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Abortion in Connecticut is legal. 67% of adults said in a poll by the Pew Research Center that abortion should be legal in all or most cases. Abortions took place early in the state's history. People at that time talked about abortions using euphemisms. The death of Sarah Grosvenor following unsuccessful abortion resulted in a prosecution in colonial Connecticut. Connecticut became the first statue to criminalize abortion after codifying its common law in 1821. Later, such laws were justified as trying to protect the life of the women from bad actors providing unsafe abortion services. The state was one of ten states in 2007 to have a customary informed consent provision for abortions. In 1965, the US Supreme Court heard the case of Griswold v. Connecticut. The Supreme Court struck laws the banned the sale of, use of and giving of prescriptions for contraceptives, even for married couples. The US Supreme Court's decision in 1973's Roe v. Wade ruling meant the state could no longer regulate abortion in the first trimester. In 2019, state law said, "the decision to terminate a pregnancy prior to the viability of the fetus shall be solely that of the pregnant woman in consultation with her physician."
The number of abortion clinics in the state has been declining in recent years, going from 46 in 1982 to 43 in 1992 to 21 in 2014. There were 10,625 legal abortions performed in Connecticut in 2014, and 9,888 in 2015. In 1964, Gerri Santoro of Connecticut died trying to obtain an illegal abortion and her photo became the symbol of the pro-choice movement. Abortion rights activists in the state participated in the #StoptheBans movement in May 2019. Anti-abortion rights organizations were created in the state in the late 1960s.
## Contents
* 1 Terminology
* 2 Context
* 3 History
* 3.1 Legislative history
* 3.2 Judicial history
* 3.3 Clinic history
* 4 Statistics
* 5 Experiences getting abortions
* 6 Deaths as a result of illegal abortions
* 7 Abortion rights views and activities
* 7.1 Protests
* 8 Anti-abortion activities and views
* 8.1 Activism
* 8.2 Organizations
* 9 Footnotes
* 10 References
## Terminology[edit]
Main article: Abortion
See also: Definitions of abortion
The abortion debate most commonly relates to the "induced abortion" of an embryo or fetus at some point in a pregnancy, which is also how the term is used in a legal sense.[note 1] Some also use the term "elective abortion", which is used in relation to a claim to an unrestricted right of a woman to an abortion, whether or not she chooses to have one. The term elective abortion or voluntary abortion describes the interruption of pregnancy before viability at the request of the woman, but not for medical reasons.[1]
Anti-abortion advocates tend to use terms such as "unborn baby", "unborn child", or "pre-born child",[2][3] and see the medical terms "embryo", "zygote", and "fetus" as dehumanizing.[4][5] Both "pro-choice" and "pro-life" are examples of terms labeled as political framing: they are terms which purposely try to define their philosophies in the best possible light, while by definition attempting to describe their opposition in the worst possible light. "Pro-choice" implies that the alternative viewpoint is "anti-choice", while "pro-life" implies the alternative viewpoint is "pro-death" or "anti-life".[6] The Associated Press encourages journalists to use the terms "abortion rights" and "anti-abortion".[7]
## Context[edit]
See also: Abortion in the United States
Free birth control correlates to teenage girls having a fewer pregnancies and fewer abortions. A 2014 New England Journal of Medicine study found such a link. At the same time, a 2011 study by Center for Reproductive Rights and Ibis Reproductive Health also found that states with more abortion restrictions have higher rates of maternal death, higher rates of uninsured pregnant women, higher rates of infant and child deaths, higher rates of teen drug and alcohol abuse, and lower rates of cancer screening.[8]
According to a 2017 report from the Center for Reproductive Rights and Ibis Reproductive Health, states that tried to pass additional constraints on a women's ability to access legal abortions had fewer policies supporting women's health, maternal health and children's health. These states also tended to resist expanding Medicaid, family leave, medical leave, and sex education in public schools.[9] According to Megan Donovan, a senior policy manager at the Guttmacher Institute, states have legislation seeking to protect a woman's right to access abortion services have the lowest rates of infant mortality in the United States.[9]
Poor women in the United States had problems paying for menstrual pads and tampons in 2018 and 2019. Almost two-thirds of American women could not pay for them. These were not available through the federal Women, Infants, and Children Program (WIC).[10] Lack of menstrual supplies has an economic impact on poor women. A study in St. Louis found that 36% had to miss days of work because they lacked adequate menstrual hygiene supplies during their period. This was on top of the fact that many had other menstrual issues including bleeding, cramps and other menstrual induced health issues.[10] Connecticut, Florida, Illinois, Maryland, Massachusetts, Minnesota, New Jersey, New York, Nevada, and Pennsylvania all had exemptions for essential hygiene products like tampons and menstrual pads as of November 2018.[11][12][13][14]
## History[edit]
Sarah Grosvenor was involved in a colonial court hearing after an unsuccessful abortion resulted in her death. After a seemingly successful surgical abortion performed by Dr. John Hallowell, Grosvenor became sick. She died on September 14, 1742 in her hometown of Pomfret, Connecticut after surgical complications.[15][16][17]
Three years after Grosvenor's death, her case was taken to court. Historians believe the incident came to the attention of the court after years of gossip and rumors. Zerviah and Sarah's friend Abigail Nightingale testified in court, recounting what Grosvenor had confessed to both of them separately from her death bed. The court identified her physician, John Hallowell, and her lover, Amasa Sessions, as responsible for her murder. The court charged the individuals for both putting Sarah into bad health and the attempted abortion, as it was done in an attempt to conceal her pregnancy. The court hearing ended in Amasa's innocence and the conviction of Hallowell with a misdemeanor. The court case did not acknowledge Grosvenor's abortion as murder of the fetus, even though Zerviah had testified that Grosvenor had felt the child move from within her. It has been understood by historians that Amasa was deemed innocent as he had lost his lover and had not performed the operation that resulted in her death.[17][18][19][20] Grosvenor's case has been argued as one of the most well known surgical abortion cases in colonial America.[15]
Abortions took place early in the state's history. People at that time talked about abortions using euphemisms.[21]
### Legislative history[edit]
Connecticut was the first state in the nation to make abortion a criminal offense. The state did this by statue in 1821, codifying what was already found in the state's common law.[22][23][24] The 1821 Connecticut law targeted apothecaries who sold "poisons" to women for purposes of inducing an abortion, and New York made post-quickening abortions a felony and pre-quickening abortions a misdemeanor in 1829.[25][23] In the 19th century, bans by state legislatures on abortion were about protecting the life of the mother given the number of deaths caused by abortions; state governments saw themselves as looking out for the lives of their citizens.[22] By 1950, the state legislature would pass a law that stating that a woman who had an abortion or actively sought to have an abortion regardless of whether she went through with it were guilty of a criminal offense.[22]
The state was one of ten states in 2007 to have a customary informed consent provision for abortions.[26] 17 states including Connecticut use their own funds to cover all or most "medically necessary" abortions sought by low-income women under Medicaid, 13 of which are required by State court orders to do so.[27] In 2017, Washington State, New Mexico, Illinois, Alaska, Maryland, Massachusetts, Connecticut, and New Jersey allow qualified non-physicians to prescribe drugs for medical abortions only.[28] In August 2018, the state had a law to protect the right to have an abortion.[29] As of May 14, 2019, the state prohibited abortions after the fetus was viable, generally some point between week 24 and 28. This period uses a standard defined by the US Supreme Court in 1973 with the Roe v. Wade ruling.[30] In 2019, state law said, "the decision to terminate a pregnancy prior to the viability of the fetus shall be solely that of the pregnant woman in consultation with her physician."[31] In May 2019, the state was debating a bill about Crisis Pregnancy Centers (CPCs). The proposed bill would prohibit them from engaging in deceptive advertising, but was never passed because they proved to not have deceived their patients.[31][32]
### Judicial history[edit]
The Connecticut Supreme Court said in 1904, "The public policy that underlies this legislation is based largely on protection due to the woman, protection against her own weakness as well as the criminal list and greed of others. The criminal intent and moral turpitude involved in the violation, by a woman, of the restraint put upon her control over her own person is widely different than that which attends the man who, in clear violation of the law, and for pay and gain of any kind, inflicts an injury on the body of a woman endangering health and perhaps life."[22]
In 1965, the US Supreme Court heard the case of Griswold v. Connecticut. The Supreme Court struck laws the banned the sale of, use of and giving of prescriptions for contraceptives, even for married couples. The Supreme Court ruled that people had an expectation of a "right to privacy" when it came to making personal decisions about reproductive decisions.[33] The US Supreme Court's decision in 1973's Roe v. Wade ruling meant the state could no longer regulate abortion in the first trimester.[22]
### Clinic history[edit]
Number of abortion clinics in Connecticut by year
See also: Abortion clinic
Between 1982 and 1992, the number of abortion clinics in the state decreased by 3, going from 46 in 1982 to 43 in 1992.[34] In 2014, there were 21 abortion clinics in the state.[35] In 2014, 15% of the counties in the state did not have an abortion clinic. That year, 5% of women in the state aged 15 – 44 lived in a county without an abortion clinic.[29] In March 2016, there were 17 Planned Parenthood clinics in the state.[36] In 2017, there were 17 Planned Parenthood clinics in a state with a population of 812,634 women aged 15 – 49 of which 17 offered abortion services.[37]
## Statistics[edit]
In the period between 1972 and 1974, there were zero recorded illegal abortion deaths in the state.[38] In 1990, 443,000 women in the state faced the risk of an unintended pregnancy.[34] In 2014, 67% of adults said in a poll by the Pew Research Center that abortion should be legal in all or most cases.[39] In 2017, the state had an infant mortality rate of 4.5 deaths per 1,000 live births.[9]
Number of reported abortions, abortion rate and percentage change in rate by geographic region and state in 1992, 1995 and 1996[40] Census division and state Number Rate % change 1992–1996
1992 1995 1996 1992 1995 1996
Total 1,528,930 1,363,690 1,365,730 25.9 22.9 22.9 –12
New England 78,360 71,940 71,280 25.2 23.6 23.5 –7
Connecticut 19,720 16,680 16,230 26.2 23 22.5 –14
Maine 4,200 2,690 2,700 14.7 9.6 9.7 –34
Massachusetts 40,660 41,190 41,160 28.4 29.2 29.3 3
New Hampshire 3,890 3,240 3,470 14.6 12 12.7 –13
Rhode Island 6,990 5,720 5,420 30 25.5 24.4 –19
Number, rate, and ratio of reported abortions, by reporting area of residence and occurrence and by percentage of abortions obtained by out-of-state residents, US CDC estimates Location Residence Occurrence % obtained by
out-of-state residents
Year Ref
No. Rate^ Ratio^^ No. Rate^ Ratio^^
Connecticut 19,720 26.2 1992 [40]
Connecticut 16,680 23 1995 [40]
Connecticut 16,230 22.5 1996 [40]
Connecticut 10,625 15.5 293 10,611 15.5 292 2.6 2014 [41]
Connecticut 9,888 14.5 277 9,938 14.6 278 2.7 2015 [42]
Connecticut 9,954 14.8 276 10,031 14.9 279 2.9 2016 [43]
^number of abortions per 1.000 women aged 15–44; ^^number of abortions per 1,000 live births
## Experiences getting abortions[edit]
Then 18-year-old Connecticut resident Vikki Wachtel went to New York City to get an abortion at Bellevue Hospital in October 1970, where she had post-abortion complications. Her abortion took place only five months after abortion became legal in New York State. Of her experience, she said, "The staff made us feel like we were about to commit a crime. [...] It was MY CHOICE to not have a child in 1970 and it must remain a woman's choice to do so on a national level. [...] These overreaching and restrictive laws will only make abortions more dangerous, not eliminate them."[44]
## Deaths as a result of illegal abortions[edit]
In 1964, Gerri Santoro of Connecticut died trying to obtain an illegal abortion and her photo became the symbol of the pro-choice movement.[45][24] A photo of her dead body was published in April 1973 in Ms. magazine, making her death a rallying cry for many in the abortion rights movement.[24]
## Abortion rights views and activities[edit]
### Protests[edit]
Women from the state participated in marches supporting abortion rights as part of a #StoptheBans movement in May 2019.[46]
## Anti-abortion activities and views[edit]
### Activism[edit]
In 1965, a Supreme Court decision in Griswold v. Connecticut set a precedent for an expansive right to privacy in the area of reproductive healthcare. In the late 1960s, in response to nationwide abortion-rights efforts, a number of organizations were formed to mobilize opinion against the legalization of abortion.[47]
### Organizations[edit]
Family Institute of Connecticut, an interdenominational, conservative tax-exempt nonprofit organization whose stated goal is to encourage and strengthen the family as the foundation of society and to promote Judeo-Christian ethical and moral values in the culture and government of Connecticut.[48][49][50]
## Footnotes[edit]
1. ^ According to the Supreme Court's decision in Roe v. Wade:
> (a) For the stage prior to approximately the end of the first trimester, the abortion decision and its effectuation must be left to the medical judgement of the pregnant woman's attending physician. (b) For the stage subsequent to approximately the end of the first trimester, the State, in promoting its interest in the health of the mother, may, if it chooses, regulate the abortion procedure in ways that are reasonably related to maternal health. (c) For the stage subsequent to viability, the State in promoting its interest in the potentiality of human life may, if it chooses, regulate, and even proscribe, abortion except where it is necessary, in appropriate medical judgement, for the preservation of the life or health of the mother.
Likewise, Black's Law Dictionary defines abortion as "knowing destruction" or "intentional expulsion or removal".
## References[edit]
1. ^ Watson, Katie (20 Dec 2019). "Why We Should Stop Using the Term "Elective Abortion"". AMA Journal of Ethics. 20: E1175-1180. doi:10.1001/amajethics.2018.1175. PMID 30585581. Retrieved 17 May 2019.
2. ^ Chamberlain, Pam; Hardisty, Jean (2007). "The Importance of the Political 'Framing' of Abortion". The Public Eye Magazine. 14 (1).
3. ^ "The Roberts Court Takes on Abortion". New York Times. November 5, 2006. Retrieved January 18, 2008.
4. ^ Brennan 'Dehumanizing the vulnerable' 2000
5. ^ Getek, Kathryn; Cunningham, Mark (February 1996). "A Sheep in Wolf's Clothing – Language and the Abortion Debate". Princeton Progressive Review.
6. ^ "Example of "anti-life" terminology" (PDF). Archived from the original (PDF) on 2011-07-27. Retrieved 2011-11-16.
7. ^ Goldstein, Norm, ed. The Associated Press Stylebook. Philadelphia: Basic Books, 2007.
8. ^ Castillo, Stephanie (2014-10-03). "States With More Abortion Restrictions Hurt Women's Health, Increase Risk For Maternal Death". Medical Daily. Retrieved 2019-05-27.
9. ^ a b c "States pushing abortion bans have highest infant mortality rates". NBC News. Retrieved 2019-05-25.
10. ^ a b Mundell, E.J. (January 16, 2019). "Two-Thirds of Poor U.S. Women Can't Afford Menstrual Pads, Tampons: Study". US News & World Report. Retrieved May 26, 2019.
11. ^ Larimer, Sarah (January 8, 2016). "The 'tampon tax,' explained". The Washington Post. Archived from the original on December 11, 2016. Retrieved December 10, 2016.
12. ^ Bowerman, Mary (July 25, 2016). "The 'tampon tax' and what it means for you". USA Today. Archived from the original on December 11, 2016. Retrieved December 10, 2016.
13. ^ Hillin, Taryn. "These are the U.S. states that tax women for having periods". Splinter. Retrieved 2017-12-15.
14. ^ "Election Results 2018: Nevada Ballot Questions 1-6". KNTV. Retrieved 2018-11-07.
15. ^ a b "Taking the Trade: Abortion and Gender Relations in Eighteenth-Century New England Village". The William and Mary Quarterly. 48 (1).
16. ^ The New England Historical and Genealogical Register. New England Historic and Genealogical Society. n.d.
17. ^ a b Smith, Merrill. Women's Roles in Eighteenth-Century America.
18. ^ "Giving Birth". Lotions, Potions, Pills, and Magic: Health Care in Early America.
19. ^ Cheu, Maggie. "Now and Then: How Coverture Ideology Informs the Rhetoric of Abortion". Texas Journal of Women and the Law.
20. ^ Doan, Alesha (2007). Opposition & Intimidation: The Abortion Wars & Strategies of Political Harassment. U of Michigan.
21. ^ "When Abortion Was a Crime". www.theatlantic.com. Retrieved 2019-05-22.
22. ^ a b c d e Buell, Samuel (1991-01-01). "Criminal Abortion Revisited". New York University Law Review. 66: 1774–1831.
23. ^ a b Tribune, Chicago. "Timeline of abortion laws and events". chicagotribune.com. Retrieved 2019-05-23.
24. ^ a b c Larson, Jordan. "Timeline: The 200-Year Fight for Abortion Access". The Cut. Retrieved 2019-05-25.
25. ^ Alford, Suzanne M. (2003). "Is Self-Abortion a Fundamental Right?". Duke Law Journal. 52 (5): 1011–29. JSTOR 1373127. PMID 12964572. Archived from the original on 2019-01-22. Retrieved 2019-05-22.
26. ^ "State Policy On Informed Consent for Abortion" (PDF). Guttmacher Policy Review. Fall 2007. Retrieved May 22, 2019.
27. ^ Francis Roberta W. "Frequently Asked Questions". Equal Rights Amendment. Alice Paul Institute. Archived from the original on 2009-04-17. Retrieved 2009-09-13.
28. ^ "Study: Abortions Are Safe When Performed By Nurse Practitioners, Physician Assistants, Certified Nurse Midwives". Retrieved 25 January 2017.
29. ^ a b businessinsider (2018-08-04). "This is what could happen if Roe v. Wade fell". Business Insider (in Spanish). Retrieved 2019-05-24.
30. ^ Lai, K. K. Rebecca (2019-05-15). "Abortion Bans: 8 States Have Passed Bills to Limit the Procedure This Year". The New York Times. ISSN 0362-4331. Retrieved 2019-05-24.
31. ^ a b "Are there *any* states working to protect abortion rights?". Well+Good. 2019-05-17. Retrieved 2019-05-25.
32. ^ Udoma, Ebong. "Connecticut House Considers Regulation Of Crisis Pregnancy Centers". www.wshu.org. Retrieved 2019-05-25.
33. ^ "Timeline of Important Reproductive Freedom Cases Decided by the Supreme Court". American Civil Liberties Union. Retrieved 2019-05-25.
34. ^ a b Arndorfer, Elizabeth; Michael, Jodi; Moskowitz, Laura; Grant, Juli A.; Siebel, Liza (December 1998). A State-By-State Review of Abortion and Reproductive Rights. DIANE Publishing. ISBN 9780788174810.
35. ^ Gould, Rebecca Harrington, Skye. "The number of abortion clinics in the US has plunged in the last decade — here's how many are in each state". Business Insider. Retrieved 2019-05-23.
36. ^ Bohatch, Emily. "27 states with the most Planned Parenthood clinics". thestate. Retrieved 2019-05-24.
37. ^ "Here's Where Women Have Less Access to Planned Parenthood". Retrieved 2019-05-23.
38. ^ Cates, Willard; Rochat, Roger (March 1976). "Illegal Abortions in the United States: 1972–1974". Family Planning Perspectives. 8 (2): 86. doi:10.2307/2133995. JSTOR 2133995. PMID 1269687.
39. ^ "Views about abortion by state - Religion in America: U.S. Religious Data, Demographics and Statistics". Pew Research Center. Retrieved 23 May 2019.
40. ^ a b c d "Abortion Incidence and Services in the United States, 1995-1996". Guttmacher Institute. 2005-06-15. Retrieved 2019-06-02.
41. ^ Jatlaoui, Tara C. (2017). "Abortion Surveillance — United States, 2014". MMWR. Surveillance Summaries. 66 (24): 1–48. doi:10.15585/mmwr.ss6624a1. ISSN 1546-0738. PMID 29166366.
42. ^ Jatlaoui, Tara C. (2018). "Abortion Surveillance — United States, 2015". MMWR. Surveillance Summaries. 67 (13): 1–45. doi:10.15585/mmwr.ss6713a1. ISSN 1546-0738. PMC 6289084. PMID 30462632.
43. ^ Jatlaoui, Tara C. (2019). "Abortion Surveillance — United States, 2016". MMWR. Surveillance Summaries. 68. doi:10.15585/mmwr.ss6811a1. ISSN 1546-0738.
44. ^ "Would overturning abortion rights turn back clock to 1973?". The Public's Radio. 2019-05-26. Retrieved 2019-05-26.
45. ^ Johnson, Linnea. "Something Real: Jane and Me. Memories and Exhortations of a Feminist Ex-Abortionist". CWLU Herstory Project. Archived from the original on 2011-07-25. Retrieved 2010-05-23.
46. ^ Bacon, John. "Abortion rights supporters' voices thunder at #StopTheBans rallies across the nation". USA TODAY. Retrieved 2019-05-25.
47. ^ "The American Historian: Abolishing Abortion: The History of the Pro-Life Movement in America". tah.oah.org. Retrieved 2019-04-05.
48. ^ "The Team - Family Institute of Connecticut".
49. ^ Catholic Bishops Urge 'Yes' Vote On Constitutional Convention Archived 2008-10-24 at the Wayback Machine Hartford Courant, Christopher Keating, October 11, 2008
50. ^ "Vision - Family Institute of Connecticut".
Abortion in the United States by state
States
* Alabama
* Alaska
* Arizona
* Arkansas
* California
* Colorado
* Connecticut
* Delaware
* Florida
* Georgia
* Hawaii
* Idaho
* Illinois
* Indiana
* Iowa
* Kansas
* Kentucky
* Louisiana
* Maine
* Maryland
* Massachusetts
* Michigan
* Minnesota
* Mississippi
* Missouri
* Montana
* Nebraska
* Nevada
* New Hampshire
* New Jersey
* New Mexico
* New York
* North Carolina
* North Dakota
* Ohio
* Oklahoma
* Oregon
* Pennsylvania
* Rhode Island
* South Carolina
* South Dakota
* Tennessee
* Texas
* Utah
* Vermont
* Virginia
* Washington
* West Virginia
* Wisconsin
* Wyoming
Federal district
Washington, D.C.
Insular areas
* American Samoa
* Guam
* Northern Mariana Islands
* Puerto Rico
* U.S. Virgin Islands
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Abortion in Connecticut
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None
| 8,100 |
wikipedia
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https://en.wikipedia.org/wiki/Abortion_in_Connecticut
| 2021-01-18T18:51:43 |
{"wikidata": ["Q64876907"]}
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Diffuse alveolar damage
Micrograph showing hyaline membranes, the key histologic feature of diffuse alveolar damage. H&E stain.
SpecialtyRespirology
Diffuse alveolar damage (DAD) is a histologic term used to describe specific changes that occur to the structure of the lungs during injury or disease. Most often DAD is described in association with the early stages of acute respiratory distress syndrome (ARDS).[1] It is important to note that DAD can be seen in situations other than ARDS (such as acute interstitial pneumonia) and that ARDS can occur without DAD.[1]
## Contents
* 1 Definitions
* 1.1 Berlin Criteria: as stated on UpToDate (2020)[4]
* 2 Histology/Progression
* 3 Causes/Mechanism
* 4 Diagnosis
* 5 Treatment
* 6 Prognosis
* 7 References
## Definitions[edit]
* Diffuse alveolar damage (DAD): an acute lung condition with the presence of hyaline membranes.[2] These hyaline membranes are made up of dead cells, surfactant, and proteins.[1] The hyaline membranes deposit along the walls of the alveoli, where gas exchange typically occurs, thereby making gas exchange difficult.
* Acute respiratory distress syndrome (ARDS): a potentially life threatening condition where the alveoli are damaged thereby letting fluid leak into the lungs which makes it difficult to exchange gases and oxygenate the blood.[3] It is the general practice of the medical community to use the Berlin criteria to diagnose ARDS. All criteria must be present to make a diagnosis of ARDS.
### Berlin Criteria: as stated on UpToDate (2020)[4][edit]
1. Timing: onset of respiratory symptoms within one week of a injury/insult.
2. Chest Imaging: either chest x-ray or CT scan, must show bilateral opacities that cannot be fully explained by other conditions such as effusion, lung/lobar collapse, or lung nodules.
3. Origin of Edema: respiratory failure that cannot be fully explained by cardiac failure or fluid overload, this needs objective assessment such as an echocardiogram.
4. Impaired Oxygenation: this can be determined by looking at the ratio of arterial oxygen tension to fraction of inspired oxygen (PaO2/FiO2) that can be obtained based on an arterial blood gas test. Note: all PaO2/FiO2 ratios used in the determination of the severity of ARDS require that the patient be on a ventilator at a setting that includes 5 cm H2O or more of positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP).
Level of ARDS PaO2/FiO2 Range PEEP/CPAP
Mild ARDS 201-300 ≥5 cm H2O
Moderate ARDS 101-200
Severe ARDS <100
## Histology/Progression[edit]
The epithelial lining of alveoli are composed of two different types of cells. Alveolar type I epithelial cells comprise about 80% of the alveolar surface area and are primarily responsible for gas exchange.[5] Alveolar type II epithelial cells play the critical roles of producing surfactant, moving water out of the airspaces, and regenerating alveolar epithelium.[5] The alveolar type II epithelial cells are more resistant to damage, so after an insult to the alveoli, most of the damage will occur to the alveolar type I epithelial cells.[5]
Left side demonstrate the structure of a normal alveolus including the difference between type I and type II alveolar epithelial cells. Right side depicts what occurs after injury to the alveolus during the acute/exudative phase.
Once the initial insult has damaged the alveoli and begun the process of DAD, the condition will typically progress in three phases: exudative, proliferative, and fibrotic.[6] Below are the description of the phases, paraphrased from Sweeney et al (2016).[6]
* Exudative Phase (1–7 days): After the initial insult to the alveoli, immune cells (neutrophils and macrophages) are recruited to the alveoli, which can cause more damage through their nonspecific defensive mechanisms. Since the epithelial lining is damaged it allows plasma and proteins to leak in to the airspace, accumulating fluid (otherwise known as edema). Additionally, since the epithelial lining is damaged there is limited ability to pump this edema out of the airspace and back in to the interstitium. The presence of this edema has the following detrimental impacts:
* The edema contributes to the deposition of a hyaline membrane (composed of dead cells, surfactant, and proteins) along the alveolar walls. Hyaline membranes are characteristic of DAD.
* The edema interferes with the naturally occurring surfactant, which is critical for reducing surface tension and allowing alveoli to remain open and allow air in for gas exchange.
* Proliferative/Organizing Phase (1–3 weeks): This phase is characterized by recovery. The epithelial lining is repopulated with alveolar type II epithelial cells which will eventually differentiate into alveolar type I epithelial cells. While the type II epithelial cells are repopulating the epithelial surface they are also performing the critical task of transporting the edema out of the airspace and back into the interstitium. Meanwhile in the airspace, macrophages are clearing cellular debris.
* Fibrotic Phase (after 3 weeks, if occurs): not all courses of DAD result in a fibrotic phase. This phase occurs if the alveolar collagen that is deposited during the acute exudative phase fails to be resorbed, resulting in limitations of alveolar expanse and subsequently gas exchange.
## Causes/Mechanism[edit]
It is important to note that DAD can occur in settings other than ARDS and that ARDS can occur with histology other than DAD. That being said, the histologic finding of DAD is often associated with the clinical syndrome ARDS but it can also be seen in conditions such as acute interstitial pneumonia (essentially ARDS but without a known inciting cause), acute exacerbation of idiopathic pulmonary fibrosis, and primary graft dysfunction after lung transplant.[1] The most common causes of ARDS are pneumonia, non-pulmonary sepsis, and aspiration.[7]
To reiterate, the hallmark of DAD is hyaline membrane formation.[1] There is an similar process which occurs in newborns called hyaline membrane disease, although the preferred term is surfactant-deficiency disorder, that also has the formation of hyaline membranes.[8] This disorder typically develops due to prematurity, especially when the infant is delivered prior to 36 weeks since surfactant doesn't start being produced till 35 weeks gestation.[8] The lack of surfactant causes alveolar collapse and subsequent damage to the epithelial lining of the alveoli, causing the same path of damage described in the above section.
## Diagnosis[edit]
In order to make a diagnosis of DAD a biopsy of the lung must be obtained, processed, and examined microscopically. As described above, the hallmark of diagnosing DAD is the presence of hyaline membranes.[1] Most frequently DAD is associated with ARDS, but since there are clinical criteria (see Berlin criteria above) upon which we can diagnose ARDS, it is often unnecessary in all cases to obtained invasive biopsies of the lung. Additionally, there are limitations of the biopsy test since it is possible to sample a potentially normal area of lung even though there is DAD in the rest of the lung, resulting in a false negative.[1]
## Treatment[edit]
The most important factor for treating DAD or ARDS is to treat the underlying cause of the injury to the lungs,[9] for example pneumonia or sepsis. These patients will have problems with oxygenation, meaning they will likely need a breathing tube, medications to keep them comfortable (sedative, paralytic, and/or analgesic), and a mechanical ventilator to breath for them.[10] The mechanical ventilator will often be set to a setting of at least 5 cm H2O of positive end-expiratory pressure (PEEP) to keep the alveoli from collapsing during exhalation.[9] Other treatments to improve oxygenation may include prone positioning or extracorporeal membrane oxygenation (ECMO).[6]
## Prognosis[edit]
As expected, the mortality rates increase as the severity of the ARDS increases with mortality rates at approximately 35%, 40%, and 46% for mild, moderate, and severe, respectively.[11] It has been revealed that patients with ARDS that show DAD on histology are at a high mortality rate of 71.9% compared to 45.5% in patients with ARDS but without DAD.[12] Of the patients who succumb to ARDS, the most common cause of death is septic shock with multi organ dysfunction syndrome.[13]
Among survivors upon discharge, many will have impairments in their lung function. The majority (approximately 80%) of patient will have decrease diffusion capacity while fewer patients (approximately 20%) will have issues with airflow (either obstructive or restrictive).[14] These airflow issues will typically resolve within six months and the diffusion issues will resolve within five years.[14]
## References[edit]
1. ^ a b c d e f g Cardinal-Fernández, Pablo; Lorente, José A.; Ballén-Barragán, Aída; Matute-Bello, Gustavo (June 2017). "Acute Respiratory Distress Syndrome and Diffuse Alveolar Damage. New Insights on a Complex Relationship". Annals of the American Thoracic Society. 14 (6): 844–850. doi:10.1513/AnnalsATS.201609-728PS. ISSN 2329-6933. PMID 28570160.
2. ^ Berry, Gerald J; Rouse, Robert V (November 20, 2010). "Acute Interstitial Pneumonia - Diffuse Alveolar Damage". surgpathcriteria.stanford.edu. Retrieved 2020-04-03.
3. ^ "Acute Respiratory Distress Syndrome (ARDS) | American Lung Association | American Lung Association". www.lung.org. Retrieved 2020-04-03.
4. ^ Siegel, Mark D (March 2020). "Acute Respiratory Distress Syndrome: Clinical Features, Diagnosis, and Complications in Adults". UpToDate. Retrieved 2020-04-03.
5. ^ a b c Manicone, Anne M (2009-01-01). "Role of the pulmonary epithelium and inflammatory signals in acute lung injury". Expert Review of Clinical Immunology. 5 (1): 63–75. doi:10.1586/177666X.5.1.63 (inactive 2021-01-15). ISSN 1744-666X. PMC 2745180. PMID 19885383.CS1 maint: DOI inactive as of January 2021 (link)
6. ^ a b c Sweeney, Rob Mac; McAuley, Daniel F. (2016-11-12). "Acute respiratory distress syndrome". The Lancet. 388 (10058): 2416–2430. doi:10.1016/S0140-6736(16)00578-X. ISSN 0140-6736. PMC 7138018. PMID 27133972.
7. ^ Rezoagli, Emanuele; Fumagalli, Roberto; Bellani, Giacomo (July 2017). "Definition and epidemiology of acute respiratory distress syndrome". Annals of Translational Medicine. 5 (14): 282. doi:10.21037/atm.2017.06.62. ISSN 2305-5839. PMC 5537110. PMID 28828357.
8. ^ a b Agrawal, Rishi. "Respiratory distress syndrome | Radiology Reference Article | Radiopaedia.org". Radiopaedia. Retrieved 2020-04-09.
9. ^ a b Yoshikawa, A.; Fukuoka, J. "Acute respiratory distress syndrome (ARDS) / diffuse alveolar damage (DAD)". www.pathologyoutlines.com. Retrieved 2020-04-09.
10. ^ Siegel, Mark D; Siemieniuk, Reed (March 25, 2020). "Acute Respiratory Distress Syndrome: Supportive Care and Oxygenation in Adults". UpToDate. Retrieved April 9, 2020.
11. ^ Bellani, Giacomo; Laffey, John G.; Pham, Tài; Fan, Eddy; Brochard, Laurent; Esteban, Andres; Gattinoni, Luciano; van Haren, Frank; Larsson, Anders; McAuley, Daniel F.; Ranieri, Marco (2016-02-23). "Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries". JAMA. 315 (8): 788–800. doi:10.1001/jama.2016.0291. ISSN 1538-3598. PMID 26903337.
12. ^ Kao, Kuo-Chin; Hu, Han-Chung; Chang, Chih-Hao; Hung, Chen-Yiu; Chiu, Li-Chung; Li, Shih-Hong; Lin, Shih-Wei; Chuang, Li-Pang; Wang, Chih-Wei; Li, Li-Fu; Chen, Ning-Hung (2015-05-15). "Diffuse alveolar damage associated mortality in selected acute respiratory distress syndrome patients with open lung biopsy". Critical Care (London, England). 19: 228. doi:10.1186/s13054-015-0949-y. ISSN 1466-609X. PMC 4449559. PMID 25981598.
13. ^ Stapleton, Renee D.; Wang, Bennet M.; Hudson, Leonard D.; Rubenfeld, Gordon D.; Caldwell, Ellen S.; Steinberg, Kenneth P. (August 2005). "Causes and timing of death in patients with ARDS". Chest. 128 (2): 525–532. doi:10.1378/chest.128.2.525. ISSN 0012-3692. PMID 16100134.
14. ^ a b Siegel, Mark D (March 2020). "Acute Respiratory Distress Syndrome: Prognosis and Outcomes in Adults". UpToDate. Retrieved 2020-04-09.
* v
* t
* e
Diseases of the respiratory system
Upper RT
(including URTIs,
common cold)
Head
sinuses
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nose
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* Mediastinal emphysema
Other/general
* Respiratory failure
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* Coronavirus disease 2019
* Idiopathic pulmonary haemosiderosis
* Pulmonary alveolar proteinosis
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Diffuse alveolar damage
|
c1262020
| 8,101 |
wikipedia
|
https://en.wikipedia.org/wiki/Diffuse_alveolar_damage
| 2021-01-18T18:56:05 |
{"umls": ["C1262020"], "wikidata": ["Q5275407"]}
|
Prader-Willi habitus, osteopenia, and camptodactyly syndrome is characterized by intellectual disability, short stature, obesity, genital abnormalities, and hand and/or toe contractures. It has only been described in two brothers and in one isolated case in a different family. Other symptoms included unusual face, deformity of the spinal column, osteoporosis and a history of frequent fractures. It is similar to Prader-Willi syndrome, but the authors concluded that it is a different condition. The cause was unknown in the reported cases.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Prader-Willi habitus, osteopenia, and camptodactyly
|
c0796189
| 8,102 |
gard
|
https://rarediseases.info.nih.gov/diseases/5426/prader-willi-habitus-osteopenia-and-camptodactyly
| 2021-01-18T17:58:13 |
{"mesh": ["C538276"], "omim": ["264010"], "umls": ["C0796189"], "orphanet": ["3409"], "synonyms": ["Urban-Rogers-Meyer syndrome"]}
|
Gundrum (1922) described 9 (8 male, 1 female) cases in 3 generations. Most performed catheterization daily on themselves.
GU \- Urinary bladder atony Inheritance \- Autosomal dominant ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
URINARY BLADDER, ATONY OF
|
c0403645
| 8,103 |
omim
|
https://www.omim.org/entry/191800
| 2019-09-22T16:32:10 |
{"omim": ["191800"], "icd-9": ["596.4"]}
|
Simple-type schizophrenia
Other namesSimple schizophrenia, simple deteriorative disorder, schizophrenia simplex, deficit schizophrenia, deficit syndrome
SpecialtyPsychiatry
Simple-type schizophrenia is a sub-type of schizophrenia included in the International Classification of Diseases (ICD-10).[1] It is not included in the current Diagnostic and Statistical Manual of Mental Disorders (DSM-5) or the upcoming ICD-11.[2] Simple-type schizophrenia is characterized by negative ("deficit") symptoms, such as avolition, apathy, anhedonia, reduced affect display, lack of initiative, lack of motivation, low activity; with absence of hallucinations or delusions of any kind.
Simple schizophrenia was included as a proposed diagnosis for further study in the appendix of the former DSM-IV.[3]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Diagnosis
* 3.1 Classification
* 3.1.1 ICD
* 3.1.1.1 ICD-9
* 3.1.1.2 ICD-10
* 3.1.2 DSM
* 4 Treatment
* 5 History
* 6 Controversy
* 7 References
* 8 External links
## Signs and symptoms[edit]
It has possibly the earliest onset compared to all other schizophrenias, considered to begin in some within childhood. Symptoms of schizophrenia simplex include an absence of will, impoverished thinking and flattening of affect. There is a gradual deterioration of functioning with increased amotivation and reduced socialization.[4][5] It is considered to be rarely diagnosed and is a schizophrenia without psychotic symptoms.[6]
In a study of patients in a Massachusetts hospital, persons suffering with simple schizophrenia were found to make attempts at reality fulfillment with respect to the more primitive needs; tending toward the achievement of fulfillment of these needs rather than engaging in fantasy as is typically found as a reaction to environmental stimuli by the psychotic person.[7]
## Causes[edit]
A progressive state of simple dementia results often in cases of adolescent onset juvenile general paresis. Paresis is caused by placental-foetal transfer of infection and results in intellectual (mental) subnormality. Occurrence of this type of paresis is altogether uncommon (Lishman 1998).[8]
## Diagnosis[edit]
### Classification[edit]
#### ICD[edit]
The WHO first listed the condition in the 6th revision of the International Classification of Diseases ICD-6 (1949) and it stayed in the manual until the present version ICD-10.[9]
##### ICD-9[edit]
The ICD-9 simple-type schizophrenia description:
> A psychosis in which there is insidious development of oddities of conduct, inability to meet the demands of society, and decline in total performance. Delusions and hallucinations are not in evidence and the condition is less obviously psychotic than are the hebephrenic, catatonic and paranoid types of schizophrenia. With increasing social impoverishment vagrancy may ensue and the patient becomes self-absorbed, idle and aimless. Because the schizophrenic symptoms are not clear-cut, diagnosis of this form should be made sparingly, if at all.
>
> — ICD-9 (1977). Schizophrenic psychoses: 295.0 Simple type.[10]
##### ICD-10[edit]
These are the current criteria:
> Slowly progressive development over a period of at least one year, of all three of the following:
>
> (a) A significant and consistent change in the overall quality of some aspects of personal behaviour, manifest as loss of drive and interests, aimlessness, idleness, a self-absorbed attitude and social withdrawal.
>
> (b) Gradual appearance and deepening of negative symptoms such as marked apathy, paucity of speech, underactivity, blunting of affect, passivity and lack of initiative, and poor non-verbal communication.
>
> (c) Marked decline in social, scholastic or occupational performance.
>
> 2\. Absence, at any time, of any symptoms referred to in G1 in F20.0 - F20.3 [11] and of hallucinations or well formed delusions of any kind, i.e. the subject must never have met the criteria for any other type of schizophrenia, or any other psychotic disorder.
>
> 3\. Absence of evidence of dementia or any other organic mental disorder.
>
> — Simple schizophrenia (F20.6), ICD-10.[12]
The ICD is currently in revision 10, and the ICD-11 was accepted in May 2019 will come into effect in 2022. In the ICD-11, there is no longer a diagnostic category of simple schizophrenia, and all subtypes of schizophrenia have been eliminated.[2][9][13]
#### DSM[edit]
Simple-type schizophrenia also appeared in the first two editions of the DSM as an official diagnosis:[9]
> This psychosis is characterized chiefly by a slow and insidious reduction of external attachments and interests and by apathy and indifference leading to impoverishment of interpersonal relations, mental deterioration, and adjustment on a lower level of functioning. In general, the condition is less dramatically psychotic than are the hebephrenic, catatonic, and paranoid types of schizophrenia. Also, it contrasts with schizoid personality, in which there is little or no progression of the disorder.
>
> — 295.0 Schizophrenia, simple type. DSM-II (1968).[14]
But after that, it was omitted in later versions and has since then never returned as a formal diagnosis in any DSM. However, DSM-IV (1994) and DSM-IV-TR (2000) included Simple Schizophrenia in the appendix under the proposed category of simple deteriorative disorder. The provisional research criteria for it were:
> Progressive development over a period of at least a year of all of the following:
>
> (1) marked decline in occupational or academic functioning
>
> (2) gradual appearance and deepening of negative symptoms such as affective flattening, alogia, and avolition
>
> (3) poor interpersonal rapport, social isolation or social withdrawal
>
> B. Criterion A for Schizophrenia has never been met.
>
> C. The symptoms are not better accounted for by Schizotypal or Schizoid Personality Disorder, a Psychotic Disorder, a Mood Disorder, an Anxiety Disorder, a dementia, or Mental Retardation and are not due to the direct physiological effects of a substance or a general medical condition.
>
> — DSM-IV-TR. Appendix B: Criteria Sets and Axes Provided for Further Study.[3]
## Treatment[edit]
The use of antipsychotic medication is commonly the first line of treatment; however, the effectiveness after treatment is in question.
L-DOPA is effective against reduced affect display and emotional withdrawal, aloofness from society, apathy.[15]
## History[edit]
The early idea that a person with schizophrenia might present solely with symptoms and indications of deterioration (i.e. presenting with no accessory symptoms [16][17]) was identified as dementia simplex.[18]
ICD-10 specifies the continuation of symptoms for a period of two years in the diagnosis of simple schizophrenia. This is because of disagreement on the classification validity of the sub-type, that having been retained by the ICD classification, has been omitted from DSM classifications.[19] Symptoms identified earlier to dementia simplex are now DSM-attributed by way of improvements in diagnostic technique to other classifications such as neurodegenerative disorders.[20]
Early observations that concur with symptoms of the dementia praecox of the form classified later as simplex began in 1838 with Jean Esquirol.[21] In 1860, Bénédict Morel introduced the term dementia précoce and Langdon Down provided in 1887 the most complete description to that date of the clinical manifestation that Charpentier described in 1890 as dementia précoce simple des enfant normaux.[22][23]
The description of simple schizophrenia is inter-changeable with describing symptoms as a form of dementia praecox known as simple dementing, at least in the time when the Swiss psychiatrists Otto Diem and Eugen Bleuler were studying it.[24] In 1893, Emil Kraepelin considered there were four types of schizophrenia,[25] and was amongst the first to identify three of them (dementia hebephrenica, dementia paranoides, dementia catatonica). The simplex type was added by Eugen Bleuler to the earlier ones identified by Kraepelin in 1899 and subsequently given a basic outline in 1903 by Otto Diem publishing a monograph on dementia praecox in the simple dementing form.[26][27] This was based on a survey of two males having had a relatively normal childhood but who then fell into patterns of living tending towards vagrancy.[16]
A description of a cerebral disorder in relation to organic factors and in the context of general paralysis of the insane only; with no reference to schizophrenia, shows a disorder with features of generalized dementia (Lishman 1998).[8] In 1951, a film was made showing the clinical characteristics of simple-type schizophrenia.[28]
## Controversy[edit]
Definition of this type of schizophrenia is without unity or is controversial.[29] The diagnosis was discontinued in the DSM system, although it was recommended for reinclusion.[30] It was subsequently confirmed as having imprecise diagnostic criteria based on collective descriptions lacking in agreement.[31]
However, in an experiment with a small sample size, five patients with a diagnosis of simple deteriorative disorder (DSM-IV) were found to have grey matter deficits, atrophy and reduced cerebral perfusion in the frontal areas.[32] Whitwell et al. found justification to retain the classification on the basis of fulfillment of "dimensional" considerations of classification, as opposed to criticisms resulting from disagreement in considerations of classification using orientation from other categories.[33]
## References[edit]
1. ^ World Health Organization (1993) – The ICD-10 Classification of Mental and Behavioural Disorders. "Simple schizophrenia" is classified F20.6.
2. ^ a b "ICD-11 - Mortality and Morbidity Statistics". icd.who.int. Retrieved 2019-08-22.
3. ^ a b American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Washington, D. C. p. 771. ISBN 978-0-89042-025-6.
4. ^ Description of Simple Schizophrenia in DSM-IV-TR, provided by Brown University. p.5-6.
5. ^ Lou, Bai Ceng (2000). Soothing the Troubled Mind: Treatment and Prevention of Schizophrenia with Acupuncture and Moxibustion. Paradigm Publications. p. 21. ISBN 9780912111605.
6. ^ Mueser, Kim Tornvall (2008). Clinical Handbook of Schizophrenia. Guilford Press. ISBN 978-1-59385-652-6.
7. ^ Kant, Otto (1948). "Clinical investigation of simple schizophrenia". The Psychiatric Quarterly. 22 (1–4): 141–151. doi:10.1007/BF01572410. PMID 18861121. S2CID 41481804.
8. ^ a b Organic psychiatry: the psychological consequences of cerebral disorder. Wiley-Blackwell, 12 Jan 1998. 1998-02-11. ISBN 9780865428201. Retrieved 2012-02-12.
9. ^ a b c Donata Lukosiute (2016). "The diagnostic challenge of simple schizophrenia: a case report." AND PSYCHOPHARMACOLOGY biologinė psichiatrija ir psichofarmakologija: 22.
10. ^ World Health Organization (1977). Manual of the international statistical classification of diseases, injuries, and causes of death (PDF). Vol. 1. Jeneva. p. 183.
11. ^ F20.0 = Paranoid schizophrenia, F20.1 = Hebephrenic schizophrenia, F20.2 = Catatonic schizophrenia, F20.3 = Undifferentiated schizophrenia (same reference)
12. ^ World Health Organization (1993) - The ICD-10 Classification of Mental and Behavioural Disorders. p.82.
13. ^ ICD-11 Beta Draft (February 2017)
14. ^ American Psychiatric Association (1968). Diagnostic and Statistical Manual of Mental Disorders, 2nd Edition. Washington, D. C. p. 33.
15. ^ Gerlach J., Lühdorf K. (1975). "The effect of L-dopa on young patients with simple schizophrenia, treated with neuroleptic drugs: a double-blind cross-over trial with Madopar and placebo". Psychopharmacologia. 44 (1): 105–10. doi:10.1007/bf00421193. PMID 706. S2CID 20599379.
16. ^ a b Health.am (2009): Early schizophrenia concepts.
17. ^ James E. Maddux, Barbara A. Winstead Psychopathology: foundations for a contemporary understanding Routledge, 2005 Retrieved 2012-02-06
18. ^ Serra-Mestres, J.; Gregory, C. A. (2000). "Simple Schizophrenia Revisited: A Clinical, Neuropsychological, and Neuroimaging Analysis of Nine Cases" (PDF). Schizophrenia Bulletin. 26 (2): 479–493. doi:10.1093/oxfordjournals.schbul.a033467. PMID 10885645.
19. ^ Armenian Medical Network - subtypes-of-schizophrenia Retrieved 2012-01-31 [content is found under heading Course and sub-types of schizophrenia]
20. ^ Daniel R. Weinberger (U.S. National Institute of Health), Paul Harrison (University Department of Psychiatry Oxford) - Schizophrenia - 736 pages John Wiley & Sons, 13 Jul 2011 Retrieved 2012-01-22 ISBN 1-4443-4774-8
21. ^ Jean-Etienne-Dominique Esquirol - Des maladies mentales considerées sous les rapports médical, hygiènique et médico-légal Chez J.-B. Baillière, 1838. (original from the Complutense University of Madrid)
22. ^ Joseph Zelmanowits - A Historical Note on the Simple Dementing Form of Schizophrenia Proc R Soc Med. 1953 November; 46(11): 931–933. Proceedings of the Royal Society of Medicine Retrieved 2012-02-01
23. ^ Zelmanowits, J. (1953-11-01). "A historical note on the simple dementing form of schizophrenia". Proceedings of the Royal Society of Medicine. 46 (11): 931–933. doi:10.1177/003591575304601107. PMC 1918676. PMID 13112246.
24. ^ J.K. Wing and N. Agrawal (ed, S. R. Hirsch. - Professor of Psychiatry Emeritus, D. R. Weinberger - Chief, Clinical Brain Disorders Branch Intramural Research Program [1] Retrieved 2012-01-31
25. ^ Ben Green 2009 - Problem-Based Psychiatry - 253 pages Radcliffe Publishing, 2009 Retrieved 2012-01-22 ISBN 1-84619-042-8
26. ^ John Cutting, Michael Shepherd: The clinical roots of the schizophrenia concept. Article by Otto Diem, 1903.
27. ^ Gregory, Carol A.; McKenna, Peter J.; Hodges, John R. (1998). "Dementia of frontal type and simple schizophrenia: Two sides of the same coin?". Neurocase. 4 (1): 1–6. doi:10.1080/13554799808410601.
28. ^ Canadian Medical Association Journal - Schizophrenia: Simple-type Deteriorated—1951; Sound; B & W; 11 minutes \- Can Med Assoc J. 1959 September 15; 81(6): 499. PMC1831211 Retrieved 2012-01-22
29. ^ Jordi Serra-Mestres, Carol A.Gregory et al. Simple schizophrenia revisited : A Clinical, Neuorphysiological and Neoroimaging analysis of Nine Cases (PDF). Wilfrid Laurier Univ. Press (1997). Retrieved 2012-01-22.
30. ^ Black, D. W.; Boffeli, T. J. (1989). "Simple schizophrenia: past, present, and future". The American Journal of Psychiatry. 146 (10): 1267–1273. doi:10.1176/ajp.146.10.1267. PMID 2675642.
31. ^ Black, D. W.; Boffeli, T. J. (1990). "Simple schizophrenia: revisited". Comprehensive Psychiatry. 31 (4): 344–349. doi:10.1016/0010-440x(90)90041-p. PMID 2387146.
32. ^ Suzuki, Michio (2005). "Prefrontal abnormalities in patients with simple schizophrenia: Structural and functional brain-imaging studies in five cases". Psychiatry Research: Neuroimaging. 140 (2): 157–171. doi:10.1016/j.pscychresns.2005.06.005. PMID 16243494. S2CID 5984461.
33. ^ Whitwell, Susannah; Bramham, Jessica; Moriarty, John (2005). "Simple schizophrenia or disorganisation syndrome? A case report and review of the literature". Advances in Psychiatric Treatment. 11 (6): 398–403. doi:10.1192/apt.11.6.398.
## External links[edit]
Classification
D
* ICD-10: F20.6
* ICD-10-CM: F20.89
* ICD-9-CM: 295.0
* v
* t
* e
Mental and behavioral disorders
Adult personality and behavior
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Symptoms and uncategorized
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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 inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Simple-type schizophrenia
|
None
| 8,104 |
wikipedia
|
https://en.wikipedia.org/wiki/Simple-type_schizophrenia
| 2021-01-18T18:54:46 |
{"icd-9": ["295.00", "295.0"], "icd-10": ["F20.6"], "wikidata": ["Q2855814"]}
|
L-2-hydroxyglutaric aciduria is an inherited metabolic condition that is associated with progressive brain damage. Signs and symptoms of this condition typically begin during infancy or early childhood and may include developmental delay, seizures, speech difficulties, macrocephaly and abnormalities in a part of the brain called the cerebellum, which is involved in coordinating movement (i.e. balance and muscle coordination). L-2-hydroxyglutaric aciduria is caused by changes (mutations) in the L2HGDH gene and is inherited in an autosomal recessive manner. Treatment is focused on alleviating the signs and symptoms of the condition, such as medications to control seizures.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
L-2-hydroxyglutaric aciduria
|
c1855995
| 8,105 |
gard
|
https://rarediseases.info.nih.gov/diseases/10472/l-2-hydroxyglutaric-aciduria
| 2021-01-18T17:59:33 |
{"omim": ["236792"], "orphanet": ["79314"], "synonyms": ["L-2-hydroxyglutaric acidemia"]}
|
Oral manifestations of systematic disease are signs and symptoms of disease occurring elsewhere in the body detected in the oral cavity and oral secretions. High blood sugar can be detected by sampling saliva.[1] Saliva sampling may be a non-invasive way to detect changes in the gut microbiome and changes in systemic disease. Another example is tertiary syphilis, where changes to teeth can occur.[2] Syphilis infection can be associated with longitudinal furrows of the tongue.
Mineral and vitamin deficiencies can cause the tongue to appear beefy red and feel sore. Those deficiencies are iron, folate, and vitamin B12. A hairy tongue may be an indication of Epstein Barr virus infection and is usually seen in those infected with HIV. Other systemic diseases that can cause the tongue to form aphthous ulcers are: Crohn's disease and ulcerative colitis, Behcet's Syndrome, pemphigus vulgaris, herpes simplex, histoplasmosis, and reactive arthritis.[3]
## Contents
* 1 Cardiovascular and haematological system
* 2 Respiratory system
* 3 Renal System
* 4 Digestive System
* 5 Endocrine System
* 6 Skeletal System
* 7 Immune System
* 8 Nervous System
* 9 Muscular System
* 10 References.
## Cardiovascular and haematological system[edit]
A heart attack is a blood vessel in the heart being constricted either by a blood clot or atherosclerosis formation. A heart attack can cause pain the chest; sometimes this pain can radiate up to the jaw. (Malik et al., 2013)[4]
Calcium channel blockers (CCBs) are medications prescribed for the treatment of a number of heart conditions and primarily to treat high blood pressure. They can cause gingival hypertrophy (overgrowth), particularly dihydropyridine and nifidipine. Poor dental hygiene and inflamed gums are a risk factor. The overgrowth is not permanent, it is suggested that if the medication is stopped then the overgrowth can reduce[ however, this is a decision that would have to be made in conjunction with the patient’s dentist and cardiologist as the risk of stopping some medications outweigh any advantage gained (Livada and Shiloah, 2013)[5]
Nicorandil is a medication that is prescribed for the treatment of angina. It can cause major apthous-like ulcer formation (BNF, 2020).[6]
Iron, folate and Vitamin B12 deficiencies – The most commonest cause of iron deficiencies is low ferritin; this can cause the tongue to appear beefy red and appear sore. It can also present in the mouth as angular chelitis, which is an infection caused by either staphylococcus or candidiasis, and can make the corners of the mouth appear red and crispy.
Sickle cell disease is a hereditary genetic condition that results in deformed red blood cells to be formed. Sickle patients can suffer from sickle crisis, these are painful events in which if in the jaw can mimic dental pain and facial swelling can also occur during a crisis. The dental pulp can be affected by sickling and there may be a delayed eruption and hypoplasia of the dentition. Sickle patients are also at an increased risk of developing infection.
Thalasseamias is a group of inherited genetic disorders that affect the haemoglobin synthesis; it can result in either a reduced or absent globin chain production. If beta thalassaemia major is left untreated or under transfused, there is expansion of ineffective bone marrow, this leads to bony deformities resulting in dental malocclusion. Beta thalassaemia major patients may also be on bisphosphonates and are therefore at risk of developing osteonecrosis of the jaw.
Thrombocytopenia is a deficiency of platelets in the blood. It can present as red blood blisters in the mouth.
## Respiratory system[edit]
Patients suffering from respiratory conditions like asthma and COPD can be prescribed steroidal inhalers to help strengthen their lungs. They must ensure after use that they rinse their mouths, otherwise there is an increase of dental caries, xerostomia, candidiasis, ulceration and gingivitis/periodontitis (Godara et al., 2011).[7]
## Renal System[edit]
There are a number of oral complications following renal transplantation. Ciclosporin is an immunosuppressant medication that is used to help prevent patients from rejecting the transplanted kidney (BNF, 2020). Due to the immunosuppression (suppressed immune system), these patients are more likely to suffer from gingival hyperplasia, apthous ulceration, herpes simplex virus, oral leucoplakia; which may transform into squamous cell carcinoma, candidiasis infection or Kaposi’s sarcoma (BNF, 2020).[6]
## Digestive System[edit]
There are many specific diseases of the gastrointestinal (GI) tract which have an impact on oral health. Systemic disease can affect the upper GI tract such as Dysphagia, Dysmotility, Gastro-oesophageal reflux (GORD) and Peptic Ulcer's; or lower in the tract such as Coeliac’s, Crohn’s disease, Ulcerative Colitis and Familial Adenomatous Polyposis (FAP).[8]
Dysphagia is defined as a difficulty in swallowing. Structurally it worsens when eating solids and neurologically it is worse with fluids.[9] Structural problems may include malignancy, stricture and pharyngeal pouching which can lead to halitosis, regurgitation of undigested food and high feeling of dysphagia. Neurological problems may be related to the patient having Multiple Sclerosis (MS), Motor Neurone Disease (MND) or having suffered from a Stroke.[10] Dysphagia may present as a barrier to care in the dental setting as the patient may require high volume suction in order to maintain patient comfort and reduce the risk of aspiration of dental material/ fluids.
GORD can present as retrosternal pain, acid brash and a hoarse voice. Risk factors for GORD are obesity, diet, smoking and hiatus hernia. Complications of which being oesophagitis, Barrett's oesophagus, Strictures and ulcers. Common management of GORD include lifestyle measures, proton pump inhibitors and rarely surgery. The is a clear relationship between GORD and dental erosion and therefore can be detrimental to hard tissues i.e. teeth and also soft tissues of the mouth.[11]
Crohn's Disease is a patchy disease which can affect any area of the GI tract from the oral cavity to the anus. The manifestations depend on the affected area. The oral manifestations present as Orofacial Granulomatosis, an inflammatory condition affecting the oral mucosa. It is non-caveating granulomas and has a "Cobblestone" appearance. OFG can be isolated or a manifestation of Crohn's and can be treated with local or systemic corticosteroids. Aggravating factor of which is cinnamon, therefore a cinnamon-free diet is recommended.[8]
Eating disorders are a psychological problem which has an impact on the GI tract. Two common eating disorders are Anorexia Nervosa and Bulimia Nervosa. Anorexia Nervosa is a refusal to maintain a "normal" body weight with a fear of weight gain and distorted perception of body image. Bulimia Nervosa is binge-eating followed by attempts to restrict weight gain and can include purging. Eating disorder oral manifestation is severe palatal erosion due to vomiting. There is occlusal erosion of the maxillary teeth causing the incised edges of the incisors to be thin and knife-edged. Occlusal surfaces have a flat to cupped-out appearance.[12] Extra-orally eating disorders may present with swollen parotid glands.
Other oral manifestations of GI disease is Angular Stomatitis, commonly seen in iron-deficient anaemia and mouth ulcers in Crohn's disease.
## Endocrine System[edit]
Diabetes Mellitus has two main types: Type 1, autoimmune destruction of beta-cells leading to reduced insulin production and Type 2, the body becomes increasingly resistant to the effects of insulin leading to the bodies inability to regulate plasma glucose levels resulting in a fall in insulin production. Diabetes has numerous implications on oral health. Patient with Diabetes have increase extent and severity of Periodontal Disease, increased prevalence of Dental Caries due to Xerostomia, can suffer from Burning Mouth Syndrome and Candidal infections as well as experiencing altered taste sensation, altered tooth eruption and hypertrophy of the parotid glands. Other oral health problems include chronic hyperglycaemia, infection, delayed wound healing and Lichen Planus/Lichenoid reactions.[13]
The oral manifestations of Acromegaly predominate as spacing of the lower incisor teeth and widening of the mandible. Other complications include visual field defects, headaches, Diabetes, Sleep apnoea, Hypertension, Arthralgia and Arthritis and Carpal Tunnel Syndrome.[13] Arthralgia and Carpal Tunnel Syndrome both have an impact on a patients’ ability to maintain good oral hygiene practice and therefore may predispose them to Dental caries and Periodontal Disease. It is imperative these patients are given Enhanced Prevention in order to reduce the risk of Dental Caries and Periodontal Disease.
Another endocrine disorder that may present orally is Addison’s Disease. Signs include skin hyperpigmentation, alabaster-coloured pale skin, low blood pressure, postural hypotension. Skin pigmentation have increased deposition in the palmer skin creases, nails and gingiva.[13] Management of Addison’s is with steroids. During dental treatment the patient may require an increased dose of steroids based on treatment need.
## Skeletal System[edit]
Osteopgenesis imperfecta, also known as brittle bone disease, is caused by a gene mutation affecting the collagen genes, patients generally present with a large number of fractures from minor injuries. Teeth, if affected, are of the appearance of dentinogenesis imperfecta.
Osteoporosis is a very common disease associated with a decreased bone mineral density, it mainly affects post menopausal women whose oestrogen levels have dropped. It is managed with the used of bisphosphonates. Prior to placement on bisphosphonates, a dental check must be done to extract any hopeless teeth as extractions in patients who have prolonged used of bisphosphonates are at risk of MRONJ. (SDCEP,2017)
## Immune System[edit]
Human Immunodeficiency Virus (HIV) infects and destroys cells of the immune system, principally the CD4+ T-Helper lymphocytes. As well as lymphocytes, CD4 receptors are also present on the surface of macrophages and monocytes, cells in the brain, skin, and probably many other sites.The normal CD4 count is 500-1500 therefore patient’s with HIV have a CD4 count less than 500. Patients that are HIV positive have increased risk of developing infections and tumours. The severity of illness is greater the lower the CD4 count. A CD4 count less than 200 is a diagnosis of Acquired Immunodeficiency Syndrome (AIDS). Oral manifestation of HIV include candidiasis, Oral Hairy Leukoplakia, oral ulcers, oral warts, oral lymphoma and Kaposi Sarcoma.[13] Other presentations include gingivitis and oral malignancies. Treatment and management of HIV is based around highly active anti-retroviral therapy (HAART). HAART has been proven to significantly lower prevalence of oral lesions, particularly oral candidiasis and oral hairy leukoplakia.[14]
## Nervous System[edit]
This section is empty. You can help by adding to it. (February 2020)
## Muscular System[edit]
This section is empty. You can help by adding to it. (February 2020)
## References.[edit]
1. ^ Nascimento, Marcelle; Goodson, J. Max; Hartman, Mor-Li; Shi, Ping; Hasturk, Hatice; Yaskell, Tina; Vargas, Jorel; Song, Xiaoqing; Cugini, Maryann; Barake, Roula; Alsmadi, Osama; Al-Mutawa, Sabiha; Ariga, Jitendra; Soparkar, Pramod; Behbehani, Jawad; Behbehani, Kazem (2017). "The salivary microbiome is altered in the presence of a high salivary glucose concentration". PLOS One. 12 (3): e0170437. Bibcode:2017PLoSO..1270437G. doi:10.1371/journal.pone.0170437. ISSN 1932-6203. PMC 5331956. PMID 28249034.
2. ^ https://www2a.cdc.gov/stdtraining/ready-to-use/Manuals/Syphilis/syphilis-notes-2013.pdf
3. ^ "The Tongue in Diagnosis - Stanford Medicine 25". Stanford University. Retrieved 7 May 2017.
4. ^ Malik, Muhammad Ajmal; Alam Khan, Shahzad; Safdar, Sohail; Taseer, Ijaz-Ul-Haque (April 2013). "Chest Pain as a presenting complaint in patients with acute myocardial infarction (AMI)". Pakistan Journal of Medical Sciences. 29 (2): 565–568. doi:10.12669/pjms.292.2921. ISSN 1682-024X. PMC 3809224. PMID 24353577.
5. ^ Livada, R.; Shiloah, J. (January 2014). "Calcium channel blocker-induced gingival enlargement". Journal of Human Hypertension. 28 (1): 10–14. doi:10.1038/jhh.2013.47. ISSN 1476-5527. PMID 23739159.
6. ^ a b "BNF is only available in the UK". NICE. Retrieved 2020-02-20.
7. ^ Godara, Navneet; Godara, Ramya; Khullar, Megha (2011). "Impact of inhalation therapy on oral health". Lung India. 28 (4): 272–275. doi:10.4103/0970-2113.85689. ISSN 0970-2113. PMC 3213714. PMID 22084541.
8. ^ a b Rolands, ChristeffiMabel (2015). "Oral health presentations and considerations in gastrointestinal diseases". Journal of Indian Academy of Oral Medicine and Radiology. 27 (3): 412. doi:10.4103/0972-1363.170475. ISSN 0972-1363.
9. ^ Scully, Crispian, author. (2016-05-26). Scully's handbook of medical problems in dentistry. ISBN 978-0-7020-4648-3. OCLC 972835394.CS1 maint: multiple names: authors list (link)
10. ^ Logemann, JA; Curro, FA; Pauloski, B; Gensler, G (2013-04-11). "Aging effects on oropharyngeal swallow and the role of dental care in oropharyngeal dysphagia". Oral Diseases. 19 (8): 733–737. doi:10.1111/odi.12104. ISSN 1354-523X. PMID 23574512.
11. ^ BARTLETT, D.W.; EVANS, D.F.; SMITH, B.G.N. (May 1996). "The relationship between gastro-oesophageal reflux disease and dental erosion". Journal of Oral Rehabilitation. 23 (5): 289–297. doi:10.1111/j.1365-2842.1996.tb00855.x. ISSN 0305-182X. PMID 8736440.
12. ^ Milosevic, A. (1999-02-13). "Eating disorders and the dentist". British Dental Journal. 186 (3): 109–113. doi:10.1038/sj.bdj.4800036a. ISSN 0007-0610.
13. ^ a b c d Wray, L. (September 2011). "The diabetic patient and dental treatment: an update". British Dental Journal. 211 (5): 209–215. doi:10.1038/sj.bdj.2011.724. ISSN 0007-0610. PMID 21904352.
14. ^ Hamza, Omar JM; Matee, Mecky IN; Simon, Elison NM; Kikwilu, Emil; Moshi, Mainen J; Mugusi, Ferdinand; Mikx, Frans HM; Verweij, Paul E; van der Ven, André JAM (2006-08-18). "Oral manifestations of HIV infection in children and adults receiving highly active anti-retroviral therapy [HAART] in Dar es Salaam, Tanzania". BMC Oral Health. 6 (1): 12. doi:10.1186/1472-6831-6-12. ISSN 1472-6831. PMC 1559688. PMID 16916469.
* v
* t
* e
Oral and maxillofacial pathology
Lips
* Cheilitis
* Actinic
* Angular
* Plasma cell
* Cleft lip
* Congenital lip pit
* Eclabium
* Herpes labialis
* Macrocheilia
* Microcheilia
* Nasolabial cyst
* Sun poisoning
* Trumpeter's wart
Tongue
* Ankyloglossia
* Black hairy tongue
* Caviar tongue
* Crenated tongue
* Cunnilingus tongue
* Fissured tongue
* Foliate papillitis
* Glossitis
* Geographic tongue
* Median rhomboid glossitis
* Transient lingual papillitis
* Glossoptosis
* Hypoglossia
* Lingual thyroid
* Macroglossia
* Microglossia
* Rhabdomyoma
Palate
* Bednar's aphthae
* Cleft palate
* High-arched palate
* Palatal cysts of the newborn
* Inflammatory papillary hyperplasia
* Stomatitis nicotina
* Torus palatinus
Oral mucosa – Lining of mouth
* Amalgam tattoo
* Angina bullosa haemorrhagica
* Behçet's disease
* Bohn's nodules
* Burning mouth syndrome
* Candidiasis
* Condyloma acuminatum
* Darier's disease
* Epulis fissuratum
* Erythema multiforme
* Erythroplakia
* Fibroma
* Giant-cell
* Focal epithelial hyperplasia
* Fordyce spots
* Hairy leukoplakia
* Hand, foot and mouth disease
* Hereditary benign intraepithelial dyskeratosis
* Herpangina
* Herpes zoster
* Intraoral dental sinus
* Leukoedema
* Leukoplakia
* Lichen planus
* Linea alba
* Lupus erythematosus
* Melanocytic nevus
* Melanocytic oral lesion
* Molluscum contagiosum
* Morsicatio buccarum
* Oral cancer
* Benign: Squamous cell papilloma
* Keratoacanthoma
* Malignant: Adenosquamous carcinoma
* Basaloid squamous carcinoma
* Mucosal melanoma
* Spindle cell carcinoma
* Squamous cell carcinoma
* Verrucous carcinoma
* Oral florid papillomatosis
* Oral melanosis
* Smoker's melanosis
* Pemphigoid
* Benign mucous membrane
* Pemphigus
* Plasmoacanthoma
* Stomatitis
* Aphthous
* Denture-related
* Herpetic
* Smokeless tobacco keratosis
* Submucous fibrosis
* Ulceration
* Riga–Fede disease
* Verruca vulgaris
* Verruciform xanthoma
* White sponge nevus
Teeth (pulp, dentin, enamel)
* Amelogenesis imperfecta
* Ankylosis
* Anodontia
* Caries
* Early childhood caries
* Concrescence
* Failure of eruption of teeth
* Dens evaginatus
* Talon cusp
* Dentin dysplasia
* Dentin hypersensitivity
* Dentinogenesis imperfecta
* Dilaceration
* Discoloration
* Ectopic enamel
* Enamel hypocalcification
* Enamel hypoplasia
* Turner's hypoplasia
* Enamel pearl
* Fluorosis
* Fusion
* Gemination
* Hyperdontia
* Hypodontia
* Maxillary lateral incisor agenesis
* Impaction
* Wisdom tooth impaction
* Macrodontia
* Meth mouth
* Microdontia
* Odontogenic tumors
* Keratocystic odontogenic tumour
* Odontoma
* Dens in dente
* Open contact
* Premature eruption
* Neonatal teeth
* Pulp calcification
* Pulp stone
* Pulp canal obliteration
* Pulp necrosis
* Pulp polyp
* Pulpitis
* Regional odontodysplasia
* Resorption
* Shovel-shaped incisors
* Supernumerary root
* Taurodontism
* Trauma
* Avulsion
* Cracked tooth syndrome
* Vertical root fracture
* Occlusal
* Tooth loss
* Edentulism
* Tooth wear
* Abrasion
* Abfraction
* Acid erosion
* Attrition
Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures
* Cementicle
* Cementoblastoma
* Gigantiform
* Cementoma
* Eruption cyst
* Epulis
* Pyogenic granuloma
* Congenital epulis
* Gingival enlargement
* Gingival cyst of the adult
* Gingival cyst of the newborn
* Gingivitis
* Desquamative
* Granulomatous
* Plasma cell
* Hereditary gingival fibromatosis
* Hypercementosis
* Hypocementosis
* Linear gingival erythema
* Necrotizing periodontal diseases
* Acute necrotizing ulcerative gingivitis
* Pericoronitis
* Peri-implantitis
* Periodontal abscess
* Periodontal trauma
* Periodontitis
* Aggressive
* As a manifestation of systemic disease
* Chronic
* Perio-endo lesion
* Teething
Periapical, mandibular and maxillary hard tissues – Bones of jaws
* Agnathia
* Alveolar osteitis
* Buccal exostosis
* Cherubism
* Idiopathic osteosclerosis
* Mandibular fracture
* Microgenia
* Micrognathia
* Intraosseous cysts
* Odontogenic: periapical
* Dentigerous
* Buccal bifurcation
* Lateral periodontal
* Globulomaxillary
* Calcifying odontogenic
* Glandular odontogenic
* Non-odontogenic: Nasopalatine duct
* Median mandibular
* Median palatal
* Traumatic bone
* Osteoma
* Osteomyelitis
* Osteonecrosis
* Bisphosphonate-associated
* Neuralgia-inducing cavitational osteonecrosis
* Osteoradionecrosis
* Osteoporotic bone marrow defect
* Paget's disease of bone
* Periapical abscess
* Phoenix abscess
* Periapical periodontitis
* Stafne defect
* Torus mandibularis
Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities
* Bruxism
* Condylar resorption
* Mandibular dislocation
* Malocclusion
* Crossbite
* Open bite
* Overbite
* Overeruption
* Overjet
* Prognathia
* Retrognathia
* Scissor bite
* Maxillary hypoplasia
* Temporomandibular joint dysfunction
Salivary glands
* Benign lymphoepithelial lesion
* Ectopic salivary gland tissue
* Frey's syndrome
* HIV salivary gland disease
* Necrotizing sialometaplasia
* Mucocele
* Ranula
* Pneumoparotitis
* Salivary duct stricture
* Salivary gland aplasia
* Salivary gland atresia
* Salivary gland diverticulum
* Salivary gland fistula
* Salivary gland hyperplasia
* Salivary gland hypoplasia
* Salivary gland neoplasms
* Benign: Basal cell adenoma
* Canalicular adenoma
* Ductal papilloma
* Monomorphic adenoma
* Myoepithelioma
* Oncocytoma
* Papillary cystadenoma lymphomatosum
* Pleomorphic adenoma
* Sebaceous adenoma
* Malignant: Acinic cell carcinoma
* Adenocarcinoma
* Adenoid cystic carcinoma
* Carcinoma ex pleomorphic adenoma
* Lymphoma
* Mucoepidermoid carcinoma
* Sclerosing polycystic adenosis
* Sialadenitis
* Parotitis
* Chronic sclerosing sialadenitis
* Sialectasis
* Sialocele
* Sialodochitis
* Sialosis
* Sialolithiasis
* Sjögren's syndrome
Orofacial soft tissues – Soft tissues around the mouth
* Actinomycosis
* Angioedema
* Basal cell carcinoma
* Cutaneous sinus of dental origin
* Cystic hygroma
* Gnathophyma
* Ludwig's angina
* Macrostomia
* Melkersson–Rosenthal syndrome
* Microstomia
* Noma
* Oral Crohn's disease
* Orofacial granulomatosis
* Perioral dermatitis
* Pyostomatitis vegetans
Other
* Eagle syndrome
* Hemifacial hypertrophy
* Facial hemiatrophy
* Oral manifestations of systemic disease
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Oral manifestations of systemic disease
|
c0029166
| 8,106 |
wikipedia
|
https://en.wikipedia.org/wiki/Oral_manifestations_of_systemic_disease
| 2021-01-18T19:04:26 |
{"mesh": ["D009912"], "wikidata": ["Q30314793"]}
|
A number sign (#) is used with this entry because benign familial neonatal-infantile seizures-3 (BFIS3) is caused by heterozygous mutation in the SCN2A gene (182390) on chromosome 2q24.
See also early infantile epileptic encephalopathy-11 (EIEE11; 613721), a more severe disorder that also results from mutations in the SCN2A gene.
Description
Benign familial neonatal-infantile seizures is an autosomal dominant disorder in which afebrile seizures occur in clusters during the first year of life, without neurologic sequelae (Shevell et al., 1986).
For a general phenotypic description and a discussion of genetic heterogeneity of benign familial infantile seizures, see BFIS1 (601764).
BFIS1 has a slightly later onset than BFIS3, while benign neonatal seizures (see BFNS1, 121200) has a slightly earlier onset.
Clinical Features
Kaplan and Lacey (1983) reported a family in which 12 members had idiopathic neonatal or early infantile seizures inherited in an autosomal dominant pattern. Affected individuals had normal psychomotor development and did not develop subsequent seizures. At age 3.5 days, the proband developed seizures consisting of eye-blinking and lip-smacking or rhythmic twitching of the left arm and leg with the head turned to the right. A few subsequent seizures occurred, but all ceased after 6 months of age. Age at onset in other affected family members ranged from 2 days to 3.5 months, but ceased in all patients by age 7 months. Seizures occurred in clusters, usually 5 to 15, over a period of hours to a couple of days after onset. None of the patients developed a subsequent seizure disorder, and all had normal intellectual and motor development. The authors suggested the term 'benign familial neonatal-infantile seizures' to describe the disorder.
Shevell et al. (1986) described 2 families demonstrating autosomal dominant inheritance of benign familial neonatal seizures (BFNC; see 121200) over 3 generations. None of the patients had seizures after the first 10 months of life, with long-term follow-up ranging from 10 months to 56 years. Development was normal, and antiepileptic drug therapy did not appear to modify either seizure recurrence or long-term outcome. Lewis et al. (1996) studied one of the pedigrees described by Shevell et al. (1986), with the inclusion of additional individuals. Several individuals had onset at 3 to 3.5 months, later than that typical for BFNC, which has onset within the first week of life. Noting that the age at onset in benign familial infantile convulsions (BFIC; see 601764) is typically between 4 and 8 months, the authors concluded that the age at onset in this family was intermediate between that seen in BFNC and BFIC. Lewis et al. (1996) termed BFNC and BFIC 'benign familial convulsions of early life.'
Berkovic et al. (2004) reported 5 families with benign familial neonatal-infantile seizures. Age at onset ranged from 2 days to 7 months (mean 11.2 weeks). Seizures were predominantly afebrile partial seizures with secondary generalization. Focal motor manifestations were usually noted first, typically head and eye deviation, although apnea and staring also occurred. All patients stopped having seizures by age 12 months with no subsequent neurologic deficits.
### Clinical Variability
Sugawara et al. (2001) reported a 6-year-old Japanese boy with normal development who had onset of febrile seizures at age 8 months, and later had 5 episodes of brief afebrile atonic seizures lasting less than 10 seconds since age 4 years. EEG showed single spikes over the right frontal region. Both parents, who were not related, had a history of febrile seizures in childhood. Genetic analysis identified a heterozygous mutation in the SCN2A gene (R188W; 182390.0001) in the boy and the father, but not the mother. Although the authors suggested a link to GEFS+ (604233), they noted that assignment of the phenotype in this patient was difficult because both parents had febrile seizures, which have a high frequency in the general population. Berkovic et al. (2004) concluded that there is little support for an association between SCN2A and GEFS+, despite the report of Sugawara et al. (2001). Berkovic et al. (2004) also stated that seizures with fever occasionally do occur in BFNIS.
Mapping
By genomewide analysis of a large Italian family with benign familial neonatal-infantile epilepsy, Malacarne et al. (2001) mapped the disease locus within a 0.7-cM interval of chromosome 2q24, between markers D2S399 and D2S2330. The maximum multipoint hlod score of 6.29 was obtained under the hypothesis of genetic heterogeneity. Although Malacarne et al. (2001) reported that their affected family had infantile seizures, Berkovic et al. (2004) noted that onset was around 3 months of age, which is more consistent with a diagnosis of neonatal-infantile seizures. Three of 8 families studied by Malacarne et al. (2001) showed linkage to 2q, suggesting that the clustering of 2q24-linked families in southern Italy may indicate a recent founder effect. In their series, 40% of the families with BFIC were not linked to 19q (BFIC1) or 2q.
### Exclusion Studies
The phenotype in the family originally studied by Shevell et al. (1986) was excluded by Leppert et al. (1993) from linkage to chromosome 20 where the BFNC1 locus (121200) maps. Lewis et al. (1996) excluded linkage of the phenotype in this family to chromosome 8 where the BFNC2 (121201) locus maps.
Molecular Genetics
In the family reported by Shevell et al. (1986) and Lewis et al. (1996), and in a second family in which seizure onset occurred predominantly after 1 month of age, Heron et al. (2002) found mutations in the SCN2A gene in affected individuals: a leu1563-to-val (182390.0003) mutation in the family of Shevell et al. (1986), and a leu1330-to-phe (182390.0002) mutation in the second family. Both of these mutations disrupted a conserved leucine, and both were predicted to reduce the rate of inactivation of the sodium channel, leading to increased ion flow through the channel and hyperexcitability.
In affected members of multiple families, including those originally reported by Kaplan and Lacey (1983) and Malacarne et al. (2001), Berkovic et al. (2004) identified mutations in the SCN2A gene (182390.0004-182390.0007).
INHERITANCE \- Autosomal dominant RESPIRATORY \- Apnea during seizure spells \- Cyanosis NEUROLOGIC Central Nervous System \- Seizures, partial, afebrile \- Secondary generalized tonic-clonic seizures may occur \- Seizures occur in clusters over 1 or several days \- Seizures often begin focally with head and eye deviation \- Rigidity during seizures \- Staring episodes during seizures \- Ictal EEG shows focal onset, often posterior region of brain \- Normal psychomotor development \- Normal interictal EEG MISCELLANEOUS \- Onset ranges from 2 days to 7 months (most at 2-3 months) \- Seizures are easily controlled by medications \- Spontaneous resolution by 12 months of age with no recurrence later in life \- See also benign familial infantile convulsions (BFIC1, 601764 ) \- See also benign neonatal epilepsy (EBN1, 121200 ) MOLECULAR BASIS \- Caused by mutation in the alpha-1-subunit of the voltage-gated type II sodium channel gene (SCN2A, 182390.0002 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
SEIZURES, BENIGN FAMILIAL INFANTILE, 3
|
c0220669
| 8,107 |
omim
|
https://www.omim.org/entry/607745
| 2019-09-22T16:08:45 |
{"doid": ["0060169"], "mesh": ["D020936"], "omim": ["607745"], "orphanet": ["140927", "306"], "synonyms": ["Alternative titles", "CONVULSIONS, BENIGN FAMILIAL INFANTILE, 3", "SEIZURES, BENIGN FAMILIAL NEONATAL-INFANTILE"]}
|
## Description
Catechol-O-methyltransferase (COMT; EC 2.1.1.6) is one of the major mammalian enzymes involved in the metabolic degradation of catecholamines (summary by Gogos et al., 1998). COMT catalyzes the transfer of a methyl group from S-adenosyl-methionine (SAM) to a hydroxyl group on a catechol nucleus (e.g., dopamine, norepinephrine, or catechol estrogen) (summary by Chen et al., 2004).
Cloning and Expression
Lundstrom et al. (1991) isolated cDNA clones for COMT from a human placenta cDNA library using synthetic oligonucleotides as probes. The clones contained an open reading frame that potentially coded for a 24.4-kD polypeptide, presumably corresponding to the cytoplasmic form of COMT. DNA analysis suggested that the human, as well as the rat, dog, and monkey, has 1 gene for COMT.
Mapping
Wilson et al. (1984) excluded tight and close linkage of COMT with 21 and 15 loci, respectively. A lod score of 1.27 at theta = 0.1 was found between COMT and phosphogluconate dehydrogenase (PGD; 172200), which is on chromosome 1.
In studies of mouse-human cell hybrids with a method permitting direct detection of COMT isozymes in autoradiozymograms, Brahe et al. (1986) located the COMT gene on human chromosome 22. By study of DNAs from a panel of human-hamster somatic cell hybrid lines, Grossman et al. (1991, 1992) mapped COMT to 22q11.1-q11.2. Winqvist et al. (1991) assigned COMT to 22q11.2 by means of Southern blot analysis of somatic cell hybrids and chromosomal in situ hybridization. They concluded that COMT is located proximal to the breakpoint cluster region (BCR) involved in chronic myeloid leukemia (151410). Bucan et al. (1993) mapped the homologous murine gene to chromosome 16, where, as in the human, it is closely linked to the lambda light chain genes.
During experiments aimed at building a contiguous group of YACs spanning 22q11, Dunham et al. (1992) found that the HP500 sequence often deleted in the velocardiofacial syndrome (VCFS; 192430) was located within the same 450-kb YAC as the COMT gene. They raised the question of whether low COMT might be responsible for psychotic illness, which is a feature of the VCF syndrome in adolescents and adults (Shprintzen et al., 1992).
Biochemical Features
Gustavson et al. (1973, 1982) reported that COMT activity was about 40% higher in Down syndrome children than in normal controls. They attributed this to dosage effect owing to a presumed location of the COMT gene on chromosome 21. Brahe et al. (1986) studied the expression of human COMT in interspecies somatic cell hybrids and found 27% discordance between human chromosome 21 and human COMT, suggesting that an assignment of the human COMT gene to chromosome 21 was very unlikely.
Molecular Genetics
### COMT Activity Polymorphism
Catechol-O-methyltransferase catalyzes the transfer of a methyl group from S-adenosylmethionine to catecholamines, including the neurotransmitters dopamine, epinephrine, and norepinephrine. This O-methylation results in one of the major degradative pathways of the catecholamine transmitters. In addition to its role in the metabolism of endogenous substances, COMT is important in the metabolism of catechol drugs used in the treatment of hypertension, asthma, and Parkinson disease. In blood COMT is found mainly in erythrocytes; in leukocytes it exhibits low activity. Weinshilboum and Raymond (1977) found bimodality for red cell catechol-O-methyltransferase activity. Of a randomly selected population, 23% had low activity. Segregation analysis of family data suggested that low activity is recessive. Scanlon et al. (1979) found that homozygotes have a thermolabile enzyme. Thus, the site of the low COMT mutation is presumably the structural locus. Levitt and Baron (1981) confirmed the bimodality of human erythrocyte COMT. They further showed thermolability of the enzyme in 'low COMT' samples, suggesting a structural alteration in the enzyme. Autosomal codominant inheritance of the gene coding for erythrocyte COMT activity was adduced by Floderus and Wetterberg (1981) and by Weinshilboum and Dunnette (1981). Gershon and Goldin (1981) concluded that codominant inheritance was consistent with the family data. Spielman and Weinshilboum (1981) suggested that the inheritance of red cell COMT is intermediate, or codominant, there being 3 phenotypes corresponding to the 3 genotypes in a 2-allele system. The COMT of persons with low enzyme activity is more thermolabile than that of persons with high activity.
### Susceptibility to Obsessive-Compulsive Disorder
Karayiorgou et al. (1997, 1999) found an association between obsessive-compulsive disorder (OCD; 164230) and COMT; the homozygous low activity genotype of the COMT gene was associated with risk for OCD in males. Alsobrook et al. (2002) used a family-based genetic design in haplotype relative risk (HRR) and transmission disequilibrium test (TDT) analyses of the association between OCD and COMT. Fifty-six OCD probands and their parents were genotyped for the COMT locus. Analysis of allele and genotype frequencies between the proband genotypes and the control (parental nontransmitted) genotypes failed to replicate the previous finding of gender divergence and gave no evidence of overall association; furthermore, no linkage was detected by TDT. However, further analysis of the COMT allele frequencies by proband gender gave evidence of a mildly significant association with the low activity COMT allele in female probands (P = 0.049), but not in male probands.
### Susceptibility to Schizophrenia
The COMT gene is a strong candidate for schizophrenia susceptibility (see 181500), owing to the role of COMT in dopamine metabolism and the location of the gene within the deleted region in VCFS, a disorder associated with high rates of schizophrenia. Shifman et al. (2002) found a highly significant association between schizophrenia and a COMT haplotype in a large case-control sample in Ashkenazi Jews. In addition to the functional val158-to-met polymorphism (116790.0001; rs4680), this haplotype included 2 noncoding SNPs at either end of the COMT gene (rs737865 and rs165599). With this background information, Bray et al. (2003) postulated that the COMT susceptibility haplotype is associated with low COMT expression. To test their hypothesis, they applied quantitative measures of allele-specific expression using mRNA from human brain. They demonstrated that COMT is subject to allelic differences in expression in human brain and that the COMT haplotype implicated in schizophrenia by Shifman et al. (2002) is associated with lower expression of COMT mRNA. They also showed that the 3-prime flanking region SNP that in the study of Shifman et al. (2002) gave greatest evidence for association with schizophrenia is transcribed in human brain and exhibits significant differences in allelic expression, with lower relative expression of the associated allele. They concluded that the haplotype implicated in schizophrenia susceptibility is likely to exert its effect, directly or indirectly, by downregulating COMT expression.
