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Clouston syndrome is a form of ectodermal dysplasia, a group of about 150 conditions characterized by abnormal development of some or all of the ectodermal structures, which include the skin, hair, nails, teeth, and sweat glands. Specifically, Clouston syndrome is characterized by abnormalities of the hair, nails, and skin, with the teeth and sweat glands being unaffected.
In infants with Clouston syndrome, scalp hair is sparse, patchy, and lighter in color than the hair of other family members; it is also fragile and easily broken. By puberty, the hair problems may worsen until all the hair on the scalp is lost (total alopecia). The eyelashes, eyebrows, underarm (axillary) hair, and pubic hair are also sparse or absent.
Abnormal growth of fingernails and toenails (nail dystrophy) is also characteristic of Clouston syndrome. The nails may appear white in the first years of life. They grow slowly and gradually become thick and misshapen. In some people with Clouston syndrome, nail dystrophy is the most noticeable feature of the disorder.
Many people with Clouston syndrome have thick skin on the palms of the hands and soles of the feet (palmoplantar hyperkeratosis); areas of the skin, especially over the joints, that are darker in color than the surrounding skin (hyperpigmentation); and widened and rounded tips of the fingers (clubbing).
## Frequency
The prevalence of Clouston syndrome is unknown. Cases have been reported in many populations; the disorder is especially common among people of French-Canadian descent.
## Causes
Clouston syndrome is caused by mutations in the GJB6 gene. This gene provides instructions for making a protein called gap junction beta 6, more commonly known as connexin 30. Connexin 30 is a member of the connexin protein family. Connexin proteins form channels called gap junctions, which permit the transport of nutrients, charged atoms (ions), and signaling molecules between neighboring cells. The size of the gap junction and the types of particles that move through it are determined by the particular connexin proteins that make up the channel. Gap junctions made with connexin 30 transport potassium ions and certain small molecules.
Connexin 30 is found in several different tissues throughout the body, including the skin (especially on the palms of the hands and soles of the feet), hair follicles, and nail beds, and plays a role in the growth and development of these tissues.
GJB6 gene mutations that cause Clouston syndrome change single protein building blocks (amino acids) in the connexin 30 protein. Although the effects of these mutations are not fully understood, they lead to abnormalities in the growth, division, and maturation of cells in the hair follicles, nails, and skin.
### Learn more about the gene associated with Clouston syndrome
* GJB6
## Inheritance Pattern
This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Clouston syndrome | c0162361 | 4,400 | medlineplus | https://medlineplus.gov/genetics/condition/clouston-syndrome/ | 2021-01-27T08:25:53 | {"gard": ["2056"], "mesh": ["D004476"], "omim": ["129500"], "synonyms": []} |
Chromosomal deletion smaller than 5 million base pairs (5 Mb) spanning several genes that is too small to be detected by conventional methods
Microdeletion syndrome is a syndrome caused by a chromosomal deletion smaller than 5 million base pairs (5 Mb) spanning several genes that is too small to be detected by conventional cytogenetic methods or high resolution karyotyping (2–5 Mb).[1][2] Detection is done by fluorescence in situ hybridization (FISH). Larger chromosomal deletion syndromes are detectable using karyotyping techniques.
## Examples[edit]
* DiGeorge syndrome or velocardiofacial syndrome[3] – most common microdeletion syndrome
* Prader–Willi syndrome[4][5]
* Angelman syndrome[4]
* Neurofibromatosis type 1[6]
* Neurofibromatosis type II[7][8]
* Williams syndrome[9]
* Miller–Dieker syndrome[10]
* Smith–Magenis syndrome[11]
* Rubinstein–Taybi syndrome[12]
* Wolf–Hirschhorn syndrome[13]
## References[edit]
1. ^ H. William Taeusch; Roberta A. Ballard; Christine A. Gleason; Mary Ellen Avery (2005). Avery's Diseases of the Newborn. Elsevier Health Sciences. pp. 210–215. ISBN 0-7216-9347-4.
2. ^ "Microdeletion syndrome". Genetics Home Reference. 17 April 2014. Retrieved 19 April 2014.
3. ^ Shaikh, TH; Kurahashi, H; Saitta, SC; O'Hare, AM; Hu, P; Roe, BA; Driscoll, DA; McDonald-McGinn, DM; Zackai, EH; Budarf, ML; Emanuel, BS (1 March 2000). "Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: genomic organization and deletion endpoint analysis". Human Molecular Genetics. 9 (4): 489–501. doi:10.1093/hmg/9.4.489. PMID 10699172.
4. ^ a b Buiting, K; Saitoh, S; Gross, S; Dittrich, B; Schwartz, S; Nicholls, RD; Horsthemke, B (April 1995). "Inherited microdeletions in the Angelman and Prader-Willi syndromes define an imprinting centre on human chromosome 15". Nature Genetics. 9 (4): 395–400. doi:10.1038/ng0495-395. PMID 7795645.
5. ^ Runte, M; Varon, R; Horn, D; Horsthemke, B; Buiting, K (February 2005). "Exclusion of the C/D box snoRNA gene cluster HBII-52 from a major role in Prader-Willi syndrome". Human Genetics. 116 (3): 228–30. doi:10.1007/s00439-004-1219-2. PMID 15565282.
6. ^ Pasmant, E; Sabbagh, A; Spurlock, G; Laurendeau, I; Grillo, E; Hamel, MJ; Martin, L; Barbarot, S; Leheup, B; Rodriguez, D; Lacombe, D; Dollfus, H; Pasquier, L; Isidor, B; Ferkal, S; Soulier, J; Sanson, M; Dieux-Coeslier, A; Bièche, I; Parfait, B; Vidaud, M; Wolkenstein, P; Upadhyaya, M; Vidaud, D; members of the NF France, Network (June 2010). "NF1 microdeletions in neurofibromatosis type 1: from genotype to phenotype". Human Mutation. 31 (6): E1506-18. doi:10.1002/humu.21271. PMID 20513137.
7. ^ Rouleau, GA; Merel, P; Lutchman, M; Sanson, M; Zucman, J; Marineau, C; Hoang-Xuan, K; Demczuk, S; Desmaze, C; Plougastel, B (10 June 1993). "Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2". Nature. 363 (6429): 515–21. Bibcode:1993Natur.363..515R. doi:10.1038/363515a0. PMID 8379998.
8. ^ Beck, Megan; Peterson, Jess F.; McConnell, Juliann; McGuire, Marianne; Asato, Miya; Losee, Joseph E.; Surti, Urvashi; Madan-Khetarpal, Suneeta; Rajkovic, Aleksandar; Yatsenko, Svetlana A. (May 2015). "Craniofacial abnormalities and developmental delay in two families with overlapping 22q12.1 microdeletions involving the gene". American Journal of Medical Genetics Part A. 167 (5): 1047–1053. doi:10.1002/ajmg.a.36839. PMID 25810350.
9. ^ Tassabehji, M; Metcalfe, K; Karmiloff-Smith, A; Carette, MJ; Grant, J; Dennis, N; Reardon, W; Splitt, M; Read, AP; Donnai, D (January 1999). "Williams syndrome: use of chromosomal microdeletions as a tool to dissect cognitive and physical phenotypes". American Journal of Human Genetics. 64 (1): 118–25. doi:10.1086/302214. PMC 1377709. PMID 9915950.
10. ^ Huang, HC; Bautista, SL; Chen, BS; Chang, KP; Chen, YJ; Wuu, SW (1996). "Miller-Dieker syndrome with microdeletion of chromosome 17p13.3: report of one case". Zhonghua Minguo Xiao Er Ke Yi Xue Hui Za Zhi [Journal]. Zhonghua Minguo Xiao Er Ke Yi Xue Hui. 38 (6): 472–6. PMID 9473821.
11. ^ Bi, W; Yan, J; Stankiewicz, P; Park, SS; Walz, K; Boerkoel, CF; Potocki, L; Shaffer, LG; Devriendt, K; Nowaczyk, MJ; Inoue, K; Lupski, JR (May 2002). "Genes in a refined Smith-Magenis syndrome critical deletion interval on chromosome 17p11.2 and the syntenic region of the mouse". Genome Research. 12 (5): 713–28. doi:10.1101/gr.73702. PMC 186594. PMID 11997338.
12. ^ Wójcik, C; Volz, K; Ranola, M; Kitch, K; Karim, T; O'Neil, J; Smith, J; Torres-Martinez, W (February 2010). "Rubinstein-Taybi syndrome associated with Chiari type I malformation caused by a large 16p13.3 microdeletion: a contiguous gene syndrome?". American Journal of Medical Genetics Part A. 152A (2): 479–83. doi:10.1002/ajmg.a.33303. PMID 20101707.
13. ^ Rauch, A; Schellmoser, S; Kraus, C; Dörr, HG; Trautmann, U; Altherr, MR; Pfeiffer, RA; Reis, A (1 April 2001). "First known microdeletion within the Wolf-Hirschhorn syndrome critical region refines genotype-phenotype correlation". American Journal of Medical Genetics. 99 (4): 338–42. doi:10.1002/ajmg.1203. PMID 11252005.
## Further reading[edit]
* H. William Taeusch; Roberta A. Ballard; Christine A. Gleason; Mary Ellen Avery (2005). Avery's Diseases of the Newborn. Elsevier Health Sciences. pp. 210–215. ISBN 0-7216-9347-4.
* Microdeletions and Molecular Genetics
* Microdeletion syndromes (chromosomes 1 to 11) on UpToDate
* List of 100 microdeletion/duplication syndromes detected by array-CGH on GENOMA
* Schwartz, Stuart; Graf, Michael D. (Sep 13, 2002). "Ch 19. Microdeletion Syndromes: Characteristics and Diagnosis". Molecular Cytogenetics : Protocols and Applications. Methods in Molecular Biology. 204. pp. 275–290. doi:10.1385/1-59259-300-3:275. PMID 12397804.
* Vissers, LE; Stankiewicz, P (2012). "Microdeletion and microduplication syndromes". Methods in Molecular Biology. 838: 29–75. doi:10.1007/978-1-61779-507-7_2. ISBN 978-1-61779-506-0. PMID 22228006.
* Slavotinek, Anne (2012). "Microdeletion Syndromes". eLS. doi:10.1002/9780470015902.a0005549.pub2. ISBN 978-0470016176.
* 13 chromosomal disorders you may not have heard of
* v
* t
* e
Mutation
Mechanisms of mutation
* Insertion
* Deletion
* Substitution
* Transversion
* Transition
Mutation with respect to structure
Point mutation
* Nonsense mutation
* Missense mutation
* Conservative mutation
* Silent mutation
* Frameshift mutation
* Dynamic mutation
Large-scale mutation
* Chromosomal translocations
* Chromosomal inversions
Mutation with respect to overall fitness
* Deleterious mutation
* Advantageous mutation
* Neutral mutation
* Nearly neutral mutation
* Synonymous mutation
* Nonsynonymous mutation
* v
* t
* e
Chromosome abnormalities
Autosomal
Trisomies/Tetrasomies
* Down syndrome
* 21
* Edwards syndrome
* 18
* Patau syndrome
* 13
* Trisomy 9
* Tetrasomy 9p
* Warkany syndrome 2
* 8
* Cat eye syndrome/Trisomy 22
* 22
* Trisomy 16
Monosomies/deletions
* (1q21.1 copy number variations/1q21.1 deletion syndrome/1q21.1 duplication syndrome/TAR syndrome/1p36 deletion syndrome)
* 1
* Wolf–Hirschhorn syndrome
* 4
* Cri du chat syndrome/Chromosome 5q deletion syndrome
* 5
* Williams syndrome
* 7
* Jacobsen syndrome
* 11
* Miller–Dieker syndrome/Smith–Magenis syndrome
* 17
* DiGeorge syndrome
* 22
* 22q11.2 distal deletion syndrome
* 22
* 22q13 deletion syndrome
* 22
* genomic imprinting
* Angelman syndrome/Prader–Willi syndrome (15)
* Distal 18q-/Proximal 18q-
X/Y linked
Monosomy
* Turner syndrome (45,X)
Trisomy/tetrasomy,
other karyotypes/mosaics
* Klinefelter syndrome (47,XXY)
* XXYY syndrome (48,XXYY)
* XXXY syndrome (48,XXXY)
* 49,XXXYY
* 49,XXXXY
* Triple X syndrome (47,XXX)
* Tetrasomy X (48,XXXX)
* 49,XXXXX
* Jacobs syndrome (47,XYY)
* 48,XYYY
* 49,XYYYY
* 45,X/46,XY
* 46,XX/46,XY
Translocations
Leukemia/lymphoma
Lymphoid
* Burkitt's lymphoma t(8 MYC;14 IGH)
* Follicular lymphoma t(14 IGH;18 BCL2)
* Mantle cell lymphoma/Multiple myeloma t(11 CCND1:14 IGH)
* Anaplastic large-cell lymphoma t(2 ALK;5 NPM1)
* Acute lymphoblastic leukemia
Myeloid
* Philadelphia chromosome t(9 ABL; 22 BCR)
* Acute myeloblastic leukemia with maturation t(8 RUNX1T1;21 RUNX1)
* Acute promyelocytic leukemia t(15 PML,17 RARA)
* Acute megakaryoblastic leukemia t(1 RBM15;22 MKL1)
Other
* Ewing's sarcoma t(11 FLI1; 22 EWS)
* Synovial sarcoma t(x SYT;18 SSX)
* Dermatofibrosarcoma protuberans t(17 COL1A1;22 PDGFB)
* Myxoid liposarcoma t(12 DDIT3; 16 FUS)
* Desmoplastic small-round-cell tumor t(11 WT1; 22 EWS)
* Alveolar rhabdomyosarcoma t(2 PAX3; 13 FOXO1) t (1 PAX7; 13 FOXO1)
Other
* Fragile X syndrome
* Uniparental disomy
* XX male syndrome/46,XX testicular disorders of sex development
* Marker chromosome
* Ring chromosome
* 6; 9; 14; 15; 18; 20; 21, 22
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Microdeletion syndrome | c1954751 | 4,401 | wikipedia | https://en.wikipedia.org/wiki/Microdeletion_syndrome | 2021-01-18T18:48:29 | {"wikidata": ["Q10329580"]} |
## Clinical Features
Zori et al. (1998) reported a 5-generation family in which multiple males were affected with a relatively mild form of nonprogressive arthrogryposis affecting only the lower limbs. All had involvement of the knee joint, with either a flexion or extension defect, about half had involvement of the hip joint, including 1 patient with dislocated hips, and all but 2 had involvement of the ankle joints. Five patients had congenital vertical tali and 1 had flat feet. The contractures resulted in gait impairment, but all affected individuals were ambulatory. Several surgical reports described abnormally thin tendons across affected joints. Skeletal muscle biopsies from 2 patients were essentially normal, and nerve conduction studies from 1 patient were normal. No female family members were affected. Zori et al. (1998) noted that the phenotype in this family was most consistent with type III X-linked arthrogryposis described by Hall et al. (1982) (see 301830).
Inheritance
The transmission pattern of ACLLX in the family reported by Zori et al. (1998) was consistent with X-linked recessive inheritance.
Mapping
In a 5-generation family with X-linked recessive arthrogryposis affecting the lower limbs, Zori et al. (1998) mapped the disease locus to a 29-cM region between DXS1220 and DXS1205 on chromosome Xq23-q27 (maximum pairwise lod score of 2.71 at DXS42).
INHERITANCE \- X-linked recessive SKELETAL Pelvis \- Hip contractures Limbs \- Knee contractures \- Ankle contractures Feet \- Vertical tali \- Flat feet NEUROLOGIC Central Nervous System \- Gait difficulties due to contractures of the lower limbs MISCELLANEOUS \- One family has been reported (last curated May 2012) \- Nonprogressive disorder \- Affected individuals remain ambulatory ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| ARTHROGRYPOSIS, CONGENITAL, LOWER LIMB, X-LINKED | c1846273 | 4,402 | omim | https://www.omim.org/entry/300158 | 2019-09-22T16:20:51 | {"omim": ["300158"], "synonyms": ["Alternative titles", "ARTHROGRYPOSIS, X-LINKED, TYPE V, FORMERLY"]} |
This section relies largely or entirely on a single source. Relevant discussion may be found on the talk page. Please help improve this article by introducing citations to additional sources.
Find sources: "Abortion in Algeria" – news · newspapers · books · scholar · JSTOR (June 2019)
Algeria is the most restricted country in the region regarding abortion. There are many laws and punishments regarding abortion. If there are posters, publicity, public meetings, group meetings that have to do with abortion, anyone involved can be punished.
## Contents
* 1 The 3 grounds
* 2 Before August 14, 2018
* 3 Secret abortion clinics
* 4 Abortion and Rape
* 5 International Campaign for Women’s Right to Safe Abortion
* 6 References
## The 3 grounds[edit]
A government bill on health issues proposed to make abortions legal on three grounds. One being that a woman could have an abortion if they were psychologically and or mentally at risk. The second one being non-viable or severe fetal abnormality or disease. The third ground being that the health or the life of the woman will be at risk if the pregnancy was to continue. When the woman is to see the doctor, the doctor must get the consent of that woman and inform her of the whole situation.
This is the text that was published when the bill was passed, “Therapeutic termination of pregnancy is intended to preserve the health of the mother and when her life or psychological and mental balance is seriously threatened by pregnancy. The detailed rules for the application of this article are laid down by regulation.”[citation needed]
## Before August 14, 2018[edit]
source:[1]
This new law for abortion was being debated for way too long in the National Assembly. Before this, Algerians only option for abortion was to go to clinics or “Tunisia”. These clinics did not have any safety or good hygiene environments. The clinics did not meet any of the standards therefore would be risking the woman's life.
There have been many cases of death of a pregnant woman and where there have been fetuses’ and newborns found in dumpsters and trash cans. This shows that there has been a huge distress of a woman seeking an abortion.
## Secret abortion clinics[edit]
There have been secret abortion clinics in Algeria. Many of the clients were young girls who made a mistake and wanted it to go away. Other clients were women who were housewives and when the husband found out about the babies, the mothers were forced to give them up. One common reason why these women go to the secret abortion clinics is because they don't want to be pushed away from their families. Another reason being that they are truly not ready to care to a child. These women do a lot to get these illegal abortions done for example saving money for long periods of time and selling jewelry.[citation needed]
## Abortion and Rape[edit]
In 1998, there was a big uproar about abortion in Algeria's laws because of women being raped by Islamic Rebels. There were obvious ground rules, but women wanted a change. Women wanted to have the right to get an abortion if they had been raped. While the decisions were being made for four long years, 1,600 young women had been abducted by roving bands of the Armed Islamic Group.
The ground of rape was no included in the three grounds for the new law on abortion. A journalist made the point that the three group points and the ground point of rape used to be included when Algeria was fighting for independence but is not anymore. This is implying that the country has gone backwards since then in terms of abortion.[citation needed]
## International Campaign for Women’s Right to Safe Abortion[edit]
This is a campaign that supports Women's rights and protects so they can live in a safe environment. On the website they talk about many problems that are going on all over the world that involve women. One of the important topics they talk about on this website and campaign is Abortion in Algeria. This campaign works with many people and protest with the women to get women the support they need with abortion. The campaign keeps people up to date and gives money to make a difference in theses women's lives.[citation needed]
## References[edit]
1. ^ "ALGERIA – Abortion has not been legalised in Algeria". International Campaign for Women's Right to Safe Abortion. Retrieved 2018-11-27.
“Abortion Finally Legalized in Algeria.” Sexuality Policy Watch, 15 Aug. 2018, sxpolitics.org/abortion-finally-legalized-in-algeria/18834.
International Campaign for Women's Right. “ALGERIA – Abortion Has Not Been Legalized in Algeria.” Safe Abortion Womens Right, 21 Aug. 2018, www.safeabortionwomensright.org/algeria-abortion-has-not-been-legalised-in-algeria/.
“The Tragedy of Secret Abortion Clinics in Algeria: The ‘Lucrative Crime’ – الشروق أونلاين.”, 8 Mar. 2012, www.echoroukonline.com/the-tragedy-of-secret-abortion-clinics-in-algeria-the-lucrative-crime/.
* v
* t
* e
Abortion in Africa
Sovereign states
* Algeria
* Angola
* Benin
* Botswana
* Burkina Faso
* Burundi
* Cameroon
* Cape Verde (Cabo Verde)
* Central African Republic
* Chad
* Comoros
* Democratic Republic of the Congo
* Republic of the Congo
* Djibouti
* Egypt
* Equatorial Guinea
* Eritrea
* Eswatini (Swaziland)
* Ethiopia
* Gabon
* The Gambia
* Ghana
* Guinea
* Guinea-Bissau
* Ivory Coast (Côte d'Ivoire)
* Kenya
* Lesotho
* Liberia
* Libya
* Madagascar
* Malawi
* Mali
* Mauritania
* Mauritius
* Morocco
* Mozambique
* Namibia
* Niger
* Nigeria
* Rwanda
* São Tomé and Príncipe
* Senegal
* Seychelles
* Sierra Leone
* Somalia
* South Africa
* South Sudan
* Sudan
* Tanzania
* Togo
* Tunisia
* Uganda
* Zambia
* Zimbabwe
States with limited
recognition
* Sahrawi Arab Democratic Republic
* Somaliland
Dependencies and
other territories
* Canary Islands / Ceuta / Melilla (Spain)
* Madeira (Portugal)
* Mayotte / Réunion (France)
* Saint Helena / Ascension Island / Tristan da Cunha (United Kingdom)
* v
* t
* e
Abortion
Main topics
* Definitions
* History
* Methods
* Abortion debate
* Philosophical aspects
* Abortion law
Movements
* Abortion-rights movements
* Anti-abortion movements
Issues
* Abortion and mental health
* Beginning of human personhood
* Beginning of pregnancy controversy
* Abortion-breast cancer hypothesis
* Anti-abortion violence
* Abortion under communism
* Birth control
* Crisis pregnancy center
* Ethical aspects of abortion
* Eugenics
* Fetal rights
* Forced abortion
* Genetics and abortion
* Late-term abortion
* Legalized abortion and crime effect
* Libertarian perspectives on abortion
* Limit of viability
* Malthusianism
* Men's rights
* Minors and abortion
* Natalism
* One-child policy
* Paternal rights and abortion
* Prenatal development
* Reproductive rights
* Self-induced abortion
* Sex-selective abortion
* Sidewalk counseling
* Societal attitudes towards abortion
* Socialism
* Toxic abortion
* Unsafe abortion
* Women's rights
By country
Africa
* Algeria
* Angola
* Benin
* Botswana
* Burkina Faso
* Burundi
* Cameroon
* Cape Verde
* Central African Republic
* Chad
* Egypt
* Ghana
* Kenya
* Namibia
* Nigeria
* South Africa
* Uganda
* Zimbabwe
Asia
* Afghanistan
* Armenia
* Azerbaijan
* Bahrain
* Bangladesh
* Bhutan
* Brunei
* Cambodia
* China
* Cyprus
* East Timor
* Georgia
* India
* Iran
* Israel
* Japan
* Kazakhstan
* South Korea
* Malaysia
* Nepal
* Northern Cyprus
* Philippines
* Qatar
* Saudi Arabia
* Singapore
* Turkey
* United Arab Emirates
* Vietnam
* Yemen
Europe
* Albania
* Andorra
* Austria
* Belarus
* Belgium
* Bosnia and Herzegovina
* Bulgaria
* Croatia
* Czech Republic
* Denmark
* Estonia
* Finland
* France
* Germany
* Greece
* Hungary
* Iceland
* Ireland
* Italy
* Kazakhstan
* Latvia
* Liechtenstein
* Lithuania
* Luxembourg
* Malta
* Moldova
* Monaco
* Montenegro
* Netherlands
* North Macedonia
* Norway
* Poland
* Portugal
* Romania
* Russia
* San Marino
* Serbia
* Slovakia
* Slovenia
* Spain
* Sweden
* Switzerland
* Ukraine
* United Kingdom
North America
* Belize
* Canada
* Costa Rica
* Cuba
* Dominican Republic
* El Salvador
* Guatemala
* Mexico
* Nicaragua
* Panama
* Trinidad and Tobago
* United States
Oceania
* Australia
* Micronesia
* Fiji
* Kiribati
* Marshall Islands
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*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
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*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
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*[NC]: neurogenic claudication
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*[CI]: confidence interval
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*[CEEs]: conjugated estrogens
| Abortion in Algeria | None | 4,403 | wikipedia | https://en.wikipedia.org/wiki/Abortion_in_Algeria | 2021-01-18T18:50:28 | {"wikidata": ["Q19568843"]} |
Haff disease
Other namesHaffkrankheit
Satellite photo of the Vistula Lagoon, formerly known as Frisches Haff. Haff disease was first described in the location of Königsberg.[1]
SpecialtyToxicology
Haff disease is the development of rhabdomyolysis (swelling and breakdown of skeletal muscle, with a risk of acute kidney failure) within 24 hours of ingesting fish.[2]
## Contents
* 1 History
* 1.1 Poison
* 2 References
* 3 Secondary sources
* 4 External links
## History[edit]
The disease was first described in 1924 in the vicinity of Königsberg, Germany (now Kaliningrad, Russia) on the Baltic coast, in people staying around the northern part of the Vistula Lagoon (German: Frisches Haff).[3]
Over the subsequent fifteen years, about 1000 cases were reported in people, birds and cats, usually in the summer and fall, and a link was made with the consumption of fish (burbot, eel and pike).[2] Since that time, only occasional reports have appeared of the condition, mostly from the Soviet Union and Germany.[2]
In 1997, six cases of Haff disease were reported in California and Missouri, all after the consumption of buffalo fish (Ictiobus cyprinellus).[4]
In July and August 2010, dozens of people contracted rhabdomyolysis after eating Procambarus clarkii in Nanjing, China. A month later, the Chinese authorities claimed they were victims of Haff disease.[5]
An outbreak was reported in Brooklyn, New York on 18 November 2011, when two household members were stricken by the syndrome after eating buffalo fish.[6] On February 4, 2014 two cases of Haff disease were reported in Cook County, Illinois following the consumption of buffalo fish.[7]
A group from Brazil identified a Haff disease outbreak in the State of Bahia that lasted from December 2016 to April 2017,[8] with 67 cases identified. In August 2018, a couple from São Paulo, southeastern Brazil, fell ill and needed semi-intensive hospital care after eating fish of the species known in Portuguese as "arabaiana" or "olho-de-boi" (ox-eye), possibly the southern yellowtail amberjack, Seriola lalandi, which they had bought in the city of Fortaleza, State of Ceará, northeastern Brazil, and, according to them, looked "perfect". The day following their admission to hospital the patients already presented an alteration of their urine, which, according to the woman who fell ill, "was very dark, indeed looked like Coca-Cola".[9]
### Poison[edit]
The exact nature of the poison is still unclear. In the U.S. outbreak, the source of the fish was traced by the Centers for Disease Control and Prevention, and studies of other fish from the same sources showed a hexane-soluble (and hence non-polar lipid) substance that induced similar symptoms in mice; other food-borne poisons commonly found in fish could not be detected.[2] It cannot be inactivated by cooking, as all six CDC cases had consumed cooked or fried fish.[2] Palytoxin has been proposed as a disease model.[10] It has also been suggested that the toxin may have thiaminase activity (i.e. it degrades thiamine, also known as vitamin B1).[11]
## References[edit]
1. ^ "Haff disease" at Dorland's Medical Dictionary
2. ^ a b c d e Buchholz U, Mouzin E, Dickey R, Moolenaar R, Sass N, Mascola L (2000). "Haff disease: from the Baltic Sea to the U.S. shore". Emerging Infect. Dis. 6 (2): 192–5. doi:10.3201/eid0602.000215. PMC 2640861. PMID 10756156.
3. ^ Lentz O (1925). "Über die Haffkrankheit". Med Klin (in German). 1: 4–8.
4. ^ Centers for Disease Control and Prevention (CDC) (1998). "Haff disease associated with eating buffalo fish--United States, 1997". MMWR Morb. Mortal. Wkly. Rep. 47 (50): 1091–3. PMID 9883771.
5. ^ 病征确由龙虾引发 与"Haff病"基本一致, archived from the original on 2016-03-14, retrieved 2010-09-08
6. ^ https://a816-[permanent dead link] health29ssl.nyc.gov/sites/NYCHAN/Lists/AlertUpdateAdvisoryDocuments/2011%20DOHMH%20Haff%20Disease%20advisory.pdf (sign in may be required)
7. ^ State of Illinois Department of Public Health (4 February 2014). "Illinois Department of Public Health Warns of Buffalo Fish Causing Illness". Press Release. Retrieved 5 February 2014.
8. ^ FIOCRUZ, Fundação Oswaldo Cruz (in Portuguese), "Estudo descreve surto de enfermidade conhecida como “doença da urina preta” em Salvador"; 28 July 2017, https://portal.fiocruz.br/noticia/estudo-descreve-surto-de-enfermidade-conhecida-como-doenca-da-urina-preta-em-salvador
9. ^ Folha de S. Paulo (in Portuguese), "Carne de peixe contaminada provoca doença rara em casal de São Paulo", 04 October 2018; https://www1.folha.uol.com.br/equilibrioesaude/2018/10/carne-de-peixe-contaminada-provoca-doenca-rara-em-casal-de-sao-paulo.shtml
10. ^ Langley RL, Bobbitt WH (2003). "Haff disease after eating salmon". South. Med. J. 100 (11): 1147–50. doi:10.1097/SMJ.0b013e3181583673. PMID 17984750.
11. ^ Kumagai, Michio (2003). Freshwater Management: Global Versus Local Perspectives. Berlin: Springer. p. 88. ISBN 978-4-431-00488-2.
## Secondary sources[edit]
* Jürgen W. Schmidt: Die "Haffkrankheit" in Ostpreussen im Herbst 1932, in: Preussenland - Mitteilungen der Historischen Kommission für Ost- und Westpreussische Landesforschung und aus dem Geheimen Staatsarchiv Preussischer Kulturbesitz Heft 2/2009 (47. Jg.) pp. 57–60
## External links[edit]
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D
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*[AA]: Adrenergic agonist
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| Haff disease | None | 4,404 | wikipedia | https://en.wikipedia.org/wiki/Haff_disease | 2021-01-18T18:48:58 | {"icd-9": ["985.1"], "wikidata": ["Q2045954"]} |
A number sign (#) is used with this entry because Bruck syndrome-2 (BRKS2) is caused by homozygous mutation in the PLOD2 gene (601865), which encodes telopeptide lysyl hydroxylase, on chromosome 3q24.
For a phenotypic description and a discussion of genetic heterogeneity of Bruck syndrome, see Bruck syndrome-1 (259450).
Clinical Features
Ha-Vinh et al. (2004) described a child with Bruck syndrome who was the offspring of healthy nonconsanguineous Turkish parents. At birth, pterygia were present at the left elbow and at both knees, and extension of these joints was limited. Contractures were also present at the wrists, and there were bilateral clubfeet. Bilateral inguinal hernias were present. A fracture of the left arm was recognized immediately after birth, and the boy had 2 more fractures in the first 3 months of life. His urine contained high levels of hydroxyproline but low levels of collagen crosslinks degradation products.
Van der Slot et al. (2003) stated that they were unaware of any phenotypic differences between Bruck syndromes 1 and 2.
Biochemical Features
Bank et al. (1999) reported that the molecular defect underlying Bruck syndrome is a deficiency of bone-specific telopeptide lysyl hydroxylase, which results in aberrant crosslinking of bone collagen. Bank et al. (1999) found that lysine residues within the telopeptides of type I collagen (see 120150) in bone are underhydroxylated, leading to aberrant crosslinking, but that the lysine residues in the triple helix are normally modified. In contrast to bone, cartilage and ligament showed unaltered telopeptide hydroxylation in Bruck syndrome, as evidenced by normal patterns of crosslinking. The results provided evidence that collagen crosslinking is regulated primarily by tissue-specific enzymes that hydroxylate only telopeptide lysine residues and not those destined for the helical portion of the molecule. Bank et al. (1999) proposed that the form of lysyl hydroxylase that specifically hydroxylates lysyl residues in the alpha-helix should be termed helical lysyl hydroxylase. Because they mapped Bruck syndrome in 1 family to chromosome 17p12, they proposed this site for the gene encoding telopeptide-specific lysyl hydroxylase; however, the gene was later found to be PLOD2 on chromosome 3 in patients with Bruck syndrome-2 (van der Slot et al., 2003).
Molecular Genetics
In 2 families with Bruck syndrome in which linkage to chromosome 17p12 was excluded, van der Slot et al. (2003) identified homozygous missense mutations in exon 17 of the PLOD2 gene (601865.0001-601865.0002). Parents of both families were heterozygous for the respective mutations. Mutation analysis of a family showing linkage to chromosome 17p12 did not reveal any mutations in the exons, intron/exon boundaries, or promoter region of the PLOD2 gene.
In a child with Bruck syndrome, the offspring of healthy nonconsanguineous Turkish parents, Ha-Vinh et al. (2004) identified homozygosity for a novel mutation in exon 17 of the PLOD2 gene, resulting in an arg598-to-his substitution (601865.0003). The mutation was close to the mutations identified by van der Slot et al. (2003), suggesting a functionally important hotspot.
Puig-Hervas et al. (2012) screened for mutations in 6 consanguineous unrelated Egyptian families with Bruck syndrome and identified homozygous changes in the PLOD2 gene in 4 families and in the FKBP10 gene (610968) in 2 (see 607083). Two of the probands had an LH2(long) isoform-specific homozygous mutation consisting of a single-nucleotide duplication in the alternative exon 13a of the PLOD2 gene (1559dupC; 601865.0004), indicating that specific inactivation of the longer protein isoform is sufficient to cause Bruck syndrome 2.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature CHEST Ribs Sternum Clavicles & Scapulae \- Pectus carinatum GENITOURINARY External Genitalia (Male) \- Inguinal hernia SKELETAL \- Osteopenia \- Congenital joint contracture (elbow and knees) \- Bone fragility Skull \- Wormian bones Spine \- Platyspondyly (thoracic vertebrae) Limbs \- Femoral bowing Feet \- Clubfeet SKIN, NAILS, & HAIR Skin \- Pterygia LABORATORY ABNORMALITIES \- Elevated urinary hydroxyproline MOLECULAR BASIS \- Caused by mutation in the procollagen-lysine, 2-oxoglutarate 5-dioxygenase (lysine hydroxylase) 2 gene (PLOD2, 601865.0001 ) ▲ Close
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*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
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*[MAOIs]: 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
| BRUCK SYNDROME 2 | c0432253 | 4,405 | omim | https://www.omim.org/entry/609220 | 2019-09-22T16:06:32 | {"doid": ["0060231"], "omim": ["609220"], "orphanet": ["2771"], "synonyms": ["Alternative titles", "OSTEOGENESIS IMPERFECTA WITH CONGENITAL JOINT CONTRACTURES"]} |
## Summary
### Clinical characteristics.
21-hydroxylase deficiency (21-OHD) is the most common cause of congenital adrenal hyperplasia (CAH), a family of autosomal recessive disorders involving impaired synthesis of cortisol from cholesterol by the adrenal cortex. In 21-OHD CAH, excessive adrenal androgen biosynthesis results in virilization in all individuals and salt wasting in some individuals. A classic form with severe enzyme deficiency and prenatal onset of virilization is distinguished from a non-classic form with mild enzyme deficiency and postnatal onset. The classic form is further divided into the simple virilizing form (~25% of affected individuals) and the salt-wasting form, in which aldosterone production is inadequate (≥75% of individuals). Newborns with salt-wasting 21-OHD CAH are at risk for life-threatening salt-wasting crises. Individuals with the non-classic form of 21-OHD CAH present postnatally with signs of hyperandrogenism; females with the non-classic form are not virilized at birth.
### Diagnosis/testing.
The diagnosis of classic 21-OHD CAH is established in newborns with characteristic clinical features, elevated serum 17-OHP, and elevated adrenal androgens. The diagnosis of non-classic 21-OHD is established by comparison of baseline serum 17-OHP and ACTH-stimulated serum 17-OHP or early morning elevated 17-OHP. Identification of biallelic pathogenic variants in CYP21A2 confirms the clinical diagnosis and allows for family studies.
### Management.
Treatment of manifestations: Classic 21-OHD CAH: glucocorticoid replacement therapy, which needs to be increased during periods of stress. Salt-wasting form: mineralocorticoid 9α-fludrohydrocortisone therapy and often sodium chloride. Females who are virilized at birth may require feminizing genitoplasty and/or vaginal dilation. Symptomatic individuals with non-classic 21-OHD CAH may require treatment.
Prevention of primary manifestations: Newborn screening programs aim to identify infants with classic 21-OHD CAH in order to initiate glucocorticoid and mineralocorticoid treatment prior to a potentially life-threatening salt-wasting crisis.
Surveillance: Monitor:
* Efficacy of glucocorticoid and mineralocorticoid replacement therapy every three to four months while children are actively growing, and less often thereafter;
* For testicular adrenal rest tumors in males every three to five years after onset of puberty;
* Weight, bone mineral density, fertility, cardiovascular and metabolic risks in adults.
Evaluation of relatives at risk: It is appropriate to measure 17-hydroxyprogesterone (17-OHP) of at-risk sibs to facilitate early diagnosis and treatment.
### Genetic counseling.
21-OHD CAH is inherited in an autosomal recessive manner. Most parents are heterozygous for a pathogenic variant. Approximately 1% of pathogenic variants are de novo; thus, 1% of probands have only one parent who is heterozygous. In some instances during evaluation of a proband, a parent not previously known to be affected may be found to have biallelic pathogenic variants and the non-classic form of 21-OHD CAH. At conception, if the parents of a proband are both known to be heterozygotes, each sib 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. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the pathogenic variants in the family are known.
## Diagnosis
### Suggestive Findings
21-hydroxylase-deficient congenital adrenal hyperplasia (21-OHD CAH) should be suspected in the following individuals:
* Females who are virilized at birth, or who become virilized postnatally, or who have precocious puberty or adrenarche. Virilization affects maturation, growth (leading to tall stature), and sex hormone-sensitive areas (external genitalia, skin, and hair) (leading to secondary sexual characteristics).
* Males with masculinization in childhood (i.e., premature adrenarche)
* Any infant with a salt-losing crisis in the first four weeks of life. Individuals with untreated or poorly controlled salt wasting may have a decreased serum concentration of sodium, chloride, and total carbon dioxide (CO2), an increased serum concentration of potassium, and inappropriately increased urine concentration of sodium.
* An infant with elevated 17-OHP concentration detected as positive newborn screening
Note: Females with 21-OHD CAH have a normal 46,XX karyotype; males with 21-OHD CAH have a normal 46,XY karyotype.
#### Newborn Screening
Newborn screening for 21-OHD CAH serves two purposes:
* To identify infants, especially males, with the classic form of 21-OHD CAH who are at risk for life-threatening salt-wasting crises
* To expedite the diagnosis of females with ambiguous genitalia
Note: Newborn screening rarely detects individuals with the non-classic form of 21-OHD CAH [Votava et al 2005].
For US state-by-state screening information, including states with mandated newborn screening for 21-OHD CAH, see Baby's First Test. The concentration of 17-OHP is measured on a filter paper blood spot sample obtained by the heel-stick technique as used for newborn screening for other disorders.
* The majority of screening programs use a single screening test without retesting of samples with questionable 17-OHP concentrations. See Speiser et al [2010] (full text).
* To improve efficacy of screening, some screening programs reevaluate samples with borderline first-tier test results with a second-tier test and some implement repeat screening in this situation [Sarafoglou et al 2012, Chan et al 2013]. Because of the high false-positive rate of immunoassay methods, liquid chromatography-tandem mass spectrometry was recommended as a second-tier test [Speiser et al 2010]. Some programs measure the concentration of different hormones (17-OHP, 21-deoxycortisol, and cortisol) as a second-tier test on samples with a positive first-tier test result [Janzen et al 2007]. Some US states mandate organic solvent extraction prior to immunoassay of dried blood spots in order to increase specificity.
Note: (1) Results on blood samples taken in the first 24 hours of life are elevated in all infants and may give false-positive results. (2) False-positive results may also be observed in low birth-weight infants or premature infants. Therefore, birth weight- or gestational age-adjusted normative data is used to determine if a test result is screen positive. (3) False-negative results may be observed in neonates receiving dexamethasone for management of unrelated problems.
### Establishing the Diagnosis
21-OHD CAH. The diagnosis is established in a newborn with the following laboratory findings:
* Serum 17-OHP is markedly elevated.
* Adrenal androgens are elevated; Δ4-androstenedione, 21 deoxycortisol, and progesterone are increased in males and females with 21-OHD CAH; Testosterone and adrenal androgen precursors (Δ4-androstenedione, DHEA) are increased in affected females and prepubertal males.
* Plasma renin activity is markedly elevated in individuals with the salt-wasting form of 21-OHD CAH.
Note: In individuals with the salt-wasting form of 21-OHD CAH, the serum concentration of aldosterone is inappropriately low compared to the level of plasma renin activity (PRA) elevation. A reduced ratio of aldosterone to PRA indicates impaired aldosterone synthesis and can differentiate those individuals with the salt-wasting form of CAH from those with the simple virilizing form of CAH after the newborn period [Nimkarn et al 2007].
