Q424227"]} |
## Summary
### Clinical characteristics.
Costeff syndrome is characterized by optic atrophy and/or choreoathetoid movement disorder with onset before age ten years. Optic atrophy is associated with progressive decrease in visual acuity within the first years of life, sometimes associated with infantile-onset horizontal nystagmus. Most individuals have chorea, often severe enough to restrict ambulation. Some are confined to a wheelchair from an early age. Although most individuals develop spastic paraparesis, mild ataxia, and occasional mild cognitive deficit in their second decade, the course of the disease is relatively stable.
### Diagnosis/testing.
The diagnosis of Costeff syndrome is established in a proband with suggestive findings by identification of biallelic OPA3 pathogenic variants on molecular genetic testing.
### Management.
Treatment of manifestations: Supportive and often provided by a multidisciplinary team; treatment of visual impairment, spasticity, and movement disorder as in the general population.
Agents/circumstances to avoid: Use of tobacco, alcohol, and medications known to impair mitochondrial function.
### Genetic counseling.
Costeff syndrome is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an OPA3 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an unaffected carrier, and a 25% chance of being unaffected and not a carrier. When both OPA3 pathogenic variants have been identified in an affected family member, carrier testing for at-risk family members, prenatal testing for pregnancies at increased risk, and preimplantation genetic testing are possible.
## Diagnosis
### Suggestive Findings
The diagnosis of Costeff syndrome is suspected in a child with the following clinical and laboratory findings and family history consistent with autosomal recessive inheritance.
#### Clinical Findings
Early in the disease course
* Relatively normal early development and growth
* Bilateral early-onset optic atrophy (pathologically pale optic discs, attenuated papillary vasculature, and visual evoked potentials that show bilateral prolonged latencies consistent with optic atrophy)
* Choreoathetoid movement disorder
Later in the disease course
* Progressive spasticity
* Cerebellar ataxia
* Cognitive deterioration (in a minority of individuals)
#### Laboratory Findings
Increased urinary excretion of 3-methylglutaconate (3-MGC) and 3-methylglutaric acid (3-MGA). In Costeff syndrome, urinary 3-MGC and 3-MGA (measured using gas chromatography-mass spectrometry) are mildly increased. Note: (1) In Costeff syndrome, the excretion of 3-MGC and 3-MGA is variable, sometimes even overlapping that of normal controls; furthermore, 3-MGC and 3-MGA are not always easy to detect on urine organic acid analysis. (2) Because laboratories both within and between countries use different methods, they have very different reference ranges; thus, the gender- and age-specific reference range determined by each reference laboratory should be used.
### Establishing the Diagnosis
The diagnosis of Costeff syndrome is established in a proband with suggestive findings and biallelic OPA3 pathogenic variants identified by molecular genetic testing (Table 1).
Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing or multigene panel) and comprehensive genomic testing (exome sequencing and genome sequencing) depending on the phenotype.
Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of Costeff syndrome is broad, individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those in whom the diagnosis of Costeff syndrome has not been considered are more likely to be diagnosed using genomic testing (see Option 2).
#### Option 1
Single-gene testing. Sequence analysis of OPA3 is performed first to detect small intragenic deletions/insertions and missense, nonsense, and splice site variants. Note: Depending on the sequencing method used, single-exon, multiexon, or whole-gene deletions/duplications may not be detected. If no variant is detected by the sequencing method used, the next step could be to perform gene-targeted deletion/duplication analysis to detect (multi)exon and whole-gene deletions or duplications; to date, however, deletions/duplications have not been identified as a cause of Costeff syndrome.
Note: Targeted analysis for the c.143-1G>C pathogenic variant, which has been identified in all affected individuals of Iraqi Jewish descent, can be performed first in this population.
A multigene panel that includes OPA3 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
#### Option 2
Comprehensive genomic testing does not require the clinician to determine which gene(s) are likely involved. Exome sequencing is most commonly used; genome sequencing is also possible.
If exome sequencing is not diagnostic, exome array (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis; to date, however, deletions/duplications have not been identified as a cause of Costeff syndrome.
For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
### Table 1.
Molecular Genetic Testing Used in Costeff Syndrome
View in own window
Gene 1MethodProportion of Pathogenic Variants 2 Detectable by Method
OPA3Targeted analysis for the c.143-1G>C pathogenic variant in the Iraqi Jewish population 3100%
Sequence analysis 4100% 5
Gene-targeted deletion/duplication analysis 6Unknown 7
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
See Molecular Genetics for information on variants detected in this gene.
3\.
The variant c.143-1G>C accounts for 100% of pathogenic variants in the Iraqi Jewish population [Anikster et al 2001].
4\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
5\.
Data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2017]
6\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.
7\.
No data on detection rate of gene-targeted deletion/duplication analysis are available.
## Clinical Characteristics
### Clinical Description
Most individuals with Costeff syndrome present within the first ten years of life with decreased visual acuity and/or choreoathetoid movement disorder. Although most develop spastic paraparesis, mild ataxia, and occasional mild cognitive deficit in their second decade, the course of the disease is relatively stable.
The following description of the phenotypic features of Costeff syndrome is based on two reports:
* Elpeleg et al [1994] reported on 36 affected individuals, 11 of whom were previously unreported and 25 of whom had been previously reported.
* Yahalom et al [2014] reported on 28 individuals (age range: 6 months – 68 years) six of whom were previously unreported and 22 of whom had been previously reported by Elpeleg et al [1994].
#### Optic Atrophy
Optic atrophy manifests as decreased visual acuity within the first years of life, sometimes associated with infantile-onset horizontal nystagmus.
In 36 individuals with Costeff syndrome, visual acuity decreased with age:
* In two children age two years, visual acuity appeared to be normal.
* In 14 individuals age three to 21 years (14.2±5.5), visual acuity was 6/21 or less.
* In 20 individuals age five to 37 years (18±9.5), visual acuity was 3/60 or less.
Some children have strabismus and gaze apraxia.
#### Motor Disability
Motor disability is primarily caused by extrapyramidal dysfunction and spasticity.
Extrapyramidal dysfunction. Most individuals have chorea, often severe enough to restrict ambulation. Some are confined to a wheelchair from an early age. In 36 individuals with Costeff syndrome, extrapyramidal involvement caused the following in 32 individuals:
* Major disability in 17 individuals age two to 37 years (mean 16.1±17.8)
* Minor disability in maintaining stable posture and fine motor activities in 12 individuals age two to 26 years (11.7±8.1)
* Mild manifestations with no resulting disability in three individuals age 15 to 36 years
No extrapyramidal involvement was observed in four individuals ages 13 to 32 years.
Spasticity. Unstable spastic gait, increased tendon reflexes, and Babinski sign may be seen. In 36 individuals with Costeff syndrome, spasticity was age-related:
* Nine individuals age two to 12 years (5.9±3.5) did not have spasticity.
* Four individuals age 11 to 26 years had mild spasticity but no related disability.
* Eleven individuals age 13 to 37 years (21.4±9.3) had mild spasticity-related disability.
* Twelve individuals age nine to 26 years (17.0±4.8) had severe spasticity-related disability.
Cerebellar dysfunction is usually mild. Ataxia and dysarthria caused mostly mild disability in 18 of the 36 individuals reported by Elpeleg et al [1994].
#### Cognitive Impairment
Cognitive impairment was previously noted in some individuals. Of 36 individuals:
* Nineteen individuals age two to 36 years (16.±18.7) had an IQ of 71 or higher.
* Thirteen individuals age two to 37 years (14.7±9.2) had an IQ between 55 and 71.
* Four individuals age nine to 26 years had an IQ between 40 and 54.
More recently, however, a study of the neuropsychological profile of 16 adults with Costeff syndrome reported intact global cognition and learning abilities and strong auditory memory performance [Sofer et al 2015].
#### Other
Several affected individuals were reported to have married, four of whom (all female) had healthy offspring [Yahalom et al 2014].
Affected adults in the seventh decade of life have been reported [Yahalom et al 2014]; life expectancy beyond the seventh decade is unknown.
Seizures are not typical in Costeff syndrome. Partial seizures were reported in one individual. In addition, two individuals with Costeff syndrome were reported with electrical status epilepticus during slow-wave sleep (ESESS) (also known as continuous spike-wave of slow sleep (CSWSS) [Carmi et al 2015, Kessi et al 2018].
Cranial nerve functions, sensation, and muscle tone are normal.
No cardiac or structural brain abnormalities have been reported.
The level of 3-methylglutaconate (3-MGC) or 3-methylglutaric acid (3-MGA) in urine does not correlate with the degree of neurologic damage.
Electroretinogram is normal.
### Genotype-Phenotype Correlations
Genotype-phenotype correlations cannot be made due to the limited number of OPA3 pathogenic variants identified to date.
All individuals of Iraqi Jewish origin with Costeff syndrome have the same pathogenic variant (c.143-1G>C); however, phenotypic severity varies, even within the same family.
### Nomenclature
Costeff syndrome has also been referred to as "optic atrophy plus syndrome" and "Costeff optic atrophy syndrome."
### Prevalence
Costeff syndrome has been reported in more than 40 individuals of Iraqi Jewish origin [Anikster et al 2001], but also in pan ethnic populations, including families of Kurdish-Turkish descent [Kleta et al 2002], Afghani descent [Gaier et al 2019], and others. Of note, as the vast majority of affected individuals are still of Iraqi Jewish descent residing in Israel, it must be underscored that some families originate from the Iraqi area, including Iran and Syria. Individuals with Costeff syndrome have also been diagnosed from outside of Israel, including recently in the United States [Author, personal observation].
The carrier rate in Iraqi Jews was initially estimated at 1:10 [Anikster et al 2001]; however, subsequent screening tests showed the carrier rate to be 1:20-1:30 [Author, personal observation].
## Differential Diagnosis
### 3-Methylglutaconic Aciduria
Increased urinary excretion of the branched-chain organic acid 3-methylglutaconate (3-MGC) is a relatively common finding in children investigated for suspected inborn errors of metabolism [Gunay-Aygun 2005]. 3-MGC is an intermediate of leucine degradation and the mevalonate shunt pathway that links sterol synthesis with mitochondrial acetyl-CoA metabolism (Figure 1).
#### Figure 1.
Metabolic pathway diagram showing branched-chain organic acid 3-MGC as an intermediate of leucine degradation and the mevalonate shunt pathway that links sterol synthesis with mitochondrial acetyl-CoA
A classification of inborn errors of metabolism with 3-methylglutaconic aciduria (3-MGCA) as the discriminative feature was published by Wortmann et al [2013a] and Wortmann et al [2013b]. Clinical features (Table 2) and biochemical findings of syndromes associated with 3-MGCA vary. Tissues with higher requirements for oxidative metabolism, such as the central nervous system and cardiac and skeletal muscle, are predominantly affected. The only disorder in which the exact source of 3-MGC is known (a block of leucine degradation) is AUH defect, the rarest 3-MGCA, caused by primary deficiency of the mitochondrial enzyme 3-methylglutaconyl-CoA hydratase (3-MGCH).
### Table 2.
Inborn Errors of Metabolism Associated with 3-Methylglutaconic Aciduria
View in own window
3-MGCAGeneMOIDisorderKey Clinical Characteristics in Addition to 3-MGCA 1
Discriminating feature 2AGKARSengers syndrome (see Mitochondrial DNA Maintenance Defects Overview)Cataracts; cardiomyopathy (DD)
AUHARAUH defect (OMIM 250950)
* Nonspecific speech & language delay w/o metabolic derangement in some individuals & w/hypoglycemia & metabolic acidosis in others
* Failure to thrive, ID, & DD common
* Microcephaly & progressive neurologic impairment w/spastic quadriplegia, seizures, & dystonia reported 3
CLPBARCLPB deficiencyCataracts; central hypopnea; DD & ID; movement disorder; neutropenia (epilepsy)
DNAJC19ARDNAJC19 defect (DCMA syndrome) (OMIM 610198)
* Cardiomyopathy; DD & ID; growth restriction; cerebellar ataxia; may be assoc w/optic atrophy
* Seen in Dariusleut Hutterite population of Canada. 4
HTRA2ARMGCA8 (OMIM 617248)Cataracts; central hypopnea; DD & ID; epilepsy; movement disorder; neutropenia
OPA3ARCosteff syndromeDD; movement disorders; optic atrophy
SERAC1ARSERAC1 defect (MEGDEL syndrome)DD & ID; deafness; movement disorder (epilepsy & optic atrophy)
TAZXLTAZ defect (Barth syndrome)Cardiomyopathy 5; skeletal myopathy; DD; growth restriction; neutropenia
TIMM50ARMGCA9 (OMIM 617698)DD & ID; epilepsy
TMEM70ARTMEM70 defectCardiomyopathy; DD & ID
Occasional featurePOLGPOLG disordersEncephalopathy w/intractable epilepsy & hepatic failure; DD or dementia, lactic acidosis, & myopathy
SUCLA2ARSUCLA2 mtDNA depletion syndrome, encephalomyopathic form w/methylmalonic aciduriaHypotonia; epilepsy; muscular atrophy; movement disorder; growth retardation
SUCLG1ARSUCLG1 mtDNA depletion syndrome, encephalomyopathic form w/methylmalonic aciduriaHypotonia; uncontrolled movement; hearing loss; DD
3-MGCA = 3-methylglutaconic aciduria; DD = developmental delay; ID = intellectual disability; MOI = mode of inheritance; XL = X-linked
1\.
Features shown in ( )s are rare.
2\.
Adapted from Kovacs-Nagy et al [2018], Table 1
3\.
Sweetman & Williams [2001], Ijlst et al [2002], Illsinger et al [2004]
4\.
Davey et al [2006]
5\.
Dilated cardiomyopathy presents within the first year of life or even prenatally [Barth et al 2004].
### Clinical Findings of Costeff Syndrome
Behr syndrome. The clinical picture of Behr syndrome is most similar to Costeff syndrome [Copeliovitch et al 2001]. Behr syndrome is an autosomal recessive disorder caused by pathogenic variants in OPA1 (OMIM 210000) associated with childhood-onset optic atrophy and spinocerebellar degeneration characterized by ataxia, spasticity, intellectual disability, posterior column sensory loss, and peripheral neuropathy.
Ataxia, an obligatory finding in Behr syndrome, is not seen in approximately half of individuals with Costeff syndrome; conversely, most individuals with Behr syndrome do not manifest extrapyramidal dysfunction, one of the major features of Costeff syndrome. Given that some individuals with Costeff syndrome do not have extrapyramidal dysfunction, it is not possible to distinguish Behr syndrome from Costeff syndrome based on clinical findings alone. Costeff syndrome can be distinguished from Behr syndrome by the presence of elevated excretion of 3-MGC and 3-MGA in urine.
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with Costeff syndrome, the evaluations summarized in Table 3 (if not performed as part of the evaluation that led to the diagnosis) are recommended.
### Table 3.
Recommended Evaluations Following Initial Diagnosis in Individuals with Costeff Syndrome
View in own window
System/ConcernEvaluationComment
Optic atrophyComplete ophthalmologic examAssess:
* Extraocular movement, best corrected visual acuity, color vision testing, visual field testing, visual evoked potentials, fundus exam;
* Need for visual aids.
Motor disabilityComplete neurologic examAssess for extrapyramidal dysfunction, spasticity, cerebellar dysfunction
Refer to neuromuscular clinic (OT/PT / rehabilitation specialist).To assess:
* Gross motor & fine motor skills
* Mobility, activities of daily living, & need for adaptive devices
* Need for PT (to improve gross motor skills) &/or OT (to improve fine motor skills)
Feeding
difficultiesGastroenterology/nutrition/ feeding team evalTo incl eval of aspiration risk & nutritional status
Development
(children)Developmental assessment
* To incl motor, adaptive, cognitive, & speech/language eval
* Eval for early intervention / special education
Cognitive
impairment
(older children
& adults)To incl motor, speech/language eval; general cognitive skillsFrontotemporal & executive deficits; perform formal neuropsychological eval.
Genetic
counselingBy genetics professionals 1To inform individuals & families re nature, MOI, & implications of Costeff syndrome in order to facilitate medical & personal decision making
Family support/
ResourcesContact w/a patient advocacy organization may provide additional benefit.
Assess need for:
* Social work involvement for caregiver support;
* Help coordinating multidisciplinary care.
MOI = mode of inheritance; OT = occupational therapy; PT = physical therapy
1\.
Medical geneticist, certified genetic counselor, certified advanced genetic nurse
### Treatment of Manifestations
Treatment is supportive. A multidisciplinary team including a neurologist, orthopedic surgeon, ophthalmologist, biochemical geneticist, and physical therapist is required for the care of affected individuals.
### Table 4.
Treatment of Manifestations in Individuals with Costeff Syndrome
View in own window
Manifestation/ConcernTreatmentConsiderations/Other
Visual impairmentStandard treatment(s) as recommended by ophthalmologist
* Eval for visual aids
* Community vision services through early intervention or school district
SpasticityOrthopedics / physical medicine & rehabilitation / PT/OT incl stretching to help avoid contractures & fallsConsider need for positioning & mobility devices, disability parking placard.
Poor weight gain /
Failure to thriveFeeding therapyLow threshold for clinical feeding eval &/or radiographic swallowing study if clinical signs or symptoms of dysphagia
DDSee DD/ID Management Issues.
Family/Community
* Ensure appropriate social work involvement to connect families w/local resources, respite, & support.
* Coordination of care to manage multiple subspecialty appointments, equipment, medications, & supplies
* Ongoing assessment of need for palliative care involvement &/or home nursing
* Consider involvement in adaptive sports or Special Olympics.
DD = developmental delay; ID = intellectual disability; OT = occupational therapy; PT = physical therapy
#### Developmental Disability / Intellectual Disability Management Issues
The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.
Ages 0-3 years. Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy as well as infant mental health services, special educators, and sensory impairment specialists. In the US, early intervention is a federally funded program available in all states that provides in-home services to target individual therapy needs.
Ages 3-5 years. In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social, or cognitive delay. The early intervention program typically assists with this transition. Developmental preschool is center based; for children too medically unstable to attend, home-based services are provided.
All ages. Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider:
* Individualized education plan (IEP) services:
* An IEP provides specially designed instruction and related services to children who qualify.
* IEP services will be reviewed annually to determine whether any changes are needed.
* As required by special education law, children should be in the least restrictive environment feasible at school and included in general education as much as possible and when appropriate.
* Vision and hearing consultants should be a part of the child's IEP team to support access to academic material.
* PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Beyond that, private supportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.
* As a child enters the teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21.
* A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text.
* Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a US public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.
* Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.
#### Motor Dysfunction
Gross motor dysfunction
* Physical therapy is recommended to maximize mobility and to reduce the risk for later-onset orthopedic complications (e.g., contractures, scoliosis, hip dislocation).
* Consider use of durable medical equipment and positioning devices as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers).
* For muscle tone abnormalities including hypertonia or dystonia, consider involving appropriate specialists to aid in management of baclofen, tizanidine, Botox®, anti-parkinsonian medications, or orthopedic procedures.
Fine motor dysfunction. Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and writing.
Oral motor dysfunction should be assessed at each visit and clinical feeding evaluations and/or radiographic swallowing studies should be obtained for choking/gagging during feeds, poor weight gain, frequent respiratory illnesses or feeding refusal that is not otherwise explained. Assuming that the individual is safe to eat by mouth, feeding therapy (typically from an occupational or speech therapist) is recommended to help improve coordination or sensory-related feeding issues. Feeds can be thickened or chilled for safety. When feeding dysfunction is severe, an NG-tube or G-tube may be necessary.
Communication issues. Consider evaluation for alternative means of communication (e.g., Augmentative and Alternative Communication [AAC]) for individuals who have expressive language difficulties. An AAC evaluation can be completed by a speech-language pathologist who has expertise in the area. The evaluation will consider cognitive abilities and sensory impairments to determine the most appropriate form of communication. AAC devices can range from low-tech, such as picture exchange communication, to high-tech, such as voice-generating devices. Contrary to popular belief, AAC devices do not hinder verbal development of speech, and in many cases can improve it.
### Surveillance
### Table 5.
Recommended Surveillance for Individuals with Costeff Syndrome
View in own window
System/ConcernEvaluationFrequency
Visual impairment
* Ophthalmologic exam incl best corrected visual acuity, color vision testing, & visual field testing
* Appropriateness of visual aids
Annually
Pyramidal dysfunction / Spasticity / Cerebellar dysfunction
* Neurologic exam for progression of findings
* Orthopedics (eval of Achilles tendon shortening); OT/PT eval
* Speech & language assessment
Feeding & nutritionBy feeding teamAs needed
Orthopedic involvement 1Eval by orthopediac surgeon
Family/CommunityAssess family need for social work support (e.g., palliative/respite care, home nursing, other local resources) & care coordination.At each visit
OT = occupational therapy; PT = physical therapy
1\.
Shortening of Achilles tendon
### Agents/Circumstances to Avoid
The following should be avoided:
* Tobacco and alcohol use
* Medications known to impair mitochondrial function
### 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
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Costeff Syndrome | c0574084 | 3,019 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1473/ | 2021-01-18T21:32:37 | {"mesh": ["C535311"], "synonyms": ["3-Methylglutaconic Aciduria Type 3", "OPA3 Defect"]} |
A number sign (#) is used with this entry because of evidence that autosomal recessive nonsyndromic mental retardation-2 (MRT2) is caused by homozygous mutation in the gene encoding cereblon (CRBN; 609262) on chromosome 3p26.
Clinical Features
Higgins et al. (2000) used a private genealogic database to reconstruct the relationships among 32 individuals from 5 nuclear families in a single pedigree in which 10 members had nonsyndromic mental retardation. Standard IQ ranged from 50 to 70, consistent with mild mental retardation. IQ scores were lower in males than females. Developmental milestones were mildly delayed. There were no dysmorphic or autistic features. The kindred was consanguineous, and the evidence clearly indicated autosomal recessive inheritance. Several branches traced back to a founder couple who arrived in America in 1849 from a town in the Rhineland-Palatinate region of Germany.
Sheereen et al. (2017) reported several members of a consanguineous Saudi family with severe intellectual disability, self-mutilating behavior, and seizures. The 25-year-old proband had intractable seizures, self-mutilating behavior with severe intellectual disability, developmental delay, and speech delay. He had no dysmorphic or coarse features. Self-mutilating behavior began around 4 years of age. The proband had 2 similarly affected sisters, but they did not need anticonvulsant medication by age 13 years. Two nephews of the proband, aged 4 and 3 years, had severe attention deficit-hyeractivity disorder and were only able to walk at age 2 years. The older nephew had seizures and no speech, whereas the younger nephew had only febrile seizures. Brain imaging in the proband was unremarkable. His EEG showed slow background in the range of delta, sometimes intermixed with theta activities, and there were frequent spikes and waves over the left hemisphere. His biochemistry profile revealed low calcium and uric acid levels.
Mapping
By genomewide analysis of a large pedigree with nonsyndromic mental retardation, Higgins et al. (2000) identified a candidate disease locus, designated MRT2A, on chromosome 3p25-pter. Multipoint linkage analysis refined the critical region to a 6.71-cM interval flanked by the markers D3S3525 and D3S1560.
Higgins et al. (2004) delimited the MRT2A minimal critical region to a 4.2-Mb interval of chromosome 3p26.3-p26.1, flanked by markers D3S630 and D3S1304, containing 9 known genes. None of the 9 genes could be shown to contain a mutation related to mental retardation.
Molecular Genetics
In the family with nonsyndromic mental retardation described by Higgins et al. (2000), Higgins et al. (2004) identified a homozygous nonsense mutation in the CRBN gene (R419X; 609262.0001) that segregated with the phenotype.
In affected members of consanguineous Saudi family with severe intellectual disability, self-mutilating behavior, and seizures, Sheereen et al. (2017) identified a homozygous missense mutation in the CRBN gene (C392R; 609262.0002) that segregated with the phenotype. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing.
INHERITANCE \- Autosomal recessive NEUROLOGIC Central Nervous System \- Mental retardation, mild (IQ range from 50 to 70, family A) \- Mildly delayed developmental milestones (family A) \- No autistic features (family A) \- Mental retardation, severe (family B) \- Seizures (family B) \- Attention deficit hyperactivity disorder (ADHD, family B) Behavioral Psychiatric Manifestations \- Self-mutilating behavior (family B) MISCELLANEOUS \- Males may be more affected than females \- Based on independent reports of 2 families (last curated August 2017) MOLECULAR BASIS \- Caused by mutation in the cereblon gene (CRBN, 609262.0001 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| MENTAL RETARDATION, AUTOSOMAL RECESSIVE 2 | c1843942 | 3,020 | omim | https://www.omim.org/entry/607417 | 2019-09-22T16:09:18 | {"doid": ["0060308"], "mesh": ["C564404"], "omim": ["607417"], "orphanet": ["88616"], "synonyms": ["Alternative titles", "NS-ARID", "MENTAL RETARDATION, AUTOSOMAL RECESSIVE 2A", "AR-NSID"]} |
Bond et al. (1970) made the following observations: Methane (CH4) in man is derived solely from the metabolism of the colonic flora. Respiratory CH4 excretion is a simple but reliable indicator of intestinal CH4 production. In the adult population about one-third excrete large amounts of CH4 whereas the others excrete very little. No adult changed his excretion status over a period of 1 year. Children below the age of 3 excrete no CH4. If both parents excrete CH4 all offspring over age 7 excrete CH4. The concordance between marriage partners was random. Eleven of 12 identical twins and 14 of 16 fraternal twins were concordant. The genetics of this trait is unclear. Levitt and Duane (1972) noted that floating of stools is related more to gas content, especially methane, than to fat. Engel (1973) never found enteric CH4 production in the first month of life. He suspected that babies acquire methane-producing bacteria from their mothers, since there was a 5-fold difference in frequency of CH4 production depending on whether the mother was or was not a producer. Because of a lack of correlation with fathers and because an adult can convert from consistently negative to consistently positive, Engel doubted a genetic basis. Haines et al. (1977) observed that 80% of colon cancer patients had detectable methane in their breath, compared with 39% of nonmalignant colonic disease patients and 40% of persons without colon disease. This suggested a difference in anaerobic intestinal flora in colon cancer. Whether the difference antedated or followed the development of cancer was unclear.
Respiratory \- Methane excretion \- Increased methane excretion with colon cancer GI \- Methane production by colonic flora Inheritance \- Unclear \- ? autosomal recessive ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| METHANE PRODUCTION | None | 3,021 | omim | https://www.omim.org/entry/250650 | 2019-09-22T16:25:16 | {"omim": ["250650"]} |
A drug-related embryofetopathy that can occur when an embryo/fetus is exposed to trimethadione and that is characterized by pre- and post-natal growth retardation, intellectual deficit, developmental and speech delay, craniofacial anomalies (with some similarities to those seen in fetal valproate syndrome), and less commonly, cleft palate, malformations of the heart, urogenital system and limbs. Trimethadione is an antiepileptic drug that has been removed from the market in Europe and is no longer used much in other countries due to teratogenicity and potential side effects.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Fetal trimethadione syndrome | c0265373 | 3,022 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1913 | 2021-01-23T18:26:09 | {"mesh": ["C537798"], "umls": ["C0265373"], "icd-10": ["Q86.8"]} |
A number sign (#) is used with this entry because deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures syndrome (DOORS) is caused by homozygous or compound heterozygous mutation in the TBC1D24 gene (613577) on chromosome 16p13.
Description
The DOOR syndrome is an acronym for deafness, onychodystrophy, osteodystrophy, and mental retardation. Cantwell (1975) suggested this designation for the disorder, which can also include triphalangeal thumbs, seizures, and abnormal dermatoglyphics. Inheritance is autosomal recessive.
See also DDOD syndrome (124480), which shows autosomal dominant inheritance of congenital deafness and onychodystrophy without mental retardation.
Clinical Features
Walbaum et al. (1970) described a brother and sister with mental retardation, perceptive deafness, dysplasia of the fingernails, triphalangeal thumbs, hypoplasia of the terminal phalanges, and 'decapsalidic' fingerprints, i.e., an arch pattern on each finger. The patient reported by Qazi and Smithwick (1970) may have had the same disorder.
Eronen et al. (1985) reported a constellation of features in a male infant who had 2 double first cousins, females, who had died with the same disorder. The patients had absence of the distal phalanges and nails of all 10 digits, cystic dysplasia of the kidneys, and dilated right cerebral ventricle. The 2 cousins died at age 2 years and 2 hours, respectively. The proband and the older surviving cousin had convulsions. Le Merrer et al. (1992) described this syndrome in 2 unrelated children. Absence or hypoplasia of the distal phalanges of the toes and fingers was a particularly striking feature. Expression of the renal and cerebral manifestations was variable. One patient had seizures with abnormal EEG and a double kidney with 2 ureters and 2 renal arteries; he died at the age of 6 months. Both patients showed a large nose with wide nasal tip.
Lin et al. (1993) reported what they considered to be the seventeenth case of the recessive form of the DOOR syndrome. The parents were not known to be consanguineous. The patient had developmental delay, severe sensorineural deafness, and abnormal nails and phalanges in the hands and feet. Urinary 2-oxoglutarate excretion was normal. There were no seizures in infancy.
Rajab et al. (2000) reported an additional 4 cases of DOOR syndrome in 2 related sibships from an extended Omani family. The children had deafness, onychodystrophy, osteodystrophy, microcephaly, and global developmental retardation with progressive blindness. Seizures, which were associated with hypsarrhythmia, were frequent and difficult to control and ultimately were the cause of death in 2 patients. An MRI of the brain in 1 patient showed a number of abnormalities including markedly reduced myelination. The urine organic acid analysis showed a 10-fold increase of 2-oxoglutarate. In 1 patient the placenta was noted to have multiple fluid-filled cysts. Rajab et al. (2000) suggested that there may be genetic heterogeneity in the autosomal recessive form of this syndrome, and that the presence of increased 2-oxoglutarate is associated with a more severe phenotype, which is frequently lethal.
Surendran et al. (2002) studied the activity of 2-oxoglutarate decarboxylase in the fibroblasts and white blood cells of 4 patients with autosomal recessive DOOR syndrome and found significantly lower levels as compared to controls.
Felix et al. (2002) reported 3 cases of DOOR syndrome in unrelated Brazilian children. One of the cases also had a congenital cardiac defect. None had organic acid abnormalities.
James et al. (2007) reported an infant girl with features of DOOR syndrome, including sensorineural deafness, distal phalangeal hypoplasia of the hands and feet, hypoplastic nails, and increased urinary 2-oxoglutaric acid and 2-hydroxyglutaric acid. She had coarse facial features with high forehead, mild hypertelorism, epicanthal folds, broad nasal bridge with prominent nasal tip and nares, long philtrum, and large mouth. She had poor feeding, recurrent respiratory infections, and died at age 10 months.
In a literature review, James et al. (2007) identified 32 patients with DOOR syndrome compiled from 18 publications. Universal features included profound deafness, usually from infancy, malformations of the nails and digits, and mental retardation. Most patients had coarse facial features with broad nasal bridge, anteverted nares, everted lower lip, and high-arched palate. Ophthalmologic anomalies were reported in 43% of patients, including optic atrophy and blindness, high myopia, and iris hypoplasia. Other neurologic abnormalities included neonatal hypotonia, seizures, and peripheral neuropathy. Less common findings included dental, renal, and cardiac anomalies. The disorder follows a progressive course and 32% die in early childhood from seizures or respiratory distress. James et al. (2007) postulated a neurometabolic etiology.
Mihci et al. (2008) reported DOOR syndrome in a patient born after conception with intracytoplasmic sperm injection. Her dizygotic twin was unaffected and healthy. The affected girl demonstrated speech delay, classic facial features of DOOR syndrome, and malformations of the nails and digits. She did not have organic acid abnormalities and showed only mild neurologic involvement.
Campeau et al. (2014) reported 11 patients from 9 unrelated families with DOORS syndrome. All patients had the 5 classic features of the disorder, including developmental delay and intellectual disability, deafness, abnormal fingers with short terminal phalanges, abnormal fingernails, and seizures. All but one had abnormal toes and toenails, and 3 had triphalangeal thumbs. Seizure types were variable and included generalized tonic-clonic, complex partial, focal clonic, and infantile spasms. Six patients had increased urinary 2-oxoglutaric acid.
Biochemical Features
Patton et al. (1987) described 3 further cases, 2 of which were from consanguineous Pakistani families. The patients showed an increase of 2-oxoglutarate in the plasma and an increase of 2-oxoglutarate and its metabolite alpha-hydroxy-glutarate in the urine. Patton et al. (1987) stated that similar levels of 2-oxoglutarate had been found in 1 of the patients reported by Nevin et al. (1982).
Inheritance
Sanchez et al. (1981) reported 2 affected sisters who were the offspring of second-cousin parents. Nevin et al. (1982) reported parental consanguinity. Qazi and Nangia (1984) reported affected brother and sister. Patton et al. (1987) described 3 further cases, 2 of which were from consanguineous Pakistani families.
Molecular Genetics
In 11 affected individuals from 9 unrelated families with deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures syndrome, Campeau et al. (2014) identified homozygous or compound heterozygous mutations in the TBC1D24 gene (see, e.g., 613577.0007-613577.0011). The mutations in the first families were found by whole-exome sequencing and confirmed by Sanger sequencing. Most of the mutations were missense substitutions; functional studies were not performed. The 9 families were ascertained from a larger cohort of 26 families with clinical features suggestive of the disorder. The remaining families did not carry TBC1D24 mutations, indicating genetic heterogeneity.
History
Although the patients reported by Eronen et al. (1985) and Le Merrer et al. (1992) were initially thought to have a novel distinct syndrome, Winter (1993) concluded that the disorder in those patients was identical to DOOR syndrome.
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Microcephaly \- Narrow bifrontal diameter Face \- Coarse facies \- Long philtrum Ears \- Deafness, sensorineural, profound \- Low-set ears Eyes \- Optic atrophy \- Blindness \- High myopia \- Cataracts Nose \- Broad nasal bridge \- Large nose \- Bulbous nasal tip \- Anteverted nares Mouth \- Thick, everted lower lip \- Downturned corners of the mouth \- High-arched palate CARDIOVASCULAR Heart \- Congenital heart defects (less common) GENITOURINARY Kidneys \- Cystic renal dysplasia (less common) \- Renal aplasia (less common) SKELETAL Hands \- Small or absent distal phalanges \- Triphalangeal thumbs Feet \- Small or absent distal phalanges SKIN, NAILS, & HAIR Nails \- Small or absent nails on the hands and feet NEUROLOGIC Central Nervous System \- Mental retardation \- Hypotonia \- Seizures \- Cerebral atrophy \- Dilated ventricles \- Dandy-Walker malformation (rare) Peripheral Nervous System \- Peripheral polyneuropathy \- Hyporeflexia LABORATORY ABNORMALITIES \- Increased serum and urinary 2-oxoglutarate MISCELLANEOUS \- DOOR is acronym for Deafness, Onychodystrophy, Osteodystrophy, mental Retardation, and Seizures \- Presence of additional features is variable \- Progressive disorder MOLECULAR BASIS \- Caused by mutation in the TBC1 domain family, member 24 gene (TBC1D24, 613577.0007 ) ▲ Close
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| DEAFNESS, ONYCHODYSTROPHY, OSTEODYSTROPHY, MENTAL RETARDATION, AND SEIZURES SYNDROME | c0795927 | 3,023 | omim | https://www.omim.org/entry/220500 | 2019-09-22T16:28:58 | {"mesh": ["C538204"], "omim": ["220500"], "orphanet": ["3231", "79500"], "synonyms": ["DOOR SYNDROME", "Alternative titles", "DIGITORENOCEREBRAL SYNDROME", "DRC SYNDROME", "BRACHYDACTYLY DUE TO ABSENCE OF DISTAL PHALANGES", "ERONEN SYNDROME"], "genereviews": ["NBK274566"]} |
See also: polyuria
Frequent urination
Other namesUrinary frequency
SpecialtyUrology
Frequent urination is the need to urinate more often than usual. Diuretics are medications that will increase urinary frequency. Nocturia is the need of frequent urination at night.[1] The most common cause of urinary frequency for women and children is a urinary tract infection. The most common cause of urinary frequency in older men is an enlarged prostate.[2]
Frequent urination is strongly associated with frequent incidents of urinary urgency, which is the sudden need to urinate. It is often, though not necessarily, associated with urinary incontinence and polyuria (large total volume of urine). However, in other cases, urinary frequency involves only normal volumes of urine overall.[3][citation needed]
## Contents
* 1 Definition
* 2 Causes
* 3 Diagnosis
* 4 Treatment
* 5 See also
* 6 References
* 7 External links
## Definition[edit]
The normal number of times varies according to the age of the person. Among young children, urinating 8 to 14 times each day is typical. This decreases to 6 to 12 times per day for older children, and to four to six times per day among teenagers.[4]
## Causes[edit]
The most common causes of frequent urination are:[citation needed]
* Interstitial cystitis[5]
* Urinary tract infection (UTI)[1][6]
* Enlarged prostate
* Urethral inflammation/infection
* Vaginal inflammation/infection
Less common causes of frequent urination are:[citation needed]
* Alcohol
* Anxiety
* Bladder cancer
* Caffeine[7]
* Diabetes mellitus
* Pregnancy[8]
* Psychiatric medications such as clozapine
* Radiation therapy to the pelvis
* Brain or nervous system diseases
* Stroke
* Tumor or growth in the pelvis[1]
* Kidney stones[2]
## Diagnosis[edit]
Diagnosis of the underlying cause requires a careful and thorough evaluation.[9]
## Treatment[edit]
Treatment depends on the underlying cause or condition.[10]
## See also[edit]
* Nocturnal enuresis
## References[edit]
1. ^ a b c "Frequent or urgent urination: MedlinePlus Medical Encyclopedia". medlineplus.gov. 5 December 2017. Retrieved 2017-12-19.
2. ^ a b "Urinary Frequency - Genitourinary Disorders - Merck Manuals Professional Edition". Merck Manuals Professional Edition. Retrieved 2017-12-19.
3. ^ "Frequent urination". Mayo Clinic. 12 July 2005. Retrieved 10 May 2020.
4. ^ Gary Robert Fleisher, Stephen Ludwig, Fred M. Henretig. (2006) Textbook of Pediatric Emergency Medicine. Lippincott Williams & Wilkins. ISBN 9780781750745. p. 663
5. ^ "What is Interstitial Cystitis (IC)?". www.cdc.gov. Centers for Disease Control and Prevention. February 9, 2016. Retrieved 2017-12-19. This article incorporates text from this source, which is in the public domain.
6. ^ "Urinary Tract Infection, Community Antibiotic Use". www.cdc.gov. Centers for Disease Control and Prevention. 2017-10-04. Retrieved 2017-12-19. This article incorporates text from this source, which is in the public domain.
7. ^ Bradley CS, Erickson BA, Messersmith EE, Pelletier-Cameron A, Lai HH, Kreder KJ, Yang CC, Merion RM, Bavendam TG, Kirkali Z (November 2017). "Evidence of the Impact of Diet, Fluid Intake, Caffeine, Alcohol and Tobacco on Lower Urinary Tract Symptoms: A Systematic Review". J. Urol. 198 (5): 1010–1020. doi:10.1016/j.juro.2017.04.097. PMC 5654651. PMID 28479236.
8. ^ "What are some common signs of pregnancy?". Eunice Kennedy Shriver National Institute of Child Health and Human Development. 12 July 2013. Archived from the original on 19 March 2015. Retrieved 14 March 2015.
9. ^ Gaschignard, N; Bouchot, O (15 June 1999). "[Micturation abnormalities. Pollakiuria, dysuria, vesicular retention, burning micturation, precipitant urination: diagnostic orientation]". La Revue du praticien. 49 (12): 1361–3. PMID 10488671.
10. ^ Kuffel, A; Kapitza, KP; Löwe, B; Eichelberg, E; Gumz, A (October 2014). "[Chronic pollakiuria: cystectomy or psychotherapy]". Der Urologe. Ausg. A. 53 (10): 1495–9. doi:10.1007/s00120-014-3618-x. PMID 25214314.
## External links[edit]
Classification
D
External resources
* MedlinePlus: 003140
* v
* t
* e
Symptoms and signs relating to the urinary system
Pain
* Dysuria
* Renal colic
* Costovertebral angle tenderness
* Vesical tenesmus
Control
* Urinary incontinence
* Enuresis
* Diurnal enuresis
* Giggling
* Nocturnal enuresis
* Post-void dribbling
* Stress
* Urge
* Overflow
* Urinary retention
Volume
* Oliguria
* Anuria
* Polyuria
Other
* Lower urinary tract symptoms
* Nocturia
* urgency
* frequency
* Extravasation of urine
* Uremia
Eponymous
* Addis count
* Brewer infarcts
* Lloyd's sign
* Mathe's sign
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Frequent urination | c0042023 | 3,024 | wikipedia | https://en.wikipedia.org/wiki/Frequent_urination | 2021-01-18T18:46:10 | {"umls": ["C0042023"], "wikidata": ["Q352585"]} |
Congenital hypoplastic anemia
Other namesConstitutional aplastic anemia
SpecialtyHematology
Congenital hypoplastic anemia is a type of aplastic anemia which is primarily due to a congenital disorder.
Associated genes include TERC, TERT, IFNG, NBS1, PRF1, and SBDS.[1]
Examples include:
* Fanconi anemia
* Diamond–Blackfan anemia
## References[edit]
1. ^ Online Mendelian Inheritance in Man (OMIM): 609135
## External links[edit]
Classification
D
* ICD-10: D61.0
* ICD-9-CM: 284.0
* OMIM: 609135
* MeSH: D029502
* 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
This article about a disease of the blood or immune system is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Congenital hypoplastic anemia | c0949116 | 3,025 | wikipedia | https://en.wikipedia.org/wiki/Congenital_hypoplastic_anemia | 2021-01-18T18:58:49 | {"gard": ["6149"], "mesh": ["D029502"], "umls": ["C0702159", "C0949116"], "orphanet": ["68383"], "wikidata": ["Q5160440"]} |
Not to be confused with Psychosis.
Sycosis is an inflammation of hair follicles, especially of the beard area,[1][2][3] and generally classified as papulopustular[1][3] and chronic.[2]
## Types[edit]
Types include:
* Sycosis barbae
* Lupoid sycosis
* Tinea sycosis
* Herpetic sycosis
## References[edit]
1. ^ a b thefreedictionary.com > sycosis citing: Dorland's Medical Dictionary for Health Consumers. 2007
2. ^ a b thefreedictionary.com > sycosis citing: The American Heritage® Medical Dictionary Copyright © 2007
3. ^ a b thefreedictionary.com > sycosis citing: Miller-Keane Encyclopedia & Dictionary of Medicine, Nursing, and Allied Health, Seventh Edition. © 2003
Look up sycosis in Wiktionary, the free dictionary.
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Medicine
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This infection-related cutaneous condition article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
This dermatology article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Sycosis | c0039023 | 3,026 | wikipedia | https://en.wikipedia.org/wiki/Sycosis | 2021-01-18T18:37:46 | {"mesh": ["D005499"], "umls": ["C0039023"], "wikidata": ["Q2346445"]} |
Vitamin D-dependent rickets is a disorder of bone development that leads to softening and weakening of the bones (rickets). There are several forms of the condition that are distinguished primarily by their genetic causes: type 1A (VDDR1A), type 1B (VDDR1B), and type 2A (VDDR2A). There is also evidence of a very rare form of the condition, called type 2B (VDDR2B), although not much is known about this form.
The signs and symptoms of vitamin D-dependent rickets begin within months after birth, and most are the same for all types of the condition. The weak bones often cause bone pain and delayed growth and have a tendency to fracture. When affected children begin to walk, they may develop abnormally curved (bowed) legs because the bones are too weak to bear weight. Impaired bone development also results in widening of the areas near the ends of bones where new bone forms (metaphyses), especially in the knees, wrists, and ribs. Some people with vitamin D-dependent rickets have dental abnormalities such as thin tooth enamel and frequent cavities. Poor muscle tone (hypotonia) and muscle weakness are also common in this condition, and some affected individuals develop seizures.
In vitamin D-dependent rickets, there is an imbalance of certain substances in the blood. An early sign in all types of the condition is low levels of the mineral calcium (hypocalcemia), which is essential for the normal formation of bones and teeth. Affected individuals also develop high levels of a hormone involved in regulating calcium levels called parathyroid hormone (PTH), which leads to a condition called secondary hyperparathyroidism. Low levels of a mineral called phosphate (hypophosphatemia) also occur in affected individuals. Vitamin D-dependent rickets types 1 and 2 can be grouped by blood levels of a hormone called calcitriol, which is the active form of vitamin D; individuals with VDDR1A and VDDR1B have abnormally low levels of calcitriol and individuals with VDDR2A and VDDR2B have abnormally high levels.
Hair loss (alopecia) can occur in VDDR2A, although not everyone with this form of the condition has alopecia. Affected individuals can have sparse or patchy hair or no hair at all on their heads. Some affected individuals are missing body hair as well.
## Frequency
Rickets affects an estimated 1 in 200,000 children. The condition is most often caused by a lack of vitamin D in the diet or insufficient sun exposure rather than genetic mutations. Genetic forms of rickets, including vitamin D-dependent rickets, are much less common. The prevalence of the different types of vitamin D-dependent rickets is unknown. VDDR1A is more common in the French Canadian population than in other populations.
## Causes
Each type of vitamin D-dependent rickets has a different genetic cause: VDDR1A is caused by CYP27B1 gene mutations, VDDR1B is caused by CYP2R1 gene mutations, and VDDR2A is caused by VDR gene mutations. The genetic cause of VDDR2B is unknown. These genes are involved in the body's response to vitamin D, an important vitamin that can be acquired from foods in the diet or made by the body with the help of sunlight exposure. Vitamin D helps maintain the proper balance of several minerals in the body, including calcium and phosphate. These minerals are needed for many functions, including the breakdown of substances (metabolic processes), signaling between cells, and the deposition of minerals in developing bones (bone mineralization). One of vitamin D's major roles is to control the absorption of calcium and phosphate from the intestines into the bloodstream.
The CYP2R1 gene provides instructions for making an enzyme called 25-hydroxylase, and the CYP27B1 gene provides instructions for making an enzyme called 1-alpha-hydroxylase (1α-hydroxylase). These enzymes carry out the reactions that convert vitamin D to its active form, calcitriol. Once converted, calcitriol attaches (binds) to a protein called vitamin D receptor (VDR), which is produced from the VDR gene. The resulting calcitriol-VDR complex then binds to particular regions of DNA and regulates the activity of vitamin D-responsive genes. By turning these genes on or off, the calcitriol-VDR complex helps control the absorption of calcium and phosphate and other processes that regulate calcium levels in the body. The VDR protein is also involved in hair growth through a process that does not require calcitriol binding.
Mutations in any of these genes prevent the body from responding to vitamin D. CYP2R1 and CYP27B1 gene mutations reduce or eliminate the activity of the respective enzyme, which means vitamin D is not converted to its active form. The absence of calcitriol means vitamin D-responsive genes are not turned on (activated). VDR gene mutations alter the vitamin D receptor, often preventing the receptor from interacting with calcitriol or with DNA. As a result VDR cannot regulate gene activity, even with normal amounts of calcitriol in the body.
Without activation of vitamin D-responsive genes, absorption of calcium and phosphate falls, leading to hypocalcemia and hypophosphatemia. The lack of calcium and phosphate slows bone mineralization, which leads to soft, weak bones and other features of vitamin D-dependent rickets. Low levels of calcium stimulate production of PTH, resulting in secondary hyperparathyroidism. Hypocalcemia can also cause muscle weakness and seizures in individuals with vitamin D-dependent rickets. Certain abnormalities in the VDR protein also impair hair growth, causing alopecia in some people with VDDR2A.
### Learn more about the genes associated with Vitamin D-dependent rickets
* CYP27B1
* CYP2R1
* VDR
## Inheritance Pattern
Vitamin D-dependent rickets is almost always inherited in an autosomal recessive pattern, which means both copies of the respective 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.
In at least one family with VDDR1B, individuals with a mutation in one copy of the CYP2R1 gene had mild symptoms of vitamin D-dependent rickets, and those with a mutation in both copies had the typical signs and symptoms of the condition. This inheritance pattern is referred to as incomplete autosomal dominance.
In very rare cases, VDDR2A may be inherited in an autosomal dominant pattern. Autosomal dominant inheritance means one copy of the altered VDR gene in each cell is sufficient to cause the disorder. In these cases, an affected person has one parent with the condition.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Vitamin D-dependent rickets | c0268689 | 3,027 | medlineplus | https://medlineplus.gov/genetics/condition/vitamin-d-dependent-rickets/ | 2021-01-27T08:24:43 | {"mesh": ["C562688"], "omim": ["264700", "600081", "277440", "600785"], "synonyms": []} |
A number sign (#) is used with this entry because autosomal recessive severe congenital neutropenia-6 (SCN6) is caused by homozygous mutation in the JAGN1 gene (616012) on chromosome 3p25.
For a phenotypic description and a discussion of genetic heterogeneity of severe congenital neutropenia, see SCN1 (202700).
Clinical Features
Boztug et al. (2014) reported 14 patients from 9 families with severe congenital neutropenia. Patients presented in early childhood with recurrent bacterial infections of the upper and lower respiratory tract and skin. Laboratory studies showed neutropenia. Bone marrow biopsy showed maturational arrest of granulocytes at the promyelocyte/myelocyte stage. Electron microscopy of patient neutrophils showed an abnormal and enlarged endoplasmic reticulum (ER) with almost complete absence of granules, as well as evidence of increased ER stress. Patient cells showed increased apoptosis compared to control cells. One patient died at age 5 years; the others, aged 5 to 28 years, were alive and well. Two patients underwent hematopoietic bone marrow transplantation.
Inheritance
The transmission pattern of SCN6 in the families reported by Boztug et al. (2014) was consistent with autosomal recessive inheritance. Most of the families were consanguineous.
Molecular Genetics
In 14 patients from 9 families with autosomal recessive SCN6, Boztug et al. (2014) identified 9 different homozygous mutations in the JAGN1 gene (see, e.g., 616012.0001-616012.0005). The mutation in 1 family was found by linkage analysis, followed by candidate gene sequencing and exome and Sanger sequencing; subsequent mutations were found by direct sequencing of the JAGN1 gene in 74 individuals with SCN. Most of the mutations were missense mutations; 1 patient had a truncating mutation. There were no apparent genotype/phenotype correlations. JAGN1-mutant neutrophils showed abnormal N-glycomic profiles with a marked reduction in the fucosylation of all multiantennary glycans. O-glycosylation patterns were normal. Patients showed a poor response to GCSF (CSF3; 138970) treatment, and JAGN1-deficient neutrophils showed decreased amounts of GCSF receptors (CSF3R; 138971), possibly resulting from the N-glycosylation defect.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature (in some patients) Other \- Failure to thrive (in some patients) HEAD & NECK Ears \- Recurrent otitis media RESPIRATORY \- Recurrent respiratory infections SKIN, NAILS, & HAIR Skin \- Skin abscesses IMMUNOLOGY \- Recurrent bacterial infections \- Neutropenia \- Maturational arrest of granulocytes at the promyelocyte/myelocyte stage seen on bone marrow biopsy MISCELLANEOUS \- Onset in early childhood \- Poor response to G-CSF treatment MOLECULAR BASIS \- Caused by mutation in the jagunal homolog 1 gene (JAGN1, 616012.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| NEUTROPENIA, SEVERE CONGENITAL, 6, AUTOSOMAL RECESSIVE | c4014954 | 3,028 | omim | https://www.omim.org/entry/616022 | 2019-09-22T15:50:12 | {"omim": ["616022"], "orphanet": ["423384"], "synonyms": []} |
## Description
Keloid is a dermal fibroproliferative growth caused by pathologic wound healing following skin injury. Keloid is defined as a scar growing continuously and invasively beyond the confines of the original wound and is characterized by excessive fibroblast proliferation and deposition of extracellular matrix and collagen fibers. Local tissue factors, especially wound tension or infection, and endocrine factors are known to be involved in keloid formation. However, the fact that the incidence of keloid is higher in darker-skinned individuals suggests that genetic factors also play an important role (summary by Nakashima et al., 2010).
Clinical Features
Overgrowth of connective tissue of the skin occurs after trauma. Bloom (1956) described cases in 5 generations. Bohrod (1937) speculated that sexual selection favored the genotype of keloid formation. He presented evidence that cicatrization was practiced as a pubertal rite by Africans and that 'good' scar formers may have been on the average more fertile. Cosman et al. (1961) found a familial incidence of 3%. McKusick (1972) reported a transverse keloid over the upper sternum in father and son who recalled no trauma preceding the development of the keloid.
Peltonen et al. (1991) applied molecular genetic techniques to the analysis of keloids. They concluded that the initial step in the development of fibrotic reaction in keloids involves the expression of the TGFB1 gene (190180) by the neovascular endothelial cells, thus activating the adjacent fibroblasts to express markedly elevated levels of the gene product, as well as the products of the type I (120150, 120160) and type VI (120220, 120240, 120250) collagen genes.
Marneros et al. (2001) studied the clinical and genetic characteristics of 14 pedigrees with familial keloids. The ethnicity of these families was mostly African American but included Caucasian, Japanese, and African Caribbean. Pedigrees accounted for 341 family members, of whom 96 displayed keloids. A female predominance was seen. Syndromes associated with keloids, namely Rubinstein-Taybi (180849) and Goeminne (314300) syndromes, were not found in these families. Additionally, linkage to the gene loci of these syndromes and X-chromosomal linkage were excluded. The pattern of inheritance observed in these families was consistent with an autosomal dominant mode with incomplete clinical penetrance and variable expression.
Mapping
### Associations Pending Confirmation
Nakashima et al. (2010) performed a multistage genomewide association study in 824 Japanese individuals with keloid and 3,205 Japanese controls and identified significant associations of keloid with 4 SNPs in 3 chromosomal regions. The most significant association with keloid was observed at rs873549 on chromosome 1q41 (combined p = 5.89 x 10(-23); odds ratio, 1.77). Associations on chromosome 3q22.3-q23 were observed at 2 separate linkage disequilibrium (LD) blocks, with rs1511412 in an LD block including the FOXL2 gene (605597) (p = 2.31 x 10(-13); OR, 1.87), and with rs940187 in another LD block (p = 1.80 x 10(-13); OR, 1.98). In addition, association with keloid was found with rs8032158 in the NEDD4 gene (602278) on chromosome 15q21.3 (p = 5.96 x 10(-13); OR, 1.51).
Inheritance \- Autosomal dominant Skin \- Keloids ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| KELOID FORMATION | c3149494 | 3,029 | omim | https://www.omim.org/entry/148100 | 2019-09-22T16:39:19 | {"omim": ["148100"]} |
This article needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed.
Find sources: "Congestive hepatopathy" – news · newspapers · books · scholar · JSTOR (September 2015)
Congestive hepatopathy
Other namesNutmeg liver and Chronic passive congestion of the liver
Micrograph of congestive hepatopathy demonstrating perisinusoidal fibrosis and centrilobular (zone III) sinusoidal dilation. Liver biopsy. Trichrome stain.
SpecialtyGastroenterology, hepatology
Congestive hepatopathy, is liver dysfunction due to venous congestion, usually due to congestive heart failure. The gross pathological appearance of a liver affected by chronic passive congestion is "speckled" like a grated nutmeg kernel; the dark spots represent the dilated and congested hepatic venules and small hepatic veins. The paler areas are unaffected surrounding liver tissue. When severe and longstanding, hepatic congestion can lead to fibrosis; if congestion is due to right heart failure, it is called cardiac cirrhosis.[1]
## Contents
* 1 Signs and symptoms
* 2 Pathophysiology
* 3 Diagnosis
* 4 Treatment
* 5 See also
* 6 References
* 7 External links
## Signs and symptoms[edit]
Signs and symptoms depend largely upon the primary lesions giving rise to the condition. In addition to the heart or lung symptoms, there will be a sense of fullness and tenderness in the right hypochondriac region. Gastrointestinal catarrh is usually present, and vomiting of blood may occur. There is usually more or less jaundice. Owing to portal obstruction, ascites occurs, followed later by generalised oedema. The stools are light or clay-colored, and the urine is colored by bile. On palpation, the liver is found enlarged and tender, sometimes extending several inches below the costal margin of the ribs.[citation needed]
## Pathophysiology[edit]
CT appearance of liver in congestive hepatopathy, sometimes referred to as a nutmeg liver. Due to congestion, contrast does not flow through the liver in a normal manner. Axial and coronal images in the portal venous phase.
Increased pressure in the sublobular branches of the hepatic veins causes an engorgement of venous blood, and is most frequently due to chronic cardiac lesions, especially those affecting the right heart (e.g., right-sided heart failure), the blood being dammed back in the inferior vena cava and hepatic veins. Central regions of the hepatic lobules are red–brown and stand out against the non-congested, tan-coloured liver. Centrilobular necrosis occurs.
Macroscopically, the liver has a pale and spotty appearance in affected areas, as stasis of the blood causes pericentral hepatocytes (liver cells surrounding the central venule of the liver) to become deoxygenated compared to the relatively better-oxygenated periportal hepatocytes adjacent to the hepatic arterioles. This retardation of the blood also occurs in lung lesions, such as chronic interstitial pneumonia, pleural effusions, and intrathoracic tumors.
## Diagnosis[edit]
It is diagnosed with laboratory testing, including liver function tests, and radiology imaging, including ultrasounds.[2] [3]
## Treatment[edit]
Treatment is directed largely to removing the cause, or, where that is impossible, to modifying effects of the heart failure.[4] Thus, therapy aimed at improving right heart function will also improve congestive hepatopathy. True nutmeg liver is usually secondary to left-sided heart failure causing congestive right heart failure, so treatment options are limited.
## See also[edit]
* Ischemic hepatitis
## References[edit]
1. ^ Giallourakis CC, Rosenberg PM, Friedman LS (2002). "The liver in heart failure". Clin Liver Dis. 6 (4): 947–67, viii–ix. doi:10.1016/S1089-3261(02)00056-9. PMID 12516201.
2. ^ Alvarez, Alicia M.; Mukherjee, Debabrata (2011). "Liver Abnormalities in Cardiac Diseases and Heart Failure". The International Journal of Angiology. 20 (3): 135–142. doi:10.1055/s-0031-1284434. PMC 3331650. PMID 22942628.
3. ^ Morales A, Hirsch M, Schneider D, González G. Congestive hepatopathy: the role of the radiologist in the diagnosis. https://doi.org/10.5152/dir.2020.19673
4. ^ "Congestive Hepatopathy - Hepatic and Biliary Disorders". Merck Manuals Professional Edition. Retrieved 7 January 2020.
## External links[edit]
Classification
D
* ICD-10: K76.1
* ICD-9-CM: 573.8
* v
* t
* e
Diseases of the digestive system
Upper GI tract
Esophagus
* Esophagitis
* Candidal
* Eosinophilic
* Herpetiform
* Rupture
* Boerhaave 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
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Congestive hepatopathy | c0156195 | 3,030 | wikipedia | https://en.wikipedia.org/wiki/Congestive_hepatopathy | 2021-01-18T18:38:37 | {"umls": ["C0156195"], "wikidata": ["Q2334877"]} |
A number sign (#) is used with this entry because of evidence that familial focal epilepsy with variable foci-3 (FFEVF3) is caused by heterozygous mutation in the NPRL3 gene (600928) on chromosome 16p13.
Description
Familial focal epilepsy with variable foci (FFEVF) is an autosomal dominant form of epilepsy characterized by focal seizures arising from different cortical regions, including the temporal, frontal, parietal, and occipital lobes. Seizure types commonly include temporal lobe epilepsy (TLE), frontal lobe epilepsy (FLE), and nocturnal frontal lobe epilepsy (NFLE). A subset of patients have structural brain abnormalities, particularly focal cortical dysplasia (FCD). There is significant incomplete penetrance, with many unaffected mutation carriers within a family (summary by Ricos et al., 2016).
For a discussion of genetic heterogeneity of FFEVF, see FFEVF1 (604364).
Clinical Features
Ricos et al. (2016) reported 10 patients from 5 unrelated families with FFEVF3. Seizure types included NFLE, TLE, and FLE. One patient had neonatal seizures and another had intellectual disability and autism spectrum disorder. Additional clinical details were limited.
Sim et al. (2016) reported a family in which 4 children had FFEVF3. The proband, who was the most severely affected, presented with clonic seizures on the first day of life. Electroencephalogram (EEG) showed a focal suppression burst pattern. The 3 other patients had onset of focal or nocturnal seizures between 2 and 6 years of age. EEG studies were consistent with focal origin. Two patients had abnormal brain imaging suggesting focal cortical dysplasia, and both underwent resection, which confirmed FCD. The proband had global developmental delay, left hemiplegia, and hemianopia, but the other 3 children had normal development. Two additional unrelated patients with focal seizures associated with focal cortical dysplasia were also described. One had onset of focal seizures at age 4 months, whereas the other had onset at age 15 months. Brain resection in both patients confirmed FCD. One had normal cognition and the other had language delay; both had residual hemiparesis.
Weckhuysen et al. (2016) reported 2 unrelated families with FFEVF3. One family, of French descent, included 10 individuals with epilepsy and/or febrile seizures, sometimes with secondary generalization. Patients had onset of focal and nocturnal seizures in the first decade (range, 2 months to 8 years), although a few patients had later onset. EEG tended to show focal spike-wave complexes. Brain imaging was not performed, unavailable, or normal in most patients, but abnormal in 1; this patient had brain resection with documented FCD and hippocampal sclerosis. Several patients became seizure-free during young adulthood. One affected family member was found dead at age 23 years, with a diagnosis of possible SUDEP (sudden death in epilepsy). The second family, of Swiss descent, had 5 affected individuals with focal epilepsy. Three had onset of seizures in the first 5 years of life, 1 had onset at age 14 years, and the fifth had onset at age 51 years. One patient had imaging evidence of FCD: abnormal gyration, increased cortical thickness, and abnormal signals in the right frontoparietal area.
Inheritance
The transmission pattern of FFEVF3 in the families reported by Ricos et al. (2016) was consistent with autosomal dominant inheritance with incomplete penetrance.