In 38 populations representing all major regions of the world, Palmatier et al. (2004) studied the frequency of the schizophrenia-associated COMT haplotype reported by Shifman et al. (2002) as well as a 7-site COMT haplotype. Their results supported the relevance of the COMT P2 promoter to schizophrenia. The population data showed that the schizophrenia-associated haplotype varies significantly in frequency around the world and has significant heterogeneity when other markers in COMT are also considered.
Lee et al. (2005) screened for 17 known polymorphisms in the COMT gene in 320 Korean patients with schizophrenia and 379 controls. They identified a positive association of schizophrenia with a nonsynonymous SNP (rs6267) at codon 72/22 (membrane/soluble-bound form) causing an ala-to-ser substitution (A72S; 116790.0002). Lee et al. (2005) showed that the A72S substitution was correlated with reduced COMT enzyme activity, and their results supported previous reports that the COMT haplotypes implicated in schizophrenia are associated with low COMT expression.
### Susceptibility to Anorexia Nervosa
Frisch et al. (2001) found an association between anorexia nervosa (AN; 606788) and the COMT val158 allele (V158M; 116790.0001) in a family-based study of 51 Israeli-Jewish AN trios. Gabrovsek et al. (2004) could not replicate this finding in a combined sample of 372 European AN families, suggesting that the findings of Frisch et al. (2001) were specific to a particular population and that val158 is in linkage disequilibrium with other molecular variations in the COMT gene, or its vicinity, which were the direct cause of genetic susceptibility to anorexia nervosa. Michaelovsky et al. (2005) studied 85 Israeli-Jewish AN trios, including the original sample of Frisch et al. (2001), comprising 66 anorexia nervosa restricting (AN-R) and 19 binge-eating/purging patients. They performed a family-based TDT analysis for 7 SNPs in the COMT-ARVCF (602269) region including the V158M polymorphism. TDT analysis of 5-SNP haplotypes in the AN-R group revealed overall statistically significant transmission disequilibrium for 'haplotype B' (COMT 186C, 408G, 472G [val158] and ARVCF 659C[pro220] and 524T[val175]) (P less than 0.001), while 'haplotype A' (COMT 186T, 408C, 472A[met158] and ARVCF 659T[leu220] and 524C[ala175]) was preferentially not transmitted (P = 0.01). Haplotype B was associated with increased risk (RR of 3.38), while haplotype A exhibited a protective effect (RR of 0.40) for AN-R. Preferential transmission of the risk alleles and haplotypes from parents was mostly contributed by fathers.
### Associations Pending Confirmation
Sweet et al. (2005) conducted a study to determine if COMT genetic variation was associated with a risk of psychosis in Alzheimer disease (AD; see 114300). The study included a case-control sample of 373 individuals diagnosed with AD with or without psychosis. Subjects were characterized for alleles at 3 loci previously associated with schizophrenia, rs737865, rs4680, and rs165599, and for a C/T transition adjacent to an estrogen response element (ERE6) in the COMT P2 promoter region. Single-locus and haplotype tests of association were conducted. Logit models were used to examine independent and interacting effects of alleles at the associated loci and all analyses were stratified by sex. In female subjects, rs4680 demonstrated a modest association with AD plus psychosis; rs737865 demonstrated a trend towards an association. There was a highly significant association of AD plus psychosis with a 4-locus haplotype, which resulted from additive effects of alleles at rs4680 and ERE6/rs737865 (the latter were in linkage disequilibrium). In male subjects, no single-locus test was significant, although a strong association between AD with psychosis and the 4-locus haplotype was observed. That association appeared to result from interaction of the ERE6/rs737865, rs4680, rs165599 loci. Genetic variation in COMT was associated with AD plus psychosis and thus appears to contribute to psychosis risk across disorders.
Three common haplotypes of the human COMT gene are divergent at 2 synonymous and 1 nonsynonymous position (Diatchenko et al., 2005). One is rs4633, which is either a C or T, but both code for a histidine at amino acid 62; the other is rs4818, which can be a G or C, but both code for a leucine at nucleotide 136; the nonsynonymous haplotype is represented by rs4680, a met158-to-val change change (116790.0001). Nackley et al. (2006) noted that the 3 common haplotypes code for differences in COMT enzymatic activity and are associated with pain sensitivity. Haplotypes divergent in synonymous changes exhibited the largest difference in COMT enzymatic activity, due to a reduced amount of translated protein. The major COMT haplotypes varied with respect to mRNA local stem-loop structures, such that the most stable structure was associated with the lowest protein levels and enzymatic activity. Site-directed mutagenesis that eliminated the stable structure restored the amount of translated protein. Nackley et al. (2006) concluded that their data highlighted the functional significance of synonymous variations and suggested the importance of haplotypes over SNPs for analysis of genetic variations.
Animal Model
Gogos et al. (1998) generated mice deficient for COMT. They measured the basal concentrations of brain catecholamines in the striatum, frontal cortex, and hypothalamus of adult male and female mutants and analyzed locomotor activity, anxiety-like behaviors, sensorimotor gating, and aggressive behavior. Mutant mice demonstrated sexually dimorphic and region-specific changes of dopamine levels, notably in the frontal cortex. Homozygous COMT-deficient female (but not male) mice displayed impairment in emotional reactivity in the dark/light exploratory model of anxiety. Furthermore, heterozygous COMT-deficient male mice exhibited increased aggressive behavior. Gogos et al. (1998) concluded that their results provided conclusive evidence for an important sex- and region-specific contribution of COMT in the maintenance of steady-state levels of catecholamines in the brain and suggested a role for COMT in some aspects of emotional and social behavior in mice.
Kanasaki et al. (2008) showed that pregnant mice deficient in COMT showed a preeclampsia-like phenotype resulting from absence of 2-methoxyestradiol (2-ME), a natural metabolite of estradiol that is elevated during the third trimester of normal human pregnancy. Administration of 2-ME ameliorated all preeclampsia-like features without toxicity in Comt -/- pregnant mice and suppressed placental hypoxia, Hif1a (603348) expression, and soluble Flt1 (165070) elevation. The levels of COMT and 2-ME were significantly lower in women with severe preeclampsia. Kanasaki et al. (2008) suggested that Comt-null mice may provide a model for preeclampsia and that 2-ME may serve as a diagnostic marker as well as a therapeutic agent for preeclampsia.
Duplications of human chromosome 22q11.2 (608363) are associated with elevated rates of mental retardation, autism, and many other behavioral phenotypes. Suzuki et al. (2009) determined the developmental impact of overexpression of an approximately 190-kb segment of human 22q11.2, which includes the genes TXNRD2 (606448), COMT, and ARVCF (602269), on behaviors in bacterial artificial chromosome (BAC) transgenic mice. BAC transgenic mice and wildtype mice were tested for their cognitive capacities, affect- and stress-related behaviors, and motor activity at 1 and 2 months of age. BAC transgenic mice approached a rewarded goal faster (i.e., incentive learning), but were impaired in delayed rewarded alternation during development. In contrast, BAC transgenic and wildtype mice were indistinguishable in rewarded alternation without delays, spontaneous alternation, prepulse inhibition, social interaction, anxiety-, stress-, and fear-related behaviors, and motor activity. Compared with wildtype mice, BAC transgenic mice had a 2-fold higher level of COMT activity in the prefrontal cortex, striatum, and hippocampus. Suzuki et al. (2009) suggested that overexpression of this 22q11.2 segment may enhance incentive learning and impair the prolonged maintenance of working memory, but has no apparent affect on working memory per se, affect- and stress-related behaviors, or motor capacity. High copy numbers of this 22q11.2 segment may contribute to a highly selective set of phenotypes in learning and cognition during development.
Inheritance \- Autosomal recessive (22q11.2) Lab \- Catechol-O-methyltransferase deficiency Metabolic \- Catecholamine transmitter degradation ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
CATECHOL-O-METHYLTRANSFERASE
|
c1861822
| 8,108 |
omim
|
https://www.omim.org/entry/116790
| 2019-09-22T16:43:36 |
{"omim": ["116790"]}
|
Acromegaly is a hormonal disorder that results from the pituitary gland producing too much growth hormone (GH). It is most often diagnosed in middle-aged adults, although symptoms can appear at any age. Signs and symptoms include abnormal growth and swelling of the hands and feet; bone changes that; alter various facial features; arthritis; carpal tunnel syndrome; enlargement of body organs; and various other symptoms. The condition is usually caused by benign tumors on the pituitary called adenomas. Rarely, it is caused by tumors of the pancreas, lungs, and other parts of the brain stimulating the pituitary gland to produce GH. It is sporadic in 95% of the cases, but almost 50% of the childhood-onset cases have an identifiable gene mutation, most commonly in the AIP gene or GPR101 gene. Treatment may include hormones, radiotherapy, and surgery. When left untreated, it can result in serious illness and premature death. When GH-producing tumors occur in childhood, the disease that results is called gigantism rather than acromegaly.
Acromegaly may also be part of other genetic syndromes such as multiple endocrine neoplasia syndrome type 1 and type 4, hereditary paraganglioma-pheochromocytoma syndrome, McCune-Allright syndrome, neurofibromatosis or Carney complex.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Acromegaly
|
c0001206
| 8,109 |
gard
|
https://rarediseases.info.nih.gov/diseases/5725/acromegaly
| 2021-01-18T18:02:20 |
{"mesh": ["D000172"], "orphanet": ["963"], "synonyms": ["Somatotroph adenoma", "Growth hormone excess", "Pituitary giant"]}
|
A number sign (#) is used with this entry because of evidence that DFNB67 is caused by homozygous mutation in the lipoma HMGIC fusion partner-like 5 gene (LHFPL5; 609427) on chromosome 6p21.
Clinical Features
Shabbir et al. (2006) reported 2 large consanguineous Pakistani families segregating autosomal recessive congenital, bilateral, profound, nonsyndromic deafness. No vestibular dysfunction was detected.
Kalay et al. (2006) reported 2 Turkish consanguineous families with autosomal recessive nonsyndromic deafness. Affected individuals presented with bilateral severe to profound sensorineural hearing loss without vestibular abnormalities. In each affected individual, hearing impairment was noticed by the parents in the first 6 months of life.
Mapping
Shabbir et al. (2006) mapped a novel locus for nonsyndromic deafness, DFNB67, to chromosome 6p21.1-p22.3 in a large consanguineous Pakistani family.
Kalay et al. (2006) mapped autosomal recessive nonsyndromic hearing loss in 2 large consanguineous Turkish families to 6p21.3 in an interval overlapping with the loci DFNB53 (COL11A2; 120290), DFNB66 (610212), and DFNB67. Fine mapping excluded DFNB53.
Molecular Genetics
In 2 consanguineous Pakistani families segregating nonsyndromic deafness, Shabbir et al. (2006) identified homozygous mutations in the LHFPL5 gene (609427.0001-609427.0002) as the cause of the disorder.
In 2 large Turkish consanguineous families with autosomal recessive nonsyndromic hearing loss mapped to chromosome 6p21.3, Kalay et al. (2006) identified homozygous mutations in the LHFPL5 gene, a 1-bp deletion (649delG; 609427.0003) and a missense mutation (609427.0004). Further screening of index patients from 96 Turkish autosomal recessive nonsyndromic hearing loss families and 90 Dutch patients identified 1 additional Turkish patient carrying the 649delG mutation. Haplotype analysis showed that this last mutation was located on a common haplotype. Mutation screening of the homologous LHFPL3 (609719) and LHFPL4 (610240) genes did not reveal any disease-causing mutation. The findings suggested that LHFPL5 is essential for normal function of the human cochlea. In all these families affected individuals presented with bilateral profound hearing loss but without vestibular abnormalities. Thus the phenotype is different from that of the 'hurry-scurry' mouse (hscy), carrying mutation in the Lhfpl5 gene, in which deafness is associated with vestibular dysfunction (Longo-Guess et al., 2005).
INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Hearing loss, congenital, bilateral, severe to profound \- No vestibular dysfunction MISCELLANEOUS \- Prelingual onset MOLECULAR BASIS \- Caused by mutation in the LHFP-like protein-5 gene (LHFPL5, 609427.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
DEAFNESS, AUTOSOMAL RECESSIVE 67
|
c1853223
| 8,110 |
omim
|
https://www.omim.org/entry/610265
| 2019-09-22T16:04:45 |
{"doid": ["0110518"], "mesh": ["C565207"], "omim": ["610265"], "orphanet": ["90636"], "synonyms": ["Autosomal recessive isolated neurosensory deafness type DFNB", "Autosomal recessive isolated sensorineural deafness type DFNB", "Autosomal recessive non-syndromic neurosensory deafness type DFNB"], "genereviews": ["NBK1434"]}
|
Not to be confused with Sjögren's syndrome, an autoimmune disorder which can cause many problems including dry skin.
Sjögren–Larsson syndrome
Other namesSLS
Two brothers (21 and 25 years old) with generalized dryness of skin with fine scales mainly around the umbilicus and in the flexural folds, one of Sjögren–Larsson syndrome characteristics.
SpecialtyMedical genetics
Sjögren–Larsson syndrome is a rare autosomal recessive form of ichthyosis with neurological symptoms.[1]:485[2]:564[3] It can be identified by a triad of medical disorders. The first is ichthyosis, which is a buildup of skin to form a scale-like covering that causes dry skin and other problems. The second identifier is paraplegia which is characterized by leg spasms. The final identifier is intellectual delay.
SLS is caused by a mutation in the fatty aldehyde dehydrogenase gene found on chromosome 17.[4] In order for a child to receive SLS both parents must be carriers of the SLS gene. If they are carriers their child has a ¼ chance of getting the disease. In 1957 Sjögren and Larsson proposed that the Swedes with the disease all descended from a common ancestor 600 years ago. Today only 30–40 persons in Sweden have this disease.[5]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Diagnosis
* 4 Treatment
* 5 Eponym
* 6 See also
* 7 References
* 8 Further reading
* 9 External links
## Signs and symptoms[edit]
T2-weighted MRI images of a 25 year-old male with Sjögren–Larsson syndrome revealing dysmyelination in the deep periventricular white matter and reduced brain volume in the frontal lobe.
* Dry and scaly skin similar to all other ichtyosiforms (types of ichthyosis).
* Neurological problems – this can often cause mild paralysis in the legs
* Mild to moderate intellectual disability.
* Often associated ocular features, which include pigmentary changes in the retina.
The usual presentation of crystalline maculopathy is from the age of 1-2 years onwards.
## Causes[edit]
It is associated with a deficiency of the enzyme fatty aldehyde dehydrogenase (ALDH3A2) which is encoded on the short arm of chromosome 17 (17p11.2). At least 11 distinct mutations have been identified.[6]
Without a functioning fatty aldehyde dehydrogenase enzyme, the body is unable to break down medium- and long-chain fatty aldehydes which then build up in the membranes of the skin and brain.[4]
This condition is inherited in an autosomal recessive pattern.
## Diagnosis[edit]
Diagnosis is made with a blood test which sees if the activity of the fatty aldehyde dehydrogenase enzyme is normal.[4] Gene sequencing can also be used, which can additionally be used by would-be parents to see if they are carriers.[4]
## Treatment[edit]
The ichthyosis is usually treated with topical ointment.[4] Anti-convulsants are used to treat seizures[4] and the spasms may be improved with surgery.[4]
## Eponym[edit]
It was characterized by Torsten Sjögren and Tage Konrad Leopold Larsson (1905–1998), a Swedish medical statistician.[7][8] It should not be confused with Sjögren's syndrome, which is a distinct condition named after a different person, Henrik Sjögren.Didn't!
## See also[edit]
* Shabbir syndrome
* List of cutaneous conditions
## References[edit]
1. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0.
2. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
3. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
4. ^ a b c d e f g "Sjogren-Larsson syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2020-10-31.
5. ^ "Sjögren-Larssons syndrom".
6. ^ Sillén A, Anton-Lamprecht I, Braun-Quentin C, et al. (1998). "Spectrum of mutations and sequence variants in the FALDH gene in patients with Sjögren–Larsson syndrome". Hum. Mutat. 12 (6): 377–84. doi:10.1002/(SICI)1098-1004(1998)12:6<377::AID-HUMU3>3.0.CO;2-I. PMID 9829906.
7. ^ synd/1678 at Who Named It?
8. ^ SJOGREN T, LARSSON T (1957). "Oligophrenia in combination with congenital ichthyosis and spastic disorders; a clinical and genetic study". Acta Psychiatr Neurol Scand Suppl. 113: 1–112. PMID 13457946.
## Further reading[edit]
* Sjögren, K. G. Torsten; Larsson, Tage K. (1957). "Oligophrenia in combination with congenital ichtyosis and spastic disorders; a clinical and genetic study". Acta Psychiatrica et Neurologica Scandinavica. Copenhagen. 32 (supplement 113): 9–105. doi:10.1111/j.1600-0447.1956.tb04725.x. PMID 13457946. S2CID 72058188.
## External links[edit]
Classification
D
* ICD-10: Q87.1 (ILDS Q87.136)
* ICD-9-CM: 757.1 (CDC/BPA 757.120)
* OMIM: 270200
* MeSH: D016111
* DiseasesDB: 30051
External resources
* eMedicine: derm/706
* Orphanet: 816
* v
* t
* e
Inborn error of lipid metabolism: fatty-acid metabolism disorders
Synthesis
* Biotinidase deficiency (BTD)
Degradation
Acyl
transport
* Carnitine
* CPT1
* CPT2
* CDSP
* CACTD
* Adrenoleukodystrophy (ALD)
Beta
oxidation
General
* Acyl CoA dehydrogenase
* Short-chain SCADD
* Medium-chain MCADD
* Long-chain 3-hydroxy LCHAD
* Very long-chain VLCADD
* Mitochondrial trifunctional protein deficiency (MTPD): Acute fatty liver of pregnancy
Unsaturated
* 2,4 Dienoyl-CoA reductase deficiency (DECRD)
Odd chain
* Propionic acidemia (PCC deficiency)
Other
* 3-hydroxyacyl-coenzyme A dehydrogenase deficiency (HADHD)
* Glutaric acidemia type 2 (MADD)
To
acetyl-CoA
* Malonic aciduria (MCD)
Aldehyde
* Sjögren–Larsson syndrome (SLS)
* v
* t
* e
Congenital malformations and deformations of integument / skin disease
Genodermatosis
Congenital ichthyosis/
erythrokeratodermia
AD
* Ichthyosis vulgaris
AR
* Congenital ichthyosiform erythroderma: Epidermolytic hyperkeratosis
* Lamellar ichthyosis
* Harlequin-type ichthyosis
* Netherton syndrome
* Zunich–Kaye syndrome
* Sjögren–Larsson syndrome
XR
* X-linked ichthyosis
Ungrouped
* Ichthyosis bullosa of Siemens
* Ichthyosis follicularis
* Ichthyosis prematurity syndrome
* Ichthyosis–sclerosing cholangitis syndrome
* Nonbullous congenital ichthyosiform erythroderma
* Ichthyosis linearis circumflexa
* Ichthyosis hystrix
EB
and related
* EBS
* EBS-K
* EBS-WC
* EBS-DM
* EBS-OG
* EBS-MD
* EBS-MP
* JEB
* JEB-H
* Mitis
* Generalized atrophic
* JEB-PA
* DEB
* DDEB
* RDEB
* related: Costello syndrome
* Kindler syndrome
* Laryngoonychocutaneous syndrome
* Skin fragility syndrome
Ectodermal dysplasia
* Naegeli syndrome/Dermatopathia pigmentosa reticularis
* Hay–Wells syndrome
* Hypohidrotic ectodermal dysplasia
* Focal dermal hypoplasia
* Ellis–van Creveld syndrome
* Rapp–Hodgkin syndrome/Hay–Wells syndrome
Elastic/Connective
* Ehlers–Danlos syndromes
* Cutis laxa (Gerodermia osteodysplastica)
* Popliteal pterygium syndrome
* Pseudoxanthoma elasticum
* Van der Woude syndrome
Hyperkeratosis/
keratinopathy
PPK
* diffuse: Diffuse epidermolytic palmoplantar keratoderma
* Diffuse nonepidermolytic palmoplantar keratoderma
* Palmoplantar keratoderma of Sybert
* Meleda disease
* syndromic
* connexin
* Bart–Pumphrey syndrome
* Clouston's hidrotic ectodermal dysplasia
* Vohwinkel syndrome
* Corneodermatoosseous syndrome
* plakoglobin
* Naxos syndrome
* Scleroatrophic syndrome of Huriez
* Olmsted syndrome
* Cathepsin C
* Papillon–Lefèvre syndrome
* Haim–Munk syndrome
* Camisa disease
* focal: Focal palmoplantar keratoderma with oral mucosal hyperkeratosis
* Focal palmoplantar and gingival keratosis
* Howel–Evans syndrome
* Pachyonychia congenita
* Pachyonychia congenita type I
* Pachyonychia congenita type II
* Striate palmoplantar keratoderma
* Tyrosinemia type II
* punctate: Acrokeratoelastoidosis of Costa
* Focal acral hyperkeratosis
* Keratosis punctata palmaris et plantaris
* Keratosis punctata of the palmar creases
* Schöpf–Schulz–Passarge syndrome
* Porokeratosis plantaris discreta
* Spiny keratoderma
* ungrouped: Palmoplantar keratoderma and spastic paraplegia
* desmoplakin
* Carvajal syndrome
* connexin
* Erythrokeratodermia variabilis
* HID/KID
Other
* Meleda disease
* Keratosis pilaris
* ATP2A2
* Darier's disease
* Dyskeratosis congenita
* Lelis syndrome
* Dyskeratosis congenita
* Keratolytic winter erythema
* Keratosis follicularis spinulosa decalvans
* Keratosis linearis with ichthyosis congenita and sclerosing keratoderma syndrome
* Keratosis pilaris atrophicans faciei
* Keratosis pilaris
Other
* cadherin
* EEM syndrome
* immune system
* Hereditary lymphedema
* Mastocytosis/Urticaria pigmentosa
* Hailey–Hailey
see also Template:Congenital malformations and deformations of skin appendages, Template:Phakomatoses, Template:Pigmentation disorders, Template:DNA replication and repair-deficiency disorder
Developmental
anomalies
Midline
* Dermoid cyst
* Encephalocele
* Nasal glioma
* PHACE association
* Sinus pericranii
Nevus
* Capillary hemangioma
* Port-wine stain
* Nevus flammeus nuchae
Other/ungrouped
* Aplasia cutis congenita
* Amniotic band syndrome
* Branchial cyst
* Cavernous venous malformation
* Accessory nail of the fifth toe
* Bronchogenic cyst
* Congenital cartilaginous rest of the neck
* Congenital hypertrophy of the lateral fold of the hallux
* Congenital lip pit
* Congenital malformations of the dermatoglyphs
* Congenital preauricular fistula
* Congenital smooth muscle hamartoma
* Cystic lymphatic malformation
* Median raphe cyst
* Melanotic neuroectodermal tumor of infancy
* Mongolian spot
* Nasolacrimal duct cyst
* Omphalomesenteric duct cyst
* Poland anomaly
* Rapidly involuting congenital hemangioma
* Rosenthal–Kloepfer syndrome
* Skin dimple
* Superficial lymphatic malformation
* Thyroglossal duct cyst
* Verrucous vascular malformation
* Birthmark
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Sjögren–Larsson syndrome
|
c0037231
| 8,111 |
wikipedia
|
https://en.wikipedia.org/wiki/Sj%C3%B6gren%E2%80%93Larsson_syndrome
| 2021-01-18T18:31:52 |
{"gard": ["7654"], "mesh": ["D016111"], "umls": ["C0037231"], "icd-9": ["757.1"], "icd-10": ["Q87.1"], "orphanet": ["816"], "wikidata": ["Q2291208"]}
|
Lymphedema–distichiasis syndrome
Other namesLymphedema with distichiasis[1]
Lymphedema–distichiasis syndrome is inherited in an autosomal dominant manner
Lymphedema–distichiasis syndrome is a medical condition associated with the FOXC2 gene.[2]:849 People with this hereditary condition have a double row of eyelashes, which is called distichiasis, and a risk of swollen limbs due to problems in the lymphatic system.
## Contents
* 1 Genetics
* 2 Mutations
* 3 Symptoms
* 4 Syndrome diagnosis and management
* 5 See also
* 6 Notes
* 7 References
* 8 External links
## Genetics[edit]
Lymphedema-distichiasis is inherited in an autosomal dominant fashion.[3] It is estimated that only ¼ of diagnosed individuals did not inherit the condition but rather acquired the syndrome via a de novo mutation.[4] Symptoms emerge between the life stages of puberty to early adulthood (around 30 years old).[citation needed] This is the result of a mutation in the FOXC2 gene.[5]
## Mutations[edit]
p.Y41F, a missense mutation, is also located in FOXC2 AD-1. p.Y41F is one of eleven mutations found in the FOXC2 gene. It was determined that of these 11 mutations, one was nonsense, six were missense, and four were frameshift mutations.[6]
## Symptoms[edit]
The main symptoms of lymphedema-distichiasis are limb swelling and a double row of eyelashes. Symptoms that have been noted in some but not all cases include cysts, light sensitivity, cardiac defects, cleft palate, and eye problems such as astigmatism and cornea scarring.[5]
## Syndrome diagnosis and management[edit]
Currently, the most accurate test to determine if an individual is affected by lymphedema-distichiasis syndrome is done via Sanger sequencing, which includes whole genome analysis and single gene and multigene testing.[3][7] Sequenced DNA that exhibits mutations in the FOXC2 gene are considered confirmed clinical diagnoses. In addition to Sanger sequencing, Multiplex Ligation Probe Amplification (MLPA) can be used to determine if duplications and deletions in FOXC2 are present in an individual, making it a practical testing mechanism.[3] Lastly, diagnosis is sometimes determined without genome testing. If an individual exhibits multiple symptoms of lymphedema-distichiasis and has a medical history consistent with known lymphedema-distichiasis symptoms, then their diagnosis is confirmed via clinical evaluation.[8]
Lymphedema-distichiasis is a rare genetic disease, it is unknown how many individuals are affected and what the frequency of the condition is.[9] As a result, there are few syndrome management techniques: Symptoms of distichiasis can be minimized via eyelash plucking, electrolysis and other various treatments.[7] Limb swelling can be reduced using compression clothing and bandages. Lastly, rapid treatment of broken skin and cellulitis lessens severity of symptoms.[7]
## See also[edit]
* Lymphedema
* Aagenaes syndrome
* List of cutaneous conditions
## Notes[edit]
1. ^ "Lymphedema-distichiasis syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 21 April 2019.
2. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6.
3. ^ a b c Rakhmanov, Yeltay; Maltese, Paolo Enrico; Paolacci, Stefano; Marinelli, Carla; Bertelli, Matteo (2018-09-01). "Genetic testing for lymphedema-distichiasis syndrome". The EuroBiotech Journal. 2 (s1): 13–15. doi:10.2478/ebtj-2018-0026. ISSN 2564-615X.
4. ^ Kolin, Talia (1991-07-01). "Hereditary Lymphedema and Distichiasis". Archives of Ophthalmology. 109 (7): 980. doi:10.1001/archopht.1991.01080070092042. ISSN 0003-9950. PMC 6693661. PMID 2064580.
5. ^ a b Fang, Jianming; Dagenais, Susan L.; Erickson, Robert P.; Arlt, Martin F.; Glynn, Michael W.; Gorski, Jerome L.; Seaver, Laurie H.; Glover, Thomas W. (December 2000). "Mutations in FOXC2 (MFH-1), a Forkhead Family Transcription Factor, Are Responsible for the Hereditary Lymphedema-Distichiasis Syndrome". The American Journal of Human Genetics. 67 (6): 1382–1388. doi:10.1086/316915. ISSN 0002-9297. PMC 1287915. PMID 11078474.
6. ^ van Steensel, M.A.M.; Damstra, R.J.; Heitink, M.; Bladergroen, R.S.; Veraart, J.; Steijlen, Peter M.; van Geel, M. (December 2009). "Novel missense mutations in theFOXC2gene alter transcriptional activity". Human Mutation. 30 (12): E1002–E1009. doi:10.1002/humu.21127. ISSN 1059-7794. PMID 19760751.
7. ^ a b c Mansour, Sahar; Brice, Glen W.; Jeffery, Steve; Mortimer, Peter (1993), Adam, Margaret P.; Ardinger, Holly H.; Pagon, Roberta A.; Wallace, Stephanie E. (eds.), "Lymphedema-Distichiasis Syndrome", GeneReviews®, University of Washington, Seattle, PMID 20301630, retrieved 2020-04-15
8. ^ "Lymphedema-Distichiasis Syndrome". NORD (National Organization for Rare Disorders). Retrieved 2020-04-15.
9. ^ Reference, Genetics Home. "Lymphedema-distichiasis syndrome". Genetics Home Reference. Retrieved 2020-04-15.
## References[edit]
* Mangion J, Rahman N, Mansour S, Brice G, Rosbotham J, Child A, Murday V, Mortimer P, Barfoot R, Sigurdsson A, Edkins S, Sarfarazi M, Burnand K, Evans A, Nunan T, Stratton M, Jeffery S (1999). "A gene for lymphedema-distichiasis maps to 16q24.3". Am J Hum Genet. 65 (2): 427–32. doi:10.1086/302500. PMC 1377941. PMID 10417285.
## External links[edit]
Classification
D
* ICD-10: Q82.0
* OMIM: 153400
* MeSH: C537710
* DiseasesDB: 30530
External resources
* GeneReviews: Lymphedema-Distichiasis Syndrome
* Orphanet: 33001
* GeneReview/NIH/UW entry on Lymphedema-Distichiasis Syndrome
* v
* t
* e
Genetic disorders relating to deficiencies of transcription factor or coregulators
(1) Basic domains
1.2
* Feingold syndrome
* Saethre–Chotzen syndrome
1.3
* Tietz syndrome
(2) Zinc finger
DNA-binding domains
2.1
* (Intracellular receptor): Thyroid hormone resistance
* Androgen insensitivity syndrome
* PAIS
* MAIS
* CAIS
* Kennedy's disease
* PHA1AD pseudohypoaldosteronism
* Estrogen insensitivity syndrome
* X-linked adrenal hypoplasia congenita
* MODY 1
* Familial partial lipodystrophy 3
* SF1 XY gonadal dysgenesis
2.2
* Barakat syndrome
* Tricho–rhino–phalangeal syndrome
2.3
* Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome
* Denys–Drash syndrome
* Duane-radial ray syndrome
* MODY 7
* MRX 89
* Townes–Brocks syndrome
* Acrocallosal syndrome
* Myotonic dystrophy 2
2.5
* Autoimmune polyendocrine syndrome type 1
(3) Helix-turn-helix domains
3.1
* ARX
* Ohtahara syndrome
* Lissencephaly X2
* MNX1
* Currarino syndrome
* HOXD13
* SPD1 synpolydactyly
* PDX1
* MODY 4
* LMX1B
* Nail–patella syndrome
* MSX1
* Tooth and nail syndrome
* OFC5
* PITX2
* Axenfeld syndrome 1
* POU4F3
* DFNA15
* POU3F4
* DFNX2
* ZEB1
* Posterior polymorphous corneal dystrophy
* Fuchs' dystrophy 3
* ZEB2
* Mowat–Wilson syndrome
3.2
* PAX2
* Papillorenal syndrome
* PAX3
* Waardenburg syndrome 1&3
* PAX4
* MODY 9
* PAX6
* Gillespie syndrome
* Coloboma of optic nerve
* PAX8
* Congenital hypothyroidism 2
* PAX9
* STHAG3
3.3
* FOXC1
* Axenfeld syndrome 3
* Iridogoniodysgenesis, dominant type
* FOXC2
* Lymphedema–distichiasis syndrome
* FOXE1
* Bamforth–Lazarus syndrome
* FOXE3
* Anterior segment mesenchymal dysgenesis
* FOXF1
* ACD/MPV
* FOXI1
* Enlarged vestibular aqueduct
* FOXL2
* Premature ovarian failure 3
* FOXP3
* IPEX
3.5
* IRF6
* Van der Woude syndrome
* Popliteal pterygium syndrome
(4) β-Scaffold factors
with minor groove contacts
4.2
* Hyperimmunoglobulin E syndrome
4.3
* Holt–Oram syndrome
* Li–Fraumeni syndrome
* Ulnar–mammary syndrome
4.7
* Campomelic dysplasia
* MODY 3
* MODY 5
* SF1
* SRY XY gonadal dysgenesis
* Premature ovarian failure 7
* SOX10
* Waardenburg syndrome 4c
* Yemenite deaf-blind hypopigmentation syndrome
4.11
* Cleidocranial dysostosis
(0) Other transcription factors
0.6
* Kabuki syndrome
Ungrouped
* TCF4
* Pitt–Hopkins syndrome
* ZFP57
* TNDM1
* TP63
* Rapp–Hodgkin syndrome/Hay–Wells syndrome/Ectrodactyly–ectodermal dysplasia–cleft syndrome 3/Limb–mammary syndrome/OFC8
Transcription coregulators
Coactivator:
* CREBBP
* Rubinstein–Taybi syndrome
Corepressor:
* HR (Atrichia with papular lesions)
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Lymphedema–distichiasis syndrome
|
c0265345
| 8,112 |
wikipedia
|
https://en.wikipedia.org/wiki/Lymphedema%E2%80%93distichiasis_syndrome
| 2021-01-18T18:46:49 |
{"gard": ["333"], "mesh": ["C537710"], "umls": ["C0265345"], "orphanet": ["33001"], "wikidata": ["Q3508768"]}
|
Ground itch refers to the inflammatory reaction resulting from certain helminthic invasions into the skin.[1]
## Contents
* 1 Presentation
* 2 Cause
* 3 See also
* 4 References
## Presentation[edit]
Effects due to Penetration by larvae [2]
* Maculopapular rash
* Localized erythema
* Intense itching ( usually between the toes )
## Cause[edit]
The responsible agents include:[citation needed]
* Threadworms
* Strongyloides stercoralis
* Hookworms
* Ancylostoma duodenale
* Necator americanus
* Ancylostoma braziliense
## See also[edit]
* Cutaneous larva migrans
* Hookworm disease
## References[edit]
1. ^ Principles of Pediatric Dermatology - Chapter14 : SKIN MANIFESTATIONS OF MEDICAL HELMINTHES
2. ^ Farrar, Jeremy; Hotez, Peter J.; Junghanss, Thomas; Kang, Gagandeep; Lalloo, David; White, Nicholas J. (2013-10-26). Manson's tropical diseases. Farrar, Jeremy,, Manson, Patrick, Sir, 1844-1922. (23rd ed.). Philadelphia, Pennsylvania. ISBN 9780702053061. OCLC 862232541.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Ground itch
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c0546999
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| 2021-01-18T19:08:32 |
{"mesh": ["D007815"], "wikidata": ["Q5610941"]}
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State of indifference, or the suppression of emotions
For other uses, see Apathy (disambiguation).
Mental state in terms of challenge level and skill level, according to Csikszentmihalyi's flow model.[1] (Click on a fragment of the image to go to the appropriate article)
Part of a series on
Emotions
* Acceptance
* Affection
* Amusement
* Anger
* Angst
* Anguish
* Annoyance
* Anticipation
* Anxiety
* Apathy
* Arousal
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* Boredom
* Confidence
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* v
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* e
Apathy is a lack of feeling, emotion, interest, or concern about something. It is a state of indifference, or the suppression of emotions such as concern, excitement, motivation, or passion. An apathetic individual has an absence of interest in or concern about emotional, social, spiritual, philosophical, virtual, or physical life and the world.
The apathetic may lack a sense of purpose, worth, or meaning in their life. They may also exhibit insensibility or sluggishness. In positive psychology, apathy is described as a result of the individuals' feeling they do not possess the level of skill required to confront a challenge (i.e. "flow"). It may also be a result of perceiving no challenge at all (e.g. the challenge is irrelevant to them, or conversely, they have learned helplessness). Apathy is something that all people face in some capacity and is a natural response to disappointment, dejection, and stress. As a response, apathy is a way to forget about these negative feelings.[citation needed] This type of common apathy is usually felt only in the short term, but sometimes it becomes a long-term or even lifelong state, often leading to deeper social and psychological issues.
Apathy should be distinguished from reduced affect display, which refers to reduced emotional expression but not necessarily reduced emotion.
Pathological apathy, characterised by extreme forms of apathy, is now known to occur in many different brain disorders,[2] including neurodegenerative conditions often associated with dementia such as Alzheimer's disease,[3] and psychiatric disorders such as schizophrenia.[4] Although many patients with pathological apathy also suffer from depression, several studies have shown that the two syndromes are dissociable: apathy can occur independently of depression and vice versa.[2]
## Contents
* 1 Etymology
* 2 History and other views
* 2.1 Technology
* 2.2 Social origin
* 2.3 In the school system
* 2.4 Bystander
* 2.5 Communication
* 3 Measurement of Apathy
* 3.1 Apathy Evaluation Scale
* 3.2 Apathy Motivation Index
* 3.3 Dimensional Apathy Scale
* 4 Medical aspects | Pathological apathy
* 4.1 Depression
* 4.2 Alzheimer's disease
* 4.3 Anxiety
* 4.4 Other
* 5 See also
* 6 Notes
* 7 References
* 8 External links
## Etymology[edit]
Although the word apathy was first used in 1594[5] and is derived from the Greek ἀπάθεια (apatheia), from ἀπάθης (apathēs, "without feeling" from a- ("without, not") and pathos ("emotion")),[6] it is important not to confuse the two terms. Also meaning "absence of passion," "apathy" or "insensibility" in Greek, the term apatheia was used by the Stoics to signify a (desirable) state of indifference towards events and things which lie outside one's control (that is, according to their philosophy, all things exterior, one being only responsible for one's own representations and judgments).[7] In contrast to apathy, apatheia is considered a virtue, especially in Orthodox monasticism.[citation needed] In the Philokalia the word dispassion is used for apatheia, so as not to confuse it with apathy.[citation needed]
## History and other views[edit]
Christians have historically condemned apathy as a deficiency of love and devotion to God and his works.[8] This interpretation of apathy is also referred to as Sloth and is listed among the Seven Deadly Sins. Clemens Alexandrinus used the term to draw to Christianity philosophers who aspired after virtue.
The modern concept of apathy became more well known after World War I, when it was one of the various forms of "shell shock". Soldiers who lived in the trenches amidst the bombing and machine gun fire, and who saw the battlefields strewn with dead and maimed comrades, developed a sense of disconnected numbness and indifference to normal social interaction when they returned from combat.
In 1950, US novelist John Dos Passos wrote: "Apathy is one of the characteristic responses of any living organism when it is subjected to stimuli too intense or too complicated to cope with. The cure for apathy is comprehension."
### Technology[edit]
Apathy is a normal way for humans to cope with stress. Being able to "shrug off" disappointments is considered an important step in moving people forward and driving them to try other activities and achieve new goals. Coping seems to be one of the most important aspects of getting over a tragedy and an apathetic reaction may be expected. With the addition of the handheld device and the screen between people, apathy has also become a common occurrence on the net as users observe others being bullied, slandered, threatened or sent disturbing images. The bystander effect grows to an apathetic level as people lose interest in caring for others who are not in their "circle" and may even participate in their harassment.
### Social origin[edit]
There may be other factors contributing to a person's apathy. Activist David Meslin argues that people often care, and that apathy is often the result of social systems actively obstructing engagement and involvement. He describes various obstacles that prevent people from knowing how or why they might get involved in something. Meslin focuses on design choices that unintentionally or intentionally exclude people. These include: capitalistic media systems that have no provisions for ideas that are not immediately (monetarily) profitable, government and political media (e.g. notices) that make it difficult for potentially interested individuals to find relevant information, and media portrayals of heroes as "chosen" by outside forces rather than self-motivated. He moves that we redefine social apathy to think of it, not as a population that is stupid or lazy, but as a result of poorly designed systems that fail to invite others to participate.[9][10]
Apathy has been socially viewed as worse than things such as hate or anger. Not caring whatsoever, in the eyes of some, is even worse than having distaste for something. Author Leo Buscaglia is quoted as saying "I have a very strong feeling that the opposite of love is not hate-it's apathy. It's not giving a damn." Helen Keller claimed that apathy is the "worst of them all" when it comes to the various evils of the world. French social commentator and political thinker Charles de Montesquieu stated that "the tyranny of a prince in an oligarchy is not so dangerous to the public welfare as the apathy of a citizen in the democracy."[11] As can be seen by these quotes and various others, the social implications of apathy are great. Many people believe that not caring at all can be worse for society than individuals who are overpowering or hateful.
### In the school system[edit]
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Apathy in students, especially those in high school, is a growing problem .[citation needed] Apathy in schools is most easily recognized by students being unmotivated or, quite commonly, being motivated by outside factors. For example, when asked about their motivation for doing well in school, fifty percent of students cited outside sources such as "college acceptance" or "good grades". On the contrary, only fourteen percent cited "gaining an understanding of content knowledge or learning subject material" as their motivation to do well in school. As a result of these outside sources, and not a genuine desire for knowledge, students often do the minimum amount of work necessary to get by in their classes.[citation needed] This then leads to average grades and test grades but no real grasping of knowledge.[citation needed] Many students cited that "assignments/content was irrelevant or meaningless" and that this was the cause of their apathetic attitudes toward their schooling. These apathetic attitudes lead to teacher and parent frustration.[12] Other causes of apathy in students include situations within their home life, media influences, peer influences, and school struggles and failures. Some of the signs for apathetic students include declining grades, skipping classes, routine illness, and behavioral changes both in school and at home.
### Bystander[edit]
Also known as the bystander effect, bystander apathy occurs when, during an emergency, those standing by do nothing to help but instead stand by and watch. Sometimes this can be caused by one bystander observing other bystanders and imitating their behavior. If other people are not acting in a way that makes the situation seem like an emergency that needs attention, often other bystanders will act in the same way.[13] The diffusion to responsibility can also be to blame for bystander apathy. The more people that are around in emergency situations, the more likely individuals are to think that someone else will help so they do not need to. This theory was popularized by social psychologists in response to the 1964 Kitty Genovese murder. The murder took place in New York and the victim, Genovese, was stabbed to death as bystanders reportedly stood by and did nothing to stop the situation or even call the police.[14] Latane and Darley are the two psychologists who did research on this theory. They performed different experiments that placed people into situations where they had the opportunity to intervene or do nothing. The individuals in the experiment were either by themselves, with a stranger(s), with a friend, or with a confederate. The experiments ultimately led them to the conclusion that there are many social and situational factors that are behind whether a person will react in an emergency situation or simply remain apathetic to what is occurring.
### Communication[edit]
Apathy is one psychological barrier to communication. An apathetic listener creates a communication barrier by not caring or paying attention to what they are being told. An apathetic speaker, on the other hand, tends to not relate information well and, in their lack of interest, may leave out key pieces of information that need to be communicated. Within groups, an apathetic communicator can be detrimental. Their lack of interest or passion can inhibit the other group members in what they are trying to accomplish. Within interpersonal communication, an apathetic listener can make the other feel that they are not cared for or about. Overall, apathy is a dangerous barrier to successful communication. Apathetic speakers and listeners are individuals that have no care for what they are trying to communicate, or what is being communicated to them.
## Measurement of Apathy[edit]
Several different questionnaires and clinical interview instruments have been used to measure pathological apathy or, more recently, apathy in healthy people.
### Apathy Evaluation Scale[edit]
Developed by Robert Marin in 1991, the Apathy Evaluation Scale (AES) was the first method developed to measure apathy in clinical populations. Centered around evaluation, the scale can either be self-informed or other-informed. The three versions of the test include self, informant such as a family member, and clinician. The scale is based around questionnaires that ask about topics including interest, motivation, socialization, and how the individual spends their time. The individual or informant answers on a scale of "not at all", "slightly", "somewhat" or "a lot". Each item on the evaluation is created with positive or negative syntax and deals with cognition, behavior, and emotion. Each item is then scored and, based on the score, the individual's level of apathy can be evaluated.[15]
### Apathy Motivation Index[edit]
The Apathy Motivation Index (AMI) was developed to measure different dimensions of apathy in healthy people. Factor analysis identified three distinct axes of apathy: behavioural, social and emotional.[16] The AMI has since been used to examine apathy in patients with Parkinson's disease who, overall, showed evidence of behavioural and social apathy, but not emotional apathy.[17]
### Dimensional Apathy Scale[edit]
The Dimensional Apathy Scale (DAS) is a multidimensional apathy instrument for measuring subtypes of apathy in different clinical populations and healthy adults. It was developed using factor analysis, quantifying Executive apathy (lack of motivation for planning, organising and attention), Emotional apathy (emotional indifference, neutrality, flatness or blunting) and Initiation apathy (lack of motivation for self-generation of thought/action). There is a self-rated version of the DAS[18] and an informant/carer-rated version of the DAS.[19] Further a clinical brief DAS has also been developed.[20] It has been validated for use in motor neurone disease, dementia and Parkinson's disease, showing to differentiate profiles of apathy subtypes between these conditions[21]
## Medical aspects | Pathological apathy[edit]
### Depression[edit]
Main article: Major depressive disorder
Mental health journalist and author John McManamy argues that although psychiatrists do not explicitly deal with the condition of apathy, it is a psychological problem for some depressed people, in which they get a sense that "nothing matters", the "lack of will to go on and the inability to care about the consequences".[22] He describes depressed people who "...cannot seem to make [themselves] do anything", who "can't complete anything", and who do not "feel any excitement about seeing loved ones".[22] He acknowledges that the Diagnostic and Statistical Manual of Mental Disorders does not discuss apathy.
In a Journal of Neuropsychiatry and Clinical Neurosciences article from 1991, Robert Marin, MD, claimed that pathological apathy occurs due to brain damage or neuropsychiatric illnesses such as Alzheimer's, Parkinson's, or Huntington's disease, stroke. Marin argues that apathy is a syndrome associated with many different brain disorders.[22] This has now been shown to be the case across a range of neurological and psychiatric conditions.[2]
A review article by Robert van Reekum, MD, et al. from the University of Toronto in the Journal of Neuropsychiatry (2005) claimed that an obvious relationship between depression and apathy exists in some populations.[23] However, although many patients with depression suffer from apathy, several studies have shown that apathy can occur independently of depression, and vice versa.[2]
Apathy can be associated with depression, a manifestation of negative disorders in schizophrenia, or a symptom of various somatic and neurological disorders.[24][2]
### Alzheimer's disease[edit]
Depending upon how it has been measured, apathy affects 19–88% percent of individuals with Alzheimer's disease (mean prevalence of 49% across different studies).[3] It is a neuropsychiatric symptom associated with functional impairment. Brain imaging studies have demonstrated changes in the anterior cingulate cortex, orbitofrontal cortex, dorsolateral prefrontal cortex and ventral striatum in Alzheimer's patients with apathy.[25] Cholinesterase inhibitors, used as the first line of treatment for the cognitive symptoms associated with dementia, have also shown some modest benefit for behavior disturbances such as apathy.[26] The effects of donepezil, galantamine and rivastigmine have all been assessed but, overall, the findings have been inconsistent, and it is estimated that apathy in ~60% of Alzheimer's patients does not respond to treatment with these drugs.[3] Methylphenidate, a dopamine and noradrenaline reuptake blocker, has received increasing interest for the treatment of apathy. Management of apathetic symptoms using methylphenidate has shown promise in randomized placebo controlled trials of Alzheimer's patients.[27][28][29] A phase III multi-centered randomized placebo-controlled trial of methylphenidate for the treatment of apathy is currently underway and planned for completion in August 2020.[30]
### Anxiety[edit]
While apathy and anxiety may appear to be separate, and different, states of being, there are many ways that severe anxiety can cause apathy. First, the emotional fatigue that so often accompanies severe anxiety leads to one's emotions being worn out, thus leading to apathy. Second, the low serotonin levels associated with anxiety often lead to less passion and interest in the activities in one's life which can be seen as apathy. Third, negative thinking and distractions associated with anxiety can ultimately lead to a decrease in one's overall happiness which can then lead to an apathetic outlook about one's life. Finally, the difficulty enjoying activities that individuals with anxiety often face can lead to them doing these activities much less often and can give them a sense of apathy about their lives. Even behavioral apathy may be found in individuals with anxiety in the form of them not wanting to make efforts to treat their anxiety.[31]
### Other[edit]
Often, apathy is felt after witnessing horrific acts, such as the killing or maiming of people during a war, e.g. posttraumatic stress disorder. It is also known to be a distinct psychiatric syndrome[citation needed] that is associated with many conditions, some of which are: CADASIL syndrome, depression, Alzheimer's disease, Chagas disease, Creutzfeldt–Jakob disease, dementia (and dementias such as Alzheimer's disease, vascular dementia, and frontotemporal dementia), Korsakoff's syndrome, excessive vitamin D, hypothyroidism, hyperthyroidism, general fatigue, Huntington's disease, Pick's disease, progressive supranuclear palsy (PSP), brain damage, schizophrenia, schizoid personality disorder, bipolar disorder,[citation needed] autism spectrum disorders, ADHD, and others. Some medications and the heavy use of drugs such as opiates or GABA-ergic drugs may bring apathy as a side effect.[citation needed]
## See also[edit]
* Callous and unemotional traits
* Compassion fatigue
* Detachment (philosophy)
* Reduced affect display
## Notes[edit]
1. ^ Csikszentmihalyi, M., Finding Flow, 1997, p. 31.
2. ^ a b c d e Husain, Masud; Roiser, Jonathan P. (26 June 2018). "Neuroscience of apathy and anhedonia: a transdiagnostic approach". Nature Reviews Neuroscience. 19 (8): 470–484. doi:10.1038/s41583-018-0029-9. PMID 29946157. S2CID 49428707.
3. ^ a b c Nobis, Lisa; Husain, Masud (2018). "Apathy in Alzheimer's disease". Current Opinion in Behavioral Sciences. 22: 7–13. doi:10.1016/j.cobeha.2017.12.007. PMC 6095925. PMID 30123816.
4. ^ Bortolon, C.; Macgregor, A.; Capdevielle, D.; Raffard, S. (2018). "Apathy in schizophrenia: A review of neuropsychological and neuroanatomical studies". Neuropsychologia. 118 (Pt B): 22–33. doi:10.1016/j.neuropsychologia.2017.09.033. PMID 28966139. S2CID 13411386.
5. ^ "Apathy - Definition and More from the Free Merriam-Webster Dictionary". Merriam-webster.com. Retrieved 25 February 2014.
6. ^ "Henry George Liddell, Robert Scott, A Greek-English Lexicon, ἀπάθ-εια". Perseus.tufts.edu. Retrieved 25 February 2014.
7. ^ William Fleming (1857). The vocabulary of philosophy, mental, moral, and metaphysical. p.&34. Reprinted by Kessinger Publishing as paperback (2006; ISBN 978-1-4286-3324-7) and in hardcover (2007; ISBN 978-0-548-12371-3).
8. ^ "Greek Lexicon :: G543 (KJV)". V3.blueletterbible.org. Archived from the original on 2 October 2017. Retrieved 25 February 2014.
9. ^ "Dave Meslin: The antidote to apathy | Video on". Ted.com. Retrieved 25 February 2014.
10. ^ "Dave Meslin | Profile on". Ted.com. 17 July 2010. Retrieved 25 February 2014.
11. ^ "12 Famous Quotes About Apathy". psysci.co. 30 April 2015. Archived from the original on 27 May 2015. Retrieved 30 April 2015.
12. ^ "Finding the Root Cause of Student Apathy". Pan.intrasun.tcnj.edu. Archived from the original on 24 March 2013. Retrieved 25 February 2014.
13. ^ "Latane and Darley: Bystander Apathy". Faculty.babson.edu. Retrieved 25 February 2014.
14. ^ "Bystander Effect". Psychology Today. Archived from the original on 4 November 2013. Retrieved 25 February 2014.
15. ^ "Apathy Evaluation Scale (Self rated)" (PDF). Dementia-assessment.com.au. Archived from the original (PDF) on 26 January 2014. Retrieved 25 February 2014.
16. ^ Ang, Y.S.; Lockwood, P.; Apps, M.A.; Muhammed, K.; Husain, M. (2017). "Distinct Subtypes of Apathy Revealed by the Apathy Motivation Index". PLOS ONE. 12 (1): e0169938. Bibcode:2017PLoSO..1269938A. doi:10.1371/journal.pone.0169938. PMC 5226790. PMID 28076387.
17. ^ Ang, Y.S.; Lockwood, P.L.; Kienast, A.; Plant, O.; Drew, D.; Slavkova, E.; Tamm, M.; Husain, M. (2018). "Differential impact of behavioral, social, and emotional apathy on Parkinson's disease". Annals of Clinical and Translational Neurology. 5 (10): 1286–1291. doi:10.1002/acn3.626. PMC 6186939. PMID 30349863.
18. ^ Radakovic, R.; Abrahams, S. (2014). "Developing a new apathy measurement scale: DAS" (PDF). Psychiatry Research. 219 (3): 658–63. doi:10.1016/j.psychres.2014.06.010. PMID 24972546. S2CID 16313833.
19. ^ Radakovic, R.; Stephenson, L.; Colville, S.; Swingler, R.; Chandran, S.; Abrahams, S. (2016). "Multidimensional apathy in ALS: validation of the Dimensional Apathy Scale" (PDF). Journal of Neurology, Neurosurgery & Psychiatry. 87 (6): 663–9. doi:10.1136/jnnp-2015-310772. PMID 26203157. S2CID 15540782.
20. ^ Radakovic, R.; McGrory, S.; Chandran, S.; Swingler, R.; Pal, S.; Stephenson, L.; Colville, S.; Newton, J.; Starr, J.M.; Abrahams, S. (2020). "The brief Dimensional Apathy Scale: A short clinical assessment of apathy" (PDF). The Clinical Neuropsychologist. 34 (2): 423–435. doi:10.1080/13854046.2019.1621382. PMID 26203157. S2CID 173994534.
21. ^ Radakovic, R.; Abrahams, S. (2018). "Multidimensional apathy: evidence from neurodegenerative disease" (PDF). Current Opinion in Behavioral Sciences. 22: 42–49. doi:10.1016/j.cobeha.2017.12.022. S2CID 53173573.
22. ^ a b c John McManamy. "Apathy Matters - Apathy and Depression: Psychiatry may not care about apathy, but that doesn't mean you shouldn't Archived 20 August 2014 at the Wayback Machine".[self-published source?]
23. ^ van Reekum, Robert; Stuss, Donald T.; Ostrander, Laurie (February 2005). "Apathy: Why Care?". The Journal of Neuropsychiatry and Clinical Neurosciences. 17 (1): 7–19. doi:10.1176/jnp.17.1.7. PMID 15746478.
24. ^ Andersson, S.; Krogstad, J. M.; Finset, A. (1 March 1999). "Apathy and depressed mood in acquired brain damage: relationship to lesion localization and psychophysiological reactivity". Psychological Medicine. 29 (2): 447–456. doi:10.1017/s0033291798008046. PMID 10218936.
25. ^ Le Heron, Campbell; Apps, Matthew; Husain, Masud (2018). "The anatomy of apathy: A neurocognitive framework for amotivated behaviour". Neuropsychologia. 118 (Pt B): 54–67. doi:10.1016/j.neuropsychologia.2017.07.003. PMC 6200857. PMID 28689673.
26. ^ Malloy, Paul F. (2 November 2005). "Apathy and Its Treatment in Alzheimer's Disease and Other Dementias". Psychiatric Times.
27. ^ Herrmann, Nathan; Rothenburg, Lana S.; Black, Sandra E.; Ryan, Michelle; Liu, Barbara A.; Busto, Usoa E.; Lanctôt, Krista L. (June 2008). "Methylphenidate for the Treatment of Apathy in Alzheimer Disease". Journal of Clinical Psychopharmacology. 28 (3): 296–301. doi:10.1097/JCP.0b013e318172b479. PMID 18480686. S2CID 30971352.
28. ^ Rosenberg, Paul B.; Lanctôt, Krista L.; Drye, Lea T.; Herrmann, Nathan; Scherer, Roberta W.; Bachman, David L.; Mintzer, Jacobo E.; ADMET, Investigators (15 August 2013). "Safety and Efficacy of Methylphenidate for Apathy in Alzheimer's Disease". The Journal of Clinical Psychiatry. 74 (8): 810–816. doi:10.4088/JCP.12m08099. PMC 3902018. PMID 24021498.
29. ^ Lanctôt, Krista L.; Chau, Sarah A.; Herrmann, Nathan; Drye, Lea T.; Rosenberg, Paul B.; Scherer, Roberta W.; Black, Sandra E.; Vaidya, Vijay; Bachman, David L.; Mintzer, Jacobo E. (29 October 2013). "Effect of methylphenidate on attention in apathetic AD patients in a randomized, placebo-controlled trial". International Psychogeriatrics. 26 (2): 239–246. doi:10.1017/S1041610213001762. PMC 3927455. PMID 24169147.
30. ^ Clinical trial number NCT02346201 for "Apathy in Dementia Methylphenidate Trial 2 (ADMET2)" at ClinicalTrials.gov
31. ^ "Apathy: Anxiety's Unusual Symptom". Calm Clinic. Retrieved 25 February 2014.
## References[edit]
* This article incorporates text from a publication now in the public domain: Chambers, Ephraim, ed. (1728). Cyclopædia, or an Universal Dictionary of Arts and Sciences (1st ed.). James and John Knapton, et al. Missing or empty `|title=` (help)
## External links[edit]
Wikiquote has quotations related to: Apathy
* The Roots of Apathy – Essay By David O. Solmitz
* Apathy – McMan's Depression and Bipolar Web, by John McManamy
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* exhaustion
* expression
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* and bullying
* intimacy
* isolation
* lability
* labor
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* literacy
* prosody
* reasoning
* responsivity
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* Emotionality
* bounded
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* and culture
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* Gender and emotional expression
* Group affective tone
* Interactions between the emotional and executive brain systems
* Meta-emotion
* Pathognomy
* Pathos
* Social emotional development
* Stoic passions
* Theory
* affect
* appraisal
* discrete emotion
* somatic marker
* constructed emotion
* v
* t
* e
Narcissism
Types
* Collective
* Egomania
* Flying monkeys
* Healthy
* Malignant
* Narcissistic personality disorder
* Spiritual
* Workplace
Characteristics
* Betrayal
* Boasting
* Egocentrism
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* Fantasy
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Cultural phenomena
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* Selfie
Related articles
* Codependency
* Counterdependency
* Dark triad
* Ego ideal
* "Egomania" (film)
* Egotheism
* Empire-building
* God complex
* History of narcissism
* Messiah complex
* Micromanagement
* Narcissism of small differences
* Narcissistic leadership
* Narcissistic parent
* Narcissistic Personality Inventory
* Narcissus (mythology)
* On Narcissism
* Sam Vaknin
* Self-love
* Self-serving bias
* Spoiled child
* The Culture of Narcissism
* Workplace bullying
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Apathy
|
c0085632
| 8,114 |
wikipedia
|
https://en.wikipedia.org/wiki/Apathy
| 2021-01-18T19:07:54 |
{"mesh": ["D057565"], "umls": ["C0085632"], "wikidata": ["Q309406"]}
|
A number sign (#) is used with this entry because of evidence that dilated cardiomyopathy with woolly hair, palmoplantar keratoderma, and tooth agenesis (DCWHKTA) is caused by heterozygous mutation in the desmoplakin gene (DSP; 125647).
Carvajal syndrome (DCWHK; 605676), which has overlapping features but no abnormalities of dentition, is caused by homozygous mutation in DSP.
Clinical Features
Norgett et al. (2006) reported a father and daughter with palmoplantar keratoderma, woolly hair, and cardiomyopathy. The proband presented at 3 years of age with hyperkeratosis and fissuring of the skin of the palms and soles, which also extended over the Achilles tendon, and she had woolly, unmanageable hair. One month after her birth, her father, who apparently had similar hair and skin, died suddenly from arrhythmogenic right ventricular dysplasia. There were no other affected family members. Examination of the proband at 14 years of age showed psoriasiform hyperkeratosis of the knees, elbows, and shins, with prominence around hair follicles. She had striate keratoderma of the palms and focal keratoderma of the soles, which spread over the Achilles tendon. Her hair was kinky and woolly, with short sparse hairs in the frontal scalp. She also had absent molars and premolar teeth but normal nails and normal hearing. Echocardiography (ECG) suggested biventricular cardiomyopathy, and 24-hour electrocardiography showed nonsustained ventricular tachycardia which, together with the history of sudden death in her father, prompted implantation of a cardiac defibrillator. Repeat echocardiograms showed progression of left ventricular dilation with severe global impairment of systolic function, and she died at age 18 years due to persistent dysrhythmia despite activation of the defibrillator.
Chalabreysse et al. (2011) described a father and 2 sons with palmoplantar keratoderma, woolly hair, tooth agenesis ranging from 1 missing tooth to oligodontia, and mild to severe dilated cardiomyopathy. The mother and another son and daughter were unaffected, as were the parents and sibship of the father. The proband had episodes of loss of consciousness that had begun in his teens as well as electrocardiographic abnormalities, including incomplete right bundle branch block and nonsustained ventricular tachycardia; he required heart transplantation in his 20s due to severe cardiomyopathy. He also had marked oligodontia, with only 4 permanent molars and several persisting primary teeth. His older brother and father had milder dilated cardiomyopathy and fewer missing teeth. The proband's explanted heart showed biventricular enlargement with no hypertrophy; microscopic examination revealed fatty and fibrofatty replacement in the anterior and posterior walls of the right ventricle, most severe in the epicardial layer, as well as in the interventricular septum. The left ventricle had no fatty replacement, but showed areas of mutilating fibrosis.
Boule et al. (2012) studied a father and son with dilated cardiomyopathy who also exhibited woolly hair, palmoplantar keratoderma, and tooth agenesis. The 29-year-old father had been diagnosed with dilated cardiomyopathy and left ventricular dysfunction at 12 years of age after the incidental finding of an enlarged heart on chest x-ray. Woolly hair, palmoplantar keratoderma, leukonychia, and absence of third molars (agenesis of 4 teeth) were noted. The patient had no history of syncope or palpitations; electrocardiogram showed QRS prolongation and depolarization abnormalities. ECG showed biventricular dilation and hypokinesia, with apical aneurysm and excessive trabeculations of the right ventricle. Holter electrocardiogram registered more than 500 premature ventricular beats per day. A diagnosis of arrhythmogenic right ventricular cardiomyopathy was made, and a cardioverter-defibrillator was implanted. His 10-year-old son had woolly hair, palmoplantar keratoderma, brittle nails without leukonychia, and agenesis of 10 teeth. At 5 years of age his echocardiogram was normal, but at age 10 years, after an episode of chest pain with significant elevation of cardiac troponin, electrocardiography showed multiple isolated premature ventricular beats with epsilon wave in V1, and ECG showed dilation of the right ventricular infundibulum.
### Clinical Variability
Boyden et al. (2016) described 3 unrelated children, 1 girl and 2 boys, who had erythrokeratodermia at birth or shortly thereafter and also exhibited scant woolly hair, sparse or absent eyebrows and eyelashes, enamel defects with multiple caries of primary teeth and variable tooth agenesis of secondary dentition, palmoplantar keratoderma, onychodystrophy of all nails, and moderate to severe dilated cardiomyopathy. One of the boys died at age 3 years from heart failure, whereas the remaining 2 children had relatively preserved ventricular function. All 3 exhibited marked erythema of the skin, associated with ichthyotic fine white scaling and pruritus that was unresponsive to oral or systemic therapy. Skin histopathology showed psoriasiform hyperplasia and a reduced granular cell layer, as well as compact orthohyperkeratosis in 2 patients and parakeratosis in 1 patient. Serum IgE and eosinophil counts were normal. Boyden et al. (2016) designated the phenotype 'erythrokeratodermia-cardiomyopathy (EKC)' syndrome.
Molecular Genetics
In a DNA sample from a girl who died at age 18 years with dilated cardiomyopathy, palmoplantar keratoderma, woolly hair, and tooth agenesis, Norgett et al. (2006) analyzed the candidate gene desmoplakin (DSP; 125647) and identified a heterozygous 30-bp insertion (125647.0015). The mutation was not present in her unaffected mother or 160 control chromosomes; no DNA was available from her deceased, similarly affected father.
Chalabreysse et al. (2011) screened the DSP and plakoglobin (JUP; 173325) genes in the proband of a family with DCWHKTA and identified a heterozygous missense mutation in the DSP gene (S597L; 125647.0016); no mutations were found in the JUP gene. The proband's affected father was also heterozygous for the DSP missense mutation, but his affected older brother declined genetic testing. The mutation was not found in the unaffected mother, paternal grandparents, or 2 unaffected sibs.
In a father and son with DCWHKTA, Boule et al. (2012) analyzed the desmosomal genes DSP, JUP, PKP2 (602861), DSG2 (125671), and DSC2 (125645), and identified heterozygosity for a missense mutation in the DSP gene (T564I; 125647.0017). No mutations were detected in the other genes, and the DSP mutation was not found in 600 control chromosomes.
Boyden et al. (2016) analyzed exome data from a cohort of 496 kindreds with disorders of keratinization and identified 3 unrelated children with dilated cardiomyopathy, woolly hair, erythrokeratoderma, and tooth agenesis who were heterozygous for de novo tightly clustered missense mutations in the DSP gene: Q616P (125647.0021), H618P (125647.0022), and L622P (125647.0023).
INHERITANCE \- Autosomal dominant HEAD & NECK Teeth \- Tooth agenesis, variable \- Poorly mineralized enamel \- Recurrent caries of primary teeth \- Gingival recession \- Gingival erythema CARDIOVASCULAR Heart \- Cardiomyopathy, dilated \- Biventricular enlargement \- Biventricular decreased contractility \- Fatty and fibrofatty replacement of cardiomyocytes in right ventricle \- Fibrosis of left ventricle \- Apical aneurysm, right ventricle (rare) \- Excessive trabeculation in right ventricle (rare) \- Syncope (in some patients) \- Premature ventricular beats \- Ventricular tachycardia, nonsustained \- Incomplete right bundle branch block (in some patients) SKIN, NAILS, & HAIR Skin \- Palmoplantar keratoderma \- Striated keratoderma of palms (in some patients) \- Focal keratoderma of soles (in some patients) \- Hyperkeratosis \- Fissuring \- Erythrokeratodermia \- Ichthyosis (in some patients) \- Pruritis (in some patients) Skin Histology \- Psoriasiform hyperplasia \- Reduced granular cell layer \- compact orthohyperkeratosis \- Parakeratosis Nails \- Onychodystrophy (in some patients) \- Leukonychia (rare) \- Brittle nails (rare) Hair \- Woolly hair \- Diffuse hypotrichosis (in some patients) MISCELLANEOUS \- Risk of sudden death due to cardiac arrhythmias \- Tooth agenesis ranges from 1 missing tooth to marked oligodontia MOLECULAR BASIS \- Caused by mutation in the desmoplakin gene (DSP, 125647.0015 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
CARDIOMYOPATHY, DILATED, WITH WOOLLY HAIR, KERATODERMA, AND TOOTH AGENESIS
|
c1854063
| 8,115 |
omim
|
https://www.omim.org/entry/615821
| 2019-09-22T15:50:52 |
{"mesh": ["C535581"], "omim": ["615821"], "orphanet": ["65282"]}
|
For the orchid genus, see Microtis (plant). For the gastropod genus, see Microtis (gastropod). For the vole genus, see Microtus. For the butterfly genus, see Microtia (butterfly).
Microtia
Unilateral grade III microtia (more often affecting the right ear).
SpecialtyMedical genetics
Microtia is a congenital deformity where the pinna (external ear) is underdeveloped. A completely undeveloped pinna is referred to as anotia. Because microtia and anotia have the same origin, it can be referred to as microtia-anotia.[1] Microtia can be unilateral (one side only) or bilateral (affecting both sides). Microtia occurs in 1 out of about 8,000–10,000 births. In unilateral microtia, the right ear is most commonly affected. It may occur as a complication of taking Accutane (isotretinoin) during pregnancy.[2]
## Contents
* 1 Classification
* 2 Causes and Risk Factors
* 3 Diagnosis
* 4 Treatment
* 4.1 Hearing
* 4.2 External ear
* 4.2.1 Related conditions
* 5 Notable cases
* 6 References
* 7 Further reading
* 8 External links
## Classification[edit]
According to the Altman-classification, there are four grades of microtia:[3]
* Grade I: A less than complete development of the external ear with identifiable structures and a small but present external ear canal
* Grade II: A partially developed ear (usually the top portion is underdeveloped) with a closed stenotic external ear canal producing a conductive hearing loss.
* Grade III: Absence of the external ear with a small peanut-like vestige structure and an absence of the external ear canal and ear drum. Grade III microtia is the most common form of microtia.
* Grade IV: Absence of the total ear or anotia.
## Causes and Risk Factors[edit]
The etiology of microtia in children remains uncertain but there are some cases that associate the cause of microtia with genetic defects in multiple or single genes, altitude, and gestational diabetes.[3] Risk factors gathered from studies include infants born underweight, women gravidity and parity, and medication use while pregnant.[3][4][5] Genetic inheritance has not been fully studied but in the few studies available, it has shown to occur during the early stages of pregnancy.[3]
## Diagnosis[edit]
At birth, lower grade microtia is difficult to visually diagnose with a physical exam. While higher grade microtia can be visually diagnosed due to noticeable abnormalities.[3] Infants that have noticeable abnormalities are closely monitored by physicians and hearing specialists.[6]
## Treatment[edit]
The goal of medical intervention is to provide the best form and function to the underdeveloped ear.[7]
### Hearing[edit]
Typically, testing is first done to determine the quality of hearing. This can be done as early as in the first two weeks with a BAER test (Brain Stem Auditory Response Test).[8][9] At age 5–6, CT or CAT scans of the middle ear can be done to elucidate its development and clarify which patients are appropriate candidates for surgery to improve hearing. For younger individuals, this is done under sedation.
The hearing loss associated with congenital aural atresia is a conductive hearing loss—hearing loss caused by inefficient conduction of sound to the inner ear. Essentially, children with aural atresia have hearing loss because the sound cannot travel into the (usually) healthy inner ear—there is no ear canal, no eardrum, and the small ear bones (malleus/hammer, incus/anvil, and stapes/stirrup) are underdeveloped. "Usually" is in parentheses because rarely, a child with atresia also has a malformation of the inner ear leading to a sensorineural hearing loss (as many as 19% in one study).[10] Sensorineural hearing loss is caused by a problem in the inner ear, the cochlea. Sensorineural hearing loss is not correctable by surgery, but properly fitted and adjusted hearing amplification (hearing aids) generally provide excellent rehabilitation for this hearing loss. If the hearing loss is severe to profound in both ears, the child may be a candidate for a cochlear implant (beyond the scope of this discussion).
Unilateral sensorineural hearing loss was not generally considered a serious disability by the medical establishment before the nineties; it was thought that the afflicted person was able to adjust to it from birth. In general, there are exceptional advantages to gain from an intervention to enable hearing in the microtic ear, especially in bilateral microtia. Children with untreated unilateral sensorineural hearing loss are more likely to have to repeat a grade in school and/or need supplemental services (e.g., FM system – see below) than their peers.[11][12]
Children with unilateral sensorineural hearing loss often require years of speech therapy in order to learn how to enunciate and understand spoken language. What is truly unclear, and the subject of an ongoing research study, is the effect of unilateral conductive hearing loss (in children with unilateral aural atresia) on scholastic performance. If atresia surgery or some form of amplification is not used, special steps should be taken to ensure that the child is accessing and understanding all of the verbal information presented in school settings. Recommendations for improving a child's hearing in the academic setting include preferential seating in class, an FM system (the teacher wears a microphone, and the sound is transmitted to a speaker at the child's desk or to an ear bud or hearing aid the child wears), a bone-anchored hearing aid (BAHA), or conventional hearing aids. Age for BAHA implantation depends on whether the child is in Europe (18 months) or the US (age 5). Until then it is possible to fit a BAHA on a softband[13][14]
It is important to note that not all children with aural atresia are candidates for atresia repair. Candidacy for atresia surgery is based on the hearing test (audiogram) and CT scan imaging. If a canal is built where one does not exist, minor complications can arise from the body's natural tendency to heal an open wound closed. Repairing aural atresia is a very detailed and complicated surgical procedure which requires an expert in atresia repair.[15] While complications from this surgery can arise, the risk of complications is greatly reduced when using a highly experienced otologist. Atresia patients who opt for surgery will temporarily have the canal packed with gelatin sponge and silicone sheeting to prevent closure. The timing of ear canal reconstruction (canalplasty) depends on the type of external ear (Microtia) repair desired by the patient and family. Two surgical teams in the USA are currently able to reconstruct the canal at the same time as the external ear in a single surgical stage (one stage ear reconstruction).
In cases where a later surgical reconstruction of the external ear of the child might be possible, positioning of the BAHA implant is critical. It may be necessary to position the implant further back than usual to enable successful reconstructive surgery – but not so far as to compromise hearing performance. If the reconstruction is ultimately successful, it is easy to remove the percutaneous BAHA abutment. If the surgery is unsuccessful, the abutment can be replaced and the implant re-activated to restore hearing.
### External ear[edit]
The age when outer ear surgery can be attempted depends upon the technique chosen. The earliest is 7 for Rib Cartilage Grafts. However, some surgeons recommend waiting until a later age, such as 8–10 when the ear is closer to adult size. External ear prostheses have been made for children as young as 5.
For auricular reconstruction, there are several different options:
1. Rib Cartilage Graft Reconstruction: This surgery may be performed by specialists in the technique.[16][17][18][19][20] It involves sculpting the patient's own rib cartilage into the form of an ear. Because the cartilage is the patient's own living tissue, the reconstructed ear continues to grow as the child does. In order to be sure that the rib cage is large enough to provide the necessary donor tissue, some surgeons wait until the patient is 8 years of age;[19][20] however, some surgeons with more experience with this technique may begin the surgery on a child aged six.[17][18][21] The major advantage of this surgery is that the patient's own tissue is used for the reconstruction. This surgery varies from two to four stages depending on the surgeon's preferred method. A novel one stage ear reconstruction technique is performed by a few select surgeons. One team is able to reconstruct the entire external ear and ear canal in one operation.
2. Reconstruct the ear using a polyethylene plastic implant (also called Medpor): This is a 1–2 stage surgery that can start at age 3 and can be done as an outpatient without hospitalization. Using the porous framework, which allows the patient's tissue to grow into the material and the patient's own tissue flap, a new ear is constructed in a single surgery. A small second surgery is performed in 3–6 months if needed for minor adjustments. Medpor was developed by John Reinisch.[22] This surgery should only be performed by experts in the techniques involved.[23] The use of porous polyethylene implants for ear reconstruction was initiated in the 1980s by Alexander Berghaus.[24]
3. Ear Prosthesis: An auricular (ear) prosthesis is custom made by an anaplastologist to mirror the other ear.[25] Prosthetic ears can appear very realistic. They require a few minutes of daily care. They are typically made of silicone, which is colored to match the surrounding skin and can be attached using either adhesive or with titanium screws inserted into the skull to which the prosthetic is attached with a magnetic or bar/clip type system. These screws are the same as the BAHA (bone anchored hearing aid ) screws and can be placed simultaneously. The biggest advantage over any surgery is having a prosthetic ear that allows the affected ear to appear as normal as possible to the natural ear. The biggest disadvantage is the daily care involved and knowing that the prosthesis is not real.
#### Related conditions[edit]
Aural atresia is the underdevelopment of the middle ear and canal and usually occurs in conjunction with microtia. Atresia occurs because patients with microtia may not have an external opening to the ear canal, though. However, the cochlea and other inner ear structures are usually present. The grade of microtia usually correlates to the degree of development of the middle ear.[9] [15] Microtia is usually isolated, but may occur in conjunction with hemifacial microsomia, Goldenhar Syndrome or Treacher-Collins Syndrome.[26] It is also occasionally associated with kidney abnormalities (rarely life-threatening), and jaw problems, and more rarely, heart defects and vertebral deformities.[18]
## Notable cases[edit]
* Paul Stanley, vocalist and rhythm guitarist of Kiss, was born with grade III microtia of his right ear.
## References[edit]
1. ^ Online Mendelian Inheritance in Man (OMIM): Microtia-Anotia - 600674
2. ^ Pretest self assessment and review for the USMLE, pediatrics, 12th edition, question 84, general pediatrics
3. ^ a b c d e Luquetti, Daniela V.; Heike, Carrie L.; Hing, Anne V.; Cunningham, Michael L.; Cox, Timothy C. (January 2012). "Microtia: Epidemiology & Genetics". American Journal of Medical Genetics. Part A. 158A (1): 124–139. doi:10.1002/ajmg.a.34352. ISSN 1552-4825. PMC 3482263. PMID 22106030.
4. ^ Forrester, Mathias B.; Merz, Ruth D. (December 2005). "Descriptive epidemiology of anotia and microtia, Hawaii, 1986-2002". Congenital Anomalies. 45 (4): 119–124. doi:10.1111/j.1741-4520.2005.00080.x. ISSN 0914-3505. PMID 16359491.
5. ^ Zhang, Qing-guo; Zhang, Jiao; Yu, Pei; Shen, Hao (October 2009). "Environmental and genetic factors associated with congenital microtia: a case-control study in Jiangsu, China, 2004 to 2007". Plastic and Reconstructive Surgery. 124 (4): 1157–1164. doi:10.1097/PRS.0b013e3181b454d8. ISSN 1529-4242. PMID 19935299.
6. ^ Bly, Randall A.; Bhrany, Amit D.; Murakami, Craig S.; Sie, Kathleen C.Y. (November 2016). "Microtia Reconstruction". Facial Plastic Surgery Clinics of North America. 24 (4): 577–591. doi:10.1016/j.fsc.2016.06.011. ISSN 1064-7406. PMC 5950715. PMID 27712823.
7. ^ Thomas, Daniel J. (August 2016). "Could 3D bioprinted tissues offer future hope for microtia treatment?". International Journal of Surgery (London, England). 32: 43–44. doi:10.1016/j.ijsu.2016.06.036. ISSN 1743-9159. PMID 27353851.
8. ^ De la Cruz A, Kesser BW (1999). "Management of the Unilateral Atretic Ear". In Pensak M (ed.). Controversies in Otolaryngology–Head and Neck Surgery. New York: Thieme Medical Publishers. pp. 381–385.
9. ^ a b Kountakis SE, Helidonis E, Jahrsdoerfer RA (1995). "Microtia grade as an indicator of middle ear development in aural atresia". Arch Otolaryngol Head Neck Surg. 121 (8): 885–6. doi:10.1001/archotol.1995.01890080053010. PMID 7619415.
10. ^ Vrabec JT, Lin JW (2010). "Inner Ear Anomalies in Congenital Aural Atresia". Otology & Neurotology. 31: 1421. doi:10.1097/mao.0b013e3181f7ab62.
11. ^ Bess FH, Tharpe AM (1986). "Case History Data on Unilaterally Hearing-Impaired Children". Ear and Hearing. 7: 14–19. doi:10.1097/00003446-198602000-00004.
12. ^ Bess FH, Tharpe AM (1988). "Performance and Management of Children with Unilateral Sensorineural Hearing Loss". Cand Audiol Supple. 30: 75–9. PMID 3067327.
13. ^ Nicholson N, Christensen L, Dornhoffer J, Martin P, Smith-Olinde L (2011). "Verification of speech spectrum audibility for pediatric baha softband users with craniofacial anomalies". The Cleft Palate-Craniofacial Journal. 48 (1): 56–65. doi:10.1597/08-178. PMID 20180710.
14. ^ Verhagen CV, Hol MK, Coppens-Schellekens W, Snik AF, Cremers CW (2008). "The Baha Softband. A new treatment for young children with bilateral congenital aural atresia". International Journal of Pediatric Otorhinolaryngology. 72 (10): 1455–9. doi:10.1016/j.ijporl.2008.06.009. PMID 18667244.
15. ^ a b Jahrsdoerfer RA, Kesser BW (1995). "Issues on Aural Atresia for the facial Plastic Surgeon". Facial Plastic Surgery. 11 (4): 274–277. doi:10.1055/s-2008-1064543. PMID 9046615.
16. ^ Tanzer RC (1959). "Total Reconstruction of the External Ear". Plastic & Reconstructive Surgery. 23: 1–15. doi:10.1097/00006534-195901000-00001.
17. ^ a b Brent B (1999). "Technical Advances with Autogenous Rib Cartilage Grafts—A Personal Review of 1,200 Cases". Plastic & Reconstructive Surgery. 104 (2): 319–334. doi:10.1097/00006534-199908000-00001. PMID 10654675.
18. ^ a b c Brent B (1992). "Auricular Repair with Autogenous Rib Cartilage Grafts: Two Decades of Experience with 600 Cases". Plastic & Reconstructive Surgery. 90 (3): 355–374. doi:10.1097/00006534-199209000-00001.
19. ^ a b Firmin F (1992). "Microtie Reconstruction par la Technique de Brent". Annals Chirurgie Plastica Esthetica. 1: 119.
20. ^ a b Nagata S (1994). "Modification of the Stages in Total Reconstruction of the Auricle: Part I. Grafting the Three-Dimensional Costal Cartilage Framework for Lobule-Type Microtia". Plastic & Reconstructive Surgery. 93 (2): 221–30. doi:10.1097/00006534-199402000-00001. PMID 8310014.
21. ^ Brent B (2000). "The Team Approach to Treating the Microtia-Atresia Patient". Otolaryngologic Clinics of North America. 33 (6): 1353–65, viii. doi:10.1016/s0030-6665(05)70286-3. PMID 11449792.
22. ^ "MEDPOR Reconstruction For Mictrotia". Cedars-Sinai Medical Center. Retrieved 19 October 2011.
23. ^ Reinisch JF, Lewin S (2009). "Ear reconstruction using a porous polyethylene framework and temporoparietal fascia flap". Facial Plast Surg. 25 (3): 181–9. doi:10.1055/s-0029-1239448. PMID 19809950.
24. ^ Alexander Berghaus. Implantate für die rekonstruktive Chirurgie der Nase und des Ohres. Sammelwerk=Laryngo-Rhino-Otologie. Vol.86. 2007. Page 67–76. DOI=10.1055/s-2007-966301
25. ^ Tanner PB; Mobley SR. (2006). "External Auricular and Facial Prosthetics: A Collaborative Effort of the Reconstructive Surgeon and Anaplastologist. Auricular Surgery: Aesthetic and Reconstructive". Facial Plast Surg Clin North Am. 14 (2): 137–45, vi–vii. doi:10.1016/j.fsc.2006.01.003. PMID 16750771.
26. ^ Huston Katsanis S, Cutting GR (July 2004). "Treacher Collins Syndrome". GeneReviews. PMID 20301704.
## Further reading[edit]
* Bennun RD, Mulliken JB, Kaban LB, Murray JE (December 1985). "Microtia: a microform of hemifacial microsomia". Plast. Reconstr. Surg. 76 (6): 859–65. doi:10.1097/00006534-198512000-00010. PMID 4070453.
* Thorne, Charles (2013) " Ear Reconstruction: Microtia". Grabb & Smith's Plastic Surgery, 7th ed. Pages 283-294.
## External links[edit]
Classification
D
* ICD-10: Q17.2
* ICD-9-CM: 744.23
* OMIM: 600674
* MeSH: D065817
* DiseasesDB: 29876
External resources
* eMedicine: ped/3003
* Orphanet: 83463
* v
* t
* e
Congenital malformations and deformations of ears
Size
* Macrotia
* Microtia
* Anotia
Position
* Low-set ears
Other
* Accessory auricle
* Mondini dysplasia
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Microtia
|
c0152423
| 8,116 |
wikipedia
|
https://en.wikipedia.org/wiki/Microtia
| 2021-01-18T18:59:49 |
{"mesh": ["D065817"], "umls": ["C0152423"], "icd-9": ["744.23"], "icd-10": ["Q17.2"], "wikidata": ["Q1759560"]}
|
A cosmopolitan fungal infection due to Cryptococcus neoformans.
## Epidemiology
Annual incidence has been estimated at between 1/5,000 and 1/50,000 depending on the geographic region. Immunodeficient patients are the main target.
## Clinical description
Primary pulmonary cryptococcosis is usually asymptomatic, but disseminates throughout the organism, particularly to the central nervous system causing subacute meningoencephalitis. Mucocutaneous infection is frequent.
## Etiology
C. neoformans is an encapsulated yeast that reproduces by budding. It is abundant in the ground, in fruit, milk, and pigeon droppings. Infection is acquired via the respiratory or digestive route, rarely through the skin, and disseminates in the organism by blood or the lymphatic system. Interhuman transmission does not occur.
## Diagnostic methods
Diagnosis is made after detection of encapsulated yeast in cerebrospinal fluid or other affected organs, or in cultures.
## Differential diagnosis
Differential diagnoses include the other species of Cryptococcus.
## Management and treatment
Amphotericin B and newer antifungal drugs (triazoles) sterilize the lesions. The treatment should be continued for as long as the patient is immunodeficient.
## Prognosis
The prognosis is usually good if treatment is well conducted.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Cryptococcosis
|
c0010414
| 8,117 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1546
| 2021-01-23T16:55:53 |
{"gard": ["6218"], "mesh": ["D003453"], "umls": ["C0010414"], "icd-10": ["B45.0", "B45.1", "B45.2", "B45.3", "B45.7", "B45.8", "B45.9"]}
|
Yao syndrome (formerly called NOD2-associated autoinflammatory disease) is a disorder involving episodes of fever and abnormal inflammation affecting many parts of the body, particularly the skin, joints, and gastrointestinal system. Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). In people with Yao syndrome, part of the immune system called the innate immune response is turned on (activated) abnormally, which causes fevers and inflammation-related damage to tissues and organs. Based on this process, Yao syndrome is classified as an autoinflammatory disease. Autoinflammatory diseases are distinct from autoimmune diseases; these two groups of diseases involve abnormalities in different parts of the immune system.
The episodes of fever and inflammation associated with Yao syndrome can last for several days and occur weeks to months apart. During these episodes, most affected individuals develop reddened, inflamed areas on the skin called erythematous patches or plaques. This reddening occurs most commonly on the face, chest, and back but can also affect the arms and legs. Episodes of joint pain and inflammation similar to arthritis are common, particularly in the legs, as is swelling of the ankles and feet. Inflammation also affects the gastrointestinal system, causing attacks of abdominal pain, bloating, and cramping with diarrhea in more than half of affected individuals. Dry eyes and dry mouth (described as "sicca-like" symptoms, which refers to dryness) are reported in about half of people with this disease. Other potential signs and symptoms of Yao syndrome include mouth sores, chest pain, and enlargement of various glands.
Yao syndrome is usually diagnosed in adulthood. It is a long-lasting (chronic) disease, and episodes can recur for many years.