* Identification of biallelic pathogenic variants in CYP21A2 (see Table 2)
Non-classic 21-OHD CAH. The diagnosis is established in a proband based on the results of ONE of the two following laboratory tests (see Figure 1 and Table 1):
#### Figure 1.
17-OHP nomogram for the diagnosis of steroid 21-hydroxylase deficiency (60-minute Cortrosyn™ stimulation test). The data for this nomogram was collected between 1982 and 1991 at the Department of Pediatrics, the New York Hospital-Cornell Medical (more...)
* 60-minute ACTH stimulation test. The serum concentration of 17-OHP measured at baseline and at 60 minutes after intravenous injection of a standard 250-µg bolus of synthetic ACTH (Cortrosyn™) are plotted on the nomogram in Figure 1.
* 17-hydroxyprogesterone (17-OHP). A single early-morning (<8AM) measurement of plasma 17-OHP concentration (baseline values in affected individuals are not always elevated; see Table 1)
Note: Normal ranges of 17-OHP for gender and pubertal status vary by laboratory, reflecting the methods used. In adult females, normal ranges depend on the phase of the menstrual cycle.
### Table 1.
Diagnosis of 21-OHD CAH after Infancy Based on 17 OHP Levels
View in own window
Classic FormNon-Classic FormUnaffected
Baseline 17-OHP level>10,000 ng/dL or 300 nmol/L200-10,000 ng/dL or 6-300 nmol/L 1<200 ng/dL or 6 nmol/L 1
17-OHP level after ACTH stimulation>10,000 ng/dL or 300 nmol/L1,000-10,000 ng/dL or 31-300 nmol/L<1,000 ng/dL or 50 nmol/L
Modified from Speiser et al [2010]
1\.
Randomly measured 17-OHP can be normal in the non-classic form.
Molecular testing. Identification of biallelic pathogenic variants in CYP21A2 (see Table 2) confirms the diagnosis and allows for family studies. Molecular testing approaches can include single-gene testing, use of a multigene panel, and more comprehensive genomic testing:
* Single-gene testing. Sequence analysis of CYP21A2 is performed first and followed by gene-targeted deletion/duplication analysis if only one or no pathogenic variant is found.
Note: A large-scale gene conversion (see Molecular Genetics) can replace a large segment of functional CYP21A2 sequence with a segment of the CYP21A1P pseudogene that is nonfunctional as a result of more than one deleterious variant [Mao et al 2002]. Thus, when targeted analysis detects multiple pathogenic variants, it is possible that the pathogenic variants are either in trans configuration (i.e., are on separate chromosomes, one inherited from each parent) or in cis configuration (i.e., are on the same chromosome and thus represent only one mutated allele rather than two; most likely arising from gene conversion). To avoid diagnostic errors, studying both parents as well as the proband is recommended to confirm the pathogenic variants and to determine if they are in cis configuration or trans configuration.
* A multigene panel that includes CYP21A2 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, genome sequencing, and mitochondrial sequencing may be considered if serial single-gene testing (and/or use of a multigene panel) fails to confirm a diagnosis in an individual with features of 21-OHD CAH.
For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
### Table 2.
Molecular Genetic Testing Used in 21-Hydroxylase-Deficient Congenital Adrenal Hyperplasia
View in own window
Gene 1MethodProportion of Probands with Pathogenic Variants 2 Detectable by Method
CYP21A2Sequence analysis 3~70%-80% 4
Gene-targeted deletion/duplication analysis 5~20%-30% 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\.
The majority of individuals from heterogeneous populations with 21-OHD CAH are compound heterozygotes [Krone et al 2000, New et al 2013].
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\.
Approximately 20% of mutated alleles are deleted for a 30-kb gene segment that encompasses the 3' end of the CYP21A1P pseudogene, all of the adjacent C4B complement gene, and the 5' end of CYP21A2 (see Molecular Genetics).
## Clinical Characteristics
### Clinical Description
21-hydroxylase-deficient congenital adrenal hyperplasia (21-OHD CAH) occurs in a classic form and a non-classic form (Table 3).
In classic 21-OHD CAH prenatal exposure to potent androgens such as testosterone and Δ4-androstenedione at critical stages of sexual development virilizes the external genitalia of genetic females, often resulting in genital ambiguity at birth. The classic form is further divided into the simple virilizing form (~25% of individuals) and the salt-wasting form, in which aldosterone production is inadequate (≥75% of individuals). Newborns with salt-wasting CAH caused by 21-OHD CAH are at risk for life-threatening salt-wasting crises.
Individuals with the non-classic form of 21-OHD CAH have only moderate enzyme deficiency and present postnatally with signs of hyperandrogenism; females with the non-classic form are not virilized at birth.
### Table 3.
Clinical Features in Individuals with Classic and Non-Classic 21-OHD CAH
View in own window
Feature21-OHD CAH
ClassicNon-Classic
Prenatal virilizationPresent in femalesAbsent
Postnatal virilizationMales and femalesVariable
Salt wasting~75% of all individualsAbsent
Cortisol deficiency~100%Rare
#### Classic Simple Virilizing 21-OHD CAH
Excess adrenal androgen production in utero results in genital virilization at birth in 46,XX females. In affected females, the excess androgens result in varying degrees of enlargement of the clitoris, fusion of the labioscrotal folds, and formation of a urogenital sinus. Because anti-müllerian hormone (AMH) is not secreted, the müllerian ducts develop normally into a uterus and fallopian tubes in affected females. It is not possible to distinguish between classic simple virilizing 21-OHD CAH and classic salt-wasting 21-OHD CAH based solely on the degree of virilization of an affected female at birth.
After birth, both females and males with classic simple virilizing 21-OHD CAH who do not receive glucocorticoid replacement therapy develop signs of androgen excess including precocious development of pubic and axillary hair, acne, rapid linear growth, and advanced bone age. Untreated males have progressive penile enlargement and small testes. Untreated females have clitoral enlargement, hirsutism, male pattern baldness, menstrual abnormalities, and reduced fertility.
The initial growth in the young child with untreated 21-OHD CAH is rapid; however, potential height is reduced and short adult stature results from premature epiphyseal fusion. Even if treatment with cortisol replacement therapy begins at an early age and secretion of excess adrenal androgens is controlled, individuals with 21-OHD CAH do not generally achieve the expected adult height. Bone age may be advanced compared to chronologic age.
Pubertal development. In boys and girls with proper glucocorticoid therapy and suppression of excessive adrenal androgen production, onset of puberty usually occurs at the appropriate chronologic age. However, exceptions occur even among individuals in whom the disease is well controlled [Trinh et al 2007].
It should be noted that in some previously untreated children, the start of glucocorticoid replacement therapy triggers true precocious puberty. This central precocious puberty may occur when glucocorticoid treatment releases the hypothalamic pituitary axis from inhibition by estrogens derived from excess adrenal androgen secretion.
Fertility. For most females who are adequately treated, menses are normal after menarche and pregnancy is possible [Lo et al 1999]. Overall fertility rates, however, are reported to be low. Reported reasons include inadequate vaginal introitus leading to unsatisfactory intercourse, pain with vaginal penetration [Gastaud et al 2007], elevated androgens leading to ovarian dysfunction, and psychosexual behaviors around gender identity and selection of sexual partner(s). Chronic anovulation, elevated progestin levels, and aberrant endometrial implantation have also been identified as reasons for subfertility [Witchel 2012].
In males, the main cause of subfertility is the presence of testicular adrenal rest tumors, which are thought to originate from aberrant adrenal tissue. In addition, hypogonadotropic hypogonadism may result from suppression of LH secretion by the pituitary by excessive adrenal androgens and their aromatization products [Ogilvie et al 2006a].
Adrenal medulla. In individuals with classic 21-OHD CAH, deficiency of cortisol also affects the development and functioning of the adrenal medulla, resulting in lower epinephrine and metanephrine concentrations than those found in unaffected individuals [Merke et al 2000].
Classic salt-wasting 21-OHD CAH. When the loss of 21-hydroxylase function is severe, adrenal aldosterone secretion is insufficient for sodium reabsorption by the distal renal tubules, resulting in salt wasting as well as cortisol deficiency and androgen excess. Infants with renal salt wasting have poor feeding, weight loss, failure to thrive, vomiting, dehydration, hypotension, hyponatremia, and hyperkalemic metabolic acidosis progressing to adrenal crisis (azotemia, vascular collapse, shock, and death). Adrenal crisis can occur as early as age one to four weeks.
Affected males who are not detected in a newborn screening program are at high risk for a salt-wasting adrenal crisis because their normal male genitalia do not alert medical professionals to their condition; they are often discharged from the hospital after birth without diagnosis and experience a salt-wasting crisis at home. Conversely, the ambiguous genitalia of females with the salt-wasting form usually prompts early diagnosis and treatment.
Although an overt salt-wasting crisis classifies the child as a salt waster, some degree of aldosterone deficiency, determined by the adrenal capacity to produce aldosterone in response to renin stimulation, was found in all forms of 21-OHD CAH [Nimkarn et al 2007].
#### Non-Classic 21-OHD CAH
Non-classic 21-OHD CAH may present at any time postnatally, with symptoms of androgen excess including acne, premature development of pubic hair, accelerated growth, advanced bone age, and as in classic 21-OHD CAH, reduced adult stature as a result of premature epiphyseal fusion [New 2006]. The mildly reduced synthesis of cortisol observed in individuals with non-classic 21-OHD CAH is not clinically significant.
Females with non-classic 21-OHD CAH. It is difficult to predict which affected women will show signs of virilization [Kashimada et al 2008]. Females with non-classic 21-OHD CAH are born with normal genitalia; postnatal symptoms may include hirsutism, frontal baldness, delayed menarche, menstrual irregularities, and infertility. Approximately 60% of adult women with non-classic 21-OHD CAH have hirsutism only; approximately 10% have hirsutism and a menstrual disorder; and approximately 10% have a menstrual disorder only. Many women with non-classic 21-OHD CAH develop polycystic ovaries. Non-classic 21-OHD CAH was identified in 2.2%-10% of women with hyper-androgenism [New 2006, Escobar-Morreale et al 2008, Fanta et al 2008]. The fertility rate among untreated women is reported to be 50% [Pang 1997].
Males with non-classic 21-OHD CAH. Little has been published about males with non-classic 21-OHD CAH. They may have early beard growth and an enlarged phallus with relatively small testes. Typically, they do not have impaired gonadal function; they tend to have normal sperm counts [New 2006]. Bilateral adrenocortical incidentoma was reported as the sole finding in an adult male with non-classic CAH [Nigawara et al 2008].
Gender role behavior. Prenatal androgen exposure in females with classic forms of 21-OHD CAH has a virilizing effect on the external genitalia and childhood behavior. Changes in childhood play behavior correlated with reduced female gender satisfaction and reduced heterosexual interest in adulthood. Affected adult females are more likely to have gender dysphoria, and experience less heterosexual interest and reduced satisfaction with the assignment to the female sex. Prenatal androgen exposure correlates with a decrease in self-reported femininity by adult females, but not an increase in self-reported masculinity by adult females [Long et al 2004].
The rates of bisexual and homosexual orientation, which were increased in women with all forms of 21-OHD CAH, were found to correlate with the degree of prenatal androgenization. Bisexual/homosexual orientation was correlated with global measures of masculinization of nonsexual behavior and predicted independently by the degree of both prenatal androgenization and masculinization of childhood behavior [Meyer-Bahlburg et al 2008].
In contrast, males with 21-OHD CAH do not show a general alteration in childhood play behavior, core gender identity, or sexual orientation [Hines et al 2004].
Pathogenesis. When the function of 21-hydroxylating cytochrome 450 is inadequate, the cortisol production pathway is blocked, leading to the accumulation of 17-hydroxyprogesterone (17-OHP). The excess 17-OHP is shunted into the intact androgen pathway where the 17,20-lyase enzyme converts the 17-OHP to Δ4-androstenedione, which is converted into androgens. Since the mineralocorticoid pathway requires minimal 21-hydroxylase activity, mineralocorticoid deficiency (salt wasting) is a feature of the most severe form of the disease.
The lack of steroid product impairs the negative feedback control of adrenocorticotropin (ACTH) secretion from the pituitary, leading to chronic stimulation of the adrenal cortex by ACTH, resulting in adrenal hyperplasia.
### Genotype-Phenotype Correlations
A study by New et al [2013] that included the largest cohort of individuals with 21-OHD CAH demonstrated that the predictability of phenotype was less certain than previously thought. A direct genotype-phenotype correlation was found in approximately 50% of genotypes. The most unreliable predictions occurred in the simple virilizing form, where a wide phenotypic variety was observed with the same genotype. However, a strong correlation was noted for some genotypes that were exclusively found in salt-wasting and non-classic forms. For example, the Val281Leu pathogenic variant is exclusively associated with the non-classic form. In individuals with this form, the phenotype reflected the pathogenic variant with the less severe phenotypic effect of the two alleles.
Alleles can be grouped as severe or mild, based on residual enzyme activity (Table 4).
* Salt-wasting 21-OHD CAH usually has the most severe pathogenic variants (e.g., homozygous deletions).
* Non-classic 21-OHD CAH usually has one mild allele or both mild alleles.
In the context of prenatal diagnosis, it is important to distinguish classic and non-classic genotypes in order to determine the need to offer prenatal treatment.
* In families in which the proband is a virilized female, predicting the risk of genital virilization in subsequent affected female fetuses is feasible.
* In families in which the proband is a male, predicting the risk of genital virilization in subsequent affected female fetuses based on genotype is less reliable.
Classic 21-OHD CAH. The genotype for the classic form of 21-OHD CAH is predicted to be a severe pathogenic variant on both CYP21A2 alleles, with completely abolished enzyme activity determined by in vitro expression studies.
Note: The single-nucleotide variants c.293-13A>G or c.293-13C>G, among the most frequent pathogenic variants in classic 21-OHD CAH, cause premature splicing of the intron and a shift in the translational reading frame. Although most individuals (>90%) who are homozygous for one of these pathogenic variants have salt-wasting 21-OHD CAH, variation in severity of salt wasting is observed. This genotype-phenotype non-concordance can be explained by increased alternate splicing that can occur when the normal splicing is abolished by the splice site variant, allowing some protein production but with variable activity [Higashi et al 1988].
Among affected individuals who were compound heterozygotes for the pathogenic single-nucleotide variant p.Ile173Asn and a second severe variant, 76% had the simple virilizing phenotype while 23% had the salt wasting phenotype [New et al 2013]. It is postulated that subtle variations in transcription regulation or downstream protein translation may account for reduced 21-OH enzyme activity.
Non-classic 21-OHD CAH. Individuals with non-classic CAH are predicted to have two mild variants or one mild and one severe variant. Approximately two-thirds of individuals with non-classic 21-OHD CAH are compound heterozygotes. Pathogenic missense variants p.Pro31Leu in exon 1 and p.Val282Leu in exon 7 reduce enzyme activity and are generally associated with this form of the disease. However, variation in the phenotype associated with one mild variant can be observed:
* In a small number (<3%) of affected individuals with the p.Val282Leu or p.Pro31Leu pathogenic variant and a severe variant, the classic phenotype was observed when a non-classic phenotype was expected.
* In a very small percentage of affected individuals with the p.Ile173Asn pathogenic variant and a severe variant, the non-classic phenotype (rather than the expected classic phenotype) was observed [Stikkelbroeck et al 2003].
### Table 4.
Grouping of Common CYP21A2 Pathogenic Variants by Residual Enzyme Activity
View in own window
Enzyme ActivityPhenotypeCYP21A2 Pathogenic Variant
0%Severe
(classic)Whole-gene deletion (null variant)
Large-gene conversion
p.Gly111ValfsTer21
p.[Ile237Asn;Val238Glu;Met240Lys]
p.Leu308PhefsTer6
p.Gln319Ter
p.Arg357Trp
<1% 1c.293-13A>G
c.293C>G
2%-11%p.Ile173Asn
~20%-50%Mild (non-classic)p.Pro31Leu
p.Val282Leu
p.Pro454Ser
From Krone et al [2000]
1\.
Minimal residual activity
Contiguous gene deletion. A contiguous gene deletion involving CYP21A2 and TNX led to a combination of Ehler-Danlos syndrome, hypermobility type and 21-OHD CAH [Burch et al 1997, Schalkwijk et al 2001].
### Nomenclature
Terms used in the past for 21-OHD CAH include adrenogenital syndrome (AG syndrome) and congenital adrenocortical hyperplasia.
The non-classic form of 21-OHD CAH was previously referred to as the "attenuated" or "late-onset" form.
The salt-wasting form of 21-OHD CAH has also been called "salt-losing CAH."
### Prevalence
Classic 21-OHD CAH. Analysis of data from almost 6.5 million newborns screened in different populations worldwide has demonstrated an overall incidence of 1:15,000 live births for the classic form of 21-OHD [van der Kamp & Wit 2004].
Prevalence in specific populations:
* 1:300 in Yup'ik Eskimos of Alaska
* 1:5,000 in Saudi Arabia
* 1:10,000-1:16,000 in Europe and North America
* 1:21,000 in Japan
* 1:23,000 in New Zealand
Non-classic 21-OHD CAH. The prevalence of non-classic 21-OHD CAH in the general heterogeneous population of New York City was estimated at 1:100. The highest ethnic-specific non-classic disease prevalence (1:27) is found among Ashkenazi Jews. Other ethnic groups exhibiting high non-classic disease prevalence are: Hispanics (1:40), Slavs (1:50), and Italians (1:300) [Speiser et al 1985].
## Differential Diagnosis
The production of cortisol in the zona fasciculata of the adrenal cortex occurs in five major enzyme-mediated steps. Congenital adrenal hyperplasia (CAH) results from deficiency in any one of these enzymes; impaired cortisol synthesis leads to chronic elevations of ACTH and overstimulation of the adrenal cortex resulting in hyperplasia. The five forms of CAH are summarized in Table 5. Impaired enzyme function at each step of adrenal cortisol biosynthesis leads to a unique combination of retained precursors and deficient products. The most common enzyme deficiency, accounting for more than 90% of all CAH, is 21-hydroxylase deficiency (21-OHD).
### Table 5.
Enzyme Deficiencies Resulting in CAH
View in own window
% of CAHDeficient EnzymeSubstrateProductAndrogenMineralo-corticoid
Unknown 1Steroidogenic acute regulatory protein (STAR)\--Mediates cholesterol transport across mitochondrial membraneDeficiency 2Deficiency 3
Unknown 13β-hydroxysteroid dehydrogenase (3β-HSD)Pregnenolone,
17-OH pregnenolone,
DHEAProgesterone,
17-OHP,
Δ 4-androstenedioneDeficiency 2Deficiency 3
Unknown 117α-hydroxylasePregnenolone17-OH pregnenoloneDeficiency 2Excess 4
Progesterone17-OH (17-OHP)
>90%21-hydroxylaseProgesteroneDeoxycorticosterone (DOC)Excess 5Deficiency 3
17-hydroxy progesterone11-deoxycortisol
5%11β-hydroxylaseDeoxycorticosteroneCorticosteroneExcess 5Excess 4
1\.
Unknown because of rarity of disease
2\.
Males undervirilized at birth
3\.
Associated with salt wasting
4\.
Associated with hypertension
5\.
Females virilized at birth or later
Non-classic 21-OHD CAH should be considered in females who present with any of the variable hyperandrogenic symptoms. A general occurrence rate of 1%-3% is reported in females with hyperandrogenism, but in certain populations the prevalence is much higher.
Cytochrome P450 oxidoreductase deficiency. A rare form of CAH not included in Table 5 is cytochrome P450 oxidoreductase deficiency, caused by mutation of POR. Urinary steroid excretion indicates an apparent combined partial deficiency of the two steroidogenic enzymes P450C17 (17-hydroxylase) and P450C21 (21-hydroxylase). Of note, cytochrome P450 oxidoreductase is important in the electron transfer from NADPH to both enzymes.
The phenotypic spectrum of cytochrome P450 oxidoreductase deficiency ranges from isolated steroid abnormalities to classic Antley-Bixler syndrome (ABS). Individuals with POR deficiency have cortisol deficiency, ranging from clinically insignificant to life threatening. Newborn males have ambiguous genitalia, including small penis and undescended testes; newborn females have vaginal atresia, fused labia minora, hypoplastic labia majora, and/or large clitoris. Craniofacial features of ABS, at the most severe end of the POR spectrum, can include craniosynostosis, choanal stenosis or atresia, stenotic external auditory canals, and hydrocephalus. Skeletal anomalies can include radiohumeral synostosis, neonatal fractures, congenital bowing of the long bones, camptodactyly, joint contractures, arachnodactyly, and clubfeet. Inheritance is autosomal recessive.
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with 21-hydroxylase-deficient congenital adrenal hyperplasia (21-OHD CAH), the following evaluations are recommended:
To assess for salt wasting
* Plasma renin activity (PRA)
* Serum electrolytes
To distinguish classic from non-classic forms of 21-OHD CAH
* Baseline 17-OHP, Δ4-androstenedione, cortisol, and aldosterone
* ACTH stimulation test to compare stimulated concentration of 17-OHP to the baseline level
To assess the degree of prenatal virilization in females
* Careful physical examination of the external genitalia and its orifices
* Vaginogram to assess the anatomy of urethra and vagina
To assess the degree of postnatal virilization in both males and females
* Bone maturation assessment by bone age
* Serum concentration of adrenal androgens (unconjugated dehydroepiandrosterone [DHEA], Δ4-androstenedione, and testosterone)
Consultation with a clinical geneticist and/or genetic counselor is recommended for those individuals with a new diagnosis of 21-OHD CAH.
### Treatment of Manifestations
Clinical practice guidelines for the treatment of individuals with congenital adrenal hyperplasia due to 21-hydroxylase deficiency have been published [Speiser et al 2010] (full text).
It is imperative to make the diagnosis of 21-OHD CAH as quickly as possible in order to initiate therapy and arrest the effects of cortisol deficiency and mineralocorticoid deficiency, if present.
A multidisciplinary team of specialists in pediatric endocrinology, pediatric urology/surgery, clinical genetics, and psychology is essential for the diagnosis and management of the individual with ambiguous genitalia [Hughes et al 2006]. A pioneer project of CAH comprehensive care centers was implemented [Auchus et al 2010]. Two CAH comprehensive care centers which can provide multidisciplinary care from diagnosis through all stages of growth and development have been designated in the United States.
#### Classic 21-OHD CAH
Glucocorticoid replacement therapy. The goal of glucocorticoid replacement therapy is to replace deficient steroids, minimize adrenal sex hormone and glucocorticoid excess, prevent virilization, optimize growth, and promote fertility [Clayton et al 2002].
* Hydrocortisone in tablet form is the treatment of choice in growing children. The use of oral hydrocortisone suspension is discouraged. Treatment for CAH principally involves glucocorticoid replacement therapy, usually in the form of hydrocortisone (10-15 mg/m2/24 hours) given orally in two or three daily divided doses [New et al 2013]. Glucocorticoid therapy for children involves balancing suppression of adrenal androgen secretion against iatrogenic Cushing's syndrome in order to maintain a normal linear growth rate and normal bone maturation.
Note: Overtreatment with glucocorticosteroids can result in cushingoid features and should be avoided. It often occurs when serum concentration of 17-OHP is reduced to the physiologic range for age. An acceptable range for serum concentration of 17-OHP in the treated individual is higher (100-1,000 ng/dL) than normal, provided androgens are maintained in an appropriate range for gender and pubertal status.
* During periods of stress (e.g., surgery, febrile illness, shock, major trauma), all individuals with classic 21-OHD CAH require increased amounts of glucocorticoids. Typically, two to three times the normal dose is administered orally or by intramuscular injection when oral intake is not tolerated.
* Affected individuals should carry medical information regarding emergency steroid dosing.
* Individuals with classic 21-OHD CAH require lifelong administration of glucocorticoids. After linear growth is complete, more potent glucocorticoids (e.g., prednisone and dexamethasone) that tend to suppress growth in childhood can be used.
Mineralocorticoid replacement therapy. Treatment with 9α-fludrohydrocortisone (Florinef®) (0.05-0.2 mg/day orally) and sodium chloride (1-2 g/day added to formula or foods) is necessary in individuals with the salt-wasting form of 21-OHD CAH.
* All individuals with the classic form should be treated with both 9α-fludrohydrocortisone and sodium chloride supplement in the newborn period and early infancy [Speiser et al 2010].
* Sodium chloride supplementation may not be necessary after infancy; the amount of mineralocorticoid required daily may likewise decrease with age.
Feminizing genitoplasty. Per the 2006 joint LWPES/ESPE (Lawson Wilkins Pediatric Endocrine Society/European Society for Paediatric Endocrinology) consensus statement [Lee et al 2006]:
"Surgery should only be considered in cases of severe virilization (Prader III-V) and be performed in conjunction, when appropriate, with repair of the common urogenital sinus. Because orgasmic function and erectile sensation may be disturbed by clitoral surgery, the surgical procedure should be anatomically based to preserve erectile function and the innervation of the clitoris. Emphasis is on functional outcome rather than a strictly cosmetic appearance. It is generally felt that surgery that is performed for cosmetic reasons in the first year of life relieves parental distress and improves attachment between the child and the parents; the systematic evidence for this belief is lacking."
The Endocrine Society clinical practice guidelines [Speiser et al 2010] (full text) state:
"[C]litoral and perineal reconstruction [should] be considered in infancy and performed by an experienced surgeon in a center with similarly experienced pediatric endocrinologists, mental health professionals, and social work services."
* Although there are no randomized controlled studies of either the best age or the best methods for feminizing surgery, the recommended procedures are neurovascular-sparing clitoroplasty and vaginoplasty using total or partial urogenital mobilization.
* When necessary, vaginoplasty is usually performed in late adolescence because routine vaginal dilation is required to maintain a patent vagina.
Precocious puberty. The true precocious puberty that may occur in 21-OHD CAH can be treated with analogs of luteinizing hormone-releasing hormone (LHRH).
Testicular adrenal rest tumors. Response of testicular adrenal rest tumors to intensified glucocorticoid treatment may decrease the tumor size and improve testicular function [Bachelot et al 2008]. Testis-sparing surgery is considered in males who fail medical treatment, but the outcome has not been favorable, perhaps because of long-standing obstruction of the tubules [Claahsen-van der Grinten et al 2008]. Assistive reproductive technologies (ART) may also be considered to achieve fertility [Sugino et al 2006].
Transition from adolescence to adulthood. Improved care for individuals with 21-OHD CAH has resulted in a good prognosis and normal life expectancy. However, a prospective cross-sectional study of adults with 21-OHD CAH in the UK showed the following [Arlt et al 2010]:
* Affected individuals were significantly shorter and had a higher body mass index.
* Women with classic CAH had increased diastolic blood pressure.
* Metabolic abnormalities were common among studied individuals, and included obesity (41%), hypercholesterolemia (46%), insulin resistance (29%), osteopenia (40%), and osteoporosis (7%). Subjective health status was significantly impaired and fertility compromised.
Transition of pediatric individuals to medical care in the adult setting is an important step to ensure optimal lifelong treatment, aiming to achieve good health with a normal life expectancy and quality of life [Reisch et al 2011].
* Care for adults with CAH requires a multidisciplinary approach, including psychological support by specialists [Ogilvie et al 2006a].
Adrenalectomy. Bilateral adrenalectomy has been reported as a treatment of individuals with severe 21-OHD CAH who are homozygous for a null variant and who have a history of poor control with hormone replacement therapy [Van Wyk et al 1996, Meyers & Grua 2000]. It is thought that these individuals may be more successfully treated as individuals with Addison disease; however, compliance with the medication regimen postoperatively is exceedingly important. Thus, bilateral adrenalectomy can be considered only in selected individuals who have failed medical therapy; the risk for non-compliance must be considered before surgery [Speiser et al 2010].
Only small series of adults undergoing adrenalectomy have been reported (see review in Bachelot et al [2008]), the largest of which included five persons [Ogilvie et al 2006b]. The three main indications for adrenalectomy were: infertility, virilization, and obesity. Improvements in all three areas were noted in all reported individuals. More long-term data are needed to determine the outcome of those undergoing adrenalectomy, since the potential increase in ACTH postoperatively can worsen adrenal rest tissues.
#### Non-Classic 21-OHD CAH
Individuals with non-classic 21-OHD CAH do not always require treatment. Many are asymptomatic throughout their lives, or symptoms may develop during puberty, after puberty, or post partum.
* The hyperandrogenic symptoms that require treatment include advanced bone age, early pubic hair, precocious puberty, tall stature, and early arrest of growth in children; infertility, cystic acne, and short stature in both adult males and females; hirsutism, frontal balding, polycystic ovaries, and irregular menstrual periods in females; and testicular adrenal rest tissue in males [New 2006].
* In previously treated individuals, an option of discontinuing therapy when symptoms resolve should be offered [Speiser et al 2010].
Traditionally, individuals with non-classic 21-OHD CAH have been treated with lower amounts of glucocorticoid than those required for individuals with classic 21-OHD CAH.
### Prevention of Primary Manifestations
Salt-wasting crisis. Newborn screening programs aim to identify infants with classic 21-OHD CAH in order to initiate glucocorticoid and mineralocorticoid treatment prior to a potentially life-threatening salt-wasting crisis.
See Treatment of Manifestations, Glucocorticoid replacement therapy and Mineralocorticoid replacement therapy.
### Prevention of Secondary Complications
Short stature. Short stature may result from glucocorticoid-induced growth suppression caused by over-treatment with glucocorticoids or from advanced skeletal maturation caused by inadequate glucocorticoid treatment. Evidence derived from observational studies suggests that the final height of individuals with CAH treated with glucocorticoids is lower than the population norm and lower than expected given parental height [Muthusamy et al 2010]. See Therapies Under Investigation for a discussion of treatment of short stature in individuals with CAH.
### Surveillance
The following evaluations should be performed every three to four months when children are actively growing. Evaluation may be less often thereafter. The frequency of evaluation should vary depending on individual needs [Speiser et al 2010].
Efficacy of glucocorticoid replacement therapy is monitored by measurement of the following:
* Early-morning serum concentrations of 17-OHP, Δ4-androstenedione, and testosterone approximately every three months during infancy and every three to six months thereafter. (In some instances, measurement of urinary pregnantriols and 17 ketosteroids in a 24-hour urine sample may help assess hormonal control. However, the process of urine collection makes it less practical than a simple blood draw.)
* Linear growth, weight gain, pubertal development, and clinical signs of cortisol and androgen excess
* Bone age to assess osseous maturation (at 6- to 12-month intervals)
Efficacy of mineralocorticoid replacement therapy is monitored by measurement of the following:
* Blood pressure
* Early morning plasma renin activity or direct renin assay in a controlled position (usually upright)
Monitoring for testicular abnormalities in males. Periodic imaging of the testes either by ultrasonography or MRI should begin after puberty and be repeated every three to five years.
Monitoring fertility and metabolic risks in adults. In affected adults, periodic measurements and/or monitoring of the following should be performed:
* Fecundity and fertility
* Weight
* Lipid profile
* Blood pressure
* Bone mineral density
Imaging studies. No routine adrenal imaging or bone mineral density is recommended [Speiser et al 2010].
### Agents/Circumstances to Avoid
Physical stress such as febrile illness, gastroenteritis with dehydration, surgery accompanied by general anesthesia, and major trauma can precipitate an adrenal crisis in individuals with classic CAH. Increased doses of glucocorticoids are recommended in these situations.
### Evaluation of Relatives at Risk
If prenatal testing for 21-OHD CAH has not been performed, it is appropriate to evaluate newborn sibs of a proband in order to facilitate early diagnosis and treatment.
* Serum 17-OHP concentration should be measured in addition to newborn screening.
* Molecular genetic testing is indicated if the pathogenic variants in the family are known.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Pregnancy Management
Pregnant females with classic 21-OHD CAH. Pregnant females who have classic salt-wasting 21-OHD CAH need to be monitored closely by an endocrinologist during pregnancy. Maintenance doses of glucocorticoid and mineralocorticoid usually need to be increased because adrenal androgens tend to increase during pregnancy. Despite excess production of maternal adrenal androgens, the genitalia of their female fetuses are not virilized [Lo et al 1999].
### Therapies Under Investigation
Affected female fetus with genital ambiguity. Through molecular genetic testing of fetal DNA, defects in 21-OHD CAH synthesis can be diagnosed in utero. Genital ambiguity in female fetuses may be reduced or eliminated by suppressing fetal androgen production through administration of dexamethasone to the mother beginning early in gestation and continuing until delivery. Prenatal treatment should continue to be considered experimental and should only be used within the context of a formal IRB-approved clinical trial. Noninvasive prenatal diagnostic methods for earlier diagnosis of affected female fetuses have been developed and may eliminate the unnecessary prenatal treatment of males and unaffected females [New et al 2014, Tardy-Guidollet et al 2014].
Treatment of short stature. Injections of human growth hormone alone or in combination with gonadotropin-releasing hormone (GnRH) may be used to improve height prognosis in individuals with 21-OHD CAH who have significant growth failure [Lin-Su et al 2011]. Aromatase inhibitors to slow bone age advancement have been used. However, these approaches are considered experimental treatment and should not be used outside of formally approved clinical trials [Speiser et al 2010].
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[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
| 21-Hydroxylase-Deficient Congenital Adrenal Hyperplasia | None | 4,406 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1171/ | 2021-01-18T21:45:42 | {"synonyms": ["21-OHD CAH", "Virilizing Adrenal Hyperplasia"]} |
A rare infectious disease caused by the Gram-negative bacillus Burkholderia (pseudomonas) pseudomallei, also called Whitmore bacillus. The infection can be acute, subacute, or chronic and affects the skin, the lungs, or the whole body.
## Epidemiology
The disease is endemic in Southeast Asia and North Australia but cases are seen across the tropics. A rising number of cases are being reported in Europe. Men are predominantly affected (sex ratio: 1.4:1).
## Clinical description
Melioidosis may occur in any age group, but is more frequent between 40 and 60 years of age. The incubation period varies from two days to months or years. The acute form of the disease is characterized by respiratory infections (necrotizing pneumonia) and septicemia (with high fever, severe headaches, diarrhea, vomiting, skin lesions, and abscesses). The subacute and chronic forms are characterized by local abscesses and suppurative lesions, most commonly affecting the lung (tuberculosis-like lesions), liver, intestine, and spleen, as well as the skin, lymph nodes, brain and bones.
## Etiology
.Melioidosis is caused by Burkholderia pseudomallei, an environmental saprophyte found in wet soil, mud, pooled surface water and rice paddies. Infection may occur through direct contact of skin abrasions, wounds and burns with contaminated soil or water, or through ingestion or inhalation. Diabetes, renal failure, thalassemia, and heavy alcohol consumption are often independent risk factors for melioidosis.
## Diagnostic methods
The diagnosis is based on analysis of cultures and identification of the pathogen. Other diagnostic methods include hemagglutination (IHA), direct immunofluorescence, enzyme-linked immunosorbent assays (ELISAs), complement fixation tests or PCR assays. These methods can also help to estimate the prevalence of the infection in a given population. Imaging exams are performed to assess the full extent of disease.
## Differential diagnosis
Differential diagnosis includes tuberculosis, pneumonia, and other infectious diseases such as plague, typhoid fever and syphilis.
## Management and treatment
The pathogen is sensitive to a range of antibiotics. Treatment consists of an intensive phase of at least two weeks with intravenous ceftazidime or meropenem (imipenem is also used) followed by a couple of months of oral antibiotics, e.g. with co-trimoxazole.
## Prognosis
Reported mortality varies between 15%-40% of cases depending on among others the resources available to treat patients across different regions in the world. Early recognition and adequate treatment is key. Relapses can occur.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Melioidosis | c0025229 | 4,407 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=31202 | 2021-01-23T17:44:24 | {"gard": ["9546"], "mesh": ["D008554"], "omim": ["615557"], "umls": ["C0025229"], "icd-10": ["A24.1", "A24.2", "A24.3", "A24.4"]} |
Kallmann syndrome (KS) is a developmental genetic disorder characterized by the association of congenital hypogonadotropic hypogonadism (CHH) due to gonadotropin-releasing hormone (GnRH) deficiency, and anosmia or hyposmia (with hypoplasia or aplasia of the olfactory bulbs).
## Epidemiology
The prevalence is estimated at 1/8,000 males and 1/40,000 females, but is probably underestimated.
## Clinical description
Most cases are diagnosed at the time of puberty due to lack of sexual development, but KS may also be suspected in infancy in males with cryptorchidism, micropenis or associated non reproductive signs. The main clinical features consist of the absence of complete spontaneous puberty and a partial or total impairment of the sense of smell (anosmia) in both sexes. Untreated adult males usually have decreased bone density and muscle mass, decreased testicular volume (< 4 mL), erectile dysfunction, diminished libido and infertility. Untreated adult females almost always experience primary amenorrhea with absent, little or normal breast development. Rare presentations include unilateral (occasionally bilateral and lethal at birth) renal agenesis, hearing impairment, cleft lip or palate, dental agenesis or bimanual synkinesis persisting beyond childhood.
## Etiology
KS is caused by impaired development of the olfactory system and disrupted embryonic migration of the GnRH-synthesizing neurons from the olfactory epithelium to the hypothalamic region of the brain. The majority of reported cases are sporadic but familial forms have been described. Causative genes include: KAL1 (Xp22.32), in the X-linked recessive form, FGFR1 (8p12), FGF8 (10q25-q26), CHD7 (8q12.2) and SOX10 (22q13.1) in the AD form, and PROKR2 (20p12.3) and PROK2 (3p21.1), in both the AR and oligogenic forms. More evidence is needed to determine if other genes (ex: SEMA3A), presumably involved in KS, are indeed causal.
## Diagnostic methods
Diagnostic methods consist of hormone evaluation (sex steroids, gonadal peptides and pituitary gonadotropin dosage), as well as evaluation of the sense of smell (olfactometry). Morphological analysis of the olfactory bulbs by MRI can be useful, especially in young children. Genetic testing can identify a disease causing mutation, and is mandatory before starting infertility treatment.
## Differential diagnosis
Differential diagnoses include isolated congenital gonadotropin deficiency and CHARGE syndrome (see these terms).
## Antenatal diagnosis
In a familial context of FGFR1, FGF8, KAL1, or CHD7 mutations, bone abnormalities, cleft lip/palate, renal agenesis, or multiple developmental defects can be found in the fetus by ultrasonography.
## Genetic counseling
Genetic counseling should be adapted to each family, taking into account the potential mode of inheritance (AD/AR, X-linked, or presumably oligogenic) and the great variability in clinical expression, even within the same family, as well as the risk, in sporadic cases, of neomutations.
## Management and treatment
Hormonal replacement therapy is used to induce puberty, and later, fertility. Testosterone esters are usually used and sometimes human chorionic gonadotropin (hCG) injections in combination with follicle-stimulating hormone (FSH) or in monotherapy are given to males to achieve normal virilization and increased testicular volume. In adults combined gonadotropin therapy is mandatory to stimulate spermatogenesis. In females, estrogen is administered to induce breast development and genital development along with progestin to establish endometrial cyclicity. Pulsatile GnRH administration or exogenous gonadotropins are used to induce folliculogenesis and ovulation and therefore to restore fertility. There is currently no treatment for anosmia.
## Prognosis
KS is not a life threatening disease. With hormonal treatment, pubertal feminization or virilization occurs in all patients. Fertility, when desired, is achieved in most cases but cryptorchidism has a poor prognosis in males.
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Kallmann syndrome | c0162809 | 4,408 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=478 | 2021-01-23T18:38:23 | {"gard": ["10771"], "mesh": ["D017436"], "omim": ["147950", "244200", "308700", "610628", "612370", "612702", "614837", "614838", "614840", "614858", "614880", "614897", "615266", "615267", "615269", "615270", "615271", "616030", "618841"], "umls": ["C0162809"], "icd-10": ["E23.0"], "synonyms": ["Congenital hypogonadotropic hypogonadism with anosmia", "Olfacto-genital pathological sequence"]} |
Chemotherapy-induced hyperpigmentation
SpecialtyDermatoogy
Chemotherapy-induced hyperpigmentation is caused by many chemotherapeutic agents (especially the antibiotics bleomycin, and daunorubicin) and the alkylating agents (cyclophosphamide and busulfan).[1]:132
## See also[edit]
* Skin lesion
## References[edit]
1. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
## External links[edit]
Classification
D
* ICD-10: Y43.1-Y43.3
* ICD-9-CM: E933.1
* v
* t
* e
Adverse drug reactions
Antibiotics
* Penicillin drug reaction
* Sulfonamide hypersensitivity syndrome
* Urticarial erythema multiforme
* Adverse effects of fluoroquinolones
* Red man syndrome
* Jarisch–Herxheimer reaction
Hormones
* Steroid acne
* Steroid folliculitis
Chemotherapy
* Chemotherapy-induced acral erythema
* Chemotherapy-induced hyperpigmentation
* Scleroderma-like reaction to taxanes
* Hydroxyurea dermopathy
* Exudative hyponychial dermatitis
Anticoagulants
* Anticoagulant-induced skin necrosis
* Warfarin necrosis
* Vitamin K reaction
* Texier's disease
Immunologics
* Adverse reaction to biologic agents
* Leukotriene receptor antagonist-associated Churg–Strauss syndrome
* Methotrexate-induced papular eruption
* Adverse reaction to cytokines
Other drugs
* Anticonvulsant hypersensitivity syndrome
* Allopurinol hypersensitivity syndrome
* Vaccine adverse event
* Eczema vaccinatum
* Bromoderma
* Halogenoderma
* Iododerma
General
Skin and body membranes
* Acute generalized exanthematous pustulosis
* Bullous drug reaction
* Drug-induced acne
* Drug-induced angioedema
* Drug-related gingival hyperplasia
* Drug-induced lichenoid reaction
* Drug-induced lupus erythematosus
* Drug-induced nail changes
* Drug-induced pigmentation
* Drug-induced urticaria
* Stevens–Johnson syndrome
* Injection site reaction
* Linear IgA bullous dermatosis
* Toxic epidermal necrolysis
* HIV disease-related drug reaction
* Photosensitive drug reaction
Other
* Drug-induced pseudolymphoma
* Fixed drug reaction
* Serum sickness-like reaction
This cutaneous condition article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Chemotherapy-induced hyperpigmentation | None | 4,409 | wikipedia | https://en.wikipedia.org/wiki/Chemotherapy-induced_hyperpigmentation | 2021-01-18T18:42:39 | {"icd-9": ["E933.1"], "icd-10": ["Y43.3", "Y43.1"], "wikidata": ["Q5090628"]} |
A number sign (#) is used with this entry because mucopolysaccharidosis type VII (MPS7) is caused by homozygous or compound heterozygous mutation in the gene encoding beta-glucuronidase (GUSB; 611499) on chromosome 7q11.