Molecular Genetics
In 10 patients from 5 unrelated families with focal epilepsy with FFEVF3, Ricos et al. (2016) identified 5 different heterozygous mutations in the NPRL3 gene (see, e.g., 600928.0001-600928.0002), including 3 truncating mutations and 2 missense mutations. There was evidence of incomplete penetrance. The mutation in 1 large family was found by exome sequencing; the remaining probands were ascertained from a cohort of 404 individuals with focal epilepsy who underwent targeted sequencing for genes in the GATOR1 complex. Functional studies of the variants and studies of patient cells were not performed. The findings suggested that loss of function of the GATOR1 complex due to NPRL3 mutations can cause deregulated cellular growth and may play an important role in cortical dysplasia and focal epilepsy.
In 4 members of a family with FFEVF3, Sim et al. (2016) identified a heterozygous frameshift mutation in the NPRL3 gene (600928.0002). The mutation, which was found by whole-exome sequencing, showed incomplete penetrance in the family. Sequence analysis of the NPRL3 gene in 52 individuals with FCD identified 2 unrelated patients with heterozygous mutations (see, e.g., 600928.0003). Resected dysplastic brain tissue from 3 patients with truncating mutations showed a 50% decrease in NPRL3, consistent with haploinsufficiency, as well as evidence of activation of the mTOR (601231) pathway. Sim et al. (2016) suggested that therapy for this disorder may eventually include the use of mTOR inhibitors or highly focal brain resections aimed at removing only dysplastic tissue.
In affected members of 2 unrelated families with FFEVF3 and FCD, Weckhuysen et al. (2016) identified 2 different heterozygous truncating mutations in the NPRL3 gene (600928.0004-600928.0005). The mutations, which were found by sequencing a targeted epilepsy gene panel in 93 probands with focal epilepsy with or without FCD, were confirmed by Sanger sequencing. NRPL3 mutations thus occurred in 2.1% of probands studied.
INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Seizures, focal \- Frontal lobe epilepsy \- Nocturnal frontal lobe epilepsy \- Temporal lobe epilepsy \- Focal cortical dysplasia (in some patients) MISCELLANEOUS \- Onset in early childhood \- Incomplete penetrance MOLECULAR BASIS \- Caused by mutation in the nitrogen permease-regulator-like 3 gene (NPRL3, 600928.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| EPILEPSY, FAMILIAL FOCAL, WITH VARIABLE FOCI 3 | c4310708 | 3,031 | omim | https://www.omim.org/entry/617118 | 2019-09-22T15:46:46 | {"omim": ["617118"], "orphanet": ["98820"], "synonyms": ["FFEVF", "Familial partial epilepsy with variable foci"]} |
For a discussion of genetic heterogeneity of quantitative trait loci for stature (STQTL), see STQTL1 (606255).
Mapping
Hirschhorn et al. (2001) analyzed genomewide scans in 4 populations using a variance-components method, using stature as a quantitative trait locus, and found strong evidence for linkage to chromosome 12p11.2-q14 in a Finnish population (maximum lod = 3.35 at markers D12S10990-D12S398, p less than 0.05).
Xu et al. (2002) performed segregation and linkage analyses for adult height in a population of 200 Dutch families, each of which was ascertained through a proband with asthma. Modest support for linkage to 12q1 was observed; lod = 1.86 at D12S375.
Timpson et al. (2009) performed a genomewide association study of bone mineral density (see 601884) and related traits in 1,518 children from the Avon Longitudinal Study of Parents and Children (ALSPAC). There was an association between bone mineral density and 4 SNPs (rs2016266, rs4759021, rs6580942, rs10876432) on chromosome 12p13 surrounding the SP7 (606633) and AAAS (605378) genes. Metaanalysis of 2 previous studies revealed strong association between the 4 SNPs in the 12p13 region and adult lumbar spine bone mineral density (p = 9.9 x 10(-11)). The authors genotyped a further 3,692 children from ALSPAC and confirmed the association in the combined ALSPAC set with whole body bone mineral density in children under age 9 (combined set p = 3.1 x 10(-5) for rs2016266). Moreover, all 4 SNPs were associated with height in ALSPAC children (p = 3.7 x 10(-5) for rs2016266), but not with weight or body mass index, and adjusting for height in the combined ALSPAC set attenuated the associations with bone mineral density. Timpson et al. (2009) concluded that genetic variants in the region of the SP7 gene are associated with bone mineral density in children and adults, probably through primary effects on growth.
Molecular Genetics
Lorentzon et al. (2000) investigated the vitamin D receptor (VDR; 601769) gene polymorphisms, BsmI and TaqI, in 90 healthy Caucasian males. Boys with the BB genotype were shorter at birth (p = 0.01) and grew less from birth to age 16.9 +/- 0.3 (p = 0.01) than their Bb and bb counterparts. Both during puberty (age 16.9 +/- 0.3) and after puberty (age 19.3 +/- 0.7), the BB boys were shorter (p = 0.005 - 0.008). The VDR allelic variants alone contributed to 8% of the total variation in adult height.
In a study of the VDR and adult height in 1,873 white subjects from 406 nuclear families, Xiong et al. (2005) found within-family associations with height at BsmI and TaqI loci (p = 0.048 and 0.039, respectively). Analyses based on BsmI/TaqI haplotypes showed linkage (p = 0.05) and association (p = 0.001) with height.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| STATURE QUANTITATIVE TRAIT LOCUS 3 | c1853475 | 3,032 | omim | https://www.omim.org/entry/606257 | 2019-09-22T16:10:34 | {"omim": ["606257"]} |
Lymphomatoid granulomatosis
SpecialtyHematology and oncology
Lymphomatoid granulomatosis (LYG or LG) is a very rare lymphoproliferative disorder first characterized in 1972.[1] Lymphomatoid means lymphoma-like and granulomatosis denotes the microscopic characteristic of the presence of granulomas with polymorphic lymphoid infiltrates and focal necrosis within it.
LG most commonly affects middle aged people,[2] but has occasionally been observed in young people.[3] Males are found to be affected twice as often as females.[4]
## Contents
* 1 Causes
* 2 Pathophysiology
* 3 Treatment
* 4 Prognosis
* 5 See also
* 6 References
* 7 External links
## Causes[edit]
Lymphomatoid granulomatosis involves malignant B cells and reactive, non-malignant T cells and is almost always associated with infection of the malignant B cells by the Epstein-Barr virus; it is therefore considered to be a form of the Epstein-Barr virus-associated lymphoproliferative diseases.[5] The disease is believed to be induced by a combination of Epstein Barr virus infection and immunosuppression through immunosuppressive drugs (with case reports of methotrexate[6][7][8][9][10][11][12][13][14] and azathioprine[15][16]), infections such as HIV or chronic viral hepatitis or endogenous T cell defects.[17]
## Pathophysiology[edit]
The onset of the disease results in proliferation of EBV-infected malignant B-cells and a cytotoxic T-cell response which in turn leads to organ infiltration and dysfunction of the affected organs. The disease typically always relapse after successful treatment due to inability of the immune system and current viral drugs to eliminate an EBV-infection. If the onset of the disease can be linked to use of immunosuppressive drugs then discontinuation of these drugs may hinder a relapse. Organs usually affected are the skin, lungs, central nervous system while liver and kidney are affected to lesser extent. The pulmonary complications are usually what leads to death, however, CNS involvement that affects up to one third of the patients can be very severe with mental status changes, ataxia, hemiparesis, seizures, unconsciousness and death, typically followed in that order.[17]
The disease has been seen to transform to diffuse large B-cell lymphoma[18] and while LG is graded I-III based on the number of large EBV-positive B-cells, grade II and III can be considered as a variant of T-cell rich diffuse large B-cell lymphoma.[4][19]
## Treatment[edit]
Treatment depends on the grade (I-III) but typically consist of cortisone, rituximab and chemotherapy (etoposide, vincristine, cyclophosphamide, doxorubicin). Methotrexate has been seen to induce LG.[6][7] Interferon alpha has been used by the US National Cancer Institute with varying results.[20] In recent years hematopoietic stem cell transplantation has been performed on LG-patients with relative good success; a 2013 study identifying 10 cases found that 8 patients survived the treatment and were disease free several years later. Two of the disease free patients later died, one from suicide and one from graft versus host disease after a second transplantation 4 years later. The remaining two patients died from sepsis after the transplantation.[21]
## Prognosis[edit]
The current mortality is over 60% after 5 years. However, due to hematopoietic stem cell transplantation being performed only in recent years, this number could potentially be lowered in the future. In people with CNS involvement, treatment with Interferon alpha at the US National Cancer Institute resulted in complete remission in 90% of patients.[20]
## See also[edit]
* List of cutaneous conditions
## References[edit]
1. ^ Liebow, Averill A.; Carrington, Charles R.B.; Friedman, Paul J. (1972). "Lymphomatoid granulomatosis". Human Pathology. 3 (4): 457–558. doi:10.1016/S0046-8177(72)80005-4. PMC 1518397. PMID 4638966.
2. ^ Song, Joo Y.; Pittaluga, Stefania; Dunleavy, Kieron; Grant, Nicole; White, Therese; Jiang, Liuyan; Davies-Hill, Theresa; Raffeld, Mark; Wilson, Wyndham H.; Jaffe, Elaine S. (2015). "Lymphomatoid Granulomatosis—A Single Institute Experience". The American Journal of Surgical Pathology. 39 (2): 141–56. doi:10.1097/PAS.0000000000000328. PMC 4293220. PMID 25321327.
3. ^ Tacke, Zwanique C. A.; Eikelenboom, M. Judith; Vermeulen, R. Jeroen; Van Der Knaap, Marjo S.; Euser, Anne M.; Van Der Valk, Paul; Kaspers, Gertjan J. L. (2014). "Childhood Lymphomatoid Granulomatosis: A Report of 2 Cases and Review of the Literature". Journal of Pediatric Hematology/Oncology. 36 (7): e416–22. doi:10.1097/MPH.0000000000000090. PMID 24390446.
4. ^ a b Katzenstein, Anna-Luise A.; Doxtader, Erika; Narendra, Sonia (2010). "Lymphomatoid Granulomatosis". The American Journal of Surgical Pathology. 34 (12): e35–48. doi:10.1097/PAS.0b013e3181fd8781. PMID 21107080.
5. ^ Rezk SA, Zhao X, Weiss LM (September 2018). "Epstein-Barr virus (EBV)-associated lymphoid proliferations, a 2018 update". Human Pathology. 79: 18–41. doi:10.1016/j.humpath.2018.05.020. PMID 29885408.
6. ^ a b Ochi, N.; Yamane, H.; Yamagishi, T.; Monobe, Y.; Takigawa, N. (2013). "Methotrexate-Induced Lymphoproliferative Disease: Epstein-Barr Virus-Associated Lymphomatoid Granulomatosis". Journal of Clinical Oncology. 31 (20): e348–50. doi:10.1200/JCO.2012.46.2770. PMID 23733760.
7. ^ a b Blanchart, K; Paciencia, M; Seguin, A; Chantepie, S; Du Cheyron, D; Charbonneau, P; Galateau-Salle, F; Terzi, N (2014). "Fatal pulmonary lymphomatoid granulomatosis in a patient taking methotrexate for rheumatoid arthritis". Minerva Anestesiologica. 80 (1): 119–20. PMID 23857444.
8. ^ Oiwa, Hiroshi; Mihara, Keichiro; Kan, Takanobu; Tanaka, Maiko; Shindo, Hajime; Kumagai, Kazuhiko; Sugiyama, Eiji (2014). "Grade 3 Lymphomatoid Granulomatosis in a Patient Receiving Methotrexate Therapy for Rheumatoid Arthritis". Internal Medicine. 53 (16): 1873–5. doi:10.2169/internalmedicine.53.2593. PMID 25130128.
9. ^ Yamakawa, T; Kurosawa, M; Yonezumi, M; Suzuki, S; Suzuki, H (2014). "メトトレキサート中止と脳病変への放射線照射が奏効したメトトレキサート関連リンパ腫様肉芽腫症" [Methotrexate-related lymphomatoid granulomatosis successfully treated with discontinuation of methotrexate and radiotherapy to brain]. Rinsho Ketsueki (in Japanese). 55 (3): 321–6. doi:10.11406/rinketsu.55.321. PMID 24681935.
10. ^ Kobayashi, Shinichi; Kikuchi, Yuichi; Sato, Kimiya; Matsukuma, Susumu; Matsuki, Yasunori; Horikoshi, Hideyuki; Nagumo, Morichika; Kobayashi, Ayako; Masuoka, Kazuhiro; Kimura, Fumihiko; Oshima, Satoshi; Hakozaki, Yukiya; Kondo, Toshiro (2013). "Reversible iatrogenic, MTX-associated EBV-driven lymphoproliferation with histopathological features of a lymphomatoid granulomatosis in a patient with rheumatoid arthritis". Annals of Hematology. 92 (11): 1561–4. doi:10.1007/s00277-013-1741-1. PMID 23529185.
11. ^ Inaba, M; Ushijim, S; Hirata, N; Saisyoji, T; Kitaoka, M; Yoshinaga, T (2011). "Methotrexate-related lymphomatoid granulomatosis in a patient with rheumatoid arthritis". Nihon Kokyuki Gakkai Zasshi. 49 (8): 597–601. PMID 21894776.
12. ^ Schalk, Enrico; Krogel, Christian; Scheinpflug, Katrin; Mohren, Martin (2009). "Lymphomatoid Granulomatosis in a Patient with Rheumatoid Arthritis Receiving Methotrexate: Successful Treatment with the Anti-CD20 Antibody Mabthera". Onkologie. 32 (7): 440–1. doi:10.1159/000218356. PMID 19556825.
13. ^ Shimada, K.; Matsui, T.; Kawakami, M.; Nakayama, H.; Ozawa, Y.; Mitomi, H.; Tohma, S. (2007). "Methotrexate‐related lymphomatoid granulomatosis: A case report of spontaneous regression of large tumours in multiple organs after cessation of methotrexate therapy in rheumatoid arthritis". Scandinavian Journal of Rheumatology. 36 (1): 64–7. doi:10.1080/03009740600902403. PMID 17454938.
14. ^ Kameda, Hideto; Okuyama, Ayumi; Tamaru, Jun-Ichi; Itoyama, Shinji; Iizuka, Atsushi; Takeuchi, Tsutomu (2007). "Lymphomatoid granulomatosis and diffuse alveolar damage associated with methotrexate therapy in a patient with rheumatoid arthritis". Clinical Rheumatology. 26 (9): 1585–9. doi:10.1007/s10067-006-0480-2. PMID 17200802.
15. ^ Barakat, Athar; Grover, Karan; Peshin, Rohit (2014). "Rituximab for pulmonary lymphomatoid granulomatosis which developed as a complication of methotrexate and azathioprine therapy for rheumatoid arthritis". SpringerPlus. 3: 751. doi:10.1186/2193-1801-3-751. PMC 4320142. PMID 25674479.
16. ^ Connors, William; Griffiths, Cameron; Patel, Jay; Belletrutti, Paul J (2014). "Lymphomatoid granulomatosis associated with azathioprine therapy in Crohn disease". BMC Gastroenterology. 14: 127. doi:10.1186/1471-230X-14-127. PMC 4105046. PMID 25022612.
17. ^ a b Roschewski, Mark; Wilson, Wyndham H. (2012). "Lymphomatoid Granulomatosis". The Cancer Journal (Submitted manuscript). 18 (5): 469–74. doi:10.1097/PPO.0b013e31826c5e19. PMID 23006954.
18. ^ Boone, J. M.; Zhang, D; Fan, F (2013). "Lymphomatoid granulomatosis: A case report with unique clinical and histopathologic features". Annals of Clinical and Laboratory Science. 43 (2): 181–5. PMID 23694794.
19. ^ Tagliavini, E; Rossi, G; Valli, R; Zanelli, M; Cadioli, A; Mengoli, M. C.; Bisagni, A; Cavazza, A; Gardini, G (2013). "Lymphomatoid granulomatosis: A practical review for pathologists dealing with this rare pulmonary lymphoproliferative process" (PDF). Pathologica. 105 (4): 111–6. PMID 24466760.
20. ^ a b Dunleavy, Kieron; Roschewski, Mark; Wilson, Wyndham H. (2012). "Lymphomatoid Granulomatosis and Other Epstein-Barr Virus Associated Lymphoproliferative Processes". Current Hematologic Malignancy Reports (Submitted manuscript). 7 (3): 208–15. doi:10.1007/s11899-012-0132-3. PMC 6317897. PMID 22814713.
21. ^ Siegloch, Kristina; Schmitz, Norbert; Wu, Huei-Shan; Friedrichs, Birte; Van Imhoff, Gustaaf W.; Montoto, Silvia; Holler, Ernst; Ribera, Josep Maria; Delage, Robert; Dührsen, Ulrich; Castillo, Nerea del; Harrison, Beth; Dreger, Peter; Sureda, Anna; Working Party Lymphoma of the European Group for Blood Marrow Transplantation (EBMT) (2013). "Hematopoietic Stem Cell Transplantation in Patients with Lymphomatoid Granulomatosis: A European Group for Blood and Marrow Transplantation Report". Biology of Blood and Marrow Transplantation. 19 (10): 1522–5. doi:10.1016/j.bbmt.2013.07.023. PMID 23948061.
## External links[edit]
Classification
D
* ICD-O: 9766/1
* MeSH: D008230
* DiseasesDB: 33208
External resources
* eMedicine: med/1369
* v
* t
* e
Leukaemias, lymphomas and related disease
B cell
(lymphoma,
leukemia)
(most CD19
* CD20)
By
development/
marker
TdT+
* ALL (Precursor B acute lymphoblastic leukemia/lymphoma)
CD5+
* naive B cell (CLL/SLL)
* mantle zone (Mantle cell)
CD22+
* Prolymphocytic
* CD11c+ (Hairy cell leukemia)
CD79a+
* germinal center/follicular B cell (Follicular
* Burkitt's
* GCB DLBCL
* Primary cutaneous follicle center lymphoma)
* marginal zone/marginal zone B-cell (Splenic marginal zone
* MALT
* Nodal marginal zone
* Primary cutaneous marginal zone lymphoma)
RS (CD15+, CD30+)
* Classic Hodgkin lymphoma (Nodular sclerosis)
* CD20+ (Nodular lymphocyte predominant Hodgkin lymphoma)
PCDs/PP
(CD38+/CD138+)
* see immunoproliferative immunoglobulin disorders
By infection
* KSHV (Primary effusion)
* EBV
* Lymphomatoid granulomatosis
* Post-transplant lymphoproliferative disorder
* Classic Hodgkin lymphoma
* Burkitt's lymphoma
* HCV
* Splenic marginal zone lymphoma
* HIV (AIDS-related lymphoma)
* Helicobacter pylori (MALT lymphoma)
Cutaneous
* Diffuse large B-cell lymphoma
* Intravascular large B-cell lymphoma
* Primary cutaneous marginal zone lymphoma
* Primary cutaneous immunocytoma
* Plasmacytoma
* Plasmacytosis
* Primary cutaneous follicle center lymphoma
T/NK
T cell
(lymphoma,
leukemia)
(most CD3
* CD4
* CD8)
By
development/
marker
* TdT+: ALL (Precursor T acute lymphoblastic leukemia/lymphoma)
* prolymphocyte (Prolymphocytic)
* CD30+ (Anaplastic large-cell lymphoma
* Lymphomatoid papulosis type A)
Cutaneous
MF+variants
* indolent: Mycosis fungoides
* Pagetoid reticulosis
* Granulomatous slack skin
aggressive: Sézary disease
* Adult T-cell leukemia/lymphoma
Non-MF
* CD30-: Non-mycosis fungoides CD30− cutaneous large T-cell lymphoma
* Pleomorphic T-cell lymphoma
* Lymphomatoid papulosis type B
* CD30+: CD30+ cutaneous T-cell lymphoma
* Secondary cutaneous CD30+ large-cell lymphoma
* Lymphomatoid papulosis type A
Other
peripheral
* Hepatosplenic
* Angioimmunoblastic
* Enteropathy-associated T-cell lymphoma
* Peripheral T-cell lymphoma not otherwise specified (Lennert lymphoma)
* Subcutaneous T-cell lymphoma
By infection
* HTLV-1 (Adult T-cell leukemia/lymphoma)
NK cell/
(most CD56)
* Aggressive NK-cell leukemia
* Blastic NK cell lymphoma
T or NK
* EBV (Extranodal NK-T-cell lymphoma/Angiocentric lymphoma)
* Large granular lymphocytic leukemia
Lymphoid+
myeloid
* Acute biphenotypic leukaemia
Lymphocytosis
* Lymphoproliferative disorders (X-linked lymphoproliferative disease
* Autoimmune lymphoproliferative syndrome)
* Leukemoid reaction
* Diffuse infiltrative lymphocytosis syndrome
Cutaneous lymphoid hyperplasia
* Cutaneous lymphoid hyperplasia
* with bandlike and perivascular patterns
* with nodular pattern
* Jessner lymphocytic infiltrate of the skin
General
* Hematological malignancy
* leukemia
* Lymphoproliferative disorders
* Lymphoid leukemias
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Lymphomatoid granulomatosis | c0024307 | 3,033 | wikipedia | https://en.wikipedia.org/wiki/Lymphomatoid_granulomatosis | 2021-01-18T19:05:42 | {"gard": ["6943"], "mesh": ["D008230"], "umls": ["C0024307"], "orphanet": ["86869"], "wikidata": ["Q3775784"]} |
A number sign (#) is used with this entry because of evidence that Galloway-Mowat syndrome-3 (GAMOS3) is caused by homozygous or compound heterozygous mutation in the OSGEP gene (610107) on chromosome 14q11.
Description
Galloway-Mowat syndrome is a renal-neurologic disease characterized by early-onset nephrotic syndrome associated with microcephaly, gyral abnormalities of the brain, and delayed psychomotor development. Most patients have dysmorphic facial features, often including hypertelorism, ear abnormalities, and micrognathia. Other features, such as arachnodactyly and visual impairment, are more variable. Most patients die in the first years of life (summary by Braun et al., 2017).
For a general phenotypic description and a discussion of genetic heterogeneity of GAMOS, see GAMOS1 (251300).
Clinical Features
Chen et al. (2007) reported an infant with Galloway-Mowat syndrome. Prenatal ultrasound late in gestation revealed intrauterine growth retardation, microcephaly, and oligohydramnios. Postnatally, the infant had hypotonia, a sloping forehead, hypertelorism, epicanthal folds, microphthalmos, low-set floppy ears, small midface, high-arched palate, and micrognathia. At age 1 month, he showed developmental delay, proteinuria, and hypoalbuminemia. Brain MRI showed gyral abnormalities, frontal pachygyria, and deficient myelination. He died of multiple organ failure at age 2 months.
Edvardson et al. (2017) reported 2 sibs, born of consanguineous Arab Muslim parents, with GAMOS3 resulting in death between 6 and 8 years of age. Soon after birth, both patients showed dysmorphic features, failure to thrive, acquired microcephaly, and hypotonia. They had severely delayed psychomotor development with very few words; 1 patient was never able to sit unsupported. Both also developed a renal tubulopathy with decreased serum magnesium due to renal wasting. One of the patients developed a hypertensive crisis and the other also had hypocalcemia. Dysmorphic features were somewhat variable, but included upturned nose, downward slanting palpebral fissures, high-arched palate, microphthalmia, nystagmus, strabismus, pectus excavatum, and cryptorchidism. Brain imaging of 1 patient showed cerebellar atrophy, whereas brain imaging of the other patient showed nonspecific leukodystrophy. One patient had hypoplastic left heart, aortic coarctation, coloboma, arachnodactyly, and ichthyosis, which may have resulted from a concurrent 1q21.1 duplication of several genes that occurred only in this patient and not in the sib.
Braun et al. (2017) reported 28 patients from 24 families with GAMOS3. Several of the patients had previously been reported (Lin et al., 2001; Chen et al., 2005; Chen et al., 2007; Chen et al., 2011; Bailey and Georges, 2007). The families were of multiple ethnic origins, including Caucasian European, Turkish, Jordanian, Iranian, and American Indian, but almost half were of Taiwanese or East Asian descent; only 3 of the families were consanguineous. Most patients developed nephrotic syndrome with proteinuria in the first days or months of life followed shortly by end-stage renal disease, although 1 patient presented at age 3.5 years and another at age 13 years and did not have end-stage renal disease. Two sibs from 1 family (KW) did not have renal disease at ages 2.5 years and 7 months, respectively. Renal biopsy, when performed, usually showed focal segmental glomerulosclerosis (FSGS) or diffuse mesangial sclerosis (DMS); several biopsies showed diffuse foot process effacement. Almost all patients had primary microcephaly, developmental delay with speech delay, seizures, hypotonia, and spasticity. Brain imaging showed variable abnormalities, including gyral anomalies with lissencephaly, simplified gyral patterns, pachygyria, poor myelination, cerebral atrophy, dilated ventricles, atrophic corpus callosum, and cerebellar hypoplasia. Two sibs in 1 Turkish family (PN553) did not have microcephaly or significant neurologic deficits. Most patients had variable dysmorphic facial features, including narrow forehead, large low-set ears, floppy ears, micrognathia, beaked nose, epicanthal folds, hypertelorism, and deep-set eyes. Other common features included intrauterine growth retardation, short stature, camptodactyly, arachnodactyly, clenched hands, dislocated hips, edema, and visual or hearing impairment. Most of the patients died before 3 years of age.
### Prenatal Findings
Chen et al. (2005) noted that oligohydramnios may be an associated prenatal sonographic finding in GAMOS, and Chen et al. (2011) found that intrauterine growth retardation, microcephaly, and oligohydramnios are significant ultrasound findings in fetuses affected by GAMOS. Brain gyral abnormalities, poor myelination, and cerebellar atrophy can also be observed by imaging during fetal development.
Inheritance
The transmission pattern of GAMOS3 in the families reported by Braun et al. (2017) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 2 sibs, born of consanguineous Arab Muslim parents, with GAMOS3, Edvardson et al. (2017) identified a homozygous missense mutation in the OSGEP gene (R325Q; 610107.0001). The mutation, which was found by exome sequencing, segregated with the disorder in the family. Expression of the homologous mutation in yeast (R376Q) into yeast depleted of kae1 (the ortholog of OSGEP) failed to fully rescue the t6A synthesis defect, compared to expression of the wildtype allele. Edvardson et al. (2017) concluded that decreased t6A synthesis resulting from the R325Q mutation interfered with global protein production, resulting in a severe neurologic disorder.
In affected members of 24 families with GAMOS3, Braun et al. (2017) identified homozygous or compound heterozygous mutations in the OSGEP gene (see, e.g., 610107.0001-610107.0008). The mutation in the first family (B57) (I14F; 610107.0004) was found by a combination of homozygosity mapping and whole-exome sequencing. Subsequent mutations were identified by whole-exome sequencing and high-throughput exon sequencing of the OSGEP gene. Several of the OSGEP mutations were recurrent and represented founder alleles in certain populations (610107.0001, 610107.0002, 610107.0004, and 610107.0008). Complementation studies showed that the GAMOS3 OSGEP mutations were unable to restore growth defects or t6A levels in kae1-null yeast, and the mutations fell into 2 functional classes: either hypomorphic or amorphic alleles. The mutations were also unable to rescue the proliferation defect in human podocytes with shRNA-mediated knockdown of OSGEP. These findings indicated that the identified human disease alleles impaired protein functionality. However, none of the OSGEP mutations abrogated intermolecular interactions among KEOPS complex proteins, of which OSGEP is one. Knockdown of OSGEP using shRNA in human podocytes resulted in decreased t6A levels, inhibition of nascent protein synthesis, decreased cell proliferation, activation of the unfolded protein response with ER stress and upregulation of the ER-associated proteasomal degradation system, and increased apoptosis associated with activation of the DNA damage response (DDR). Knockdown of OSGEP also disrupted the formation of the sublamellar actin network in human podocytes and decreased podocyte migration. Fibroblasts derived from 1 patient (patient CP) with an R325Q mutation (610107.0001) showed increased phosphorylated H2AX (601772), consistent with activation of the DDR response. Braun et al. (2017) concluded that OSGEP mutations impair both the canonical and noncanonical functions of the KEOPS complex, resulting in several potential pathogenic mechanisms, including translational attenuation, activation of DDR signaling, increased apoptosis, and defects in actin regulation, which would have major effects on neurons and podocytes. The GAMOS3 families were part of a cohort of 91 GAMOS families who underwent genetic studies: mutations in 3 other genes of the KEOPS complex (LAGE3, TP53RK, and TPRKB) were also identified; mutations in these 4 genes were found in a total of 32 GAMOS families.
Animal Model
Braun et al. (2017) found that CRISPR/Cas9-mediated knockdown of the osgep gene in zebrafish larvae resulted in primary microcephaly and increased apoptosis in the brain compared to controls. Knockdown fish also showed early lethality. Mouse embryos with CRISPR/Cas9 knockdown also showed a microcephaly phenotype, with significantly shorter cerebral cortex lengths, cortex-midbrain midline lengths, and cortex widths compared to wildtype embryos. Neither mutant fish nor mutant mice had a renal phenotype, possibly a result of early lethality masking renal involvement that may have occurred in older animals.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature Other \- Intrauterine growth retardation \- Failure to thrive HEAD & NECK Head \- Microcephaly Face \- Narrow forehead \- Sloping forehead \- Micrognathia \- Small midface Ears \- Floppy ears \- Low-set ears \- Abnormal ears Eyes \- Hypertelorism \- Deep-set eyes \- Epicanthal folds \- Microphthalmia \- Strabismus \- Downslanting palpebral fissures \- Impaired vision Mouth \- Small mouth \- High-arched palate CARDIOVASCULAR Vascular \- Hypertension ABDOMEN Gastrointestinal \- Hiatal hernia GENITOURINARY Kidneys \- Nephrotic syndrome \- End-stage renal disease \- Focal segmental glomerulosclerosis seen on renal biopsy \- Diffuse mesangial sclerosis \- Foot process effacement \- Abnormalities of the glomerular basement membrane SKELETAL Pelvis \- Hip dislocation Hands \- Arachnodactyly \- Camptodactyly MUSCLE, SOFT TISSUES \- Hypotonia \- Edema NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Intellectual disability \- Speech delay \- Seizures \- Spasticity \- Gyral abnormalities \- Simplified gyral pattern \- Pachygyria \- Lissencephaly \- Cerebellar atrophy \- Cerebral atrophy \- Enlarged ventricles \- Thin corpus callosum \- Poor myelination PRENATAL MANIFESTATIONS Amniotic Fluid \- Oligohydramnios LABORATORY ABNORMALITIES \- Proteinuria \- Hypoalbuminemia MISCELLANEOUS \- Onset at birth or in the first months of life \- Progressive renal failure in most patients \- Most patients die in early childhood MOLECULAR BASIS \- Caused by mutation in the O-sialoglycoprotein endopeptidase gene (OSGEP, 610107.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| GALLOWAY-MOWAT SYNDROME 3 | c0795949 | 3,034 | omim | https://www.omim.org/entry/617729 | 2019-09-22T15:45:00 | {"doid": ["0080245"], "mesh": ["C537548"], "omim": ["617729"], "orphanet": ["2065"]} |
Autosomal recessive multiple epiphyseal dysplasia
Autosomal recessive multiple epiphyseal dysplasia has an autosomal recessive pattern of inheritance.
Autosomal recessive multiple epiphyseal dysplasia (ARMED), also called epiphyseal dysplasia, multiple, 4 (EDM4), multiple epiphyseal dysplasia with clubfoot or –with bilayered patellae,[1] is an autosomal recessive[2] congenital disorder affecting cartilage and bone development. The disorder has relatively mild signs and symptoms, including joint pain, scoliosis, and malformations of the hands, feet, and knees.[3]
Some affected individuals are born with an inward- and downward-turning foot (a clubfoot). An abnormality of the kneecap called a double-layered patella is also relatively common. Although some people with recessive multiple epiphyseal dysplasia have short stature as adults, most are of normal height. The incidence is unknown as many cases are not diagnosed due to mild symptoms.
## Contents
* 1 Cause and Genetics
* 2 Diagnosis
* 3 Treatment
* 4 See also
* 5 References
* 6 External links
## Cause and Genetics[edit]
Mutations in the SLC26A2 (DTDST) gene, located at human chromosome 5q32-33.1, are the cause of ARMED.[2][4] It is considered a milder disorder within a spectrum of skeletal disorders caused by mutations in the gene, which encodes a protein that is essential for the normal development of cartilage and its conversion to bone.[3] Mutations in the SLC26A2 gene alter the structure of developing cartilage, preventing bones from forming properly and resulting in associated skeletal maldevelopment.[3]
The disorder is inherited in an autosomal recessive manner.[2] This means the defective gene responsible for the disorder is located on an autosome (chromosome 5 is 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.
## Diagnosis[edit]
This section is empty. You can help by adding to it. (November 2017)
## Treatment[edit]
This section is empty. You can help by adding to it. (November 2017)
## See also[edit]
* Multiple epiphyseal dysplasia
## References[edit]
1. ^ Online Mendelian Inheritance in Man (OMIM): 226900
2. ^ a b c Hinrichs, T.; Superti-Furga, A.; Scheiderer, W. -D.; Bonafé, L.; Brenner, R.; Mattes, T. (June 2010). "Recessive multiple epiphyseal dysplasia (rMED) with homozygosity for C653S mutation in the DTDST gene - phenotype, molecular diagnosis and surgical treatment of habitual dislocation of multilayered patella: case report". BMC Musculoskeletal Disorders (Free full text). 11: 110. doi:10.1186/1471-2474-11-110. PMC 2902411. PMID 20525296.
3. ^ a b c "Recessive multiple epiphyseal dysplasia at Genetics Home Reference". Retrieved July 22, 2010.
4. ^ Online Mendelian Inheritance in Man (OMIM): 606718
## External links[edit]
Classification
D
* OMIM: 226900
* MeSH: C535504
* DiseasesDB: 30716
* Online Mendelian Inheritance in Man (OMIM): 226900
* Epiphyseal dysplasia, multiple, 4; Multiple epiphyseal dysplasia, autosomal recessive at NIH's Office of Rare Diseases
* "Multiple Epiphyseal Dysplasia, Recessive". GeneReviews -- NCBI Bookshelf.
* v
* t
* e
Osteochondrodysplasia
Osteodysplasia//
osteodystrophy
Diaphysis
* Camurati–Engelmann disease
Metaphysis
* Metaphyseal dysplasia
* Jansen's metaphyseal chondrodysplasia
* Schmid metaphyseal chondrodysplasia
Epiphysis
* Spondyloepiphyseal dysplasia congenita
* Multiple epiphyseal dysplasia
* Otospondylomegaepiphyseal dysplasia
Osteosclerosis
* Raine syndrome
* Osteopoikilosis
* Osteopetrosis
Other/ungrouped
* FLNB
* Boomerang dysplasia
* Opsismodysplasia
* Polyostotic fibrous dysplasia
* McCune–Albright syndrome
Chondrodysplasia/
chondrodystrophy
(including dwarfism)
Osteochondroma
* osteochondromatosis
* Hereditary multiple exostoses
Chondroma/enchondroma
* enchondromatosis
* Ollier disease
* Maffucci syndrome
Growth factor receptor
FGFR2:
* Antley–Bixler syndrome
FGFR3:
* Achondroplasia
* Hypochondroplasia
* Thanatophoric dysplasia
COL2A1 collagen disease
* Achondrogenesis
* type 2
* Hypochondrogenesis
SLC26A2 sulfation defect
* Achondrogenesis
* type 1B
* Autosomal recessive multiple epiphyseal dysplasia
* Atelosteogenesis, type II
* Diastrophic dysplasia
Chondrodysplasia punctata
* Rhizomelic chondrodysplasia punctata
* Conradi–Hünermann syndrome
Other dwarfism
* Fibrochondrogenesis
* Short rib – polydactyly syndrome
* Majewski's polydactyly syndrome
* Léri–Weill dyschondrosteosis
* v
* t
* e
Genetic disorder, membrane: Solute carrier disorders
1-10
* SLC1A3
* Episodic ataxia 6
* SLC2A1
* De Vivo disease
* SLC2A5
* Fructose malabsorption
* SLC2A10
* Arterial tortuosity syndrome
* SLC3A1
* Cystinuria
* SLC4A1
* Hereditary spherocytosis 4/Hereditary elliptocytosis 4
* SLC4A11
* Congenital endothelial dystrophy type 2
* Fuchs' dystrophy 4
* SLC5A1
* Glucose-galactose malabsorption
* SLC5A2
* Renal glycosuria
* SLC5A5
* Thyroid dyshormonogenesis type 1
* SLC6A19
* Hartnup disease
* SLC7A7
* Lysinuric protein intolerance
* SLC7A9
* Cystinuria
11-20
* SLC11A1
* Crohn's disease
* SLC12A3
* Gitelman syndrome
* SLC16A1
* HHF7
* SLC16A2
* Allan–Herndon–Dudley syndrome
* SLC17A5
* Salla disease
* SLC17A8
* DFNA25
21-40
* SLC26A2
* Multiple epiphyseal dysplasia 4
* Achondrogenesis type 1B
* Recessive multiple epiphyseal dysplasia
* Atelosteogenesis, type II
* Diastrophic dysplasia
* SLC26A4
* Pendred syndrome
* SLC35C1
* CDOG 2C
* SLC39A4
* Acrodermatitis enteropathica
* SLC40A1
* African iron overload
see also solute carrier family
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Autosomal recessive multiple epiphyseal dysplasia | c1847593 | 3,035 | wikipedia | https://en.wikipedia.org/wiki/Autosomal_recessive_multiple_epiphyseal_dysplasia | 2021-01-18T18:34:48 | {"gard": ["9793"], "mesh": ["C535504"], "wikidata": ["Q3042144"]} |
Cap myopathy is a disorder that primarily affects skeletal muscles, which are muscles that the body uses for movement. People with cap myopathy have muscle weakness (myopathy) and poor muscle tone (hypotonia) throughout the body, but they are most severely affected in the muscles of the face, neck, and limbs. The muscle weakness, which begins at birth or during childhood, can worsen over time.
Affected individuals may have feeding and swallowing difficulties in infancy. They typically have delayed development of motor skills such as sitting, crawling, standing, and walking. They may fall frequently, tire easily, and have difficulty running, climbing stairs, or jumping. In some cases, the muscles used for breathing are affected, and life-threatening breathing difficulties can occur.
People with cap myopathy may have a high arch in the roof of the mouth (high-arched palate), severely drooping eyelids (ptosis), and a long face. Some affected individuals develop an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis).
The name cap myopathy comes from characteristic abnormal cap-like structures that can be seen in muscle cells when muscle tissue is viewed under a microscope. The severity of cap myopathy is related to the percentage of muscle cells that have these caps. Individuals in whom 70 to 75 percent of muscle cells have caps typically have severe breathing problems and may not survive childhood, while those in whom 10 to 30 percent of muscle cells have caps have milder symptoms and can live into adulthood.
## Frequency
Cap myopathy is a rare disorder that has been identified in only a small number of individuals. Its exact prevalence is unknown.
## Causes
Mutations in the ACTA1, TPM2, or TPM3 genes can cause cap myopathy. These genes provide instructions for producing proteins that play important roles in skeletal muscles.
The ACTA1 gene provides instructions for making a protein called skeletal alpha (α)-actin, which is part of the actin protein family. Actin proteins are important for cell movement and the tensing of muscle fibers (muscle contraction). Thin filaments made up of actin molecules and thick filaments made up of another protein called myosin are the primary components of muscle fibers and are important for muscle contraction. Attachment (binding) and release of the overlapping thick and thin filaments allows them to move relative to each other so that the muscles can contract. The mutation in the ACTA1 gene that causes cap myopathy results in an abnormal protein that may interfere with the proper assembly of thin filaments. The cap structures in muscle cells characteristic of this disorder are composed of disorganized thin filaments.
The TPM2 and TPM3 genes provide instructions for making proteins that are members of the tropomyosin protein family. Tropomyosin proteins regulate muscle contraction by attaching to actin and controlling its binding to myosin. The specific effects of TPM2 and TPM3 gene mutations are unclear, but researchers suggest they may interfere with normal actin-myosin binding between the thin and thick filaments, impairing muscle contraction and resulting in the muscle weakness that occurs in cap myopathy.
### Learn more about the genes associated with Cap myopathy
* ACTA1
* TPM2
* TPM3
## Inheritance Pattern
Cap myopathy is an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases are not inherited; they result from new mutations in the gene and occur in people with no history of the disorder in their family.
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Cap myopathy | c1836448 | 3,036 | medlineplus | https://medlineplus.gov/genetics/condition/cap-myopathy/ | 2021-01-27T08:25:22 | {"gard": ["11915"], "mesh": ["C538348"], "omim": ["609284", "609285"], "synonyms": []} |
A number sign (#) is used with this entry Potocki-Shaffer syndrome is a contiguous gene deletion syndrome involving genes on chromosome 11p11.2.
Description
Potocki-Shaffer syndrome is a rare contiguous gene deletion syndrome due to haploinsufficiency of the 11p12-p11.2 region and is characterized by craniofacial abnormalities, developmental delay, intellectual disability, multiple exostoses (168500), and biparietal foramina (605957) (summary by Swarr et al., 2010).
Clinical Features
Bartsch et al. (1996) described a contiguous gene syndrome due to deletion in the proximal short arm of chromosome 11 in 8 patients belonging to 4 families. One patient had been reported by Lorenz et al. (1990) as an unusual case of acrocephalosyndactyly. Three of the patients had been reported by Shaffer et al. (1993). Bartsch et al. (1996) used microsatellite markers to characterize the extent of the deletion in each case. In addition to multiple exostoses and enlarged parietal foramina, 5 of the 8 patients showed brachycephaly with a somewhat turricephalic skull shape. The patient reported by Lorenz et al. (1990) and 1 of the patients reported by Shaffer et al. (1993) were described in the original publications to have a Saethre-Chotzen-like phenotype (101400). Cutaneous syndactyly between fingers 2 and 5 was present in the first of these 2 patients. The absence of craniofacial dysostosis in 1 family with the contiguous gene syndrome that showed enlarged parietal foramina and multiple exostoses and in families with autosomal inheritance of isolated enlarged parietal foramina suggested that there is a specific 11p gene involved in craniofacial dysostosis. Five of the patients were severely retarded but 3 patients from 1 family were mentally normal; thus, a specific mental retardation gene may be involved in the deletion. No evidence of imprinting was found; deletions of paternal origin were found in 2 patients and of maternal origin in 5. Bartsch et al. (1996) studied the deletions by cytogenetic and/or molecular methods and found them to be located between the centromere and D11S914 in a region of approximately 20 cM. Their study confirmed the presence of a multiple exostoses gene on 11p and suggested that the gene for isolated foramina parietalia permagna and genes associated with craniofacial dysostosis and mental retardation reside in the same chromosomal region.
Potocki and Shaffer (1996) reported an additional patient with an 11p12-p11.2 deletion. Cytogenetic and molecular analysis demonstrated a de novo, paternally derived deletion for markers tightly linked to the EXT2 locus (133701).
Using FISH, Wu et al. (2000) tested for the presence or heterozygous deletion of a BAC clone containing ALX4 (605420) on 11p in 2 patients with the Potocki-Shaffer syndrome and found that the clone was deleted in these patients. The authors stated that the involvement of Alx4 in murine skull development (Qu et al., 1997), its bone-specific expression pattern, the finding that Alx4 is a dosage-sensitive gene in the mouse, and the localization of a human genomic clone containing ALX4 to 11p11.2, with hemizygosity in patients with deletion of 11p11.2 who have biparietal foramina, supported the contention that ALX4 is a candidate gene for parietal foramina in the Potocki-Shaffer syndrome. Mavrogiannis et al. (2001) identified ALX4 as the gene which in haploid state causes the parietal foramina in proximal 11p deletion syndrome.
Hall et al. (2001) described an instructive family in which members in 5 generations had the Potocki-Shaffer syndrome with multiple exostoses and biparietal foramina but no mental retardation or craniofacial abnormalities. They showed that the EXT2 gene and the ALX4 gene were deleted, thus accounting for the multiple exostoses and biparietal foramina, respectively. The results indicated that the genes related to mental retardation and craniofacial abnormalities that sometimes occur in this syndrome must be located outside of the D11S1785-D11S1385 region.
Chuang et al. (2005) reported a family with inherited Potocki-Shaffer syndrome. The phenotypically normal mother had an interstitial deletion of chromosome 11 (11p11.2-p11.12) with neocentric marker chromosome formation. The marker chromosome contained the deleted material on 11p11.2 and was probably a ring. The patient inherited a maternal deleted chromosome 11 but not the marker chromosome, thus resulting in an unbalanced karyotype along with the phenotype of Potocki-Shaffer syndrome. Chuang et al. (2005) concluded that the deleted region in this case, 11p11.2-p11.12, was a previously unreported site of constitutional neocentromere formation and that this was also the first report describing deletion of 11p11.2-p11.12 and neocentromere formation resulting in inherited Potocki-Shaffer syndrome.
McGaughran et al. (1995) reported a patient with the combination of 2 deletion syndromes, WAGR (194072) and Potocki-Shaffer syndrome. Bremond-Gignac et al. (2005) described a second case of the combination. The latter patient also had obesity which, in combination with WAGR, is referred to as WAGRO. The patient presented with aniridia, cataract, nystagmus, corneal ulcers, and bilateral congenital ptosis. A left nephroblastoma was detected at 15 months of age. Other features included moderate developmental delay, growth deficiency, facial dysmorphism, multiple exostoses, and cranial lacunae. High-resolution and molecular cytogenetics confirmed a del(11)(p11.2p14.1) deletion. The deletion included the EXT2 (608210), ALX4, WT1 (607102), and PAX6 (607108) genes.
Wakui et al. (2005) constructed a panel of 11p deletions using cell lines derived from 10 patients with Potocki-Shaffer syndrome, including 6 patients who were newly identified. Analysis of the deleted regions using FISH, microsatellite analysis, and DNA array-based comparative genomic hybridization demonstrated that the full spectrum of PSS manifests when deletions are at least 2.1 Mb, spanning from D11S1393 to D11D1385/D11S1319, and encompassing the EXT2 and ALX4 genes. However, 1 patient with parietal foramina retained the ALX4 gene, and Wakui et al. (2005) suggested that ALX4 in this patient was functionally haploinsufficient due to a position effect. Results from 2 patients without mental retardation suggested that a gene related to mental retardation may be located between D11S554 and D11S1385/D11S1319.
In a 3-generation family with Potocki-Shaffer syndrome without mental defect or learning difficulties, Mavrogiannis et al. (2006) mapped the outer limits of the chromosome 11p deletion at D11S4173 distally and D11S554 proximally. FISH mapping determined that the deleted segment was eccentrically placed with respect to the ALX4 gene. The findings delineated a mental retardation locus to within 1.1 Mb of 11p11.2 between D11S1361 and D11S1344, thus confirming the findings of Wakui et al. (2005).
Swarr et al. (2010) evaluated 6 individuals diagnosed with PSS by cytogenetic methods through a multidisciplinary protocol-driven clinical assessment combined with retrospective chart reviews. All 6 patients had developmental delay and intellectual disability; 3 of the 6 patients had autistic features, and another child had occasional aggressive and self-injurious behaviors. Myopia, strabismus, and mild to moderate sensorineural hearing loss were also common. The patients had similar dysmorphic features, including microcephaly, brachycephaly, epicanthus, and sparse eyebrows laterally, prominent nasal bridge with broad, depressed nasal tip, hypoplastic nares, short philtrum, downturned mouth, and micrognathia.
Cytogenetics
Kim et al. (2012) identified 3 patients with balanced translocations disrupting the PHF21A (608325) gene in the PSS critical region. The patients had intellectual disability and craniofacial anomalies seen in PSS but did not have other manifestations of the contiguous gene deletion syndrome. Kim et al. (2012) concluded that the PHF21A gene is responsible for the intellectual disability and craniofacial anomalies seen in PSS. One of these patients had been reported by Dollfus et al. (1998) as having a phenotype suggestive of Gillespie syndrome (206700); Kim et al. (2012) noted that the translocation in this patient disrupted both the PHF21A and the ARHGAP6 (300118) genes.
Clinical Management
Based on their study of 6 patients with Potocki-Shaffer syndrome and a review of 31 reported patients, Swarr et al. (2010) proposed the following recommendations: referral to early childhood intervention and developmental-behavioral specialist at the time of diagnosis; a full skeletal survey at the time of diagnosis or by age 3 years, whichever is later; a screening for strabismus and nystagmus by their primary care provider at every well-child examination; referral to a pediatric ophthalmologist by age 6 months or at the time of diagnosis, whichever is later; evaluation for sensorineural hearing loss by 3 months of age, if not done previously; and a behavioral audiogram at 1 year of age, and audiograms obtained annually thereafter, at least through the age of speech development. Swarr et al. (2010) also recommended that FISH studies be performed on the parents of children diagnosed with PSS to assess for a balanced chromosomal rearrangement that would increase recurrence risk of PSS in future offspring.
Skel \- Multiple exostoses Limbs \- Cutaneous syndactyly between fingers 2 and 5 Neuro \- Mental retardation Skull \- Parietal foramina \- Brachycephaly \- Turricephaly \- Craniofacial dysostosis Inheritance \- Contiguous gene syndrome (11p13-p11 region) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| POTOCKI-SHAFFER SYNDROME | c1832588 | 3,037 | omim | https://www.omim.org/entry/601224 | 2019-09-22T16:15:13 | {"mesh": ["C538356"], "omim": ["601224"], "orphanet": ["52022"], "synonyms": ["Alternative titles", "PSS", "CHROMOSOME 11p11.2 DELETION SYNDROME", "PROXIMAL 11p DELETION SYNDROME", "DEFECT11 SYNDROME"]} |
New-onset refractory status epilepticus is an acute encephalopathy with inflammation-mediated status epilepticus characterized by an acute refractory status epilepticus, typically of the tonic-clonic type, following prodromal symptoms of confusion, fever, fatigue, headache, symptoms of gastrointestinal or upper respiratory tract infection, behavioral changes or hallucinations. Brain MRI abnormalities and abnormal findings in CSF, including pleocytosis and/or elevated protein levels, are frequently found during acute episode. Treatment-resistant epilepsy, cognitive and psychiatric impairments are usual consequences.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| New-onset refractory status epilepticus | None | 3,038 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=363558 | 2021-01-23T17:57:39 | {"gard": ["12244"], "icd-10": ["G41.8"], "synonyms": ["NORSE"]} |
A number sign (#) is used with this entry because of evidence that optic atrophy-9 (OPA9) is caused by compound heterozygous mutation in the ACO2 gene (100850) on chromosome 22q13. One such family has been reported.
For a discussion of genetic heterogeneity of optic atrophy, see OPA1 (165500).
Clinical Features
Metodiev et al. (2014) reported 2 French brothers, aged 41 and 36 years, with isolated optic neuropathy. The patients presented at ages 5 and 3 years with decreased visual acuity and pallor of the optic discs. In their twenties, they had severely reduced visual acuity, paracentral scotoma, red-green dyschromatopsia, and temporal optic atrophy at the fundus. The optic atrophy remained stable, and they had no overt extraocular symptoms.
Inheritance
The transmission pattern of OPA9 in the family reported by Metodiev et al. (2014) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 2 French brothers with isolated optic atrophy, Metodiev et al. (2014) identified compound heterozygous missense mutations in the ACO2 gene (L74V, 100850.0002 and G661R, 100850.0003). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Patient cells showed decreased ACO2 activity (31-66% of controls) and significantly decreased ACO2 protein levels. The mutant proteins were unable to completely rescue respiratory growth defects in an aco1 (100880)-deficient yeast strain at 37 degrees Celsius. ACO1 activity was also reduced in patient cells.
Nomenclature
This form of OPA was previously designated OPA8 in OMIM; however, the OPA8 symbol had already been used in the literature for a form of OPA mapping to chromosome 16 (616648).
INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Decreased visual acuity \- Optic atrophy \- Pallor of the optic disk \- Paracentral scotoma \- Red-green dyschromatopsia \- Reduction in the temporal superior and inferior retinal nerve fiber layers MISCELLANEOUS \- Two brothers in a French family have been reported (last curated March 2015) \- Onset in first decade MOLECULAR BASIS \- Caused by mutation in the mitochondrial aconitase gene (ACO2, 100850.0002 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| OPTIC ATROPHY 9 | c4225384 | 3,039 | omim | https://www.omim.org/entry/616289 | 2019-09-22T15:49:21 | {"omim": ["616289"], "orphanet": ["98676"], "synonyms": ["Autosomal recessive non-syndromic optic atrophy"]} |
Extragonadal germinoma is a rare, malignant germ cell tumor that occur in the midline of the body as a result of abnormal germ cell migration during embryogenesis. Clinical manifestations are variable and depend on the location and size of the tumor. Central nervous system tumor might present with headache, visual disturbances, endocrine abnormalities, and signs of increased intracranial pressure. A mediastinal tumor commonly presents with chest pain, dyspnea, cough and fever. Abdominal mass with or without pain, backache and weight loss are common clinical presentations in retroperitoneal 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
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Extragonadal germinoma | c0206660 | 3,040 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=182127 | 2021-01-23T18:33:42 | {"gard": ["2005"], "mesh": ["D018237"], "umls": ["C0206660"]} |
A rare, progressive metabolic liver disease due to marked to complete lysosomal acid lipase deficiency and characterized by dyslipidemia and massive lipid accumulation leading to hepatomegaly and liver dysfunction, splenomegaly, accelerated atherosclerosis.
## Epidemiology
Based on allele frequency, worldwide birth prevalence is estimated at 1/177,000; however, birth prevalence is lower in populations with Finnish, Ashkenazi Jewish, and South or East Asian ancestry.
## Clinical description
Presentation is along a clinical continuum with variable rates of progression and severity. The early-onset, rapidly progressive form, Wolman disease, presents in the neonatal or infantile period with non-specific symptoms of massive hepatosplenomegaly, liver failure, diarrhea/steatorrhea and vomiting, resulting in malabsorption, and cachexia. Adrenal calcifications occur in approximately half of infants. The later onset form, cholesteryl ester storage disease (CESD), presents between childhood and adulthood with a more variable clinical course that ranges from insidious to symptomatic. Progressive lysosomal lipid accumulation leads to the characteristic liver pathology and dysfunction (including hepatomegaly, liver fibrosis and/or cirrhosis, and elevated serum transaminases), dyslipidemia (elevated serum LDL-cholesterol and triglycerides, with normal to low HDL-cholesterol concentrations), premature atherosclerosis, splenomegaly and, eventually, end-stage liver failure. Secondary complications are variable and may include portal hypertension, ascites, cachexia, esophageal varices, gastrointestinal bleeding, coronary artery disease, aneurysm, stroke, anemia and thrombocytopenia. Approximately one-third of children experience severe gastrointestinal symptoms, including frequent diarrhoea, vomiting, abdominal pain, malabsorption and steatorrhoea.
## Etiology
The disease is due to mutations in the gene LIPA (10q23.2-q23.3) encoding the enzyme lysosomal acid lipase (LAL). LAL hydrolyzes cholesteryl esters and triglycerides, and thus LAL deficiency results in gradual accumulation of these lipids in the liver, spleen, and other organs. The variable phenotype is due to the amount of residual LAL activity, less than 1% for Wolman disease and between 1-12% for CESD.
## Diagnostic methods
The disease is suspected on clinical presentation of hepatomegaly, elevated transaminases, total cholesterol, low-density lipoprotein, and triglycerides, and low high-density lipoprotein. Liver biopsy shows microvesicular steatosis and/or fibrosis or cirrhosis. Immunostaining for lysosomal fat accumulation may facilitate diagnosis. Confirmation is by assessment of LAL activity on dry blood spot testing or in leukocytes and/or presence of a LIPA gene mutation.
## Differential diagnosis
Differential diagnosis includes familial hypercholesterolemia, non-alcoholic fatty liver disease, cryptogenic cirrhosis, and combined hyperlipidemia, as well as other lysosomal storage disorders.
## Antenatal diagnosis
Prenatal molecular genetic testing is possible in affected families.
## Genetic counseling
The pattern of inheritance is autosomal recessive and genetic counseling is recommended. The sibling recurrence risk is 25%.
## Management and treatment
Supportive measures include statins and cholestyramine to cholesterol, and liver transplant for end-stage liver failure. Patients should follow a diet low in cholesterol and triglycerides, and nutritional status should be monitored.. Magnetic resonance imaging to assess liver and spleen volumes may be useful. Enzyme replacement therapy (ERT) with the enzyme sebelipase alfa (authorized in Europe and the US) is available; however, the long-term clinical efficacy is yet to be determined. In infants with severe disease, ERT improves 1-year survival rates. In patients with later-onset disease, ERT reduces alanine aminotransferase levels and liver fat content, and improves the lipid parameters. Anemia and thrombocytopenia should be treated with standard approaches.
## Prognosis
In Wolman disease, patients rarely survive beyond infancy. In CESD, the prognosis and life expectancy is variable depending on the severity of the disease and timely diagnosis. The long-term prognosis with ERT is, as yet, unknown.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Lysosomal acid lipase deficiency | c2936797 | 3,041 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=275761 | 2021-01-23T18:24:51 | {"gard": ["12097"], "mesh": ["C531854"], "omim": ["278000"], "umls": ["C2936797"], "icd-10": ["E75.5"], "synonyms": ["LAL deficiency"]} |
Juvenile myoclonic epilepsy is an epilepsy syndrome characterized by myoclonic jerks (quick jerks of the arms or legs), generalized tonic-clonic seizures (GTCSs), and sometimes, absence seizures. The seizures of juvenile myoclonic epilepsy often occur when people first awaken in the morning. Seizures can be triggered by lack of sleep, extreme fatigue, stress, or alcohol consumption. Onset typically occurs around adolesence in otherwise healthy children. The causes of juvenile myoclonic epilepsy are very complex and not completely understood. Mutations in one of several genes, including the GABRA1 and the EFHC1 genes, can cause or increase susceptibility to this condition. Although patients usually require lifelong treatment with anticonvulsants, their overall prognosis is generally good.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Juvenile myoclonic epilepsy | c0270853 | 3,042 | gard | https://rarediseases.info.nih.gov/diseases/6808/juvenile-myoclonic-epilepsy | 2021-01-18T17:59:39 | {"mesh": ["D020190"], "omim": ["254770"], "umls": ["C0270853"], "synonyms": ["Petit mal, impulsive", "JME", "EJM", "Janz syndrome", "Myoclonic epilepsy, juvenile, 1"]} |
Sea-blue histiocytosis, also known as inherited lipemic splenomegaly, is an extremely rare condition characterized by elevated triglyceride levels (hypertriglyceridemia) and an enlarged spleen (splenomegaly). The disorder is so named because certain white blood cells, known as histiocytes, appear bright blue when stained and viewed under the microscope. Additional signs and symptoms may include a low platelet count (thrombocytopenia), liver function abnormalities, and heart disease. It is one of a group of related fat (lipid) disorders caused by certain changes in the APOE gene. The genetic change associated with this condition is inherited in an autosomal dominant manner though other factors, such as a patient's gender, the patient's lipid levels, and the genetic makeup of the other APOE gene may play a role in how the condition is expressed. There are currently no formal treatment guidelines. Management may involve the coordinated care of several different specialists including cardiologists, gastroenterologists, and hematologists. Patients with splenomegaly should be careful to avoid contact sports. Removal of the spleen (splenectomy) has been reported to make the condition worse.
Sea-blue histiocytes can also be a secondary finding associated with a wide range of disorders, including myelodysplastic syndromes, lymphomas, chronic myelogenous leukemia, idiopathic thrombocytopenic purpura, Niemann-Pick disease, and Norum disease. In these cases, treatment depends on the underlying disorder.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Sea-Blue histiocytosis | c0036489 | 3,043 | gard | https://rarediseases.info.nih.gov/diseases/8241/sea-blue-histiocytosis | 2021-01-18T17:57:47 | {"mesh": ["D012618"], "omim": ["269600"], "umls": ["C0036489"], "orphanet": ["158029"], "synonyms": ["Histiocytosis, sea-blue", "Sea-Blue histiocyte disease", "Inherited Lipemic Splenomegaly"]} |
A subtype of Autosomal dominant Charcot-Marie-Tooth disease type 2 characterized by the childhood onset of distal weakness and areflexia (with earlier and more severe involvement of the lower extremities), reduced sensory modalities (primarily pain and temperature sensation), foot deformities, postural tremor, scoliosis and contractures. Optic atrophy, vocal cord palsy with dysphonia, sensorineural hearing loss, spinal cord abnormalities and hydrocephalus have also been reported.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Autosomal dominant Charcot-Marie-Tooth disease type 2A2 | c1836485 | 3,044 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99947 | 2021-01-23T17:30:08 | {"mesh": ["C563757"], "omim": ["609260"], "umls": ["C1836485"], "icd-10": ["G60.0"], "synonyms": ["CMT2A2"]} |
Congenital cytomegalovirus infection
Micrograph of a cytomegalovirus (CMV) infection of the placenta (CMV placentitis). The characteristic large nucleus of a CMV infected cell is seen off-centre at the bottom-right of the image. H&E stain
SpecialtyPediatrics
Congenital cytomegalovirus (CMV) infection refers to a condition where cytomegalovirus is transmitted in the prenatal period. CMV is a member of the virus family herpesviridae and is the most common intrauterine infection.[1]
Human cytomegalovirus is one of the vertically transmitted infections that lead to congenital abnormalities. Others include toxoplasmosis, rubella, herpes simplex, and syphilis.
## Contents
* 1 Presentation
* 2 Prevention
* 2.1 Childcare
* 2.2 CMV Testing and Diagnosis
* 3 Epidemiology
* 4 References
* 5 External links
## Presentation[edit]
For infants who are infected by their mothers before birth, two potential adverse scenarios exist:
* Generalized infection may occur in the infant, and can cause complications such as low birth weight, microcephaly, seizures, petechial rash similar to the "blueberry muffin" rash of congenital rubella syndrome, and moderate hepatosplenomegaly (with jaundice). Though severe cases can be fatal, with supportive treatment most infants with CMV disease will survive. However, from 80% to 90% will have complications within the first few years of life that may include hearing loss, vision impairment, and varying degrees of learning disability.