## Frequency
Yao syndrome has an estimated prevalence of 1 in 10,000 to 1 in 100,000 people worldwide. Studies suggest that it is among the most common systemic (affecting the whole body) autoinflammatory diseases in adults. For unknown reasons, Yao syndrome appears to affect women more frequently than men.
## Causes
The causes of Yao syndrome are complex. This condition likely results from a combination of genetic and environmental factors, many of which are unknown.
Certain variations in the NOD2 gene increase the risk of developing Yao syndrome. The NOD2 protein plays several essential roles in the immune system's response to foreign invaders, including inflammatory reactions. Studies suggest that most people with Yao syndrome have at least one variation in the NOD2 gene, and some have two or more. It is unclear what effect these variations have on the amount or function of the NOD2 protein, or how they might contribute to abnormal inflammation in people with Yao syndrome. Researchers suspect that environmental factors such as infections may also play a role in triggering the disease in people with genetic variants that increase their risk.
### Learn more about the gene associated with Yao syndrome
* NOD2
## Inheritance Pattern
Because Yao syndrome appears to be a complex disease without a single genetic cause, it does not have a straightforward pattern of inheritance. A small percentage of affected individuals have a family history of the disease. Many people who have one or more of the NOD2 gene variants associated with Yao syndrome never develop the disease.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Yao syndrome
|
c4310620
| 8,118 |
medlineplus
|
https://medlineplus.gov/genetics/condition/yao-syndrome/
| 2021-01-27T08:25:21 |
{"omim": ["617321"], "synonyms": []}
|
A number sign (#) is used with this entry because of evidence that autosomal recessive spastic ataxia-8 (SPAX8) with hypomyelinating leukodystrophy is caused by homozygous mutation in the NKX6-2 gene (605955) on chromosome 8q21.
Description
Spastic ataxia-8 with hypomyelinating leukodystrophy is an autosomal recessive progressive neurodegenerative disorder characterized by onset of primarily motor dysfunction within the first year of life. Affected individuals initially have hypotonia and later develop ataxia, spasticity, and a pyramidal syndrome with weakness and loss of ambulation. Other features may include dystonia, dysarthria, and abnormal eye movements. Brain imaging shows cerebellar atrophy and hypomyelinating leukodystrophy. One family with cognitive impairment has also been reported (summary by Chelban et al., 2017).
For a discussion of genetic heterogeneity of spastic ataxia, see SPAX1 (108600).
Clinical Features
Chelban et al. (2017) reported 7 patients from 3 unrelated consanguineous families with SPAX8. The patents presented within the first year of life with a progressive neurodegenerative disorder with primarily motor features, including spasticity, ataxia, and abnormal eye movements such as nystagmus, hypometric saccades, and impaired up-gaze. Initial features included hypotonia, which developed into a pyramidal syndrome with weakness and hyperreflexia mainly involving the lower limbs, as well as truncal and limb ataxia, dysarthria, and head titubation. Several patients had cervical and/or limb dystonia. Four patients in the first 2 families were adults ranging in age from 23 to 44 years. One never achieved walking and was wheelchair-bound early in life, and another became wheelchair-bound later in life. Another member of the first family was wheelchair-bound at age 8. Five patients from the first 2 families had normal cognitive development and function, whereas 2 sibs in a consanguineous Saudi Arabian family also had severe global psychomotor delay with cognitive impairment. Brain imaging showed cerebellar atrophy and hypomyelinating leukodystrophy in all patients tested. None had sensory deficits, and nerve conduction velocities performed in 1 family were normal.
Inheritance
The transmission pattern of SPAX8 in the families reported by Chelban et al. (2017) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 7 patients from 3 unrelated families with SPAX8, Chelban et al. (2017) identified homozygous mutations in the NKX6-2 gene (K41X, 605955.0001 and L163V, 605955.0002). The mutations, which were found by exome sequencing, segregated with the disorder in the families. Cells from a patient with the nonsense mutation showed absence of the truncated protein, consistent with a complete loss of function; functional studies and studies of patient cells with the missense mutation were not performed. Using in silico analysis, gene-regulatory networks, and coexpression data in humans, Chelban et al. (2017) concluded that NKX6-2 is involved in the genesis and development of oligodendrocytes.
Animal Model
Southwood et al. (2004) found that Nkx6-2-null mice had deficits in motor coordination and nerve conduction in the central nervous system. These abnormalities were associated with myelination defects at paranodal junctions, particularly in the optic nerve, and aberrant expression of downstream genes involved in cytoskeletal and cell adhesion functions. The findings suggested a role for Nkx6-2 in the regulation of axon-glial interactions at myelin paranodes.
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Head titubation Eyes \- Nystagmus \- Hypometric saccades \- Abnormal eye movements \- Limited eye movements MUSCLE, SOFT TISSUES \- Hypotonia, neonatal NEUROLOGIC Central Nervous System \- Delayed motor development \- Truncal ataxia \- Limb ataxia \- Spasticity \- Pyramidal signs \- Lack of ambulation \- Loss of ambulation \- Dysarthria \- Dystonia \- Cognitive impairment (1 family) \- Cerebellar atrophy \- Hypomyelinating leukodystrophy Peripheral Nervous System \- Hyperreflexia MISCELLANEOUS \- Onset in first year of life \- Progressive disorder \- Most patients become wheelchair-bound \- Three consanguineous families have been reported (last curated July 2017) MOLECULAR BASIS \- Caused by mutation in the homolog of the Drosophila NK6 transcription factor related, locus 2 gene (NKX6-2, 605955.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
SPASTIC ATAXIA 8, AUTOSOMAL RECESSIVE, WITH HYPOMYELINATING LEUKODYSTROPHY
|
c4479653
| 8,119 |
omim
|
https://www.omim.org/entry/617560
| 2019-09-22T15:45:36 |
{"doid": ["0080252"], "omim": ["617560"], "orphanet": ["527497"], "synonyms": ["Autosomal recessive hypomyelinating leukodystrophy-progressive spastic ataxia", "SPAX8"], "genereviews": ["NBK531509"]}
|
Gamma-aminobutyric acid transaminase (GABA-T) deficiency is an extremely rare disorder of GABA metabolism characterized by a severe neonatal-infantile epileptic encephalopathy (manifesting with symptoms such as seizures, hypotonia, hyperreflexia and developmental delay) and growth acceleration.
## Epidemiology
Five patients from three affected families have been reported in the literature to date.
## Clinical description
Onset occurs in the neonatal/infantile period. Manifestations reported include hypotonia, impaired psychomotor development, hyperreflexia, lethargy, seizures, high-pitched cry, accelerated linear growth and developmental delay. The phenotype of GABA-T deficiency is more severe than what is seen in succinic semialdehyde dehydrogenase (SSADH) deficiency (see this term), although some patients have survived infancy but with severe neurodevelopmental impairment including myoclonic seizures and choreoathetosis.
## Etiology
GABA-T deficiency is caused by a mutation in the ABAT gene (16p13.2) encoding mitochondrial 4-aminobutyrate aminotransferase (GABA-T). GABA-T is responsible for catalyzing the conversion of gamma-aminobutyrate to succinate semialdehyde in the GABA metabolic pathway. A mutation in this gene leads to an increased accumulation of GABA in central nervous tissue, leading to encephalopathy.
## Genetic counseling
GABA-T deficiency is inherited in an autosomal recessive manner.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Gamma-aminobutyric acid transaminase deficiency
|
c0342708
| 8,120 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2066
| 2021-01-23T19:04:18 |
{"gard": ["194"], "mesh": ["C535407"], "omim": ["613163"], "umls": ["C0342708"], "icd-10": ["E72.8"], "synonyms": ["GABA transaminase deficiency"]}
|
A severe form of phenylketonuria (PKU) due to phenylalanine hydroxylase deficiency, an inborn error of amino acid metabolism, characterized in untreated patients by severe intellectual deficit and neuropsychiatric complications.
## Epidemiology
Exact prevalence is not known but is estimated to be about 1/15,000 births. Significant geographic variability is reported. Caucasians appear to be affected more than other ethnic groups. Males and females are affected equally.
## Clinical description
Late diagnosed patients present mostly with progressive developmental delay associated with severe signs including stunted growth, microcephaly, seizures, tremors, eczema, vomiting, musty odor, and subsequently behavioral (hyperactivity) and motor disorders. Untreated patients develop profound, permanent intellectual impairment and deterioration of cognitive performance and motor skills. Demyelination and decreased dopamine, norepinephrine, and serotonin production have been found in patients who do not pursue dietary restrictions into adulthood. Complications later on include exaggerated deep tendon reflexes, tremor, and paraplegia or hemiplegia. In treated patients, clinical signs vary based on treatment and diet compliance, and may include psychiatric disorders such as attention deficit-hyperactivity disorder and depression.
## Etiology
Classical PKU is related to a complete or near-complete deficiency of phenylalanine hydroxylase. The disorder is caused by variants in the PAH gene (12q22-q24.2) coding for phenylalanine (Phe) hydroxylase. The resulting deficiency in phenylalanine hydroxylase leads to toxic accumulation of Phe in the blood and brain.
## Diagnostic methods
Classical PKU is usually diagnosed via neonatal screening programs with detection of hyperphenylalaninemia (HPA). Detection is standard in most industrialized countries. PKU is diagnosed at plasma or blood Phe concentrations higher than 120 micromol/L in the untreated state and elevated Phe/Tyr ratio (>2.0). In the absence of early detection through neonatal screening, suspicion is based on clinical signs and symptoms. Diagnosis is confirmed by determination of plasma or blood Phe levels.
## Differential diagnosis
Differential diagnosis includes other forms of HPA such as tetrahydrobiopterin (BH4) deficiency. Neonates with increased Phe may have BH4 deficiency or PKU. An abnormal pattern of pterins in dried blood spots or urine or reduced dihydropteridine reductase activity in dried blood spots indicate BH4 deficiency. A BH4 loading test should be performed to determine whether patients are BH4-responsive or unresponsive.
## Antenatal diagnosis
Prenatal testing can be performed by molecular testing of the PAH gene if the disease-causing variants have been identified in an affected family member.
## Genetic counseling
Inheritance is autosomal recessive.
## Management and treatment
Management involves restriction of dietary Phe, i.e. all high-protein foods, to normalize blood levels thus preventing the cognitive dysfunction, along with Phe-free medical formula to provide protein and other essential nutrients. Patients tolerate less than 250-350 mg of dietary Phe per day. Levels of Phe tolerance should be determined individually on a regular basis. Current recommendations call for lifelong maintenance of limited Phe intake. However, monitoring of levels is essential to avoid deficiencies of Phe and tyrosine. Foods containing aspartame should be avoided as aspartame releases Phe when digested. Female patients should be particularly cautious during pregnancy due to the fetotoxic effects of high maternal plasma Phe. When properly managed, the disease course is mostly favorable, but some neuropsychiatric complications may occur. Treatment and dietary compliance are the most important factors affecting outcome and prognosis.
## Prognosis
The prognosis is good when diagnosis is made early and compliance is high.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Classic phenylketonuria
|
c0751434
| 8,121 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79254
| 2021-01-23T17:36:01 |
{"mesh": ["D010661"], "umls": ["C0751434"], "icd-10": ["E70.0"], "synonyms": ["Classic PKU"]}
|
Linear focal elastosis is a rare, acquired, dermis elastic tissue disorder characterized by asymptomatic, palpable, hypertrophic or atrophic, yellowish or red, indurated, horizontal, striae-like linear plaques distributed symmetrically across the mid and lower back. No systemic involvement has been described. Skin biopsy reveals a focal increase in abnormal elastic tissue with abundant, wavy, fragmented and aggregated, basophilic elastic fibers in the reticular dermis.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Linear focal elastosis
|
None
| 8,122 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=228236
| 2021-01-23T18:51:29 |
{"synonyms": ["Elastotic striae", "Linear focal dermal elastosis"]}
|
This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.
Find sources: "Hereditary inclusion body myopathy" – news · newspapers · books · scholar · JSTOR (September 2009) (Learn how and when to remove this template message)
Hereditary inclusion body myopathy
Other namesHereditary inclusion body myopathy type 2
Hereditary inclusion body myopathies (HIBM) are a group of rare genetic disorders which have different symptoms. Generally, they are neuromuscular disorders characterized by muscle weakness developing in young adults. Hereditary inclusion body myopathies comprise both autosomal recessive and autosomal dominant muscle disorders that have a variable expression (phenotype) in individuals, but all share similar structural features in the muscles.
HIBMs are a group of muscle wasting disorders, which are uncommon in the general world population. One autosomal recessive form of HIBM is known as IBM2 or GNE myopathy, which is a common genetic disorder amongst people of Iranian Jewish descent.[1] IBM2 has also been identified in other minorities throughout the world, including people of Asian (Japanese and others), European, and South American origin, as well as Muslim people in the Middle Eastern, Palestinian, and Iranian origin. In Japan and many East Asian countries, this disorder is known as Distal Myopathy with Rimmed Vacuoles (DMRV).
IBM2 causes progressive muscle weakness and wasting. Muscle wasting usually starts around the age of 20 – 30 years, although young onset at 17 and old onset at 52 has been recorded. As such, it affects the most productive times of our lives. It can progress to marked disability within 10 to 15 years, confining many people with IBM2 to a wheelchair. The weakness and severity can vary from person to person. In some, weakness in the legs is noticed first. In few others, the hands are weakened more rapidly than the legs. Weakness is progressive, which means the muscle becomes weaker over time. IBM2 does not seem to affect the brain, internal organs or sensation. The quadriceps are relatively spared, and remain strong until the late stages of disease, which is the reason IBM2 is often referred to as Quadriceps Sparing Myopathy (QSM).
## Contents
* 1 Signs and symptoms
* 2 Genetics
* 3 Mechanisms
* 4 Diagnosis
* 4.1 Classification
* 5 Treatment
* 6 Prognosis
* 7 Research
* 8 History
* 9 See also
* 10 References
* 11 External links
## Signs and symptoms[edit]
Some early signs of HIBMs includes:
* Difficulty walking on heels, and difficulty running;
* Weak index finger;
* Frequent loss of balance.
* On muscle biopsy, the typical finding includes inclusion bodies, rimmed vacuoles and accumulation of aberrant proteins similar to those found in senile plaques of Alzheimer's disease (amyloid beta, hyperphosphorylated tau, amongst others)[citation needed]
## Genetics[edit]
The different forms have different mutations and inheritance patterns. See the detailed descriptions for details
## Mechanisms[edit]
The exact mechanisms of these diseases are not well understood. GNE/MNK a key enzyme in the sialic acid biosynthetic pathway, and loss-of-function mutations in GNE/MNK may lead to a lack of sialic acid, which in turn could affect sialoglycoproteins. GNE knockout mice show problems similar to people with IBM and in people with IBM dystroglycan has been found to lack sialic acid. However, the part of the dystroglycan that is important in muscle function does not seem to be affected. Another protein, neural cell adhesion molecule is under-sialyated in people with IBM, but as of 2016 it had no known role in muscle function.[2]
## Diagnosis[edit]
The most useful information for accurate diagnosis is the symptoms and weakness pattern. If the quadriceps are spared but the hamstrings and iliopsoas are severely affected in a person between ages of 20 - 40, it is very likely HIBM will be at the top of the differential diagnosis. The doctor may order any or all of the following tests to ascertain if a person has IBM2:
* Blood test for serum Creatine Kinase (CK or CPK);
* Nerve Conduction Study (NCS) / Electomyography (EMG);
* Muscle Biopsy;
* Magnetic Resonance Imaging (MRI) or Computer Tomography (CT) Scan to determine true sparing of quadriceps;
* Blood Test or Buccal swab for genetic testing;
### Classification[edit]
Types of hereditary inclusion body myopathy:
* IBM2 is the most common form, and is an autosomal recessive form, caused by mutations in the GNE gene; this form mainly affects leg muscles, but with an unusual distribution that spares the quadriceps.[2][3][4][5] The incidence of this form is about 10 per million per year.[6] There are two forms: a quadriceps sparing myopathy (autosomal recessive form of inclusion body myopathy) and Nonaka type distal myopathy (distal myopathy with rimmed vacuoles). While occurring worldside it is most common in Jews of Persian origin. The GNE gene ecodes the rate-limiting, bifunctional enzyme of sialic acid biosynthesis, uridine diphosphate-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase. Disease occurs when both copies in the genome are non functional. The pathophysiology is still unclear. Cardiac involvement may occur.
* IBM3 is a sometimes autosomal dominant and sometimes autosomal recessive form caused by mutations in MYHC2A; it is relatively mild muscle disorder.[7][8][9]
* Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia (IBMPFD), now more commonly referred to as multisystem proteinopathy (MSP), is an autosomal dominant condition caused by mutations in VCP, HNRPA2B1 or HNRNPA1; it is a multisystem degenerative disorder that can affect muscle, bone, and/or the central nervous system.[10][11][12]
The condition now called Desmin-related myofibrillar myopathy (also called myofibrillar myopathy-1) was formerly called inclusion body myopathy 1 (IBM1).[13]
More types of HIMBs, linked to other genes, may be identified in the future.
## Treatment[edit]
Treatment is palliative, not curative (as of 2009).[14]
Treatment options for lower limb weakness such as foot drop can be through the use of Ankle Foot Orthoses (AFOs) which can be designed or selected by an Orthotist based upon clinical need of the individual. Sometimes tuning of rigid AFOs can enhance knee stability.
## Prognosis[edit]
A 2009 review noted that muscle weakness usually begins after age 20 and after 20–30 years, the person usually requires a wheel chair for mobility. There was no mention of increased mortality.[14]
## Research[edit]
Because lack of sialic acid appears to be part of the pathology of IBM caused by GNE mutations, clinical trials with sialic acid supplements, and with a precursor of sialic acid, N-Acetylmannosamine, have been conducted, and as of 2016 further trials were planned.[2]
## History[edit]
Hereditary inclusion body myopathy (IBM) constitutes a unique group of neuromuscular disorders characterized by adult-onset slowly progressive distal and proximal weakness, and a typical muscle pathology including rimmed vacuoles and filamentous inclusions. Autosomal dominant (IMB3; OMIM 605637 [1]) and autosomal recessive (IBM2; OMIM 600737 [2]) forms have been described. The autosomal recessive form, first characterized in Jews of Persian descent, is a myopathy that affects mainly leg muscles, but with an unusual distribution that spares the quadriceps, so-called quadriceps-sparing myopathy (QSM). This disorder was subsequently found in other Middle Eastern families, the gene was mapped to 9p13-p12, and in 104 affected persons from 47 Middle Eastern families the same mutation in homozygous state was found in the GNE gene.[15] Affected individuals in families of other ethnic origins were found to be compound heterozygotes for other distinct mutations in the GNE gene. From OMIM 603824. [3]
## See also[edit]
* Inclusion body myositis, a more common and non-hereditary form.
* Valosin-containing protein (VCP); mutations in VCP cause multisystem proteinopathy (MSP) which can present (among others) as a rare form of inclusion body myopathy.
## References[edit]
1. ^ Pogoryelova, Oksana; González Coraspe, José Andrés; Nikolenko, Nikoletta; Lochmüller, Hanns; Roos, Andreas (December 2018). "GNE myopathy: from clinics and genetics to pathology and research strategies". Orphanet Journal of Rare Diseases. 13 (1): 70. doi:10.1186/s13023-018-0802-x. PMID 29720219.
2. ^ a b c Broccolini, Aldobrando; Mirabella, Massimiliano (April 2015). "Hereditary inclusion-body myopathies". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1852 (4): 644–650. doi:10.1016/j.bbadis.2014.08.007. PMID 25149037.
3. ^ "Inclusion body myopathy 2". NIH Genetic and Rare Diseases Information Center. Retrieved 19 September 2016. "Alternative names include: Inclusion body myopathy, autosomal recessive; Inclusion body myopathy, quadriceps-sparing; QSM; Hereditary inclusion body myopathy; HIBM; Distal myopathy with rimmed vacuoles; DMRV; Nonaka myopathy; Rimmed vacuole myopathy; Quadriceps Sparing Myopathy; GNE myopathy"
4. ^ "OMIM Entry # 605820 - Nonaka Myopathy". Online Mendelian Inheritance in Man. Retrieved 19 September 2016.
5. ^ "ORPHA602: GNE myopathy". OrphaNet. Retrieved 19 September 2016.
6. ^ Carrillo N, Malicdan MC, Huizing M (2018). "GNE myopathy: Etiology, diagnosis, and therapeutic challenges". Neurotherapeutics. 15 (4): 900–914. doi:10.1007/s13311-018-0671-y. PMC 6277305. PMID 30338442.CS1 maint: multiple names: authors list (link)
7. ^ "Inclusion body myopathy 3". NIH Genetic and Rare Diseases Information Center. Retrieved 19 September 2016. "Other Names: IBM3; Myopathy with congenital joint contractures, ophthalmoplegia, and rimmed vacuoles; Inclusion body myopathy autosomal dominant; Hereditary inclusion body myopathy - joint contractures - ophthalmoplegia; Hereditary inclusion body myopathy type 3; HIBM3"
8. ^ "ORPHA79091: Hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome". OrphaNet. Retrieved 19 September 2016.
9. ^ "OMIM# 605637 - Myopathy, Proximal, and Ophthalmoplegia; MYPOP". Online Mendelian Inheritance in Man. Retrieved 19 September 2016. "Myopathy With Congenital Joint Contractures, Ophthalmoplegia, And Rimmed Vacuoles Inclusion Body Myopathy 3, Autosomal Dominant, Formerly; IBM3, Formerly"
10. ^ "Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia". NIH - Genetic and Rare Diseases Information Center. Retrieved 19 September 2016. "Other Names: IBMPFD; Inclusion body myopathy with Paget disease of bone and frontotemporal dementia; Limb-girdle muscular dystrophy with Paget disease of bone; Pagetoid amyotrophic lateral sclerosis; Pagetoid neuroskeletal syndrome"
11. ^ "ORPHA52430: Inclusion body myopathy with Paget disease of bone and frontotemporal dementia". OrphaNet. Retrieved 19 September 2016.
12. ^ OMIM 167320 for VCP gene; OMIM 615422 for HNRPA2B1 gene; OMIM 615424 for HNRNPA1
13. ^ "OMIM # 601419 - Myopathy, Myofibrillar 1; MFM1". Online Mendelian Inheritance in Man. Retrieved 19 September 2016. "Alternative names: Myopathy, Myofibrillar, Desmin-Related. Desminopathy, Primary. Desmin-Related Myopathy; DRM. Myofibrillar Myopathy With Arrhythmogenic Right Ventricular Cardiomyopathy. Desmin-Related Myopathy With Arrhythmogenic Right Ventricular Cardiomyopathy. Arrhythmogenic Right Ventricular Dysplasia, Familial, 7, Formerly. ARVD7, Formerly. Arrhythmogenic Right Ventricular Cardiomyopathy 7, Formerly; ARVC7, Formerly. Inclusion Body Myopathy 1, Autosomal Dominant, Formerly. IBM1, Formerly. Cardiomyopathy, Dilated, 1f And Limb-Girdle Muscular Dystrophy Type 1d, Formerly. CMD1f And LGMD1d, Formerly. Cardiomyopathy, Dilated, with Conduction Defect and Muscular Dystrophy; CDCD3, formerly."
14. ^ a b Huizing, Marjan; Krasnewich, Donna M. (2009-09-01). "Hereditary Inclusion Body Myopathy: A decade of progress". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. Genetic Glycosylation Diseases. 1792 (9): 881–887. doi:10.1016/j.bbadis.2009.07.001. PMC 2748147. PMID 19596068.
15. ^ Eisenberg I, Avidan N, Potikha T, et al. (2001). "The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is mutated in recessive hereditary inclusion body myopathy". Nat. Genet. 29 (1): 83–7. doi:10.1038/ng718. PMID 11528398.
## External links[edit]
* GeneReviews/NCBI/NIH/UW entry on Inclusion Body Myopathy 2
* GeneReviews/NCBI/NIH/UW entry on Inclusion Body Myopathy with Paget Disease of Bone and/or Frontotemporal Dementia
Classification
D
* ICD-10: G71.8
* OMIM: 605820
External resources
* Orphanet: 602
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Hereditary inclusion body myopathy
|
c1853926
| 8,123 |
wikipedia
|
https://en.wikipedia.org/wiki/Hereditary_inclusion_body_myopathy
| 2021-01-18T18:37:33 |
{"mesh": ["C536816"], "wikidata": ["Q5737853"]}
|
A number sign (#) is used with this entry because this form of congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A6; MDDGA6), previously designated Walker-Warburg syndrome (WWS) or muscle-eye-brain disease (MEB), is caused by homozygous or compound heterozygous mutation in the LARGE gene (603590) on chromosome 22q12. LARGE is a novel member of the N-acetylglucosaminyltransferase gene family.
Mutation in the LARGE gene can also cause a less severe form of congenital muscular dystrophy-dystroglycanopathy with mental retardation (type B6; MDDGB6; 608840).
Description
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A), which includes both the more severe Walker-Warburg syndrome (WWS) and the slightly less severe muscle-eye-brain disease (MEB), is an autosomal recessive disorder with characteristic brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and death usually in the first years of life. It represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of DAG1 (128239), collectively known as 'dystroglycanopathies' (Godfrey et al., 2007).
For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (236670).
Clinical Features
Historically, the most severe forms of the dystroglycanopathies were described as Walker-Warburg syndrome (WWS) and muscle-eye-brain disease (MEB); these designations have been retained here when used in the literature.
### LARGE-Related Walker-Warburg Syndrome
Van Reeuwijk et al. (2007) reported 2 Saudi sibs, born of consanguineous parents, with Walker-Warburg syndrome. At birth, both showed severe hypotonia, absent deep tendon reflexes, widened anterior fontanels, and ophthalmic changes, including cataract, optic atrophy, and retinal dysplasia. Both had increased serum creatine kinase and dystrophic muscle biopsies. Brain CT scan showed ventricular dilatation, absence of the inferior cerebellar vermis, and hypoplastic cerebellum; 1 of the sibs had hydrocephalus and Dandy-Walker malformation. The sibs died at age 6 and 2 months, respectively.
Godfrey et al. (2007) identified 1 patient with LARGE-related WWS in a larger study of 92 patients with muscular dystrophy and evidence of a dystroglycanopathy. Although clinical details were limited, the patient had prenatal onset, feeding difficulties, increased serum creatine kinase, contractures, retinal dysplasia, low IQ, and death at age 8 weeks. Brain MRI showed hydrocephalus, white matter abnormalities, cerebellar hypoplasia, and lissencephaly.
Clement et al. (2008) reported a 4-week-old patient with LARGE-related WWS. The patient had mental retardation and retinal dysplasia. Brain MRI showed ventricular dilatation, diffuse white matter abnormalities, hypoplastic and dysplastic cerebellum, posterior concavity of the brainstem, pontine hypoplasia, and posterior cobblestone lissencephaly. The study was part of a larger study of 27 patients with various genetic forms of muscular dystrophy due to defective dystroglycan glycosylation.
### LARGE-Related Muscle-Eye-Brain Disease
Clement et al. (2008) reported a patient with LARGE-related MEB. The patient had congenital muscular dystrophy, increased serum creatine kinase, mental retardation, and myopia. Brain MRI showed ventricular dilatation, abnormal white matter changes, cerebellar cysts, dysplastic cerebellar vermis, posterior concavity of the brainstem, pontine hypoplasia with a cleft, and frontoparietal polymicrogyria.
Molecular Genetics
In 2 Saudi sibs with WWS, van Reeuwijk et al. (2007) identified a homozygous 63-kb intragenic deletion in the LARGE gene (603590.0003), including part of intron 8, exon 9, intron 9, exon 10, and most of intron 10. The unaffected parents were heterozygous for the deletion.
In 1 of 81 Italian patients with congenital muscular dystrophy and defective glycosylation of alpha-dystroglycan, Mercuri et al. (2009) identified a homozygous mutation in the LARGE gene (W495R; 603590.0004). The phenotype was consistent with Walker-Warburg syndrome. The patient had head control, but also had increased serum creatine kinase, absent alpha-dystroglycan on muscle biopsy, and mental retardation.
In a patient with MEB, Clement et al. (2008) identified compound heterozygosity for 2 mutations in the LARGE gene (603590.0005 and 603590.0006).
INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Retinal dysplasia \- Optic atrophy \- Cataract SKELETAL \- Contractures Skull \- Widened anterior fontanelles MUSCLE, SOFT TISSUES \- Hypotonia, severe \- Muscular dystrophy \- Muscle biopsy shows decreased glycosylation of alpha-dystroglycan (DAG1, 128239 ) NEUROLOGIC Central Nervous System \- Mental retardation \- Areflexia \- Cobblestone lissencephaly \- Ventricular dilatation \- Absence of the cerebellar vermis \- Hypoplasia of the cerebellum \- Dysplastic cerebellum \- Hydrocephalus \- White matter changes \- Pontine hypoplasia \- Dandy-Walker malformation (in 1 of 4 patients) LABORATORY ABNORMALITIES \- Increased serum creatine kinase MISCELLANEOUS \- Onset prenatally or at birth \- Four patients have been reported MOLECULAR BASIS \- Caused by mutation in the acetylglucosaminyltransferase-like protein gene (LARGE, 603590.0003 ) ▲ 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 inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 6
|
c0265221
| 8,124 |
omim
|
https://www.omim.org/entry/613154
| 2019-09-22T15:59:25 |
{"doid": ["0111242"], "mesh": ["D058494"], "omim": ["613154"], "orphanet": ["899", "588"], "synonyms": ["Alternative titles", "WALKER-WARBURG SYNDROME OR MUSCLE-EYE-BRAIN DISEASE, LARGE-RELATED"]}
|
Combined oxidative phosphorylation defect type 20 is a rare mitochondrial oxidative phosphorylation disorder characterized by variable combination of psychomotor delay, hypotonia, muscle weakness, seizures, microcephaly, cardiomyopathy and mild dysmorphic facial features. Variable types of structural brain anomalies have also been reported. Biochemical studies typically show decreased activity of mitochondrial complexes (mainly complex I).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Combined oxidative phosphorylation defect type 20
|
c4014660
| 8,125 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=420728
| 2021-01-23T17:16:35 |
{"omim": ["615917"], "icd-10": ["E88.8"], "synonyms": ["COXPD20"]}
|
Congenital estrogen deficiency
Other namesAromatase deficiency
Congenital estrogen deficiency is inherited in an autosomal recessive manner.
Congenital estrogen deficiency is a congenital form of hypoestrogenism in which the body is unable to produce or use estrogens.[1] Such conditions include:
* Aromatase deficiency, a condition in which aromatase is absent and androgens cannot be converted into estrogens.
* Estrogen insensitivity syndrome, a condition in which the estrogen receptor is defective and unable to respond to estrogens.
## See also[edit]
* Aromatase excess syndrome
* Hyperestrogenism
## References[edit]
1. ^ Rochira V, Balestrieri A, Madeo B, et al. (June 2001). "Congenital estrogen deficiency: in search of the estrogen role in human male reproduction". Mol. Cell. Endocrinol. 178 (1–2): 107–15. doi:10.1016/S0303-7207(01)00432-4. PMID 11403900. S2CID 24955164.
## External links[edit]
Classification
D
* ICD-10: E25.8
* OMIM: 613546
External resources
* Orphanet: 91
This genetic disorder article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Congenital estrogen deficiency
|
None
| 8,126 |
wikipedia
|
https://en.wikipedia.org/wiki/Congenital_estrogen_deficiency
| 2021-01-18T18:55:02 |
{"wikidata": ["Q5160428"]}
|
Maize lethal necrosis disease (MLN disease, MLND, corn lethal necrosis) is a viral disease affecting maize (corn) predominantly in East Africa, Southeast Asia and South America, which was recognised in 2010. It is caused by simultaneous infection with two viruses, maize chlorotic mottle virus (MCMoV) of the Tombusviridae family and a virus from the Potyviridae group: maize dwarf mosaic virus (MDMV), wheat streak mosaic virus (WSMV), sugarcane mosaic virus (SCMV), Johnsongrass mosaic virus (JGMV) or others.[1][2]
Spread of the disease is driven by expansion in the range of maize chlorotic mottle virus, which is thought to be transmitted by species of thrips including maize thrips (Frankliniella williamsi) and possibly western flower thrips, Frankliniella occidentalis. The potyviruses responsible for MLN are transmitted by several species of aphids and, in the case of wheat streak mosaic virus, wheat curl mite. Disease is associated with the presence of maize thrips and the growth of several crops of maize annually.[2]
In late 2014, it was reported that MLND could cut Kenya's maize production by as much as 30%.[3] In early March 2015, the middle of the rainy season, losses were estimated at 10%.[4]
## Contents
* 1 Symptoms
* 2 Management
* 3 Sources
* 4 References
## Symptoms[edit]
Leaves of infected plants become yellow from the tip and margins to the centre. Older leaves (bottom of plant) remain green. Ears and leaves dry up and sometimes look like a mature plant. The whole plant dies and maize cobs remain without kernels. MLND symptoms can be confused with symptoms of nutrient deficiency but plants affected by MLND appear only in some areas and are scattered or clumped in a field while nutrient deficiency appears on many plants over large areas of a field.[5]
In the early stages, MLND causes long yellow stripes on leaves. Unlike maize streak virus disease though, the streaks of MLND are wider. As the disease advances, the maize leaves become yellow and dry out from the outside edges towards the midrib. MLND can also cause dwarfing and premature aging of the plants. Finally, the entire plant dries out and dies. Dead plants can then be seen scattered across the field among healthy looking plants. Late infected plants don’t tassel and tend to produce poor grain filled cobs.[6]
## Management[edit]
Partners of the CABI-led programme, Plantwise recommend where possible using certified, disease-free seed. They also recommend not moving infected maize plants and seeds to disease-free areas. Plantwise and partners also recommend rotating with non-cereal crops (e.g. beans, faba bean, chickpea etc.) for at least 2-3 years/seasons and removing alternate hosts including, sorghum, grasses, millet, wheat, oats, sudan grass.[6][7][8]
The Ministry of Agriculture and Natural Resources of Ethiopia recommend uprooting and burning of diseased plants.[7]
Another method of prevention is to leave land fallow for 2 months especially where maize is produced using irrigation. It is also recommended to plough and expose soil to sunlight for at least 2 months.[7]
MLN resistance is an important trait to maize breeders.[9] Forward genetics is increasingly being used.[9]
## Sources[edit]
This article incorporates text from a free content work. Licensed under CC-BY-SA License statement/permission on Wikimedia Commons. Text taken from Plantwise Factsheets for Farmers: Control vectors of Maize Lethal Necrotic Disease, Joyce G. Kessy, CABI. To learn how to add open license text to Wikipedia articles, please see this how-to page. For information on reusing text from Wikipedia, please see the terms of use.
This article incorporates text from a free content work. Licensed under CC-BY-SA License statement/permission on Wikimedia Commons. Text taken from Plantwise Factsheet for Farmers: Prevention and detection of Maize Lethal Necrosis Disease, Hiwot Lemma, Daniel W. Michael, Mhreteab Tsegay, CABI. To learn how to add open license text to Wikipedia articles, please see this how-to page. For information on reusing text from Wikipedia, please see the terms of use.
This article incorporates text from a free content work. Licensed under CC-BY-SA License statement/permission on Wikimedia Commons. Text taken from PMDG: Maize Lethal Necrosis Disease (MLND) (Ethiopia), Kassahun Sedessa (EIAR), Mebrahtom G/kidan (TBoARD), Habtie Abate (S/Gondar Agri Dept, Amhara), CABI. To learn how to add open license text to Wikipedia articles, please see this how-to page. For information on reusing text from Wikipedia, please see the terms of use.
This article incorporates text from a free content work. Licensed under CC-BY-SA License statement/permission on Wikimedia Commons. Text taken from PMDG: Maize lethal necrosis disease in maize (Zambia), Mathews Matimelo (ZARI), CABI. To learn how to add open license text to Wikipedia articles, please see this how-to page. For information on reusing text from Wikipedia, please see the terms of use.
## References[edit]
1. ^ "Maize Lethal Necrosis Disease (MLND) - A snapshot". FAO. June 2013. Retrieved 2015-04-08.
2. ^ a b Margaret G. Redinbaugh, Lucy R. Stewart (2018). "Maize Lethal Necrosis: An Emerging, Synergistic Viral Disease". Annual Review of Virology. 5 (1): 301–22. doi:10.1146/annurev-virology-092917-043413. PMID 30059641.CS1 maint: uses authors parameter (link)
3. ^ Joseph Burite (2014-10-23). "Kenyan Corn-Disease Outbreak May Cut Output by 30% This Year". Bloomberg. Retrieved 2015-04-08.
4. ^ "Kenya: Disease Hits Kenya Maize Expectations". East African Business Week. 2015-03-08. Retrieved 2015-04-08.
5. ^ "Plantwise Knowledge Bank | Control vectors of Maize Lethal Necrotic Disease". www.plantwise.org. Retrieved 2020-06-22.
6. ^ a b "Plantwise Knowledge Bank | Prevention and detection of Maize Lethal Necrosis Disease". www.plantwise.org. Retrieved 2020-06-22.
7. ^ a b c "Plantwise Knowledge Bank | Maize Lethal Necrosis Disease (MLND)". www.plantwise.org. Retrieved 2020-06-22.
8. ^ "Plantwise Knowledge Bank | Maize lethal necrosis disease in maize". www.plantwise.org. Retrieved 2020-06-22.
9. ^ a b Cairns, Jill (2020-11-19). "Faster results at a lower cost". CIMMYT. Retrieved 2020-11-21.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Maize lethal necrosis disease
|
None
| 8,127 |
wikipedia
|
https://en.wikipedia.org/wiki/Maize_lethal_necrosis_disease
| 2021-01-18T18:53:21 |
{"wikidata": ["Q18414907"]}
|
Familial thrombocytosis is a type of thrombocytosis, a sustained elevation of platelet numbers, which affects the platelet/megakaryocyte lineage and may create a tendency for thrombosis and hemorrhage but does not cause myeloproliferation.
## Epidemiology
The prevalence of familial thrombocytosis is not known.
## Clinical description
The disease usually presents at birth but can be discovered at any time during life and thus can affect all ages. Patients present with thrombocytosis which is often discovered on a routine blood test. The clinical presentation is similar to sporadic essential thrombocythemia (ET; see this term) and may include impaired microcirculation resulting in brief episodes of fainting and dizziness, an increased risk of thrombotic events, hemorrhage, and mild splenomegaly. Patients with mutations in the MPL gene also experience frequent development of bone marrow fibrosis and seem to be free of hemorrhagic complications. The course of the disease is milder than sporadic ET and is devoid of the risk of leukemic transformation or progression toward myelofibrosis with myeloid metaplasia.
## Etiology
Familial thrombocytosis is caused by germline mutations in the THPO gene (3q26.3-q27) or in the MPL (MPL S505N) gene (1p34)
## Diagnostic methods
Diagnosis is based on the observation of elevated levels of platelets (over 450 x 109/L) and the elimination of secondary causes of thrombocythemia. Genetic testing is required to confirm the diagnosis.
## Differential diagnosis
Differential diagnoses include causes of thrombocytosis with myeloproliferative neoplasm including chronic myeloid leukemia, polycythemia vera, primary myelofibrosis, sporadic or familial ET and myelodysplasic disorders with thrombocytosis including sideroblastic anemia or 5q- syndrome (see these terms), although these can be excluded by the presence of myeloproliferation. Differential diagnoses also include causes of secondary thrombocytosis including iron deficiency, malignancy, chronic inflammatory disease, splenectomy or aspleny and protracted marrow regeneration.
## Genetic counseling
Transmission is autosomal dominant with high penetrance.
## Management and treatment
Treatment is based on low dose aspirin at diagnosis. There is no consensus for using platelet lowering therapy despite an increased risk of thrombosis. Patients may have an increased risk of thrombotic events and hemorrhage.
## Prognosis
The predominant clinical feature is impaired microcirculation resulting in brief episodes of fainting and dizziness responding well to aspirin when the THPO gene is mutated and an increased risk of thrombosis and a frequent development of marrow fibrosis when MPL gene is mutated. All these may affect life expectancy.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Familial thrombocytosis
|
c3277671
| 8,128 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=71493
| 2021-01-23T18:39:29 |
{"omim": ["187950", "300331", "601977", "614521"], "icd-10": ["D75.2"], "synonyms": ["Familial thrombocythemia", "Hereditary thrombocythemia"]}
|
Lid lag is the static situation in which the upper eyelid is higher than normal with the globe in downgaze.[1] It is most often a sign of thyroid eye disease, but may also occur with cicatricial changes to the eyelid or congenital ptosis. Lid lag differs from Von Graefe's sign in that the latter is a dynamic process. It can also be the manifestation of chemosis (swelling (or edema) of the conjunctiva)
## References[edit]
1. ^ Harvey, JT; Anderson, RL (1981). "Lid lag and lagophthalmos: a clarification of terminology". Ophthalmic Surg. 12 (5): 338–40.
This medical sign article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Lid lag
|
c0234664
| 8,129 |
wikipedia
|
https://en.wikipedia.org/wiki/Lid_lag
| 2021-01-18T19:07:18 |
{"umls": ["C0234664"], "wikidata": ["Q25098595"]}
|
A number sign (#) is used with this entry because of evidence that autosomal dominant nonsyndromic sensorineural deafness-12 (DFNA12), which has also been designated DFNA8, is caused by mutation in the gene encoding alpha-tectorin (TECTA; 602574) on chromosome 11q23.
Autosomal recessive deafness-21 (DFNB21; 603629) is an allelic disorder.
Clinical Features
Kirshhofer et al. (1995, 1998) reported an Austrian family in which 11 individuals spanning 4 generations had autosomal dominant nonsyndromic sensorineural deafness. The hearing loss was moderate to severe, showed prelingual onset, and was relatively stable or nonprogressive. The degree of hearing impairment was similar in all affected members, regardless of age or sex. Pure tone audiometry showed hearing loss between 60 and 80 dB, with a maximum at 2,000 Hz (severe range 1,000 to 6,000 kHz) and a U-shaped curve. The disorder in this family was designated DFNA8. The studies indicated a cochlear lesion.
Verhoeven et al. (1997) reported a Belgian family with autosomal dominant mid-frequency (500 to 2,000 Hz) hearing loss with prelingual onset. There was no progression with age. Hearing loss ranged from mild to moderately severe. The disorder in this family was designated DFNA12.
Kirshhofer et al. (1998) contended that the phenotypes of the Austrian family reported by them and the Belgian family reported by Verhoeven et al. (1997) were slightly different. Whereas there was little interindividual variability in the Austrian family, the Belgian family showed interindividual variability. However, Mustapha et al. (1999) concluded that DFNA8 and DFNA12 represent the same form of autosomal dominant deafness.
Balciuniene et al. (1998, 1999) reported a large Swedish family with autosomal dominant nonsyndromic hearing loss of postlingual onset. Nine individuals had a more severe phenotype, with severe hearing loss with onset at a mean age of 9 years. Audiogram showed decreased hearing particularly at high frequencies (6 to 8 kHz) with up to an 80-dB drop at age 50. Some individuals had a milder phenotype, with mild hearing loss only at high frequencies (4 to 6 kHz) with a mean age of onset at 19 years. The hearing loss was progressive.
Moreno-Pelayo et al. (2001) reported a Spanish family in which 9 members had sensorineural nonsyndromic deafness. Onset was postlingual, occurring in the first or second decades. Audiometric testing showed mid frequency hearing loss, a U-shaped audiogram, and progressive hearing loss. Genetic analysis identified a heterozygous mutation in the TECTA gene (602574.0008).
Meyer et al. (2007) reported a family segregating 2 forms of deafness: autosomal dominant DFNA12 and autosomal recessive DFNB1 (220290). Analysis of audiograms by audioprofiling suggested that 2 sibs in the family had a different form of deafness compared to the others. Molecular genetic studies identified a heterozygous mutation in the TECTA gene (C1837R; 602574.0008) in those with mid to high frequency hearing loss, a U-shaped audiogram, and childhood onset; the 2 sibs with down-sloping high-frequency hearing loss and childhood onset were found to be compound heterozygous for 2 mutations in the GJB2 gene (L90P; 121011.0016 and V37I; 121011.0023). Meyer et al. (2007) emphasized the utility of audiogram profiling in heritable hearing loss to determine candidate gene involvement.
Mapping
In initial studies of an Austrian family with autosomal dominant nonsyndromic sensorineural deafness, Kirshhofer et al. (1995) found linkage to a locus on chromosome 15q15-q21; this locus was designated DFNA8. However, in later publications, Kirshhofer et al. (1996, 1998) mapped the disorder in the same family to 11q and retained the DFNA8 designation for this family. Further studies yielded a maximum lod score of 3.6 at marker D11S934 on 11q; the lod score for the locus on chromosome 15 was reduced to 1.81.
By linkage analysis of a Belgian family with autosomal dominant hearing loss, Verhoeven et al. (1997) identified a candidate locus, designated DFNA12, on chromosome 11q22-q24 (lod scores in excess of 6.0). Analysis of key recombinants mapped the gene to a 36-cM interval on 11q22-q24, between markers D11S4120 and D11S912 (Verhoeven et al., 1997).
In a Swedish family with autosomal dominant nonsyndromic hearing loss of postlingual progressive type, Balciuniene et al. (1998) found evidence for linkage both to the DFNA12 region on 11q and to the DFNA2 region (600101) on 1p32. A detailed analysis of the phenotypes and haplotypes shared by the affected individual supported the notion that 2 genes segregated together with hearing impairment in the family. Severely affected family members had haplotypes linked to the disease allele on both chromosomes 1 and 11, whereas individuals with milder hearing loss had haplotypes linked to the disease allele on either chromosome 1 or chromosome 11. These observations suggested an additive effect of 2 genes, each gene resulting in a mild, sometimes undiagnosed, phenotype, together resulting in a more severe phenotype; this would be an example of digenic inheritance.
Van Camp et al. (1997) used the designation DFNA12 for the disorder in a Belgian family showing prelingual deafness and linkage to 11q22-q24.
Molecular Genetics
In affected members of the Belgian family with DFNA12 reported by Verhoeven et al. (1997, 1997), Verhoeven et al. (1998) identified a heterozygous mutation in the TECTA gene (602574.0001).
In affected members of the Austrian family with DFNA8 reported by Kirshhofer et al. (1995, 1998), Verhoeven et al. (1998) identified a heterozygous mutation in the TECTA gene (Y1870C; 602574.0002).
In the kindred reported by Balciuniene et al. (1998), Balciuniene et al. (1999) identified a heterozygous mutation in the TECTA gene (C1057S; 602574.0004). The mutation was present in all severely affected individuals and in some mildly affected individuals.
Genotype/Phenotype Correlations
Applying statistical analysis, Plantinga et al. (2006) found a significant association between TECTA mutations in the zona pellucida and zona adhesin domains and mid and high frequency hearing impairment, respectively. Cysteine-replacing mutations were associated with progressive hearing impairment.
INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Hearing loss, sensorineural \- Affects mid- to high-frequencies \- U-shaped audiogram MISCELLANEOUS \- Onset may be prelingual or in childhood \- Hearing loss may be stable or progressive \- Allelic disorder to autosomal recessive deafness 21 (DFNB21, 603629 ) MOLECULAR BASIS \- Caused by mutation in the alpha-tectorin gene (TECTA, 602574.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
DEAFNESS, AUTOSOMAL DOMINANT 12
|
c1832187
| 8,130 |
omim
|
https://www.omim.org/entry/601543
| 2019-09-22T16:14:38 |
{"doid": ["0110544"], "mesh": ["C563295"], "omim": ["601543"], "orphanet": ["90635"], "synonyms": ["Autosomal dominant non-syndromic sensorineural hearing loss type DFNA", "Autosomal dominant isolated sensorineural hearing loss type DFNA", "DEAFNESS, AUTOSOMAL DOMINANT 8", "Autosomal dominant non-syndromic neurosensory deafness type DFNA", "Alternative titles", "Autosomal dominant isolated neurosensory deafness type DFNA", "Autosomal dominant isolated neurosensory hearing loss type DFNA", "Autosomal dominant isolated sensorineural deafness type DFNA", "Autosomal dominant non-syndromic neurosensory hearing loss type DFNA"], "genereviews": ["NBK1434"]}
|
A number sign (#) is used with this entry because of evidence that susceptibility to autism-19 (AUTS19) is conferred by variation in the EIF4E gene (133440) on chromosome 4q23.
For a phenotypic description and a discussion of genetic heterogeneity of autism, see 209850.
Cytogenetics
Neves-Pereira et al. (2009) identified a boy with classic autism and a de novo balanced 46,XY,t(4;5)(q23;q31.3) translocation. There was no family history of autism and the child had no dysmorphic features other than a double hair whorl on the crown. He demonstrated a typical and severe autistic phenotype. The breakpoint on chromosome 4 maps 56 kb downstream of EIF4E (133440), a region found to be associated with autism (Yonan et al., 2003; Schellenberg et al., 2006).
Molecular Genetics
To investigate a role for the EIF4E gene in autism susceptibility, Neves-Pereira et al. (2009) screened 120 multiplex families with 2 autistic sibs from the Autism Genetic Research Exchange (AGRE) collection for mutations in the coding regions and promoter of EIF4E. In 2 independent families direct sequencing revealed a heterozygous single-base insertion in the EIF4E promoter region (133440.0001) in the proband. In both of the families the variant was present in the second autistic sib and the father. The variant was not found in 1,020 anonymous control samples.
Animal Model
Gkogkas et al. (2013) demonstrated that knockout of the eukaryotic translation initiation factor 4E-binding protein-2 (EIF4EBP2; 602224) (an EIF4E repressor downstream of MTOR, 601231) or Eif4e overexpression leads to increased translation of neuroligins, which are postsynaptic proteins that are causally linked to autism spectrum disorders (ASDs). Mice with knockout of Eif4ebp2 exhibit an increased ratio of excitatory to inhibitory synaptic inputs and autistic-like behaviors (i.e., social interaction deficits, altered communication, and repetitive/stereotyped behaviors). Pharmacologic inhibition of Eif4e activity or normalization of neuroligin-1 (600568), but not neuroligin-2 (606479), protein levels restored the normal excitation/inhibition ratio and rectified the social behavior deficits. Thus, Gkogkas et al. (2013) concluded that translational control by EIF4E regulates the synthesis of neuroligins, maintaining the excitation-to-inhibition balance, and its dysregulation engenders ASD-like phenotypes.
Santini et al. (2013) found that genetically increasing the levels of Eif4e in mice results in exaggerated cap-dependent translation and aberrant behaviors reminiscent of autism, including repetitive and perseverative behaviors and social interaction deficits. Moreover, these autistic-like behaviors are accompanied by synaptic pathophysiology in the medial prefrontal cortex, striatum, and hippocampus. The autistic-like behaviors displayed by the Eif4e transgenic mice are corrected by intracerebroventricular infusions of the cap-dependent translation inhibitor 4EGI-1. Santini et al. (2013) concluded that their findings demonstrated a causal relationship between exaggerated cap-dependent translation, synaptic dysfunction, and aberrant behaviors associated with autism.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
AUTISM, SUSCEPTIBILITY TO, 19
|
c3554495
| 8,131 |
omim
|
https://www.omim.org/entry/615091
| 2019-09-22T15:53:13 |
{"omim": ["615091"]}
|
This article needs to be updated. Please update this article to reflect recent events or newly available information. (April 2017)
Follicle-stimulating hormone insensitivity
Other namesOvarian insensitivity to FSH, Granulosa cell hypoplasia
Follicle-stimulating hormone (FSH) insensitivity, or ovarian insensitivity to FSH in females, also referable to as ovarian follicle hypoplasia or granulosa cell hypoplasia in females, is a rare autosomal recessive genetic and endocrine syndrome affecting both females and males, with the former presenting with much greater severity of symptomatology. It is characterized by a resistance or complete insensitivity to the effects of follicle-stimulating hormone (FSH), a gonadotropin which is normally responsible for the stimulation of estrogen production by the ovaries in females and maintenance of fertility in both sexes. The condition manifests itself as hypergonadotropic hypogonadism (decreased or lack of production of sex steroids by the gonads despite high circulating levels of gonadotropins), reduced or absent puberty (lack of development of secondary sexual characteristics, resulting in sexual infantilism if left untreated), amenorrhea (lack of menstruation), and infertility in females, whereas males present merely with varying degrees of infertility and associated symptoms (e.g., decreased sperm production).[1][2]
A related condition is luteinizing hormone (LH) insensitivity (termed Leydig cell hypoplasia when it occurs in males), which presents with similar symptoms to those of FSH insensitivity but with the symptoms in the respective sexes reversed (i.e., hypogonadism and sexual infantilism in males and merely problems with fertility in females); however, males also present with feminized or ambiguous genitalia (also known as pseudohermaphroditism), whereas ambiguous genitalia does not occur in females with FSH insensitivity. Despite their similar causes, LH insensitivity is considerably more common in comparison to FSH insensitivity.[1]
## Contents
* 1 Signs and symptoms
* 2 Cause
* 3 Diagnosis
* 4 Treatment
* 5 See also
* 6 References
## Signs and symptoms[edit]
In females, FSH insensitivity results in diminished development of ovarian follicles and granulosa cells and low to normal estrogen levels, elevated to very elevated gonadotropin levels, and low inhibin B levels, whereas males present with diminished Sertoli cell proliferation and moderately elevated FSH levels, normal to slightly elevated LH levels, normal testosterone levels, and reduced inhibin B levels.[1][2][3]
Due in part to elevated LH levels, which stimulate androgen production by theca cells in the ovaries, and due in part to FSH insensitivity, resulting in a lack of aromatase in nearby granulosa cells that normally convert androgens into estrogens, it could be expected that females with FSH insensitivity might present with symptoms of hyperandrogenism at puberty. However, this has not been found to be the case. This may be in part because FSH, via stimulation of granulosa cells and the resultant secretion of yet-unidentified paracrine factors (but possibly including inhibin B), has been shown to significantly enhance the LH-mediated stimulation of androgen production by theca cells.[4][5] In addition, theca cells predominantly secrete the relatively weak androgen androstenedione, whereas granulosa cells, signaled to do so by FSH under normal circumstances, convert androstenedione into its more potent relative testosterone (which is subsequently converted into estradiol).[6] Hence, in females, FSH insensitivity may not only result in deficiencies in estrogen production by granulosa cells, but in diminished androgen synthesis by both theca and granulosa cells as well, which could potentially explain why hyperandrogenism does not occur.[citation needed]
FSH insensitivity presents itself in females as two clusters of symptoms: 1) hypergonadotropic hypogonadism or hypoestrogenism, resulting in a delayed, reduced, or fully absent puberty and associated sexual infantilism (if left untreated), reduced uterine volume, and osteoporosis; and 2) ovarian dysgenesis or failure, resulting in primary or secondary amenorrhea, infertility, and normal sized to slightly enlarged ovaries. Males on the other hand are significantly less affected, presenting merely with partial or complete infertility, reduced testicular volume, and oligozoospermia (reduced spermatogenesis).[1][2]
## Cause[edit]
FSH insensitivity is caused by inactivating mutations of the follicle-stimulating hormone receptor (FSHR) and thus an insensitivity of the receptor to FSH. This results in an inability of the granulosa cells in ovarian follicles to respond to FSH in females, in turn resulting in diminished estrogen production by the ovaries and loss of menstrual cycles, and an inability of Sertoli cells in the seminiferous tubules of the testicles to respond to FSH in males, which in turn results in impaired spermatogenesis.[1][2]
## Diagnosis[edit]
This section is empty. You can help by adding to it. (February 2017)
## Treatment[edit]
Hormone replacement therapy with estrogen may be used to treat symptoms of hypoestrogenism in females with the condition. There are currently no known treatments for the infertility caused by the condition in either sex.[citation needed]
## See also[edit]
* Hypogonadism and hypergonadotropic hypogonadism
* Gonadal dysgenesis and premature ovarian failure
* Leydig cell hypoplasia (or LH insensitivity)
* Gonadotropin-releasing hormone insensitivity
* Inborn errors of steroid metabolism
* Isolated 17,20-lyase deficiency
* Combined 17α-hydroxylase/17,20-lyase deficiency
* 17β-Hydroxysteroid dehydrogenase III deficiency
* Aromatase deficiency and estrogen insensitivity syndrome
## References[edit]
1. ^ a b c d e Mark A. Sperling (25 April 2008). Pediatric Endocrinology E-Book. Elsevier Health Sciences. p. 35. ISBN 978-1-4377-1109-7. Retrieved 10 June 2012.
2. ^ a b c d Eberhard Nieschlag; Hermann M. Behre; Susan Nieschlag (3 December 2009). Andrology: Male Reproductive Health and Dysfunction. Springer. p. 225. ISBN 978-3-540-78354-1. Retrieved 10 June 2012.
3. ^ Allen M. Spiegel (23 January 1998). G Proteins, Receptors, and Disease. Humana Press. p. 159. ISBN 978-0-89603-430-3. Retrieved 10 June 2012.
4. ^ Barnes RB, Rosenfield RL, Namnoum A, Layman LC (October 2000). "Effect of follicle-stimulating hormone on ovarian androgen production in a woman with isolated follicle-stimulating hormone deficiency". The New England Journal of Medicine. 343 (16): 1197–8. doi:10.1056/NEJM200010193431614. PMID 11041762.
5. ^ Wachs DS, Coffler MS, Malcom PJ, Shimasaki S, Chang RJ (May 2008). "Increased androgen response to follicle-stimulating hormone administration in women with polycystic ovary syndrome". The Journal of Clinical Endocrinology and Metabolism. 93 (5): 1827–33. doi:10.1210/jc.2007-2664. PMC 2386684. PMID 18285408.
6. ^ Richard Evan Jones; Kristin H. López (17 March 2006). Human Reproductive Biology. Academic Press. pp. 38–39. ISBN 978-0-12-088465-0. Retrieved 11 June 2012.
* v
* t
* e
Pituitary disease
Hyperpituitarism
Anterior
* Acromegaly
* Hyperprolactinaemia
* Pituitary ACTH hypersecretion
Posterior
* SIADH
General
* Nelson's syndrome
* Hypophysitis
Hypopituitarism
Anterior
* Kallmann syndrome
* Growth hormone deficiency
* Hypoprolactinemia
* ACTH deficiency/Secondary adrenal insufficiency
* GnRH insensitivity
* FSH insensitivity
* LH/hCG insensitivity
Posterior
Neurogenic diabetes insipidus
General
* Empty sella syndrome
* Pituitary apoplexy
* Sheehan's syndrome
* Lymphocytic hypophysitis
* Pituitary adenoma
* v
* t
* e
Genetic disorders relating to deficiencies of transcription factor or coregulators
(1) Basic domains
1.2
* Feingold syndrome
* Saethre–Chotzen syndrome
1.3
* Tietz syndrome
(2) Zinc finger
DNA-binding domains
2.1
* (Intracellular receptor): Thyroid hormone resistance
* Androgen insensitivity syndrome
* PAIS
* MAIS
* CAIS
* Kennedy's disease
* PHA1AD pseudohypoaldosteronism
* Estrogen insensitivity syndrome
* X-linked adrenal hypoplasia congenita
* MODY 1
* Familial partial lipodystrophy 3
* SF1 XY gonadal dysgenesis
2.2
* Barakat syndrome
* Tricho–rhino–phalangeal syndrome
2.3
* Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome
* Denys–Drash syndrome
* Duane-radial ray syndrome
* MODY 7
* MRX 89
* Townes–Brocks syndrome
* Acrocallosal syndrome
* Myotonic dystrophy 2
2.5
* Autoimmune polyendocrine syndrome type 1
(3) Helix-turn-helix domains
3.1
* ARX
* Ohtahara syndrome
* Lissencephaly X2
* MNX1
* Currarino syndrome
* HOXD13
* SPD1 synpolydactyly
* PDX1
* MODY 4
* LMX1B
* Nail–patella syndrome
* MSX1
* Tooth and nail syndrome
* OFC5
* PITX2
* Axenfeld syndrome 1
* POU4F3
* DFNA15
* POU3F4
* DFNX2
* ZEB1
* Posterior polymorphous corneal dystrophy
* Fuchs' dystrophy 3
* ZEB2
* Mowat–Wilson syndrome
3.2
* PAX2
* Papillorenal syndrome
* PAX3
* Waardenburg syndrome 1&3
* PAX4
* MODY 9
* PAX6
* Gillespie syndrome
* Coloboma of optic nerve
* PAX8
* Congenital hypothyroidism 2
* PAX9
* STHAG3
3.3
* FOXC1
* Axenfeld syndrome 3
* Iridogoniodysgenesis, dominant type
* FOXC2
* Lymphedema–distichiasis syndrome
* FOXE1
* Bamforth–Lazarus syndrome
* FOXE3
* Anterior segment mesenchymal dysgenesis
* FOXF1
* ACD/MPV
* FOXI1
* Enlarged vestibular aqueduct
* FOXL2
* Premature ovarian failure 3
* FOXP3
* IPEX
3.5
* IRF6
* Van der Woude syndrome
* Popliteal pterygium syndrome
(4) β-Scaffold factors
with minor groove contacts
4.2
* Hyperimmunoglobulin E syndrome
4.3
* Holt–Oram syndrome
* Li–Fraumeni syndrome
* Ulnar–mammary syndrome
4.7
* Campomelic dysplasia
* MODY 3
* MODY 5
* SF1
* SRY XY gonadal dysgenesis
* Premature ovarian failure 7
* SOX10
* Waardenburg syndrome 4c
* Yemenite deaf-blind hypopigmentation syndrome
4.11
* Cleidocranial dysostosis
(0) Other transcription factors
0.6
* Kabuki syndrome
Ungrouped
* TCF4
* Pitt–Hopkins syndrome
* ZFP57
* TNDM1
* TP63
* Rapp–Hodgkin syndrome/Hay–Wells syndrome/Ectrodactyly–ectodermal dysplasia–cleft syndrome 3/Limb–mammary syndrome/OFC8
Transcription coregulators
Coactivator:
* CREBBP
* Rubinstein–Taybi syndrome
Corepressor:
* HR (Atrichia with papular lesions)
* v
* t
* e
Inborn errors of steroid metabolism
Mevalonate
pathway
* HMG-CoA lyase deficiency
* Hyper-IgD syndrome
* Mevalonate kinase deficiency
To cholesterol
* 7-Dehydrocholesterol path: Hydrops-ectopic calcification-moth-eaten skeletal dysplasia
* CHILD syndrome
* Conradi-Hünermann syndrome
* Lathosterolosis
* Smith–Lemli–Opitz syndrome
* desmosterol path: Desmosterolosis
Steroids
Corticosteroid
(including CAH)
* aldosterone: Glucocorticoid remediable aldosteronism
* cortisol/cortisone: CAH 17α-hydroxylase
* CAH 11β-hydroxylase
* both: CAH 3β-dehydrogenase
* CAH 21-hydroxylase
* Apparent mineralocorticoid excess syndrome/11β-dehydrogenase
Sex steroid
To androgens
* 17α-Hydroxylase deficiency
* 17,20-Lyase deficiency
* Cytochrome b5 deficiency
* 3β-Hydroxysteroid dehydrogenase deficiency
* 17β-Hydroxysteroid dehydrogenase deficiency
* 5α-Reductase deficiency
* Pseudovaginal perineoscrotal hypospadias
To estrogens
* Aromatase deficiency
* Aromatase excess syndrome
Other
* X-linked ichthyosis
* Antley–Bixler syndrome
* v
* t
* e
Cell surface receptor deficiencies
G protein-coupled receptor
(including hormone)
Class A
* TSHR (Congenital hypothyroidism 1)
* LHCGR (Luteinizing hormone insensitivity, Leydig cell hypoplasia, Male-limited precocious puberty)
* FSHR (Follicle-stimulating hormone insensitivity, XX gonadal dysgenesis)
* GnRHR (Gonadotropin-releasing hormone insensitivity)
* EDNRB (ABCD syndrome, Waardenburg syndrome 4a, Hirschsprung's disease 2)
* AVPR2 (Nephrogenic diabetes insipidus 1)
* PTGER2 (Aspirin-induced asthma)
Class B
* PTH1R (Jansen's metaphyseal chondrodysplasia)
Class C
* CASR (Familial hypocalciuric hypercalcemia)
Class F
* FZD4 (Familial exudative vitreoretinopathy 1)
Enzyme-linked receptor
(including
growth factor)
RTK
* ROR2 (Robinow syndrome)
* FGFR1 (Pfeiffer syndrome, KAL2 Kallmann syndrome)
* FGFR2 (Apert syndrome, Antley–Bixler syndrome, Pfeiffer syndrome, Crouzon syndrome, Jackson–Weiss syndrome)
* FGFR3 (Achondroplasia, Hypochondroplasia, Thanatophoric dysplasia, Muenke syndrome)
* INSR (Donohue syndrome
* Rabson–Mendenhall syndrome)
* NTRK1 (Congenital insensitivity to pain with anhidrosis)
* KIT (KIT Piebaldism, Gastrointestinal stromal tumor)
STPK
* AMHR2 (Persistent Müllerian duct syndrome II)
* TGF beta receptors: Endoglin/Alk-1/SMAD4 (Hereditary hemorrhagic telangiectasia)
* TGFBR1/TGFBR2 (Loeys–Dietz syndrome)
GC
* GUCY2D (Leber's congenital amaurosis 1)
JAK-STAT
* Type I cytokine receptor: GH (Laron syndrome)
* CSF2RA (Surfactant metabolism dysfunction 4)
* MPL (Congenital amegakaryocytic thrombocytopenia)
TNF receptor
* TNFRSF1A (TNF receptor associated periodic syndrome)
* TNFRSF13B (Selective immunoglobulin A deficiency 2)
* TNFRSF5 (Hyper-IgM syndrome type 3)
* TNFRSF13C (CVID4)
* TNFRSF13B (CVID2)
* TNFRSF6 (Autoimmune lymphoproliferative syndrome 1A)
Lipid receptor
* LRP: LRP2 (Donnai–Barrow syndrome)
* LRP4 (Cenani–Lenz syndactylism)
* LRP5 (Worth syndrome, Familial exudative vitreoretinopathy 4, Osteopetrosis 1)
* LDLR (LDLR Familial hypercholesterolemia)
Other/ungrouped
* Immunoglobulin superfamily: AGM3, 6
* Integrin: LAD1
* Glanzmann's thrombasthenia
* Junctional epidermolysis bullosa with pyloric atresia
EDAR (EDAR hypohidrotic ectodermal dysplasia)
* PTCH1 (Nevoid basal-cell carcinoma syndrome)
* BMPR1A (BMPR1A juvenile polyposis syndrome)
* IL2RG (X-linked severe combined immunodeficiency)
See also
cell surface receptors
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Follicle-stimulating hormone insensitivity
|
None
| 8,132 |
wikipedia
|
https://en.wikipedia.org/wiki/Follicle-stimulating_hormone_insensitivity
| 2021-01-18T18:38:49 |
{"gard": ["4179"], "wikidata": ["Q5464647"]}
|
Autosomal recessive congenital methemoglobinemia is an inherited condition that mainly affects the function of red blood cells. Specifically, it alters a molecule within these cells called hemoglobin. Hemoglobin carries oxygen to cells and tissues throughout the body. In people with autosomal recessive congenital methemoglobinemia, some of the normal hemoglobin is replaced by an abnormal form called methemoglobin, which is unable to deliver oxygen to the body's tissues. As a result, tissues in the body become oxygen deprived, leading to a bluish appearance of the skin, lips, and nails (cyanosis).
There are two forms of autosomal recessive congenital methemoglobinemia: types I and II. People with type I have cyanosis from birth and may experience weakness or shortness of breath related to the shortage of oxygen in their tissues. People with type II have cyanosis as well as severe neurological problems. After a few months of apparently normal development, children with type II develop severe brain dysfunction (encephalopathy), uncontrolled muscle tensing (dystonia), and involuntary limb movements (choreoathetosis); also, the size of their head remains small and does not grow in proportion with their body (microcephaly). People with type II have severe intellectual disability; they can recognize faces and usually babble but speak no words. They can sit unassisted and grip objects but have impaired motor skills that leave them unable to walk. In type II, growth is often slowed. Abnormal facial muscle movements can interfere with swallowing, which can lead to feeding difficulties and further slow growth.
People with autosomal recessive congenital methemoglobinemia type I have a normal life expectancy, but people with type II often do not survive past early adulthood.
## Frequency
The incidence of autosomal recessive congenital methemoglobinemia is unknown.
## Causes
Autosomal recessive congenital methemoglobinemia is caused by mutations in the CYB5R3 gene. This gene provides instruction for making an enzyme called cytochrome b5 reductase 3. This enzyme is involved in transferring negatively charged particles called electrons from one molecule to another. Two versions (isoforms) of this enzyme are produced from the CYB5R3 gene. The soluble isoform is present only in red blood cells, and the membrane-bound isoform is found in all other cell types.
Each hemoglobin molecule contains four iron atoms, which are needed to carry oxygen. In normal red blood cells, the iron in hemoglobin is ferrous (Fe2+), but it can spontaneously become ferric (Fe3+). When hemoglobin contains ferric iron, it is methemoglobin. The soluble isoform of cytochrome b5 reductase 3 changes ferric iron back to ferrous iron so hemoglobin can deliver oxygen to tissues. Normally, red blood cells contain less than 2 percent methemoglobin.
The membrane-bound isoform is widely used in the body. This isoform is necessary for many chemical reactions, including the breakdown and formation of fatty acids, the formation of cholesterol, and the breakdown of various molecules and drugs.
CYB5R3 gene mutations that cause autosomal recessive congenital methemoglobinemia type I typically reduce enzyme activity or stability. As a result, the enzyme cannot efficiently change ferric iron to ferrous iron, leading to a 10 to 50 percent increase in methemoglobin within red blood cells. This increase in methemoglobin and the corresponding decrease in normal hemoglobin reduces the amount of oxygen delivered to tissues. The altered enzyme activity affects only red blood cells because other cells can compensate for a decrease in enzyme activity, but red blood cells cannot.
Mutations that cause autosomal recessive congenital methemoglobinemia type II usually result in a complete loss of enzyme activity. Cells cannot compensate for a complete loss of this enzyme, which results in a 10 to 70 percent increase in methemoglobin within red blood cells. This increase in methemoglobin and the corresponding decrease in normal hemoglobin leads to cyanosis. The lack of enzyme activity in other cells leads to the neurological features associated with type II. Researchers suspect that the neurological problems are caused by impaired fatty acid and cholesterol formation, which reduces the production of a fatty substance called myelin. Myelin insulates nerve cells and promotes the rapid transmission of nerve impulses. This reduced ability to form myelin (hypomyelination) leads to a loss of nerve cells, particularly in the brain. The loss of these cells likely contributes to the encephalopathy and movement disorders characteristic of autosomal recessive congenital methemoglobinemia type II.
### Learn more about the gene associated with Autosomal recessive congenital methemoglobinemia
* CYB5R3
## Inheritance Pattern
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Autosomal recessive congenital methemoglobinemia
|
c0268193
| 8,133 |
medlineplus
|
https://medlineplus.gov/genetics/condition/autosomal-recessive-congenital-methemoglobinemia/
| 2021-01-27T08:25:28 |
{"mesh": ["C537841"], "omim": ["250800"], "synonyms": []}
|
Multicentric Castleman disease (MCD) is a rare disease that affects the lymph nodes and related tissues. It is a form of Castleman disease that is "systemic" and involves multiple regions of lymph nodes (as opposed to unicentric Castleman disease, which involves a single lymph node or single region of lymph nodes). The signs and symptoms of MCD are often nonspecific, and are mild in some people but life-threatening in others. Symptoms may include enlarged lymph nodes in multiple regions, fever, weight loss, nausea, rash, and/or an enlarged large liver and spleen. The disease is diagnosed based on the symptoms present, laboratory test results, imaging studies, and results of a biopsy of the lymph nodes which shows specific features when studied under the microscope. In some cases, MCD is caused by human herpesvirus-8 (HHV-8) and is referred to as HHV-8-associated MCD. In other cases, the cause is not known and it is referred to as HHV-8 negative MCD, or idiopathic MCD (iMCD). Treatment of MCD is challenging, and treatment options and outcomes depend on the type and severity in each person.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Multicentric Castleman Disease
|
c1334815
| 8,134 |
gard
|
https://rarediseases.info.nih.gov/diseases/9644/multicentric-castleman-disease
| 2021-01-18T17:58:56 |
{"mesh": ["C537372"], "orphanet": ["93686"], "synonyms": ["MCD", "Plasmablastic multicentric Castleman disease", "PMCD", "Multicentric plasma cell variant of Castleman's disease", "Idiopathic multicentric Castleman's disease", "Multicentric giant lymph node hyperplasia"]}
|
Tulip fingers are a cutaneous condition, a combined allergic and irritant contact dermatitis caused by contact with tulip bulbs.[1]
## See also[edit]
* Textile dermatitis
* 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. 258. ISBN 1-4160-2999-0.
* v
* t
* e
Dermatitis and eczema
Atopic dermatitis
* Besnier's prurigo
Seborrheic dermatitis
* Pityriasis simplex capillitii
* Cradle cap
Contact dermatitis
(allergic, irritant)
* plants: Urushiol-induced contact dermatitis
* African blackwood dermatitis
* Tulip fingers
* other: Abietic acid dermatitis
* Diaper rash
* Airbag dermatitis
* Baboon syndrome
* Contact stomatitis
* Protein contact dermatitis
Eczema
* Autoimmune estrogen dermatitis
* Autoimmune progesterone dermatitis
* Breast eczema
* Ear eczema
* Eyelid dermatitis
* Topical steroid addiction
* Hand eczema
* Chronic vesiculobullous hand eczema
* Hyperkeratotic hand dermatitis
* Autosensitization dermatitis/Id reaction
* Candidid
* Dermatophytid
* Molluscum dermatitis
* Circumostomy eczema
* Dyshidrosis
* Juvenile plantar dermatosis
* Nummular eczema
* Nutritional deficiency eczema
* Sulzberger–Garbe syndrome
* Xerotic eczema
Pruritus/Itch/
Prurigo
* Lichen simplex chronicus/Prurigo nodularis
* by location: Pruritus ani
* Pruritus scroti
* Pruritus vulvae
* Scalp pruritus
* Drug-induced pruritus
* Hydroxyethyl starch-induced pruritus
* Senile pruritus
* Aquagenic pruritus
* Aquadynia
* Adult blaschkitis
* due to liver disease
* Biliary pruritus
* Cholestatic pruritus
* Prion pruritus
* Prurigo pigmentosa
* Prurigo simplex
* Puncta pruritica
* Uremic pruritus
Other
* substances taken internally: Bromoderma
* Fixed drug reaction
* Nummular dermatitis
* Pityriasis alba
* Papuloerythroderma of Ofuji
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 inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Tulip fingers
|
None
| 8,135 |
wikipedia
|
https://en.wikipedia.org/wiki/Tulip_fingers
| 2021-01-18T19:05:13 |
{"wikidata": ["Q7852078"]}
|
Streptococcal toxic-shock syndrome (streptococcal TSS) is an acute disease mediated by the production of superantigenic toxins characterized by the sudden onset of fever and other febrile symptoms, pain, multisystem organ involvement and potentially leading to coma, shock and death due to a Streptococcus pyogenes infection.
## Epidemiology
The annual incidence is estimated to range between 1/300,000 - 1/1,000,000.
## Clinical description
Streptococcal TSS usually presents with a sudden onset of pain, often mimicking peritonitis or located in the extremities in previously healthy adults. General flu-like symptoms such as high fever, myalgia, nausea, diarrhea and vomiting are signs of streptococcal TSS and most patients develop hypotension soon after hospital admission. Signs of soft tissue infection can also be present manifesting with localized erythema and swelling which can lead to necrotizing fasciitis in some cases. A diffuse scarlatina-like erythema occurs in about 10% of cases. Other serious manifestations include confusion, shock, renal dysfunction, acute respiratory distress syndrome (ARDS; see this term) and coma. In some cases streptococcal TSS can be associated with acute adrenal insufficiency (see this term).
## Etiology
Streptococcal TSS is caused by an infection with Streptococcus pyogenes, also known as group A streptococcus (GAS), and is usually associated with skin infections, child birth, and surgeries. Infection occurs at a site of trauma or can follow viral infections (influenza or varicella). Streptococcal TSS is the result of toxins released by the bacteria that cause a massive immune reaction involving mainly cytokines and chemokines. This reaction is related to the activation of T cells by the production of superantigens that circumvent the normal pathway of antigen presentation. Group C and G Streptococcus are also rarely associated.
## Diagnostic methods
Clinical symptoms along with laboratory analysis are the basis for diagnosis of streptococcal TSS. Patients with fever, multisystem organ failure and shock are tested for GAS in their blood or a normally sterile site (e.g. cerebrospinal, pleural or peritoneal fluid) and those who test positive are given a diagnosis of streptococcal TSS. Bacteremia is present in most patients with streptococcal TSS (approximately 60%) which is not the case in staphylococcal TSS (see this term) where it is seen in approximately 5% of cases.
## Differential diagnosis
Differential diagnoses include staphylococcal TSS, septic shock, typhoid fever, Rocky Mountain spotted fever, leptospirosis (see these terms), peritonitis, pneumonia, pelvic inflammatory disease, pericarditis, acute myocardial infarction, meningococcemia, viral/ drug/ allergic rash.
## Management and treatment
The onset of streptococcal TSS is sudden and requires immediate medical treatment in an intensive care setting. Treatment involves antibiotics (beta-lactam antibiotics and clindamycin) along with supportive therapy (fluid resuscitation, inotropes and vassopressors) and intravenous immunoglobins that block superantigens. Corticosteroids and recombinant activated protein C (derotrecogin-alpha) can also be helpful in some cases. Dialysis may be necessary for those with renal dysfunction and oxygen supplementation along with mechanical ventilation is required for patients with ARDS. Suspected necrotizing fasciitis may require debridement.
## Prognosis
The prognosis varies, with streptococcal TSS having a mortality rate of 30-80% in adults and 5-8% in children.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Streptococcal toxic-shock syndrome
|
c0343532
| 8,136 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99918
| 2021-01-23T16:52:42 |
{"umls": ["C0343532"], "icd-10": ["A48.3"], "synonyms": ["Streptococcal TSS"]}
|
Skin condition characterized by small bumps caused by overproduction of keratin.
Keratosis pilaris
Other namesFollicular keratosis, lichen pilaris
Condition on a calf
SpecialtyDermatology
Keratosis pilaris (KP) (also follicular keratosis, lichen pilaris, or colloquially chicken skin[1]) is a common, autosomal dominant, genetic condition of the skin's hair follicles characterized by the appearance of possibly itchy, small, gooseflesh-like bumps, with varying degrees of reddening or inflammation.[2] It most often appears on the outer sides of the upper arms (the forearms can also be affected), thighs, face, back, and buttocks;[2] KP can also occur on the hands, and tops of legs, sides, or any body part except glabrous (hairless) skin (like the palms or soles of feet).[3] Often the lesions can appear on the face, which may be mistaken for acne.[4]
There are several types of KP and it has been associated with pregnancy, type 1 diabetes mellitus, obesity, dry skin, allergic diseases (e.g., atopic dermatitis), and rarely cancer.[1] Many rarer types of the disorder are part of inherited genetic syndromes.[1]
The cause of KP is not completely understood. As of 2018, KP is thought to be due to abnormalities in the process of depositing the protein keratin in hair follicles, abnormalities in the hair shaft, or both.[1] KP is usually diagnosed by a medical professional based on the appearance of the skin but dermoscopy can be used as well if the diagnosis is unclear.[1] Variants of the ABCA12 gene have been associated with KP.[5]
KP is the most common disorder of the hair follicle in children.[1] It is unclear how common KP is in adults with estimates ranging from 0.75% to 34% of the population.[1] No single approach has been found to completely cure KP, but treatments can improve the cosmetic appearance of the condition. Treatment includes the application of topical preparations of moisturizers and medications such as glycolic acid, lactic acid, salicylic acid, urea, or retinoids to the skin.[1] Fractional carbon dioxide lasers and Nd:YAG laser therapies are also effective.[1]
## Contents
* 1 Signs and symptoms
* 2 Pathophysiology
* 3 Diagnosis
* 3.1 Differential diagnosis
* 3.2 Classification
* 4 Additional images
* 5 Treatment
* 6 Epidemiology
* 7 See also
* 8 References
* 9 External links
## Signs and symptoms[edit]
KP results in small, rough bumps on the surface of the skin. They are skin-colored bumps the size of a grain of sand, many of which are surrounded by a slight pink color in light skinned people and dark spots in dark skinned people.[4] Most people with KP do not have symptoms, but the bumps in the skin can occasionally be itchy.[6] Irritation due to scratching KP bumps can result in redness and inflammation.
Though people with KP experience the condition year-round, the problem can become exacerbated, with the bumps likely to look and feel more pronounced in color and texture, during the colder months when moisture levels in the air are lower.[7] The symptoms may also worsen during pregnancy or after childbirth.[8] It is speculated that increased sun exposure can mitigate the symptoms of KP.
## Pathophysiology[edit]
KP occurs when the human body produces excess amounts of the skin protein keratin, resulting in the formation of small, raised bumps in the skin often with surrounding redness.[6] The excess keratin, which is the same color of the person's natural skin tone, surrounds and entraps the hair follicles in the pore. This causes the formation of hard plugs (process known as hyperkeratinization).[4] Many KP bumps contain an ingrown hair that has coiled.[2] This is a result of the keratinized skin's "capping off" the hair follicle, preventing the hair from exiting. The hair grows encapsulated inside the follicle. KP is more common in patients affected by atopic diseases such as allergic rhinitis and atopic dermatitis.
KP subtypes are occasionally part of genetically inherited syndromes associated with intellectual disability, neuro-cardio-facial-cutaneous syndromes, RASopathies, ectodermal dysplasias, and certain myopathies.[1]
## Diagnosis[edit]
Physicians can often diagnose KP simply by examining the skin without specialized tests.[4] However, a dermatologist can use dermoscopy to confirm the diagnosis and assess if a person with KP is responding to treatment.[2] Physicians will often consider family history and the presence of symptoms when making the diagnosis.[9] Those with this condition are generally encouraged to contact a physician if the bumps are bothersome and do not improve with over-the-counter lotions.[4]
### Differential diagnosis[edit]
Several medications can cause a skin eruption similar to KP. Medications known to produce this type of skin eruption include cyclosporine, BRAF inhibitors, and tyrosine kinase inhibitors.[1]
### Classification[edit]
There are several different types of KP. Variations of KP include KP rubra (red, inflamed bumps which can be on arms, head, legs), KP alba (rough, bumpy skin with no irritation), KP rubra faceii (reddish rash on the cheeks), KP atrophicans, keratosis follicularis spinulosa decalvans, atrophoderma vermiculatum, KP atrophicans faciei, erythromelanosis follicularis faciei et colli, and papular profuse precocious KP.[1][6]
KP is commonly described in association with other dry skin conditions, such as ichthyosis vulgaris, dry skin and atopic dermatitis, including those of asthma and allergies.[1]
KP does not bear any known, long-term health implications, nor is it associated with increased mortality or morbidity.[10] It is not related to goose bumps, which results from muscle contractions, except that both occur in the area where the hair shaft exits the skin.
## Additional images[edit]
* Keratosis Pilaris on Lower Extremity
* Keratosis Pilaris on Back of Upper Arm
* Keratosis pilaris arm
## Treatment[edit]
KP is medically harmless,[2] but many individuals may seek treatment as the condition can cause emotional distress.[8] Topical creams and lotions are currently the most commonly used treatment for KP, specifically those consisting of moisturizing or keratolytic treatments, including urea, lactic acid, glycolic acid, salicylic acid, vitamin D, fish oil, or topical retinoids such as tretinoin.[11] Improvement of the skin often takes months and the bumps are likely to return. Limiting time in the shower and using gentle exfoliation to unplug pores can help.[8][12] Many products are available that apply abrasive materials to and alpha or beta hydroxy acids to assist with exfoliation.
Some cases of KP have been successfully treated with laser therapy, which involves passing intense bursts of light into targeted areas of the skin.[13] Depending on the body's response to the treatment, multiple sessions over the course of a few months may be necessary.
## Epidemiology[edit]
Worldwide, KP affects an estimated 30 to 50% of the adult population and approximately 50 to 80% of all adolescents. It is more common in women than in men, and it is often present in otherwise healthy individuals.[11] The skin condition is prevalent in persons of all ethnicities, and no particular ethnicity is at higher risk for developing KP. Although KP may manifest in persons of any age, it usually appears within the first decade of life and is more common in young children.[10] In most cases, the condition gradually improves before age 30; however, it can persist longer.[8]
## See also[edit]
* Ichthyosis linearis circumflexa
## References[edit]
1. ^ a b c d e f g h i j k l m Wang, JF; Orlow, SJ (July 2018). "Keratosis Pilaris and its Subtypes: Associations, New Molecular and Pharmacologic Etiologies, and Therapeutic Options". American Journal of Clinical Dermatology. 19 (5): 733–757. doi:10.1007/s40257-018-0368-3. PMID 30043128. S2CID 51715063.
2. ^ a b c d e Panchaprateep R, Tanus A, Tosti A (March 2015). "Clinical, dermoscopic, and histopathologic features of body hair disorders". Journal of the American Academy of Dermatology. 72 (5): 890–900. doi:10.1016/j.jaad.2015.01.024. PMID 25748313.
3. ^ Alai, Nili. "Keratosis Pilaris (KP)". MedicineNet. Retrieved 2008-10-06.
4. ^ a b c d e Berman, Kevin. "Keratosis pilaris". MedlinePlus. Retrieved 2008-06-19.
5. ^ Liu F, Yang Y, Zheng Y, Liang YH, Zeng K (September 2018). "Mutation and expression of ABCA12 in keratosis pilaris and nevus comedonicus". Molecular Medicine Reports. 18 (3): 3153–3158. doi:10.3892/mmr.2018.9342. PMC 6102636. PMID 30066947.
6. ^ a b c Hwang S, Schwartz RA (September 2008). "Keratosis pilaris: a common follicular hyperkeratosis". Cutis. 82 (3): 177–80. PMID 18856156.
7. ^ "Keratosis pilaris ("chicken skin")". NHS Choices. 2017-10-24.
8. ^ a b c d "Keratosis pilaris: Self-management". Mayo Clinic.
9. ^ Mayo Clinic Staff. "Tests and Diagnosis". Mayo Clinic. Retrieved 2013-10-31
10. ^ a b Alai, Nili; Arash Michael Saemi; Raul Del Rosario. "Keratosis Pilaris". eMedicine. Medscape (WebMD). and "Pathophysiology". Medscape (WebMD). Retrieved February 5, 2018.
11. ^ a b Yosipovitch G, DeVore A, Dawn A (June 2007). "Obesity and the skin: skin physiology and skin manifestations of obesity". Journal of the American Academy of Dermatology. 56 (6): 901–16. doi:10.1016/j.jaad.2006.12.004. PMID 17504714.
12. ^ Mayo Clinic Staff (5 January 2016). "Self-management - Keratosis Pilaris". mayoclinic.org. Mayo Foundation. Retrieved 11 April 2016.