Description
Mucopolysaccharidosis type VII is an autosomal recessive lysosomal storage disease characterized by the inability to degrade glucuronic acid-containing glycosaminoglycans. The phenotype is highly variable, ranging from severe lethal hydrops fetalis to mild forms with survival into adulthood. Most patients with the intermediate phenotype show hepatomegaly, skeletal anomalies, coarse facies, and variable degrees of mental impairment (Shipley et al., 1993). MPS VII was the first autosomal mucopolysaccharidosis for which chromosomal assignment was achieved.
Clinical Features
Sly et al. (1973) reported a boy with skeletal changes consistent with a mucopolysaccharidosis, hepatosplenomegaly, and granular inclusions in granulocytes. He had hernias, unusual facies, protruding sternum, thoracolumbar gibbus, vertebral deformities, and mental deficiency. Fibroblasts demonstrated deficiency of beta-glucuronidase activity, at less than 2% of control values. Both parents and several sibs of the mother showed an intermediate level of the enzyme. Shipley et al. (1993) provided follow-up of the patient reported by Sly et al. (1973). Additional features included cardiac valvular anomalies and progressive skeletal deformities of the thorax, spine, hip, and knee joints. He died suddenly at age 19 years, possibly of a cardiac arrhythmia.
Gitzelmann et al. (1978) described 2 brothers in whom MPS VII was unusually mild. Asymptomatic thoracic kyphosis and mild scoliosis were the main clinical features. Hernia, hepatosplenomegaly, corneal clouding, and dwarfing were absent. Radiologic signs were mild, confined to the spine, and consisted of irregularities of upper and lower vertebral plates, of vertebral flattening and some osteophytic changes. Both patients excreted excessive amounts of acid mucopolysaccharides in urine. Both had granulations in polymorphonuclear cells and to a lesser degree in monocytes. Cultured skin fibroblasts also had metachromatic granules; they showed about 10% of normal beta-glucuronidase activity. The older brother, aged 19 years, was the oldest known case.
Sewell et al. (1982) reported a 6-year-old Turkish girl with MPS VII who presented in infancy with facial asymmetry, deformed feet, and delayed motor development. At age 5 years, she had disproportionate dwarfism, sternal protrusion, kyphosis, scoliosis, and hypertrichosis. She had a small umbilical hernia and mild liver enlargement. Motor function was normal, but speech was delayed. Radiographic examination showed widening of the iliac wings and broad ribs. Beta-glucuronidase activity in serum was essentially absent, but was 5.6% of control values in cultured fibroblasts. In a review of reported cases, Sewell et al. (1982) suggested that MPS VII comprises 3 main clinical groups: an early severe lethal form (Beaudet et al., 1975); an 'intermediate' form with slight organomegaly and moderate skeletal anomalies (the patient reported by Sewell et al., 1982); and a very mild form in which patients present later and show longer survival (Gitzelmann et al., 1978).
Pfeiffer et al. (1977) reported a girl with a mild form of MPS VII. Storch et al. (2003) provided a detailed clinical follow-up of this girl. The disorder was first diagnosed at the age of 7 years based on the clinical features of short stature, mild craniofacial dysmorphism, corneal opacity, a broad-based gait, and mild mental retardation. X-ray evaluation showed signs of dysostosis multiplex. Urinary excretion of total glycosaminoglycans was increased and consisted of dermatan, chondroitin, and heparan sulfate. Decreased beta-glucuronidase activity was found in serum, lymphocytes, and cultured skin fibroblasts. The patient completed her schooling for the mentally retarded and worked in her parents' business as a switchboard operator. By the age of 34 years, spasticity, especially of the upper limbs, had increased. Cervical MRI and CT scans showed a dense pseudoarthrosis with odontoid dysplasia, a hypoplastic atlantal arch, and narrowed intervertebral foramina in segments C2-C4. Anterior, and especially posterior, ligamentous structures in segments C1-C3 were thickened and caused spinal cord compression with central signal hypodensities. Surgical relief of the spinal cord compression was performed. At the age of 37 years, the patient was 146 cm tall and showed macrocephaly, mild facial dysmorphism, macroglossia, and prognathia. Corneal opacity was mild and had not progressed since the age of 5 years; hearing was normal. She also had sternal protrusion, thoracolumbar scoliosis, lumbar lordosis, and contractions of the large joints. Neurologic examination showed spastic tetraplegia with hyperactive deep tendon reflexes and positive Babinski signs. The patient died unexpectedly at the age of 37 years, presumably as a consequence of cardiac arrest. In this patient, Storch et al. (2003) identified compound heterozygosity for 2 mutations in the GUSB gene (611499.0013; 611499.0014).
Stangenberg et al. (1992) and de Kremer et al. (1992) described phenotypic extremes in beta-glucuronidase deficiency: a case with fetal hydrops presenting at 18 weeks' gestation and a chronic oligosymptomatic variant in a 20-year-old male with severe skeletal dysplasia, respectively. In the former case the parents were first cousins and there had been 2 previous similar fetal deaths. In the latter case there was no hepatosplenomegaly, hernia, corneal clouding, or neurologic abnormalities. Although the patient had Alder-type granulations in his polymorphonuclear leukocytes, the urine did not contain a significant excess of mucopolysaccharides. The most striking changes of spondyloepiphyseal dysplasia were in the thoracic spine, with flattening and collapse in T7, T8, and T10 vertebral bodies, and in the femoral capital epiphyses, which showed irregularities and fragmentation.
Walter-Nicolet et al. (2003) described a 1-year-old Algerian girl with MPS VII, born to consanguineous parents, who presented with nonimmune hydrops fetalis. She had facial dysmorphism, hepatosplenomegaly, and hypertrophic cardiomyopathy. The mother, aged 27, had experienced 2 unexplained spontaneous abortions at 18 and 12 weeks of gestation. Hydrops fetalis was discovered at 20 weeks' gestation with ascites, bilateral pleural effusion, and hydramnios. Brain ultrasound scan showed a moderate bilateral hydrocephalus confirmed by cerebral MRI. Clinical features noted at birth included facial dysmorphism with coarsened facies, hypertelorism, epicanthus, anti-mongoloid eyelids, short nose with anteversion of the nostrils; pterygium colli; and hepatosplenomegaly. Axial hypotonia and peripheral hypertonia were present. Echocardiography showed moderate hypertrophic cardiomyopathy. Brain ultrasound scan showed moderate ventricular dilatation at 9 and 11 mm with normal brain morphology. Skeletal radiography was normal.
Montano et al. (2016) collected clinical information on 56 patients from 11 countries with MPS VII in order to assess the phenotype. Ten patients had neonatal nonimmune hydrops fetalis (NIHF), 13 had an infantile or adolescent form of the disorder with a history of hydrops fetalis, and 33 had an infantile or adolescent form without known hydrops fetalis. Twenty (36%) were confirmed to have died. The patients had a wide range of clinical manifestations from mild to severe. Patients with mild or moderate manifestations had coarse facial features, corneal clouding, frequent upper respiratory infections, and milder skeletal abnormalities. Patients with more severe phenotypes showed short stature and greater skeletal dysplasia, macrocephaly, recurrent ear infections, gingival hypertrophy, hepatosplenomegaly, hernias, and cognitive impairment. Other common features included valvular heart disease, cardiomyopathy, and compromised respiratory function associated with recurrent infections and structural chest abnormalities. The presence of NIHF did not predict the severity of the disease course if the patient survived infancy. Five patients underwent bone marrow transplantation and 1 patient underwent enzyme replacement therapy with recombinant human GUS.
Biochemical Features
By immunoassay, Bell et al. (1977) identified cross-reactive antigen in cultured fibroblasts from 4 unrelated patients with deficiency of beta-glucuronidase activity. Titration patterns suggested allelic heterogeneity.
Diagnosis
### Prenatal Diagnosis
Lissens et al. (1991) described a case of beta-glucuronidase deficiency presenting as nonimmune hydrops fetalis diagnosed at 26 weeks of gestation. The deficiency was disclosed on cultured amniotic fluid cells and in fetal plasma and was confirmed post-abortion. In a second pregnancy, a normal beta-glucuronidase activity was found in extracts of chorionic villi obtained at 10 weeks of gestation.
Kagie et al. (1992) demonstrated beta-glucuronidase deficiency as a cause of hydrops fetalis by study of the amniotic fluid obtained at 25 weeks' gestation.
Van Eyndhoven et al. (1998) diagnosed beta-glucuronidase deficiency as the cause of nonimmune hydrops fetalis by enzymatic assay of chorionic villi. In their patient, hydrops fetalis had occurred in 2 previous pregnancies. Chorionic villus sampling performed in the eleventh week of the subsequent pregnancy indicated that the fetus was affected. After termination in the twelfth week, signs of early hydrops fetalis were observed.
Van Dorpe et al. (1996) described a family in which 3 consecutive fetuses were affected. Striking ascites and fetal hydrops were noted in the first fetus, and the pregnancy was terminated. Microscopic study revealed prominently vacuolated Hofbauer cells in the placenta and foamy macrophages in liver, spleen, bone marrow, and other organs. Greatly reduced activity of beta-glucuronidase in cultured skin fibroblasts confirmed the diagnosis of MPS VII. Edema of the neck and back in the next pregnancy led to a presumptive diagnosis of MPS VII, which was confirmed by the finding of very low enzyme activity in chorionic villus cells. The morphologic manifestations were the same in all 3 cases. Van Dorpe et al. (1996) emphasized the significance of morphologic examination of the fetus and placenta for the diagnosis of MPS VII.
Population Genetics
Khan et al. (2017) analyzed the epidemiology of the mucopolysaccharidoses in Japan and Switzerland and compared them to similar data from other countries. Data for Japan was collected between 1982 and 2009, and 467 cases with MPS were identified. The combined birth prevalence was 1.53 per 100,000 live births. The highest birth prevalence was 0.84 for MPS II (309900), accounting for 55% of all MPS. MPS I (see 607014), III (see 252900), and IV (see 253000) accounted for 15%, 16%, and 10%, respectively. MPS VI (253200) and VII were more rare and accounted for 1.7% and 1.3%, respectively. A retrospective epidemiologic data collection was performed in Switzerland between 1975 and 2008 (34 years), and 41 living MPS patients were identified. The combined birth prevalence was 1.56 per 100,000 live births. The highest birth prevalence was 0.46 for MPS II, accounting for 29% of all MPS. MPS I, III, and IV accounted for 12%, 24%, and 24%, respectively. As seen in the Japanese population, MPS VI and VII were more rare and accounted for 7.3% and 2.4%, respectively. The high birth prevalence of MPS II in Japan was comparable to that seen in other East Asian countries where this MPS accounted for approximately 50% of all forms of MPS. Birth prevalence was also similar in some European countries (Germany, Northern Ireland, Portugal and the Netherlands) although the prevalence of other forms of MPS was also reported to be higher in these countries.
Clinical Management
Yamada et al. (1998) reported that allogeneic bone marrow transplant in a 12-year-old Japanese girl with MPS VII resulted in improved motor function and activities of daily living, decreased upper respiratory and ear infections, but no improvement in cognitive function.
Molecular Genetics
In 2 unrelated Japanese patients with MPS VII, Tomatsu et al. (1991) identified 2 different homozygous mutations in the GUSB gene (611499.0001 and 611499.0002, respectively).
Using RT-PCR-SSCP and direct sequencing to screen for mutations in the GUSB cDNA, Vervoort et al. (1996) studied 17 MPS VII patients with hydrops fetalis or early and severe clinical presentation. In addition to 6 of 12 previously reported mutations, they detected 14 novel mutations. The mutations in hydropic fetuses were widely scattered in the GUSB gene. Analysis of 3 polymorphic sites in the mutant alleles allowed exclusion of identity by descent for some recurrent mutations.
Vervoort et al. (1997) identified 5 novel mutations in the GUSB gene in 5 MPS VII patients. Four patients presented with hydrops fetalis and 1 with an early infantile form of the disorder.
Tomatsu et al. (2002) stated that more than 45 different mutations in the GUSB gene had been identified in patients with MPS VII, approximately 90% of which were point mutations.
Animal Model
See 611499 for information on animal models of MPS VII.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature Other \- Postnatal growth deficiency HEAD & NECK Head \- Macrocephaly Face \- Coarse facies Ears \- Hearing loss Eyes \- Variable degree of corneal opacities \- Heavy eyebrows Mouth \- Enlarged tongue \- Widely spaced teeth \- Abnormal dentition \- Gingival hypertrophy Neck \- Short neck CARDIOVASCULAR Heart \- Valvular heart disease \- Cardiomyopathy RESPIRATORY \- Decreased pulmonary function \- Recurrent upper respiratory infections CHEST Ribs Sternum Clavicles & Scapulae \- Flaring of lower ribs \- Pectus carinatum \- Chest deformities ABDOMEN External Features \- Umbilical hernia \- Inguinal hernia Liver \- Hepatomegaly Spleen \- Splenomegaly SKELETAL \- Dysostosis multiplex Skull \- J-shaped sella turcica Spine \- Scoliosis \- Kyphosis \- Platyspondyly \- Thoracolumbar gibbus \- Odontoid hypoplasia \- Anterior beaking of lower thoracic and lumbar vertebrae Pelvis \- Acetabular dysplasia \- Narrow sciatic notches Limbs \- Joint contractures \- Genu valgum Hands \- Pointed proximal metacarpals Feet \- Metatarsus adductus \- Talipes equinovarus SKIN, NAILS, & HAIR Hair \- Hirsutism NEUROLOGIC Central Nervous System \- Mental retardation \- Poor speech \- Hydrocephalus \- Neurodegeneration PRENATAL MANIFESTATIONS \- Hydrops fetalis LABORATORY ABNORMALITIES \- Beta-glucuronidase deficiency in fibroblasts and leukocytes \- Dermatan and heparan sulfate excretion in urine \- Coarse metachromatic granules in white blood cells \- Chondroitin 4-, 6-sulfate excretion in urine MISCELLANEOUS \- Wide spectrum of severity MOLECULAR BASIS \- Caused by mutation in the beta-glucuronidase gene (GUSB, 611499.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| MUCOPOLYSACCHARIDOSIS, TYPE VII | c0085132 | 4,410 | omim | https://www.omim.org/entry/253220 | 2019-09-22T16:24:54 | {"doid": ["12803"], "mesh": ["D016538"], "omim": ["253220"], "icd-10": ["E76.29"], "orphanet": ["584"], "synonyms": ["Alternative titles", "MPS VII", "SLY SYNDROME", "BETA-GLUCURONIDASE DEFICIENCY", "GUSB DEFICIENCY"]} |
## Description
Cleft palate as an isolated malformation behaves as an entity distinct from cleft lip with or without cleft palate (see 119530).
Dominantly inherited cleft soft palate in 4 generations has been reported (Jenkins and Stady, 1980); see 119570.
Inheritance
Curtis et al. (1961) estimated that the risk of recurrence in subsequently born children is about 2% if 1 child has it, 6% if 1 parent has it, and 15% if 1 parent and 1 child have it. As for cleft lip with or without cleft palate, the genetics is apparently complex.
Shields et al. (1981) analyzed family data on 561 Danish probands with nonsyndromic isolated cleft palate and concluded that neither a multifactorial-threshold model nor a single major locus model is completely compatible with the distribution of cases. They proposed the existence of 2 classes of nonsyndromic cleft palate: (1) familial CP, which appears to have an autosomal dominant component to its etiology, and (2) nonfamilial CP, which, by demonstrating an increasing frequency of CP with time and a maternal age effect, appears to be related to environmental factors.
Carter et al. (1982) reported the findings in a large series of patients who had been treated surgically for nonsyndromic cleft palate between 1920 and 1939. The probands for the family study were 167 who could be traced and who had had children. Of their 384 children, 11 had cleft palate (2.9%); of their 398 sibs, 5 had cleft palate; of their 117 grandchildren, 1 was affected; and of their 517 nephews and nieces, 1 was affected. The authors suggested that the etiology is probably heterogeneous with some families showing modified dominant inheritance.
Christensen et al. (1992) found that in the Danish population, surgical files provided more than 95% ascertainment for cleft lip (with or without cleft palate) without associated malformations/syndromes. However, surgical files were a poor source for studying isolated cleft palate and could not be used to study the prevalence of associated malformations or syndromes. The male-to-female ratio was 0.88 in surgically treated cases of CP, but was 1.5 in nonoperated CP cases, making the overall sex ratio for CP 1.1 (95% confidence limits, 0.86 to 1.4). The sex ratio for CP without associated malformations was 1.1 with similar confidence limits. One of the major criteria in CP multifactorial threshold models, namely, higher CP liability among male CP relatives, must be reconsidered if other studies confirm that a CP sex-ratio reversal to male predominance occurs when high ascertainment is achieved.
Christensen and Mitchell (1996) estimated the prevalence of nonsyndromic CP in Denmark, obtained estimates of the risks to first-, second-, and third-degree relatives, and analyzed the data for mode of inheritance. A total of 2,301 CP cases were born in Denmark during the period 1936 to 1987; 1,952 (84.8%) of these cases were nonsyndromic. This corresponded to a point prevalence of 5.1 nonsyndromic CP cases per 10,000 live births. The corresponding figure for the period 1952 to 1987 was 5.8 per 10,000 live births. The recurrence risks for the 3 classes of relatives of 1,364 nonsyndromic CP probands were 2.74%, 0.28%, and 0.00%, respectively. Analyses of these data were considered consistent with CP being determined by several interacting loci.
Mapping
In studies of 15 sibships with 2 or more sibs with isolated cleft palate, Van Dyke et al. (1983) could demonstrate no close linkage with HLA.
Molecular Genetics
### Associations Pending Confirmation
The transforming growth factor-alpha gene (TGFA; 190170) on chromosome 2q33 has been implicated as a susceptibility locus for nonsyndromic cleft lip with or without cleft palate (see OFC2, 602996). Shiang et al. (1993) and Hwang et al. (1995) suggested that it may also play a role in the etiology of nonsyndromic CP.
Van den Boogaard et al. (2000) identified a stop codon in the MSX1 gene (142983.0002) on chromosome 4p16.1 in a 3-generation Dutch family with tooth agenesis (106600) and combinations of cleft palate only and cleft lip and cleft palate, providing further evidence for this gene in orofacial clefting.
See 173490.0011-173490.0013 for discussion of an association between isolated cleft palate and mutation in the PDGFRA gene on chromosome 4q12.
INHERITANCE \- Autosomal dominant HEAD & NECK Mouth \- Cleft palate, isolated ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| CLEFT PALATE, ISOLATED | c0008925 | 4,411 | omim | https://www.omim.org/entry/119540 | 2019-09-22T16:43:21 | {"doid": ["0110213"], "mesh": ["D002972"], "omim": ["119540"], "orphanet": ["2014"], "synonyms": ["Alternative titles", "CLEFT PALATE"]} |
Presence of four copies of the short arm of chromosome 9
See also: Trisomy 9
Tetrasomy 9p
Other namesIsochromosome 9p
Chromosome 9, the chromosome involved in this condition
Tetrasomy 9p (also known tetrasomy 9p syndrome) is a rare chromosomal disorder characterized by the presence of two extra copies of the short arm of chromosome 9 (called the p arm), in addition to the usual two.[1] Symptoms of tetrasomy 9p vary widely among affected individuals but typically include varying degrees of delayed growth, abnormal facial features and intellectual disability.[1] Symptoms of the disorder are comparable to those of trisomy 9p.[2]
## Contents
* 1 Symptoms
* 2 Causes
* 3 Mechanism
* 3.1 Mosaicism
* 4 Diagnosis
* 5 Management
* 6 Prognosis
* 6.1 Recurrence risk
* 7 References
* 8 External links
## Symptoms[edit]
The symptoms and prognosis of tetrasomy 9p are highly variable.[3] The severity of the symptoms is largely determined by the size of the isochromosome, the specific regions of chromosome 9p that are duplicated, as well as the number and type of tissues that are affected in the mosaic form.[4]
Most patients exhibit some degree of intellectual disability, abnormal skeletal and muscular development, and abnormal facial structures.[1] Cognitive symptoms range from slight learning disabilities to severe deficits in intellectual functioning.[4] Due to abnormal development of the muscles, individuals often experience limited or delayed mobility.[2] Atypical facial features are characteristic of the syndrome, including widely spaced eyes, a large nose, and unusually positioned ears.[1][4] Additionally, patients often have extra skin around the neck and widely spaced nipples.[4] A wide range of renal, digestive, cardiac, respiratory, and nervous system abnormalities have been observed.[4]
Though rare, a few cases of phenotypically normal individuals with tetrasomy 9p have been documented.[1][3]
## Causes[edit]
Tetrasomy 9p is caused by the presence of two additional copies of the short arm of chromosome 9. These two extra copies are found in the cell as an isochromosome, in addition to the normal 46 chromosomes.[4] An isochromosome is formed when one of the arms of a chromosome is duplicated (in this case, the short arm), and the other is lost (in this case, the long arm), forming a chromosome with two identical arms.[3] Varying amounts of the short arm may be incorporated into the isochromosome, and occasionally, small regions of DNA from the long arm are included as well.[4]
The disorder is almost never inherited; it most commonly arises through the improper distribution of chromosomes during the formation of eggs or sperm.[1]
## Mechanism[edit]
The tetrasomy is typically caused by the incorrect distribution of chromosomes during meiosis or mitosis, called nondisjunction.[4] When cell division occurs normally, each daughter cell receives one short arm and one long arm of each chromosome. However, errors during this process may cause one daughter cell to receive two short arms of chromosome 9, while the other cell receives two long arms. The identical arms are subsequently connected via a centromere. In most cases, isochromosomes of 9p contain two centromeres, called a dicentric chromosome.[4]
The tetrasomy can also be formed independently of cell division. Double stranded breaks in the short arm of chromosome 9 may be repaired incorrectly, resulting in the formation of an isochromosome of 9p with a single centromere.[4] This isochromosome can then be passed on during cell division.
### Mosaicism[edit]
In most cases, affected individuals carry the tetrasomy in every cell in their bodies.[2] However, some patients have the tetrasomy in some of their tissues but not in others; this is referred to as the mosaic form of the syndrome, and often results in less severe symptoms.[2] Non-mosaic tetrasomy 9p is most often the result of abnormal chromosome separation during the formation of eggs or sperm. In contrast, the mosaic form is often a result of a nondisjunction event that occurs early in embryonic development.[2] The type and number of tissues affected in the mosaic form is dependent upon the timing and location of the abnormal division within the developing embryo.
## Diagnosis[edit]
After birth, galactose-1-phosphate uridyltransferase (GALT) activity in the infant's blood is measured.[2] GALT is regulated by a protein encoded on chromosome 9p, so irregular levels of GALT activity may indicate an underlying chromosomal abnormality.[2] Abnormal results are followed by analysis of blood, skin, and inner cheek cells, typically via fluorescence in situ hybridization,[4] which allows genetic counsellors to physically view the chromosomal composition of the cells.[5] Analysis of more than one tissue type is necessary in order to determine if the tetrasomy is present in its mosaic form.[1] If tetrasomy 9p is confirmed, chromosomal analysis of additional tissue types may be performed in order to estimate the ratio of affected cells in the body.[3]
## Management[edit]
This section is empty. You can help by adding to it. (December 2017)
## Prognosis[edit]
Though the outcome for individuals with either form of the tetrasomy is highly variable, mosaic individuals consistently experience a more favourable outcome than those with the non-mosaic form.[3] Some affected infants die shortly after birth, particularly those with the non-mosaic tetrasomy.[1] Many patients do not survive to reproductive age, while others are able to function relatively normally in a school or workplace setting.[1] Early diagnosis and intervention has been shown to have a strong positive influence on the prognosis.[1]
### Recurrence risk[edit]
Since tetrasomy 9p is not usually inherited, the risk of a couple having a second child with the disorder is minimal.[4] While patients often do not survive to reproductive age, those who do may or may not be fertile.[1] The risk of a patient's child inheriting the disorder is largely dependent on the details of the individual's case.[1]
## References[edit]
1. ^ a b c d e f g h i j k l "Tetrasomy 9p" (PDF). rarechromo.org. Unique: Rare Chromosome Disorder Support Group. Retrieved November 29, 2015.
2. ^ a b c d e f g "Chromosome 9, Tetrasomy 9p". National Organization for Rare Disorders. Retrieved 2015-11-29.
3. ^ a b c d e Lazebnik, Noam; Cohen, Leslie (2015-07-01). "Prenatal diagnosis and findings of tetrasomy 9p". Journal of Obstetrics and Gynaecology Research. 41 (7): 997–1002. doi:10.1111/jog.12706. ISSN 1447-0756. PMID 25944096.
4. ^ a b c d e f g h i j k l "Tetrasomy 9p Syndrome". Atlas of Genetic Diagnosis and Counseling. Humana Press. 2006-01-01. pp. 947–949. doi:10.1007/978-1-60327-161-5_179. ISBN 978-1-58829-681-8.
5. ^ Grass, Frank S.; Parke, James C.; Kirkman, Henry N.; Christensen, Vicky; Roddey, O. F.; Wade, Ronald V.; Knuston, Cam; Spence, J. Edward (1993-11-01). "Tetrasomy 9p: Tissue-limited idic(9p) in a child with mild manifestations and a normal CVS result. Report and review". American Journal of Medical Genetics. 47 (6): 812–816. doi:10.1002/ajmg.1320470603. ISSN 1096-8628. PMID 7506483.
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*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
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*[ND]: No data
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*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
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| Tetrasomy 9p | c0795832 | 4,412 | wikipedia | https://en.wikipedia.org/wiki/Tetrasomy_9p | 2021-01-18T18:50:44 | {"gard": ["42"], "mesh": ["C538027"], "umls": ["C0795832"], "orphanet": ["3310"], "wikidata": ["Q7706739"]} |
Immersion foot
Trench foot as seen on an unidentified soldier during World War I
SpecialtyDermatology
Immersion foot syndromes are a class of foot injury caused by water absorption in the outer layer of skin.[1][2] There are different subclass names for this condition based on the temperature of the water to which the foot is exposed. These include trench foot, tropical immersion foot, and warm water immersion foot.[3]:26–7 In one 3-day military study, it was found that submersion in water allowing for a higher skin temperature resulted in worse skin maceration and pain.[4]
## Contents
* 1 Causes
* 1.1 Trench foot
* 1.2 Tropical immersion foot
* 1.3 Warm water immersion foot
* 2 Diagnosis
* 3 Prevention
* 4 References
* 5 External links
## Causes[edit]
### Trench foot[edit]
Main article: Trench foot
Trench foot is a medical condition caused by prolonged exposure of the feet to damp, unsanitary, and cold conditions. The use of the word trench in the name of this condition is a reference to trench warfare, mainly associated with World War I. Affected feet may become numb, affected by erythrosis (turning red) or cyanosis (turning blue) as a result of poor vascular supply, and feet may begin to have a decaying odour due to the possibility of the early stages of necrosis setting in. As the condition worsens, feet may also begin to swell. Advanced trench foot often involves blisters and open sores, which lead to fungal infections; this is sometimes called tropical ulcer (jungle rot).
If left untreated, trench foot usually results in gangrene, which can cause the need for amputation. If trench foot is treated properly, complete recovery is normal, though it is marked by severe short-term pain when feeling returns. As with other cold-related injuries, trench foot leaves sufferers more susceptible to it in the future.[citation needed]
### Tropical immersion foot[edit]
Tropical immersion foot (also known as "Paddy foot",[3] and "Paddy-field foot"[5]) is a skin condition of the feet seen after continuous immersion of the feet in water or mud of temperature above 22 degrees Celsius (roughly 72 degrees Fahrenheit ) for two to ten days.[3]:27
### Warm water immersion foot[edit]
Warm water immersion foot is a skin condition of the feet that results after exposure to warm, wet conditions for 48 hours or more and is characterized by maceration ("pruning"), blanching, and wrinkling of the soles, padding of toes (especially the big toe) and padding of the sides of the feet.
Foot maceration occur whenever exposed for prolonged periods to moist conditions. Large watery blisters appear which are painful when they open and begin to peel away from the foot itself. The heels, sides and bony prominences are left with large areas of extremely sensitive, red tissue, exposed and prone to infection. As the condition worsens, more blisters develop due to prolonged dampness which eventually covers the entire heel and/or other large, padded sections of the foot, especially the undersides as well as toes. Each layer in turn peels away resulting in deep, extremely tender, red ulcers.
Healing occurs only when the feet are cleansed, dried and exposed to air for weeks. Scarring is permanent with dry, thin skin that appears red for up to a year or more. The padding of the feet returns but healing can be painful as the nerves repair with characteristics of diabetic neuropathy. Antibiotics and/or antifungal are sometimes prescribed.
Foot immersion is a common problem with homeless individuals wearing one pair of socks and shoes for extensive periods of time, especially wet shoes and sneakers from rain and snow. The condition is exacerbated by excessive dampness of the feet for prolonged periods of time. Fungus and bacterial infections prosper in the warm, dark, wet conditions and are characterized by a sickly odor that is distinct to foot immersion.[3]:27[5]
## Diagnosis[edit]
This section is empty. You can help by adding to it. (May 2018)
## Prevention[edit]
In the British Army, policies were developed to help the soldiers keep their feet dry - the surest way of preventing the disease. Soldiers were told to dry their feet, and keep them dry by changing socks several times a day. After the first year of the First World War, British troops were instructed to keep at least three pairs of socks with them and to frequently change them. The use of whale oil was also successful in combating trench foot. A British battalion in front line positions could be expected to use ten gallons of whale-oil every day.[6]
## References[edit]
1. ^ "Trench Foot or Immersion Foot". cdc.gov. Center for Disease Control and Prevention. Retrieved 10 June 2017.
2. ^ Wrenn, K (April 1991). "Immersion foot. A problem of the homeless in the 1990s". Archives of Internal Medicine. 151 (4): 785–8. doi:10.1001/archinte.151.4.785. PMID 2012466.
3. ^ a b c d James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.
4. ^ Taplin, David; Zaias, Nardo; Blank, Harvey (6 November 1967). "The role of temperature in tropical immersion foot syndrome". The Journal of the American Medical Association. 202 (6): 546–549. doi:10.1001/jama.1967.03130190152032. PMID 6072324. Retrieved 10 June 2017.
5. ^ a b Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
6. ^ Simkin, John (August 2014). "Trench Foot". Spartacus Educational. Retrieved April 10, 2019.
## External links[edit]
Classification
D
* ICD-10: T69.0
* ICD-9-CM: 991.4
* MeSH: D007102
* DiseasesDB: 31219
* v
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Consequences of external causes
Temperature
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Immersion foot syndromes
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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
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*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Immersion foot syndromes | c0020941 | 4,413 | wikipedia | https://en.wikipedia.org/wiki/Immersion_foot_syndromes | 2021-01-18T18:34:13 | {"mesh": ["D007102"], "icd-10": ["T69.0"], "wikidata": ["Q7846175"]} |
A rare immune-mediated inflammatory demyelinating disorder of the spinal cord with motor, sensory and autonomic involvement.
## Epidemiology
Annual incidence is estimated at between 1/1,000,000 and 1/250,000 depending on the study. Onset may occur at any age and both sexes may be affected.
## Clinical description
The spinal cord inflammation is focal and the signs and symptoms are usually bilateral and depend on the extent and site of the lesion, with the thoracic spinal cord being the most common localization. Progression to nadir occurs between 4 hours and 21 days after onset. Motor involvement is characterized by limb weakness, stiffness and muscle spasms. If the upper spinal cord is involved then respiratory function may be impaired. Back pain, paraesthesia, numbness and neuropathic pain are common sensory manifestations. Uncomfortable band-like sensations around the torso and radicular pain have also been reported. Autonomic anomalies include sexual dysfunction, urinary urge/retention and bowel urgency/retention. Autonomic dysreflexia (ADR), resulting in rapid onset of hypertension and bradycardia, is a complication seen in patients with spinal cord lesions at T6 or above and usually with severe myelitis.
## Etiology
By definition, the etiology of idiopathic acute transverse myelitis (ATM) is unknown. A history of viral illness (usually upper respiratory infection) often precedes onset of symptoms by three weeks and idiopathic ATM is believed to be associated with a late immune response against a recent microbial infection that inadvertently targets the spinal cord.
## Diagnostic methods
The diagnostic approach revolves around confirming the diagnosis of myelitis (MRI revealing transverse spinal cord lesions and swelling, with longitudinally extensive lesions in some cases), and excluding secondary causes (brain MRI, serology and analysis of cerebrospinal fluid to rule out secondary ATM; see this term), which may be associated with a relapsing disease course requiring preventative treatments.
## Differential diagnosis
Acute compressive lesions (such as metastases and epidural abscess) and infarction of the spinal cord should also be included in the differential diagnosis.
## Management and treatment
Acute treatment may include corticosteroid therapy and plasma exchange. The benefits of intravenous immunoglobulins and cyclophosphamide remain to be established. Long-term management is mainly symptomatic and should include rehabilitative therapy.
## Prognosis
The prognosis is variable and unpredictable. Recovery may begin between 2 and 12 weeks after the onset of symptoms. Full recovery (occurring in only a third of patients) may take years and permanent sequelae are frequent (moderate disability in one third of patients and severe disability in the remaining third).
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*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
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*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
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| Idiopathic acute transverse myelitis | None | 4,414 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=139423 | 2021-01-23T18:25:23 | {"icd-10": ["G37.3"], "synonyms": ["ATM/TM"]} |
Abortion in Denmark was fully legalized on 1 October 1973,[1] allowing the procedure to be done on-demand if a woman's pregnancy has not exceeded its twelfth week.[1] According to the law of Denmark, the patient must be over the age of 18 to decide on an abortion alone; parental consent is required if she is a minor.[1] An abortion can be performed after 12 weeks if the woman's life or health are in danger. A woman may also be granted an authorization to abort after 12 weeks if certain circumstances are proved to be present (such as poor socioeconomic condition of the woman; risk of birth defects in the baby; the pregnancy being the result of rape; mental health risk to mother).[2]
Abortion was first allowed in 1939 by application; if the doctors deemed the pregnancy fell into one of three categories (harmful or fatal to the mother, high risk for birth defects, or a pregnancy borne out of rape), a woman could legally have her pregnancy terminated.[3] A little more than half of the applications received in 1954 and 1955 were accepted; the low acceptance rates were linked to a surge of illegal abortions performed outside the confines of hospitals.[3] An addendum to the 1939 law was passed on 24 March 1970,[1] allowing on-demand abortions only for women under the age of 18 who were deemed "ill-equipped for motherhood," and women over the age of 38.[3]
The 1973 law is still valid today and nullifies the 1970 law.[1]
As of 2013[update], the abortion rate was 12.1 abortions per 1000 women aged 15–49 years, which is below average for the Nordic countries (Denmark, Finland, Iceland, Norway and Sweden).[4] The vast majority of Danes support access to legal abortions. In 2007, polls found that 95% supported the right.[5]
## Faroe Islands[edit]
Abortion on the Faroe Islands is still governed by the Danish law of 1956, which restricts abortions to the aforementioned three circumstances (pregnancy harmful or fatal to the mother, high risk for birth defects, or a pregnancy borne out of rape), as Danish politicians were historically unwilling to impose the Danish abortion law on the more conservative Faroese population.[6][7] Abortion policy was formally devolved to the Faroese Parliament in 2018.[8][9]
The abortion rate in the Faroe Islands is about one-third the rate in Denmark.[10] Additionally, some Faroese women travel to Denmark to have the procedure done.[11]
## Greenland[edit]
Abortion in Greenland was legalized on 12 June 1975, under legislation equivalent to the Danish law.[12]
The abortion rate in Greenland is among the highest in the world, and about five times higher than in Denmark, with the number of abortions exceeding live births in some years. Despite being treated as a public health concern, the rate remains high.[13][14]
## References[edit]
1. ^ a b c d e Lovtidende for Kongeriget Danmark, Part A, 6 July 1973, No. 32, pp. 993-995
2. ^ http://cyber.law.harvard.edu/population/abortion/Denmark.abo.htm
3. ^ a b c The rocky road to abortion on demand
4. ^ Heino, Anna; Gissler, Mika (26 March 2015). "Induced abortions in the Nordic countries 2013". THL. Retrieved 12 January 2016.
5. ^ Thimmer, Niels (11 February 2007). "Dansk støtte til fri abort i Portugal". avisen.dk. Retrieved 12 November 2016.
6. ^ "Question S 1361 for the minister of justice" (in Danish). Folketinget. 9 January 2004. Retrieved 1 June 2018.
7. ^ Tin, Hjalte (16 October 2004). "Abort-imperialisme" [Abortion imperialism] (in Danish). Dagbladet Information. Retrieved 1 June 2018.
8. ^ Funch, Maja (20 April 2018). "Færøerne ruster sig til hård debat om fri abort" [The Faroe Islands prepare themselves for a tough debate on legalized abortion]. Kristeligt Dagblad (in Danish). Archived from the original on 28 June 2020. Retrieved 28 June 2020.
9. ^ Færøernes overtagelse af sagsområdet person-, familie- og arveretten [The Faroese acquisition of the personal, family and inheritance areas of law] (pdf) (in Danish). Børne- og Socialministeriet (Ministry for Children and Social Affairs). 2016. pp. 5, 15. ISBN 978-87-999120-9-4. Archived (PDF) from the original on 28 June 2020.
10. ^ "Number of induced abortions 2000-2009". ArcticStat. Retrieved 11 July 2018.[permanent dead link]
11. ^ "Færøske gravide får abort i Danmark" [Faroese women get an abortion in Denmark] (in Danish). Berlingske Tidende. 30 August 2008. Retrieved 11 July 2018.
12. ^ "Lov for Grønland om svangerskabsafbrydelse" [Law for Greenland about termination of pregnancy]. Law No. 232 of 12 June 1975 (PDF). Archived from the original (PDF) on 31 May 2018. Retrieved 1 June 2018.
13. ^ "Stadig masser af aborter i Grønland" [Still many abortions in Greenland] (in Danish). DR. 3 July 2007. Retrieved 1 June 2018.
14. ^ "Der er for mange aborter i Grønland" [There are too many abortions in Greenland] (in Danish). Naalakkersuisut. 18 September 2015. Retrieved 1 June 2018.
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| Abortion in Denmark | None | 4,415 | wikipedia | https://en.wikipedia.org/wiki/Abortion_in_Denmark | 2021-01-18T18:52:51 | {"wikidata": ["Q4668454"]} |
A number sign (#) is used with this entry because mild mononeuropathy of the median nerve (MNMN) is caused by heterozygous mutation in the SH3TC2 gene (608206).
Charcot-Marie-Tooth disease type 4C (CMT4C; 601596) is a more severe neuropathy caused by homozygous or compound heterozygous mutation in the SH3TC2 gene. See also carpal tunnel syndrome (115430).
Clinical Features
Lupski et al. (2010) reported a 3-generation family with variable severity of a peripheral neuropathy. The family was ascertained through 4 sibs with a phenotype consistent with autosomal recessive CMT4C caused by compound heterozygous mutations in the SH3TC2 gene: R954X (608206.0005) and Y169H (608206.0008). Three additional family members who were heterozygous for the R954X mutation, resulting in loss of function, had a subtle mild mononeuropathy of the median nerve (MNMN) consistent with carpal tunnel syndrome. This involvement of the median nerve was also seen in the patients with CMT4C. Lupski et al. (2010) concluded that haploinsufficiency of SH3TC2 may confer susceptibility to carpal tunnel syndrome. Two additional family members who were heterozygous for the Y169H mutation had an apparently autosomal dominant patchy axonal polyneuropathy, as shown by electrophysiologic studies. They had a definite median nerve mononeuropathy at the wrist associated with evidence of a more widespread axonal neuropathy. The phenotype was similar to that of hereditary neuropathy with liability to pressure palsies (HNPP; 162500). The authors postulated a toxic gain of function for the Y169H-mutant protein. Lupski et al. (2010) commented on the subtle, apparently autosomal dominant phenotypes segregating independently with the respective SH3TC2 mutations.