* Another 5% to 10% of infants who are infected but without symptoms at birth will subsequently have varying degrees of hearing and mental or coordination problems. CMV is the most common cause of non-genetic sensorineural hearing loss in children. The onset of hearing loss can occur at any point during childhood, although commonly within the first decade. It is progressive and can affect both ears. The earlier the mother contracts the virus during pregnancy the more severe the effects are on the fetus, similarly the incidence of SNHL is dependent on which trimester of pregnancy CMV is contracted. The virus accounts for 20% of sensorineural hearing loss in children. [2][1]
These risks appear to be almost exclusively associated with women who previously have not been infected with CMV and who are having their first infection with the virus during pregnancy. There appears to be little risk of CMV-related complications for women who have been infected at least 6 months prior to conception. For this group, which makes up 50% to 80% of the women of child-bearing age, the rate of newborn CMV infection is 1%, and these infants appear to have no significant illness or abnormalities.[3]
The virus can also be transmitted to the infant at delivery from contact with genital secretions or later in infancy through breast milk. However, these infections usually result in little or no clinical illness in the infant. CMV can also be transferred through blood transfusions and close contact with large groups of children.[4]
To summarise, during a pregnancy when a woman who has never had CMV infection becomes infected with CMV, there is a risk that after birth the infant may have CMV-related complications, the most common of which are associated with hearing loss, visual impairment, or diminished mental and motor capabilities. On the other hand, healthy infants and children who acquire CMV after birth have few, if any, symptoms or complications. However, infants born preterm and infected with CMV after birth (especially via breastmilk[5]) may experience cognitive and motor impairments later in life.[6][7]
Symptoms associated with CMV, such as hearing loss, can result in further developmental delay. A delay in general speech and language development is more common in children with CMV.[8] Children with symptomatic CMV have been found to have a greater incidence of long-term neurological and neurodevelopmental complications than children with fetal alcohol syndrome or down syndrome.[4]
Congenital cytomegalovirus infection can be an important cause of intraventricular hemorrhage and neonatal encephalopathy.[9]
## Prevention[edit]
Recommendations for pregnant women with regard to CMV infection:[citation needed]
* Throughout the pregnancy, practice good personal hygiene, especially handwashing with soap and water, after contact with diapers or oral secretions (particularly with a child who is in day care). Sharing of food, eating and drinking utensils, and contact with toddlers' saliva should be avoided.
* Women who develop a mononucleosis-like illness during pregnancy should be evaluated for CMV infection and counseled about the possible risks to the unborn child.
* Laboratory testing for antibody to CMV can be performed to determine if a woman has already had CMV infection.
* Recovery of CMV from the cervix or urine of women at or before the time of delivery does not warrant a cesarean section.
* The demonstrated benefits of breast-feeding outweigh the minimal risk of acquiring CMV from the breast-feeding mother.
* There is no need to either screen for CMV or exclude CMV-excreting children from schools or institutions because the virus is frequently found in many healthy children and adults.
Treatment with hyperimmune globulin in mothers with primary CMV infection has been shown to be effective in preventing congenital disease in several studies.[10][11][12][13] One study did not show significant decrease in the risk of congenital cytomegalovirus infection.[14]
### Childcare[edit]
Most healthy people working with infants and children face no special risk from CMV infection. However, for women of child-bearing age who previously have not been infected with CMV, there is a potential risk to the developing unborn child (the risk is described above in the Pregnancy section). Contact with children who are in day care, where CMV infection is commonly transmitted among young children (particularly toddlers), may be a source of exposure to CMV. Since CMV is transmitted through contact with infected body fluids, including urine and saliva, child care providers (meaning day care workers, special education teachers, as well as mothers) should be educated about the risks of CMV infection and the precautions they can take.[15] Day care workers appear to be at a greater risk than hospital and other health care providers, and this may be due in part to the increased emphasis on personal hygiene in the health care setting.[citation needed]
Recommendations for individuals providing care for infants and children:
* Employees should be educated concerning CMV, its transmission, and hygienic practices, such as handwashing, which minimize the risk of infection.[citation needed]
* Susceptible nonpregnant women working with infants and children should not routinely be transferred to other work situations.[citation needed]
* Pregnant women working with infants and children should be informed of the risk of acquiring CMV infection and the possible effects on the unborn child.[citation needed]
* Routine laboratory testing for CMV antibody in female workers is not specifically recommended due to its high occurrence, but can be performed to determine their immune status.[citation needed]
### CMV Testing and Diagnosis[edit]
People infected with CMV develop antibodies to it, initially IgM later IgG indicating current infection and immunity respectively. The virus can be diagnosed through viral isolation, or using blood, urine, or saliva samples. [1]
When infected with CMV, most women have no symptoms, but some may have symptoms resembling mononucleosis. Women who develop a mononucleosis-like illness during pregnancy should consult their medical provider.[citation needed]
The Centers for Disease Control and Prevention (CDC) does not recommend routine maternal screening for CMV infection during pregnancy because there is no test that can definitively rule out primary CMV infection during pregnancy. Women who are concerned about CMV infection during pregnancy should practice CMV prevention measures. Considering that the CMV virus is present in saliva, urine, tears, blood, mucus, and other bodily fluids, frequent hand washing with soap and water is important after contact with diapers or oral secretions, especially with a child who is in daycare or interacting with other young children on a regular basis.[citation needed]
A diagnosis of congenital CMV infection can be made if the virus is found in an infant's urine, saliva, blood, or other body tissues during the first week after birth. Antibody tests cannot be used to diagnose congenital CMV; a diagnosis can only be made if the virus is detected during the first week of life. Congenital CMV cannot be diagnosed if the infant is tested more than one week after birth.[citation needed]
Visually healthy infants are not routinely tested for CMV infection although only 10–20% will show signs of infection at birth[citation needed] though up to 80% may go onto show signs of prenatal infection in later life. If a pregnant woman finds out that she has become infected with CMV for the first time during her pregnancy, she should have her infant tested for CMV as soon as possible after birth.[citation needed]
Treatment for CMV infection should start at 1 month of age and should occur for 6 months. The options for treatment are intravenous ganciclovir and oral valganciclovir. After diagnosis, it is important to further investigate any possible evidence of end-organ disease and symptoms through blood tests, imaging, ophthalmology tests, and hearing tests.[2]
## Epidemiology[edit]
Worldwide, approximately 1 in 100 to 500 babies are born with congenital CMV. Approximately 1 in 3000 will show symptoms and 1 in 7000 will die.[16] Congenital HCMV infection occurs when the mother suffers a primary infection (or reactivation) during pregnancy. Due to the lower seroprevalence of HCMV in industrialized countries and higher socioeconomic groups, congenital infections are actually less common in poorer communities, where more women of child-bearing age are already seropositive. In industrialized countries up to 8% of HCMV seronegative mothers contract primary HCMV infection during pregnancy, of which roughly 50% will transmit to the fetus.[17] Between 10-15% of infected fetuses are then born with symptoms,[2] which may include pneumonia, gastrointestinal, retinal and neurological disease.[18][19] 10-15% of asymptomatic babies will develop long term neurological effects. SNHL is found in 35% of children with CMV, cognitive deficits have been found in 66% of children with CMV, and death occurs in 4% of children.[1] HCMV infection occurs in roughly 1% of all neonates with those who are not congenitally infected contracting the infection possibly through breast milk.[20][21][22] Other sources of neonatal infection are bodily fluids which are known to contain high titres in shedding individuals: saliva (<107copies/ml) and urine (<105copies/ml )[23][24] seem common routes of transmission.
The incidence of primary CMV infection in pregnant women in the United States varies from 1% to 3%. Healthy pregnant women are not at special risk for disease from CMV infection. When infected with CMV, most women have no symptoms and very few have a disease resembling infectious mononucleosis. It is their developing fetuses that may be at risk for congenital CMV disease. CMV remains the most important cause of congenital viral infection in the United States. HCMV is the most common cause of congenital infection in humans and intrauterine primary infections are more common than other well-known infections and syndromes, including Down Syndrome, Fetal Alcohol Syndrome, Spina Bifida, and Pediatric HIV/AIDS.[citation needed]
## References[edit]
1. ^ a b c d Dobbie, Allison M. (2017). "Evaluation and management of cytomegalovirus-associated congenital hearing loss". Current Opinion in Otolaryngology & Head and Neck Surgery. 25 (5): 390–395. doi:10.1097/moo.0000000000000401. ISSN 1068-9508. PMID 28857892.
2. ^ a b c Lim, Yinru; Lyall, Hermione (2017). "Congenital cytomegalovirus – who, when, what-with and why to treat?". Journal of Infection. 74 (1): S89–S94. doi:10.1016/s0163-4453(17)30197-4. ISSN 0163-4453. PMID 28646968.
3. ^ Ryan KJ, Ray CG, eds. (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. pp. 556, 566–9. ISBN 978-0-8385-8529-0.
4. ^ a b Coleman, J. L; Steele, R. W (2017). "Preventing Congenital Cytomegalovirus Infection". Clinical Pediatrics. 56 (12): 1085–1084. doi:10.1177/0009922817724400. PMID 28825308. S2CID 39691206.
5. ^ Maschmann, J.; Hamprecht, K.; Dietz, K.; Jahn, G.; Speer, C. P. (2001). "Cytomegalovirus Infection of Extremely Low—Birth Weight Infants via Breast Milk". Clinical Infectious Diseases. 33 (12): 1998–2003. doi:10.1086/324345. PMID 11712092.
6. ^ Brecht, K; Goelz, R; Bevot, A; Krägeloh- Mann, I; Wilke, M; Lidzba, K (2015). "Postnatal Human Cytomegalovirus Infection in Preterm Infants Has Long-Term Neuropsychological Sequelae". The Journal of Pediatrics. 166 (4): 834–9.e1. doi:10.1016/j.jpeds.2014.11.002. PMID 25466679.
7. ^ Bevot, Andrea; Hamprecht, Klaus; Krägeloh-Mann, Ingeborg; Brosch, Sibylle; Goelz, Rangmar; Vollmer, Brigitte (1 April 2012). "Long-term outcome in preterm children with human cytomegalovirus infection transmitted via breast milk". Acta Paediatrica. 101 (4): e167–e172. doi:10.1111/j.1651-2227.2011.02538.x. PMID 22111513.
8. ^ Korndewal, Marjolein J Oudesluys-Murphy, Anne Marie Kroes, Aloys C M Vossen, Ann C T M de Melker, Hester E (December 2017). "Congenital Cytomegalovirus Infection: Child Development, Quality of Life and Impact on Daily Life". The Pediatric Infectious Disease Journal. 36 (12): 1141–1147. doi:10.1097/INF.0000000000001663. OCLC 1018138960. PMID 28650934. S2CID 20122101.CS1 maint: multiple names: authors list (link)
9. ^ Suksumek, N; Scott, JN; Chadha, R; Yusuf, K (July 2013). "Intraventricular hemorrhage and multiple intracranial cysts associated with congenital cytomegalovirus infection". Journal of Clinical Microbiology. 51 (7): 2466–8. doi:10.1128/JCM.00842-13. PMC 3697656. PMID 23678057.
10. ^ Nigro, G.; Adler, S.P.; La Torre, R.; Best, A.M. (2005). "Passive immunization during pregnancy for congenital cytomegalovirus infection". N. Engl. J. Med. 353 (13): 1350–1362. doi:10.1056/nejmoa043337. PMID 16192480.
11. ^ Visentin, S.; Manara, R.; Milanese, L.; Da Roit, A.; Salviato, E.; Citton, V.; Magno, F.M.; Morando, C. (2012). "Early primary cytomegalovirus infection in pregnancy: maternal hyperimmunoglobulin therapy improves outcomes among infants at 1 year of age". Clin Infect Dis. 55 (4): 497–503. doi:10.1093/cid/cis423. PMID 22539662.
12. ^ Nigro, G.; Adler, S.P.; Parruti, G.; Anceschi, M.M.; Coclite, E.; pezone, I.; Di Renzo, G.C. (2012). "Immunoglobulin therapy of fetal cytomegalovirus infection occurring in the first half of pregnancy--a case-control study of the outcome in children". J Infect Dis. 205 (2): 215–227. doi:10.1093/infdis/jir718. PMID 22140265.
13. ^ Buxmann, H.; Stackelberg, O.M.; Schlosser, R.L.; Enders, G.; Gonser, M.; Meyer-Wittkopf, M.; Hamprecht, K.; Enders, M. (2012). "Use of cytomegalovirus hyperimmunoglobulin for prevention of congenital cytomegalovirus disease: a retrospective analysis". J Perinat Med. 40 (4): 439–446. doi:10.1515/jpm-2011-0257. PMID 22752777.
14. ^ Revello, M. G.; Lazzarotto, T.; Guerra, B.; Spinillo, A.; Ferrazzi, E.; Kustermann, A.; Guaschino, S.; Vergani, P.; Todros, T.; Frusca, T.; Arossa, A.; Furione, M.; Rognoni, V.; Rizzo, Nicola; Gabrielli, Liliana; Klersy, Catherine; Gerna, G. (2014). "A Randomized Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus" (PDF). N Engl J Med. 370 (14): 1316–1326. doi:10.1056/NEJMoa1310214. hdl:2434/262989. ISSN 0028-4793. PMID 24693891.
15. ^ Pickering, Larry; Baker, Carol; Kimberlin, David; Long, Sarah (2012). 2012 Report of the Committee on Infectious Diseases (PDF) (29 ed.). Elk Grove Village, IL: American Academy of Pediatrics. p. 145. ISBN 978-1-58110-703-6. Retrieved 20 November 2016.
16. ^ Butler, Declan (5 July 2016). "Zika raises profile of more common birth-defect virus". Nature. 535 (17): 17. Bibcode:2016Natur.535...17B. doi:10.1038/535017a. PMID 27383962.
17. ^ Adler, Stuart P. (December 2005). "Congenital Cytomegalovirus Screening". The Pediatric Infectious Disease Journal. 24 (12): 1105–1106. doi:10.1097/00006454-200512000-00016. PMID 16371874.
18. ^ Barry Schoub; Zuckerman, Arie J.; Banatvala, Jangu E.; Griffiths, Paul E. (2004). "Chapter 2C Cytomegalovirus". Principles and Practice of Clinical Virology. Chichester: John Wiley & Sons. pp. 85–122. ISBN 978-0-470-84338-3.
19. ^ Vancíková Z, Dvorák P (2001). "Cytomegalovirus infection in immunocompetent and immunocompromised individuals--a review". Curr. Drug Targets Immune Endocr. Metabol. Disord. 1 (2): 179–87. doi:10.2174/1568008013341334. PMID 12476798.
20. ^ Kerrey BT, Morrow A, Geraghty S, Huey N, Sapsford A, Schleiss MR (2006). "Breast milk as a source for acquisition of cytomegalovirus (HCMV) in a premature infant with sepsis syndrome: detection by real-time PCR". J. Clin. Virol. 35 (3): 313–6. doi:10.1016/j.jcv.2005.09.013. PMID 16300992.
21. ^ Schleiss MR; Dror, Yigal (2006). "Role of breast milk in acquisition of cytomegalovirus infection: recent advances". Curr. Opin. Pediatr. 18 (1): 48–52. doi:10.1097/01.mop.0000192520.48411.fa. PMID 16470162.
22. ^ Schleiss MR (2006). "Acquisition of human cytomegalovirus infection in infants via breast milk: natural immunization or cause for concern?". Rev. Med. Virol. 16 (2): 73–82. doi:10.1002/rmv.484. PMID 16287195.
23. ^ Kearns AM, Turner AJ, Eltringham GJ, Freeman R (2002). "Rapid detection and quantification of CMV DNA in urine using LightCycler-based real-time PCR". J. Clin. Virol. 24 (1–2): 131–4. doi:10.1016/S1386-6532(01)00240-2. PMID 11744437.
24. ^ Yoshikawa T, Ihira M, Taguchi H, Yoshida S, Asano Y (2005). "Analysis of shedding of 3 beta-herpesviruses in saliva from patients with connective tissue diseases". J. Infect. Dis. 192 (9): 1530–6. doi:10.1086/496890. PMID 16206067.
## External links[edit]
* Cytomegalovirus (CMV)—NHS Choices
* CMV: Congenital CMV Infection—CDC
Classification
D
* ICD-10: P35.1
* ICD-9-CM: 771.1
External resources
* MedlinePlus: 001343
* eMedicine: article/963090
* v
* t
* e
Vertically transmitted infections
Gestational
* Viruses
* Congenital rubella syndrome
* Congenital cytomegalovirus infection
* Neonatal herpes simplex
* Hepatitis B
* Congenital varicella syndrome
* HIV
* Fifth disease
* Bacteria
* Congenital syphilis
* Other
* Toxoplasmosis
* transplacental
* TORCH complex
During birth
* transcervical
* Candidiasis
* Gonorrhea
* Listeriosis
Late pregnancy
* Listeriosis
* Congenital cytomegalovirus infection
By breastfeeding
* Breastfeeding
* Tuberculosis
* HIV
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Congenital cytomegalovirus infection | c0349499 | 3,045 | wikipedia | https://en.wikipedia.org/wiki/Congenital_cytomegalovirus_infection | 2021-01-18T19:04:53 | {"gard": ["1480", "1409"], "umls": ["C0349499"], "icd-9": ["771.1"], "icd-10": ["P35.1"], "orphanet": ["294"], "wikidata": ["Q5160416"]} |
Letterer–Siwe disease
Other namesAcute and disseminated Langerhans cell histiocytosis
This condition is inherited in an autosomal recessive manner
SpecialtyOncology
Letterer–Siwe disease is one of the four recognized clinical syndromes of Langerhans cell histiocytosis (LCH). It causes approximately 10% of LCH disease and is the most severe form.[1] Prevalence is estimated at 1:500,000 and the disease almost exclusively occurs in children less than three years old.[2] The name is derived from the names of Erich Letterer and Sture Siwe.
## Contents
* 1 Presentation
* 2 Cause
* 3 Diagnosis
* 4 Prognosis
* 5 References
* 6 External links
## Presentation[edit]
Letterer-Siwe is characterized by skin lesions, ear drainage, lymphadenopathy, osteolytic lesions, and hepatosplenomegaly. The skin lesions are scaly and may involve the scalp, ear canals, and abdomen.[3]
## Cause[edit]
Oncogenic mutation of BRAF 50-70% cases[citation needed]
## Diagnosis[edit]
The diagnosis was established by histopathology and electron microscopy.--2. In Abt-Letterer-Siwe disease, the racket-like Langerhans cell granules are found by electron microscopy within the specific infiltrating cells. The demonstration of these organelles allows the unequivocal diagnosis in cases with uncharacteristic clinical or histopathological appearance. The same structures are characteristic of Hand-Schüller-Christian disease and of eosinophilic granuloma. The electron microscopic findings confirm the grouping of these three diseases together as "histiocytosis X".{[citation needed]
## Prognosis[edit]
The disease is often rapidly fatal, with a five-year survival rate of 50%. The development of thrombocytopenia is a poor prognostic sign.[1]
## References[edit]
1. ^ a b "Langerhans Cell Histiocytosis - Hematology and Oncology - Merck Manuals Professional Edition". Merck Manuals Professional Edition. Retrieved 2017-05-19.
2. ^ RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Letterer Siwe disease". www.orpha.net. Retrieved 2017-05-19.
3. ^ "Langerhans cell histiocytosis | DermNet New Zealand". www.dermnetnz.org. Retrieved 2017-05-19.
## External links[edit]
Classification
D
* ICD-10: C96.0
* ICD-9-CM: 202.5
* ICD-O: 9722/3
* OMIM: 246400
* MeSH: C538636
* DiseasesDB: 5906
External resources
* Orphanet: 99870
* v
* t
* e
Histiocytosis
WHO-I/Langerhans cell histiocytosis/
X-type histiocytosis
* Letterer–Siwe disease
* Hand–Schüller–Christian disease
* Eosinophilic granuloma
* Congenital self-healing reticulohistiocytosis
WHO-II/non-Langerhans cell histiocytosis/
Non-X histiocytosis
* Juvenile xanthogranuloma
* Hemophagocytic lymphohistiocytosis
* Erdheim-Chester disease
* Niemann–Pick disease
* Sea-blue histiocyte
* Benign cephalic histiocytosis
* Generalized eruptive histiocytoma
* Xanthoma disseminatum
* Progressive nodular histiocytosis
* Papular xanthoma
* Hereditary progressive mucinous histiocytosis
* Reticulohistiocytosis (Multicentric reticulohistiocytosis, Reticulohistiocytoma)
* Indeterminate cell histiocytosis
WHO-III/malignant histiocytosis
* Histiocytic sarcoma
* Langerhans cell sarcoma
* Interdigitating dendritic cell sarcoma
* Follicular dendritic cell sarcoma
Ungrouped
* Rosai–Dorfman disease
This dermatology article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Letterer–Siwe disease | c0023381 | 3,046 | wikipedia | https://en.wikipedia.org/wiki/Letterer%E2%80%93Siwe_disease | 2021-01-18T18:46:16 | {"mesh": ["C538636"], "umls": ["C0023381"], "icd-9": ["202.50"], "icd-10": ["C96.0"], "orphanet": ["99870"], "wikidata": ["Q6533637"]} |
Psychotic depression
Other namesDepressive psychosis
Drawing depicting the sadness and the detachment from reality that people with psychotic depression have
SpecialtyPsychiatry
SymptomsHallucinations, delusions, anhedonia, psychomotor retardation, sleep problems,[1]
ComplicationsSuicide, self-harm
Usual onset20-40 years old
Durationdays to weeks,sometimes more
Differential diagnosisSchizoaffective disorder, schizophrenia
TreatmentMedication, cognitive behavioral therapy
MedicationAnti-depressants, Anti-psychotics
Psychotic depression, also known as depressive psychosis, is a major depressive episode that is accompanied by psychotic symptoms.[2] It can occur in the context of bipolar disorder or major depressive disorder.[2] It can be difficult to distinguish from schizoaffective disorder, a diagnosis that requires the presence of psychotic symptoms for at least two weeks without any mood symptoms present.[2] Unipolar psychotic depression requires that the psychotic features occur only during episodes of major depression.[3] Diagnosis using the DSM-5 involves meeting the criteria for a major depressive episode, along with the criteria for "mood-congruent or mood-incongruent psychotic features" specifier.[4]
## Contents
* 1 Signs and symptoms
* 2 Cause
* 3 Pathophysiology
* 4 Diagnosis
* 4.1 Differential diagnosis
* 5 Treatment
* 6 Research
* 7 Prognosis
* 8 References
## Signs and symptoms[edit]
Individuals with psychotic depression experience the symptoms of a major depressive episode, along with one or more psychotic symptoms, including delusions and/or hallucinations.[2] Delusions can be classified as mood congruent or incongruent, depending on whether or not the nature of the delusions is in keeping with the individual's mood state.[2] Common themes of mood congruent delusions include guilt, persecution, punishment, personal inadequacy, or disease.[5] Half of patients experience more than one kind of delusion.[2] Delusions occur without hallucinations in about one-half to two-thirds of patients with psychotic depression.[2] Hallucinations can be auditory, visual, olfactory (smell), or haptic (touch), and are congruent with delusional material.[2] Affect is sad, not flat. Severe anhedonia, loss of interest, and psychomotor retardation are typically present.[6]
## Cause[edit]
Psychotic symptoms tend to develop after an individual has already had several episodes of depression without psychosis.[2] However, once psychotic symptoms have emerged, they tend to reappear with each future depressive episode.[2] The prognosis for psychotic depression is not considered to be as poor as for schizoaffective disorders or primary psychotic disorders.[2] Still, those who have experienced a depressive episode with psychotic features have an increased risk of relapse and suicide compared to those without psychotic features, and they tend to have more pronounced sleep abnormalities.[2][5]
Family members of those who have experienced psychotic depression are at increased risk for both psychotic depression and schizophrenia.[2]
Most patients with psychotic depression report having an initial episode between the ages of 20 and 40. As with other depressive episodes, psychotic depression tends to be episodic, with symptoms lasting for a certain amount of time and then subsiding. While psychotic depression can be chronic (lasting more than 2 years), most depressive episodes last less than 24 months. A study conducted by Kathleen S. Bingham found that patients receiving appropriate treatment for psychotic depression went into "remission". They reported a quality of life similar to that of people without PD.[7]
## Pathophysiology[edit]
There are a number of biological features that may distinguish psychotic depression from non-psychotic depression. The most significant difference may be the presence of an abnormality in the hypothalamic pituitary adrenal axis (HPA). The HPA axis appears to be dysregulated in psychotic depression, with dexamethasone suppression tests demonstrating higher levels of cortisol following dexamethasone administration (i.e. lower cortisol suppression).[2] Those with psychotic depression also have higher ventricular-brain ratios than those with non-psychotic depression.[2]
## Diagnosis[edit]
### Differential diagnosis[edit]
See also: Depression (differential diagnoses)
Psychotic symptoms are often missed in psychotic depression, either because patients do not think their symptoms are abnormal or they attempt to conceal their symptoms from others.[2] On the other hand, psychotic depression may be confused with schizoaffective disorder.[2] Due to overlapping symptoms, differential diagnosis includes also dissociative disorders.[8]
## Treatment[edit]
Several treatment guidelines recommend either the combination of a second-generation antidepressant and atypical antipsychotic or tricyclic antidepressant monotherapy or electroconvulsive therapy (ECT) as the first-line treatment for unipolar psychotic depression.[9][10][11][12] There is some evidence indicating that combination therapy with an antidepressant plus an antipsychotic is more effective in treating psychotic depression than either antidepressant treatment alone or placebo.[13]
Pharmaceutical treatments can include tricyclic antidepressants, atypical antipsychotics, or a combination of an antidepressant from the newer, more well tolerated SSRI or SNRI categories and an atypical antipsychotic.[10] Olanzapine may be an effective monotherapy in psychotic depression,[14] although there is evidence that it is ineffective for depressive symptoms as a monotherapy;[10][15] and olanzapine/fluoxetine is more effective.[10][15] Quetiapine monotherapy may be particularly helpful in psychotic depression since it has both antidepressant and antipsychotic effects and a reasonable tolerability profile compared to other atypical antipsychotics.[16][17][18] The current drug-based treatments of psychotic depression are reasonably effective but can cause side effects, such as nausea, headaches, dizziness, and weight gain.[19] Tricyclic antidepressants may be particularly dangerous, because overdosing has the potential to cause fatal cardiac arrhythmias.[10]
In the context of psychotic depression, the following are the most well-studied antidepressant/antipsychotic combinations
First-generation
* Amitriptyline/perphenazine[20]
* Amitriptyline/haloperidol[21]
Second-generation
* Venlafaxine/quetiapine[22]
* Olanzapine/fluoxetine[15]
* Olanzapine/sertraline[23]
In modern practice of ECT a therapeutic clonic seizure is induced by electric current via electrodes placed on an anaesthetised, unconscious patient. Despite much research the exact mechanism of action of ECT is still not known.[24] ECT carries the risk of temporary cognitive deficits (e.g., confusion, memory problems), in addition to the burden of repeated exposures to general anesthesia.[25]
## Research[edit]
Efforts are made to find a treatment which targets the proposed specific underlying pathophysiology of psychotic depression. A promising candidate was mifepristone,[26] which by competitively blocking certain neuro-receptors, renders cortisol less able to directly act on the brain and was thought to therefore correct an overactive HPA axis. However, a Phase III clinical trial, which investigated the use of mifepristone in PMD, was terminated early due to lack of efficacy.[27]
Transcranial magnetic stimulation (TMS) is being investigated as an alternative to ECT in the treatment of depression. TMS involves the administration of a focused electromagnetic field to the cortex to stimulate specific nerve pathways.
Research has shown that psychotic depression differs from non-psychotic depression in a number of ways:[28] potential precipitating factors,[29][30][31] underlying biology,[32][33][34][35] symptomatology beyond psychotic symptoms,[36][37] long-term prognosis,[38][39] and responsiveness to psychopharmacological treatment and ECT.[40]
## Prognosis[edit]
The long-term outcome for psychotic depression is generally poorer than for non-psychotic depression.[10]
## References[edit]
1. ^ "Psychotic Depression". WebMD.
2. ^ a b c d e f g h i j k l m n o p q Hales E and Yudofsky JA, eds, The American Psychiatric Press Textbook of Psychiatry, Washington, DC: American Psychiatric Publishing, Inc., 2003
3. ^ "Unipolar major depression with psychotic features: Epidemiology, clinical features, assessment, and diagnosis". www.uptodate.com. Retrieved 2016-05-29.
4. ^ American Psychiatric Association (2013). Diagnostic and statistical manual of mental disorders (5th ed. Washington DC: American Psychiatric Association. ISBN 9780890425558.
5. ^ a b Practice Guideline for the Treatment of Patients with Major Depressive Disorder (PDF). APA Practice Guidelines (3rd ed.). American Psychiatric Association. 2010. doi:10.1176/appi.books.9780890423387.654001. ISBN 978-0-89042-338-7. Retrieved April 6, 2013.
6. ^ Rothschild, A.J., 2009. Clinical Manual for Diagnosis and Treatment of Psychotic Depression. American Psychiatric Publishing, Inc. Washington DC, USA ISBN 978-1-58562-292-4
7. ^ Bingham, Kathleen (2019). "Health-related quality of life in remitted psychotic depression". Journal of Affective Disorders.
8. ^ Shibayama M (2011). "Differential diagnosis between dissociative disorders and schizophrenia". Psychiatria et Neurologia Japonica. 113 (9): 906–911. PMID 22117396.
9. ^ "Somatic Treatment of an Acute Episode of Unipolar Psychotic Depression". WebMD LLC. 2013. Retrieved 4 October 2013.
10. ^ a b c d e f Taylor, David; Patron, Carol; Kapur, Shitij (2012). Maudsley Prescribing Guidelines in Psychiatry (11th ed.). West Sussex: John Wiley & Sons, Inc. pp. 233–234. ISBN 9780470979693.
11. ^ Wijkstra, J; Lijmer, J; Balk, FJ; Geddes, JR; Nolen, WA (2006). "Pharmacological treatment for unipolar psychotic depression: Systematic review and meta-analysis". British Journal of Psychiatry. 188 (5): 410–5. doi:10.1192/bjp.bp.105.010470. PMID 16648526.
12. ^ Leadholm, Anne Katrine K.; Rothschild, Anthony J.; Nolen, Willem A.; Bech, Per; Munk-Jørgensen, Povl; Ostergaard, Søren Dinesen (2013). "The treatment of psychotic depression: Is there consensus among guidelines and psychiatrists?". Journal of Affective Disorders. 145 (2): 214–20. doi:10.1016/j.jad.2012.07.036. PMID 23021823.
13. ^ Wijkstra, Jaap; Lijmer, Jeroen; Burger, Huibert; Cipriani, Andrea; Geddes, John; Nolen, Willem A. (2015-07-30). "Pharmacological treatment for psychotic depression" (PDF). The Cochrane Database of Systematic Reviews (7): CD004044. doi:10.1002/14651858.CD004044.pub4. ISSN 1469-493X. PMID 26225902.
14. ^ Schatzberg, AF (2003). "New approaches to managing psychotic depression" (PDF). The Journal of Clinical Psychiatry. 64 Suppl 1: 19–23. PMID 12625801.
15. ^ a b c Rothschild, Anthony J.; Williamson, Douglas J.; Tohen, Mauricio F.; Schatzberg, Alan; Andersen, Scott W.; Van Campen, Luann E.; Sanger, Todd M.; Tollefson, Gary D. (August 2004). "A double-blind, randomized study of olanzapine and olanzapine/fluoxetine combination for major depression with psychotic features". The Journal of Clinical Psychopharmacology. 24 (4): 365–373. doi:10.1097/01.jcp.0000130557.08996.7a. PMID 15232326.
16. ^ Weisler, R; Joyce, M; McGill, L; Lazarus, A; Szamosi, J; Eriksson, H; Moonstone Study, Group (2009). "Extended release quetiapine fumarate monotherapy for major depressive disorder: Results of a double-blind, randomized, placebo-controlled study". CNS Spectrums. 14 (6): 299–313. doi:10.1017/S1092852900020307. PMID 19668121.
17. ^ Bortnick, Brian; El-Khalili, Nizar; Banov, Michael; Adson, David; Datto, Catherine; Raines, Shane; Earley, Willie; Eriksson, Hans (2011). "Efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR) monotherapy in major depressive disorder: A placebo-controlled, randomized study". Journal of Affective Disorders. 128 (1–2): 83–94. doi:10.1016/j.jad.2010.06.031. PMID 20691481.
18. ^ Maneeton, Narong; Maneeton, Benchalak; Srisurapanont, Manit; Martin, Stephen D (2012). "Quetiapine monotherapy in acute phase for major depressive disorder: A meta-analysis of randomized, placebo-controlled trials". BMC Psychiatry. 12: 160. doi:10.1186/1471-244X-12-160. PMC 3549283. PMID 23017200.
19. ^ Mayo Clinic http://www.mayoclinic.com/health/antidepressants/MH00062
20. ^ Spiker, DG; Weiss, JC; Dealy, RS; Griffin, SJ; Hanin, I; Neil, JF; Perel, JM; Rossi, AJ; Soloff, PH (1985). "The pharmacological treatment of delusional depression". American Journal of Psychiatry. 142 (4): 430–436. doi:10.1176/ajp.142.4.430. PMID 3883815.
21. ^ Muller-Siecheneder, Florian; Muller, Matthias J.; Hillert, Andreas; Szegedi, Armin; Wetzel, Hermann; Benkert, Otto (1998). "Risperidone versus haloperidol and amitriptyline in the treatment of patients with a combined psychotic and depressive syndrome". The Journal of Clinical Psychopharmacology. 18 (2): 111–120. doi:10.1097/00004714-199804000-00003. PMID 9555596.
22. ^ Rothschild, Anthony J.; Williamson, Douglas J.; Tohen, Mauricio F.; Schatzberg, Alan; Andersen, Scott W.; Van Campen, Luann E.; Sanger, Todd M.; Tollefson, Gary D. (2004). "A double-blind, randomized study of olanzapine and olanzapine/fluoxetine combination for major depression with psychotic features". The Journal of Clinical Psychopharmacology. 24 (2): 365–373. doi:10.1097/01.jcp.0000130557.08996.7a. PMID 15232326.
23. ^ Meyers, BS; Flint, AJ; Rothschild, AJ; Mulsant, BH; Whyte, EM; Peasley-Miklus, C; Papademetriou, E; Leon, AC; Heo, M; Stop-Pd, Group (August 2009). "A double-blind randomized controlled trial of olanzapine plus sertraline vs olanzapine plus placebo for psychotic depression: the study of pharmacotherapy of psychotic depression (STOP-PD)". Archives of General Psychiatry. 66 (8): 838–847. doi:10.1001/archgenpsychiatry.2009.79. PMC 2840400. PMID 19652123.
24. ^ Bolwig, T. (2011). "How does electroconvulsive therapy work? Theories on its mechanism". The Canadian Journal of Psychiatry. 56 (1): 13–18. doi:10.1177/070674371105600104. PMID 21324238.
25. ^ "Electroconvulsive therapy (ECT): Risks". MayoClinic.com. 2012-10-25. Retrieved 2013-10-04.
26. ^ Belanoff, Joseph K.; Flores, Benjamin H.; Kalezhan, Michelle; Sund, Brenda; Schatzberg, Alan F. (October 2001). "Rapid reversal of psychotic depression using mifepristone". Journal of Clinical Psychopharmacology. 21 (5): 516–21. doi:10.1097/00004714-200110000-00009. PMID 11593077.
27. ^ Mifepristone#cite ref-20
28. ^ Ostergaard, SD; Rothschild, AJ; Uggerby, P; Munk-Jørgensen, P; Bech, P; Mors, O (2012). "Considerations on the ICD-11 classification of psychotic depression". Psychotherapy and Psychosomatics. 81 (3): 135–44. doi:10.1159/000334487. PMID 22398817.
29. ^ Østergaard, Søren Dinesen; Petrides, Georgios; Dinesen, Peter Thisted; Skadhede, Søren; Bech, Per; Munk-Jørgensen, Povl; Nielsen, Jimmi (2013). "The Association between Physical Morbidity and Subtypes of Severe Depression". Psychotherapy and Psychosomatics. 82 (1): 45–52. doi:10.1159/000337746. PMID 23147239.
30. ^ Østergaard, Søren Dinesen; Waltoft, Berit Lindum; Mortensen, Preben Bo; Mors, Ole (2013). "Environmental and familial risk factors for psychotic and non-psychotic severe depression". Journal of Affective Disorders. 147 (1–3): 232–40. doi:10.1016/j.jad.2012.11.009. PMID 23228568.
31. ^ Domschke, Katharina; Lawford, Bruce; Young, Ross; Voisey, Joanne; Morris, C. Phillip; Roehrs, Tilmann; Hohoff, Christa; Birosova, Eva; Arolt, Volker; Baune, Bernhard T. (2011). "Dysbindin (DTNBP1) – A role in psychotic depression?". Journal of Psychiatric Research. 45 (5): 588–95. doi:10.1016/j.jpsychires.2010.09.014. PMID 20951386.
32. ^ Nelson, JC; Davis, JM (1997). "DST studies in psychotic depression: A meta-analysis". The American Journal of Psychiatry. 154 (11): 1497–503. doi:10.1176/ajp.154.11.1497. PMID 9356556.
33. ^ Posener, JA; Debattista, C; Williams, GH; Chmura Kraemer, H; Kalehzan, BM; Schatzberg, AF (2000). "24-Hour monitoring of cortisol and corticotropin secretion in psychotic and nonpsychotic major depression". Archives of General Psychiatry. 57 (8): 755–60. doi:10.1001/archpsyc.57.8.755. PMID 10920463.
34. ^ Cubells, JF; Price, LH; Meyers, BS; Anderson, GM; Zabetian, CP; Alexopoulos, GS; Nelson, JC; Sanacora, G; Kirwin, P; Carpenter, L; Malison, RT; Gelernter, J (2002). "Genotype-controlled analysis of plasma dopamine beta-hydroxylase activity in psychotic unipolar major depression". Biological Psychiatry. 51 (5): 358–64. doi:10.1016/S0006-3223(01)01349-X. PMID 11904129.
35. ^ Meyers, BS; Alexopoulos, GS; Kakuma, T; Tirumalasetti, F; Gabriele, M; Alpert, S; Bowden, C; Meltzer, HY (1999). "Decreased dopamine beta-hydroxylase activity in unipolar geriatric delusional depression". Biological Psychiatry. 45 (4): 448–52. doi:10.1016/S0006-3223(98)00085-7. PMID 10071716.
36. ^ Maj, M; Pirozzi, R; Magliano, L; Fiorillo, A; Bartoli, L (2007). "Phenomenology and prognostic significance of delusions in major depressive disorder: A 10-year prospective follow-up study". The Journal of Clinical Psychiatry. 68 (9): 1411–7. doi:10.4088/JCP.v68n0913. PMID 17915981.
37. ^ Østergaard, SD; Bille, J; Søltoft-Jensen, H; Lauge, N; Bech, P (2012). "The validity of the severity-psychosis hypothesis in depression". Journal of Affective Disorders. 140 (1): 48–56. doi:10.1016/j.jad.2012.01.039. PMID 22381953.
38. ^ Coryell, W; Leon, A; Winokur, G; Endicott, J; Keller, M; Akiskal, H; Solomon, D (1996). "Importance of psychotic features to long-term course in major depressive disorder". The American Journal of Psychiatry. 153 (4): 483–9. doi:10.1176/ajp.153.4.483. PMID 8599395.
39. ^ Ostergaard, SD; Bertelsen, A; Nielsen, J; Mors, O; Petrides, G (2013). "The association between psychotic mania, psychotic depression and mixed affective episodes among 14,529 patients with bipolar disorder" (PDF). Journal of Affective Disorders. 147 (1–3): 44–50. doi:10.1016/j.jad.2012.10.005. PMID 23122529.
40. ^ Birkenhäger, TK; Pluijms, EM; Lucius, SA (2003). "ECT response in delusional versus non-delusional depressed inpatients". Journal of Affective Disorders. 74 (2): 191–5. doi:10.1016/S0165-0327(02)00005-8. PMID 12706521.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Psychotic depression | c0743072 | 3,047 | wikipedia | https://en.wikipedia.org/wiki/Psychotic_depression | 2021-01-18T19:00:17 | {"icd-9": ["298.0"], "wikidata": ["Q2914583"]} |
Davison and Rabiner (1940) described 2 brothers and a sister with onset of symptoms in the late 20s. Autopsy was performed in one. It is not clear that an entity distinct from others discussed here was involved.
Misc \- Third decade onset Neuro \- Corticopallidodegeneration \- Disseminated encephalomyelopathy \- Spastic pseudosclerosis Inheritance \- Autosomal recessive ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| SPASTIC PSEUDOSCLEROSIS | c0599464 | 3,048 | omim | https://www.omim.org/entry/270900 | 2019-09-22T16:22:14 | {"mesh": ["C563024"], "omim": ["270900"], "synonyms": ["Alternative titles", "DISSEMINATED ENCEPHALOMYELOPATHY", "CORTICOPALLIDODEGENERATION"]} |
Jaw cysts
SpecialtyOral and Maxillofacial Surgery, Dentistry
A cyst is a pathological epithelial lined cavity that fills with fluid or soft material and usually grows from internal pressure generated by fluid being drawn into the cavity from osmosis (hydrostatic pressure). The bones of the jaws, the mandible and maxilla, are the bones with the highest prevalence of cysts in the human body. This is due to the abundant amount of epithelial remnants that can be left in the bones of the jaws. The enamel of teeth is formed from ectoderm (the precursor germ layer to skin and mucosa), and so remnants of epithelium can be left in the bone during odontogenesis (tooth development). The bones of the jaws develop from embryologic processes which fuse together, and ectodermal tissue may be trapped along the lines of this fusion.[1] This "resting" epithelium (also termed cell rests) is usually dormant or undergoes atrophy, but, when stimulated, may form a cyst. The reasons why resting epithelium may proliferate and undergo cystic transformation are generally unknown, but inflammation is thought to be a major factor.[1] The high prevalence of tooth impactions and dental infections that occur in the bones of the jaws is also significant to explain why cysts are more common at these sites.
Cysts that arise from tissue(s) that would normally develop into teeth are referred to as odontogenic cysts. Other cysts of the jaws are termed non-odontogenic cysts.[2] Non-odontogenic cysts form from tissues other than those involved in tooth development, and consequently may contain structures such as epithelium from the nose. As the cyst grows from hydraulic pressure it causes the bone around it to resorb, and may cause movement of teeth or other vital structures such as nerves and blood vessels, or resorb the roots of teeth. Most cysts do not cause any symptoms, and are discovered on routine dental radiographs.[1] Some cysts may not require any treatment, but if treatment is required, it usually involves some minor surgery to partially or completely remove the cyst in a one or two-stage procedure.
## Contents
* 1 Classification
* 1.1 Odontogenic cysts
* 1.2 Developmental/ Non-odontogenic cysts
* 1.2.1 Developmental cysts of the jaws
* 1.2.2 Developmental cysts of the soft tissues around the jaws
* 1.2.3 Developmental cysts of questionable cause
* 2 Signs and symptoms
* 3 Diagnosis
* 4 Treatment
* 5 Prognosis
* 6 Epidemiology
* 7 References
* 8 External links
## Classification[edit]
### Odontogenic cysts[edit]
Dental panoramic radiograph showing dentigerous cyst associated with an impacted lower right wisdom tooth in the right mandible (arrowed, appears on the lower left of the image).
Relative incidence of odontogenic cysts.[3]
Main article: odontogenic cyst
Odontogenic cysts have histologic origins in the cells of the dental structures. Some are inflammatory while others are developmental.
* Radicular cyst is the most common (up to two thirds of all cysts of the jaws). This inflammatory cyst originated from a reaction to dental pulp necrosis.
* Dentigerous cyst, the second most prevalent cyst, is associated with the crown of non-erupted tooth.
* Odontogenic keratocyst This lesion may be associated with the Nevoid basal cell carcinoma syndrome.
* Buccal bifurcation cyst which appears in the buccal bifurcation region of the mandibular first molars in the second half of the first decade of life.[4]
* Eruption cyst; a small cyst in the gingiva as a tooth erupts, forming from the degenerating dental follicle
* Primordial cyst; previous thought to be a unique entity. Most primordial cysts have proven to be Keratocystic odontogenic tumors
* Orthokeratinized odontogenic cyst; a variant of the Keratocystic odontogenic tumor
* Gingival cyst of the newborn; an inclusion cyst from remnants of the dental lamina on a newborn gingiva
* Gingival cyst of the adult; a soft tissue variant of the lateral periodontal cyst
* Lateral periodontal cyst; a non-inflammatory cyst (vs a radicular cyst) on the side of a tooth derived from remanents of the dental lamina
* Calcifying odontogenic cyst; a rare lesion with cystic and neoplastic features and significant diversity in presentation, histology and prognosis
* Glandular odontogenic cyst; cyst with respiratory like epithelial lining and the potential for recurrence with characteristics similar to a central variant of low-grade mucoepidermoid carcinoma
### Developmental/ Non-odontogenic cysts[edit]
There are several development cysts of the head and neck most of which form in the soft tissues rather than the bone. There are also several cysts, previously thought to arise from epithelial remanents trapped in embryonic lines of fusion, most of which are now believed to be odontogenic in origin or have an unknown cause. Their names are included for the sake of completeness.
#### Developmental cysts of the jaws[edit]
* Nasopalatine duct cyst, the most common development jaw cyst, appears only in the mid-line of the maxilla.
#### Developmental cysts of the soft tissues around the jaws[edit]
* Palatal cysts of the newborn (Epstein's pearls)
* Nasolabial cyst (nasoalveolar cyst)
* Epidermoid cyst of the skin
* Dermoid cyst
* Thyroglossal duct cyst
* Branchial cleft cyst (Cervical lymphoepitelial cyst)
* Oral lymphoepithelial cyst
#### Developmental cysts of questionable cause[edit]
* Globulomaxillary cyst
* Median palatal cyst
* Median mandibular cyst
## Signs and symptoms[edit]
Cysts rarely cause any symptoms, unless they become secondarily infected.[1] The signs depend mostly upon the size and location of the cyst.
If the cyst has not expanded beyond the normal anatomical boundaries of the bone, then there will be no palpable lump outside or inside the mouth. The vast majority of cysts expand slowly, and the surrounding bone has time to increase its density around the lesion, which is the body's attempt to isolate the lesion.
Cysts that have expanded beyond the normal anatomic boundaries of a bone are still often covered with a thin layer of new bone. At this stage, there may be a sign termed "eggshell cracking", where the thinned cortical plate cracks when pressure is applied.
A lump may be felt, which may feel hard if there is still bone covering the cyst, or fluctuant if the cyst has eroded through the bone surrounding it.[5] A cyst may become acutely infected, and discharge into the oral cavity via a sinus. Adjacent teeth may be loosened, tilted or even moved bodily.[6] Rarely, roots of teeth are resorbed, depending upon the type of cyst.
The inferior alveolar nerve runs through the mandible and supplies sensation to the lower lip and chin. As most cysts expand slowly, there will be no altered sensation (anesthesia or paraesthesia), since the inferior alveolar canal is harmlessly enveloped or displaced over time. More aggressive cysts, or acute infection of any cyst may cause altered sensation. Sometimes, they cause higher risk of pathological fracture of lower jaw, especially around angle of mandible.[6]
## Diagnosis[edit]
Most cysts are discovered as a chance finding on routine dental radiography.[7] They are often asymptomatic unless there has been long-standing with significant enlargement (causing bony expansion or egg-shell cracking feeling[7]) or secondary infection.
On an x-ray, cysts appear as radiolucent (dark) areas with radiopaque (white) borders. On an x-ray, cysts appear as radiolucent (dark) areas with radiopaque (white) borders in the jaw. [7]However, cysts in maxillary sinus, also known as antrum, can appear radiopaque as the surrounding air absorbs fewer photons than the cystic fluid content.
Cysts are usually unilocular, but may also be multilocular. Sometimes aspiration (fine needle aspiration) is used to aid diagnosis of a cystic lesion; e.g., fluid aspirated from a radicular cyst may appear straw-colored and display shimmering due to cholesterol content.[5] Almost always, the cyst lining is sent to a pathologist for histopathologic examination after it has been surgically removed. This means that the exact diagnosis of the type of cyst is often made in retrospect, and definitive treatment can be made for the patient.
## Treatment[edit]
As many cysts of the jaws have similar presentations and treatment options, it is common to perform one of the following treatment options and send the cyst lining to histopathology to provide a retrospective definitive diagnosis.
Cysts treatment is limited to surgical removal for the majority of cysts. There are two techniques used to manage cysts with the deciding factor being the size of the cyst.[8]
* Enucleation—removal of the entire cyst. A mucoperiosteal flap is raised overlying the cyst and the entire cyst subsequently removed. The defect is completely closed by the placement of sutures to realign the margins of the flap. Advantages of this technique include: the entire cyst lining is removed for histopathological assessment and reduced post-operative care requirements.
* Marsupialization—the creation of a window into the wall of a cyst by raising a mucoperiosteal flap and attaching the cyst lining to the oral mucosa - allowing the contents to be drained. The window is left open, and the lack of pressure within the cyst causes the lesion to shrink, as the surrounding bone starts to fill in again. With this technique, the window must be prevented from closing by the use of a “plug”. As this window is kept open to shrink the size of the cyst, there are additional care requirements. This includes home-based cleaning of the cavity – to remove food debris. Marsupialization may be performed on a dentigerous cyst, allowing the tooth to erupt and prevent extraction.
* Enucleation following marsupialization—marsupialization is carried out as a single procedure, but usually it is followed by a second procedure (enucleation) to remove the cyst. This may be undertaken when cysts are very large, and their removal would leave a significant surgical defect or risk jaw fracture.
* Enucleation with curettage—this is the removal of the cyst and some of the surrounding bone, which may contain remnants of the lining of the cyst. Curettage may be undertaken if the cyst lining is thin and fragile or if the cyst was infected. Following curettage, the defect is irrigated to flush out any debris.[9]
The exception to these treatments; is the management of cysts which have a higher rate of recurrence – for example odontogenic keratocysts. Options to reduce the recurrence rate include: curettage post enucleation, Carnoy’s solution (treatment of the cavity with a potent fixative) or mandibular resection. These treatments are less conservative than the above options.
## Prognosis[edit]
The prognosis depends upon the type, size and location of a cyst. Most cysts are entirely benign, and some may require no treatment. Rarely, some cystic lesions represent locally aggressive tumors that may cause destruction of surrounding bone if left untreated. This type of cyst are usually removed with a margin of healthy bone to prevent recurrence of new cysts. If a cyst expands to a very large size, the mandible may be weakened such that a pathologic fracture occurs.
After treatments, the patient should be informed of the risk of recurrence. Some people are more susceptible than others. This can be due to their oral and dental condition or inherited condition.[10] In some cases, there are some cysts remain after the surgery called the residual cysts and most of them arise from a periapical cyst. Glandular odontogenic cysts tend to recur after curettage.[11]
The radicular cyst is the most common type of cyst(65-70%) followed by dentigerous(15-18%).[12] The most common odontogenic cyst is a follicular(dentigerous) cyst. Rarely, the walls of this type of cyst can progress into mucoepidermoid carcinoma, ameloblastoma or squamous carcinoma if the cyst is not properly removed early enough.[11]
## Epidemiology[edit]
Periapical cysts (also called radicular cysts) are by far the most common cyst occurring in the jaws.[5]
Jaw cysts affect around 3.5% of the population.10 They are more common in males than females at a ratio of 1.6:1 and most people get them between their 40s and 60s. The order of the jaw cysts from most common to least common is; radicular cysts, dentigerous cysts, residual cysts and odontogenic keratocysts. Radicular lesions are most commonly found in the anterior region of the maxilla12 – usually around the canines.11 The majority of cysts are of inflammatory origin12. They are most commonly found in the posterior mandible11
## References[edit]
1. ^ a b c d Hupp JR, Ellis E, Tucker MR (2008). Contemporary oral and maxillofacial surgery (5th ed.). St. Louis, Mo.: Mosby Elsevier. pp. 450–456. ISBN 9780323049030.
2. ^ Neville, Brad W.; Damm, Douglas D.; Allen, Carl M.; Bouquot, Jerry E. (2002). Oral & Maxillofacial Pathology (2nd ed.). Philadelphia, PA: W.B. Saunders Company. pp. 590–609. ISBN 978-0-7216-9003-2.
3. ^ Leandro Bezerra Borges; Francisco Vagnaldo Fechine; Mário Rogério Lima Mota; Fabrício Bitu Sousa; Ana Paula Negreiros Nunes Alves (2012). "Odontogenic lesions of the jaw: a clinical-pathological study of 461 cases". Revista Gaúcha de Odontologia. 60 (1).
4. ^ Zadik Y, Yitschaky O, Neuman T, Nitzan DW (May 2011). "On the Self-Resolution Nature of the Buccal Bifurcation Cyst". J Oral Maxillofac Surg. 69 (7): e282–4. doi:10.1016/j.joms.2011.02.124. PMID 21571416.[dead link]
5. ^ a b c Wray D, Stenhouse D, Lee D, Clark AJ (2003). Textbook of general and oral surgery. Edinburgh [etc.]: Churchill Livingstone. pp. 229–237. ISBN 978-0443070839.
6. ^ a b Current diagnosis & treatment in otolaryngology : head & neck surgery. Lalwani, Anil K. (3rd ed.). New York: McGraw Hill Medical. 2012. ISBN 978-0-07-162439-8. OCLC 704526362.CS1 maint: others (link)
7. ^ a b c Whaites, Eric (2013-06-20). Essentials of dental radiography and radiology. Drage, Nicholas (Fifth ed.). Edinburgh. ISBN 978-0-7020-4599-8. OCLC 854310114.
8. ^ Contemporary oral and maxillofacial surgery. Hupp, James R., Ellis, Edward, DDS., Tucker, Myron R. (5th ed.). St. Louis, Mo.: Mosby Elsevier. 2008. ISBN 978-0-323-04903-0. OCLC 187293319.CS1 maint: others (link)
9. ^ Odell, E. W. (2017-05-02). Cawson's Essentials of Oral Pathology and Oral Medicine. [Place of publication not identified]. ISBN 978-0-7020-7389-2. OCLC 1054910269.
10. ^ "Dental cysts | Cambridge University Hospitals". www.cuh.nhs.uk. Retrieved 2020-02-23.
11. ^ a b Dios, Pedro Diz (2016-05-17). Oral medicine and pathology at a glance. Scully, Crispian, Almeida, Oslei Paes de, Bagan, Jose, Taylor, Adalberto Mosqueda, Scully, Crispian, Preceded by (work) (Second ed.). Chichester, West Sussex. ISBN 978-1-119-12135-0. OCLC 942611369.
12. ^ Evidence-based oral surgery : a clinical guide for the general dental practitioner. Ferneini, Elie M., Goupil, Michael T. Cham, Switzerland. 2019-02-18. ISBN 978-3-319-91361-2. OCLC 1088721095.CS1 maint: others (link)
## External links[edit]
Classification
D
* ICD-10: K04.8, K09.1, K09.2, K09.8, K09.9 and K10.0
* MeSH: D007570
* v
* t
* e
Oral and maxillofacial pathology
Lips
* Cheilitis
* Actinic
* Angular
* Plasma cell
* Cleft lip
* Congenital lip pit
* Eclabium
* Herpes labialis
* Macrocheilia
* Microcheilia
* Nasolabial cyst
* Sun poisoning
* Trumpeter's wart
Tongue
* Ankyloglossia
* Black hairy tongue
* Caviar tongue
* Crenated tongue
* Cunnilingus tongue
* Fissured tongue
* Foliate papillitis
* Glossitis
* Geographic tongue
* Median rhomboid glossitis
* Transient lingual papillitis
* Glossoptosis
* Hypoglossia
* Lingual thyroid
* Macroglossia
* Microglossia
* Rhabdomyoma
Palate
* Bednar's aphthae
* Cleft palate
* High-arched palate
* Palatal cysts of the newborn
* Inflammatory papillary hyperplasia
* Stomatitis nicotina
* Torus palatinus
Oral mucosa – Lining of mouth
* Amalgam tattoo
* Angina bullosa haemorrhagica
* Behçet's disease
* Bohn's nodules
* Burning mouth syndrome
* Candidiasis
* Condyloma acuminatum
* Darier's disease
* Epulis fissuratum
* Erythema multiforme
* Erythroplakia
* Fibroma
* Giant-cell
* Focal epithelial hyperplasia
* Fordyce spots
* Hairy leukoplakia
* Hand, foot and mouth disease
* Hereditary benign intraepithelial dyskeratosis
* Herpangina
* Herpes zoster
* Intraoral dental sinus
* Leukoedema
* Leukoplakia
* Lichen planus
* Linea alba
* Lupus erythematosus
* Melanocytic nevus
* Melanocytic oral lesion
* Molluscum contagiosum
* Morsicatio buccarum
* Oral cancer
* Benign: Squamous cell papilloma
* Keratoacanthoma
* Malignant: Adenosquamous carcinoma
* Basaloid squamous carcinoma
* Mucosal melanoma
* Spindle cell carcinoma
* Squamous cell carcinoma
* Verrucous carcinoma
* Oral florid papillomatosis
* Oral melanosis
* Smoker's melanosis
* Pemphigoid
* Benign mucous membrane
* Pemphigus
* Plasmoacanthoma
* Stomatitis
* Aphthous
* Denture-related
* Herpetic
* Smokeless tobacco keratosis
* Submucous fibrosis
* Ulceration
* Riga–Fede disease
* Verruca vulgaris
* Verruciform xanthoma
* White sponge nevus
Teeth (pulp, dentin, enamel)
* Amelogenesis imperfecta
* Ankylosis
* Anodontia
* Caries
* Early childhood caries
* Concrescence
* Failure of eruption of teeth
* Dens evaginatus
* Talon cusp
* Dentin dysplasia
* Dentin hypersensitivity
* Dentinogenesis imperfecta
* Dilaceration
* Discoloration
* Ectopic enamel
* Enamel hypocalcification
* Enamel hypoplasia
* Turner's hypoplasia
* Enamel pearl
* Fluorosis
* Fusion
* Gemination
* Hyperdontia
* Hypodontia
* Maxillary lateral incisor agenesis
* Impaction
* Wisdom tooth impaction
* Macrodontia
* Meth mouth
* Microdontia
* Odontogenic tumors
* Keratocystic odontogenic tumour
* Odontoma
* Dens in dente
* Open contact
* Premature eruption
* Neonatal teeth
* Pulp calcification
* Pulp stone
* Pulp canal obliteration
* Pulp necrosis
* Pulp polyp
* Pulpitis
* Regional odontodysplasia
* Resorption
* Shovel-shaped incisors
* Supernumerary root
* Taurodontism
* Trauma
* Avulsion
* Cracked tooth syndrome
* Vertical root fracture
* Occlusal
* Tooth loss
* Edentulism
* Tooth wear
* Abrasion
* Abfraction
* Acid erosion
* Attrition
Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures
* Cementicle
* Cementoblastoma
* Gigantiform
* Cementoma
* Eruption cyst
* Epulis
* Pyogenic granuloma
* Congenital epulis
* Gingival enlargement
* Gingival cyst of the adult
* Gingival cyst of the newborn
* Gingivitis
* Desquamative
* Granulomatous
* Plasma cell
* Hereditary gingival fibromatosis
* Hypercementosis
* Hypocementosis
* Linear gingival erythema
* Necrotizing periodontal diseases
* Acute necrotizing ulcerative gingivitis
* Pericoronitis
* Peri-implantitis
* Periodontal abscess
* Periodontal trauma
* Periodontitis
* Aggressive
* As a manifestation of systemic disease
* Chronic
* Perio-endo lesion
* Teething
Periapical, mandibular and maxillary hard tissues – Bones of jaws
* Agnathia
* Alveolar osteitis
* Buccal exostosis
* Cherubism
* Idiopathic osteosclerosis
* Mandibular fracture
* Microgenia
* Micrognathia
* Intraosseous cysts
* Odontogenic: periapical
* Dentigerous
* Buccal bifurcation
* Lateral periodontal
* Globulomaxillary
* Calcifying odontogenic
* Glandular odontogenic
* Non-odontogenic: Nasopalatine duct
* Median mandibular
* Median palatal
* Traumatic bone
* Osteoma
* Osteomyelitis
* Osteonecrosis
* Bisphosphonate-associated
* Neuralgia-inducing cavitational osteonecrosis
* Osteoradionecrosis
* Osteoporotic bone marrow defect
* Paget's disease of bone
* Periapical abscess
* Phoenix abscess
* Periapical periodontitis
* Stafne defect
* Torus mandibularis
Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities
* Bruxism
* Condylar resorption
* Mandibular dislocation
* Malocclusion
* Crossbite
* Open bite
* Overbite
* Overeruption
* Overjet
* Prognathia
* Retrognathia
* Scissor bite
* Maxillary hypoplasia
* Temporomandibular joint dysfunction
Salivary glands
* Benign lymphoepithelial lesion
* Ectopic salivary gland tissue
* Frey's syndrome
* HIV salivary gland disease
* Necrotizing sialometaplasia
* Mucocele
* Ranula
* Pneumoparotitis
* Salivary duct stricture
* Salivary gland aplasia
* Salivary gland atresia
* Salivary gland diverticulum
* Salivary gland fistula
* Salivary gland hyperplasia
* Salivary gland hypoplasia
* Salivary gland neoplasms
* Benign: Basal cell adenoma
* Canalicular adenoma
* Ductal papilloma
* Monomorphic adenoma
* Myoepithelioma
* Oncocytoma
* Papillary cystadenoma lymphomatosum
* Pleomorphic adenoma
* Sebaceous adenoma
* Malignant: Acinic cell carcinoma
* Adenocarcinoma
* Adenoid cystic carcinoma
* Carcinoma ex pleomorphic adenoma
* Lymphoma
* Mucoepidermoid carcinoma
* Sclerosing polycystic adenosis
* Sialadenitis
* Parotitis
* Chronic sclerosing sialadenitis
* Sialectasis
* Sialocele
* Sialodochitis
* Sialosis
* Sialolithiasis
* Sjögren's syndrome
Orofacial soft tissues – Soft tissues around the mouth
* Actinomycosis
* Angioedema
* Basal cell carcinoma
* Cutaneous sinus of dental origin
* Cystic hygroma
* Gnathophyma
* Ludwig's angina
* Macrostomia
* Melkersson–Rosenthal syndrome
* Microstomia
* Noma
* Oral Crohn's disease
* Orofacial granulomatosis
* Perioral dermatitis
* Pyostomatitis vegetans
Other
* Eagle syndrome
* Hemifacial hypertrophy
* Facial hemiatrophy
* Oral manifestations of systemic disease
* v
* t
* e
Cystic diseases
Respiratory system
* Langerhans cell histiocytosis
* Lymphangioleiomyomatosis
* Cystic bronchiectasis
Skin
* stratified squamous: follicular infundibulum
* Epidermoid cyst and Proliferating epidermoid cyst
* Milia
* Eruptive vellus hair cyst
* outer root sheath
* Trichilemmal cyst and Pilar cyst and Proliferating trichilemmal cyst and Malignant trichilemmal cyst
* sebaceous duct
* Steatocystoma multiplex and Steatocystoma simplex
* Keratocyst
* nonstratified squamous: Cutaneous ciliated cyst
* Hidrocystoma
* no epithelium: Pseudocyst of the auricle
* Mucocele
* other and ungrouped: Cutaneous columnar cyst
* Keratin implantation cyst
* Verrucous cyst
* Adenoid cystic carcinoma
* Breast cyst
Human musculoskeletal system
* Cystic hygroma
Human digestive system
* oral cavity: Cysts of the jaws
* Odontogenic cyst
* Periapical cyst
* Dentigerous cyst
* Odontogenic keratocyst
* Nasopalatine duct cyst
* liver: Polycystic liver disease
* Congenital hepatic fibrosis
* Peliosis hepatis
* bile duct: Biliary hamartomas
* Caroli disease
* Choledochal cysts
* Bile duct hamartoma
Nervous system
* Cystic leukoencephalopathy
Genitourinary system
* Polycystic kidney disease
* Autosomal dominant polycystic kidney
* Autosomal recessive polycystic kidney
* Medullary cystic kidney disease
* Nephronophthisis
* Congenital cystic dysplasia
Other conditions
* Hydatid cyst
* Von Hippel–Lindau disease
* Tuberous sclerosis
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Cysts of the jaws | c0022361 | 3,049 | wikipedia | https://en.wikipedia.org/wiki/Cysts_of_the_jaws | 2021-01-18T19:02:51 | {"mesh": ["D007570"], "wikidata": ["Q17085172"]} |
A number sign (#) is used with this entry because of evidence that Gillessen-Kaesbach-Nishimura syndrome (GIKANIS) is caused by homozygous mutation in the ALG9 gene (606941) on chromosome 11q23.