13. ^ Schoch, Jennifer J.; Tollefson, Megha M.; Witman, Patricia; Davis, Dawn M. R. (July 2016). "Successful Treatment of Keratosis Pilaris Rubra with Pulsed Dye Laser". Pediatric Dermatology. 33 (4): 443–446. doi:10.1111/pde.12892. ISSN 1525-1470. PMID 27282957. S2CID 32102128.
## External links[edit]
Wikimedia Commons has media related to Keratosis pilaris.
Classification
D
* ICD-9-CM: 757.39
* OMIM: 604093
* MeSH: C537412
* DiseasesDB: 32387
External resources
* MedlinePlus: 001462
* eMedicine: ped/1246 derm/211
* The American Academy of Dermatology
* The American Osteopathic College of Dermatology \- Article on keratosis pilaris
* v
* t
* e
Diseases of the skin and appendages by morphology
Growths
Epidermal
* Wart
* Callus
* Seborrheic keratosis
* Acrochordon
* Molluscum contagiosum
* Actinic keratosis
* Squamous-cell carcinoma
* Basal-cell carcinoma
* Merkel-cell carcinoma
* Nevus sebaceous
* Trichoepithelioma
Pigmented
* Freckles
* Lentigo
* Melasma
* Nevus
* Melanoma
Dermal and
subcutaneous
* Epidermal inclusion cyst
* Hemangioma
* Dermatofibroma (benign fibrous histiocytoma)
* Keloid
* Lipoma
* Neurofibroma
* Xanthoma
* Kaposi's sarcoma
* Infantile digital fibromatosis
* Granular cell tumor
* Leiomyoma
* Lymphangioma circumscriptum
* Myxoid cyst
Rashes
With
epidermal
involvement
Eczematous
* Contact dermatitis
* Atopic dermatitis
* Seborrheic dermatitis
* Stasis dermatitis
* Lichen simplex chronicus
* Darier's disease
* Glucagonoma syndrome
* Langerhans cell histiocytosis
* Lichen sclerosus
* Pemphigus foliaceus
* Wiskott–Aldrich syndrome
* Zinc deficiency
Scaling
* Psoriasis
* Tinea (Corporis
* Cruris
* Pedis
* Manuum
* Faciei)
* Pityriasis rosea
* Secondary syphilis
* Mycosis fungoides
* Systemic lupus erythematosus
* Pityriasis rubra pilaris
* Parapsoriasis
* Ichthyosis
Blistering
* Herpes simplex
* Herpes zoster
* Varicella
* Bullous impetigo
* Acute contact dermatitis
* Pemphigus vulgaris
* Bullous pemphigoid
* Dermatitis herpetiformis
* Porphyria cutanea tarda
* Epidermolysis bullosa simplex
Papular
* Scabies
* Insect bite reactions
* Lichen planus
* Miliaria
* Keratosis pilaris
* Lichen spinulosus
* Transient acantholytic dermatosis
* Lichen nitidus
* Pityriasis lichenoides et varioliformis acuta
Pustular
* Acne vulgaris
* Acne rosacea
* Folliculitis
* Impetigo
* Candidiasis
* Gonococcemia
* Dermatophyte
* Coccidioidomycosis
* Subcorneal pustular dermatosis
Hypopigmented
* Tinea versicolor
* Vitiligo
* Pityriasis alba
* Postinflammatory hyperpigmentation
* Tuberous sclerosis
* Idiopathic guttate hypomelanosis
* Leprosy
* Hypopigmented mycosis fungoides
Without
epidermal
involvement
Red
Blanchable
Erythema
Generalized
* Drug eruptions
* Viral exanthems
* Toxic erythema
* Systemic lupus erythematosus
Localized
* Cellulitis
* Abscess
* Boil
* Erythema nodosum
* Carcinoid syndrome
* Fixed drug eruption
Specialized
* Urticaria
* Erythema (Multiforme
* Migrans
* Gyratum repens
* Annulare centrifugum
* Ab igne)
Nonblanchable
Purpura
Macular
* Thrombocytopenic purpura
* Actinic/solar purpura
Papular
* Disseminated intravascular coagulation
* Vasculitis
Indurated
* Scleroderma/morphea
* Granuloma annulare
* Lichen sclerosis et atrophicus
* Necrobiosis lipoidica
Miscellaneous
disorders
Ulcers
*
Hair
* Telogen effluvium
* Androgenic alopecia
* Alopecia areata
* Systemic lupus erythematosus
* Tinea capitis
* Loose anagen syndrome
* Lichen planopilaris
* Folliculitis decalvans
* Acne keloidalis nuchae
Nail
* Onychomycosis
* Psoriasis
* Paronychia
* Ingrown nail
Mucous
membrane
* Aphthous stomatitis
* Oral candidiasis
* Lichen planus
* Leukoplakia
* Pemphigus vulgaris
* Mucous membrane pemphigoid
* Cicatricial pemphigoid
* Herpesvirus
* Coxsackievirus
* Syphilis
* Systemic histoplasmosis
* Squamous-cell carcinoma
* v
* t
* e
Congenital malformations and deformations of integument / skin disease
Genodermatosis
Congenital ichthyosis/
erythrokeratodermia
AD
* Ichthyosis vulgaris
AR
* Congenital ichthyosiform erythroderma: Epidermolytic hyperkeratosis
* Lamellar ichthyosis
* Harlequin-type ichthyosis
* Netherton syndrome
* Zunich–Kaye syndrome
* Sjögren–Larsson syndrome
XR
* X-linked ichthyosis
Ungrouped
* Ichthyosis bullosa of Siemens
* Ichthyosis follicularis
* Ichthyosis prematurity syndrome
* Ichthyosis–sclerosing cholangitis syndrome
* Nonbullous congenital ichthyosiform erythroderma
* Ichthyosis linearis circumflexa
* Ichthyosis hystrix
EB
and related
* EBS
* EBS-K
* EBS-WC
* EBS-DM
* EBS-OG
* EBS-MD
* EBS-MP
* JEB
* JEB-H
* Mitis
* Generalized atrophic
* JEB-PA
* DEB
* DDEB
* RDEB
* related: Costello syndrome
* Kindler syndrome
* Laryngoonychocutaneous syndrome
* Skin fragility syndrome
Ectodermal dysplasia
* Naegeli syndrome/Dermatopathia pigmentosa reticularis
* Hay–Wells syndrome
* Hypohidrotic ectodermal dysplasia
* Focal dermal hypoplasia
* Ellis–van Creveld syndrome
* Rapp–Hodgkin syndrome/Hay–Wells syndrome
Elastic/Connective
* Ehlers–Danlos syndromes
* Cutis laxa (Gerodermia osteodysplastica)
* Popliteal pterygium syndrome
* Pseudoxanthoma elasticum
* Van der Woude syndrome
Hyperkeratosis/
keratinopathy
PPK
* diffuse: Diffuse epidermolytic palmoplantar keratoderma
* Diffuse nonepidermolytic palmoplantar keratoderma
* Palmoplantar keratoderma of Sybert
* Meleda disease
* syndromic
* connexin
* Bart–Pumphrey syndrome
* Clouston's hidrotic ectodermal dysplasia
* Vohwinkel syndrome
* Corneodermatoosseous syndrome
* plakoglobin
* Naxos syndrome
* Scleroatrophic syndrome of Huriez
* Olmsted syndrome
* Cathepsin C
* Papillon–Lefèvre syndrome
* Haim–Munk syndrome
* Camisa disease
* focal: Focal palmoplantar keratoderma with oral mucosal hyperkeratosis
* Focal palmoplantar and gingival keratosis
* Howel–Evans syndrome
* Pachyonychia congenita
* Pachyonychia congenita type I
* Pachyonychia congenita type II
* Striate palmoplantar keratoderma
* Tyrosinemia type II
* punctate: Acrokeratoelastoidosis of Costa
* Focal acral hyperkeratosis
* Keratosis punctata palmaris et plantaris
* Keratosis punctata of the palmar creases
* Schöpf–Schulz–Passarge syndrome
* Porokeratosis plantaris discreta
* Spiny keratoderma
* ungrouped: Palmoplantar keratoderma and spastic paraplegia
* desmoplakin
* Carvajal syndrome
* connexin
* Erythrokeratodermia variabilis
* HID/KID
Other
* Meleda disease
* Keratosis pilaris
* ATP2A2
* Darier's disease
* Dyskeratosis congenita
* Lelis syndrome
* Dyskeratosis congenita
* Keratolytic winter erythema
* Keratosis follicularis spinulosa decalvans
* Keratosis linearis with ichthyosis congenita and sclerosing keratoderma syndrome
* Keratosis pilaris atrophicans faciei
* Keratosis pilaris
Other
* cadherin
* EEM syndrome
* immune system
* Hereditary lymphedema
* Mastocytosis/Urticaria pigmentosa
* Hailey–Hailey
see also Template:Congenital malformations and deformations of skin appendages, Template:Phakomatoses, Template:Pigmentation disorders, Template:DNA replication and repair-deficiency disorder
Developmental
anomalies
Midline
* Dermoid cyst
* Encephalocele
* Nasal glioma
* PHACE association
* Sinus pericranii
Nevus
* Capillary hemangioma
* Port-wine stain
* Nevus flammeus nuchae
Other/ungrouped
* Aplasia cutis congenita
* Amniotic band syndrome
* Branchial cyst
* Cavernous venous malformation
* Accessory nail of the fifth toe
* Bronchogenic cyst
* Congenital cartilaginous rest of the neck
* Congenital hypertrophy of the lateral fold of the hallux
* Congenital lip pit
* Congenital malformations of the dermatoglyphs
* Congenital preauricular fistula
* Congenital smooth muscle hamartoma
* Cystic lymphatic malformation
* Median raphe cyst
* Melanotic neuroectodermal tumor of infancy
* Mongolian spot
* Nasolacrimal duct cyst
* Omphalomesenteric duct cyst
* Poland anomaly
* Rapidly involuting congenital hemangioma
* Rosenthal–Kloepfer syndrome
* Skin dimple
* Superficial lymphatic malformation
* Thyroglossal duct cyst
* Verrucous vascular malformation
* Birthmark
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Keratosis pilaris
|
c0263383
| 8,137 |
wikipedia
|
https://en.wikipedia.org/wiki/Keratosis_pilaris
| 2021-01-18T18:35:46 |
{"mesh": ["C537412"], "umls": ["C0263383"], "icd-9": ["757.39"], "wikidata": ["Q1637035"]}
|
## Clinical Features
Platelets of humans, as well as of other primates and some cats, aggregate in response to adrenaline. Scrutton et al. (1981) observed decreased responsiveness to adrenaline in platelets from 5 apparently normal, unrelated human subjects. In 4 of these, the trait was shown to be inherited (with 1 instance of male-to-male transmission). In 3 of the probands and their affected relatives, depressed responsiveness to collagen and vasopressin, but normal responsiveness to ADP and thrombin, was observed. Mixing experiments excluded the existence of a circulating inhibitor of platelet function. None of the 'affected' persons had a bleeding disorder.
Inheritance \- Autosomal dominant Lab \- Defective platelet aggregation in response to adrenaline Heme \- No bleeding disorder ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
PLATELET RESPONSIVENESS TO ADRENALINE, DEPRESSED
|
c1868200
| 8,138 |
omim
|
https://www.omim.org/entry/173580
| 2019-09-22T16:36:08 |
{"omim": ["173580"]}
|
A number sign (#) is used with this entry because of evidence that early infantile epileptic encephalopathy-71 (EIEE71) is caused by homozygous or compound heterozygous mutation in the glutaminase gene (GLS; 138280) on chromosome 2q32.
For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
Description
Early infantile epileptic encephalopathy-71 (EIEE71) is characterized by early neonatal refractory seizures, respiratory failure, structural brain abnormalities and cerebral edema, with death within weeks after birth. Glutamine levels are significantly increased (z score 3.2-11.7). Three patients have been described (summary by Rumping et al., 2018).
Clinical Features
Rumping et al. (2018) reported 3 patients from 2 unrelated families who presented soon after birth with severe hypotonia and respiratory insufficiency requiring mechanical ventilation. The patients developed early-onset refractory seizures associated with a burst-suppression pattern on EEG, and brain imaging showed a simplified frontal gyral pattern with an anterior-to-posterior gradient and deep and subcortical white matter involvement. Gliosis, loss of basal ganglia volume, and cerebral edema were also present. All patients died within the first weeks of life. In 1 of the families, a sib had previously died of a similar disorder. Glutamine levels were significantly increased in the affected individuals (z scores 3.2 and 11.7).
Inheritance
The transmission pattern of EIEE71 in the families reported by Rumping et al. (2018) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 3 patients from 2 unrelated families with EIEE71, Rumping et al. (2018) identified homozygous or compound heterozygous mutations in the GLS gene (138280.0001-138280.0003). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The mutations were predicted to result in a loss of function, and newborn Guthrie cards from affected individuals in 1 family (family 2) showed significantly increased glutamine, consistent with a loss of GLS function.
INHERITANCE \- Autosomal recessive RESPIRATORY \- Respiratory insufficiency \- Respiratory failure MUSCLE, SOFT TISSUES \- Hypotonia, neonatal, severe NEUROLOGIC Central Nervous System \- Epileptic encephalopathy \- Lack of spontaneous movements \- Seizures, refractory, early-onset \- EEG shows burst-suppression pattern \- Brain imaging shows simplified gyral structure \- Volume loss of the brain LABORATORY ABNORMALITIES \- Newborn Guthrie card shows increased glutamine MISCELLANEOUS \- Onset at birth \- Death in first weeks of life \- Two unrelated families have been reported (last curated February 2019) MOLECULAR BASIS \- Caused by mutation in the glutaminase gene (GLS, 138280.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 71
|
None
| 8,139 |
omim
|
https://www.omim.org/entry/618328
| 2019-09-22T15:42:29 |
{"omim": ["618328"], "synonyms": ["Alternative titles", "GLUTAMINASE DEFICIENCY WITH NEONATAL EPILEPTIC ENCEPHALOPATHY"]}
|
A rare cerebellar malformation characterized by congenital complete or partial fusion of the cerebellar hemispheres, dentate nuclei, and middle cerebellar peduncles, and complete or partial absence of the vermis. It may occur as an isolated anomaly or together with other malformations of the brain and is associated with variable clinical manifestations including developmental delay, ataxia, dysarthria, oculomotor abnormalities, seizures, and involuntary head movements, among others.
## Epidemiology
The exact prevalence is unknown. A value of 4 in 3000 paediatric magnetic resonance imaging (MRI) scans was reported in one study and around 50 cases have been reported in the literature.
## Clinical description
Other cerebral anomalies often associated with RS include fusion of the dentate nuclei, deformation of the fourth ventricle, and fusion of the cerebral peduncles. Supratentorial findings include hydrocephalus, fusion of the thalami, anomalies of the corpus callosum and septo-optic dysplasia. Extracerebral anomalies are also sometimes present: mild dysmorphism, anomalies of the hands and/or feet; ophthalmologic, cardiac, renal, uterine and anal abnormalities and Hirschsprung disease. Syndromic associations have also been reported: Gomez-Lopez-Hernandez syndrome (or cerebellotrigeminodermal dysplasia), RS with bilateral temporoparietal alopecia, anaesthesia in the trigeminal territory and craniostenosis.
## Etiology
The aetiology remains to be confirmed.
## Management and treatment
Management is symptomatic, requiring medical, educative, psychological and social care.
## Prognosis
The neurological prognosis is variable, ranging from a normal IQ to more or less severe intellectual deficit with ataxia, dysarthria, strabismus and/or nystagmus, behavioural problems (such as obsessive-compulsive and auto-aggressive behaviour).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Rhombencephalosynapsis
|
c1866130
| 8,140 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=59315
| 2021-01-23T17:11:41 |
{"umls": ["C1866130"], "icd-10": ["Q04.3"]}
|
A number sign (#) is used with this entry because the phenotype results from mutation in the MTRNR2 gene (561010).
A dose-related toxic effect of chloramphenicol occurs presumably in all persons who take enough. In about 1 in every 19,000 persons taking the drug, an idiosyncratic reaction occurs. Human cells resistant to chloramphenicol have been isolated, by using ethidium bromide as a mutagen specific for mitochondrial DNA (Spolsky and Eisenstadt, 1972). That chloramphenicol resistance is determined by the mitochondrial DNA (i.e., is cytoplasmically inherited) is demonstrated by the fact that enucleated resistant cells transmit the character to sensitive cells when fused with them (Bunn et al., 1974; Wallace et al., 1975). The fusion of enucleated cytoplasts from cells carrying mitochondrial markers with intact cells, resulting in the formation of viable 'cybrids', is a useful approach to the study of mitochondrial genetics. Sendai virus and polyethylene glycol facilitate formation of cybrids, just as they facilitate fusion of whole cells. By the above method, Mitchell and Attardi (1978) demonstrated transfer of chloramphenicol resistance, presumably mitochondrial, in a human cell line.
Fine (1978) gave a general discussion of mitochondrial inheritance. 'The sensitivity of mitochondria to many antibiotics may reflect a legacy of mitochondria as the evolutionary descendants of bacteria which invaded the primitive pre-eukaryotes aeons ago.' Of 3 recorded instances of familial chloramphenicol toxicity, 2 involved identical twins and the other involved a man and his sister's daughter (Nagao and Mauer, 1969; Rosenthal and Blackman, 1965). Thus, all were examples of matroclinous (matrilineal) ties, consistent with mitochondrial inheritance. Because of the likelihood that mutation occurs in mitochondrial DNA, the mitochondria of any individual are, presumably, heterogeneous; the cell or the individual is heteroplasmic. During successive somatic cell divisions of ontogeny, sorting out of the different mitochondria probably occurs so that 'homochondric' cell lines might develop. ('Homoplasmic' is the term more generally used.) One would expect a graded phenotype determined by mitochondrial genes, if one assumes that there are multiple types of mitochondria and that the proportions and absolute numbers of the several types vary between cells, tissues and organisms. This is consistent, as pointed out by Fine (1978), with the wide range of severity of chloramphenicol sensitivity and the fact that bone marrow cells from persons who have recovered from chloramphenicol toxicity are less sensitive than normal controls when exposed in vitro (Howell et al., 1975). Only cells with a preponderance of resistant mitochondria may persist. In yeast, monosubstitutions in mtDNA have been identified in correlation with antibiotic resistance. Kearsey and Craig (1981) found sequence differences in a chloramphenicol-resistant cell line derived from HeLa. Mutation occurred at a position similar to that altered in a yeast mutant, namely, a highly conserved region of the large (16S) rRNA gene (see Anderson et al., 1981). The precise nucleotide changes in 16S rRNA (MTRNR2; 561010) are known, e.g., a T-to-C transition in nucleotide 2991 (Blanc et al., 1981; Kearsey and Craig, 1981) and a C-to-A transversion in nucleotide 2939 (Blanc et al., 1981). Howell and Lee (1989) demonstrated a variety of point mutations in the mitochondrial chromosome responsible for chloramphenicol resistance in mice.
As stated earlier, unusual sensitivity to chloramphenicol or streptomycin (580000), resulting from mitochondrial mutations, is perhaps not surprising because of the origin of the mitochondrion as a bacterium-like organism that took up a symbiotic intracellular existence. Indeed, Altmann (1890), who first recognized mitochondria as ubiquitous intracellular structures, thought that they were elementary organisms living inside cells because of their resemblance to bacteria. Benda (1898) observed intracellular thread-like structures during spermatogenesis and introduced the name mitochondrion, meaning 'thread' (mitos) and 'granule' (chondrion).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
CHLORAMPHENICOL TOXICITY
|
c1838989
| 8,141 |
omim
|
https://www.omim.org/entry/515000
| 2019-09-22T16:16:50 |
{"omim": ["515000"], "synonyms": ["Alternative titles", "ANEMIA, CHLORAMPHENICOL-INDUCED"]}
|
For a discussion of genetic heterogeneity of optic atrophy, see OPA1 (165500).
Clinical Features
Went et al. (1975) described a kindred in which 8 males in 7 sibships of 3 generations (connected through females) had optic atrophy with early childhood onset and slow progression. Volker-Dieben et al. (1974) documented in detail the ophthalmologic and neurologic features. Affected males were distributed in 6 sibships of 3 generations. Affected males, in several instances at least, had mental retardation and showed minor abnormalities on neurologic examination: hyperactive knee jerks, absent ankle jerks, extensor plantar reflexes, dysarthria, tremor, dysdiadochokinesia, difficulty with tandem gait, etc. No abnormality was described in obligatory heterozygotes. Volker-Dieben et al. (1974) were of the view that the disorder was different from that reported by Lysen and Oliver (1947) in 8 males over 4 generations. Assink et al. (1997) noted that the optic discs in the affected members of the Dutch family were sharply outlined and completely pale. They also noted very slow progression of visual acuity.
Katz et al. (2006) reported 6 males affected with optic atrophy in a 3-generation family from Idaho. Affected individuals had decreased visual acuity from early childhood; visual acuities ranged from 20/30 to 20/100, and all had significant optic nerve pallor. Obligate female carriers were clinically unaffected. No other neurologic abnormalities were observed in any family members.
Mapping
In a Dutch family with optic atrophy, Volker-Dieben et al. (1974) excluded close linkage with the Xg blood group.
Assink et al. (1997) conducted linkage studies on the Dutch kindred described by Volker-Dieben et al. (1974) and Went et al. (1975). Close linkage without recombination was found at the MAOB locus (309860); maximum lod score = 4.19. Multipoint linkage analysis placed the gene in the Xp11.4-p11.21 interval between markers DXS993 and DXS991, whereas any other localization along the X chromosome could be excluded.
Preliminary linkage analysis in the family reported by Katz et al. (2006) yielded a maximum lod score of 1.81 for DXS1204, DXS991, and DXS7132, suggesting linkage to the OPA2 locus. The extended disease haplotype of this family was distinct from that of the family described by Assink et al. (1997).
Eyes \- Early onset optic atrophy Neuro \- Mental retardation \- Hyperactive knee jerks \- Absent ankle jerks \- Extensor plantar reflexes \- Dysarthria \- Tremor \- Dysdiadochokinesis \- Abnormal tandem gait Inheritance \- X-linked ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
OPTIC ATROPHY 2
|
c1839576
| 8,142 |
omim
|
https://www.omim.org/entry/311050
| 2019-09-22T16:17:30 |
{"doid": ["5723"], "mesh": ["C537125"], "omim": ["311050"], "orphanet": ["98890"], "synonyms": ["Alternative titles", "OPTIC ATROPHY, X-LINKED", "OPTIC ATROPHY, NON-LEBER TYPE, WITH EARLY ONSET"]}
|
Pseudopolyps
Colonic pseudopolyps of a patient with intractable ulcerative colitis. Colectomy specimen.
SpecialtyGastroenterology, Pathology
ComplicationsBowel obstruction
Differential diagnosisFamilial adenomatous polyposis
Pseudopolyps are projecting masses of scar tissue that develop from granulation tissue during the healing phase in repeated cycle of ulceration (especially in inflammatory bowel disease). Inflammatory tissue without malignant potential,[1] pseudopolyps may represent either regenerating mucosal islands between areas of ulceration, edematous polypoid tags or granulation tissue covered by epithelium.[2] There are reported cases when localized giant pseudopolyposis resulted in intestinal obstruction.[3]
Residual mucosal islands between ulcerated and denuded areas of mucosa may have a polypoid appearance and are referred to as pseudopolyps.[4] Polyposis syndromes, such as familial adenomatous polyposis, could give rise to a similar appearance on imaging, although the clinical presentation would differ from that of inflammatory pseudopolyposis.[5]
Numerous, confluent ulcerations with bulging of the edematous residual mucosa determine a cobblestone appearance at endoscopy.[6][7]
## References[edit]
1. ^ Ulcerative Colitis: Pseudopolyps; http://www.endoatlas.com/ib_uc_03.html
2. ^ Joffe, N (November 1977). "Localised giant pseudopolyposis secondary to ulcerative or granulomatous colitis". Clinical Radiology. 28 (6): 609–16. doi:10.1016/s0009-9260(77)80038-x. PMID 589915.
3. ^ Freeman, A. H.; Berridge, F. R.; Dick, A. P.; Gleeson, J. A.; Zeegen, R. (1978). "Pseudopolyposis in Crohn's disease". The British Journal of Radiology. 51 (610): 782–787. doi:10.1259/0007-1285-51-610-782. PMID 709018.
4. ^ Sinha, Rakesh; Rajiah, Prabhakar; Murphy, Paul; Hawker, Peter; Sanders, Scott (2009). "Utility of High-Resolution MR Imaging in Demonstrating Transmural Pathologic Changes in Crohn Disease". Radiographics. 29 (6): 1847–1867. doi:10.1148/rg.296095503. PMID 19959525.
5. ^ Arluk, GM; Pickhardt, PJ (26 February 2004). "Images in clinical medicine. Inflammatory pseudopolyposis in Crohn's disease". The New England Journal of Medicine. 350 (9): 923. doi:10.1056/NEJMicm020629. PMID 14985490.
6. ^ Atlas of Gastroenterological Endoscopy, Crohn´s disease. http://www.endoskopischer-atlas.de/k43e.htm
7. ^ http://medical-dictionary.thefreedictionary.com/Cobblestone+Appearance
## External links[edit]
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Pseudopolyps
|
c0032568
| 8,143 |
wikipedia
|
https://en.wikipedia.org/wiki/Pseudopolyps
| 2021-01-18T18:33:14 |
{"umls": ["C0032568"], "wikidata": ["Q1488684"]}
|
## Clinical Features
In 2 Norwegian kindreds, Aagenaes et al. (1968, 1970) described a syndrome of hereditary recurrent cholestasis and lymphedema. Jaundice became evident soon after birth and recurred in episodes throughout life. Edema in the legs, which was due to hypoplasia of the lymphatic vessels, began at about school age and progressed. In 1 kindred, 16 individuals in 7 interconnected sibships appear to have been affected. One instance of affected mother and daughter may have resulted from the fact that the father was a heterozygote. Aagenaes (1974) described 2 additional unrelated families. In 1 family, with a single affected individual, the parents were first cousins once removed; in the other, nonconsanguineous family, 3 of 6 sibs were affected. Liver histology showed giant cell transformation in infancy and some fibrosis or cirrhosis in later childhood. The family reported by Sharp and Krivit (1971) was also Norwegian, living in Minnesota. Aagenaes (1974) therefore suggested the designation 'hereditary cholestasis of Norwegian type,' when cholestasis is combined with lymphedema.
Morris et al. (1997) reported an affected mother and daughter in a nonconsanguineous family of British origin. Morris et al. (1997) suggested that the most likely explanation was a de novo autosomal dominant mutation in the mother, either allelic with or at a locus distinct from that in the previously described families.
Aagenaes (1998) gave a comprehensive review of the syndrome that bears his name with a description of new cases and follow-up from infancy to adulthood. The original observations (Aagenaes et al., 1968) involved 16 patients from the southwest of Norway. The patients belonged to 7 sibships; consanguinity was frequent, and autosomal recessive inheritance was proposed. Fourteen patients had been diagnosed in Norway since 1970. Nine of these belonged to the first large family reported. Two brothers of consanguineous parents belonged to a small family described in 1974 (Aagenaes, 1974); 2 sibs and 1 other sporadic patient appeared to be unrelated to any of these other families. A complicated pedigree of the original family showing the multiple affected individuals was displayed (Figure 8). Of the 21 patients born before 1970, 11 died in early childhood. Nine of these died in early infancy, mainly of bleeding because of unavailability of vitamin K at the time. Two died of cirrhosis in later childhood. Of the patients born before 1970, 6 women and 4 men survived childhood. One woman died at the age of 50 years, and 9 were still alive at ages ranging from 30 to 61 years. There had been no new Norwegian cases identified in the previous 6 years.
Aagenaes (2001) pointed out that the common denominator of the syndrome that bears his name is a 'relatively generalized' lymphatic anomaly, suggesting that the defect resides in lymphangiogenesis.
Drivdal et al. (2006) stated that 40 Norwegian patients have been known to have cholestasis-lymphedema syndrome, of whom 25 were still alive at the date of the report. Nine died in infancy or early childhood, mainly of bleeding before vitamin K treatment was available; 4 died of cirrhosis at ages 2, 7, 8, and 50 years, respectively; and 2 died of unrelated causes in late adulthood. Of those patients still living, 3 underwent liver transplantation in infancy, and 2 had slow progression to cirrhosis. Analysis of 15 Norwegian patients over age 10 years with the disorder but without signs or symptoms of cholestasis showed significantly increased serum transaminase levels compared to controls, and albumin was decreased in older patients. Lymphedema ranged from moderate to massive. Retrospectively, it appeared that those with remission of liver disease by about 2 to 2.5 years of age showed a better prognosis. Drivdal et al. (2006) concluded that more than 50% of patients with Norwegian cholestasis-lymphedema syndrome can expect a normal life span given proper nutritional and vitamin treatment and that most patients have a relatively good prognosis compared to patients with other types of hereditary neonatal cholestasis.
Mapping
Bull et al. (2000) performed a genome screen, using DNA from 8 Norwegian patients with cholestasis-lymphedema syndrome and from 7 unaffected relatives, all from an extended pedigree. Regions potentially shared identical by descent in patients were further characterized in a larger set of Norwegian patients. The patients manifested extensive allele and haplotype sharing over a 6.6-cM region on chromosome 15 between markers D15S979 and D15S652.
INHERITANCE \- Autosomal recessive ABDOMEN Liver \- Neonatal cholestatic liver disease \- Hepatomegaly \- Cirrhosis Spleen \- Splenomegaly Gastrointestinal \- Infantile malabsorption SKIN, NAILS, & HAIR Skin \- Jaundice \- Erysipelas MUSCLE, SOFT TISSUES \- Lymphedema LABORATORY ABNORMALITIES \- Conjugated hyperbilirubinemia \- Elevated transaminases \- Elevated alkaline phosphatase \- Elevated serum bile acids \- Hyperlipidemia MISCELLANEOUS \- Onset of lymphedema before puberty \- Onset of cholestatic jaundice 2-4 weeks of age and resolved during childhood \- Recurrent cholestatic episodes in puberty, following surgery or severe trauma, and pregnancy ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
CHOLESTASIS-LYMPHEDEMA SYNDROME
|
c0268314
| 8,144 |
omim
|
https://www.omim.org/entry/214900
| 2019-09-22T16:29:45 |
{"doid": ["6691"], "mesh": ["C535330"], "omim": ["214900"], "orphanet": ["1414"], "synonyms": ["Alternative titles", "CHLS", "AAGENAES SYNDROME", "LYMPHEDEMA-CHOLESTASIS SYNDROME"]}
|
"Skin Cancer" redirects here. For the book by Robert A. Schwartz, see Skin Cancer: Recognition and Management.
Skin cancer
A basal-cell skin cancer. Note the pearly appearance and telangiectasia.
SpecialtyOncology and dermatology
SymptomsBasal-cell: painless raised area of skin that may be shiny with small blood vessel running over it or ulceration[1]
Squamous-cell: hard lump with a scaly top[2]
Melanoma: mole that has changed in size, shape, color, or has irregular edges[3]
TypesBasal-cell skin cancer (BCC), squamous-cell skin cancer (SCC), melanoma[1]
CausesUltraviolet radiation from the Sun or tanning beds[4]
Risk factorsLight skin, poor immune function[1][5]
Diagnostic methodTissue biopsy[3]
PreventionDecreasing exposure to ultraviolet radiation, sunscreen[6][7]
TreatmentSurgery, radiation therapy, fluorouracil[1]
Frequency5.6 million (2015)[8]
Deaths111,700 (2015)[9]
Skin cancers are cancers that arise from the skin. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body.[10] There are three main types of skin cancers: basal-cell skin cancer (BCC), squamous-cell skin cancer (SCC) and melanoma.[1] The first two, along with a number of less common skin cancers, are known as nonmelanoma skin cancer (NMSC).[5][11] Basal-cell cancer grows slowly and can damage the tissue around it but is unlikely to spread to distant areas or result in death.[5] It often appears as a painless raised area of skin that may be shiny with small blood vessels running over it or may present as a raised area with an ulcer.[1] Squamous-cell skin cancer is more likely to spread.[5] It usually presents as a hard lump with a scaly top but may also form an ulcer.[2] Melanomas are the most aggressive. Signs include a mole that has changed in size, shape, color, has irregular edges, has more than one color, is itchy or bleeds.[3]
More than 90% of cases are caused by exposure to ultraviolet radiation from the Sun.[4] This exposure increases the risk of all three main types of skin cancer.[4] Exposure has increased, partly due to a thinner ozone layer.[5][12] Tanning beds are another common source of ultraviolet radiation.[4] For melanomas and basal-cell cancers, exposure during childhood is particularly harmful.[6] For squamous-cell skin cancers, total exposure, irrespective of when it occurs, is more important.[4] Between 20% and 30% of melanomas develop from moles.[6] People with lighter skin are at higher risk[1][13] as are those with poor immune function such as from medications or HIV/AIDS.[5][14] Diagnosis is by biopsy.[3]
Decreasing exposure to ultraviolet radiation and the use of sunscreen appear to be effective methods of preventing melanoma and squamous-cell skin cancer.[6][7] It is not clear if sunscreen affects the risk of basal-cell cancer.[7] Nonmelanoma skin cancer is usually curable.[5] Treatment is generally by surgical removal but may, less commonly, involve radiation therapy or topical medications such as fluorouracil.[1] Immunotherapy might be the only hope for individuals with multiple malignancies such as Xeroderma Pigmentosum and Gorlin syndrome.[15] Treatment of melanoma may involve some combination of surgery, chemotherapy, radiation therapy and targeted therapy.[3] In those people whose disease has spread to other areas of the body, palliative care may be used to improve quality of life.[3] Melanoma has one of the higher survival rates among cancers, with over 86% of people in the UK and more than 90% in the United States surviving more than 5 years.[16][17]
Skin cancer is the most common form of cancer, globally accounting for at least 40% of cancer cases.[5][18] The most common type is nonmelanoma skin cancer, which occurs in at least 2–3 million people per year.[6][19] This is a rough estimate, however, as good statistics are not kept.[1] Of nonmelanoma skin cancers, about 80% are basal-cell cancers and 20% squamous-cell skin cancers.[11] Basal-cell and squamous-cell skin cancers rarely result in death.[6] In the United States, they were the cause of less than 0.1% of all cancer deaths.[1] Globally in 2012, melanoma occurred in 232,000 people and resulted in 55,000 deaths.[6] White people in Australia, New Zealand and South Africa have the highest rates of melanoma in the world.[6][20] The three main types of skin cancer have become more common in the last 20 to 40 years, especially in those areas with mostly White people.[5][6]
## Contents
* 1 Classification
* 2 Signs and symptoms
* 2.1 Basal-cell skin cancer
* 2.2 Squamous-cell skin cancer
* 2.3 Melanoma
* 2.4 Other
* 3 Causes
* 4 Pathophysiology
* 5 Diagnosis
* 6 Prevention
* 7 Treatment
* 7.1 Reconstruction
* 8 Prognosis
* 9 Epidemiology
* 9.1 Melanoma
* 9.2 Non-melanoma
* 10 References
* 11 External links
## Classification[edit]
There are three main types of skin cancer: basal-cell skin cancer (basal-cell carcinoma) (BCC), squamous-cell skin cancer (squamous-cell carcinoma) (SCC) and malignant melanoma.
Cancer Description Illustration
Basal-cell carcinoma Note the pearly translucency to fleshy color, tiny blood vessels on the surface, and sometimes ulceration which can be characteristics. The key term is translucency.
Squamous-cell skin carcinoma Commonly presents as a red, crusted, or scaly patch or bump. Often a very rapidly growing tumor.
Malignant melanoma These are commonly asymmetrical in shape and/or pigment distribution, with an irregular border, color variation, and often greater than 6 mm diameter.[21]
Basal-cell carcinomas are most commonly present on sun-exposed areas of the skin, especially the face. They rarely metastasize and rarely cause death. They are easily treated with surgery or radiation. Squamous-cell skin cancers are also common, but much less common than basal-cell cancers. They metastasize more frequently than BCCs. Even then, the metastasis rate is quite low, with the exception of SCC of the lip, ear, and in people who are immunosuppressed. Melanoma are the least frequent of the three common skin cancers. They frequently metastasize, and potentially cause death once they spread.
Less common skin cancers include: dermatofibrosarcoma protuberans, Merkel cell carcinoma, Kaposi's sarcoma, keratoacanthoma, spindle cell tumors, sebaceous carcinomas, microcystic adnexal carcinoma, Paget's disease of the breast, atypical fibroxanthoma, leiomyosarcoma, and angiosarcoma.
BCC and SCC often carry a UV-signature mutation indicating that these cancers are caused by UVB radiation via direct DNA damage. However malignant melanoma is predominantly caused by UVA radiation via indirect DNA damage. The indirect DNA damage is caused by free radicals and reactive oxygen species. Research indicates that the absorption of three sunscreen ingredients into the skin, combined with a 60-minute exposure to UV, leads to an increase of free radicals in the skin, if applied in too little quantity and too infrequently.[22] However, the researchers add that newer creams often do not contain these specific compounds, and that the combination of other ingredients tends to retain the compounds on the surface of the skin. They also add that frequent re-application reduces the risk of radical formation.
## Signs and symptoms[edit]
There are a variety of different skin cancer symptoms. These include changes in the skin that do not heal, ulcering in the skin, discolored skin, and changes in existing moles, such as jagged edges to the mole and enlargement of the mole.
### Basal-cell skin cancer[edit]
Basal-cell skin cancer (BCC) usually presents as a raised, smooth, pearly bump on the sun-exposed skin of the head, neck, torso or shoulders. Sometimes small blood vessels (called telangiectasia) can be seen within the tumor. Crusting and bleeding in the center of the tumor frequently develops. It is often mistaken for a sore that does not heal. This form of skin cancer is the least deadly, and with proper treatment can be completely eliminated, often without significant scarring.
### Squamous-cell skin cancer[edit]
Squamous-cell skin cancer (SCC) is commonly a red, scaling, thickened patch on sun-exposed skin. Some are firm hard nodules and dome shaped like keratoacanthomas. Ulceration and bleeding may occur. When SCC is not treated, it may develop into a large mass. Squamous-cell is the second most common skin cancer. It is dangerous, but not nearly as dangerous as a melanoma.
### Melanoma[edit]
Most melanoma consist of various colours from shades of brown to black. A small number of melanoma are pink, red or fleshy in colour; these are called amelanotic melanoma and tend to be more aggressive. Warning signs of malignant melanoma include change in the size, shape, color or elevation of a mole. Other signs are the appearance of a new mole during adulthood or pain, itching, ulceration, redness around the site, or bleeding at the site. An often-used mnemonic is "ABCDE", where A is for "asymmetrical", B for "borders" (irregular: "Coast of Maine sign"), C for "color" (variegated), D for "diameter" (larger than 6 mm – the size of a pencil eraser) and E for "evolving."[23][24]
### Other[edit]
Merkel cell carcinomas are most often rapidly growing, non-tender red, purple or skin colored bumps that are not painful or itchy. They may be mistaken for a cyst or another type of cancer.[25]
## Causes[edit]
Ultraviolet radiation from sun exposure is the primary environmental cause of skin cancer.[26][27][28] This can occur in professions such as farming. Other risk factors that play a role include:
* Light skin color [27]
* Age [27]
* Smoking tobacco[27]
* HPV infections increase the risk of squamous-cell skin cancer.[27]
* Some genetic syndromes[27] including congenital melanocytic nevi syndrome which is characterized by the presence of nevi (birthmarks or moles) of varying size which are either present at birth, or appear within 6 months of birth. Nevi larger than 20 mm (3/4") in size are at higher risk for becoming cancerous.
* Chronic non-healing wounds.[27] These are called Marjolin's ulcers based on their appearance, and can develop into squamous-cell skin cancer.
* Ionizing radiation such as X-rays, environmental carcinogens, and artificial UV radiation (e.g. tanning beds).[27] It is believed that tanning beds are the cause of hundreds of thousands of basal and squamous-cell skin cancer.[29] The World Health Organization now places people who use artificial tanning beds in its highest risk category for skin cancer.[30] Alcohol consumption, specifically excessive drinking increase the risk of sunburns.[31]
* The use of many immunosuppressive medications increases the risk of skin cancer. Cyclosporin A, a calcineurin inhibitor for example increases the risk approximately 200 times, and azathioprine about 60 times.[32]
* Deliberate exposure of sensitive skin not normally exposed to sunlight during alternative wellness behaviors such as perenium sunning.
## Pathophysiology[edit]
Micrograph of melanoma, fine-needle aspiration (FNA), field stain
A malignant epithelial tumor that primarily originates in the epidermis, in squamous mucosa or in areas of squamous metaplasia is referred to as a squamous-cell carcinoma.[33]
Macroscopically, the tumor is often elevated, fungating, or may be ulcerated with irregular borders. Microscopically, tumor cells destroy the basement membrane and form sheets or compact masses which invade the subjacent connective tissue (dermis). In well differentiated carcinomas, tumor cells are pleomorphic/atypical, but resembling normal keratinocytes from prickle layer (large, polygonal, with abundant eosinophilic (pink) cytoplasm and central nucleus).[33]
Their disposal tends to be similar to that of normal epidermis: immature/basal cells at the periphery, becoming more mature to the centre of the tumor masses. Tumor cells transform into keratinized squamous cells and form round nodules with concentric, laminated layers, called "cell nests" or "epithelial/keratinous pearls". The surrounding stroma is reduced and contains inflammatory infiltrate (lymphocytes). Poorly differentiated squamous carcinomas contain more pleomorphic cells and no keratinization.[33]
A molecular factor involved in the disease process is mutation in gene PTCH1 that plays an important role in the Sonic hedgehog signaling pathway.[34]
## Diagnosis[edit]
Diagnosis is by biopsy and histopathological examination.[3]
Non-invasive skin cancer detection methods include photography, dermatoscopy, sonography, confocal microscopy, Raman spectroscopy, fluorescence spectroscopy, terahertz spectroscopy, optical coherence tomography, the multispectral imaging technique, thermography, electrical bio-impedance, tape stripping and computer-aided analysis.[35]
Dermatoscopy may be useful in diagnosing basal cell carcinoma in addition to skin inspection.[36]
There is insufficient evidence that optical coherence tomography (OCT) is useful in diagnosing melanoma or squamous cell carcinoma. OCT may have a role in diagnosing basal cell carcinoma but more data is needed to support this.[37]
Computer-assisted diagnosis devices have been developed that analyze images from a dermatoscope or spectroscopy and can be used by a diagnostician to aid in the detection of skin cancer. CAD systems have been found to be highly sensitive in the detection of melanoma, but have a high false-positive rate. There is not yet enough evidence to recommend CAD as compared to traditional diagnostic methods.[38]
High-frequency ultrasound (HFUS) is of unclear usefulness in the diagnosis of skin cancer.[39] There is insufficient evidence for reflectance confocal microscopy to diagnose basal cell or squamous cell carcinoma or any other skin cancers.[40]
## Prevention[edit]
Sunscreen is effective and thus recommended to prevent melanoma[41] and squamous-cell carcinoma.[42] There is little evidence that it is effective in preventing basal-cell carcinoma.[43] Other advice to reduce rates of skin cancer includes avoiding sunburning, wearing protective clothing, sunglasses and hats, and attempting to avoid sun exposure or periods of peak exposure.[44] The U.S. Preventive Services Task Force recommends that people between 9 and 25 years of age be advised to avoid ultraviolet light.[45]
The risk of developing skin cancer can be reduced through a number of measures including decreasing indoor tanning and mid day sun exposure, increasing the use of sunscreen,[45] and avoiding the use of tobacco products.
There is insufficient evidence either for or against screening for skin cancers.[46] Vitamin supplements and antioxidant supplements have not been found to have an effect in prevention.[47] Evidence for reducing melanoma risk from dietary measures is tentative, with some supportive epidemiological evidence, but no clinical trials.[48]
Zinc oxide and titanium oxide are often used in sun screen to provide broad protection from UVA and UVB ranges.[49]
Eating certain foods may decrease the risk of sunburns but this is much less than the protection provided by sunscreen.[50]
A meta-analysis of skin cancer prevention in high risk individuals found evidence that topical application of T4N5 liposome lotion reduced the rate of appearance of basal cell carcinomas in people with xeroderma pigmentosum, and that acitretin taken by mouth may have a skin protective benefit in people following kidney transplant.[51]
## Treatment[edit]
Treatment is dependent on the specific type of cancer, location of the cancer, age of the person, and whether the cancer is primary or a recurrence. For a small basal-cell cancer in a young person, the treatment with the best cure rate (Mohs surgery or CCPDMA) might be indicated. In the case of an elderly frail man with multiple complicating medical problems, a difficult to excise basal-cell cancer of the nose might warrant immunotherapy[52] or radiation therapy (slightly lower cure rate) or no treatment at all. Topical chemotherapy might be indicated for large superficial basal-cell carcinoma for good cosmetic outcome, whereas it might be inadequate for invasive nodular basal-cell carcinoma or invasive squamous-cell carcinoma.[citation needed] In general, melanoma is poorly responsive to radiation or chemotherapy.
For low-risk disease, radiation therapy (external beam radiotherapy[53] or brachytherapy), topical chemotherapy (imiquimod or 5-fluorouracil) and cryotherapy (freezing the cancer off) can provide adequate control of the disease; all of them, however, may have lower overall cure rates than certain type of surgery. Other modalities of treatment such as photodynamic therapy, epidermal radioisotope therapy,[54] topical chemotherapy, electrodesiccation and curettage can be found in the discussions of basal-cell carcinoma and squamous-cell carcinoma.
Mohs' micrographic surgery (Mohs surgery) is a technique used to remove the cancer with the least amount of surrounding tissue and the edges are checked immediately to see if tumor is found. This provides the opportunity to remove the least amount of tissue and provide the best cosmetically favorable results. This is especially important for areas where excess skin is limited, such as the face. Cure rates are equivalent to wide excision. Special training is required to perform this technique. An alternative method is CCPDMA and can be performed by a pathologist not familiar with Mohs surgery.
In the case of disease that has spread (metastasized), further surgical procedures or chemotherapy may be required.[55]
Treatments for metastatic melanoma include biologic immunotherapy agents ipilimumab, pembrolizumab, and nivolumab; BRAF inhibitors, such as vemurafenib and dabrafenib; and a MEK inhibitor trametinib.[56]
### Reconstruction[edit]
Currently, surgical excision is the most common form of treatment for skin cancers. The goal of reconstructive surgery is restoration of normal appearance and function. The choice of technique in reconstruction is dictated by the size and location of the defect. Excision and reconstruction of facial skin cancers is generally more challenging due to presence of highly visible and functional anatomic structures in the face.
When skin defects are small in size, most can be repaired with simple repair where skin edges are approximated and closed with sutures. This will result in a linear scar. If the repair is made along a natural skin fold or wrinkle line, the scar will be hardly visible. Larger defects may require repair with a skin graft, local skin flap, pedicled skin flap, or a microvascular free flap. Skin grafts and local skin flaps are by far more common than the other listed choices.
Skin grafting is patching of a defect with skin that is removed from another site in the body. The skin graft is sutured to the edges of the defect, and a bolster dressing is placed atop the graft for seven to ten days, to immobilize the graft as it heals in place. There are two forms of skin grafting: split thickness and full thickness. In a split thickness skin graft, a shaver is used to shave a layer of skin from the abdomen or thigh. The donor site regenerates skin and heals over a period of two weeks. In a full thickness skin graft, a segment of skin is totally removed and the donor site needs to be sutured closed.[57]
Split thickness grafts can be used to repair larger defects, but the grafts are inferior in their cosmetic appearance. Full thickness skin grafts are more acceptable cosmetically. However, full thickness grafts can only be used for small or moderate sized defects.
Local skin flaps are a method of closing defects with tissue that closely matches the defect in color and quality. Skin from the periphery of the defect site is mobilized and repositioned to fill the deficit. Various forms of local flaps can be designed to minimize disruption to surrounding tissues and maximize cosmetic outcome of the reconstruction. Pedicled skin flaps are a method of transferring skin with an intact blood supply from a nearby region of the body. An example of such reconstruction is a pedicled forehead flap for repair of a large nasal skin defect. Once the flap develops a source of blood supply form its new bed, the vascular pedicle can be detached.[58]
## Prognosis[edit]
The mortality rate of basal-cell and squamous-cell carcinoma is around 0.3%, causing 2000 deaths per year in the US. In comparison, the mortality rate of melanoma is 15–20% and it causes 6500 deaths per year.[59]:29,31 Even though it is much less common, malignant melanoma is responsible for 75% of all skin cancer-related deaths.[60]
The survival rate for people with melanoma depends upon when they start treatment. The cure rate is very high when melanoma is detected in early stages, when it can easily be removed surgically. The prognosis is less favorable if the melanoma has spread to other parts of the body.[61] As of 2003 the overall five-year cure rate with Mohs' micrographic surgery was around 95 percent for recurrent basal cell carcinoma.[62]
Australia and New Zealand exhibit one of the highest rates of skin cancer incidence in the world, almost four times the rates registered in the United States, the UK and Canada. Around 434,000 people receive treatment for non-melanoma skin cancers and 10,300 are treated for melanoma. Melanoma is the most common type of cancer in people between 15–44 years in both countries. The incidence of skin cancer has been increasing.[63] The incidence of melanoma among Auckland residents of European descent in 1995 was 77.7 cases per 100,000 people per year, and was predicted to increase in the 21st century because of "the effect of local stratospheric ozone depletion and the time lag from sun exposure to melanoma development."[64]
## Epidemiology[edit]
Age-standardized death from melanoma and other skin cancers per 100,000 inhabitants in 2004[65]
no data
<0.7
0.7–1.4
1.4–2.1
2.1–2.8
2.8–3.5
3.5–4.2
4.2–4.9
4.9–5.6
5.6–6.3
6.3–7
7–7.7
>7.7
Skin cancers result in 80,000 deaths a year as of 2010, 49,000 of which are due to melanoma and 31,000 of which are due to non-melanoma skin cancers.[66] This is up from 51,000 in 1990.[66]
More than 3.5 million cases of skin cancer are diagnosed annually in the United States, which makes it the most common form of cancer in that country. One in five Americans will develop skin cancer at some point of their lives. The most common form of skin cancer is basal-cell carcinoma, followed by squamous cell carcinoma. Unlike for other cancers, there exists no basal and squamous cell skin cancers registry in the United States.[67]
### Melanoma[edit]
In the US in 2008, 59,695 people were diagnosed with melanoma, and 8,623 people died from it.[68] In Australia more than 12,500 new cases of melanoma are reported each year, out of which more than 1,500 die from the disease. Australia has the highest per capita incidence of melanoma in the world.[69]
Although the rates of many cancers in the United States is falling, the incidence of melanoma keeps growing, with approximately 68,729 melanomas diagnosed in 2004 according to reports of the National Cancer Institute.[70]
Melanoma is the fifth most common cancer in the UK (around 13,300 people were diagnosed with melanoma in 2011), and the disease accounts for 1% all cancer deaths (around 2,100 people died in 2012).[71]
### Non-melanoma[edit]
Approximately 2,000 people die from basal or squamous cell skin cancers (non-melanoma skin cancers) in the United States each year. The rate has dropped in recent years. Most of the deaths happen to people who are elderly and might not have seen a doctor until the cancer had spread; and people with immune system disorders.[67]
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## External links[edit]
Classification
D
* ICD-10: C43-C44
* ICD-9-CM: 172, 173
* ICD-O: 8010–8720
* MeSH: D012878
External resources
* MedlinePlus: 001442
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* Pigmented hairy epidermal nevus syndrome
* Systematized epidermal nevus
* Phakomatosis pigmentokeratotica
Other nevus
* Nevus unius lateris
* Patch blue nevus
* Unilateral palmoplantar verrucous nevus
* Zosteriform speckled lentiginous nevus
Ungrouped
* Cutaneous horn
* v
* t
* e
Skin cancer of the dermis
Dermis
* Benign fibrous histiocytoma/dermatofibrosarcoma protuberans
* Dermatofibrosarcoma protuberans
Subcutaneous
tumors
Connective and
vascular
* see Template:Soft tissue tumors and sarcomas, Template:Vascular tumors, Template:Myeloid malignancy (for mastocytosis)
Other
urogenital:
* Hirsuties coronae glandis
neuro:
* Solitary neurofibroma
* Cutaneous meningioma
* Ganglioneuroma
* Schwannoma
* Palisaded encapsulated neuroma
* Infantile neuroblastoma
* Neuroma cutis
bone/cartilage:
* Chordoma
* Extraskeletal chondroma
nevus:
* Nevus anemicus
* Nevus flammeus
* Nevus flammeus nuchae
* Nevus lipomatosus superficialis
* Nevus oligemicus
* Connective tissue nevus
* Midline nevus flammeus
* Porokeratotic eccrine ostial and dermal duct nevus
histiocytoma:
* Pleomorphic undifferentiated sarcoma
* Plexiform fibrohistiocytic tumor
* Progressive nodular histiocytoma
* Teratoma
* Adenoma sebaceum
* Metastatic carcinoma
* Giant-cell tumor of the tendon sheath
* Glomus tumor
* Granular cell tumor
* Carcinoid
* Desmoid tumor
* Neurothekeoma
* Angiokeratoma
* Zosteriform metastasis
* Keratinizing metaplasia
* Epithelioid sarcoma
* v
* t
* e
Cancers of skin and associated structures
Glands
Sweat gland
Eccrine
* Papillary eccrine adenoma
* Eccrine carcinoma
* Eccrine nevus
* Syringofibroadenoma
* Spiradenoma
Apocrine
* Cylindroma
* Dermal cylindroma
* Syringocystadenoma papilliferum
* Papillary hidradenoma
* Hidrocystoma
* Apocrine gland carcinoma
* Apocrine nevus
Eccrine/apocrine
* Syringoma
* Hidradenoma or Acrospiroma/Hidradenocarcinoma
* Ceruminous adenoma
Sebaceous gland
* Nevus sebaceous
* Muir–Torre syndrome
* Sebaceous carcinoma
* Sebaceous adenoma
* Sebaceoma
* Sebaceous nevus syndrome
* Sebaceous hyperplasia
* Mantleoma
Hair
* Pilomatricoma/Malignant pilomatricoma
* Trichoepithelioma
* Multiple familial trichoepithelioma
* Solitary trichoepithelioma
* Desmoplastic trichoepithelioma
* Generalized trichoepithelioma
* Trichodiscoma
* Trichoblastoma
* Fibrofolliculoma
* Trichilemmoma
* Trichilemmal carcinoma
* Proliferating trichilemmal cyst
* Giant solitary trichoepithelioma
* Trichoadenoma
* Trichofolliculoma
* Dilated pore
* Isthmicoma
* Fibrofolliculoma
* Perifollicular fibroma
* Birt–Hogg–Dubé syndrome
Hamartoma
* Basaloid follicular hamartoma
* Folliculosebaceous cystic hamartoma
* Folliculosebaceous-apocrine hamartoma
Nails
* Neoplasms of the nailbed
A medical condition involving uncontrolled growth of skin cells
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Skin cancer
|
c0007114
| 8,145 |
wikipedia
|
https://en.wikipedia.org/wiki/Skin_cancer
| 2021-01-18T18:53:49 |
{"gard": ["10421"], "mesh": ["D012878"], "umls": ["C0007114"], "icd-9": ["172", "173"], "icd-10": ["C44", "C43"], "wikidata": ["Q192102"]}
|
Hooft et al. (1962), of Ghent, Belgium, described a family in which 2 sisters had retarded physical development, erythematosquamous eruption, opaque leukonychia, mental retardation, and low serum lipids. One had tapetoretinal degeneration. Acanthocytosis and disturbance of intestinal absorption were not present; see abetalipoproteinemia (200100).
Eyes \- Tapetoretinal degeneration Neuro \- Mental retardation Inheritance \- Autosomal recessive Nails \- Opaque leukonychia Lab \- Low serum lipids Growth \- Retarded physical development Skin \- Erythematosquamous eruption ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
HOOFT DISEASE
|
c0268479
| 8,146 |
omim
|
https://www.omim.org/entry/236300
| 2019-09-22T16:27:04 |
{"mesh": ["C535329"], "omim": ["236300"]}
|
"GERD" redirects here. For other uses, see Gerd.
Gastroesophageal reflux disease
Other namesBritish: Gastro-oesophageal reflux disease (GORD);[1] gastric reflux disease, acid reflux disease, reflux, gastroesophageal reflux
X-ray showing radiocontrast from the stomach (white material below diaphragm) entering the esophagus (three vertical collections of white material in the mid-line of the chest) due to severe reflux
Pronunciation
* /ɡæstroʊɪˌsɒfəˈdʒiːəl ˈriːflʌks/[2][3][4] GERD /ɡɜːrd/
SpecialtyGastroenterology
SymptomsTaste of acid, heartburn, bad breath, chest pain, breathing problems[5]
ComplicationsEsophagitis, esophageal strictures, Barrett's esophagus[5]
DurationLong term[5][6]
CausesInadequate closure of the lower esophageal sphincter[5]
Risk factorsObesity, pregnancy, smoking, hiatal hernia, taking certain medicines[5]
Diagnostic methodGastroscopy, upper GI series, esophageal pH monitoring, esophageal manometry[5]
Differential diagnosisPeptic ulcer disease, esophageal cancer, esophageal spasm, angina[7]
TreatmentLifestyle changes, medications, surgery[5]
MedicationAntacids, H2 receptor blockers, proton pump inhibitors, prokinetics[5][8]
Frequency~15% (Western populations)[8]
Gastroesophageal reflux disease (GERD), also known as acid reflux, is a long-term condition in which stomach contents rise up into the esophagus, resulting in either symptoms or complications.[5][6] Symptoms include the taste of acid in the back of the mouth, heartburn, bad breath, chest pain, regurgitation, breathing problems, and wearing away of the teeth.[5] Complications include esophagitis, esophageal stricture, and Barrett's esophagus.[5]
Risk factors include obesity, pregnancy, smoking, hiatal hernia, and taking certain medicines.[5] Medications involved may include antihistamines, calcium channel blockers, antidepressants and sleeping pills.[5] Acid reflux is due to poor closure of the lower esophageal sphincter, which is at the junction between the stomach and the esophagus.[5] Diagnosis among those who do not improve with simpler measures may involve gastroscopy, upper GI series, esophageal pH monitoring, or esophageal manometry.[5]
Treatment options include lifestyle changes; medications; and sometimes surgery for those who do not improve with the first two measures.[5] Lifestyle changes include not lying down for three hours after eating, raising the head of the bed, losing weight, avoiding foods which result in symptoms, and stopping smoking.[5] Medications include antacids, H2 receptor blockers, proton pump inhibitors, and prokinetics.[5][8]
In the Western world, between 10 and 20% of the population is affected by GERD.[8] Occasional gastroesophageal reflux without troublesome symptoms or complications is even more common.[5] The classic symptoms of GERD were first described in 1925, when Friedenwald and Feldman commented on heartburn and its possible relationship to a hiatal hernia.[9] In 1934 gastroenterologist Asher Winkelstein described reflux and attributed the symptoms to stomach acid.[10]
## Contents
* 1 Signs and symptoms
* 1.1 Adults
* 1.2 Children
* 1.3 Mouth
* 1.4 Barrett's esophagus
* 2 Causes
* 3 Diagnosis
* 3.1 Endoscopy
* 3.2 Severity
* 3.3 Differential diagnosis
* 4 Treatment
* 4.1 Lifestyle changes
* 4.2 Medications
* 4.2.1 Proton-pump inhibitors
* 4.2.2 Antacids
* 4.2.3 Other agents
* 4.3 Surgery
* 4.4 Special populations
* 4.4.1 Pregnancy
* 4.4.2 Babies
* 5 Epidemiology
* 6 History
* 7 Research
* 8 See also
* 9 References
* 10 Further reading
## Signs and symptoms[edit]
### Adults[edit]
The most common symptoms of GERD in adults are an acidic taste in the mouth, regurgitation, and heartburn.[11] Less common symptoms include pain with swallowing/sore throat, increased salivation (also known as water brash), nausea,[12] chest pain, and coughing.
GERD sometimes causes injury of the esophagus. These injuries may include one or more of the following:
* Reflux esophagitis – inflammation of esophageal epithelium which can cause ulcers near the junction of the stomach and esophagus
* Esophageal strictures – the persistent narrowing of the esophagus caused by reflux-induced inflammation
* Barrett's esophagus – intestinal metaplasia (changes of the epithelial cells from squamous to intestinal columnar epithelium) of the distal esophagus[13]
* Esophageal adenocarcinoma – a form of cancer[12]
GERD sometimes causes injury of the larynx (LPR).[14][15] Other complications can include aspiration pneumonia.[16]
### Children[edit]
GERD may be difficult to detect in infants and children, since they cannot describe what they are feeling and indicators must be observed. Symptoms may vary from typical adult symptoms. GERD in children may cause repeated vomiting, effortless spitting up, coughing, and other respiratory problems, such as wheezing. Inconsolable crying, refusing food, crying for food and then pulling off the bottle or breast only to cry for it again, failure to gain adequate weight, bad breath, and burping are also common. Children may have one symptom or many; no single symptom is universal in all children with GERD.
Of the estimated 4 million babies born in the US each year, up to 35% of them may have difficulties with reflux in the first few months of their lives, known as 'spitting up'.[17] Most children will outgrow their reflux by their first birthday. However, a small number will not, particularly when a family history of GERD is present.[citation needed]
### Mouth[edit]
Frontal view of severe tooth erosion in GERD.[18]
Severe tooth erosion in GERD.[18]
Acid reflux into the mouth can cause breakdown of the enamel, especially on the inside surface of the teeth. A dry mouth, acid or burning sensation in the mouth, bad breath and redness of the palate may occur.[19] Other not so common symptoms of GERD include difficulty in swallowing, water brash which is flooding of the mouth with saliva, chronic cough, hoarse voice, nausea and vomiting.[18]
Signs of enamel erosion are the appearance of a smooth, silky-glazed, sometimes dull, enamel surfaces with the absence of perikymata, together with intact enamel along the gum margin.[20] It will be evident in people with restorations as tooth structure typically dissolves much faster than the restorative material, causing it to seem as if it “stands above” the surrounding tooth structure.[21]
### Barrett's esophagus[edit]
Main article: Barrett's esophagus
GERD may lead to Barrett's esophagus, a type of intestinal metaplasia,[13] which is in turn a precursor condition for esophageal cancer. The risk of progression from Barrett's to dysplasia is uncertain, but is estimated at about 20% of cases.[22] Due to the risk of chronic heartburn progressing to Barrett's, EGD every five years is recommended for people with chronic heartburn, or who take drugs for chronic GERD.[23]
## Causes[edit]
A comparison of a healthy condition to GERD
Acid reflux is due to poor closure of the lower esophageal sphincter, which is at the junction between the stomach and the esophagus.[5] Factors that can contribute to GERD:
* Hiatal hernia, which increases the likelihood of GERD due to mechanical and motility factors.[24][25]
* Obesity: increasing body mass index is associated with more severe GERD.[26] In a large series of 2,000 patients with symptomatic reflux disease, it has been shown that 13% of changes in esophageal acid exposure is attributable to changes in body mass index.[27]
Factors that have been linked with GERD, but not conclusively:
* Obstructive sleep apnea[28][29]
* Gallstones, which can impede the flow of bile into the duodenum, which can affect the ability to neutralize gastric acid[medical citation needed]
In 1999, a review of existing studies found that, on average, 40% of GERD patients also had H. pylori infection.[30] The eradication of H. pylori can lead to an increase in acid secretion,[31] leading to the question of whether H. pylori-infected GERD patients are any different than non-infected GERD patients. A double-blind study, reported in 2004, found no clinically significant difference between these two types of patients with regard to the subjective or objective measures of disease severity.[32]
## Diagnosis[edit]
Endoscopic image of 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 or difficulty swallowing.
The diagnosis of GERD is usually made when typical symptoms are present.[33] Reflux can be present in people without symptoms and the diagnosis requires both symptoms or complications and reflux of stomach content.[34]
Other investigations may include esophagogastroduodenoscopy (EGD). Barium swallow X-rays should not be used for diagnosis.[33] Esophageal manometry is not recommended for use in diagnosis, being recommended only prior to surgery.[33] Ambulatory esophageal pH monitoring may be useful in those who do not improve after PPIs and is not needed in those in whom Barrett's esophagus is seen.[33] Investigation for H. pylori is not usually needed.[33]
The current gold standard for diagnosis of GERD is esophageal pH monitoring. It is the most objective test to diagnose the reflux disease and allows monitoring GERD patients in their response to medical or surgical treatment. One practice for diagnosis of GERD is a short-term treatment with proton-pump inhibitors, with improvement in symptoms suggesting a positive diagnosis. Short-term treatment with proton-pump inhibitors may help predict abnormal 24-hr pH monitoring results among patients with symptoms suggestive of GERD.[35]
### Endoscopy[edit]
Endoscopy, the looking down into the stomach with a fibre-optic scope, is not routinely needed if the case is typical and responds to treatment.[33] It is recommended when people either do not respond well to treatment or have alarm symptoms, including dysphagia, anemia, blood in the stool (detected chemically), wheezing, weight loss, or voice changes.[33] Some physicians advocate either once-in-a-lifetime or 5- to 10-yearly endoscopy for people with longstanding GERD, to evaluate the possible presence of dysplasia or Barrett's esophagus.[36]
Biopsies performed during gastroscopy may show:
* Edema and basal hyperplasia (nonspecific inflammatory changes)
* Lymphocytic inflammation (nonspecific)
* Neutrophilic inflammation (usually due to reflux or Helicobacter gastritis)
* Eosinophilic inflammation (usually due to reflux): The presence of intraepithelial eosinophils may suggest a diagnosis of eosinophilic esophagitis (EE) if eosinophils are present in high enough numbers. Less than 20 eosinophils per high-power microscopic field in the distal esophagus, in the presence of other histologic features of GERD, is more consistent with GERD than EE.[37]
* Goblet cell intestinal metaplasia or Barrett's esophagus
* Elongation of the papillae
* Thinning of the squamous cell layer
* Dysplasia
* Carcinoma
Reflux changes may not be erosive in nature, leading to "nonerosive reflux disease".
### Severity[edit]
Severity may be documented with the Johnson-DeMeester's scoring system:[38] 0 - None 1 - Minimal - occasional episodes 2 - Moderate - medical therapy visits 3 - Severe - interfere with daily activities
### Differential diagnosis[edit]
Other causes of chest pain such as heart disease should be ruled out before making the diagnosis.[33] Another kind of acid reflux, which causes respiratory and laryngeal signs and symptoms, is called laryngopharyngeal reflux (LPR) or "extraesophageal reflux disease" (EERD). Unlike GERD, LPR rarely produces heartburn, and is sometimes called silent reflux.[citation needed]
## Treatment[edit]
The treatments for GERD may include food choices, lifestyle changes, medications, and possibly surgery. Initial treatment is frequently with a proton-pump inhibitor such as omeprazole.[33] In some cases, a person with GERD symptoms can manage them by taking over-the-counter drugs.[39][40][41] This is often safer and less expensive than taking prescription drugs.[39] Some guidelines recommend trying to treat symptoms with an H2 antagonist before using a proton-pump inhibitor because of cost and safety concerns.[39]
### Lifestyle changes[edit]
Certain foods may promote GERD, but most dietary interventions have little effect.[42] Some evidence suggests that reduced sugar intake and increased fiber intake can help.[43] Avoidance of specific foods and not eating before lying down are recommended for those having GERD symptoms.[34] Foods that may precipitate GERD include coffee, alcohol, chocolate, fatty foods, acidic foods, and spicy foods.[34]
Weight loss may be effective in reducing the severity and frequency of symptoms.[44] Elevating the head of the entire bed with blocks, or using a wedge pillow that elevates the individual's shoulders and head, may inhibit GERD when lying down.[45] Although moderate exercise may improve symptoms in people with GERD, vigorous exercise may worsen them.[42]
Abstinence from smoking or alcohol does not appear to significantly relieve symptoms.[44]
### Medications[edit]
Main article: Drugs for acid-related disorders
The primary medications used for GERD are proton-pump inhibitors, H2 receptor blockers and antacids with or without alginic acid.[8] The use of acid suppression therapy is a common response to GERD symptoms and many people get more of this kind of treatment than their case merits.[39][46][47][48][49][50] The overuse of acid suppression is a problem because of the side effects and costs.[39][47][48][49][50]
#### Proton-pump inhibitors[edit]
Proton-pump inhibitors (PPIs), such as omeprazole, are the most effective, followed by H2 receptor blockers, such as ranitidine.[34] If a once daily PPI is only partially effective they may be used twice a day.[34] They should be taken one half to one hour before a meal.[33] There is no significant difference between PPIs.[33] When these medications are used long term, the lowest effective dose should be taken.[34] They may also be taken only when symptoms occur in those with frequent problems.[33] H2 receptor blockers lead to roughly a 40% improvement.[51]
#### Antacids[edit]
The evidence for antacids is weaker with a benefit of about 10% (NNT=13) while a combination of an antacid and alginic acid (such as Gaviscon) may improve symptoms 60% (NNT=4).[51] Metoclopramide (a prokinetic) is not recommended either alone or in combination with other treatments due to concerns around adverse effects.[8][34] The benefit of the prokinetic mosapride is modest.[8]
#### Other agents[edit]
Sucralfate has a similar effectiveness to H2 receptor blockers; however, sucralfate needs to be taken multiple times a day, thus limiting its use.[8] Baclofen, an agonist of the GABAB receptor, while effective, has similar issues of needing frequent dosing in addition to greater adverse effects compared to other medications.[8]
### Surgery[edit]
The standard surgical treatment for severe GERD is the Nissen fundoplication. In this procedure, the upper part of the stomach is wrapped around the lower esophageal sphincter to strengthen the sphincter and prevent acid reflux and to repair a hiatal hernia.[52] It is recommended only for those who do not improve with PPIs.[33] Quality of life is improved in the short term compared to medical therapy, but there is uncertainty in the benefits over surgery versus long-term medical management with proton pump inhibitors.[53] When comparing different fundoplication techniques, partial posterior fundoplication surgery is more effective than partial anterior fundoplication surgery,[54] and partial fundoplication has better outcomes than total fundoplication.[55]
Esophagogastric dissociation is an alternative procedure that is sometimes used to treat neurologically impaired children with GERD.[56][57] Preliminary studies have shown it may have a lower failure rate[58] and a lower incidence of recurrent reflux.[57]
In 2012 the U.S. Food and Drug Administration (FDA) approved a device called the LINX, which consists of a series of metal beads with magnetic cores that are placed surgically around the lower esophageal sphincter, for those with severe symptoms that do not respond to other treatments. Improvement of GERD symptoms is similar to those of the Nissen fundoplication, although there is no data regarding long-term effects. Compared to Nissen fundoplication procedures, the procedure has shown a reduction in complications such as gas bloat syndrome that commonly occur.[59] Adverse responses include difficulty swallowing, chest pain, vomiting, and nausea. Contraindications that would advise against use of the device are patients who are or may be allergic to titanium, stainless steel, nickel, or ferrous iron materials. A warning advises that the device should not be used by patients who could be exposed to, or undergo, magnetic resonance imaging (MRI) because of serious injury to the patient and damage to the device.[60]
In those with symptoms that do not improve with PPIs surgery known as transoral incisionless fundoplication may help.[61] Benefits may last for up to six years.[62]
### Special populations[edit]
#### Pregnancy[edit]
In pregnancy, dietary modifications and lifestyle changes may be attempted, but often have little effect. Calcium-based antacids are recommended if these changes are not effective. Aluminum- and magnesium hydroxide -based antacids are also safe, as is ranitidine[63] and PPIs.[33]
#### Babies[edit]
Babies may see relief with smaller, more frequent feedings, more frequent burping during feedings, holding baby in upright position 30 minutes after feedings, keep baby's head elevated while laying on the back, remove milk and soy from mothers diet or feed milk protein free formula.[64] They may also be treated with medicines such as ranitidine or proton pump inhibitors.[65] Proton pump inhibitors however have not been found to be effective in this population and there is a lack of evidence for safety.[66]
## Epidemiology[edit]
In Western populations, GERD affects approximately 10% to 20% of the population and 0.4% newly develop the condition.[8] For instance, an estimated 3.4 million to 6.8 million Canadians are GERD sufferers. The prevalence rate of GERD in developed nations is also tightly linked with age, with adults aged 60 to 70 being the most commonly affected.[67] In the United States 20% of people have symptoms in a given week and 7% every day.[8] No data support sex predominance with regard to GERD.[medical citation needed]
## History[edit]
An obsolete treatment is vagotomy ("highly selective vagotomy"), the surgical removal of vagus nerve branches that innervate the stomach lining. This treatment has been largely replaced by medication. Vagotomy by itself tended to worsen contraction of the pyloric sphincter of the stomach, and delayed stomach emptying. Historically, vagotomy was combined with pyloroplasty or gastroenterostomy to counter this problem.[citation needed]
## Research[edit]
A number of endoscopic devices have been tested to treat chronic heartburn.
* Endocinch, puts stitches in the lower esophogeal sphincter (LES) to create small pleats to help strengthen the muscle. However, long-term results were disappointing, and the device is no longer sold by Bard.[68]
* Stretta procedure, uses electrodes to apply radio-frequency energy to the LES. A 2015 systematic review and meta-analysis in response to the systematic review (no meta-analysis) conducted by SAGES did not support the claims that Stretta was an effective treatment for GERD.[69] A 2012 systematic review found that it improves GERD symptoms.[70]
* NDO Surgical Plicator creates a plication, or fold, of tissue near the gastroesophageal junction, and fixates the plication with a suture-based implant. The company ceased operations in mid-2008, and the device is no longer on the market.
* Transoral incisionless fundoplication, which uses a device called Esophyx, may be effective.[71]
## See also[edit]
* Esophageal motility disorder
* Esophageal motility study
## References[edit]
1. ^ Carroll, Will (14 October 2016). Gastroenterology & Nutrition: Prepare for the MRCPCH. Key Articles from the Paediatrics & Child Health journal. Elsevier Health Sciences. p. 130. ISBN 9780702070921. "Gastro-oesophageal reflux disease (GORD) is defined as 'gastrooesophageal reflux' associated with complications including oesophagitis..."
2. ^ "Definition of "gastro-" - Collins American English Dictionary". Archived from the original on 8 December 2015.
3. ^ "Definition of "esophagus" - Collins American English Dictionary". Archived from the original on 8 December 2015.
4. ^ "reflux noun - Definition, pictures, pronunciation and usage notes - Oxford Advanced American Dictionary at OxfordLearnersDictionaries.com". Archived from the original on 8 December 2015.
5. ^ a b c d e f g h i j k l m n o p q r s t "Acid Reflux (GER & GERD) in Adults". National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). 5 November 2015. Archived from the original on 22 February 2020. Retrieved 21 February 2020.
6. ^ a b Kahrilas PJ, Shaheen NJ, Vaezi MF (October 2008). "American Gastroenterological Association Institute technical review on the management of gastroesophageal reflux disease". Gastroenterology. 135 (4): 1392–1413, 1413.e1–5. doi:10.1053/j.gastro.2008.08.044. PMID 18801365.
7. ^ Kahan, Scott (2008). In a Page: Medicine. Lippincott Williams & Wilkins. p. 124. ISBN 9780781770354. Archived from the original on 8 September 2017.
8. ^ a b c d e f g h i j k Hershcovici T, Fass R (April 2011). "Pharmacological management of GERD: where does it stand now?". Trends in Pharmacological Sciences. 32 (4): 258–64. doi:10.1016/j.tips.2011.02.007. PMID 21429600.
9. ^ Granderath, Frank Alexander; Kamolz, Thomas; Pointner, Rudolph (2006). Gastroesophageal Reflux Disease: Principles of Disease, Diagnosis, and Treatment. Springer Science & Business Media. p. 161. ISBN 9783211323175.
10. ^ Arcangelo, Virginia Poole; Peterson, Andrew M. (2006). Pharmacotherapeutics for Advanced Practice: A Practical Approach. Lippincott Williams & Wilkins. p. 372. ISBN 9780781757843.
11. ^ Zajac P, Holbrook A, Super ME, et al. (March–April 2013). "An overview: Current clinical guidelines for the evaluation, diagnosis, treatment, and management of dyspepsia". Osteopathic Family Physician. 5 (2): 79–85. doi:10.1016/j.osfp.2012.10.005.
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13. ^ a b Shaheen NJ, Falk GW, Iyer PG, et al. (January 2016). "ACG Clinical Guideline: Diagnosis and Management of Barrett's Esophagus". Am. J. Gastroenterol. 111 (1): 30–50, quiz 51. doi:10.1038/ajg.2015.322. PMID 26526079. S2CID 2274838.
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20. ^ Lussi A, Jaeggi T (March 2008). "Erosion--diagnosis and risk factors". Clinical Oral Investigations. 12 Suppl 1: S5–13. doi:10.1007/s00784-007-0179-z. ISSN 1432-6981. PMC 2238777. PMID 18228059.
21. ^ Donovan T (2009). "Dental erosion". Journal of Esthetic and Restorative Dentistry. 21 (6): 359–364. doi:10.1111/j.1708-8240.2009.00291.x. ISSN 1708-8240. PMID 20002921.
22. ^ and Barrett's Esophagus. Retrieved on 1 February 2009.
23. ^ "Patient information: Barrett's esophagus (Beyond the Basics)". June 2009. Archived from the original on 9 September 2017.
24. ^ Sontag SJ (1999). "Defining GERD". Yale J Biol Med. 72 (2–3): 69–80. PMC 2579007. PMID 10780568.
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27. ^ Ayazi S, Hagen JA, Chan LS, et al. (August 2009). "Obesity and gastroesophageal reflux: quantifying the association between body mass index, esophageal acid exposure, and lower esophageal sphincter status in a large series of patients with reflux symptoms". J. Gastrointest. Surg. 13 (8): 1440–7. doi:10.1007/s11605-009-0930-7. PMC 2710497. PMID 19475461.
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33. ^ a b c d e f g h i j k l m n Katz PO, Gerson LB, Vela MF (March 2013). "Guidelines for the diagnosis and management of gastroesophageal reflux disease". American Journal of Gastroenterology. 108 (3): 308–28. doi:10.1038/ajg.2012.444. PMID 23419381.
34. ^ a b c d e f g Kahrilas PJ, Shaheen NJ, Vaezi MF, et al. (October 2008). "American Gastroenterological Association Medical Position Statement on the management of gastroesophageal reflux disease". Gastroenterology. 135 (4): 1383–91, 1391.e1–5. doi:10.1053/j.gastro.2008.08.045. PMID 18789939. Lay summary.
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45. ^ "Can a Specially Designed Body Pillow Prevent Your Acid Reflux?". Cleveland Clinic, Digestive Health Team. 16 June 2017.
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48. ^ a b Heidelbaugh JJ, Kim AH, Chang R, Walker PC (2012). "Overutilization of proton-pump inhibitors: What the clinician needs to know". Therapeutic Advances in Gastroenterology. 5 (4): 219–232. doi:10.1177/1756283X12437358. PMC 3388523. PMID 22778788.
49. ^ a b Forgacs I, Loganayagam A (2008). "Overprescribing proton pump inhibitors". BMJ. 336 (7634): 2–3. doi:10.1136/bmj.39406.449456.BE. PMC 2174763. PMID 18174564.
50. ^ a b McKay AB, Wall D (2008). "Overprescribing PPIs: An old problem". BMJ. 336 (7636): 109.1–109. doi:10.1136/bmj.39458.462338.3A. PMC 2206261. PMID 18202040.
51. ^ a b Tran T, Lowry AM, El-Serag HB (2007). "Meta-analysis: the efficacy of over-the-counter gastro-oesophageal reflux disease drugs". Aliment Pharmacol Ther. 25 (2): 143–53. doi:10.1111/j.1365-2036.2006.03135.x. PMID 17229239. S2CID 24358990.
52. ^ Abbas AE, Deschamps C, Cassivi SD, et al. (2004). "The role of laparoscopic fundoplication in Barrett's esophagus". Annals of Thoracic Surgery. 77 (2): 393–6. doi:10.1016/S0003-4975(03)01352-3. PMID 14759403.
53. ^ Garg SK, Gurusamy KS (November 2015). "Laparoscopic fundoplication surgery versus medical management for gastro-oesophageal reflux disease (GORD) in adults". Cochrane Database of Systematic Reviews (11): CD003243. doi:10.1002/14651858.CD003243.pub3. PMID 26544951.
54. ^ Kurian AA, Bhayani N, Sharata A, et al. (January 2013). "Partial anterior vs partial posterior fundoplication following transabdominal esophagocardiomyotomy for achalasia of the esophagus: meta-regression of objective postoperative gastroesophageal reflux and dysphagia". JAMA Surg. 148 (1): 85–90. doi:10.1001/jamasurgery.2013.409. PMID 23324843.
55. ^ Ramos RF, Lustosa SA, Almeida CA, et al. (October–December 2011). "Surgical treatment of gastroesophageal reflux disease: total or partial fundoplication? systematic review and meta-analysis". Arquivos de Gastroenterologia. 48 (4): 252–60. doi:10.1590/s0004-28032011000400007. PMID 22147130.
56. ^ Gatti C, di Abriola GF, Villa M, et al. (May 2001). "Esophagogastric dissociation versus fundoplication: Which is best for severely neurologically impaired children?". Journal of Pediatric Surgery. 36 (5): 677–680. doi:10.1053/jpsu.2001.22935. ISSN 0022-3468. PMID 11329564.
57. ^ a b Morabito A, Lall A, Lo Piccolo R, et al. (May 2006). "Total esophagogastric dissociation: 10 years' review". Journal of Pediatric Surgery. 41 (5): 919–922. doi:10.1016/j.jpedsurg.2006.01.013. ISSN 0022-3468. PMID 16677883.
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59. ^ Badillo R, Francis D (2014). "Diagnosis and treatment of gastroesophageal reflux disease". World Journal of Gastrointestinal Pharmacology and Therapeutics. 5 (3): 105–12. doi:10.4292/wjgpt.v5.i3.105. PMC 4133436. PMID 25133039.
60. ^ Medical Device Approvals: LINX Reflux Management System - P100049 Archived 10 November 2013 at the Wayback Machine, U.S. Food and Drug Administration, U.S. Department of Health and Human Services, Update of 17 January 2014
61. ^ Jain D, Singhal S (March 2016). "Transoral Incisionless Fundoplication for Refractory Gastroesophageal Reflux Disease: Where Do We Stand?". Clinical Endoscopy. 49 (2): 147–56. doi:10.5946/ce.2015.044. PMC 4821522. PMID 26878326.
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64. ^ "Infant acid reflux - Diagnosis and treatment - Mayo Clinic". www.mayoclinic.org. Retrieved 28 September 2018.
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66. ^ van der Pol RJ, Smits MJ, van Wijk MP, et al. (May 2011). "Efficacy of proton-pump inhibitors in children with gastroesophageal reflux disease: a systematic review". Pediatrics. 127 (5): 925–35. doi:10.1542/peds.2010-2719. PMID 21464183. S2CID 207164814.
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## Further reading[edit]
* Lichtenstein DR, Cash BD, Davila R, et al. (August 2007). "Role of endoscopy in the management of GERD" (PDF). Gastrointestinal Endoscopy. 66 (2): 219–24. doi:10.1016/j.gie.2007.05.027. PMID 17643692. Lay summary.
* Hirano I, Richter JE (March 2007). "ACG practice guidelines: esophageal reflux testing". American Journal of Gastroenterology. 102 (3): 668–85. CiteSeerX 10.1.1.619.3818. PMID 17335450.
* Katz PO, Gerson LB, Vela MF (March 2013). "Guidelines for the diagnosis and management of gastroesophageal reflux disease". American Journal of Gastroenterology. 108 (3): 308–28. doi:10.1038/ajg.2012.444. PMID 23419381.
Classification
D
* ICD-10: K21
* ICD-9-CM: 530.81
* OMIM: 109350
* MeSH: D005764
* DiseasesDB: 23596
External resources
* MedlinePlus: 000265
* eMedicine: med/857 ped/1177 radio/300
* v
* t
* e
Diseases of the digestive system
Upper GI tract
Esophagus
* Esophagitis
* Candidal
* Eosinophilic
* Herpetiform
* Rupture
* Boerhaave syndrome
* Mallory–Weiss syndrome
* UES
* Zenker's diverticulum
* LES
* Barrett's esophagus
* Esophageal motility disorder
* Nutcracker esophagus
* Achalasia
* Diffuse esophageal spasm
* Gastroesophageal reflux disease (GERD)
* Laryngopharyngeal reflux (LPR)
* Esophageal stricture
* Megaesophagus
* Esophageal intramural pseudodiverticulosis
Stomach
* Gastritis
* Atrophic
* Ménétrier's disease
* Gastroenteritis
* Peptic (gastric) ulcer
* Cushing ulcer
* Dieulafoy's lesion
* Dyspepsia
* Pyloric stenosis
* Achlorhydria
* Gastroparesis
* Gastroptosis
* Portal hypertensive gastropathy
* Gastric antral vascular ectasia
* Gastric dumping syndrome
* Gastric volvulus
* Buried bumper syndrome
* Gastrinoma
* Zollinger–Ellison syndrome
Lower GI tract
Enteropathy
Small intestine
(Duodenum/Jejunum/Ileum)
* Enteritis
* Duodenitis
* Jejunitis
* Ileitis
* Peptic (duodenal) ulcer
* Curling's ulcer
* Malabsorption: Coeliac
* Tropical sprue
* Blind loop syndrome
* Small bowel bacterial overgrowth syndrome
* Whipple's
* Short bowel syndrome
* Steatorrhea
* Milroy disease
* Bile acid malabsorption
Large intestine
(Appendix/Colon)
* Appendicitis
* Colitis
* Pseudomembranous
* Ulcerative
* Ischemic
* Microscopic
* Collagenous
* Lymphocytic
* Functional colonic disease
* IBS
* Intestinal pseudoobstruction / Ogilvie syndrome
* Megacolon / Toxic megacolon
* Diverticulitis/Diverticulosis/SCAD
Large and/or small
* Enterocolitis
* Necrotizing
* Gastroenterocolitis
* IBD
* Crohn's disease
* Vascular: Abdominal angina
* Mesenteric ischemia
* Angiodysplasia
* Bowel obstruction: Ileus
* Intussusception
* Volvulus
* Fecal impaction
* Constipation
* Diarrhea
* Infectious
* Intestinal adhesions
Rectum
* Proctitis
* Radiation proctitis
* Proctalgia fugax
* Rectal prolapse
* Anismus
Anal canal
* Anal fissure/Anal fistula
* Anal abscess
* Hemorrhoid
* Anal dysplasia
* Pruritus ani
GI bleeding
* Blood in stool
* Upper
* Hematemesis
* Melena
* Lower
* Hematochezia
Accessory
Liver
* Hepatitis
* Viral hepatitis
* Autoimmune hepatitis
* Alcoholic hepatitis
* Cirrhosis
* PBC
* Fatty liver
* NASH
* Vascular
* Budd–Chiari syndrome
* Hepatic veno-occlusive disease
* Portal hypertension
* Nutmeg liver
* Alcoholic liver disease
* Liver failure
* Hepatic encephalopathy
* Acute liver failure
* Liver abscess
* Pyogenic
* Amoebic
* Hepatorenal syndrome
* Peliosis hepatis
* Metabolic disorders
* Wilson's disease
* Hemochromatosis
Gallbladder
* Cholecystitis
* Gallstone / Cholelithiasis
* Cholesterolosis
* Adenomyomatosis
* Postcholecystectomy syndrome
* Porcelain gallbladder
Bile duct/
Other biliary tree
* Cholangitis
* Primary sclerosing cholangitis
* Secondary sclerosing cholangitis
* Ascending
* Cholestasis/Mirizzi's syndrome
* Biliary fistula
* Haemobilia
* Common bile duct
* Choledocholithiasis
* Biliary dyskinesia
* Sphincter of Oddi dysfunction
Pancreatic
* Pancreatitis
* Acute
* Chronic
* Hereditary
* Pancreatic abscess
* Pancreatic pseudocyst
* Exocrine pancreatic insufficiency
* Pancreatic fistula
Other
Hernia
* Diaphragmatic
* Congenital
* Hiatus
* Inguinal
* Indirect
* Direct
* Umbilical
* Femoral
* Obturator
* Spigelian
* Lumbar
* Petit's
* Grynfeltt-Lesshaft
* Undefined location
* Incisional
* Internal hernia
* Richter's
Peritoneal
* Peritonitis
* Spontaneous bacterial peritonitis
* Hemoperitoneum
* Pneumoperitoneum
* Medicine portal
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Gastroesophageal reflux disease
|
c0017168
| 8,147 |
wikipedia
|
https://en.wikipedia.org/wiki/Gastroesophageal_reflux_disease
| 2021-01-18T18:45:43 |
{"mesh": ["D005764"], "umls": ["C0017168"], "wikidata": ["Q223591"]}
|
A number sign (#) is used with this entry because of evidence that brain small vessel disease-1 with or without ocular anomalies (BSVD1) is caused by heterozygous mutation in the COL4A1 gene (120130) on chromosome 13q34.