INHERITANCE \- Autosomal dominant NEUROLOGIC Peripheral Nervous System \- Mononeuropathy of the median nerve \- Carpal tunnel syndrome \- More widespread axonal polyneuropathy may occur \- Patchy axonal neuropathy MISCELLANEOUS \- Allelic disorder to autosomal recessive Charcot-Marie-Tooth disease type 4C ( 601596 ) MOLECULAR BASIS \- Caused by mutation in the SH3 domain and tetratricopeptide repeat domain 2 gene (SH3TC2, 608206.0005 ) ▲ Close
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*[NET]: Norepinephrine transporter
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*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| MONONEUROPATHY OF THE MEDIAN NERVE, MILD | c3150596 | 4,416 | omim | https://www.omim.org/entry/613353 | 2019-09-22T15:58:53 | {"omim": ["613353"], "synonyms": ["Alternative titles", "CARPAL TUNNEL SYNDROME, SUSCEPTIBILITY TO"]} |
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Find sources: "Infantile neuroaxonal dystrophy" – news · newspapers · books · scholar · JSTOR (March 2011) (Learn how and when to remove this template message)
Infantile neuroaxonal dystrophy
Infantile neuroaxonal dystrophy has an autosomal recessive pattern of inheritance.
SpecialtyNeurology
Infantile neuroaxonal dystrophy is a rare pervasive developmental disorder that primarily affects the nervous system. Individuals with infantile neuroaxonal dystrophy typically do not have any symptoms at birth, but between the ages of about 6 and 18 months they begin to experience delays in acquiring new motor and intellectual skills, such as crawling or beginning to speak. Eventually they lose previously acquired skills.
## Contents
* 1 Cause
* 2 Pathophysiology
* 3 Diagnosis
* 4 Management
* 5 Research
* 6 References
* 7 Further reading
* 8 External links
## Cause[edit]
This condition is inherited in an autosomal recessive pattern, which means two copies of the gene (PLA2G6) in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder each carry one copy of the altered gene but do not show signs and symptoms of the disorder.[citation needed]
## Pathophysiology[edit]
Mutations in the PLA2G6 gene have been identified in most individuals with infantile neuroaxonal dystrophy. The PLA2G6 gene provides instructions for making an enzyme called an A2 phospholipase. This enzyme family is involved in metabolizing phospholipids. Phospholipid metabolism is important for many body processes, including helping to keep the cell membrane intact and functioning properly. Specifically, the A2 phospholipase produced from the PLA2G6 gene, sometimes called PLA2 group VI, helps to regulate the levels of a compound called phosphatidylcholine, which is abundant in the cell membrane.[citation needed]
Mutations in the PLA2G6 gene impair the function of the PLA2 group VI enzyme. This impairment of enzyme function may disrupt cell membrane maintenance and contribute to the development of spheroid bodies in the nerve axons. Although it is unknown how changes in this enzyme's function lead to the signs and symptoms of infantile neuroaxonal dystrophy, phospholipid metabolism problems have been seen in both this disorder and a related disorder called pantothenate kinase-associated neurodegeneration. These disorders, as well as the more common Alzheimer disease and Parkinson disease, also are associated with changes in brain iron metabolism. Researchers are studying the links between phospholipid defects, brain iron, and damage to nerve cells, but have not determined how the iron accumulation that occurs in some individuals with infantile neuroaxonal dystrophy may contribute to the features of this disorder.[citation needed]
A few individuals with infantile neuroaxonal dystrophy have not been found to have mutations in the PLA2G6 gene. The genetic cause of the condition in these cases is unknown; there is evidence that at least one other gene may be involved.[citation needed]
Mutations in the NAGA gene, resulting in alpha-N-acetylgalactosaminidase deficiency, cause an infantile neuroaxonal dystrophy known as Schindler disease.[1]
## Diagnosis[edit]
In some cases, signs and symptoms of infantile neuroaxonal dystrophy first appear later in childhood or during the teenage years and progress more slowly. Children with infantile neuroaxonal dystrophy experience progressive difficulties with movement. Generally they have muscles that are at first weak and "floppy" (hypotonic), and then gradually become very stiff (spastic). Eventually, affected children lose the ability to move independently. Lack of muscle strength causes difficulty with feeding and breathing problems that can lead to frequent infections, such as pneumonia. Seizures occur in some affected children.[citation needed]
Rapid, involuntary eye movements (nystagmus), eyes that do not look in the same direction (strabismus), and vision loss due to deterioration (atrophy) of the optic nerve are characteristic of infantile neuroaxonal dystrophy. Hearing loss may also develop. Children with this disorder experience progressive deterioration of cognitive functions (dementia), and eventually lose awareness of their surroundings.[citation needed]
Infantile neuroaxonal dystrophy is characterized by the development of swellings called spheroid bodies in the axons, the fibers that extend from nerve cells (neurons) and transmit impulses to muscles and other neurons. A part of the brain called the cerebellum, which helps to control movements, may also be damaged. In some individuals with infantile neuroaxonal dystrophy, abnormal amounts of iron accumulate in a specific region of the brain called the basal ganglia.
## Management[edit]
Currently, only palliative treatment is available: alleviation of spasticity and seizures, baclofen for relieving dystonia, physiotherapeutic treatment and measures such as gastric feeding tube or tracheostomy to prevent aspirational pneumonia.[2]
## Research[edit]
An open-label clinical study for long-term evaluation of efficacy, safety, tolerability, and pharmacokinetics of a deuterium-enhanced polyunsaturated fatty acid RT001, which, when taken with food, can protect the neuronal cells from degeneration, started in the Summer 2018.[3]
The loss of iPLA2-VIA, the fly homolog of PLA2G6, reduces lifespan, impairs synaptic transmission, and causes neurodegeneration. Phospholipases typically hydrolyze glycerol phospholipids, but loss of iPLA2-VIA does not affect the phospholipid composition of brain tissue but rather causes an elevation in ceramides. Reducing ceramides with drugs, including myriocin or desipramine, alleviates lysosomal stress and suppresses neurodegeneration.[4]
## References[edit]
1. ^ Wang AM, Schindler D, Desnick R (November 1990). "Schindler disease: the molecular lesion in the alpha-N-acetylgalactosaminidase gene that causes an infantile neuroaxonal dystrophy". J. Clin. Invest. 86 (5): 1752–6. doi:10.1172/JCI114901. PMC 296929. PMID 2243144.
2. ^ https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=35069
3. ^ https://clinicaltrials.gov/ct2/show/NCT03570931
4. ^ Bellen, Hugo J.; Wang, Liping; Lin, Wen-Wen; Zuo, Zhongyuan; Tan, Kai Li; Mao, Dongxue; Chen, Kuchuan; Lee, Pei-Tseng; Lin, Guang (2018-10-02). "Phospholipase PLA2G6, a Parkinsonism-Associated Gene, Affects Vps26 and Vps35, Retromer Function, and Ceramide Levels, Similar to α-Synuclein Gain". Cell Metabolism. 28 (4): 605–618.e6. doi:10.1016/j.cmet.2018.05.019. ISSN 1550-4131. PMID 29909971.
## Further reading[edit]
* GeneReview/NIH/UW entry on Infantile Neuroaxonal Dystrophy
* National Library of Medicine. Genetics Home Reference - Infantile neuroaxonal dystrophy
## External links[edit]
Classification
D
* OMIM: 256600
* MeSH: D019150
* DiseasesDB: 32201
External resources
* GeneReviews: PLA2G6-Associated Neurodegeneration
* v
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Diseases relating to the peripheral nervous system
Mononeuropathy
Arm
median nerve
* Carpal tunnel syndrome
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ulnar nerve
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* See Template:Cranial nerve disease
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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
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*[MAOIs]: 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
| Infantile neuroaxonal dystrophy | c2931102 | 4,417 | wikipedia | https://en.wikipedia.org/wiki/Infantile_neuroaxonal_dystrophy | 2021-01-18T19:10:51 | {"gard": ["3957"], "mesh": ["C536071"], "umls": ["C2931102"], "orphanet": ["2174", "35069"], "wikidata": ["Q6029060"]} |
Dent disease type 2 is a type of Dent disease in which patients have the manifestations of Dent disease type 1 associated with extra-renal features.
## Epidemiology
About 20 cases have been reported to date.
## Clinical description
All of them had hypercalciuria and low-molecular-weight (LMW) proteinuria. In addition, these patients may also have nephrocalcinosis, nephrolithiasis, hematuria, hypophosphatemia and/or renal insufficiency. Only a minority (approximately one fourth) of these patients have been observed to have mild intellectual deficit, hypotonia and sub-clinical cataract. The presence of intellectual impairment and sub-clinical cataract were so mild as to dissuade the clinicians from considering a diagnosis of Lowe syndrome (see this term), which is characterized by congenital cataracts, delayed motor milestones, some degree of intellectual impairment in almost all affected males, growth retardation, rickets and renal proximal tubulopathy. Moreover, the patients with Dent disease type 2 and mild intellectual deficit were adults, who had not, over time, developed more overt features of Lowe syndrome.
## Etiology
The reported patients share mutations in the OCRL1 gene with the oculocerebrorenal syndrome of Lowe.
## Genetic counseling
The disease follows an X-linked recessive mode of inheritance.
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*[DOR]: δ-opioid receptor
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*[TCAs]: Tricyclic antidepressants
*[MAOIs]: 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
| Dent disease type 2 | c1845167 | 4,418 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93623 | 2021-01-23T18:47:41 | {"gard": ["10645"], "mesh": ["C564487"], "omim": ["300555"], "umls": ["C1845167"], "icd-10": ["N25.8"], "synonyms": ["Nephrolithiasis type 2"]} |
Working at Sloan-Kettering, Rettig et al. (1984) mapped the loci that code for 2 cell surface glycoproteins defined by monoclonal antibodies. AbAJ9 defined a glycoprotein of 140,000 MW and AbT87 a glycoprotein of 60,000 MW. Both antibodies reacted with a wide variety of cultured human cell types but not with rodent cell lines. The authors termed the loci coding these glycoproteins MSK1 and MSK2 (158040), after the usual practice of using the initials of the laboratory. By analysis of rodent-human somatic cell hybrids, MSK1 was assigned to 1p21-cen and MSK2 to 1q41-qter. Because of the lack of reactivity of human red cells, as well as the location of the loci on chromosome 1, they concluded that MSK1 and MSK2 are unrelated to any of the blood groups mapped to no. 1: Rh, Sc, Rd, Fy, Do. Furthermore, tissue distribution, subcellular localization, and biochemical properties as well as regional mapping indicate that they are distinct from enzymes mapped to chromosome 1.
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| ANTIGEN DEFINED BY MONOCLONAL ANTIBODY AJ9 | c1834757 | 4,419 | omim | https://www.omim.org/entry/158030 | 2019-09-22T16:38:11 | {"omim": ["158030"], "synonyms": ["Alternative titles", "MSK1"]} |
Osteopetrosis refers to a group of rare, inherited skeletal disorders characterized by increased bone density and abnormal bone growth. Symptoms and severity can vary greatly, ranging from neonatal onset with life-threatening complications (such as bone marrow failure) to the incidental finding of osteopetrosis on X-ray. Depending on severity and age of onset, features may include fractures, short stature, compressive neuropathies (pressure on the nerves), hypocalcemia with attendant tetanic seizures, and life-threatening pancytopenia. In rare cases, there may be neurological impairment or involvement of other body systems. Osteopetrosis may be caused by mutations in at least 10 genes. Inheritance can be autosomal recessive, autosomal dominant, or X-linked recessive with the most severe forms being autosomal recessive. Management depends on the specific symptoms and severity and may include vitamin D supplements, various medications, and/or surgery. Adult osteopetrosis requires no treatment by itself, but complications may require intervention.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Osteopetrosis autosomal dominant type 1 | c1843330 | 4,420 | gard | https://rarediseases.info.nih.gov/diseases/4151/osteopetrosis-autosomal-dominant-type-1 | 2021-01-18T17:58:31 | {"mesh": ["C536056"], "omim": ["607634"], "orphanet": ["2783"], "synonyms": ["OPTA1", "Autosomal dominant osteopetrosis type 1"]} |
Gordon syndrome, also known as distal arthrogryposis type 3, is an extremely rare multiple congenital malformation syndrome characterized by congenital contractures of hand and feet with variable degrees of severity of camptodactyly, clubfoot and, less frequently, cleft palate. Intelligence is normal but in some cases, additional abnormalities, such as short stature, kyphoscoliosis, ptosis, micrognathia, and cryptorchidism may also be present. Gordon syndrome, Marden-Walker syndrome and arthrogryposis with oculomotor limitation and electroretinal anomalies clinically and genetically overlap, and could represent variable expressions of the same condition.
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Gordon syndrome | c0220666 | 4,421 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=376 | 2021-01-23T18:56:37 | {"gard": ["2553"], "mesh": ["C537288"], "omim": ["114300"], "umls": ["C0220666"], "icd-10": ["Q68.8"], "synonyms": ["Camptodactyly-cleft palate-clubfoot syndrome", "Distal arthrogryposis type 3", "Distal arthrogryposis type IIA"]} |
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Dacryocystocele
Nasolacrimal duct
SpecialtyNeurology
Dacryocystocele (Dacryocystitis) or timo cyst is a benign, bluish-gray mass in the inferomedial canthus that develops within a few days or weeks after birth. The uncommon condition forms as a result as a consequence of narrowing or obstruction of the nasolacrimal duct, usually during prenatal development. Nasolacrimal duct obstruction disrupts the lacrimal drainage system, eventually creating a swelling cyst in the lacrimal sac area by the nasal cavity. The location of the cyst can cause respiratory dysfunction, compromising the airway. The obstruction ultimately leads to epiphora, an abundance of tear production.[1]
## Contents
* 1 Signs and symptoms
* 2 Cause
* 3 Pathophysiology
* 4 Diagnosis
* 5 Prevention/ Treatment
* 5.1 Complications
* 6 Prognosis
* 7 Epidemiology
* 8 Research Directions
* 9 References
* 10 Further reading
* 11 External links
## Signs and symptoms[edit]
Dacryocystocele is a condition that can occur to all, at any age. However, the population most affected by this rare condition are infants. The intensity of the symptoms may vary depending on the type of dacryocystocele. There are three types of dacrycystocele: acute, congenital and chronic. Acute dacryocystocele is a bacterial infection, that includes symptoms such as fever and pus from the eye region. While, chronic dacryocystocele is less severe. People with the chronic form of the condition experience symptoms of pain or discomfort from the corner of the eye. Congenital is the dacryocystocele form that appears in infants. The infant may have watering or discharge from the eyes.[1]
Common symptoms of all types of dacryocystocele include:
* Pain surrounding the outer corner of the eye and areas around.
* Redness
* Swelling of the eyelid
* Reoccurring conjunctivitis
* Epiphora (overproduction of tears)
* Pus or discharge
* Fever
## Cause[edit]
The nasolacrimal ducts drain the excess tears from our eyes into the nasal cavity. In dacryocystocele there this tube gets blocked on either end and as a result when mucoid fluid collects in the intermediate patent section it forms a cystic structure.
The infection is often caused by:
* injury to eye or nose area
* nasal abscess
* abnormal mass inside of the nose
* inflammation
* surgery (nasal or sinus)
* cancer
* sinusitis
## Pathophysiology[edit]
The nasolacrimal system is located within the maxillary bone. The purpose of the nasolacrimal ducts is to drain tears from the eye area of the lacrimal sac and eventually through the nasal cavity. Dacryocystocele is caused by blockage on the nasolacrimal duct, as a result when mucoid fluid collects in the intermediate patent section it forms a cystic structure. The cyst is formed by the eye and nose region. A blockage of epiphora can become an area for infections to take over. Once an infection occurs, the lacrimal sac will inflame causing swelling and the cystic formation.
## Diagnosis[edit]
The diagnosis can be made prenatally; routine obstetric ultrasound can identify the characteristic hypoechoic lesion inferior and medial to the globe. It is important to distinguish a dacrocystocele from the more serious encephalocele, which is a neural tube defect.
A dacryocystocele can be diagnosed postpartum with a non-invasive ultrasound (US).
Among the adult population, several tests can be ordered to further diagnose the condition. Initially, a physician would use a patient's medical history or any visible symptoms that can indicate of having the condition. Tests that are used to diagnose a patient include:[1]
* Examination of discharge from the eye
* Blood culture
* X-ray (can help diagnose skeletal abnormality)
* CT Scan (useful in suspected cases of mass)
* Dacryocystography (DCG)
* Nasal endoscopy
* Dye disappearance test: indicates if there is blockage in the eye
## Prevention/ Treatment[edit]
To relieve dacryocystocele symptoms, a warm compress is placed on the affected area to help open up the ducts. Taking over the counter medication, such as anti-inflammatory and pain relievers are recommended in order to reduce fever and pain symptoms.[citation needed]
Since dacryocystocele is an infection of the tear sacs, the condition is resolved by taking oral antibiotics. With acute dacryocystocele the mass may spontaneously resolve or with pressure directed toward the nose. With time the cyst will outgrow the blockage. However, with chronic dacryocystocele, the nasolacrimal duct probing may be required to open the obstruction. Surgery may be needed to widen the tear ducts in order to reduce the blockage occurring in the eye area. The procedure for the surgery is called dacryocystorhinostomy, laser is used to remove some of the bone structure on the nose in order to widen the tear duct.[citation needed]
### Complications[edit]
If the infection is not treated early in the course of the condition, dacryocystocele can lead to life-threatening illnesses:[citation needed]
* Meningitis
* Sepsis
* Orbital cellulitis
* Sinusitis
* Brain abscess
## Prognosis[edit]
Recovery for acute dacryocystocele would be a couple of days to 2 weeks, with the help of antibiotics. However, with chronic dacryocystocele recovery time varies. This recovery time all depends if the person with chronic dacryocystocele receives surgery for the condition. Recovery time for the surgery (specifically DCR), is between three to six months. The success rate of the surgery is 93%- 97%.
Mortality and morbidity rates with this condition are significantly low. This condition can have a high success rate if treated early, particularly among infants with congenital dacryocystocele.[2]
## Epidemiology[edit]
Dacryocystocele is most prominent among infants, the prevalence is 1 in 3884 live births.[2]
90% of the infants with the condition recover by the time they turn a year old. Among the adult population, those 40 years old and older are more likely to develop the condition, especially women. 75% percent of dacryocystocele cases in adult are from women.[2] Women have narrower nasal ducts than men, and are more prone to develop the condition.
Dacryocystocele becomes more prevalent among people with the following pre-existing conditions:
* Deviated septum
* Rhinitis
## Research Directions[edit]
In 2018, a research study was conducted in Northwest Iran among patients with dacryocystocele. The purpose of the research experiment was to examine bacterial and antibiotic susceptibility among the group with the condition. A total of 129 patients with dacryocystitis participated in the study. Patients under the age of eighteen needed written consent for participation. All patients that were referred to the clinic of ophthalmology were selected to participate, exclusion for participation was taken into consideration if the patient had previous treatment with antibiotics.
In order to go forward with the study, nasolacrimal duct discharges were injected into growth medium to isolate and determine microbial agent stains present in the discharges. To test the antibiotic susceptibility among dacryocystocele patients a disc diffusion method was utilize.
From the 129 patients that participated in the experiment, 83 were female and 46 were male patients. Results from the culture sample demonstrated that S. aureus, S. epidermidis, and S. pneumonaie were the most common strains of microorganisms among patients with actue dacryocystitis. However, patients with chronic dacryocystitis, they demonstrated prevalance among the S. epidermidis, Pseudomonas spp., S aureus, and C. albicans strains.
Results from the antibiotic susceptibility tests demonstrated that patients in the Northwest region of Iran were most sensitive to the following antibiotics: ciprofloxacin, ceftriaxone, vancomycin, chloramphenicol, gentamicin, and erthromycin. It is concluded that ciprofloxacin and vancomycin are the most effective medications among the patients with the condition in the region of Iran. This study was beneficial to determine which medications worked best to treat the people of Northwest Iran more adequately. Other regions around the world should take consideration of this study in order to treat dacryocystocele effectively in their regions.[3]
## References[edit]
1. ^ a b c "Dacryocystitis : Symptoms, Diagnosis and Management". AIMU. 28 February 2017.
2. ^ a b c Taylor, Roger S.; Ashurst, John V. (26 June 2020). "Dacryocystitis". StatPearls. StatPearls Publishing. PMID 29261989.
3. ^ Eslami, Fatemeh; Basir, Hamid Reza Ghasemi; Moradi, Abbas; Farah, Shokoufe Heidari (25 September 2018). "Microbiological study of dacryocystitis in northwest of Iran". Clinical Ophthalmology. 12: 1859–1864. doi:10.2147/OPTH.S175463. PMC 6165732. PMID 30310264.
## Further reading[edit]
* Shekunov, Julia; Griepentrog, Gregory J.; Diehl, Nancy N.; Mohney, Brian G. (October 2010). "Prevalence and clinical characteristics of congenital dacryocystocele". Journal of AAPOS. 14 (5): 417–420. doi:10.1016/j.jaapos.2010.07.006. PMC 3115742. PMID 21035068.
* Pujari, Amar (9 December 2016). "Congenital dacryocystocele". BMJ Case Reports. 2016: bcr2016218029. doi:10.1136/bcr-2016-218029. PMC 5174909. PMID 27941115.
* Cavazza, S; Laffi, GL; Lodi, L; Tassinari, G; Dall’Olio, D (December 2008). "Congenital dacryocystocele: diagnosis and treatment". Acta Otorhinolaryngologica Italica. 28 (6): 298–301. PMC 2689544. PMID 19205594.
## External links[edit]
* Dacryocystitis at eMedicine
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Dacryocystocele | c0155241 | 4,422 | wikipedia | https://en.wikipedia.org/wiki/Dacryocystocele | 2021-01-18T18:30:50 | {"umls": ["C0155241"], "wikidata": ["Q3011658"]} |
Mucocutaneous venous malformations (VMCMs) are hereditary vascular malformations characterized by the presence of small, multifocal, bluish-purple venous lesions involving the skin and mucosa.
## Epidemiology
Prevalence is unknown but around 20 families have been identified so far.
## Clinical description
The multifocal venous lesions are usually small (< 2cm in diameter), and are present at birth. They are soft and usually compressible and undergo proportionate growth with age. There is significant clinical variation with respect to the size, location and number of lesions, even between affected individuals from the same family. Classically, one individual in a given family has a large lesion. Small lesions are usually asymptomatic, whereas larger lesions can cause pain and invade subcutaneous muscle. New lesions appear with time. Patients with VMCMs have normal mental and physical development.
## Etiology
VMCMs are associated with amino acid substitutions (R849W and Y897S) in the tyrosine-protein kinase endothelial cell receptor (TEK/TIE2; 9p21). Approximately 90% of individuals who have a mutation in the TEK gene develop mucocutaneous venous malformations by 20 years of age; conversely, approximately 10% of individuals with a TEK mutation are clinically unaffected.
## Diagnostic methods
Diagnosis is based on clinical evaluation of the cutaneous lesions. Doppler ultrasound examination can be used to confirm slow blood flow, and MRI can be used to confirm the venous component and extent of the lesions. Ultrasound examination reveals saccular compressible venous-like cavities. Molecular genetic testing for confirmation of the diagnosis is available on a research basis.
## Differential diagnosis
The differential diagnosis should include glomuvenous malformations (GVMs, which are deeper purple in color than VMCMs, painful on palpation, and more superficial than venous malformations; see this term) and Blue rubber bleb nevus syndrome (characterized by the association of cutaneous and mucosal venous-like lesions with gastrointestinal lesions; see this term).
## Antenatal diagnosis
Prenatal diagnosis is feasible for affected families in which the disease-causing mutation has been identified, but is not widely available.
## Genetic counseling
VMCMs are transmitted in an autosomal dominant manner with incomplete penetrance. Paradominant inheritance (presence of a germline mutation and a somatic mutation) appears to be involved in disease expression and may explain the variability in clinical phenotype. Genetic counseling should be provided for affected families, informing patients of a 50% risk of inheriting the disease-causing mutation and of the variability in clinical expression. There is no anticipation in reported families.
## Management and treatment
The principle treatment approach is sclerotherapy, alone or in combination with plastic and reconstructive surgery depending on the size and location of the lesions. Ethanol (96%) for injection is the most commonly used sclerosing agent and obtained EU orphan drug designation in April 2005 for the treatment of congenital venous malformations. When D-dimers are elevated, indicating activation of coagulation, low-molecular-weight heparin can be used to treat the associated pain. Female patients should avoid using oral contraceptives with high estrogen levels.
## Prognosis
The prognosis for patients is good, malignant transformation has not been reported and the life expectancy for patients is not reduced.
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Mucocutaneous venous malformations | c1838437 | 4,423 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2451 | 2021-01-23T17:04:50 | {"mesh": ["C563977"], "omim": ["600195"], "umls": ["C1838437"], "icd-10": ["Q27.8"], "synonyms": ["Cutaneous and mucosal venous malformation", "VMCM"]} |
A rare congenital limb malformation characterized by mostly posterior, less frequently also anterior or lateral dislocation of the radial head from its position in the humeroradial joint. It is bilateral in the majority of cases and can occur as an isolated feature or in association with other congenital malformations and as part of a number of syndromes. The defect may at first cause only mild symptoms such as pain and limitation of flexion of the elbow, but may eventually lead to joint instability, dysplastic changes of the radial head, and arthritis.
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Isolated congenital radial head dislocation | c0265561 | 4,424 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=295032 | 2021-01-23T17:24:25 | {"umls": ["C0265561"], "icd-10": ["Q68.8"], "synonyms": ["Isolated congenital elbow dislocation"]} |
A rare autosomal recessive primary immunodeficiency characterized by partial T lymphopenia (in particular cytotoxic CD8+ cells) and decreased expression of the T cell receptor (TCR)/CD3 complex with impaired proliferative response to TCR-dependent stimuli, while the mature memory T cell pool is comparatively well preserved, and B cells, natural killer cells, and immunoglobulins are typically normal. The clinical phenotype is highly heterogeneous, ranging from asymptomatic to infancy-onset of severe recurrent infections, as well as occurrence of autoimmune disease or enteropathy.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Combined immunodeficiency due to CD3gamma deficiency | c3810107 | 4,425 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=169082 | 2021-01-23T17:18:35 | {"omim": ["615607"], "icd-10": ["D81.2"]} |
Orthner et al. (1973) reported 2 sisters with onset of ALS at 38 and 39 years of age, and death after 14 and 26 months, respectively. Weakness began in the arms and later involved the legs. Bulbar signs and symptoms followed. Autopsy showed marked loss of motor neurons. Polyglucosan bodies were found in perikarya in the cortex and cerebellum. Barz et al. (1976) reported 2 sporadic cases.
Muscle \- Distal weakness in arms then legs \- Progressive atrophy Neuro \- Bulbar signs \- Motor neuron loss Lab \- Polyglucosan bodies in perikarya, cortex and cerebellum Inheritance \- Autosomal recessive ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[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
| AMYOTROPHIC LATERAL SCLEROSIS WITH POLYGLUCOSAN BODIES | c0002736 | 4,426 | omim | https://www.omim.org/entry/205250 | 2019-09-22T16:31:05 | {"mesh": ["D000690"], "omim": ["205250"], "orphanet": ["803"]} |
A form of potassium-aggravated myotonia (PAM) which shows dramatic improvement with the use of acetazolamide (ACZ).
## Epidemiology
Prevalence is unknown.
## Clinical description
Symptoms generally manifest during childhood (before 10 years old), with myotonia of the facial, limbs and/or intercostal muscles that is triggered by potassium ingestion, fasting and mildly by cold exposure and exercise. Muscle stiffness is generally painful. Additional clinical signs include generalized muscle hypertrophy, percussion myotonia of proximal upper extremity muscles, thenar eminence and tongue and myotonia in the eyelids. Paralysis or weakness is never observed.
## Etiology
ACZ-responsive myotonia is a sodium muscle channelopathy due to missense mutations of the SCN4A gene, encoding the alpha subunit of the skeletal muscle voltage-gated sodium channel Nav1.4.
## Genetic counseling
Transmission is autosomal dominant.
## Management and treatment
Myotonia is dramatically improved with ACZ but when ACZ does not control myotonia or when side-effects occur such as kidney stone formation, mexiletine can be used as replacement therapy.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Acetazolamide-responsive myotonia | c2931826 | 4,427 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99736 | 2021-01-23T18:55:50 | {"mesh": ["C538353"], "omim": ["608390"], "icd-10": ["G71.1"], "synonyms": ["ACZ-responsive congenital myotonia", "ACZ-responsive myotonia", "Acetazolamide-responsive congenital myotonia", "Myotonia-painful contractions syndrome", "Painful congenital myotonia", "Painful myotonia"]} |
## Clinical Features
Der Kaloustian et al. (1992) described a brother and sister born to nonconsanguineous French Canadian parents who presented with the same characteristic facial appearance, unilateral radioulnar synostosis, generalized hypotonia, and developmental retardation. Both had dolichocephaly with macrocephaly, a long narrow face, and a prominent nose. The radioulnar synostosis was of type 2, i.e., the fusion was located just distal to the proximal radial epiphysis and was associated with congenital dislocation of the radial head. See 179300.
Koc et al. (2008) reported 2 Turkish sibs, born of consanguineous parents, with clinical features similar to those described by Der Kaloustian et al. (1992). The proband was a 12-year-old girl with hypotonia and bilateral type 2 radioulnar synostosis apparent after birth. She had speech delay, delayed motor milestones, and an IQ of 63. Dysmorphic features included sloping forehead, deep-set eyes, wide nasal root and bridge, prominent columella, short philtrum, narrow palate, prognathism, dimples on the shoulders, cafe-au-lait spots, mild scoliosis, and lumbar lordosis. She also had long hyperextensible fingers and long toes. Echocardiography showed mild mitral valve prolapse and tricuspid deficiency. Her 10-year-old brother had mental retardation, mild hearing loss, and similar dysmorphic findings as his sister. However, he did not have radioulnar synostosis, which Koc et al. (2008) suggested may be a variable feature of this syndrome.
HEENT \- Dolichocephaly \- Macrocephaly \- Long narrow face \- Prominent nose Limbs \- Radioulnar synostosis \- Congenital radial head dislocation Neuro \- Generalized hypotonia \- Developmental retardation Inheritance \- Autosomal recessive ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[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
| RADIOULNAR SYNOSTOSIS, UNILATERAL, WITH DEVELOPMENTAL RETARDATION AND HYPOTONIA | c2931776 | 4,428 | omim | https://www.omim.org/entry/266255 | 2019-09-22T16:22:55 | {"mesh": ["C538217"], "omim": ["266255"], "orphanet": ["3270"]} |
Pullorum disease in poultry is caused by the bacterium Salmonella pullorum. The disease affects mainly young chicks, but can also affect older chickens, and other domestic fowl.[1]
The historical name for this disease is bacillary white diarrhea.[2]
Treatment of Pullorum is not recommended, as the goal is the eradication of the disease.[citation needed]
In Canada, Pullorum is a "reportable" disease - all suspected cases must be reported to Canadian Food Inspection Agency (CFIA). Canada has been considered free of the disease since the 1980s.[citation needed]
## References[edit]
1. ^ "Fact Sheet - Pullorum Disease and Fowl Typhoid". Retrieved 2020-03-29.
2. ^ Davison, Sherrill (October 2019). "Pullorum Disease in Poultry". Merck Manual. Retrieved 2020-03-29.
This article about a disease, disorder, or medical condition is a stub. You can help Wikipedia by expanding it.
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*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Pullorum disease | c0275785 | 4,429 | wikipedia | https://en.wikipedia.org/wiki/Pullorum_disease | 2021-01-18T19:07:33 | {"wikidata": ["Q11276425"]} |
A number sign (#) is used with this entry because of evidence that distal myopathy-5 (MPD5) is caused by compound heterozygous mutation in the ADSSL1 gene (612498) on chromosome 14q32.
Description
Distal myopathy-5 is an autosomal recessive, slowly progressive muscle disorder characterized by adolescent onset of distal muscle weakness and atrophy predominantly affecting the lower limbs. Other features include facial weakness and hyporeflexia. Patients remain ambulatory even after long disease duration (summary by Park et al., 2016).
Clinical Features
Park et al. (2016) reported 3 brothers, born of unrelated Korean parents, with onset of distal myopathy between 13 and 15 years of age. They also reported a female from an unrelated Korean family with a similar disorder. All had normal early motor development, and presented in the teenage years with slowly progressive mild facial muscle weakness as well as muscle weakness and atrophy of the lower limbs, with less severe findings in the upper limbs. Deep tendon reflexes were diminished. Imaging showed initial involvement of the gastrocnemius muscles, which had fatty replacement, followed by involvement of the quadriceps muscle after long disease duration. All patients were able to walk and climb stairs 10 to 17 years after symptom onset. Laboratory studies showed mildly elevated serum creatine kinase. Muscle biopsy showed marked variation in fiber size, a predominance of type 1 fibers, increased internal nuclei, few rimmed vacuoles, fiber splitting, increased fibrosis, and disorganized myofibrillar networks. There was no sensory impairment, joint contractures, high-arched palate, bulbar symptoms, or cardiac involvement.
Inheritance
The transmission pattern of MPD5 in the families reported by Park et al. (2016) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 4 patients from 2 unrelated Korean families with MPD5, Park et al. (2016) identified compound heterozygous mutations in the ADSSL1 gene (D304N, 612498.0001; c.1048delA, 612498.0002). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in both families. Haplotype analysis suggested a founder effect for both mutations. Patient muscle samples showed decreased expression of the mutant missense protein and no expression of the truncated protein, which was attributed to increased degradation of the mutant proteins. In vitro studies in cultured mouse muscle cells and zebrafish indicated that the mutations resulted in a loss of function.
Animal Model
Park et al. (2016) found that morpholino knockdown of the adssl1 ortholog in zebrafish embryos resulted in muscle damage characterized by abnormal birefringence that may have been due to detachment of fibers from the myotendinous junctions. Staining with myosin heavy chain antibodies showed that there were lesions in the muscle fibers, with loosely packed myofibers and disorganized fiber patterns due to abundant gaps.
INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Facial weakness MUSCLE, SOFT TISSUES \- Muscle weakness, distal, predominantly lower limbs \- Muscle weakness, distal, upper limbs \- Muscle atrophy, distal \- Dystrophic changes seen on muscle biopsy \- Variation in fiber size \- Type 1 fiber predominance \- Internal nuclei \- Fiber splitting \- Increased fibrosis \- Occasional rimmed vacuoles \- Disorganized myofibrillar networks \- Chronic myopathy seen on EMG \- Fatty replacement in the gastrocnemius muscles seen on MRI NEUROLOGIC Peripheral Nervous System \- Hyporeflexia, lower limbs LABORATORY ABNORMALITIES \- Mildly increased serum creatine kinase MISCELLANEOUS \- Onset in adolescence (13 to 15 years) \- Slowly progressive \- Patients remain ambulatory even after long disease duration \- Two unrelated Korean families have been reported (last curated July 2016) MOLECULAR BASIS \- Caused by mutation in the adenylosuccinate synthase-like 1 gene (ADSSL1, 612498.0001 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| MYOPATHY, DISTAL, 5 | c4310754 | 4,430 | omim | https://www.omim.org/entry/617030 | 2019-09-22T15:47:10 | {"omim": ["617030"], "orphanet": ["482601"], "synonyms": ["ADSSL1-related distal myopathy"]} |
Motor disorder
SpecialtyNeurology
Motor disorders are disorders of the nervous system that cause abnormal and involuntary movements. They can result from damage to the motor system.[1]
Motor disorders are defined in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) – published in 2013 to replace the fourth text revision (DSM-IV-TR) – as a new sub-category of neurodevelopmental disorders. The DSM-5 motor disorders include developmental coordination disorder, stereotypic movement disorder, and the tic disorders including Tourette syndrome.[2]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Diagnosis
* 4 References
## Signs and symptoms[edit]
Motor disorders are malfunctions of the nervous system that cause involuntary or uncontrollable movements or actions of the body.[3] These disorders can cause lack of intended movement or an excess of involuntary movement.[4] Symptoms of motor disorders include tremors, jerks, twitches, spasms, contractions, or gait problems.
Tremor is the uncontrollable shaking of an arm or a leg. Twitches or jerks of body parts may occur due to a startling sound or unexpected, sudden pain. Spasms and contractions are temporary abnormal resting positions of hands or feet. Spasms are temporary while contractions could be permanent. Gait problems are problems with the way one walks or runs. This can mean an unsteady pace or dragging of the feet along with other possible irregularities.[3]
## Causes[edit]
Pathological changes of certain areas of the brain are the main causes of most motor disorders.[4] Causes of motor disorders by genetic mutation usually affect the cerebrum.[5] The way humans move requires many parts of the brain to work together to perform a complex process. The brain must send signals to the muscles instructing them to perform a certain action. There are constant signals being sent to and from the brain and the muscles that regulate the details of the movement such as speed and direction, so when a certain part of the brain malfunctions, the signals can be incorrect or uncontrollable causing involuntary or uncontrollable actions or movements.[4]
## Diagnosis[edit]
This section is empty. You can help by adding to it. (August 2018)
## References[edit]
1. ^ Knierim J. "Chapter 6: Disorders of the Motor System". The University of Texas Health Science Center at Houston. Archived from the original on November 17, 2017. Retrieved October 5, 2013.
2. ^ American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders (Fifth ed.). Arlington, VA: American Psychiatric Publishing. pp. 74–85. ISBN 978-0-89042-555-8.
3. ^ a b Stone, Jon. "Functional Tremor/ Spasms / Walking Problems and Other Functional Movement Disorders." Movement Disorders. Neurology Research Fund of the Department of Clinical Neurosciences, 2015. Web.
4. ^ a b c Mandal, Ananya, MD. "What Are Movement Disorders?" News-Medical.net. AZO Network, 14 Oct. 2014. Web. 10 Nov. 2016.
5. ^ Esra, Tara, and Khodakhah, Kamran. Pathophysiology of Cerebellar-induced Motor Disorders (2012): ProQuest Dissertations and Theses. Web.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
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| Motor disorder | c0221163 | 4,431 | wikipedia | https://en.wikipedia.org/wiki/Motor_disorder | 2021-01-18T19:02:28 | {"mesh": ["D000068079"], "icd-10": ["F98.4", "F95.2", "F82"], "wikidata": ["Q16342771"]} |
Spastic paraplegia type 8 is part of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are divided into two types: pure and complex. The pure types involve only the nerves and muscles controlling the lower limbs and bladder, whereas the complex types also have significant involvement of the nervous system in other parts of the body. Spastic paraplegia type 8 is a pure hereditary spastic paraplegia.
Like all hereditary spastic paraplegias, spastic paraplegia type 8 involves spasticity of the leg muscles and muscle weakness. People with this condition can also experience exaggerated reflexes (hyperreflexia), a decreased ability to feel vibrations, muscle wasting (amyotrophy), and reduced bladder control. The signs and symptoms of spastic paraplegia type 8 usually appear in early to mid-adulthood. As the muscle weakness and spasticity get worse, some people may need the aid of a cane, walker, or wheelchair.
## Frequency
The prevalence of all hereditary spastic paraplegias combined is estimated to be 1 to 18 in 100,000 people worldwide. Spastic paraplegia type 8 likely accounts for only a small percentage of all spastic paraplegia cases.
## Causes
Mutations in the WASHC5 gene cause spastic paraplegia type 8. The WASHC5 gene provides instructions for making a protein called strumpellin. Strumpellin is active (expressed) throughout the body, although its exact function is unknown. The protein's structure suggests that strumpellin may interact with the structural framework inside cells (the cytoskeleton) and may attach (bind) to other proteins.
WASHC5 gene mutations are thought to change the structure of the strumpellin protein. It is unknown how the altered strumpellin protein causes the signs and symptoms of spastic paraplegia type 8.
### Learn more about the gene associated with Spastic paraplegia type 8
* WASHC5
## Inheritance Pattern
Spastic paraplegia type 8 is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Spastic paraplegia type 8 | c1863704 | 4,432 | medlineplus | https://medlineplus.gov/genetics/condition/spastic-paraplegia-type-8/ | 2021-01-27T08:24:54 | {"gard": ["9591"], "mesh": ["C580458"], "omim": ["603563"], "synonyms": []} |
## Description
Hereditary congenital facial paresis (HCFP) is the isolated dysfunction of the facial nerve (CN VII).
HCFP is considered to be distinct from Moebius syndrome (157900), which shares some of the same clinical features.
### Genetic Heterogeneity of Hereditary Congenital Facial Paresis
One locus for HCFP (HCFP1) has been mapped to chromosome 3q. Another locus (HCFP2; 604185) has been mapped to chromosome 10q. HCFP3 (614744) is caused by mutation in the HOXB1 gene (142968) on chromosome 17q21.
Clinical Features
Skyberg and Van der Hagen (1965) observed congenital unilateral hereditary facial palsy in 4 generations of a family with 16 probably affected persons. Autosomal dominant inheritance was suggested. The stapedial reflex was absent, suggesting involvement of the motor nucleus of the facial nerve. Carmena and Gomez Marcano (1943) reported 4 affected generations in a Spanish family. Autopsy in 3 cases showed partial agenesis of the facial motor nucleus. Wittig et al. (1967) observed congenital facial diplegia in 3 generations of a family. Masaki (1971) reported father and a son and daughter with bilateral facial paralysis. Ocular movements were normal. Anderson et al. (1979) reported a family with aplasia cutis congenita in 3 and possibly 4 generations, to a total of 7 or 8 affected persons. In 4 of these there was also unilateral facial palsy and in 6 there was ear abnormality, usually lop ear. No male-to-male transmission was noted.