Homozygous mutation in the ALG9 gene can also cause congenital disorder of glycosylation type Il (CDG1L; 608776).
Description
Gillessen-Kaesbach-Nishimura syndrome is an autosomal recessive multiple congenital anomaly disorder characterized by skeletal dysplasia, dysmorphic facial features, and variable visceral abnormalities, including polycystic kidneys, diaphragmatic hernia, lung hypoplasia, and congenital heart defects. It may be lethal in utero or early in life. The disorder is at the severe end of the phenotypic spectrum of congenital disorders of glycosylation (summary by Tham et al., 2016).
Clinical Features
Gillessen-Kaesbach et al. (1993) reported the cases of 3 pairs of sibs from unrelated families who presented with polycystic kidneys of the type thought to be specific for autosomal recessive polycystic kidney disease (see ARPKD, 263200) and with microbrachycephaly, hypertelorism with telecanthus, large posteriorly angulated and fleshy ears, and various congenital malformations including congenital heart defects. Two of the families were Turkish with consanguineous parents.
Nishimura et al. (1998) reported 2 Japanese sibs, children of consanguineous parents, with a lethal mesomelic osteochondrodysplasia. They were born at 34 and 35 weeks' gestation, respectively. The older sib died during labor and the younger at 1 week of age. The older sib had facial dysmorphism, including abundant hair, sloping forehead, aniridia, long palpebral fissures, prominent nasal bridge with beaked nose, flat philtrum with upturned upper lip, micrognathia with cleft palate, and low-set fleshy ears. There were multiple joint contractures and mesomelic shortening of the limbs, but the fingers and toes were not stubby. Radiographs showed mesomelic shortening of the forearms with bowed and thickened radii and ulnae, lack or partial ossification of the cervical vertebral bodies, round ilia, delayed ossification of the pubic bones, and thick, sclerotic occiput. Autopsy showed diaphragmatic hernia, abnormal lung lobulation, periportal hepatic fibrosis, cystic dilation of the bile ducts, and mild ductal dilation of the pancreas. There was a multilocular cyst in the right kidney, but no cystic dysplasia. Other features included microcephaly with ectopic gray matter and focal laminar necrosis and migration abnormalities in the cerebellum. The younger sib had similar features, although autopsy was not performed. Both also had thrombocytopenia. Nishimura et al. (1998) noted the phenotypic similarities to the patients reported by Gillessen-Kaesbach et al. (1993).
Hallermann et al. (2000) reported 2 male sibs with a syndrome similar to that described by Gillessen-Kaesbach et al. (1993). The patients had polycystic kidneys and hepatic fibrosis typical of that observed in autosomal recessive polycystic kidney disease, along with skeletal and facial anomalies. Skeletal abnormalities included 'butterfly' vertebrae, distinctive shape of the iliac bones, and brachymelia. The facial anomalies included hypertelorism, epicanthic folds, and anteverted nares.
Tham et al. (2016) reported a stillborn girl, born of consanguineous Turkish parents, and 2 fetuses, conceived of consanguineous Iraqi parents, with a lethal multiple congenital malformation disorder detected in utero. The first fetus had a ventricular septal defect, double outlet right ventricle with anomalous outflow tract, and enlarged hyperechogenic polycystic kidneys associated with oligohydramnios. Prenatal ultrasound of the fetuses in the second family showed echogenic kidneys with hydronephrosis and brachymelia. All 3 patients had overlapping dysmorphic features, including hypertelorism, beaked nose, hypoplastic alae nasi, microretrognathia, low-set and posteriorly rotated ears, short neck, and short extremities with ulnar deviation of the hands and deformed feet. Other features included lung hypoplasia with abnormal lung lobulation. Radiographic studies showed decreased ossification of the frontoparietal bones, thickening of the occipital bones, deficient ossification of the cervical vertebral bodies and pubic bones, round pelvis, and short tubular bones with metaphyseal flaring. Analysis of spleen tissue showed underglycosylation of transferrin (190000), consistent with a congenital disorder of glycosylation.
Inheritance
The transmission pattern of Gillessen-Kaesbach-Nishimura syndrome in the families reported by Tham et al. (2016) was consistent with autosomal recessive inheritance.
Mapping
By homozygosity mapping in 2 unrelated families segregating Gillessen-Kaesbach-Nishimura syndrome, Tham et al. (2016) identified a common haplotype in affected members of both families. Combined analysis of the polymorphic markers and SNPs from whole-exome sequencing indicated that the shared homozygous region encompassed 1.75-2.18 Mb, including the ALG9 gene, on chromosome 11.
### Exclusion Studies
Hallermann et al. (2000) performed linkage analysis using markers from the 6p21.1-p12 region (to which a form of ARPKD (see 263200) had been mapped) in the sibs they reported with ARPKD and associated features. The sibs had different haplotypes, thus excluding the locus on chromosome 6p.
Molecular Genetics
In a stillborn girl and 2 fetuses from 2 unrelated consanguineous families with GIKANIS, Tham et al. (2016) identified a homozygous truncating mutation in the ALG9 gene (606941.0003). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Haplotype analysis suggested a founder effect. The 2 fetuses from the second family were also homozygous for a rare missense variant (D968H) affecting a highly conserved residue in the ANK3 gene (600465); mutation in the ANK3 gene is associated with autosomal recessive mental retardation-37 (MRT37; 615493). The parents were heterozygous carriers of the ANK3 variant.
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Microcephaly \- Brachycephaly Face \- Micrognathia \- Retrognathia \- Flat philtrum Ears \- Low-set ears \- Posteriorly rotated ears \- Fleshy ears Eyes \- Hypertelorism Nose \- Beaked nose \- Hypoplastic alae nasi Neck \- Short neck CARDIOVASCULAR Heart \- Congenital heart defects RESPIRATORY Lung \- Lung hypoplasia \- Abnormal lung lobation CHEST Diaphragm \- Diaphragmatic hernia ABDOMEN Liver \- Periportal fibrosis Pancreas \- Dilated pancreatic ducts GENITOURINARY Kidneys \- Polycystic kidneys SKELETAL \- Skeletal dysplasia \- Joint contractures Skull \- Thick occipital bone \- Decreased ossification of the skull Spine \- Absent or decreased ossification of the vertebral bodies Pelvis \- Absent ossification of the pubic rami \- Round pelvis \- Ovoid ischia Limbs \- Brachymelia \- Short tubular bones \- Metaphyseal broadening Hands \- Ulnar deviation of the hands Feet \- Abnormal feet position MISCELLANEOUS \- Onset in utero \- May be lethal in utero \- Three patients from 2 unrelated families have been shown to carry the same ALG9 mutation (last curated May 2016) MOLECULAR BASIS \- Caused by mutation in the homolog of the S. cerevisiae ALG9 gene (ALG9, 606941.0003 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| GILLESSEN-KAESBACH-NISHIMURA SYNDROME | c2931006 | 3,050 | omim | https://www.omim.org/entry/263210 | 2019-09-22T16:23:18 | {"mesh": ["C535750"], "omim": ["263210"], "orphanet": ["79328"], "synonyms": ["Alternative titles", "POLYCYSTIC KIDNEY DISEASE, AUTOSOMAL RECESSIVE, WITH MICROBRACHYCEPHALY, HYPERTELORISM, AND BRACHYMELIA"]} |
Eczema herpeticum
SpecialtyInfectious disease
Eczema herpeticum is a rare but severe disseminated infection that generally occurs at sites of skin damage produced by, for example, atopic dermatitis, burns, long term usage of topical steroids or eczema.[1] It is also known as Kaposi varicelliform eruption, Pustulosis varioliformis acute and Kaposi-Juliusberg dermatitis.
Some sources reserve the term "eczema herpeticum" when the cause is due to human herpes simplex virus,[2] and the term "Kaposi varicelliform eruption" to describe the general presentation without specifying the virus.[3]
This condition is most commonly caused by herpes simplex virus type 1 or 2, but may also be caused by coxsackievirus A16, or vaccinia virus.[1] It appears as numerous umbilicated vesicles superimposed on healing atopic dermatitis. it is often accompanied by fever and lymphadenopathy. Eczema herpeticum can be life-threatening in babies.
## Contents
* 1 Presentation
* 2 Treatment
* 3 History
* 4 See also
* 5 References
* 6 External links
## Presentation[edit]
In addition to the skin, this infection affects multiple organs, including the eyes, brain, lung, and liver, and can be fatal.
## Treatment[edit]
It can be treated with systemic antiviral drugs, such as aciclovir or valganciclovir.[4] Foscarnet may also be used for immunocompromised host with Herpes simplex and acyclovir-resistant Herpes simplex.
## History[edit]
Eczema herpeticum was first described by Hungarian dermatologist Moriz Kaposi in 1887.[5] Fritz Juliusberg coined the term Pustulosis varioliformis acute in 1898. Eczema herpeticum is caused by Herpes simplex virus HV1, the virus that causes cold sores; it can also be caused by other related viruses.
## See also[edit]
* Herpes simplex
* List of cutaneous conditions
## References[edit]
1. ^ a b Olson J, Robles DT, Kirby P, Colven R (2008). "Kaposi varicelliform eruption (eczema herpeticum)". Dermatology Online Journal. 14 (2): 18. PMID 18700121.
2. ^ "eczema herpeticum" at Dorland's Medical Dictionary
3. ^ "Kaposi varicelliform eruption" at Dorland's Medical Dictionary
4. ^ Brook I, Frazier EH, Yeager JK (April 1998). "Microbiology of infected eczema herpeticum". Journal of the American Academy of Dermatology. 38 (4): 627–9. doi:10.1016/S0190-9622(98)70130-6. PMID 9555806.
5. ^ Reitamo, Sakari; Luger, Thomas A; Steinhoff, Martin (2008). Textbook of atopic dermatitis. Informa Healthcare. p. 70. ISBN 978-1841842462.
## External links[edit]
Classification
D
* ICD-10: B00.0
* ICD-9-CM: 054.0
* MeSH: D007617
* DiseasesDB: 31391
* SNOMED CT: 186535001
External resources
* eMedicine: article/1132622
* Eczema Herpeticum photo library at Dermnet
* v
* t
* e
Skin infections, symptoms and signs related to viruses
DNA virus
Herpesviridae
Alpha
HSV
* Herpes simplex
* Herpetic whitlow
* Herpes gladiatorum
* Herpes simplex keratitis
* Herpetic sycosis
* Neonatal herpes simplex
* Herpes genitalis
* Herpes labialis
* Eczema herpeticum
* Herpetiform esophagitis
Herpes B virus
* B virus infection
VZV
* Chickenpox
* Herpes zoster
* Herpes zoster oticus
* Ophthalmic zoster
* Disseminated herpes zoster
* Zoster-associated pain
* Modified varicella-like syndrome
Beta
* Human herpesvirus 6/Roseolovirus
* Exanthema subitum
* Roseola vaccinia
* Cytomegalic inclusion disease
Gamma
* KSHV
* Kaposi's sarcoma
Poxviridae
Ortho
* Variola
* Smallpox
* Alastrim
* MoxV
* Monkeypox
* CPXV
* Cowpox
* VV
* Vaccinia
* Generalized vaccinia
* Eczema vaccinatum
* Progressive vaccinia
* Buffalopox
Para
* Farmyard pox: Milker's nodule
* Bovine papular stomatitis
* Pseudocowpox
* Orf
* Sealpox
Other
* Yatapoxvirus: Tanapox
* Yaba monkey tumor virus
* MCV
* Molluscum contagiosum
Papillomaviridae
HPV
* Wart/plantar wart
* Heck's disease
* Genital wart
* giant
* Laryngeal papillomatosis
* Butcher's wart
* Bowenoid papulosis
* Epidermodysplasia verruciformis
* Verruca plana
* Pigmented wart
* Verrucae palmares et plantares
* BPV
* Equine sarcoid
Parvoviridae
* Parvovirus B19
* Erythema infectiosum
* Reticulocytopenia
* Papular purpuric gloves and socks syndrome
Polyomaviridae
* Merkel cell polyomavirus
* Merkel cell carcinoma
RNA virus
Paramyxoviridae
* MeV
* Measles
Togaviridae
* Rubella virus
* Rubella
* Congenital rubella syndrome ("German measles" )
* Alphavirus infection
* Chikungunya fever
Picornaviridae
* CAV
* Hand, foot, and mouth disease
* Herpangina
* FMDV
* Foot-and-mouth disease
* Boston exanthem disease
Ungrouped
* Asymmetric periflexural exanthem of childhood
* Post-vaccination follicular eruption
* Lipschütz ulcer
* Eruptive pseudoangiomatosis
* Viral-associated trichodysplasia
* Gianotti–Crosti syndrome
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Eczema herpeticum | c0936250 | 3,051 | wikipedia | https://en.wikipedia.org/wiki/Eczema_herpeticum | 2021-01-18T19:08:18 | {"mesh": ["D007617"], "umls": ["C0854331", "C0936250", "C0153037"], "wikidata": ["Q3718816"]} |
Abnormally reduced sweating
Hypohidrosis
SpecialtyDermatology, neurology
Prognosishyperthermia, heat stroke and death
Hypohidrosis is a disorder in which a person exhibits diminished sweating in response to appropriate stimuli. In contrast with hyperhidrosis, which is a socially troubling yet often benign condition, the consequences of untreated hypohidrosis include hyperthermia, heat stroke and death.[1] An extreme case of hypohydrosis in which there is a complete absence of sweating and the skin is dry is termed anhidrosis.
## Contents
* 1 Causes
* 2 Diagnosis
* 3 Management
* 4 Citations
* 5 General references
## Causes[edit]
Medications
* Anticholinergic agents
* Opioids
* Botulinum toxin
* Alpha-2 receptor antagonists
* Clonidine
* Barbiturates
* Zonisamide
* Topiramate
Physical agents
* Tumors
* Burns
* Radiation
* Surgery
* Scars
* Sores
Dermatological
* X-linked hypohidrotic ectodermal dysplasia
* Incontinentia pigmenti
* Bazex disease
* Fabry disease
* Miliaria
* Sjögren syndrome
* Systemic sclerosis
* Graft-versus-host disease
Neuropathic
* Multiple system atrophy
* Dementia with Lewy bodies
* Multiple sclerosis
* Cerebrovascular accident
* Tumour
* Encephalitis
* Cervical myelopathy
* Diabetes mellitus
* Guillain–Barré syndrome
* Hereditary sensory and autonomic neuropathy
* Alcoholism
* Amyloidosis
* Ross syndrome
* Pure autonomic failure
* Horner's syndrome
## Diagnosis[edit]
Sweat is readily visualized by a topical indicator such as iodinated starch (Minor test) or sodium alizarin sulphonate, both of which undergo a dramatic colour change when moistened by sweat. A thermoregulatory sweat test can evaluate the body’s response to a thermal stimulus by inducing sweating through a hot box ⁄ room, thermal blanket or exercise. Failure of the topical indicator to undergo a colour change during thermoregulatory sweat testing indicates hypohidrosis, and further tests may be required to localize the lesion.
Magnetic resonance imaging of the brain and ⁄ or spinal cord is the best modality for evaluation when the lesion is suspected to be localized to the central nervous system.
Skin biopsies are useful when anhidrosis occurs as part of a dermatological disorder. Biopsy results may reveal the sweat gland destruction, necrosis or fibrosis, in addition to the findings of the primary dermatological disorder.
## Management[edit]
The treatment options for hypohidrosis and anhidrosis is limited. Those with hypohidrosis should avoid drugs that can aggravate the condition (see medication-causes). They should limit activities that raise the core body temperature and if exercises are to be performed, they should be supervised and be performed in a cool, sheltered and well-ventilated environment. In instances where the cause is known, treatment should be directed at the primary pathology. In autoimmune diseases, such as Sjögren syndrome and systemic sclerosis, treatment of the underlying disease using immunosuppressive drugs may lead to improvement in hypohidrosis. In neurological diseases, the primary pathology is often irreversible. In these instances, prevention of further neurological damage, such as good glycaemic control in diabetes, is the cornerstone of management. In acquired generalized anhidrosis, spontaneous remission may be observed in some cases. Numerous cases have been reported to respond effectively to systemic corticosteroids. Although an optimum dose and regime has not been established, pulse methylprednisolone (up to 1000 mg/day) has been reported to have good effect.[citation needed]
## Citations[edit]
1. ^ Chia, K. Y.; Tey, H. L. (2012). "Approach to hypohidrosis". Journal of the European Academy of Dermatology and Venereology. 27 (7): 799–804. doi:10.1111/jdv.12014. PMID 23094789.
## General references[edit]
* http://www.mayoclinic.com/health/anhidrosis/DS01050[full citation needed]
* MedlinePlus Encyclopedia: Sweating - absent
Classification
D
* ICD-10: L74.4
* ICD-9-CM: 705.0
* MeSH: D007007
* DiseasesDB: 21064
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Hypohidrosis | c0003028 | 3,052 | wikipedia | https://en.wikipedia.org/wiki/Hypohidrosis | 2021-01-18T18:52:52 | {"mesh": ["D007007"], "umls": ["C0003028"], "wikidata": ["Q545408"]} |
Androphy et al. (1985) described a kindred in which a 56-year-old man had EDV, none of his 5 sons or 5 daughters had EDV, and 4 of his grandsons (through 2 daughters) had EDV. All were infected with human papillomavirus 3 (HPV 3) and with HPV 8. The proband, who had onset of warts at age 5 years with no regression over the next 50 years and with extension to cover about 10% of his skin surface, had squamous carcinoma arising on sun-exposed areas of the face, ears, neck, back, arms, and hands over the previous 25 years. Other pedigrees have suggested autosomal inheritance although whether dominant as suggested by some families or recessive as suggested by parental consanguinity (see 226400) is not certain.
Inheritance \- X-linked form Skin \- Epidermodysplasia verruciformis \- Human papillomavirus (HPV 3 and HPV 8) infection \- Warts \- Squamous skin carcinoma ▲ Close
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| EPIDERMODYSPLASIA VERRUCIFORMIS, X-LINKED | c0014522 | 3,053 | omim | https://www.omim.org/entry/305350 | 2019-09-22T16:18:20 | {"mesh": ["D004819"], "omim": ["305350"], "orphanet": ["302"]} |
Acquired pure red cell aplasia (PRCA) is a bone marrow disorder characterized by a reduction of red blood cells (erythrocytes) produced by the bone marrow. Signs and symptoms may include fatigue, lethargy, and/or abnormal paleness of the skin (pallor) due to the anemia the caused by the disorder. In most cases, the cause of acquired PRCA is unknown (idiopathic). In other cases it may occur secondary to autoimmune disorders, tumors of the thymus gland (thymomas), hematologic cancers, solid tumors, viral infections, or certain drugs. Treatment depends on the cause of the condition (if known) but often includes transfusions for individuals who are severely anemic and have cardiorespiratory failure.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Acquired pure red cell aplasia | c0340961 | 3,054 | gard | https://rarediseases.info.nih.gov/diseases/10898/acquired-pure-red-cell-aplasia | 2021-01-18T18:02:21 | {"orphanet": ["98872"], "synonyms": ["Adult pure red cell aplasia", "Idiopathic pure red cell aplasia", "Acquired PRCA"]} |
Erysipeloid
Cellular and colonial morphology of Erysipelothrix rhusiopathiae
Pronunciation
* gram staning or bloog Agar culture
SpecialtyInfectious disease
In humans, Erysipelothrix rhusiopathiae infections most commonly present in a mild cutaneous form known as erysipeloid[1] or fish poisoning.[2] E. rhusiopathiae can cause an indolent cellulitis, more commonly in individuals who handle fish and raw meat.[3] Erysipelothrix rhusiopat also causes Swine Erysipelas. It is common in domestic pigs and can be transmitted to humans who work with swine. It gains entry typically by abrasions in the hand. Bacteremia and endocarditis are uncommon but serious sequelae.[4][5] Due to the rarity of reported human cases, E. rhusiopathiae infections are frequently misidentified at presentation.[1]
## Contents
* 1 Diagnosis
* 2 Treatment
* 3 See also
* 4 References
* 5 External links
## Diagnosis[edit]
This section is empty. You can help by adding to it. (June 2018)
## Treatment[edit]
The treatment of choice is a single dose of benzathine benzylpenicillin given by intramuscular injection, or a five-day to one-week course of either oral penicillin or intramuscular procaine benzylpenicillin.[6] Erythromycin or doxycycline may be given instead to people who are allergic to penicillin. E. rhusiopathiae is intrinsically resistant to vancomycin.[6]
## See also[edit]
* Erysipeloid of Rosenbach
## References[edit]
1. ^ a b Brooke C, Riley T (1999). "Erysipelothrix rhusiopat: bacteriology, epidemiology and clinical manifestations of an occupational pathogen". J Med Microbiol. 48 (9): 789–99. doi:10.1099/00222615-48-9-789. PMID 10482289.
2. ^ "THE SHIP CAPTAIN'S MEDICAL GUIDE" (PDF). p. 190.
3. ^ Lehane L, Rawlin G (2000). "Topically acquired bacterial zoonoses from fish: a review". Med J Aust. 173 (5): 256–9. doi:10.5694/j.1326-5377.2000.tb125632.x. PMID 11130351.
4. ^ Brouqui P, Raoult D (2001). "Endocarditis due to rare and fastidious bacteria". Clin Microbiol Rev. 14 (1): 177–207. doi:10.1128/CMR.14.1.177-207.2001. PMC 88969. PMID 11148009.
5. ^ Nassar I, de la Llana R, Garrido P, Martinez-Sanz R (2005). "Mitro-aortic infective endocarditis produced by Erysipelothrix rhusiopathiae: case report and review of the literature". J Heart Valve Dis. 14 (3): 320–4. PMID 15974525.
6. ^ a b Vinetz J (October 4, 2007). "Erysipelothrix rhusiopathiae". Point-of-Care Information Technology ABX Guide. Johns Hopkins University. Archived from the original on June 7, 2008. Retrieved March 10, 2009. Retrieved on October 28, 2008. Freely available with registration.
## External links[edit]
Classification
D
* ICD-10: A26
* ICD-9-CM: 027.1
* MeSH: D004887
* DiseasesDB: 4432
External resources
* MedlinePlus: 000632
* eMedicine: derm/602
* v
* t
* e
* Firmicutes (low-G+C) Infectious diseases
* Bacterial diseases: G+
Bacilli
Lactobacillales
(Cat-)
Streptococcus
α
optochin susceptible
* S. pneumoniae
* Pneumococcal infection
optochin resistant
* Viridans streptococci: S. mitis
* S. mutans
* S. oralis
* S. sanguinis
* S. sobrinus
* S. anginosus group
β
A
* bacitracin susceptible: S. pyogenes
* Group A streptococcal infection
* Streptococcal pharyngitis
* Scarlet fever
* Erysipelas
* Rheumatic fever
B
* bacitracin resistant, CAMP test+: S. agalactiae
* Group B streptococcal infection
ungrouped
* Streptococcus iniae
* Cutaneous Streptococcus iniae infection
γ
* D
* BEA+: Streptococcus bovis
Enterococcus
* BEA+: Enterococcus faecalis
* Urinary tract infection
* Enterococcus faecium
Bacillales
(Cat+)
Staphylococcus
Cg+
* S. aureus
* Staphylococcal scalded skin syndrome
* Toxic shock syndrome
* MRSA
Cg-
* novobiocin susceptible
* S. epidermidis
* novobiocin resistant
* S. saprophyticus
Bacillus
* Bacillus anthracis
* Anthrax
* Bacillus cereus
* Food poisoning
Listeria
* Listeria monocytogenes
* Listeriosis
Clostridia
Clostridium (spore-forming)
motile:
* Clostridium difficile
* Pseudomembranous colitis
* Clostridium botulinum
* Botulism
* Clostridium tetani
* Tetanus
nonmotile:
* Clostridium perfringens
* Gas gangrene
* Clostridial necrotizing enteritis
Finegoldia (non-spore forming)
* Finegoldia magna
Mollicutes
Mycoplasmataceae
* Ureaplasma urealyticum
* Ureaplasma infection
* Mycoplasma genitalium
* Mycoplasma pneumoniae
* Mycoplasma pneumonia
Anaeroplasmatales
* Erysipelothrix rhusiopathiae
* Erysipeloid
* 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
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Erysipeloid | c1276801 | 3,055 | wikipedia | https://en.wikipedia.org/wiki/Erysipeloid | 2021-01-18T19:01:48 | {"mesh": ["D004887"], "icd-9": ["027.1"], "icd-10": ["A26"], "wikidata": ["Q1607983"]} |
Paramyotonia congenita
Other namesParamyotonia congenita of von Eulenburg or Eulenburg disease[1]
This condition is inherited in an autosomal dominant manner
SpecialtyNeurology
Paramyotonia congenita (PC), is a rare congenital autosomal dominant neuromuscular disorder characterized by “paradoxical” myotonia.[2] This type of myotonia has been termed paradoxical because it becomes worse with exercise whereas classical myotonia, as seen in myotonia congenita, is alleviated by exercise. PC is also distinguished as it can be induced by cold temperatures. Although more typical of the periodic paralytic disorders, patients with PC may also have potassium-provoked paralysis. PC typically presents within the first decade of life and has 100% penetrance. Patients with this disorder commonly present with myotonia in the face or upper extremities. The lower extremities are generally less affected. While some other related disorders result in muscle atrophy, this is not normally the case with PC. This disease can also present as hyperkalemic periodic paralysis and there is debate as to whether the two disorders are actually distinct.[3]
## Contents
* 1 Symptoms and signs
* 2 Pathophysiology
* 3 Diagnosis
* 4 Treatment
* 5 Epidemiology
* 6 History
* 7 References
* 8 Notes
* 9 Further reading
* 10 External links
## Symptoms and signs[edit]
Patients typically complain of muscle stiffness that can continue to focal weakness. This muscle stiffness cannot be walked off, in contrast to myotonia congenita. These symptoms are increased (and sometimes induced) in cold environments. For example, some patients have reported that eating ice cream leads to a stiffening of the throat. For other patients, exercise consistently induces symptoms of myotonia or weakness. Typical presentations of this are during squatting or repetitive fist clenching. Some patients also indicate that specific foods are able to induce symptoms of paramyotonia congenita. Isolated cases have reported that carrots and watermelon are able to induce these symptoms. The canonical definition of this disorder precludes permanent weakness in the definition of this disorder. In practice, however, this has not been strictly adhered to in the literature.[citation needed]
## Pathophysiology[edit]
Paramyotonia congenita (as well as hyperkalemic periodic paralysis and the potassium-aggravated myotonias) is caused by mutations in a sodium channel, SCN4A. The phenotype of patients with these mutations is indicated in Table 1. These mutations affect fast inactivation of the encoded sodium channel. There are also indications that some mutations lead to altered activation and deactivation. The result of these alterations in channel kinetics is that there is prolonged inward (depolarizing) current following muscle excitation. There is also the introduction of a “window current” due to changes in the voltage sensitivity of the channel’s kinetics. These lead to a general increase in cellular excitability,[citation needed] as shown in figure 1.
Figure 1. Theoretical simulation of a muscle membrane potential in response to 150 ms depolarizing pulse of −45 pA. (A) Normal muscle produces only a single action potential due to such stimulus. This is due to inactivation of sodium channels, preventing their further activation even during depolarization. (B) Myotonic muscle, however, is hyperexcitable and able to produce action potentials for the duration of the stimulus pulse. This model adapted from Cannon, 1993.[4]
There has been one study of a large number of patients with paramyotonia congenita. Of 26 kindreds, it found that 17 (71%) had a mutation in SCN4A while 6 (29%) had no known mutation. There is no large difference between these two groups except that patients with no known mutation have attacks precipitated less by cold but more by hunger, are much more likely to have normal muscle biopsies, and show less decreased compound muscle action potentials when compared to patients with known mutations.[5]
Table 1. Summary of mutations found in patients diagnosed with paramyotonia congenita and their resulting phenotypes Mutation Region Myotonia Weakness References
Cold Exercise/
Activity Potassium Cold Exercise/
Activity Potassium
R672C D2S4 ? ? ? ? ? ? [5]
I693T D2S4-S5 N ? ? Y Y Y [6]
T704M* D2S5 Y ? ? Y Y Y [7],[8],[9],[10]
S804F** D2S6 Y Y Y ? Y N [11]
A1152D D3S4-S5 Y ? ? ? ? ? [12]
A1156T* D3S4-S5 Y ? ? ? Y ? [3],[11]
V1293I D3S4 Y Y N ? ? N
G1306V** D3-4 Y Y Y ? ? Y [13],[14]
T1313A D3-4 Y Y N Y Y N [15]
T1313M D3-4 Y Y N Y Y**** N [13],[16]
M1360V* D4S1 ? ? ? Y Y ? [17]
M1370V* D4S1 Y Y N N N Y [18]
L1433R D4S3 Y Y Y ? Y***** N [16]
R1448C D4S4 Y Y N N Y N [6],[10],[19],[20]
R1448H D4S4 Y Y Y Y Y ? [10],[16],[19],[20]
R1448P D4S4 Y Y ? Y ? N [21]
R1448S D4S4 Y Y N ? Y N [22]
R1456E D4S4 Y Y N N N N [23]
V1458F*** D4S4 ? ? ? ? ? ? [24]
F1473S*** D4S4-S5 ? ? ? ? ? ? [24]
M1592V* D4S6 Y Y Y Y Y Y [10],[16],[25],[26],[27],[28],[29]
E1702K C-term ? ? N ? ? N [5]
F1795I C-term Y ? ? ? ? ? [30]
*
**
***
****
*****
Symptoms of both PC and hyperKPP (Periodica paralytica paramyotonica)
Also diagnosed as a Potassium-aggravated myotonia
Original case reports unpublished.
When exercised in a cold environment
After muscles were cooled
This table was adapted from Vicart et al., 2005.[31] "Cold" refers to symptoms either occurring or significantly worsening with cold temperatures. Likewise, "Exercise/Activity" refers to symptom onset or severity worsening with exercise and/or more general movement like hand clenching. "Potassium" refers to ingestion of food high in potassium or other disorders which are known to increase serum potassium levels. Mutation region nomenclature is: domain number (e.g., D1) followed by segment number (e.g., S4). Thus, D2S3 indicates that the mutation is in the 3rd membrane spanning loop of the 2nd domain. Some mutations occur between segments and are denoted similarly (e.g., D4S4-S5 occurs between the 4th and 5th segments of the 4th domain). Other mutations are located between domains and are denoted DX-Y where X and Y are domain numbers. C-term refers to the carboxy-terminus.
## Diagnosis[edit]
Diagnosis of paramyotonia congenita is made upon evaluation of patient symptoms and case history. Myotonia must increase with exercise or movement and usually must worsen in cold temperatures. Patients that present with permanent weakness are normally not characterized as having PC. Electromyography may be used to distinguish between paramyotonia congenita and myotonia congenita.[32],[33] Clinicians may also attempt to provoke episodes or myotonia and weakness/paralysis in patients in order to determine whether the patient has PC, hyperkalemic periodic paralysis, or one of the potassium-aggravated myotonias. Genomic sequencing of the SCN4A gene is the definitive diagnostic determinant.[citation needed]
## Treatment[edit]
Some patients do not require treatment to manage the symptoms of paramyotonia congenita. Others require treatment for their muscle stiffness and often find mexiletine to be helpful. Others have found acetazolamide to be helpful as well.[34] Avoidance of myotonia triggering events is also an effective method of mytonia prevention.[citation needed]
## Epidemiology[edit]
Paramyotonia congenita is considered an extremely rare disorder, though little epidemiological work has been done. Prevalence is generally higher in European-derived populations and lower among Asians. Epidemiological estimates have been provided for the German population. There, it was estimated that the prevalence of PC is between 1:350,000 (0.00028%) and 1:180,000 (0.00056%).[20] However, the German population of patients with PC is not uniformly distributed across the country. Many individuals with PC herald from the Ravensberg area in North-West Germany, where a founder effect seems to be responsible for most cases.[20][35] The prevalence here is estimated at 1:6000 or 0.017%.
## History[edit]
Originally thought to be separate from hyperkalemic periodic paralysis and the sodium channel myotonias, there is now considerable disagreement as to whether these disorders represent separate entities or overlapping phenotypes of a complex disorder spectrum. It was once thought that paramyotonia congenita was more common in males. Observation of the most recent generation has shown this to be untrue. On average, half of children in a family inherit the disorder regardless of gender.[36]
## References[edit]
1. ^ Facts About Myopathies | MDA Publications Archived 2007-08-05 at the Wayback Machine
2. ^ Eulenburg A (1886). "Über eine familiäre durch 6 Generationen verfolgbare Form kongenitaler Paramyotonie". Neurol. Zentralbl. 12: 265–72.
3. ^ a b de Silva S, Kuncl R, Griffin J, Cornblath D, Chavoustie S (1990). "Paramyotonia congenita or hyperkalemic periodic paralysis? Clinical and electrophysiological features of each entity in one family". Muscle Nerve. 13 (1): 21–6. doi:10.1002/mus.880130106. PMID 2325698.
4. ^ Cannon S, Brown R, Corey D (1993). "Theoretical reconstruction of myotonia and paralysis caused by incomplete inactivation of sodium channels". Biophys J. 65 (1): 270–88. Bibcode:1993BpJ....65..270C. doi:10.1016/S0006-3495(93)81045-2. PMC 1225722. PMID 8396455.
5. ^ a b c Miller T, Dias da Silva M, Miller H, Kwiecinski H, Mendell J, Tawil R, McManis P, Griggs R, Angelini C, Servidei S, Petajan J, Dalakas M, Ranum L, Fu Y, Ptácek L (2004). "Correlating phenotype and genotype in the periodic paralyses". Neurology. 63 (9): 1647–55. doi:10.1212/01.wnl.0000143383.91137.00. PMID 15534250. S2CID 36507153.
6. ^ a b Plassart E, Eymard B, Maurs L, Hauw J, Lyon-Caen O, Fardeau M, Fontaine B (1996). "Paramyotonia congenita: genotype to phenotype correlations in two families and report of a new mutation in the sodium channel gene". J Neurol Sci. 142 (1–2): 126–33. doi:10.1016/0022-510X(96)00173-6. PMID 8902732. S2CID 8785846.
7. ^ Ptácek L, George A, Griggs R, Tawil R, Kallen R, Barchi R, Robertson M, Leppert M (1991). "Identification of a mutation in the gene causing hyperkalemic periodic paralysis". Cell. 67 (5): 1021–7. doi:10.1016/0092-8674(91)90374-8. PMID 1659948. S2CID 12539865.
8. ^ Kim J, Hahn Y, Sohn E, Lee Y, Yun J, Kim J, Chung J (2001). "Phenotypic variation of a Thr704Met mutation in skeletal sodium channel gene in a family with paralysis periodica paramyotonica". J Neurol Neurosurg Psychiatry. 70 (5): 618–23. doi:10.1136/jnnp.70.5.618. PMC 1737343. PMID 11309455.
9. ^ Brancati F, Valente E, Davies N, Sarkozy A, Sweeney M, LoMonaco M, Pizzuti A, Hanna M, Dallapiccola B (2003). "Severe infantile hyperkalaemic periodic paralysis and paramyotonia congenita: broadening the clinical spectrum associated with the T704M mutation in SCN4A". J Neurol Neurosurg Psychiatry. 74 (9): 1339–41. doi:10.1136/jnnp.74.9.1339. PMC 1738672. PMID 12933953.
10. ^ a b c d Ptáĉek L, Tawil R, Griggs R, Meola G, McManis P, Barohn R, Mendell J, Harris C, Spitzer R, Santiago F (1994). "Sodium channel mutations in acetazolamide-responsive myotonia congenita, paramyotonia congenita, and hyperkalemic periodic paralysis". Neurology. 44 (8): 1500–3. doi:10.1212/wnl.44.8.1500. PMID 8058156. S2CID 28470701.
11. ^ a b McClatchey A, McKenna-Yasek D, Cros D, Worthen H, Kuncl R, DeSilva S, Cornblath D, Gusella J, Brown R (1992). "Novel mutations in families with unusual and variable disorders of the skeletal muscle sodium channel". Nat Genet. 2 (2): 148–52. doi:10.1038/ng1092-148. PMID 1338909. S2CID 12492661.
12. ^ Bouhours M, Luce S, Sternberg D, Willer J, Fontaine B, Tabti N (2005). "A1152D mutation of the Na+ channel causes paramyotonia congenita and emphasizes the role of DIII/S4-S5 linker in fast inactivation". J Physiol. 565 (Pt 2): 415–27. doi:10.1113/jphysiol.2004.081018. PMC 1464511. PMID 15790667.
13. ^ a b McClatchey A, Van den Bergh P, Pericak-Vance M, Raskind W, Verellen C, McKenna-Yasek D, Rao K, Haines J, Bird T, Brown R (1992). "Temperature-sensitive mutations in the III-IV cytoplasmic loop region of the skeletal muscle sodium channel gene in paramyotonia congenita". Cell. 68 (4): 769–74. doi:10.1016/0092-8674(92)90151-2. PMID 1310898. S2CID 31831830.
14. ^ Lerche H, Heine R, Pika U, George A, Mitrovic N, Browatzki M, Weiss T, Rivet-Bastide M, Franke C, Lomonaco M (1993). "Human sodium channel myotonia: slowed channel inactivation due to substitutions for a glycine within the III-IV linker". J Physiol. 470: 13–22. doi:10.1113/jphysiol.1993.sp019843. PMC 1143902. PMID 8308722.
15. ^ Bouhours M, Sternberg D, Davoine C, Ferrer X, Willer J, Fontaine B, Tabti N (2004). "Functional characterization and cold sensitivity of T1313A, a new mutation of the skeletal muscle sodium channel causing paramyotonia congenita in humans". J Physiol. 554 (Pt 3): 635–47. doi:10.1113/jphysiol.2003.053082. PMC 1664790. PMID 14617673.
16. ^ a b c d Ptacek L, Gouw L, Kwieciński H, McManis P, Mendell J, Barohn R, George A, Barchi R, Robertson M, Leppert M (1993). "Sodium channel mutations in paramyotonia congenita and hyperkalemic periodic paralysis". Ann Neurol. 33 (3): 300–7. doi:10.1002/ana.410330312. PMID 8388676. S2CID 33366273.
17. ^ Wagner S, Lerche H, Mitrovic N, Heine R, George A, Lehmann-Horn F (1997). "A novel sodium channel mutation causing a hyperkalemic paralytic and paramyotonic syndrome with variable clinical expressivity". Neurology. 49 (4): 1018–25. doi:10.1212/wnl.49.4.1018. PMID 9339683. S2CID 18008683.
18. ^ Okuda S, Kanda F, Nishimoto K, Sasaki R, Chihara K (2001). "Hyperkalemic periodic paralysis and paramyotonia congenita--a novel sodium channel mutation". J Neurol. 248 (11): 1003–4. doi:10.1007/s004150170059. PMID 11757950. S2CID 26927085.
19. ^ a b Ptácek L, George A, Barchi R, Griggs R, Riggs J, Robertson M, Leppert M (1992). "Mutations in an S4 segment of the adult skeletal muscle sodium channel cause paramyotonia congenita". Neuron. 8 (5): 891–7. doi:10.1016/0896-6273(92)90203-P. PMID 1316765. S2CID 41160865.
20. ^ a b c d Meyer-Kleine C, Otto M, Zoll B, Koch M (1994). "Molecular and genetic characterization of German families with paramyotonia congenita and demonstration of founder effect in the Ravensberg families". Hum Genet. 93 (6): 707–10. doi:10.1007/BF00201577. PMID 8005599. S2CID 39722069.
21. ^ Lerche H, Mitrovic N, Dubowitz V, Lehmann-Horn F (1996). "Paramyotonia congenita: the R1448P Na+ channel mutation in adult human skeletal muscle". Ann Neurol. 39 (5): 599–608. doi:10.1002/ana.410390509. PMID 8619545. S2CID 8092621.
22. ^ Bendahhou S, Cummins T, Kwiecinski H, Waxman S, Ptácek L (1999). "Characterization of a new sodium channel mutation at arginine 1448 associated with moderate Paramyotonia congenita in humans". J Physiol. 518 (2): 337–44. doi:10.1111/j.1469-7793.1999.0337p.x. PMC 2269438. PMID 10381583.
23. ^ Sasaki R, Takano H, Kamakura K, Kaida K, Hirata A, Saito M, Tanaka H, Kuzuhara S, Tsuji S (1999). "A novel mutation in the gene for the adult skeletal muscle sodium channel alpha-subunit (SCN4A) that causes paramyotonia congenita of von Eulenburg". Arch Neurol. 56 (6): 692–6. doi:10.1001/archneur.56.6.692. PMID 10369308.
24. ^ a b Lehmann-Horn F, Rüdel R, Ricker K (1993). "Non-dystrophic myotonias and periodic paralyses. A European Neuromuscular Center Workshop held 4–6 October 1992, Ulm, Germany". Neuromuscul Disord. 3 (2): 161–8. doi:10.1016/0960-8966(93)90009-9. PMID 7689382. S2CID 20892960.
25. ^ Lehmann-Horn F, Rüdel R, Ricker K, Lorković H, Dengler R, Hopf H (1983). "Two cases of adynamia episodica hereditaria: in vitro investigation of muscle cell membrane and contraction parameters". Muscle Nerve. 6 (2): 113–21. doi:10.1002/mus.880060206. PMID 6304507.
26. ^ Fontaine B, Khurana T, Hoffman E, Bruns G, Haines J, Trofatter J, Hanson M, Rich J, McFarlane H, Yasek D (1990). "Hyperkalemic periodic paralysis and the adult muscle sodium channel alpha-subunit gene". Science. 250 (4983): 1000–2. Bibcode:1990Sci...250.1000F. doi:10.1126/science.2173143. PMID 2173143.
27. ^ Rojas C, Wang J, Schwartz L, Hoffman E, Powell B, Brown R (1991). "A Met-to-Val mutation in the skeletal muscle Na+ channel alpha-subunit in hyperkalaemic periodic paralysis". Nature. 354 (6352): 387–9. Bibcode:1991Natur.354..387R. doi:10.1038/354387a0. PMID 1659668. S2CID 4372717.
28. ^ Heine R, Pika U, Lehmann-Horn F (1993). "A novel SCN4A mutation causing myotonia aggravated by cold and potassium". Hum Mol Genet. 2 (9): 1349–53. doi:10.1093/hmg/2.9.1349. PMID 8242056.
29. ^ Kelly P, Yang W, Costigan D, Farrell M, Murphy S, Hardiman O (1997). "Paramyotonia congenita and hyperkalemic periodic paralysis associated with a Met 1592 Val substitution in the skeletal muscle sodium channel alpha subunit--a large kindred with a novel phenotype". Neuromuscul Disord. 7 (2): 105–11. doi:10.1016/S0960-8966(96)00429-4. PMID 9131651. S2CID 1174464.
30. ^ Wu F, Gordon E, Hoffman E, Cannon S (2005). "A C-terminal skeletal muscle sodium channel mutation associated with myotonia disrupts fast inactivation". J Physiol. 565 (Pt 2): 371–80. doi:10.1113/jphysiol.2005.082909. PMC 1464529. PMID 15774523.
31. ^ Vicart S, Sternberg D, Fontaine B, Meola G (2005). "Human skeletal muscle sodium channelopathies". Neurol Sci. 26 (4): 194–202. doi:10.1007/s10072-005-0461-x. PMID 16193245. S2CID 27141272.
32. ^ Subramony S, Malhotra C, Mishra S (1983). "Distinguishing paramyotonia congenita and myotonia congenita by electromyography". Muscle Nerve. 6 (5): 374–9. doi:10.1002/mus.880060506. PMID 6888415.
33. ^ Streib E; Lane, Russell J. M.; Turnbull, Douglass M.; Hudgson, Peter; Walton, John; Brumback, Roger A.; Gerst, Jeffery W.; Heckmatt, John Z.; et al. (1984). "Evoked response testing in myotonic syndromes". Muscle Nerve. 7 (7): 590–2. doi:10.1002/mus.880070709. PMID 6544373.
34. ^ Taminato T, Mori-Yoshimura M, Miki J, Sasaki R, Satoh N, Oya Y, Nishino I, Takahashi Y (2020) Paramyotonia congenita with persistent distal and facial muscle weakness: A case report with literature review. J Neuromuscul Dis
35. ^ Becker PE, Paramyotonia congenita (Eulenberg) in Fortschritte der allgemeinen und klinischen Humangenetik. Thieme, Stuttgart (1970).
36. ^ Lee, GM; Kim, JB (June 2011). "Hyperkalemic periodic paralysis and paramyotonia congenita caused by a de novo mutation in the SCN4A gene". Neurology Asia. 16 (2): 163–6.
## Notes[edit]
* Lehmann-Horn F, Rüdel R, Ricker K (1993). "Non-dystrophic myotonias and periodic paralyses. A European Neuromuscular Center Workshop held 4–6 October 1992, Ulm, Germany". Neuromuscul Disord. 3 (2): 161–8. doi:10.1016/0960-8966(93)90009-9. PMID 7689382. S2CID 20892960.
* Cannon S (2006). "Pathomechanisms in channelopathies of skeletal muscle and brain". Annu Rev Neurosci. 29: 387–415. doi:10.1146/annurev.neuro.29.051605.112815. PMID 16776591.
## Further reading[edit]
* Paramyotonia congenita FAQ at the Periodic Paralysis News Desk. The site also hosts a mailing list for patients with the disorder and medical professionals interested in it.
* Fact page from the Muscular Dystrophy Association
## External links[edit]
Classification
D
* ICD-10: G71.1
* ICD-9-CM: 359.2
* OMIM: 168300
* MeSH: D020967
* DiseasesDB: 32105
External resources
* MedlinePlus: 000316
* eMedicine: neuro/308
* Orphanet: 684
* v
* t
* e
Diseases of muscle, neuromuscular junction, and neuromuscular disease
Neuromuscular-
junction disease
* autoimmune
* Myasthenia gravis
* Lambert–Eaton myasthenic syndrome
* Neuromyotonia
Myopathy
Muscular dystrophy
(DAPC)
AD
* Limb-girdle muscular dystrophy 1
* Oculopharyngeal
* Facioscapulohumeral
* Myotonic
* Distal (most)
AR
* Calpainopathy
* Limb-girdle muscular dystrophy 2
* Congenital
* Fukuyama
* Ullrich
* Walker–Warburg
XR
* dystrophin
* Becker's
* Duchenne
* Emery–Dreifuss
Other structural
* collagen disease
* Bethlem myopathy
* PTP disease
* X-linked MTM
* adaptor protein disease
* BIN1-linked centronuclear myopathy
* cytoskeleton disease
* Nemaline myopathy
* Zaspopathy
Channelopathy
Myotonia
* Myotonia congenita
* Thomsen disease
* Neuromyotonia/Isaacs syndrome
* Paramyotonia congenita
Periodic paralysis
* Hypokalemic
* Thyrotoxic
* Hyperkalemic
Other
* Central core disease
Mitochondrial myopathy
* MELAS
* MERRF
* KSS
* PEO
General
* Inflammatory myopathy
* Congenital myopathy
* v
* t
* e
Diseases of ion channels
Calcium channel
Voltage-gated
* CACNA1A
* Familial hemiplegic migraine 1
* Episodic ataxia 2
* Spinocerebellar ataxia type-6
* CACNA1C
* Timothy syndrome
* Brugada syndrome 3
* Long QT syndrome 8
* CACNA1F
* Ocular albinism 2
* CSNB2A
* CACNA1S
* Hypokalemic periodic paralysis 1
* Thyrotoxic periodic paralysis 1
* CACNB2
* Brugada syndrome 4
Ligand gated
* RYR1
* Malignant hyperthermia
* Central core disease
* RYR2
* CPVT1
* ARVD2
Sodium channel
Voltage-gated
* SCN1A
* Familial hemiplegic migraine 3
* GEFS+ 2
* Febrile seizure 3A
* SCN1B
* Brugada syndrome 6
* GEFS+ 1
* SCN4A
* Hypokalemic periodic paralysis 2
* Hyperkalemic periodic paralysis
* Paramyotonia congenita
* Potassium-aggravated myotonia
* SCN4B
* Long QT syndrome 10
* SCN5A
* Brugada syndrome 1
* Long QT syndrome 3
* SCN9A
* Erythromelalgia
* Febrile seizure 3B
* Paroxysmal extreme pain disorder
* Congenital insensitivity to pain
Constitutively active
* SCNN1B/SCNN1G
* Liddle's syndrome
* SCNN1A/SCNN1B/SCNN1G
* Pseudohypoaldosteronism 1AR
Potassium channel
Voltage-gated
* KCNA1
* Episodic ataxia 1
* KCNA5
* Familial atrial fibrillation 7
* KCNC3
* Spinocerebellar ataxia type-13
* KCNE1
* Jervell and Lange-Nielsen syndrome
* Long QT syndrome 5
* KCNE2
* Long QT syndrome 6
* KCNE3
* Brugada syndrome 5
* KCNH2
* Short QT syndrome
* KCNQ1
* Jervell and Lange-Nielsen syndrome
* Romano–Ward syndrome
* Short QT syndrome
* Long QT syndrome 1
* Familial atrial fibrillation 3
* KCNQ2
* BFNS1
Inward-rectifier
* KCNJ1
* Bartter syndrome 2
* KCNJ2
* Andersen–Tawil syndrome
* Long QT syndrome 7
* Short QT syndrome
* KCNJ11
* TNDM3
* KCNJ18
* Thyrotoxic periodic paralysis 2
Chloride channel
* CFTR
* Cystic fibrosis
* Congenital absence of the vas deferens
* CLCN1
* Thomsen disease
* Myotonia congenita
* CLCN5
* Dent's disease
* CLCN7
* Osteopetrosis A2, B4
* BEST1
* Vitelliform macular dystrophy
* CLCNKB
* Bartter syndrome 3
TRP channel
* TRPC6
* FSGS2
* TRPML1
* Mucolipidosis type IV
Connexin
* GJA1
* Oculodentodigital dysplasia
* Hallermann–Streiff syndrome
* Hypoplastic left heart syndrome
* GJB1
* Charcot–Marie–Tooth disease X1
* GJB2
* Keratitis–ichthyosis–deafness syndrome
* Ichthyosis hystrix
* Bart–Pumphrey syndrome
* Vohwinkel syndrome)
* GJB3/GJB4
* Erythrokeratodermia variabilis
* Progressive symmetric erythrokeratodermia
* GJB6
* Clouston's hidrotic ectodermal dysplasia
Porin
* AQP2
* Nephrogenic diabetes insipidus 2
See also: ion channels
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Paramyotonia congenita | c0221055 | 3,056 | wikipedia | https://en.wikipedia.org/wiki/Paramyotonia_congenita | 2021-01-18T18:36:40 | {"gard": ["7325"], "mesh": ["D020967", "C538616"], "umls": ["C1868617"], "icd-9": ["359.2"], "icd-10": ["G71.1"], "orphanet": ["684"], "wikidata": ["Q493103"]} |
A number sign (#) is used with this entry because of evidence that autosomal recessive Emery-Dreifuss muscular dystrophy-3 (EDMD3) is caused by homozygous mutation in the LMNA gene (150330) on chromosome 1q21.
Heterozygous mutation in the LMNA gene causes EDMD2 (181350).
Description
Emery-Dreifuss muscular dystrophy is characterized classically by the triad of weakness of the shoulder and pelvic girdle muscles, contractures of the elbows, neck, and Achilles tendon, and cardiac involvement, most commonly arrhythmias (summary by Jimenez-Escrig et al., 2012).
For a discussion of genetic heterogeneity of EDMD, see 310300.
Clinical Features
Raffaele di Barletta et al. (2000) reported an unusual case of a 40-year-old man with what they termed a congenital muscular dystrophy or a severe form of atypical Emery-Dreifuss muscular dystrophy. He was born of first-cousin parents, suggesting recessive inheritance of the disorder. The patient had experienced difficulties when he started walking at age 14 months. At age 5 years, he could not stand because of contractures. At age 40 years, he presented severe and diffuse muscle wasting and was confined to a wheelchair. His intelligence was normal, and detailed cardiologic examination revealed no cardiac problems. His parents were unaffected; specialized cardiologic and muscular examinations excluded abnormalities in the parents.
Jimenez-Escrig et al. (2012) reported 4 adult sibs, born of consanguineous Spanish parents, with progressive limb-girdle muscular dystrophy with variable age at onset and variable severity. One patient had onset of gait difficulties at age 4 years, 2 had onset of gait difficulties at age 14, and the fourth presented with diplopia and dizziness at age 24. The 3 patients with onset in the first and second decades had muscle weakness and atrophy of the shoulder and pelvic girdle muscles, variable contractures of the heel cord, elbows, and neck, and progressive areflexic lower limb weakness. Two patients became wheelchair-bound at ages 25 and 35 years, respectively. The sib with later onset developed paresthesia and motor discoordination in the upper limbs, as well as later onset of weakness and atrophy of the pelvic and shoulder girdle muscles. Cardiac examination revealed that all 4 had supraventricular premature beats, with ventricular premature beats in 2 patients. Laboratory studies showed increased serum creatine kinase. Muscle biopsy showed dystrophic changes, with increased fiber size variability, increased connective tissue, and signs of necrosis and regeneration. The patients' father and paternal aunt had no muscular symptoms, but developed cardiac symptoms late in life.
### Clinical Variability
Wiltshire et al. (2013) reported a Hutterite family of predominantly Leherleut ancestry in which a brother and sister developed progressive limb-girdle muscular dystrophy associated with contractures in the first or second decades. The sister was more severely affected and became wheelchair-bound by age 30. She also had severe scoliosis resulting in restrictive lung disease. Both sibs had features of partial lipodystrophy with loss of subcutaneous fat, and the sister had an aged appearance. The sister had isolated hypertension, whereas the brother had chronic atrial fibrillation. Laboratory studies showed increased creatine kinase, increased triglycerides, and increased LDL cholesterol. These 2 sibs were found to be homozygous for a missense mutation in the LMNA gene (R482Q; 150330.0010). Two other sibs and both parents were heterozygous for this mutation: these individuals had abnormal lipid profiles, but only the mother showed lipodystrophy of the extremities, a phenotype consistent with FPLD2 (151660).
Inheritance
The transmission pattern of EDMD3 in the family reported by Jimenez-Escrig et al. (2012) was consistent with autosomal recessive inheritance.
Molecular Genetics
In a 40-year-old man with EDMD3, Raffaele di Barletta et al. (2000) identified a homozygous mutation in the LMNA gene (H222Y; 150330.0014). Both unaffected parents were heterozygous for the mutation.
In 4 sibs, born of consanguineous Spanish parents, with EDMD3, Jimenez-Escrig et al. (2012) identified a homozygous missense mutation in the LMNA gene (R225Q; 150330.0054). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder and was not found in 200 control chromosomes. Functional studies of the variant were not performed. Two heterozygous carriers had no muscular symptoms, but developed cardiac arrhythmias late in life.
In 2 sibs from a family of Hutterite descent with EDMD3 and features of partial lipodystrophy, Wiltshire et al. (2013) identified a homozygous missense mutation in the LMNA gene (R482Q; 150330.0010).
Population Genetics
Wiltshire et al. (2013) found the frequency of the LMNA R482Q mutation to be 1.45% in Dariusleut and Leherleut Hutterites in Alberta, Canada.
INHERITANCE \- Autosomal recessive HEAD & NECK Neck \- Neck contractures CARDIOVASCULAR Heart \- Premature supraventricular and ventricular contractions \- Arrhythmias SKELETAL Spine \- Scoliosis (in some patients) Limbs \- Elbow contractures Feet \- Heel cord contractures MUSCLE, SOFT TISSUES \- Muscle weakness, proximal, upper and lower limbs \- Muscle atrophy, proximal, upper and lower limbs \- Gait difficulties \- Muscle biopsy shows dystrophic changes \- Partial lipodystrophy (abnormal distribution of subcutaneous adipose tissue) (1 family) NEUROLOGIC Peripheral Nervous System \- Loss of reflexes in the lower limbs LABORATORY ABNORMALITIES \- Increased serum creatine kinase \- Increased triglycerides (1 family) \- Increased LDL cholesterol (1 family) MISCELLANEOUS \- Variable age at onset, usually first or second decade \- Progressive disorder \- Heterozygous mutation carriers may have late-onset cardiac arrhythmias \- Three unrelated families have been reported (last curated August 2015) MOLECULAR BASIS \- Caused by mutation in the lamin A/C gene (LMNA, 150330.0010 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| EMERY-DREIFUSS MUSCULAR DYSTROPHY 3, AUTOSOMAL RECESSIVE | c0410189 | 3,057 | omim | https://www.omim.org/entry/616516 | 2019-09-22T15:48:38 | {"doid": ["0070248"], "mesh": ["D020389"], "omim": ["616516"], "orphanet": ["261", "98855"]} |
Prepubertal hypertrichosis
SpecialtyDermatology
Prepubertal hypertrichosis is a cutaneous condition characterized by increased hair growth,[1] and is a relatively common finding in otherwise healthy infants and children, most often occurring in individuals of Mediterranean or South Asian descent.[2]
## See also[edit]
* Hypertrichosis
* List of cutaneous conditions
## References[edit]
1. ^ Hair Growth Vitamins Retrieved 19 June 2011
2. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
This dermatology article is a stub. You can help Wikipedia by expanding it.
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*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Prepubertal hypertrichosis | None | 3,058 | wikipedia | https://en.wikipedia.org/wiki/Prepubertal_hypertrichosis | 2021-01-18T18:43:11 | {"wikidata": ["Q7240676"]} |
Older age of a mother at conception and its associated health effects
For effects associated with father's age, see Paternal age effect.
Advanced maternal age, in a broad sense, is the instance of a woman being of an older age at a stage of reproduction, although there are various definitions of specific age and stage of reproduction.[1] The variability in definitions is in part explained by the effects of increasing age occurring as a continuum rather than as a threshold effect.[1]
In Western, Northern, and Southern Europe, first-time mothers are on average 27 to 29 years old, up from 23 to 25 years at the start of the 1970s. In a number of European countries (Spain), the mean age of women at first childbirth has crossed the 30 year threshold.[2] This process is not restricted to Europe. Asia, Japan and the United States are all seeing average age at first birth on the rise, and increasingly the process is spreading to countries in the developing world such as China, Turkey and Iran. In the U.S., the average age of first childbirth was 26.9 in 2018.[3]
Advanced maternal age is associated with adverse reproductive effects such as increased risk of infertility,[4] and that the children have chromosomal abnormalities.[5] The corresponding paternal age effect is less pronounced.[6][7]
## Contents
* 1 History
* 2 Examples
* 3 Possible factors that influence childbearing age
* 4 Effects
* 4.1 Decreased fertility
* 4.2 Risk of birth defects
* 4.3 Other effects
* 5 Changes in interpregnancy interval
* 6 Ovarian aging
* 7 See also
* 8 References
* 8.1 Citations
* 8.2 Sources
* 9 Further reading
* 10 External links
## History[edit]
Having children later was not exceptional in the past, when families were larger and women often continued bearing children until the end of their reproductive age. What is so radical about this recent transformation is that it is the age at which women give birth to their first child which is becoming comparatively high, leaving an ever more constricted window of biological opportunity for second and subsequent children, should they be desired. Unsurprisingly, high first-birth ages and high rates of birth postponement are associated with the arrival of low, and lowest-low fertility.[8]
This association has now become especially clear, since the postponement of first births in a number of countries has now continued unabated for more than three decades, and has become one of the most prominent characteristics of fertility patterns in developed societies. A variety of authors (in particular Lesthaeghe) have argued that fertility postponement constitutes the ‘hallmark’ of what has become known as the “second demographic transition”.
Others have proposed that the postponement process itself constitutes a separate 'third transition'.[9] On this latter view, modern developed societies exhibit a kind of dual fertility pattern, with the majority of births being concentrated either among very young or increasingly older mothers. This is sometimes known as the 'rectangularisation' of fertility patterns.