Description
Brain small vessel disease-1 is an autosomal dominant disorder with variable manifestations resulting from disruption of vascular basement membranes, particularly in the cerebral vasculature. The increased fragility of these vessels render them susceptible to hemorrhage, as early as in utero or by birth trauma, although the risk remains throughout life and some patients may present in adulthood. This genetic predisposition may extend beyond hemorrhagic stroke to include retinal and renal vascular defects. Clinical features thus reflect the location and severity of the vascular defect, including impaired neurologic development or function, hemiplegia, seizures, and variable ocular anomalies. The disturbed vasculature leads to cerebral degeneration, and brain imaging typically shows 'porencephaly,' hemosiderin deposition, calcifications, lacunar infarcts, enlarged ventricles, and leukoencephalopathy. Some patients may show 'schizencephaly' on brain imaging, which is also attributed to encephaloclastic processes, such as vascular injury. The disorder shows variable penetrance and expressivity (summary by Merello et al., 2008, Gould et al., 2006; Shah et al., 2012; van der Knaap et al., 2006; Yoneda et al., 2013).
'Porencephaly' is a term used for any cavitation or cerebrospinal fluid-filled cyst in the brain. One form, called encephaloclastic, or type 1, porencephaly, is usually unilateral and results from focal destructive lesions such as fetal vascular occlusion or birth trauma. Another form, called 'schizencephalic', or type 2, porencephaly, is usually symmetric and may represent a primary defect or arrest in the development of the cerebral ventricles. Encephaloclastic porencephaly is more common (Airaksinen, 1984; Sensi et al., 1990).
### Genetic Heterogeneity of Brain Small Vessel Disease
See also BSVD2 (614483), caused by mutation in the COL4A2 gene (120090) on chromosome 13q34; and BSVD3 (618360), caused by mutation in the COLGALT1 gene (617531) on chromosome 19p13.
Clinical Features
Berg et al. (1983) provided the first description of familial porencephaly. In 1 family, a grandmother was hemiparetic; of her 9 children, 1 had seizures, 1 had hemiparesis and 1 had both, and all 3 children of her oldest son had porencephaly. In a second family, 2 sibs had porencephaly.
The same disorder appears to have been reported by Smit et al. (1984). Van der Knaap et al. (2006) provided follow-up of the family reported by Smit et al. (1984). Reexamination of the 3 affected individuals, a mother and her son and daughter, showed leukoencephalopathy in all 3 and lacunar infarcts, microbleeds, and macrobleeds in the mother. She had divergent squint at age 4 years, and CT scan at age 24 years, following the diagnosis of her children, showed porencephaly and mild diffuse hypodensity of the white matter. She had several stroke-like episodes in her forties. Examination at age 54 years showed mild expressive dysphasia, central facial paresis, and hemiparesis. Her son presented with developmental delay and hemiparesis at age 8 months. CT scan showed porencephaly, and he also had seizures, no active speech, and cognitive defects. Examination at age 33 years showed mild convergent squint, mild central facial paresis, and pseudobulbar dysfunction with masseter reflex and drooling. He had a severe spastic hemiparesis, extensor plantar responses, and polar cataracts. Her daughter developed progressive hydrocephalus at age 6 weeks. Pneumoencephalography showed dilated right lateral ventricle with midline shift. CT scan showed destruction of large parts of the right hemisphere with calcium deposits. She had seizures and delayed psychomotor development but learned to speak. Examination at age 30 years showed mild divergent squint, mild facial paresis, and pseudobulbar dysarthria. She also had hemiparesis and nuclear cataract. Electron microscopy of skin biopsies in the 2 offspring showed striking abnormalities, with about 20% of capillaries having a thickened and fragmented basement membrane. Van der Knaap et al. (2006) concluded that mutations in the COL4A1 gene are a major risk factor for microangiopathy and ischemic insult.
Airaksinen (1984) reported 2 affected sibs who were born after normal full-term pregnancies. One child was diagnosed with cerebral palsy at age 4 months after developing restlessness, abnormal movements, increased muscle tone, and seizures. Brain imaging showed a right-sided dilatation of lateral ventricles and a parietal porencephalic cyst. Her younger brother showed abnormal primitive reflexes and opisthotonos at 6 weeks of age. Brain imaging showed a right-sided cyst and dilated ventricles. Both children were severely handicapped.
Zonana et al. (1986) evaluated 2 families in which 6 persons were affected with infantile hemiplegia and 5 of these were shown to have congenital porencephaly. In the first family, a brother and sister were affected; a 42-year-old uncle had right-sided hemiplegia since infancy and a left-sided porencephalic cyst. In the second family, the proband was seen at 8.5 months of age for left-sided hemiplegia, and the father was said to have mild left-sided hemiplegia since infancy. A paternal uncle's son was said to have mild right-sided hemiplegia since infancy, but examination was impossible. Computerized tomography in patients with familial porencephaly usually shows unilateral enlargement of the lateral ventricle, although a few have had bilateral involvement. The frontal horn usually shows the most enlargement.
Vilain et al. (2002) performed cerebral imaging in 3 of 6 members of a family who had congenital hemiplegia and found porencephaly in all. Cerebral imaging in 3 asymptomatic obligate carriers in this family, including MRI in 1, was normal, indicating that cerebral imaging is unreliable as a means of detecting obligate carriers of familial porencephaly.
Aguglia et al. (2004) reported a 3-generation Italian family in which 9 individuals had type 1 porencephaly inherited in an autosomal dominant pattern. A high rate of miscarriages was reported. Four patients had a severe phenotype with unilateral porencephalic cyst, pyramidal signs, tetraparesis, limb dystonia, seizures, exotropia, visual field defects, and low IQ. The other affected members manifested some of these features. Three patients had perinatal asphyxia, and 4 patients had mitral valve prolapse. The pattern of brain abnormalities were consistent with in utero insults occurring late in the second trimester.
Vahedi et al. (2003) reported a French Caucasian family in which 6 of 8 members were affected over 3 generations by a retinal and central nervous system (CNS) disease consistent with an autosomal dominant pattern of inheritance. All 6 affected members of this family had retinal arteriolar tortuosity, including 1 member with retinal hemorrhage (Gould et al., 2006). Vahedi et al. (2003) noted hypopigmentation of the fundus. In addition, 2 of the genotypically affected persons had infantile hemiparesis, and 3 had migraine with aura. Neuroimaging showed diffuse leukoencephalopathy associated with dilated perivascular spaces in all affected family members. Microbleeds in several areas were observed on MRI scan of the brain, suggesting involvement of the cerebral vasculature in this family. Two members of the family had a fatal intracerebral hemorrhage. One died after cerebral trauma at age 33, and the second had a fatal intracerebral hemorrhage at age 40 while receiving anticoagulant therapy.
Vahedi et al. (2007) provided follow-up of the family reported by Vahedi et al. (2003) and Gould et al. (2006). During a 7-year period, 2 patients died from intracranial hemorrhage. None of 4 affected individuals reported stroke or retinal hemorrhage, and none had dementia. Follow-up brain MRI showed diffuse leukoencephalopathy in 3 of 4 patients. All had dilated perivascular spaces, and 3 had silent microbleeds mainly in the deep white matter. There was no progression of MRI signal abnormalities in severity, number, or location between baseline and follow-up imaging. The oldest affected family member was age 74 years at follow-up. Vahedi et al. (2007) concluded that mutation carriers show diversity in clinical expression and that some may remain clinically asymptomatic.
Sibon et al. (2007) reported a French Canadian family in which 5 individuals had diffuse small vessel disease of the brain and anterior chamber ocular malformations of the Axenfeld-Rieger type. The proband was a 37-year-old woman who had early onset of congenital cataract, congenital glaucoma, microcornea, peripheral opacities, and unilateral amblyopia. She developed sudden right hemiplegia at age 35, and brain imaging showed diffuse leukoencephalopathy. There were also periventricular diffuse white matter hyperintensities suggestive of old infarcts, as well as hypointensities in the basal ganglia and cerebellum suggestive of past microbleeds. She did not have retinal hemorrhages or arteriolar tortuosity. She later developed left retinal detachment, right spastic paraparesis, central facial palsy, and severe depression. The proband's daughter, brother, sister, and mother also had anterior chamber ocular anomalies and diffuse leukoencephalopathy. One patient had infantile hemiparesis and left paraventricular porencephaly. Retinal vessel tortuosity was not observed. Sibon et al. (2007) noted that Van Agtmael et al. (2005) had described a mouse Col4a1 mutant with ocular anterior segment dysgenesis consistent with Axenfeld-Rieger anomaly.
De Vries et al. (2009) reported 2 Dutch sibs with antenatal intracerebral hemorrhage and porencephaly. The sibs were born at 34 and 31 weeks' gestation, respectively. The first infant had a possible antenatal trauma at 23 weeks' gestation. Routine brain imaging in both infants at birth showed resolving intracranial hemorrhages in the left lateral ventricles with an ipsilateral porencephalic cyst and small cystic lesions in the periventricular white matter of the contralateral hemisphere. At age 18 months, the older child had right-sided hemiplegia, strabismus associated with a quadrant hemianopia, but no cataract or tortuosity of the retinal arteries. His developmental quotient was 68. At age 9 months, the second child had increased tone of the lower limbs and strabismus. Brain MRI of the mother showed mild ventricular dilatation and multiple hyperintense lesions in the periventricular white matter of both hemispheres, but no dilated perivascular spaces or evidence of microbleed. Her father had a history of transient ischemic attacks and died at age 52 years after a severe intracranial hemorrhage. MRI of the father showed porencephalic dilatation of the left lateral ventricle and hyperintense lesions in the periventricular white matter of both hemispheres. Genetic analysis identified a heterozygous mutation in the COL4A1 gene (G1580R; 120130.0011) in both sibs and the mother. De Vries et al. (2009) suggested that COL4A1 mutation carriers are at risk for intracranial hemorrhage from fetal life into adulthood and that antenatal intracerebral hemorrhage can lead to porencephaly in the newborn infant.
Coupry et al. (2010) reexamined affected members of the French Canadian family originally described by Sibon et al. (2007) and reported a similarly affected mother and daughter from an unrelated family. Additional ocular features observed in the French Canadian family included strabismus; myopia; increased intraocular pressure, which in 1 patient was intractable and resulted in glaucoma; microcornea; corneal opacities, with corneal neovascularization in 1 patient; corectopia, with polycoria in 1 patient; iridocorneal synechiae, with iridogoniodysgenesis in 1 patient; and macular hemorrhage, peripapillary atrophy, and choroidal atrophy in 1 patient. The affected mother from the second, unrelated family presented at age 47 years with acute hemiparesis due to spontaneous left lenticular nucleus hemorrhage. Two weeks later, she experienced left central facial palsy and dysarthria due to a contralateral subcortical cerebral hemorrhage. Brain MRI revealed extensive periventricular leukoencephalopathy and 2 recent cerebral hemorrhages. Eye examination showed severe hyperopia and lens opacities without visual impairment. Her 10-year-old daughter had bilateral congenital cataract, prominent Schwalbe line (posterior embryotoxon), and relative microcornea; brain MRI showed periventricular leukoencephalopathy. Both mother and daughter had a history of migraine headaches, which occurred without aura in the daughter.
Shah et al. (2012) performed a retrospective review of the clinical records of 4 unrelated families with COL4A1 mutations in which 5 affected children had recurrent childhood-onset strokes, infantile hemiplegia/spastic quadriplegia, and infantile spasms (seizures). Ocular features such as congenital cataracts, astigmatism, hypermetropia, and nystagmus were noted; 1 patient also exhibited microphthalmia and anterior segment dysgenesis. Microcephaly and developmental delay or learning difficulties were present in 3 cases. In 3 of the families, one or more family members were affected in multiple generations, with a total of 11 affected individuals identified. Shah et al. (2012) noted wide intrafamilial variation in clinical presentation: in 1 family, the female proband was severely affected with microcephaly, seizures, developmental delay, microphthalmia, congenital cataracts, and anterior segment dysgenesis, with white matter changes on brain MRI, while her mutation-positive mother had only congenital cataracts, with no neurologic symptoms and no abnormalities detected on MRI.
Lemmens et al. (2013) reported 2 unrelated families, of Belgian and Dutch descent, with brain small vessel disease with hemorrhage. In the Belgian family, the 48-year-old male proband had a history of retinal detachment and developed an acute left-sided hemiparesis due to a right thalamic hemorrhage. Skin biopsy of this patient showed ultrastructural abnormalities of the capillaries, with increased basement membrane thickness, focal interruptions, and formations of pools of fragmented basement membranes. His 21-year-old daughter showed hemiparesis at age 1 year, which was associated with unilateral porencephaly potentially caused by stroke in utero. Brain MRI as a young adult showed supratentorial white matter abnormalities. The proband's 74-year-old mother reported no neurologic abnormalities, but brain MRI showed severe white matter disease. In the Dutch family, 4 affected family members were described. The phenotype was variable but included unilateral porencephaly with hemiparesis and intracerebral hemorrhages confirmed by brain imaging.
Rodahl et al. (2013) restudied a large 4-generation family, originally described by Odland (1981), in which there was variable presentation of anterior segment dysgenesis accompanied in some individuals by cerebrovascular disease. Examination revealed that the ocular malformations and their severity varied considerably among family members. Corneal clouding was present bilaterally in 5 individuals and unilaterally in 2; visual acuity in the patients with corneal opacities ranged from 20/25 to light perception. All 7 patients with corneal clouding also exhibited an irregular Schwalbe line, and anterior synechiae extending to the Schwalbe line were present in 5; no family member had elevated intraocular pressure. Iris hypoplasia was present in 6 of the 7 family members with corneal clouding, and the remaining individual had mild sectorial involvement. Mild corectopia was seen in 3 of the 7 patients, and 3 patients underwent cataract surgery before 45 years of age. One patient exhibited fundus abnormalities consisting of irregular vessels around the optic disc. Cerebral hemorrhage occurred at birth or within the first year of life in 3 patients, resulting in spastic paraparesis, hemiparesis, and/or impaired psychomotor development. Signs of cerebral involvement developed in 3 more family members within the first decade of life: 1 had multiple intracerebral hemorrhages, 1 had ischemic cerebellar stroke and optic neuritis, and 1 died from a neurologic disease of unclear origin. Brain CT and/or MRI scans were available in 8 affected individuals, of which 5 showed extensive leukoencephalopathy, 1 showed mild white matter lesions, and 2 were normal; signs of previous hemorrhage were present in 5 individuals. Other systemic abnormalities observed included slight dysphonia in 2 patients, 1 of whom also had hearing loss and cardiomyopathy, and another patient exhibited supraventricular tachycardia. In addition, there were 6 family members who had minor ocular anomalies but no neurologic disease.
Yoneda et al. (2013) reported 15 Japanese probands with mutations in the COL4A1 gene. The brain imaging finding represented a phenotypic spectrum. Ten of the patients had porencephaly, which is clinically associated with hemi- or quadriparesis, seizures, and intellectual disability. Five patients had imaging more consistent with schizencephaly, which is characterized by transmantle clefts bordered by polymicrogyria in adjacent cortex. One patient had both schizencephaly and porencephaly. The brain abnormalities in about half of the patients were associated with calcification or hemosiderin deposition. Two patients had pontocerebellar atrophy, 1 had cerebellar hypoplasia, and 1 had focal cortical dysplasia. Other variable features included ocular abnormalities (4 patients), increased serum creatine kinase levels (6 patients), and hemolytic anemia (5 patients). Two patients had evidence of antenatal hemorrhage, and 2 others had evidence of severe hemorrhagic destructive lesions. Five mutations were confirmed as de novo events; 1 mutation cosegregated with familial porencephaly, and 2 mutations were inherited from asymptomatic parents.
Meuwissen et al. (2015) reported the experience of the Erasmus University Medical Center in sequencing the COL4A1 and COL4A2 genes in 183 index patients, mostly with cerebral hemorrhage or porencephaly, between 2005 and 2013. In total, 21 COL4A1 and 3 COL4A2 mutations were identified, mostly in children with porencephaly or other patterns of parenchymal hemorrhage, with a high de novo mutation rate of 40% (10/24). A review of the literature brought the total to 137 individuals with a COL4A1 mutation, 54 of whom had periventricular leukencephaly or small vessel disease and 53 had porencephaly. Sixteen had cerebral calcifications or microbleeds, and 15 had intracerebral hemorrhage. Twelve had cerebellar atrophy. Other brain MRI complications were rarer. Ophthalmologic findings included 29 with cataracts, 26 with retinal arteriol tortuosity, 10 with strabismus, and 10 with iris hypoplasia, as well as 9 with posterior embryotoxon. Renal cysts and hematuria were present in 4 patients each. Elevated creatine kinase was present in 25, and 18 had muscle cramps.
Matsumoto et al. (2015) reported the prenatal sonographic findings in a patient who had a de novo mutation in the COL4A1 gene. Mild ventriculomegaly was seen at 21 weeks' gestation, progressive dilatation of bilateral ventricle and multiple hyperechogenic lesions at 25 weeks, and a large open cleft extending to the ependymal zone at 28 weeks. Neonatal brain CT showed bilateral open-lip schizencephaly, cortical atrophy, and absence of corpus callosum.
Zagaglia et al. (2018) examined the prevalence and manifestation of epilepsy among 55 previously reported and 44 newly identified patients with mutations in the COL4A1 and COL4A2 genes. The vast majority of patients had mutations in the COL4A1 gene (only 5 patients had COL4A2 mutations). Among 123 previously reported patients, 55 had epilepsy; among the 44 newly identified patients, 38 had epilepsy. Among the new patients, the mean age at seizure onset was 15.4 months, and most (73.7%) had focal onset. Almost 40% developed status epilepticus. About half of patients with focal seizures had porencephaly, and focal seizures tended to localize to the porencephalic region. However, about 50% with focal seizures did not have porencephaly; these patients had diffuse brain abnormalities, including enlarged ventricles, periventricular leukoencephalopathy and extensive white matter loss. Drug resistance was reported in 66.6%. Of the 55 published patients with epilepsy, 5 of 11 with focal seizures had porencephaly; overall, porencephaly was found in 31 of 55 (56%) of published patients. Epilepsy was the presenting feature in 7% of the published patients and 13% of the newly identified patients. Impaired intellectual development was found in 39 of 55 previously published cases and in 36 of 38 new patients; motor abnormalities showed a more insidious onset. There were a few cases of adult patients with normal neurologic examinations who had a milder seizure phenotype phenotype. Zagaglia et al. (2018) noted the nonspecific brain imaging abnormalities in patients without frank porencephaly.
Clinical Management
Because of reduced penetrance with possible modifying factors and variable phenotype in patients with COL4A1 or COL4A2 mutations, Meuwissen et al. (2015) recommended initial workup in families with a mutation, including neurologic, ophthalmologic, renal, and cardiac screening in mutation carriers and first-degree relatives with a 50% chance of harboring the mutation.
Inheritance
In families with porencephaly or schizencephaly reported by Yoneda et al. (2013), transmission was consistent with autosomal dominant inheritance with incomplete penetrance.
Sensi et al. (1990) described a family with type 2 porencephaly in which male-to-male transmission was observed.
The transmission pattern of small vessel disease with hemorrhage in the families reported by Lemmens et al. (2013) was consistent with autosomal dominant inheritance.
The family reported by Haar and Dyken (1977) may have had this disorder; see 306960.
Mapping
In affected members of an Italian family with a diagnosis of autosomal dominant type 1 porencephaly, Aguglia et al. (2004) found linkage of the disorder to a locus on chromosome 13qter (maximum multipoint lod score of 3.16 at marker D13S285).
In 7 affected individuals from a 4-generation family with multiple ocular anomalies, brain hemorrhage, and extensive leukoencephalopathy, Rodahl et al. (2013) performed a genomewide scan using SNP markers and identified a shared 14-cM interval at the terminal part of chromosome 13q, extending from 110,173,324 to 115,045,259 (GRCh37). This region included the COL4A1 gene.
Molecular Genetics
Gould et al. (2005) assessed families previously described by Smit et al. (1984) and Aguglia et al. (2004) with brain small vessel disease for mutations in the COL4A1 gene. The first family had a heterozygous gly-to-arg substitution at codon 1236 (120130.0001); the second family had a heterozygous gly-to-ser substitution at codon 749 (120130.0002). Both mutations changed conserved glycine residues within the Gly-X-Y repeats in the triple helical domain.
Phenotypic similarities between Col4a1 (120130)-mutant mice and the French family with small vessel disease reported by Vahedi et al. (2003) prompted Gould et al. (2006) to assess the family for COL4A1 mutations. Upon sequence analysis of the COL4A1 gene, Gould et al. (2006) identified a heterozygous mutation (G562E; 120130.0003).
In affected members of 3 unrelated Dutch families with BSVD1, Breedveld et al. (2006) identified heterozygous missense mutations in the COL4A1 gene (120130.0004-120130.0005). Two of the families (families A and B) had previously been reported by Mancini et al. (2004).
In 5 affected members of a French Canadian family with leukoencephalopathy associated with Axenfeld-Rieger and other ocular anomalies, Sibon et al. (2007) identified heterozygosity for a missense mutation in the COL4A1 gene (G720D; 120130.0010).
In a mother and daughter with migraine headaches, ocular anomalies, periventricular leukoencephalopathy, and cerebral hemorrhage, Coupry et al. (2010) directly sequenced the COL4A1 gene and identified a heterozygous missense mutation (G755R; 120130.0020).
In 5 affected children from 4 unrelated families with recurrent stroke, infantile hemiplegia/spastic quadriplegia, infantile spasms, and ocular anomalies, Shah et al. (2012) identified heterozygosity for 4 different missense mutations in the COL4A1 gene, including the G755R substitution in 1 boy and a G773R substitution (120130.0021) in 2 sibs.
Yoneda et al. (2013) identified heterozygous COL4A1 mutations in 10 (16.4%) of 61 patients with porencephaly who did not have mutations in the COL4A2 gene and in 5 (50%) of 10 additional patients who also showed schizencephaly on brain imaging (see, e.g., G1326R; 120130.0017). The patients with schizencephaly also had hemosiderin deposition and calcification, consistent with an encephaloclastic process. Nine mutations occurred at highly conserved glycine residues in the gly-X-Y repeat of the collagen triple-helical domain, and Yoneda et al. (2013) noted that impairment of the collagen IV heterotrimer assembly caused by mutant COL4A1 is a common pathologic mechanism. The findings also demonstrated that COL4A1 mutations can result in both porencephaly and schizencephaly on brain imaging, supporting the same pathologic mechanism for these 2 imaging findings.
In affected members of 2 unrelated families, one Belgian and the other Dutch, with brain small vessel disease with hemorrhage, Lemmens et al. (2013) identified 2 different heterozygous truncating mutations in the COL4A1 gene (120130.0018 and 120130.0019). Analysis of patient cells suggested that the mutations caused haploinsufficiency rather than a dominant-negative effect. However, the affection status of members of the Dutch family differed in the text and figure 1 of the article, calling into question the segregation of the mutation (120130.0019) with the phenotype. Lemmens (2014) stated that 'Some of the patients were only clinically or genetically assessed which made statements about affection status difficult at the time.'
In 9 affected members of a 4-generation family with multiple ocular anomalies, brain hemorrhage, and extensive leukoencephalopathy mapping to chromosome 13q, Rodahl et al. (2013) identified a heterozygous missense mutation in the COL4A1 gene (N1627K; 120130.0022). The mutation was present in all 7 family members who had corneal clouding with other ocular and neurologic symptoms as well as in 2 relatives with minimal ocular anomalies and neurologic disease; however, it was not found in 6 family members who had minor ocular anomalies but no neurologic symptoms, or in 185 blood-donor controls.
Deml et al. (2014) reported a Hispanic brother and sister with congenital cataracts, marked microcornea, moderate microphthalmia, and mild intellectual disability, who were both negative for mutation in 71 known microphthalmia-associated genes. By performing whole-exome sequencing in the sibs, the authors identified heterozygosity for the G773R missense mutation in the COL4A1 gene. The mutation, which was confirmed by Sanger sequencing, was not found in blood samples from their unaffected parents or in a maternal buccal sample, suggesting that 1 parent had gonadal mosaicism for the COL4A1 mutation. Brain MRI at age 6 years in the sister showed nonspecific changes compatible with a small vessel disease process, but magnetic resonance angiography was normal. Analysis of COL4A1 in 24 additional patients with anophthalmia/microphthalmia of unknown genetic etiology revealed heterozygosity for another missense mutation (G708R; 120130.0023) in a 5-year-old Indian girl with congenital cataract, bilateral microcornea and Peters anomaly, unilateral microphthalmia, and unilateral retinal detachment. She had no history of developmental delay, and the only nonocular clinical feature reported was clinodactyly; imaging studies were not performed. The mutation was not found in her mother, and her father was unavailable for screening. Deml et al. (2014) stated that microphthalmia had been reported in 4 of 97 previously published cases of COL4A1-associated cerebrovascular disease.
Animal Model
Gould et al. (2005) identified and characterized a novel mouse mutant generated by random mutagenesis with severe perinatal cerebral hemorrhage. In addition to cerebral hemorrhage, mutant mice were smaller than control littermates and had multiple pleiotropic phenotypes including ocular abnormalities, mild renal abnormalities, and reduced fertility that appeared to be influenced by genetic context. Homozygous mutant mice were not viable after midembryogenesis, and about 50% of heterozygous mice died within a day of birth. The authors suggested that reduced viability may be explained by variability in the severity and/or location of cerebral hemorrhages that were externally visible in most mutant pups. Detailed analysis of a subset of postnatal day 0 pups identified cerebral hemorrhages in 12 of 12 mutant pups but in 0 of 9 littermate controls. About 18% of adult heterozygous mutant mice had obvious porencephalic lesions (6 of 33) that were not observed in wildtype controls (0 of 17). Mutant mice carried a splice site mutation causing excision of exon 40 of the Col4a1 gene. COL4A1 gives strength to basement membranes. Gould et al. (2005) found that compared with controls, mice heterozygous for the Col4a1 exon 40 deletion had uneven basement membranes with inconsistent density and focal disruptions. The major site of hemorrhage was the brain.
Gould et al. (2006) showed that a mutation in the mouse Col4a1 gene, encoding procollagen type IV alpha-1, predisposes both newborn and adult mice to intracranial hemorrhage. Surgical delivery of mutant mice alleviated birth-associated trauma and hemorrhage. Although surgical delivery prevented cerebral hemorrhage, it did not prevent perinatal death. Newborn pups were often cyanotic and in respiratory distress. Mutant pups had compact lungs with few or no terminal air spaced visible. This finding suggested that respiratory defects contributed to perinatal mortality.
Van Agtmael et al. (2005) identified an allelic series of 3 induced dominant mouse mutants with missense mutations in the Col4a1 gene: Svc (small with vacuolar cataracts), Raw (retinal arteriolar wiring), and Bru (bruised). Bru heterozygotes showed ocular anterior segment defects similar to Axenfeld-Rieger anomaly, including iris defects, corneal opacities, vacuolar cataracts, iris/corneal adhesions, buphthalmos, and optic nerve cupping, as well as retinal detachment. Bru mice also developed a renal glomerulopathy. The Raw mice showed a silvery appearance of the retinal arterioles. The observed phenotypes were associated with generalized basement membrane defects, but showed a high degree of tissue-specific variability. All mutations affected crucial glycine residues in a Gly-Xaa-Yaa repeat in the central collagen domain.
Mao et al. (2015) tested the effects of a Col4a1 mutation in 2 different genetic backgrounds in mice to compare how genetic context influences ocular dysgenesis, intraocular pressure (IOP), and progression to glaucoma. Col4a1 mutant mice maintained on a C57BL/6J (B6) background were crossed to either 129S6/SvEvTac or CAST/EiJ and the F1 progeny analyzed. The CAST/EiJ inbred strain had a relatively uniform and profound suppression on the effects of the Col4a1 mutation, and mutant CASTB6F1 mice were only mildly affected. In contrast, mutant 129B6F1 mice had more variable and severe anterior segment dysgenesis and IOP dysregulation that were associated with glaucomatous signs including lost or damaged retinal ganglion cell axons and excavation of the optic nerve head.
INHERITANCE \- Autosomal dominant HEAD & NECK Face \- Facial paresis Eyes \- Visual field defects \- Exotropia \- Retinal arteriolar tortuosity \- Hypopigmentation of the fundus \- Scotomas, episodic \- Blurred vision, episodic \- Astigmatism (in some patients) \- Amblyopia (reported in 1 family) \- Strabismus (reported in 1 family) \- Myopia (reported in 1 family) \- Hyperopia (in some patients) \- Decreased visual acuity (rare) \- Congenital cataracts (in some patients) \- High intraocular pressure (reported in 1 family) \- Glaucoma (rare) \- Microphthalmia (in some patients) \- Microcornea (in some patients) \- Corneal opacities (in some patients) \- Corneal neovascularization (rare) \- Axenfeld-Rieger anomalies (in some patients) \- Iris hypoplasia (in some patients) \- Corectopia (in some patients) \- Polycoria (rare) \- Iridogoniodysgenesis (rare) \- Iridocorneal synechiae (in some patients) \- Prominent or irregular Schwalbe line (in some patients) \- Macular hemorrhage and Fuchs spots (rare) \- Peripapillary atrophy (rare) \- Choroidal atrophy (rare) CARDIOVASCULAR Vascular \- Cerebral hemorrhage NEUROLOGIC Central Nervous System \- Migraine with or without aura \- Infantile hemiparesis \- Central facial palsy (in some patients) \- Porencephaly (in some patients) \- Seizures (in some patients) \- Intellectual disability \- Diffuse periventricular leukoencephalopathy \- White matter hyperintensities (MRI, T2 images) suggestive of old infarcts \- Deep hypointensities (MRI, T2) suggestive of past microbleeds \- Dilated perivascular spaces Porencephaly (in some patients) \- Schizencephaly (in some patients) \- Fluid-filled cavity within the cerebral hemispheres, can be unilateral or bilateral and may or may not communicate with cerebrospinal fluid (CSF) spaces \- Focal cortical dysplasia \- Calcifications \- Hemosiderin deposition \- Hydrocephalus \- Hemiplegia \- Tetraparesis \- Spasticity \- Pyramidal signs \- Extensor plantar responses \- Limb dystonia \- Ischemic stroke \- Microbleeds \- Leukoencephalopathy \- Cerebellar atrophy HEMATOLOGY \- Hemolytic anemia LABORATORY ABNORMALITIES \- Increased serum creatine kinase MISCELLANEOUS \- Variable age of onset (range birth to 45 years) \- Onset usually in childhood \- Variable severity (mild symptoms to severe handicap) \- Incomplete penetrance \- A subset of patients may have congenital abnormalities of the ocular anterior segment MOLECULAR BASIS \- Caused by mutation in the collagen, type IV, alpha-1 gene (COL4A1, 120130.0001 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
BRAIN SMALL VESSEL DISEASE 1 WITH OR WITHOUT OCULAR ANOMALIES
|
c1867983
| 8,148 |
omim
|
https://www.omim.org/entry/175780
| 2019-09-22T16:35:56 |
{"doid": ["0090125"], "mesh": ["D065708"], "omim": ["175780"], "orphanet": ["99810", "2940", "36383"], "synonyms": ["Alternative titles", "HEMIPLEGIA, INFANTILE, WITH PORENCEPHALY", "BRAIN SMALL VESSEL DISEASE WITH HEMORRHAGE", "RETINAL ARTERIOLAR TORTUOSITY, INFANTILE HEMIPARESIS, AND LEUKOENCEPHALOPATHY, AUTOSOMAL DOMINANT", "BRAIN SMALL VESSEL DISEASE WITH AXENFELD-RIEGER ANOMALY", "LEUKOENCEPHALOPATHY WITH AXENFELD-RIEGER ANOMALY", "PORENCEPHALY, TYPE 1, FORMERLY", "PORENCEPHALY, TYPE 1, AUTOSOMAL DOMINANT, FORMERLY", "PORENCEPHALY 1, FORMERLY"], "genereviews": ["NBK7046"]}
|
A rare, genetic motor neuron disease characterized by late childhood- or adolescent-onset of slowly progressive, severe, distal limb muscle weakness and wasting, in association with pyramidal signs, normal sensation, and absence of bulbar involvement, leading to degeneration of motor neurons in the brain and spinal cord.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Amyotrophic lateral sclerosis type 4
|
c1865409
| 8,149 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=357043
| 2021-01-23T18:41:28 |
{"gard": ["10502"], "mesh": ["C566550"], "omim": ["602433"], "umls": ["C1865409"], "icd-10": ["G12.2"], "synonyms": ["ALS4", "Distal hereditary motor neuropathy with upper motor neuron signs", "dHMN with upper motor neuron signs"]}
|
Glomus vagale tumor is a type of paraganglioma, which is a tumor that develops in the paraganglia (a group of cells that are found near nerve cell bunches called ganglia). Glomus vagale tumors, specifically, grow in the paraganglia located near the vagus nerve, an important cranial nerve which serves many functions including empowering the vocal cords and the muscles of swallowing. In most cases, the tumors are benign, although rare cancerous cases have been reported. Signs and symptoms vary based on the size and location of the tumor but may include a neck mass, tinnitus (ringing or buzzing in the ears), difficulty swallowing, hoarseness, pain, cough, and/or cranial nerve paralysis. Some tumors may not be associated with any concerning features and are diagnosed by chance during imaging studies performed to investigate other conditions. In many cases, the underlying cause of glomus vagale tumors is poorly understood. Approximately 40-50% of affected people report a family history of the condition. Glomus vagale tumors can be associated with inherited syndromes caused by genetic changes (mutations) in succinate dehydrogenase subunits (i.e. SDHB, SDHD, SDHA, SDHAF2, SDHC) or the MAX gene. Treatment usually includes surgery.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Glomus vagale tumor
|
c0474819
| 8,150 |
gard
|
https://rarediseases.info.nih.gov/diseases/8620/glomus-vagale-tumor
| 2021-01-18T18:00:18 |
{"synonyms": ["Vagal paraganglioma"]}
|
This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.
Find sources: "Catel–Manzke syndrome" – news · newspapers · books · scholar · JSTOR (May 2008) (Learn how and when to remove this template message)
Catel–Manzke syndrome
Other namesHyperphalangy-clinodactyly of index finger with Pierre Robin syndrome
Catel–Manzke syndrome is a rare genetic disorder characterized by distinctive abnormalities of the index fingers; the classic features of Pierre Robin syndrome; occasionally with additional physical findings.
## Contents
* 1 Diagnosis
* 2 Prevalence
* 3 References
* 4 External links
## Diagnosis[edit]
This section is empty. You can help by adding to it. (December 2017)
## Prevalence[edit]
Currently there are only around 26 people in the world that are known to have this rare condition. Inheritance is thought to be X-linked recessive.[1]
## References[edit]
1. ^ Online Mendelian Inheritance in Man (OMIM): 302380
## External links[edit]
Classification
D
* ICD-10: Q87.8
* OMIM: 302380
* MeSH: C535347
* DiseasesDB: 33832
External resources
* Orphanet: 1388
* v
* t
* e
Congenital abnormality syndromes
Craniofacial
* Acrocephalosyndactylia
* Apert syndrome
* Carpenter syndrome
* Pfeiffer syndrome
* Saethre–Chotzen syndrome
* Sakati–Nyhan–Tisdale syndrome
* Bonnet–Dechaume–Blanc syndrome
* Other
* Baller–Gerold syndrome
* Cyclopia
* Goldenhar syndrome
* Möbius syndrome
Short stature
* 1q21.1 deletion syndrome
* Aarskog–Scott syndrome
* Cockayne syndrome
* Cornelia de Lange syndrome
* Dubowitz syndrome
* Noonan syndrome
* Robinow syndrome
* Silver–Russell syndrome
* Seckel syndrome
* Smith–Lemli–Opitz syndrome
* Snyder–Robinson syndrome
* Turner syndrome
Limbs
* Adducted thumb syndrome
* Holt–Oram syndrome
* Klippel–Trénaunay–Weber syndrome
* Nail–patella syndrome
* Rubinstein–Taybi syndrome
* Gastrulation/mesoderm:
* Caudal regression syndrome
* Ectromelia
* Sirenomelia
* VACTERL association
Overgrowth syndromes
* Beckwith–Wiedemann syndrome
* Proteus syndrome
* Perlman syndrome
* Sotos syndrome
* Weaver syndrome
* Klippel–Trénaunay–Weber syndrome
* Benign symmetric lipomatosis
* Bannayan–Riley–Ruvalcaba syndrome
* Neurofibromatosis type I
Laurence–Moon–Bardet–Biedl
* Bardet–Biedl syndrome
* Laurence–Moon syndrome
Combined/other,
known locus
* 2 (Feingold syndrome)
* 3 (Zimmermann–Laband syndrome)
* 4/13 (Fraser syndrome)
* 8 (Branchio-oto-renal syndrome, CHARGE syndrome)
* 12 (Keutel syndrome, Timothy syndrome)
* 15 (Marfan syndrome)
* 19 (Donohue syndrome)
* Multiple
* Fryns 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 inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Catel–Manzke syndrome
|
c1844887
| 8,151 |
wikipedia
|
https://en.wikipedia.org/wiki/Catel%E2%80%93Manzke_syndrome
| 2021-01-18T18:53:32 |
{"gard": ["28"], "mesh": ["C535347"], "umls": ["C1844887"], "orphanet": ["1388"], "wikidata": ["Q5051865"]}
|
Teunissen–Cremers syndrome
Other namesStapes ankylosis with broad thumbs and toes
SpecialtyOrthopedic
Teunissen–Cremers syndrome is a genetic disorder that presents with skeleton defects some of which can include the bones of the inner ear, fingers and toes.[1] This can result in conductive hearing loss and finger deformities.[1][2]
## References[edit]
1. ^ a b Hirshoren, N; Gross, M; Banin, E; Sosna, J; Bargal, R; Raas-Rothschild, A (Jul–Aug 2008). "P35S mutation in the NOG gene associated with Teunissen–Cremers syndrome and features of multiple NOG joint-fusion syndromes". European Journal of Medical Genetics. 51 (4): 351–7. doi:10.1016/j.ejmg.2008.02.008. PMID 18440889.
2. ^ Toriello, Helga V.; Smith, Shelley D. (2013). Hereditary Hearing Loss and Its Syndromes. Oxford University Press. p. 405. ISBN 9780199313884.
Bert Teunissen, Cor Cremers. An autosomal dominant inherited syndrome with congenital stapes ankylosis. Laryngoscope 100: April 1990, 380-384
## External links[edit]
Classification
D
* ICD-10: Q87.8
* OMIM: 184460
External resources
* Orphanet: 140917
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Teunissen–Cremers syndrome
|
c1866656
| 8,152 |
wikipedia
|
https://en.wikipedia.org/wiki/Teunissen%E2%80%93Cremers_syndrome
| 2021-01-18T18:51:30 |
{"mesh": ["C536943"], "umls": ["C1866656"], "orphanet": ["140917"], "wikidata": ["Q7707070"]}
|
Biotinidase deficiency
Other namesBTD
Biocytin, one of the in vivo subtrates of biotinidase.
SpecialtyEndocrinology
Biotinidase deficiency is an autosomal recessive metabolic disorder in which biotin is not released from proteins in the diet during digestion or from normal protein turnover in the cell. This situation results in biotin deficiency.
Biotin is an important water-soluble nutrient that aids in the metabolism of fats, carbohydrates, and proteins. Biotin deficiency can result in behavioral disorders, lack of coordination, learning disabilities and seizures. Biotin supplementation can alleviate and sometimes totally stop such symptoms.
## Contents
* 1 Signs and symptoms
* 2 Genetics
* 3 Pathophysiology
* 4 Diagnosis
* 5 Treatment
* 5.1 Dietary Concerns
* 6 Epidemiology
* 7 See also
* 8 References
* 9 Further reading
* 10 External links
## Signs and symptoms[edit]
Signs and symptoms of a biotinidase deficiency can appear several days after birth. These include seizures, hypotonia and muscle/limb weakness, ataxia, paresis, hearing loss, optic atrophy, skin rashes (including seborrheic dermatitis and psoriasis), and alopecia. If left untreated, the disorder can rapidly lead to coma and death.[citation needed]
Biotinidase deficiency can also appear later in life. This is referred to as "late-onset" biotinidase deficiency. The symptoms are similar, but perhaps more mild, because if an individual survives the neonatal period they likely have some residual activity of biotin-related enzymes. Studies[1][2] have noted individuals who were asymptomatic until adolescence or early adulthood. One study pointed out that untreated individuals may not show symptoms until age 21.[3] Furthermore, in rare cases, even individuals with profound deficiencies of biotinidase can be asymptomatic.[1]
Symptom severity is predictably correlated with the severity of the enzyme defect. Profound biotinidase deficiency refers to situations where enzyme activity is 10% or less.[2] Individuals with partial biotinidase deficiency may have enzyme activity of 10-30%.[2]
Functionally, there is no significant difference between dietary biotin deficiency and genetic loss of biotin-related enzyme activity. In both cases, supplementation with biotin can often restore normal metabolic function and proper catabolism of leucine and isoleucine.[citation needed]
The symptoms of biotinidase deficiency (and dietary deficiency of biotin) can be quite severe. A 2004 case study from Metametrix[4] detailed the effects of biotin deficiency, including aggression, cognitive delay, and reduced immune function.
## Genetics[edit]
Biotinidase deficiency has an autosomal recessive pattern of inheritance.
Mutations in the BTD gene cause biotinidase deficiency. Biotinidase is the enzyme that is made by the BTD gene. Many mutations that cause the enzyme to be nonfunctional or to be produced at extremely low levels have been identified. Biotin is a vitamin that is chemically bound to proteins. (Most vitamins are only loosely associated with proteins.) Without biotinidase activity, the vitamin biotin cannot be separated from foods and therefore cannot be used by the body. Another function of the biotinidase enzyme is to recycle biotin from enzymes that are important in metabolism (processing of substances in cells). When biotin is lacking, specific enzymes called carboxylases cannot process certain proteins, fats, or carbohydrates. Specifically, two essential branched-chain amino acids (leucine and isoleucine) are metabolized differently.[citation needed]
Individuals lacking functional biotinidase enzymes can still have normal carboxylase activity if they ingest adequate amounts of biotin. The standard treatment regimen calls for 5–10 mg of biotin per day.[5]
Biotinidase deficiency is inherited in an autosomal recessive pattern, which means the defective gene is located on an autosome, and two copies of the defective gene - one from each parent - must be inherited for a person to be affected by the disorder. The parents of a child with an autosomal recessive disorder are usually not affected by the disorder, but are carriers of one copy of the defective gene. If both parents are carriers for the biotinidase deficiency, there is a 25% chance that their child will be born with it, a 50% chance the child will be a carrier, and a 25% chance the child will be unaffected.[citation needed]
The chromosomal locus is at 3p25. The BTD gene has 4 exons of lengths 79 bp, 265 bp, 150 bp and 1502 bp, respectively. There are at least 21 different mutations that have been found to lead to biotinidase deficiency. The most common mutations in severe biotinidase deficiency (<10% normal enzyme activity) are: p.Cys33PhefsX36, p.Gln456His, p.Arg538Cys, p.Asp444His, and p.[Ala171Thr;Asp444His]. Almost all individuals with partial biotinidase deficiency (10-30% enzyme activity) have the mutation p.Asp444His in one allele of the BTD gene in combination with a second allele.[6]
## Pathophysiology[edit]
Symptoms of the deficiency are caused by the inability to reuse biotin molecules that are needed for cell growth, production of fatty acids and the metabolism of fats and amino acids. If left untreated, the symptoms can lead to later problems such as comas or death. Unless treatment is administered on a regular basis, symptoms can return at any point during the lifespan.[citation needed]
## Diagnosis[edit]
Biotinidase deficiency can be found by genetic testing. This is often done at birth as part of newborn screening in several states throughout the United States. Results are found through testing a small amount of blood gathered through a heel prick of the infant. As not all states require that this test be done, it is often skipped in those where such testing is not required. Biotinidase deficiency can also be found by sequencing the BTD gene, particularly in those with a family history or known familial gene mutation.[citation needed]
## Treatment[edit]
Treatment is possible but unless continued daily, problems may arise. Currently, this is done through supplementation of 5–10 mg of oral biotin a day. If symptoms have begun to show, standard treatments can take care of them, such as hearing aids for poor hearing.[citation needed]
### Dietary Concerns[edit]
Raw eggs should be avoided in those with biotin deficiency, because egg whites contain high levels of the anti-nutrient avidin. The name avidin literally means that this protein has an "avidity" (Latin: "to eagerly long for") for biotin. Avidin binds irreversibly to biotin and this compound is then excreted in the urine.[citation needed]
## Epidemiology[edit]
Based on the results of worldwide screening of biotinidase deficiency in 1991, the incidence of the disorder is:[citation needed] 5 in 137,401 for profound biotinidase deficiency
* One in 109,921 for partial biotinidase deficiency
* One in 61,067 for the combined incidence of profound and partial biotinidase deficiency
* Carrier frequency in the general population is approximately one in 120.
## See also[edit]
* Biotin
* Biotin deficiency
* Multiple carboxylase deficiency
* Holocarboxylase synthetase deficiency
* 3-Methylcrotonyl-CoA carboxylase deficiency
## References[edit]
1. ^ a b Wolf, Barry; Norrgard, Karen; Pomponio, Robert J.; Mock, Donald M.; Secor Mcvoy, Julie R.; Fleischhauer, Kristin; Shapiro, Steven; Blitzer, Miriam G.; Hymes, Jeanne (1997). "Profound biotinidase deficiency in two asymptomatic adults". American Journal of Medical Genetics. 73 (1): 5–9. doi:10.1002/(SICI)1096-8628(19971128)73:1<5::AID-AJMG2>3.0.CO;2-U. PMID 9375914.
2. ^ a b c McVoy, Julie R. Secor; Levy, Harvey L.; Lawler, Michael; Schmidt, Michael A.; Ebers, Douglas D.; Hart, Suzanne; Pettit, Denise Dove; Blitzer, Miriam G.; Wolf, Barry (1990). "Partial biotinidase deficiency: Clinical and biochemical features". The Journal of Pediatrics. 116 (1): 78–83. doi:10.1016/S0022-3476(05)81649-X. PMID 2295967.
3. ^ Möslinger, Dorothea; Mühl, Adolf; Suormala, Terttu; Baumgartner, Regula; Stöckler-Ipsiroglu, Sylvia (2003). "Molecular characterisation and neuropsychological outcome of 21 patients with profound biotinidase deficiency detected by newborn screening and family studies". European Journal of Pediatrics. 162: S46–9. doi:10.1007/s00431-003-1351-3. PMID 14628140. S2CID 6490712.
4. ^ http://www.metametrix.com/learning-center/case-studies/2004/biotin-detoxification-needs-in-cognitively-delayed-adult
5. ^ Wolf, Barry (2011). "Biotinidase Deficiency". In Pagon, Roberta A; Bird, Thomas D; Dolan, Cynthia R; Stephens, Karen; et al. (eds.). GeneReviews.[page needed]
6. ^ Biotinidase Deficiency (Report). Retrieved May 19, 2011.
## Further reading[edit]
* Dobrowolski, Steven F.; Angeletti, Janine; Banas, Richard A.; Naylor, Edwin W. (2003). "Real time PCR assays to detect common mutations in the biotinidase gene and application of mutational analysis to newborn screening for biotinidase deficiency". Molecular Genetics and Metabolism. 78 (2): 100–7. doi:10.1016/S1096-7192(02)00231-7. PMID 12618081.
* McMahon, Robert J. (2002). "Biotin in metabolism and molecular biology". Annual Review of Nutrition. 22: 221–39. doi:10.1146/annurev.nutr.22.121101.112819. PMID 12055344.
* C. Neto, E.; Schulte, J.; Rubim, R.; Lewis, E.; Demari, J.; Castilhos, C.; Brites, A.; Giugliani, R.; et al. (2004). "Newborn screening for biotinidase deficiency in Brazil: biochemical and molecular characterizations". Brazilian Journal of Medical and Biological Research. 37 (3): 295–9. doi:10.1590/S0100-879X2004000300001. PMID 15060693.
* Weber, Peter; Scholl, Sabine; Baumgartner, E Regula (2007). "Outcome in patients with profound biotinidase deficiency: relevance of newborn screening". Developmental Medicine & Child Neurology. 46 (7): 481–4. doi:10.1111/j.1469-8749.2004.tb00509.x. PMID 15230462.
* Wolf, Barry (2003). "Biotinidase deficiency: New directions and practical concerns". Current Treatment Options in Neurology. 5 (4): 321–8. doi:10.1007/s11940-003-0038-4. PMID 12791199. S2CID 25158348.
## External links[edit]
* OMIM entries on Biotinidasa deficiency
Classification
D
* ICD-10: E53.8
* ICD-10-CM: D81.810
* ICD-9-CM: 277.6
* OMIM: 253260
* MeSH: D028921
* DiseasesDB: 29822
External resources
* eMedicine: ped/239
* Orphanet: 79241
* v
* t
* e
Metabolic disorders of vitamins, coenzymes, and cofactors
B7 Biotin/MCD
* Biotinidase deficiency
* Holocarboxylase synthetase deficiency
Other B
* B5 (Pantothenate kinase-associated neurodegeneration)
* B12 (Methylmalonic acidemia)
Other vitamin
* Familial isolated vitamin E deficiency
Nonvitamin cofactor
* Tetrahydrobiopterin deficiency
* Molybdenum cofactor deficiency
* v
* t
* e
Inborn error of lipid metabolism: fatty-acid metabolism disorders
Synthesis
* Biotinidase deficiency (BTD)
Degradation
Acyl
transport
* Carnitine
* CPT1
* CPT2
* CDSP
* CACTD
* Adrenoleukodystrophy (ALD)
Beta
oxidation
General
* Acyl CoA dehydrogenase
* Short-chain SCADD
* Medium-chain MCADD
* Long-chain 3-hydroxy LCHAD
* Very long-chain VLCADD
* Mitochondrial trifunctional protein deficiency (MTPD): Acute fatty liver of pregnancy
Unsaturated
* 2,4 Dienoyl-CoA reductase deficiency (DECRD)
Odd chain
* Propionic acidemia (PCC deficiency)
Other
* 3-hydroxyacyl-coenzyme A dehydrogenase deficiency (HADHD)
* Glutaric acidemia type 2 (MADD)
To
acetyl-CoA
* Malonic aciduria (MCD)
Aldehyde
* Sjögren–Larsson syndrome (SLS)
This article incorporates public domain material from the United States National Library of Medicine document: "Genetics Home Reference".
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Biotinidase deficiency
|
c1854698
| 8,153 |
wikipedia
|
https://en.wikipedia.org/wiki/Biotinidase_deficiency
| 2021-01-18T18:51:56 |
{"gard": ["894"], "mesh": ["C565365", "D028921"], "umls": ["C1854698"], "icd-9": ["277.6"], "orphanet": ["79241"], "wikidata": ["Q776026"]}
|
Pyometra
Other namesPyometritis
A canine pyometric uterus immediately after surgery to remove it. It is extremely distended with purulent material.
SpecialtyObstetrics, gynecology
Pyometra or pyometritis is a uterine infection. Though it is most commonly known as a disease of the unaltered female dog, it is also a notable human disease. It is also seen in female cattle, horses, goats, sheep, swine, cats (queens), rabbits, hamsters, ferrets, rats and guinea pigs. Pyometra is an important disease to be aware of for any dog or cat owner because of the sudden nature of the disease and the deadly consequences if left untreated. It has been compared to acute appendicitis in humans, because both are essentially empyemas within an abdominal organ.
## Contents
* 1 Signs and symptoms
* 2 Cause
* 2.1 Hormonal influences and mis-mating shots
* 3 Treatment
* 3.1 Surgical treatment
* 4 Stump Pyometra
* 5 References
* 6 External links
## Signs and symptoms[edit]
The most obvious symptom of open pyometra is a discharge of pus from the vulva in a female that has recently been in heat. However, symptoms of closed pyometra are less obvious. Symptoms of both types include vomiting, loss of appetite, depression, and increased drinking and urinating.[1] Fever is seen in less than a third of female dogs with pyometra.[2] Closed pyometra is a more serious condition than open pyometra not only because there is no outlet for the infection, but also because a diagnosis of closed pyometra can easily be missed due to its insidious nature. Bloodwork may show dehydration and/or increased white blood cell count. X-rays will show an enlarged uterus, and ultrasound will confirm the presence of a fluid filled uterus.[3]
## Cause[edit]
Uterus of a dog.
The risk of developing pyometra differs between dog breeds.[4] Pyometra is a result of hormonal and structural changes in the uterus lining. This can happen at any age, whether she has bred or not, and whether it is her 1st or 10th heat (although it becomes more common as the dog gets older). The main risk period for a female is for eight weeks after her peak standing heat (or estrous cycle) has ended.[2] Normally during this period, the cervix, which was open during her heat, begins to close, and the inner lining begins to adapt back to normal. However, cystic hyperplasia of the endometrium (inner lining of the uterus) – known as cystic endometrial hyperplasia (CEH) – may occur at this time for some animals, as an inappropriate response to progesterone.
Under these circumstances, bacteria (especially E. coli) that have migrated from the vagina into the uterus find the environment favorable to growth, especially since progesterone also causes mucus secretion, closes the cervix (preventing uterine drainage), and decreases uterine contractility.[5] The condition of the cervix is a major factor in the severity of the condition.
* If the cervix is open, the infected material can leave the body, and this is far easier and safer to treat. This is known as open pyometra.
* If the cervix is fully closed, there is no discharge from the vulva, and like in appendicitis, the uterus may rupture and pus escapes into the abdomen, causing peritonitis and possible rapid death. This is known as closed pyometra.[6]
Pyometra in a dog
### Hormonal influences and mis-mating shots[edit]
Females that have received estradiol as a mismating shot (abortifacient) in diestrus are at risk for more severe disease because estrogen increases the number of progesterone receptors in the endometrium. 25 percent of females receiving estradiol in diestrus develop pyometra.[3] Pyometra is less common in female cats because progesterone is only released by the ovaries after mating.[7] Also in cats, the risk of developing the disease differs depending on breed.[8]
## Treatment[edit]
The most important aspect of treatment of pyometra is quick action to provide supportive care. Female dogs are often septic and in shock (see septic shock).[1] Intravenous fluids and antibiotics should be given immediately. Once the female dog has been stabilized, then the treatment of choice is an emergency spay. In livestock the treatment of choice for minor cases is Dinopost Tremethamine (Lutalyse). Supportive antibiotic treatment may be recommended also. Severe cases require surgery.[7][9]
### Surgical treatment[edit]
Spaying (ovariohysterectomy) completely and promptly removes the infection, prevents uterine rupture and peritonitis, and of course prevents recurrence, in most cases. Spayed animals do very rarely develop pyometra in the uterine stump. Even so, ovariohysterectomy is currently considered the most effective and safest treatment.
## Stump Pyometra[edit]
Stump pyometra is a serious health condition that may occur in female dogs that underwent ovariohysterectomy (spaying), particularly if there is residual functional ovarian tissue. In this condition, the remaining stump of the resected uterus becomes infected and filled with a purulent fluid. The symptoms are similar to those of true pyometra. The risk of this condition is significantly reduced if no ovarian tissue remains from the original ovariohysterectomy. Diagnosis of a stump pyometra may be challenging as pyometra is often discounted as a possibility if the dog has been previously spayed.
## References[edit]
1. ^ a b "Pyometra". American College of Veterinary Surgeons. 2004. Archived from the original on 2006-02-21. Retrieved 2006-12-14.
2. ^ a b Ettinger, Stephen J.; Feldman, Edward C. (1995). Textbook of Veterinary Internal Medicine (4th ed.). W.B. Saunders Company. ISBN 0-7216-6795-3.
3. ^ a b Wingfield, Wayne E. (1997). Hanley & Belfus, Inc. (ed.). Veterinary Emergency Medicine Secrets. ISBN 1-56053-215-7.
4. ^ Jitpean, S; Hagman, R; Ström Holst, B; Höglund, OV; Pettersson, A; Egenvall, A (December 2012). "Breed Variations in the Incidence of Pyometra and Mammary Tumours in Swedish Dogs". Reproduction in Domestic Animals. 47: 347–350. doi:10.1111/rda.12103.
5. ^ Romagnoli, Stefano (2002). "Canine Pyometra: Pathogenesis, Therapy and Clinical Cases". Proceedings of the 27th World Congress of the World Small Animal Veterinary Association. Retrieved 2006-12-14.
6. ^ Brooks, Wendy C. (2003). "Pyometra". The Pet Health Library. VeterinaryPartner.com. Retrieved 2006-12-14.
7. ^ a b "Pyometra". The Merck Veterinary Manual. 2006. Retrieved 2006-12-14.
8. ^ Hagman, R; Ström Holst, B; Möller, L; Egenvall, A (1 July 2014). "Incidence of pyometra in Swedish insured cats". Theriogenology. 82 (1): 114–20. doi:10.1016/j.theriogenology.2014.03.007. PMID 24726694.
9. ^ Höglund, Odd Viking; Lövebrant, Johanna; Olsson, Ulf; Höglund, Katja (17 November 2016). "Blood pressure and heart rate during ovariohysterectomy in pyometra and control dogs: a preliminary investigation". Acta Veterinaria Scandinavica. 58 (1). doi:10.1186/s13028-016-0263-y. PMC 5112883. PMID 27855712.
## External links[edit]
Classification
D
* ICD-10: N71, O85
* ICD-9-CM: 615
* MeSH: D055119
* DiseasesDB: 4283
External resources
* Patient UK: Pyometra
* Pyometra from The Pet Health Library
* Pyometra Surgery Photos and Description from The Pet Center
* v
* t
* e
Female diseases of the pelvis and genitals
Internal
Adnexa
Ovary
* Endometriosis of ovary
* Female infertility
* Anovulation
* Poor ovarian reserve
* Mittelschmerz
* Oophoritis
* Ovarian apoplexy
* Ovarian cyst
* Corpus luteum cyst
* Follicular cyst of ovary
* Theca lutein cyst
* Ovarian hyperstimulation syndrome
* Ovarian torsion
Fallopian tube
* Female infertility
* Fallopian tube obstruction
* Hematosalpinx
* Hydrosalpinx
* Salpingitis
Uterus
Endometrium
* Asherman's syndrome
* Dysfunctional uterine bleeding
* Endometrial hyperplasia
* Endometrial polyp
* Endometriosis
* Endometritis
Menstruation
* Flow
* Amenorrhoea
* Hypomenorrhea
* Oligomenorrhea
* Pain
* Dysmenorrhea
* PMS
* Timing
* Menometrorrhagia
* Menorrhagia
* Metrorrhagia
* Female infertility
* Recurrent miscarriage
Myometrium
* Adenomyosis
Parametrium
* Parametritis
Cervix
* Cervical dysplasia
* Cervical incompetence
* Cervical polyp
* Cervicitis
* Female infertility
* Cervical stenosis
* Nabothian cyst
General
* Hematometra / Pyometra
* Retroverted uterus
Vagina
* Hematocolpos / Hydrocolpos
* Leukorrhea / Vaginal discharge
* Vaginitis
* Atrophic vaginitis
* Bacterial vaginosis
* Candidal vulvovaginitis
* Hydrocolpos
Sexual dysfunction
* Dyspareunia
* Hypoactive sexual desire disorder
* Sexual arousal disorder
* Vaginismus
* Urogenital fistulas
* Ureterovaginal
* Vesicovaginal
* Obstetric fistula
* Rectovaginal fistula
* Prolapse
* Cystocele
* Enterocele
* Rectocele
* Sigmoidocele
* Urethrocele
* Vaginal bleeding
* Postcoital bleeding
Other / general
* Pelvic congestion syndrome
* Pelvic inflammatory disease
External
Vulva
* Bartholin's cyst
* Kraurosis vulvae
* Vestibular papillomatosis
* Vulvitis
* Vulvodynia
Clitoral hood or clitoris
* Persistent genital arousal disorder
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Pyometra
|
c0034215
| 8,154 |
wikipedia
|
https://en.wikipedia.org/wiki/Pyometra
| 2021-01-18T19:07:26 |
{"mesh": ["D055112"], "umls": ["C0034215"], "icd-9": ["615"], "icd-10": ["N71"], "wikidata": ["Q1147908"]}
|
Isotretinoin embryopathy is an association of malformations caused by the teratogenic effect of isotretinoin, an oral synthetic vitamin A derivative, which is used to treat severe recalcitrant cystic acne. Exposure to isotretinoin during the first trimester of pregnancy has been associated with an increased risk of spontaneous abortions and severe birth defects including serious craniofacial (microcephaly, asymmetric crying facies, microphthalmia, developmental abnormalities of the external ear, ocular hypertelorism), cardio vascular (conotruncal heart defects, aortic arch abnormalities), and central nervous system (hydrocephalus, microcephaly, lissencephaly, Dandy-Walker malformation, cognitive deficit) anomalies and thymic aplasia. Isoretinoin is contraindicated during pregnancy.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Isotretinoin syndrome
|
c0432364
| 8,155 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2305
| 2021-01-23T17:17:18 |
{"mesh": ["C535542"], "umls": ["C0432364", "C2930972"], "icd-10": ["Q86.8"], "synonyms": ["Isotretinoin embryopathy", "Retinoic acid embryopathy", "Retinoids embryopathy"]}
|
Volkmann's contracture
Other namesVolkmann's ischaemic contracture
SpecialtyOrthopaedics
Volkmann's contracture is a permanent flexion contracture of the hand at the wrist, resulting in a claw-like deformity of the hand and fingers. Passive extension of fingers is restricted and painful.[1]
## Contents
* 1 Causes
* 2 Prevention and treatment
* 3 History
* 4 References
* 5 External links
## Causes[edit]
Any fracture in the elbow region or upper arm may lead to Volkmann's ischemic contracture, but it is especially associated with supracondylar fracture of the humerus.
Volkmann's contracture results from acute ischaemia and necrosis of the muscle fibres of the flexor group of muscles of the forearm, especially the flexor digitorum profundus and flexor pollicis longus. The muscles become fibrotic and shortened.
The condition is caused by obstruction on the brachial artery near the elbow, possibly from improper use of a tourniquet, improper use of a plaster cast, or compartment syndrome. It is also caused by fractures of the forearm bones if they cause bleeding from the major blood vessels of the forearm.
## Prevention and treatment[edit]
Prevention of the condition requires restoration of blood flow after injury and reduction of compartmental pressure on the muscles. Any splints, bandages, or other devices that might be obstructing circulation must be removed. A fasciotomy may be required to reduce pressure in the muscle compartment. If the contracture occurs, surgery to release the fixed tissues may help with the deformity and function of the hand.
## History[edit]
It is named after Richard von Volkmann (1830–1889), the 19th century German doctor who first described it,[2] in a paper on "non-Infective Ischemic conditions of various fascial compartments in the extremities".[3] Because the contracture occurred at the same time as the paralysis, he considered a nerve cause to be unlikely.[4]
## References[edit]
1. ^ Robert C. France (30 December 2003). Introduction to sports medicine & athletic training. Cengage Learning. pp. 426–. ISBN 978-1-4018-1199-0. Retrieved 15 April 2010.
2. ^ R. Volkmann. Die ischämischen Muskellähmungen und Kontracturen. Centralblatt für Chirurgie, Leipzig, 1881, 8: 801–803.
3. ^ synd/2865 at Who Named It?
4. ^ American Surgical Association (1913). Annals of surgery. J. B. Lippincott. pp. 555–. Retrieved 15 April 2010.
## External links[edit]
Classification
D
* ICD-10: T79.6
* ICD-9-CM: 958.6
* MeSH: D054061
* DiseasesDB: 13991
External resources
* MedlinePlus: 001221
* eMedicine: orthoped/578
* Volkmanns_contracture at the Duke University Health System's Orthopedics program
* v
* t
* e
Trauma
Principles
* Polytrauma
* Major trauma
* Traumatology
* Triage
* Resuscitation
* Trauma triad of death
Assessment
Clinical prediction rules
* Revised Trauma Score
* Injury Severity Score
* Abbreviated Injury Scale
* NACA score
Investigations
* Diagnostic peritoneal lavage
* Focused assessment with sonography for trauma
Management
Principles
* Advanced trauma life support
* Trauma surgery
* Trauma center
* Trauma team
* Damage control surgery
* Early appropriate care
Procedures
* Resuscitative thoracotomy
Pathophysiology
Injury
* MSK
* Bone fracture
* Joint dislocation
* Degloving
* Soft tissue injury
* Resp
* Flail chest
* Pneumothorax
* Hemothorax
* Diaphragmatic rupture
* Pulmonary contusion
* Cardio
* Internal bleeding
* Thoracic aorta injury
* Cardiac tamponade
* GI
* Blunt kidney trauma
* Ruptured spleen
* Neuro
* Penetrating head injury
* Traumatic brain injury
* Intracranial hemorrhage
Mechanism
* Blast injury
* Blunt trauma
* Burn
* Penetrating trauma
* Crush injury
* Stab wound
* Ballistic trauma
* Electrocution
Region
* Abdominal trauma
* Chest trauma
* Facial trauma
* Head injury
* Spinal cord injury
Demographic
* Geriatric trauma
* Pediatric trauma
Complications
* Posttraumatic stress disorder
* Wound healing
* Acute lung injury
* Crush syndrome
* Rhabdomyolysis
* Compartment syndrome
* Contracture
* Volkmann's contracture
* Embolism
* air
* fat
* Chronic traumatic encephalopathy
* Subcutaneous emphysema
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Volkmann's contracture
|
c0042951
| 8,156 |
wikipedia
|
https://en.wikipedia.org/wiki/Volkmann%27s_contracture
| 2021-01-18T19:02:59 |
{"mesh": ["D054061"], "umls": ["C0042951"], "wikidata": ["Q1968751"]}
|
Granuloma gluteale infantum
SpecialtyDermatology
Granuloma gluteale infantum is a cutaneous condition that appears in the anogenital region of infants as a complication of diaper dermatitis.[1]
According to some, no granulomas are found.[2]
## See also[edit]
* Superficial granulomatous pyoderma
* List of cutaneous conditions
## References[edit]
1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
2. ^ De Zeeuw R, Van Praag MC, Oranje AP (2000). "Granuloma gluteale infantum: a case report". Pediatr Dermatol. 17 (2): 141–3. doi:10.1046/j.1525-1470.2000.01734.x. hdl:1765/56610. PMID 10792807.
## External links[edit]
Classification
D
External resources
* eMedicine: article/1111205
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 inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Granuloma gluteale infantum
|
c0343871
| 8,157 |
wikipedia
|
https://en.wikipedia.org/wiki/Granuloma_gluteale_infantum
| 2021-01-18T18:30:12 |
{"umls": ["C0343871"], "wikidata": ["Q5596828"]}
|
A number sign (#) is used with this entry because of evidence that hereditary neutrophilia is caused by heterozygous mutation in the CSF3R gene (138971) on chromosome 1p34. One such family has been reported.
Clinical Features
Herring et al. (1974) described an apparently autosomal dominant form of lifelong, persistent neutrophilia in a mother and 3 of her 4 children. The neutrophils were morphologically and functionally normal. Associated findings were hepatosplenomegaly, histiocytes of Gaucher type, and thickened calvaria due to widened diploe. Leukocyte alkaline phosphatase, serum vitamin B12 levels and heat-labile serum alkaline phosphatase were elevated. The course was benign. No previous report was found. This disorder differs from the familial myeloproliferative syndrome (254700) by the mode of inheritance and benign course. It is also distinct from hereditary eosinophilia (131400).
Plo et al. (2009) described a 3-generation family in which 12 of 16 members had chronic neutrophilia, with median white blood cell (WBC) counts of 21,350 cells per cubic millimeter involving greater than 70% segmented neutrophils or band cells and less than 10% immature granulocytes; median neutrophil counts were 16,900 cells per cubic millimeter. All affected individuals were clinically asymptomatic except the proband, who presented with a unique episode of systemic inflammatory response syndrome that combined fever, tachycardia, dyspnea, pleural and pericardial effusion, hepatosplenomegaly, and weight loss. He had a WBC of 102,000 cells per cubic millimeter, with 75% segmented neutrophils and 20% immature granulocytes; bone marrow analysis showed an increase in granulocyte precursors without an excess of blasts. After this episode, the patient returned to chronic neutrophilia, but 18 months later he developed a myelodysplastic syndrome involving refractory anemia with an excess of blasts (RAEB); bone marrow aspirate showed marked dysgranulopoiesis but no dyserythropoiesis or dysmegakaryopoiesis, and cytogenetic analysis revealed a clonal abnormality (chromosome 3q26 deletion) in 70% of metaphases.
Inheritance
The families with neutrophilia reported by Herring et al. (1974) and Plo et al. (2009) indicated autosomal dominant inheritance.
Molecular Genetics
In a 3-generation family segregating autosomal dominant neutrophilia, Plo et al. (2009) sequenced the CSF3R gene and identified a heterozygous activating mutation (T617N; 138971.0001) in all 12 affected individuals that was not found in the 4 unaffected family members.
INHERITANCE \- Autosomal dominant HEMATOLOGY \- Neutrophilia \- Segmented neutrophils or band cells greater than 70% MISCELLANEOUS \- Most patients clinically asymptomatic \- Myelodysplastic syndrome developed in 1 of 12 mutation-positive patients MOLECULAR BASIS \- Caused by mutation in the granulocyte colony-stimulating factor-3 receptor gene (CSF3R, 138971.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
NEUTROPHILIA, HEREDITARY
|
c0543669
| 8,158 |
omim
|
https://www.omim.org/entry/162830
| 2019-09-22T16:37:24 |
{"doid": ["0090120"], "mesh": ["C563010"], "omim": ["162830"], "orphanet": ["279943"]}
|
Blue rubber bleb nevus syndrome is a condition in which the blood vessels do not develop properly in an area of the skin or other body organ (particularly the intestines). The malformed blood vessels appear as a spot or lesion called a nevus. The underlying blood vessel malformations are present from birth even though the nevus may not be visible until later in life. The size, number, location, and severity of these malformations vary from person to person. Affected areas on the skin can be painful or tender to the touch and may be prone to sweating (hyperhidrosis). Nevi in the intestines can bleed spontaneously and cause anemia or more serious complications. Other symptoms vary depending on the organ affected. Treatment is tailored to the individual depending on the location and symptoms caused by the affected areas.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Blue rubber bleb nevus syndrome
|
c0346072
| 8,159 |
gard
|
https://rarediseases.info.nih.gov/diseases/5940/blue-rubber-bleb-nevus-syndrome
| 2021-01-18T18:01:46 |
{"mesh": ["C536240"], "omim": ["112200"], "umls": ["C0346072"], "orphanet": ["1059"], "synonyms": ["Bean syndrome", "Blue rubber bleb nevus", "BRBNS"]}
|
Spotted fever
SpecialtyInfectious disease
A spotted fever is a type of tick-borne disease which presents on the skin.[1] They are all caused by bacteria of the genus Rickettsia. Typhus is a group of similar diseases also caused by Rickettsia bacteria, but spotted fevers and typhus are different clinical entities.Transmission process: When the tick latches on, it needs to be removed under 2 hours. If not noticed or unremoved it takes only 10 hours for the tick to transmit the (disease) to the human
The phrase apparently originated in Spain in the 17th century and was ‘loosely applied in England to typhus or any fever involving petechial eruptions.’ During the 17th and 18th centuries, it was thought to be "cousin-germane" to and herald of the bubonic plague, a disease which periodically afflicted the city of London and its environs during the 16th and 17th centuries, most notably during the Great Plague of 1665.[2]
Types of spotted fevers include:
* Mediterranean spotted fever
* Rocky Mountain spotted fever
* Queensland tick typhus
* Helvetica spotted fever
## References[edit]
1. ^ "spotted fever" at Dorland's Medical Dictionary
2. ^ Daniel Defoe, A Journal of the Plague Year, ed. Louis Landa (Oxford, 2010) 219.
## External links[edit]
Classification
D
* ICD-10: A77
* ICD-9-CM: 082.0
* MeSH: D000073605
* v
* t
* e
Proteobacteria-associated Gram-negative bacterial infections
α
Rickettsiales
Rickettsiaceae/
(Rickettsioses)
Typhus
* Rickettsia typhi
* Murine typhus
* Rickettsia prowazekii
* Epidemic typhus, Brill–Zinsser disease, Flying squirrel typhus
Spotted
fever
Tick-borne
* Rickettsia rickettsii
* Rocky Mountain spotted fever
* Rickettsia conorii
* Boutonneuse fever
* Rickettsia japonica
* Japanese spotted fever
* Rickettsia sibirica
* North Asian tick typhus
* Rickettsia australis
* Queensland tick typhus
* Rickettsia honei
* Flinders Island spotted fever
* Rickettsia africae
* African tick bite fever
* Rickettsia parkeri
* American tick bite fever
* Rickettsia aeschlimannii
* Rickettsia aeschlimannii infection
Mite-borne
* Rickettsia akari
* Rickettsialpox
* Orientia tsutsugamushi
* Scrub typhus
Flea-borne
* Rickettsia felis
* Flea-borne spotted fever
Anaplasmataceae
* Ehrlichiosis: Anaplasma phagocytophilum
* Human granulocytic anaplasmosis, Anaplasmosis
* Ehrlichia chaffeensis
* Human monocytotropic ehrlichiosis
* Ehrlichia ewingii
* Ehrlichiosis ewingii infection
Rhizobiales
Brucellaceae
* Brucella abortus
* Brucellosis
Bartonellaceae
* Bartonellosis: Bartonella henselae
* Cat-scratch disease
* Bartonella quintana
* Trench fever
* Either B. henselae or B. quintana
* Bacillary angiomatosis
* Bartonella bacilliformis
* Carrion's disease, Verruga peruana
β
Neisseriales
M+
* Neisseria meningitidis/meningococcus
* Meningococcal disease, Waterhouse–Friderichsen syndrome, Meningococcal septicaemia
M−
* Neisseria gonorrhoeae/gonococcus
* Gonorrhea
ungrouped:
* Eikenella corrodens/Kingella kingae
* HACEK
* Chromobacterium violaceum
* Chromobacteriosis infection
Burkholderiales
* Burkholderia pseudomallei
* Melioidosis
* Burkholderia mallei
* Glanders
* Burkholderia cepacia complex
* Bordetella pertussis/Bordetella parapertussis
* Pertussis
γ
Enterobacteriales
(OX−)
Lac+
* Klebsiella pneumoniae
* Rhinoscleroma, Pneumonia
* Klebsiella granulomatis
* Granuloma inguinale
* Klebsiella oxytoca
* Escherichia coli: Enterotoxigenic
* Enteroinvasive
* Enterohemorrhagic
* O157:H7
* O104:H4
* Hemolytic-uremic syndrome
* Enterobacter aerogenes/Enterobacter cloacae
Slow/weak
* Serratia marcescens
* Serratia infection
* Citrobacter koseri/Citrobacter freundii
Lac−
H2S+
* Salmonella enterica
* Typhoid fever, Paratyphoid fever, Salmonellosis
H2S−
* Shigella dysenteriae/sonnei/flexneri/boydii
* Shigellosis, Bacillary dysentery
* Proteus mirabilis/Proteus vulgaris
* Yersinia pestis
* Plague/Bubonic plague
* Yersinia enterocolitica
* Yersiniosis
* Yersinia pseudotuberculosis
* Far East scarlet-like fever
Pasteurellales
Haemophilus:
* H. influenzae
* Haemophilus meningitis
* Brazilian purpuric fever
* H. ducreyi
* Chancroid
* H. parainfluenzae
* HACEK
Pasteurella multocida
* Pasteurellosis
* Actinobacillus
* Actinobacillosis
Aggregatibacter actinomycetemcomitans
* HACEK
Legionellales
* Legionella pneumophila/Legionella longbeachae
* Legionnaires' disease
* Coxiella burnetii
* Q fever
Thiotrichales
* Francisella tularensis
* Tularemia
Vibrionaceae
* Vibrio cholerae
* Cholera
* Vibrio vulnificus
* Vibrio parahaemolyticus
* Vibrio alginolyticus
* Plesiomonas shigelloides
Pseudomonadales
* Pseudomonas aeruginosa
* Pseudomonas infection
* Moraxella catarrhalis
* Acinetobacter baumannii
Xanthomonadaceae
* Stenotrophomonas maltophilia
Cardiobacteriaceae
* Cardiobacterium hominis
* HACEK
Aeromonadales
* Aeromonas hydrophila/Aeromonas veronii
* Aeromonas infection
ε
Campylobacterales
* Campylobacter jejuni
* Campylobacteriosis, Guillain–Barré syndrome
* Helicobacter pylori
* Peptic ulcer, MALT lymphoma, Gastric cancer
* Helicobacter cinaedi
* Helicobacter cellulitis
This infectious disease article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Spotted fever
|
c0038041
| 8,160 |
wikipedia
|
https://en.wikipedia.org/wiki/Spotted_fever
| 2021-01-18T18:49:17 |
{"gard": ["4998"], "mesh": ["D000073605"], "umls": ["C0038041"], "orphanet": ["102022"], "wikidata": ["Q9274700"]}
|
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Most cases of back pain are related to issues in human musculoskeletal system and are not related to severe diseases.[1] Musculoskeletal problems also called mechanical because many of them linked to vertebrae physical motions.[2]
## Contents
* 1 Description
* 2 Back pain recurrence risk reduction
* 3 References
* 4 External links
## Description[edit]
Back pain itself is not considered a diagnosis, but rather a symptom of underlying (in most cases musculoskeletal) problems.[2] following:
* Vertebrae misalignment, which can cause nerve interference (also called subluxation),[3] muscle tension, or muscle spasm[4][5]
* Strained muscles[6]
* Sprained ligaments[6]
* Ruptured disks,[6] which also called "slipped",[7] or herniated disks[2]
* Degenerative discs (lose their cushioning ability).[2] The degeneration usually caused by repetitive strain, or injury, or aging.[8]
* Irritated joints[6]
## Back pain recurrence risk reduction[edit]
* Use safe lifting technique,[1] don't bend over, and maintain your back straight when lifting heavy objects[6]
* Push instead of pulling when moving heavy objects[6]
* Stay active: regular exercises and physical activities help to maintain back muscles and ligaments strong. In turn, strong back muscles provide better support for spine to keep the vertebrae properly aligned, which can ease the back pain and reduce the risk of chronic back pain returning.[2][9] Although, for acute back pain exercises usually not recommended and physical activity should be slow, but it is critical to keep moving as much as possible, because inactivity leads to weakening back muscles and ligaments, and to gain more weight, which might exacerbate back pain.[2][10]
* Sit Up Straight! The way you sit may either cause or help to prevent back pain.[10]
* Maintain proper posture: In many cases poor posture (also called bad posture) is the root cause of back pain because of more stress on the disks and less back muscles activity.[1][10] Most common bad posture samples are round back, sway back, forward head, excessive anterior and exterior pelvis tilts.[10] Proper standing, sitting, and lifting techniques help to reduce the risk of back pain returning.[7] Good posture trains and strengthens back muscles naturally. Maintaining good posture when walking, standing, and sitting in addition to standard medical treatments (and alternative therapies such as chiropractic manipulations[6]) is likely to address the roots of many back pain problems.[10]
## References[edit]
1. ^ a b c American Chiropractic Association (ACA). "Back Pain Facts & Statistics". Archived from the original on 2011-10-21. Retrieved 2011-10-20.
2. ^ a b c d e f National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). "Handout on Health: Back Pain". Publication Date: July 2010. Retrieved 2011-10-23.
3. ^ American Chiropractic Association (ACA). "The Saga of Chiropractic". Archived from the original on 2012-06-01. Retrieved 2011-10-20.
4. ^ J.W. Brantingham, DC. "Journal of Chiropractic. Volume 22. Number 8. Professional Papers. A Survey of Literature…" (PDF). American Chiropractic Association (ACA). Publication Date: August, 1985.[permanent dead link]
5. ^ K. Erickson, DC. "Surprising Ways a Chiropractor Can Help You" (PDF). American Chiropractic Association (ACA). Publication Date: November, 2008. Archived from the original (PDF) on 2012-06-01. Retrieved 2011-11-17.
6. ^ a b c d e f g American Chiropractic Association (ACA). "Does Back Pain Go Away on Its Own?". Archived from the original on 2012-04-28. Retrieved 2011-10-20.
7. ^ a b American Academy of Orthopedic Surgeons (AAOS). "Herniated Disk". Retrieved 2011-10-20.
8. ^ American Physical Therapy Association (APTA). "Study: Physical Therapy is Effective for Low Back Pain". Retrieved 2011-10-20.
9. ^ American Academy of Orthopedic Surgeons (AAOS). "Low Back Pain". Retrieved 2011-10-20.
10. ^ a b c d e American Osteopathic Association (AOA). "Prevention, The Best Treatment for Back Pain". Retrieved 2011-10-20.
## External links[edit]
* Back and spine at Curlie
* Low Back Pain Fact Sheet at National Institute of Neurological Disorders and Stroke
* What's causing your lower back pain? at Harvard Health
* Low back pain at MedlinePlus Medical Encyclopedia
* Back Pain at UW Orthopaedics and Sports Medicine
* Low Back Pain – Causes, Diagnosis and Treatment at American Association of Neurological Surgeons
* v
* t
* e
Spinal disease
Deforming
Spinal curvature
* Kyphosis
* Lordosis
* Scoliosis
Other
* Scheuermann's disease
* Torticollis
Spondylopathy
inflammatory
* Spondylitis
* Ankylosing spondylitis
* Sacroiliitis
* Discitis
* Spondylodiscitis
* Pott disease
non inflammatory
* Spondylosis
* Spondylolysis
* Spondylolisthesis
* Retrolisthesis
* Spinal stenosis
* Facet syndrome
Back pain
* Neck pain
* Upper back pain
* Low back pain
* Coccydynia
* Sciatica
* Radiculopathy
Intervertebral disc disorder
* Schmorl's nodes
* Degenerative disc disease
* Spinal disc herniation
* Facet joint arthrosis
* v
* t
* e
Pain
By region/system
Head and neck
* Headache
* Neck
* Odynophagia (swallowing)
* Toothache
Respiratory system
* Sore throat
* Pleurodynia
Musculoskeletal
* Arthralgia (joint)
* Bone pain
* Myalgia (muscle)
* Acute
* Delayed-onset
Neurologic
* Neuralgia
* Pain asymbolia
* Pain disorder
* Paroxysmal extreme pain disorder
* Allodynia
* Chronic pain
* Hyperalgesia
* Hypoalgesia
* Hyperpathia
* Phantom pain
* Referred pain
* Congenital insensitivity to pain
* congenital insensitivity to pain with anhidrosis
* congenital insensitivity to pain with partial anhidrosis
Other
* Pelvic pain
* Proctalgia
* Back
* Low back pain
Measurement and testing
* Pain scale
* Cold pressor test
* Dolorimeter
* Grimace scale (animals)
* Hot plate test
* Tail flick test
* Visual analogue scale
Pathophysiology
* Nociception
* Anterolateral system
* Posteromarginal nucleus
* Substance P
Management
* Analgesia
* Anesthesia
* Cordotomy
* Pain eradication
Related concepts
* Pain threshold
* Pain tolerance
* Suffering
* SOCRATES
* Philosophy of pain
* Cancer pain
* Drug-seeking behavior
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Musculoskeletal causes of back pain
|
None
| 8,161 |
wikipedia
|
https://en.wikipedia.org/wiki/Musculoskeletal_causes_of_back_pain
| 2021-01-18T18:54:16 |
{"wikidata": ["Q17147935"]}
|
Glossopharyngeal neuralgia is a disorder that is associated with repeated episodes of severe pain in the tongue, throat, ear, and tonsils. These areas are all connected to the ninth cranial nerve, also called the glossopharyngeal nerve. Episodes of pain may last from a few seconds to a few minutes and usually occur on one side of the face. The pain may be triggered by swallowing, speaking, laughing, chewing, or coughing.
Glossopharyngeal neuralgia is thought to be caused by irritation of the glossopharyngeal nerve, but the exact cause of the irritation is sometimes unknown. Laboratory and imaging tests can be used to diagnose the disorder and rule out serious underlying problems. The goal of treatment is to control pain, and the most effective drugs are anti-seizure medications and anti-depressants. Surgery to sever or take pressure off of the glossopharyngeal nerve may be needed in severe cases.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Glossopharyngeal neuralgia
|
c0154731
| 8,162 |
gard
|
https://rarediseases.info.nih.gov/diseases/6519/glossopharyngeal-neuralgia
| 2021-01-18T18:00:18 |
{"mesh": ["D020435"], "umls": ["C0154731"], "synonyms": []}
|
A number sign (#) is used with this entry because of evidence that Joubert syndrome-13 (JBTS13) is caused by homozygous or compound heterozygous mutation in the TCTN1 gene (609863) on chromosome 12q24.
For a phenotypic description and a discussion of genetic heterogeneity of Joubert syndrome, see 213300.
Clinical Features
Garcia-Gonzalo et al. (2011) reported 2 sisters, born of consanguineous Bangladeshi parents, with Joubert syndrome. Brain MRI showed cerebellar vermis hypoplasia and the molar tooth sign, the characteristic radiographic feature of Joubert syndrome. One girl also had bilateral frontotemporal pachygyria. Ophthalmologic assessment and renal ultrasounds were normal at ages 7 years and 4 years, respectively.