Van der Wiel (1957) reported a large Dutch family in which 46 persons in 6 generations had congenital facial paralysis. Inheritance was clearly autosomal dominant. Kremer et al. (1996) examined 31 family members, including 20 affected, who were part of the family reported by van der Wiel (1957). The proband had asymmetric weakness of the facial muscles and unequal involvement of the muscles of the 3 branches of the facial nerve. He was born with facial weakness similar to his grandmother and many of her sibs. EMG showed enlarged polyphasic action potentials of the right orbicularis oculi and orbicularis oris muscles. The right blink reflex was absent and there was a conduction block of the facial nerve to the right orbicularis muscles and prolonged distal motor latency to the orbicularis oculi muscles. His affected brother showed slight asymmetric weakness of the orbicularis oculi muscles. Notably, his obligate carrier mother had no hint of facial muscle weakness on clinical examination and electromyography of her facial muscles revealed no abnormalities.
### Neuropathologic Findings
Verzijl et al. (2005) provided postmortem neuropathologic findings of 3 affected family members of the Dutch family reported by van der Wiel (1957) and Kremer et al. (1996). All 3 cases had a grossly normal brainstem with no hypoplasia or malformation of the rhombencephalon. The corticospinal tracts were fully developed. Microscopic examination of the brainstem revealed significantly decreased numbers of neurons in the vicinity of the facial nerve motor nuclei bilaterally compared to controls. The facial nerve roots and nerves were poorly developed, consisting of a few fine fibers only. The decreased neurons corresponded to the ipsilateral clinical weakness. The findings were distinct from those seen in Moebius syndrome, in which the authors found developmental disruption of the entire brainstem and long tracts. Verzijl et al. (2005) concluded that HCFP is a distinct disorder from Moebius syndrome, and suggested that HCFP may be a primary disorder of the fourth rhombomere, from which facial motoneurons arise.
Mapping
By linkage analysis of a large Dutch family with congenital facial paresis, Kremer et al. (1996) identified a candidate locus on chromosome 3q21-q22 (maximum lod score of 5.76 at theta = 0.0 with D3S1292).
Michielse et al. (2006) performed linkage analysis in a large Pakistani family with dominant congenital facial palsy and obtained a maximum 2-point lod score of 6.90 (theta = 0.0) on chromosome 3q21 at marker GDB:11524498. Haplotype analysis defined a 3.0-Mb critical linkage interval between D3S3607 and GDB:11524498. Penetrance was 100% in this family, with no obligate carriers or unaffected members carrying the at-risk haplotype. Michielse et al. (2006) refined the critical region in the Dutch family reported by Kremer et al. (1996) to 5.7 cM between markers D3S1589 and D3S3514 and noted that the critical region of the Pakistani family is entirely within the critical region of the Dutch family.
Molecular Genetics
Using RNA in situ hybridization, van der Zwaag et al. (2005) identified 4 genes within the HCFP1 critical region, Klf15 (606465), Ccdc37, Tmcc1 (616242), and Podxl2 (616627), that were expressed at spatial and temporal positions during embryonic mouse development that correlated with HCFP regions in humans. They concluded that these 4 genes are primary candidates for HCFP1.
### Exclusion Studies
In a large Pakistani family with dominant congenital facial palsy mapping to chromosome 3q21, Michielse et al. (2006) sequenced 7 candidate genes, KLF15, CCDC37, PODXL2 (616627), TMCC1, PLXNA1 (601055), PLXND1 (604282), and GATA2 (137295), but did not identify any causative mutations; deletions or duplications were excluded by multiplex ligation-dependent probe amplification (MLPA) in all 7 genes.
INHERITANCE \- Autosomal dominant HEAD & NECK Face \- Facial palsy, unilateral or bilateral \- Facial muscle weakness of muscles innervated by CN VII Eyes \- Absent corneal reflex response NEUROLOGIC Central Nervous System \- Facial palsy, unilateral or bilateral MISCELLANEOUS \- Nonprogressive disorder \- Occurs in the absence of trauma \- Genetic heterogeneity (see HCFP2, 604185 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| FACIAL PARESIS, HEREDITARY CONGENITAL, 1 | c1832284 | 4,433 | omim | https://www.omim.org/entry/601471 | 2019-09-22T16:14:42 | {"omim": ["601471"], "orphanet": ["306527"], "synonyms": ["Alternative titles", "FACIAL PALSY, CONGENITAL, UNILATERAL OR BILATERAL", "MOEBIUS SYNDROME 2, FORMERLY", "MOBIUS SYNDROME 2, FORMERLY"]} |
Hereditary sensory neuropathy type IA is a condition characterized by nerve abnormalities in the legs and feet (peripheral neuropathy). Many people with this condition experience prickling or tingling sensations (paresthesias), numbness, and a reduced ability to feel pain and sense hot and cold. Some affected individuals do not lose sensation, but instead feel shooting pains in their legs and feet. As the disorder progresses, the sensory abnormalities can affect the hands, arms, shoulders, joints, and abdomen. Affected individuals may also experience muscle wasting and weakness as they get older. Weakness in the ankle muscles can make walking difficult. As the condition progresses, some people with hereditary sensory neuropathy type IA require wheelchair assistance.
Individuals with hereditary sensory neuropathy type IA typically get open sores (ulcers) on their feet or hands or infections of the soft tissue of the fingertips (whitlows) that are slow to heal. Because affected individuals cannot feel the pain of these sores, they may not seek immediate treatment. Without treatment, the ulcers can become infected and may require amputation of the surrounding area or limb.
Some people with hereditary sensory neuropathy type IA develop hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss). Hearing loss typically develops in middle to late adulthood.
The signs and symptoms of hereditary sensory neuropathy type IA can begin anytime between adolescence and late adulthood. While the features of this condition tend to worsen over time, affected individuals have a normal life expectancy if signs and symptoms are properly treated.
## Frequency
Hereditary sensory neuropathy type IA is a rare condition; its prevalence is estimated to be 1 to 2 per 100,000 individuals.
## Causes
Mutations in the SPTLC1 gene cause hereditary sensory neuropathy type IA. The SPTLC1 gene provides instructions for making one part (subunit) of an enzyme called serine palmitoyltransferase (SPT). The SPT enzyme is involved in making certain fats called sphingolipids. Sphingolipids are important components of cell membranes and play a role in many cell functions.
SPTLC1 gene mutations reduce the amount of functional SPTLC1 subunit that is produced, which results in an SPT enzyme with altered activity. This altered enzyme makes molecules called deoxysphingoid bases, which it does not normally produce. Because of this new function, the SPT enzyme's production of sphingolipid is reduced. Overall, there does not seem to be a decrease in sphingolipid production because the body is able to compensate for the SPT enzyme's reduced production. When accumulated, deoxysphingoid bases are toxic to nerve cells (neurons). The gradual destruction of neurons caused by the buildup of these toxic molecules results in loss of sensation and muscle weakness in people with hereditary sensory neuropathy type IA. Although the SPT enzyme does not produce a normal amount of sphingolipids, the body is able to compensate, and there does not seem to be an overall reduction of these fats in the body.
### Learn more about the gene associated with Hereditary sensory neuropathy type IA
* SPTLC1
## Inheritance Pattern
This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Hereditary sensory neuropathy type IA | c0020071 | 4,434 | medlineplus | https://medlineplus.gov/genetics/condition/hereditary-sensory-neuropathy-type-ia/ | 2021-01-27T08:24:54 | {"gard": ["6635"], "mesh": ["D009477"], "omim": ["162400"], "synonyms": []} |
An X-linked syndromic intellectual disability characterized by a few months of normal development, followed by progressive neurodegenerative course with gradual loss of vision, development of spastic tetraplegia, convulsions, microcephaly, failure to thrive, and early death.
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| X-linked neurodegenerative syndrome, Hamel type | None | 4,435 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=85336 | 2021-01-23T19:11:13 | {"icd-10": ["G31.8"]} |
A number sign (#) is used with this entry because of evidence that early infantile epileptic encephalopathy-58 (EIEE58) is caused by heterozygous mutation in the NTRK2 gene (600456) on chromosome 9q21.
Description
EIEE58 is a severe neurodevelopmental disorder characterized by onset of refractory seizures in the first days or months of life. Affected individuals have global developmental delay with intellectual disability, usually with absent speech and inability to walk. Additional features include optic atrophy with poor or absent visual fixation, hypotonia, and spasticity (summary by Hamdan et al., 2017).
For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
Clinical Features
Hamdan et al. (2017) reported 4 unrelated children with onset of seizures in the first days or months of life. The patients had moderate to severe intellectual disability with poor or absent speech; 2 had autistic features, mainly stereotypic behaviors. The patients were severely disabled with difficulty walking or inability to walk and poor or absent eye contact. Seizures were generalized infantile spasms, focal, or of multiple types, and were difficult to control. At least 1 patient had status epilepticus. EEG abnormalities included diffuse slowing, multifocal spikes, and hypsarrhythmia. Brain imaging showed optic nerve hypoplasia in all patients. Additional features included acquired microcephaly, feeding difficulties with poor overall growth, hypotonia, spasticity, hyperreflexia, nystagmus, and poor fine or voluntary movements.
Molecular Genetics
In 4 unrelated patients with EIEE58, Hamdan et al. (2017) identified a de novo heterozygous missense mutation in the NTRK2 gene (Y434C; 600456.0003). The mutations were found by whole-exome or whole-genome sequencing. Functional studies of the variant were not performed. The patients were ascertained from several large cohorts of patients with seizures and developmental delay who underwent genetic studies.
INHERITANCE \- Autosomal dominant GROWTH Other \- Poor overall growth HEAD & NECK Head \- Microcephaly, acquired (in some patients) Eyes \- Optic nerve atrophy \- Visual impairment \- Poor visual fixation \- Nystagmus ABDOMEN Gastrointestinal \- Feeding difficulties MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Epileptic encephalopathy \- Delayed psychomotor development \- Intellectual disability, severe \- Poor or absent speech \- Spastic diplegia \- Spasticity \- Hyperreflexia \- Inability to walk \- Poor voluntary movements \- Seizures, refractory \- Seizures, multiple types \- EEG abnormalities \- Hypsarrhythmia \- Status epilepticus (in some patients) \- Delayed myelination (in some patients) Behavioral Psychiatric Manifestations \- Autistic features \- Stereotypic behaviors MISCELLANEOUS \- Onset of seizures in the first days or months of life \- De novo mutation \- Four unrelated patients have been reported (last curated January 2018) MOLECULAR BASIS \- Caused by mutation in the neurotrophic tyrosine kinase, receptor, type 2 gene NTRK2 gene ( 600456.0003 ) ▲ Close
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 58 | c4693367 | 4,436 | omim | https://www.omim.org/entry/617830 | 2019-09-22T15:44:39 | {"doid": ["0080285"], "omim": ["617830"], "orphanet": ["442835"], "synonyms": ["Undetermined EOEE"]} |
A number sign (#) is used with this entry because of evidence that Laurin-Sandrow syndrome (LSS) is caused by heterozygous mutation in an SHH (600725) regulatory element (ZRS) that resides in intron 5 of the LMBR1 gene (605522).
Clinical Features
Sandrow et al. (1970) described a father and daughter with ulnar and fibular dimelia and peculiar facies. At birth the father was noted to have hand and foot anomalies described as syndactyly and polydactyly. Operations to correct digital webs and remove several supernumerary toes were performed. Bilateral clefts enlarged the inferior posterior margins of the nares. The daughter had identical nasal clefts and mirror hands, with fusion of 10 digits in rosebud fashion bilaterally. The fibula and ulna were duplicated bilaterally and the radius and tibia were missing. Sandrow et al. (1970) considered that the case reported by Laurin et al. (1964) was 'almost identical' to their 2 cases. That was a boy who had complete polysyndactyly of his hands, which were held in a 'semicupped position,' and 'perfect mirror feet.' He also had bilateral absence of the radius and tibia with bilateral reduplication of the ulna and fibula.
Kogekar et al. (1993) described a single case and Martin et al. (1993) described an affected father and daughter. It is clear that abnormalities of the nose are particularly characteristic. Martin et al. (1993) pictured a deep groove in the columella of both father and daughter. The mirror-image hands had 'rosebud' appearance because of syndactyly. The mirror-image feet resulted in a fused midline hallux.
Martinez-Frias et al. (1994) described an isolated case. They pictured the particular nose with hypoplastic nasal alae and very sharp columella. They proposed that the disorder be called Laurin-Sandrow syndrome.
Hatchwell and Dennis (1996) reported a girl with mirror hands and feet and associated groove of the nasal columella. She was said to represent the sixth reported case of this combination of congenital anomalies. Mutation in a HOX gene was suggested by Hatchwell and Dennis (1996) as a likely candidate for the syndrome.
Matsumoto et al. (1997) found reports of 7 patients with mirror hands and feet. Parent-to-child transmission was reported in 2 families.
Kantaputra (2001) described a Thai man with Laurin-Sandrow syndrome, the ninth reported case. He had an underdeveloped nasal bone, scar-like seams under the nose, large heads of the mandibular condyles, and brachymesophalangy of toes as newly observed findings of the syndrome. He also had mental retardation. He showed duplication of the ulna with nonopposable triphalangeal thumbs and polydactyly of 1 finger. Mirror-image polydactyly of the toes was present. There were 9 toes on the right and 8 on the left. Synostosis of severely malformed tarsal bones was noted.
Kjaer et al. (2005) reported a father and son with nasal and limb defects characteristic of Laurin-Sandrow syndrome. Both individuals had distinct nasal defects, triphalangeal thumb, upper limb postaxial polydactyly, total syndactyly of all fingers, and lower limb preaxial mirror image polydactyly with tibia and fibula appearing alike. In the son, lower limb vessels were investigated by ultrasound and flow Doppler measurements. Bilaterally, 2 posterior tibial arteries were located medially and laterally, respectively, each ending in a separate plantar arcade supplying the toes with at least 1 vessel between every metatarsus. The anterior tibial artery was also duplicated and located in front of each of the 2 identical zeugopods ending in 2 sets of dorsal arcades. An additional and larger vessel was located between the 2 sets of duplicated vessels. These findings suggested that vessel formation in the lower limb is closely linked to the early patterning of the posteriorly located fibula and not tibia, which may seem surprising in the light of the anatomic nomenclature (e.g., of the anterior and posterior tibial artery).
Marino-Enriquez et al. (2008) reported a female infant, born at 33-weeks' gestation with multiple anomalies suggestive of LSS, who died at age 45 minutes. Postmortem examination showed abnormal face with prominent forehead, flat nose, hypertelorism, deep longitudinal groove in the columella, and inverse V-shaped mouth. There was polysyndactyly of the hands and feet with symmetric configuration and fusion of the nails. There were 7 metacarpals in each hand and foot. One foot had 12 toes, and the other had 11 toes, and both feet had an additional finger-shaped appendage on the internal aspect. Both tibiae were shorter than the fibulae; the forearm bones showed no abnormalities. Brain anomalies included absence of the olfactory sulci, ventricular dilatation, ectopic neurons, and diffuse gliosis. In a review of reports of the disorder, Marino-Enriquez et al. (2008) noted marked heterogeneity in the terminology and classification of polydactyly. The authors proposed that the entity LSS only be used in cases with symmetric tetramelic polysyndactyly, especially 'cup-shaped' hands and mirror feet, in association with nasal anomalies.
### Segmental Laurin-Sandrow Syndrome
Innis and Hedera (2004) reported 2 unrelated boys with isolated left mirror hand and ulnar duplication. One patient had preaxial polydactyly of the left hand and limited flexion and extension of the left elbow and wrist. The left hand had 8 fingers and no thumb. Radiographic analysis showed absence of the radius and ulnar duplication; the left shoulder and upper arm were normal. The second child had a flexed wrist with 7 digits on the left hand and no thumb. Radiographic analysis of the left upper limb showed 2 ulnae and 7 triphalangeal digits. His father had a unilateral clubfoot and his mother had a mild hallux valgus. Neither child had nasal abnormalities. Innis and Hedera (2004) suggested that these patients had 'segmental' Laurin-Sandrow syndrome due to somatic mutation involving the precursor cells of the left upper limb.
Inheritance
Martin et al. (1993) thought that autosomal dominant inheritance was likely in their family. Martinez-Frias et al. (1994) stated that their sporadic case was born to a 39-year-old father, supporting the assumption of autosomal dominant new mutation.
Father-to-son transmission of Laurin-Sandrow syndrome in the family reported by Kjaer et al. (2005) excluded X-linked inheritance.
Cytogenetics
Ohashi et al. (1995) and Kim et al. (1997) reported a Japanese boy with mirror-image polydactyly who had a de novo 46,XY,t(2;14)(p23.3;q13) karyotype. Although the patient had no other anomalies, such as nasal and long-bone abnormalities, they considered that the disorder was a variant of mirror hands and feet and hypothesized that a gene that may determine anterior-posterior pattern in early developing limbs had been disrupted by a translocation breakpoint.
Matsumoto et al. (1997) identified a YAC clone spanning a translocation breakpoint at 14q13. They confirmed that the breakpoint was located between 2 specific loci within a distance of 0.6 cM. In a later study, Matsumoto et al. (1997) constructed a 1.2-Mb high-resolution physical map with a contig composed of 16 bacterial artificial chromosomes (BACs) and 6 P1-derived artificial chromosomes (PACs) at a region around the breakpoint, extending from the loci D14S75 to D14S728.
In the Japanese boy with postaxial mirror-image polydactyly and a de novo balanced chromosomal translocation, t(2;14)(p23.3;q13), who was originally reported by Ohashi et al. (1995) and Kim et al. (1997) and studied by Matsumoto et al. (1997), Kondoh et al. (2002) identified a novel gene, MIPOL1 (606850), that was disrupted at the 14q13 breakpoint. Two other unrelated patients with limb anomalies similar to mirror-image polydactyly failed to show mutations in the MIPOL1 gene. At the other breakpoint, 2p23.3, only the neuroblastoma-amplified protein gene (NAG) was identified, and it is located at least 50 kb centromeric to the breakpoint, making it unlikely to be causative for mirror-image polydactyly.
Molecular Genetics
In affected individuals from 3 families with Laurin-Sandrow syndrome, Lohan et al. (2014) screened for copy number variation in the 7q36 chromosomal region and detected heterozygosity for 3 different microduplications of the ZRS region in intron 5 of the LMBR1 gene (605522.0018-605522.0020), with duplication lengths varying from 16 to 75 kb. The array CGH results were confirmed by qPCR in the 3 index patients, and the microduplications segregated with disease in each family. Lohan et al. (2014) noted that compared with previously reported ZRS microduplication-associated syndromes, the family with the shortest duplication (16 kb; 605522.0008) had the most complex phenotype: the affected father and son, originally reported by Kjaer et al. (2005), exhibited bilateral complete syndactyly of the hands, aplasia of the patella and tibia, duplication of the fibula, and preaxial mirror-image polysyndactyly of the feet. In contrast, the family with the largest reported duplication (589 kb; 605522.0009) had triphalangeal thumb-polysyndactyly syndrome (see 174500).
INHERITANCE \- Autosomal dominant HEAD & NECK Nose \- Cleft nares, bilateral \- Grooved columella \- Hypoplastic alae nasi SKELETAL Limbs \- Zeugopodial duplication, symmetrical \- Ulnar duplication \- Fibular duplication \- Absent radius \- Dysplastic tibia \- Absent tibia \- Dislocation of the patella \- Absent patella Hands \- Autopodial duplication, symmetrical \- Duplication of bones of the hand \- Dysplastic carpal bones \- Syndactyly \- Polydactyly, preaxial or postaxial \- Cup-shaped hands \- Triphalangeal thumb Feet \- Short, broad feet \- Autopodial duplication, symmetrical \- Dysplastic tarsal bones \- Duplication of bones of the feet \- Syndactyly \- Polydactyly, preaxial or postaxial MISCELLANEOUS \- Limb malformations are variable MOLECULAR BASIS \- Caused by mutation in the ZRS regulatory element located in the homolog of the mouse limb region 1 gene (LMBR1, 605522.0018 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| LAURIN-SANDROW SYNDROME | c1851100 | 4,437 | omim | https://www.omim.org/entry/135750 | 2019-09-22T16:41:12 | {"doid": ["0111350"], "mesh": ["C535689"], "omim": ["135750"], "orphanet": ["2378"], "synonyms": ["Alternative titles", "SANDROW SYNDROME", "MIRROR HANDS AND FEET WITH NASAL DEFECTS", "TETRAMELIC MIRROR-IMAGE POLYDACTYLY", "MIRROR-IMAGE POLYDACTYLY", "FIBULA AND ULNA, DUPLICATION OF, WITH ABSENCE OF TIBIA AND RADIUS"]} |
Intestinal metaplasia
Intestinal metaplasia (top middle of image) of the gastric antrum and adenocarcinoma of the stomach (left/centre of image). H&E stain.
Intestinal metaplasia is the transformation (metaplasia) of epithelium (usually of the stomach or the esophagus) into a type of epithelium resembling that found in the intestine. In the esophagus, this is called Barrett's esophagus. Chronic inflammation caused by H. pylori infection in the stomach and GERD in the esophagus are seen as the primary instigators of metaplasia and subsequent adenocarcinoma formation. Initially, the transformed epithelium resembles the small intestine lining; in the later stages it resembles the lining of the colon. It is characterized by the appearance of goblet cells and expression of intestinal cell markers such as the transcription factor, CDX2.
## Risk factors[edit]
People of East Asian ethnicity with gastric intestinal metaplasia are at increased risk of stomach cancer.[1]
## References[edit]
1. ^ Choi, AY; Strate, LL; Fix, MC; Schmidt, RA; Ende, AR; Yeh, MM; Inadomi, JM; Hwang, JH (April 2018). "Association of gastric intestinal metaplasia and East Asian ethnicity with the risk of gastric adenocarcinoma in a U.S. population". Gastrointestinal Endoscopy. 87 (4): 1023–1028. doi:10.1016/j.gie.2017.11.010. PMID 29155082.
## External links[edit]
* AGA Clinical Practice Guidelines on Management of Gastric Intestinal Metaplasia
* Intestinal metaplasia (definition) – mondofacto.com.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Intestinal metaplasia | c0334037 | 4,438 | wikipedia | https://en.wikipedia.org/wiki/Intestinal_metaplasia | 2021-01-18T18:47:04 | {"umls": ["C0334037"], "wikidata": ["Q872095"]} |
Autosomal recessive congenital stationary night blindness is a disorder of the retina, which is the specialized tissue at the back of the eye that detects light and color. People with this condition typically have difficulty seeing and distinguishing objects in low light (night blindness). For example, they may not be able to identify road signs at night or see stars in the night sky. They also often have other vision problems, including loss of sharpness (reduced acuity), nearsightedness (myopia), involuntary movements of the eyes (nystagmus), and eyes that do not look in the same direction (strabismus).
The vision problems associated with this condition are congenital, which means they are present from birth. They tend to remain stable (stationary) over time.
## Frequency
Autosomal recessive congenital stationary night blindness is likely a rare disease; however, its prevalence is unknown.
## Causes
Mutations in several genes can cause autosomal recessive congenital stationary night blindness. Each of these genes provide instructions for making proteins that are found in the retina. These proteins are involved in sending (transmitting) visual signals from cells called rods, which are specialized for vision in low light, to cells called bipolar cells, which relay the signals to other retinal cells. This signaling is an essential step in the transmission of visual information from the eyes to the brain.
Mutations in two genes, GRM6 and TRPM1, cause most cases of this condition. These genes provide instructions for making proteins that are necessary for bipolar cells to receive and relay signals. Mutations in other genes involved in the same bipolar cell signaling pathway are likely responsible for a small percentage of cases of autosomal recessive congenital stationary night blindness.
Gene mutations that cause autosomal recessive congenital stationary night blindness disrupt the transmission of visual signals between rod cells and bipolar cells or interfere with the bipolar cells' ability to pass on these signals. As a result, visual information received by rod cells cannot be effectively transmitted to the brain, leading to difficulty seeing in low light. The cause of the other vision problems associated with this condition is unclear. It has been suggested that the mechanisms that underlie night blindness can interfere with other visual systems, causing myopia, reduced visual acuity, and other impairments.
Some people with autosomal recessive congenital stationary night blindness have no identified mutation in any of the known genes. The cause of the disorder in these individuals is unknown.
### Learn more about the genes associated with Autosomal recessive congenital stationary night blindness
* GRM6
* TRPM1
Additional Information from NCBI Gene:
* CABP4
* GPR179
* LRIT3
* SLC24A1
## Inheritance Pattern
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Autosomal recessive congenital stationary night blindness | c4041558 | 4,439 | medlineplus | https://medlineplus.gov/genetics/condition/autosomal-recessive-congenital-stationary-night-blindness/ | 2021-01-27T08:24:34 | {"mesh": ["C536122"], "omim": ["610427", "257270", "613216", "613830", "614565", "615058"], "synonyms": []} |
Excessive fear of hospitals
Nosocomephobia
SpecialtyPsychology
Nosocomephobia (no-so-comb-phobia) is defined as the excessive fear of hospitals.[1][2][3]
Dr. Marc Siegel, a physician and clinical professor at New York University Medical Center says, "It's perfectly understandable why many people feel the way they do about a hospital stay," and continues, "You have control of your life ... up until you're admitted to a hospital."[4]
Former U.S. President Richard Nixon, allegedly had an irrational fear of hospitals; even purportedly refusing to get a treatment for a blood clot in 1974, saying, "if I go into the hospital, I'll never come out alive."[5][6]
Nosocomephobia comes from the Greek νοσοκομεῖον (nosokomeion), "hospital"[7] and φόβος (phobos), "fear".[8][9]
## See also[edit]
* Nosophobia
* List of phobias
## References[edit]
1. ^ Semple, David; Roger Smyth; Jonathan Burns; Rajan Darjee; Andrew McIntosh (2005). Oxford handbook of psychiatry. Oxford University Press. ISBN 978-0-19-852783-1.
2. ^ Glenn, Harrold. "The Ultimate Self-Hypnosis Cure for the Phobia of Hospitals (Nosocomephobia)". Diviniti Publishing Ltd. Retrieved 29 November 2009.
3. ^ "Nosocomephobia". The Personal Genome. Archived from the original on 5 October 2018. Retrieved 29 November 2009.
4. ^ Kirchheimer, Sid. "How to Survive a Stay in the Hospital". Web MD. medicinenet.com. Retrieved 29 November 2009.
5. ^ "Nixon Rejecting Care in Hospital". UPI. Spokane Daily Chronicle. 16 September 1974. Archived from the original on 1 October 2015. Retrieved 28 November 2009.
6. ^ "Doctor Tells Nixon's Fear of Hospital". Associated Press (AP). Toledo Blade. September 15, 1974. Retrieved 28 November 2009.[dead link]
7. ^ νοσοκομεῖον, Henry George Liddell, Robert Scott, A Greek-English Lexicon, on Perseus
8. ^ φόβος, Henry George Liddell, Robert Scott, A Greek-English Lexicon, on Perseus
9. ^ Thomas, Charles (2001). The words of medicine: sources, meanings, and delights. University of Michigan: Charles C. Thomas. ISBN 0-398-07132-2.
This abnormal psychology–related article is a stub. You can help Wikipedia by expanding it.
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*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Nosocomephobia | None | 4,440 | wikipedia | https://en.wikipedia.org/wiki/Nosocomephobia | 2021-01-18T18:48:01 | {"wikidata": ["Q3344353"]} |
Hypokalemic periodic paralysis is a condition that causes episodes of extreme muscle weakness typically beginning in childhood or adolescence. Most often, these episodes involve a temporary inability to move muscles in the arms and legs. Attacks cause severe weakness or paralysis that usually lasts from hours to days. Some people may have episodes almost every day, while others experience them weekly, monthly, or only rarely. Attacks can occur without warning or can be triggered by factors such as rest after exercise, a viral illness, or certain medications. Often, a large, carbohydrate-rich meal or vigorous exercise in the evening can trigger an attack upon waking the following morning. Although affected individuals usually regain their muscle strength between attacks, some develop persistent muscle weakness later in life.
People with hypokalemic periodic paralysis typically have reduced levels of potassium in their blood (hypokalemia) during episodes of muscle weakness. Researchers are investigating how low potassium levels may be related to the muscle abnormalities in this condition.
## Frequency
Although its exact prevalence is unknown, hypokalemic periodic paralysis is estimated to affect 1 in 100,000 people. Men tend to experience symptoms of this condition more often than women.
## Causes
Mutations in the CACNA1S or SCN4A gene can cause hypokalemic periodic paralysis. These genes provide instructions for making proteins that play essential roles in muscles used for movement (skeletal muscles). For the body to move normally, skeletal muscles must tense (contract) and relax in a coordinated way. Muscle contractions are triggered by the flow of certain positively charged atoms (ions) into muscle cells. The CACNA1S and SCN4A proteins form channels that control the flow of these ions. The channel formed by the CACNA1S protein transports calcium ions into cells, while the channel formed by the SCN4A protein transports sodium ions.
Mutations in the CACNA1S or SCN4A gene alter the usual structure and function of calcium or sodium channels. The altered channels are "leaky," allowing ions to flow slowly but continually into muscle cells, which reduces the ability of skeletal muscles to contract. Because muscle contraction is needed for movement, a disruption in normal ion transport leads to episodes of severe muscle weakness or paralysis.
A small percentage of people with the characteristic features of hypokalemic periodic paralysis do not have identified mutations in the CACNA1S or SCN4A gene. In these cases, the cause of the condition is unknown.
### Learn more about the genes associated with Hypokalemic periodic paralysis
* CACNA1S
* SCN4A
## Inheritance Pattern
This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Hypokalemic periodic paralysis | c3714580 | 4,441 | medlineplus | https://medlineplus.gov/genetics/condition/hypokalemic-periodic-paralysis/ | 2021-01-27T08:25:16 | {"gard": ["6729"], "omim": ["170400", "613345"], "synonyms": []} |
Pigment-dispersion syndrome is an eye disorder that occurs when pigment granules that normally adhere to the back of the iris (the colored part of the eye) flake off into the clear fluid produced by the eye (aqueous humor). These pigment granules may flow towards the drainage canals of the eye, slowly clogging them and raising the pressure within the eye (intraocular pressure or IOP). This rise in eye pressure can cause damage to the optic nerve (the nerve in the back of the eye that carries visual images to the brain). If the optic nerve becomes damaged, pigment-dispersion syndrome becomes pigmentary glaucoma. This happens in about 30% of cases. Pigment-dispersion syndrome commonly presents between the second and fourth decades, which is earlier than other types of glaucoma. While men and women are affected in equal numbers, men develop pigmentary glaucoma up to 3 times more often than women. Myopia (nearsightedness) appears to be an important risk factor in the development of pigment-dispersion syndrome and is present in up to 80% of affected individuals. The condition may be sporadic or follow an autosomal dominant pattern of inheritance with reduced penetrance . At least one gene locus on chromosome 7 has been identified. Pigment-dispersion syndrome can be treated with eye drops or other medications. In some cases, laser surgery may be performed.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Pigment-dispersion syndrome | c1271398 | 4,442 | gard | https://rarediseases.info.nih.gov/diseases/4356/pigment-dispersion-syndrome | 2021-01-18T17:58:19 | {"mesh": ["C563184"], "umls": ["C1271398"], "orphanet": ["26823"], "synonyms": []} |
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: "Soft tissue injury" – news · newspapers · books · scholar · JSTOR (March 2018) (Learn how and when to remove this template message)
A soft tissue injury (STI) is the damage of muscles, ligaments and tendons throughout the body. Common soft tissue injuries usually occur from a sprain, strain, a one off blow resulting in a contusion or overuse of a particular part of the body. Soft tissue injuries can result in pain, swelling, bruising and loss of function.[1]
## Contents
* 1 Signs and symptoms
* 1.1 Sprains
* 1.2 Strains
* 1.3 Bruising (contusion)
* 1.4 Tendinitis
* 2 Diagnosis
* 2.1 Classifications
* 2.1.1 Acute injuries
* 2.1.2 Overuse injuries
* 2.2 Commonly injured tissues
* 3 Management
* 3.1 RICE method: (Rest, Ice, Compression, Elevation)
* 3.2 No HARM Protocol: (Heat, Alcohol, Re-injury, Massage)
* 3.3 Treatment
* 4 References
* 5 Sources
## Signs and symptoms[edit]
### Sprains[edit]
Main article: Sprain
A sprain is a type of acute injury which results from the stretching or tearing of a ligament. Depending on the severity of the sprain, the movement on the joint can be compromised since ligaments aid in the stability and support of joints. Sprains are commonly seen in vulnerable areas such as the wrists, knees and ankles. They can occur from movements such as falling on an outstretched hand or a twisting of the ankle or foot.[2]
The severity of a sprain can be classified:
* Grade 1: Only some of the fibers in the ligament are torn, and the injured site is moderately painful and swollen. Function in the joint will be unaffected for the most part.
* Grade 2: Many of the ligament fibers are torn, and pain and swelling is moderate. The functionality of the joint is compromised.
* Grade 3: The soft tissue is completely torn, and functionality and strength on the joint is completely compromised. In most cases, surgery is needed to repair the damage.[3]
### Strains[edit]
Main article: Strain (injury)
A strain is a type of acute injury that occurs to the muscle or tendon. Similar to sprains, it can vary in severity, from a stretching of the muscle or tendon to a complete tear of the tendon from the muscle. Some of the most common places that strains occur are in the foot, back of the leg (hamstring), or back.[2]
### Bruising (contusion)[edit]
Main article: Bruise
A contusion is the discoloration of the skin, which results from underlying muscle fibers and connective tissue being crushed.This can happen in a variety of ways such as a direct blow to the skin, or a fall taken against a hard surface. The discoloration in the skin is present when blood begins to pool around the injury.
### Tendinitis[edit]
Main article: Tendinitis
Tendinitis is a type of overuse injury to the tendons, which demonstrates signs of inflammation of tendons around a joint. Tendinitis is the most common cause of shoulder pain and also leg pain . Tendinitis occurs when there is repetitive stress on the subacromial bursa, which causes the bones to make contact with the tendons and irritate them.
## Diagnosis[edit]
### Classifications[edit]
#### Acute injuries[edit]
Bruising is a type of acute soft tissue injury
Any type of injury that occurs to the body through sudden trauma, such as a fall, twist or blow to the body. A few examples of this type of injury would be sprains, strains and contusions.[4]
#### Overuse injuries[edit]
An overuse injury occurs when a certain activity is repeated frequently and the body does not have enough time to recover between occurrences. Examples include bursitis and tendinitis.[4]
### Commonly injured tissues[edit]
With examples of each. Parentheses indicate location in body
* Ligaments
Anterior cruciate ligament (knee), medial collateral ligament (knee), ulnar collateral ligaments (wrist/hand), interspinous ligaments (vertebrae)
* Muscles
Biceps brachii (upper arm), rectus femoris (thigh), transverse abdominis (abdominals)
* Tendons
Patellar tendon (knee), calcaneal/Achilles tendon (foot/lower leg), biceps tendon (shoulder/elbow)
* Nerves
Brachial plexus (shoulder), ulnar nerve (elbow/hand), peroneal nerve (ankle/foot), cranial nerves I-XII(head)
* Bones
Femur (leg), humerus (arm), ribs (torso), metatarsals I-VI (foot), metacarpals I-VI (hand)
* Cartilage
Menisci (knee), intervertebral discs (spine), acetabulum (hip)
## Management[edit]
### RICE method: (Rest, Ice, Compression, Elevation)[edit]
The RICE method is an effective procedure used in the initial treatment of a soft tissue injury.
Rest: It is suggested that the patient take a break from the activity that caused the injury in order to give the injury time to heal.
Ice: The injury should be iced on and off in 20 minute intervals, avoiding direct contact of the ice with the skin.
Compression: Bandaging the injury will compress it, and prevent any further bleeding or swelling from occurring.
Elevation: Elevating the injury above the heart while resting will aid in the reduction of swelling.
### No HARM Protocol: (Heat, Alcohol, Re-injury, Massage)[edit]
This method should not be used within the first 48–72 hours after the injury in order to speed up the recovery process.
Heat: Applying heat to the injured area can cause blood flow and swelling to increase.
Alcohol: Alcohol can inhibit the ability to feel if the injury is becoming more aggravated, as well as increasing blood flow and swelling.
Re-injury: Avoid any activities that could aggravate the injury and cause further damage.
Massage: Massaging an injured area can promote blood flow and swelling, and potentially cause more damage if done too early.[3]
### Treatment[edit]
If severe pain persists after the first 24hours it is recommended that an individual consult with a professional who can make a diagnosis and implement a treatment plan so the patient can return to everyday activities.[5] To make a full diagnosis, a professional may use nerve conduction studies to localize nerve dysfunction (e.g. carpal tunnel syndrome), assess severity, and help with prognosis. Electrodiagnosis also helps differentiate between myopathy and neuropathy.
Ultimately, the best method of imaging soft tissue is magnetic resonance imaging (MRI), though it is cost-prohibitive and carries a high false positive rate.
## References[edit]
1. ^ Lovering, 2008
2. ^ a b "Soft Tissue Injuries (Sprains and Strains)". Victoria State Government.
3. ^ a b "Sprains, Strains, and Other Soft Tissue Injuries". American Academy of Orthopedic Surgeons.
4. ^ a b "Soft Tissue Injuries". Sports Medicine Australia.
5. ^ Flegel, 2004
## Sources[edit]
* Flegel, Melinda J. (2004). Sport first aid: A coach’s guide to preventing and responding to injuries. Hong Kong, Japan: Human Kinetics.
* Lindsay, R., Watson, G., Hickmont, D., Broadfoot, A., & Bruynel, L. (1994). Treat your own strains sprains and bruises. New Zealand: Spinal Publications.
* Lovering, R.M. (2008). "Physical therapy and related interventions". In P.M. Tiidus (ed.), Skeletal muscle damage and repair (pp. 219–230). United States of America: Human Kinetics.
* Prentice, William E. "Tissue Response to Injury", Principles of Athletic Training: A Competency Based Approach. 14th ed. New York: McGraw Hill Companies, 2011. 260-277.
* Subotnick, Steven (1991). Sports and Exercise Injuries: Conventional, Homeopathic and Alternative Treatments. California, United States of America: North Atlantic Books.
* v
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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 inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Soft tissue injury | c0037578 | 4,443 | wikipedia | https://en.wikipedia.org/wiki/Soft_tissue_injury | 2021-01-18T19:02:51 | {"mesh": ["D017695"], "wikidata": ["Q7554047"]} |
Alcohol consumption in Russia remains among the highest in the world. According to a 2011 report by the World Health Organization, annual per capita consumption of alcohol in Russia was about 15.76 litres, the fourth-highest volume in Europe. It has dropped to less than 10 litres as of 2019.[1] Another dangerous trait of Russian alcohol consumption pattern was the high volume of spirits compared with other alcoholic drinks (such as beer or red wine).[2]
Russia currently implements a variety of anti-alcoholism measures (banning spirits and beer trade at night, raising taxes). According to medical officials, these policies have resulted in a considerable fall of alcohol consumption volumes, to 13.5 litres by 2013, with wine and beer overtaking spirits as the main source of beverage alcohol.[3] These levels are comparable with European Union averages. Alcohol producers claim that falling legal consumption is accompanied by growth in sales of illegally produced drink.[4]
High volumes of alcohol consumption have serious negative effects on Russia's social fabric and bring political, economic and public health ramifications. Alcoholism has been a problem throughout the country's history because drinking is a pervasive, socially acceptable behaviour in Russian society[5] and alcohol has also been a major source of government revenue for centuries. It has repeatedly been targeted as a major national problem,[6][7] with mixed results. Alcoholism in Russia has, according to some authors, acquired a character of a national disaster[8][9] and has the scale of a humanitarian catastrophe.[10]
## Contents
* 1 History
* 1.1 20th century
* 1.2 21st century
* 2 Impact
* 2.1 Demographic
* 2.2 Economic
* 2.3 Social
* 2.3.1 Suicide
* 3 Treatment
* 4 See also
* 5 References
* 6 Further reading
## History[edit]
See also: Prohibition in the Russian Empire and the Soviet Union
Legend holds that the tenth-century Russian prince Vladimir the Great rejected Islam as a state religion for the country because of its prohibition of alcohol.[11] Historically, alcohol has been tolerated or even encouraged as a source of revenue.[12]
In the 1540s, Ivan the Terrible began setting up kabaks (кабак) or taverns in his major cities to help fill his coffers;[12][13] a third of Russian men were in debt to the kabaks by 1648.[13] By 1860, vodka, the national drink, was the source of 40% of the government's revenue.[13]
### 20th century[edit]
In 1909 average alcohol consumption was said to be 11 bottles per capita per year. An estimated 4% of the population of St.Petersburg were estimated to be alcoholics in 1913.[14]
At the beginning of World War I, prohibition was introduced in the Russian Empire, limiting the sale of hard liquor to restaurants.
After the Bolshevik Party came to power, they made repeated attempts to reduce consumption in the Soviet Union.[12] However, by 1925, vodka had reappeared in state-run stores.[13] Joseph Stalin reestablished a state monopoly to generate revenue.[12]
Soviet leaders Nikita Khrushchev,[15] Leonid Brezhnev,[15] Yuri Andropov, and Konstantin Chernenko all tried to stem alcoholism.[12] Mikhail Gorbachev increased controls on alcohol in 1985;[16] he attempted to impose a partial prohibition, which involved a massive anti-alcohol campaign, severe penalties against public drunkenness and alcohol consumption, and restrictions on sales of liquor. The campaign was temporarily successful in reducing per capita alcohol consumption and improving quality-of-life measures such as life expectancies and crime rates, but it was deeply unpopular among the population and it ultimately failed.