## Examples[edit]
In the USA, the average age at which women bore their first child advanced from 21.4 years old in 1970[10] to 26.9 in 2018.[3]
The German Federal Institute for Population Research claimed in 2015 the percentage for women with an age of at least 35 giving birth to a child was 25.9%. This figure rose from 7.6% in 1981.[11]
## Possible factors that influence childbearing age[edit]
There are many factors that may influence childbearing age in women, although they are mostly correlations without certain causations. For instance, older maternal age at first childbirth is associated with higher educational attainment and income.[12]
Two studies show that generous parental leave allowances in Britain encourage young motherhood and that parental-leave allowance reduces postponement in Sweden.[13]
## Effects[edit]
### Decreased fertility[edit]
Cumulative percentage and average age for women reaching subfertility, sterility, irregular menstruation and menopause.[14]
Main article: Age and female fertility
A woman's fertility peaks lasts during the twenties and first half of thirties, after which it starts to decline, with advanced maternal age causing an increased risk of female infertility.
According to Henri Leridon, PhD, an epidemiologist with the French Institute of Health and Medical Research, of women trying to get pregnant, without using fertility drugs or in vitro fertilization:[4]
* At age 30
* 75% will have a conception ending in a live birth within one year
* 91% will have a conception ending in a live birth within four years.
* At age 35
* 66% will have a conception ending in a live birth within one year
* 84% will have a conception ending in a live birth within four years.
* At age 40
* 44% will have a conception ending in a live birth within one year
* 64% will have a conception ending in a live birth within four years.[4]
### Risk of birth defects[edit]
The risk of having a Down syndrome pregnancy in relation to a mother's age.
A woman's risk of having a baby with chromosomal abnormalities increases with her age. Down syndrome is the most common chromosomal birth defect, and a woman's risk of having a baby with Down syndrome is:[5]
* At age 20, 1 in 1,441
* At age 25, 1 in 1,383
* At age 30, 1 in 959
* At age 35, 1 in 338
* At age 40, 1 in 84
* At age 45, 1 in 32
### Other effects[edit]
Advanced maternal age is associated with adverse outcomes in the perinatal period, which may be caused by detrimental effects on decidual and placental development.[15]
The risk of the mother dying before the child becomes an adult increases by more advanced maternal age, such as can be demonstrated by the following data from France in 2007:[16]
Maternal age at childbirth 20 25 30 35 40 45
Risk of mother not surviving until child's 18th birthday (in %)[16] 0.6 1.0 1.6 2.6 3.8 5.5
The above table is not to be confused with maternal mortality.
Advanced maternal age continues to be associated with a range of adverse pregnancy outcomes including low birth weight, pre-term birth, stillbirth, unexplained fetal death, and increased rates of Caesarean section. However, over time, improvements in (and improvements in access to) medical services and social resources have decreased the negative association between older maternal age and low birth weight.[17]
On the other hand, advanced maternal age is associated with a more stable family environment, higher socio-economic position, higher income and better living conditions, as well as better parenting practices,[16] (including better disciplinary methods[18]). A qualitative study on couples in the United States who used in-vitro fertilization to conceive their first child when the woman was aged 40 or older at the time of delivery found that 72% of the women and 57% of the men believed that they had enhanced emotional preparedness for parenting which benefitted both their children and themselves.[19] In quantitative studies, mother’s older age at first birth has been associated with increases in children’s psychiatric health,[20] language skills,[20] cognitive ability,[21] and fewer social and emotional difficulties.[18] Further, a study in the United Kingdom showed that older maternal age at first birth was associated with fewer hospital admissions and fewer unintentional injuries for children up to age 5 and a greater likelihood of having had all of their immunizations by 9 months of age– all outcomes used as indicators of child wellbeing in reports from the World Health Organisation.[22] Finally, although older maternal age doesn’t necessarily imply older paternal age, researchers have suggested links between older paternal age and improved child outcomes, including increased IQ and educational attainment[23] and increased telomeric length, which is associated with greater longevity.[24] However, it is more or less uncertain whether these entities are effects of advanced maternal age, are contributors to advanced maternal age, or common effects of a certain state such as personality type.
## Changes in interpregnancy interval[edit]
Kalberer et al.[25] have shown that despite the older maternal age at birth of the first child, the time span between the birth of the first and the second child (= interpregnancy interval) decreased over the last decades. If purely biological factors were at work, it could be argued that interpregnancy interval should have increased, as fertility declines with age, which would make it harder for the woman to get a second child after postponed birth of the first one. This not being the case shows that sociologic factors (see above) prime over biological factors in determining interpregnancy interval.
With technology developments cases of post-menopausal pregnancies have occurred, and there are several known cases of older women carrying a pregnancy to term, usually with in vitro fertilization of a donor egg. A 61-year-old Brazilian woman with implantation of a donor egg expected gave birth to twins in October 2012.[26][27]
## Ovarian aging[edit]
As women age, they experience a decline in reproductive performance leading to menopause.[28] This decline is tied to a decline in the number of ovarian follicles. Although about 1 million oocytes are present at birth in the human ovary, only about 500 (about 0.05%) of these ovulate, and the rest do not (ovarian follicle atresia). The decline in ovarian reserve appears to occur at a constantly increasing rate with age,[29] and leads to nearly complete exhaustion of the reserve by about age 51. As ovarian reserve and fertility decline with age, there is also a parallel increase in pregnancy failure and meiotic errors resulting in chromosomally abnormal conceptions.
Titus et al.[30] have proposed an explanation for the decline in ovarian reserve with age. They showed that as women age, double-strand breaks accumulate in the DNA of their primordial follicles. Primordial follicles are immature primary oocytes surrounded by a single layer of granulosa cells. An enzyme system is present in oocytes that normally accurately repairs DNA double-strand breaks. This repair system is referred to as homologous recombinational repair, and it is especially active during meiosis. Meiosis is the general process by which germ cells are formed in eukaryotes, and it appears to be an adaptation for efficiently removing damages in germ line DNA by homologous recombinational repair (see Origin and function of meiosis). Human primary oocytes are present at an intermediate stage of meiosis, that is prophase I (see Oogenesis). Titus et al.[30] also showed that expression of four key DNA repair genes that are necessary for homologous recombinational repair (BRCA1, MRE11, Rad51 and ATM) decline in oocytes with age. This age-related decline in ability to repair double-strand damages can account for the accumulation of these damages, which then likely contributes to the decline in ovarian reserve.
Women with an inherited mutation in the DNA repair gene BRCA1 undergo menopause prematurely,[31] suggesting that naturally occurring DNA damages in oocytes are repaired less efficiently in these women, and this inefficiency leads to early reproductive failure. Genomic data from about 70,000 women were analyzed to identify protein-coding variation associated with age at natural menopause.[32] Pathway analyses identified a major association with DNA damage response genes, particularly those expressed during meiosis and including a common coding variant in the BRCA1 gene.
## See also[edit]
* List of countries by age at first marriage
* Childlessness
* Fertility factor (demography)
* Pregnancy over age 50
* Teenage pregnancy
## References[edit]
### Citations[edit]
1. ^ a b Effect of advanced age on fertility and pregnancy in women Archived 19 June 2016 at the Wayback Machine at UpToDate. Author: Ruth C Fretts. Section Editor: Louise Wilkins-Haug. Deputy Editor: Vanessa A Barss. This topic last updated: 3 December 2012.
2. ^ "SF2.3: Mean age of mothers at first childbirth" (PDF). Archived from the original (PDF) on 22 December 2014. Retrieved 27 May 2014.
3. ^ a b "Archived copy". Archived from the original on 12 November 2019. Retrieved 8 September 2017.CS1 maint: archived copy as title (link)
4. ^ a b c Leridon, H. (1 July 2004). "Can assisted reproduction technology compensate for the natural decline in fertility with age? A model assessment". Human Reproduction. 19 (7): 1548–1553. doi:10.1093/humrep/deh304. PMID 15205397.
5. ^ a b Morris, J.K.; Mutton, D.E.; Alberman, E. (March 2002). "Revised estimates of the maternal age specific live birth prevalence of Down's syndrome". Journal of Medical Screening. 9 (1): 2–6. doi:10.1136/jms.9.1.2. PMID 11943789.
6. ^ Tournaye, Herman (June 2009). "Male Reproductive Ageing". In Bewley, Susan; Ledger, William; Nikolaou, Dimitrios (eds.). Reproductive Ageing. Cambridge University Press. pp. 95–104. ISBN 978-1-906985-13-4. Archived from the original on 4 November 2020. Retrieved 24 October 2020.
7. ^ Kidd, Sharon A; Eskenazi, Brenda; Wyrobek, Andrew J (February 2001). "Effects of male age on semen quality and fertility: a review of the literature". Fertility and Sterility. 75 (2): 237–248. doi:10.1016/s0015-0282(00)01679-4. PMID 11172821.
8. ^ "U.S. Women More Likely to Have Children Than a Decade Ago". Pew Research Center’s Social & Demographic Trends Project. 18 January 2018. Retrieved 29 October 2020.
9. ^ Kohler, Hans-Peter; Billari, Francesco C.; Ortega, Jose Antonio (December 2002). "The Emergence of Lowest-Low Fertility in Europe During the 1990s". Population and Development Review. 28 (4): 641–680. doi:10.1111/j.1728-4457.2002.00641.x.
10. ^ Mathews, TJ. "Delayed Childbearing: More Women Are Having Their First Child Later in Life" (PDF). 2009. CDC. Archived (PDF) from the original on 25 November 2017. Retrieved 26 August 2013.
11. ^ "Jedes vierte Neugeborene hat eine Mutter über 34 Jahre" [Every fourth newborn has a mother over 34 years of age] (PDF) (in German). Archived from the original (PDF) on 22 December 2017. Retrieved 20 December 2017.
12. ^ Shadyab, Aladdin H.; Gass, Margery L. S.; Stefanick, Marcia L.; Waring, Molly E.; Macera, Caroline A.; Gallo, Linda C.; Shaffer, Richard A.; Jain, Sonia; LaCroix, Andrea Z. (January 2017). "Maternal Age at Childbirth and Parity as Predictors of Longevity Among Women in the United States: The Women's Health Initiative". American Journal of Public Health. 107 (1): 113–119. doi:10.2105/AJPH.2016.303503. PMC 5308150. PMID 27854529.
13. ^ Balbo, Nicoletta; Billari, Francesco C.; Mills, Melinda (February 2013). "Fertility in Advanced Societies: A Review of Research". European Journal of Population. 29 (1): 1–38. doi:10.1007/s10680-012-9277-y. PMC 3576563. PMID 23440941.
14. ^ te Velde, E. R.; Pearson, PL (1 March 2002). "The variability of female reproductive ageing". Human Reproduction Update. 8 (2): 141–154. doi:10.1093/humupd/8.2.141. PMID 12099629.
15. ^ Nelson, S.M.; Telfer, E.E.; Anderson, R.A. (1 January 2013). "The ageing ovary and uterus: new biological insights". Human Reproduction Update. 19 (1): 67–83. doi:10.1093/humupd/dms043. PMC 3508627. PMID 23103636.
16. ^ a b c Schmidt, L.; Sobotka, T.; Bentzen, J. G.; Nyboe Andersen, A.; ESHRE Reproduction and Society Task Force (1 January 2012). "Demographic and medical consequences of the postponement of parenthood". Human Reproduction Update. 18 (1): 29–43. doi:10.1093/humupd/dmr040. PMID 21989171.
17. ^ Goisis, Alice; Schneider, Daniel C.; Myrskylä, Mikko (2 September 2018). "Secular changes in the association between advanced maternal age and the risk of low birth weight: A cross-cohort comparison in the UK". Population Studies. 72 (3): 381–397. doi:10.1080/00324728.2018.1442584. PMID 29582702. S2CID 2977607.
18. ^ a b Trillingsgaard, Tea; Sommer, Dion (4 March 2018). "Associations between older maternal age, use of sanctions, and children's socio-emotional development through 7, 11, and 15 years" (PDF). European Journal of Developmental Psychology. 15 (2): 141–155. doi:10.1080/17405629.2016.1266248. S2CID 53061283. Archived (PDF) from the original on 19 July 2018. Retrieved 19 July 2019.
19. ^ Mac Dougall, K.; Beyene, Y.; Nachtigall, R. D. (1 April 2012). "'Inconvenient biology:' advantages and disadvantages of first-time parenting after age 40 using in vitro fertilization". Human Reproduction. 27 (4): 1058–1065. doi:10.1093/humrep/des007. PMC 3303492. PMID 22333985.
20. ^ a b Goisis, A. (2 September 2015). "How Are Children of Older Mothers Doing? Evidence from the United Kingdom" (PDF). Biodemography and Social Biology. 61 (3): 231–251. doi:10.1080/19485565.2014.1001887. PMID 26652679. S2CID 10071445. Archived (PDF) from the original on 20 July 2018. Retrieved 19 July 2019.
21. ^ Goisis, Alice; Schneider, Daniel C; Myrskylä, Mikko (1 June 2017). "The reversing association between advanced maternal age and child cognitive ability: evidence from three UK birth cohorts". International Journal of Epidemiology. 46 (3): 850–859. doi:10.1093/ije/dyw354. PMC 5837600. PMID 28177512.
22. ^ Sutcliffe, A. G.; Barnes, J.; Belsky, J.; Gardiner, J.; Melhuish, E. (21 August 2012). "The health and development of children born to older mothers in the United Kingdom: observational study using longitudinal cohort data". BMJ. 345 (aug21 1): e5116. doi:10.1136/bmj.e5116. PMC 3424227. PMID 22915663.
23. ^ Janecka, M; Rijsdijk, F; Rai, D; Modabbernia, A; Reichenberg, A (June 2017). "Advantageous developmental outcomes of advancing paternal age". Translational Psychiatry. 7 (6): e1156. doi:10.1038/tp.2017.125. PMC 5537646. PMID 28632201.
24. ^ Eisenberg, D. T. A.; Hayes, M. G.; Kuzawa, C. W. (26 June 2012). "Delayed paternal age of reproduction in humans is associated with longer telomeres across two generations of descendants". Proceedings of the National Academy of Sciences. 109 (26): 10251–10256. Bibcode:2012PNAS..10910251E. doi:10.1073/pnas.1202092109. PMC 3387085. PMID 22689985.
25. ^ Kalberer, Urs; Baud, David; Fontanet, Arnaud; Hohlfeld, Patrick; de Ziegler, Dominique (December 2009). "Birth records from Swiss married couples analyzed over the past 35 years reveal an aging of first-time mothers by 5.1 years while the interpregnancy interval has shortened" (PDF). Fertility and Sterility. 92 (6): 2072–2073. doi:10.1016/j.fertnstert.2009.05.078. PMID 19608170. Archived (PDF) from the original on 19 July 2018. Retrieved 19 July 2019.
26. ^ "Woman, 61, pregnant". The Sydney Morning Herald. 27 September 2011. Archived from the original on 27 April 2016. Retrieved 8 February 2013.
27. ^ Moreno, Carolina (26 October 2012). "LOOK: 61 Year-Old Woman Gives Birth To Twins". HuffPost. Archived from the original on 3 August 2016. Retrieved 13 October 2017.
28. ^ "Menopause". medlineplus.gov. Archived from the original on 16 October 2020. Retrieved 29 October 2020.
29. ^ Hansen KR, Knowlton NS, Thyer AC, Charleston JS, Soules MR, Klein NA (2008). "A new model of reproductive aging: the decline in ovarian non-growing follicle number from birth to menopause". Hum. Reprod. 23 (3): 699–708. doi:10.1093/humrep/dem408. PMID 18192670.
30. ^ a b Titus S, Li F, Stobezki R, Akula K, Unsal E, Jeong K, Dickler M, Robson M, Moy F, Goswami S, Oktay K (2013). "Impairment of BRCA1-related DNA double-strand break repair leads to ovarian aging in mice and humans". Sci Transl Med. 5 (172): 172ra21. doi:10.1126/scitranslmed.3004925. PMC 5130338. PMID 23408054.
31. ^ Rzepka-Górska I, Tarnowski B, Chudecka-Głaz A, Górski B, Zielińska D, Tołoczko-Grabarek A (2006). "Premature menopause in patients with BRCA1 gene mutation". Breast Cancer Res. Treat. 100 (1): 59–63. doi:10.1007/s10549-006-9220-1. PMID 16773440. S2CID 19572648.
32. ^ Day FR, Ruth KS, Thompson DJ, et al. (2015). "Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair". Nat. Genet. 47 (11): 1294–303. doi:10.1038/ng.3412. PMC 4661791. PMID 26414677.
### Sources[edit]
* Lorentzon, M.; et al. (2012). "Advancing Maternal Age Is Associated With Lower Bone Mineral Density In Young Adult Male Offspring". Osteoporosis International. 23 (2): 475–482. doi:10.1007/s00198-011-1558-5. PMC 3261413. PMID 21350896.
* Nilsen, AB; et al. (2012). "Characteristics Of Women Who Are Pregnant With Their First Baby At An Advanced Age". Acta Obstetricia et Gynecologica Scandinavica. 91 (3): 353–362. doi:10.1111/j.1600-0412.2011.01335.x. PMID 22150020. S2CID 38149716.
* Khashan, Ali S.; et al. (2013). "Advanced Maternal Age And Adverse Pregnancy Outcome: Evidence From A Large Contemporary Cohort". PLOS ONE. 8 (2): 1–9. Bibcode:2013PLoSO...856583K. doi:10.1371/journal.pone.0056583. PMC 3577849. PMID 23437176.
* Jabcosson, B.; Ladfords, L.; Milsom, I. (2004). "Advanced Maternal Age and Adverse Perinatal Outcome". Obstetrics & Gynecology. 104 (4): 727–733. doi:10.1097/01.aog.0000140682.63746.be. PMID 15458893. S2CID 8652247.
## Further reading[edit]
* Gavrilov, L. A.; Gavrilova, N. S. (2000). "Human longevity and parental age at conception". In Robine, J.-M.; Kirkwood, T. B. L.; Allard, M. (eds.). Sex and Longevity: Sexuality, Gender, Reproduction, Parenthood. Berlin, Heidelberg: Springer-Verlag. pp. 7–31. ISBN 3-540-67740-2.
* Gavrilov, L. A.; Gavrilova, N. S. (1997). "Parental age at conception and offspring longevity". Reviews in Clinical Gerontology. 7: 5–12. doi:10.1017/S0959259897000026.
* Hofmeister, Heather; Mills, Melinda; Blossfeld, Hans-Peter (2006). "Globalization, Uncertainty and Women's Mid-Career Life Courses: A Theoretical Framework". In Blossfeld, Hans-Peter; Hofmeister, Heather (eds.). Globalization, uncertainty and women's careers : an international comparison. Cheltenham. pp. 3–31. ISBN 1-84542-664-9.
* Lesthaeghe, R.; Neels, K. (2002). "From the first to the second demographic transition: An interpretation of the spatial continuity of demographic innovation in France, Belgium and Switzerland". European Journal of Population. 18 (4): 325–360. doi:10.1023/A:1021125800070. S2CID 878879.
* Sobotka, Tomás (2004). Postponement of childbearing and low fertility in Europe (Thesis). hdl:11370/7fe0743c-9766-4ae9-befe-3edae1006c6e.
## External links[edit]
* The Fertility Bust, Charlemagne, The Economist, 9 February 2006
* Kohler, Hans-Peter; Billari, Francesco C.; Ortega, José Antonio (2006). "Low fertility in Europe: Causes, implications and policy options". In Harris, Fred R. (ed.). The Baby Bust: Who Will Do the Work? who Will Pay the Taxes?. Rowman & Littlefield. pp. 48–109. ISBN 978-0-7425-3855-9.
* Postponement of childbearing and low fertility in Europe Power Point presentation by Tomas Sobotka
* InterNational Council on Infertility Information Dissemination
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Advanced maternal age | c0854271 | 3,059 | wikipedia | https://en.wikipedia.org/wiki/Advanced_maternal_age | 2021-01-18T18:51:42 | {"umls": ["C0854271"], "wikidata": ["Q4686351"]} |
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Esophageal dysphagia
SpecialtyGastroenterology
Esophageal dysphagia is a form of dysphagia where the underlying cause arises from the body of the esophagus, lower esophageal sphincter, or cardia of the stomach, usually due to mechanical causes or motility problems.[1]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Differential diagnosis
* 4 Diagnostic tools
* 5 Treatment
* 6 References
* 7 External links
## Signs and symptoms[edit]
Patients usually complain of dysphagia (the feeling of food getting stuck several seconds after swallowing), and will point to the suprasternal notch or behind the sternum as the site of obstruction.
## Causes[edit]
If there is dysphagia to both solids and liquids, then it is most likely a motility problem. If there is dysphagia initially to solids but progresses to also involve liquids, then it is most likely a mechanical obstruction. Once a distinction has been made between a motility problem and a mechanical obstruction, it is important to note whether the dysphagia is intermittent or progressive. An intermittent motility dysphagia likely can be diffuse esophageal spasm (DES) or nonspecific esophageal motility disorder (NEMD). Progressive motility dysphagia disorders include scleroderma or achalasia with chronic heartburn, regurgitation, respiratory problems, or weight loss. Intermittent mechanical dysphagia is likely to be an esophageal ring. Progressive mechanical dysphagia is most likely due to peptic stricture or esophageal cancer.[2]
Schematically the above can be presented as a tree diagram:
Esophageal
dysphagia
Solids & liquids
(Neuromuscular)Solids only
(Mechanical obstruction)
ProgressiveIntermittentIntermittentProgressive
SclerodermaAchalasiaDiffuse esophageal
spasmLower esophageal ringCancerPeptic stricture
## Differential diagnosis[edit]
Endoscopic image of a non-cancerous peptic stricture, or narrowing of the esophagus, near the junction with the stomach. This is a complication of chronic gastroesophageal reflux disease, and can be a cause of dysphagia. The stricture is about 3 to 5 mm in diameter. The blood that is visible is from the endoscope bumping into the stricture.
Esophageal stricture, or narrowing of the esophagus, is usually a complication of acid reflux, most commonly due to gastroesophageal reflux disease (GERD). These patients are usually older and have had GERD for a long time. Esophageal stricture can also be due to other causes, such as acid reflux from Zollinger–Ellison syndrome, trauma from a nasogastric tube placement, and chronic acid exposure in patients with poor esophageal motility from scleroderma. Other non-acid related causes of peptic strictures include infectious esophagitis, ingestion of chemical irritant, pill irritation, and radiation. Peptic stricture is a progressive mechanical dysphagia, meaning patients will complain of initial intolerance to solids followed by inability to tolerate liquids. When the diameter of the stricture is less than 12 mm the patient will always have dysphagia, while dysphagia is not seen when the diameter of the stricture is above 30 mm. Symptoms relating to the underlying cause of the stricture usually will also be present.
Main article: Esophageal stricture
Esophageal cancer also presents with progressive mechanical dysphagia. Patients usually come with rapidly progressive dysphagia first with solids then with liquids, weight loss (> 10 kg), and anorexia (loss of appetite). Esophageal cancer usually affects the elderly. Esophageal cancers can be either squamous cell carcinoma or adenocarcinoma. Adenocarcinoma is the most prevalent in the US and is associated with patients with chronic GERD who have developed Barrett's esophagus (intestinal metaplasia of esophageal mucosa). Squamous cell carcinoma is more prevalent in Asia and is associated with tobacco smoking and alcohol use.
Main article: esophageal cancer
Esophageal rings and webs, are actual rings and webs of tissue that may occlude the esophageal lumen.
* Rings \--- Also known as Schatzki rings from the discoverer, these rings are usually mucosal rings rather than muscular rings, and are located near the gastroesophageal junction at the squamo-columnar junction. Presence of multiple rings may suggest eosinophilic esophagitis. Rings cause intermittent mechanical dysphagia, meaning patients will usually present with transient discomfort and regurgitation while swallowing solids and then liquids, depending on the constriction of the ring.
* Webs \--- Usually squamous mucosal protrusion into the esophageal lumen, especially anterior cervical esophagus behind the cricoid area. Patients are usually asymptomatic or have intermittent dysphagia. An important association of esophageal webs is to the Plummer–Vinson syndrome in iron deficiency, in which case patients will also have anemia, koilonychia, fatigue, and other symptoms of anemia.
Main article: esophageal web
Achalasia is an idiopathic motility disorder characterized by failure of lower esophageal sphincter (LES) relaxation as well as loss of peristalsis in the distal esophagus, which is mostly smooth muscle. Both of these features impair the ability of the esophagus to empty contents into the stomach. Patients usually complain of dysphagia to both solids and liquids. Dysphagia to liquids, in particular, is a characteristic of achalasia. Other symptoms of achalasia include regurgitation, night coughing, chest pain, weight loss, and heartburn. The combination of achalasia, adrenal insufficiency, and alacrima (lack of tear production) in children is known as the triple-A (Allgrove) syndrome. In most cases the cause is unknown (idiopathic), but in some regions of the world, achalasia can also be caused by Chagas disease due to infection by Trypanosoma cruzi.
Main article: achalasia
Scleroderma is a disease characterized by atrophy and sclerosis of the gut wall, most commonly of the distal esophagus (~90%). Consequently, the lower esophageal sphincter cannot close and this can lead to severe gastroesophageal reflux disease (GERD). Patients typically present with progressive dysphagia to both solids and liquids secondary to motility problems or peptic stricture from acid reflux.
Main article: scleroderma
Spastic motility disorders include diffuse esophageal spasm (DES), nutcracker esophagus, hypertensive lower esophageal sphincter, and nonspecific spastic esophageal motility disorders (NEMD).
* DES can be caused by many factors that affect muscular or neural functions, including acid reflux, stress, hot or cold food, or carbonated drinks. Patients present with intermittent dysphagia, chest pain, or heartburn.
Rare causes of esophageal dysphagia not mentioned above
* Diverticulum
* Aberrant subclavian artery, or (dysphagia lusoria)
* Cervical osteophytes
* Enlarged aorta
* Enlarged left atrium
* Mediastinal tumor
## Diagnostic tools[edit]
Once a patient complains of dysphagia they should have an upper endoscopy (EGD). Commonly patients are found to have esophagitis and may have an esophageal stricture. Biopsies are usually done to look for evidence of esophagitis even if the EGD is normal. Usually no further testing is required if the diagnosis is established on EGD. Repeat endoscopy may be needed for follow up.
If there is a suspicion of a proximal lesion such as:
* history of surgery for laryngeal or esophageal cancer
* history of radiation or irritating injury
* achalasia
* Zenker's diverticulum
a barium swallow may be performed before endoscopy to help identify abnormalities that might increase the risk of perforation at the time of endoscopy.
If achalasia suspected an upper endoscopy is required to exclude a malignancy as a cause of the findings on barium swallow. Manometry is performed next to confirm. A normal endoscopy should be followed by manometry, and if manometry is also normal, the diagnosis is functional dysphagia.
## Treatment[edit]
The patient is generally sent for a GI, pulmonary, or ENT, depending on the suspected underlying cause. Consultations with a speech therapist and registered dietitian nutritionist (RDN) are also needed, as many patients may need dietary modifications such as thickened fluids.
## References[edit]
1. ^ Palmer, Jeffrey B.; Drennan, Jennifer C.; Baba, Mikoto (15 April 2000). "Evaluation and Treatment of Swallowing Impairments". American Family Physician. 61 (8): 2453–2462.
2. ^ Spieker, Michael R. (15 June 2000). "Evaluating Dysphagia". American Family Physician. 61 (12): 3639–3648. PMID 10892635.
## External links[edit]
Classification
D
* ICD-10: R13
* ICD-9-CM: 787.24
* MeSH: D003680
* DiseasesDB: 17942
External resources
* MedlinePlus: 003115
* eMedicine: pmr/194
* v
* t
* e
Symptoms and signs relating to the human digestive system or abdomen
Gastrointestinal
tract
* Nausea
* Vomiting
* Heartburn
* Aerophagia
* Pagophagia
* Dysphagia
* oropharyngeal
* esophageal
* Odynophagia
* Bad breath
* Xerostomia
* Hypersalivation
* Burping
* Wet burp
* Goodsall's rule
* Chilaiditi syndrome
* Dance's sign
* Aaron's sign
* Arapov's sign
* Markle sign
* McBurney's point
* Sherren's triangle
* Radiologic signs: Hampton's line
* Klemm's sign
Accessory
* liver: Councilman body
* Mallory body
* biliary: Boas' sign
* Courvoisier's law
* Charcot's cholangitis triad/Reynolds' pentad
* cholecystitis (Murphy's sign
* Lépine's sign
* Mirizzi's syndrome)
* Nardi test
Defecation
* Flatulence
* Fecal incontinence
* Encopresis
* Fecal occult blood
* Rectal tenesmus
* Constipation
* Obstructed defecation
* Diarrhea
* Rectal discharge
* Psoas sign
* Obturator sign
* Rovsing's sign
* Hamburger sign
* Heel tap sign
* Aure-Rozanova's sign
* Dunphy sign
* Alder's sign
* Lockwood's sign
* Rosenstein's sign
Abdomen
Pain
* Abdominal pain
* Acute abdomen
* Colic
* Baby colic
* Abdominal guarding
* Blumberg sign
Distension
* Abdominal distension
* Bloating
* Ascites
* Tympanites
* Shifting dullness
* Ascites
* Fluid wave test
Masses
* Abdominal mass
* Hepatosplenomegaly
* Hepatomegaly
* Splenomegaly
Other
* Jaundice
* Mallet-Guy sign
* Puddle sign
* Ballance's sign
* Aortic insufficiency
* Castell's sign
* Kehr's sign
* Cullen's sign
* Grey Turner's sign
Hernia
* Howship–Romberg sign
* Hannington-Kiff sign
Other
* Cupola sign
* Fothergill's sign
* Carnett's sign
* Sister Mary Joseph nodule
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Esophageal dysphagia | c0267072 | 3,060 | wikipedia | https://en.wikipedia.org/wiki/Esophageal_dysphagia | 2021-01-18T19:04:51 | {"mesh": ["D003680"], "icd-9": ["787.24"], "icd-10": ["R13"], "wikidata": ["Q3533161"]} |
Progressive bifocal chorioretinal dystrophy (PBCRA) is an inherited condition of the eye characterized by a large wasted region of the macula, lesions in the area of the retina closest to the nose (the nasal retina), nystagmus (fast, uncontrollable movements of the eyes), myopia (nearsightedness), poor vision, and slow disease progression. Widespread abnormalities of rod and cone function has been described. PBCRA is caused by mutations in a gene which has mapped to a region on chromosome 6q, close to the macular dystrophy retinal 1 (MCDR1) locus. It is inherited in an autosomal dominant fashion. To date, there is no effective treatment for this condition.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Progressive bifocal chorioretinal atrophy | c1833321 | 3,061 | gard | https://rarediseases.info.nih.gov/diseases/10123/progressive-bifocal-chorioretinal-atrophy | 2021-01-18T17:58:09 | {"mesh": ["C535356"], "omim": ["600790"], "umls": ["C1833321"], "orphanet": ["75373"], "synonyms": ["Chorioretinal atrophy, progressive bifocal", "PBCRA", "CRAPB"]} |
The costocoracoid ligament (of which an autosomal dominant congenital shortness has been described; see 122580) contains rests of chondrocytes and has the potential to ossify, notably in response to trauma. Spontaneous ossification of the costocoracoid ligament has also been reported. Nutter (1941) found radiologic evidence of ossification of the clavicular and coracoid insertions of the costocoracoid ligament in 1.2% of unselected shoulder x-rays. Formation of a true synovial joint between the insertional processes of the coracoid and the clavicle has often been described, including 1 large family in which the condition appeared to be inherited as an autosomal dominant trait (De Haas et al., 1965). In affected persons, formation of a costocoracoid joint can be either unilateral or bilateral. No medical or functional deficits have been noted.
Joints \- Coracoclavicular joint anomaly \- Costocoracoid ligament ossification Inheritance \- Autosomal dominant ▲ Close
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| CORACOCLAVICULAR JOINT, ANOMALOUS | c1852561 | 3,062 | omim | https://www.omim.org/entry/121350 | 2019-09-22T16:43:00 | {"mesh": ["C565161"], "omim": ["121350"]} |
This article does not cite any sources. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.
Find sources: "Intraocular hemorrhage" – news · newspapers · books · scholar · JSTOR (July 2018) (Learn how and when to remove this template message)
Intraocular hemorrhage
Schematic diagram of the human eye en
SpecialtyOphthalmology
Intraocular hemorrhage is bleeding (hemorrhage) into the eyeball (oculus in Latin. It may be the result of physical trauma (direct injury to the eye) or medical illness. Severe bleeding may cause high pressures inside the eye, leading to blindness.
## Contents
* 1 Types
* 2 Causes
* 3 Diagnosis
* 4 Treatment
* 5 References
* 6 External links
## Types[edit]
The types of ocular hemorrhages are classified based on where the bleeding is occurring:
* Subconjunctival hemorrhage (bleeding just underneath the conjunctiva)
* Intraocular hemorrhages:
* Hyphema (in the anterior chamber)
* In the posterior segment of eyeball:
* Vitreous hemorrhage (into the vitreous)
* Subretinal hemorrhage (under the retina)
* Submacular hemorrhage (under the macula)
## Causes[edit]
Different causes may cause bleeding in different locations.
* Terson's syndrome (as a result of subarachnoid hemorrhage)
* Hemophilia (a severe bleeding disorder, usually hereditary)
* Anticoagulants and thrombolysis (medication to reduce blood clotting tendency or to disperse blood clots, respectively)
The major causes of bleeding are injury diabetes mellitus hypertension.
## Diagnosis[edit]
Intraocular hemorrhage is typically diagnosed with slit lamp examination.
## Treatment[edit]
This section is empty. You can help by adding to it. (September 2017)
## References[edit]
## External links[edit]
Classification
D
* ICD-9-CM: 360.43
* MeSH: D005130
* v
* t
* e
* Diseases of the human eye
Adnexa
Eyelid
Inflammation
* Stye
* Chalazion
* Blepharitis
* Entropion
* Ectropion
* Lagophthalmos
* Blepharochalasis
* Ptosis
* Blepharophimosis
* Xanthelasma
* Ankyloblepharon
Eyelash
* Trichiasis
* Madarosis
Lacrimal apparatus
* Dacryoadenitis
* Epiphora
* Dacryocystitis
* Xerophthalmia
Orbit
* Exophthalmos
* Enophthalmos
* Orbital cellulitis
* Orbital lymphoma
* Periorbital cellulitis
Conjunctiva
* Conjunctivitis
* allergic
* Pterygium
* Pseudopterygium
* Pinguecula
* Subconjunctival hemorrhage
Globe
Fibrous tunic
Sclera
* Scleritis
* Episcleritis
Cornea
* Keratitis
* herpetic
* acanthamoebic
* fungal
* Exposure
* Photokeratitis
* Corneal ulcer
* Thygeson's superficial punctate keratopathy
* Corneal dystrophy
* Fuchs'
* Meesmann
* Corneal ectasia
* Keratoconus
* Pellucid marginal degeneration
* Keratoglobus
* Terrien's marginal degeneration
* Post-LASIK ectasia
* Keratoconjunctivitis
* sicca
* Corneal opacity
* Corneal neovascularization
* Kayser–Fleischer ring
* Haab's striae
* Arcus senilis
* Band keratopathy
Vascular tunic
* Iris
* Ciliary body
* Uveitis
* Intermediate uveitis
* Hyphema
* Rubeosis iridis
* Persistent pupillary membrane
* Iridodialysis
* Synechia
Choroid
* Choroideremia
* Choroiditis
* Chorioretinitis
Lens
* Cataract
* Congenital cataract
* Childhood cataract
* Aphakia
* Ectopia lentis
Retina
* Retinitis
* Chorioretinitis
* Cytomegalovirus retinitis
* Retinal detachment
* Retinoschisis
* Ocular ischemic syndrome / Central retinal vein occlusion
* Central retinal artery occlusion
* Branch retinal artery occlusion
* Retinopathy
* diabetic
* hypertensive
* Purtscher's
* of prematurity
* Bietti's crystalline dystrophy
* Coats' disease
* Sickle cell
* Macular degeneration
* Retinitis pigmentosa
* Retinal haemorrhage
* Central serous retinopathy
* Macular edema
* Epiretinal membrane (Macular pucker)
* Vitelliform macular dystrophy
* Leber's congenital amaurosis
* Birdshot chorioretinopathy
Other
* Glaucoma / Ocular hypertension / Primary juvenile glaucoma
* Floater
* Leber's hereditary optic neuropathy
* Red eye
* Globe rupture
* Keratomycosis
* Phthisis bulbi
* Persistent fetal vasculature / Persistent hyperplastic primary vitreous
* Persistent tunica vasculosa lentis
* Familial exudative vitreoretinopathy
Pathways
Optic nerve
Optic disc
* Optic neuritis
* optic papillitis
* Papilledema
* Foster Kennedy syndrome
* Optic atrophy
* Optic disc drusen
Optic neuropathy
* Ischemic
* anterior (AION)
* posterior (PION)
* Kjer's
* Leber's hereditary
* Toxic and nutritional
Strabismus
Extraocular muscles
Binocular vision
Accommodation
Paralytic strabismus
* Ophthalmoparesis
* Chronic progressive external ophthalmoplegia
* Kearns–Sayre syndrome
palsies
* Oculomotor (III)
* Fourth-nerve (IV)
* Sixth-nerve (VI)
Other strabismus
* Esotropia / Exotropia
* Hypertropia
* Heterophoria
* Esophoria
* Exophoria
* Cyclotropia
* Brown's syndrome
* Duane syndrome
Other binocular
* Conjugate gaze palsy
* Convergence insufficiency
* Internuclear ophthalmoplegia
* One and a half syndrome
Refraction
* Refractive error
* Hyperopia
* Myopia
* Astigmatism
* Anisometropia / Aniseikonia
* Presbyopia
Vision disorders
Blindness
* Amblyopia
* Leber's congenital amaurosis
* Diplopia
* Scotoma
* Color blindness
* Achromatopsia
* Dichromacy
* Monochromacy
* Nyctalopia
* Oguchi disease
* Blindness / Vision loss / Visual impairment
Anopsia
* Hemianopsia
* binasal
* bitemporal
* homonymous
* Quadrantanopia
subjective
* Asthenopia
* Hemeralopia
* Photophobia
* Scintillating scotoma
Pupil
* Anisocoria
* Argyll Robertson pupil
* Marcus Gunn pupil
* Adie syndrome
* Miosis
* Mydriasis
* Cycloplegia
* Parinaud's syndrome
Other
* Nystagmus
* Childhood blindness
Infections
* Trachoma
* Onchocerciasis
This article about an ophthalmic disease is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Intraocular hemorrhage | c0015402 | 3,063 | wikipedia | https://en.wikipedia.org/wiki/Intraocular_hemorrhage | 2021-01-18T18:53:51 | {"mesh": ["D005130"], "umls": ["C0015402"], "wikidata": ["Q17067160"]} |
This article may require cleanup to meet Wikipedia's quality standards. The specific problem is: the writing style should be improved Please help improve this article if you can. (November 2012) (Learn how and when to remove this template message)
A hand imitating an ulnar claw. The metacarpophalangeal joints of the 4th and 5th fingers are extended and the Interphalangeal joints of the same fingers are flexed.
An ulnar claw, also known as claw hand, or 'spinster's claw' is a deformity or an abnormal attitude of the hand that develops due to ulnar nerve damage causing paralysis of the lumbricals. A claw hand presents with a hyperextension at the metacarpophalangeal joints and flexion at the proximal and distal interphalangeal joints of the 4th and 5th fingers. The patients with this condition can make a full fist but when they extend their fingers, the hand posture is referred to as claw hand. The ring- and little finger can usually not fully extend at the proximal interphalangeal joint (PIP).
This can be commonly confused with the "hand of benediction or pope's blessing", which is caused by proximal (at elbow level) median nerve damage.
## Contents
* 1 Presentation
* 1.1 Ulnar nerve symptoms
* 2 Causes
* 3 Pathogenesis
* 3.1 Ulnar paradox
* 4 Prevention
* 4.1 Dupuytren's contracture
* 4.2 Klumpke paralysis
* 5 Treatment
* 6 Incidence
* 7 References
* 8 External links
## Presentation[edit]
Patients exhibiting an ulnar claw are also very frequently unable to spread (abduct) or pull together (adduct) their fingers against resistance. This occurs because the ulnar nerve also innervates the palmar and dorsal interossei of the hand. Patients with this deficit will become increasingly easy to identify over time as the paralysed first dorsal interosseous muscle atrophies, leaving a prominent hollowing between the thumb and forefinger.
### Ulnar nerve symptoms[edit]
The ulnar nerve runs from the shoulder to the hand, and damage to it results in the Ulnar claw. It is linked to palsy, which is a result of peripheral neuropathy. There is a range of ways that damage to the nerve can occur. Leaning on the elbow can lead to long-term wear and tear due to the prolonged pressure of the weight of the upper body. Symptoms resulting from leaning on the nerve can include numbness and tingling fingers.
## Causes[edit]
Common occupations such as cyclist, motorcyclist, and desk jobs prolong movement and elbow leaning. These activities involve pressure to the palms, which leads to cumulative damage to the nerve.[1] When using a pizza cutter or similar hand tools which require downward pressure during use, applying upper body weight to push down on the tool over time can cause damage to the nerve.[2]
## Pathogenesis[edit]
An ulnar claw may follow an ulnar nerve lesion[3] which results in the partial or complete denervation of the ulnar (medial) two lumbricals of the hand. Since the ulnar nerve also innervates the 3rd and 4th lumbricals, which flex the MCP joints (aka the knuckles), their denervation causes these joints to become extended by the now unopposed action of the long finger extensors (namely the extensor digitorum and the extensor digiti minimi). The lumbricals and interossei also extend the IP (interphalangeal) joints of the fingers by insertion into the extensor hood; their paralysis results in weakened extension. The combination of hyperextension at the MCP and flexion at the IP joints gives the hand its claw like appearance.[4]
### Ulnar paradox[edit]
The ulnar nerve also innervates the ulnar (medial) half of the flexor digitorum profundus muscle (FDP). If the ulnar nerve lesion occurs more proximally (closer to the elbow), the flexor digitorum profundus muscle may also be denervated.[5] As a result, flexion of the IP joints is weakened, which reduces the claw-like appearance of the hand.[6] (Instead, the fourth and fifth fingers are simply paralyzed in their fully extended position.) This is called the "ulnar paradox" because one would normally expect a more proximal and thus debilitating injury to result in a more deformed appearance.
Simply put, as reinnervation occurs along the ulnar nerve after a high lesion, the deformity will get worse (FDP reinnervated) as the patient recovers - hence the use of the term "paradox". A simple way to remember this is: 'the closer to the Paw, the worse the Claw'.
## Prevention[edit]
Preventive therapy is recommended to preserve the function of the fingers. This may include physical exercise, stretching, proper bodily function and myofascial release (massage, foam roller). Exercises are focused on the forearm muscles, such as the extensor carpi ulnaris; extensor digitorum to antagonize the flexion of the fingers.
Massaging the forearm muscles also alleviates the tightness that occurs with muscles exertion. Stretching allows the muscles more flexibility, decreasing interference with the innervations of the ulnar nerve to the fingers.
Main article: Hand of benediction
The so-called "Hand of Benediction" is caused by median nerve lesions. The hand will show hyperextension of the metacarpophalangeal joints (MCP) from the unopposed extensor digitorum as well as weakened extension and flexion of the Interphalangeal (IP) joints of the 2nd and 3rd digits (index and middle) due to deficits in the radial lumbricals and lateral half of the flexor digitorum profundus. The pathogenesis is similar to that of ulnar clawing (loss of the relevant lumbricals and the flexor digitorum profundus along with unopposed action of forearm extensors), and a median claw hand will appear similar to an ulnar claw when the patient with a median claw is asked to make a fist.
The following signs may be used to clinically distinguish median nerve clawing from ulnar nerve clawing.
Ulnar nerve Median nerve
Deficit is primarily in 4th and 5th fingers Deficit is primarily in 2nd and 3rd fingers.
Deficit is most prominent at rest and when the patient is asked to extend his fingers. Deficit is most prominent when the patient is asked to make a fist.
Often accompanied by inability to abduct or adduct the 2nd, 3rd, 4th, and 5th finger. Often accompanied by difficulty opposing the thumb.
Often accompanied by apparent atrophy of the first dorsal interosseous muscle of the hand Often accompanied by wasting of muscles of the thenar eminence
### Dupuytren's contracture[edit]
Main article: Dupuytren's contracture
Dupuytren's contracture is a deformity of the hand due to thickening and fibrosis of the palmar aponeurosis and eventual contracture of the 4th and 5th digits. Presenting as a small hard nodule in the base of the ring finger, it tends to affect the ring and little finger as puckering and adherence of the palmar aponeurosis to the skin. Eventually the MCP and IP joints of the 4th and 5th digits become permanently flexed. This claw appearance can be distinguished from an ulnar claw in that the MCP is flexed in Dupuytren’s but hyperextended in ulnar nerve injuries.
### Klumpke paralysis[edit]
Main article: Klumpke paralysis
A claw hand can result of injuries to the inferior brachial plexus (C8 - T1). The condition may arise from the limb being suddenly pulled upward. For example, Klumpke paralysis can occur from excessive pulling of the infant's forelimb during parturition.
## Treatment[edit]
Treatments excluding surgery can include physical therapy and occupational therapy rehabilitation. Range of motion can be regained by using hand splints to stretch the impaired hand and to prevent overstretching. Using splints will initiate flexion in the metacarpophalangeal joints while also allowing extensions and flexion in the interphalangeal joints, thus increasing range of motion.
Beneficial exercise will be any that strengthens the interosseous muscles and lumbricals. By exercising individual fingers and thumb in adduction and abduction motion in pronation position, interosseous muscles will gain strength. Exercises to strengthen lumbricals, strengthen flexion in the metacarpophalangeal joint, and extension in the interphalangeal joints are beneficial. Repetitive motion of pronation and supination are also effective exercises for rehabilitation. Exercising pronation and supination with a handle or screwdriver attachment will help stimulate the nerves. A lateral pinch and recurring grip can also be applied for supination and pronation.
## Incidence[edit]
Older males are more likely to have ulnar mononeuropathy than females without regard to BMI.[7] 95% of females with a BMI less than a 22.0 have a higher risk of ulnar nerve damage from a lack of adipose “cushion”, and external compression at the elbow is a more important cause of ulnar mononeuropathy among females than males.[7] Both males and females with high grip strength, such as string musicians, are more susceptible to ulnar mononeuropathy, as are those who experience severe or sustained compression of the ulnar nerve.[7]
## References[edit]
1. ^ Akuthota, V.; Plastaras, C.; Lindberg, K.; Tobey, J.; Press, J.; Garvan, C. (Aug 2005). "The effect of long-distance bicycling on ulnar and median nerves: an electrophysiologic evaluation of cyclist palsy". Am J Sports Med. 33 (8): 1224–30. doi:10.1177/0363546505275131. PMID 16000656. S2CID 3114623.
2. ^ Jones, HR. (Aug 1988). "Pizza cutter's palsy". N Engl J Med. 319 (7): 450. doi:10.1056/nejm198808183190718. PMID 3398902.
3. ^ Neiman R, Maiocco B, Deeney VF (1998). "Ulnar nerve injury after closed forearm fractures in children". J Pediatr Orthop. 18 (5): 683–5. doi:10.1097/00004694-199809000-00026. PMID 9746426.
4. ^ http://teachmeanatomy.info/the-ulnar-nerve/
5. ^ "medCampus". www.medcampus.io. 2019. Retrieved 2020-10-11.
6. ^ http://www.orthoteers.org/content/documents/Exam_hand.pdf
7. ^ a b c Richardson JK., Green DF., Jamieson SC., Valentin FC (April 2001). "Gender, body mass and age as risk factors for ulnar mononeuropathy at the elbow" (PDF). Muscle Nerve. 24 (4): 551–4. doi:10.1002/mus.1039. hdl:2027.42/34633. PMID 11268028. S2CID 9823171.CS1 maint: multiple names: authors list (link)
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| Ulnar claw | c4025799 | 3,064 | wikipedia | https://en.wikipedia.org/wiki/Ulnar_claw | 2021-01-18T18:32:58 | {"wikidata": ["Q3071050"]} |
## Summary
### Clinical description.
In adults, X-linked spondyloepiphyseal dysplasia tarda (X-linked SEDT) is characterized by disproportionately short stature with short trunk and arm span significantly greater than height. At birth, affected males are normal in length and have normal body proportions. Affected males exhibit linear growth deficiency beginning around age six to eight years. Final adult height is typically 137-163 cm. Progressive joint and back pain with osteoarthritis ensues; hip, knee, and shoulder joints are commonly involved but to a variable degree. Hip replacement is often required as early as age 40 years. Interphalangeal joints are typically spared. Motor and cognitive milestones are normal.
### Diagnosis/testing.
The clinical diagnosis of X-linked SEDT can be established in a male proband with characteristic radiographic findings (which typically appear prior to puberty) including: multiple epiphyseal abnormalities, platyspondyly with characteristic superior and inferior "humping" seen on lateral view, scoliosis, hypoplastic odontoid process, short femoral necks, and coxa vara; evidence of premature osteoarthritis appears in young adulthood. The molecular diagnosis of X-linked SEDT can be established in a male proband with suggestive findings and a hemizygous pathogenic variant in TRAPPC2 identified by molecular genetic testing. The molecular diagnosis of X-linked SEDT can be established in a female proband with osteoarthritis and a heterozygous pathogenic variant in TRAPPC2 identified by molecular genetic testing.
### Management.
Treatment of manifestations: Treatment for scoliosis and kyphoscoliosis per orthopedic surgeon; surgical intervention may include spine surgery (correction of scoliosis or kyphosis). Pain management as needed for osteoarthritis; joint replacement (hip, knee, shoulder) as needed.
Surveillance: Cervical spine films prior to school age and before any surgical procedure involving general anesthesia to assess for clinically significant odontoid hypoplasia. Annual follow up for assessment scoliosis and joint pain.
Agents/circumstances to avoid: Extreme neck flexion and extension in individuals with odontoid hypoplasia. Activities and occupations that place undue stress on the spine and weight-bearing joints.
Evaluation of relatives at risk: Presymptomatic testing in males at risk may obviate unnecessary diagnostic testing for other causes of short stature and/or osteoarthritis.
### Genetic counseling.
By definition, X-linked SEDT is inherited in an X-linked manner. When performed, molecular genetic testing of all mothers of affected sons determined that regardless of family history all were carriers of a pathogenic variant in TRAPPC2. Carrier females are at a 50% risk of transmitting the TRAPPC2 pathogenic variant in each pregnancy: males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be carriers and will not be affected. None of the sons of an affected male will be affected; all daughters will be carriers of the TRAPPC2 pathogenic variant. Carrier testing of at-risk female relatives and prenatal testing for pregnancies at increased risk are possible if the pathogenic variant in the family has been identified.
## Diagnosis
No consensus clinical diagnostic criteria for X-linked spondyloepiphyseal dysplasia tarda have been published.
### Suggestive Findings
X-linked spondyloepiphyseal dysplasia tarda (X-linked SEDT) should be suspected in males with the following findings:
* Disproportionate short stature in adolescence or adulthood and a relatively short trunk and barrel-shaped chest. Upper- to lower-body segment ratio is usually about 0.8. Arm span typically exceeds height by 10-20 cm. Short neck, dorsal kyphosis, and lumbar hyperlordosis may be evident by puberty.
* Early-onset osteoarthritis, especially in the hip joints
* A family history consistent with X-linked recessive inheritance. A positive family history is contributory but not necessary.
* Absence of cleft palate and retinal detachment (frequently present in SED congenita; see Differential Diagnosis)
### Establishing the Diagnosis
The clinical diagnosis of X-linked SEDT can be established in a male proband with characteristic radiographic findings or the molecular diagnosis can be established in a male proband with suggestive findings and a hemizygous pathogenic variant in TRAPPC2 identified by molecular genetic testing (see Table 1) if radiographic findings are inconclusive.
#### Radiographic Findings
The following radiographic findings may not be manifest in an affected male in early childhood and typically appear prior to puberty (Figure 1):
#### Figure 1.
Radiographs of a male age 31 years with SEDT A. Platyspondyly with superior and inferior humping of vertebral bodies
* Multiple epiphyseal abnormalities
* Platyspondyly (flattened vertebral bodies) with characteristic superior and inferior "humping" seen on lateral view; narrow disc spaces in adulthood
* Scoliosis / kyphoscoliosis
* Hypoplastic odontoid process
* Short femoral necks
* Coxa vara
* Evidence of premature osteoarthritis beginning in young adulthood
Radiographs of symptomatic males should be reviewed by a radiologist experienced with bone dysplasias.
#### Molecular Genetic Testing
Testing approaches can include single-gene testing and a multigene panel:
* Single-gene testing. Sequence analysis of TRAPPC2 is performed first to detect small intragenic deletions/insertions and missense, nonsense, and splice site variants. Note: Depending on the sequencing method used, single-exon, multiexon, or whole-gene deletions/duplications may not be detected. If no variant is detected by the sequencing method used, the next step is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications.
Note: Lack of amplification by PCR prior to sequence analysis can suggest a putative (multi)exon or whole-gene deletion on the X chromosome in affected males; confirmation requires additional testing by gene-targeted deletion/duplication analysis.
* A multigene panel that includes TRAPPC2 and other genes of interest (see Differential Diagnosis) may also be considered. This method may be especially useful if expert radiographic interpretation is not available. 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 X-linked Spondyloepiphyseal Dysplasia Tarda
View in own window
Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method
TRAPPC2Sequence analysis 3, 484% 5
Gene-targeted deletion/duplication analysis 616% 7
Unknown 8NARare
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\.
Lack of amplification by PCR prior to sequence analysis can suggest a putative (multi)exon or whole-gene deletion on the X chromosome in affected males; confirmation requires additional testing by gene-targeted deletion/duplication analysis.
5\.
Data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2017]
6\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.
7\.
Males initially suspected on sequence analysis of having a deletion in whom the deletion is subsequently confirmed by deletion/duplication analysis
8\.
It is unknown whether negative molecular analysis reflects locus heterogeneity or clinical misdiagnosis.
## Clinical Characteristics
### Clinical Description
Males. At birth, affected males are normal in length and have normal body proportions. Affected males exhibit linear growth deficiency beginning around grade school (age 6-8 years). Adults with X-linked spondyloepiphyseal dysplasia tarda (X-linked SEDT) have disproportionately short stature with short trunk and arm span significantly greater than height. Final adult height is typically 137-163 cm [Whyte et al 1999, Jones et al 2013, Rimoin et al 2013].
Scoliosis/kyphoscoliosis and odontoid hypoplasia are known radiographic features. Data on the incidence, onset, and severity of these features have not been published.
Osteoarthritis. Progressive joint and back pain with osteoarthritis ensues; hip, knee, and shoulder joints are commonly involved to variable degrees. Hip replacement is often required as early as age 40 years. Interphalangeal joints are typically spared.
Affected males achieve normal motor and cognitive milestones. Life span and intelligence appear normal.
Heterozygous females. Carrier females typically show no phenotypic changes, but mild symptoms of osteoarthritis have been reported [Whyte et al 1999].
### Genotype-Phenotype Correlations
Data are inadequate to reliably correlate clinical severity to a specific TRAPPC2 pathogenic variant. All pathogenic variants identified thus far, irrespective of their molecular basis, result in an almost identical phenotype, including the true null variants.
### Nomenclature
Spondyloepiphyseal dysplasia is a general term that describes the radiographic abnormalities seen in several skeletal dysplasias, including pseudoachondroplasia. The "congenita" form is evident at birth, whereas the "tarda" form is usually evident by school age.
SED tarda commonly refers to the X-linked recessive form of the disorder, although rare autosomal dominant and autosomal recessive "tarda" forms have been described.
### Prevalence
The prevalence is 1:150,000-1:200,000 [Wynne-Davies & Gormley 1985].
Pathogenic variants in TRAPPC2 have been found in several populations including European [Gedeon et al 2001], Japanese [Matsui et al 2001], and Chinese [Shu et al 2002], an observation suggesting that no specific population is at increased risk.
## Differential Diagnosis
X-linked spondyloepiphyseal dysplasia tarda (X-linked SEDT) is distinguished from other forms of spondyloepiphyseal dysplasia (SED) by its later onset and X-linked inheritance (see Table 2).
### Table 2.
Forms of Spondyloepiphyseal Dysplasia of Interest in the Differential Diagnosis of X-Linked Spondyloepiphyseal Dysplasia Tarda
View in own window
Gene(s)DisorderMOIClinical Features of Differential Diagnosis DisorderDistinguishing Features/
Comment
CCN6
(WISP3)Progressive pseudorheumatoid dysplasia (PED)ARPredominant involvement of articular cartilage w/progressive joint stiffness & enlargement & w/o inflammation. Onset (age ~3-6 yrs) begins w/involvement of interphalangeal joints; later involvement of large joints & spine causes significant joint contractures, gait disturbance, & scoliosis &/or kyphosis, → abnormal posture & significant morbidity. Short stature (<3rd centile) becomes evident in adolescence.Unlike X-linked SEDT, joint swelling & hand involvement are common features of PED.
COL2A1SED congenita (SEDC) (See Type II Collagen Disorders Overview.)AD 1Usually evident at birth w/disproportionate short stature, short extremities, broad chest, characteristic facies, myopia, & ↑ incidence of cleft palate & hearing loss. Delayed/poor ossification of vertebrae & pubic bones; long bones are short w/hypoplastic epiphyses. ↑ risk for tracheolaryngomalacia & related respiratory complications & retinal detachment. ↑ risk for cervical instability.SED congenita is most common form of SED.
Spondyloperipheral dysplasia (See Type II Collagen Disorders Overview.)ADMild-to-moderate disproportionate short stature & short extremities, brachydactyly type E, short ulnae, variable clubfeet, cleft palate, myopia, & hearing loss; ovoid vertebra, delayed ossification of pubic bones, & flattened & irregular epiphyses in long bones. Premature hip arthrosis causes joint pain.
COL2A1
COL9A1
COL9A2
COL9A3
COL11A1
COL11A2Stickler syndromeAD
AR 2Connective tissue disorder; can incl high myopia, hearing loss (both conductive & sensorineural); midfacial underdevelopment & cleft palate (either alone or as part of Robin sequence); & mild SED &/or precocious arthritis.
COL9A1
COL9A2
COL9A3
COMP
MATN3Multiple epiphyseal dysplasia, autosomal dominant (MED)ADPresents early in childhood, usually w/pain in hips &/or knees after exercise; affected children complain of fatigue w/long-distance walking; waddling gait may be present. Adult height in lower range of normal or mildly shortened; limbs relatively short compared to trunk; progressive pain & joint deformity → early-onset osteoarthritis esp of large weight-bearing joints.By definition, spine in MED is normal, although Schmorl bodies & irregular vertebral end plates may be observed.
GALNS
GLB1Morquio syndrome (MPS IVA & MPS IVB) (See GLB1 Disorders.)ARDysostosis multiplex, odontoid hypoplasia, short stature, hepatomegaly & cloudy corneas
AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance; MPS = mucopolysaccharidosis; SED = spondyloepiphyseal dysplasia; SEDT = spondyloepiphyseal dysplasia tarda
1\.
Rare instances of autosomal recessive inheritance in SEDC have been reported (see Type II Collagen Disorders Overview).
2\.
Stickler syndrome caused by pathogenic variants in COL2A1, COL11A1, or COL11A2 is inherited in an autosomal dominant manner; Stickler syndrome caused by pathogenic variants in COL9A1, COL9A2, or COL9A3 is inherited in an autosomal recessive manner.
Other
* SED tarda, autosomal forms (rare). A dominant form (OMIM 184100) may be caused by pathogenic variants in COL2A1; a recessive form has been described clinically but not molecularly defined.
* Scheuermann disease (OMIM 181440) is a term applied to premature osteoarthritis of the spine regardless of etiology.
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with X-linked spondyloepiphyseal dysplasia tarda (X-linked SEDT), the evaluations summarized in Table 3 (if not performed as part of the evaluation that led to the diagnosis) are recommended:
### Table 3.
Recommended Evaluations Following Initial Diagnosis in Individuals with X-linked Spondyloepiphyseal Dysplasia Tarda
View in own window
System/ConcernEvaluationComment
SkeletonComplete radiographic survey to incl scoliosis series if clinically indicatedTo assess extent of skeletal manifestations
Cervical spine
* Flexion-extension radiographs of cervical spine
* Flexion-extension MRI if instability & compression seen on radiographs or interpretation on radiographs is limited (e.g., in young patients w/delayed ossification in upper cervical spine)
To assess for clinically significant odontoid hypoplasia
Genetic
counselingBy genetics professionals 1To inform patients & their families re nature, MOI, & implications of SEDT in order to facilitate medical & personal decision making
MOI= mode of inheritance
1\.
Medical geneticist, certified genetic counselor, certified advanced genetic nurse
### Treatment of Manifestations
### Table 4.
Treatment of Manifestations in Individuals with X-linked Spondyloepiphyseal Dysplasia Tarda
View in own window
Manifestation/
ConcernTreatmentConsiderations/
Other
Odontoid
hypoplasiaPrecautions during intubation/surgery to avoid hyperextensionObtain cervical spinal films prior to any surgical procedure involving general anesthesia to assess for clinically significant odontoid hypoplasia.
Scoliosis/
Kyphoscoliosis
* Treatment per orthopedic surgeon
* Spine surgery (correction of scoliosis or kyphosis) may be indicated.
Osteoarthritis
* Chronic pain management
* Surgical intervention may incl joint replacement (hip, knee, shoulder).
### Surveillance
### Table 5.
Recommended Surveillance for Individuals with X-linked Spondyloepiphyseal Dysplasia Tarda
View in own window
System/ConcernEvaluationFrequency
Odontoid hypoplasiaFlexion-extension radiographs of cervical spineObtain prior to school age to assess for clinically significant odontoid hypoplasia.
Scoliosis/
KyphoscoliosisClinical eval w/spine radiographs if clinically indicatedAnnually
OsteoarthritisClinical eval for osteoarthritisAnnually
### Agents/Circumstances to Avoid
The following should be avoided:
* In individuals with odontoid hypoplasia, extreme neck flexion and extension
* Activities and occupations that place undue stress on the spine and weight-bearing joints
### Evaluation of Relatives at Risk
If the TRAPPC2 pathogenic variant in the family is known, presymptomatic genetic testing of at-risk males allows early diagnosis and may obviate unnecessary diagnostic testing for other causes of short stature and/or osteoarthritis.
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.