Srour et al. (2015) reported a 27-week-old male fetus with JBTS13. Clinical features in the report were sparse, but included the molar tooth sign on brain imaging, abnormal gyration of the frontal lobes, and limb abnormalities.
Inheritance
The transmission pattern of JBTS13 in the family reported by Srour et al. (2015) was consistent with autosomal recessive inheritance.
Molecular Genetics
By homozygosity mapping followed by candidate gene sequencing, Garcia-Gonzalo et al. (2011) identified a homozygous splice site mutation in the TCTN1 gene (609863.0001) in 2 sisters, born of consanguineous Bangladeshi parents, with JBTS13. The TCTN1 gene was found to interact with multiple other proteins in a large complex that localizes to the transition zone between the basal body and axoneme in cilia.
In a 27-week-old male fetus with JBTS13, Srour et al. (2015) identified compound heterozygous mutations in the TCTN1 gene (609863.0001 and 609863.0002). The mutations were found by whole-exome sequencing. Functional studies and studies of patient cells were not performed.
INHERITANCE \- Autosomal recessive GENITOURINARY Kidneys \- Normal renal ultrasound at ages 4 and 7 (in 2 family) SKELETAL Limbs \- Limb anomalies (in some patients) NEUROLOGIC Central Nervous System \- Cerebellar vermis hypoplasia \- Molar tooth sign seen on brain MRI \- Frontotemporal pachygyria MISCELLANEOUS \- Two sibs and an unrelated fetus have been reported (last curated February 2016) MOLECULAR BASIS \- Caused by mutation in the tectonic family, member 1 gene (TCTN1, 609863.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
JOUBERT SYNDROME 13
|
c3280031
| 8,163 |
omim
|
https://www.omim.org/entry/614173
| 2019-09-22T15:56:15 |
{"doid": ["0110982"], "omim": ["614173", "213300"], "orphanet": ["475"], "synonyms": ["CPD IV", "Cerebelloparenchymal disorder IV", "Classic Joubert syndrome", "Joubert syndrome type A", "Joubert-Boltshauser syndrome", "Pure Joubert syndrome"], "genereviews": ["NBK1325"]}
|
Burke et al. (1988) described a male infant and his 2 sisters who died in the neonatal period with congenital adrenal hypoplasia of the 'miniature adult' type, in which the fetal cortex is nearly absent and the miniature adrenal cortex consists almost exclusively of permanent cortex. The glomerulosa and fasciculata are usually present. The male, who died at 4 days of age, had micropenis and undescended testes with deficient Leydig cells. Although there were no gross or microscopic structural defects of the brain or pituitary gland, lack of luteinizing hormone (LH) was demonstrated in the pituitary gland by immunohistochemical study. The 2 sisters likewise showed selective absence of LH in pituitary cells on immunostaining. Glycerol kinase (GK) activity was reduced, as it is in X-linked adrenal hypoplasia in which there is associated deletion of the neighboring locus on Xp that codes for this enzyme. Burke et al. (1988) concluded, however, that the reduced GK activity was related to the apparently autosomal recessive disorder through some other mechanism. The authors considered the possibility that the primary defect might lie in luteinizing hormone releasing hormone (LHRH; 152760), but were unable to obtain convincing evidence of this from DNA studies. The authors provided a tabular review of the differences between the cytomegalic and the 'miniature adult' forms of congenital adrenal hypoplasia. They also provided a tabular review of the reported cases of each type (see 240200).
Endocrine \- Adrenal hypoplasia, 'miniature adult'type GU \- Micropenis \- Cryptorchidism Lab \- Leydig cells deficient \- LH absent 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 inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
ADRENAL HYPOPLASIA, CONGENITAL, WITH ABSENT PITUITARY LUTEINIZING HORMONE
|
c1859978
| 8,164 |
omim
|
https://www.omim.org/entry/202150
| 2019-09-22T16:31:25 |
{"mesh": ["C565976"], "omim": ["202150"], "orphanet": ["95700"]}
|
IgG4-related dacryoadenitis and sialoadenitis (Mikulicz disease) is an IgG4-related sclerosing disease (see this term) characterized by persistent, usually painless, bilateral enlargement of the lacrimal, parotid, and submandibular glands associated with elevated levels of serum immunoglobulin (Ig) G4 and with lymphocyte and IgG4-positive plasmacyte infiltration. It predominantly causes mouth and eye dryness but can also affect other organs such as the lungs, liver, and kidneys, and be accompanied by complications such as autoimmune pancreatitis (AIP), retroperitoneal fibrosis, and tubulointerstitial nephritis (see these terms).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
IgG4-related dacryoadenitis and sialadenitis
|
c0026103
| 8,165 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79078
| 2021-01-23T18:09:48 |
{"gard": ["7043"], "mesh": ["D008882"], "umls": ["C0026103"], "icd-10": ["K11.8"], "synonyms": ["Chronic dacryoadenitis and sialadenitis", "Mikulicz disease"]}
|
A number sign (#) is used with this entry because of evidence that Danon disease, also known as X-linked vacuolar cardiomyopathy and myopathy, is caused by mutation in the gene encoding lysosome-associated membrane protein-2 (LAMP2; 309060).
Description
Danon disease is an X-linked dominant disorder predominantly affecting cardiac muscle. Skeletal muscle involvement and mental retardation are variable features. The accumulation of glycogen in muscle and lysosomes originally led to the classification of Danon disease as a variant of glycogen storage disease II (Pompe disease; 232300) with 'normal acid maltase' or alpha-glucosidase (GAA; 606800) (Danon et al., 1981). However, Nishino et al. (2000) stated that Danon disease is not a glycogen storage disease because glycogen is not always increased.
Sugie et al. (2005) classified Danon disease as a form of autophagic vacuolar myopathy, characterized by intracytoplasmic autophagic vacuoles with sarcolemmal features. The characteristic vacuole is believed to be an autolysosome surrounded by secondarily-generated membranes containing sarcolemmal proteins, basal lamina, and acetylcholinesterase activity.
X-linked myopathy with excessive autophagy (XMEA; 310440) is a distinct disorder with similar pathologic features.
Clinical Features
Antopol et al. (1940) described 2 brothers who died in the second decade of life with heart failure. Autopsy of 1 patient showed glycogen storage disease limited to the myocardium. Mehrizi and Oppenheimer (1960) reported 2 related patients with heart failure associated with unusual deposition of glycogen in the myocardium.
Danon et al. (1981) reported 2 unrelated males with mental retardation, hypertrophic cardiomyopathy, and proximal muscle weakness. One patient had hepatomegaly. Examination of skeletal muscle biopsies showed features suggestive of a lysosomal glycogen storage disease. However, acid alpha-glucosidase activity was normal, excluding a diagnosis of Pompe disease, or glycogen storage disease type II (GSD II). Both patients died at the age of 17 years. Riggs et al. (1983) described lysosomal storage disease with normal acid maltase activity in 2 brothers. One of the brothers showed muscle weakness at age 3 years. Both patients had Wolff-Parkinson-White electrocardiographic findings.
Bergia et al. (1986) reported a kindred in which 2 sisters gave birth to a total of 3 sons with mental retardation, scapuloperoneal muscular weakness, and hypertrophic cardiomyopathy. Intellectual deterioration began at about age 5 years. Hypertrophic cardiomyopathy manifesting itself in the teens led to death at ages 17 and 21 years in 2 of the patients. On evaluation in their teens, the affected males showed wasting of distal muscle groups, positive Gowers maneuver, and predominant humeroperoneal distribution of muscle weakness. Creatine kinase was elevated as was also lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase. A marked myopia was also present. The mother of 2 of the patients, a presumed carrier of the mutant gene, had evidence of cardiomyopathy without elevated serum muscle enzymes.
Tripathy et al. (1988) described an 18-year-old black male who developed manifestations of complete atrioventricular nodal block; endomyocardial biopsy showed membrane-bound glycogen resembling the findings of GSD II. The glycogenosis appeared to be limited to the myocardium because the rest of the physical examination, the histology, and enzyme studies of muscle and skin fibroblasts were normal.
Dworzak et al. (1994) described a Sicilian family in which 3 males and 2 females over 3 generations were affected with lysosomal glycogen storage myopathy with normal acid maltase. Cardiac disease had led to the death of a woman in the first generation and of one of her sons. The proband, his sister, and her son, were alive and had been studied in detail. The index case underwent heart transplant. His 32-year-old sister had atrial fibrillation and mild left ventricular enlargement with systolic dysfunction on echocardiogram. She also had mild intellectual impairment, limb weakness, and mild muscle involvement on muscle biopsy. Dworzak et al. (1994) stated that this was the first case of a female with multisystem involvement.
In skeletal muscle biopsies from 3 patients with Danon disease, Murakami et al. (1995) found intracytoplasmic vacuoles with occasional folds or indentations in the sarcolemma that were connected to the membrane enclosing the vacuoles. Immunohistochemical studies showed that the vacuolar membranes contained acetylcholinesterase and proteins of the sarcolemma and basal lamina.
Sugie et al. (2002) described the clinicopathologic features of 20 affected men and 18 affected women from 13 families with Danon disease confirmed by genetic analysis. All patients had cardiomyopathy. Men were affected before the age of 20 years, whereas most affected women developed cardiomyopathy in adulthood. Eighteen of 20 male patients (90%) and 6 of 18 female patients (33%) had skeletal myopathy; 14 of 20 male patients (70%) and 1 of 18 female patients (6%) had mental retardation. Muscle histology revealed basophilic vacuoles that contained acid phosphatase-positive material within membranes that lacked LAMP2. Heart transplantation was the most effective treatment for the otherwise lethal cardiomyopathy.
Laforet et al. (2004) reported a patient with Danon disease who had features of axonal Charcot-Marie-Tooth disease (see, e.g., CMT2A1; 118210), including pes cavus, distal muscular atrophy of the lower limb, and distal sensory loss. He also developed progressive visual loss due to retinopathy as a young adult.
Lobrinus et al. (2005) reported a Swiss family with Danon disease confirmed by genetic analysis. There were 4 affected males and 2 affected females. The proband developed severe left ventricular cardiomyopathy with ventricular arrhythmia in adolescence. He had diffuse muscular atrophy with mild proximal and axial weakness and markedly increased serum creatine kinase. IQ was 76. Two first cousins had mild muscle involvement, normal intelligence, and cardiac involvement with cardiac symptom onset in adolescence. The mother of the 2 cousins died suddenly at age 40 years from cardiomyopathy. Cardiac muscle biopsy from the proband and 1 cousin showed hypertrophic cardiomyocytes with enlarged and irregular nuclei and vacuolated cytoplasm, as well as absence of LAMP2 protein. Electron microscopy showed that the vacuoles contained degenerating mitochondria, glycogen, small vesicles, and granular debris. Although skeletal muscle biopsies from all 3 patients showed normal morphology and normal glycogen content, all had complete absence of the LAMP2 protein. Cytoplasmic vacuoles could be seen in about 10% of skeletal muscle fibers in the proband and in approximately 1% of fibers in 1 cousin. No vacuoles were observed in the skeletal muscle of the other cousin. There was immunoreactivity to complement components C5b-9 of the membrane attack complex in some of the vacuoles, but not on the fiber surface.
Balmer et al. (2005) reported a mother and son with Danon disease confirmed by genetic analysis. The boy presented at age 2.5 years with mild left ventricular hypertrophy and mild myopathy. His heart disease progressed, resulting in death at age 16 years shortly before planned heart transplantation. His affected mother developed severe dilated cardiomyopathy and died at age 46 years. Postmortem analysis showed fibrosis and necrosis of the myocardium. Balmer et al. (2005) emphasized that cardiac transplantation is the only effective therapeutic option in Danon disease.
Prall et al. (2006) reported the ophthalmic manifestations of genetically proven Danon disease in 4 females and 2 males. The females demonstrated a peripheral pigmentary retinopathy, lens changes, myopia, abnormal electroretinogram, and abnormal visual fields. The males demonstrated a nearly complete loss of pigment in the retinal pigment epithelium. Prall et al. (2006) suggested that retinopathy could potentially be used to identify asymptomatic carriers.
Schorderet et al. (2007) identified diffuse retinal dysfunction, affecting the cones more than the rods, in 2 brothers and their maternal aunt with Danon disease caused by a mutation in LAMP2. Expression of the disease was milder in the aunt, who was an obligate carrier, than in the hemizygous boys, possibly due to lyonization.
Taylor et al. (2007) identified genetically confirmed Danon disease (309060.0012) in and reported long-term follow-up on the family that presented with dilated cardiomyopathy and was linked to the DMD gene (300337) by Towbin et al. (1993). The original female proband and her 3 sons had dilated cardiomyopathy; subsequently, 3 other male relatives developed severe concentric cardiac hypertrophy associated with Wolff-Parkinson-White syndrome. Other features in this family included skeletal myopathy with high serum creatine kinase, mild cognitive impairment in males, and a pigmentary retinopathy in females. Cardiac biopsy specimens showed extensive vacuolar changes in an affected adult male, but the skeletal muscle biopsy in a 13-month-old mutation-carrying male showed no vacuolization by standard histology. Taylor et al. (2007) concluded that X-linked dilated cardiomyopathy may be the presenting sign of Danon syndrome and that the absence of vacuolar myopathy in biopsies from young patients may not exclude Danon disease.
Maron et al. (2009) reported the clinical course and outcome of 7 young patients (6 boys and 1 girl) in whom LAMP2 mutations were previously identified by Arad et al. (2005). Over a mean follow-up period of 8.6 years and by ages 14 to 24 years, the patients developed left ventricular systolic dysfunction and cavity enlargement, with adverse clinical consequences including death from progressive refractory heart failure in 4 patients, sudden death in 1, aborted cardiac arrest in 1, and cardiac transplantation in 1. Left ventricular hypertrophy was particularly marked, with massive ventricular septal thickness in 2 patients of 60 mm and 65 mm at age 23 and 14 years, respectively. In 6 patients, a ventricular preexcitation pattern at study entry was associated with markedly increased R-wave or S-wave voltages and deeply inverted T-waves. Autopsy findings included a combination of histopathologic features that were consistent with lysosomal storage disease, such as clusters of vacuolated myocytes, but also typical of CMH due to sarcomere protein mutations (see, e.g., 192600), such as myocyte disarray, small vessel disease, and myocardial scarring. Maron et al. (2009) noted that 7 female LAMP2 obligate carriers in 2 of the families, aged 19 to 51 years, had remained asymptomatic, underscoring the striking differences in clinical phenotypes and outcomes between female carriers and affected male patients.
Boucek et al. (2011) presented data on 82 patients with Danon disease from 36 families. Men were severely affected with cognitive disabilities (100%), hypertrophic cardiomyopathy (88%), and muscle weakness (80%). Men had a high morbidity and were unlikely to reach the age of 25 years without a cardiac transplantation. Women were less severely affected but reported higher than expected levels of cognitive (47%) and skeletal muscle complaints (50%) and manifesting an equal prevalence of dilated cardiomyopathy and hypertrophic cardiomyopathy. Combining their data with that of 63 other Danon disease case reports in the literature, Boucek et al. (2011) determined that the average ages of first symptom, cardiac transplantation, and death were 12.1, 17.9, and 19.0 years in men and 27.9, 33.7, and 34.6 years in women, respectively. Boucek et al. (2011) concluded that women with Danon disease present with clinical symptoms and events approximately 15 years after men and report a higher proportion of cognitive and skeletal muscle problems than had been recognized.
Inheritance
Byrne et al. (1986) described a family in which 7 members of 3 generations had cardioskeletal myopathy with accumulation of glycogen in lysosomes but normal acid maltase levels. Cardiomyopathy dominated the clinical picture with death between ages 18 and 40 years. There was no male-to-male transmission, but 3 affected females were as severely affected as the 4 males.
Dworzak et al. (1994) found reports of 12 young boys with mild myopathy, varying degrees of mental retardation, and severe cardiomyopathy, whose skeletal muscle examination showed lysosomal glycogen storage not due to acid maltase deficiency. Only 2 cases were sporadic. All of the 10 other cases had a brother or male relative in the maternal line who was either equally affected or had died from heart disease in the second decade. In most cases females were also affected, but cardiomyopathy was the only reported phenotypic expression. The females generally died in the fourth decade. The pattern suggested X-linked dominant inheritance.
Molecular Genetics
In 10 unrelated patients with Danon disease, Nishino et al. (2000) identified 10 different mutations in the LAMP2 gene (see, e.g., 309060.0001-309060.0006). All of the mutations resulted in premature termination of the LAMP2 protein. Several patients had previously been reported by Danon et al. (1981), Dworzak et al. (1994), Riggs et al. (1983), and Byrne et al. (1986). Western blot analysis of skeletal muscle biopsies from the patients showed marked deficiency or complete absence of the LAMP2 protein. From these results, and the finding that Lamp2-deficient mice manifest a singular vacuolar cardioskeletal myopathy, Nishino et al. (2000) concluded that primary LAMP2 deficiency is the cause of Danon disease. The authors stated that this was the first example of human cardiomyopathy caused by mutations in a lysosomal structural protein rather than an enzymatic protein.
Charron et al. (2004) analyzed the LAMP2 gene in 50 patients with hypertrophic cardiomyopathy (CMH; see 192600) who were negative for mutations in 9 sarcomeric genes and did not have autosomal dominant inheritance. The authors identified 2 different mutations in the LAMP2 gene (309060.0008 and 309060.0009) in 2 patients, both with skeletal muscle weakness on examination and PAS-positive sarcoplasmic vacuoles on skeletal muscle biopsy by light microscopy, who died at ages 22 and 25 years, respectively. The prevalence of Danon disease was therefore 1% of patients with CMH (2 of 197 patients initially screened with CMH in this study) or 4% of enrolled index cases (2 of 50 index patients who were screened for LAMP2 mutations). Danon disease was responsible for 50% of the cases of CMH with clinical skeletal myopathy (2 of 4 patients); none of the 41 patients with isolated CMH had Danon disease.
In genetic analyses of 24 subjects with increased left ventricular wall thickness and electrocardiogram suggesting ventricular preexcitation, Arad et al. (2005) found 4 LAMP2 mutations (see, e.g., 309060.0010). Clinical features associated with defects in LAMP2 included male sex, severe hypertrophy, early onset (at 8 to 17 years of age), ventricular preexcitation, and asymptomatic elevations of 2 serum proteins. Mutations in heterozygous state appeared to be responsible for unusual heart disease in some females.
In the family ('XLCM-2') that presented with dilated cardiomyopathy and was linked to the DMD gene by Towbin et al. (1993), Taylor et al. (2007) identified a 1-bp deletion in the LAMP2 gene (309060.0012).
Genotype/Phenotype Correlations
In a male patient with hypertrophic cardiomyopathy, exercise intolerance, and hyperCKemia consistent with a mild form of Danon disease, Musumeci et al. (2005) identified a missense mutation in the LAMP2 gene (309060.0011). The patient did not have muscle weakness or mental retardation. Musumeci et al. (2005) noted that all previous mutations in the LAMP2 gene causing Danon disease resulted in premature termination of the protein, and stated that this was the first missense mutation reported in the LAMP2 gene.
Nomenclature
Although this disorder was originally described as a type of glycogen storage disease, Danon et al. (1981) recognized that acid alpha-glucosidase and other enzymes of glycogen metabolism were normal in affected patients. The subsequent identification of the structural lysosome-associated membrane protein-2 gene as responsible for the disorder enabled the proper identification of Danon disease as resulting from a defect of the lysosomal membrane (Nishino et al., 2000). Former designations for this disorder are retained here for historical purposes.
INHERITANCE \- X-linked dominant HEAD & NECK Eyes \- Moderate central loss of visual acuity in males (20/60) \- Normal to near-normal visual acuity in carrier females (20/30-20/20) \- Fine lamellar white opacities on slit lamp exam in carrier females \- Near complete loss of peripheral retinal pigment in males \- Peppered pigmentary mottling of peripheral retinal pigment in carrier females \- Nonspecific changes on electroretinogram in carrier females CARDIOVASCULAR Heart \- Hypertrophic cardiomyopathy \- Dilated cardiomyopathy \- Cardiomegaly \- Arrhythmias \- Wolff-Parkinson-White syndrome \- Hypokinesia \- Decreased contractility \- Biopsy shows hypertrophic cardiomyocytes \- Cardiomyocytes have irregular nuclei \- Cardiomyocytes show glycogen accumulation in myofibrils and lysosomes \- Cardiomyocytes contain vacuolated cytoplasm with degenerated mitochondria, glycogen, and granular debris \- Myocardial fibrosis \- Myocardial necrosis \- Severely decreased or absent LAMP2 protein SKELETAL Feet \- Pes cavus (uncommon) MUSCLE, SOFT TISSUES \- Proximal muscle weakness (85% of patients) \- Diffuse muscle atrophy \- Exercise intolerance \- Muscle cramps with exercise \- EMG shows myopathic changes \- Muscle biopsy shows sarcoplasmic PAS-positive vacuoles \- Muscle biopsy shows glycogen accumulation in myofibrils and lysosomes \- Indentations or folds of the sarcolemma are connected to the membranes enclosing the vacuoles \- Vacuoles are autophagocytic \- Vacuolar membranes immunostain with sarcolemmal proteins \- Severely decreased or absent LAMP2 protein \- Positive staining for complement C5b-9 membrane attack complex proteins within vacuoles, but not on muscle fiber membrane \- Normal alpha-glucosidase or acid maltase activity (GAA, 606800 ) NEUROLOGIC Central Nervous System \- Mental retardation (70%) \- Cognitive impairment, mild \- Delayed development LABORATORY ABNORMALITIES \- Increased serum creatine kinase MISCELLANEOUS \- Phenotypic variability \- Not all patients have skeletal muscle symptoms or mental retardation \- Sudden death in affected males occurs in teens \- Sudden death in affected females occurs in the forties \- Females often show milder phenotype with later onset of cardiac symptoms MOLECULAR BASIS \- Caused by mutation in the lysosome associated membrane protein-2 gene (LAMP2, 309060.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
DANON DISEASE
|
c0878677
| 8,166 |
omim
|
https://www.omim.org/entry/300257
| 2019-09-22T16:20:37 |
{"doid": ["0050437"], "mesh": ["D052120"], "omim": ["300257"], "orphanet": ["34587"], "synonyms": ["Alternative titles", "VACUOLAR CARDIOMYOPATHY AND MYOPATHY, X-LINKED", "PSEUDOGLYCOGENOSIS II", "ANTOPOL DISEASE", "LYSOSOMAL GLYCOGEN STORAGE DISEASE WITHOUT ACID MALTASE DEFICIENCY, FORMERLY", "GLYCOGEN STORAGE DISEASE IIb", "GSD IIb, FORMERLY"]}
|
Myoclonus-dystonia syndrome (MDS) is a rare movement disorder characterized by mild to moderate dystonia along with 'lightning-like' myoclonic jerks.
## Epidemiology
The estimated prevalence of MDS in Europe is 1/500,000.
## Clinical description
Disease onset usually occurs in the first or second decade of life. Myoclonus is usually the presenting manifestation and is described as swift ''lightning-like'' jerks that can rarely appear at rest but that are usually triggered by complex motor tasks such as drawing and writing. These movements mainly affect the neck, arms and trunk but can also rarely be seen in the legs or the larynx. In two thirds of cases, dystonia is also experienced in the form of focal or cervical dystonia (see these terms), which may be only mild and does not exacerbate with time. Postural and other forms of tremor have sometimes been reported. MDS is often associated with depression, anxiety, panic attacks, obsessive-compulsive behavior and personality disorders and alcohol abuse. Isolated torticollis is seen in extremely rare cases.
## Etiology
The only known causative gene of MDS is the epsilon-sarcoglycan (SGCE) gene (7q21.3), encoding a transmembrane protein that is part of the dystrophin-associated glycoprotein complex found in skeletal and cardiac muscle. The epsilon-sarcoglycan protein is also abundant in monoaminergic neurons, cerebellar Purkinje cells, the cortex and the hippocampus of the brain. In one family with MDS, linkage to chromosome 18p has been reported (named DYT15), but the gene has not yet been identified.
## Diagnostic methods
Diagnosis is based on the presence of characteristic clinical symptoms. Neuroimaging studies are normal. Genetic molecular testing of SGCE can confirm the diagnosis.
## Differential diagnosis
Differential diagnosis includes cervical dystonia, Dopa-responsive dystonia, Tourette syndrome, familial cortical myoclonus, Wilson disease, spinocerebellar ataxia type 3 (SCA3) and type 14 (SCA14), ataxia with vitamin E deficiency, genetic disorders with myoclonus as a major component (e.g. Unverricht-Lundborg disease, Lafora disease) (see these terms) and other secondary forms of dystonia.
## Antenatal diagnosis
Prenatal testing is possible in families where a disease-causing mutation is identified.
## Genetic counseling
MDS is inherited in an autosomal dominant manner. However, the SGCE gene is maternally imprinted, therefore in most cases (95%) a patient who inherits the mutation from their mother will remain healthy and only those that inherit the mutation from their father will develop MDS. De novo mutations also occur. Genetic counseling is recommended in those with a known mutation.
## Management and treatment
Treatment plans are individualized to a patient's presenting symptoms. Benzodiazepines (clonazepam) and antiepileptic drugs (valproate, levetiracetam) are effective in relieving myoclonus and tremor, but patients should be carefully monitored. Similarly, alcohol frequently improves symptoms temporarily, but its long term use is not recommended. Injections of botulinum toxin can relieve focal and cervical dystonia. If these treatments fail or are insufficient, bilateral deep brain stimulation (DBS) of the internal globus pallidum (Gpi) and the central intermediate nucleus (VIM) of the thalamus have shown positive results in providing lasting relief from both myoclonus and dystonia. Gpi stimulation is often sufficient in treating MDS, and may be favored over VIM stimulation, which generally has very little effect on dystonia. In a staged surgical procedure, quadruple stimulation (VIM and Gpi) may also be considered in selected cases.
## Prognosis
Patients with MDS have normal life-expectancy, but quality of life can be severely affected.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Myoclonus-dystonia syndrome
|
c1834570
| 8,167 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=36899
| 2021-01-23T17:57:59 |
{"gard": ["7139"], "mesh": ["C536096"], "omim": ["159900", "616398"], "umls": ["C1834570"], "icd-10": ["G24.1"], "synonyms": ["Alcohol-responsive dystonia", "Hereditary essential myoclonus", "Myoclonic dystonia"]}
|
## Clinical Features
Fryns et al. (1988) described an apparently new form of mesomelia in father and daughter. Other than hypoplasia of the ulna with severe radial bowing, there were no other abnormalities in the skeleton; specifically, the tibiae and fibulae were completely normal. The father was 179 cm tall, with an arm span of 144 cm. At age 6 months, the daughter was at the fifth percentile for length. The father and mother of the father were 47 and 45 years old, respectively, at the time of his birth.
Megarbane and Ghanem (2005) reported a Lebanese father and son with isolated upper limb mesomelic dysplasia and normal stature. The 8-year-old boy had prominent bowed radii, limitation of motion of the elbows, dislocation of the radial heads, prominent joints, and ulnar deviation of both hands. X-ray examination revealed short and thick ulnae, and short, thick, and bowed radii, with subluxation of the radial heads. The boy's father had a milder phenotype, with more involvement of the right arm than the left. The parents were consanguineous, but the mother and an older sib were unaffected.
Inheritance
Megarbane and Ghanem (2005) noted that the vertical mode of transmission in their family and in the family reported by Fryns et al. (1988) suggested autosomal dominant inheritance with variable expressivity.
INHERITANCE \- Autosomal dominant SKELETAL Limbs \- Mesomelia, severe (arms only) \- Ulnar hypoplasia, distal \- Radial bowing, severe (adult) \- Short, dysplastic radii \- Short, dysplastic ulnae Hands \- Ulnar deviation of hands ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
ULNAR HYPOPLASIA
|
c1860614
| 8,168 |
omim
|
https://www.omim.org/entry/191440
| 2019-09-22T16:32:14 |
{"mesh": ["C538069"], "omim": ["191440"], "orphanet": ["2497"], "synonyms": ["Alternative titles", "UPPER LIMB MESOMELIC DYSPLASIA"]}
|
The stromal corneal dystrophies refer to a group of rare genetically determined corneal dystrophies (CDs) characterized by lesions affecting the corneal stroma, and variable effects on vision depending on the type of dystrophy.
## Epidemiology
Prevalence of this group of corneal dystrophies is unknown, but all are rare.
## Clinical description
Age of onset is variable. Eleven subtypes of stromal corneal dystrophy have been identified: Pre-Descemet CD, Type I and Type II lattice CD, Type I and type II granular CD, Macular CD, Schnyder CD, Congenital stromal CD, Fleck CD, Posterior amorphous CD and Central cloudy dystrophy of François (see these terms).
## Etiology
Like most corneal dystrophies, stromal forms are mostly genetically determined and mutations in the following genes have been identified as causing stromal lesions: TGFBI (5q31), CHST6 (16q22), UBIAD1 (1p36.22), DCN (12q23), and PIKFYVE (2q34).
## Genetic counseling
An autosomal dominant pattern of inheritance has been reported for all subtypes, with the exception of macular CD which is transmitted as an autosomal recessive trait.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Stromal corneal dystrophy
|
c0038457
| 8,169 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98626
| 2021-01-23T16:56:03 |
{"mesh": ["D003317"], "umls": ["C0038457"], "icd-10": ["H18.5"]}
|
X-linked intellectual disability, Siderius type is characterised by mild to borderline intellectual deficit associated with cleft lip/palate. Preaxial polydactyly, large hands and cryptorchidism are sometimes present. The syndrome has been described in seven boys from two families. Transmission is X-linked and the syndrome is caused by mutations in the PHF8 gene, localised to the p11.21 region of the X chromosome.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
X-linked intellectual disability, Siderius type
|
c1846055
| 8,170 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=85287
| 2021-01-23T19:11:28 |
{"gard": ["9704"], "mesh": ["C537333"], "omim": ["300263"], "umls": ["C1846055"], "icd-10": ["Q87.8"]}
|
A rare multiple congenital anomalies/dysmorphic syndrome characterized by facial dysmorphism (brachycephaly, long, narrow, triangular face, prominent forehead, hypertelorism, flat philtrum, microstomia, thin lips, hypoplastic maxilla), marfanoid habitus with arachnodactyly, and moderate to severe intellectual disability. Additional features may include clinodactyly, triphalangeal thumbs, hammer-shaped toes, hyperextensible joints, hypotonia, hyperreflexia and underdeveloped musculature. Delayed external genitalia development, as well as seizures and mitral regurgitation have been reported in some cases. There have been no further descriptions in the literature since 1995.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Arachnodactyly-intellectual disability-dysmorphism syndrome
|
None
| 8,171 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1130
| 2021-01-23T18:58:08 |
{"gard": ["1858", "764"], "icd-10": ["Q87.8"], "synonyms": ["De Die-Smulders-Vles-Fryns syndrome"]}
|
Mental disorder characterized by recurring, multiple, and current, clinically significant complaints about somatic symptoms
Somatization disorder
Other namesBriquet's syndrome
Play media
SpecialtyPsychiatry, clinical psychology
SymptomsVariable physical symptoms that can include headaches,generalized pain,changes in bowel movements,fatigue,weakness,pain with sex[1],distress about these symtoms
Risk factorsDepression, anxiety, substance abuse, parental neglect, abuse
Differential diagnosisConversion disorder, real physical illness
TreatmentCognitive behavioral therapy, electroconvulsive therapy
Somatization disorder is a mental disorder characterized by recurring, multiple, and current, clinically significant complaints about somatic symptoms. It was recognized in the DSM-IV-TR classification system, but in the latest version DSM-5, it was combined with undifferentiated somatoform disorder to become somatic symptom disorder, a diagnosis which no longer requires a specific number of somatic symptoms.[2] ICD-10, the latest version of the International Statistical Classification of Diseases and Related Health Problems, still includes somatization syndrome.[3]
## Contents
* 1 Criteria
* 1.1 DSM-5
* 1.2 DSM-IV-TR
* 1.3 ICD-10
* 2 Cause
* 2.1 Neuroimaging evidence
* 3 Treatments
* 4 Epidemiology
* 5 See also
* 6 References
* 7 External links
## Criteria[edit]
### DSM-5[edit]
In the DSM-5 the disorder has been renamed somatic symptom disorder (SSD), and includes SSD with predominantly somatic complaints (previously referred to as somatization disorder), and SSD with pain features (previously known as pain disorder).[4]
### DSM-IV-TR[edit]
The DSM-IV-TR diagnostic criteria are:[5]
* A history of somatic complaints over several years, starting prior to the age of 30.
* Such symptoms cannot be fully explained by a general medical condition or substance use or, when there is an associated medical condition, the impairments due to the somatic symptoms are more severe than generally expected.
* Complaints are not feigned as in malingering or factitious disorder.
The symptoms do not all have to occur at the same time, but may occur over the course of the disorder. A somatization disorder itself is chronic but fluctuating that rarely remits completely. A thorough physical examination of the specified areas of complaint is critical for somatization disorder diagnosis. Medical examination would provide object evidence of subjective complaints of the individual.[5]
Diagnosis of somatization disorder is difficult because it is hard to determine to what degree psychological factors are exacerbating subjective feelings of pain. For instance, chronic pain is common in 30% of the U.S. population,[6] making it difficult to determine whether or not the pain is due to predominately psychological factors.
### ICD-10[edit]
In ICD-10, the latest version of the International Statistical Classification of Diseases and Related Health Problems, somatization syndrome is described as:[3]
> "The main features are multiple, recurrent and frequently changing physical symptoms of at least two years duration. Most patients have a long and complicated history of contact with both primary and specialist medical care services, during which many negative investigations or fruitless exploratory operations may have been carried out. Symptoms may be referred to any part or system of the body. The course of the disorder is chronic and fluctuating, and is often associated with disruption of social, interpersonal, and family behaviour."
ICD-10 also includes the following subgroups of somatization syndrome:[3]
* Undifferentiated somatoform disorder.
* Hypochondriasis.
* Somatoform autonomic dysfunction.
* Persistent somatoform pain disorder.
* Other somatoform disorders, such ones predominated by dysmenorrhoea, dysphagia, pruritus and torticollis.
* Somatoform disorder, unspecified.
## Cause[edit]
Although somatization disorder has been studied and diagnosed for more than a century, there is debate and uncertainty regarding its pathophysiology. Most current explanations focus on the concept of a misconnection between the mind and the body. Genetics probably contributes a very small amount to development of the disorder.[7]
One of the oldest explanations for somatization disorder advances the theory that it is a result of the body's attempt to cope with emotional and psychological stress. The theory states that the body has a finite capacity to cope with psychological, emotional, and social distress, and that beyond a certain point symptoms are experienced as physical, principally affecting the digestive, nervous, and reproductive systems. There are many different feedback systems where the mind affects the body; for instance, headaches are known to be associated with psychological factors,[8] and stress and the hormone cortisol are known to have a negative impact on immune functions. This might explain why somatization disorders are more likely in people with irritable bowel syndrome, and why patients with SSD are more likely to have a mood or anxiety disorder.[5] There is also a much increased incidence of SSD in people with a history of physical, emotional or sexual abuse.[9]
Another hypothesis for the cause of somatization disorder is that people with the disorder have heightened sensitivity to internal physical sensations and pain.[10] A biological sensitivity to somatic feelings could predispose a person to developing SSD. It is also possible that a person's body might develop increased sensitivity of nerves associated with pain and those responsible for pain perception, as a result of chronic exposure to stressors.[11]
Cognitive theories explain somatization disorder as arising from negative, distorted, and catastrophic thoughts and reinforcement of these cognitions. Catastrophic thinking could lead a person to believe that slight ailments, such as mild muscle pain or shortness of breath, are evidence of a serious illness such as cancer or a tumor. These thoughts can then be reinforced by supportive social connections. A spouse who responds more to his or her partner's pain cues makes it more likely that he or she will express greater pain.[12] Children of parents who are preoccupied or overly attentive to the somatic complaints of their children are more likely to develop somatic symptoms.[13] Severe cognitive distortions can make a person with SSD limit the behaviors he or she engages in, and cause increased disability and impaired functioning.[14]
### Neuroimaging evidence[edit]
A recent review of the cognitive–affective neuroscience of somatization disorder suggested that catastrophization in patients with somatization disorders tends to present a greater vulnerability to pain. The relevant brain regions include the dorsolateral prefrontal, insular, rostral anterior cingulate, premotor, and parietal cortices.[15][16]
## Treatments[edit]
To date, cognitive behavioral therapy (CBT) is the best established treatment for a variety of somatoform disorders including somatization disorder.[17][18][19] CBT aims to help patients realize their ailments are not catastrophic and to enable them to gradually return to activities they previously engaged in, without fear of "worsening their symptoms". Consultation and collaboration with the primary care physician also demonstrated some effectiveness.[19][20] The use of antidepressants is preliminary but does not yet show conclusive evidence.[19][21] Electroconvulsive shock therapy (ECT) has been used in treating somatization disorder among the elderly; however, the results were still debatable with some concerns around the side effects of using ECT.[22] Overall, psychologists recommend addressing a common difficulty in patients with somatization disorder in the reading of their own emotions. This may be a central feature of treatment; as well as developing a close collaboration between the GP, the patient and the mental health practitioner.[23]
## Epidemiology[edit]
Somatization disorder is estimated to occur in 0.2% to 2% of females,[24][25] and 0.2% of males.
There are cultural differences in the prevalence of somatization disorder. For example, somatization disorder and symptoms were found to be significantly more common in Puerto Rico.[26] In addition the diagnosis is also more prevalent among African Americans and those with less than a high school education or lower socioeconomic status.[27]
There is usually co-morbidity with other psychological disorders, particularly mood disorders or anxiety disorders.[5][28] Research also showed comorbidity between somatization disorder and personality disorders, especially antisocial, borderline, narcissistic, histrionic, avoidant, and dependent personality disorder.[29]
About 10-20 percent of female first degree relatives also have somatization disorder and male relatives have increased rates of alcoholism and sociopathy.[30]
## See also[edit]
* Psychology portal
* Body-centred countertransference
* Culture-bound syndrome
* Hypochondriasis
* Medically unexplained symptoms
* Psychosomatic illness
## References[edit]
1. ^ https://my.clevelandclinic.org/health/diseases/17976-somatic-symptom-disorder-in-adults
2. ^ "Highlights of Changes from DSM-IV-TR to DSM-5" (PDF). American Psychiatric Association. May 17, 2013. Retrieved September 6, 2013.
3. ^ a b c "ICD-10 Version:2015". Retrieved 2015-05-23.
4. ^ Association, American Psychiatric (2013). Diagnostic and Statistical Manual of Mental DisordersAmerican Psychiatric Associati (5th ed.). Arlington: AMERICAN PSYCHIATRIC PUBLISHING. ISBN 978-0890425558.
5. ^ a b c d American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision: DSM-IV-TR. Washington, DC: American Psychiatric Association. pp. 486–490. ISBN 978-0-89042-025-6.
6. ^ Hoffman BM, Papas RK, Chatkoff DK, Kerns RD (January 2007). "Meta-analysis of psychological interventions for chronic low back pain". Health Psychol. 26 (1): 1–9. doi:10.1037/0278-6133.26.1.1. PMID 17209691.
7. ^ Kato K, Sullivan PF, Evengård B, Pedersen NL (March 2009). "A population-based twin study of functional somatic syndromes". Psychol Med. 39 (3): 497–505. doi:10.1017/S0033291708003784. PMC 3947533. PMID 18578896.
8. ^ Martin PR, MacLeod C (August 2009). "Behavioral management of headache triggers: Avoidance of triggers is an inadequate strategy". Clin Psychol Rev. 29 (6): 483–95. doi:10.1016/j.cpr.2009.05.002. PMID 19556046.
9. ^ Pribor E. F.; Yutzy S. H.; Dean J. T.; Wetzel R. D. (1993). "Briquet's Syndrome, dissociation and abuse". American Journal of Psychiatry. 150 (10): 1507–1511. CiteSeerX 10.1.1.474.4552. doi:10.1176/ajp.150.10.1507. PMID 8379555.
10. ^ Katzer A, Oberfeld D, Hiller W, Gerlach AL, Witthöft M (May 2012). "Tactile perceptual processes and their relationship to somatoform disorders". J Abnorm Psychol. 121 (2): 530–43. CiteSeerX 10.1.1.702.448. doi:10.1037/a0026536. PMID 22149912.
11. ^ Farrugia D, Fetter H (2009). "Chronic pain: Biological understanding and treatment suggestions for mental health counselors". Journal of Mental Health Counseling. 31 (3): 189–200. doi:10.17744/mehc.31.3.f2l6hk4834p82483.
12. ^ Williamson D, Robinson ME, Melamed B (January 1997). "Pain behavior, spouse responsiveness, and marital satisfaction in patients with rheumatoid arthritis". Behav Modif. 21 (1): 97–118. doi:10.1177/01454455970211006. PMID 8995045.
13. ^ Watt MC, O'Connor RM, Stewart SH, Moon EC, Terry L (2008). "Specificity of childhood learning experiences in relation to anxiety sensitivity and illness/injury sensitivity: Implications for health anxiety and pain". Journal of Cognitive Psychotherapy. 22 (2): 128–143. CiteSeerX 10.1.1.579.8368. doi:10.1891/0889-8391.22.2.128.
14. ^ "Somatization disorder". Encyclopedia of Mental Disorders. Retrieved October 10, 2008.
15. ^ Stein DJ, Muller J (May 2008). "Cognitive-affective neuroscience of somatization disorder and functional somatic syndromes: reconceptualizing the triad of depression-anxiety-somatic symptoms". CNS Spectr. 13 (5): 379–84. doi:10.1017/S1092852900016540. PMID 18496475.
16. ^ García-Campayo J, Fayed N, Serrano-Blanco A, Roca M (March 2009). "Brain dysfunction behind functional symptoms: neuroimaging and somatoform, conversive, and dissociative disorders". Curr Opin Psychiatry. 22 (2): 224–31. doi:10.1097/YCO.0b013e3283252d43. PMID 19553880.
17. ^ Allen LA, Woolfolk RL, Escobar JI, Gara MA, Hamer RM (July 2006). "Cognitive-behavioral therapy for somatization disorder: a randomized controlled trial". Arch. Intern. Med. 166 (14): 1512–8. doi:10.1001/archinte.166.14.1512. PMID 16864762.
18. ^ Mai F (October 2004). "Somatization disorder: a practical review". Can J Psychiatry. 49 (10): 652–62. doi:10.1177/070674370404901002. PMID 15560311.
19. ^ a b c Kroenke K (December 2007). "Efficacy of treatment for somatoform disorders: a review of randomized controlled trials". Psychosom Med. 69 (9): 881–8. doi:10.1097/PSY.0b013e31815b00c4. PMID 18040099.
20. ^ Smith GR, Monson RA, Ray DC (May 1986). "Psychiatric consultation in somatization disorder. A randomized controlled study". N. Engl. J. Med. 314 (22): 1407–13. doi:10.1056/NEJM198605293142203. PMID 3084975.
21. ^ Stahl SM (July 2003). "Antidepressants and somatic symptoms: therapeutic actions are expanding beyond affective spectrum disorders to functional somatic syndromes". J Clin Psychiatry. 64 (7): 745–6. PMID 12934972.
22. ^ Zorumski CF, Rubin EH, Burke WJ (June 1988). "Electroconvulsive therapy for the elderly: a review". Hosp Community Psychiatry. 39 (6): 643–7. doi:10.1176/ps.39.6.643. PMID 3042587.
23. ^ Kenny M, Egan J (February 2011). "Somatization disorder: What clinicians need to know" (PDF). The Irish Psychologist. 37 (4): 93–96. Retrieved 9 December 2011.
24. ^ deGruy F, Columbia L, Dickinson P (July 1987). "Somatization disorder in a family practice". J Fam Pract. 25 (1): 45–51. PMID 3598478.
25. ^ Lichstein PR (March 1986). "Caring for the patient with multiple somatic complaints". South. Med. J. 79 (3): 310–4. doi:10.1097/00007611-198603000-00013. PMID 3952541.
26. ^ Canino G, Bird H, Rubio-Stipec M, Bravo M (2000). "The epidemiology of mental disorders in the adult population of Puerto Rico". Revista Interamericana de Psicologia. 34 (1X): 29–46.
27. ^ Noyes R, Stuart S, Watson DB, Langbehn DR (2006). "Distinguishing between hypochondriasis and somatization disorder: a review of the existing literature". Psychother Psychosom. 75 (5): 270–81. doi:10.1159/000093948. PMID 16899963.
28. ^ Lieb, Roselind; Meinlschmidt, Gunther; Araya, Ricardo. (2007). "Epidemiology of the association between somatoform disorders and anxiety and depressive disorders: An update". Psychosomatic Medicine. 69 (9): 860–863. doi:10.1097/psy.0b013e31815b0103. PMID 18040095.
29. ^ Bornstein, Robert F; Gold, Stephanie H (2008). "Comorbidity of personality disorders and somatization disorder: A meta-analytic review". Journal of Psychopathology and Behavioral Assessment. 30 (2): 154–161. doi:10.1007/s10862-007-9052-2.
30. ^ Stern, Theodore (2008). Massachusetts General Hospital comprehensive clinical psychiatry (1st ed.). Philadelphia, PA: Mosby/Elsevier. p. 323. ISBN 9780323047432.
## External links[edit]
Classification
D
* ICD-10: F45.0
* ICD-9-CM: 300.81
* MeSH: D013001
* DiseasesDB: 1645
* SNOMED CT: 397923000
External resources
* eMedicine: ped/3015
* 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
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* Sundowning
* Vascular dementia
* Wandering
Other
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* Organic brain syndrome
* Post-concussion syndrome
Neurotic, stress-related and somatoform
Adjustment
* Adjustment disorder with depressed mood
Anxiety
Phobia
* Agoraphobia
* Social anxiety
* Social phobia
* Anthropophobia
* Specific social phobia
* Specific phobia
* Claustrophobia
Other
* Generalized anxiety disorder
* OCD
* Panic attack
* Panic disorder
* Stress
* Acute stress reaction
* PTSD
Dissociative
* Depersonalization disorder
* Dissociative identity disorder
* Fugue state
* Psychogenic amnesia
Somatic symptom
* Body dysmorphic disorder
* Conversion disorder
* Ganser syndrome
* Globus pharyngis
* Psychogenic non-epileptic seizures
* False pregnancy
* Hypochondriasis
* Mass psychogenic illness
* Nosophobia
* Psychogenic pain
* Somatization disorder
Physiological and physical behavior
Eating
* Anorexia nervosa
* Bulimia nervosa
* Rumination syndrome
* Other specified feeding or eating disorder
Nonorganic sleep
* Hypersomnia
* Insomnia
* Parasomnia
* Night terror
* Nightmare
* REM sleep behavior disorder
Postnatal
* Postpartum depression
* Postpartum psychosis
Sexual dysfunction
Arousal
* Erectile dysfunction
* Female sexual arousal disorder
Desire
* Hypersexuality
* Hypoactive sexual desire disorder
Orgasm
* Anorgasmia
* Delayed ejaculation
* Premature ejaculation
* Sexual anhedonia
Pain
* Nonorganic dyspareunia
* Nonorganic vaginismus
Psychoactive substances, substance abuse and substance-related
* Drug overdose
* Intoxication
* Physical dependence
* Rebound effect
* Stimulant psychosis
* Substance dependence
* Withdrawal
Schizophrenia, schizotypal and delusional
Delusional
* Delusional disorder
* Folie à deux
Psychosis and
schizophrenia-like
* Brief reactive psychosis
* Schizoaffective disorder
* Schizophreniform disorder
Schizophrenia
* Childhood schizophrenia
* Disorganized (hebephrenic) schizophrenia
* Paranoid schizophrenia
* Pseudoneurotic schizophrenia
* Simple-type schizophrenia
Other
* Catatonia
Symptoms and uncategorized
* Impulse control disorder
* Klüver–Bucy syndrome
* Psychomotor agitation
* Stereotypy
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Somatization disorder
|
c0520482
| 8,172 |
wikipedia
|
https://en.wikipedia.org/wiki/Somatization_disorder
| 2021-01-18T19:01:05 |
{"mesh": ["D013001"], "umls": ["C0520482"], "icd-9": ["300.8"], "icd-10": ["F45.0"], "wikidata": ["Q1374020"]}
|
A number sign (#) is used with this entry because hereditary coproporphyria (HCP) is caused by heterozygous mutation in the CPOX gene (612732) on chromosome 3q12. Harderoporphyria is a distinctive subtype of HCP, caused by homozygous or compound heterozygous mutation in the CPOX gene.
Description
Hereditary coproporphyria, an acute hepatic porphyria, is characterized by acute attacks of neurologic dysfunction often provoked by drugs, fasting, menstrual cycle, or infectious diseases. Skin photosensitivity may also be present. Inheritance is usually autosomal dominant, but autosomal recessive inheritance can also occur. Excretion of large amounts of coproporphyrin III, mostly in feces and urine, is observed. Harderoporphyria is a rare homozygous erythropoietic variant form of HCP, characterized by neonatal hemolytic anemia, sometimes accompanied by skin lesions, and massive excretion of harderoporphyrin in feces. During childhood and adulthood, a mild residual anemia is chronically observed (review by Schmitt et al., 2005).
Clinical Features
The first case of coproporphyria, reported by Berger and Goldberg (1955), was the offspring of first-cousin parents, both of whom showed excessive excretion of coproporphyrin III. The authors suggested that the disorder is autosomal dominant and that their proband was homozygous.
Barnes and Whittaker (1965) described 4 of 5 sibs who were affected. The parents were not tested. Marked elevation of coproporphyria in the feces differentiated the condition from acute intermittent porphyria (AIP; 176000) in which stool porphyrins are usually normal and from variegate porphyria (VP; 176200) in which both coproporphyrin and protoporphyrin fractions are increased in the stool. The proband experienced typical acute porphyria. Constipation and abdominal colic were striking features in these patients.
Goldberg et al. (1967) added 20 new cases. A massive excretion of coproporphyrin III in the urine and predominantly in the feces was demonstrated. Attacks resembling those of AIP were precipitated by drugs, and during attacks porphobilinogen and delta-aminolevulinic acid were excreted in the urine in excess. Photosensitivity is occasionally present and the only manifestations may be psychiatric. About half of cases are asymptomatic. This is an hepatic form of porphyria.
In the family of Haeger-Aronsen et al. (1968), 13 persons in 5 sibships of 2 generations showed latent coproporphyria, in addition to the symptomatic proband.
Cripps and Peters (1970) found that tranquilizers, including meprobamate and chlorpromazine, precipitated attacks.
McIntyre et al. (1971) noted that increased hepatic delta-aminolevulinic acid synthetase has been demonstrated in 3 forms of hereditary porphyria: AIP, VP, and coproporphyria.
In cultured skin fibroblasts, Elder et al. (1976) found that the activity of coproporphyrinogen oxidase was about half normal. Similar findings were reported for leukocytes (Brodie et al., 1977). In the homozygous patient reported by Grandchamp et al. (1977), activity of coproporphyrinogen oxidase was only 2% of control values.
Andrews et al. (1984) found 27 cases of coproporphyria in a kindred in which 135 members were screened for fecal porphyrins. Of the 135, 6 females and 1 male had probably suffered clinical attacks; the M:F ratio of cases revealed by screening was 13:14. The proband had her first attack at age 84 years; diazepam and nitrazepam were incriminated in her attack, and other drugs in the other patients. The late manifestation is indicated by the fact that this report was from a department of geriatric medicine. The earliest attack in an affected person was at age 14 years.
Barohn et al. (1994) described acute peripheral neuropathy with hereditary coproporphyria. This is a common feature of AIP but is rare with this form of porphyria.
Gross et al. (2002) reported the molecular, enzymatic, and clinical study of a family with hereditary coproporphyria in which the proband was a 30-year-old woman suffering from acute crises with abdominal, neurologic, and psychiatric complaints. The proband's father, 1 brother, and a sister were found to be new carriers. The patient was treated with intravenous interval therapy with heme arginate for 10 months, with good clinical and metabolic response.
### Harderoporphyria
In 3 sibs (2 boys, 1 girl) with intense jaundice and hemolytic anemia at birth, Nordmann et al. (1983) found a high level of coproporphyrin in the urine and feces. The pattern of fetal porphyrin excretion was atypical because the major porphyrin was harderoporphyrin (more than 60%; normal, less than 20%). Homozygosity was suggested by the fact that the level of lymphocyte coproporphyrinogen III oxidase was 10% of controls in the sibs and 50% of normal in both parents (who showed only mild abnormalities of porphyrin excretion). The mutant enzyme showed abnormal kinetics.
Doss et al. (1984) likewise reported a case of the harderoporphyria variant. The parents were related, and the enzyme level was 7% in the patient and 53% in the mother; thus, homozygosity was suggested. The proband had severe jaundice, hemolytic anemia, and hepatosplenomegaly at birth. At age 10 slight photosensitivity and mild, compensated hemolytic anemia prompted diagnostic search for porphyria.
Schmitt et al. (2005) reported a fifth patient with harderoporphyria. They demonstrated that harderoporphyric patients exhibit iron overload secondary to dyserythropoiesis.
Hasanoglu et al. (2011) reported a Turkish male infant, born of consanguineous parents, with harderoporphyria. He presented with neonatal jaundice, hemolytic anemia, and severe cutaneous photosensitivity. At age 1.5 months, he had an acute porphyric attack characterized by hepatosplenomegaly, elevated liver enzymes, red urine, metabolic acidosis, and severe Coombs-negative hemolytic anemia. The child died at age 5 months. Laboratory studies showed increased urinary porphyrins, increased aminolevulinic acid, and porphobilinogen; fecal porphyrins were not measured.
Inheritance
Dominant inheritance of coproporphyria seems adequately established (Goldberg et al. (1967)). The disorder shows incomplete penetrance (Hasanoglu et al., 2011).
Rare cases of coproporphyria are homozygous (see, e.g., Grandchamp et al., 1977 and Martasek et al., 1994).
Schmitt et al. (2005) noted that all 5 reported cases of harderoporphyria have homozygous or compound heterozygous mutations, indicating recessive inheritance.
Diagnosis
In a study of a large family with genetically confirmed HCP, Allen et al. (2005) found that measurement of fecal coproporphyrin III:I ratio is a highly sensitive test for the detection of asymptomatic HCP. The proband was a 35-year-old man who presented with unexplained severe abdominal pain and was found to have an increased fecal coproporphyrin III:I ratio of 12.7. Total urine porphyrins were also elevated. There were 13 asymptomatic mutation carriers; all had an increased fecal coproporphyrin III:I ratio (mean 14.0, normal less than 1.0), and 11 (85%) had increased fecal total porphyrin. Eight (62%) of the 13 asymptomatic carriers had increased urinary total porphyrin (up to 3-fold) due to excess coproporphyrin III. All individuals studied were older than 10 years of age; the sensitivity of the test for those under 10 years of age was uncertain. Plasma fluorescence emission scanning for porphyrin was not a useful indicator.
Molecular Genetics
In the homozygous patient with coproporphyria reported by Grandchamp et al. (1977), Martasek et al. (1994) demonstrated an arg231-to-trp mutation in the CPO gene (612732.0001).
In the 3 sibs with the harderoporphyria variant reported by Nordmann et al. (1983), Lamoril et al. (1995) demonstrated a K404E missense mutation in exon 6 of the CPO gene (see 612732.0003).
Lamoril et al. (2001) studied 17 unrelated British patients with HCP. They identified 10 novel and 4 previously reported CPO mutations in 15 of the 17 patients. All but 1 mutation were restricted to a single family, with a predominance of missense mutations. Both patients in whom mutations were not identified had an unequivocal diagnosis of HCP. Complete deletions of the CPO gene were excluded by showing that both patients were heterozygous for at least 1 intragenic SNP. It is probable that the causative mutations either lie outside the regions that were sequenced or were partial deletions or insertions not detected by the PCR-based methods. The findings of this study demonstrated that single copies of CPO mutations that are known or predicted to cause 'homozygous' HCP or harderoporphyria can produce typical HCP in adults and demonstrated that the severity of the phenotype does not correlate with the degree of inactivation by mutation of the coproporphyrinogen oxidase enzyme.
In 5 of 9 Swedish families with HCP, Wiman et al. (2002) identified mutations in the CPO gene. In each of 2 of the families, a novel mutation was identified: ser208 to phe (S208F; 612732.0010) and arg328 to cys (R328C; 612732.0011). In the affected members of the other 3 families, 2 previously reported mutations, R331W (612732.0001) and R447C (612732.0009), were shown to coexist on 1 allele. This was the first report of patients carrying 2 HCP-related mutations on the same allele.
Genotype/Phenotype Correlations
Schmitt et al. (2005) noted that all 5 reported patients (from 3 families) with harderoporphyria had a K404E mutation (612732.0003) in the CPOX gene in homozygosity or compound heterozygosity with a null mutation. Biochemical and expression studies revealed that only a few missense mutations, restricted to 5 amino acids encoded by exon 6 (D400-K404), may accumulate significant amounts of harderoporphyrin. All types of mutations occurring elsewhere throughout the CPOX gene resulted in coproporphyrin accumulation and subsequently typical HCP. They stated that this was the first metabolic disorder in which clinical expression of overt disease depended on the location and type of mutation, resulting either in acute hepatic or in erythropoietic porphyria.
In a Turkish male infant, born of consanguineous parents, with harderoporphyria, Hasanoglu et al. (2011) identified a homozygous H327R mutation in the CPOX gene (612732.0014). The mutation occurred at a highly conserved residue involved in the enzyme's conversion of harderoporphyrinogen to protoporphyrinogen IX. The unaffected parents and an unaffected brother were all heterozygous for the mutation. Functional studies of the variant were not performed, but structural analysis suggested that it would alter the enzyme's structure and affect the second decarboxylation step. The findings expanded the genotype/phenotype correlations for this disease.
INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Tachycardia (hereditary coproporphyria, HCP) Vascular \- Hypertension (HCP) RESPIRATORY Lung \- Respiratory paralysis (HCP) ABDOMEN Liver \- Hepatomegaly (harderoporphyria) Spleen \- Splenomegaly (harderoporphyria) Gastrointestinal \- Abdominal pain (HCP) \- Severe constipation \- Vomiting (HCP) \- Diarrhea (HCP) SKIN, NAILS, & HAIR Skin \- Photosensitivity (harderoporphyria and HCP) \- Jaundice (harderoporphyria) NEUROLOGIC Central Nervous System \- Acute episodes of neuropathic symptoms (HCP) \- Paresis (HCP) Peripheral Nervous System \- Peripheral neuropathy Behavioral Psychiatric Manifestations \- Anxiety (HCP) \- Depression (HCP) \- Insomnia (HCP) \- Disorientation (HCP) \- Hallucinations (HCP) \- paranoia (HCP) HEMATOLOGY \- Neonatal hemolytic anemia (harderoporphyria) LABORATORY ABNORMALITIES \- Decreased coproporphyrinogen oxidase activity (HCP, lymphocytes, 50% of normal) \- Increased coproporphyrin isomer III:I ratio (HCP, feces) \- Increased harderoporphyrin excretion (feces, harderoporphyria) \- Markedly decreased coproporphyrinogen oxidase activity (harderoporphyria, lymphocytes) MISCELLANEOUS \- Mutations in the CPO gene cause 3 clinically distinct disorders, hereditary coproporphyria (HCP), 'homozygous' variant hereditary coproporphyria, or harderoporphyria \- Attacks rarely occur before puberty (HCP) \- Attacks precipitated by drugs, alcohol, and endocrine factors (HCP) \- No abdominal symptoms or neurologic symptoms in harderoporphyria \- Incomplete penetrance MOLECULAR BASIS \- Caused by mutation in the coproporphyrinogen oxidase gene (CPO, 612732.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
COPROPORPHYRIA, HEREDITARY
|
c0162531
| 8,173 |
omim
|
https://www.omim.org/entry/121300
| 2019-09-22T16:42:55 |
{"doid": ["13269"], "mesh": ["D046349"], "omim": ["121300"], "icd-10": ["E80.29"], "orphanet": ["79273"], "synonyms": ["Alternative titles", "COPROPORPHYRINOGEN OXIDASE DEFICIENCY", "CPOX DEFICIENCY", "CPO DEFICIENCY", "CPX DEFICIENCY"], "genereviews": ["NBK114807"]}
|
Sotos syndrome
Other namesCerebral gigantism or Sotos-Dodge syndrome
Sotos syndrome is an autosomal dominant inherited condition
SpecialtyMedical genetics
Sotos syndrome is a rare genetic disorder characterized by excessive physical growth during the first years of life. Excessive growth often starts in infancy and continues into the early teen years. The disorder may be accompanied by autism,[1] mild intellectual disability, delayed motor, cognitive, and social development, hypotonia (low muscle tone), and speech impairments. Children with Sotos syndrome tend to be large at birth and are often taller, heavier, and have relatively large skulls (macrocephaly) than is normal for their age. Signs of the disorder, which vary among individuals, include a disproportionately large skull with a slightly protrusive forehead, large hands and feet, large mandible, hypertelorism (an abnormally increased distance between the eyes), and downslanting eyes. Clumsiness, an awkward gait, and unusual aggressiveness or irritability may also occur. Although most cases of Sotos syndrome occur sporadically, familial cases have also been reported. It is similar to Weaver syndrome.
## Contents
* 1 Signs and symptoms
* 2 Genetics
* 3 Diagnosis
* 4 Treatment
* 5 Prognosis
* 6 Epidemiology
* 7 See also
* 8 References
* 9 External links
## Signs and symptoms[edit]
This syndrome is characterized by overgrowth and advanced bone age. Affected individuals are dysmorphic, with macrodolichocephaly, downslanting palpebral fissures and a pointed chin. The facial appearance is most notable in early childhood. Affected infants and children tend to grow quickly; they are significantly taller than their siblings and peers, and have an unusually large skull and large head. Adult height is usually in the normal range, although Broc Brown has the condition and was named the world's tallest teenager. As of late 2016, he was 7'8" and still growing.[2]
Individuals with Sotos syndrome often have intellectual impairment,[3][4] and most also display autistic traits.[5] Frequent behavioral impairments include attention deficit hyperactivity disorder (ADHD), phobias, obsessive compulsive disorder, tantrums, and impulsive behaviors (impulse control disorder). Problems with speech and language are also common.[6] Affected individuals may often have stuttering, difficulty with sound production, or a monotone voice. Additionally, weak muscle tone (hypotonia) may delay other aspects of early development, particularly motor skills such as sitting and crawling.[citation needed]
Other signs include scoliosis, seizures, heart or kidney defects, hearing loss, and problems with vision. Some infants with this disorder experience jaundice and poor feeding. A small number of patients with Sotos syndrome have developed cancer, most often in childhood, but no single form of cancer has been associated with this condition. It remains uncertain whether Sotos syndrome increases the risk of specific types of cancer. If persons with this disorder have any increased cancer risk, their risk is only slightly greater than that of the general population.[7]
## Genetics[edit]
Mutations in the NSD1 gene cause Sotos syndrome.[8][9] The NSD1 gene provides instructions for making a protein (histone methyltransferase) that is involved in normal growth and development. The function of this protein is unknown, however. In the Japanese population, the most common genetic change leading to Sotos syndrome deletes genetic material from the region of chromosome 5 containing the NSD1 gene. In other populations, small mutations within the NSD1 gene occur more frequently. Genetic changes involving the NSD1 gene prevent one copy of the gene from producing any functional protein. It is unclear how a reduced amount of this protein during development leads to learning disabilities, overgrowth, and the other features of Sotos syndrome.[citation needed]
About 95 percent of Sotos syndrome cases occur by spontaneous mutation. Most of these cases result from new mutations involving the NSD1 gene. A few families have been described with more than one affected family member. These inherited cases enabled researchers to determine that Sotos syndrome has an autosomal dominant pattern of inheritance.[citation needed]
## Diagnosis[edit]
Diagnosis is based on physical examination, looking for excessive growth among other symptoms. There are no biochemical markers for the disease.[10]
## Treatment[edit]
Treatment is symptomatic.[10] There is no standard course of treatment for Sotos syndrome.[citation needed]
## Prognosis[edit]
Sotos syndrome is not a life-threatening disorder and patients may have a normal life expectancy. Developmental delays may improve in the school-age years; however, coordination problems may persist into adulthood, along with any learning disabilities and/or other physical or mental issues.[citation needed]
## Epidemiology[edit]
Incidence is approximately 1 in 14,000 births.[11]
## See also[edit]
* Proteus syndrome
* Beckwith-Wiedemann syndrome
* Perlman syndrome
## References[edit]
1. ^ http://www.exploringautism.org/autism/evaluation.htm
2. ^ "7-foot-tall Broc Brown: Facts". Morning News USA. Retrieved 8 March 2017.
3. ^ Lane C, Milne E, Freeth M (2016). "Cognition and Behaviour in Sotos Syndrome: A Systematic Review". PLOS ONE. 11 (2): e0149189. Bibcode:2016PLoSO..1149189L. doi:10.1371/journal.pone.0149189. PMC 4752321. PMID 26872390.
4. ^ Lane C, Milne E, Freeth M (January 2018). "The cognitive profile of Sotos syndrome" (PDF). J Neuropsychol. 13 (2): 240–252. doi:10.1111/jnp.12146. PMID 29336120.
5. ^ Lane C, Milne E, Freeth M (January 2017). "Characteristics of Autism Spectrum Disorder in Sotos Syndrome". J Autism Dev Disord. 47 (1): 135–143. doi:10.1007/s10803-016-2941-z. PMC 5222916. PMID 27771801.
6. ^ Lane C, Van Herwegen J, Freeth M (December 2018). "Parent-Reported Communication Abilities of Children with Sotos Syndrome: Evidence from the Children's Communication Checklist-2". J Autism Dev Disord. 49 (4): 1475–1483. doi:10.1007/s10803-018-3842-0. PMC 6450847. PMID 30536215.
7. ^ Reference, Genetics Home. "Sotos syndrome". Genetics Home Reference.
8. ^ Kurotaki N, Imaizumi K, Harada N, Masuno M, Kondoh T, Nagai T, et al. (April 2002). "Haploinsufficiency of NSD1 causes Sotos syndrome". Nat. Genet. 30 (4): 365–6. doi:10.1038/ng863. PMID 11896389. S2CID 205357840.
9. ^ Melchior L, Schwartz M, Duno M (March 2005). "dHPLC screening of the NSD1 gene identifies nine novel mutations--summary of the first 100 Sotos syndrome mutations". Ann. Hum. Genet. 69 (Pt 2): 222–6. doi:10.1046/j.1529-8817.2004.00150.x. PMID 15720303.
10. ^ a b "Sotos Syndrome". NORD (National Organization for Rare Disorders). Retrieved 2016-03-01.
11. ^ "Latest Australian & World News". Yahoo7 News. Archived from the original on 2013-04-01. Retrieved 2016-03-01.
## External links[edit]
Classification
D
* ICD-10: Q87.3
* ICD-9-CM: 759.89
* OMIM: 117550
* MeSH: D058495
* DiseasesDB: 29134
* sotos at NIH/UW GeneTests
* v
* t
* e
Congenital abnormality syndromes
Craniofacial
* Acrocephalosyndactylia
* Apert syndrome
* Carpenter syndrome
* Pfeiffer syndrome
* Saethre–Chotzen syndrome
* Sakati–Nyhan–Tisdale syndrome
* Bonnet–Dechaume–Blanc syndrome
* Other
* Baller–Gerold syndrome
* Cyclopia
* Goldenhar syndrome
* Möbius syndrome
Short stature
* 1q21.1 deletion syndrome
* Aarskog–Scott syndrome
* Cockayne syndrome
* Cornelia de Lange syndrome
* Dubowitz syndrome
* Noonan syndrome
* Robinow syndrome
* Silver–Russell syndrome
* Seckel syndrome
* Smith–Lemli–Opitz syndrome
* Snyder–Robinson syndrome
* Turner syndrome
Limbs
* Adducted thumb syndrome
* Holt–Oram syndrome
* Klippel–Trénaunay–Weber syndrome
* Nail–patella syndrome
* Rubinstein–Taybi syndrome
* Gastrulation/mesoderm:
* Caudal regression syndrome
* Ectromelia
* Sirenomelia
* VACTERL association
Overgrowth syndromes
* Beckwith–Wiedemann syndrome
* Proteus syndrome
* Perlman syndrome
* Sotos syndrome
* Weaver syndrome
* Klippel–Trénaunay–Weber syndrome
* Benign symmetric lipomatosis
* Bannayan–Riley–Ruvalcaba syndrome
* Neurofibromatosis type I
Laurence–Moon–Bardet–Biedl
* Bardet–Biedl syndrome
* Laurence–Moon syndrome
Combined/other,
known locus
* 2 (Feingold syndrome)
* 3 (Zimmermann–Laband syndrome)
* 4/13 (Fraser syndrome)
* 8 (Branchio-oto-renal syndrome, CHARGE syndrome)
* 12 (Keutel syndrome, Timothy syndrome)
* 15 (Marfan syndrome)
* 19 (Donohue syndrome)
* Multiple
* Fryns 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 inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Sotos syndrome
|
c0175695
| 8,174 |
wikipedia
|
https://en.wikipedia.org/wiki/Sotos_syndrome
| 2021-01-18T18:48:08 |
{"gard": ["10091"], "mesh": ["D058495"], "umls": ["CN035106"], "icd-9": ["759.89"], "orphanet": ["821"], "wikidata": ["Q1770836"]}
|
## Clinical Features
Mahjneh et al. (2003) reported a large Finnish family in which 7 individuals spanning 4 generations developed slowly progressive adult-onset distal myopathy. Age at onset ranged from 32 to 45 years with clumsiness in the hands and/or feet. Later features included steppage gait due to marked weakness of ankle dorsiflexion, contractures of the hands leading to claw hands, and weakness and wasting of the intrinsic hand muscles. Lower limb muscle weakness tended to be asymmetric. MRI showed fatty degeneration of affected muscles. Proximal muscle involvement occurred later in the disease. EMG showed myopathic changes. Serum creatine kinase was normal or slightly increased, and muscle biopsy showed severe dystrophic changes with rimmed vacuoles. Cardiac and respiratory functions were not affected. There was no evidence of linkage to Welander distal myopathy (WDM; 604454) or tibial muscular dystrophy (TMD; 600334).
Inheritance
The transmission pattern of MPD in the family reported by Mahjneh et al. (2003) was consistent with autosomal dominant inheritance.
Mapping
By genomewide analysis of the family reported by Mahjneh et al. (2003), Haravuori et al. (2004) found significant linkage to 2 distinct regions on chromosomes 8p22-q11 and 12q13-q22 (maximum multipoint lod score of 3.01 for both regions). Haravuori et al. (2004) concluded that the defective gene in this family is located on either chromosome 8 or 12, or that both loci are involved, possibly representing digenic inheritance. Sequencing excluded pathogenic mutations in the coding regions of the ANK1 (612641) and MLC1SA (609930) genes on 8p11 and 12q13, respectively.
INHERITANCE \- Autosomal dominant SKELETAL Hands \- Contractures of the hands, mild \- Claw hands \- Atrophy of thenar muscles \- Atrophy of intrinsic hand muscles Feet \- Atrophy of intrinsic foot muscles MUSCLE, SOFT TISSUES \- Distal muscle weakness, upper and lower limbs \- Distal muscle atrophy, upper and lower limbs \- Asymmetric muscle involvement \- Clumsiness \- Steppage gait \- Proximal muscle weakness occurs later \- MRI shows fatty infiltration of affected muscles \- Muscle biopsy shows dystrophic changes \- Muscle biopsy shows rimmed vacuoles \- EMG shows myopathic changes LABORATORY ABNORMALITIES \- Normal or mildly increased serum creatine kinase MISCELLANEOUS \- Onset age 32 to 45 years \- Slowly progressive ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
MYOPATHY, DISTAL, 3
|
c1864706
| 8,175 |
omim
|
https://www.omim.org/entry/610099
| 2019-09-22T16:05:11 |
{"doid": ["0111189"], "mesh": ["C566445"], "omim": ["610099"], "orphanet": ["399086"]}
|
A rare genetic, multiple congenital anomalies syndrome characterized by short stature, hand brachydactyly with hypoplastic distal phalanges, global development delay, intellectual disability, and more variably seizures, obesity, and craniofacial dysmorphism that includes microcephaly, high forehead, flat face, hypertelorism, deep set eyes, flat nasal bridge, averted nostrils, long philtrum, thin lip vermilion, and short neck.
## Epidemiology
Less than 15 cases have been reported in the literature to date.
## Clinical description
Initial presentation can be with intrauterine growth retardation or low birthweight. Symptoms of global development delay includes hypotonia, delay in achieving independent sitting and walking and marked language delay. Intellectual disability ranges from mild to severe. Ocular anomalies include strabismus, coloboma, dacryostenosis and blue sclera. Obesity develops in late infancy. Seizures can present in infancy or childhood, are phenotypically variable including absences and febrile convulsions. In addition to hypoplasia of the distal phalanges, the 4th and 5th fingers may show a marked reduction in metacarpal length; brachydactyly of the feet may also be present. Other variable features reported include bilateral absent patellae, sensorineural hearing loss, feeding difficulties in early infancy, dysphagia, kyphosis, eczema, cryptorchidism and laryngomalacia.
## Etiology
The malformation is due to a loss of function in the enzyme protein argenine N-methyltransferase 7 (encoded by PRMT7, 16q22.1) resulting in decreased levels of protein arginine methylation.
## Diagnostic methods
Diagnosis is based on presentation of clinical features, and can be confirmed by genetic testing.
## Differential diagnosis
Differential diagnosis include Albright hereditary osteodystrophies with pseudohypoparathyroidism.
## Antenatal diagnosis
There is no definitive antenatal diagnosis available, however ultrasound may show intrauterine growth retardation which should be investigated further.
## Genetic counseling
Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them that there is a 25% risk of having an affected child at each pregnancy.
## Management and treatment
Given that patients with biallelic mutations in PRMT7 present with a spectrum of multisystemic involvement, medical multidisciplinary follow-up is needed. Neurological follow up is indicated with special attention to seizures. Hearing evaluation is recommended at time of diagnosis. Surveillance should also include frequent monitoring of growth and development; regular ophthalmological follow up. Hormonal and phosphocalcic metabolism alterations have been reported in two patients so far, so this should also be tested.
## Prognosis
Developmental delay and intellectual disability had been reported in all patients to date, with variable in severity. Language is more severely affected when hearing impairment is present.
* European Reference Network
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Short stature-brachydactyly-obesity-global developmental delay syndrome
|
c4310689
| 8,176 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=464288
| 2021-01-23T17:31:43 |
{"omim": ["617157"], "synonyms": ["SBIDDS"]}
|
A rare genetic primary lymphedema characterized by unilateral or bilateral lower limb lymphedema of variable severity. The condition shows almost complete penetrance with onset in childhood or adolescence in females, whereas in males it shows incomplete penetrance with later onset of disease. Lymphoscintigraphy in more severely affected individuals reveals lymphatic abnormalities consistent with lymphangiectasia, valve dysfunction, and thoracic duct reflux.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
CELSR1-related late-onset primary lymphedema
|
None
| 8,177 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=569816
| 2021-01-23T18:26:50 |
{}
|
A rare idiopathic interstitial pneumonia characterized by prominent subpleural and parenchymal fibroelastosis and pleural fibrosis, predominantly involving the upper lobes. Signs and symptoms include non-productive cough, dyspnea, and recurrent respiratory infections. Pneumothorax is a frequently reported complication. Pulmonary function test reveals a restrictive pattern and reduced diffusing capacity. Computed tomography shows pleural thickening with signs of fibrosis (traction bronchiectasis, architectural distortion, and loss of volume), and reticulation.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Idiopathic pleuroparenchymal fibroelastosis
|
None
| 8,178 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=494428
| 2021-01-23T18:15:43 |
{"synonyms": ["IPPFE", "Idiopathic pleuropulmonary fibroelastosis"]}
|
A number sign (#) is used with this entry because of evidence that cytosolic phosphoenolpyruvate carboxykinase deficiency (PCKDC) is caused by homozygous mutation in the PCK1 gene (614168) on chromosome 20q13.
Description
Cytosolic phosphoenolpyruvate carboxykinase deficiency causes a defect in gluconeogenesis that results in a 'biochemical signature' of fasting hypoglycemia with high tricarboxylic acid cycle intermediate excretion, particularly of fumarate. Other biochemical anomalies that may be seen during metabolic crisis include ketonuria, dicarboxylic aciduria, and urea cycle dysfunction (Vieira et al., 2017).
See PCKDM (261650) for a discussion of mitochondrial PCK (PEPCK2; 614095) deficiency.
Clinical Features
Sovik et al. (1975) reported a boy who developed generalized seizures on the second day of life and was found to have severe hypoglycemia. He also had frequent attacks of cyanosis and apnea. At age 8 weeks, he showed general retardation and atrophy of the optic nerve. At age 3.5 months, he underwent subtotal pancreatectomy and treatment with diazoxide to inhibit insulin production. However, poor response of the hypoglycemia to this treatment prompted the authors to consider a defect in gluconeogenesis. By studies on the patient's liver, Vidnes and Sovik (1976, 1976) demonstrated that he had a defect of gluconeogenesis due to deficiency of cytosolic phosphoenolpyruvate carboxykinase (PCK1; 614168). The total activity of the enzyme was normal, but the enzyme showed an abnormal subcellular distribution, with virtually no activity detected in the cytosolic fraction of a liver homogenate. He died at age 2 years, 10 months. Postmortem examination showed severe cerebral atrophy, atrophy of the optic nerve, fatty infiltration of the liver, kidney, and heart, and hyperplasia of the pancreatic islets of Langerhans. The findings suggested that cytosolic PCK initiates gluconeogenesis at birth.
Adams et al. (2014) reported 2 sisters, born of nonconsanguineous parents of Ashkenazi Jewish ancestry, who had cytosolic phosphoenolpyruvate carboxykinase deficiency due to mutation in the PCK1 gene. The older sister first presented at age 20 months with fasting hypoglycemia, which was associated with fever, lethargy, and ketonuria, as well as appropriately elevated growth hormone (GH1; 139250) and cortisol levels, undetectable insulin, and normal C-peptide levels. Over the subsequent 5 years, she had at least 12 similar episodes of illness- or fasting-related hypoglycemia, sometimes associated with significant lactic acidemia. Liver biopsy at age 4 years showed no iron deposits and no abnormal lipid or glycogen, although there was mild to moderate portal inflammation, mild portal fibrosis, and patchy moderate macrovesicular steatosis. The younger sister presented at age 8 months with illness-related lethargy, fasting hypoglycemia, elevated urine lactate, and ketonuria, and like her older sister, had repeated episodes of illness- or fasting-related hypoglycemia, sometimes associated with acidosis. In addition, both sisters exhibited intellectual and motor delays, as well as dysmorphic features in the older sister. In addition to mutation in PCK1, each sister carried a mutation in a different gene known to be associated with a mental retardation phenotype (see MOLECULAR GENETICS).
Santra et al. (2016) described a 4-year-old Pakistani boy, born of third-cousin parents from a multiply consanguineous family, who presented at age 9 months with encephalopathy after 3 days of persistent diarrhea and vomiting. Evaluation revealed mild hyperammonemia and acute liver failure, with massively elevated alanine (GPT; 138200) and aspartate (GOT1; 138180) transaminases, as well as coagulopathy, hypoalbuminemia, mild hypoglycemia, and hyperlactatemia. His level of consciousness rapidly normalized after administration of intravenous dextrose. Quantitative plasma amino acid analysis was suggestive of a proximal urea cycle defect, with a strongly elevated glutamine together with low citrulline and arginine. Analysis of urine organic acids during the presenting illness showed prominent tricarboxylic acid (TCA) cycle metabolites, especially fumarate but including succinate, malate, and alpha-ketoglutarate. Liver biopsy revealed diffuse macrosteatosis without fibrosis or inflammation, and ultrasound showed a normal-sized liver for age, but with hyperechoic parenchyma. Treatment for a proximal urea cycle defect, including dietary protein restriction, was commenced. Repeat organic and amino acid analysis a month after recovery showed no evidence of the previous abnormalities and values remained normal after return to an unrestricted diet. Growth and development were normal at age 4 years.
Tangeraas et al. (2016) provided a brief report of a previously healthy Norwegian girl who presented at age 16 months with severe gastrointestinal hemorrhage following an episode of gastroenteritis, associated with extremely high alanine and aspartate aminotransferases, slightly increased coagulation time, and slightly decreased albumin level. She subsequently experienced 2 episodes of infection-associated ketotic hypoglycemia, metabolic acidosis, and elevated lactate levels. A similar biochemical profile was confirmed during a controlled fasting test, which provoked hypoglycemia after 17 hours. Urine after a 12-hour fast showed increased excretion of 3-hydroxybutarate as well as fumaric and glutaric acids.
Vieira et al. (2017) studied a Finnish sister and brother, born of distantly consanguineous parents, and an unrelated Finnish boy, with unexplained childhood hypoglycemia. The Finnish girl required a glucose infusion during the first 24 hours of life for hypoglycemia noted due to tremor and irritability; she experienced a second episode of hypoglycemia at age 14 months after an overnight fast of about 12 hours. Blood lactate and alanine aminotransferase were slightly elevated, and ammonia was normal. Ultrasound of the liver showed increased size and echogenicity suggestive of diffuse parenchymal damage. Her younger brother had no significant health issues until age 15 months, when he was found to be hypoglycemic after a 13-hour fast, with slightly elevated alanine aminotransferase but normal ammonia. Liver ultrasound 3 months later showed size at the upper limit of normal, with normal echogenicity. The third Finnish patient, an unrelated boy, was well until 4.5 years of age, when he had a seizure in the morning and was found to be hypoglycemic. He had no signs of infection, but had been very active the night before. Lactate, pyruvate, and ammonia were normal, free fatty acids were elevated, and GPT was slightly elevated. In all 3 patients, semiquantitative urine organic acid analysis demonstrated prominent TCA cycle metabolites, particularly fumarate. All were instructed in a low-fat, high-carbohydrate diet with frequent feedings, and all showed normal growth and development, at ages 5 years, 2.5 years, and 6.8 years, respectively. Except for an illness-related episode of low glucose in the girl at age 2.75 years, there were no further episodes of hypoglycemia.
Molecular Genetics
In 2 sisters who experienced multiple episodes of hypoglycemia and lactic acidosis associated with illness or fasting, who were born of nonconsanguineous parents of Ashkenazi Jewish ancestry, Adams et al. (2014) performed whole-exome sequencing and identified homozygosity for a missense mutation in the PCK1 gene (I45T; 614168.0001). Each sister was also heterozygous for a de novo mutation in another gene, RAI1 (607642) and GRIN2B (138252), respectively, each of which was known to be associated with intellectual and developmental delay, causing Smith-Magenis syndrome (SMS; 182290) in the older sister and mental retardation-6 (MRD6; 613970) in the younger sister. Adams et al. (2014) concluded that this family demonstrated that complex medical disorders can represent the cooccurrence of multiple diseases.
In a 4-year-old Pakistani boy, born of third-cousin parents from a multiply consanguineous family, who presented at age 9 months with transient acute liver failure and biochemical patterns suggestive of disturbed urea cycle, Santra et al. (2016) performed whole-exome sequencing and identified homozygosity for a 12-bp deletion in the PCK1 gene (614168.0002) that segregated fully with disease in the family. Analysis of a liver biopsy at age 3 years excluded coexistent glycogen storage disease type IX (see 306000) as a contributory factor to the patient's presentation. The authors suggested that the amino acid profile reminiscent of a proximal urea cycle defect might be due to accumulation of TCA cycle metabolites, triggering increased flux through alternative cataplerotic reactions. They noted that PEPCK deficiency may be an underrecognized but treatable cause of childhood liver failure associated with illnesses causing prolonged starvation.
In 2 Finnish sibs and an unrelated Finnish boy with unexplained childhood hypoglycemia, Vieira et al. (2017) performed whole-exome sequencing and identified homozygosity for a missense mutation in the PCK1 gene (G309R; 614168.0003) that segregated with disease in both families. Vieira et al. (2017) noted that the G309R mutation had been previously reported in a congress abstract (Tangeraas et al., 2016) as having been found in compound heterozygosity in a patient with hypoglycemia, liver dysfunction, and gastrointestinal hemorrhage. The other mutation in the latter patient was a 1-bp deletion, predicted to cause a frameshift and premature termination codon.
INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Optic nerve atrophy RESPIRATORY \- Apnea, episodic ABDOMEN Liver \- Enlarged liver \- Fatty infiltration \- Portal inflammation, mild to moderate Portal fibrosis, mild \- Patchy to diffuse macrovesicular steatosis \- Acute liver failure, transient (in 1 patient) SKIN, NAILS, & HAIR Skin \- Cyanosis NEUROLOGIC Central Nervous System \- Seizures (in some patients) \- Hepatic encephalopathy (in 1 patient) METABOLIC FEATURES \- Cytosolic phosphoenolpyruvate carboxykinase deficiency \- Impaired gluconeogenesis \- Fasting hypoglycemia \- Lactic acidemia \- Normal to elevated blood ammonia \- Elevated blood alanine aminotransferase \- Normal to high plasma glutamine \- Normal to low plasma citrulline \- Normal to low plasma arginine \- Ketonuria \- Elevated urine lactate \- Prominent tricarboxylic acid cycle metabolites in urine (particularly fumarate) MISCELLANEOUS \- Onset in infancy ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
PHOSPHOENOLPYRUVATE CARBOXYKINASE DEFICIENCY, CYTOSOLIC
|
c0268194
| 8,179 |
omim
|
https://www.omim.org/entry/261680
| 2019-09-22T16:23:28 |
{"mesh": ["C536654"], "omim": ["261680"], "icd-10": ["E74.4"], "orphanet": ["2880"], "synonyms": ["Alternative titles", "PCK1 DEFICIENCY, CYTOSOLIC", "PEPCK DEFICIENCY, CYTOSOLIC"]}
|
A number sign (#) is used with this entry because of evidence of an association between inflammatory bowel disease (IBD14) and variation in the interferon regulatory factor-5 gene (IRF5; 607218) on chromosome 7q32.
For a general description and a discussion of genetic heterogeneity of inflammatory bowel disease, including Crohn disease (CD) and ulcerative colitis (UC), see IBD1 (266600).