### 21st century[edit]
In 2006, a new alcohol excise stamp known as the EGAIS system was introduced, allowing to identify every bottle sold in Russia through a centralized data system.[17]
In 2010, Russian President Dmitry Medvedev nearly doubled the minimum price of a bottle of vodka in an effort to combat the problem.[18]
In 2012, a national ban on sales of all types of alcoholic beverages from 11 p.m. to 8 a.m. was introduced to complement regional bans.[19]
The Russian government has proposed reducing the state minimum price of vodka in reaction to the 2014–15 Russian financial crisis.[20]
In December 2016, 49 people in Irkutsk died in a mass methanol poisoning.[21] Medvedev reacted by calling for a ban on non-traditional alcoholic liquids like the bath lotion involved in this case, stating that "it's an outrage, and we need to put an end to this".[22]
In recent years, alcohol-related deaths in Russia have dropped dramatically year over year falling to 6,789 in 2017 from 28,386 in 2006 and continuing to decline into 2018. Under Vladimir Putin, new restrictions have been imposed, and officials have discussed raising the legal drinking age from 18 to 21.[23][24][dubious – discuss]
## Impact[edit]
Disability-adjusted life year for alcohol use disorders per 100,000 inhabitants in 2004.
no data
<50
50-170
170-290
290-410
410-530
530-650
650-770
770-890
890-1010
1010-1130
1130–1250
>1250
### Demographic[edit]
See also: Demographics of Russia
A study by Russian, British and French researchers published in The Lancet scrutinized deaths between 1990 and 2001 of residents of three Siberian industrial towns with typical mortality rates and determined that 52% of deaths of people between the ages of 15 and 54 were the result of alcohol abuse.[25] Lead researcher Professor David Zaridze estimated that the increase in alcohol consumption since 1987 has caused an additional three million deaths nationwide.[25]
In 2007, Gennadi Onishenko, the country's chief public health official, voiced his concern over the nearly threefold rise in alcohol consumption over the past 16 years; one in eight deaths was attributed to alcohol-related diseases, playing a major role in Russia's population decline.[16] Men are particularly hit hard: according to a U.N. National Human Development Report, Russian males born in 2006 had a life expectancy of just over 60 years, or 17 years fewer than western Europeans, while Russian females could expect to live 13 years longer than their male counterparts.[26]
In June 2009, the Public Chamber of Russia reported over 500,000 alcohol-related deaths annually, noting that Russians consume about 18 litres (4.0 imp gal; 4.8 US gal) of spirits a year, more than double the 8 litres (1.8 imp gal; 2.1 US gal) that World Health Organization experts consider dangerous.[27]
### Economic[edit]
In 1985, at the time of Gorbachev's campaign to reduce drinking, it was estimated that alcoholism resulted in $8 billion in lost production.[28]
### Social[edit]
Further information: Crime in Russia and Domestic violence in Russia
In the early 1980s, an estimated "two-thirds of murders and violent crimes were committed by intoxicated persons; and drunk drivers were responsible for 14,000 traffic deaths and 60,000 serious traffic injuries".[15] In 1995, about three quarters of those arrested for homicide were under the influence of alcohol, and 29% of respondents reported that children beaten within families were the victims of drunks and alcoholics.[29]
A 1997 report published in the Journal of Family Violence found that among male perpetrators of spousal homicide, 60–75% of offenders had been drinking prior to the incident.[29]
#### Suicide[edit]
Further information: Suicide in Russia
In 2008, suicide claimed 38,406 lives in Russia.[30] With a rate of 27.1 suicides per 100,000 people, Russia has one of the highest suicide rates in the world, although it has been steadily decreasing since it peaked at around 40 per 100,000 in the mid-late 1990s,[31] including a 30% drop from 2001 to 2006.
Heavy alcohol use is a significant factor in the suicide rate, with an estimated half of all suicides a result of alcohol abuse. This is evident by the fact that Russia's suicide rate since the mid-'90s has declined alongside per capita alcohol consumption, despite the economic crises since then; alcohol consumption is more of a factor than economic conditions.[32]
## Treatment[edit]
Prophylactoriums, medical treatment centres, were established in 1925 to treat alcoholics and prostitutes. By 1929 there were five in Moscow.[14] Chronic alcoholics evading treatment were detained for up to two years.[33]
From the 1930s and 1940s until the mid-1980s, the main treatment for alcoholism in Russia was conditioned response therapy. This treatment has since fallen out of favour, and the modern mainstream treatment has become pharmacotherapy, which involves detailed analyses of each patient, medicinal treatment, psychotherapy, sociotherapy, and other support.[34] Although Alcoholics Anonymous exists in Russia, it lacks support from the government and so is generally dismissed by the Russian population.[citation needed]
One alternative therapy for alcoholism that has been used in Russia is the practice of "coding", in which therapists pretend to insert a "code" into patients' brains with the ostensible effect that drinking even small amounts of alcohol will be extremely harmful or even lethal. Despite not being recommended in Russian clinical guidelines, it has enjoyed considerable popularity. In recent years its use has lessened, due to the spread of information about its ineffectiveness.[35][36]
## See also[edit]
* Russian Cross
* Vodka Belt
* List of federal subjects of Russia by incidence of substance abuse
* List of countries by alcohol consumption per capita
## References[edit]
1. ^ "Global stat" (PDF). 2011. Retrieved February 26, 2016.
2. ^ See, e.g., Korotayev A., Khaltourina D. Russian Demographic Crisis in Cross-National Perspective. Russia and Globalization: Identity, Security, and Society in an Era of Change. Ed. by D. W. Blum. Baltimore, MD: Johns Hopkins University Press, 2008. P. 37-78; Khaltourina, D. A., & Korotayev, A. V. 'Potential for alcohol policy to decrease the mortality crisis in Russia', Evaluation & the Health Professions, vol. 31, no. 3, Sep 2008. pp. 272–281.
3. ^ "Россияне стали меньше пить". October 17, 2013. Retrieved February 26, 2016.
4. ^ "Анализ алкогольного рынка в 2013 году - рост и падение". RosInvest. March 19, 2014. Retrieved February 26, 2016.
5. ^ See, e.g., Korotayev A., Khaltourina D. Russian Demographic Crisis in Cross-National Perspective. Russia and Globalization: Identity, Security, and Society in an Era of Change. Ed. by D. W. Blum. Baltimore, MD: Johns Hopkins University Press, 2008. P. 37-78; Khaltourina, D. A., & Korotayev, A. V. 'Potential for alcohol policy to decrease the mortality crisis in Russia', Evaluation & the Health Professions, vol. 31, no. 3, Sep 2008. pp. 272–281.
6. ^ "Russia declares war on alcoholism". RIA Novosti. January 14, 2010.
7. ^ "Each of 7 million Russian alcoholics drinks 27 liters of alcohol a year". Pravda. November 9, 2006.
8. ^ Заграев Г. Г. Алкоголизм и пьянство в России. Пути выхода из кризисной ситуации //Социологические исследования, № 8, Август 2009, C. 74-84
9. ^ Пьянство ставит крест на будущем России // Утро, 05 октября 2009 по материалам ООН: Россия перед лицом демографических вызовов Archived 2014-12-01 at the Wayback Machine — М., ПРООН, 2009, 208 страниц
10. ^ Халтурина Д. А., Коротаев А. В. Алкогольная катастрофа и возможности государственной политики в Преодоление алкогольной сверхсмертности в России М., ЛЕНАНД, 2008, 376 страниц ISBN 978-5-9710-0195-9
11. ^ Primary Chronicle, year 6494 (986)
12. ^ a b c d e McKee, Martin (1999). "Alcohol in Russia". Alcohol and Alcoholism. Oxford Journals. 34 (6): 824–829. doi:10.1093/alcalc/34.6.824. PMID 10659717.
13. ^ a b c d Claire Suddath (January 5, 2010). "A Brief History of Russians and Vodka". Time magazine. Archived from the original on 25 May 2010. Retrieved May 10, 2010.
14. ^ a b Khwaja, Barbara (26 May 2017). "Health Reform in Revolutionary Russia". Socialist Health Association. Retrieved 26 May 2017.
15. ^ a b c Dorman, Nancy D.; Towle, Leland H. (1991). "Initiatives to curb alcohol abuse and alcoholism in the former Soviet Union". Alcohol Health & Research World.
16. ^ a b Tony Halpin (April 13, 2007). "Health alert as Russia's alcohol consumption triples". The Times.
17. ^ "Russia may soon be booze free". Fin24. 2006-07-27. Retrieved 4 September 2017.
18. ^ Kate Transchel (January 18, 2010). "Opinion: Why a $3 bottle of vodka won't cut it". Global Post. Retrieved May 10, 2010.
19. ^ Khaltourina, Daria, and Andrey Korotayev. "Effects of Specific Alcohol Control Policy Measures on Alcohol-Related Mortality in Russia from 1998 to 2013." Alcohol and Alcoholism (2015): 2015) 50 (5): 592.
20. ^ Petroff, Alanna (December 31, 2014). "Russia slashing vodka prices as economy reels". CNN. Retrieved 1 January 2015.
21. ^ Nechepurenko, Ivan (19 December 2016). "In Russia, Dozens Dies After Drinking Alcohol Substitute". The New York Times. Retrieved 19 December 2016.
22. ^ Isachenkov, Vladimir (2016-12-19). "Alcohol poisoning death toll in Russian city rises to 49". Associated Press. Retrieved 2016-12-19.
23. ^ "Russia's health minister wants to raise legal drinking age to 21". Retrieved 2020-11-27.
24. ^ "ЕМИСС". www.fedstat.ru.
25. ^ a b Zaridze, David; Brennan, Paul; Boreham, Jillian; Boroda, Alex; Karpov, Rostislav; Lazarev, Alexander; Konobeevskaya, Irina; Igitov, Vladimir; et al. (2009). "Alcohol and cause-specific mortality in Russia: a retrospective case—control study of 48 557 adult deaths". The Lancet. 373 (9682): 2201–2214. doi:10.1016/S0140-6736(09)61034-5. PMC 2715218. PMID 19560602.
26. ^ "Alcohol blamed for half of '90s Russian deaths". Associated Press. June 25, 2009. Retrieved May 10, 2010.
27. ^ "Russia's alcohol consumption more than 100% above critical level". RIA Novosti. September 24, 2009.
28. ^ John Moody; James O. Jackson; Nancy Traver (October 21, 1985). "Soviet Union Fighting the Battle of the Bottle". Time magazine. Retrieved May 12, 2010.
29. ^ a b "Interpersonal Violence and Alcohol in the Russian Federation" (PDF). Violence and Injury Prevention Programme - WHO Regional Office for Europe. 2006. Retrieved February 26, 2016.
30. ^ H1 2009 demographic figures Archived 2012-02-18 at the Wayback Machine Rosstat Retrieved on August 28, 2009
31. ^ WHO Russia suicide statistics WHO retrieved on March 21, 2008
32. ^ Demoscope - Demographic, social and economic consequences of alcohol abuse in Russia Demoscope Retrieved on July 6, 2010
33. ^ Jargin, Sergei (27 July 2006). "Learning from the Russians". British Medical Journal. Retrieved 29 May 2017.
34. ^ Treatment systems overview. Strasbourg: Council of Europe Publishing. 2010. pp. 127–128. ISBN 978-92-871-6930-3. Retrieved June 14, 2011.
35. ^ Mosher, Clayton (2007). Drugs and Drug Policy. Thousand Oaks: Sage. p. 269. ISBN 978-0-7619-3007-5. Retrieved June 9, 2011.
36. ^ Finn, Peter (October 2, 2005). "Russia's 1-Step Program: Scaring Alcoholics Dry". The Washington Post. Retrieved June 9, 2011.
## Further reading[edit]
* WHO (2004). "Country Profiles. Russian Federation" (PDF). WHO Global Status Report on Alcohol..
* Jargin, SV (2010). "On the causes of alcoholism in the former Soviet Union". Alcohol and Alcoholism. 45 (1): 104–5. doi:10.1093/alcalc/agp082. PMID 19951961.
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*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Alcohol consumption in Russia | None | 4,444 | wikipedia | https://en.wikipedia.org/wiki/Alcohol_consumption_in_Russia | 2021-01-18T18:35:37 | {"wikidata": ["Q4385567"]} |
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: "Childhood rhabdomyosarcoma" – news · newspapers · books · scholar · JSTOR (September 2015) (Learn how and when to remove this template message)
Childhood rhabdomyosarcoma
SpecialtyOncology
Childhood rhabdomyosarcoma is a cancer that develops out of the cells that form skeletal muscles. These cells are called rhabdomyoblasts.
This type of malignant cancer is seen most commonly in children and adolescents. This is most commonly seen in the head and neck; however, it can be found almost anywhere in the body.[1]
## Contents
* 1 Types
* 2 Signs and symptoms
* 3 Risk Factors
* 4 Diagnosis
* 4.1 Stages
* 5 Treatment
* 6 Prognosis
* 7 References
## Types[edit]
Childhood rhabdomyosarcoma consists of three subgroups. Embryonal is the most common among children and young adults. Alveolar and anaplastic rhabdomyosarcoma occur in the teenage years.[citation needed]
* Embryonal rhabdomyosarcoma develops within the first seven weeks of the embryo's development. Rapid cell growth causes masses to form along the head, neck, urinary tract, and genital organs.
* Alveolar, the second most common group, is seen later in life.[2] During the teen years, large muscle groups come under attack, including the torso and large appendages. Aggressive treatment is needed to stop or limit progression of alveolar rhabdomyosarcoma.
* Anaplastic rhabdomyosarcoma is rarely seen in children and only precise intensive lab work can identify it.
## Signs and symptoms[edit]
The symptoms of childhood rhabdomyosarcoma are visible and prominent and include swollen red lumps where the cancer starts developing. The lumps are hard and can grow in size unless treated. Other symptoms include poor bowel movements, blood in the urine, secretions from the genitals and nose, and headaches. Various tests can determine whether these related symptoms indicate childhood rhabdomyosarcoma. CT, X-ray, MRI, bone scans, and Ultrasounds may be performed to identify the location and size of the cancer. Biopsies of the lump can be taken along with bone marrow biopsies to detect whether the cancer has spread within the marrow, the bone, and the blood supply. Further determination of how aggressive and large the cancer is requires these scans.[3][4]
## Risk Factors[edit]
Childhood rhabdomyosarcoma is difficult to diagnose. Factors that increase the likelihood of this cancer include Li-Fraumeni syndrome, type one Neurofibromatosis, Beckwith-Wiedemann syndrome, Costello syndrome, and Noonan syndrome. Each contribute to deformations of bones, tissue, and muscles.[citation needed]
## Diagnosis[edit]
### Stages[edit]
Childhood Rhabdomyosarcoma can be classified under four developing stages, each of which have their own indications and characteristics. Cancer can be spread through tissue, lymph nodes, and the blood. When it spreads, the stage level and the seriousness of the illness increases. Stage one is limited to one area and has no specific size.[4] Stage one rhabdomyosarcoma is seen in the eye and area surrounding it, the gallbladder, connecting bile ducts, and male and female genitalia. Stage two is characterized by a lump size of five centimeters. Stage three is characterized by the spread to the lymph nodes and the cancer has spread to nearby sites. The size of the lump may still be only up to five centimeters. Stage three cancer may be seen anywhere other than the mentioned stage one areas. Stage 4 is characterized by a tumor of any size that has also spread to nearby lymph nodes. However, the cancer is not strictly limited to this area and may be seen within bones, marrow, and lungs.[5]
## Treatment[edit]
Determination of treatment options depends on certain factors, some of which affect internal organs and others that affect personal appearance. When determining treatment, oncologists consider the initial location the tumor, the likelihood of body function deterioration, the effect on appearance, and the patient's potential response to chemotherapy and radiation. Surgery is the least successful of the treatment options; the tumor cannot be completely removed because it develops within the cells.[6] Chemotherapy follows surgery to shrink or eliminate the remaining cancer cells.
Stem cell research under clinical trial shows promise to replace lost cells.[citation needed]
The aggressiveness of this cancer requires the response of a large team of specialists, possibly including a pediatric surgeon, oncologist, hematologist, specialty nurse, and rehabilitation specialists. Social workers and psychologists aid recovery by building a system of emotional support. Treatment is harsh on the body and may result in side effects including mood swings, learning difficulties, memory loss, physical deformations or restrictions, and potential risk of secondary cancers.[citation needed]
## Prognosis[edit]
Childhood rhabdomyosarcoma has been fatal. Recovery rates have increased by 50 percent since 1975. In children five years of age or younger survival rates are up to 65 percent. In adolescents younger than 15 years old, the survival rate has increased up to 30 percent.[2]
## References[edit]
1. ^ American Cancer Organization. "What Is Cancer". ACS. Retrieved June 4, 2013.
2. ^ a b Drake, Amelia; MD Steve C Lee (13 April 2012). "Pathology - Rhabdomyosarcoma". Medscape: 1–4.
3. ^ Childhood Rhabdomyosarcoma Treatment
4. ^ a b Bethesda, MD. "Childhood Rhabdomyosarcoma Treatment". PDQ (NCI). Missing or empty `|url=` (help)
5. ^ Witmore, Ralph (2000). Pediatric Otolaryngology. New York, NY: Theme Medical Publishers Inc. pp. 103–111. ISBN 9780865778351.
6. ^ Pratt, Charles; Hustu Omar; Fleming Irvin (March 1972). "Coordinated treatment of childhood rhabdomyosarcoma with surgery, radiotherapy, and combination chemotherapy". Cancer Research. 32: 606–607. PMID 4551437.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Childhood rhabdomyosarcoma | c0220611 | 4,445 | wikipedia | https://en.wikipedia.org/wiki/Childhood_rhabdomyosarcoma | 2021-01-18T18:40:30 | {"wikidata": ["Q17113417"]} |
Waardenburg syndrome type 4, also known as Waardenburg-Shah syndrome, is a genetic condition that can cause hearing loss; changes in coloring (pigmentation) of the hair, skin, and eyes; and Hirschsprung disease, an intestinal disorder that causes severe constipation or blockage of the intestine. Waardenburg syndrome type 4 is further divided into types 4A, 4B, and 4C based on their genetic cause. Type 4A is caused by mutations in the EDNRB gene, mutations in EDN3 cause 4B, and mutations in SOX10 cause type 4C. This condition is usually inherited in an autosomal dominant fashion; however, some cases of type 4 appear to have an autosomal recessive pattern of inheritance.
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Waardenburg syndrome type 4 | c1848519 | 4,446 | gard | https://rarediseases.info.nih.gov/diseases/5524/waardenburg-syndrome-type-4 | 2021-01-18T17:57:09 | {"mesh": ["C536467"], "omim": ["277580", "613265", "613266"], "umls": ["C1848519"], "orphanet": ["897"], "synonyms": ["Waardenburg-Shah syndrome", "WS4", "Waardenburg-Hirschsprung disease", "Shah-Waardenburg syndrome", "Hirschsprung disease with pigmentary anomaly", "Waardenburg-Hirschsprung syndrome"]} |
A rare systemic or rheumatologic disease characterized by the triad of central nervous system (CNS) dysfunction, branch retinal artery occlusions (BRAOs) and sensorineural hearing loss (SNHL) due to autoimmune-mediated occlusions of microvessels in the brain, retina, and inner ear.
## Epidemiology
Susac syndrome (SuS) prevalence is still unknown. To date more than 500 cases have been reported worldwide. Young females (20-40 years) are more affected (female: male ratio 3.5:1). The age at onset ranges from 8 to 72 years (mean age: 32 years).
## Clinical description
Characteristic is a triad of encephalopathy (cognitive and behavioral disturbances, personality changes, psychosis, preceding headaches) and/or focal CNS dysfunction, visual dysfunction due to BRAO and SNHL. The components of the triad may not be concomitantly present and may develop successively. Three major disease courses have been suggested: monocyclic (fluctuating disease that self-limits after a maximum period of 2 years), polycyclic (relapses that continue beyond a 2 years period) and chronic-continuous.
## Etiology
The etiology and precise pathophysiology are not yet clear. According to recent data, clonally expanding autoreactive cytotoxic CD8+ T cells cause inflammation-mediated injury of the microvascular endothelium which leads to swelling of endothelial cells, vessel occlusion in the affected organ and finally micro-ischaemic damage and dysfunction.
## Diagnostic methods
The diagnosis is based on the demonstration of the typical triad. There is no singular ''marker'' of SuS. Beside the clinical examination, most relevant diagnostic tools are brain magnetic resonance imaging (MRI), retinal fluorescein angiography (FA), and audiometry. In the acute phase, T2 weighted brain MRI often shows blurry lesions in the central fibers of the corpus callosum (''snowball lesions'') which later convert into sharply defined ''punched out'' lesions. Periventricular lesions and involvement of cerebellum, brain stem and deep grey matter nuclei are also often present. FA demonstrates BRAO and fluorescein leakage, often in the retinal periphery (may then be clinically silent). Audiometry analysis reveals uni- or bilateral SNHL. Cerebrospinal fluid analysis often shows mild pleocytosis and moderate protein elevation, oligoclonal bands are uncommon. Anti endothelial cell antibodies have been reported in some cases. An early and reliable diagnosis is facilitated by application of the validated diagnostic criteria of the European Susac Consortium (EUSAC).
## Differential diagnosis
Inflammatory demyelinating CNS disease (such as multiple sclerosis, acute disseminated encephalitis, neuromyelitis optica spectrum disorders), autoimmune encephalitis, and various other diseases involving CNS, retina, and inner ear (including infections, malignancies, psychotic disorders, cerebrovascular disease, migraine, Meniere disease, isolated BRAO) and a variety of autoimmune diseases such as Cogan syndrome, Eales disease, autoimmune inner-ear disease, polyarteritis nodosa, Wegener granulomatosis, Churg-Strauss syndrome, systemic lupus erythematosus, antiphospholipid syndrome, Sjögren syndrome and Behçet disease.
## Management and treatment
No evidence-based treatment strategies exist. Empirically, pulsed glucocorticosteroid treatment is effective in the acute phase. In severe cases treatment may be complemented by cyclophosphamide and/or intravenous immunoglobulins (ivIG), methotrexate (MTX), azathioprine (AZA) or mycophenolate mofetil (MMF). After stabilization glucocorticosteroids should be very slowly tapered. Long term immunosuppressive treatment by MTX, AZA, MMF, and/or ivIG is usually necessary. More recently, positive experiences have been reported with monoclonal antibodies such as rituximab, natalizumab, and infliximab. Patients with severe hearing loss may benefit from cochlear implants.
## Prognosis
The disease usually self-limits after 2-4 years, Late relapses after decades have been reported. The final outcome shows a large variability of disability ranging from unimpairment to dementia, deafness and blindness. The majority of patients retains variable degrees of cognitive, visual and/or hearing deficits.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Susac syndrome | c2717757 | 4,447 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=838 | 2021-01-23T17:20:03 | {"gard": ["7713"], "mesh": ["D055955"], "umls": ["C2717757"], "icd-10": ["I67.7"], "synonyms": ["RED-M", "Retinocochleocerebral vasculopathy", "Retinopathy-encephalopathy-deafness associated with microangiopathy", "Retinopathy-encephalopathy-hearing loss associated with microangiopathy", "SICRET syndrome", "Small infarctions of cochlear, retinal and encephalic tissue"]} |
A number sign (#) is used with this entry because of evidence that nonphotosensitive trichothiodystrophy-7 (TTD7) is caused by homozygous or compound heterozygous mutation in the TARS gene (TARS1; 187790) on chromosome 5p13.
Description
Nonphotosensitive trichothiodystrophy-7 (TTD7) is an autosomal recessive disorder characterized by cysteine- and threonine-deficient hair that displays a diagnostic alternating light and dark 'tiger-tail' banding pattern under polarization microscopy, as well as ichthyosis (Theil et al., 2019).
For a discussion of genetic heterogeneity of trichothiodystrophy, see 601675.
Clinical Features
Theil et al. (2019) studied 2 unrelated patients with trichothiodystrophy for whom limited clinical information was available. The first patient (TTD18PV) was diagnosed by hair analysis at age 2 years, which revealed reduced cysteine and threonine content compared to normal hair. The child's hair also showed fractures (trichoschisis) and a tiger tail banding pattern under polarization microscopy. The patient showed no signs of sun-sensitive skin, but ichthyosis and follicular keratosis were reported. Other features included delayed physical development, recurrent infections of the respiratory tract, and acromandibular dysplasia. The second patient (TTD5VI) was diagnosed with TTD based on hair analysis showing the characteristic tiger-tail banding pattern. She was born with a collodion membrane, and had ichthyosis. Analysis of UV irradiation sensitivity and nucleotide excision repair capacity of patient fibroblasts confirmed the absence of DNA repair deficiency in both patients.
Molecular Genetics
In 24 patients with nonphotosensitive trichothiodystrophy who were negative for mutation in known TTD-associated genes, Theil et al. (2019) performed whole-genome and -exome sequencing and identified biallelic mutations in the TARS gene (187790.0001-187790.0003) in 2 unrelated patients, TTD18PV and TTD5VI. Sequencing the TARS gene in 24 additional patients with nonphotosensitive TTD did not reveal any biallelic mutations.
INHERITANCE \- Autosomal recessive SKIN, NAILS, & HAIR Skin \- Collodion membrane at birth \- Ichthyosis \- Follicular keratosis Hair \- Trichoschisis \- Alternating light and dark banding pattern ('tiger tail') seen under polarization microscopy \- Reduced cysteine content \- Reduced threonine content MISCELLANEOUS \- Based on report of 2 unrelated patients (last curated August 2019) \- Limited clinical information available MOLECULAR BASIS \- Caused by mutation in the threonyl-tRNA synthetase gene (TARS, 187790.0001 ) ▲ Close
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| TRICHOTHIODYSTROPHY 7, NONPHOTOSENSITIVE | None | 4,448 | omim | https://www.omim.org/entry/618546 | 2019-09-22T15:41:27 | {"omim": ["618546"]} |
The English bulldog, a typically brachycephalic dog breed, may suffer from brachycephalic syndrome.
Brachycephalic syndrome is a pathological condition affecting short nosed dogs and cats which can lead to severe respiratory distress. There are four different anatomical abnormalities that contribute to the disease, all of which occur more commonly in brachycephalic breeds:- an elongated soft palate, stenotic nares, a hypoplastic trachea, and everted laryngeal saccules (a condition which occurs secondary to the other abnormalities). Because all of these components make it more difficult to breathe, in situations of exercise, stress, or heat, an animal with these abnormalities may be unable to take deep or fast enough breaths to blow off carbon dioxide. This leads to distress and further increases respiratory rate and heart rate, creating a vicious cycle that can quickly lead to a life-threatening situation.
Brachycephalic dogs are more likely to die during air travel[1] and have been banned by many airlines.[2]
Dogs experiencing a crisis situation due to brachycephalic syndrome typically benefit from oxygen, cool temperatures, sedatives, and in some cases more advanced medical intervention, including intubation.
## Contents
* 1 Causes and risk factors
* 2 Signs and symptoms
* 2.1 Secondary conditions
* 3 Diagnosis
* 4 Treatment
* 5 Prevention
* 6 Other health problems
* 7 List of brachycephalic dog breeds
* 8 References
## Causes and risk factors[edit]
This diagram illustrates what the airway structure looks like in a brachycephalic dog; in this case, a Boxer.
* * *
1\. Nasal cavity 2. Oral cavity 3. Soft palate 4. Pharynx 5. Larynx 6. Trachea 7. Esophagus 8. Nasopharynx 9. Hard palate
* * *
The brachycephalic dog has a shorter snout which causes the airway to be shorter, that means all the parts that make up the airway get pushed closer together. Due to this phenomenon, a brachycephalic dog has an elongated soft palate which can cause most of the problems with the dogs breathing. They can also have problems getting enough air in because of their elongated soft palate and shorter airway.
* Stenotic nares (narrowed nostril)
* Elongated soft palate
* Hypoplastic trachea (reduced trachea size)
* Short/irregular nasal turbinate
Muzzle length scales with the risks of brachycephalic syndrome. Other risk factors identified include neck girth and body condition score.[3]
## Signs and symptoms[edit]
* Dyspnea (breathing difficulty)
* Noisy/labored breathing
* Stridor (high pitched wheezing)
* Continued open-mouth breathing
* Extending of head and neck to keep airway open
* Sitting up or keeping chin in an elevated position when sleeping
* Sleeping with toy between teeth to keep mouth open to compensate for nasal obstruction[4]
* Cyanosis (blue/purple discoloration of the skin, due to poor blood oxygenation in the lungs )
* Sleep apnea
* Stress and heat intolerance during exercise.
* Snoring/gagging/choking/regurgitation/vomiting
* Collapse
Symptoms progress with age and typically become severe by 12 months.[4]
Despite observing clinical signs of airway obstructions, some owners of brachycephalic breeds may perceive them as normal for the breed, and may not seek veterinary intervention until a particularly severe attack happens.[5][6]
After awaking from surgery, most dogs that are intubated will try to claw out their tracheal tube. In contrast, brachycephalic dogs often seem quite happy to leave it in place as it opens the airway, making it easier to breathe.[7]
### Secondary conditions[edit]
Other conditions may be observed concurrently. These include swollen/everted laryngeal saccules, which further reduce the airway, collapsed larynx, and chronic obstructive pulmonary disease caused by the increased lung workload.
Brachycephalic syndrome has been linked to changes in the lungs, as well as the gastrointestinal tract including bronchial collapse, gastroesophageal reflux, and chronic gastritis.[8]
## Diagnosis[edit]
This syndrome is diagnosed on the basis of the dog's breed, clinical signs, and results of a physical examination by a veterinarian. Stenotic nares can usually be diagnosed on visual inspection. Diagnosis of an elongated soft palate, everted laryngeal saccules, or other associated anatomical changes in the mouth will require heavy sedation or full general anesthesia.[8]
## Treatment[edit]
Stenotic nares in a Boxer before (left) and after (right) surgery.
Treatment consists of surgery for widening the nostrils, removing the excess tissue of an elongated soft palate, or removing everted laryngeal saccules. Early treatment prevents secondary conditions from developing.
Potential complications include hemorrhages, pain, and inflammation during and after surgery. Some veterinarians are hesitant to perform soft palate correction surgery. With CO2 surgical lasers, these complications are greatly diminished.[9]
## Prevention[edit]
To prevent or limit exacerbation of symptoms, avoid stress and high heated climates. Maintain ideal body weight and avoid overfeeding. Use harnesses instead of collars to avoid pressure on the trachea.
The risk of brachycephalic syndrome increases as the muzzle becomes shorter.[3] To avoid producing affected dogs, breeders may choose to breed for more moderate features rather than for extremely short or flat faces. Dogs with breathing difficulties, or at least those serious enough to require surgery, should not be used for breeding.[10] Removing all affected animals from the breeding pool may cause some breeds to be unsustainable and outcrossing to non-brachycephalic breeds might be necessary.[11]
## Other health problems[edit]
Non-airway problems associated with brachycephalia may include
* Inflammation in skin folds
* Mating and birthing problems
* Malocclusion \- misalignment of the teeth.
* Dental crowding
Exophthalmos in a pug
* Brachycephalic ocular syndrome[11]
* Ectropion/entropion \- inward/outward rolling of eyelid
* Macropalpebral fissure
* Lagophthalmia \- inability to close eyelids fully
* Exophthalmos/eye proptosis \- abnormal protrusion of the eye
* Nasal fold trichiasis - fur around the nose fold rubs against the eye.
* Distichiasis \- abnormally placed eyelashes rubs against the eye.
* Poor tear production.
* Gastrointestinal problems[12]
## List of brachycephalic dog breeds[edit]
Breeds with less extreme brachycephalia, such as the Boxer, have less compromised thermoregulation and thus are more tolerant of vigorous exercise and heat.
* Affenpinscher
* American Bulldog
* Boston Terrier[13]
* Boxer
* Bulldog[13]
* Bullmastiff
* Cane Corso
* Chihuahua (apple-headed)
* Chow Chow[14]
* Dogue de Bordeaux
* English Mastiff
* French Bulldog[13]
* Griffon Bruxellois[13]
* Japanese Chin[13]
* King Charles Spaniel
* Lhasa Apso
* Neapolitan Mastiff
* Pekingese[13]
* Pug[13]
* Rottweiler
* Shih Tzu[13]
* Valley Bulldog
## References[edit]
1. ^ "Air Travel and Short-Nosed Dogs FAQ". American Veterinary Medical Association. Retrieved 5 November 2013.
2. ^ Haughney C (6 October 2011). "Banned by Many Airlines, These Bulldogs Fly Private". New York Times. Retrieved 5 November 2013.
3. ^ a b Short Muzzle; Short Of Breath? An Investigation Of The Effect Of Conformation On The Risk Of Brachycephalic Obstructive Airway Syndrome (BOAS) In Domestic Dogs (PDF). UFAW International Animal Welfare Science Symposium: Science in the Service of Animal Welfare: Priorities around the world. 4–5 July 2013. Retrieved 21 January 2018.
4. ^ a b Roedler FS, Pohl S, Oechtering GU (December 2013). "How does severe brachycephaly affect dog's lives? Results of a structured preoperative owner questionnaire". Veterinary Journal. 198 (3): 606–10. doi:10.1016/j.tvjl.2013.09.009. PMID 24176279.
5. ^ "Worrying numbers of "short-nosed" dog owners do not believe their pets to have breathing problems, despite observing severe clinical signs". The Royal Veterinary College. 10 May 2012. Retrieved 29 June 2013.
6. ^ Packer RM, Hendricks A, Burn CC (2012). "Do dog owners perceive the clinical signs related to conformational inherited disorders as 'normal' for the breed? A potential constraint to improving canine welfare". Animal Welfare. 21: 81–93. doi:10.7120/096272812X13345905673809.
7. ^ Johnson T. "Breathless: Bulldogs, pugs need protection from the heat". Veterinary Information Network. Retrieved 17 November 2013.
8. ^ a b "Brachycephalic Airway Syndrome in Dogs". vca_corporate. Retrieved 2019-12-21.
9. ^ Arza R (2016-09-29). "Elongated soft palate resection with a CO2 surgical laser". Aesculight. Retrieved 2017-02-06.
10. ^ "Brachycephalic syndrome". Canine Inherited Disorders Database. Archived from the original on 7 September 2013. Retrieved 5 November 2013.
11. ^ a b "Shih Tzu: Brachycephalic Ocular Syndrome". Universities Federation for Animal Welfare. 2011. Retrieved 2017-11-25.
12. ^ Poncet CM, Dupre GP, Freiche VG, Estrada MM, Poubanne YA, Bouvy BM (June 2005). "Prevalence of gastrointestinal tract lesions in 73 brachycephalic dogs with upper respiratory syndrome". The Journal of Small Animal Practice. 46 (6): 273–9. doi:10.1111/j.1748-5827.2005.tb00320.x. PMID 15971897.
13. ^ a b c d e f g h Packer RM, Hendricks A, Tivers MS, Burn CC (2015). "Impact of Facial Conformation on Canine Health: Brachycephalic Obstructive Airway Syndrome". PLOS ONE. 10 (10): e0137496. Bibcode:2015PLoSO..1037496P. doi:10.1371/journal.pone.0137496. PMC 4624979. PMID 26509577.
14. ^ Packer RM, Hendricks A, Tivers MS, Burn CC (2015-10-28). "Impact of Facial Conformation on Canine Health: Brachycephalic Obstructive Airway Syndrome". PLOS ONE. 10 (10): e0137496. Bibcode:2015PLoSO..1037496P. doi:10.1371/journal.pone.0137496. PMC 4624979. PMID 26509577.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Brachycephalic airway obstructive syndrome | None | 4,449 | wikipedia | https://en.wikipedia.org/wiki/Brachycephalic_airway_obstructive_syndrome | 2021-01-18T18:31:31 | {"wikidata": ["Q4953365"]} |
A rare, slowly progressive, chronic leukemia characterized by presence of abnormal B-lymphocytes (medium sized with abundant irregular pale cytoplasm, hair-like cytoplasmic projections/ruffled cytoplasmic border, a round or bean-shaped nucleus and absent nucleoli) in the blood or bone marrow, spleen and peripheral blood pancytopenia, notable monocytopenia, and marked susceptibility to infection. The characteristic immunophenotype is CD11c+, CD25+, CD103+ and CD123+ with a BRAF mutation in most cases.
## Epidemiology
Classic hairy cell leukemia (HCLc) accounts for 2% of all leukemia cases. Estimates of the annual incidence range between 1/213,000-2,860,000 worldwide. HCLc is observed more commonly in caucasians. Men are predominantly affected with a male:female ratio of 4:1.
## Clinical description
Disease onset is typically in middle-age or older adults with an average age of 55 years. Symptoms of HCLc are related to the disruption of normal blood cell production. Low red cell production leads to anemia, low white cell production to increased infections, and low platelet counts to bleeding or easy bruising. Abdominal discomfort is a common symptom, resulting from hepatosplenomegaly. Splenomegaly is present in most cases, and was originally classed as massive in more than 80% of cases. In recent years, massive splenomegaly is less frequent perhaps related to earlier diagnosis. Hepatomegaly with mild liver dysfunction is found in 20% of cases and lymphadenopathy is found in 10% of cases. Complications include recurrent infections, bleeding, bruising, anemia and abdominal discomfort from splenomegaly. Splenic rupture may occur. Patients with HCLc often have monocytopenia. The patients may have opportunistic infections as a result of being immunocompromised due to intrinsic disease-related immune deficiency as well as immunosuppressive treatment.
## Etiology
Etiology is unknown. Family history of blood cancers, Ashkenazi Jewish heritage, occupational or environmental exposure to chemicals (e.g. insecticides) are considered as possible risk factors. BRAFV600E mutation, which causes constitutive activation of the MAP kinase pathway, is also found in most patients with HCLc.
## Diagnostic methods
Diagnosis is based on the results of the physical examination, blood tests, and bone marrow biopsy. Abdominal computer tomography may also identify lymphadenopathy. Immunophenotypic evaluations of peripheral blood or bone marrow are essential for establishing the diagnosis. Characteristic immunophenotypic markers include CD11c, CD25, CD103, CD123 positive. BRAF-V600E mutation is also found in most patients.
## Differential diagnosis
Differential diagnoses includes hairy cell leukemia variant, splenic marginal zone lymphoma, and splenic diffuse red pulp B-cell lymphoma.
## Management and treatment
HCLc can be treated with chemotherapy (cladribine or pentostatin) or biological therapy (interferon alpha, rituximab). The purine nucleoside analogs, either cladribine (indication authorized in Europe and the USA) or pentostatin, have a higher rate of complete remission compared to biological therapies. Complete or partial remission with chemotherapy is achieved in about 80 to 90% of patients. In patients with active infection, it is important to attempt to control infection before using cladribine because of potential profound and prolonged myelosuppression. Treating patients with uncontrolled infection is challenging. Vermurafenib has been used as a bridge to effective therapy in some patients with life-threatening, uncontrolled infection and proven BRAF-positive mutation. These patients have had anecdotal improvement in hematologic parameters with control of infection; however, more evidence is required. Off-label usage of vemurafenib has been reported to be effective in hairy cell leukemia, in particular it has helped achieve remission in patients with relapsed or resistant disease. Currently, studies are in progress to examine the use of this agent in combination chemoimmunotherapy. For patients with hairy cell leukemia who have a relapse following a prolonged period of initial remission, they may be successfully re-treated with a purine analog or a combination of the purine analog and an anti-CD20 monoclonal antibody (rituximab). For those patients who have had multiple relapses or disease refractory to standard therapy, the anti-CD22 immunotoxin conjugate, moxetumomab (approved in the USA), may also be considered. Where the disease is mild and slow growing, a small number of patients may not require any immediate treatment and remain stable for many years. However, close follow-up of the hematologic parameters is required to avoid the development of serious pancytopenia.
## Prognosis
Most patients live 10 years or longer with the disease.
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Classic hairy cell leukemia | c0023443 | 4,450 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=58017 | 2021-01-23T18:30:33 | {"gard": ["6560"], "mesh": ["D007943"], "umls": ["C0023443"], "icd-10": ["C91.4"], "synonyms": ["HCL-C", "Leukemic reticuloendotheliosis"]} |
Any of the forms of odontogenic neoplasm
Odontogenic tumor
SpecialtyOncology
An odontogenic tumor is a neoplasm of the cells or tissues that initiate odontogenic processes.
Examples include:
* Adenomatoid odontogenic tumor
* Ameloblastic fibroma
* Ameloblastoma, a type of odontogenic tumor involving ameloblasts
* Ameloblastic fibrosarcoma
* Calcifying cystic odontogenic tumor
* Calcifying epithelial odontogenic tumor
* Cementoblastoma
* Cementoma
* Odontogenic keratocyst
* Odontogenic carcinoma
* Odontogenic myxoma
* Odontoma
* Squamous odontogenic tumour
## References[edit]
## External links[edit]
Classification
D
* ICD-O: 9270-9349
* MeSH: D009808
* DiseasesDB: 32246
* SNOMED CT: 3833004
* v
* t
* e
Dental tumors
Cementoblast
* Cementoblastoma
* Cementoma
Ameloblast
* Ameloblastoma
Mixed/hamartoma
* Odontoma
Other
* Adenomatoid odontogenic tumor
* Keratocystic odontogenic tumour
This article about a neoplasm is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Odontogenic tumor | c0028880 | 4,451 | wikipedia | https://en.wikipedia.org/wiki/Odontogenic_tumor | 2021-01-18T19:01:11 | {"mesh": ["D009808"], "umls": ["C0028880"], "orphanet": ["314425"], "wikidata": ["Q7077953"]} |
Congenital malaria is an extremely rare condition which occurs due to transplacental transmission of maternal infection.[1]
Clinical features include fever, irritability, feeding problems, anemia, hepatosplenomegaly and jaundice. Clinical features commence only after three weeks due to the protective effect of transplacentally transmitted antibodies.