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*[AA]: Adrenergic agonist
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*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| X-Linked Spondyloepiphyseal Dysplasia Tarda | c3541456 | 3,065 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1145/ | 2021-01-18T20:48:07 | {"mesh": ["D010009"], "synonyms": []} |
Gunal et al. (1993) described 5 members of a family who had osteopoikilosis (166700) in association with dacryocystitis. Inheritance appeared to be autosomal dominant. Chromosome analysis showed normal karyotype in all patients.
Skel \- Osteopoikilosis Inheritance \- Autosomal dominant HEENT \- Dacryocystitis ▲ 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
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| OSTEOPOIKILOSIS AND DACRYOCYSTITIS | c1833698 | 3,066 | omim | https://www.omim.org/entry/166705 | 2019-09-22T16:36:50 | {"mesh": ["C536061"], "omim": ["166705"], "orphanet": ["1562"]} |
Unilateral choanal atresia is a, usually sporadic, congenital anomaly that is more commonly seen in females than in males (2:1), where the nose is blocked by bony or soft tissue formed during embryologic development on only one side (more commonly on the right side) and which is characterized by nasal obstruction and rhinorrhea, usually presenting at birth but that may go undetected until a respiratory infection aggravates the condition.
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*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Choanal atresia, unilateral | None | 3,067 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=137917 | 2021-01-23T18:01:00 | {"icd-10": ["Q30.0"]} |
This article is about the disease. For the parasite, see Giardia.
Parasitic disease that results in diarrhea
Giardiasis
Other namesBeaver fever, giardia
Giardia cell, SEM
SpecialtyInfectious disease
SymptomsDiarrhea, abdominal pain, weight loss, nausea[1]
Usual onset1 to 3 weeks after exposure[2]
CausesGiardia duodenalis spread mainly through contaminated food or water[1]
Risk factorsHypogammaglobulinemia
Diagnostic methodStool testing[1]
Differential diagnosisIrritable bowel syndrome[1]
PreventionImproved sanitation[1]
TreatmentAntiprotozoal medications
MedicationTinidazole, metronidazole[1]
FrequencyUp to 7% (developed world), up to 30% (developing world)[1]
Giardiasis is a parasitic disease caused by Giardia duodenalis (also known as G. lamblia and G. intestinalis).[3] About 10% of those infected have no symptoms.[1] When symptoms occur they may include diarrhea, abdominal pain, and weight loss.[1] Vomiting, blood in the stool, and fever are less common.[1] Symptoms usually begin 1 to 3 weeks after exposure and without treatment may last up to six weeks.[2]
Giardia usually spreads when Giardia duodenalis cysts within feces contaminate food or water which is then eaten or drunk.[1] It may also spread between people and from other animals.[1] Risk factors include travel in the developing world, changing diapers, eating food without cooking it, and owning a dog.[1] Cysts may survive for nearly three months in cold water.[1] Diagnosis is via stool tests.[1]
Prevention is typically by improved hygiene.[1] Those without symptoms do not usually need treatment.[1] When symptoms are present treatment is typically with either tinidazole or metronidazole.[1] People who are not already lactose intolerant may become so temporarily after an infection and therefore it is often recommended milk be avoided for a few weeks.[1] Resistance to treatment may occur.[1]
Giardia is one of the most common parasitic human diseases globally.[3] In 2013, there were about 280 million people worldwide with symptomatic giardiasis.[3] Rates are as high as 7% in the developed world and 30% in the developing world.[1] The World Health Organization classified it as a neglected disease.[1]
## Contents
* 1 Signs and symptoms
* 2 Cause
* 2.1 Risk factors
* 2.2 Transmission
* 3 Pathophysiology
* 4 Diagnosis
* 5 Prevention
* 6 Treatment
* 7 Prognosis
* 8 Epidemiology
* 9 Research
* 10 Other animals
* 11 References
* 12 External links
## Signs and symptoms[edit]
Symptoms vary from none to severe diarrhea with poor absorption of nutrients.[4] The cause of this wide range in severity of symptoms is not fully known but the intestinal flora of the infected host may play a role.[5][6] Diarrhea is less likely to occur in people from developing countries.[5]
Symptoms typically develop 9–15 days after exposure,[7] but may occur as early as one day.[4] The most common and prominent symptom is chronic diarrhea which can occur for weeks or months if untreated.[8][9] Diarrhea is often greasy and foul-smelling, with a tendency to float.[8][10] This characteristic diarrhea is often accompanied by a number of other symptoms, including gas, abdominal cramps, and nausea or vomiting.[8][10] Some people also experience symptoms outside of the gastrointestinal tract such as itchy skin, hives, and swelling of the eyes and joints, although these are less common.[10] Despite its nickname "beaver fever",[11] fever occurs in only about 15% of people.[12]
Prolonged disease is often characterized by diarrhea along with malabsorption of nutrients in the intestine.[8] This malabsorption results in fatty stools, substantial weight loss, and fatigue.[8] Additionally, those suffering from giardiasis often have difficulty absorbing lactose, vitamin A, folate, and vitamin B12.[9][10] In children, prolonged giardiasis can cause failure to thrive and may impair mental development.[8][9] Symptomatic infections are well recognized as causing lactose intolerance,[13] which, while usually temporary, may become permanent.[14][15]
## Cause[edit]
Giardiasis is caused by the protozoan Giardia duodenalis.[16] The infection occurs in many animals including beavers (hence its nickname), as well as cows, other rodents, and sheep.[16] Animals are believed to play a role in keeping infections present in an environment.[16]
G. duodenalis has been sub-classified into eight genetic assemblages (designated A–H).[17] Genotyping of G. duodenalis isolated from various hosts has shown that assemblages A and B infect the largest range of host species, and appear to be the main and possibly only G. duodenalis assemblages that infect humans.[17][18]
### Risk factors[edit]
According to the CDC, "Those at greatest risk are travelers to countries where giardiasis is common, people in child care settings, those who are in close contact with someone who has the disease, people who swallow contaminated drinking water, backpackers or campers who drink untreated water from lakes or rivers, people who have contact with animals who have the disease, and men who have sex with men."[19]
In the United States, giardiasis occurs more often during the summer.[16] This is believed to be due to a greater amount of time spent on outdoor activities and traveling in the wilderness.[16]
### Transmission[edit]
Giardiasis is transmitted via the fecal-oral route with the ingestion of cysts.[7] Primary routes are personal contact and contaminated water and food.[7] The cysts can stay infectious for up to three months in cold water.[16]
Many people with Giardia infections have no or few symptoms.[20] They may, however, still spread the disease.[20]
## Pathophysiology[edit]
Life cycle of Giardia
The life cycle of Giardia consists of a cyst form and a trophozoite form.[6] The cyst form is infectious and once it has found a host, transforms into the trophozoite form.[6] This trophozoite attaches to the intestinal wall and replicates within the gut.[6] As trophozoites continue along the gastrointestinal tract, they convert back to their cyst form which are then excreted with feces.[1] Ingestion of only a few of these cysts is needed to generate infection in another host.[21]
Infection with Giardia results in decreased expression of brush border enzymes, morphological changes to the microvillus, increased intestinal permeability, and programmed cell death of small intestinal epithelial cells.[22] Both trophozoites and cysts are contained within the gastrointestinal tract and do not invade beyond it.[23]
The attachment of trophozoites causes villus flattening and inhibition of enzymes that break down disaccharide sugars in the intestines.[5][22] Ultimately, the community of microorganisms that lives in the intestine may overgrow and may be the cause of further symptoms, though this idea has not been fully investigated. The alteration of the villi leads to an inability of nutrient and water absorption from the intestine, resulting in diarrhea, one of the predominant symptoms.[22] In the case of asymptomatic giardiasis, there can be malabsorption with or without histological changes to the small intestine. The degree to which malabsorption occurs in symptomatic and asymptomatic cases is highly varied.
The species Giardia intestinalis uses enzymes that break down proteins to attack the villi of the brush border and appears to increase crypt cell proliferation and crypt length of crypt cells existing on the sides of the villi. On an immunological level, activated host T lymphocytes attack endothelial cells that have been injured in order to remove the cell.[5] This occurs after the disruption of proteins that connect brush border endothelial cells to one another.[22] The result is increased intestinal permeability.[22]
There appears to be a further increase in programmed enterocyte cell death by Giardia intestinalis, which further damages the intestinal barrier and increases permeability.[22] There is significant upregulation of the programmed cell death cascade by the parasite, and, furthermore, substantial downregulation of the anti-apoptotic protein Bcl-2 and upregulation of the proapoptotic protein Bax.[5] These connections suggest a role of caspase-dependent apoptosis in the pathogenesis of giardiasis.[5]
Giardia protects its own growth by reducing the formation of the gas nitric oxide by consuming all local arginine, which is the amino acid necessary to make nitric oxide.[5] Arginine starvation is known to be a cause of programmed cell death, and local removal is a strong apoptotic agent.[24]
## Diagnosis[edit]
* According to the CDC, detection of antigens on the surface of organisms in stool specimens is the current test of choice for diagnosis of giardiasis and provides increased sensitivity over more common microscopy techniques.[25]
* A trichrome stain of preserved stool is another method used to detect Giardia.[26]
* Microscopic examination of the stool can be performed for diagnosis.[1] This method is not preferred, however, due to inconsistent shedding of trophozoites and cysts in infected hosts.[1] Multiple samples over a period time, typically one week, must be examined.[1]
* The Entero-Test uses a gelatin capsule with an attached thread. One end is attached to the inner aspect of the host's cheek, and the capsule is swallowed. Later, the thread is withdrawn and shaken in saline to release trophozoites which can be detected with a microscope. The sensitivity of this test is low, however, and is not routinely used for diagnosis.[27]
* Immunologic enzyme-linked immunosorbent assay (ELISA) testing may be used for diagnosis.[28] These tests are capable of a 90% detection rate or more.[28]
Although hydrogen breath tests indicate poorer rates of carbohydrate absorption in those asymptomatically infected, such tests are not diagnostic of infection.[29] Serological tests are not helpful in diagnosis.[1]
## Prevention[edit]
The CDC recommends hand-washing and avoiding potentially contaminated food and untreated water.[30]
Boiling water contaminated with Giardia effectively kills infectious cysts.[31] Chemical disinfectants or filters may be used.[32][33] Iodine-based disinfectants are preferred over chlorination as the latter is ineffective at destroying cysts.[34][35]
Although the evidence linking the drinking of water in the North American wilderness and giardiasis has been questioned, a number of studies raise concern.[36] Most if not all CDC verified backcountry giardiasis outbreaks have been attributed to water. Surveillance data (for 2013 and 2014) reports six outbreaks (96 cases) of waterborne giardiasis contracted from rivers, streams or springs[37] and less than 1% of reported giardiasis cases are associated with outbreaks.[38]
Person-to-person transmission accounts for the majority of Giardia infections and is usually associated with poor hygiene and sanitation. Giardia is found on the surface of the ground, in the soil, in undercooked foods, and in water, and on hands without proper cleaning after handling infected feces.[39] Water-borne transmission is associated with the ingestion of contaminated water. In the U.S., outbreaks typically occur in small water systems using inadequately treated surface water. Venereal transmission happens through fecal-oral contamination. Additionally, diaper changing and inadequate hand washing are risk factors for transmission from infected children. Lastly, food-borne epidemics of Giardia have developed through the contamination of food by infected food-handlers.[40]
## Treatment[edit]
Treatment is not always necessary as the infection usually resolves on its own.[5] However, if the illness is acute or symptoms persist and medications are needed to treat it, a nitroimidazole medication is used such as metronidazole, tinidazole, secnidazole or ornidazole.[7]
The World Health Organization and Infectious Disease Society of America recommend metronidazole as first line therapy.[41][42] The US CDC lists metronidazole, tinidazole, and nitazoxanide as effective first-line therapies;[43] of these three, only nitazoxanide and tinidazole are approved for the treatment of giardiasis by the US FDA.[44][45][46] A meta-analysis done by the Cochrane Collaboration found that compared to the standard of metronidazole, albendazole had equivalent efficacy while having fewer side effects, such as gastrointestinal or neurologic issues.[47] Other meta-analyses have reached similar conclusions.[48] Both medications need a five to 10 day long course; albendazole is taken once a day, while metronidazole needs to be taken three times a day. The evidence for comparing metronidazole to other alternatives such as mebendazole, tinidazole or nitazoxanide was felt to be of very low quality.[47] While tinidazole has side effects and efficacy similar to those of metronidazole, it is administered with a single dose.[20]
Resistance has been seen clinically to both nitroimidazoles and albendazole, but not nitazoxanide, though nitazoxanide resistance has been induced in research laboratories.[21][49] The exact mechanism of resistance to all of these medications is not well understood.[49] In the case of nitroimidazole-resistant strains of Giardia, other drugs are available which have showed efficacy in treatment including quinacrine, nitazoxanide, bacitracin zinc, furazolidone and paromomycin.[20] Mepacrine may also be used for refractory cases.[21]
Probiotics, when given in combination with the standard treatment, has been shown to assist with clearance of Giardia.[50]
During pregnancy, paromomycin is the preferred treatment drug because of its poor intestinal absorption, resulting in less exposure to the fetus.[51] Alternatively, metronidazole can be used after the first trimester as there has been wide experience in its use for trichomonas in pregnancy.[52][53]
## Prognosis[edit]
In people with a properly functioning immune system, infection may resolve without medication.[5] A small portion, however, develop a chronic infection.[5] People with an impaired immune system are at higher risk of chronic infection.[5] Medication is an effective cure for nearly all people although there is growing drug-resistance.[1][54][21]
Children with chronic giardiasis are at risk for failure to thrive as well as more long-lasting sequelae such as growth stunting.[55] Up to half of infected people develop a temporary lactose intolerance leading symptoms that may mimic a chronic infection.[1] Some people experience post-infectious irritable bowel syndrome after the infection has cleared.[5] Giardiasis has also been implicated in the development of food allergies.[5] This is thought to be due to its effect on intestinal permeability.[5]
## Epidemiology[edit]
Rates of giardiasis in 2005 in the United States
In some developing countries Giardia is present in 30% of the population.[16] In the United States it is estimated that it is present in 3–7% of the population.[16]
The number of reported cases in the United States in 2018 was 15,584.[56] All states that classify giardiasis as a notifiable disease had cases of giardiasis.[56] The states of Illinois, Kentucky, Mississippi, North Carolina, Oklahoma, Tennessee, Texas, and Vermont did not notify the Center for Disease Control regarding cases in 2018.[56] The states with the highest number of cases in 2018 were California, New York, Florida, and Wisconsin.[56] There are seasonal trends associated with giardiasis.[57] July, August, and September are the months with the highest incidence of giardiasis in the United States.[58]
In the ECDC's (European Centre for Disease Prevention Control) annual epidemiological report containing 2014 data, 17,278 confirmed giardiasis cases were reported by 23 of the 31 countries that are members of the EU/EEA.[59] Germany reported the highest number at 4,011 cases.[59] Following Germany, the UK reported 3,628 confirmed giardiasis cases. Together, this accounts for 44% of total reported cases.[59]
## Research[edit]
Some intestinal parasitic infections may play a role in irritable bowel syndrome[60] and other long-term sequelae such as chronic fatigue syndrome.[61][62] The mechanism of transformation from cyst to trophozoites has not been characterized[6] but may be helpful in developing drug targets for treatment-resistant Giardia. The interaction between Giardia and host immunity, internal flora, and other pathogens is not well understood.[5]
The main congress about giardiasis is the "International Giardia and Cryptosporidium Conference" (IGCC). A summary of results presented at the most recent edition (2019, in Rouen, France) is available.[63]
## Other animals[edit]
In both dogs and cats, giardiasis usually responds to metronidazole and fenbendazole. Metronidazole in pregnant cats can cause developmental malformations.[64] Many cats dislike the taste of febendazole.[64] Giardiasis has been shown to decrease weight in livestock.[5]
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62. ^ Quote: "for unclear reasons, chronic sequelae, including post-infectious irritable bowel syndrome, chronic fatigue [..], malnutrition [..], cognitive impairment [..], and extra-intestinal manifestations (such as food allergy, urticaria, reactive arthritis, and inflammatory ocular manifestations), can develop and possibly persist beyond detectable parasite shedding". Quoted from: Bartelt LA, Sartor RB (2015). "Advances in understanding Giardia: determinants and mechanisms of chronic sequelae". F1000prime Reports (Review). 7: 62. doi:10.12703/P7-62. PMC 4447054. PMID 26097735.
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## External links[edit]
* Giardiasis Fact Sheet
Classification
D
* ICD-10: A07.1
* ICD-9-CM: 007.1
* MeSH: D005873
* DiseasesDB: 5213
External resources
* MedlinePlus: 000288
* eMedicine: emerg/215
* Patient UK: Giardiasis
* v
* t
* e
Parasitic disease caused by Excavata protozoa
Discicristata
Trypanosomatida
Trypanosomiasis
* T. brucei
* African trypanosomiasis
* T. cruzi
* Chagas disease
Leishmaniasis
* Leishmania major / L. mexicana / L. aethiopica / L. tropica
* Cutaneous leishmaniasis
* L. braziliensis
* Mucocutaneous leishmaniasis
* L. donovani / infantum
* Visceral leishmaniasis
Schizopyrenida
* Naegleria fowleri
* Primary amoebic meningoencephalitis
Trichozoa
Diplomonadida
* Giardia lamblia (Giardiasis)
Trichomonadida
* Trichomonas vaginalis
* Trichomoniasis
* Dientamoeba fragilis
* Dientamoebiasis
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Giardiasis | c0017536 | 3,068 | wikipedia | https://en.wikipedia.org/wiki/Giardiasis | 2021-01-18T18:40:16 | {"mesh": ["D005873"], "umls": ["C0017536"], "wikidata": ["Q326071"]} |
Neonatal autoimmune hemolytic anemia is a very rare, secondary, neonatal autoimmune disease characterized by onset of hemolytic anemia in the neonatal period associated with a positive direct antiglobulin test. Hepatosplenomegaly may be associated.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Neonatal autoimmune hemolytic anemia | None | 3,069 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=398109 | 2021-01-23T18:23:21 | {"icd-10": ["D59.1"], "synonyms": ["Neonatal AHA", "Neonatal AIHA"]} |
Type of white matter abnormality near the lateral ventricles
Axial T2 FLAIR sequence MR image of a middle-aged man with leukoaraiosis.
MRI image: Leukoaraiosis in a 90-year-old patient with cerebral atrophy.
Head CT showing periventricular white matter lesions.
Leukoaraiosis is a particular abnormal change in appearance of white matter near the lateral ventricles. It is often seen in aged individuals, but sometimes in young adults.[1][2] On MRI, leukoaraiosis changes appear as white matter hyperintensities (WMHs).[3][4] On CT scans, leukoaraiosis appears as hypodense periventricular white-matter lesions.[5]
The term "leukoaraiosis" was coined in 1986[6][7] by Hachinski, Potter, and Merskey as a descriptive term for rarefaction ("araiosis") of the white matter, showing up as decreased density on CT and increased signal intensity on T2/FLAIR sequences (white matter hyperintensities) performed as part of MRI brain scans.
These white matter changes are also commonly referred to as periventricular white matter disease, or white matter hyperintensities (WMH), due to their bright white appearance on T2 MRI scans. Many patients can have leukoaraiosis without any associated clinical abnormality. However, underlying vascular mechanisms are suspected to be the cause of the imaging findings. Hypertension, smoking, diabetes,[3] hyperhomocysteinemia, and heart disease are all risk factors for leukoaraiosis.
Leukoaraiosis has been reported to be an initial stage of Binswanger's disease but this evolution does not always happen.
## Contents
* 1 Causes
* 2 Special cases
* 3 See also
* 4 References
* 5 Further reading
## Causes[edit]
The blue arrows indicate leucoaraiosis. In the left image these may well represent transependymal CSF diapedesis due to normal pressure hydrocephalus, which in turn is suggested by the narrowed superior CSF spaces and acute callosal angle. The unilateral occurrence of these alterations in right image suggests they are probably due to vascular encephalopathy.
White matter hyperintensities can be caused by a variety of factors, including ischemia, micro-hemorrhages, gliosis, damage to small blood vessel walls, breaches of the barrier between the cerebrospinal fluid and the brain, or loss and deformation of the myelin sheath.[8] Multiple small vessel infarcts in the subcortical white matter can cause the condition, often the result of chronic hypertension leading to lipohyalinosis of the small vessels. Patients may develop subcortical dementia syndrome.[9]
## Special cases[edit]
* Ischaemic Leukoaraiosis has been defined as the leukoaraiosis present after a stroke.[10]
* Diabetes associated leukoaraiosis has been reported[11]
* CuRRL syndrome: increased Cup: Disc Ratio, Retinal GanglionCell Complex thinning, Radial Peripapillary Capillary Network Density Reduction and Leukoaraiosis[2]
* CADASIL is a hereditary cerebrovascular disorder associated with T2-hyperintense white matter lesions that have a greater extent and earlier age of onset than age-related leukoaraiosis.
## See also[edit]
* Hyperintensities
* Binswanger's disease
* Demyelinating disease
* Leukoaraiosis disease
## References[edit]
1. ^ Putaala J., Kurkinen M., Tarvos V., Salonen O., Kaste M., Tatlisumak T. (2009). "Silent brain infarcts and leukoaraiosis in young adults with first-ever ischemic stroke". Neurology. 72 (21): 1823–1829. doi:10.1212/WNL.0b013e3181a711df. PMID 19470964.CS1 maint: multiple names: authors list (link)
2. ^ a b Aik Kah, Tan (2018). "CuRRL Syndrome: A Case Series" (PDF). Acta Scientific Ophthalmology. 1 (3): 9–13.
3. ^ a b Habes M, Erus G, Toledo JB, Zhang T, Bryan N, Launer LJ, Rosseel Y, Janowitz D, Doshi J, Van der Auwera S, von Sarnowski B, Hegenscheid K, Hosten N, Homuth G, Völzke H, Schminke U, Hoffmann W, Grabe H, Davatzikos C (2016). "White matter hyperintensities and imaging patterns of brain ageing in the general population". Brain. 139 (Pt 4): 1164–79. doi:10.1093/brain/aww008. PMC 5006227. PMID 26912649.
4. ^ Yan, Shenqiang; Wan, Jinping; Zhang, Xuting; Tong, Lusha; Zhao, Song; Sun, Jianzhong; Lin, Yuehan; Shen, Chunhong; Lou, Min (2014). "Increased Visibility of Deep Medullary Veins in Leukoaraiosis: A 3-T MRI Study". Frontiers in Aging Neuroscience. 6: 144. doi:10.3389/fnagi.2014.00144. PMC 4074703. PMID 25071553.
5. ^ Kobari M, Meyer JS, Ichijo M, Oravez WT (1990). "Leukoaraiosis: correlation of MR and CT findings with blood flow, atrophy, and cognition". AJNR Am J Neuroradiol. 11 (2): 273–81. PMID 2107711.
6. ^ Hachinski, VC; Potter, P; Merskey, H (1986). "Leuko-araiosis: An ancient term for a new problem". The Canadian Journal of Neurological Sciences. 13 (4 Suppl): 533–34. doi:10.1017/S0317167100037264. PMID 3791068.
7. ^ Hachinski, V. C.; Potter, P.; Merskey, H. (1987). "Leuko-Araiosis". Archives of Neurology. 44 (1): 21–23. doi:10.1001/archneur.1987.00520130013009. PMID 3800716.
8. ^ Raz N, Yang Y, Dahle CL, Land S (2012). "Volume of white matter hyperintensities in healthy adults: contribution of age, vascular risk factors, and inflammation-related genetic variants". Biochimica et Biophysica Acta. 1822 (3): 361–69. doi:10.1016/j.bbadis.2011.08.007. PMC 3245802. PMID 21889590.
9. ^ Fauci, Anthony S.; Braunwald, Eugene; Weiner, Charles; Kasper, Dennis L.; Hauser, Stephen L.; Longo, Dan L.; Jameson, J. Larry; Loscalzo, Joseph (2008). Harrison's Principles of Internal Medicine (17th ed.). New York: McGraw-Hill. ISBN 978-0-07-149619-3.[page needed]
10. ^ O'Sullivan M, Morris RG, Huckstep B, Jones DK, Williams SCR, Markus HS (2004). "Diffusion tensor MRI correlates with executive dysfunction in patients with ischaemic leukoaraiosis". J Neurol Neurosurg Psychiatry. 75 (3): 441–47. doi:10.1136/jnnp.2003.014910. PMC 1738975. PMID 14966162.CS1 maint: multiple names: authors list (link)
11. ^ Maldjian JA, Whitlow CT, Saha BN, Kota G, Vandergriff C, Davenport EM, Divers J, Freedman BI, Bowden DW. "Automated White Matter Total Lesion Volume Segmentation in Diabetes". AJNR Am J Neuroradiol. 2013 Jul 18
## Further reading[edit]
* Pantoni, L.; Garcia, J. H. (1995). "The Significance of Cerebral White Matter Abnormalities 100 Years After Binswanger's Report : A Review". Stroke. 26 (7): 1293–301. doi:10.1161/01.STR.26.7.1293. PMID 7604429.
* Pantoni, L; Inzitari, D (1998). "New clinical relevance of leukoaraiosis. European Task Force on Age-Related White Matter-Changes" (PDF). Stroke. 29 (2): 543. doi:10.1161/01.str.29.2.543. PMID 9472903.
* Werder, SF (2010). "Cobalamin deficiency, hyperhomocysteinemia, and dementia". Neuropsychiatric Disease and Treatment. 6: 159–95. doi:10.2147/ndt.s6564. PMC 2874340. PMID 20505848.
Wikimedia Commons has media related to Leukoaraiosis.
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| Leukoaraiosis | c4020851 | 3,070 | wikipedia | https://en.wikipedia.org/wiki/Leukoaraiosis | 2021-01-18T18:44:45 | {"mesh": ["D049292"], "umls": ["C4020851", "C0948163"], "wikidata": ["Q2123166"]} |
A number sign (#) is used with this entry because of evidence that spondyloepiphyseal dysplasia with congenital joint dislocations (SEDCJD) is caused by homozygous or compound heterozygous mutation in the gene encoding carbohydrate sulfotransferase-3 (CHST3; 603799) on chromosome 10q22.
Description
Although patients with mutations in the CHST3 gene may initially be given varying diagnostic labels, they have similar clinical features, including dislocation of the knees and/or hips at birth, clubfoot, elbow joint dysplasia with subluxation and limited extension, short stature, and progressive kyphosis developing in late childhood. The disorder is usually evident at birth, with short stature and multiple joint dislocations or subluxations that dominate the neonatal clinical and radiographic picture, and affected individuals may receive an initial clinical diagnosis of Larsen syndrome (see 245600) or humerospinal dysostosis. During childhood, the dislocations improve, both spontaneously and with surgical treatment, and features of spondyloepiphyseal dysplasia become apparent, leading to arthritis of the hips and spine with intervertebral disc degeneration, rigid kyphoscoliosis, and trunk shortening by late childhood; at this stage, the clinical features are those previously described as the Omani type of SED (summary by Unger et al., 2010).
Clinical Features
Kozlowski et al. (1974) described 2 half sibs with an unusual skeletal dysplasia of which short humerus with distal bifurcation was one of the more striking features. Other features included coronal cleft vertebrae, subluxation in the elbow joints, shortening and hypotubulation of the long bones of the legs, widened iliac bones, and talipes equinovarus. Both children, brother and sister, had congenital heart disease from which 1 died at the age of 7.5 months. Kozlowski et al. (1974) suggested that the disorder was inherited as a 'dominant trait with variable penetrance.' They stressed, however, that it was not certain that the children had different fathers or that the father or fathers were normal.
Cortina et al. (1979) reported a 2-year-old boy with humeral bifurcation, elbow subluxation, and coronal cleft vertebrae. The patient had a cardiac murmur, but cardiac status was not fully investigated.
Hall (1997) reported a 6-month-old boy with short limbs, limited movement at elbow joints, dislocated right knee, and bilateral talipes equinovarus, who also had small thick ears and hypertelorism. Radiography showed short, mildly bowed long bones, slight widening of metaphyses, dislocated right knee, mild platyspondyly with partially fused coronal clefts in the thoracolumbar vertebrae, bifid distal humeri, generalized brachydactyly, and mildly thin ribs. Evaluation of a heart murmur by electrocardiography demonstrated a thickened mitral valve.
Rajab et al. (2004) described what appeared to be a distinct type of spondyloepiphyseal dysplasia (SED) in a large inbred kindred in Oman. They evaluated 8 individuals from 2 consanguineous sibships, 1 male and 7 females between ages 2 and 22 years. The families were thought to be related through distant consanguineous loops. The clinical features included near to normal length at birth, short stature with final adult height of 110 to 139 cm, shortening of the upper segment due to severe progressive kyphoscoliosis, severe arthritic changes with joint dislocations, rhizomelic limbs, genu valgum, cubitus valgus, mild brachydactyly, camptodactyly, microdontia, and normal intelligence. Radiologic studies showed minor metaphyseal changes but major manifestations in the spine and the epiphyses. During the first year of life, the vertebral bodies were of normal height, but the endplates were irregular and the intervertebral space was narrow. With age, the vertebral endplates became increasingly irregular, the intervertebral space diminished further, and individual vertebrae started to fuse, resulting in a severe short-trunk dwarfism with kyphoscoliosis. The epiphyses were small, and precocious osteoarthropathy involving small and large joints was observed; the elbow, wrist, and hip joints were affected starting in infancy and showed restricted movement. Osteoarthropathy and spinal involvement resulted in physical handicap by early adulthood. Rajab et al. (2004) designated this disorder 'spondyloepiphyseal dysplasia, Omani type.'
Megarbane and Ghanem (2004) reported a 5-year-old Lebanese boy with severe pre- and postnatal short stature, disproportionately short limbs, and multiple joint dislocations including left hip, knees, and radial heads. Other features included a frontal cowlick, high-arched palate, flat nape, and pectus excavatum. Radiologically he had anisospondyly with coronal clefts of the thoracolumbar vertebrae, subluxation of the radial heads, bilateral hip dislocation, hypoplastic left capital femoral epiphysis, short femoral necks, diffuse osseous demineralization, and delayed bone age.
Perez-Aytes et al. (2005) reported a case of humerospinal dysostosis in a boy who was born with rhizomelic shortening of limbs and talipes equinovarus. X-ray findings showed short long bones, vertebral coronal clefts, and distal humeral bifurcation. At 2 years of age, he had short stature, a short thorax, limitation of elbow extension, and genua valga. Psychomotor development was within normal limits. Perez-Aytes et al. (2005) also provided follow-up information on the patient reported by Cortina et al. (1979). At 27 years of age, he had undergone multiple orthopedic surgical interventions primarily for leg deformities. He had severe spine deformities, a short thorax, and limited movement of the elbow joints. His intellectual development was normal, and he worked as a computer expert. There was no cardiac involvement in either patient.
Megarbane (2007) reported a 5-year-old Lebanese girl, born of first-cousin parents, who had severe pre- and postnatal short stature, bilateral dislocation of hips, knees, and elbows, and right clubfoot. Skeletal investigation disclosed an anisospondyly, absence of ossification of the odontoid apophysis, incomplete fusion of the neural arches of the cervical vertebrae, abnormal L3 and L4 vertebrae, partial agenesis of the coccyx, abnormal and subluxated radial heads, bilateral dislocation of the hips, dysplastic acetabula, pseudoacetabula, hypoplasia of the femoral heads, short femoral necks, short long bones with thin diaphyses, widening of the medullary canal and thinning of the cortical canal, slightly enlarged metaphysis, and diffuse osseous demineralization. Bone age was delayed. Megarbane (2007) noted similarities to the features of an unrelated 5-year-old Lebanese boy originally reported by Megarbane and Ghanem (2004) and provided follow-up on the boy at 9 years of age. On x-ray, in addition to previously described findings, he had narrow disc spaces at C3-C4 and C4-C5, subluxation of C4-C5, marked lumbar lordosis and dorsal kyphosis, herniation of the discs of the dorsolumbar spine, irregular vertebral endplates of the vertebrae of the thoracolumbar spine, lumbar spina bifida occulta, abnormal carpal bones with extra-carpal bones on the left hand, abnormal tarsal bones, accessory medial cuneiforms, slightly flared metaphyses, and abnormal epiphyses.
Van Roij et al. (2008) studied 2 Turkish sibs, born of second-cousin parents, with progressive spondyloepiphyseal dysplasia from early childhood. The authors stated that several elements of their clinical presentation differed significantly from the original description of the disorder and suggested that the clinical phenotype should be extended to include congenital joint dislocation, clubfoot, ventricular septal defect, deafness, markedly variable metacarpal shortening, and accessory carpal ossification centers.
Tuysuz et al. (2009) reported a 13-year-old girl and her 11.5-year-old brother, born of consanguineous Turkish parents, who had parogressive skeletal dysplasia with severe spinal involvement, short stature, and premature arthrosis and joint contractures, features consistent with the 'Omani type' of spondyloepiphyseal dysplasia. The sibs also displayed mild facial dysmorphism not previously described in Omani SED, including a broad forehead, mild hypertelorism, sparse and high-arched eyebrows, long philtrum, and small cystic ears. Both patients had systolic murmurs; echocardiography revealed mild mitral regurgitation in the sister, and moderate mitral, tricuspid, and aortic regurgitation in her brother. Their 33-year-old paternal uncle, born of consanguineous parents, was also affected and had a similar facial appearance associated with severe short-trunk dwarfism, pectus carinatus, severe kyphoscoliosis, prominence of large joints, and short fourth metacarpals bilaterally. Limited extension of the elbow, hip, and knee joints, precocious osteoarthropathy of the hip joints, genu valgum, hallux valgus, and pes planus were also noted. Evaluation of a systolic murmur by echocardiography revealed moderate mitral, tricuspid, and aortic regurgitation and aortic stenosis. Radiographically the patients had irregularity of vertebral endplates, scoliosis, and narrowing of the intervertebral spaces, which in the uncle had progressed to absence of intervertebral spaces with subsequent fused vertebrae and severe kyphoscoliosis. In addition, the patients had small, irregular epiphyses in the limbs, subluxation of elbow joints, big femoral epiphyses, and irregular, small tibial epiphyses. The hands showed irregular, small, and accessory carpal ossification centers, brachydactyly, and bilateral metacarpal shortening of the third and fourth fingers in the sister and of the fourth finger in the uncle.
Tanteles et al. (2013) reported 2 Somalian half sibs with CHST3-associated chondrodysplasia who demonstrated the intrafamilial variability of the disorder. The proband was a 14-year-old girl who presented at 5.5 years of age with short stature and genua valga. Her mother did not recall congenital joint dislocations. The girl had marked restriction of forearm pronation, fixed flexion deformities at the hips, stiff spine with minimal lumbar flexion, and thoracic kyphosis with mild scoliosis. Her clinical course was characterized by rapid progression of spinal deformities and large joint contractures, and she was using a wheelchair most of the day by age 10. Her 3-year-old maternal half brother presented at birth with bilateral knee dislocation and talipes equinovarus. He had marked lumbar lordosis at age 2 years but no evidence of scoliosis. Both patients exhibited high anterior hairline, thick eyebrows, hypertelorism, and conductive hearing loss; the girl also had mild mitral valve regurgitation.
Mapping
Using genomewide linkage analysis in the consanguineous Omani kindred with spondyloepiphyseal dysplasia originally described by Rajab et al. (2004), Thiele et al. (2004) mapped the underlying gene to a 4.5-cM interval on chromosome 10q23.
Molecular Genetics
In affected members of the consanguineous Omani kindred with spondyloepiphyseal dysplasia originally described by Rajab et al. (2004), Thiele et al. (2004) identified homozygosity for a missense mutation in the CHST3 gene (R304Q; 608637.0001). They concluded that this form of SED is caused by deficiency in a specific sulfation of chondroitin sulfate side chains.
Hermanns et al. (2008) identified homozygosity or compound heterozygosity for 9 different mutations in the CHST3 gene (see, e.g., 603799.0002-603799.0006) in 6 unrelated patients born with joint dislocations, including 3 patients who carried a diagnosis of recessive Larsen syndrome (245600) and 3 who had been diagnosed with humerospinal dysostosis (HSD); 1 of the latter patients (see 603799.0005) was the boy originally reported by Cortina et al. (1979). None of the patients had the typical flattened facies of Larsen syndrome. Hermanns et al. (2008) stated that the single feature most useful in recognizing CHST3 deficiency seemed to be dysostotic changes in the thoracolumbar spine, namely, widening of the interpedicular distance at L1 on anteroposterior projection and the short and cleft vertebral bodies on lateral projection, which was seen in their patients and was mentioned by both Kozlowski et al. (1974) and Cortina et al. (1979) in their descriptions of HSD; Hermanns et al. (2008) noted that this radiologic feature was also recognizable in Figure 1 of the report on Omani-type SED by Rajab et al. (2004). Given the relatively narrow phenotypic spectrum of these conditions, Hermanns et al. (2008) suggested that the disorders previously designated as Omani-type spondyloepiphyseal dysplasia and humerospinal dysostosis, as well as some patients given a diagnosis of recessive Larsen syndrome, might represent different age-related descriptions of the same condition.
In 2 Turkish sibs with spondyloepiphyseal dysplasia and joint dislocations, born of consanguineous parents, van Roij et al. (2008) identified homozygosity for a missense mutation in the CHST3 gene (L286P; 603799.0007). In contrast to the consistent widening of the interpedicular distance at L1 seen in the patients studied by Hermanns et al. (2008), both sibs had narrowing of the interpedicular distance in the lumbar region.
In 2 sibs with spondyloepiphyseal dysplasia and their affected uncle from a consanguineous Turkish pedigree, Tuysuz et al. (2009) identified homozygosity for a missense mutation in the CHST3 gene (T141M; 603799.0009). In contrast to the multiple congenital joint dislocations reported in other patients with CHST3 mutations, these patients had only elbow joint dysplasia with radial subluxation and limitation of extension. Tuysuz et al. (2009) noted that their patients also had accessory carpal ossification centers and variable metacarpal shortening similar to the Turkish sibs described by van Roij et al. (2008).
Unger et al. (2010) identified homozygous or compound heterozygous mutations in CHST3 in patients with spondyloepiphyseal dysplasia and congenital joint dislocations from 17 families. The patients had presented with various diagnoses, including 15 who had been diagnosed with Larsen syndrome (see, e.g., 603799.0011 and 603799.0012), 2 with chondrodysplasia with multiple dislocations (previously reported by Megarbane and Ghanem, 2004 and Megarbane, 2007; see, e.g., 603799.0002), 1 with humerospinal dysostosis (originally reported by Hall, 1997; see 603799.0010), 1 with Desbuquois syndrome (see 251450), and 1 with spondyloepiphyseal dysplasia. Unger et al. (2010) reviewed the features of these patients and the 6 patients previously found to have mutations in CHST3 by Hermanns et al. (2008), and stated that the clinical and radiographic pattern of joint dislocations, vertebral changes, normal carpal age, lack of facial flattening, and recessive inheritance is characteristic and distinguishes CHST3 deficiency from other disorders with congenital dislocations.
In 2 Somalian half sibs with chondrodysplasia, Tanteles et al. (2013) identified homozygosity for a missense mutation in the CHST3 gene (603799.0013). Their unaffected parents were heterozygous for the mutation; the sibs had different fathers, who both originated from the same village.
History
Distal humeral bifurcation was noted in association with humeroradioulnar synostosis and tridactylous ectrosyndactyly by Gollop and Coates (1983) and Leroy and Speeckaert (1984). This is presumably a separate disorder.
INHERITANCE \- Autosomal recessive GROWTH Height \- Normal birth length \- Length <3rd percentile by 6 months \- Short stature, prenatal and postnatal \- Adult height 110-130cm HEAD & NECK Face \- Broad forehead (in some patients) \- Long philtrum (in some patients) Ears \- Small ears \- Deafness Eyes \- Hypertelorism \- Sparse and high-arched eyebrows (in some patients) Mouth \- High-arched palate Teeth \- Microdontia \- Widely spaced teeth \- Delayed dentition Neck \- Short neck CARDIOVASCULAR Heart \- Ventricular septal defect \- Hypertrophy of all 4 chambers of heart \- Mitral valve, thickening to severe stenosis \- Mitral regurgitation, mild to moderate \- Tricuspid valve, thickening to severe stenosis \- Tricuspid regurgitation, moderate \- Aortic valve, mild stenosis \- Aortic regurgitation, moderate \- Pulmonary valve, mild stenosis Vascular \- Pulmonary hypertension CHEST External Features \- Broad chest (neonate) \- Hunched up shoulders (more prominent in adults) \- Barrel-shaped chest (more prominent in adults) Breasts \- Widely spaced nipples SKELETAL \- Diffuse osseous demineralization \- Spondyloepiphyseal dysplasia \- Delayed bone age \- Joint dislocations, congenital or in young adult (knee, hip, shoulder) \- Joint contractures, onset school age (shoulder, ankle) Spine \- Kyphosis (onset 3-6 months) \- Coronal cleft vertebrae \- Scoliosis \- Kyphoscoliosis, severe progressive (>12 years old) \- Intervertebral space narrowing, progressive \- Endplate irregularity, progressive \- Interpedicular distance widened at L1 on anteroposterior projection \- Interpedicular distance narrowed in lumbar area \- Short and cleft vertebral bodies on lateral projection \- Vertebral body notching, superior and inferior \- Lumbar lordosis Pelvis \- Limited hip abduction/extension (progressive from birth) \- Iliac bones widened \- Iliac bones prominent Limbs \- Elbow dislocation/subluxation \- Fixed elbow flexion (birth) \- Joint enlargement (knee, elbow, wrist) \- Rhizomelic shortening \- Genu valgum (present at 1 year) \- Cubitus valgus \- Arthropathy, progressive \- Arthralgias (onset early school age) \- Small flat epiphyses \- Shoulder dislocation \- Humerus, distal bifurcation (in some patients) \- Ulna, proximal bowing \- Ulna, shortened \- Knee dislocation/subluxation \- Knee extension limited \- Capital femoral epiphyses, hypoplasia of \- Femoral neck, short \- Tibia, anterolateral bowing \- Long bones of legs, hypotubulation of Hands \- Brachydactyly \- Camptodactyly (present at birth) \- Interdigital skin webs \- Transverse palmar crease \- Laterally displaced fifth finger (adults) \- Short metacarpals \- Short phalanges \- Hypoplastic terminal phalanges \- Accessory carpal ossification centers \- Variable metacarpal shortening Feet \- Camptodactyly (present at birth) \- Club feet \- Talipes equinovarus \- Pes planus \- Accessory ossification centers SKIN, NAILS, & HAIR Skin \- Transverse palmar crease NEUROLOGIC Central Nervous System \- Normal intelligence \- Delayed gross motor development MISCELLANEOUS \- Waddling gait MOLECULAR BASIS \- Caused by mutation in the carbohydrate sulfotransferase 3 gene (CHST3, 603799.0001 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| SPONDYLOEPIPHYSEAL DYSPLASIA WITH CONGENITAL JOINT DISLOCATIONS | c2931649 | 3,071 | omim | https://www.omim.org/entry/143095 | 2019-09-22T16:40:07 | {"doid": ["0050813"], "mesh": ["C537874"], "omim": ["143095"], "orphanet": ["263463"], "synonyms": ["Alternative titles", "HUMEROSPINAL DYSOSTOSIS", "SPONDYLOEPIPHYSEAL DYSPLASIA, OMANI TYPE", "CHONDRODYSPLASIA WITH MULTIPLE DISLOCATIONS"], "genereviews": ["NBK62112"]} |
A number sign (#) is used with this entry because of evidence that axonal Charcot-Marie-Tooth disease type 2Z (CMT2Z) is caused by heterozygous mutation in the MORC2 gene (616661) on chromosome 22q12.
Description
Charcot-Marie-Tooth disease type 2Z (CMT2Z) is an autosomal dominant peripheral neuropathy characterized by onset, usually in the first decade, of distal lower limb muscle weakness and sensory impairment. The disorder is progressive, and affected individuals tend to develop upper limb and proximal muscle involvement in an asymmetric pattern, resulting in severe disability late in adulthood (summary by Sevilla et al., 2016).
For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210).
Clinical Features
Frith et al. (1994) described 21 cases in a large Australian family (CMT105) with autosomal dominant peroneal muscular atrophy associated with extensor plantar responses in some cases. The onset of the disease was typically within the first 2 decades. Spasticity was not a feature. Peripheral nerve conduction velocity showed normal or only mildly slowed motor nerve conductions with reduced amplitudes of sensory action potentials. Sural nerve biopsies demonstrated absence of significant myelination and no onion bulb formation. The electrical, physiologic, and biopsy results were similar to those found in axonal HMSN II (CMT2). Vucic et al. (2003) also studied the large family previously reported by Frith et al. (1994). The mean age of onset was 12.8 years (range 4 to 47) with difficulty walking and running. Patients had marked distal weakness and wasting of the lower limbs with sensory loss. Many patients had pes cavus and hammertoes. There were mild pyramidal signs in many, but not all, patients, including mild increases in tone, brisk reflexes, and extensor plantar responses, but no clonus or spastic gait. Four patients had spastic dysphonia. In this family, Zhu et al. (2005) excluded mutations in the MFN2 gene (608507).
Albulym et al. (2016) reported follow-up of family CMT105. Sixteen affected family members were examined. Patients had early onset of a length-dependent axonal motor and sensory neuropathy. Initially the distal lower and upper limbs were primarily affected, but over decades, the weakness spread proximally. Many required a wheelchair later in life. Pyramidal features included increased muscle tone and extensor plantar reflexes without over spasticity. Learning difficulties were present in many affected individuals. Three individuals had a distinctive high-pitched speech, and 2 had mild pigmentary retinal changes. Nerve biopsy showed a reduction of myelinated axons.
Sevilla et al. (2016) reported a 4-generation family in which 7 individuals had sensorimotor peripheral neuropathy. Five patients, ranging in age from 17 to 75 years, were still living at the time of report. The first symptoms appeared in the first or second decade, and most presented with cramping in the lower limbs associated with distal lower limb weakness and sensory loss. Hand weakness appeared after distal lower limb paresis in most patients. Asymmetric proximal muscle weakness, including neck flexion weakness, frequently appeared later in the disease course. The oldest family member was wheelchair-bound; he had significant disability of the upper limbs as well as urinary incontinence associated with absent detrusor contractility. Two of the patients had hearing loss. Sevilla et al. (2016) also reported 2 unrelated patients with sporadic disease. These patients presented after birth or in infancy with hypotonia, muscle weakness, and delayed motor development. One patient was lost to follow-up at age 19 months, whereas the other showed a progressive disease course with severe proximal and distal muscle weakness affecting the upper and lower limbs at age 45 years; she was wheelchair-bound. Electrophysiologic studies of all patients showed normal or near-normal motor nerve conduction velocities with decreased amplitudes of compound muscle and sensory nerve action potentials. Electromyography showed chronic neurogenic changes and spontaneous activity at rest, including fasciculations and myokymia. MRI, performed on 2 unrelated patients, showed fatty replacement of muscle in the legs. Sural nerve biopsy, also performed on 2 unrelated patients, showed predominant loss of large myelinated fibers with occasional small onion bulbs and regenerative clusters and thin myelin sheaths. There was a multifocal pattern of myelinated fiber loss, which was consistent with the observed asymmetric and random-like pattern of muscle weakness.
Albulym et al. (2016) reported 4 unrelated patients with CMT2Z. All had onset of progressive walking difficulties due to distal and later proximal muscle weakness and atrophy as well as distal sensory impairment. Three patients became wheelchair-bound between 25 and 40 years of age. Nerve conduction studies were consistent with a motor and sensory axonal neuropathy. None had upper motor neuron signs. Two patients were noted to have hand weakness, including one with finger contractures. One patient had developmental delay and another had mild learning difficulties.
Inheritance
The transmission pattern of CMT2Z in the family reported by Sevilla et al. (2016) was consistent with autosomal dominant inheritance.
Molecular Genetics
In affected members of a family with CMT2Z, Sevilla et al. (2016) identified a heterozygous missense mutation in the MORC2 gene (R190W; 616661.0001). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Direct sequencing of the MORC2 gene in 52 unrelated probands with CMT2 identified 2 patients with de novo heterozygous missense mutations: 1 patient had the R190W mutation, and the other had a S25L mutation (616661.0002). Functional studies of the variants were not performed.
In affected members of a large Australian family (CMT105), originally reported by Frith et al. (1994), Albulym et al. (2016) identified a heterozygous missense mutation in the MORC2 gene (R252W; 616661.0001). The mutation, which was found by a combination of linkage analysis and whole-exome sequencing, segregated with the disorder in the family. Analysis of 45 unrelated probands with CMT2 identified 4 additional families with heterozygous MORC2 missense mutations: 2 families carried R252W and 2 carried a different missense mutation (E236G; 616661.0003). Functional studies of the variants and studies of patient cells were not performed.
INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Hearing loss (in 2 members of 1 family) Neck \- Neck flexion weakness, later in the disease course GENITOURINARY Bladder \- Urinary incontinence (in some patients) SKELETAL Spine \- Scoliosis (in some patients) Hands \- Claw hands (in some patients) Feet \- Pes cavus MUSCLE, SOFT TISSUES \- Muscle cramps \- Distal muscle weakness, upper and lower limbs, due to peripheral neuropathy \- Proximal muscle weakness, upper and lower limbs, due to peripheral neuropathy, later in disease course \- Muscle atrophy, upper and lower limbs \- Foot drop \- Difficulty walking \- Hypotonia \- Spontaneous muscle activity \- Fasciculations \- Myokymia \- Increased muscle tone (in some patients) NEUROLOGIC Central Nervous System \- Delayed development (in some patients) \- Learning disabilities (in some patients) \- Pyramidal signs (in some patients) \- Extensors plantar responses (in some patients) Peripheral Nervous System \- Axonal sensorimotor peripheral neuropathy \- Decreased motor and sensory action potential amplitudes \- Distal sensory impairment \- Hypo- or areflexia \- Nerve conduction velocities normal or near-normal \- Sural nerve biopsy shows loss of large myelinated fibers \- Onion bulbs (rare) \- Regenerative fibers (rare) \- Thinly myelinated axons \- Fibrosis VOICE \- High-pitched voice (1 family) MISCELLANEOUS \- Onset in first or second decade (range infancy to young adults) \- Variable phenotype \- Slowly progressive \- Some patients may become wheelchair-bound \- Asymmetric muscle involvement MOLECULAR BASIS \- Caused by mutation in the MORC family, CW-type zinc finger protein 2 gene (MORC2, 616661.0001 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2Z | c4225243 | 3,072 | omim | https://www.omim.org/entry/616688 | 2019-09-22T15:48:18 | {"doid": ["0110181"], "omim": ["616688"], "orphanet": ["466768"], "synonyms": ["CMT2Z", "Alternative titles", "CHARCOT-MARIE-TOOTH DISEASE, AXONAL, AUTOSOMAL DOMINANT, TYPE 2Z", "CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 2Z", "Autosomal dominant Charcot-Marie-Tooth disease type 2 due to MORC2 mutation"]} |
## Clinical Features
Shirakami et al. (1986) reported plasma fibronectin (135600) deficiency in 8 members of 1 family. Enzyme levels were about half-normal in the deficient persons, who were distributed in 3 generations and 4 sibships. The proband, a 31-year-old woman, had keloids at sites of surgery and burns but no other abnormalities. No keloids were found in the deficient relatives. Specifically, there was no unusual susceptibility to infections, bleeding diathesis, or hyperextensibility of joints or skin, as has been observed in a form of Ehlers-Danlos syndrome with fibronectin abnormalities (225310). There were no homozygotes, but a possible homozygote with first-cousin parents died soon after birth.
Inheritance
The pedigree pattern in the family with plasma fibronectin deficiency reported by Shirakami et al. (1986) was consistent with autosomal dominant inheritance.
INHERITANCE \- Autosomal dominant LABORATORY ABNORMALITIES \- Plasma fibronectin deficiency ▲ Close
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| PLASMA FIBRONECTIN DEFICIENCY | c2675436 | 3,073 | omim | https://www.omim.org/entry/614101 | 2019-09-22T15:56:28 | {"omim": ["614101"]} |
Florid cemento-osseous dysplasia (FCOD) is a rare fibro-osseous lesion in the jaw that predominantly affects middle-aged women of African descent. It is generally asymptomatic or may manifest with pain and gingival swelling. Radiologically, it is characterized by multiple dense lobulated bone lesions, often symmetrically located in various regions of the jaw.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Florid cemento-osseous dysplasia | c0555197 | 3,074 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=83451 | 2021-01-23T18:16:26 | {"gard": ["10173"], "mesh": ["C537063"], "umls": ["C0555197"], "icd-10": ["D16.4", "D16.5"], "synonyms": ["Florid osseous dysplasia", "Focal cemento-osseous dysplasia"]} |
Isolated ATP synthase deficiency is a rare, genetic, mitochondrial oxidative phosphorylation disorder that may present with a wide range of symptoms (including muscular hypotonia, hypertrophic cardiomyopathy, psychomotor delay, encephalopathy, peripheral neuropathy, lactic acidosis, 3-methylglutaconic aciduria) and clinical syndromes (including NARP and MILS).
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Isolated ATP synthase deficiency | c3276276 | 3,075 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=254913 | 2021-01-23T17:27:49 | {"omim": ["604273", "614053", "615228", "618120", "618683"], "icd-10": ["E88.8"], "synonyms": ["Isolated mitochondrial respiratory chain complex V deficiency"]} |
Urachal diverticulum is the rarest type of congenital urachal anomaly (see this term) resulting from the failure of the distal urachus to close at its point of connectivity to the bladder that is usually asymptomatic but can be associated with recurrent urinary tract infections and other complications.
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Urachal diverticulum | c0431743 | 3,076 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=431347 | 2021-01-23T17:37:51 | {"icd-10": ["Q64.4"], "synonyms": ["Vesicourachal diverticulum"]} |
Cor triatriatum is an extremely rare congenital (present at birth) heart defect. The human heart normally has four chambers, two ventricles and two atria. The two atria are normally separated from each other by a partition called the atrial septum and the two ventricles by the ventricle septum. In cor triatriatum there is a small extra chamber above the left atrium (cor triatriatum sinistrum) or right atrium (cor triatriatum dextrum). The presence of this extra atrial chamber can cause slowed passage of the blood from the lungs to the heart and, over time, lead to features of congestive heart failure and obstruction. In children, cor triatriatum may be associated with major congenital cardiac problems. In adults, it is often an isolated finding. Treatment depends upon the symptoms present and may include medical or surgical approaches.
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Cor triatriatum | c0009995 | 3,077 | gard | https://rarediseases.info.nih.gov/diseases/6194/cor-triatriatum | 2021-01-18T18:01:05 | {"mesh": ["D003310"], "umls": ["C0009995"], "orphanet": ["1463"], "synonyms": ["Triatrial heart"]} |
Rotor syndrome is a relatively mild condition characterized by elevated levels of a substance called bilirubin in the blood (hyperbilirubinemia). Bilirubin is produced when red blood cells are broken down. It has an orange-yellow tint, and buildup of this substance can cause yellowing of the skin or whites of the eyes (jaundice). In people with Rotor syndrome, jaundice is usually evident shortly after birth or in childhood and may come and go; yellowing of the whites of the eyes (also called conjunctival icterus) is often the only symptom.
There are two forms of bilirubin in the body: a toxic form called unconjugated bilirubin and a nontoxic form called conjugated bilirubin. People with Rotor syndrome have a buildup of both unconjugated and conjugated bilirubin in their blood, but the majority is conjugated.
## Frequency
Rotor syndrome is a rare condition, although its prevalence is unknown.
## Causes
The SLCO1B1 and SLCO1B3 genes are involved in Rotor syndrome. Mutations in both genes are required for the condition to occur. The SLCO1B1 and SLCO1B3 genes provide instructions for making similar proteins, called organic anion transporting polypeptide 1B1 (OATP1B1) and organic anion transporting polypeptide 1B3 (OATP1B3), respectively. Both proteins are found in liver cells; they transport bilirubin and other compounds from the blood into the liver so that they can be cleared from the body. In the liver, bilirubin is dissolved in a digestive fluid called bile and then excreted from the body.
The SLCO1B1 and SLCO1B3 gene mutations that cause Rotor syndrome lead to abnormally short, nonfunctional OATP1B1 and OATP1B3 proteins or an absence of these proteins. Without the function of either transport protein, bilirubin is less efficiently taken up by the liver and removed from the body. The buildup of this substance leads to jaundice in people with Rotor syndrome.
### Learn more about the genes associated with Rotor syndrome
* SLCO1B1
* SLCO1B3
## Inheritance Pattern
This condition is inherited in an autosomal recessive pattern. In autosomal recessive inheritance, both copies of a gene in each cell have mutations. In Rotor syndrome, an affected individual must have mutations in both the SLCO1B1 and the SLCO1B3 gene, so both copies of the two genes are altered. The parents of an individual with this condition each carry one altered copy of both genes, but they do not show signs and symptoms of the condition.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Rotor syndrome | c0220991 | 3,078 | medlineplus | https://medlineplus.gov/genetics/condition/rotor-syndrome/ | 2021-01-27T08:24:40 | {"gard": ["218"], "mesh": ["D006933"], "omim": ["237450"], "synonyms": []} |
Viral pulmonary disease of humans
Hantavirus pulmonary syndrome
Other namesFour Corners disease
Progression of hantavirus pulmonary syndrome
SpecialtyPulmonology
SymptomsFever, cough, shortness of breath, headaches, muscle pains, lethargy, nausea, diarrhea
ComplicationsRespiratory failure, cardiac failure[1]
CausesHantaviruses spread by rodents
Differential diagnosisCommunity acquired pneumonia, leptospirosis, tularemia, pneumonic plague[1]
PreventionRodent control
TreatmentSupportive, including mechanical ventilation
MedicationNone
PrognosisPoor
Deaths36–40% mortality
Hantavirus pulmonary syndrome (HPS) is one of two potentially fatal syndromes of zoonotic origin caused by species of hantavirus.[2] These include Black Creek Canal virus (BCCV), New York orthohantavirus (NYV), Monongahela virus (MGLV), Sin Nombre orthohantavirus (SNV), and certain other members of Hantavirus genera that are native to the United States and Canada.[3]
Specific rodents are the principal hosts of the hantaviruses including the hispid cotton rat (Sigmodon hispidus) in southern Florida, which is the principal host of Black Creek Canal virus.[4][5] The deer mouse (Peromyscus maniculatus) in Canada and the Western United States is the principal host of Sin Nombre virus.[6][7] The white-footed mouse (Peromyscus leucopus) in the eastern United States is the principal host of New York virus.[8] In South America, the long-tailed mouse (Oligoryzomys longicaudatus) and other species of the genus Oligoryzomys have been documented as the reservoir for Andes virus.[9][10][11]
## Contents
* 1 Signs and symptoms
* 2 Mechanism
* 3 Transmission
* 4 Prevention
* 5 Diagnosis and treatment
* 6 Epidemiology
* 7 See also
* 8 References
* 9 External links
## Signs and symptoms[edit]
Initially, HPS has a incubation phase of 2–4 weeks, in which patients remain asymptomatic.[1] Subsequently, patients can experience 3–5 days of flu-like prodromal phase symptoms, including fever, cough, muscle pain, headache, lethargy, shortness of breath, nausea, vomiting and diarrhea.[1]
## Mechanism[edit]
In the following 5–7 day cardiopulmonary phase, the patient's condition rapidly deteriorates into acute respiratory failure, characterized by the sudden onset of shortness of breath with rapidly evolving pulmonary edema, as well as cardiac failure, with hypotension, tachycardia and shock.[1] In this phase, patients may develop acute respiratory distress syndrome. It is often fatal despite mechanical ventilation and intervention with diuretics. After the cardiopulmonary phase, patients can enter a diuretic phase of 2–3 days characterized by symptom improvement and diuresis. Subsequent convalescence can last months to years.[1] Overall, patient mortality from HPS is 36%.[citation needed]
## Transmission[edit]
The hispid cotton rat, indigenous to southern Florida, is the carrier of the Black Creek Canal virus
The virus can be transmitted to humans by a direct bite or inhalation of aerosolized virus, shed from stool, urine, or saliva from a natural reservoir rodent.[1] In general, droplet and/or fomite transfer has not been shown in the hantaviruses in either the pulmonary or hemorrhagic forms.[12][13]
## Prevention[edit]
Rodent control in and around the home or dwellings remains the primary prevention strategy, as well as eliminating contact with rodents in the workplace and at campsites. Closed storage sheds and cabins are often ideal sites for rodent infestations. Airing out of such spaces prior to use is recommended. People are advised to avoid direct contact with rodent droppings and wear a mask while cleaning such areas to avoid inhalation of aerosolized rodent secretions.[14]
## Diagnosis and treatment[edit]
The preferred method for diagnosis of Hantavirus Pulmonary Syndrome is serological testing which identifies both acute (IgM) and remote infections (IgG), however PCR may also be used to identify early infections.[15] There is no cure or vaccine for HPS. Treatment involves supportive therapy, including mechanical ventilation with supplemental oxygen during the critical respiratory-failure stage of the illness.[1] Although ribavirin can be used to treat hantavirus infections, it is not recommended as a treatment for HPS due to unclear clinical efficacy and likelihood of medication side effects.[1] Early recognition of HPS and admission to an intensive care setting offers the best prognosis.[citation needed]
## Epidemiology[edit]
Hantavirus pulmonary syndrome was first recognized during the 1993 outbreak in the Four Corners region of the southwestern United States. It was identified by Dr. Bruce Tempest. It was originally called Four Corners disease, but the name was changed to Sin Nombre virus after complaints by Native Americans that the name "Four Corners" stigmatized the region.[16] It has since been identified throughout the United States.
## See also[edit]
* Viruses portal
* 1993 Four Corners hantavirus outbreak
* Sweating sickness
* Calabazo virus
* Rockport virus
## References[edit]
1. ^ a b c d e f g h i Barros, N; McDermott, S; Wong, AK; Turbett, SE (16 April 2020). "Case 12-2020: A 24-Year-Old Man with Fever, Cough, and Dyspnea". New England Journal of Medicine. 382 (16): 1544–1553. doi:10.1056/NEJMcpc1916256. PMID 32294350.
2. ^ Koster FT. Levy H. "Hantavirus cardiopulmonary syndrome: a new twist to an established pathogen", In: Fong IW, editor; Alibek K, editor. New and Evolving Infections of the 21st Century, New York: Springer-Verlag New York, Inc.; 2006. pp. 151–170.