Molecular Genetics
Because the IRF5 gene had been shown to be associated with systemic lupus erythematosus (SLE; see 152700) and rheumatoid arthritis (RA; see 180300), Dideberg et al. (2007) investigated whether the IRF5 gene plays a role in inflammatory bowel disease. They genotyped 12 polymorphisms in the IRF5 gene in 2 Belgian cohorts; the first cohort included 1,007 IBD patients (748 CD; 254 UC) and 241 controls, and the second included 687 IBD patients (488 CD; 192 UC) and 311 controls. In the first cohort, a strong association with IBD was observed for a 5-bp insertion (CGGGG; 607218.0001) polymorphism in the promoter region of IRF5 (p = 1.9 x 10(-5), OR = 1.81). The association was particularly strong among UC patients (p = 5.3 x 10(-8), OR = 2.42), and was detectable also in CD patients (p = 6.8 x 10(-4), OR = 1.63). The association of the CGGGG insertion was confirmed in the second cohort for IBD (p = 3.2 x 10(-5), OR = 1.59) as well as for both subgroups. The p values for the combined cohorts were 1.4 x 10(-8) for IBD, 3.3 x 10(-6) for CD, and 7.9 x 10(-10) for UC. The insertion of one CGGGG unit was predicted to create an additional binding site for the transcription factor SP1 (189906).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
INFLAMMATORY BOWEL DISEASE 14
|
c2677100
| 8,180 |
omim
|
https://www.omim.org/entry/612245
| 2019-09-22T16:02:03 |
{"mesh": ["C567383"], "omim": ["612245"]}
|
Pearson marrow-pancreas syndrome is a severe disorder that usually begins in infancy. It causes problems with the development of blood-forming (hematopoietic) cells in the bone marrow that have the potential to develop into different types of blood cells. For this reason, Pearson marrow-pancreas syndrome is considered a bone marrow failure disorder. Function of the pancreas and other organs can also be affected.
Most affected individuals have a shortage of red blood cells (anemia), which can cause pale skin (pallor), weakness, and fatigue. Some of these individuals also have low numbers of white blood cells (neutropenia) and platelets (thrombocytopenia). Neutropenia can lead to frequent infections; thrombocytopenia sometimes causes easy bruising and bleeding. When visualized under the microscope, bone marrow cells from affected individuals may appear abnormal. Often, early blood cells (hematopoietic precursors) have multiple fluid-filled pockets called vacuoles. In addition, red blood cells in the bone marrow can have an abnormal buildup of iron that appears as a ring of blue staining in the cell after treatment with certain dyes. These abnormal cells are called ring sideroblasts.
In people with Pearson marrow-pancreas syndrome, the pancreas does not work as well as usual. The pancreas produces and releases enzymes that aid in the digestion of fats and proteins. Reduced function of this organ can lead to high levels of fats in the liver (liver steatosis). The pancreas also releases insulin, which helps maintain correct blood sugar levels. A small number of individuals with Pearson marrow-pancreas syndrome develop diabetes, a condition characterized by abnormally high blood sugar levels that can be caused by a shortage of insulin. In addition, affected individuals may have scarring (fibrosis) in the pancreas.
People with Pearson marrow-pancreas syndrome have a reduced ability to absorb nutrients from the diet (malabsorption), and most affected infants have an inability to grow and gain weight at the expected rate (failure to thrive). Another common occurrence in people with this condition is buildup in the body of a chemical called lactic acid (lactic acidosis), which can be life-threatening. In addition, liver and kidney problems can develop in people with this condition.
About half of children with this severe disorder die in infancy or early childhood due to severe lactic acidosis or liver failure. Many of those who survive develop signs and symptoms later in life of a related disorder called Kearns-Sayre syndrome. This condition causes weakness of muscles around the eyes and other problems.
## Frequency
Pearson marrow-pancreas syndrome is a rare condition; its prevalence is unknown.
## Causes
Pearson marrow-pancreas syndrome is caused by defects in mitochondria, which are structures within cells that use oxygen to convert the energy from food into a form cells can use. This process is called oxidative phosphorylation. Although most DNA is packaged in chromosomes within the nucleus (nuclear DNA), mitochondria also have a small amount of their own DNA, called mitochondrial DNA (mtDNA). This type of DNA contains many genes essential for normal mitochondrial function. Pearson marrow-pancreas syndrome is caused by single, large deletions of mtDNA, which can range from 1,000 to 10,000 DNA building blocks (nucleotides). The most common deletion, which occurs in about 20 percent of affected individuals, removes 4,997 nucleotides.
The mtDNA deletions involved in Pearson marrow-pancreas syndrome result in the loss of genes that provide instructions for proteins involved in oxidative phosphorylation. These deletions impair oxidative phosphorylation and decrease the energy available to cells. It is not clear how loss of mtDNA leads to the specific signs and symptoms of Pearson marrow-pancreas syndrome, although the features of the condition are likely related to a lack of cellular energy.
### Learn more about the chromosome associated with Pearson marrow-pancreas syndrome
* mitochondrial dna
## Inheritance Pattern
Pearson marrow-pancreas syndrome is generally not inherited but arises from new (de novo) mutations that likely occur in early embryonic development.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Pearson marrow-pancreas syndrome
|
c0342784
| 8,181 |
medlineplus
|
https://medlineplus.gov/genetics/condition/pearson-marrow-pancreas-syndrome/
| 2021-01-27T08:24:51 |
{"gard": ["7343"], "omim": ["557000"], "synonyms": []}
|
Charcot-Marie-Tooth disease type 4C (CMT4C) is a subtype of Charcot-Marie-Tooth type 4 characterized by childhood or adolescent-onset of a relatively mild, demyelinating sensorimotor neuropathy that contrasts with a severe, rapidly progressing, early-onset scoliosis, and the typical CMT phenotype (i.e. distal muscle weakness and atrophy, sensory loss, and often foot deformity). A wide spectrum of nerve conduction velocities are observed and cranial nerve involvement and kyphoscoliosis have also been reported.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Charcot-Marie-Tooth disease type 4C
|
c1866636
| 8,182 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99949
| 2021-01-23T18:07:31 |
{"gard": ["9201"], "mesh": ["C535423"], "omim": ["601596"], "umls": ["C1866636"], "icd-10": ["G60.0"], "synonyms": ["CMT4C"]}
|
Macrocephaly-capillary malformation
Other namesMacrocephaly-cutis marmorata telangiectatica congenita syndrome, Megalencephaly-cutis marmorata telangiectatica congenita syndrome
A newborn child with M-CM syndrome. A port-wine stain is visible under the nose. On the right side of a cheek, capillary malformations are present.
Macrocephaly-capillary malformation (M-CM) is a multiple malformation syndrome causing abnormal body and head overgrowth and cutaneous, vascular, neurologic, and limb abnormalities. Though not every patient has all features, commonly found signs include macrocephaly, congenital macrosomia, extensive cutaneous capillary malformation (naevus flammeus or port-wine stain type birthmark over much of the body; a capillary malformation of the upper lip or philtrum is seen in many patients with this condition), body asymmetry (also called hemihyperplasia or hemihypertrophy), polydactyly or syndactyly of the hands and feet, lax joints, doughy skin, variable developmental delay and other neurologic problems such as seizures and low muscle tone.
## Contents
* 1 Genetics
* 2 Diagnosis
* 3 Treatment
* 4 Prognosis
* 5 History
* 6 References
* 7 External links
## Genetics[edit]
Mosaic mutations in PIK3CA have been found to be the genetic cause of M-CM.[1] Other overgrowth conditions with distinct phenotypes have also been found to be caused by mosaic mutations in PIK3CA. How different mutations in this gene result in a variety of defined clinical syndromes is still being clarified.[2][3][4] Mutations in PIK3CA have not been found in a non-mosaic state in any of these disorders, so it is unlikely that the conditions could be inherited.
## Diagnosis[edit]
Diagnosis is usually based on clinical observation. Various sets of criteria have been suggested to identify the disorder in an individual patient, all of which include macrocephaly and a number of the following: somatic overgrowth, cutis marmorata, midline facial birthmark, polydactyly/syndactyly, asymmetry (hemihyperplasia or hemihypertrophy), hypotonia at birth, developmental delay, connective tissue defect and frontal bossing.[5][6] Currently no consensus exists about which diagnostic criteria are definitive and so evaluation by a medical geneticist or other clinician with familiarity with the syndrome is usually needed to provide diagnostic certainty. It is not clear if there are some features which are mandatory to make the diagnosis, but macrocephaly appears essentially universal though may not be congenital. The distinctive vascular abnormalities of the skin often fade over time, making the diagnosis challenging in older children with this condition.[citation needed]
The brain can be affected in several ways in this syndrome. Some children are born with structural brain anomalies such as cortical dysplasia or polymicrogyria. While developmental delay is nearly universal in this syndrome it is variable in severity, with the majority having mild to moderate delays and a minority having severe cognitive impairment. Some patients are affected with a seizure disorder. White matter abnormalities on magnetic resonance imaging (MRI), suggesting a delay in white matter myelination, is commonly seen in early childhood. Some patients may have asymmetry of the brain, with one side being noticeably larger than the other.
One interesting phenomenon that seems very common in this syndrome is the tendency for disproportionate brain growth in the first few years of life, with crossing of percentiles on the head circumference growth charts. A consequence of this disproportionate brain growth appears to be a significantly increased risk of cerebellar tonsillar herniation (descent of the cerebellar tonsils through the foramen magnum of the skull, resembling a Chiari I malformation neuroradiologically) and ventriculomegaly/hydrocephalus.[7] Such cerebellar tonsil herniation may occur in up to 70% of children with M-CM.
The medical literature suggests that there is a risk of cardiac arrhythmias in early childhood.[8][9] The cause for this is unknown. In addition, a variety of different congenital cardiac malformations have been reported in a small number of patients with this disorder.[10][11]
Like other syndromes associated with disproportionate growth, there appears to be a slightly increased risk of certain types of childhood malignancies in M-CM (such as Wilms' tumor). However, the precise incidence of these malignancies is unclear.
## Treatment[edit]
There is no cure for this condition. Treatment is supportive and varies depending on how symptoms present and their severity. Some degree of developmental delay is expected in almost all cases of M-CM, so evaluation for early intervention or special education programs is appropriate. Rare cases have been reported with no discernible delay in academic or school abilities.
Physical therapy and orthopedic bracing can help young children with gross motor development. Occupational therapy or speech therapy may also assist with developmental delays. Attention from an orthopedic surgeon may be required for leg length discrepancy due to hemihyperplasia.
Children with hemihyperplasia are thought to have an elevated risk for certain types of cancers. Recently published management guidelines recommend regular abdominal ultrasounds up to age eight to detect Wilms' tumor. AFP testing to detect liver cancer is not recommended as there have been no reported cases of hepatoblastoma in M-CM patients.[1]
Congenital abnormalities in the brain and progressive brain overgrowth can result in a variety of neurological problems that may require intervention. These include hydrocephalus, cerebellar tonsillar herniation (Chiari I), seizures and syringomyelia. These complications are not usually congenital, they develop over time often presenting complications in late infancy or early childhood, though they can become problems even later. Baseline brain and spinal cord MRI imaging with repeat scans at regular intervals is often prescribed to monitor the changes that result from progressive brain overgrowth.
Assessment of cardiac health with echocardiogram and EKG may be prescribed and arrhythmias or abnormalities may require surgical treatment.
## Prognosis[edit]
Prognosis varies widely depending on severity of symptoms, degree of intellectual impairment, and associated complications. Because the syndrome is rare and so newly identified, there are no long term studies.[citation needed]
## History[edit]
This disorder was recognized as a distinct syndrome in 1997 and named macrocephaly-cutis marmorata telangiectasia congenita or M-CMTC.[12][13] A new name, macrocephaly-capillary malformation, abbreviated M-CM, was recommended in 2007.[14] This new name was chosen to more accurately describe the skin markings associated with this disorder. In January 2012, a paper proposed new names for the syndrome: megalencephaly-capillary malformation or megalencephaly-capillary malformation-polymicrogyria with an abbreviation of MCAP.[15]
## References[edit]
1. ^ a b Rivière, JB.; Mirzaa, GM.; O'Roak, BJ.; Beddaoui, M.; Alcantara, D.; Conway, RL.; St-Onge, J.; Schwartzentruber, JA.; et al. (2012). "De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes". Nat Genet. 44 (8): 934–40. doi:10.1038/ng.2331. PMC 3408813. PMID 22729224.
2. ^ Kurek, KC.; Luks, VL.; Ayturk, UM.; Alomari, AI.; Fishman, SJ.; Spencer, SA.; Mulliken, JB.; Bowen, ME.; et al. (Jun 2012). "Somatic mosaic activating mutations in PIK3CA cause CLOVES syndrome". American Journal of Human Genetics. 90 (6): 1108–15. doi:10.1016/j.ajhg.2012.05.006. PMC 3370283. PMID 22658544.
3. ^ Lee, JH.; Huynh, M.; Silhavy, JL.; Kim, S.; Dixon-Salazar, T.; Heiberg, A.; Scott, E.; Bafna, V.; et al. (2012). "De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly". Nat Genet. 44 (8): 941–5. doi:10.1038/ng.2329. PMC 4417942. PMID 22729223.
4. ^ Lindhurst, MJ.; Parker, VE.; Payne, F.; Sapp, JC.; Rudge, S.; Harris, J.; Witkowski, AM.; Zhang, Q.; et al. (2012). "Mosaic overgrowth with fibroadipose hyperplasia is caused by somatic activating mutations in PIK3CA". Nat Genet. 44 (8): 928–33. doi:10.1038/ng.2332. PMC 3461408. PMID 22729222.
5. ^ Franceschini P, Licata D, Di Cara G, Guala A, Franceschini D, Genitori L (2000). "Macrocephaly-Cutis marmorata telangiectatica congenita without cutis marmorata?". American Journal of Medical Genetics. 90 (4): 265–9. doi:10.1002/(SICI)1096-8628(20000214)90:4<265::AID-AJMG1>3.0.CO;2-S. PMID 10710221.
6. ^ Robertson SP, Gattas M, Rogers M, Adès LC (2000). "Macrocephaly--cutis marmorata telangiectatica congenita: report of five patients and a review of the literature". Clin Dysmorphol. 9 (1): 1–9. doi:10.1097/00019605-200009010-00001. PMID 10649789.
7. ^ Conway RL, Pressman BD, Dobyns WB, Danielpour M, Lee J, Sanchez-Lara PA, et al. (2007). "Neuroimaging findings in macrocephaly-capillary malformation: a longitudinal study of 17 patients". American Journal of Medical Genetics. 143A (24): 2981–3008. doi:10.1002/ajmg.a.32040. PMC 6816457. PMID 18000912.
8. ^ Yano S, Watanabe Y (2001). "Association of arrhythmia and sudden death in macrocephaly-cutis marmorata telangiectatica congenita syndrome". American Journal of Medical Genetics. 102 (2): 149–52. doi:10.1002/ajmg.1428. PMID 11477607.
9. ^ Kuint, J.; Globus, O.; Ben Simon, GJ.; Greenberger, S. (2012). "Macrocephaly-capillary malformation presenting with fetal arrhythmia". Pediatr Dermatol. 29 (3): 384–6. doi:10.1111/j.1525-1470.2011.01677.x. PMID 22329570.
10. ^ Erener Ercan, T.; Oztunc, F.; Celkan, T.; Bor, M.; Kizilkilic, O.; Vural, M.; Perk, Y.; Islak, C.; Tuysuz, B. (Mar 2012). "Macrocephaly-Capillary Malformation Syndrome in a Newborn With Tetralogy of Fallot and Sagittal Sinus Thrombosis". J Child Neurol. 28 (1): 115–9. doi:10.1177/0883073812439346. PMID 22451530. S2CID 206549770.
11. ^ Dueñas-Arias, JE.; Arámbula-Meraz, E.; Frías-Castro, LO.; Ramos-Payán, R.; Quibrera-Matienzo, JA.; Luque-Ortega, F.; Aguilar-Medina, EM. (Sep 2009). "Tetralogy of Fallot associated with macrocephaly-capillary malformation syndrome: a case report and review of the literature". Journal of Medical Case Reports. 3 (1): 9215. doi:10.4076/1752-1947-3-9215. PMC 2827170. PMID 20210980.
12. ^ Clayton-Smith J, Kerr B, Brunner H, Tranebjaerg L, Magee A, Hennekam RC, et al. (1997). "Macrocephaly with cutis marmorata, haemangioma and syndactyly--a distinctive overgrowth syndrome". Clin Dysmorphol. 6 (4): 291–302. doi:10.1097/00019605-199710000-00001. PMID 9354837.
13. ^ Moore CA, Toriello HV, Abuelo DN, Bull MJ, Curry CJ, Hall BD, et al. (1997). "Macrocephaly-cutis marmorata telangiectatica congenita: a distinct disorder with developmental delay and connective tissue abnormalities". American Journal of Medical Genetics. 70 (1): 67–73. doi:10.1002/(SICI)1096-8628(19970502)70:1<67::AID-AJMG13>3.0.CO;2-V. PMID 9129744.
14. ^ Toriello HV, Mulliken JB (2007). "Accurately renaming macrocephaly-cutis marmorata telangiectatica congenita (M-CMTC) as macrocephaly-capillary malformation (M-CM)". American Journal of Medical Genetics. 143A (24): 3009. doi:10.1002/ajmg.a.31971. PMID 17963258. S2CID 6067902.
15. ^ Mirzaa, GM.; Conway, RL.; Gripp, KW.; Lerman-Sagie, T.; Siegel, DH.; deVries, LS.; Lev, D.; Kramer, N.; et al. (Feb 2012). "Megalencephaly-capillary malformation (MCAP) and megalencephaly-polydactyly-polymicrogyria-hydrocephalus (MPPH) syndromes: two closely related disorders of brain overgrowth and abnormal brain and body morphogenesis". American Journal of Medical Genetics. 158A (2): 269–91. doi:10.1002/ajmg.a.34402. PMID 22228622. S2CID 25253301.
## External links[edit]
* Genetics Home Reference
Classification
D
* ICD-10: Q87.3
* OMIM: 602501
* MeSH: C536142
* DiseasesDB: 34862
External resources
* GeneReviews: PIK3CA-Related Segmental Overgrowth
* Orphanet: 60040
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Macrocephaly-capillary malformation
|
c1865285
| 8,183 |
wikipedia
|
https://en.wikipedia.org/wiki/Macrocephaly-capillary_malformation
| 2021-01-18T18:50:18 |
{"gard": ["6950"], "mesh": ["C536142"], "umls": ["C1865285"], "orphanet": ["60040"], "wikidata": ["Q17162578"]}
|
A rare hereditary motor and sensory neuropathy disorder characterized by the typical CMT phenotype (slowly progressive distal muscle weakness and atrophy in upper and lower limbs, distal sensory loss in extremities, reduced or absent deep tendon reflexes and foot deformities) associated with focal segmental glomerulosclerosis (manifesting with proteinuria and progression to end-stage renal disease). Mild or moderate sensorineural hearing loss may also be associated. Nerve biopsy reveals both axonal and demyelinating changes and nerve conduction velocities vary from the demyelinating to axonal range (typically between 25-50m/sec).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Autosomal dominant intermediate Charcot-Marie-Tooth disease type E
|
c3280845
| 8,184 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93114
| 2021-01-23T18:12:35 |
{"gard": ["12011"], "omim": ["614455"], "icd-10": ["G60.0"], "synonyms": ["CMTDIE", "Charcot-Marie-Tooth disease-nephropathy syndrome"]}
|
A number sign (#) is used with this entry because of evidence that familial paragangliomas-1 (PGL1) is caused by heterozygous mutation in the SDHD gene (602690), which encodes the small subunit of cytochrome B in succinate-ubiquinone oxidoreductase, on chromosome 11q23.
Description
Paragangliomas, also referred to as 'glomus body tumors,' are tumors derived from paraganglia located throughout the body. Nonchromaffin types primarily serve as chemoreceptors (hence, the tumor name 'chemodectomas') and are located in the head and neck region (i.e., carotid body, jugular, vagal, and tympanic regions), whereas chromaffin types have endocrine activity, conventionally referred to as 'pheochromocytomas,' and are usually located below the head and neck (i.e., adrenal medulla and pre- and paravertebral thoracoabdominal regions). PGL can manifest as nonchromaffin head and neck tumors only, adrenal and/or extraadrenal pheochromocytomas only, or a combination of the 2 types of tumors (Baysal, 2002; Neumann et al., 2004).
The triad of gastric leiomyosarcoma, pulmonary chondroma, and extraadrenal paraganglioma constitutes a syndrome that occurs mainly in young women and is known as the Carney triad (604287). This triad is not to be confused with the other Carney syndrome of myxoma, spotty pigmentation, and endocrinopathy (160980).
Baysal (2008) provided a review of the molecular pathogenesis of hereditary paraganglioma.
### Genetic Heterogeneity of Paragangliomas
See also PGL4 (115310), caused by mutation in the SDHB gene (185470) on chromosome 1p36; PGL3 (605373), caused by mutation in the SDHC gene (602413) on chromosome 1q21; PGL2 (601650), caused by mutation in the SDHAF2 gene (613019) on chromosome 11q13; PGL5 (614165), caused by mutation in the SDHA gene (600857) on chromosome 5p15; PGL6 (618464), caused by mutation in the SLC25A11 gene (604165) on chromosome 17p13; and PGL7 (618475), caused by mutation in the DLST gene (126063) on chromosome 14q24.
Clinical Features
Kroll et al. (1964) found carotid body tumors in 12 members of a family in an autosomal dominant pattern of inheritance. Resler et al. (1966) reported a patient with bilateral carotid body tumors and a glomus jugulare tumor. The authors noted that familial carotid body tumors tended to be multiple. Familial glomus jugulare tumors were likely described in 3 affected sisters reported in 1937 by Goekoop (cited by Rosen, 1952). Also see Ladenheim and Sachs (1961). Bartels (1949) identified carotid body tumors in members of 3 successive generations of a family.
Wilson (1970) reviewed familial reports of carotid body tumors and described a family with male-to-male transmission and a skipped generation. Pratt (1973) reviewed the literature and reported 8 new cases of either unilateral or bilateral carotid body tumors in 4 generations of a kindred. In 1 generation of this family, 4 sisters had bilateral tumors and 1 brother had unilateral tumors. None of the 8 tumors reported were malignant. Chedid and Jao (1974) identified carotid body tumors in 6 members of 2 consecutive generations of a family. Four also had chronic obstructive pulmonary disease with persistently high arterial pCO(2) and low pO(2). The authors theorized that the tumors started as hyperplasia secondary to the stimulus of these altered blood gases. Nissenblatt (1978) reported a young woman with hypoplastic right heart syndrome who developed a carotid body tumor at age 28 years. He suggested a connection between low-oxygen situations such as high altitude living, emphysema, and cyanotic congenital heart disease, and the development of carotid body tumors.
Grufferman et al. (1980) reported 2 sisters with carotid body tumors and reviewed reports of 88 familial and 835 nonfamilial CBT cases. Familial cases had an equal sex ratio and followed autosomal dominant inheritance. Bilateral disease occurred in 31.8% of familial cases and 4.4% of sporadic cases. Six percent of all patients developed second primary tumors, mostly other paragangliomas. Parry et al. (1982) reviewed the records of 222 histologically diagnosed cases of carotid body tumors, including 146 females and 76 males. The mean age at tumor development was 44.7 years. In 16 patients who had other extraadrenal paragangliomas, suggesting a multiple primary tumor syndrome, the diagnosis occurred earlier (mean, 35.4 years; p less than 0.01). Five patients also developed thyroid cancer. Familial cases were more often bilateral and diagnosed slightly earlier.
Van Baars et al. (1982) provided a review of the literature of familial nonchromaffin paragangliomas. Carotid body tumors were the most common, followed by glomus jugulare, glomus vagale, and glomus tympanicum.
Parkin (1981) reported 2 unrelated families with a hereditary syndrome of pheochromocytoma associated with multiple glomus tumors of the head and neck. DeAngelis et al. (1987) reported the occurrence of pheochromocytoma and multiple paragangliomas in a patient with neurofibromatosis (162200). Karasov et al. (1982) described a sporadic case of a girl with a record number of 21 paragangliomas removed between the ages of 13 and 17 years, with evidence of remaining tumors. The tumors were catecholamine-producing. Khafagi et al. (1987) reported 2 unrelated adults, both of whom had a positive family history of paraganglioma. Both had malignant nonfunctional paragangliomas detected by uptake of iodine-131 metaiodobenzylguanidine; this agent proved to be of therapeutic value in the management of unresectable metastases.
Van Schothorst et al. (1998) reported 10 families with head and neck paragangliomas who originated from the same geographic region in the Netherlands. The carotid bifurcation was the most frequently affected site (57% of all head and neck tumors), and multiple paragangliomas occurred in 66% of patients. Three patients from different families developed a pheochromocytoma. No affected offspring of female carriers was observed, and all affected family members received the disease gene from their father.
Prontera et al. (2008) reported an Italian family with PGL1. The proband was a 49-year-old man who presented with throat pain, dysphonia, dyspnea, and mild hypertension, and was found to have bilateral carotid chemodectomas with multiple highly vascularized laryngeal and carotid paragangliomas. Family history revealed that the father, who died at age 71 of lung cancer, was diagnosed at age 66 with bilateral paragangliomas in the pericarotid region. The 55-year-old sister of the proband developed multiple laryngeal and carotid paragangliomas at age 52. The proband and his sister both carried a heterozygous truncating mutation in the SDHD gene.
Hensen et al. (2010) used the Kaplan-Meier method to calculate the age-specific penetrance of paragangliomas in 243 members of a large 7-generation Dutch family (Oosterwijk et al., 1996) with PGL1 caused by a founder mutation in the SDHD gene (D92Y; 602690.0004). The age at onset of symptoms ranged from 14 to 47 years. By clinical signs and symptoms alone, the penetrance reached a maximum of 57% by age 47 years. When MRI detection of occult paragangliomas was included, penetrance was estimated at 54% by age 40, 68% by age 60, and 87% by age 70. Multiple tumors were found in 65%, and 8% of paraganglioma patients had pheochromocytomas. One (3%) patient developed a malignant paraganglioma. None of 11 instances of maternal transmission of the mutation resulted in the development of paragangliomas. The findings indicated that the majority of mutation carriers will eventually develop head and neck paragangliomas, although Hensen et al. (2010) stated that the penetrance in this study was lower than some previous estimates. Hensen et al. (2010) emphasized the importance of including clinically unaffected mutation carriers in estimates of penetrance.
Among 47 asymptomatic carriers of SDHD mutations screened by physical examination or MRI, Heesterman et al. (2013) found that 28 (59.6%) carried a total of 57 tumors, including 38 carotid body tumors, 17 vagal body tumors, and 2 jugulotympanic tumors. Multiple tumors were seen in 34% of patients. Two patients (4.3%) had a sympathetic paraganglioma. The report indicated that a high percentage of asymptomatic SDHD mutation carriers have occult head and neck paragangliomas.
Inheritance
### Maternal Imprinting
From a study of 15 pedigrees, van der Mey et al. (1989) concluded that familial paragangliomas, which they referred to as hereditary glomus tumors, were inherited almost exclusively through the paternal line, a finding inconsistent with simple autosomal dominant transmission. They suggested a role for genomic imprinting, in which the maternally derived gene is inactivated during female oogenesis and can be reactivated only during spermatogenesis. Heutink et al. (1992) stated that all individuals with hereditary paragangliomas had inherited the disease gene from their father; expression of the phenotype was not observed in the offspring of an affected female until subsequent transmission of the gene through a male carrier. The observations strongly suggested genomic imprinting.
Baysal et al. (1997) noted that the age of onset of symptoms was significantly different between fathers and children: affected children had an earlier age of onset in 39 of 57 father-child pairs.
### Maternal Inheritance
Pigny et al. (2008) reported what they believed to be the first description of a paraganglioma kindred with maternal transmission of the mutated SDHD (602690) allele. A boy received the W43X mutation (602690.0023) from his mother and developed a glomus tympanicum paraganglioma at 11 years of age. He shared only the 11q23 haplotype with the other affected members of the family. Pigny et al. (2008) concluded that maternal transmission of a SDHD-linked paraganglioma, even if a rare event, can occur.
Mapping
In a large Dutch pedigree with hereditary paragangliomas, Heutink et al. (1992) found linkage with marker D11S147 located at chromosome 11q23-qter (maximum lod score of 6.0 at theta = 0.0 ). Likelihood calculations yielded a very high odds ratio in favor of genomic imprinting versus absence of genomic imprinting. Devilee et al. (1992) performed haplotyping in this large Dutch family using 15 markers in the region 11q13-q23. Two recombination events placed the PGL locus distal to STMY (185260) and proximal to D11S836, thus excluding the oncogenes INT2 (164950) and ETS1 (164720) as the site of the mutation. In an affected PGL family that showed imprinting, Mariman et al. (1995) found linkage to the locus on distal 11q.
In patients with familial nonchromaffin paragangliomas, Devilee et al. (1994) found loss of heterozygosity (LOH) only on chromosome 11, with a marked clustering on the distal half of the long arm. In all 8 cases in which they could determine the parental origin, the allele undergoing loss was maternally derived. However, LOH in all tumors was only partial, and it was not clear whether this represented an allelic imbalance or cellular heterogeneity. In a later study, van Schothorst et al. (1998) performed LOH analysis for the 11q22-q23 region on DNA-aneuploid tumor cells, enriched by flow sorting, and on purified chief cell fractions obtained by single-cell microdissection. Complete LOH was found in both types of cells, indicating that the chief cells were clonal proliferated tumor cells.
Oosterwijk et al. (1996) gave the location of the PGL1 gene as 11q22.3-q23. They offered genetic counseling on the basis of DNA linkage diagnosis in an extended Dutch pedigree. Presymptomatic testing of the paternal allele was performed in 16 cases; 4 of these appeared to have the at-risk haplotype and in 2 of the 4 a glomus tumor was subsequently detected on MRI. In 1 case linkage results were inconclusive because of recombination and 1 person did not want to learn his test result. The maternal allele was tested for carrier status in 4 cases of which 1 appeared to be a carrier.
Baysal et al. (1997) reported linkage of paraganglioma to chromosome 11q23 in 3 of 6 North American families. Recombinants narrowed the critical region to a 4.5-Mb interval flanked by the markers D11S1647 and D11S622. Partial allelic loss of strictly maternal origin was detected in 5 of 19 tumors. Milunsky et al. (1997) confirmed linkage to 11q23 in studies of 3 affected families. The inheritance pattern was consistent with genetic imprinting; the disorder was transmitted only by males.
Another 10 families with hereditary head and neck paragangliomas were ascertained by van Schothorst et al. (1998) from the same geographic region as that from which the large PGL1-linked Dutch family originated (Heutink et al., 1992). They determined the disease-linked haplotype, as defined by 13 markers encompassing a large interval on 11q21-q23, in these families and showed that alleles were identical for 6 contiguous markers spanning a genetic distance of 6 cM and containing PGL1. Despite this strong indication of a common ancestor, no kinship between the families could be demonstrated through genealogic surveys going back to 1800. Baysal et al. (1999) reevaluated the haplotype data of the multigenerational Dutch PGL1-linked family, using 2 additional single tandem repeat polymorphisms (STRPs) contained within the PGL1 critical interval proposed by van Schothorst et al. (1998). They excluded this interval, and instead predicted a nonoverlapping, more proximal 2-Mb critical interval between markers D11S1647 and D11S897. Analysis of 4 new American PGL families defined the telomeric border of the critical region as D11S1347. Among 3 unrelated American PGL families, significant haplotype sharing within this new interval was observed, strongly suggesting that they originated from a common ancestor. In sum, the authors refined the PGL1 locus to a 1.5-Mb region between D11S1986 and D11S1347.
Molecular Genetics
Astrom et al. (2003) stated that a large number of PGL1 families had been reported from the Netherlands and that there may be Dutch founder mutations.
In affected members of families with hereditary paraganglioma, Baysal et al. (2000) identified mutations in the SDHD gene (602690.0001-602690.0005), including the Dutch founder mutation (602690.0004).
Gimm et al. (2000) identified several mutations in the SDHD gene in unrelated patients. One patient had a pheochromocytoma and a carotid body paraganglioma (see 602690.0010); 2 unrelated patients, 1 with an extraadrenal intraabdominal pheochromocytoma with involvement of the jugular fossa, suggesting malignancy, and 1 with an isolated intestinal lipoma, had the same mutation (602690.0011); and a 33-year-old woman had 2 extraadrenal pheochromocytomas, 1 intraabdominal and 1 intrathoracic (see 602690.0002). Finally, the authors identified a somatic SDHD mutation in a pheochromocytoma (602690.0003).
In 7 families with familial paragangliomas, Milunsky et al. (2001) identified mutations in the SDHD gene (602690.0006-602690.0009). Three unrelated families had the same mutation (602690.0003), suggesting a founder effect. A restriction enzyme assay was developed for initial screening for the common mutation.
Paragangliomas of the central nervous system are rare, occur almost exclusively in the cauda equina of the spinal cord, and are considered nonfamilial. In a spinal paraganglioma and similar cerebellar tumors that developed 22 years later in the same patient, Masuoka et al. (2001) identified a mutation in the SDHD gene (602690.0011). There was no family history of paragangliomas, but DNA from white blood cells of this patient showed the same sequence alterations, indicating the presence of a germline mutation.
Cascon et al. (2002) performed mutation analysis of the SDHD gene in 25 consecutive, unrelated patients with pheochromocytoma and/or paraganglioma, with or without family history. There were 18 patients with pheochromocytoma, 4 with paraganglioma alone, and 3 with both, who had tested negative for germline mutations in the VHL (608537) and RET (164761) genes. Two novel truncating mutations were detected, a 4-bp deletion (602690.0022) in an apparently sporadic case of paraganglioma and pheochromocytoma, and a nonsense mutation (602690.0023) in a patient with paraganglioma with a family history of pheochromocytoma.
In a patient of German descent with sporadic bilateral carotid body paragangliomata, Leube et al. (2004) identified a frameshift mutation in the SDHD gene (602690.0020).
Mhatre et al. (2004) performed a mutation screen of the SDHB, SDHC, and SDHD genes in blood and tumor samples of 14 sporadic and 3 familial cases of head and neck paragangliomas. Germline mutations in SDHB and SDHD were identified in 2 of the 3 affected individuals with familial PGL, whereas no germline or somatic mutations were identified in the 14 sporadic cases. The presence of mutations within SDHB and SDHD in 2 of the 3 samples of familial PGL and absence of mutations in sporadic cases is consistent with a significant contribution of these genes to familial but not sporadic PGL.
Heterogeneity
### Carotid Body Paragangliomas with Sensorineural Hearing Loss
Badenhop et al. (2001) studied 4 families with familial carotid body paragangliomas, 2 of which exhibited coinheritance of PGL and sensorineural hearing loss or tinnitus. Sequence analysis identified mutations in exon 1 and exon 3 of the SDHD gene, including a novel 2-bp deletion in exon 3 creating a premature stop codon at position 67 (602690.0013); a novel 3-bp deletion in exon 3 resulting in the loss of tyr93 (602690.0014); a missense mutation in exon 3 resulting in a pro81-to-leu substitution (602690.0003); and a novel G-to-C substitution in exon 1 resulting in a met1-to-val substitution (602690.0015). The PGL1 region contains another gene, DPP2/TIMM8B (606659), a homolog of the X-linked TIMM8A gene (300356), mutations in which cause dystonia and deafness seen in Mohr-Tranebjaerg syndrome (304700). The authors found no base changes in the TIMM8B gene; thus, it would seem that the association of paraganglioma with sensorineural hearing loss cannot be explained by the proximity of the TIMM8B and SDHD genes.
Genotype/Phenotype Correlations
In a review of several studies, Baysal et al. (2002) found that 83 cases of paragangliomas-1 in 'unrelated' families and patients were attributable to 3 founder populations in the Netherlands, in stark contrast to 25 distinct SDHD mutations reported among 43 independent familial and nonfamilial cases in other parts of the world. Astrom et al. (2003) interpreted this finding as suggesting that low altitudes in the Netherlands reduce penetrance and relax the natural selection on SDHD mutations. They studied the influence of altitude on the phenotype of PGL1 in 58 patients from 23 families. Patients who were diagnosed with single tumors at their first clinical evaluation lived at lower average altitudes and were exposed to lower altitude-years than those with multiple tumors (p less than 0.012). Nonsense/splicing mutation carriers developed symptoms 8.5 years earlier than missense mutation carriers (p less than 0.012). Pheochromocytomas developed in 6 patients, 5 of whom had nonsense mutations. Patients with pheochromocytomas also lived at higher average altitudes and were exposed to higher altitude-years than those without them. Astrom et al. (2003) concluded that collectively, these data suggested that higher altitudes and nonsense/splicing mutations are associated with increased severity in PGL1 and supported the hypothesis that SDHD mutations impair oxygen sensing.
In a population-based genetic study of 334 unrelated patients with adrenal or extraadrenal pheochromocytomas and 83 patients with head and neck paragangliomas, Neumann et al. (2004) found that 12% of patients had a mutation in either the SDHB or SDHD gene, with equal distribution between the 2 genes (25 and 24 patients with mutations in the SDHB and SDHD genes, respectively). Mean age at diagnosis was similar between the 2 groups (approximately 30 years). Inheritance of SDHD mutations was consistent with maternal imprinting. Examination of relatives yielded a total of 32 and 34 manifesting carriers of SDHB and SDHD mutations, respectively. Multiple tumors occurred in 28% of SDHB carriers and 74% of SDHD carriers; adrenal pheochromocytomas occurred in 28% of SDHB carriers and 53% of SDHD carriers, whereas extraadrenal pheochromocytomas were identified in 48% of SDHB carriers and 21% of SDHD carriers; head and neck paragangliomas occurred in 31% of SDHB carriers and 79% of SDHD carriers; and malignancy occurred in 34% of SDHB carriers but no SDHD carriers. Two related SDHB carriers had renal cell carcinoma, and 1 SDHB and 1 SDHD carrier each had papillary thyroid carcinoma. Age-related penetrance for carriers of the 2 mutations was similar: SDHB and SDHD carriers showed 77% and 86% penetrance by age 50 years, respectively.
Benn et al. (2006) determined genotype/phenotype associations in a cohort of patients with pheochromocytoma/paraganglioma syndromes and SDHB or SDHD mutations. SDHB mutation carriers were more likely than SDHD mutation carriers to develop extraadrenal pheochromocytomas and malignant disease, whereas SDHD mutation carriers had a greater propensity to develop head and neck paragangliomas and multiple tumors. For the index cases, there was no difference between 43 SDHB and 19 SDHD mutation carriers in the time to first diagnosis (34 vs 28 years, respectively; p = 0.3). However, when all 112 mutation carriers were included, the estimated age-related penetrance was different for SDHB versus SDHD mutation carriers (p = 0.008).
Population Genetics
Hensen et al. (2012) determined the mutation frequency of 4 succinate dehydrogenase genes in a total of 1,045 patients from 340 Dutch families with paraganglioma and pheochromocytoma. Mutations were identified in 690 cases from 239 families. The most commonly affected gene in mutation carriers was SDHD (87.1%), followed by SDHAF2 (6.7%), SDHB (5.9%), and SDHC (0.3%). Almost 70% of all carriers had the founder mutation D92Y (602690.0004) in SDHD; approximately 89% of all SDH mutation carriers had 1 of 6 Dutch founder mutations. The dominance of SDHD mutations was unique to the Netherlands, contrasting with the higher prevalence of SDHB mutations found elsewhere.
Nomenclature
Strauchen (2002) noted that the interchangeable use of 'paraganglioma' and 'glomus tumor' was a 'common point of confusion.' He emphasized that the glomus tumor is a tumor of modified perivascular smooth muscle, which frequently presents as a painful subungual mass, and is unrelated to tumors of the adrenal and extraadrenal paraganglia. Jugulotympanic paraganglioma is often referred to as a 'glomus jugulare tumor.' This tumor arises from minute, anatomically dispersed paraganglia located at the base of the skull and temporal bone and is closely related to similar tumors of the carotid body and other extraadrenal paraganglia. It is unrelated to the much more common glomus tumor of skin and soft tissue. See 138000 for an inherited form of smooth muscle tissue glomus tumors.
History
The glomus jugulare was first discovered by Stacy R. Guild at Johns Hopkins in 1941 (Guild (1941, 1953)).
INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Pulsatile tinnitus (tympanic paraganglioma) \- Conductive hearing loss (in a subset of patients) CARDIOVASCULAR Heart \- Palpitations (with pheochromocytoma) \- Tachycardia (with pheochromocytoma) Vascular \- Hypertension (with pheochromocytoma) RESPIRATORY Larynx \- Vocal cord paralysis (caused by tumor impingement) SKIN, NAILS, & HAIR Skin \- Diaphoresis (with pheochromocytoma) NEUROLOGIC Central Nervous System \- Headache (with pheochromocytoma) \- Cranial nerve palsies can arise with head and neck paragangliomas Behavioral Psychiatric Manifestations \- Anxiety (with pheochromocytoma) VOICE \- Hoarse voice (caused by tumor impingement) \- Loss of voice NEOPLASIA \- Paragangliomas \- Multiple tumors in 74% of patients \- Paragangliomas, head and neck (79%) \- Chemodectomas \- Carotid body tumors (most common location) \- Glomus jugular tumors \- Vagal nerve tumors (glomus vagale) \- Tympanic nerve tumors (glomus tympanicum) \- Pheochromocytoma, adrenal (53%) \- Pheochromocytoma, extraadrenal (21%) LABORATORY ABNORMALITIES \- Elevated catecholamines (in patients with pheochromocytoma) MISCELLANEOUS \- Cells of origin are part of the diffuse neuroendocrine system (DNES) \- Adult onset (mean 30 years, range 5-60 years) \- Maternal imprinting \- Penetrance 86% by 50 years of age \- Signs and symptoms depend on tumor location and activity \- Patients may have head and neck paragangliomas only, adrenal or extraadrenal pheochromocytomas only, or both \- See also PGL2 ( 601650 ), PGL3 ( 605373 ), and PGL4 ( 115310 ) MOLECULAR BASIS \- Caused by mutations in the succinate dehydrogenase complex subunit D gene (SDHD, 602690.0001 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
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*[Ki]: Inhibitor constant
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*[DOR]: δ-opioid receptor
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*[MAOIs]: Monoamine oxidase inhibitors
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*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
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|
PARAGANGLIOMAS 1
|
c0030421
| 8,185 |
omim
|
https://www.omim.org/entry/168000
| 2019-09-22T16:36:39 |
{"doid": ["0050773"], "mesh": ["D010235"], "omim": ["168000"], "orphanet": ["29072"], "synonyms": ["PARAGANGLIOMAS, FAMILIAL NONCHROMAFFIN, 1", "GLOMUS TUMORS, FAMILIAL, 1", "GLOMUS JUGULARE TUMORS", "Familial pheochromocytoma-paraganglioma", "CAROTID BODY TUMORS", "PARAGANGLIOMATA", "CHEMODECTOMAS", "PARAGANGLIOMAS, FAMILIAL, 1", "Alternative titles", "PARAGANGLIOMA, CAROTID BODY"], "genereviews": ["NBK1548"]}
|
## Summary
### Clinical characteristics.
Smith-Magenis syndrome (SMS) is characterized by distinctive physical features (particularly facial features that progress with age), developmental delay, cognitive impairment, behavioral abnormalities, sleep disturbance, and childhood-onset abdominal obesity. Infants have feeding difficulties, failure to thrive, hypotonia, hyporeflexia, prolonged napping or need to be awakened for feeds, and generalized lethargy. The majority of individuals function in the mild-to-moderate range of intellectual disability. The behavioral phenotype, including significant sleep disturbance, stereotypies, and maladaptive and self-injurious behaviors, is generally not recognized until age 18 months or older and continues to change until adulthood. Sensory issues are frequently noted; these may include avoidant behavior, as well as repetitive seeking of textures, sounds, and experiences. Toileting difficulties are common. Significant anxiety is common as are problems with executive functioning, including inattention, distractibility, hyperactivity, and impulsivity. Maladaptive behaviors include frequent outbursts / temper tantrums, attention-seeking behaviors, opposition, aggression, and self-injurious behaviors including self-hitting, self-biting, skin picking, inserting foreign objects into body orifices (polyembolokoilamania), and yanking fingernails and/or toenails (onychotillomania). Among the stereotypic behaviors described, the spasmodic upper-body squeeze or "self-hug" seems to be highly associated with SMS. An underlying developmental asynchrony, specifically emotional maturity delayed beyond intellectual functioning, may also contribute to maladaptive behaviors in people with SMS.
### Diagnosis/testing.
The diagnosis of SMS is established in a proband who has suggestive clinical findings and either a heterozygous deletion at chromosome 17p11.2 that includes RAI1 or a heterozygous intragenic RAI1 pathogenic variant.
### Management.
Treatment of manifestations: Early-childhood intervention programs; individualized special education for school-aged children; speech/language, physical, occupational, and behavior therapy and vocational training support later in life. Affected individuals may also benefit from monitored trials of psychotropic medication to increase attention and/or decrease hyperactivity, and therapeutic management of sleep disorders. Standard treatment for epilepsy, obesity, gastroesophageal reflux disease, constipation, hypercholesterolemia, palatal anomalies, scoliosis, ophthalmologic issues, recurrent otitis media, hearing loss, cardiac anomalies, renal anomalies, mild immunodeficiency, hypothyroidism, and growth hormone deficiency. Respite care and psychosocial support for family members are recommended.
Surveillance: Annual multidisciplinary evaluations for general health and well-being and to plan for educational and vocational or other individualized interventions. In particular, periodic neurodevelopmental assessments and/or consultation with a developmental pediatrician to monitor progress and refer for additional services, evaluations, or support. School-aged children should have periodic comprehensive evaluation to give input to the individualized education program (IEP). Annual otolaryngology, audiology, and ophthalmology evaluations. Measurement of growth parameters and nutritional status at each visit. Monitor for the development and/or progression of seizures and scoliosis. Annual fasting lipid profile, thyroid function tests, and screening urinalysis for occult urinary tract infections. Annual family psychosocial assessments are also recommended to assess support for caregivers and sibs. Repeat quantitative immunoglobulins/vaccine titers as clinically indicated.
Agents/circumstances to avoid. When starting a new medication, care should be taken to track sleep and behavior changes over several days or weeks to monitor for potential side effects (e.g., increased appetite, weight gain) and adverse reactions and/or to determine potential efficacy.
### Genetic counseling.
Smith-Magenis syndrome (SMS) is caused by a heterozygous deletion of or a heterozygous pathogenic variant in RAI1 on chromosome 17p11.2. The majority of 17p11.2 deletions are de novo, while deleterious variants in RAI1 can be de novo or inherited. Complex familial chromosome rearrangements leading to del(17)(p11.2) and SMS occur but are rare. Although SMS usually occurs as the result of a de novo deletion of 17p11.2, rare instances of vertical transmission from an affected parent to a child, parental germline mosaicism, and complex familial chromosome rearrangements leading to del(17)(p11.2) and SMS have been reported. If the SMS-related genetic alteration has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible. In the rare instance of a complex familial chromosome rearrangement, prenatal testing is possible for a pregnancy at increased risk using prenatal chromosomal microarray analysis (CMA) or FISH on fetal cells.
## Diagnosis
### Suggestive Findings
Smith-Magenis syndrome (SMS) should be suspected in individuals with the following clinical findings:
* A subtly distinctive facial appearance (see Clinical Description) that becomes more evident with age (see Figure 1, Figure 2, Figure 3)
* Mild-to-moderate infantile hypotonia with feeding difficulties and failure to thrive
* Peripheral neuropathy
* Some level of developmental delay and/or intellectual disability, including early speech delays (expressive greater than receptive speech) with or without associated hearing loss
* A distinct neurobehavioral phenotype that includes stereotypic and maladaptive behaviors and sleep disturbance (see Clinical Description)
* Short stature (prepubertal)
* Minor skeletal anomalies, including brachydactyly
* Ophthalmologic abnormalities
* Otolaryngologic abnormalities
#### Figure 1.
Infants with SMS. Female age nine months (left) and male age 30 months (right). Note brachycephaly, broad forehead, upslanting palpebral fissures, short upturned nose, and characteristic downturned "tent"-shaped vermilion of the upper lip with mild micrognathia. (more...)
#### Figure 2.
Early school-age SMS showing male age four years (left) and female age five years (right); the female is also pictured at age 15 years in Figure 3. Note broad forehead, deep-set eyes, midface retrusion.
#### Figure 3.
Adolescent females with SMS caused by mutation of RAI1 (left) and deletion 17p11.2 (right). Note short philtrum with relative prognathism resulting from midface retrusion that persists with age; downturned upper lip is more notable at rest (non-smiling). (more...)
### Establishing the Diagnosis
The diagnosis of SMS is established in a proband with suggestive clinical features and one of the following on molecular genetic testing (see Table 1):
* A heterozygous deletion of 17p11.2
* A heterozygous pathogenic variant involving RAI1
When the phenotypic findings suggest the diagnosis of SMS, molecular genetic testing approaches can include chromosomal microarray analysis, single-gene testing, or use of a multigene panel:
* Chromosomal microarray analysis (CMA) typically is performed first. CMA uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including RAI1) that cannot be detected by sequence analysis.
Note: Although a visible interstitial deletion of chromosome 17p11.2 can be detected in all individuals with the common approximately 3.5-Mb deletion by a routine G-banded analysis provided the resolution is adequate (≥550 band), it is not uncommon for the deletion to be overlooked particularly when the indication for the cytogenetic study is other than SMS. Therefore, CMA has now replaced G-banded cytogenetic analysis and FISH analysis as a first-line test in the diagnosis of SMS.
If CMA does not detect a deletion of 17p11.2 and the diagnosis of SMS is still suspected, single-gene testing of RAI1 or a multigene panel that includes RAI1 may be considered.
* Single-gene testing. Sequence analysis of RAI1, which detects small intragenic deletions/insertions and missense, nonsense, and splice site variants, may be considered next. If no pathogenic variant is detected through sequence analysis of RAI1, gene-targeted deletion/duplication analysis, which can detect intragenic deletions or duplications of RAI1, may be considered.
* An intellectual disability multigene panel that includes RAI1 and other genes of interest (see Differential Diagnosis) may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (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.
When the phenotype is indistinguishable from many other inherited disorders characterized by developmental delay / intellectual disability, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is the best option. Exome sequencing is most commonly used; genome sequencing is also possible.
If exome sequencing is not diagnostic, exome array (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis.
For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
### Table 1.
Molecular Genetic Testing Used in Smith-Magenis Syndrome
View in own window
Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method
RAI1CMA (recommended first) 3~90%-95%
Sequence analysis 45%-10% 5
Gene-targeted deletion/duplication analysis 6Unknown
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\.
A chromosomal microarray (CMA) that includes probe coverage of RAI1 can detect deletions of 17p11.2 (interstitial deletion, complex rearrangements, or derivative chromosomes).
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\.
Sequence analysis (particularly of exon 3, in which all pathogenic variants have been found to date) detects RAI1 pathogenic variants in individuals with SMS when cytogenetic and FISH studies are negative for the 17p11.2 deletion [Vilboux et al 2011, Vieira et al 2012, Dubourg et al 2014, Falco 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. Breakpoints of large deletions and/or deletion of adjacent genes may not be determined.
## Clinical Characteristics
### Clinical Description
Smith-Magenis syndrome (SMS) has a clinically recognizable phenotype that includes physical, developmental, and behavioral features (Table 2). The phenotypic features can be subtle in infancy and early childhood, frequently delaying diagnosis until school age, when the characteristic facial appearance and behavioral phenotype may be more readily apparent.
### Table 2.
Clinical Features of Smith-Magenis Syndrome
View in own window
FrequencySystemFinding
>75% of
individualsCraniofacial/
Skeletal/
Growth
* Brachycephaly
* Midface retrusion
* Relative prognathism w/age
* Broad, square-shaped face
* Everted, "tented" vermilion of the upper lip
* Deep-set, close-spaced eyes
* Short broad hands
* Dental anomalies (missing premolars; taurodontism)
* >90%ile for weight, w/abdominal fat deposition (esp after age 10 yrs)
Neurobehavioral
* Infantile hypotonia
* Generalized complacency/lethargy (infancy)
* Oral sensorimotor dysfunction (early childhood)
* Sensory processing issues
* Developmental delay / cognitive impairment
* Speech/language impairment
* Sleep disturbance
* Inverted circadian rhythm of melatonin
* Attention-seeking behaviors
* Inattention ± hyperactivity
* Tantrums, behavioral dysregulation
* Impulsivity
* Stereotypic behaviors
* Self-injurious behaviors
* Hyporeflexia
* Signs of peripheral neuropathy
Otolaryngologic
* Middle-ear & laryngeal anomalies
* Hearing loss (79%)
* Hyperacusis (74%)
* Hoarse, deep voice
Common
(50%-75% of
individuals)
* Short stature
* Scoliosis
* Mild ventriculomegaly of brain
* Hyperacusis
* Tracheobronchial problems
* Velopharyngeal insufficiency
* Ocular abnormalities (strabismus, myopia, iris anomalies, &/or microcornea)
* REM sleep abnormalities
* Hypercholesterolemia/hypertriglyceridemia
* Chronic constipation
* Abnormal EEG w/out overt seizures
* Features of autism spectrum disorder
Less common
(25%-50% of
individuals)
* Cardiac defects
* Thyroid function abnormalities
* Seizures (11%-30%)
* Immune function abnormalities (esp low IgA)
Occasional
(<25% of
individuals)
* Renal / urinary tract abnormalities
* EEG abnormalities in absence of clinical seizures 1
* Forearm abnormalities
* Cleft lip/palate
* Retinal detachment
Greenberg et al [1996], Chen et al [1997], Allanson et al [1999], Smith et al [2002], Potocki et al [2003], Gropman et al [2006], Smith et al [2006], Edelman et al [2007], Smith & Gropman [2010], Burns et al [2010]
1\.
Frequency varies by study.
Facial appearance. The facial appearance is characterized by a broad square-shaped face, brachycephaly, prominent forehead, synophrys, mildly upslanted palpebral fissures, deep-set eyes, broad nasal bridge, midfacial retrusion (formerly known as midfacial hypoplasia), short, full-tipped nose with reduced nasal height, micrognathia in infancy (see Figure 1) changing to relative prognathia with age, and a distinct appearance of the mouth, with fleshy everted vermilion of the upper lip.
The facial appearance of SMS becomes more recognizable in early childhood (see Figure 2, Figure 3), with persisting midfacial retrusion, relative prognathism, and heavy brows with coarsening facial appearance.
Neurologic
* Hypotonia is reported in virtually all infants, accompanied by hyporeflexia (84%) and generalized complacency and lethargy.
* Clinical signs of peripheral neuropathy are seen in approximately 75%, regardless of deletion size [Gropman et al 2006].
* In infancy / early childhood, these include infantile hypotonia, hyporeflexia, relative insensitivity to pain, and mild intention tremor (6-8 Hz) of upper extremity.
* In later childhood, affected children often exhibit a characteristic appearance of the legs and feet observed in peripheral nerve syndromes or neuropathies (i.e, "inverted champagne bottle appearance") with pes cavus or pes planus deformity, and unusual gait (foot flap).
* Toe-walking (60%) may persist despite the absence of tight heel cords [Smith & Gropman 2010].
* By childhood approximately 20% of affected individuals have a head circumference below the third centile [Smith & Gropman 2010].
* Pubertal onset of catamenial seizures has also been observed in some females coinciding with menses [Smith & Gropman 2010].
* Stroke-like episodes have been reported in three individuals with SMS, including:
* A male born with bilateral cleft lip/palate and congenital heart defect who developed a left hemiparesis at age 4.5 years [Smith & Gropman 2010];
* A female age ten years with ventricular septal defect, who was diagnosed with Moyamoya disease and had evidence of ischemic changes at age five years [Girirajan et al 2007];
* A female age 32 years with evidence of severe atherosclerotic disease of the intracranial vessels documented after she suffered an ischemic infarct postoperatively following repeat cardiac surgery [Chaudhry et al 2007].
Therefore, pre-surgical evaluation for possible premature cerebrovascular disease is recommended for individuals with SMS who require open-heart surgery in adolescence or adulthood [Chaudhry et al 2007].
Neurodevelopmental features. Developmental delays are evident in early childhood, with the majority of individuals with SMS functioning in the mild-to-moderate range of intellectual disability. Due to the maladaptive behaviors and sleep deficits, true intellectual ability may not be accurately assessed in many individuals and test scores may not be representative of an individual's current level of functioning. When reported, measured developmental or intelligence quotients range from 20 to 78 with a mean score of approximately 50.
* Gross and fine motor skills are delayed in the first year of life and may be exacerbated by generalized hypotonia. Issues related to sensory integration are frequently noted [Hildenbrand & Smith 2012].
* Speech/language
* In infancy, crying is infrequent and often hoarse.
* The vast majority of infants show markedly decreased babbling and vocalization for age.
* By age two to three years, significant expressive language deficits relative to receptive language skills are recognized [Wolters et al 2009].
* With appropriate intervention and a total communication program that includes sign/gesture language and other augmentative communication approaches, verbal speech generally develops by school age; however, articulation problems usually persist. Speech intensity may be mildly elevated with a rapid rate and moderate explosiveness, accompanied by hypernasality and hoarse vocal quality.
* Cognitive abilities
* Affected individuals typically have relative weaknesses observed in sequential processing and short-term memory.
* Relative strengths are in long-term memory and perceptual closure (i.e., a process whereby an incomplete visual stimulus is perceived to be complete: "parts of a whole").
Behavioral phenotype. The behavioral phenotype, which includes sleep disturbance (see Sleep disturbance), maladaptive and self-injurious behaviors (SIB), and stereotypies is generally not recognized until age 18 months or older and escalates with age, often coinciding with expected life-cycle stages: 18-24 months, school age, and onset of puberty [Gropman et al 2006].
* Maladaptive behaviors in people with SMS reflect a complex interplay between physiology and environment that may be further compounded by an underlying developmental asynchrony: specifically, emotional maturity delayed beyond intellectual functioning [Finucane & Haas-Givler 2009].
* With age, the gap between intellectual attainment and emotional development appears to widen for many people with SMS, and this disparity poses significant behavioral and programmatic challenges in older children and adults.
* One study found that 90% of individuals with SMS (between ages 4 and 18 years) demonstrated significant social impairment (35% mild/moderate; 55% severe range per the Social Responsiveness Scale) per parent report, with symptoms similar to children with autistic disorder or other developmental disorders [Laje et al 2010b].
* The degree of sleep disturbance remains one of the strongest predictors of maladaptive behavior [Dykens & Smith 1998, Arron et al 2011, Sloneem et al 2011].
* Although maladaptive behaviors, aggression, and SIB may continue, a relative "calming" of behavioral concerns may occur in adulthood.
Self-injurious behaviors (SIB) are present in the vast majority of individuals after age two years [Arron et al 2011, Sloneem et al 2011].
* A direct correlation exists between the number of different types, intensity, and frequency of SIB and the level of intellectual impairment.
* Two behaviors distinctive to SMS, nail yanking (onychotillomania) and insertion of foreign objects into body orifices (polyembolokoilamania), range from 25% to 90% of affected individuals depending on the age and group studied (see Genotype-Phenotype Correlations).
* Nail yanking generally does not become a major problem until later childhood.
* Object insertion in ear(s) is most prevalent in both children and adults; other body orifices (nose, vagina, and rectum) are generally not reported until late teens/adulthood [Gropman et al 2007].
* The overall prevalence of SIB increases with age, as does the number of different types of SIB exhibited [Finucane et al 2001], which may include:
* Self-hitting (71%)
* Self-biting (77%)
* Skin picking (65%)
Note: Given the high rates of SIB, including self-insertion of objects or digits into body orifices, caution must be taken when evaluating individuals with SMS for maltreatment or abuse. Although individuals with intellectual impairment are at high risk for maltreatment, abuse may also be incorrectly suspected due to SIB or self-insertion behaviors.
Sensory integration issues are present and persist throughout childhood. A prominent pattern of sensory processing difficulties is recognized, characterized by an imbalance in neurologic thresholds and a fluctuation between active and passive self-regulation [Hildenbrand & Smith 2012].
Other maladaptive behaviors may include:
* Head banging, which may begin as early as age 18 months
* Frequent outbursts / temper tantrums
* Attention-seeking behaviors (especially from adults)
* Impulsivity, which may increase over time, particularly in females [Martin et al 2006]
* Inattention with or without hyperactivity
* Oppositional behaviors
* Aggression
* Rapid mood shifts
* Anxiety, which can become a major issue in adolescence and adulthood
* Toileting difficulties
Sterotypies common to SMS include:
* The spasmodic upper-body squeeze or "self-hug" behavior, which may provide an effective clinical diagnostic marker for the syndrome.
* Mouthing of hands or objects that persists from early childhood to ages where this is not socially acceptable.
* Teeth grinding
* Body rocking
* Spinning or twirling objects
* Finger lick and repetitive page turning ("lick and flip") behavior [Vieira et al 2012]
Sleep disturbance. The abnormal diurnal (inverted) circadian rhythm of melatonin appears pathognomic in SMS, documented in an estimated 95% of affected individuals [Boone et al 2011, Spruyt et al 2016]. Further data [Boudreau et al 2009] suggest that the sleep disturbance cannot be caused solely by aberrant melatonin synthesis and/or degradation as previously suggested [Potocki et al 2000b, De Leersnyder et al 2001, Chik et al 2010, Nováková et al 2012]. While not inverted, the 24-hour circadian rhythm of body temperature is phase advanced by about three hours relative to controls [Smith et al 2019].
The sleep disturbance is characterized by fragmented and shortened sleep cycles with frequent nocturnal and early morning awakenings and excessive daytime sleepiness [Greenberg et al 1996, Smith et al 1998, Potocki et al 2000b, De Leersnyder et al 2001, Smith & Duncan 2005].
* Parents usually do not recognize significant sleep problems before age 12-18 months, although fragmented sleep with reduced total sleep time has been documented as early as age six months [Duncan et al 2003, Gropman et al 2006].
* Disrupted sleep becomes a major problem in early childhood and is a major issue for caregivers, who themselves may become sleep deprived [Foster et al 2010].
* Diminished REM sleep was documented in more than half of those undergoing polysomnography [Greenberg et al 1996, Potocki et al 2000b].
* Actigraphy-based sleep estimates document developmental differences in nocturnal arousal patterns by age and time of night [Gropman et al 2007, Smith et al 2019].
* Affected individuals have a reduction in 24-hour and night sleep compared to healthy pediatric controls, with estimated sleep about one hour less than expected across all ages.
This is evidenced by decreased total night sleep, lower sleep efficiency, earlier sleep onset and final sleep offset, increased waking after sleep onset (WASO), and increased duration of daytime naps (beyond typical age) [Smith et al 2019].
* Developmental sleep changes from childhood through adolescence/adulthood are evidenced by an age-related variation in the timing of wake onset (but not sleep onset) and WASO [Smith et al 2019].
* Age differences are also associated with different patterns of sleep for SMS compared to pediatric controls [Smith et al 2019]:
* In those younger than age ten years, late-night activity was greater in individuals with SMS than in pediatric controls.
* Older individuals with SMS (>10 years) exhibited less late-night activity but increased early-night activity, consistent with poor "settling" and delayed sleep pattern observed in adolescent controls.
* Due to the propensity of weight gain as affected individuals age, obstructive sleep apnea may also develop and can contribute to the overall sleep disturbance.
Growth and feeding
* At birth, weight, length, and head circumference are generally in the normal range.
* Feeding difficulties in infancy leading to failure to thrive are common, including marked oral motor dysfunction with poor suck and swallow and textural aversion.
* In early infancy, length and weight gradually decelerate; short stature (height <5th centile) is frequently observed (67%) especially at young ages, but may not persist into adulthood.
* Dietary preferences, hyperphagia, and food foraging at night (especially at older ages), coupled with a general sedentary lifestyle and psychotropic medication side effects (affecting appetite / weight gain), contribute to obesity (increased BMI), typically beginning in school-aged children (ages 6-9 years).
* Obesity may lead to increased risk for related health issues (e.g., type 2 diabetes) in adulthood.
* Hypercholesterolemia that is not associated with diet or BMI values is recognized in more than 50% of individuals with SMS [Smith et al 2002].
Gastrointestinal. Gastroesophageal reflux and constipation are frequently reported.
Oral and dental anomalies
* Oral sensorimotor dysfunction is a major issue, including:
* Lingual weakness, asymmetry, and/or limited mobility
* Weak bilabial seal (64%)
* Palatal abnormalities (64%), although cleft lip and/or palate occur in fewer than 25% of affected individuals
* Open-mouth posture with tongue protrusion and frequent drooling
* A high prevalence (~90%) of dental anomalies, specifically tooth agenesis (especially premolars) and taurodontism, has been reported. This is accompanied by an age-related increase in dental caries, restored teeth, and poor gingival health due to decreased oral hygiene, supporting the need for increased dental care in adolescent years [Tomona et al 2006].
Musculoskeletal
* Mild-to-moderate scoliosis, most commonly of the mid-thoracic region, is seen in approximately 60% of affected individuals age four years and older, although vertebral anomalies are seen in only a few.
* Hands and feet remain small.
* Markedly flat or highly arched feet and unusual gait are generally observed.
Ocular abnormalities are present in approximately 85% of affected individuals and include strabismus, progressive myopia, iris anomalies, and/or microcornea. About 20% of affected individuals older than age ten years experience retinal detachment, which may be due to a combination of aggressive/self-injurious behaviors and high myopia.
Ears and hearing
* Otitis media occurs frequently (≥3 episodes/year) and often leads to tympanostomy tube placement (85%).
* Hearing loss is documented in more than 79% [Brendal et al 2017], with conductive loss most common before age ten years.
A pattern of fluctuating and progressive hearing decline occurs with age, including sensorineural loss (48%) between age 11 years and adulthood [Brendal et al 2017].
* Hyperacusis, or oversensitivity to certain frequencies/sounds tolerable to listeners with normal hearing, is reported in approximately 74% [Brendal et al 2017].
Laryngeal anomalies, including polyps, nodules, edema, or partial vocal cord paralysis, are common.
* Velopharyngeal insufficiency and/or structural vocal-fold abnormalities without reported vocal hyperfunction are seen in the vast majority of individuals with SMS.
* Functional impairments in voice (hoarseness) may contribute to the marked delays in expressive speech.
Cardiovascular defects are identified in fewer than 50% of affected individuals with SMS who have a deletion of 17p11.2 but have not been reported in those who have a heterozygous pathogenic variant in RAI1. Cardiac anomalies may include mild tricuspid or mitral valve stenosis or regurgitation, ventricular septal defects, supravalvular aortic or pulmonic stenosis, atrial septal defects, and tetralogy of Fallot [Smith & Gropman 2010].
Genitourinary anomalies are found in between 15% and 35% of affected individuals who have a deletion of 17p11.2 but have not been reported in those who have a heterozygous pathogenic variant in RAI1. Anomalies may include the following [Smith et al 1986, Greenberg et al 1996, Chou et al 2002, Myers et al 2007]:
* Duplication of the collecting system
* Unilateral renal agenesis and ectopic kidney
* Ureterovesicular obstruction
* Malposition of the ureterovesicular junction
Additionally, a vast majority of affected individuals have nocturnal enuresis in childhood. Genital anomalies reported include cryptorchidism, shawl, or undeveloped scrotum in males, and infantile cervix and/or hypoplastic uterus in females [Smith & Gropman 2010].
Immunologic. More than 50% of affected individuals have low serum immunoglobulin profiles, which may increase susceptibility to sinopulmonary infections. Recurrent otitis media (88%), upper respiratory infections (61%), pneumonia (47%), and/or sinusitis (42%) requiring antibiotics are frequently reported [Perkins et al 2017].
Endocrine. The specific incidence of endocrine abnormalities in individuals with SMS remains undefined.
* About 25% of affected individuals have mild hypothyroidism.
* Puberty typically occurs within the normal time frame; however, precocious puberty (premature adrenarche), premature ovarian failure [Smith, personal communication], and delayed sexual maturation have been observed.
* While short stature occurs in SMS, only one published case of isolated growth hormone deficiency has been reported [Itoh et al 2004]. When growth hormone profiles are studied, peak levels appear in the proper phase of the day with levels only slightly below normal controls [De Leersnyder et al 2001, De Leersnyder et al 2006].
* Adrenal aplasia/hypoplasia was described in one affected male age 11 months who died unexpectedly after palatoplasty [Denny et al 1992].
Dermatology. In addition to skin problems due to self-injurious behaviors, a minority of affected individuals have rosy cheeks (which may be related to drooling and/or eczema) and/or hyperkeratosis (~20%) over the hands, feet, or knees.
* Complaints of dry skin remain common especially among those with an RAI1 pathogenic variant (100%) compared to those with a 17p11.2 deletion (44%) [Edelman et al 2007].
* Hair and skin color often appears fairer compared to other family members.
Malignancy. Risk of cancer appears to be no greater than in the general population for most individuals with SMS.
* At least two affected individuals who developed melanoma are known [Smith, personal experience].
* The common deletion results in haploinsufficiency of FLCN that is associated with Birt-Hogg- Dubé (BHD) syndrome, raising a theoretic concern for increased risk of renal carcinoma in individuals with SMS [Menko et al 2009]. BHD syndrome is a hereditary cancer syndrome characterized by increased risk of cutaneous fibrofolliculomas, pulmonary cysts, spontaneous pneumothorax, and renal tumors. While unstudied, the co-occurrence of renal tumors in a few unrelated adults with SMS [Smith et al 2014, Dardour et al 2016] suggests that precautionary cancer surveillance may be considered in adulthood for individuals with co-occurring BHD syndrome.
Prognosis. Insufficient longitudinal data are available to accurately determine life expectancy. One would expect that, in the absence of major organ involvement, the life expectancy of individuals with SMS would not differ from that of individuals with cognitive impairment at large. Anecdotally, the oldest known individual with SMS lived to age 88 years [Smith & Magenis, personal communication]. In the month prior to her death, she was reportedly her usual alert, happy, "SMS" self with ongoing sleep issues and was being treated for chronic recurrent sinusitis. Four days prior to death she suffered an apparent right-sided stroke with left-sided weakness. No autopsy was performed.
### Genotype-Phenotype Correlations
Deletion of 17p11.2. Parental origin of the 17p deletion has not been documented to affect the phenotype, suggesting that imprinting does not play a role in the expression of the typical SMS phenotype.
Note: See Genetically Related Disorders for information about individuals who have larger deletions of 17p that extend distally to include PMP22.
Pathogenic variant in RAI1
* Higher rates of onychotillomania and polyembolokoilamania (90%) have been reported in those with a heterozygous pathogenic variant in RAI1 compared to those with a 17p11.2 deletion (40%) [Edelman et al 2007].
* The risk of obesity and obesity-related health issues is higher in individuals with a heterozygous pathogenic variant in RAI1 compared to those with a 17p11.2 deletion [Alaimo et al 2014].
* Individuals with a heterozygous pathogenic variant in RAI1 typically do not have short stature or other organ system involvement [Slager et al 2003, Bi et al 2004, Girirajan et al 2005].
### Prevalence
The birth incidence is estimated at 1:25,000 births [Greenberg et al 1991]; the actual prevalence may be closer to 1:15,000 [Smith et al 2005]. The vast majority of individuals have been identified in the last five to ten years as a result of improved whole-genome analysis techniques.
## Differential Diagnosis
Smith-Magenis syndrome (SMS) should be distinguished from other syndromes that include developmental delay, infantile hypotonia, short stature, distinctive facies, and a behavioral phenotype. The pervasive behavioral aspects and circadian sleep disorder associated with inverted melatonin secretion can help distinguish Smith-Magenis syndrome (SMS) from other neurodevelopmental disorders. However, because the phenotype of SMS is broad and changes with time, all disorders with intellectual disability (ID) without other distinctive findings should be considered in the differential diagnosis. To date more than 180 such disorders with ID have been identified. See OMIM Phenotypic Series: Autosomal dominant ID, Autosomal recessive ID, Nonsyndromic X-linked ID, and Syndromic X-linked ID.
## Management
Management guidelines for SMS have been published by PRISMS. See Medical Management Guidelines and Management Checklist (pdfs).
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with Smith-Magenis syndrome (SMS), the recommended evaluations summarized in Table 3 (if not performed as part of the evaluation that led to diagnosis) are recommended.
### Table 3.
Recommended Evaluations Following Initial Diagnosis
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System/ConcernEvaluationComment
Neurologic
* EEG in individuals who have clinical seizures
* Neuroimaging (MRI or CT scan) in accordance w/findings such as seizures &/or motor asymmetry
For those w/out overt seizures, EEG may be helpful to evaluate for possible subclinical events in which treatment may improve attention &/or behavior; a change in behavior or attention warrants reevaluation.
DevelopmentDevelopmental assessment
* To incl motor, adaptive, cognitive, & speech/language evaluation
* Evaluation for early intervention / special education
BehaviorNeuropsychological evaluationIn individuals age >12 mos: screen for behavior problems incl sleep disturbances, ADHD, anxiety, &/or traits suggestive of ASD.
Sleep/
Respiratory
* Sleep history w/particular attention to sleep/wake schedules & signs/symptoms of obstructive sleep apnea
* Polysomnogram (overnight sleep study) to evaluate for obstructive sleep apnea in those w/evidence of sleep-disordered breathing
Sleep diaries may prove helpful in documenting sleep/wake schedules.
Growth/
FeedingAssessment of growth parameters for failure to thrive in infancy & obesity in older individualsConsider referral to gastroenterologist for those w/failure to thrive; consider nutrition &/or full feeding eval.
Consider assessment of oral motor dysfunction & suck/swallowing issues in infancy.
Fasting lipid profile in adolescents & adultsEval for hypercholesterolemia
GastrointestinalAssessment:
* For signs/symptoms of GERD
* For constipation
* Of caloric intake
MouthAssessment for palatal defects & dental anomalies (if teeth have erupted)Consider referral to pediatric dentist.
MusculoskeletalSpine radiographs to assess for vertebral anomalies & scoliosis
EyesOphthalmologic evalAttention to evidence of strabismus, microcornea, iris anomalies, & refractive error
ENT
* Audiologic assessment for conductive &/or SNHL
* Consider eval for velopharyngeal insufficiency in those w/functional impairments
CardiovascularEchocardiogram to assess for a congenital heart defect
GenitourinaryUltrasound exam for renal/urologic anomaliesFurther urologic evals may be needed if history of frequent urinary tract infections.
ImmunologicQualitative immunoglobulins 1 incl vaccine titers (incl pneumococcus)Consider eval by immunologist, as prophylactic strategies to prevent infections may benefit some.
EndocrineThyroid function studies to incl TSH & either T4 or free T4 2
DermatologicSkin assessmentFor evidence of self-injurious behaviors, eczema, & hyperkeratosis
MiscellaneousConsultation w/clinical geneticist &/or genetic counselorTo incl genetic counseling
Family supports/resources
* Use of community or online resources incl Parent to Parent
* Need for social work involvement for parental support
* Need for home nursing referral
ADHD = attention-deficit/hyperactivity disorder; ASD = autism spectrum disorder; GERD = gastroesophageal reflux disease; SNHL = sensorineural hearing loss; TSH = thyroid-stimulating hormone
1\.
To include quantitative serum immunoglobulins (IgG, IgA, IgM)
2\.
Screening for adrenal function should be considered in individuals with larger deletions extending into 17p12.
### Treatment of Manifestations
The following are appropriate.
### Table 4.
Treatment of Manifestations in Individuals with Smith-Magenis Syndrome
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Manifestation/ConcernTreatmentConsiderations/Other
EpilepsyStandard treatment w/AEDs by an experienced neurologist
* Many AEDs may be effective; none has been demonstrated effective specifically for this disorder.
* Education of parents/caregivers 1
Developmental delay /
Intellectual disabilitySee Developmental Delay / Intellectual Disability Management Issues.
Speech/
Language delay 2
* Identify & treat swallowing/feeding problems & optimize oral sensorimotor development.
* Develop skills related to swallowing & speech production by increasing sensory input, fostering movement of the articulators, increasing oral motor endurance, & decreasing hypersensitivity.
Behavior issues 3
* Develop comprehensive behavior support plan for home & school at onset of maladaptive behaviors (typically starting in early elementary school).
* Develop structured school program w/one-on-one support & curricula matched to known cognitive & behavior profile of SMS.
* Behavioral therapies incl special education techniques emphasizing individualized instruction, structure, & routine to minimize behavioral outbursts in school
Insight about vulnerabilities & relative strengths in sensory processing patterns may aid caregivers in adapting activity demands, modifying environments, & facilitating appropriate & supportive social interactions. 4
Psychiatric
disorderPsychotropic medication & psychological services to ↓ maladaptive behaviors, ↑ attention &/or ↓ hyperactivity, ↓ anxiety, & stabilize mood.
* Atypical patterns of sensory processing & more problematic/atypical behaviors may become more prominent w/↑ age.
* No single medication regimen is consistently effective. 5
Sleep disorder 6MelatoninEarly anecdotal reports of therapeutic benefit from melatonin (low dose; <3 mg) taken at bedtime suggest variable improvement of sleep w/out major adverse reactions. 7
Oral β-1-adrenergic antagonistsA single uncontrolled study reported suppression of daytime melatonin peaks & subjectively improved behavior. 8
Acebutolol w/melatoninAn uncontrolled trial combined daytime dose of acebutolol w/evening oral dose of melatonin (6 mg at 8 pm) & found that nocturnal plasma concentration of melatonin was restored & nighttime sleep improved w/disappearance of nocturnal awakenings. 9
Enclosed bed system for containment during sleep
ObesityStandard treatment 10Focus on staying active & fit starting at young age
Gastroesophageal
reflux diseaseStandard treatment
ConstipationStandard treatment
HypercholesterolemiaDietary modifications &/or medication in accordance w/standard practice
Palatal anomaliesStandard treatmentConsideration of referral to multidisciplinary craniofacial clinic
ScoliosisStandard treatment per orthopedist
Ophthalmologic
abnormalitiesStandard treatment per ophthalmologist &/or optometrist
Recurrent otitis mediaStandard treatmentMay incl insertion of tympanostomy tubes
Hearing lossHearing aids may be helpful as per otolaryngologist.Community hearing services through early intervention or school district
Cardiac anomaliesStandard treatment
Renal anomaliesStandard treatment
Mild immunodeficiencyStandard treatmentMay incl prophylactic antibiotics
HypothyroidismThyroid replacement therapy
Growth hormone
deficiencyGrowth hormone treatmentGrowth hormone treatment has been reported; 11 controlled studies have not evaluated its efficacy.
Impact on parents
& sibsRespite care, annual family psychosocial screenings, & family psychosocial support
* Combination of ID, severe behavioral abnormalities, & sleep disturbance takes a significant toll on parents & sibs.
* Incl family support services & resources as essential components of a holistic management plan.
AEDs = antiepileptic drugs; ID = intellectual disability
1\.
Education of parents/caregivers regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for children diagnosed with epilepsy, see Epilepsy & My Child Toolkit.
2\.
The ability to develop expressive language appears to depend on the early use of sign language and intervention by speech/language pathologists.
3\.
The potential for more problematic or atypical behaviors with increased age underscores the need for early and ongoing intervention and caregiver education [Hildenbrand & Smith 2012].
4\.
Parents report high rates of depression and anxiety, and family stress is significantly higher in families of people with SMS than in those of children w/nonspecific developmental disabilities [Hodapp et al 1998, Foster et al 2010].
5\.
Based on an extensive review of psychotropic medication use in a large cohort of individuals with SMS (n=62), use of polypharmacy and/or serial trials with minimal effectiveness was observed. Benzodiazepines obtained the lowest mean efficacy score in the "slightly worse" range, suggesting that use of these drugs may be detrimental to individuals with SMS [Laje et al 2010a].
6\.
Sleep management is a challenge for physicians and parents. Prior to beginning any trial, a child's medical status and baseline sleep pattern must be considered. No well-controlled treatment trials have been reported.
7\.
Dosages should be kept low (≤3 mg). However, melatonin dispensed over the counter is not regulated by the FDA; thus, dosages may not be exact. No early and controlled melatonin treatment trials have been conducted. A monitored trial of four to six weeks on melatonin may be worth considering in affected individuals with sleep disturbance.
8\.
Nine individuals with SMS were treated with oral β-1-adrenergic antagonists (acebutolol 10 mg/kg) [De Leersnyder et al 2001]. This treatment, however, did not restore nocturnal plasma concentration of melatonin.
9\.
Parents also reported subjective improvement in daytime behaviors with increased concentration. Contraindications to the use of β-1-adrenergic antagonists include asthma, pulmonary problems, some cardiovascular disease, and diabetes mellitus.
10\.
Dietary changes with portion management in addition to increased movement and physical activity, limiting sedentary activity, and discouraging nighttime eating
11\.
Itoh et al [2004], Spadoni et al [2004]
#### 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. Evaluation and referral for services including occupational therapy, physical therapy, speech/language therapy, feeding therapy, special education services, and infant mental health services. In the US, early intervention is a federally funded program available in all states and 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 and to support parents in maximizing quality of life. Some issues to consider:
* IEP services:
* An IEP provides specially designed instruction and related services to children who qualify.
* IEP services will be reviewed annually to determine if 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.
* Accommodation for a scheduled nap during the school day (ideally in late morning or after lunch but not after 3 pm) should be included in the IEP.
* Vision and hearing consultants should be a part of the child's IEP team to support access to academic material.
* PT, OT, and speech/language 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 teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, most school districts in the US are 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., scoliosis).
* Consider use of durable medical equipment and positioning devices as needed (e.g., walkers, orthotics).
Fine motor dysfunction. Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and handwriting.
Oral motor dysfunction should be reassessed 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 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.
#### Social/Behavioral Concerns
Children may qualify for and benefit from interventions based on the principles of applied behavior analysis (ABA). The goals of ABA therapy include teaching and maintaining new skills, generalizing these skills to different environments, reducing maladaptive behaviors, and fostering social interaction. Behavior Support Plans and therapeutic interventions should be developed by a team, often under the supervision of a board-certified behavior analyst (BCBA) or psychologist. The strategies and interventions should be developed by professionals who are familiar with physical, medical, behavioral, and learning characteristics associated with SMS.
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 Smith-Magenis Syndrome
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System/ConcernEvaluationFrequency
NeurologicMonitoring of those w/seizures as clinically indicated 1Each visit
DevelopmentMultidisciplinary team eval (incl physical, occupational, & speech therapy evals & psychological assessment) to assist in development of an IEP 2, 3Annually
Psychiatric/
BehavioralBehavior assessment for attention, aggressive or self-injurious behaviorEach visit
Growth/FeedingMeasurement of growth parametersEach visit
Eval of nutritional status & safety of oral intake
GastrointestinalFasting lipid profileAnnually in adolescents & adults
ENT/MouthOtolaryngologic follow up for assessment & mgmt of otitis media & other sinus abnormalitiesAnnually
Audiologic eval to monitor for conductive or SNHL annually or as clinically indicated
MusculoskeletalMonitoring for scoliosis
EyesOphthalmologic eval
GenitourinaryRoutine urinalysis to evaluate for occult urinary tract infections
EndocrineThyroid function, incl free T4 & TSH
FamilyScreening of family functioning, mental health, & resource needs leading to provision of appropriate referrals to community agencies
ImmunologicRepeat qualitative immunoglobulins incl vaccine titers (esp pneumococcus)As clinically indicated
IEP = individualized educational program; SNHL = sensorineural hearing loss
1\.
Assess for new manifestations such as seizures or changes in behavior.
2\.
Particularly in school-aged children
3\.
Periodic neurodevelopmental assessments and/or developmental/behavioral pediatric consultation can be an important adjunct to the team evaluation.
### Agents/Circumstances to Avoid
Use of psychotropic medications in SMS often begins in childhood with use of sleep aids and trials of different psychotropic medications to control behavior, with mixed response; no single regimen has shown consistent efficacy and adverse reactions to some medications have been reported [Laje et al 2010a]. Polypharmacy is also an issue. Lacking well-controlled trials, when starting a new medication, care should be taken to track sleep and behavior changes over several days/weeks to monitor for potential side effects (e.g., increased appetite, weight gain) and adverse reactions and/or to determine potential efficacy.
### 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.
### Other
Pharmacologic intervention should be considered on an individual basis with recognition that some medications may exacerbate sleep or behavioral problems and may cause weight gain.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Smith-Magenis Syndrome
|
c0795864
| 8,186 |
gene_reviews
|
https://www.ncbi.nlm.nih.gov/books/NBK1310/
| 2021-01-18T20:56:12 |
{"mesh": ["D058496"], "synonyms": ["del(17)(p11.2)"]}
|
Oppenheim's sign
Differential diagnosisPyramidal tract damage
Oppenheim's sign is dorsiflexion of the great toe elicited by irritation downward of the medial side of the tibia.[1] It is one of a number of Babinski-like responses.
The sign's presence indicates a damage to the pyramidal tract.
It is named for Hermann Oppenheim.[2][3]
## Refer[edit]
1. ^ Swartz, Mark H. (2006). Textbook of Physical Diagnosis: History and Examination With STUDENT CONSULT Online Access. Philadelphia: Saunders. p. 694. ISBN 1-4160-0307-X.
2. ^ synd/1573 at Who Named It?
3. ^ H. Oppenheim. Zur Pathologie der Hautreflexe der unteren Extremitäten. Monatsschrift für Psychiatrie und Neurologie, 1902, 12: 421-423.
* v
* t
* e
Symptoms and signs relating to the nervous system
Neurological examination · Cranial nerve examination
Central nervous system
Head
* Battle's sign
* Kernig's sign
* Macewen's sign
* Myerson's sign
* Stroop test
* Hirano body
Other
* increased intracranial pressure
* Cushing's triad
* Lhermitte's sign
* Charcot's neurologic triad
Peripheral nervous system
Reflexes
Combination
* Jendrassik maneuver
Legs
* Plantar reflex
* Chaddock reflex
* Oppenheim's sign
* Westphal's sign
Arms
* Hoffmann's sign
Other
Arms
* Froment's sign
* carpal tunnel syndrome
* Tinel sign
* Phalen maneuver
Legs
* Gowers' sign
* Hoover's sign
* Lasègue's sign
* Trendelenburg's sign
Torso
* Beevor's sign
General
* Pain stimulus
This medical sign article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Oppenheim's sign
|
c1532837
| 8,187 |
wikipedia
|
https://en.wikipedia.org/wiki/Oppenheim%27s_sign
| 2021-01-18T18:55:25 |
{"wikidata": ["Q1503727"]}
|
## Summary
### Clinical characteristics.
Pyruvate carboxylase (PC) deficiency is characterized in most affected individuals by failure to thrive, developmental delay, recurrent seizures, and metabolic acidosis. Three clinical types are recognized:
* Type A (infantile form), in which most affected children die in infancy or early childhood
* Type B (severe neonatal form), in which affected infants have hepatomegaly, pyramidal tract signs, and abnormal movement and die within the first three months of life
* Type C (intermittent/benign form), in which affected individuals have normal or mildly delayed neurologic development and episodic metabolic acidosis
### Diagnosis/testing.
The diagnosis of PC deficiency is established in a proband by identification of PC enzyme deficiency in fibroblasts or lymphoblasts. In individuals with PC deficiency, fibroblast PC enzyme activity is usually less than 5% of that observed in controls. The diagnosis of PC deficiency can also be established in a proband by identification of biallelic pathogenic variants in PC on molecular genetic testing.