## References[edit]
1. ^ Enweronu-Laryea, Christabel C; Adjei, George O; Mensah, Benjamin; Duah, Nancy; Quashie, Neils B (2013). "Prevalence of congenital malaria in high-risk Ghanaian newborns: a cross-sectional study". Malaria Journal. 12 (1): 17. doi:10.1186/1475-2875-12-17. PMC 3565937. PMID 23311646.
## External links[edit]
* (P37.3) Congenital falciparum malaria
* (P37.4) Other congenital malaria
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Congenital malaria | c0276832 | 4,452 | wikipedia | https://en.wikipedia.org/wiki/Congenital_malaria | 2021-01-18T18:41:45 | {"icd-10": ["P37.4", "P37.3"], "wikidata": ["Q25324142"]} |
A rare inherited bleeding disorder due to reduced activity of factor II (FII, prothrombin) and characterized by mucocutaneous and soft tissue bleeding symptoms.
## Epidemiology
Factor II deficiency is the most rare coagulation factor deficiency. Prevalence of homozygous forms is estimated at 1/2,000,000. Both sexes are equally affected.
## Clinical description
Congenital FII deficiency can manifest at any age, with severe forms of the disease manifesting early in life. Common clinical signs include epistaxis, menorrhagia, oral cavity bleedings, mucosal bleeding, soft tissue bleeding, hemarthrosis, easy bruising, and prolonged bleeding after tooth extraction, trauma or surgery. Severe forms may present intracranial hemorrhage. The severity of the bleeding manifestations correlates with the FII levels. Thromboembolic manifestations have been described in case of dysprothrombinemia.
## Etiology
Inherited FII deficiency is caused by mutations in the F2 gene (11p11-q12) encoding prothrombin.
## Diagnostic methods
Diagnosis is based on prolonged prothrombin and activated partial thromboplastin times (PT, aPTT) and on low FII coagulant activity measured using a PT based assay. Molecular testing is available, but is unnecessary for diagnosis.
## Differential diagnosis
Differential diagnoses include deficiencies of factors V, VII, X, VIII, IX, XI, XIII or acquired deficiencies in FII (lupus anticoagulant).
## Antenatal diagnosis
Prenatal diagnosis is available for the most severe forms.
## 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 of the 25% risk of having an affected child at each pregnancy.
## Management and treatment
Prothrombin Complex Concentrates (PCCs) or fresh frozen plasma (if PCCs are not available) are usually used to treat hemorrhagic episodes.
## Prognosis
Prognosis is good with early diagnosis and adequate treatment.
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Congenital factor II deficiency | c0020640 | 4,453 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=325 | 2021-01-23T17:41:16 | {"mesh": ["D007020"], "omim": ["613679"], "umls": ["C0020640", "C0272317", "C3203356"], "icd-10": ["D68.2"], "synonyms": ["Dysprothrombinemia", "Hypoprothrombinemia", "Prothrombin deficiency"]} |
Hemoglobin C
SpecialtyHematology
Hemoglobin c (abbreviated as HbC) is an abnormal hemoglobin in which glutamic acid residue at the 6th position of the β-globin chain is replaced with a lysine residue due to a point mutation in the HBB gene.[1] It produces sickle cell trait but not the disease, as it causes only mild sickling of the RBCs. Thus, it is the least dangerous among sickle cell trait-producing hemoglobins such as HbS and HbO.
HbC was discovered by Harvey Itano and James V. Neel in 1950 from two African-American families. It has since been then established that it is most common among people in West Africa. It confers survival benefits as individual with HbC is naturally resistant to malaria, albeit incompletely, due to Plasmodium falciparum.
## Contents
* 1 Discovery
* 2 Symptoms and signs
* 2.1 Erythrocyte Abnormalities
* 2.2 Combinations with other conditions
* 3 Genetics
* 4 Resistance to Malaria
* 5 Diagnosis
* 6 Prevention
* 7 Treatment
* 8 Prognosis
* 9 Epidemiology
* 10 References
* 11 External links
## Discovery[edit]
Studying the molecular basis of sickle cell disease, Linus Pauling and Harvey Itano at the California Institute of Technology discovered in 1949 that the disease was due to abnormal hemoglobin called HBS.[2][3] In 1950, Itano and James V. Neel discovered from two African-American families a different blood condition very similar to sickle cell disease.[4][5] Five of the ten individuals indicated sickled RBCs. But the condition was harmless as the individuals had no anaemia. Thus, it was not clear whether it was involved in sickle cell disease. Genetically, the abnormal hemoglobin was only in heterozygous condition.[6] The next year, Neel and his colleagues established that the hemoglobin is associated with sickle cell disease.[7]
The hemoglobin was named hemoglobin III,[8] but hemoglobin C was eventually used.[9][10] By 1954, it was found that the mutant hemoglobin was highly prevalent in West Africa.[11][12] In 1960, Vernon Ingram and J. A. Hunt at the University of Cambridge discovered that the mutation was a single amino acid replacement of glutamic acid with lysine.[13]
## Symptoms and signs[edit]
Hemoglobin C causes mild disease and does not cause clinical symptoms. Under homozygous condition (HbC/HbC) there can be a mild to moderate enlargement of the spleen, splenomegaly, as well as hemolytic anemia (which is the form of anemia due to abnormal breakdown of red blood cells prematurely) and sometimes jaundice.[1][14] Too much hemoglobin C can reduce the number and size of red blood cells in the body, which is the cause of mild anemia.[15] Some persons with this disease may develop gallstones that require treatment.[16] Continued hemolysis may produce pigmented gallstones, an unusual type of gallstone composed of the dark-colored contents of red blood cells.[17]
### Erythrocyte Abnormalities[edit]
Target cells, microspherocytes, and HbC crystals can be seen on microscopic examination of blood smears from homozygous patients.
### Combinations with other conditions[edit]
HbC can combine with other abnormal hemoglobins and cause serious hemoglobinopathies. Individuals with sickle cell–hemoglobin C (HbSC), have inherited the gene for sickle cell disease (HbS) from one parent and the gene for hemoglobin C disease (HbC) from the other parent. Since HbC does not polymerize as readily as HbS, there is less sickling in most cases. There are fewer acute vaso-occlusive events and therefore in some cases fewer sickle cell crises. The peripheral smear demonstrates mostly target cells and only a few sickle cells. However, persons with hemoglobin SC disease (HbSC) have more significant retinopathy, ischemic necrosis of bone, and priapism than those with pure SS disease.[18]
There are also few cases HbC in combination with HbO, Hb D and β thalassemia.[1]
## Genetics[edit]
Hemoglobin C is produced when a point mutation in the HBB gene causes amino acid substitution of glutamic acid to lysine at the 6th position of the β-globin chain of the hemoglobin. The mutation can be homozygous, occurring on both the chromosomes (alleles), or heterozygous, affecting only one allele.[1] Under heterozygous condition, people are said to have hemoglobin C trait, or as hemoglobin C carriers, and they have one gene for HbC with either one HbA gene or HbS gene. Their red blood cells contain both hemoglobin C and either normal hemoglobin A or hemoglobin S. Hemoglobin C mutation is an autosomal recessive disorder that results from the biparental inheritance of the allele that encodes for hemoglobin C.[17] If both parents are carriers of hemoglobin C, there is a chance of having a child with hemoglobin C disease. Assuming both parents are carriers, there is a 25% chance of having a child with hemoglobin C disease, a 50% chance of having a child who is a carrier of hemoglobin C, and a 25% chance of having a child who is neither a carrier nor affected by hemoglobin C disease.[15]
This mutated form reduces the normal plasticity of host erythrocytes causing a hemoglobinopathy. In those who are heterozygous for the mutation, about 28–44% of total hemoglobin (Hb) is HbC, and no anemia develops. In homozygotes, nearly all Hb is in the HbC form, resulting in mild hemolytic anemia, jaundice and enlargement of spleen.[1]
## Resistance to Malaria[edit]
Individuals with HbC have reduced risk of P. falciparum malaria infection.[19] HbC has been described as being more advantageous than HbS because, even in homozygous individuals, it is usually non-fatal.[20] However, in contrast to HbS, it does not prevent malaria due to P. vivax,[21] and is less effective in resistance to falciparum malaria in heterozygous conditions.[19] Homozygous HbC is more resistant to heterozygous condition, or to thalassemias.[22][23] But HbC mutation does not prevent the infection. P. falciparum do not survive in heterozygous hemoglobins, but can survive in homozygous hemoglobins.[22] HbC reduced the binding force (cytoadherence) of P. falciparum by reducing the activity of PfEMP1.[24] Evidences indicate that HbC reduced the level of PfEMP1, which is required for effective binding and invasion of RBC by the malarial parasite.[25] It has been predicted that with the trend of HbC mutation and falciparum prevalence, HbC would replace HbS in central West Africa in the future.[22]
## Diagnosis[edit]
Physical examination may show an enlarged spleen. Tests that may be done include: Complete Blood Count (CBC), Hemoglobin electrophoresis, Peripheral blood smear, and Blood hemoglobin.[16]
## Prevention[edit]
Genetic counseling may be appropriate for high-risk couples who wish to have a baby.[26]
## Treatment[edit]
Usually no treatment is needed. Folic acid supplementation may help produce normal red blood cells and improve the symptoms of anemia [26]
## Prognosis[edit]
Overall, hemoglobin C disease is one of the more benign hemoglobinopathies.[17] Mild-to-moderate reduction in RBC lifespan may accompany from mild hemolytic anemia. Individuals with hemoglobin C disease have sporadic episodes of musculoskeletal (joint) pain.[17] People with hemoglobin C disease can expect to lead a normal life.[26]
## Epidemiology[edit]
Hemoglobin C is found most abundantly in areas of West Africa, such as Nigeria, where Yorubas live.[27][28][29] Hemoglobin C gene is found in 2-3% of African-Americans[15] while 8% of African-Americans have hemoglobin S (Sickle) gene. Thus Hemoglobin SC disease is significantly more common than Hemoglobin CC disease. The trait also affects people whose ancestors came from Italy, Greece, Latin America, and the Caribbean region.[15] However, it is possible for a person of any race or nationality to have hemoglobin C trait. In terms of geographic distribution, the hemoglobin C allele is found at the highest frequencies in West Africa, where it has been associated with protection against malaria.[14] Hemoglobin C disease is present at birth, though some cases may not be diagnosed until adulthood. Both males and females are affected equally.[17]
## References[edit]
1. ^ a b c d e Karna, Bibek; Jha, Suman K.; Al Zaabi, Eiman (2020), "Hemoglobin C Disease", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 32644469, retrieved 2020-10-26
2. ^ Pauling L, Itano HA (November 1949). "Sickle cell anemia a molecular disease". Science. 110 (2865): 543–8. Bibcode:1949Sci...110..543P. doi:10.1126/science.110.2865.543. PMID 15395398.
3. ^ Serjeant GR (December 2010). "One hundred years of sickle cell disease". British Journal of Haematology. 151 (5): 425–9. doi:10.1111/j.1365-2141.2010.08419.x. PMID 20955412. S2CID 44763460.
4. ^ Hiernauz, J.; Linhard, J.; Livingstone, F. B.; Neel, J. V.; Robinson, A.; Zuelzer, W. W. (1956). "Date on the occurrence of hemoglobin C and other abnormal hemoglobins in some African populations". American Journal of Human Genetics. 8 (3): 138–150. PMC 1716688. PMID 13362221.
5. ^ Huehns, E. R. (1970). "Diseases due to abnormalities of hemoglobin structure". Annual Review of Medicine. 21: 157–178. doi:10.1146/annurev.me.21.020170.001105. PMID 4912473.
6. ^ Itano, H. A.; Neel, J. V. (1950). "A new inherited abnormality of human hemoglobin". Proceedings of the National Academy of Sciences of the United States of America. 36 (11): 613–617. Bibcode:1950PNAS...36..613I. doi:10.1073/pnas.36.11.613. PMC 1063254. PMID 14808148.
7. ^ Kaplan, E.; Zuelzer, W. W.; Neel, J. V. (1951). "A new inherited abnormality of hemoglobin and its interaction with sickle cell hemoglobin". Blood. 6 (12): 1240–1249. doi:10.1182/blood.V6.12.1240.1240. PMID 14886398.
8. ^ White, J. C.; Beaver, G. H. (1954). "A review of the varieties of human haemoglobin in health and disease". Journal of Clinical Pathology. 7 (3): 175–200. doi:10.1136/jcp.7.3.175. PMC 1023791. PMID 13192193.
9. ^ Singer, Karl; Singer, Lily (1953). "Studies on Abnormal Hemoglobins". Blood. 8 (11): 1008–1023. doi:10.1182/blood.V8.11.1008.1008.
10. ^ Schell, Norman B. (1956). "SICKLE-CELL-HEMOGLOBIN-C DISEASE: Report of a Case with Electrophoretic Studies of Hemoglobin in Family Members". A.M.A. Journal of Diseases of Children. 91 (1): 38–44. doi:10.1001/archpedi.1956.02060020040008. PMID 13275117.
11. ^ Edington, G.M; Lehmann, H (1954). "A case of sickle cell — Haemoglobin C disease and a survey of haemoglobin C incidence in West Africa". Transactions of the Royal Society of Tropical Medicine and Hygiene. 48 (4): 332–336. doi:10.1016/0035-9203(54)90104-2. PMID 13187564.
12. ^ Edington, G. M.; Lehmann, H. (1956). "The Distribution of Haemoglobin C in West Africa". Man. 56: 34. doi:10.2307/2793520. JSTOR 2793520.
13. ^ Hunt, J.A.; Ingram, V.M. (1960). "Abnormal human haemoglobins". Biochimica et Biophysica Acta. 42: 409–421. doi:10.1016/0006-3002(60)90818-0. PMID 13716852.
14. ^ a b Fairhurst, Rick M.; Casella, James F. (2004). "Homozygous Hemoglobin C Disease". New England Journal of Medicine. 350 (26): e24. doi:10.1056/NEJMicm030486. PMID 15215497.
15. ^ a b c d "Hemoglobin C Trait". Stjude.org. Retrieved 2015-03-03.
16. ^ a b "Updating PubMed Health - National Library of Medicine - PubMed Health". Ncbi.nlm.nih.gov. 2014-11-12. Retrieved 2015-03-03.
17. ^ a b c d e Hemoglobin C Disease at eMedicine
18. ^ Nagel, Ronald L.; Fabry, Mary E.; Steinberg, Martin H. (2003). "The paradox of hemoglobin SC disease". Blood Reviews. 17 (3): 167–78. doi:10.1016/S0268-960X(03)00003-1. PMID 12818227.
19. ^ a b Taylor, Steve M.; Parobek, Christian M.; Fairhurst, Rick M. (2012). "Haemoglobinopathies and the clinical epidemiology of malaria: a systematic review and meta-analysis". The Lancet. 12 (6): 457–468. doi:10.1016/S1473-3099(12)70055-5. PMC 3404513. PMID 22445352.
20. ^ Travassos, Mark A.; Coulibaly, Drissa; Laurens, Matthew B.; Dembélé, Ahmadou; Tolo, Youssouf; Koné, Abdoulaye K.; Traoré, Karim; Niangaly, Amadou; Guindo, Aldiouma; Wu, Yukun; Berry, Andrea A. (2015). "Hemoglobin C Trait Provides Protection From Clinical Falciparum Malaria in Malian Children". The Journal of Infectious Diseases. 212 (11): 1778–1786. doi:10.1093/infdis/jiv308. PMC 4633765. PMID 26019283.
21. ^ Kreuels, Benno; Kreuzberg, Christina; Kobbe, Robin; Ayim-Akonor, Matilda; Apiah-Thompson, Peter; Thompson, Benedicta; Ehmen, Christa; Adjei, Samuel; Langefeld, Iris; Adjei, Ohene; May, Jürgen (2010). "Differing effects of HbS and HbC traits on uncomplicated falciparum malaria, anemia, and child growth". Blood. 115 (22): 4551–4558. doi:10.1182/blood-2009-09-241844. PMID 20231425.
22. ^ a b c Modiano, D.; Luoni, G.; Sirima, B. S.; Simporé, J.; Verra, F.; Konaté, A.; Rastrelli, E.; Olivieri, A.; Calissano, C.; Paganotti, G. M.; D'Urbano, L. (2001). "Haemoglobin C protects against clinical Plasmodium falciparum malaria". Nature. 414 (6861): 305–308. Bibcode:2001Natur.414..305M. doi:10.1038/35104556. PMID 11713529. S2CID 4360808.
23. ^ Taylor, Steve M.; Parobek, Christian M.; Fairhurst, Rick M. (2012). "Haemoglobinopathies and the clinical epidemiology of malaria: a systematic review and meta-analysis". The Lancet Infectious Diseases. 12 (6): 457–468. doi:10.1016/S1473-3099(12)70055-5. PMC 3404513. PMID 22445352.
24. ^ Fairhurst, Rick M.; Baruch, Dror I.; Brittain, Nathaniel J.; Ostera, Graciela R.; Wallach, John S.; Hoang, Holly L.; Hayton, Karen; Guindo, Aldiouma; Makobongo, Morris O.; Schwartz, Owen M.; Tounkara, Anatole (2005). "Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protect against malaria". Nature. 435 (7045): 1117–1121. Bibcode:2005Natur.435.1117F. doi:10.1038/nature03631. PMID 15973412. S2CID 4412263.
25. ^ Fairhurst, Rick M.; Bess, Cameron D.; Krause, Michael A. (2012). "Abnormal PfEMP1/knob display on Plasmodium falciparum-infected erythrocytes containing hemoglobin variants: fresh insights into malaria pathogenesis and protection". Microbes and Infection. 14 (10): 851–862. doi:10.1016/j.micinf.2012.05.006. PMC 3396718. PMID 22634344.
26. ^ a b c MedlinePlus Encyclopedia: Hemoglobin C disease
27. ^ Akinyanju, Olufemi O. (1989). "A Profile of Sickle Cell Disease in Nigeria". Annals of the New York Academy of Sciences. 565 (1): 126–36. Bibcode:1989NYASA.565..126A. doi:10.1111/j.1749-6632.1989.tb24159.x. PMID 2672962. S2CID 24734397.
28. ^ Fairhurst, R. M.; Fujioka, H.; Hayton, K.; Collins, K. F.; Wellems, T. E. (2003). "Aberrant development of Plasmodium falciparum in hemoglobin CC red cells: implications for the malaria protective effect of the homozygous state". Blood. 101 (8): 3309–15. doi:10.1182/blood-2002-10-3105. PMID 12480691.
29. ^ Edington, G. M.; Lehmann, H. (1956). "36. The Distribution of Haemoglobin C in West Africa". Man. 56: 34–36. doi:10.2307/2793520. ISSN 0025-1496. JSTOR 2793520.
## External links[edit]
* Hemoglobin+C at the US National Library of Medicine Medical Subject Headings (MeSH)
* Hemoglobin+C+Disease at the US National Library of Medicine Medical Subject Headings (MeSH)
Classification
D
* ICD-10: D58.2
* ICD-9-CM: 282.7
* MeSH: D006445
* DiseasesDB: 29693
External resources
* MedlinePlus: 000572
* eMedicine: article/200853
* v
* t
* e
Proteins that contain heme (hemoproteins)
Globins
Hemoglobin
Subunits
Alpha locus on 16:
* α
* HBA1
* HBA2
* pseudo
* ζ
* HBZ
* θ
* HBQ1
* μ
* HBM
Beta locus on 11:
* β
* HBB
* δ
* HBD
* γ
* HBG1
* HBG2
* ε
* HBE1
Tetramers
stages of development:
Embryonic
* HbE Gower 1 (ζ2ε2)
* HbE Gower 2 (α2ε2)
* HbE Portland I (ζ2γ2)
* HbE Portland II (ζ2β2)
Fetal
* HbF/Fetal (α2γ2)
* HbA (α2β2)
Adult
* HbA (α2β2)
* HbA2 (α2δ2)
* HbF/Fetal (α2γ2)
pathology:
* HbH (β4)
* Barts (γ4)
* HbS (α2βS2)
* HbC (α2βC2)
* HbE (α2βE2)
* HbO (α2βO2)
Compounds
* Carboxyhemoglobin
* Carbaminohemoglobin
* Oxyhemoglobin/Deoxyhemoglobin
* Sulfhemoglobin
Other human
* Glycated hemoglobin
* Methemoglobin
Nonhuman
* Chlorocruorin
* Erythrocruorin
Other
human:
* Myoglobin
* Metmyoglobin
* Neuroglobin
* Cytoglobin
plant:
* Leghemoglobin
Other
* Cytochrome
* Cytochrome b
* Cytochrome P450
* Methemalbumin
see also disorders of globin and globulin proteins
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Hemoglobin C | c0019021 | 4,454 | wikipedia | https://en.wikipedia.org/wiki/Hemoglobin_C | 2021-01-18T19:06:07 | {"gard": ["2640"], "mesh": ["D006445"], "umls": ["C0019021"], "icd-9": ["282.7"], "orphanet": ["2132"], "wikidata": ["Q409030"]} |
Involuntary twitches
Hypnic jerk
Other namesHypnagogic jerk, sleep start, sleep twitch, myoclonic jerk, night start
SpecialtySleep medicine
Causescaffeine, dreams, anxiety
A hypnic jerk, hypnagogic jerk, sleep start, sleep twitch, myoclonic jerk, or night start is a brief and sudden involuntary contraction of the muscles of the body which occurs when a person is beginning to fall asleep, often causing the person to jump and awaken suddenly for a moment. Hypnic jerks are one form of involuntary muscle twitches called myoclonus.
Physically, hypnic jerks resemble the "jump" experienced by a person when startled, sometimes accompanied by a falling sensation.[1] Hypnic jerks are associated with a rapid heartbeat, quickened breathing, sweat, and sometimes "a peculiar sensory feeling of 'shock' or 'falling into the void'".[2] It can also be accompanied by a vivid dream experience or hallucination.[3] A higher occurrence is reported in people with irregular sleep schedules.[4] Men have also been known to experience this at a higher rate than women. Moreover, when particularly frequent and severe, hypnic jerks have been reported as a cause of sleep-onset insomnia.[3]
Hypnic jerks are common physiological phenomena.[5] Around 70% of people experience them at least once in their lives with 10% experiencing it daily.[6][7] They are benign and do not cause any neurological sequelae.[7]
## Contents
* 1 Causes
* 2 Treatment
* 3 See also
* 4 References
## Causes[edit]
According to the American Academy of Sleep Medicine there is a wide range of potential causes, including anxiety, stimulants like caffeine and nicotine, stress, and strenuous activities in the evening. It also may be facilitated by fatigue or sleep deprivation.[7] However, most hypnic jerks occur essentially at random in healthy people.[citation needed][8] Nevertheless, these repeated, intensifying twitches can cause anxiety in some individuals and a disruption to their sleep onset.[6]
Sometimes, hypnic jerks are mistaken for another form of movement during sleep. For example, hypnic jerks can be confused with restless leg syndrome, periodic limb movement disorder, hypnagogic foot tremor, rhythmic movement disorder, and hereditary or essential startle syndrome, including the hyperplexia syndrome. But some phenomena can help to distinguish hypnic jerk from these other conditions. For example, the occurrence of hypnic jerk arises only at sleep onset and it happens without any rhythmicity or periodicity of the movements and EMG bursts. Also, other pertinent history allows to differentiate it.[6]
This physiological phenomenon can also be mistaken for myoclonic seizure but it can also be distinguished by different criteria such as the fact that hypnic jerk occurs at sleep onset only or that the EEG is normal and constant. In addition, unlike seizures, there are no tongue bites, urinary incontinence and postictal confusion in hypnic jerk. This phenomenon can therefore be confused with other more serious conditions.[6]
Scientists do not know exactly why this phenomenon occurs and are still trying to understand it. None of the several theories that have attempted to explain it has been fully accepted.[9] One hypothesis posits that the hypnic jerk is a form of reflex, initiated in response to normal bodily events during the lead-up to the first stages of sleep, including a decrease in blood pressure and the relaxation of muscle tissue.[10] Another theory postulates that the body mistakes the sense of relaxation that is felt when falling asleep as a sign that the body is falling. As a consequence, it causes a jerk to wake the sleeper up so they can catch themselves.[11] A researcher at the University of Colorado suggested that a hypnic jerk could be "an archaic reflex to the brain's misinterpretation of muscle relaxation with the onset of sleep as a signal that a sleeping primate is falling out of a tree. The reflex may also have had selective value by having the sleeper readjust or review his or her sleeping position in a nest or on a branch in order to assure that a fall did not occur", but evidence is lacking.[2]
During an epilepsy and intensive care study, the lack of a preceding spike discharge measured on an epilepsy monitoring unit, along with the presence only at sleep onset, helped differentiate hypnic jerks from epileptic myoclonus.[12]
According to a study on sleep disturbances in the Journal of Neural Transmission, a hypnic jerk occurs during the non-rapid eye movement sleep cycle and is an "abrupt muscle action flexing movement, generalized or partial and asymmetric, which may cause arousal, with an illusion of falling".[13] Hypnic jerks are more frequent in childhood with 4 to 7 per hour in the age range from 8 to 12 years old, and they decrease toward 1 or 2 per hour by 65 to 80 years old.[13]
## Treatment[edit]
There are ways to reduce hypnic jerks, including reducing consumption of stimulants such as nicotine or caffeine, avoiding physical exertion prior to sleep, and consuming sufficient magnesium.[14][15]
Some medication can also help to reduce or eliminate the hypnic jerks. For example, low-dose clonazepam at bedtime may make the twitches disappear over time.[6]
In addition, some people may develop a fixation on these hypnic jerks leading to increased anxiety, worrying about the disruptive experience. This increased anxiety and fatigue increases the likelihood of experiencing these jerks, resulting in a positive feedback loop.[16]
## See also[edit]
* Exploding head syndrome
* Hypnagogia
* Periodic limb movement disorder
* Rapid eye movement
* Sleep paralysis
## References[edit]
1. ^ "Brain Basics: Understanding Sleep" (PDF). National Institute of Neurological Disorders and Stroke. 2006. Retrieved 2019-07-03. "Many also experience sudden muscle contractions called hypnic myoclonia, often preceded by a sensation of starting to fall. These sudden movements are similar to the “jump” we make when startled."
2. ^ a b Lauren F Friedman (2014-05-21). "Why You Sometimes Feel Like You're Falling And Jerk Awake When Trying To Fall Asleep". Business Insider. Retrieved 2016-07-17.
3. ^ a b Oswald, Ian (1959). "Sudden Bodily Jerks on Falling Asleep". Brain. 82 (1): 92–103. doi:10.1093/brain/82.1.92. ISSN 0006-8950.
4. ^ "Basics of Sleep Behavior: NREM and REM Sleep". Sleep Stllabus. Archived from the original on 2011-07-18. Retrieved 2019-07-03. "These muscular contractions, called sleep related myoclonias are not pathological events, although they tend to occur more frequently with stress or unusual or irregular sleep schedules."
5. ^ Sander, Howard; Geisse, Hildegarde; Quinto, Christine; Sachdeo, Rajesh; Chokroverty, Sudhansu (1998). "Sensory sleep starts". Journal of Neurology, Neurosurgery & Psychiatry. 64 (5). doi:10.1136/jnnp.64.5.690. PMC 2170079.
6. ^ a b c d e Chokroverty, Sudhansu; Bhat, Sushanth; Gupta, Divya (2013). "Intensified Hypnic Jerks: A Polysomnographic and Polymyographic Analysis". Journal of Clinical Neurophysiology. 30 (4): 403-410. doi:10.1097/WNP.0b013e31829dde98.
7. ^ a b c Vetrugno, Roberto; Montagna, Pasquale (2011). "Sleep-to-wake transition movement disorders". Sleep medicine. 12. doi:10.1016/j.sleep.2011.10.005.
8. ^ Syring, Kaitlyn (2008-02-28). "A case of the jerks". The University Daily Kansan. Archived from the original on 2010-07-26. Retrieved 2019-10-16.
9. ^ Sleep Advisor. "Hypnic (Hypnagogic) Jerking Explained – The Comprehensive Guide For 2019". Sleep Advisor. Retrieved 27 June 2019.
10. ^ Castro, Joseph. "Why Do People 'Twitch' When Falling Asleep?". LiveScience.
11. ^ "Complete Guide to Hypnic Jerks". Hack to Sleep: a guide to better sleep. Retrieved 1 July 2019.
12. ^ Bruce J Fisch, MD (23 October 2009). Epilepsy and Intensive Care Monitoring: Principles and Practice. Demos Medical Publishing. ISBN 978-1-935281-59-7.
13. ^ a b Askenasy, J. J. M. (2003). "Sleep Disturbances in Parkinsonism". Journal of Neural Transmission. Springer-Verlag. 110: 125–50. doi:10.1007/s007020300001.
14. ^ Sathe, Harshal; Karia, Sagar; Desousa, Avinash; Shah, Nilesh (2015). "Hypnic jerks possibly induced by escitalopram". Journal of Neurosciences in Rural Practice. 6 (3): 423-424. doi:10.4103/0976-3147.158797. PMC 4481805.
15. ^ Shebak, Shady; Bader, Geoffrey (2015). "Midazolam and Low Magnesium Associated With Myoclonic Jerks: A Case Report". The Primary Care Companion for CNS Disorders. 17 (2). doi:10.4088/PCC.14l01724. PMC 4560178.
16. ^ Green, Ethan (April 16, 2013). "Hypnic Jerks: How To Avoid Waking With A Jolt". No Sleepless Nights. Retrieved 3 July 2019.
Classification
D
* v
* t
* e
Sleep and sleep disorders
Stages of sleep cycles
* Rapid eye movement (REM)
* Non-rapid eye movement
* Slow-wave
Brain waves
* Alpha wave
* Beta wave
* Delta wave
* Gamma wave
* K-complex
* Mu rhythm
* PGO waves
* Sensorimotor rhythm
* Sleep spindle
* Theta wave
Sleep disorders
Dyssomnia
* Excessive daytime sleepiness
* Hypersomnia
* Insomnia
* Kleine–Levin syndrome
* Narcolepsy
* Night eating syndrome
* Nocturia
* Sleep apnea
* Catathrenia
* Central hypoventilation syndrome
* Obesity hypoventilation syndrome
* Obstructive sleep apnea
* Periodic breathing
* Sleep state misperception
Circadian rhythm
disorders
* Advanced sleep phase disorder
* Cyclic alternating pattern
* Delayed sleep phase disorder
* Irregular sleep–wake rhythm
* Jet lag
* Non-24-hour sleep–wake disorder
* Shift work sleep disorder
Parasomnia
* Bruxism
* Nightmare disorder
* Night terror
* Periodic limb movement disorder
* Rapid eye movement sleep behavior disorder
* Sleepwalking
* Somniloquy
Benign phenomena
* Dreams
* Exploding head syndrome
* Hypnic jerk
* Hypnagogia / Sleep onset
* Hypnopompic state
* Sleep paralysis
* Sleep inertia
* Somnolence
* Nocturnal clitoral tumescence
* Nocturnal penile tumescence
* Nocturnal emission
Treatment
* Sleep diary
* Sleep hygiene
* Sleep induction
* Hypnosis
* Lullaby
* Somnology
* Polysomnography
Other
* Sleep medicine
* Behavioral sleep medicine
* Sleep study
Daily life
* Bed
* Bunk bed
* Daybed
* Four-poster bed
* Futon
* Hammock
* Mattress
* Sleeping bag
* Bed bug
* Bedding
* Bedroom
* Bedtime
* Bedtime story
* Bedtime toy
* Biphasic and polyphasic sleep
* Chronotype
* Dream diary
* Microsleep
* Mouth breathing
* Nap
* Nightwear
* Power nap
* Second wind
* Siesta
* Sleep and creativity
* Sleep and learning
* Sleep deprivation / Sleep debt
* Sleeping while on duty
* Sleepover
* Snoring
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Hypnic jerk | c2732862 | 4,455 | wikipedia | https://en.wikipedia.org/wiki/Hypnic_jerk | 2021-01-18T18:41:52 | {"wikidata": ["Q1308944"]} |
A number sign (#) is used with this entry because of evidence that myoclonic dystonia-26 (DYT26) is caused by heterozygous mutation in the KCTD17 gene (616386) on chromosome 22q12.
Description
Myoclonic dystonia-26 is an autosomal dominant neurologic disorder characterized by onset of myoclonic jerks affecting the upper limbs in the first or second decade of life. The disorder is progressive, and patients later develop dystonia with predominant involvement of the craniocervical regions and sometimes the trunk and/or lower limbs. Dystonia dominates the clinical picture (summary by Mencacci et al., 2015).
Clinical Features
Mencacci et al. (2015) reported 2 unrelated families with myoclonic dystonia. The first family was of British origin and consisted of 7 individuals with onset of movement disorder symptoms between 5 and 20 years of age. All affected family members presented with myoclonic jerks or a jerky tremor predominantly affecting the upper limbs. Dystonia of the upper limbs and craniocervical region occurred later. Symptoms included spasmodic dysphonia, facial myoclonus, blepharospasm, torticollis, and dystonic head jerks. At least 1 patient had dystonia of the trunk and feet in late adulthood. Two patients had psychiatric symptoms of anxiety, social phobia, and depression. Older individuals were more severely affected, consistent with the progressive nature of the disorder. None of the patients reported improvement of the symptoms with alcohol. The proband of the second family, which was of German origin, was a 62-year-old man who developed arm jerks and difficulty writing in childhood. Torticollis and a jerky head tremor appeared around age 40 and became progressively debilitating. He underwent surgery with pallidal deep brain stimulation at age 58, resulting in marked improvement. At age 62, he had generalized dystonia with prominent craniocervical involvement and myoclonic jerks of the upper limbs. A brother and deceased father were reportedly similarly affected, but DNA samples from these individuals were not available.
Inheritance
The transmission pattern of DYT26 in the families reported by Mencacci et al. (2015) was consistent with autosomal dominant inheritance.
Molecular Genetics
In affected members of a British family with DYT26, Mencacci et al. (2015) identified a heterozygous missense mutation in exon 4 of the KCTD17 gene (R145H; 616386.0001). The mutation, which was found by a combination of linkage analysis and whole-exome sequencing, segregated with the disorder in the family. Sequencing the KCTD17 gene in 87 additional probands with familial myoclonic dystonia identified the same R145H mutation in a German proband. No KCTD17 mutations were found by direct screening of exon 4 in 358 patients with sporadic myoclonic dystonia. Studies of patient fibroblasts showed reduced and delayed cytosolic calcium signaling in response to stimulation, reduced calcium stores in the endoplasmic reticulum, and reduced intracellular calcium stores compared to controls.
INHERITANCE \- Autosomal dominant HEAD & NECK Head \- Head jerks Face \- Facial myoclonus Eyes \- Blepharospasm Neck \- Torticollis NEUROLOGIC Central Nervous System \- Dystonia predominantly of the upper limbs and craniocervical regions \- Myoclonus \- Laryngeal dystonia \- Dysarthria \- Truncal dystonia (in some patients) \- Lower limb dystonia (in some patients) Behavioral Psychiatric Manifestations \- Psychiatric symptoms (in some patients) \- Depression (in some patients) \- Anxiety (in some patients) VOICE \- Dysphonia MISCELLANEOUS \- Onset in first or second decades \- Myoclonus is presenting symptom \- Dystonia occurs later \- Progressive disorder \- Symptoms are not relieved by alcohol \- Two unrelated families of European descent have been reported (last curated May 2015) MOLECULAR BASIS \- Caused by mutation in the potassium channel tetramerization domain-containing protein 17 gene (KCTD17, 616386.0001 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| DYSTONIA 26, MYOCLONIC | c1834570 | 4,456 | omim | https://www.omim.org/entry/616398 | 2019-09-22T15:49:10 | {"doid": ["0090036"], "mesh": ["C536096"], "omim": ["616398"], "orphanet": ["36899"]} |
## Description
Reticular pigmentary retinal dystrophy is a form of patterned dystrophy (see MDPT1, 169150) characterized by a reticular pattern of pigmentation that likely appears in infancy and may be fully developed at age 15 years. Indirect funduscopy has shown that the condition is bilateral and symmetric and that the pigmentary deposits are localized below the neuroepithelium, very likely in the pigment epithelium. The reticulum extends from the macula in all directions, sparing the midperiphery and periphery. Visual acuity is unaffected or only minimally affected in advanced stages. Retinal function testing is normal, although the electrooculogram and dark adaptation can be at the lower limit of normal values (summary by Schauwvlieghe et al., 2013).
Clinical Features
This condition, first described by Sjogren (1950), is characterized by a peculiar network of black pigmented lines in the posterior pole of the retina, resembling a fishnet with knots. In late stages the network disappears and drusen appear. Deutman and Rumke (1969) described the disorder in a Dutch brother and sister whose parents were second cousins. The parents in the family reported by Sjogren (1950) were also related. Deafness and spherophakia in that family were probably independent recessive traits.
Schauwvlieghe et al. (2013) described 3 children with reticular dystrophy, 2 North American sisters, aged 10 years and 14 years, and an unrelated 12-year-old Belgian boy. In all 3 patients, both retinas showed the typical symmetric deep reticular pattern of pigmentation, forming a fishnet with knots. The peripapillary, parafoveal, and peripheral fundus were spared. Fluorescein angiography in the sisters revealed a wider area of involvement than was clinically apparent, and blocked the background fluorescence in a fishnet shape, indicating that the pigmented material that accumulated in the retinal pigment epithelium (RPE) blocks background fluorescence. Variation in the presence of autofluorescent chromophores was observed, with the older sister and the unrelated boy exhibiting a milder and more punctiform hyperautofluorescence of the net, whereas the younger sister showed a more intense hyperautofluorescent pattern. Spectral-domain optical coherence tomography showed material between the RPE and Bruch membrane, which the authors suggested was likely a mixture of pigment and lipofuscin. In addition, there was RPE thickening alternating with less-well delineated or even atrophic-appearing areas, with a normal-appearing choroid. Multifocal electroretinography did not show any changes in the hyperpigmented areas, suggesting that photoreceptors were well preserved and that the underlying choroid was intact.
Inheritance
Schauwvlieghe et al. (2013) noted that 2 sisters with reticular pattern dystrophy whose parents were unaffected suggests autosomal recessive inheritance. Autosomal dominant inheritance has been suggested by others (see 179840).
Molecular Genetics
### Exclusion Studies
In a 12-year-old Belgian boy with reticular pattern dystrophy, Schauwvlieghe et al. (2013) excluded mutation in the ABCA4 (601691) and PRPH2 (179605) genes, as well as in the 3242A-G mutation in the MTTL1 gene (590050.0001).
INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Retinal dystrophy \- Black pigmented network in retinal posterior pole \- Fishnet-with-knots pattern of retinal pigmentation \- Drusen (in older patients) \- Accumulated material between the retinal pigment epithelium (RPE) and Bruch membrane \- Thickened of RPE alternating with atrophic-appearing areas MISCELLANEOUS \- Visual acuity is well preserved until advanced stages of disease \- Two sisters and one unrelated boy have been described (last curated September 2016) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| RETINAL DYSTROPHY, RETICULAR PIGMENTARY, OF POSTERIOR POLE | c1867332 | 4,457 | omim | https://www.omim.org/entry/267800 | 2019-09-22T16:22:42 | {"mesh": ["C566721"], "omim": ["267800"], "orphanet": ["99002"]} |
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: "Posterior circulation infarct" – news · newspapers · books · scholar · JSTOR (May 2008) (Learn how and when to remove this template message)
Posterior circulation infarct
Circle of Willis. Posterior circulation represented by bottom half of diagram.
SpecialtyNeurology
Posterior circulation infarct (POCI) is a type of cerebral infarction affecting the posterior circulation supplying one side of the brain.
Posterior circulation stroke syndrome (POCS) refers to the symptoms of a patient who clinically appears to have had a posterior circulation infarct, but who has not yet had any diagnostic imaging (e.g. CT Scan) to confirm the diagnosis.
It can cause the following symptoms:
* Cranial nerve palsy AND contralateral motor/sensory defect
* Bilateral motor or sensory defect
* Eye movement problems (e.g.nystagmus)
* Cerebellar dysfunction
* Isolated homonymous hemianopia
* Vertigo
It has also been associated with deafness.[1]
## See also[edit]
* Stroke
* Artery of Percheron
## References[edit]
1. ^ Lee H (2008). "Sudden deafness related to posterior circulation infarction in the territory of the nonanterior inferior cerebellar artery: frequency, origin, and vascular topographical pattern". Eur. Neurol. 59 (6): 302–6. doi:10.1159/000121421. PMID 18408371.