3. ^ Nichol ST. Beaty BJ. Elliott RM. Goldbach R, et al. Family Bunyaviridae. In: Fauquet CM, editor; Mayo MA, editor; Maniloff J, editor; Desselberger U, et al., editors. Virus Taxonomy: 8th Report of the International Committee on Taxonomy of Viruses. San Diego, CA: Elsevier Academic Press;
4. ^ Rollin PE. Ksiazek TG. Elliott LH. Ravkov EV, et al. "Isolation of Black Creek Canal virus, a new hantavirus from Sigmodon hispidus in Florida", J Med Virol. 1995;46:35–39. [PubMed]
5. ^ Glass GE. Livingstone W. Mills JN. Hlady WG, et al. "Black Creek Canal virus infection in Sigmodon hispidus in southern Florida", Am J Trop Med Hyg. 1998;59:699–703. PubMed
6. ^ Childs JE, Ksiazek TG, Spiropoulou CF, Krebs JW, Morzunov S, Maupin GO, Gage KL, Rollin PE, Sarisky J, Enscore RE (1994). "Serologic and genetic identification of Peromyscus maniculatus as the primary rodent reservoir for a new hantavirus in the southwestern United States". J. Infect. Dis. 169 (6): 1271–80. doi:10.1093/infdis/169.6.1271. PMID 8195603.
7. ^ Drebot MA. Gavrilovskaya I. Mackow ER. Chen Z, et al. "Genetic and serotypic characterization of Sin Nombre-like viruses in Canadian Peromyscus maniculatus mice", Virus Res. 2001;75:75–86. [PubMed]
8. ^ Hjelle B. Lee SW. Song W. Torrez-Martinez N, et al. "Molecular linkage of hantavirus pulmonary syndrome to the white-footed mouse, Peromyscus leucopus: genetic characterization of the M genome of New York virus", J Virol. 1995;69:8137–8141. [PMC free article] [PubMed]
9. ^ Wells RM, Sosa Estani S, Yadon ZE, Enria D, Padula P, Pini N, Mills JN, Peters CJ, Segura EL (April–June 1997). "An unusual hantavirus outbreak in southern Argentina: person-to-person transmission? Hantavirus Pulmonary Syndrome Study Group for Patagonia". Emerg Infect Dis. 3 (2): 171–4. doi:10.3201/eid0302.970210. PMC 2627608. PMID 9204298.
10. ^ Levis S, Morzunov SP, Rowe JE, Enria D, Pini N, Calderon G, Sabattini M, St Jeor SC (March 1998). "Genetic diversity and epidemiology of hantaviruses in Argentina". J Infect Dis. 177 (3): 529–38. doi:10.1086/514221. PMID 9498428.
11. ^ Cantoni G, Padula P, Calderón G, Mills J, Herrero E, Sandoval P, Martinez V, Pini N, Larrieu E (October 2001). "Seasonal variation in prevalence of antibody to hantaviruses in rodents from southern Argentina". Trop Med Int Health. 6 (10): 811–6. doi:10.1046/j.1365-3156.2001.00788.x. PMID 11679129.
12. ^ Peters, C.J. (2006). "Emerging Infections: Lessons from the Viral Hemorrhagic Fevers". Transactions of the American Clinical and Climatological Association. 117: 189–197. PMC 1500910. PMID 18528473.
13. ^ Crowley, J.; Crusberg, T. "Ebola and Marburg Virus Genomic Structure, Comparative and Molecular Biology". Dept. of Biology & Biotechnology, Worcester Polytechnic Institute. Archived from the original on 2013-10-15.
14. ^ "CDC - Hantavirus Pulmonary Syndrome (HPS) – Hantavirus". Cdc.gov. 2013-02-06. Retrieved 2013-07-07.
15. ^ Akram, Sami (20 November 2020). "Hantavirus Cardiopulmonary Syndrome". National Center for Biotechnology Information.
16. ^ "Death at the Corners". Discover Magazine. 1993-12-01. Retrieved 2013-03-25.
## External links[edit]
* "Hantaviruses, with emphasis on Four Corners Hantavirus" by Brian Hjelle, M.D., 2001, Department of Pathology, School of Medicine, University of New Mexico
* Hantavirus Technical Information Index page, US Center for Disease Control
* Viralzone: Hantavirus
* Virus Pathogen Database and Analysis Resource (ViPR): Bunyaviridae
* Hantavirus – Occurrences and deaths in North and South America, 1993–2004, PAHO
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| Hantavirus pulmonary syndrome | c0243025 | 3,079 | wikipedia | https://en.wikipedia.org/wiki/Hantavirus_pulmonary_syndrome | 2021-01-18T18:39:41 | {"gard": ["69"], "mesh": ["D018804"], "umls": ["C0243025"], "icd-10": ["J12.8"], "orphanet": ["319247"], "wikidata": ["Q6137239"]} |
Human disease
Vitamin D deficiency
Other namesHypovitaminosis D
The normal process of Vitamin D absorption
SpecialtyEndocrinology
SymptomsUsually asymptomatic
ComplicationsRickets, osteomalacia, other associated disorders
CausesLack of vitamin D, inadequate sunlight exposure
Risk factorsAge, people with dark skin, obesity, malabsorption, bariatric surgery, breastfed infants[1]
Diagnostic methodMeasuring the concentration of calcifediol in the blood
PreventionSufficient sunlight exposure, dietary intake
TreatmentSupplements
MedicationCholecalciferol, ergocalciferol, calcifediol
FrequencyDeficiency 20-40%, severe deficiency 6-13%[2]
Vitamin D deficiency, or hypovitaminosis D is defined as a vitamin D level that is below normal. It most commonly occurs in people when they have inadequate sunlight exposure (in particular sunlight with adequate ultraviolet B rays (UVB)).[1][2][3] Vitamin D deficiency can also be caused by inadequate nutritional intake of vitamin D, disorders limiting vitamin D absorption, and conditions impairing vitamin D conversion into active metabolites—including certain liver, kidney, and hereditary disorders.[4] Deficiency impairs bone mineralization, leading to bone softening diseases such as rickets in children. It can also worsen osteomalacia and osteoporosis in adults, leading to an increased risk of bone fractures.[1][4] Muscle weakness is also a common symptom of vitamin D deficiency, further increasing the risk of fall and bone fractures in adults.[1] Vitamin D deficiency is associated with the development of schizophrenia.[5]
UVB from sunlight is a large source of vitamin D. Oily fish such as salmon, herring, and mackerel are also sources of vitamin D, as are mushrooms. Milk is often fortified with vitamin D and sometimes bread, juices, and other dairy products are fortified with vitamin D as well.[1] Many multivitamins now contain vitamin D in different amounts.[1]
## Contents
* 1 Classifications
* 2 Signs and symptoms
* 3 Pathophysiology
* 4 Risk factors
* 4.1 Age
* 4.2 Fat percentage
* 4.3 Malnutrition
* 4.4 Obesity
* 4.5 Sun exposure
* 4.6 Darker skin color
* 4.7 Malabsorption
* 4.8 Critical illness
* 5 Diagnosis
* 6 Screening
* 7 Treatment
* 7.1 Initial phase
* 7.1.1 Daily or weekly or monthly dose
* 7.1.2 Single-dose therapy
* 7.1.3 Vitamin D doses and meals
* 7.2 Maintenance phase
* 7.3 Special cases
* 8 Epidemiology
* 9 History
* 10 Research
* 11 See also
* 12 References
* 13 External links
## Classifications[edit]
Mapping of several bone diseases onto levels of vitamin D (calcidiol) in the blood[6]
Normal bone vs. Osteoporosis
Vitamin D deficiency is typically diagnosed by measuring the concentration of the 25-hydroxyvitamin D in the blood, which is the most accurate measure of stores of vitamin D in the body.[1][7][2] One nanogram per millilitre (1 ng/mL) is equivalent to 2.5 nanomoles per litre (2.5 nmol/L).
* Severe deficiency: <12 ng/mL = <30 nmol/L[2]
* Deficiency: <20 ng/mL = <50 nmol/L
* Insufficient: 20–29 ng/mL = 50–75 nmol/L
* Normal: 30–50 ng/mL = 75–125 nmol/L
Vitamin D levels falling within this normal range prevent clinical manifestations of vitamin D insufficiency as well as vitamin D toxicity.[1][7][2]
## Signs and symptoms[edit]
Child with rickets
Vitamin D deficiency may only be detected on blood tests, but is the cause of some bone diseases and is associated with other conditions:[1]
* Rickets, a childhood disease characterized by impeded growth and deformity of the long bones.[8] The earliest sign of subclinical vitamin D deficiency is craniotabes, abnormal softening or thinning of the skull.[9]
* Osteomalacia, a bone-thinning disorder that occurs exclusively in adults and is characterized by proximal muscle weakness and bone fragility.
* Osteoporosis, a condition characterized by reduced bone mineral density and increased bone fragility.
* Increased risk of fracture[10][11]
* Muscle aches, weakness, and twitching (fasciculations), due to reduced blood calcium (hypocalcemia).[3][12]
* Periodontitis, local inflammatory bone loss that can result in tooth loss.[13]
* Pre-eclampsia: There has been an association of vitamin D deficiency and women who develop pre-eclampsia in pregnancy. The exact relationship of these conditions is not well understood.[14] Maternal vitamin D deficiency may affect the baby, causing overt bone disease from before birth and impairment of bone quality after birth.[8][15]
* Respiratory infections and COVID-19: Vitamin D deficiency may increase the risk of severe acute respiratory infections and COPD.[16][17] Emerging studies have suggested a link between vitamin D deficiency and COVID-19 symptoms.[18][19] A review has shown that vitamin D deficiency is not associated with a higher chance of having COVID-19, but is associated with a greater severity of the disease, including 80% increases in the rates of hospitalization and mortality.[20]
* Schizophrenia: Vitamin D deficiency is associated with the development of schizophrenia.[5] People with schizophrenia generally have lower levels of vitamin D.[21] The environmental risk factors of seasonality of birth, latitude, and migration, linked to schizophrenia all implicate vitamin D deficiency, as do other health conditions such as maternal obesity.[5][22] Vitamin D is essential for the normal development of the nervous system.[5][21] Maternal vitamin D deficiency can cause prenatal neurodevelopmental defects, which influence neurotransmission, altering brain rhythms and the metabolism of dopamine.[21] Vitamin D receptors, CYP27B1 and CYP24A1 are found in various regions of the brain, showing that vitamin D is a neuroactive, neurosteroid hormone essential for the development of the brain and normal function.[5] Inflammation as a causative factor in schizophrenia is normally suppressed by vitamin D.[21]
## Pathophysiology[edit]
Decreased exposure of the skin to sunlight is a common cause of vitamin D deficiency.[1] People with a darker skin pigment with increased amounts of melanin may have decreased production of vitamin D.[3] Melanin absorbs ultraviolet B radiation from the sun and reduces vitamin D production.[3] Sunscreen can also reduce vitamin D production.[3] Medications may speed up the metabolism of vitamin D, causing a deficiency.[3]
Liver diseases: The liver is required to transform vitamin D into 25-hydroxyvitamin D. This is an inactive metabolite of vitamin D but is a necessary precursor (building block) to create the active form of vitamin D.[1]
Kidney disease: The kidneys are responsible for converting 25-hydroxyvitamin D to 1,25-hydroxyvitamin D. This is the active form of vitamin D in the body. Kidney disease reduces 1,25-hydroxyvitamin D formation, leading to a deficient effects of vitamin D.[1]
Intestinal conditions that result in malabsorption of nutrients may also contribute to vitamin D deficiency by decreasing the amount of vitamin D absorbed via diet.[1] In addition, a vitamin D deficiency may lead to decreased absorption of calcium by the intestines, resulting in increased production of osteoclasts that may break down a person's bone matrix.[23] In states of hypocalcemia, calcium will leave the bones and may give rise to secondary hyperparathyroidism, which is a response by the body to increase serum calcium levels.[23] The body does this by increasing uptake of calcium by the kidneys and continuing to take calcium away from the bones.[23] If prolonged, this may lead to osteoporosis in adults and rickets in children.[23]
## Risk factors[edit]
Those most likely to be affected by vitamin D deficiency are people with little exposure to sunlight.[24] Certain climates, dress habits, the avoidance of sun exposure and the use of too much sunscreen protection can all limit the production of vitamin D.[24]
### Age[edit]
Elderly people have a higher risk of having a vitamin D deficiency due to a combination of several risk factors, including: decreased sunlight exposure, decreased intake of vitamin D in the diet, and decreased skin thickness which leads to further decreased absorption of vitamin D from sunlight.[25]
### Fat percentage[edit]
Since vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol) are fat-soluble, humans and other animals with a skeleton need to store some fat. Without fat, the animal will have a hard time absorbing vitamin D2 and vitamin D3 and the lower the fat percentage, the greater the risk of vitamin deficiency, which is true in some athletes who strive to get as lean as possible.[26]
### Malnutrition[edit]
Although rickets and osteomalacia are now rare in Britain, osteomalacia outbreaks in some immigrant communities included women with seemingly adequate daylight outdoor exposure wearing typical Western clothing.[27] Having darker skin and reduced exposure to sunshine did not produce rickets unless the diet deviated from a Western omnivore pattern characterized by high intakes of meat, fish, and eggs, and low intakes of high-extraction cereals.[28][29][30] In sunny countries where rickets occurs among older toddlers and children, vitamin D deficiency has been attributed to low dietary calcium intakes. This is characteristic of cereal-based diets with limited access to dairy products.[30] Rickets was formerly a major public health problem among the US population; in Denver, where ultraviolet rays are about 20% stronger than at sea level on the same latitude,[31] almost two-thirds of 500 children had mild rickets in the late 1920s.[32] An increase in the proportion of animal protein in the 20th-century American diet coupled with increased consumption of milk fortified with relatively small quantities of vitamin D coincided with a dramatic decline in the number of rickets cases.[33][34][35] One study of children in a hospital in Uganda however showed no significant difference in vitamin D levels of malnourished children compared to non-malnourished children. Because both groups were at risk due to darker skin pigmentation, both groups had vitamin D deficiency. Nutritional status did not appear to play a role in this study.[36]
### Obesity[edit]
There is an increased risk of vitamin D deficiency in people who are considered overweight or obese based on their body mass index (BMI) measurement.[37] The relationship between these conditions is not well understood. There are different factors that could contribute to this relationship, particularly diet and sunlight exposure.[37] Alternatively, vitamin D is fat-soluble therefore excess amounts can be stored in fat tissue and used during winter, when sun exposure is limited.[38]
### Sun exposure[edit]
The use of sunscreen with a sun protection factor of 8 can theoretically inhibit more than 95% of vitamin D production in the skin.[33] In practice, however, sunscreen is applied so as to have a negligible effect on vitamin D status.[39] The vitamin D status of those in Australia and New Zealand is unlikely to have been affected by campaigns advocating sunscreen.[40] Instead, wearing clothing is more effective at reducing the amount of skin exposed to UVB and reducing natural vitamin D synthesis. Clothing which covers a large portion of the skin, when worn on a consistent and regular basis, such as the burqa, is correlated with lower vitamin D levels and an increased prevalence of vitamin D deficiency.[41]
Regions far from the equator have a high seasonal variation of the amount and intensity of sunlight. In the UK the prevalence of low vitamin D status in children and adolescents is found to be higher in winter than in summer.[42] Lifestyle factors such as indoor versus outdoor work and time spent in outdoor recreation play an important role.
Additionally, vitamin D deficiency has been associated with urbanisation in terms of both air pollution, which blocks UV light, and an increase in the number of people working indoors. The elderly are generally exposed to less UV light due to hospitalisation, immobility, institutionalisation, and being housebound, leading to decreased levels of vitamin D.[43]
### Darker skin color[edit]
The reduced pigmentation of light-skinned individuals may result in higher vitamin D levels, because of the melanin which acts like a sun-block, dark-skinned individuals, may have higher vitamin D deficiency levels.[6]
### Malabsorption[edit]
Rates of vitamin D deficiency are higher among people with untreated celiac disease,[44][45] inflammatory bowel disease, exocrine pancreatic insufficiency from cystic fibrosis, and short bowel syndrome,[45] which can all produce problems of malabsorption. Vitamin D deficiency is also more common after surgical procedures that reduce absorption from the intestine, including weight loss procedures.[46]
### Critical illness[edit]
Vitamin D deficiency is associated with increased mortality in critical illness.[47] People who take vitamin D supplements before being admitted for intensive care are less likely to die than those who do not take vitamin D supplements.[47] Additionally, vitamin D levels decline during stays in intensive care.[48] Vitamin D3 (cholecalciferol) or calcitriol given orally may reduce the mortality rate without significant adverse effects.[48]
## Diagnosis[edit]
See also: Reference ranges for blood tests § Vitamins
The serum concentration of calcifediol, also called 25-hydroxyvitamin D (abbreviated 25(OH)D), is typically used to determine vitamin D status. Most vitamin D is converted to 25(OH)D in the serum, giving an accurate picture of vitamin D status.[49] The level of serum 1,25(OH)D is not usually used to determine vitamin D status because it often is regulated by other hormones in the body such as parathyroid hormone.[49] The levels of 1,25(OH)D can remain normal even when a person may be vitamin D deficient.[49] Serum level of 25(OH)D is the laboratory test ordered to indicate whether or not a person has vitamin D deficiency or insufficiency.[49] It is also considered reasonable to treat at-risk persons with vitamin D supplementation without checking the level of 25(OH)D in the serum, as vitamin D toxicity has only been rarely reported to occur.[49]
Levels of 25(OH)D that are consistently above 200 nanograms per milliliter (ng/mL) (or 500 nanomoles per liter, nmol/L) are thought to be potentially toxic, although data from humans are sparse.[citation needed] Vitamin D toxicity usually results from taking supplements in excess.[50] Hypercalcemia is often the cause of symptoms,[50] and levels of 25(OH)D above 150 ng/mL (375 nmol/L) are usually found, although in some cases 25(OH)D levels may appear to be normal. Periodic measurement of serum calcium in individuals receiving large doses of vitamin D is recommended.[4]
## Screening[edit]
The official recommendation from the United States Preventive Services Task Force is that for persons that do not fall within an at-risk population and are asymptomatic, there is not enough evidence to prove that there is any benefit in screening for vitamin D deficiency.[51]
## Treatment[edit]
Vitamin D2 supplements
In the United States and Canada as of 2016, the amount of vitamin D recommended is 400 IU per day for children, 600 IU per day for adults, and 800 IU per day for people over age 70.[52][53] The Canadian Paediatric Society recommends that pregnant or breastfeeding women consider taking 2000 IU/day, that all babies who are exclusively breastfed receive a supplement of 400 IU/day, and that babies living north of 55°N get 800 IU/day from October to April.[54]
Treating vitamin D deficiency depends on the severity of the deficit.[55] Treatment involves an initial high-dosage treatment phase until the required serum levels are reached, followed by the maintenance of the acquired levels. The lower the 25(OH)D serum concentration is before treatment, the higher is the dosage that is needed in order to quickly reach an acceptable serum level.[55]
The initial high-dosage treatment can be given on a daily or weekly basis or can be given in form of one or several single doses (also known as stoss therapy, from the German word "Stoß" meaning push).[56]
Therapy prescriptions vary, and there is no consensus yet on how best to arrive at an optimum serum level. While there is evidence that vitamin D3 raises 25(OH)D blood levels more effectively than vitamin D2,[57] other evidence indicates that D2 and D3 are equal for maintaining 25(OH)D status.[55]
### Initial phase[edit]
#### Daily or weekly or monthly dose[edit]
For treating rickets, the American Academy of Pediatrics (AAP) has recommended that pediatric patients receive an initial two- to three-month treatment of "high-dose" vitamin D therapy. In this regime, the daily dose of cholecalciferol is 1,000 IU for newborns, 1,000 to 5,000 IU for 1- to 12-months old infants, and 5,000 IU for patients over 1 year of age.[56]
For adults, other dosages have been called for. A review of 2008/2009 recommended dosages of 1,000 IU cholecalciferol per 10 ng/ml required serum increase, to be given daily over two to three months.[58] In another proposed cholecalciferol loading dose guideline for vitamin D-deficient adults, a weekly dosage is given, up to a total amount that is proportional to the required serum increase (up to the level of 75 nml/l) and, within certain body weight limits, to body weight.[59]
According to new data and practices relevant to vitamin D levels in the general population in France to establish optimal vitamin D status and frequency of intermittent supplement dosing,[60] patients with or at high risk for osteoporosis and vitamin D deficiency should start supplementation with a loading phase consisting of 50,000 IU weekly of vitamin D for 8 weeks in patients with levels <20 ng/mL and 50,000 IU weekly for 4 weeks in patients with levels between 20 and 30 ng/mL. Subsequently, long-term supplementation should be prescribed as 50,000 IU monthly. Should pharmaceutical forms suitable for daily supplementation become available, patients displaying good treatment adherence could take a daily dose determined based on the 25(OH)D level.
Until now, there are no consistent data suggesting the ideal regimen of supplementation with vitamin D, and the question of the ideal time between doses is still of debate. Ish-Shalom et al.[61] performed a study in elderly women to compare the efficacy and safety of a daily dose of 1500 IU to a weekly dose of 10,500 IU and to a dose of 45,000 IU given every 28 days for two months. They concluded that supplementation with vitamin D can be equally achieved with daily, weekly, or monthly dosing frequencies. Another study comparing daily, weekly, and monthly supplementation of vitamin D in deficient patient was published by Takacs et al.[62] They reported an equal efficacy of 1000 IU taken daily, 7000 IU taken weekly, and 30,000 IU taken monthly. Nevertheless, these consistent findings differ from the report by Chel et al.[63] in which a daily dose was more effective than a monthly dose. In that study, the compliance calculation could be questionable, as only random samples of the returned medications were counted. In a study by De Niet et al.[64] 60 subjects with vitamin D deficiency were randomized to receive 2,000 IU vitamin D3 daily or 50,000 IU monthly. They reported a similar efficacy of the two dosing frequencies, with the monthly dose providing a more rapid normalization of vitamin D levels.
#### Single-dose therapy[edit]
Alternatively, a single-dose therapy is used for instance if there are concerns regarding the patient's compliance. The single-dose therapy can be given as an injection, but is normally given in form of an oral medication.[56]
#### Vitamin D doses and meals[edit]
The presence of a meal and the fat content of that meal may also be important. Because vitamin D is fat-soluble, it is hypothesized that absorption would be improved if patients are instructed to take their supplement with a meal. Raimundo et al.[65][66] performed different studies confirming that a high-fat meal increased the absorption of vitamin D3 as measured by serum 25(OH) D. A clinical report indicated that serum 25(OH) D levels increased by an average of 57% over a 2-month to 3-month period in 17 clinic patients after they were instructed to take their usual dose of vitamin D with the largest meal of the day.[67] Another study conducted in 152 healthy men and women concluded that diets rich in monounsaturated fatty acids may improve and those rich in polyunsaturated fatty acids may reduce the effectiveness of vitamin D3 supplements.[68] In another study performed by Cavalier E. et al.[69] 88 subjects received orally a single dose of 50,000 IU of vitamin D3 solubilized in an oily solution as two ampoules each containing 25,000 IU (D‐CURE®, Laboratories SMB SA, Brussels, Belgium) with or without a standardized high‐fat breakfast. No significant difference between fasting vs. fed conditions was observed.
### Maintenance phase[edit]
Once the desired serum level has been achieved, be it by a high daily or weekly or monthly dose or by a single-dose therapy, the AAP recommendation calls for a maintenance supplementation of 400 IU for all age groups, with this dosage being doubled for premature infants, dark-skinned infants and children, children who reside in areas of limited sun exposure (>37.5° latitude), obese patients, and those on certain medications.[56]
### Special cases[edit]
To maintain blood levels of calcium, therapeutic vitamin D doses are sometimes administered (up to 100,000 IU or 2.5 mg daily) to patients who have had their parathyroid glands removed (most commonly kidney dialysis patients who have had tertiary hyperparathyroidism, but also to patients with primary hyperparathyroidism) or with hypoparathyroidism.[70] Patients with chronic liver disease or intestinal malabsorption disorders may also require larger doses of vitamin D (up to 40,000 IU or 1 mg (1000 micrograms) daily).
## Epidemiology[edit]
The estimated percentage of the population with a vitamin D deficiency varies based on the threshold used to define a deficiency.
Percentage of US population Definition of insufficiency Study Reference
69.5% 25(OH)D less than 30 ng/mL Chowdury et al. 2014 [71]
77% 25(OH)D less than 30 ng/mL Ginde et al. 2009 [72]
36% 25(OH)D less than 20 ng/mL Ginde et al. 2009 [72]
6% 25(OH)D less than 10 ng/mL Ginde et al. 2009 [72]
Recommendations for 25(OH)D serum levels vary across authorities, and probably vary based on factors like age; calculations for the epidemiology of vitamin D deficiency depend on the recommended level used.[73]
A 2011 Institute of Medicine (IOM) report set the sufficiency level at 20 ng/ml (50 nmol/l), while in the same year The Endocrine Society defined sufficient serum levels at 30 ng/ml and others have set the level as high as 60 ng/ml.[74] As of 2011 most reference labs used the 30 ng/ml standard.[55][74][75]:435
Applying the IOM standard to NHANES data on serum levels, for the period from 1988 to 1994 22% of the US population was deficient, and 36% were deficient for the period between 2001 and 2004; applying the Endocrine Society standard, 55% of the US population was deficient between 1988 and 1994, and 77% were deficient for the period between 2001 and 2004.[74]
In 2011 the Centers for Disease Control and Prevention applied the IOM standard to NHANES data on serum levels collected between 2001 and 2006, and determined that 32% of Americans were deficient during that period (8% at risk of deficiency, and 24% at risk of inadequacy).[74][76]
## History[edit]
The role of diet in the development of rickets was determined by Edward Mellanby between 1918 and 1920.[77] In 1921, Elmer McCollum identified an antirachitic substance found in certain fats that could prevent rickets. Because the newly discovered substance was the fourth vitamin identified, it was called vitamin D.[77] The 1928 Nobel Prize in Chemistry was awarded to Adolf Windaus, who discovered the steroid 7-dehydrocholesterol, the precursor of vitamin D.
Prior to the fortification of milk products with vitamin D, rickets was a major public health problem. In the United States, milk has been fortified with 10 micrograms (400 IU) of vitamin D per quart since the 1930s, leading to a dramatic decline in the number of rickets cases.[33]
## Research[edit]
A great deal of research has been conducted to understand whether low levels of vitamin D may cause or be a result of other conditions.
Some evidence suggests vitamin D deficiency may be associated with a worse outcome for some cancers, but evidence is insufficient to recommend that vitamin D be prescribed for people with cancer.[78] Taking vitamin D supplements has no significant effect on cancer risk.[79] Vitamin D3, however, appears to decrease the risk of death from cancer but concerns with the quality of the data exist.[80]
Vitamin D deficiency is thought to play a role in the pathogenesis of non-alcoholic fatty liver disease.[81][82]
Some studies have indicated that vitamin D deficiency may play a role in immunity. Those with vitamin D deficiency may have trouble fighting off certain types of infections. It has also been thought to correlate with cardiovascular disease, type 1 diabetes, type 2 diabetes, and some cancers.[7]
Review studies have also seen associations between vitamin D deficiency and pre-eclampsia.[83]
## See also[edit]
* Hypervitaminosis D
* Vitamin D deficiency in Australia
## References[edit]
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* B2
* Riboflavin deficiency
* B3
* Pellagra
* B6
* Pyridoxine deficiency
* B7
* Biotin deficiency
* B9
* Folate deficiency
* B12
* Vitamin B12 deficiency
Other
* A: Vitamin A deficiency
* Bitot's spots
* C: Scurvy
* D: Vitamin D deficiency
* Rickets
* Osteomalacia
* Harrison's groove
* E: Vitamin E deficiency
* K: Vitamin K deficiency
Mineral deficiency
* Sodium
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* Magnesium
* Calcium
* Iron
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* Manganese
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Growth
* Delayed milestone
* Failure to thrive
* Short stature
* Idiopathic
General
* Anorexia
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*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Vitamin D deficiency | c0042870 | 3,080 | wikipedia | https://en.wikipedia.org/wiki/Vitamin_D_deficiency | 2021-01-18T18:51:53 | {"mesh": ["D014808"], "umls": ["C0042870"], "icd-9": ["268", "268.9"], "icd-10": ["E55"], "wikidata": ["Q4138762"]} |
## Summary
### Clinical characteristics.
Males with deafness-dystonia-optic neuronopathy (DDON) syndrome have prelingual or postlingual sensorineural hearing impairment in early childhood, slowly progressive dystonia or ataxia in the teens, slowly progressive decreased visual acuity from optic atrophy beginning at approximately age 20 years, and dementia beginning at approximately age 40 years. Psychiatric symptoms such as personality change and paranoia may appear in childhood and progress. The hearing impairment appears to be consistent in age of onset and progression, whereas the neurologic, visual, and neuropsychiatric signs vary in degree of severity and rate of progression. Females may have mild hearing impairment and focal dystonia.
### Diagnosis/testing.
The diagnosis of DDON syndrome is established in either a male proband who has a hemizygous TIMM8A pathogenic variant (~50% of affected males) or a female proband who has a heterozygous TIMM8A pathogenic variant (~50% of affected females) or a contiguous gene deletion of Xp22.1 involving TIMM8A (~50% of affected males and females).
### Management.
Treatment of manifestations: Educational programs for developmental and sensory deficits, including training in tactile sign language. Because auditory neuronopathy is the cause of the hearing loss, hearing aids have only variable success. Physical medicine and rehabilitation, physical and occupational therapy to improve fine and gross motor skills and mobility, to prevent contractures, and to provide adaptive devices to improve activities of daily living. Standard treatment of behavioral issues / psychiatric disorders. Ensure appropriate social work involvement to connect families with local resources, respite, and support, especially care coordination with multiple subspecialty appointments, equipment, medications, and supplies.
Surveillance: Regular neurologic evaluation and assessment for dementia and/or psychiatric manifestations; annual developmental, speech/language, vision assessments in childhood; regular physical therapy / occupational therapy for review of activities of daily living, gross motor and fine motor needs; routine follow up of the social support and social services needs of the family/caregivers.
### Genetic counseling.
DDON syndrome is inherited in an X-linked manner. If the mother of a proband with DDON syndrome has the causative genetic alteration (i.e., a TIMM8A pathogenic variant or a contiguous gene deletion of Xp22.1 involving TIMM8A), the chance of transmitting the genetic alteration in each pregnancy is 50%. Males who inherit the genetic alteration will be affected; females who inherit the genetic alteration will be heterozygotes and may have mild hearing impairment and focal dystonia. Males who reproduce pass the genetic alteration to all of their daughters and none of their sons.
Prenatal diagnosis for pregnancies at increased risk and preimplantation genetic diagnosis are possible if the DDON-causing genetic alteration in the family is known.
## Diagnosis
Formal diagnostic criteria for deafness-dystonia-optic neuronopathy (DDON) syndrome have not been established.
Scope of this chapter. Deafness-dystonia-optic neuronopathy (DDON) syndrome occurs as either a single-gene disorder resulting from a pathogenic variant in TIMM8A or a contiguous gene deletion at Xq22.1 that includes BTK and additionally causes X-linked agammaglobulinemia (XLA). XLA will not be discussed further in this chapter.
### Suggestive Findings
Deafness-dystonia-optic neuronopathy (DDON) syndrome is suspected in males with the following:
* Progressive sensorineural hearing impairment with prelingual or postlingual onset:
* Absent stapedius reflex
* Abnormal findings on auditory brain stem response testing
* Normal evoked otoacoustic emissions, indicating normal outer hair cells [Richter et al 2001]
* Normal findings on CT scan of the inner ear [Mohr & Mageroy 1960, Tranebjaerg et al 1995]
* Movement disorder (dystonia/ataxia)
* Gradual onset and slow progression of personality changes, paranoia, dementia
* Gradual decrease in visual acuity associated with optic atrophy
* Gradual onset and slow progression of dysphagia
* A family history consistent with X-linked inheritance
### Establishing the Diagnosis
The diagnosis of deafness-dystonia-optic neuronopathy (DDON) syndrome is established in a proband who has one of the following on molecular genetic testing (see Table 1) [Tranebjaerg 2012]:
* A hemizygous TIMM8A pathogenic variant in a male proband (~50% of affected males) or a heterozygous TIMM8A pathogenic variant in a female proband (~50% of affected females)
* A contiguous gene deletion of Xp22.1 involving TIMM8A (~50% of affected males and females)
Options for molecular genetic testing can include a chromosomal microarray analysis (CMA) or use of a multigene panel depending on the phenotype and family history.
Note: The clinical features of DDON in individuals with a contiguous gene deletion and in individuals with smaller pathogenic variants are indistinguishable, apart from the additional presence of X-linked agammaglobulinemia in the former.
#### Option 1
In a child with hearing loss and evidence of a family history suggestive of XLA, CMA should be performed first. CMA uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including TIMM8A) that cannot be detected by sequence analysis.
#### Option 2
In a young child with hearing impairment and no other phenotypic findings, there should be a strong suspicion of DDON if the auditory phenotype is auditory neuropathy. A deafness / hearing impairment or an auditory neuropathy multigene panel that includes TIMM8A and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For this disorder a multigene panel that also includes deletion/duplication analysis is recommended; however, breakpoints of large deletions and/or deletion of adjacent genes (e.g., BTK as described by Sedivá et al [2007]) may not be detected by these methods and would require CMA for detection (see Table 1).
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 DDON Syndrome
View in own window
Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method
TIMM8ASequence analysis 3, 422/42 5
Gene-targeted deletion/duplication analysis 620/42 7
CMA 818/42 9
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
See Molecular Genetics for information on allelic variants detected in this gene.
3\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
4\.
Lack of amplification by PCR prior to sequence analysis can suggest a putative (multi)exon or whole-gene deletion on the X chromosome in affected males; confirmation requires additional testing by gene-targeted deletion/duplication analysis
5\.
Tranebjaerg [2012], Montaut et al [2018], Wang et al [2019]
6\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. Gene-targeted deletion/duplication testing will detect deletions ranging from a single exon to the whole gene; however, breakpoints of large deletions and/or deletion of adjacent genes (e.g., those described by Sedivá et al [2007]) may not be detected by these methods.
7\.
Most deletions not detectable by sequence analysis are large deletions that include BTK. A single intragenic exon 2 deletion has been reported [Ha et al 2012].
8\.
Chromosomal microarray analysis (CMA) uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including TIMM8A) that cannot be detected by sequence analysis. The ability to determine the size of the deletion/duplication depends on the type of microarray used and the density of probes in the Xq22.1 region. CMA designs in current clinical use target the Xq22.1 region.
9\.
Tranebjaerg [2012], Szaflarska et al [2018], Wang et al [2019]
## Clinical Characteristics
### Clinical Description
Deafness-dystonia-optic neuronopathy (DDON) syndrome is a progressive disorder with prelingual or postlingual sensorineural hearing impairment in early childhood. The hearing impairment is always the presenting manifestation. Typically, DDON is associated with slowly progressive dystonia or ataxia in the teens, slowly progressive decreased visual acuity from approximately age 20 years, and dementia from approximately age 40 years. Psychiatric manifestations such as personality change and paranoia may appear in childhood and progress. The deafness and pronounced visual impairment severely compromise communication in late adulthood.
Note: The term "neuronopathy" refers to the destruction of the cell bodies of neurons and is different from "neuropathy," which is defined as a functional disturbance in the peripheral nervous system.
The hearing impairment appears to be more consistent in age of onset and progression than the neurologic, visual, and neuropsychiatric features, which vary in degree of severity and rate of progression. Life span may show extreme variation, even within a family. For example, in one large family, one member had rapidly progressive dystonia ("dystonia musculorum deformans") and died at age 16 years; other affected family members died in their sixties [Tranebjaerg et al 1995].
Audiologic features. The average age of onset of sensorineural hearing impairment is approximately 18 months, although some affected individuals have apparent congenital prelingual hearing impairment [Swerdlow & Wooten 2001, Ujike et al 2001]. The hearing impairment progresses rapidly and is typically profound before age ten years. Vestibular function is normal.
The hearing impairment results from an auditory neuropathy as shown by intact otoacoustic emissions associated with absent auditory brain stem responses in some individuals and convincing histopathologic evidence in five males with molecularly proven DDON syndrome with near-total loss of cochlear neurons and severe loss of vestibular neurons [Bahmad et al 2007, Wang et al 2019]. As expected from auditory neuropathy many individuals with DDON syndrome, at least in early stages of the disease, have intact otoacoustic emissions [Richter et al 2001, Brookes et al 2008, Wang et al 2019].
Of note, isolated hearing impairment without other manifestations of DDON syndrome has not been reported with TIMM8A pathogenic variants.
Neurologic features. The finding of gegenhalten (defined as diffuse resistance to movement of a limb) may be the first neurologic manifestation. The movement disorder may appear either as dystonia or ataxia. The onset may be as early as childhood, or much later. The movement disorder is progressive and the gait gradually becomes unstable. Affected individuals have brisk tendon reflexes, ankle clonus, and extensor plantar responses. Eventually they need a cane for walking and finally become wheelchair bound. Dystonic contractures may develop [Scribanu & Kennedy 1976, Jensen 1981, Jensen et al 1987, Tranebjaerg et al 1995, Hayes et al 1998].
Although many affected individuals develop dystonia by their thirties, some, ascertained through severely affected male relatives with a typical phenotype, have no detectable neurologic dysfunction in their thirties [Ujike et al 2001, Ha et al 2012].
Dysphagia develops late in the course and often causes aspiration pneumonia and its complications.
A mild peripheral sensory neuropathy may be present.
Spinal cord dysfunction was present in an individual with DDON syndrome with prolonged somatosensory evoked potentials and disturbed central motor conduction to lower extremities in motor evoked potentials [Binder et al 2003].
Seizures are not characteristic.
Neuropsychologic features. Behavioral abnormalities may be present from childhood, with mild intellectual disability, personality changes, restlessness, anxiety, reduced impulse control, aggressive outbursts, and compromised ability to concentrate. Later, paranoid psychiatric features may be present with fear of poisoned food, imaginary sensory impulses from skin, and imaginary foreign bodies in the eyes leading to self-mutilating behavior. Gradually, dementia develops.
Ophthalmologic features. Optic neuronopathy may be subclinical for many years [Ujike et al 2001] and may be apparent only when prolongation of the P100 wave latency is detected on visual evoked potential testing [Ponjavic et al 1996,Tranebjaerg et al 2001].
In childhood, color vision and visual fields are normal [Tranebjaerg et al 1995, Ponjavic et al 1996]. Visual impairment may first be evident in the late teens as photophobia, reduced visual acuity, acquired color vision defect, and central scotomas. Ophthalmologic examination in children reveals normal-appearing optic nerves; in adults, the optic nerves become pale. The appearance of the retina is usually normal, as are night vision and the electroretinogram [Ponjavic et al 1996].
Slowly progressive decline in visual acuity leads to legal blindness around age 30 to 40 years [Tranebjaerg et al 1995, Ponjavic et al 1996, Tranebjaerg et al 2000a, Tranebjaerg et al 2000b, Tranebjaerg et al 2001].
Other characteristics
* Males with DDON syndrome have normal fertility.
* Frequent occurrence of hip fractures in affected males appears to be associated with poor neuromuscular coordination and increased risk for stumbling rather than an abnormality in calcium metabolism or intrinsic bone abnormalities [Tranebjaerg et al 1995].
* Cardiomyopathy does not occur.
* Decrease in respiratory capacity does not occur, except for that related to aspiration pneumonia.
#### Heterozygotes
Older females from the original family described by Tranebjaerg et al [1995] possibly had mild involvement. Recently, females ascertained through families with classically affected males have been shown to have mild hearing impairment and focal dystonia (e.g., "writer's cramp") [Swerdlow & Wooten 2001, Swerdlow et al 2004]. While skewed X-chromosome inactivation may contribute to this phenomenon [Orstavik et al 1996, Plenge et al 1999], X-chromosome inactivation studies were not reported in the families with the most severely involved heterozygous females [Swerdlow & Wooten 2001, Swerdlow et al 2004].
Female probands have been reported [Swerdlow & Wooten 2001, Klempir et al 2010, Ha et al 2012].
#### Other Studies in Affected Males
Neuroimaging (CT, MRI, or PET scan) shows general brain atrophy in the majority of males from age 40 years or, in some cases, earlier [Tranebjaerg et al 2001].
More sophisticated neuroimaging studies such as PET/MRI reveal hypometabolic areas, predominantly over the right striatum and parietal cortex, and marked atrophy of the occipital lobes [Hayes et al 1998, Swerdlow & Wooten 2001, Ujike et al 2001, Binder et al 2003].
Neurophysiologic investigations show cochlear dysfunction.
Neuropathologic abnormalities include general brain atrophy and gliosis, microcalcifications, and neuronal cell death in spiral ganglion cells of the cochlea, Scarpa's ganglion, the retinal ganglion cell layer, the optic nerves, and the calcarine fissures (visual cortex) [Scribanu & Kennedy 1976, Reske-Nielsen et al 1988, Hayes et al 1998, Merchant et al 2001, Tranebjaerg et al 2001].
Otopathologic findings clearly support that DDON syndrome is an auditory neuropathy. Temporal bones from five individuals with molecularly verified DDON syndrome showed near-total loss of cochlear neurons and severe loss of vestibular neurons [Merchant et al 2001, Bahmad et al 2007].
The spinal cord is atrophic with loss of fibers in the dorsal roots and posterior columns, as seen in Friedreich ataxia [Tranebjaerg et al 2001].
Muscle biopsy shows normal enzyme activity of energy-generating systems, no structural abnormalities, and no aggregations of mitochondria. Electron microscopy reveals mild neurogenic atrophy [Tranebjaerg et al 1995, Tranebjaerg et al 2001, Binder et al 2003]. Activities of complexes I through IV of the mitochondrial respiratory chain in muscle biopsy revealed a mild deficiency for complex IV in a male with a de novo p.Gln38Ter stop variant, but no abnormalities could be demonstrated in cultivated fibroblasts [Blesa et al 2007]. No pathogenic variants were identified in the mtDNA genes encoding the complex IV subunits COI, COII, and COIII or in five tRNA mtDNA genes [Blesa et al 2007].
### Genotype-Phenotype Correlations
The limited number of affected individuals, the extremely variable clinical course, and the family-specific nature of each pathogenic variant identified limits detection of genotype-phenotype correlations.
It is noteworthy that the clinical features of DDON in individuals with a contiguous gene deletion and in individuals with smaller pathogenic variants are indistinguishable, apart from presence or absence of X-linked agammaglobulinemia in those with a contiguous gene deletion [Tranebjaerg 2012] (see Genetically Related Disorders).
### Nomenclature
In 1960, Mohr and Mageroy described an X-linked recessive childhood-onset sensorineural hearing impairment, which was believed to be nonsyndromic and thus was designated DFN-1, indicating that it was the first described X-linked nonsyndromic form of hearing impairment [Mohr & Mageroy 1960]. Tranebjaerg et al [1995] reinvestigated the family, updated the pedigree, and identified associated neurologic, visual, and behavioral findings. The syndrome was renamed Mohr-Tranebjaerg syndrome and later deafness-dystonia-optic neuronopathy (DDON) syndrome.
Opticoacoustic nerve atrophy (Jensen syndrome), reported by Jensen [1981], Jensen et al [1987], and Reske-Nielsen et al [1988], and deafness-dystonia syndrome, reported clinically in two families by Scribanu & Kennedy [1976] and Hayes et al [1998], are the same as DDON syndrome. TIMM8A pathogenic variants have been identified in individuals with these two disorders [Tranebjaerg et al 1997, Tranebjaerg et al 2000b, Tranebjaerg et al 2001].
### Prevalence
The prevalence of DDON syndrome is unknown. It has been identified in several populations worldwide.
A recent comprehensive review chapter identified 91 affected individuals from 37 families [Tranebjaerg 2012].
Dystonia of all types occurs with a prevalence between 70 and 329 per million [ESDE Collaborative Group 2000]. No large-scale molecular genetic testing of cohorts of males with dystonia has been published.
Hearing impairment has a prevalence of 1:800, approximately 1% of which is attributed to X-linked inheritance.
## Differential Diagnosis
Specific disorders that share features with deafness-dystonia-optic neuronopathy (DDON) syndrome. See Table 2.
Note: De novo pathogenic variants in TIMM8A in some families may mimic autosomal recessive inheritance and thus complicate the ability to distinguish between X-linked and autosomal causes of dystonia.
### Table 2.
Other Genes of Interest in the Differential Diagnosis of DDON Syndrome
View in own window
Gene(s) 1DisorderMOIFeatures of Differential Diagnosis Disorder
Overlapping w/DDON syndromeDistinguishing from DDON syndrome
MT-TL1 2MELASMat
* The combination of optic atrophy, hearing loss, & neurologic signs suggests mt disorders such as MELAS.
* See also Mitochondrial Disorders Overview.
* Dystonia uncommon in MELAS
* Short stature, generalized tonic-clonic seizures, recurrent headaches/vomiting, & anorexia common in MELAS
SERAC1MEGDEL syndromeARDystonia & deafnessLeigh-like features, impaired oxidative phosphorylation, & 3-methylglutaconic aciduria
SUCLA2SUCLA2-related mtDNA depletion syndrome, encephalomyopathic form w/methylmalonic aciduria 3AR
* Progressive disorder
* Dystonia & severe hearing impairment
* Hypotonia, abnormal muscle histopathology, & ↑ methylmalonic acid concentration
* Ophthalmologic findings normal
* Several cases reported from Faroe Islands
PRPS1Arts syndrome 4XLIntellectual impairment, ataxia, & hearing impairmentArts syndrome findings range from isolated hearing impairment to hearing impairment assoc w/optic atrophy, hypotonia, ataxia, ID, & signs of peripheral neuropathy, but not dystonia.
XKMcLeod neuroacanthocytosis syndromeXLMovement disorder, cognitive impairment, & psychiatric symptoms in males
* Neurodegenerative basal ganglia disease
* Neuromuscular manifestations incl (mostly subclinical) sensorimotor axonopathy & clinically relevant muscle weakness or atrophy
* Hematologic manifestations: RBC acanthocytosis, compensated hemolysis, & McLeod blood group phenotype
* Dilated cardiomyopathy & arrhythmias
CDH23
CIB2
MYO7A
PCDH15
USH1C
USH1G
USH1H 5Usher syndrome type IAR
* Visual & hearing impairment
* In individuals w/DDON, Usher may first be suspected because hearing impairment in DDON may be congenital & in Usher type II may be progressive.
* Impaired vision results from retinal dystrophy, which first manifests as impaired dark adaptation 6 (vs DDON, where appearance of retina is usually normal, as are night vision & ERG).
* No neurologic abnormalities
ADGRV1
USH2A
WHRN 5Usher syndrome type IIAR
WFS1Wolfram syndromeAR
* Optic atrophy, movement disorder, dementia, & psychiatric abnormalities may occur.
* Hearing impairment in ~60% of persons by age 20 yrs
* Consider Wolfram in simplex males (i.e., single case in a family) who appear to have DDON.
* Juvenile onset of diabetes mellitus
* Involvement of most organs
* No dystonia
FXNFriedreich ataxiaAR
* Slowly progressive ataxia w/onset age usually <25 yrs
* May be assoc w/sensorineural hearing impairment (10% of persons) & often subclinical optic atrophy (25%)
* Rarely presents w/hearing impairment or optic atrophy (hearing loss is always a presenting finding in DDON)
* Dystonia & other movement disorders uncommon
* Tendon reflexes usually (not always) depressed in Friedreich ataxia
* Cardiomyopathy common
AR = autosomal recessive; CNS = central nervous system; ERG = electroretinogram; ID = intellectual disability; Mat = maternal; MELAS = mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes; MOI = mode of inheritance; mt = mitochondrial; RBC = red blood cell; XL = X-linked
1\.
Genes are in alphabetic order.
2\.
The m.3243A>G pathogenic variant in the mitochondrial gene MT-TL1 is present in approximately 80% of individuals with MELAS. Pathogenic variants in MT-TL1nor other mtDNA genes, particularly MT-ND5, can also cause this disorder.
3\.
The disorder was identified in a Muslim family and ten remotely related individuals from the Faroe Islands, where a high carrier frequency (1 in 33) is caused by a founder variant [Ostergaard et al 2007].
4\.
See also other heredodegenerative X-linked disorders characterized by intellectual impairment, movement disorder, and hearing impairment, including Farlow syndrome (OMIM 301840), Schimke syndrome (OMIM 312840), Wells syndrome (OMIM 312910), and Schmidley syndrome (OMIM 301790).
5\.
See Phenotypic Series: Usher syndrome for additional genes associated with this phenotype in OMIM.
6\.
Ophthalmoscopy and electroretinography can be used to determine the cause of visual impairment.
Hearing impairment. Hearing impairment shows genetic heterogeneity (see Hereditary Hearing Loss and Deafness Overview). The diagnosis of DDON syndrome needs to be considered in males with prelingual hearing impairment in the absence of family history of hearing loss if more common genetic causes (e.g., DFNB1, Pendred syndrome) have been excluded. X-linked hearing impairment without additional manifestations may be linked to other DFN loci (see DFNX1 Nonsyndromic Hearing Loss and Deafness).
The presence of immunodeficiency and hearing impairment in a male should raise the possibility of a contiguous gene deletion at Xq22 involving TIMM8A and BTK.
Dystonia. Dystonias are a heterogeneous group of disorders (see Hereditary Dystonia Overview). Hearing impairment does not appear to be commonly associated with other dystonias.
## Management
### Evaluations Following Initial Diagnosis
Affected males. To establish the extent of disease and needs in a male diagnosed with deafness-dystonia-optic neuronopathy (DDON) syndrome, the evaluations summarized in Table 3 (if not performed as part of the evaluation that led to the diagnosis) are recommended.
### Table 3.
Recommended Evaluations Following Initial Diagnosis in Males with DDON Syndrome
View in own window
System/ConcernEvaluationComment
Hearing
impairmentFormal audiologic assessment w/focus on possibility of auditory neuropathyTo determine extent of hearing impairment
Speech & language assessmentTo determine speech therapy needs
Dystonia/AtaxiaNeurologic assessmentTo provide baseline information
Orthopedics / physical medicine & rehabilitation / PT / OT evaluationIncl assessment of:
* Gross motor & fine motor skills
* Mobility, activities of daily living, & need for adaptive devices
* Need for PT (to improve gross motor skills) &/or OT (to improve fine motor skills)
Vision
impairmentOphthalmologic evaluation incl VEPIncl visual acuity, color vision testing, visual field testing for evidence of central scotomas
DevelopmentDevelopmental assessment; consider specialized testing for deaf &/or visually impaired persons.Incl motor, adaptive, cognitive evaluation for early intervention / special education
Psychiatric/
BehavioralNeuropsychiatric evaluationFor individuals w/dementia &/or psychiatric disturbance
Miscellaneous/
OtherConsultation w/clinical geneticist &/or genetic counselorIncl genetic counseling
Family support/resourcesAssess:
* Use of community or online resources (e.g., Parent to Parent)
* Need for social work involvement for parental support
OT = occupational therapy; PT = physical therapy; VEP = visual evoked potential
Heterozygous females. The evaluation of a heterozygous female depends on whether she is a symptomatic proband (see Table 3) or primarily a healthy female relative of a male proband.
### Treatment of Manifestations
### Table 4.
Treatment of Manifestations in Individuals with DDON Syndrome
View in own window
Manifestation/
ConcernTreatmentConsiderations/Other
Poor visual acuity / blindnessCorrective lenses / standard treatmentCommunity vision services through early intervention or school district
Hearing impairment / deafnessTreatment of SNHL, w/focus on auditory neuropathy, depends on degree of hearing impairment. 1
* Start hearing habituation (auditory & speech training, sign language) as soon as possible.
* Community hearing services through early intervention or school district
Cochlear implant
* CT of bony landmarks & MRI of vestibular & facial nerves as part of pre-cochlear implant assessment 2, 3
* Cochlear implants may provide sound awareness & even speech recognition in presence of cochlear abnormalities. 4
* Outcome is expected to be variable in auditory neuropathy.
CommunicationDepends on degree of hearing & vision impairmentRefer to community deaf-blind services & state Deafblind Project as soon as possible after birth. 8
DystoniaPhysical medicine & rehabilitation / PT / OT
* To improve gross motor skills & mobility & prevent contractures
* To improve fine motor skills
* Provide adaptive devices to improve activities of daily living.
DD/IDSee Developmental Delay / Intellectual Disability Management Issues.
Behavioral
concernsStandard medications for obsessive-compulsive disorderBehavioral therapy combined w/stress reduction is sometimes helpful.
Behavior therapy, stress reduction, & standard medications for pervasive developmental disorderBehaviors may mimic autism but are different; 9 may be exacerbated by sensory processing issues.
Establish an appropriate method of communication & provide adequate stimulation for exploration in a safe environment for ADHD.May be more helpful than medication
Family needsEnsure appropriate social work involvement to connect families w/local resources, respite, & support.Ongoing assessment for need of home nursing
Coordinate care to manage multiple subspecialty appointments, equipment, medications, & suppliesConsider involvement in adaptive sports or Special Olympics.
ADHD = attention-deficit/hyperactivity disorder; DD/ID = developmental delay / intellectual disability; OT = occupational therapy; PT = physical therapy; SNHL = sensorineural hearing loss
1\.
See Hereditary Hearing Loss and Deafness Overview for details about treatment options.
#### Developmental Delay / Intellectual Disability Management Issues
The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.
Ages 0-3 years. Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy as well as infant mental health services, special educators, and sensory impairment specialists. In the US, early intervention is a federally funded program available in all states that provides in-home services to target individual therapy needs.
Ages 3-5 years. In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social, or cognitive delay. The early intervention program typically assists with this transition. Developmental preschool is center based; for children too medically unstable to attend, home-based services are provided.
All ages. Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider:
* Individualized education plan (IEP) services:
* An IEP provides specially designed instruction and related services to children who qualify.
* IEP services will be reviewed annually to determine whether any changes are needed.
* As required by special education law, children should be in the least restrictive environment feasible at school and included in general education as much as possible and when appropriate.
* Vision and hearing consultants should be a part of the child's IEP team to support access to academic material.
* PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Beyond that, private supportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.
* As a child enters the teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21.
* A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text.
* Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a US public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.
* Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.
#### Motor Dysfunction
Gross motor dysfunction
* Physical therapy is recommended to maximize mobility and to reduce the risk for later-onset orthopedic complications (e.g., contractures, scoliosis, hip dislocation).
* Consider use of durable medical equipment and positioning devices as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers).
* For muscle tone abnormalities including hypertonia or dystonia, consider involving appropriate specialists to aid in management of baclofen, tizanidine, Botox®, anti-parkinsonian medications, or orthopedic procedures.
Fine motor dysfunction. Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and writing.
Oral motor dysfunction should be assessed at each visit and clinical feeding evaluations and/or radiographic swallowing studies should be obtained for choking/gagging during feeds, poor weight gain, frequent respiratory illnesses, or feeding refusal that is not otherwise explained. Assuming that the child is safe to eat by mouth, feeding therapy (typically by an occupational or speech therapist) is recommended to help improve coordination or sensory-related feeding issues. Feeds can be thickened or chilled for safety. When feeding dysfunction is severe, an NG-tube or G-tube may be necessary.
Communication issues. Consider evaluation for alternative means of communication (e.g., Augmentative and Alternative Communication [AAC]) for individuals who have expressive language difficulties. An AAC evaluation can be completed by a speech-language pathologist who has expertise in the area. The evaluation will consider cognitive abilities and sensory impairments to determine the most appropriate form of communication. AAC devices can range from low-tech, such as picture exchange communication, to high-tech, such as voice-generating devices. Contrary to popular belief, AAC devices do not hinder verbal development of speech and in many cases, can improve it.
#### Social/Behavioral Concerns
Children may qualify for and benefit from interventions used in treatment of autism spectrum disorder, including applied behavior analysis (ABA). ABA therapy is targeted to the individual child's behavioral, social, and adaptive strengths and weaknesses and is typically performed one on one with a board-certified behavior analyst.
Consultation with a developmental pediatrician may be helpful in guiding parents through appropriate behavior management strategies or providing prescription medications, such as medication used to treat attention-deficit/hyperactivity disorder, when necessary.
Concerns about serious aggressive or destructive behavior can be addressed by a pediatric psychiatrist.
### Surveillance
### Table 5.
Recommended Surveillance for Individuals with DDON Syndrome
View in own window
System/ConcernEvaluationFrequency
Hearing impairmentAudiologic evaluationAnnually
Speech & language developmentBy speech & language therapistAnnually
DystoniaNeurologic examination to monitor progression of dystonia & review medicationsRegular follow up depending on rate of progression
PT/OT: review activities of daily living, gross motor & fine motor needsRegular follow up depending on rate of progression
Vision impairmentVisual acuityRegular follow up depending on rate of progression
Psychiatric/
BehavioralWhen clinically relevantIndividual follow up based on clinical findings
Developmental
progress &
educational needs
* Effect of hearing impairment, vision impairment, movement disorder, changes in behavior &/or cognitive abilities when clinically relevant
* Be aware of signs of dementia in adults.
Individual program for follow up
Family/caregiver
needsAssess need for social work support (e.g., respite care, home nursing, other local resources) & care coordination.At each visit
OT = occupational therapy; PT = physical therapy
### 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.
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*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Deafness-Dystonia-Optic Neuronopathy Syndrome | c0796074 | 3,081 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1216/ | 2021-01-18T21:31:05 | {"mesh": ["C535808"], "synonyms": ["DDON", "Mohr-Tranebjaerg Syndrome"]} |
A number sign (#) is used with this entry because Bardet-Biedl syndrome-5 (BBS5) is caused by homozygous mutation in the BBS5 gene (603650) on chromosome 2q31.
Description
BBS5 is a ciliopathy associated with severe and early-onset retinal dystrophy, postaxial polydactyly, obesity, renal dysfunction, hypogonadism, and learning difficulties (summary by Scheidecker et al., 2015). Patients described by Young et al. (1999) and Moore et al. (2005) with mutations in the BBS5 gene did not have polydactyly. The contribution of BBS5 mutations to all cases of BBS has been estimated at 2% (Li et al., 2004) and 0.40% (Zaghloul and Katsanis, 2009).
For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (209900).
Clinical Features
Young et al. (1999) reported that in 5 affected members of a BBS5 kindred, related as sibs or first cousins in 3 sibships and of ages varying from 21 to 31 years, none had polydactyly, but all had brachydactyly and/or syndactyly. All had severe visual impairment with retinal macular changes, and in the 2 males examined, the penis was small.
In a 22-year prospective cohort study of 46 patients from 26 Newfoundland families with BBS, Moore et al. (2005) found that 1 patient who had been diagnosed with Laurence-Moon syndrome (245800) was from a consanguineous family with BBS linked to the BBS5 gene. Another was a compound heterozygote for mutations in the MKKS gene (604896.0007 and 604896.0008) and had been previously reported by Katsanis et al. (2000) as having BBS6 (605231). Moore et al. (2005) concluded that the features in this population did not support the notion that BBS and LMS are distinct.
In 6 patients with molecularly confirmed BBS, including 1 patient with BBS5, Scheidecker et al. (2015) found a cone-rod pattern of dysfunction. Macular dystrophy was present in all patients, usually with central hypofluorescence surrounded by a continuous hyperfluorescent ring on fundus autofluorescence imaging. Optical coherence tomography confirmed loss of outer retinal structure within the atrophic areas.
Mapping
By a genomewide scan of pooled DNA samples using microsatellite markers in a family with BBS, Young et al. (1999) demonstrated that the BBS5 locus maps to 2q31. The 2q31 region is close to the HOXD gene cluster (142987), but refined mapping of the recombinant ancestral chromosome excluded all genes within that cluster as candidates for BBS5.
Molecular Genetics
In a patient from the consanguineous Newfoundland family with BBS described by Young et al. (1999), Li et al. (2004) detected a homozygous A-to-G transition at the +3 position of the exon 6 splice donor site of the BBS5 gene (603650.0001). An affected sib was also homozygous for the mutation; both parents were heterozygous, and 4 unaffected sibs were either heterozygous or homozygous wildtype. Li et al. (2004) identified pathogenic mutations in the BBS5 gene in several other patients with BBS. Li et al. (2004) also presented evidence that BBS5 may interact genetically with BBS1 (209901).
Hjortshoj et al. (2008) identified mutations in the BBS5 gene (603650.0005 and 603650.0006) in 5 patients from 2 unrelated non-Caucasian families with BBS.
INHERITANCE \- Autosomal recessive GROWTH Weight \- Obesity HEAD & NECK Eyes \- Retinitis pigmentosa \- Macular dystrophy GENITOURINARY External Genitalia (Male) \- Hypogenitalism \- Hypogonadism Kidneys \- Renal abnormalities SKELETAL Hands \- Brachydactyly \- Syndactyly \- Polydactyly (in some patients) NEUROLOGIC Central Nervous System \- Cognitive impairment MOLECULAR BASIS \- Caused by mutation in the BBS5 gene (BBS5, 603650.0001 ) ▲ Close
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*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| BARDET-BIEDL SYNDROME 5 | c0752166 | 3,082 | omim | https://www.omim.org/entry/615983 | 2019-09-22T15:50:19 | {"doid": ["0110127"], "mesh": ["D020788"], "omim": ["615983"], "orphanet": ["110"]} |
A number sign (#) is used with this entry because of evidence that autosomal dominant hereditary motor and sensory neuropathy type VIA with optic atrophy (HMSN6A), also referred to as Charcot-Marie-Tooth disease type 6A (CMT6A), is caused by heterozygous mutation in the mitofusin-2 gene (MFN2; 608507) on chromosome 1p36.
See also CMT2A2 (609260), an allelic disorder with overlapping features.
Description
Hereditary motor and sensory neuropathy type VI is an autosomal dominant neurologic disorder characterized by peripheral neuropathy and optic atrophy (summary by Voo et al., 2003).
### Genetic Heterogeneity of Hereditary Motor and Sensory Neuropathy Type VI
See also HMSN6B (616505), caused by mutation in the SLC25A46 gene (610826) on chromosome 5q22, and HMSN6C (618511), caused by mutation in the PDXK gene (179020) on chromosome 21q22.
For a general phenotypic description and a discussion of genetic heterogeneity of CMT, see CMT1B (118200).