### Management.
Treatment of manifestations: Intravenous glucose-containing fluids, hydration, and correction of the metabolic acidosis are the mainstays of acute management. Correction of biochemical abnormalities and supplementation with citrate, aspartic acid, and biotin may improve somatic findings but not neurologic manifestations. Orthotopic liver transplantation may be indicated in some affected individuals. Anaplerotic therapies such as triheptanoin show some promise, especially regarding the neurologic manifestations, but need to be further evaluated.
Prevention of primary manifestations: Parental education regarding factors that elicit a crisis and early signs of decompensation; written information on the child's disorder and appropriate emergency treatment to be carried at all times; minimization of intercurrent infections and environmental stressors; high-carbohydrate and high-protein diet with frequent feedings to prevent dependence on gluconeogenesis.
Prevention of secondary complications: Hospitalization for the management of fever, infection, dehydration, or trauma; intensive proactive medical support to prevent dehydration, hypotension, hypoglycemia, and increasing metabolic acidosis.
Surveillance: Regular monitoring of serum lactate concentrations.
Agents/circumstances to avoid: Fasting; the ketogenic diet.
### Genetic counseling.
PC deficiency is inherited in an autosomal recessive manner. De novo somatic pathogenic variants have been reported. If both parents are carriers, sibs of an individual with PC deficiency have a 25% chance of inheriting both pathogenic variants and being affected, a 50% chance of inheriting one pathogenic variant and being carriers, and a 25% chance of inheriting both normal genes and not being carriers. Carrier testing for at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible by molecular genetic testing if both pathogenic variants have been identified in an affected family member.
## Diagnosis
There are three clinical presentations of pyruvate carboxylase (PC) deficiency:
* Type A. Infantile or North American form
* Type B. Severe neonatal or French form
* Type C. Intermittent/benign form
### Suggestive Findings
PC deficiency should be suspected in individuals with the following clinical features and biochemical findings.
Clinical features
* Failure to thrive
* Developmental delay
* Recurrent seizures
Biochemical findings by PC deficiency type [Wang et al 2008]
* Type A. Infantile-onset mild to moderate lactic acidemia; normal lactate-to-pyruvate ratio despite acidemia
* Type B. Increased lactate-to-pyruvate ratio; decreased 3-hydroxybutyrate-to-acetoacetate ratio; elevated blood concentrations of citrulline, proline, lysine, and ammonia; low concentration of glutamine
* Type C. Episodic metabolic acidosis with normal plasma citrulline concentrations and elevated plasma lysine and proline concentrations
Biochemical abnormalities by analyte. Note: For each of the following analytes the abnormal values overlap among PC deficiency types A, B, and C. Normal values differ by laboratory.
* Lactate and pyruvate. The lack of PC enzyme activity causes the accumulation of pyruvate in the plasma, which is subsequently converted to lactate by the enzyme lactate dehydrogenase, causing an elevated plasma concentration of lactic acid. Elevated blood lactate concentrations (5.5-27.8 mmol/L; normal range 0.5-2.2) are characteristically found in PC deficiency type A (2-10 mmol/L), type B (>10 mmol/L), and type C (2-5 mmol/L). Blood pyruvate concentrations are usually elevated in PC deficiency type B (0.14-0.90 mmol/L; normal range 0.04-0.13), resulting in an elevated lactate-to-pyruvate ratio (>20). The ratio is usually normal in PC deficiency type A and C (<20).
* Amino acids. In serum and urine: high alanine, citrulline, and lysine; low aspartic acid and glutamine. Amino acid concentrations vary with the general metabolic state of the individual.
* Hyperalaninemia as a result of pyruvate shunting
* Hypercitrullinemia and hyperlysinemia caused by the block in the urea cycle secondary to a low aspartic acid
* Low aspartic acid and glutamine as a result of deficiency in the oxaloacetate precursor
* Ketonemia. 3-hydroxybutyrate and acetoacetate concentrations are increased in blood. In PC deficiency type B, the ratio of acetoacetate to 3-hydroxybutyrate is increased, reflecting a low NADH-to-NAD ratio inside the mitochondria. Lack of oxaloacetate prevents the liver from oxidizing acetyl-CoA derived from pyruvate and fatty acids. The expanded acetyl-CoA pool results in hepatic ketone body synthesis [De Vivo et al 1977].
* Hypoglycemia. Oxaloacetate deficiency limits gluconeogenesis. Note: Hypoglycemia is not a consistent finding despite the fact that PC is the first rate-limiting step in gluconeogenesis.
* Hyperammonemia results from poor ammonia disposal and decreased urea cycle function.
* Cerebrospinal fluid (CSF)
* Elevated lactate and pyruvate concentrations
* Markedly reduced glutamine concentration
* Elevated glutamic acid and proline concentrations
### Establishing the Diagnosis
The diagnosis of PC deficiency is established in a proband by identification of PC enzyme deficiency in fibroblasts or lymphoblasts by PC enzyme assay. In individuals with PC deficiency, fibroblast PC enzyme activity is usually less than 5% of that observed in controls [Wang et al 2008]. Note: Muscle PC activity is quite low in control tissue. Therefore, PC enzyme assay on muscle tissue is not recommended.
The diagnosis of PC deficiency can also be established in a proband by identification of biallelic pathogenic variants in PC on molecular genetic testing (see Table 1).
Molecular genetic testing approaches can include single-gene testing, use of a multigene panel, and more comprehensive genomic testing:
* Single-gene testing. Sequence analysis of PC is performed first and followed by gene-targeted deletion/duplication analysis if no pathogenic variant is found.
Note: (1) Pathogenic variants have been found to be mosaic, an unusual occurrence in an autosomal recessive disorder (see Genotype-Phenotype Correlations and Molecular Genetics). (2) Since PC deficiency occurs through a loss-of-function mechanism, testing for intragenic deletions or duplication could identify a disease-causing variant; such a variant has not been reported.
* A multigene panel that includes PC and other genes of interest (see Differential Diagnosis) may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
* More comprehensive genomic testing (when available) including exome sequencing, mitochondrial sequencing, and genome sequencing may be considered. Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene or genes that results in a similar clinical presentation).
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 Pyruvate Carboxylase Deficiency
View in own window
Gene 1Method 2Proportion of Probands with Pathogenic Variants 3 Detectable by Method
PCSequence analysis 495% 5
Gene-targeted deletion/duplication analysis 6Unknown 7
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
The presence of mosaicism may complicate molecular testing; see Genotype-Phenotype Correlations, Table 2, and Wang et al [2008].
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\.
Sequence analysis of the PC coding region and promoter detects pathogenic variants in 95% of affected individuals, including the most common pathogenic variants: p.Ala610Thr, p.Arg631Gln, and p.Ala847Val.
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 pyruvate carboxylase (PC) deficiency present with failure to thrive, developmental delay, recurrent seizures, and metabolic acidosis. Hypoglycemia is an inconsistent finding.
Three types of PC deficiency have been recognized, based on clinical presentation.
Type A (infantile form) is characterized by infantile onset with mild metabolic acidosis, delayed motor development, intellectual disability, failure to thrive, apathy, hypotonia, pyramidal tract signs, ataxia, nystagmus, and convulsions.
Episodes of acute vomiting, tachypnea, and acidosis are usually precipitated by metabolic or infectious stress.
Most affected children die in infancy or early childhood, although some may survive to maturity. Older individuals function at a lower-than-average level and need special care and schooling [Wang et al 2008].
Type B (severe neonatal form). Affected infants present with biochemical abnormalities, hypoglycemia, hyperammonemia, hypernatremia, anorexia, hepatomegaly, convulsions, stupor, hypotonia, pyramidal tract signs, abnormal movements (including high-amplitude tremor and dyskinesia), and abnormal ocular behavior.
Motor development is severely retarded and affected individuals have intellectual disability [Wang et al 2008].
The majority of affected infants die within the first three months of life [García-Cazorla et al 2006]; however, two affected individuals were alive at ages nine and 20 years, likely because of mosaicism [Wang et al 2008] (see Genotype-Phenotype Correlations).
Type C (intermittent/benign form) is characterized by normal or mildly delayed neurologic development and episodic metabolic acidosis. Five affected individuals have been reported [Van Coster et al 1991, Stern et al 1995, Vaquerizo Madrid et al 1997, Arnold et al 2001, Wang et al 2008]. The first individual described had normal mental and motor development at age 12 years despite several earlier episodes of metabolic acidosis [Van Coster et al 1991].
Brain MRI. Symmetric cystic lesions and gliosis in the cortex, basal ganglia, brain stem, or cerebellum; generalized hypomyelination; and hyperintensity of the subcortical frontoparietal white matter were described in some individuals with type A.
Ventricular dilation, cerebrocortical and white matter atrophy, or periventricular white matter cysts have been reported in some individuals with type B [García-Cazorla et al 2006].
Magnetic resonance spectroscopy (MRS). Brain MRS shows high levels for lactate and choline and low levels for N-acetylaspartate.
Pathophysiology. The glutamine-glutamate cycle in astrocytes requires a continuous supply of oxaloacetate provided by the reaction catalyzed by PC enzyme activity.
### Genotype-Phenotype Correlations
Type A. Seven pathogenic variants (p.Arg62Cys, p.Val145Ala, p.Arg451Cys, p.Ala610Thr, p.Arg631Gln, p.Met743Ile, and p.Ala847Val) have been identified in five individuals [Wang et al 2008].
Type B. Missense variants, deletions, and splice donor site pathogenic variants occur in homozygotes, compound heterozygotes, and individuals with mosaicism (see Table 2) [Wang et al 2008].
Type C. A heterozygous variant (p.Ser266Ala) and somatic mosaic variant (p.Ser705Ter) were observed in the first individual described [Wang et al 2008]; compound heterozygosity for the pathogenic variants p.Thr569Ala and Leu1137ValfsTer1170 was observed in the second individual described [Wang et al 2008].
Mosaicism (see Molecular Genetics) was found in five individuals [Wang et al 2008: Table 2 (type A: #6; type B: #2, #5, and #7; type C: #1)]. Four had prolonged survival; the fifth (type B: #7) died from unrelated medical complications.
Homozygous pathogenic variants. The deaths of the more severely affected individuals with type B correlated with homozygous variants, which produced very low amounts (2% and 3%) of fibroblast PC protein [Wang et al 2008: Table 2].
### Prevalence
In most populations, the birth incidence of PC deficiency is low (1:250,000).
PC deficiency is more prevalent in particular ethnic groups:
* Type A. Incidence is increased among the native North American Ojibwa, Cree, and Micmac tribes of the Algonquin-speaking peoples. The p.Ala610Thr pathogenic variant was identified in all 13 affected individuals of Ojibwa and Cree origin. In those populations the carrier frequency may be as high as 1:10 [Carbone et al 1998].
* Type B. Incidence is increased in Europe (France especially, but also Germany and England).
## Differential Diagnosis
Biotinidase deficiency results from the inability to recycle endogenous biotin and to use protein-bound biotin from the diet. Biotin binds to propionyl-coenzyme A-carboxylase, pyruvate carboxylase (PC), beta-methylcrotonyl-CoA carboxylase, and acetyl-CoA carboxylase. Deficiency affects all biotinylated enzymes and can present in the neonatal period or later in infancy with neurologic symptoms such as lethargy, seizures with metabolic acidosis, hearing loss, alopecia, and perioral/facial dermatitis. It can be effectively treated with biotin.
In the untreated state, profound biotinidase deficiency during infancy is usually characterized by neurologic and cutaneous findings that include seizures, hypotonia, and rash, often accompanied by hyperventilation, laryngeal stridor, and apnea. Older children may also have alopecia, ataxia, developmental delay, sensorineural hearing loss, optic atrophy, and recurrent infections. Individuals with partial biotinidase deficiency may have hypotonia, skin rash, and hair loss, particularly during times of stress.
Biotinidase deficiency is caused by pathogenic variants in BTD. Individuals with profound biotinidase deficiency have less than 10% of mean normal serum biotinidase activity; individuals with partial biotinidase deficiency have 10%-30% of mean normal serum biotinidase activity.
Biotinidase deficiency is inherited in an autosomal recessive manner.
Pyruvate dehydrogenase complex (PDHC) deficiency (OMIM PS312170) results from deficiency of either one of three catalytic components (E1, E2, and E3) or the regulatory component of PDHC (pyruvate dehydrogenase phosphate phosphatase). The diagnosis of PDHC deficiency is suspected in individuals with lactic acidemia who have a progressive or intermittent neurologic syndrome including: poor acquisition or loss of motor milestones, poor muscle tone, new-onset seizures, periods of incoordination (i.e., ataxia), abnormal eye movements, poor response to visual stimuli, and episodic dystonia. Blood and CSF lactate concentrations are elevated and are associated with elevations of blood and CSF concentrations of pyruvate and alanine. Blood glucose values are normal and decline only slowly with fasting because of increased pyruvate carboxylation and gluconeogenesis. Blood ketone bodies are usually not detectable, unlike PC deficiency. Also, unlike PC deficiency, PDHC deficiency usually presents with a normal lactate-to-pyruvate ratio in plasma. Typically, the CSF lactate elevations are higher than those in the blood, giving rise to the term "cerebral lactic acidosis."
Brain MRI may show varying combinations of ventricular dilatation; cerebral atrophy; hydrocephaly; partial or complete absence of the corpus callosum; absence of the medullary pyramids; abnormal and ectopic inferior olives; symmetric cystic lesions; gliosis in the cortex, basal ganglia, brain stem, or cerebellum; and generalized hypomyelination.
Brain MRS shows high lactate concentrations (giving rise to the term "cerebral lactic acidosis") and low N-acetylaspartate and choline concentrations consistent with hypomyelination.
PDHC enzyme assay, immunoblotting analysis, and sequence analysis of two of the genes known to be associated with this disorder, PDHA1 and DLAT, can help establish the diagnosis.
Respiratory chain disorder may result from pathogenic variants in nuclear genes or mitochondrial genes that encode any one of the five respiratory chain complexes. Lactate and pyruvate concentrations are elevated, and the lactate/pyruvate ratio is elevated, often above 20. Biopsied skeletal muscle may reveal ragged-red fibers, cytochrome c-oxidase negative fibers, and succinate dehydrogenase intensely positive fibers. These histologic abnormalities are commonly seen with pathogenic nuclear DNA variants causing intergenomic signaling defects and pathogenic mitochondrial DNA variants affecting protein synthesis genes. Brain MRI may reveal distinctive abnormalities, as described with Leigh syndrome or mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) [DiMauro & Schon 2008]. Nuclear gene variants are inherited in an autosomal recessive or dominant manner; mitochondrial DNA variants are inherited as maternal, non-mendelian traits.
Krebs cycle disorders are rare and the enzymyopathies are partial. Lactate and pyruvate concentrations are elevated and the lactate/pyruvate ratio is normal. Urine organic acid profile may reveal distinctive elevation of fumaric acid or other Krebs cycle intermediates, reflecting the site of the enzyme deficiency.
Gluconeogenic defects may be aggravated clinically by fasting. Blood lactate, pyruvate, and alanine concentrations are classically elevated with clinical symptoms, and blood glucose concentration is low, indicating glycogen depletion and gluconeogenic pathway block. Ketone bodies are elevated, reflecting a physiologic response to fasting, stress, and hypoglycemia.
Carbonic anhydrase VA deficiency is suspected in children with neonatal, infantile, or early-childhood metabolic hyperammonemic encephalopathy combined with hyperlactatemia and metabolites suggestive of multiple carboxylase deficiency. The diagnosis is established in a proband with these metabolic findings and biallelic pathogenic variants in CA5A.
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with pyruvate carboxylase (PC) deficiency, the evaluations summarized in this section are recommended (if not performed as part of the evaluation that led to the diagnosis):
* Blood, urine, and CSF measures of organic and amino acids; brain MRI and MRS analysis
* Evaluation by a pediatric neurologist skilled in metabolic and genetic disorders to confirm the diagnosis, guide the treatment, and determine the prognosis
* Genetic counseling for the parents regarding the risk of recurrence in future pregnancies
* Consultation with a clinical geneticist and/or genetic counselor
### Treatment of Manifestations
Treatment focuses on providing alternative energy sources, hydration, and correction of the metabolic acidosis during acute decompensation. Stimulating residual PC enzyme activity is an important goal for long-term stable metabolic status. Correction of the biochemical abnormality can reverse some symptoms, but central nervous system damage progresses regardless of treatment [DiMauro & De Vivo 1999].
"Anaplerotic therapy" is based on the concept that an energy deficit in these diseases could be improved by providing alternative substrate for both the citric acid cycle and the electron transport chain for enhanced ATP production [Roe & Mochel 2006].
* Citrate supplementation reduces the acidosis and provides substrate for the citric acid cycle [Ahmad et al 1999].
* Aspartic acid supplementation allows the urea cycle to proceed and reduces the plasma and urine ammonia concentrations but has little effect on the neurologic disturbances as the aspartate does not enter the brain freely [Ahmad et al 1999]. Lowering the body ammonia burden may mitigate the neurologic insult.
* Biotin supplementation is given to help optimize the residual PC enzyme activity but is usually of little efficacy.
* Triheptanoin, an odd-carbon triglyceride, providing a source for acetyl-CoA and anaplerotic propionyl-CoA, has been tried in one individual with biotin-unresponsive PC deficiency type B with immediate reversal (<48 h) of major hepatic failure and full correction of all biochemical abnormalities [Mochel et al 2005, Mochel 2017]. Triheptanoin provides C5-ketone bodies that can cross the blood-brain barrier, therefore providing substrates for the brain. Dietary intervention with triheptanoin is the only therapeutic approach that showed improvement of brain metabolism. However, this observation needs to be confirmed in additional affected individuals.
* Orthotopic liver transplantation has reversed the biochemical abnormalities in two affected individuals [Nyhan et al 2002].
### Prevention of Primary Manifestations
Educate parents about the factors that elicit a crisis and the early signs of decompensation.
Carry written information regarding the child's disorder and appropriate treatment in an emergency setting.
Minimize intercurrent infections and environmental stressors.
Provide a high-carbohydrate and high-protein diet with frequent feedings to help prevent dependence on gluconeogenesis.
### Prevention of Secondary Complications
Individuals with PC deficiency are very brittle metabolically. Intensive medical support is indicated proactively to prevent dehydration, hypotension, hypoglycemia, and increasing metabolic acidosis. Hospitalization is indicated for the management of fever, infection, dehydration, or trauma. The ketogenic diet is an absolute contraindication, shown to worsen the acidosis into a life-threatening range.
### Surveillance
Monitor lactate levels regularly.
### Agents/Circumstances to Avoid
Avoid the following:
* Fasting
* The ketogenic diet, which aggravates life-threatening metabolic acidosis
### Evaluation of Relatives at Risk
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Pregnancy Management
Pregnancy in a woman with PC deficiency has not been reported. However, women with the benign form (type C) could become pregnant; such a pregnancy should be closely monitored for any metabolic derangements including dehydration and acidosis.
### Therapies Under Investigation
Thiamine and lipoic acid could optimize pyruvate dehydrogenase complex (PDHC) activity, which could help reduce the plasma and urine pyruvate and lactate concentrations through an alternate route of pyruvate metabolism. Theoretically, this intervention could increase the acetyl-CoA pool and worsen the ketonemia.
* An individual with PC deficiency was responsive to treatment with thiamine.
* Two sisters with PC deficiency, severe intellectual disability and motor retardation, and Leigh syndrome improved clinically and biochemically after treatment with thiamine and lipoic acid. The precise molecular diagnosis in these individuals is uncertain.
Based on reports from the literature [Nyhan et al 2002, Mochel et al 2005], it has been suggested that a combination of orthotopic liver transplantation and anaplerotic diet be used in order to obtain both (i) long-term metabolic stability and (ii) improvement/correction of brain energy metabolism, myelination, and neurotransmission.
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Pyruvate Carboxylase Deficiency
|
c0034341
| 8,188 |
gene_reviews
|
https://www.ncbi.nlm.nih.gov/books/NBK6852/
| 2021-01-18T21:01:12 |
{"mesh": ["D015324"], "synonyms": []}
|
This article includes a list of general references, but it remains largely unverified because it lacks sufficient corresponding inline citations. Please help to improve this article by introducing more precise citations. (February 2014) (Learn how and when to remove this template message)
Myostatin-related muscle hypertrophy
Causesmutations in the MSTN gene
Myostatin-related muscle hypertrophy is a rare genetic condition characterized by reduced body fat and increased skeletal muscle size.[1] Affected individuals have up to twice the usual amount of muscle mass in their bodies, but increases in muscle strength are not usually congruent.[2] Myostatin-related muscle hypertrophy is not known to cause medical problems, and affected individuals are intellectually normal. The prevalence of this condition is unknown.
Mutations in the MSTN gene cause myostatin-related muscle hypertrophy. The MSTN gene provides instructions for making a protein called myostatin, which is active in muscles used for movement (skeletal muscles) both before and after birth. This protein normally restrains muscle growth, ensuring that muscles do not grow too large. Mutations that reduce the production of functional myostatin lead to an overgrowth of muscle tissue. Myostatin-related muscle hypertrophy has a pattern of inheritance known as incomplete autosomal dominance. People with a mutation in both copies of the gene in each cell (homozygotes) have significantly increased muscle mass. People with a mutation in one copy of the MSTN gene in each cell (heterozygotes) also have increased muscle bulk but to a lesser degree.
The effect of this growth factor was first described in cattle as “bovine muscular hypertrophy” by the British farmer H. Culley in 1807. Cattle that have a myostatin gene deletion look unusually and excessively muscular.
## Contents
* 1 Human-induced myostatin-related muscle hypertrophy
* 2 See also
* 3 References
* 4 External links
## Human-induced myostatin-related muscle hypertrophy[edit]
Researchers at Guangzhou Institutes of Biomedicine and Health in China have edited the genome of beagles to create double the amount of muscle.[3] Of the two beagles that were genetically modified, only one had increased muscle mass.[4] The ultimate aim of this project is to be able to better treat a genetic neuromuscular disease (Parkinson's disease).
Besides beagles, genetic modification has also been done in pigs[5] and fish.[6][7]
## See also[edit]
* Gene doping
* Muscle hypertrophy
* Myostatin
* Hysterical strength
* activin A
## References[edit]
1. ^ "Super Strong Kids May Hold Genetic Secrets". ABC News. Retrieved 2020-05-18.
2. ^ Amthor, H.; Macharia, R.; Navarrete, R.; Schuelke, M.; Brown, S. C.; Otto, A.; Voit, T.; Muntoni, F.; Vrbova, G.; Partridge, T.; Zammit, P.; Bunger, L.; Patel, K. (6 February 2007). "Lack of myostatin results in excessive muscle growth but impaired force generation". Proceedings of the National Academy of Sciences. 104 (6): 1835–1840. Bibcode:2007PNAS..104.1835A. doi:10.1073/pnas.0604893104. PMC 1794294. PMID 17267614. S2CID 16773360.
3. ^ Loria, Kevin (21 October 2015). "Scientists created the first genetically engineered dogs — and they are bizarrely muscular". Business Insider.
4. ^ Zou, Qingjian; Wang, Xiaomin; Liu, Yunzhong; Ouyang, Zhen; Long, Haibin; Wei, Shu; Xin, Jige; Zhao, Bentian; Lai, Sisi; Shen, Jun; Ni, Qingchun; Yang, Huaqiang; Zhong, Huilin; Li, Li; Hu, Minhua; Zhang, Quanjun; Zhou, Zhidong; He, Jiaxin; Yan, Quanmei; Fan, Nana; Zhao, Yu; Liu, Zhaoming; Guo, Lin; Huang, Jiao; Zhang, Guanguan; Ying, Jun; Lai, Liangxue; Gao, Xiang (December 2015). "Generation of gene-target dogs using CRISPR/Cas9 system". Journal of Molecular Cell Biology. 7 (6): 580–583. doi:10.1093/jmcb/mjv061. PMID 26459633.
5. ^ Cyranoski, David (July 2015). "Super-muscly pigs created by small genetic tweak". Nature. 523 (7558): 13–14. Bibcode:2015Natur.523...13C. doi:10.1038/523013a. PMID 26135425. S2CID 4447239.
6. ^ Yeh, Ying-Chun; Kinoshita, Masato; Ng, Tze Hann; Chang, Yu-Hsuan; Maekawa, Shun; Chiang, Yi-An; Aoki, Takashi; Wang, Han-Ching (12 September 2017). "Using CRISPR/Cas9-mediated gene editing to further explore growth and trade-off effects in myostatin-mutated F4 medaka (Oryzias latipes)". Scientific Reports. 7 (1): 11435. Bibcode:2017NatSR...711435Y. doi:10.1038/s41598-017-09966-9. PMC 5595883. PMID 28900124.
7. ^ Zhong, Zhaomin; Niu, Pengfei; Wang, Mingyong; Huang, Guodong; Xu, Shuhao; Sun, Yi; Xu, Xiaona; Hou, Yi; Sun, Xiaowen; Yan, Yilin; Wang, Han (15 March 2016). "Targeted disruption of sp7 and myostatin with CRISPR-Cas9 results in severe bone defects and more muscular cells in common carp". Scientific Reports. 6 (1): 22953. Bibcode:2016NatSR...622953Z. doi:10.1038/srep22953. PMC 4791634. PMID 26976234. S2CID 9192986.
## External links[edit]
* Wagner, Kathryn R.; Cohen, Julie S. "Myostatin-Related Muscle Hypertrophy". GeneReviews®. University of Washington, Seattle.
* Myostatin-related muscle hypertrophy at NIH Genetics Home Reference
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Myostatin-related muscle hypertrophy
|
c2931112
| 8,189 |
wikipedia
|
https://en.wikipedia.org/wiki/Myostatin-related_muscle_hypertrophy
| 2021-01-18T18:56:28 |
{"gard": ["10238"], "mesh": ["C536106"], "umls": ["C2931112"], "orphanet": ["275534"], "wikidata": ["Q3144217"]}
|
A number sign (#) is used with this entry because of evidence that early infantile epileptic encephalopathy-50 (EIEE50) is caused by homozygous or compound heterozygous mutation in the CAD gene (114010) on chromosome 2p23.
Description
Early infantile epileptic encephalopathy-50 is an autosomal recessive progressive neurodegenerative neurometabolic disorder characterized by delayed psychomotor development, early-onset seizures, severe developmental regression, and normocytic anemia. Onset is within the first years of life. Evidence suggests that affected children can have a favorable response to treatment with uridine (summary by Koch et al., 2017).
For a discussion of genetic heterogeneity of early infantile epileptic encephalopathy, see 308350.
Clinical Features
Ng et al. (2015) reported a 4-year-old boy (UDP4003), born of unrelated parents, with delayed psychomotor development, mild hypotonia, and a slightly wide-based gait. He was diagnosed in infancy with pan-disaccharidase deficiency and renal tubular acidosis, both of which were treated and resolved. Seizures occurred at age 17 months. Laboratory studies showed slightly increased ammonia levels and normal urinary purines and pyrimidines. Peripheral blood smear showed anisopoikilocytosis, acanthocytes, and schistocytes, and bone marrow biopsy was dyserythropoietic. Known causes of congenital anemia were excluded. Gel electrophoresis of red blood cell proteins suggested abnormal glycosylation, but glycosylation of serum transferrin was normal on several occasions. Patient serum and fibroblasts did not demonstrate dramatic changes in either N- or O-linked glycosylation.
Koch et al. (2017) reported 5 patients from 3 unrelated families with early-onset epileptic encephalopathy, 3 of whom died between 2.5 and 5 years of age. Two of the families were of Serbian Roma origin, including 1 that was consanguineous. Clinical details were available for 4 of the patients. All presented with delayed development in the first year of life, and all developed refractory seizures between 6 months and 2 years of age, followed by loss of acquired developmental skills. The patients were severely disabled, being bedridden or unable to walk, with decreased consciousness/alertness and poor communication. EEG performed in 2 patients showed multifocal sharp waves; 2 patients had status epilepticus. The patients also had normocytic anemia with anisocytosis and poikilocytosis. Brain imaging of 3 patients showed progressive global brain atrophy. All patients had normal serum transferrin isoelectric focusing and normal urinary organic acids, purines, and pyrimidines. Koch et al. (2017) referred to this disorder as an epileptic encephalopathy.
Clinical Management
Koch et al. (2017) reported significant neurologic improvement in 2 unrelated children with EIEE50 who were treated with oral uridine. One was a 3-year-old girl who had developmental arrest, could barely walk or communicate, and had seizures with abnormal EEG. Treatment with uridine resulted in developmental improvement, cessation of seizures, improved EEG abnormalities, and resolution of her anemia within 6 to 12 months. The second child was a 5.2-year-old girl who was bedridden and hypokinetic in a minimally conscious state and had frequent seizures. After treatment, she showed greater alertness and postural control with the ability to walk several steps with a walker, improved communication, significantly decreased seizure activity, and resolution of anemia.
Inheritance
The transmission pattern of EIEE50 in the families reported by Ng et al. (2015) and Koch et al. (2017) was consistent with autosomal recessive inheritance.
Molecular Genetics
In a boy with EIEE50, Ng et al. (2015) identified compound heterozygous mutations in the CAD gene (114010.0001 and 114010.0002). The mutations, which were found by exome sequencing, segregated with the disorder in the family. Metabolic flux studies of patient cells showed impaired aspartate incorporation into RNA and DNA through the de novo synthesis pathway. In addition, CTP, UTP, and nearly all UDP-activated sugars that serve as donors for glycosylation were decreased. Uridine supplementation rescued these abnormalities, suggesting a potential therapy for this disorder.
In 4 patients from 3 unrelated families with EIEE50, Koch et al. (2017) identified homozygous or compound heterozygous mutations in the CAD gene (114010.0003-114010.0005). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Functional studies of the variants were not performed, but the mutations were predicted to result in a loss of function. Fibroblasts from 1 of the patients showed reduced levels of UDP, UDP-glucose, UDP-GlcNac, CTP, and UTP, all of which could be rescued by uridine supplementation.
INHERITANCE \- Autosomal recessive ABDOMEN Gastrointestinal \- Pan-disaccharidase deficiency (patient A) GENITOURINARY Kidneys \- Renal tubular acidosis (patient A) NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Epileptic encephalopathy \- Developmental regression (after seizure onset) \- Poor speech \- Seizures, refractory \- Hypotonia \- Wide-based gait (patient A) \- Impaired consciousness \- Multifocal sharp waves seen on EEG \- Status epilepticus \- Brain imaging shows progressive brain atrophy HEMATOLOGY \- Anemia \- Anisopoikilocytosis \- Acanthocytosis \- Schistocytosis \- Dyserythropoietic bone marrow biopsy LABORATORY ABNORMALITIES \- Hyperammonemia, mild (patient A) \- Red blood cell proteins show abnormal glycosylation (patient A) \- Serum transferrin glycosylation is normal MISCELLANEOUS \- Onset in infancy (up to 2 years) \- Progressive disorder \- Death in early childhood may occur \- Favorable response to treatment with oral uridine MOLECULAR BASIS \- Caused by mutation in the carbamoyl phosphate synthetase/aspartate transcarbamoylase/dihydroorotase gene (CAD, 114010.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 50
|
c4225320
| 8,190 |
omim
|
https://www.omim.org/entry/616457
| 2019-09-22T15:48:54 |
{"doid": ["0080419"], "omim": ["616457"], "orphanet": ["448010"], "synonyms": ["Carbohydrate deficient glycoprotein syndrome type Iz", "Alternative titles", "CDG-Iz", "CDG1Z", "CDG syndrome type Iz", "CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Iz, FORMERLY", "Congenital disorder of glycosylation type 1z"]}
|
1q21.1 microduplication is a chromosomal change in which a small amount of genetic material on chromosome 1 is abnormally copied (duplicated). The duplication occurs on the long (q) arm of the chromosome at a location designated q21.1.
Some people with a 1q21.1 microduplication have developmental delay and intellectual disability that is typically mild to moderate. Individuals with this condition can also have features of autism spectrum disorder. These disorders are characterized by impaired communication and socialization skills, as well as delayed development of speech and language. Expressive language skills (vocabulary and the production of speech) tend to be more impaired than receptive language skills (the ability to understand speech) in affected individuals. In childhood, 1q21.1 microduplications may also be associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD) and other behavioral problems. Psychiatric disorders such as schizophrenia or mood disorders such as anxiety or depression occur in some affected individuals, usually during adulthood. Rarely, recurrent seizures (epilepsy) occur in people with a 1q21.1 microduplication.
Some individuals with a 1q21.1 microduplication are born with malformations of the heart, including a particular combination of heart defects known as tetralogy of Fallot. Less commonly, other physical malformations such as the urethra opening on the underside of the penis (hypospadias) in males, inward- and upward-turning feet (clubfeet), or misalignment of the hip joint (hip dysplasia) are present at birth. Individuals with a 1q21.1 microduplication may also have a larger than average head size or taller than average adult stature. Some have slightly unusual facial features such as wide-set eyes or low-set ears. As adults, individuals with a 1q21.1 microduplication may be prone to develop cysts, swollen and knotted (varicose) veins, or carpal tunnel syndrome, which is characterized by numbness, tingling, and weakness in the hands and fingers. However, there is no particular pattern of physical abnormalities that characterizes 1q21.1 microduplications. Signs and symptoms related to the chromosomal change vary even among affected members of the same family. Some people with the duplication have no identified physical, intellectual, or behavioral abnormalities.
This disease summary is from MedlinePlus Genetics, an online health information resource from the National Institutes of Health.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Chromosome 1q21.1 duplication syndrome
|
c2675891
| 8,191 |
gard
|
https://rarediseases.info.nih.gov/diseases/10591/chromosome-1q211-duplication-syndrome
| 2021-01-18T18:01:23 |
{"mesh": ["C567290"], "omim": ["612475"], "umls": ["C2675891"], "orphanet": ["250994"], "synonyms": ["1q21.1 microduplication syndrome"]}
|
Gray platelet syndrome is a bleeding disorder associated with abnormal platelets, which are small blood cells involved in blood clotting. People with this condition tend to bruise easily and have an increased risk of nosebleeds (epistaxis). They may also experience abnormally heavy or extended bleeding following surgery, dental work, or minor trauma. Women with gray platelet syndrome often have irregular, heavy periods (menometrorrhagia). These bleeding problems are usually mild to moderate, but they have been life-threatening in a few affected individuals.
A condition called myelofibrosis, which is a buildup of scar tissue (fibrosis) in the bone marrow, is another common feature of gray platelet syndrome. Bone marrow is the spongy tissue in the center of long bones that produces most of the blood cells the body needs, including platelets. The scarring associated with myelofibrosis damages bone marrow, preventing it from making enough blood cells. Other organs, particularly the spleen, start producing more blood cells to compensate; this process often leads to an enlarged spleen (splenomegaly).
## Frequency
Gray platelet syndrome appears to be a rare disorder. About 60 cases have been reported worldwide.
## Causes
Gray platelet syndrome can be caused by mutations in the NBEAL2 gene. Little is known about the protein produced from this gene. It appears to play a role in the formation of alpha-granules, which are sacs inside platelets that contain growth factors and other proteins that are important for blood clotting and wound healing. In response to an injury that causes bleeding, the proteins stored in alpha-granules help platelets stick to one another to form a plug that seals off damaged blood vessels and prevents further blood loss.
Mutations in the NBEAL2 gene disrupt the normal production of alpha-granules. Without alpha-granules, platelets are unusually large and fewer in number than usual (macrothrombocytopenia). The abnormal platelets also appear gray when viewed under a microscope, which gives this condition its name. A lack of alpha-granules impairs the normal activity of platelets during blood clotting, increasing the risk of abnormal bleeding. Myelofibrosis is thought to occur because the growth factors and other proteins that are normally packaged into alpha-granules leak out into the bone marrow. The proteins lead to fibrosis that affects the bone marrow's ability to make new blood cells.
Some people with gray platelet syndrome do not have an identified mutation in the NBEAL2 gene. In these individuals, the cause of the condition is unknown.
### Learn more about the gene associated with Gray platelet syndrome
* NBEAL2
## Inheritance Pattern
When gray platelet syndrome is caused by NBEAL2 gene mutations, it has an autosomal recessive pattern of inheritance, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene in each cell.
Gray platelet syndrome can also be inherited in an autosomal dominant pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder. An affected person often inherits the condition from one affected parent. Researchers are working to determine which gene or genes are associated with the autosomal dominant form of gray platelet 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 inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Gray platelet syndrome
|
c0272302
| 8,192 |
medlineplus
|
https://medlineplus.gov/genetics/condition/gray-platelet-syndrome/
| 2021-01-27T08:25:42 |
{"gard": ["2562"], "mesh": ["D055652"], "omim": ["139090"], "synonyms": []}
|
A number sign (#) is used with this entry because of evidence that spermatogenic failure-5 (SPGF5) is caused by homozygous or compound heterozygous mutation in the AURKC gene (603495) on chromosome 19q13.
Description
Spermatogenic failure-5 is a form of male infertility associated with large-headed, multiflagellar, polyploid spermatozoa (Dieterich et al., 2007).
For a general phenotypic description and a discussion of genetic heterogeneity of spermatogenic failure, see SPGF1 (258150).
Clinical Features
In the son of Libyan first-cousin parents, German et al. (1981) found infertility apparently related to an abnormality of spermatozoa manifested morphologically by bulky, irregularly shaped heads and as many as 4 tails. Sperm heads showed excessive DNA, approximately 4 times the normal haploid amount, as measured in Feulgen-stained preparations. By electron microscopy, 4 centrioles were demonstrated; hence, the 4 tails (German, 1989). Blood lymphocytes in metaphase had 46 chromosomes but about a third of metaphases from a dermal fibroblast line at its eighth passage had 92 chromosomes.
Semen from men with large-headed multiflagellar polyploid spermatozoa consistently show close to 100% morphologically abnormal spermatozoa with low motility, oversized irregular heads, abnormal midpiece and acrosome, and up to 6 flagella (Benzacken et al., 2001; Devillard et al., 2002).
Molecular Genetics
Dieterich et al. (2007) carried out a genomewide microsatellite scan of 10 infertile men with a large-headed sperm phenotype. Four were unrelated French citizens of African descent, all born from first-degree cousins, leading to a suspicion of autosomal recessive mode of inheritance. The small genealogic distance between the 4 index individuals and a postulated morbid ancestor chromosome present in their respective great-grandmother or great-grandfather (3 meioses) was compatible with large homozygous regions. The other 6 men all came from the Rabat region in Morocco, suggesting the possibility of a founder effect. In that case, owing to probable greater genealogic distances, Dieterich et al. (2007) expected smaller regions of homozygosity. In all 10 men, Dieterich et al. (2007) identified a region of homozygosity harboring the AURKC gene with a single-nucleotide deletion in its coding sequence (c.144delC; 603495.0001). They showed that this founder mutation resulted in premature termination of translation, yielding a truncated protein that lacks the kinase domain. They concluded that the absence of AURKC causes male infertility owing to the production of large-headed multiplex flagella polyploid spermatozoa.
Dieterich et al. (2009) established a carrier frequency of 1 in 50 for the c.144delC AURKC mutation in the Maghrebian general population. Of 62 patients with large-headed spermatozoa who were genotyped, 32 had a typical phenotype with close to 100% large-headed spermatozoa, and 31 of these patients were homozygous for c.144delC. The remaining patient with a typical phenotype was compound heterozygous for c.144delC and a missense mutation (C229Y; 603495.0002). No AURKC mutations were detected in the 30 patients who did not present with a typical phenotype. Two homozygous females were identified, and both were fertile, indicating that AURKC is dispensable in oogenesis. All spermatozoa contained homogeneous 4C DNA content and were thus blocked before the first meiotic division. The authors concluded that functional AURKC protein is necessary for male meiotic cytokinesis, whereas its absence does not impair oogenesis.
Ben Khelifa et al. (2011) studied 2 infertile brothers of Tunisian descent who both had nearly 100% large-headed spermatozoa that were 28 to 52% multiflagellate, with sperm counts of 0.8 to 0.9 x 10(6) per ml. Sequencing of the AURKC gene in the family revealed that both brothers and 1 of their sisters were compound heterozygous for the c.144delC mutation and a splice site mutation (603495.0003). Multiple intracytoplasmic sperm injection (ICSI) attempts for both brothers were unsuccessful; although fertilization could be achieved by 47 of the gametes, no pregnancy was obtained after 8 embryo transfers. Their compound heterozygous sister had not yet tried to achieve pregnancy. Noting that FISH analysis of morphologically normal-appearing sperm from AURKC-mutated men showed aneuploidy in all sperm (Chelli et al., 2010), Ben Khelifa et al. (2011) cautioned that the identification of AURKC mutations indicates that all spermatozoa will be chromosomally abnormal, and that ICSI should not be attempted even after very thorough morphologic selection.
INHERITANCE \- Autosomal recessive LABORATORY ABNORMALITIES \- Large spermatozoa \- Irregularly shaped sperm heads \- Multi-tailed spermatozoa \- Polyploid sperm heads MOLECULAR BASIS \- Caused by mutation in the Aurora kinase C gene (AURKC, 603495.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
SPERMATOGENIC FAILURE 5
|
c0403812
| 8,193 |
omim
|
https://www.omim.org/entry/243060
| 2019-09-22T16:26:20 |
{"doid": ["0070183"], "mesh": ["C562903"], "omim": ["243060"], "orphanet": ["137893", "399808"], "synonyms": ["Alternative titles", "MALE INFERTILITY WITH LARGE-HEADED, MULTIFLAGELLAR, POLYPLOID SPERMATOZOA", "INFERTILITY ASSOCIATED WITH MULTITAILED SPERMATOZOA AND EXCESSIVE DNA"]}
|
Acrogeria, Gottron type is a premature aging syndrome which includes fragile, thin skin on the hands, feet and face and slow growth. Other symptoms include visible blood vessels, easy bruising, and hair and nail abnormalities. In general, the symptoms do not appear to get worse over time. Intelligence is normal. The cause is unknown, although several genes have been associated with it. Both autosomal recessive and autosomal dominant inheritance have been reported. Diagnosis is based on a clinical exam and the symptoms. Treatment is focused on managing the symptoms.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Acrogeria, Gottron type
|
c0238590
| 8,194 |
gard
|
https://rarediseases.info.nih.gov/diseases/6543/acrogeria-gottron-type
| 2021-01-18T18:02:21 |
{"omim": ["201200"], "orphanet": ["2500"], "synonyms": ["Metageria", "Acrometageria", "Familial acrogeria", "Acrogeria", "Gottron syndrome"]}
|
For a phenotypic description and a discussion of genetic heterogeneity of psoriasis, see PSORS1 (177900).
Mapping
Veal et al. (2001) performed a genomewide linkage analysis using 271 polymorphic markers in 284 sib pairs from 158 independent families. They identified linkage at 6p21 (PSORS1) with a nonparametric linkage score (NPL) of 4.7 and at a novel locus on 1p (NPL = 3.6) in all families studied. The markers at the loci D1S197, D1S200, and D1S207 contributed to the NPL score of 3.6. Veal et al. (2001) pointed out that the EPS15 gene (600051), encoding an intracellular substrate for the EGF receptor, itself known to be overexpressed in psoriatic epidermis, lies within the critical region defined on 1p. Three further regions reached NPL scores of greater than 2.
Cargill et al. (2007) used 22,215 gene-centric SNPs in a case-control association study of psoriasis in 3 independent sample sets of white North American individuals and found a highly significant association with a SNP in the 3-prime UTR of the IL12B (161561) gene (see PSORS11; 612599). Since IL12B encodes the common IL12 p40 subunit of IL12 and IL23, Cargill et al. (2007) individually genotyped 17 SNPs in the genes encoding the other chains of these cytokines, IL12A (161560) and IL23A (605580), and their receptors: IL12RB1 (601604), IL12RB2 (601642), and IL23R (607562), which maps to chromosome 1p31.1. Haplotype analyses identified 2 IL23R missense SNPs that together marked a common psoriasis-associated haplotype in all 3 studies. Individuals homozygous for both the IL12B and the IL23R predisposing haplotypes had increased risk of disease. These data, and the previous observation that administration of an antibody specific for the IL12 p40 subunit to patients with psoriasis is highly efficacious (Kauffman et al., 2004), suggested that these genes play a fundamental role in psoriasis pathogenesis.
Capon et al. (2007) reported a significant association between the R381Q variant (607562.0001) in IL23R and protection against psoriasis among 318 British patients with the disorder. The findings were replicated in a second group of 519 British patients. Together, the association yielded an odds ratio of 0.49 (p = 0.00014), with the gln381 allele offering protection from the disease. Capon et al. (2007) noted that the arg381 residue is highly conserved among higher vertebrates and is located within the binding domain for JAK2 kinase, which is the first mediator of the IL23R signaling cascade (Parham et al., 2002).
In a genomewide association study of 1,359 patients with psoriasis and 1,400 controls, Nair et al. (2009) found a significant association between psoriasis and rs2201841 in the IL23R gene (p = 3 x 10(-7)) gene. The findings were replicated in an additional 5,048 cases and 5,051 controls, yielding a combined p value of 3 x 10(-8). The G allele conferred an odds ratio of 1.13.
Huffmeier et al. (2009) analyzed 4 variants in the IL12B and IL23R gene in 748 patients with psoriatic arthritis (see 607507), 1,114 patients with psoriasis, and 937 controls. The strongest associations in both disease groups were found with IL12B variants rs3212227 and rs6887695 (p values ranging between 2.10 x 10(-5) and 9.67 x 10(-7) with corresponding odds ratios of 1.43 to 1.50). The IL12B risk haplotype also showed an association in both groups (p value on the order of 10(-6)). The effect for rs11209026 in the IL23R gene was slightly weaker for psoriasis (p = 2.42 x 10(-6)) and psoriatic arthritis (p = 0.002). The findings confirmed previous studies that variants in the IL12B and IL23R genes are susceptibility factors for psoriasis, and extended the findings to psoriatic arthritis.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
PSORIASIS 7, SUSCEPTIBILITY TO
|
c1854124
| 8,195 |
omim
|
https://www.omim.org/entry/605606
| 2019-09-22T16:11:09 |
{"omim": ["605606"]}
|
Not to be confused with Quinism.
Cinchonism
Other namesQuinine toxicity
SpecialtyEmergency medicine
Cinchonism is a pathological condition caused by an overdose of quinine or its natural source, cinchona bark. Quinine and its derivatives are used medically to treat malaria and lupus erythematosus. In much smaller amounts, quinine is an ingredient of tonic drinks, acting as a bittering agent. Cinchonism can occur from therapeutic doses of quinine, either from one or several large doses. Quinidine (a Class 1A anti-arrhythmic) can also cause cinchonism symptoms to develop with as little as a single dose.
## Signs and symptoms[edit]
Signs and symptoms of mild cinchonism (which may occur from standard therapeutic doses of quinine) include flushed and sweaty skin, ringing of the ears (tinnitus), blurred vision, impaired hearing, confusion, reversible high-frequency hearing loss, headache, abdominal pain, rashes, drug-induced lichenoid reaction (lichenoid photosensitivity),[1] vertigo, dizziness, nausea, vomiting and diarrhea.
Large doses of quinine may lead to severe (but reversible) symptoms of cinchonism: skin rashes, deafness, somnolence, diminished visual acuity or blindness, anaphylactic shock, and disturbances in heart rhythm or conduction, and death from cardiotoxicity (damage to the heart). Quinine may also trigger a rare form of hypersensitivity reaction in malaria patients, termed blackwater fever, that results in massive hemolysis, hemoglobinemia, hemoglobinuria, and kidney failure.[citation needed] Most symptoms of cinchonism (except in severe cases) are reversible and disappear once quinine is withdrawn. Attempted suicide by intake of a large dose of quinine has caused irreversible tunnel vision and very severe visual impairment.[2]
Patients treated with quinine may also suffer from low blood sugar, especially if it is administered intravenously, and hypotension (low blood pressure).[citation needed]
Quinine, like chloroquine, inactivates enzymes in the lysosomes of cells and has an anti-inflammatory effect, hence its use in the treatment of rheumatoid arthritis. However, inactivation of these enzymes can also cause abnormal accumulation of glycogen and phospholipids in lysosomes, causing toxic myopathy. It is possible this action is the root cause of cinchonism.[citation needed]
## Notes[edit]
1. ^ Dawson, T A J (1995). "Side effect of quinine for nocturnal cramps". BMJ. 310 (6981): 738. doi:10.1136/bmj.310.6981.738a. PMC 2549119. PMID 7711556.
2. ^ Bacon, P; Spalton, D. J; Smith, S. E (1988). "Blindness from quinine toxicity". The British Journal of Ophthalmology. 72 (3): 219–24. doi:10.1136/bjo.72.3.219. PMC 1041412. PMID 3281709.
## External links[edit]
* Lin, Xi; Chen, Shanping; Tee, Daniel (May 1998). "Effects of Quinine on the Excitability and Voltage-Dependent Currents of Isolated Spiral Ganglion Neurons in Culture". Journal of Neurophysiology. 79 (5): 2503–12. doi:10.1152/jn.1998.79.5.2503. PMID 9582223.
Classification
D
* ICD-10: T37.2
* ICD-9-CM: 386.9, 961.4
* DiseasesDB: 11124
* v
* t
* e
Diseases of the outer and middle ear
Outer ear
* Otitis externa
* Otomycosis
Middle ear
and mastoid
* Otitis media
* Mastoiditis
* Bezold's abscess
* Gradenigo's syndrome
* Tympanosclerosis
* Cholesteatoma
* Perforated eardrum
Symptoms
* Ear pain
* Hearing loss
Tests
* Otoscope
* pneumatic
* tympanometry
* v
* t
* e
* Poisoning
* Toxicity
* Overdose
History of poison
Inorganic
Metals
Toxic metals
* Beryllium
* Cadmium
* Lead
* Mercury
* Nickel
* Silver
* Thallium
* Tin
Dietary minerals
* Chromium
* Cobalt
* Copper
* Iron
* Manganese
* Zinc
Metalloids
* Arsenic
Nonmetals
* Sulfuric acid
* Selenium
* Chlorine
* Fluoride
Organic
Phosphorus
* Pesticides
* Aluminium phosphide
* Organophosphates
Nitrogen
* Cyanide
* Nicotine
* Nitrogen dioxide poisoning
CHO
* alcohol
* Ethanol
* Ethylene glycol
* Methanol
* Carbon monoxide
* Oxygen
* Toluene
Pharmaceutical
Drug overdoses
Nervous
* Anticholinesterase
* Aspirin
* Barbiturates
* Benzodiazepines
* Cocaine
* Lithium
* Opioids
* Paracetamol
* Tricyclic antidepressants
Cardiovascular
* Digoxin
* Dipyridamole
Vitamin poisoning
* Vitamin A
* Vitamin D
* Vitamin E
* Megavitamin-B6 syndrome
Biological1
Fish / seafood
* Ciguatera
* Haff disease
* Ichthyoallyeinotoxism
* Scombroid
* Shellfish poisoning
* Amnesic
* Diarrhetic
* Neurotoxic
* Paralytic
Other vertebrates
* amphibian venom
* Batrachotoxin
* Bombesin
* Bufotenin
* Physalaemin
* birds / quail
* Coturnism
* snake venom
* Alpha-Bungarotoxin
* Ancrod
* Batroxobin
Arthropods
* Arthropod bites and stings
* bee sting / bee venom
* Apamin
* Melittin
* scorpion venom
* Charybdotoxin
* spider venom
* Latrotoxin / Latrodectism
* Loxoscelism
* tick paralysis
Plants / fungi
* Cinchonism
* Ergotism
* Lathyrism
* Locoism
* Mushrooms
* Strychnine
1 including venoms, toxins, foodborne illnesses.
* Category
* Commons
* WikiProject
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Cinchonism
|
c0151555
| 8,196 |
wikipedia
|
https://en.wikipedia.org/wiki/Cinchonism
| 2021-01-18T18:46:15 |
{"umls": ["C0151555"], "icd-9": ["386.9", "961.4"], "icd-10": ["T37.2"], "wikidata": ["Q936656"]}
|
## Summary
### Clinical characteristics.
Ethylmalonic encephalopathy (EE) is a severe, early-onset, progressive disorder characterized by developmental delay / mild-to-severe intellectual disability; generalized infantile hypotonia that evolves into hypertonia, spasticity, and (in some instances) dystonia; generalized tonic-clonic seizures; and generalized microvascular damage (diffuse and spontaneous relapsing petechial purpura, hemorrhagic suffusions of mucosal surfaces, and chronic hemorrhagic diarrhea). Infants sometimes have frequent vomiting and loss of social interaction. Speech is delayed and in some instances absent. Swallowing difficulties and failure to thrive are common. Children may be unable to walk without support and may be wheelchair bound. Neurologic deterioration accelerates following intercurrent infectious illness, and the majority of children die in the first decade.
### Diagnosis/testing.
The diagnosis of EE is suggested by clinical findings and the laboratory findings of increased blood lactate levels, C4- and C5-acylcarnitine esters, plasma thiosulphate, and urinary ethylmalonic acid.
The diagnosis is established by identification of biallelic pathogenic variants in ETHE1 on molecular genetic testing.
### Management.
Treatment of manifestations: Multi-specialty care that includes child neurology, pediatrics, clinical genetics, nutrition, gastroenterology, pain management, and physical therapy can help with timely detection and treatment of the multiorgan dysfunction that characterizes EE. Treatment is primarily supportive including antispastic medications, muscle relaxants, and antiepileptic drugs (AEDs). Physical therapy early in the disease course can help prevent contractures. For severe diarrhea, it is important to maintain hydration and caloric intake. Tube feeding is often necessary.
Prevention of secondary complications: Prevention of infections that could be fatal.
Surveillance: Recommendations based on individual patient findings can include: monitoring of feeding and electrolyte status particularly in those with severe diarrhea; monitoring of seizures and response to AEDs.
### Genetic counseling.
EE is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. No individuals diagnosed with EE have been known to reproduce. Once the ETHE1 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible.
## Diagnosis
### Suggestive Findings
Ethylmalonic encephalopathy (EE) should be suspected in an individual with the following clinical findings, preliminary laboratory findings, and brain MRI findings [Dionisi-Vici et al 2016].
Clinical findings
* Global neurologic impairment
* Early-onset progressive psychomotor regression
* Seizures
* Dystonia
* Diffuse microvasculature injury
* Petechiae and/or purpura
* Orthostatic acrocyanosis
* Hemorrhagic suffusions of mucosal surfaces
* Chronic hemorrhagic diarrhea
Preliminary laboratory findings
* Increased blood lactate levels (normal range: 6-22 mg/dL)
* Increased blood C4-acylcarnitine esters (normal range: <0.9 μmol/L) [Merinero et al 2006, Zafeiriou et al 2007] *
* Increased blood C5-acylcarnitine esters (normal range: <0.3 μmol/L) [Merinero et al 2006, Zafeiriou et al 2007] *
* Increased plasma thiosulphate (normal range: <4 μmol/L)
* Increased urinary ethylmalonic acid (normal range: <10 μmol/mmol creatinine) evaluated on spot urine [Merinero et al 2006, Zafeiriou et al 2007]
* More data are needed to define the range of C4/C5 acylcarnitine elevation in individuals with molecularly proven EE.
Newborn screening (NBS). Tandem mass spectroscopy can identify C4 elevation in a NBS dried blood spot; however, NBS for EE is not available in the US as there is no definitive treatment (see Therapies Under Investigation). Note: (1) NBS may be performed elsewhere in the world. (2) C4 elevation can also be found in primary short-chain acyl-CoA dehydrogenase (SCAD) deficiency [McHugh et al 2011]; an algorithm (pdf) from the American College of Medical Genetics can be used to distinguish the two disorders.
Brain MRI
* Symmetric patchy T2-weighted signals in the basal ganglia, periventricular white matter and dentate nuclei, brain stem, and cerebellar white matter. In some instances, cortical atrophy and diffuse leukoencephalopathy are present.
* Atypical neuroradiologic patterns were also reported [Grosso et al 2002, Heberle et al 2006].
### Establishing the Diagnosis
The diagnosis of ethylmalonic encephalopathy is established in a proband with suggestive clinical and laboratory findings and identification of biallelic pathogenic variants in ETHE1 on molecular genetic testing (see Table 1).
Single-gene testing is the molecular genetic testing approach indicated. Sequence analysis of ETHE1 is performed first and followed by gene-targeted deletion/duplication analysis if only one or no pathogenic variant is found.
### Table 1.
Molecular Genetic Testing Used in Ethylmalonic Encephalopathy
View in own window
Gene 1MethodProportion of Pathogenic Variants 2 in Probands Detectable by Method
ETHE1Sequence analysis 367/86 4
Gene-targeted deletion/duplication analysis 519/86 4, 6
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
See Molecular Genetics for information on allelic variants detected in this gene.
3\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. 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\.
Tiranti et al [2006], Mineri et al [2008]
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\.
Deletion of exon 4 and deletion of exons 1 to 7 have been detected frequently [Tiranti et al 2006, Mineri et al 2008].
## Clinical Characteristics
### Clinical Description
Ethylmalonic encephalopathy (EE) is a severe, early-onset, progressive disorder, typically characterized by the following major manifestations: developmental delay, progressive neurologic involvement, seizures, and vascular damage. Findings usually appear in the first years of life, in some instances during metabolic stress such as infection or fever. Affected infants typically have severe neck, trunk, and limb hypotonia and loss of head control, sometimes associated with frequent vomiting and loss of social interaction. In addition, chronic diarrhea and failure to thrive are common.
Atypical findings have also been reported [Grosso et al 2002, Di Rocco et al 2006, Heberle et al 2006, Pigeon et al 2009].
Developmental delay, evident in early infancy, manifests later as intellectual disability that ranges from mild to severe. Speech difficulties are common; in some instances speech is absent.
Progressive neurologic involvement. Hypotonia evolves into spastic quadriparesis and eventually global neurologic impairment including pyramidal signs such as hypertonia and spasticity with increased deep tendon reflexes (in particular in the lower limbs) with paraparesis. Children may be unable to walk without support and in some instances are wheelchair bound. Difficulty in swallowing is common.
Dystonia, an extrapyramidal finding, generally involves the limbs and trunk.
Neurologic deterioration accelerates following intercurrent infectious illness, and the majority of patients die in the early years, although some are still alive in the second decade of life.
Generalized seizures. Generalized tonic-clonic seizures are characterized by spasms of the neck, trunk, and arms that could evolve into status epilepticus with decreased level of consciousness.
Microvasculature injury is common and is characterized by diffuse and spontaneous relapsing petechial purpura, especially in the trunk and associated with "cutis marmorata" of the extremities.
Distal orthostatic acrocyanosis with edema of the extremities is often visible.
Hemorrhagic suffusions of mucosal surfaces and chronic hemorrhagic diarrhea are common manifestations.
#### Individuals with Atypical Findings
Of two affected individuals reported by Grosso et al [2002], one had chronic very slow neuromotor deterioration, ataxia, and dysarthria, and the other had acute neonatal onset with severe neuromotor retardation, severe generalized hypotonia, and intractable seizures.
In one individual with a molecularly confirmed diagnosis, the clinical findings suggested a connective tissue disorder (vascular fragility, joint hyperextensibility, and delayed motor development with normal cognitive development); urinary excretion of ethylmalonic acid was not abnormally increased during intercritical phases [Di Rocco et al 2006].
One individual who had the typical findings of EE also had hydronephrosis, undescended testes, mild tricuspid regurgitation, and mild dilatation of the pulmonary artery [Heberle et al 2006].
Monochorial twins had severe axial hypotonia without petechiae, orthostatic acrocyanosis, or chronic diarrhea. Other clinical findings differed markedly: one twin had an episode of coma at age three years followed by spastic quadriparesis and loss of language; the other had pyramidal involvement (mainly limited to the lower extremities) and spoke two languages [Pigeon et al 2009].
MR spectroscopy showed a lactate peak in one patient [Grosso et al 2004].
Neuropathologic findings in the brain of an infant age nine months showed widespread luminal microthrombi, acute microhemorrhages, and focal perivascular hemosiderin-laden macrophages, the latter being consistent with previous bleeding. These findings were consistent with both acute and chronic ischemic damage and corresponded with abnormal signal intensity lesions observed on repeat MRI [Giordano et al 2012].
### Genotype-Phenotype Correlations
No genotype-phenotype correlations are known to be associated with ETHE1 biallelic pathogenic variants.
### Prevalence
The prevalence of ethylmalonic encephalopathy is unknown. More than 80 individuals with features consistent with EE and a molecularly confirmed diagnosis have been reported [Tiranti et al 2004, Tiranti et al 2006, Mineri et al 2008].
To date, families with EE have been from (or could be traced to) different regions of the Mediterranean basin or the Arabian Peninsula; parental consanguinity is common.
## Differential Diagnosis
Ethylmalonic acid is a dicarboxylic organic acid produced by the carboxylation of butyrate. Ethylmalonic encephalopathy (EE) should be included in the differential diagnosis of other forms of persistent ethylmalonic aciduria, including the following:
* Defects of beta-oxidation of fatty acids with similar clinical findings (e.g., vomiting, diarrhea, difficulty with feeding, and developmental delay) such as short-chain acyl-CoA dehydrogenase (SCAD) deficiency and 3-hydroxyacyl-CoA dehydrogenase (HADH) deficiency (OMIM 231530). Petechiae, purpura, and orthostatic acrocyanosis are specific to EE [Burlina et al 1994].
* Defects of the mitochondrial electron-transfer flavoprotein pathway or glutaric aciduria type II
* Some forms of respiratory chain deficiency
Of note, brain vascular lesions appear to be a specific neuropathologic feature of EE, not seen in other forms of ethylmalonic aciduria or in disorders caused by primary respiratory chain defects such as Leigh syndrome [Giordano et al 2012, Tiranti & Zeviani 2013].
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with ethylmalonic encephalopathy (EE), the recommended evaluations following diagnosis (if not performed as part of the evaluation that led to the diagnosis) are as summarized in Table 2.
### Table 2.
Recommended Evaluations Following Initial Diagnosis of Ethylmalonic Encephalopathy (EE)
View in own window
System/ConcernEvaluationComment
NeurologicNeurologic evaluationParticularly if medications are being used to treat spasticity &/or extrapyramidal movement disorders (e.g., dystonia)
Brain MRIIndicated in any child w/EE w/seizures or spasticity who has not previously had a brain MRI
EEG and video EEGIf seizures are suspected
GastrointestinalFeeding evaluation & nutrition assessmentReferral to appropriate feeding therapist &/or nutritionist as indicated
Assessment for chronic diarrheaReferral to gastroenterologist as needed
MusculoskeletalOrthopedic evaluationReferral to orthopedist as needed
Miscellaneous/
OtherConsultation w/clinical geneticist &/or genetic counselor
### Treatment of Manifestations
Multi-specialty care that includes child neurology, pediatrics, clinical genetics, nutrition, gastroenterology, orthopedic, pain management, and physical therapy can help with timely detection and treatment of the multiorgan dysfunction that characterizes ethylmalonic encephalopathy. Treatment is primarily supportive including anti-spastic medications, muscle relaxants, and antiepileptic drugs. Physical therapy early in the disease course can help prevent contractures.
### Table 3.
Treatment of Manifestations in Individuals with Ethylmalonic Encephalopathy
View in own window
Manifestation/
ConcernTreatmentConsiderations/
Other
SpasticityAntispastic medications
DystoniaMuscle relaxants
ContracturesPhysical therapy
SeizuresAntiepileptic drugs
Severe diarrheaMaintain hydration & caloric intakeTube feeding often necessary
Poor energy metabolism & oxidative stressL-carnitine, riboflavin &/or coenzyme Q10 supplements (a cocktail of drugs generally used in mitochondrial disorders) & other vitamin therapies 1
1\.
Gorman et al [2016]
Off-label compassionate use of N-acetylcysteine (NAC) in combination with metronidazole may be considered as they are the only drugs known to slow disease progression and improve the metabolic abnormalities of EE [Viscomi et al 2010, Kılıç et al 2017].
* N-acetylcysteine (NAC), a cell-permeable precursor of glutathione, is abundant in mitochondria where it can act as one of the physiologic acceptors of the sulfur atom of hydrogen sulfide (H2S), which has deficient clearance in persons with EE.
* Metronidazole is widely used to combat infections caused by anaerobic bacteria, and can reduce the sulfide-producing bacterial load in the large intestine.
#### 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. In the US, early intervention is a federally funded program available in all states.
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.
Ages 5-21 years
* In the US, an IEP based on the individual's level of function should be developed by the local public school district. Affected children are permitted to remain in the public school district until age 21.
* Discussion about transition plans including financial, vocation/employment, and medical arrangements should begin at age 12 years. Developmental pediatricians can provide assistance with transition to adulthood.
All ages. Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies and to support parents in maximizing quality of life.
Consideration of private supportive therapies based on the affected individual's needs is recommended. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.
In the US:
* Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a 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).
* Consider use of durable medical equipment 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, Botox®, anti-parkinsonian medications, or orthopedic procedures.
Fine motor dysfunction. Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function (e.g., feeding, grooming, dressing, writing).
Oral motor dysfunction. Assuming that the individual is safe to eat by mouth, feeding therapy (typically from an occupational or speech therapist) is recommended for affected individuals who have difficulty feeding due to poor oral motor control.
Communication issues. Consider evaluation for alternative means of communication (e.g., Augmentative and Alternative Communication) for individuals who have expressive language difficulties.
### Prevention of Secondary Complications
All affected individuals should receive routine immunizations; as well as annual immunizations for influenza.
Physicians must pay particular attention to the prevention of infections that could be fatal.
### Surveillance
Surveillance should be individualized based on symptoms and organs affected.
### Table 4.
Recommended Surveillance for Individuals with Ethylmalonic Encephalopathy
View in own window
System/ConcernEvaluation/ActionFrequency
GrowthAssess growth & monitor for failure to thrive.At each visit
GastrointestinalMonitor feeding & electrolyte status, particularly in those w/severe diarrhea.
NeurologicMonitor for epileptic crisis; modify therapy according to clinical presentation &EEG findings.Routine
### Evaluation of Relatives at Risk
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Therapies Under Investigation
While clearance of circulating sulfide by a transplanted liver could be beneficial, to date only one instance of liver transplantation in EE has been reported [Dionisi-Vici et al 2016]. Although results were encouraging, follow up of this patient and experience with additional patients are necessary to determine therapeutic efficacy of liver transplantation in EE and possible relevance for national or state-mandated newborn screening, particularly in populations with relatively high prevalence of pathogenic variants.
Possible future treatments include AAV-mediated gene therapy [Di Meo et al 2012] or liver transplantation [Dionisi-Vici et al 2016].
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Ethylmalonic Encephalopathy
|
c1865349
| 8,197 |
gene_reviews
|
https://www.ncbi.nlm.nih.gov/books/NBK453432/
| 2021-01-18T21:28:20 |
{"mesh": ["C535737"], "synonyms": ["ETHE1 Deficiency"]}
|
Dilated cardiomyopathy with ataxia (DCMA) is characterized by severe early onset (before the age of three years) dilated cardiomyopathy (DCM) with conduction defects (long QT syndrome), non-progressive cerebellar ataxia, testicular dysgenesis, and 3-methylglutaconic aciduria.
## Epidemiology
To date, all cases of DCMA reported involve individuals from the Dariusleut Hutterite population, an endogamous population of the Great Plains region of Canada and the northern United States.
## Clinical description
Prenatal or postnatal growth failure, significant motor delay (due to cerebellar syndrome with ataxia) and male genital anomalies (ranging from isolated cryptorchidism to severe perineal hypospadias) are very frequent clinical signs. Additional features include optic atrophy, a mild increase in hepatic enzymes with microvesicular hepatic steatosis, a normochromic microcytic anemia, and mild to borderline non-progressive intellectual deficit.
## Etiology
DCMA is caused by mutation of the DNAJC19 gene (encoding the DNAJC19 protein localized to the mitochondria in cardiac myocytes).
## Differential diagnosis
DCMA syndrome shares some clinical features with the X-linked Barth syndrome and the other 3-methylglutaconic acidurias (types I, III and IV; see these terms).
## Genetic counseling
DCMA is an autosomal recessive condition.
## Prognosis
In a clinical study of 18 DCMA patients, over 70% of patients died from either progressive cardiac failure or sudden cardiac death. Improvement with standard medical treatment or complete resolution of the DCM has been reported in some patients.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Dilated cardiomyopathy with ataxia
|
c1857776
| 8,198 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=66634
| 2021-01-23T19:09:28 |
{"gard": ["10344", "12964"], "mesh": ["C565706"], "omim": ["610198"], "umls": ["C1857776"], "icd-10": ["E71.1"], "synonyms": ["3-methylglutaconic aciduria type 5", "DCMA syndrome", "MGA5"]}
|
Growth hormone deficiency
Other namesPituitary dwarfism
Growth hormone
SpecialtyEndocrinology
SymptomsShort height[1]
ComplicationsLow blood sugar, high cholesterol levels, poor bone density[1][2]
TypesCongenital, acquired[1]
CausesNot enough growth hormone[3]
Risk factorsGenetics, trauma, infections, tumors, radiation therapy[2]
Diagnostic methodBlood tests for growth hormone[2]
Differential diagnosisSmall for gestational age, Turner syndrome, Noonan syndrome, Prader-Willi syndrome[2]
TreatmentGrowth hormone replacement[1]
FrequencyUnclear[2]
Growth hormone deficiency (GHD) is a medical condition resulting from not enough growth hormone (GH).[3] Generally the most noticeable symptom is that an individual attains a short height.[1] Newborns may also present low blood sugar or a small penis size.[2] In adults there may be decreased muscle mass, high cholesterol levels, or poor bone density.[1]
GHD can be present at birth or develop later in life.[1] Causes may include genetics, trauma, infections, tumors, or radiation therapy.[2] Genes that may be involved include GH1, GHRHR, or BTK.[3] In a third of cases no cause is apparent.[2] The underlying mechanism generally involves problems with the pituitary gland.[2] Some cases are associated with a lack of other pituitary hormones, in which case it is known as combined pituitary hormone deficiency.[4] Diagnosis involves blood tests to measure growth hormone levels.[2]
Treatment is by growth hormone replacement using synthetic human growth hormone.[1] The frequency of the condition is unclear.[2] Most cases are initially noticed in children.[1] The genetic forms of this disease are estimated to affect about 1 in 7,000 people.[3] Most types occur equally in males and females though males are more often diagnosed.[2]
## Contents
* 1 Signs and symptoms
* 1.1 Child
* 1.2 Adults
* 2 Causes
* 3 Pathophysiology
* 4 Diagnosis
* 4.1 Classification
* 5 Treatment
* 5.1 Child
* 5.2 Adults
* 5.3 Side effects
* 6 Prognosis
* 6.1 Child
* 6.2 Adults
* 7 Epidemiology
* 8 History
* 9 See also
* 10 References
* 11 External links
## Signs and symptoms[edit]
### Child[edit]
Severe prenatal deficiency of GH, as occurs in congenital hypopituitarism, has little effect on fetal growth. However, prenatal and congenital deficiency can reduce the size of a male's penis, especially when gonadotropins are also deficient. Besides micropenis in males, additional consequences of severe deficiency in the first days of life can include hypoglycemia and exaggerated jaundice (both direct and indirect hyperbilirubinemia).[citation needed]
Even congenital GH deficiency does not usually impair length growth until after the first few months of life. From late in the first year until mid teens, poor growth and/or shortness is the hallmark of childhood GH deficiency. Growth is not as severely affected in GH deficiency as in untreated hypothyroidism, but growth at about half the usual velocity for age is typical. It tends to be accompanied by delayed physical maturation so that bone maturation and puberty may be several years delayed. When severe GH deficiency is present from birth and never treated, adult heights can be as short as 48-65 inches (122–165 cm).[citation needed]
Severe GH deficiency in early childhood also results in slower muscular development, so that gross motor milestones such as standing, walking, and jumping may be delayed. Body composition (i.e., the relative amounts of bone, muscle, and fat) is affected in many children with severe deficiency, so that mild to moderate chubbiness is common (though GH deficiency alone rarely causes severe obesity). Some severely GH-deficient children have recognizable, cherubic facial features characterized by maxillary hypoplasia and forehead prominence.[citation needed]
Other side effects in children include sparse hair growth and frontal recession, and pili torti and trichorrhexis nodosa are also sometimes present.[5]:501
### Adults[edit]
Recognised effects include:[6][7]
* Increased 5-alpha-reductase
* Reduced sex hormone-binding globulin (SHBG)
* Reduced muscle mass and strength
* Baldness in men
* Reduced bone mass and osteoporosis (Decreased bone density)
* Reduced energy
* Impaired concentration and memory loss
* Increased body fat, particularly around the waistline
* Lipid abnormalities, particularly raised LDL cholesterol
* Increased levels of fibrinogen and plasminogen activator inhibitor
* Cardiac dysfunction, including a thickened intima media
* Lack of well-being
* Depression and anxiety
* Social isolation
* Fibromyalgia syndrome
* Neuromuscular dysfunction
* Central adiposity
* Decreased muscle mass
* Insulin resistance
* Accelerated atherogenesis
* Prothrombotic state
* Decreased sweating and thermoregulation.
## Causes[edit]
Growth hormone deficiency in childhood commonly has no identifiable cause (idiopathic), and adult-onset GHD is commonly due to pituitary tumours and their treatment or to cranial irradiation.[8] A more complete list of causes includes:
* mutations of specific genes (e.g., GHRHR, GH1)
* congenital diseases such as Prader-Willi syndrome, Turner syndrome,[9] or short-stature homeobox gene deficiency[10]
* congenital malformations involving the pituitary (e.g., septo-optic dysplasia, posterior pituitary ectopia)
* chronic kidney disease[11]
* intracranial tumors in or near the sella turcica, especially craniopharyngioma
* damage to the pituitary from radiation therapy to the head (e.g. for leukemia or brain tumors), from surgery, from trauma, or from intracranial disease (e.g. hydrocephalus)
* autoimmune inflammation (hypophysitis)
* ischemic or hemorrhagic infarction from low blood pressure (Sheehan syndrome) or hemorrhage pituitary apoplexy
There are a variety of rare diseases that resemble GH deficiency, including the childhood growth failure, facial appearance, delayed bone age, and low insulin-like growth factor-1 (IGF-1) levels. However, GH testing elicits normal or high levels of GH in the blood, demonstrating that the problem is not due to a deficiency of GH but rather to a reduced sensitivity to its action. Insensitivity to GH is traditionally termed Laron dwarfism, but over the last 15 years many different types of GH resistance have been identified, primarily involving mutations of the GH binding protein or receptors.[citation needed]
## Pathophysiology[edit]
As an adult ages, it is normal for the pituitary to produce diminishing amounts of GH and many other hormones, particularly the sex steroids. Physicians therefore distinguish between the natural reduction in GH levels which comes with age, and the much lower levels of "true" deficiency. Such deficiency almost always has an identifiable cause, with adult-onset GHD without a definable cause ("idiopathic GH deficiency") extremely rare.[12] GH does function in adulthood to maintain muscle and bone mass and strength, and has poorly understood effects on cognition and mood.[citation needed]
## Diagnosis[edit]
Although GH can be readily measured in a blood sample, testing for GH deficiency is constrained by the fact that levels are nearly undetectable for most of the day. This makes simple measurement of GH in a single blood sample useless for detecting deficiency. Physicians therefore use a combination of indirect and direct criteria in assessing GHD, including:[citation needed]
* Auxologic criteria (defined by body measurements)
* Indirect hormonal criteria (IGF levels from a single blood sample)
* Direct hormonal criteria (measurement of GH in multiple blood samples to determine secretory patterns or responses to provocative testing), in particular:
* Subnormal frequency and amplitude of GH secretory peaks when sampled over several hours
* Subnormal GH secretion in response to at least two provocative stimuli
* Increased IGF1 levels after a few days of GH treatment
* Response to GH treatment
* Corroborative evidence of pituitary dysfunction
"Provocative tests" involve giving a dose of an agent that will normally provoke a pituitary to release a burst of growth hormone. An intravenous line is established, the agent is given, and small amounts of blood are drawn at 15-minute intervals over the next hour to determine if a rise of GH was provoked. Agents which have been used clinically to stimulate and assess GH secretion are arginine,[13] levodopa, clonidine, epinephrine and propranolol, glucagon and insulin. An insulin tolerance test has been shown to be reproducible, age-independent, and able to distinguish between GHD and normal adults,[13] and so is the test of choice.
Severe GH deficiency in childhood additionally has the following measurable characteristics:
* Proportional stature well below that expected for family heights, although this characteristic may not be present in the case of familial-linked GH deficiency
* Below-normal velocity of growth
* Delayed physical maturation
* Delayed bone age
* Low levels of IGF1, IGF2, IGF binding protein 3
* Increased growth velocity after a few months of GH treatment
In childhood and adulthood, the diagnosing doctor will look for these features accompanied by corroboratory evidence of hypopituitarism such as deficiency of other pituitary hormones, a structurally abnormal pituitary, or a history of damage to the pituitary. This would confirm the diagnosis; in the absence of pituitary pathology, further testing would be required.
### Classification[edit]
Growth hormone deficiency can be congenital or acquired in childhood or adult life. It can be partial or complete. It is usually permanent, but sometimes transient. It may be an isolated deficiency or occur in association with deficiencies of other pituitary hormones.[citation needed]
The term hypopituitarism is often used interchangeably with GH deficiency but more often denotes GH deficiency plus deficiency of at least one other anterior pituitary hormone. When GH deficiency (usually with other anterior pituitary deficiencies) is associated with posterior pituitary hormone deficiency (usually diabetes insipidus), the condition is termed panhypopituitarism.[citation needed]
## Treatment[edit]
Main article: Growth hormone treatment
GH deficiency is treated by replacing GH with daily injections under the skin or into muscle. Until 1985, growth hormone for treatment was obtained by extraction from human pituitary glands collected at autopsy. Since 1985, recombinant human growth hormone (rHGH) is a recombinant form of human GH produced by genetically engineered bacteria, manufactured by recombinant DNA technology. In both children and adults, costs of treatment in terms of money, effort, and the impact on day-to-day life, are substantial.[citation needed]
### Child[edit]
GH treatment is not recommended for children who are not growing despite having normal levels of growth hormone, and in the UK it is not licensed for this use.[14] Children requiring treatment usually receive daily injections of growth hormone. Most pediatric endocrinologists monitor growth and adjust dose every 3–6 months and many of these visits involve blood tests and x-rays. Treatment is usually extended as long as the child is growing, and lifelong continuation may be recommended for those most severely deficient. Nearly painless insulin syringes, pen injectors, or a needle-free delivery system reduce the discomfort. Injection sites include the biceps, thigh, buttocks, and stomach. Injection sites should be rotated daily to avoid lipoatrophy. Treatment is expensive, costing as much as US$10,000 to $40,000 a year in the US.[citation needed]
### Adults[edit]
GH supplementation is not recommended medically for the physiologic age-related decline in GH/IGF secretion.[8][12] It may be appropriate in diagnosed adult-onset deficiency, where a weekly dose approximately 25% of that given to children is given. Lower doses again are called for in the elderly to reduce the incidence of side effects and maintain age-dependent normal levels of IGF-1.[15]
In many countries, including the UK, the majority view among endocrinologists is that the failure of treatment to provide any demonstrable, measurable benefits in terms of outcomes means treatment is not recommended for all adults with severe GHD,[16] and national guidelines in the UK as set out by NICE suggest three criteria which all need to be met for treatment to be indicated:
1. Severe GH deficiency, defined as a peak GH response of <9mU/litre during an insulin tolerance test
2. Perceived impairment of quality of life, as assessed by questionnaire
3. They are already treated for other pituitary hormone disorders
Where treatment is indicated, duration is dependent upon indication.
Cost of adult treatment in the UK is 3000-4000 GBP annually.[16]
### Side effects[edit]
* Headaches
* Joint pain and muscle pain
* Fluid retention, and carpal tunnel syndrome
* Mild hypertension
* Visual problems
* Nausea and vomiting
* Paraesthesiae
* Antibody formation
* Reactions at the injection site
* Rarely, benign intracranial hypertension.[8]
## Prognosis[edit]
### Child[edit]
When treated with GH, a severely deficient child will begin to grow faster within months. In the first year of treatment, the rate of growth may increase from half as fast as other children are growing to twice as fast (e.g., from 1 inch a year to 4 inches, or 2.5 cm to 10). Growth typically slows in subsequent years, but usually remains above normal so that over several years a child who had fallen far behind in his height may grow into the normal height range. Excess adipose tissue may be reduced.[citation needed]
### Adults[edit]
GH treatment can confer a number of measurable benefits to severely GH-deficient adults, such as enhanced energy and strength, and improved bone density. Muscle mass may increase at the expense of adipose tissue. Although adults with hypopituitarism have been shown to have a reduced life expectancy, and a cardiovascular mortality rate more than double controls,[16] treatment has not been shown to improve mortality, although blood lipid levels do improve. Similarly, although measurements of bone density improve with treatment, rates of fractures have not been shown to improve.[16]
Effects on quality of life are unproven, with a number of studies finding that adults with GHD had near-normal indicators of QoL at baseline (giving little scope for improvement), and many using outdated dosing strategies. However, it may be that those adults with poor QoL at the start of treatment do benefit.[8]
## Epidemiology[edit]
The incidence of idiopathic GHD in infants is about 1 in every 3800 live births,[17] and rates in older children are rising as more children survive childhood cancers which are treated with radiotherapy, although exact rates are hard to obtain.[9]
The incidence of genuine adult-onset GHD, normally due to pituitary tumours, is estimated at 10 per million.[16]
## History[edit]
Like many other 19th century medical terms which lost precise meaning as they gained wider currency, "midget" as a term for someone with severe proportional shortness acquired pejorative connotations and is no longer used in a medical context.
Notable modern pop cultural figures with growth hormone deficiency include actor and comedian Andy Milonakis, who has the appearance and voice of an adolescent boy despite being an adult.[18][19] Argentine footballer Lionel Messi was diagnosed at age 10 with growth hormone deficiency and was subsequently treated.[20]
## See also[edit]
* Hypothalamic–pituitary–somatic axis
## References[edit]
1. ^ a b c d e f g h i "Growth hormone deficiency". Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. 2016. Retrieved 12 December 2017.
2. ^ a b c d e f g h i j k l "Growth Hormone Deficiency". NORD (National Organization for Rare Disorders). 2016. Retrieved 12 December 2017.
3. ^ a b c d "isolated growth hormone deficiency". Genetics Home Reference. February 2012. Retrieved 12 December 2017.
4. ^ "Combined pituitary hormone deficiency". Genetics Home Reference. August 2010. Retrieved 13 December 2017.
5. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
6. ^ "Human Growth Hormone Deficiency". HGH. Retrieved 20 January 2012.
7. ^ Gupta, Vishal (2011). "Adult growth hormone deficiency". Indian Journal of Endocrinology and Metabolism. Medknow. 15 (7): S197-202. doi:10.4103/2230-8210.84865. ISSN 2230-8210. PMC 3183535. PMID 22029024.
8. ^ a b c d "Human growth hormone (somatropin) in adults with growth hormone deficiency" (PDF). National Institute for Clinical Excellence. 2006-07-01. Archived from the original (PDF) on 2011-02-17. Retrieved 2009-01-16.
9. ^ a b "Growth failure (in children) - human growth hormone (HGH)" (PDF). National Institute for Clinical Excellence. 2008-09-25. Archived from the original (PDF) on 2011-10-26. Retrieved 2009-01-16.
10. ^ Rappold GA, Fukami M, Niesler B, et al. (March 2002). "Deletions of the homeobox gene SHOX (short stature homeobox) are an important cause of growth failure in children with short stature". J. Clin. Endocrinol. Metab. 87 (3): 1402–6. doi:10.1210/jc.87.3.1402. PMID 11889216.
11. ^ Saborio P, Hahn S, Hisano S, Latta K, Scheinman JI, Chan JC (October 1998). "Chronic renal failure: an overview from a pediatric perspective". Nephron. 80 (2): 134–48. doi:10.1159/000045157. PMID 9736810. S2CID 46847002.
12. ^ a b Molitch ME, Clemmons DR, Malozowski S, et al. (May 2006). "Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society Clinical Practice Guideline". J. Clin. Endocrinol. Metab. 91 (5): 1621–34. doi:10.1210/jc.2005-2227. PMID 16636129.
13. ^ a b Aimaretti G, Corneli G, Razzore P, et al. (May 1998). "Comparison between insulin-induced hypoglycemia and growth hormone (GH)-releasing hormone + arginine as provocative tests for the diagnosis of GH deficiency in adults". J. Clin. Endocrinol. Metab. 83 (5): 1615–8. doi:10.1210/jc.83.5.1615. PMID 9589665. Retrieved 2008-07-23.
14. ^ "Guidance on the use of human growth hormone (somatropin) in children with growth failure" (PDF). National Institute for Clinical Excellence. 2002-05-01. Archived from the original (PDF) on 2011-10-26. Retrieved 2009-01-16.
15. ^ "Consensus Guidelines for Adult Growth Hormone Deficiency 2007".
16. ^ a b c d e "The Use of Growth Hormone Replacement in Adult Patients with Severe Growth Hormone Deficiency" (PDF). The Society for Endocrinology. 2000-10-01. Retrieved 2009-01-18.
17. ^ "Growth Hormone Deficiency". UK Child Growth Foundation. Retrieved 2009-01-16.
18. ^ TV.com (1976-01-30). "Andy Milonakis". TV.com. Retrieved 2017-03-28.
19. ^ Maureen Ryan (2005-07-31). "Andy Milonakis, 12 going on ageless". Articles.chicagotribune.com. Retrieved 2017-03-28.
20. ^ Cazadieu, Jérôme; Juillard, Alexandre; Traïni, Frédéric (15 November 2008). "Leo Messi: La Légende d'El Enano" [Leo Messi: The Legend of El Enano]. L'Équipe via Irish Independent. Retrieved 18 July 2015.
## External links[edit]
* Am Assoc Clinical Endocrinologists \- practice guidelines and recommendations for diagnosis and treatment of GH deficiency, reflecting standard practice among U.S. endocrinologists
Classification
D
* ICD-10: E23.0
* ICD-9-CM: 253.3
* OMIM: 262400
* MeSH: D004393
* DiseasesDB: 5447
External resources
* MedlinePlus: 001176
* eMedicine: med/930
* v
* t
* e
Pituitary disease
Hyperpituitarism
Anterior
* Acromegaly
* Hyperprolactinaemia
* Pituitary ACTH hypersecretion
Posterior
* SIADH
General
* Nelson's syndrome
* Hypophysitis
Hypopituitarism
Anterior
* Kallmann syndrome
* Growth hormone deficiency
* Hypoprolactinemia
* ACTH deficiency/Secondary adrenal insufficiency
* GnRH insensitivity
* FSH insensitivity
* LH/hCG insensitivity
Posterior
Neurogenic diabetes insipidus
General
* Empty sella syndrome
* Pituitary apoplexy
* Sheehan's syndrome
* Lymphocytic hypophysitis
* Pituitary adenoma
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Growth hormone deficiency
|
c0013338
| 8,199 |
wikipedia
|
https://en.wikipedia.org/wiki/Growth_hormone_deficiency
| 2021-01-18T18:37:47 |
{"gard": ["6552"], "mesh": ["D004393"], "icd-9": ["253.3"], "icd-10": ["E23.0"], "wikidata": ["Q369262"]}
|
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