Clinical Features
Dyck et al. (1993) referred to a report by Vizioli (1889) describing a father and 2 sons with optic atrophy in association with peroneal muscular atrophy. The father became ill at age 59, one son at age 26, and the other at age 6. The older son and the father lost visual acuity and eventually became blind. Deep tendon reflexes were normal or decreased. Dyck et al. (1993) categorized this report and other cases of peroneal muscular atrophy with optic atrophy as hereditary motor and sensory neuropathy VI.
Ballet and Rose (1904) described 2 brothers with a similar phenotype. Schneider and Abeles (1937) described peroneal muscular atrophy and optic atrophy in 2 middle-aged brothers, the product of a first-cousin mating. The report was consistent with autosomal recessive inheritance. Visual deterioration began at age 7 years and progressed through adolescence when gait difficulties began. The affected sibs had 2 healthy sisters and 2 healthy brothers. Milhorat (1943) described 2 brothers, born of first-cousin parents, who developed nystagmus at age 9 years, distal muscular atrophy at age 15, and decreased visual acuity in their 20s. One sister had an illness that resembled multiple sclerosis (MS; 126200) but without peripheral neuropathy. Hoyt (1960) described a 17-year-old boy with muscle weakness beginning at 2 years of age who abruptly developed difficulty with visual acuity in the right eye and a month later in the left eye. The author commented on the similarity to Leber optic atrophy (535000).
Barreira et al. (1990) described an affected 12-year-old boy and his 10-year-old sister born to consanguineous parents. Electromyography demonstrated denervation and a marked decrease in nerve conduction velocity (NCV).
Ippel et al. (1995) reported a family with clear autosomal dominant inheritance of HMSN VIA. A father and 2 children, 1 son and 1 daughter, had both polyneuropathy and optic atrophy. Sural nerve biopsy from the father showed a mixed pattern of axonal and demyelinating neuropathy with small onion bulbs. Ippel et al. (1995) noted that several earlier reports of familial HMSN VI were consistent with autosomal recessive inheritance and proposed that HMSN VI may be genetically heterogeneous.
Chalmers et al. (1996, 1997) reported 2 unrelated HMSN VIA families that showed autosomal dominant and autosomal recessive inheritance, respectively.
Voo et al. (2003) reported a large family in which 58 members were reportedly affected by autosomal dominant HMSN VIA. Twelve affected individuals were examined by a physician and confirmed to have both peripheral neuropathy and optic atrophy; 3 other family members had either neuropathy or optic atrophy. Although there was clinical variability, most had childhood onset of progressive visual loss due to optic atrophy, abnormal gait, distal sensory impairment, and hyporeflexia. Other variable features included hearing loss, tinnitus, cogwheel ocular pursuit, and anosmia. Incomplete penetrance was observed.
Zuchner et al. (2006) reported 10 affected individuals from 6 unrelated families with HMSN VIA. Inheritance in all cases was autosomal dominant. All had a very early onset of axonal peripheral neuropathy, ranging from 1 to 10 years (mean age at onset 2.1 years). The symptoms showed severe progression, with almost all patients becoming wheelchair-bound. Features of the neuropathy included pes cavus, muscle atrophy, and distal sensory impairment for all modalities. Affected individuals in 1 family also had scoliosis and vocal cord paresis. Onset of optic atrophy was later, between 5 and 50 years of age (mean age 19 years). Most individuals experienced subacute deterioration of visual acuity with color vision defects, central scotoma, and pale optic discs. Remarkably, 60% of the patients experienced significant recovery of their visual acuity after several years. Incomplete penetrance was observed in 1 family.
### Clinical Variability
Del Bo et al. (2008) reported an Italian father and 2 sons with peripheral neuropathy and a highly variable phenotype. The father had a symmetric axonal predominantly motor polyneuropathy, spastic gait, and pes cavus, consistent with CMT2A2, as well as impaired nocturnal vision and sensorineural hearing loss, consistent with HMSN6A. He also showed cognitive decline first noted in his forties. Both sons had delayed motor and language development, decreased IQ, steppage gait, distal muscle weakness and atrophy, and axonal sensorimotor neuropathy at ages 10 and 7 years, respectively. One son also had optic nerve dysfunction. MR spectroscopy (MRS) in the father suggested a defect in mitochondrial energy metabolism in the occipital cortex. Molecular analysis identified a heterozygous mutation in the MFN2 gene (608507.0014) in all 3 individuals. Del Bo et al. (2008) suggested that central nervous system involvement and cognitive impairment may be other phenotypic features of MFN2 mutations.
Molecular Genetics
In affected members of 6 unrelated families with autosomal dominant HMSN VIA, Zuchner et al. (2006) identified 6 different heterozygous mutations in the MFN2 gene (see, e.g., 608507.0009-608507.0012).
INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Hearing loss, mild (rare) \- Tinnitus (rare) Eyes \- Optic atrophy \- Pale optic disks \- Subacute deterioration of visual acuity \- Color vision defects \- Central scotoma \- Abnormal visual-evoked potentials \- Recovery of visual acuity occurs in 60% of patients \- Cogwheel ocular pursuit \- Dysmetric saccades Nose \- Anosmia (rare) RESPIRATORY Larynx \- Vocal cord paresis in severe cases SKELETAL Spine \- Scoliosis in severe cases \- Lumbar hyperlordosis Feet \- Pes cavus NEUROLOGIC Peripheral Nervous System \- Distal limb muscle weakness due to peripheral neuropathy \- Distal limb muscle atrophy due to peripheral neuropathy \- 'Steppage' gait \- Positive Romberg sign \- Most patients become wheelchair-bound \- Proximal muscle weakness \- Distal sensory impairment of all modalities \- Hyporeflexia \- Areflexia \- Normal or mildly decreased motor nerve conduction velocity (NCV) (greater than 38 m/s) \- Nerve biopsy shows axonal degeneration/regeneration MISCELLANEOUS \- Early onset of peripheral neuropathy (mean 2.1 years, range 1 to 10 years) \- Later onset of optic atrophy (mean 19 years, range 5 to 50 years) \- Incomplete penetrance of optic atrophy \- Allelic disorder to Charcot-Marie-Tooth disease type 2A2 (CMT2A2, 609260 ) \- Autosomal recessive inheritance has also been reported MOLECULAR BASIS \- Caused by mutations in the mitofusin 2 gene (MFN2, 608507.0009 ) ▲ Close
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*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| NEUROPATHY, HEREDITARY MOTOR AND SENSORY, TYPE VIA, WITH OPTIC ATROPHY | c0393807 | 3,083 | omim | https://www.omim.org/entry/601152 | 2019-09-22T16:15:21 | {"doid": ["0080068"], "mesh": ["C562851"], "omim": ["601152"], "orphanet": ["90120"], "synonyms": ["Alternative titles", "HMSN VIA", "NEUROPATHY, HEREDITARY MOTOR AND SENSORY, TYPE VI", "PERIPHERAL NEUROPATHY AND OPTIC ATROPHY", "CHARCOT-MARIE-TOOTH DISEASE, TYPE 6A", "CHARCOT-MARIE-TOOTH DISEASE, TYPE 6"]} |
## Inheritance
From twin studies, Rife (1940) had earlier concluded that handedness is a multifactorial trait.
Annett (1964) postulated that right-handedness is an incomplete dominant, or intermediate, i.e., that dominant homozygotes are always right-handed with 'speech highly developed in the left hemisphere.' Recessive homozygotes are consistently left-handed with speech in the right hemisphere. Heterozygotes may use either hand and develop speech in either hemisphere.
Levy and Nagylaki (1972) reviewed experimental data and theoretical work on the inheritance of handedness and cerebral dominance. They found that all quantitative information was in excellent agreement with a 2-gene, 4-allele model, one locus pertaining to left or right hemispheric dominance and the other to contralateral or ipsilateral hand control relative to the dominant hemisphere.
Hicks and Kinsbourne (1976) found that hand preference of college students correlated significantly with the writing hand of their biologic parents but not with that of the stepparents.
Huheey (1977) suggested that preferential right-handedness in man has its evolutionary origin in relation to the tendency of human (and presumably prehuman) mothers to hold infants on the left side. The practice has been ascribed to imprinting and a soothing effect of the sound of the mother's heartbeat on the infant; thus, dextral mothers would be more skillful at manipulation of objects with the free hand and would be selectively favored.
Handedness appears to have remained about 93% right-handed over 5,000 years as indicated by a survey of art works (Coren and Porac, 1977).
Laland et al. (1995) presented a model of handedness that proposes that no genetic variation underlies differences in handedness and that variation in handedness among humans is the result of a combination of cultural and developmental factors, with a remaining genetic influence because handedness is a facultative trait.
Klar (1996) presented a genetic model for human handedness that hypothesized the existence of a single gene, designated RGHT (pronounced as right) by him, which confers right-handedness; individuals lacking this gene, RGHT(-)/RGHT(-), display random handedness such that one-half are left-handed (LH) and the other half are right-handed (RH). Tests of the hypothesis were presented using data from Rife (1940). These data involved the families of 687 students attending Ohio State University. Approximately half of the children of LH x LH families were LH and the remainder were RH. Reference was also made to Lefthanders International and the organization's 'Lefthander' magazine, which advertised the survey that was undertaken for these studies.
Geschwind et al. (2002) explored the relative contribution of environmental and genetic influence on cerebral asymmetry by examining the volumes of left and right cerebral cortex in a large cohort of aging identical and fraternal twins and investigated their relationship to handedness. Cerebral lobar volume was found to have a major genetic component, indicating that genes play a large role in changes in brain volume that occur with aging. Shared environment, which likely represents in utero events, had about twice the effect on the left hemisphere as on the right, consistent with less genetic control over the left hemisphere. To test the major genetic models of handedness and cerebral asymmetry, twin pairs were divided into those with 2 right handers and those with at least 1 left hander (nonright handers). Genetic factors contributed twice the influence to left and right cerebral hemispheric volumes in right-handed twin pairs, suggesting a large decrement in genetic control of cerebral volumes in the nonright-handed twin pairs. This loss of genetic determination of left and right cerebral hemispheres in the nonright-handed twin pairs is consistent with models postulating a right-hand/left-hemisphere-biasing genetic influence, a 'right-shift' genotype that is lost in left handers, resulting in decreased cerebral asymmetry.
Bishop (2001) used data from 2 twin studies to address 2 related questions. First, is there any association between handedness and specific speech and language impairment (SSLI) in children? Second, is there genetic influence on individual differences in handedness, and, if so, are the same genes implicated in the cause of SSLI? No handedness differences were found between 58 monozygotic and 26 dizygotic pairs previously recruited for an investigation into the genetic origins of SSLI and singleton controls. To investigate familial transmission of handedness, inventory data for parents and their twins were combined. The most parsimonious model of the findings was one that accounted for parent-child resemblance solely in terms of cultural transmission. Bishop (2001) concluded that, overall, there was no evidence that genes play a role in determining stable individual differences in hand preference.
Handedness is a characteristic, obviously complex in its causation, that may prove amenable to analysis of genetic contribution when a full gene map has been developed (Williamson, 1986). It is a behavioral trait that may be a model for other behavioral traits, normal and abnormal. The observation that the proportion of left-handers in populations decreases with age, diminishing from 13% in 20-year-olds to less than 1% in 80-year-olds, led to the suggestion that sinistrality may be associated with decreased life span. Reduced longevity in left-handers was also suggested by an archival study of records on 2,271 major-league baseball players (Halpern and Coren, 1988). In a questionnaire study of deceased persons identified through death certificates, Halpern and Coren (1991) found significantly more left-handers than right-handers among those who had died in accidents--a result consistent with earlier findings. Age of death in general was lower in left-handers and mixed-handers than in right-handers of either sex. Halpern and Coren (1991) stated that it is likely that the correlates of sinistrality, not sinistrality itself, are responsible for the increased risk; left-handedness may indicate covert neuropathologic features.
Schur (1986) could not demonstrate the association between handedness and an autoimmune disease, systemic lupus erythematosus (152700), which had been proposed by Geschwind and Behan (1982).
In southern Sweden, Olsson and Ingvar (1991) found that left-handedness was significantly less common among patients with breast cancer (1.5%) than among a female referent population (5%); P less than 0.0025. They interpreted the finding as support for theories suggesting that hormonal factors in early life are important both for handedness and for the risk of breast cancer.
Klar (2003) provided evidence for a link between handedness and the orientation of hair whorls on the scalp (139400), suggesting the possibility that the same system that patterns hair may also play a role in left-right asymmetry in the brain. In a sample of the general population, consisting of mostly right-handers (RH), he found that 42 (8.4%) of 500 individuals showed counterclockwise whorl rotation. Non-right-handers (NRH, i.e., left-handers and ambidextrous) displayed a random mixture of clockwise and counterclockwise swirling patterns. Confirming this finding, in another independent sample of individuals chosen because of their counterclockwise rotation, half were found to be NRH. Klar (2003) stated that these findings of coupling in RH and uncoupling in NRH unequivocally established that these traits develop from a common genetic mechanism. Another finding, concerning handedness of the progeny of discordant monozygotic twins, suggested that lefties are 1 gene apart from righties. Together, these results suggested that a single gene controls handedness, whorl orientation, and twin concordance and discordance, and that neuronal and visceral forms of bilateral asymmetry are coded by separate sets of genetic pathways. Klar (2003) discussed the sociologic impact of the results.
Mapping
In a sample of 195 reading-disabled sib pairs in the United Kingdom, Francks et al. (2002) performed a genomewide quantitative trait locus (QTL) linkage analysis using a continuous measure of relative hand skill (PegQ) rather than treating handedness as a categorical state. A QTL on chromosome 2p12-p11.2 yielded strong evidence for linkage to PegQ and another suggestive QTL on 17p11-q23 was also identified. Relative hand skill therefore appears to be a complex multifactorial phenotype with a heterogeneous background, but nevertheless is amenable to QTL-based gene mapping approaches.
Francks et al. (2003) found evidence supporting their earlier location of a QTL for relative hand skill to chromosome 2p12-q11 in a new sample of 105 pairs of adult brothers drawn from a sample of 168 unrelated male sibships (338 brothers) that was originally collected for investigating X-linked effects on handedness. The evidence of linkage had a P value of 0.00035, thus greatly exceeding significance guidelines for confirmation of linkage (guideline P = 0.01, suggested by Lander and Kruglyak, 1995). Francks et al. (2003) concluded that, although handedness variation may be etiologically complex, there is at least 1 polymorphic genetic influence that is located on 2p12-q11.
Van Agtmael et al. (2002) investigated candidate genes known to be involved in the development of left-right asymmetry in 1 informative extended family and 27 nuclear families of right-handed parents and left-handed children. Segregation analysis in the extended pedigree identified allele sharing in the NODAL (601265) and DNAHC13 regions on chromosome 10 and 1, respectively. Linkage analysis using the models of Klar (1996) and McManus (1985), and nonparametric analysis on nuclear families, subsequently excluded all candidate regions tested. Van Agtmael et al. (2002) concluded that parametric and nonparametric analysis on similar cohorts are powerful enough to identify handedness genes.
Schizophrenia (181500) and non-right-handedness are moderately associated, and both traits are often accompanied by abnormalities of asymmetrical brain morphology or function. Francks et al. (2003) found that in a sample of 191 reading-disabled sib pairs, the relative hand skill of sibs was correlated more strongly with paternal than maternal relative hand skill (p = 0.0000037 for paternal identity-by-descent sharing). Similarly, in affected sib-pair analysis of 241 schizophrenic sib pairs, the authors found linkage to schizophrenia for paternal sharing (lod = 4.72, p = 0.0000016) within 3 cM of the peak linkage to relative hand skill. Francks et al. (2003) suggested that the causative genetic effects on chromosome 2p12-q11 may be related, and they proposed that these linkages may be due to a single maternally imprinted influence on lateralized brain development that contains common functional polymorphisms.
History
Bodmer and McKie (1994) referred to the left-handedness of the Kerr family which gave rise to the layout of a Kerr castle stronghold, Ferniehirst, on the border between England and Scotland. Whereas in most castles staircases spiral clockwise, Ferniehirst has counterclockwise ones, providing left-handed swordsmen with an advantage, the bends giving a defender's left hand freedom to move over the open railing. The association between the Kerr name and left-handedness was such that throughout Scotland the expression Kerr-handed, or kerry- or corry-fisted, is said to be commonly used to mean left-handed. Bodmer and McKie (1994) quoted a survey of doctors who were asked to note the handedness of any patient bearing the surname Kerr: 'a total of 29.5 percent of the Kerrs were reported, by both British and North American doctors, to be 'left-handed or ambidextrous' compared with only 11% of a control family.' Thus, in the Kerr family, there is still a strong majority of right handers. Furthermore, the left-handedness may have been encouraged from the beginning. 'Andrew Kerr, founder of the family's Ferniehirst dynasty in 1457, was certainly left-handed and found the characteristic a powerful asset in battle.' It appears that he specifically taught his sons and armed men-servants (who, by custom, took the family name) to wield sword and axe with the left hand, and they, in turn, did the same with their sons.
Misc \- Handedness Inheritance \- Autosomal dominant vs. multifactorial ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| HAND SKILL, RELATIVE | None | 3,084 | omim | https://www.omim.org/entry/139900 | 2019-09-22T16:40:26 | {"omim": ["139900"], "synonyms": ["Alternative titles", "HANDEDNESS"]} |
A number sign (#) is used with this entry because Norrie disease (ND) is caused by mutation in the NDP gene (300658), which encodes norrin, on Xp11.
Description
Norrie disease is an X-linked recessive disorder characterized by very early childhood blindness due to degenerative and proliferative changes of the neuroretina. Approximately 50% of patients show some form of progressive mental disorder, often with psychotic features, and about one-third of patients develop sensorineural deafness in the second decade. In addition, some patients have more complex phenotypes, including growth failure and seizures (Berger et al., 1992).
Warburg (1966) noted confusion of the terms 'pseudoglioma' and microphthalmia with Norrie disease in the literature. 'Pseudoglioma' is a nonspecific term for any condition resembling retinoblastoma and can have diverse causes, including inflammation, hemorrhage, trauma, neoplasia, or congenital malformation, and often shows unilateral involvement. Thus, 'pseudoglioma' is not an acceptable clinical or pathologic diagnosis (Duke-Elder, 1958).
Clinical Features
Warburg (1961) reported 7 cases of a hereditary degenerative disease in 7 generations of a Danish family. The proband was a 12-month-old boy who was normal except for lens opacities found at initial examination at 3 months of age. He had atrophic irides and the fundus was filled with a proliferating retrolental yellowish mass. At 8 months of age, the left eye was enucleated on suspicion of retinoblastoma. Histologic examination showed a hemorrhagic necrotic mass in the posterior chamber, surrounded by undifferentiated glial tissue. Histologic diagnosis was pseudotumor of the retina, retinal hyperplasia, hyperplasia of retinal, ciliary, and iris pigment epithelium, hypoplasia and necrosis of the inner layer of the retina, cataract, and phthisis bulbi. Six relatives had a similar ocular disease. Deafness developed in 5 of these 7 patients in later years, and 4 patients had decreased mental capacity. Warburg (1961) found 48 similar cases in 9 families described in the literature under different categories which she believed belonged to this disease. She suggested that the disorder be named for Gordon Norrie (1933).
Taylor et al. (1959) reported a Greek family with this condition living in Episkopi in Cyprus, where the disorder was known as 'Episkopi blindness.' The published pedigree showed 16 affected males in 5 generations. All affected males were mentally retarded.
Roberts (1937) described a pedigree, originally reported in part by Ash (1922), in which 14 males over 4 generations had microphthalmia. Affected individuals had white patches on the cornea; 2 also had cataract and 5 had nystagmus. Of the 10 individuals for which information was available, 7 were mentally retarded and 3 had normal or above-average intelligence; there was no mental retardation in the family apart from microphthalmic individuals. Waardenburg et al. (1961) thought that the cases reported by Roberts (1937) had pseudoglioma or retinal dysplasia with secondary microphthalmia. Warburg (1966) later stated that the affected persons in Roberts' pedigree were clearly instances of Norrie disease. In only about half of the cases was the eye microphthalmic, or more precisely, phthisical. Histologic study of the eye in 1 mentally retarded blind boy from this family (Whitnall and Norman, 1940) showed changes like those observed by Warburg (1966) in Norrie disease, with small optic nerves and lateral geniculate bodies.
Stephens (1947) reported a family in which 7 males over 4 generations had isolated microphthalmia. The 2 patients who were examined also had sclerocornea. Because the phenotype was transmitted only by normal mothers to their sons, Stephens (1947) suggested that it represented a sex-linked recessive trait. Warburg (1966) noted that Stephens' patients were difficult to evaluate because they were rather old at the time of first examination and information was limited to the facts that the eyes were small and corneas cloudy, but she suggested that these patients may have had Norrie disease. In an extensive pedigree from a Canadian Indian group reported by Wilson (1949), histologic changes were similar to those of ND.
In the family reported by Forssman (1960), 'pseudoglioma' was combined with progressive mental deficiency present from infancy. These patients were first described by Dahlberg-Parrow (1956). Three of the blind boys were reexamined by Warburg (1966), who concluded that the histories and ocular findings were typical of ND.
Warburg (1963) presented 2 new families with 11 patients with Norrie disease. Patients examined varied from 2 months to 58 years of age. Earliest examinations showed pseudoglioma, synechiae, and atrophy of the iris. Blindness was found during the first month of life. Cataracts were observed by 8 months, and by 10 years, the eyes were atrophic with band-shaped corneal degeneration and dense cataract. The atrophy had advanced to opaque white cornea, obliterated anterior chamber, atrophic white iris, and cataractous lens by age 50 years. Though some afflicted had normal intelligence, many were mentally deficient. The mental retardation was a deterioration inasmuch as the affected infants seemed to be normal for the first 1 to 2 years. Five of 9 in 1 family were hard of hearing and 2 of these 5 had diabetes. The mode of inheritance in both families was X-linked recessive.
Johnston et al. (1982) described 2 Irish families with 8 affected males. Harendra de Silva and de Silva (1988) described an extensively affected family in Sri Lanka.
Woodruff et al. (1993) reported a 2-year-old girl who showed severe visual impairment resulting from cataract and total retinal detachment in the right eye with a vascularized mass behind the lens, and in the left eye a retinal fold and traction retinal detachment in the temporal periphery. She had a brother and 2 maternal uncles with Norrie disease. Woodruff et al. (1993) suggested that she was an example of a manifesting heterozygote.
Lev et al. (2007) reported a male infant with Norrie disease. At birth, he was noted to have abnormal red reflex of both eyes with bilateral vitreal opacities. CT imaging of the eyes showed small lenses attached to the cornea, opacification of the lenses, corneal opacities, and synechiae. Pars plana vitrectomy and lensectomy was performed. At age 11 months, he developed myoclonic jerks and irritability. He had significant developmental delay. Over the next few months, he continued to have seizures and showed profound mental retardation. Genetic analysis identified a mutation in the NDP gene (300658.0019).
Mapping
Warburg et al. (1965) demonstrated no linkage of Norrie disease with the Xg blood groups. Moreira-Filho and Neustein (1979) described 6 brothers with what they viewed as a variant of Norrie disease because microcephaly was present in all. Negative lod scores were obtained for linkage with Xg.
Gal et al. (1985) found close linkage of Norrie disease to the L1.28/TaqI RFLP, DXS7 (maximum lod = 3.50 at theta = 0.00) on the X chromosome, suggesting that ND may be in or slightly proximal to band Xp11.3 and near a locus for retinitis pigmentosa (RP2; 300757). Gal et al. (1985) found a peak lod score of 4.1 at theta = 0.00 for linkage with DXS7, which had been localized to Xp11.3. See Bleeker-Wagemakers et al. (1985) for the full data.
Kivlin et al. (1987) stated that no recombination had been identified between ND and the DNA marker L1.28; with their data, the total lod score became 5.42. Ngo et al. (1988) and Katayama et al. (1988) found the first recombinant between Norrie disease and the DXS7 locus. The addition of their family brought a total of published informative families to 7, with a maximum lod score of 7.58 at a recombination fraction of 0.038. They stated the assignment of the DXS7 locus (defined by probe L1.28) as Xp11.3-p11.2. Ngo et al. (1989) pointed out that a single recombination event had been reported twice (Ngo et al., 1988; Katayama et al., 1988).
Gal et al. (1988) described prenatal exclusion of ND with flanking DNA markers. In an addendum, they stated that 3 families with Norrie disease and DXS7 deletion had been reported, bringing the compiled lod score for NDP vs DXS7 linkage to 11.18 at theta = 0.00. Using a RFLP detected by the ornithine amino transferase (OAT)-related DNA sequences that map to Xp (see 258870), Ngo et al. (1989) found a suggestion of linkage to the Norrie disease locus.
Wolff et al. (1992) restudied the family with 'Episkopi blindness' originally studied by Taylor et al. (1959). DNA studies revealed no deletion of any of the probes from proximal Xq. Linkage analysis yielded positive lod scores for all informative markers; e.g., with DXS255 (Xp11.22), maximum lod = 6.54 at theta = 0.0. The findings confirmed that Episkopi blindness and Norrie disease are the same entity.
Cytogenetics
Gal et al. (1985, 1986) described a 14-year-old boy with a complex syndrome dominated by Norrie disease who appeared to have a small deletion involving DXS7; the deletion had been transmitted through 3 generations. Other features included severe mental retardation, hypogonadism, growth disturbances, and increased susceptibility to infections. De la Chapelle et al. (1985) found a deletion defined by DXS7 in 4 affected members of a family with Norrie disease. Using probe L1.28 in the study of a chorion villus sample, they showed that the male fetus of a carrier woman was unaffected.
Ohba and Yamashita (1986) presented evidence suggesting that the Norrie disease locus may be at Xp11. A female infant with typical clinical and histopathologic features of vitreoretinal dysplasia was found to have a reciprocal translocation at t(X;10)(p11;p14). Her parents and sibs had normal karyotypes. Donnai et al. (1988) found that the DXS7 locus was deleted in 2 affected brothers. OTC (300461), located at Xp21.1, and DXS84, also located at Xp21.1, were intact.
In 3 generations of a Norrie disease family with 4 affected males in 3 sibships of 2 generations, Zhu et al. (1989) demonstrated deletion of 2 loci, DXS7 and DXS77. DNA studies of chorion villus biopsy material from the fetus of an obligatory carrier indicated that the fetus had inherited the normal allele from the carrier mother. This prediction was confirmed on eye examination at age 5 months. Diergaarde et al. (1989) further refined the localization of the deletion in a Dutch case of ND.
Collins et al. (1992) reported a male with Norrie disease and 2 obligate heterozygous females who were shown to have a submicroscopic deletion involving the Norrie disease locus and the loci for MAOA (309850) and MAOB (309860). The propositus was a profoundly retarded, blind male; he also had neurologic abnormalities including myoclonus and stereotypy-habit disorder, characterized as persistent stereotypic and self-injurious behavior. Both obligate carriers had a normal IQ. In the propositus, MAO activity was undetectable; in the female heterozygotes, the levels were reduced to the range observed in patients receiving MAO-inhibiting antidepressants. One of the carriers, the mother of the propositus, met diagnostic criteria for 'chronic hypomania and schizotypal features.'
Lindsay et al. (1992) did linkage studies using a highly informative microsatellite marker, DXS426, which maps proximal to DXS7 in the interval Xp11.4-p11.23. A multiply informative crossover localized the NDP gene proximal to DXS7. In conjunction with information from 2 ND patients who had a deletion for DXS7 but not for DXS426, their data indicated that the NDP gene is between DXS7 and DXS426 on proximal Xp. Chen et al. (1992) studied the end point of the deletion in a Norrie disease patient who had been shown to lack both DXS7 and MAO coding sequences, these being closely situated telomeric to the NDP locus. The pattern of retention of subclones within the deletion patient placed the end point of the deletion within 30 to 130 kb of the proximal end of a 650-kb YAC containing DXS7 and the MAO genes. They concluded that the NDP gene lay in whole or in part in the interval of approximately 250 kb within the YAC.
Molecular Genetics
Berger et al. (1992) cloned the NDP gene and identified small deletions within the gene in several patients with Norrie disease. Berger et al. (1992) identified 11 different mutations in the NDP gene (see, e.g., 300658.0001; 300658.0002) in 12 of 17 unrelated patients with Norrie disease. The fact that only one of the point mutations was detected twice was in keeping with the high proportion of new mutations expected for an X-linked disorder with greatly reduced male reproductive fitness.
Schuback et al. (1995) identified mutations in the NDP gene in 24 of 26 kindreds with Norrie disease. The authors identified 3 previously described submicroscopic deletions encompassing the entire ND gene, 6 intragenic deletions, 8 missense mutations, 6 nonsense mutations, and 1 10-bp insertion. With the exception of 2 different mutations, each found in 2 apparently unrelated kindreds, these mutations were unique. Location of most point mutations at or near cysteine residues, potentially critical in protein tertiary structure, supported a previous protein model for norrin as a member of a cystine knot growth factor family (Meitinger et al., 1993). Although genotype-phenotype correlations were limited, patients with larger submicroscopic deletions tended to have a more severe neurologic syndrome.
Isashiki et al. (1995) tabulated known mutations in the NDP gene together with the clinical manifestations.
Genotype/Phenotype Correlations
Walker et al. (1997) described 2 mutations in exon 3 of the NDP gene, a nonsense (S73X; 300658.0020) and a missense (S101F; 300658.0021) mutation, associated with severe and less severe ocular phenotype, respectively. Affected individuals in both families presented with neither the sensorineural deafness nor the mental retardation that often accompanies Norrie disease. Whereas the ocular features of the nonsense mutation were fairly typical of Norrie disease, the missense change in the C terminus was associated with milder features. Others (Chen et al., 1993; Meindl et al., 1995) had previously made the observation that mutations in the C-terminal portion of the gene product appear to result in a less severe phenotype.
History
Clarke (1898) described possibly affected females. A man blind from probable bilateral 'pseudoglioma' married his first cousin. Of their 6 children, 2 girls and 1 boy had unilateral or bilateral 'pseudoglioma.'
In his System of Ophthalmology, Duke-Elder (1958) mistakenly classified the disorder as band-shaped keratopathy.
Sims et al. (1989) demonstrated that the Norrie disease gene is distinct from the monoamine oxidase genes, although some males with atypical Norrie disease who have a submicroscopic deletion in the region of the DXS7 locus have been shown to have disruption of the MAOA and MAOB genes. The authors studied genomic DNA from 19 males in 9 families affected with Norrie disease. No deletions or rearrangements in the region of DXS7 or MAOA were observed in the DNA of these patients. Linkage analysis between the NDP gene and the DXS7 or MAOA loci showed no recombination, with a lod score of 2.80 and 2.58 at a theta of 0.0 for MAOA and DXS7, respectively. MAO activities in fibroblasts and platelets were normal.
INHERITANCE \- X-linked recessive HEAD & NECK Ears \- Sensorineural deafness (onset in the second decade in 25 to 30% of patients) Eyes \- Intraocular retrolental masses, bilateral ('pseudoglioma') \- Blindness in infancy or very early childhood \- Retinal folds \- Retinal detachment \- Phthisical globe \- Microphthalmia \- Retinal dysgenesis \- Retinal dysplasia \- Vitreal opacities \- Corneal opacities \- Shallow anterior chamber \- Histopathology shows rosettes of immature retinal cells in vascular connective tissue \- Hyperplastic vitreous \- Hypoplastic iris \- Iris synechiae \- Cataract \- Optic atrophy NEUROLOGIC Central Nervous System \- Mental retardation, progressive (50% of patients) \- Dementia (later onset) \- Seizures (rare) Behavioral Psychiatric Manifestations \- Psychosis (25% of patients) \- Hallucinations \- Aggressive behavior MISCELLANEOUS \- Eye involvement begins at birth, neurologic involvement begins later MOLECULAR BASIS \- Caused by mutation in the norrin gene (NDP, 300658.0001 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| NORRIE DISEASE | c0266526 | 3,085 | omim | https://www.omim.org/entry/310600 | 2019-09-22T16:17:33 | {"doid": ["0060844"], "mesh": ["C537849"], "omim": ["310600"], "orphanet": ["649"], "synonyms": ["Alternative titles", "ATROPHIA BULBORUM HEREDITARIA", "EPISKOPI BLINDNESS"], "genereviews": ["NBK1331"]} |
Fetal trimethadione syndrome
Other namesGerman syndrome
Condition is caused by Trimethadione (and paramethadione)
Fetal trimethadione syndrome (also known as paramethadione syndrome, German syndrome, tridione syndrome, among others[1]) is a set of birth defects caused by the administration of the anticonvulsants trimethadione (also known as Tridione) or paramethadione to epileptic mothers during pregnancy.[2]
Fetal trimethadione syndrome is classified as a rare disease by the National Institute of Health's Office of Rare Diseases,[3] meaning it affects less than 200,000 individuals in the United States.[4]
The fetal loss rate while using trimethadione has been reported to be as high as 87%.[5]
## Contents
* 1 Presentation
* 2 Diagnosis
* 3 Treatment
* 4 References
* 5 External links
## Presentation[edit]
Fetal trimethadione syndrome is characterized by the following major symptoms as a result of the teratogenic characteristics of trimethadione.[2][6]
* Cranial and facial abnormalities which include; microcephaly, midfacial flattening, V-shaped eyebrows and a short nose
* Cardiovascular abnormalities
* Absent kidney and ureter
* Meningocele, a birth defect of the spine
* Omphalocele, a birth defect where portions of the abdominal contents project into the umbilical cord
* A delay in mental and physical development
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## 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. ^ Additional names include trimethadione embryopathy and trimethadione syndrome.
2. ^ a b Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes \- Retrieved January 2007
3. ^ Fetal trimethadione syndrome on the ORD website. Retrieved January 2007
4. ^ NIH's Office of Rare Diseases Archived 2009-02-06 at the Wayback Machine Retrieved January 2007
5. ^ Teratology and Drug Use During Pregnancy Retrieved January 2007
6. ^ The fetal trimethadione syndrome: report of an additional family and further delineation of this syndrome Retrieved January 2007
## External links[edit]
Classification
D
* ICD-10: Q86.8
* MeSH: C537798
External resources
* Orphanet: 1913
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Fetal trimethadione syndrome | c0265373 | 3,086 | wikipedia | https://en.wikipedia.org/wiki/Fetal_trimethadione_syndrome | 2021-01-18T18:55:48 | {"mesh": ["C537798"], "umls": ["C0265373"], "orphanet": ["1913"], "wikidata": ["Q5445919"]} |
A rare congenital muscular dystrophy characterized by prominent axial hypotonia, predominantly proximal muscle weakness in upper limbs and distal in lower limbs, joint contractures (initially distal, later proximal), spinal rigidity, and progressive respiratory insufficiency, in the presence of moderately elevated serum creatine kinase. Cardiac arrhythmias and sudden death have also been reported.
## Epidemiology
To date over 100 cases of congenital muscular dystrophy due to LMNA (L-CMD) have been reported in the literature; both genders are equally affected.
## Clinical description
The expressivity, severity and progression of the disease are variable but all present a predominant axial and scapula-humeral topography of muscle weakness and atrophy. Motor symptoms appear during the first two years of life and show often a rapid course. In the most severe patients, no head or trunk support are achieved. In milder patients, a more characteristic picture is observed, with a striking loss of head support (dropped-head syndrome), associated with arm weakness but relatively preserved hip and thigh strength in the initial stages. Skeletal manifestations include muscle and joint contractures, spine rigidity, scoliosis and thoracic lordosis. A progressive thoracic stiffness is associated to the respiratory insufficiency favoring recurrent respiratory infections. Severe cases might show swallowing difficulties. Cardiac arrhythmias and sudden death are not uncommon in this group of patients after the first decade or life.
## Etiology
The disorder is due to mutations in the LMNA gene (1q22), coding for type A/C lamins, two intermediate filaments that form cytoplasmic and nuclear networks and shape the nuclear envelope. Myoblasts from L-CMD patients show altered nuclear structure, defective mechanosensing responses and abnormal cell differentiation. Milder phenotypes, known as Emery-Dreifus muscular dystrophy, are also associated with LMNA mutations.
## Diagnostic methods
Diagnosis mostly relies on clinical observation, typically of early onset axial muscle weakness with distal progression, muscle and joint contractures, dropped-head syndrome, loss of walking and sitting abilities and cardiac arrhythmias in the first or second decade of life. A moderated elevation of serum creatine kinase levels reflects muscle damages. Genetic screening of mutations in the LMNA gene confirms the diagnosis.
## Differential diagnosis
Differential diagnosis includes other congenital muscular dystrophies (laminin subunit alpha 2-related CMD, Ullrich CMD due to COL6 gene defects), early onset myopathies that present increased CK levels, joint contractures or spinal stiffness (SEPN1-related myopathies, titinopathies, Pompe disease, mitochondrial myopathy in particular TK2-related), and myasthenic syndromes where loss of head support can also be observed.
## Antenatal diagnosis
Reduced fetal movements observed by prenatal ultrasounds should raise suspicions, but is not specific. In families with a proband, prenatal genetic testing may be advised due to the possibility of germinal mosaicism.
## Genetic counseling
The disorder is autosomal dominant. Almost all reported cases arise de novo, although germinal mosaicism is a possibility. Genetic counseling should be offered to affected families.
## Management and treatment
The evaluation and management of respiratory, gastro-intestinal, orthopedic and cardiac troubles associated with L-CMD require a multidisciplinary approach. Annual cardiac monitoring by Holter-ECG and ultrasound is recommended to detect cardiac arrhythmias and signs of heart failure. Implantable cardiac monitoring might be considered in some cases. BNP (brain natriuretic peptide) may help to detect cardiac insufficiency. Diuretic drugs, beta-blockers, aldosterone antagonists and ACE (angiotensin-converting-enzyme) inhibitors might improve cardiac function. Some patients have been reported to show motor improvement on corticoid treatment but prospective studies are required to confirm these results.
## Prognosis
In the first decade, respiratory insufficiency is the main cause of death. Thereafter, cardiac dysfunction and arrhythmias leading to sudden death, which are very frequent in young adults, determines the vital prognosis. Embolic complications due to conduction disorders and right heart failure may worsen the poor prognosis. Respiratory insufficiency and recurrent pulmonary infections reduce the lifespan or may lead to permanent ventilation or tracheostomy.
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*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Congenital muscular dystrophy due to LMNA mutation | c2750785 | 3,087 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=157973 | 2021-01-23T18:14:47 | {"gard": ["12585"], "mesh": ["C567708"], "omim": ["613205"], "umls": ["C2750785"], "icd-10": ["G71.2"], "synonyms": ["L-CMD", "LMNA-related congenital muscular dystrophy"]} |
Hemoglobin C disease is a condition affecting a protein in the blood (hemoglobin) which transports oxygen throughout the body. Symptoms of this condition can include fatigue, weakness, and anemia. The spleen can also become enlarged as a result of this disease. For many people with this condition, symptoms are relatively mild and the lifespan is normal. Some people with this condition do not exhibit any symptoms at all. Treatment for any symptoms that do present include taking folic acid supplements.
Hemoglobin C disease is caused by a mutation in the gene that provides instructions to the body to make hemoglobin. This mutation causes a change in the shape of the red blood cells so that oxygen isn't carried as well throughout the body.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Hemoglobin C disease | c0019021 | 3,088 | gard | https://rarediseases.info.nih.gov/diseases/2640/hemoglobin-c-disease | 2021-01-18T18:00:07 | {"mesh": ["D006445"], "orphanet": ["2132"], "synonyms": ["Hb C disease"]} |
Cockayne syndrome is a rare disease which causes short stature, premature aging (progeria), severe photosensitivity, and moderate to severe learning delay. This syndrome also includes failure to thrive in the newborn, very small head (microcephaly), and impaired nervous system development. Other symptoms may include hearing loss, tooth decay, vision problems, and bone abnormalities. There are three subtypes according to the severity of the disease and the onset of the symptoms:
* Cockayne syndrome type 1 (type A), sometimes called “classic” or "moderate" Cockayne syndrome, diagnosed during early childhood
* Cockayne syndrome type 2 (type B), sometimes referred to as the “severe” or "early-onset" type, presenting with growth and developmental abnormalities at birth
* Cockayne syndrome type 3 (type C), a milder form of the disorder
Cockayne syndrome is caused by mutations in either the ERCC8 (CSA) or ERCC6 (CSB) genes. Inheritance is autosomal recessive. Type 2 is the most severe and affected people usually do not survive past childhood. Those with type 3 live into middle adulthood. There is no cure yet. Treatment is supportive and may include educational programs for developmental delay, physical therapy, gastrostomy tube placement as needed; medications for spasticity and tremor as needed; use of sunscreens and sunglasses; treatment of hearing loss and cataracts; and other forms of treatment, as needed.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Cockayne syndrome type II | c0751038 | 3,089 | gard | https://rarediseases.info.nih.gov/diseases/1420/cockayne-syndrome-type-ii | 2021-01-18T18:01:15 | {"mesh": ["D003057"], "omim": ["133540"], "orphanet": ["90322"], "synonyms": ["Cockayne syndrome type B", "Cockayne syndrome type 2", "Cockayne syndrome type 2"]} |
IQSEC2 is a genetic condition that causes intellectual disability and sometimes other physical, neurological, or psychiatric symptoms. People with this condition can have seizures that are often difficult to control with medications. Other symptoms may include motor and language development delay, regression of learning abilities, autistic-like behavior, characteristic hand movements, and behavioral problems. Physical features may include abnormal head shape (plagiocephaly), very small head (microcephaly), reduced muscle tone (hypotonia), and crossed eyes (strabismus). This condition is caused by mutations in the IQSEC2 gene, which is located on chromosome X. Depending on the severity of the gene mutation, the features can range from only intellectual disability to a syndrome that includes the other symptoms. In general, males are more affected than females. Most cases are not inherited from a parent but are caused by a new (de novo) mutation. When the condition is inherited, the pattern is called X-linked recessive. There is no specific treatment, but early intervention and other services can support development. Seizure medications such as lamotrigine and rufinamide have been reported to control seizures in some people.
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| IQSEC2 | c2931498 | 3,090 | gard | https://rarediseases.info.nih.gov/diseases/13221/iqsec2 | 2021-01-18T17:59:44 | {"mesh": ["C567906"], "omim": ["309530"], "synonyms": ["IQSEC2-related intellectual disability", "IQSEC2-related epilepsy", "X-linked intellectual disability 1/78", "X-linked intellectual disability 1", "X-linked intellectual disability 78"]} |
Harrod syndrome is characterized by the association of intellectual deficit, facial dysmorphism (a highly arched palate, pointed chin, and small mouth, hypotelorism, a long nose and large protruding ears), arachnodactyly, hypogenitalism (undescended testes and hypospadias) and failure to thrive.
## Epidemiology
So far, it has been described in three males (including two brothers).
## Etiology
The etiology remains unknown and an autosomal recessive mode of transmission has been suggested.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Harrod syndrome | c0795970 | 3,091 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2115 | 2021-01-23T18:30:44 | {"gard": ["2601"], "mesh": ["C535635"], "omim": ["601095"], "icd-10": ["Q87.8"], "synonyms": ["Cranio-facio-digito-genital syndrome"]} |
Sinus pericranii
SpecialtyVascular surgery
Sinus pericranii (SP) is a rare disorder characterized by a congenital (or occasionally, acquired) epicranial venous malformation of the scalp.[1] Sinus pericranii is an abnormal communication between the intracranial and extracranial venous drainage pathways. Treatment of this condition has mainly been recommended for aesthetic reasons and prevention of bleeding.
## Contents
* 1 Signs and symptoms
* 2 Cause
* 3 Mechanism
* 4 Diagnosis
* 5 Treatment
* 6 See also
* 7 References
## Signs and symptoms[edit]
Sinus pericranii typically present as soft palpable masses along midline skull, which may fluctuate in size depending on body positioning. Classically, these lesions are not associated with color change of the overlying skin, such as with other vascular lesions such as hemangioma.
## Cause[edit]
The nature of this malformation remains unclear. Congenital, spontaneous, and acquired origins are accepted. The hypothesis of a spontaneous origin in the current case of SP is supported by no evidence of associated anomalies, such as cerebral aneurysmal venous malformations, systemic angiomas, venous angioma dural malformation, internal cerebral vein aneurysm, and cavernous hemangiomas.
## Mechanism[edit]
Sinus pericranii is a venous anomaly where a communication between the intracranial dural sinuses and dilated epicranial venous structures exists. That venous anomaly is a collection of nonmuscular venous blood vessels adhering tightly to the outer surface of the skull and directly communicating with intracranial venous sinuses through diploic veins. The venous collections receive blood from and drain into the intracranial venous sinuses. The varicosities are intimately associated with the periosteum, are distensible, and vary in size when changes in intracranial pressure occur.
## Diagnosis[edit]
This section is empty. You can help by adding to it. (April 2017)
## Treatment[edit]
The surgical treatment involves the resection of the extracranial venous package and ligation of the emissary communicating vein. In some cases of SP, surgical excision is performed for cosmetic reasons. The endovascular technique has been described by transvenous approach combined with direct puncture and the recently endovascular embolization with Onyx.[2]
## See also[edit]
* Mondor's disease
* List of cutaneous conditions
## References[edit]
1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 886. ISBN 978-1-4160-2999-1.
2. ^ Vasc Endovascular Surg. 2011 Jan;45(1):103-5
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Sinus pericranii | c0266494 | 3,092 | wikipedia | https://en.wikipedia.org/wiki/Sinus_pericranii | 2021-01-18T19:09:15 | {"mesh": ["D020779"], "wikidata": ["Q9378133"]} |
Nager syndrome is a rare condition that mainly affects the development of the face, hands, and arms. The severity of this disorder varies among affected individuals.
Children with Nager syndrome are born with underdeveloped cheek bones (malar hypoplasia) and a very small lower jaw (micrognathia). They often have an opening in the roof of the mouth called a cleft palate. These abnormalities frequently cause feeding problems in infants with Nager syndrome. The airway is usually partially blocked due to the micrognathia, which can lead to life-threatening breathing problems.
People with Nager syndrome often have eyes that slant downward (downslanting palpebral fissures), no eyelashes, and a notch in the lower eyelids called an eyelid coloboma. Many affected individuals have small or unusually formed ears, and about 60 percent have hearing loss caused by defects in the middle ear (conductive hearing loss). Nager syndrome does not affect a person's intelligence, although speech development may be delayed due to hearing impairment.
Individuals with Nager syndrome have bone abnormalities in their hands and arms. The most common abnormality is malformed or absent thumbs. Affected individuals may also have fingers that are unusually curved (clinodactyly) or fused together (syndactyly). Their forearms may be shortened due to the partial or complete absence of a bone called the radius. People with Nager syndrome sometimes have difficulty fully extending their elbows. This condition can also cause bone abnormalities in the legs and feet.
Less commonly, affected individuals have abnormalities of the heart, kidneys, genitalia, and urinary tract.
## Frequency
Nager syndrome is a rare condition. Its prevalence is unknown. More than 75 cases have been reported in the medical literature.
## Causes
More than half of cases of Nager syndrome are caused by mutations in the SF3B4 gene. The cause of the remainder of cases is unknown; other genes are thought to be involved in the condition.
The SF3B4 gene provides instructions for making the SAP49 protein, which is one piece of a complex called a spliceosome. Spliceosomes help process messenger RNA (mRNA), which is a chemical cousin of DNA that serves as a genetic blueprint for making proteins. The spliceosomes recognize and then remove regions from mRNA molecules that are not used in the blueprint (which are called introns).
The SAP49 protein may also be involved in a chemical signaling pathway known as the bone morphogenic protein (BMP) pathway. This signaling pathway regulates various cellular processes and is involved in the growth of cells. The SAP49 protein is particularly important for the maturation of cells that build bones and cartilage (osteoblasts and chondrocytes).
SF3B4 gene mutations that cause Nager syndrome prevent the production of functional SAP49 protein. Although the effect of this protein shortage is unknown, researchers suspect that it disrupts spliceosome formation, which may impair mRNA processing and alter the activity of genes involved in the development of several parts of the body. A loss of SAP49 may also impair BMP pathway signaling, leading to abnormal development of bones in the face, hands, and arms.
### Learn more about the gene associated with Nager syndrome
* SF3B4
## Inheritance Pattern
When caused by mutations in the SF3B4 gene, Nager syndrome follows an autosomal dominant inheritance pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family. Less commonly, an affected person inherits the mutation from one affected parent. Autosomal dominant Nager syndrome may also be caused by mutations in other genes.
Nager syndrome can also be inherited in an autosomal recessive pattern, which means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of a mutated gene, but they typically do not show signs and symptoms of the condition. Nager syndrome is suspected to have an autosomal recessive inheritance pattern when unaffected parents have more than one affected child. The genetic cause in these families is unknown.
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Nager syndrome | c0265245 | 3,093 | medlineplus | https://medlineplus.gov/genetics/condition/nager-syndrome/ | 2021-01-27T08:25:21 | {"gard": ["498"], "mesh": ["C538184"], "omim": ["154400"], "synonyms": []} |
A rare bacterial infectious disease caused by the tick-borne bacterium Rickettsia africae, characterized by acute onset of fever accompanied by myalgia, localized lymphadenitis, and a papulovesicular rash. In most cases at least one, sometimes multiple, inoculation eschars are observed. Clustering of cases is frequent.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| African tick typhus | c1320317 | 3,094 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=101334 | 2021-01-23T18:05:11 | {"mesh": ["D000073605"], "icd-10": ["A77.1"]} |
A number sign (#) is used with this entry because of evidence that severe congenital neutropenia-7 (SCN7) is caused by homozygous or compound heterozygous mutation in the CSF3R gene (138971) on chromosome 1p34.
Description
Severe congenital neutropenia-7 is an autosomal recessive immunodeficiency characterized by onset of recurrent infections in infancy or early childhood. Patients have peripheral neutropenia, although bone marrow biopsy shows normal granulocyte maturation. The neutropenia is not responsive to treatment with G-CSF, but may be responsive to GM-CSF (summary by Triot et al., 2014 and Klimiankou et al., 2015).
For a general phenotypic description and a discussion of genetic heterogeneity of severe congenital neutropenia, see SCN1 (202700).
Clinical Features
Triot et al. (2014) reported 3 sibs, born of consanguineous Turkish parents with onset of recurrent infections in infancy or early childhood. Laboratory studies showed peripheral neutropenia, but bone marrow biopsy of 2 patients showed full maturation of all 3 hematopoietic lineages without myelodysplasia. One patient died of pneumonia at age 3 months. The 2 surviving patients did not respond to treatment with recombinant G-CSF. One of the patients, who also had dextrocardia and symptoms of a primary ciliary dyskinesia, had a homozygous truncating mutation in the SPAG1 gene (603395), resulting in CILD28 (615505). Triot et al. (2014) also reported a family of Spanish descent in which a 9-month-old girl presented at age 2 months with a urinary tract infection associated with neutropenia. Bone marrow aspiration showed no maturation arrest and the presence of mature granulocytes. She also did not respond to treatment with recombinant G-CSF.
Klimiankou et al. (2015) reported a female infant with SCN diagnosed soon after birth. Bone marrow biopsy showed granulopoietic hypoplasia with reduction of all stages but no maturation arrest; erythropoiesis, lymphopoiesis, and megakaryopoiesis were normal. No expression of G-CSFR was detected on the patient's neutrophils or monocytes. The neutropenia did not respond to treatment with G-CSF, but did respond to administration of GM-CSF. The authors suggested that SCN patients who do not respond to G-CSF should be screened for germline CSF3R mutations, and that treatment with GM-CSF should be considered.
Inheritance
The transmission pattern of SCN7 in the families reported by Triot et al. (2014) was consistent with autosomal recessive inheritance.
Molecular Genetics
In affected children from 2 unrelated families with severe congenital neutropenia, Triot et al. (2014) identified biallelic mutations in the CSF3R gene (138971.0002-138971.0004). The mutation in the first family was a homozygous missense mutation (R308C; 138971.0002), which was found by a combination of homozygosity mapping and whole-exome sequencing and confirmed by Sanger sequencing. The mutation segregated with the disorder in the family. Transfection studies in bone marrow cells showed that the R308C mutant protein was retained in the endoplasmic reticulum and not expressed on the plasma membrane. Cells expressing the mutant receptor had decreased downstream signaling compared to wildtype, but signal transduction was not completely abrogated. The patient in the second family was compound heterozygous for 2 truncating mutations (138971.0003-138971.0004), consistent with a loss of function.
In a female infant with SCN7, Klimiankou et al. (2015) identified compound heterozygous truncating mutations in the CSF3R gene (138971.0005-138971.0006). The mutations, which were found by direct sequencing of the CSF3R gene, segregated with the disorder in the family. No expression of CSF3R was detected on patient neutrophils or monocytes.
INHERITANCE \- Autosomal recessive IMMUNOLOGY \- Recurrent infections \- Neutropenia \- Bone marrow shows normal myeloid maturation \- Poor response to G-CSF MISCELLANEOUS \- Onset in infancy or early childhood \- Some patients may show a response to GM-CSF treatment MOLECULAR BASIS \- Caused by mutation in the colony-stimulating factor 3 receptor, granulocyte gene (CSF3R, 138971.0001 ) ▲ Close
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| NEUTROPENIA, SEVERE CONGENITAL, 7, AUTOSOMAL RECESSIVE | c4310764 | 3,095 | omim | https://www.omim.org/entry/617014 | 2019-09-22T15:47:14 | {"omim": ["617014"], "orphanet": ["420702"], "synonyms": []} |
Desbuquois syndrome (DBQD) is a rare type of osteochondrodysplasia (a disorder of the development of bones and cartilage). Characteristics may vary in severity and can include short stature with short extremities, severe joint laxity with dislocation, osteopenia, kyphoscoliosis, distinctive facial characteristics and other abnormalities.Two forms have been distinguished on the basis of the presence (type 1) or the absence (type 2) of characteristic hand anomalies. A variant form of DBQD, Kim variant, has been described in 7 patients originating from Korea and Japan, and is characterized by short stature, joint and minor facial anomalies, together with significant hand anomalies with short bones in the hands, long fingers and advanced bone age. DBQD type 1 and Kim variant are caused by mutations in the gene CANT1. Some cases of DBQD type 2 are caused by mutations in the gene XYLT1 but in other cases the cause is unknown. It is inherited in an autosomal recessive manner. Type 1 can be associated with severe respiratory problems. Treatment for the condition is geared towards the signs and symptoms present in each individual.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Desbuquois syndrome | c0432242 | 3,096 | gard | https://rarediseases.info.nih.gov/diseases/1818/desbuquois-syndrome | 2021-01-18T18:00:54 | {"mesh": ["C535943"], "omim": ["251450", "615777"], "umls": ["C0432242"], "orphanet": ["1425"], "synonyms": ["DBQD", "Micromelic dwarfism, narrow chest, vertebral and metaphyseal abnormalities and advanced carpotarsal ossification", "Desbuquois dysplasia"]} |
Meconium aspiration syndrome is a pulmonary complication appearing in newborns with a meconium-stained amniotic fluid. Aspirated meconium can interfere with normal breathing by several mechanisms including airway obstruction, chemical irritation, infection and surfactant inactivation and induces more or less severe signs of respiratory distress at birth.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Meconium aspiration syndrome | c0025048 | 3,097 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=70588 | 2021-01-23T17:52:20 | {"gard": ["10494"], "mesh": ["D008471"], "umls": ["C0025048"], "icd-10": ["P24.0"]} |
Trichodysplasia-xeroderma syndrome is an extremely rare, syndromic hair shaft anomaly characterized by sparse, coarse, brittle, excessively dry and slow-growing scalp hair, sparse axillary and pubic hair, sparse or absent eyelashes and eyebrows and dry skin. Hair shaft analysis shows pili torti, longitudinal splitting, grooves, peeling and scaling. There have been no further descriptions in the literature since 1987.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Trichodysplasia-xeroderma syndrome | c1860822 | 3,098 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3361 | 2021-01-23T17:22:21 | {"gard": ["5261"], "mesh": ["C566032"], "omim": ["190360"], "umls": ["C1860822"]} |
Viral cardiomyopathy
SpecialtyCardiology
Viral cardiomyopathy occurs when viral infections cause myocarditis with a resulting thickening of the myocardium and dilation of the ventricles. These viruses include Coxsackie B and adenovirus, echoviruses, influenza H1N1, Epstein-Barr virus, rubella (German measles virus), varicella (chickenpox virus), mumps, measles, parvoviruses, yellow fever, dengue fever, polio, rabies and the viruses that cause hepatitis A and C as well as COVID-19 where it has been seen to cause this in persons otherwise thought to be "low risk" of the virus's effects.[1][2][3]
## See also[edit]
* Coxsackievirus-induced cardiomyopathy
* Myocarditis
## References[edit]
1. ^ Barbandi M, Cordero-Reyes A, Orrego CM, Torre-Amione G, Seethamraju H (Jan 2012). "A case series of reversible acute cardiomyopathy associated with H1N1 influenza infection". Methodist DeBakey Cardiovascular Journal. 8 (1): 42–5. doi:10.14797/mdcj-8-1-42. PMC 3405785. PMID 22891110.
2. ^ Badorff C; Lee G. H.; Knowlton K. U. (2000). "Enteroviral cardiomyopathy: bad news for the dystrophin-glycoprotein complex". Herz. 25 (3): 227–32. doi:10.1007/s000590050011. PMID 10904843. S2CID 25973717.
3. ^ Mutlu H, Alam M, Ozbilgin OF (2011). "A rare case of Epstein-Barr virus-induced dilated cardiomyopathy". Heart Lung. 40 (1): 81–7. doi:10.1016/j.hrtlng.2009.12.012. PMID 20561866.
## External links[edit]
* Myocarditis on emedicine
* v
* t
* e
Cardiovascular disease (heart)
Ischaemic
Coronary disease
* Coronary artery disease (CAD)
* Coronary artery aneurysm
* Spontaneous coronary artery dissection (SCAD)
* Coronary thrombosis
* Coronary vasospasm
* Myocardial bridge
Active ischemia
* Angina pectoris
* Prinzmetal's angina
* Stable angina
* Acute coronary syndrome
* Myocardial infarction
* Unstable angina
Sequelae
* hours
* Hibernating myocardium
* Myocardial stunning
* days
* Myocardial rupture
* weeks
* Aneurysm of heart / Ventricular aneurysm
* Dressler syndrome
Layers
Pericardium
* Pericarditis
* Acute
* Chronic / Constrictive
* Pericardial effusion
* Cardiac tamponade
* Hemopericardium
Myocardium
* Myocarditis
* Chagas disease
* Cardiomyopathy
* Dilated
* Alcoholic
* Hypertrophic
* Tachycardia-induced
* Restrictive
* Loeffler endocarditis
* Cardiac amyloidosis
* Endocardial fibroelastosis
* Arrhythmogenic right ventricular dysplasia
Endocardium /
valves
Endocarditis
* infective endocarditis
* Subacute bacterial endocarditis
* non-infective endocarditis
* Libman–Sacks endocarditis
* Nonbacterial thrombotic endocarditis
Valves
* mitral
* regurgitation
* prolapse
* stenosis
* aortic
* stenosis
* insufficiency
* tricuspid
* stenosis
* insufficiency
* pulmonary
* stenosis
* insufficiency
Conduction /
arrhythmia
Bradycardia
* Sinus bradycardia
* Sick sinus syndrome
* Heart block: Sinoatrial
* AV
* 1°
* 2°
* 3°
* Intraventricular
* Bundle branch block
* Right
* Left
* Left anterior fascicle
* Left posterior fascicle
* Bifascicular
* Trifascicular
* Adams–Stokes syndrome
Tachycardia
(paroxysmal and sinus)
Supraventricular
* Atrial
* Multifocal
* Junctional
* AV nodal reentrant
* Junctional ectopic
Ventricular
* Accelerated idioventricular rhythm
* Catecholaminergic polymorphic
* Torsades de pointes
Premature contraction
* Atrial
* Junctional
* Ventricular
Pre-excitation syndrome
* Lown–Ganong–Levine
* Wolff–Parkinson–White
Flutter / fibrillation
* Atrial flutter
* Ventricular flutter
* Atrial fibrillation
* Familial
* Ventricular fibrillation
Pacemaker
* Ectopic pacemaker / Ectopic beat
* Multifocal atrial tachycardia
* Pacemaker syndrome
* Parasystole
* Wandering atrial pacemaker
Long QT syndrome
* Andersen–Tawil
* Jervell and Lange-Nielsen
* Romano–Ward
Cardiac arrest
* Sudden cardiac death
* Asystole
* Pulseless electrical activity
* Sinoatrial arrest
Other / ungrouped
* hexaxial reference system
* Right axis deviation
* Left axis deviation
* QT
* Short QT syndrome
* T
* T wave alternans
* ST
* Osborn wave
* ST elevation
* ST depression
* Strain pattern
Cardiomegaly
* Ventricular hypertrophy
* Left
* Right / Cor pulmonale
* Atrial enlargement
* Left
* Right
* Athletic heart syndrome
Other
* Cardiac fibrosis
* Heart failure
* Diastolic heart failure
* Cardiac asthma
* Rheumatic fever
* v
* t
* e
Inflammation
Symptoms
* Flushing (Rubor)
* Fever (Calor)
* Swelling (Tumor)
* Pain (Dolor)
* Malaise
Mechanism
Acute
Plasma-derived mediators
* Bradykinin
* complement
* C3
* C5a
* MAC
* coagulation
* Factor XII
* Plasmin
* Thrombin
Cell-derived mediators
preformed:
* Lysosome granules
* biogenic amines
* Histamine
* Serotonin
synthesized on demand:
* cytokines
* IFN-γ
* IL-8
* TNF-α
* IL-1
* eicosanoids
* Leukotriene B4
* Prostaglandins
* Nitric oxide
* Kinins
Chronic
* Macrophage
* Epithelioid cell
* Giant cell
* Granuloma
Other
* Acute-phase reaction
* Vasodilation
* Increased vascular permeability
* Exudate
* Leukocyte extravasation
* Chemotaxis
Tests
* Full blood count
* Leukocytosis
* C-reactive protein
* Erythrocyte sedimentation rate
General
* Lymphadenopathy
* List of inflammed body part states
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Viral cardiomyopathy | c1411027 | 3,099 | wikipedia | https://en.wikipedia.org/wiki/Viral_cardiomyopathy | 2021-01-18T19:07:55 | {"umls": ["C1411027", "C3840127"], "wikidata": ["Q17074273"]} |
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