## External links[edit]
Classification
D
* ICD-9-CM: 433.0, 433.2
* v
* t
* e
Cerebrovascular diseases including stroke
Ischaemic stroke
Brain
* Anterior cerebral artery syndrome
* Middle cerebral artery syndrome
* Posterior cerebral artery syndrome
* Amaurosis fugax
* Moyamoya disease
* Dejerine–Roussy syndrome
* Watershed stroke
* Lacunar stroke
Brain stem
* Brainstem stroke syndrome
* Medulla
* Medial medullary syndrome
* Lateral medullary syndrome
* Pons
* Medial pontine syndrome / Foville's
* Lateral pontine syndrome / Millard-Gubler
* Midbrain
* Weber's syndrome
* Benedikt syndrome
* Claude's syndrome
Cerebellum
* Cerebellar stroke syndrome
Extracranial arteries
* Carotid artery stenosis
* precerebral
* Anterior spinal artery syndrome
* Vertebrobasilar insufficiency
* Subclavian steal syndrome
Classification
* Brain ischemia
* Cerebral infarction
* Classification
* Transient ischemic attack
* Total anterior circulation infarct
* Partial anterior circulation infarct
Other
* CADASIL
* Binswanger's disease
* Transient global amnesia
Haemorrhagic stroke
Extra-axial
* Epidural
* Subdural
* Subarachnoid
Cerebral/Intra-axial
* Intraventricular
Brainstem
* Duret haemorrhages
General
* Intracranial hemorrhage
Aneurysm
* Intracranial aneurysm
* Charcot–Bouchard aneurysm
Other
* Cerebral vasculitis
* Cerebral venous sinus thrombosis
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Posterior circulation infarct | c0393956 | 4,458 | wikipedia | https://en.wikipedia.org/wiki/Posterior_circulation_infarct | 2021-01-18T19:00:49 | {"umls": ["C0393956"], "icd-9": ["433.2", "433.0"], "wikidata": ["Q9008403"]} |
Pressure urticaria
Other namesDelayed pressure urticaria
SpecialtyDermatology
Pressure urticaria is a physical urticaria caused by pressure applied to the skin, and is characterized by the development of swelling and pain that usually occurs 3 to 12 hours after local pressure has been applied.[1]:155[2]
## See also[edit]
* Urticaria
* Skin lesion
* List of cutaneous conditions
## References[edit]
1. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
2. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. pp. 266–7. ISBN 978-1-4160-2999-1.
## External links[edit]
Classification
D
* ICD-10: L50.4 (ILDS L50.410)
* v
* t
* e
Urticaria and erythema
Urticaria
(acute/chronic)
Allergic urticaria
* Urticarial allergic eruption
Physical urticaria
* Cold urticaria
* Familial
* Primary cold contact urticaria
* Secondary cold contact urticaria
* Reflex cold urticaria
* Heat urticaria
* Localized heat contact urticaria
* Solar urticaria
* Dermatographic urticaria
* Vibratory angioedema
* Pressure urticaria
* Cholinergic urticaria
* Aquagenic urticaria
Other urticaria
* Acquired C1 esterase inhibitor deficiency
* Adrenergic urticaria
* Exercise urticaria
* Galvanic urticaria
* Schnitzler syndrome
* Urticaria-like follicular mucinosis
Angioedema
* Episodic angioedema with eosinophilia
* Hereditary angioedema
Erythema
Erythema multiforme/
drug eruption
* Erythema multiforme minor
* Erythema multiforme major
* Stevens–Johnson syndrome, Toxic epidermal necrolysis
* panniculitis (Erythema nodosum)
* Acute generalized exanthematous pustulosis
Figurate erythema
* Erythema annulare centrifugum
* Erythema marginatum
* Erythema migrans
* Erythema gyratum repens
Other erythema
* Necrolytic migratory erythema
* Erythema toxicum
* Erythroderma
* Palmar erythema
* Generalized erythema
This cutaneous condition article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Pressure urticaria | c1270880 | 4,459 | wikipedia | https://en.wikipedia.org/wiki/Pressure_urticaria | 2021-01-18T18:57:35 | {"umls": ["C1270880"], "icd-10": ["L50.4"], "wikidata": ["Q7241740"]} |
A number sign (#) is used with this entry because of evidence that fetal encasement syndrome, an autosomal recessive condition, is caused by homozygous mutation in the CHUK (600664) gene on chromosome 10q24.
Clinical Features
Lahtela et al. (2010) described a Finnish family in which 5 pregnancies occurred. The parents were healthy, and their first pregnancy ended in a first-trimester miscarriage. In the second and third pregnancies, ultrasonography revealed multiple malformations of the fetuses at 13 and 12 weeks' gestation, respectively. These pregnancies were terminated at 14 and 13 weeks, respectively. The fourth and fifth pregnancies resulted in the births of normal infants. Samples were available from the parents and the 2 affected fetuses. At ultrasound, both fetus 1 and fetus 2 had an abnormal cyst in the cranial region, a large defect of the craniofacial area, and an omphalocele, as well as immotile and hypoplastic limbs. Autopsy of fetus 1 revealed a defect in the diaphragm, tetralogy of Fallot, and a horseshoe kidney. The skull bones were underdeveloped, and there was lobulation defect in both lungs, with 4 lobes on the right and 3 on the left. All the bones that were visible were hypoplastic but normal in number and configuration. Fetus 2 had 3 lung lobes in each lung; the other inner organs appeared normal. The skeletal muscles of both fetuses were very poorly developed, probably because of lack of movement. Bone structure revealed a normal growth plate with features of chondrodystrophy. Skin sections of the limbs were very thin, with only 2 to 5 layers of epidermal cells. The structure resembled a membrane. There was no basal hyperplasia. The stratum granulosum and horny layer were absent; however, both fetuses were below the age at which keratinization of the epidermis occurs. Skin on the outer aspects of the limbs had no adnexal structures, although some primitive hair follicles were seen. There was an island of squamous epithelium within the bony structures of the head, probably representing an unopened mouth. Based on Finnish genealogic analysis, Lahtela et al. (2010) concluded that the parents shared a common ancestor who lived in the eighteenth century.
Lahtela et al. (2010) pointed to the case reported by Stevenson et al. (1987), described as a 'cocoon fetus' with a similar encasement malformation. The general appearance of the fetus, born at 27 weeks' gestation, was most striking, with microcephaly, absent pinnae, protruding optic globes and conjunctivae, gaping mouth with protruding tongue, absent mandible, folding and fusion of all parts of the extremities to the trunk, and absent external genitalia. Pathologic examination revealed normal thoracic and abdominal viscera with intraabdominal testes. Skin from the scalp and buttocks histologically showed thinned dermis with absence of sweat glands and hair follicles, and thinned epidermis with hyperkeratosis, large keratohyaline granules in the granular layer, and absence of rete ridges. Epidermis and dermis were separated in all sections examined.
Molecular Genetics
Lahtela et al. (2010) compared gene expression from the skin fibroblasts of the 2 affected fetuses and age-matched control fetuses and observed 132 differentially expressed transcripts, 91 of which represented known genes. CHUK expression was approximately 12% of that observed in control fibroblasts; Lahtela et al. (2010) therefore considered CHUK to be an excellent candidate gene. Lahtela et al. (2010) found that the 2 affected fetuses were homozygous for a nonsense mutation in the CHUK gene (600664.0001). Lahtela et al. (2010) found expression of MMP14 (600754) protein in affected fetuses but not in age-matched control fetuses.
Kalay et al. (2012) noted similarities between fetal encasement syndrome and the Bartsocas-Papas phenotype (263650) caused by mutation in the RIPK4 gene (605706). They suggested that CHUK and RIPK4 might function via closely related pathways to promote keratinocyte differentiation and epithelial growth.
Animal Model
Lahtela et al. (2010) noted that the phenotype of these human fetuses closely resembled that of CHUK-null mice as described by Hu et al. (1999), Takeda et al. (1999), and Li et al. (1999); these are fully elaborated in the ANIMAL MODEL section of the CHUK entry (600664).
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| COCOON SYNDROME | c3150891 | 4,460 | omim | https://www.omim.org/entry/613630 | 2019-09-22T15:58:05 | {"doid": ["0060647"], "omim": ["613630"], "orphanet": ["465824"], "synonyms": ["Alternative titles", "FETAL ENCASEMENT SYNDROME"]} |
Trisomy 5p is a chromosomal abnormality resulting from the duplication of a segment of variable size of the short arm of chromosome 5, which usually involves the distal band 5p15. The clinical presentation is variable but is always associated with severe intellectual deficit.
## Epidemiology
To date, more than 40 cases have been reported, the majority in association with another chromosomal anomaly.
## Clinical description
Duplication of the 5p13 band determines the characteristic phenotype of trisomy 5p (the critical region): dolichocephaly or scaphocephaly with macrocephaly, oval elongated face, epicanthus, absent malar, long philtrum, ogival palate, macroglossia, dysplasic and low-set ears, micrognathia and short neck. Fingers are long. Patients may have microphthalmia or coloboma of the iris. At birth, the fontanelles are wide. Cerebral malformations (hydrocephalus, agenesis of the corpus callosum or Dandy-Walker malformation) are common. Visceral malformations are rare. Hypotonia is severe. There is a marked susceptibility to infections, especially respiratory infections, which can be life-threatening. Intellectual deficit is severe and may be accompanied by epilepsy. Larger duplications (up to the 5p11 band) have similar dysmorphisms, but more often are associated with failure to thrive, visceral and anorectal malformations, diaphragmatic hernia and club feet. Hydramnios may complicate pregnancy.
## Etiology
The duplication may extend towards the centromere, to the 5p11 band. The majority of reported patients have a large duplication, visible on the standard karyotype. Small subtelomeric duplications are rare. Duplications that extend to the 5p14 band result in variable intellectual deficit, epilepsy and a specific phenotype. There are no established correlations between genes in the critical region and the phenotype observed. In the majority of patients the 5p duplication is associated with the deletion of another chromosome as part of a translocation (familial or de novo). ``Pure'' duplications are rare. Some patients have been reported with interstitial duplication of 5p or an extra chromosome derived from the 5p arm (possibly in the form of a 5p isochromosome); these patients have a phenotype comparable to classical duplication.
## Diagnostic methods
Diagnosis is based on standard karyotyping or molecular determination of the karyotype (FISH, MLPA, CGH array).
## Genetic counseling
In cases of de novo anomalies, the risk of recurrence is low and can be explained by the possibility of a mosaic germline parent.
## Management and treatment
Disease management does not differ from that of other patients with severe intellectual deficit and includes physical and psychomotor therapy. Respiratory infections should be treated aggressively.
## Prognosis
The prognosis is poor; many patients die in childhood as a result of neurological complications or respiratory infections.
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Trisomy 5p | c0812464 | 4,461 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1742 | 2021-01-23T17:45:37 | {"gard": ["6093"], "icd-10": ["Q92.2"], "synonyms": ["Duplication 5p", "Duplication of the short arm of chromosome 5", "Trisomy of the short arm of chromosome 5"]} |
Acute myeloblastic leukemia without maturation
Myeloblast
SpecialtyHematology
Acute myeloblastic leukemia without maturation is a quickly progressing disease in which too many immature white blood cells (not lymphocytes) are found in the blood and bone marrow.[1]
It is classified as "M1" in the FAB classification.
## References[edit]
1. ^ Acute myeloblastic leukemia at Mount Sinai Hospital
## External links[edit]
Classification
D
* ICD-O: M9873/3
* MeSH: D015470
* Acute myeloblastic leukemia entry in the public domain NCI Dictionary of Cancer Terms
This article incorporates public domain material from the U.S. National Cancer Institute document: "Dictionary of Cancer Terms".
* v
* t
* e
Myeloid-related hematological malignancy
CFU-GM/
and other granulocytes
CFU-GM
Myelocyte
AML:
* Acute myeloblastic leukemia
* M0
* M1
* M2
* APL/M3
MP
* Chronic neutrophilic leukemia
Monocyte
AML
* AMoL/M5
* Myeloid dendritic cell leukemia
CML
* Philadelphia chromosome
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Myelomonocyte
AML
* M4
MD-MP
* Juvenile myelomonocytic leukemia
* Chronic myelomonocytic leukemia
Other
* Histiocytosis
CFU-Baso
AML
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CFU-Eos
AML
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MP
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MEP
CFU-Meg
MP
* Essential thrombocytosis
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CFU-E
AML
* Erythroleukemia/M6
MP
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MD
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CFU-Mast
Mastocytoma
* Mast cell leukemia
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Mastocytosis:
* Diffuse cutaneous mastocytosis
* Erythrodermic mastocytosis
* Adult type of generalized eruption of cutaneous mastocytosis
* Urticaria pigmentosa
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Systemic mastocytosis
* Xanthelasmoidal mastocytosis
Multiple/unknown
AML
* Acute panmyelosis with myelofibrosis
* Myeloid sarcoma
MP
* Myelofibrosis
* Acute biphenotypic leukaemia
This oncology article is a stub. You can help Wikipedia by expanding it.
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*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[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
| Acute myeloblastic leukemia without maturation | c0026998 | 4,462 | wikipedia | https://en.wikipedia.org/wiki/Acute_myeloblastic_leukemia_without_maturation | 2021-01-18T18:47:43 | {"gard": ["526"], "mesh": ["D015470"], "umls": ["C0026998"], "orphanet": ["98833"], "wikidata": ["Q4677942"]} |
A rare, autosomal recessive, congenital, cerebellar ataxia disorder characterized by hypotonia from birth, marked psychomotor delay and prominent cerebellar dysfunction (manifesting with nystagmus, intention tremor, dysarthria, ataxic gait and truncal ataxia), described in an isolated population of the Grand Cayman Island. Cerebellar hypoplasia, observed on CT scan, may be associated.
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*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Cerebellar ataxia, Cayman type | c1832585 | 4,463 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=94122 | 2021-01-23T18:43:37 | {"mesh": ["C563363"], "omim": ["601238"], "umls": ["C1832585"], "icd-10": ["G11.0"], "synonyms": ["Cayman ataxia"]} |
A number sign (#) is used with this entry because of evidence that coenzyme Q10 deficiency-8 (COQ10D8) is caused by homozygous mutation in the COQ7 gene (601683) on chromosome 16p12. One such patient has been reported.
For a general phenotypic description and a discussion of genetic heterogeneity of primary coenzyme Q10 deficiency, see COQ10D1 (607426).
Clinical Features
Freyer et al. (2015) reported a 9-year-old boy, born of consanguineous Syrian parents, with a complex multisystem disorder apparent since birth. The pregnancy was complicated by oligohydramnios, fetal lung hypoplasia, and growth retardation, but the boy was born at term. At birth, he had hypotonia, contractures of the extremities, persistent pulmonary hypertension of the newborn associated with lung hypoplasia, and renal dysfunction associated with small hypoplastic kidneys. The renal dysfunction resulted in secondary systemic hypertension with left ventricular cardiac hypertrophy. However, the renal, pulmonary, and cardiac abnormalities all normalized within the first year of life. The patient also showed delayed motor development and never learned to stand or walk independently. Other features included overall growth retardation and poor feeding requiring a gastrostomy. Electrophysiologic studies showed a combined axonal and demyelinating sensorimotor polyneuropathy; brain imaging was normal. At age 9 years, he had mild learning disabilities, hearing impairment, visual dysfunction, and progressive muscle weakness resulting in an inability to sit. Laboratory studies showed mildly increased serum and cerebrospinal fluid lactate, increased urinary fumarate and malate, and combined mitochondrial respiratory complex enzyme activity deficiency in skeletal muscle and fibroblasts. CoQ10 levels were decreased in skeletal muscle and fibroblasts. CoQ10 treatment after the diagnosis of primary CoQ10 deficiency resulted in clinical improvement. Freyer et al. (2015) emphasized the prenatal onset of renal dysfunction that later normalized, suggesting that the CoQ10 is important for kidney development and function.
Inheritance
The transmission pattern of COQ10D8 in the family reported by Freyer et al. (2015) was consistent with autosomal recessive inheritance.
Molecular Genetics
In a patient with COQ10D8, Freyer et al. (2015) identified a homozygous missense mutation in the COQ7 gene (V141E; 601683.0001). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Treatment of patient cells with the CoQ10 analog 2,4-dihydroxybensoic acid (2,4DHB) was able to specifically bypass the COQ7 deficiency, increase cellular coenzyme Q10 levels, and rescue the mitochondrial biochemical defect in patient fibroblasts. Transfection of patient cells with wildtype CoQ7 also resulted in improved mitochondrial respiration.
INHERITANCE \- Autosomal recessive GROWTH Other \- Intrauterine growth retardation \- Postnatal growth retardation HEAD & NECK Ears \- Hearing impairment, sensorineural and conductive Eyes \- Visual impairment CARDIOVASCULAR Heart \- Left ventricular hypertrophy secondary to renal dysfunction and hypertension Vascular \- Hypertension secondary renal dysfunction RESPIRATORY Lung \- Fetal lung hypoplasia \- Persistent pulmonary hypertension of the newborn \- Respiratory distress, neonatal period ABDOMEN Gastrointestinal \- Feeding difficulties GENITOURINARY Kidneys \- Renal dysfunction, neonatal and infantile \- Small dysplastic kidneys SKELETAL \- Joint contractures MUSCLE, SOFT TISSUES \- Hypotonia \- Thin musculature NEUROLOGIC Central Nervous System \- Delayed motor development \- Inability to sit, stand, or walk independently \- Learning disability, mild Peripheral Nervous System \- Sensorimotor axonal and demyelinating polyneuropathy PRENATAL MANIFESTATIONS Amniotic Fluid \- Oligohydramnios LABORATORY ABNORMALITIES \- Increased serum and cerebrospinal fluid lactate, mild \- Increased urinary fumarate and malate \- Combined mitochondrial respiratory enzyme deficiency in skeletal muscle and fibroblasts \- Decreased CoQ10 levels in skeletal muscle and fibroblasts MISCELLANEOUS \- Onset at birth \- Renal dysfunction normalizes in the first year of life \- Cardiac and pulmonary dysfunction normalize in the first year of life \- Treatment with CoQ10 may result in some clinical improvement \- One patient has been reported (last curated January 2015) MOLECULAR BASIS \- Caused by mutation in the homolog of the S. cerevisiae CoQ7 gene (COQ7, 601683.0001 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| COENZYME Q10 DEFICIENCY, PRIMARY, 8 | c4225226 | 4,464 | omim | https://www.omim.org/entry/616733 | 2019-09-22T15:48:05 | {"omim": ["616733"], "genereviews": ["NBK410087"]} |
Glass delusion is an external manifestation of a psychiatric disorder recorded in Europe mainly in the late Middle Ages and early modern period (15th to 17th centuries).[1] People feared that they were made of glass "and therefore likely to shatter into pieces". One famous early sufferer was King Charles VI of France, who refused to allow people to touch him and wore reinforced clothing to protect himself from accidental "shattering".
## Contents
* 1 The delusion
* 2 Contemporary accounts
* 3 Tchaikovsky
* 4 See also
* 5 Notes
* 6 References
## The delusion[edit]
Concentration of the glass delusion among the wealthy and educated classes allowed modern scholars to associate it with a wider and better described disorder of melancholy.[2]
## Contemporary accounts[edit]
Robert Burton's The Anatomy of Melancholy (1621) touches on the subject in the commentary as one of many related manifestations[3] of the same anxiety:
> Fear of devils, death, that they shall be so sick, of some such or such disease, ready to tremble at every object, they shall die themselves forthwith, or that some of their dear friends or near allies are certainly dead; imminent danger, loss, disgrace still torment others; that they are all glass, and therefore will suffer no man to come near them; that they are all cork, as light as feathers; others as heavy as lead; some are afraid their heads will fall off their shoulders, that they have frogs in their bellies, Etc.[4]
Miguel de Cervantes based one of his short Exemplary Novels, The Glass Graduate (Spanish: El licenciado Vidriera, 1613), on the delusion of the title subject, an aspiring young lawyer.[5] The protagonist of the story falls into a grave depression after being bedridden for six months subsequent to being poisoned with a purportedly aphrodisiac potion. He claims that, being of glass, his perceptions are clearer than those of men of flesh and demonstrates by offering witty comments. After two years of illness, Rodaja is cured by a monk; no details of the cure are provided except that the monk is allegedly a miracle-maker.
The Dutch poet Constantijn Huygens wrote a Costly Folly (1622) centered on a subject who "fears everything that moves in his vicinity... the chair will be the death for him; he trembles at the bed, fearful that one will break his bum, the other smash his head".[2] His Dutch contemporary Caspar Barlaeus experienced the glass delusion.[6]
French philosopher René Descartes wrote Meditations on First Philosophy (1641), using the glass delusion as an example of an insane person whose perceived knowledge of the world differs from the majority.[7] In the Essay (Book II, Chapter XI, 13) when proposing his celebrated model of madness, John Locke also refers to the glass delusion.[8]
In modern times, the glass delusion has not completely disappeared. There are still isolated cases today. "Surveys of modern psychiatric institutions have only revealed two specific (uncorroborated) cases of the glass delusion. Foulché-Delbosc reports finding one Glass Man in a Paris asylum, and a woman who thought she was a potsherd was recorded at an asylum in Merenberg." Andy Lameijn, a psychiatrist from the Netherlands, reports that he has a male patient suffering from the delusion in Leiden.[9]
## Tchaikovsky[edit]
This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed.
Find sources: "Glass delusion" – news · newspapers · books · scholar · JSTOR (July 2020) (Learn how and when to remove this template message)
The neurotic behavior of the 19th-century Russian composer Peter Ilyich Tchaikovsky seems reminiscent of the glass delusion, centering as it did on his difficulties caused by his belief that his head would fall off while conducting if he did not hold his chin. While the legend may be exaggerated, it seems to have some basis in fact:
> In March 1868 in his first attempt [at conducting], Tchaikovsky conducted dances from The Voevoda, "and had felt that his head would fall sideways unless he fought to keep it upright" ... (per David Brown, The Final Years page 97) ... and so he avoided conducting ... In October 1886 Tchaikovsky pointed out to his patroness "all my life I have been tormented by awareness of my inability to conduct. It has seemed to me there is something shameful and disreputable in not being able to stop myself trembling with fear and horror at the very thought of going out in front of the public with a baton" ... However on Jan. 31, 1887 Tchaikovsky in his third attempt overcame his fear and conducted the premier of The Enchantress ... as a further inducement "he was not unaware that a conductor could enjoy more celebrity in his own time than a composer."[citation needed]
## See also[edit]
* Charles VI of France
* El licenciado Vidriera
* Princess Alexandra of Bavaria
## Notes[edit]
1. ^ Speak, Gill (1990). "An odd kind of melancholy: reflections on the glass delusion in Europe (1440–1680)". History of Psychiatry. 1 (2): 191–206. doi:10.1177/0957154X9000100203.
2. ^ a b Speak, "El licenciado...", p.850
3. ^ Robert Burton (1621). The Anatomy of Melancholy.
4. ^ Burton, Com.1 Sec.3 comment no. 52
5. ^ de Cervantes, Miguel (1613). The Glass Graduate (also known as The Glass Licenciate, The Glass Lawyer; Spanish: El licenciado Vidriera).
6. ^ F.F. Blok, Caspar Barlaeus : from the correspondence of a melancholic ; [translated by H.S. Lake (prose) and D.A.S. Reid (poetry)], Assen : Van Gorcum, 1976
7. ^ René Descartes (1641). Meditations on First Philosophy. ISBN 0-87484-893-8.
8. ^ Locke J (1690) An Essay Concerning Humane Understanding. London: Thomas Bassett, p71.
9. ^ "The people who think they are made of glass". BBC News. 8 May 2015. Retrieved 8 May 2015.
## References[edit]
* Speak, Gill (October 1990). "'El licenciado Vidriera' and the Glass Men of Early Modern Europe". The Modern Language Review. 85 (4): 850–865. doi:10.2307/3732644. JSTOR 3732644.
* "Music for a glass man". BBC. December 5, 2005.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Glass delusion | None | 4,465 | wikipedia | https://en.wikipedia.org/wiki/Glass_delusion | 2021-01-18T18:59:59 | {"wikidata": ["Q5567102"]} |
This article needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed.
Find sources: "Collagenopathy, types II and XI" – news · newspapers · books · scholar · JSTOR (November 2016)
The type II and XI collagenopathies are a group of disorders that affect connective tissue, the tissue that supports the body's joints and organs. These disorders are caused by defects in type II or type XI collagen. Collagens are complex molecules that provide structure, strength, and elasticity to connective tissue. Type II and type XI collagen disorders are grouped together because both types of collagen are components of the cartilage found in joints and the spinal column, the inner ear, and the jelly-like substance that fills the eyeball (the vitreous). The type II and XI collagenopathies result in similar clinical features.
## Contents
* 1 Types
* 2 Causes
* 3 Diagnosis
* 4 Treatment
* 5 References
## Types[edit]
Genetic changes are related to the following types of collagenopathy, types II and XI.
* achondrogenesis type 2
* hypochondrogenesis
* Kniest dysplasia
* otospondylomegaepiphyseal dysplasia
* spondyloepimetaphyseal dysplasia, Strudwick type
* spondyloepiphyseal dysplasia congenita
* spondyloperipheral dysplasia
* Stickler syndrome
* Weissenbacher-Zweymüller syndrome
The system for classifying collagenopathies is changing as researchers learn more about the genetic causes of these disorders. The clinical features of the type II and XI collagenopathies vary among the disorders, but there is considerable overlap. Common signs and symptoms include problems with bone development that can result in short stature, enlarged joints, spinal curvature, and arthritis at a young age. For some people, bone changes can be seen only on X-ray images. Problems with vision and hearing, as well as a cleft palate with a small lower jaw, are common. Some individuals with these disorders have distinctive facial features such as protruding eyes and a flat nasal bridge.
## Causes[edit]
Mutations in the COL11A1, COL11A2, and COL2A1 genes cause collagenopathy, types II and XI. These genes carry instructions for the protein strands that make up type II and type XI collagen. All collagen molecules are made of three protein strands (called alpha chains). The alpha chains may be identical or different, depending on the type of collagen. Type II collagen is made by combining three copies of the alpha chain made by the COL2A1 gene. Type XI collagen, on the other hand, is composed of three different alpha chains: the products of the COL2A1, COL11A1, and COL11A2 genes.
Mutations in these genes interfere with the proper assembly of type II and XI collagens or reduce the amount of these collagens. Defective or reduced numbers of collagen molecules affect the development of bones and other connective tissues, causing the signs and symptoms of the type II and XI collagenopathies.
## Diagnosis[edit]
This section is empty. You can help by adding to it. (November 2016)
## Treatment[edit]
This section is empty. You can help by adding to it. (November 2016)
## References[edit]
This article incorporates public domain text from The U.S. National Library of Medicine
* v
* t
* e
Diseases of collagen, laminin and other scleroproteins
Collagen disease
COL1:
* Osteogenesis imperfecta
* Ehlers–Danlos syndrome, types 1, 2, 7
COL2:
* Hypochondrogenesis
* Achondrogenesis type 2
* Stickler syndrome
* Marshall syndrome
* Spondyloepiphyseal dysplasia congenita
* Spondyloepimetaphyseal dysplasia, Strudwick type
* Kniest dysplasia (see also C2/11)
COL3:
* Ehlers–Danlos syndrome, types 3 & 4
* Sack–Barabas syndrome
COL4:
* Alport syndrome
COL5:
* Ehlers–Danlos syndrome, types 1 & 2
COL6:
* Bethlem myopathy
* Ullrich congenital muscular dystrophy
COL7:
* Epidermolysis bullosa dystrophica
* Recessive dystrophic epidermolysis bullosa
* Bart syndrome
* Transient bullous dermolysis of the newborn
COL8:
* Fuchs' dystrophy 1
COL9:
* Multiple epiphyseal dysplasia 2, 3, 6
COL10:
* Schmid metaphyseal chondrodysplasia
COL11:
* Weissenbacher–Zweymüller syndrome
* Otospondylomegaepiphyseal dysplasia (see also C2/11)
COL17:
* Bullous pemphigoid
COL18:
* Knobloch syndrome
Laminin
* Junctional epidermolysis bullosa
* Laryngoonychocutaneous syndrome
Other
* Congenital stromal corneal dystrophy
* Raine syndrome
* Urbach–Wiethe disease
* TECTA
* DFNA8/12, DFNB21
see also fibrous proteins
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Collagenopathy, types II and XI | None | 4,466 | wikipedia | https://en.wikipedia.org/wiki/Collagenopathy,_types_II_and_XI | 2021-01-18T19:08:37 | {"wikidata": ["Q5145912"]} |
A rare disorder of the anterior segment of the eye characterized by ocular infection by human-pathogenic fungi, most commonly Aspergillus, Candida, or Fusarium species, which gain access into the corneal stroma through a defect in the corneal epithelium. Risk factors include trauma, ocular surface disease, contact lenses, or immunocompromised state. Patients present with pain, foreign body sensation, redness, photophobia, tearing, secretion, or blurred vision. The condition may be complicated by corneal destruction and perforation, endophthalmitis, scleritis, and panophthalmitis.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Fungal keratitis | c1262117 | 4,467 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=519930 | 2021-01-23T18:34:37 | {"synonyms": ["Keratomycosis", "Mycotic keratitis"]} |
A number sign (#) is used with this entry because of evidence that nemaline myopathy-2 (NEM2) is caused by homozygous or compound heterozygous mutation in the nebulin gene (NEB; 161650) on chromosome 2q23.
Description
Nemaline myopathy-2 is an autosomal recessive skeletal muscle disorder with a wide range of severity. The most common clinical presentation is early-onset (in infancy or childhood) muscle weakness predominantly affecting proximal limb muscles. Muscle biopsy shows accumulation of Z-disc and thin filament proteins into aggregates named 'nemaline bodies' or 'nemaline rods,' usually accompanied by disorganization of the muscle Z discs. The clinical and histologic spectrum of entities caused by variants in the NEB gene is a continuum, ranging in severity from the severe form with perinatal onset and fetal death to milder forms with later onset. The distribution of weakness can vary from generalized muscle weakness, more pronounced in proximal limb muscles, to distal-only involvement, although neck flexor weakness appears to be rather consistent. Histologic patterns range from a severe usually nondystrophic disturbance of the myofibrillar pattern to an almost normal pattern, with or without nemaline bodies, sometimes combined with cores (summary by Lehtokari et al., 2014).
For a discussion of genetic heterogeneity of nemaline myopathy, see NEM3 (161800).
Mutations in the NEB gene are the most common cause of nemaline myopathy (Lehtokari et al., 2006).
Clinical Features
Wallgren-Pettersson et al. (1999) reported 41 unrelated families with NEM2 suggested by linkage analysis. All were consistent with autosomal recessive inheritance. Wallgren-Pettersson et al. (1999) noted that phenotypic classification of nemaline myopathy is difficult because the disease spectrum forms a continuum; however, the authors described 2 main forms, 'typical' and 'severe.' Typical patients had generalized hypotonia at birth, with particular involvement of the bulbar, neck flexor, and respiratory muscles. Proximal limb muscles were weaker initially, but distal limb muscle weakness eventually occurred. The extraocular muscles were spared. The facies was myopathic with a high-arched palate. The spine was hyperlordotic, sometimes rigid, and scoliosis sometimes developed at puberty. Deep tendon reflexes were decreased or absent, and the gag reflex was often absent. Chest deformities were common, but there was no cardiac involvement. Imaging showed decreased muscle density with increased fatty infiltration. Serum creatine kinase was normal or mildly elevated. Muscle biopsies characteristically showed nemaline bodies and type 1 fiber predominance. Although myopathic changes were observed, there were no dystrophic or inflammatory changes. Despite delayed motor development and waddling gait, many patients with typical disease remained ambulatory as adults. Intelligence was normal. A subset of patients had severe disease, characterized by absence of spontaneous movements or respiration at birth. These patients often had contractures or fractures at birth and usually never achieved independent sitting or ambulation.
Wallgren-Pettersson et al. (2002) reported 7 patients from 5 families with severe NEM2 confirmed by mutation in the NEB gene. Four pregnancies were complicated by polyhydramnios, and 4 patients had arthrogryposis. Most affected infants did show show spontaneous respiration or antigravity movements. Several previous infant deaths or miscarriages were reported in the families. Two affected brothers in 1 family had large fontanels, low-set ears, adducted thumbs, hypospadias, and micropenis. Another affected child had cleft palate, rocker-bottom feet, and undescended testes. Death occurred between 30 minutes and 19 months of age. Muscle biopsies showed nemaline bodies in up to 90% of muscle fibers.
Romero et al. (2009) reported a 27-year-old man with NEM2 confirmed by genetic analysis. He presented at birth with generalized hypotonia, poor spontaneous movements, and restrictive respiratory insufficiency requiring mechanical ventilation. He showed diffuse muscle weakness with axial predominance, never acquired independent ambulation, and developed multiple joint contractures. As an adult, he was quadriplegic with mild facial weakness. No cardiac symptoms were observed. Muscle biopsy showed numerous fibers with distinctive rods and well-delineated cores in type 1 fibers. Electron microscopy showed rods with characteristic striation and cores with some sarcomeric disorganization and depletion of mitochondria. The histologic findings indicated that cores, in addition to rods, may be found in patients with NEM2.
In a detailed review and update of 159 families with mutations in the nebulin gene associated with myopathies, Lehtokari et al. (2014) noted that the most common associated phenotype was nemaline myopathy (90% of families). Within this broad category, there was a range of severity. In addition, some families with NEB mutations had more diverse manifestations, including early-onset distal myopathy without nemaline bodies (4 families), a distal form of nemaline myopathy (3 families), core-rod myopathy with generalized muscle weakness (3 families), a childhood-onset distal myopathy with rods and cores (3 families), and fetal akinesia/lethal multiple pterygium syndrome (3 families).
### Fetal Akinesia/Lethal Multiple Pterygia Syndrome
Yonath et al. (2012) reported 4 unrelated pregnancies with abnormal prenatal ultrasound findings in fetuses with NEM2. In each family, 1 or both of the parents was of Ashkenazi Jewish descent, and the common exon 55 deletion (161650.0007) in the NEB gene was found in the heterozygous state in the patients and in unaffected parents. A second pathogenic NEB mutation was found in 3 of the patients; a second mutation could not be identified in 1 of the patients. Prenatal ultrasound showed polyhydramnios, decreased fetal movements, clubfoot, and clenched hands. All patients showed severe hypotonia after birth, and all died within the first months of life.
Todd et al. (2015) reported twin male fetuses, conceived of consanguineous parents, with NEM2 presenting as fetal akinesia with lethal multiple pterygia syndrome. Prenatal ultrasound showed severe hydrops in both fetuses, and the pregnancy was terminated at 16 weeks' gestation. Postmortem examination showed joint contractures consistent with arthrogryposis multiplex congenita (AMC), bilateral talipes, multiple pterygia, hypertelorism, and cystic hygromas. Muscle tissue was not obtained. A previous fetus was therapeutically aborted due to hydrops fetalis at 19 weeks' gestation.
Abdalla et al. (2017) reported 2 male fetuses, conceived of consanguineous Egyptian parents, with NEM2 presenting as fetal akinesia with lethal multiple pterygia syndrome. Both pregnancies were complicated by polyhydramnios and hydrops fetalis. Prenatal ultrasound of the second fetus at 18 weeks' gestation showed growth restriction, fetal akinesia, cystic hygroma, edema, pericardial effusion, hydrothorax, and flexion deformities. The pregnancy was terminated, and postmortem examination confirmed the findings of multiple pterygia and contractures; dysmorphic features, including hypertelorism, downslanting palpebral fissures, long philtrum, and low-set ears were also noted. Muscle biopsy was not performed.
### Distal Myopathy
Wallgren-Pettersson et al. (2007) reported 7 patients from 4 unrelated Finnish families with NEM2 presenting as distal myopathy with foot drop between the first and third decades after normal early motor development. Muscle weakness predominantly affected the ankle dorsiflexors, finger extensors, and neck flexors, resulting in walking difficulties and increased falls in some patients. The patients were unable to walk on their heels. Additional variable features included high-arched palate, slight facial weakness, dysarthria, pseudohypertrophy of the calves, and mild atrophy of proximal muscles of the upper and lower limbs. Radiographic imaging showed fatty replacement of the muscles of the anterior compartment of the lower legs. None of the patients had breathing problems or dysphagia, and serum creatine kinase was not elevated. Muscle biopsy showed myopathic changes with marked fiber size variability, fibrosis, and large hypertrophic fibers with increased internal nuclei. Rare nemaline rods or bodies were observed, although these were often apparent only on electron microscopy or with special staining. The patients were initially thought to have tibial muscular dystrophy (TMD; 600334), but molecular analysis excluded that diagnosis.
Inheritance
The transmission pattern of NEM2 in the families reported by Yonath et al. (2012) was consistent with autosomal recessive inheritance.
Mapping
Wallgren-Pettersson et al. (1995) used genetic linkage analysis from 7 European families with autosomal recessive nemaline myopathy to map a candidate disease locus, designated NEM2, to a 13-cM region on chromosome 2q21.2-q22 between markers D2S150 and D2S142 (maximum lod score of 5.34 at marker D2S151).
By radiation hybrid mapping, Pelin et al. (1997) mapped the nebulin gene to a position close to the microsatellite marker D2S2236 on 2q22. They also mapped the titin gene (188840) to the vicinity of markers D2S384 and D2S364 on 2q24.3. Pelin et al. (1997) concluded that of these 2 giant muscle proteins, the gene for nebulin resides within the candidate region for NEM2, whereas the titin gene is located outside this region.
Molecular Genetics
Pelin et al. (1999) demonstrated mutations in the NEB gene in autosomal recessive typical nemaline myopathy (161650.0001-161650.0006).
Wallgren-Pettersson et al. (2002) identified mutations in the NEB gene in patients with severe congenital nemaline myopathy (see, e.g., 161650.0003 and 161650.0004).
In 5 affected individuals from 5 Ashkenazi Jewish families with autosomal recessive typical nemaline myopathy, Anderson et al. (2004) identified a 2,502-bp deletion in the NEB gene (161650.0007), resulting in removal of exon 55.
Using denaturing high-performance liquid chromatography (DHPLC), Lehtokari et al. (2006) identified 45 novel mutations in the NEB gene in affected members of 44 unrelated families with nemaline myopathy. Mutations were identified in patients representing all clinical categories of disease severity. The majority (55%) of mutations were frameshift or nonsense mutations resulting in premature termination of the protein. Mutations were distributed throughout the gene, with no obvious hotspots. Lehtokari et al. (2006) concluded that mutations in the NEB gene are the most common cause of nemaline myopathy.
In 7 patients from 4 unrelated Finnish families, 2 of whom were consanguineous, with NEM2 manifest as distal myopathy with onset in childhood or adulthood, Wallgren-Pettersson et al. (2007) identified homozygous missense mutations in the NEB (T5681P, 161650.0008 and S4665I, 161650.0009). The mutations segregated with the disorder in the families from whom DNA was available. Functional studies of the mutation were not performed, but Wallgren-Pettersson et al. (2007) noted that both missense mutations had been found in compound heterozygosity with more disruptive NEB mutations in other families with the more severe typical form of NEM2. The findings suggested that homozygosity for a missense NEB variant may result in a milder myopathic phenotype.
In a detailed review and update of 159 families with mutations in the nebulin gene associated with myopathies, Lehtokari et al. (2014) found that the most common types of mutations were splice-site mutations (34%), followed by frameshift (32%), nonsense (23%), and finally missense (7%). The vast majority of patients had compound heterozygous mutations. There were no apparent genotype/phenotype correlations.
In twin male fetuses, conceived of consanguineous parents, with NEM2 presenting as fetal akinesia with lethal multiple pterygia syndrome, Todd et al. (2015) identified a homozygous nonsense mutation in the NEB gene (R974X; 161650.0010). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed. In affected patients from 3 additional families diagnosed with fetal akinesia, a heterozygous splice site, frameshift, or truncating mutation in the NEB gene was found. A second pathogenic mutation was not found in these patients, but there was evidence for autosomal recessive inheritance, suggesting that the affected fetuses carried a second pathogenic variant. Todd et al. (2015) noted the difficulty in screening the nebulin gene for mutations because of its large size and because next-generation sequencing data may not accurately identify pathogenic small copy number variations. These 4 families were ascertained from a cohort of 38 families with severe neuromuscular disease apparent before or at birth.
Pathogenesis
Ottenheijm et al. (2009) studied the muscular phenotype of nemaline myopathy (NM) patients with a well-defined (161650.0007) nebulin mutation (NM-NEB), resulting in deletion of exon 55 from the transcript. SDS-PAGE and Western blot analysis revealed greatly reduced nebulin levels in skeletal muscle of NM-NEB patients, with the most prominent reduction at nebulin's N-terminal end. Muscle mechanical studies indicated an approximately 60% reduced force generating capacity of NM-NEB muscle and a leftward shift of the force-sarcomere length relation in NM-NEB muscle fibers. This indicates that the mechanism for the force reduction is likely to include shorter and nonuniform thin filament lengths in NM-NEB muscle compared with control muscle. The average thin filament length was reduced from approximately 1.3-micrometer in control muscle to approximately 0.75-micrometer in NM-NEB muscle. Ottenheijm et al. (2009) hypothesized that dysregulated thin filament length may contribute to muscle weakness in nemaline myopathy patients with nebulin mutations.
Population Genetics
Anderson et al. (2004) screened for 2,503-bp deletion in a random sample of 4,090 Ashkenazi Jewish individuals, revealing a carrier frequency of 1 in 108. Lehtokari et al. (2009) identified the 2,502-bp deletion in 14 of 355 probands with nemaline myopathy from around the world; 2 of the probands had been reported by Anderson et al. (2004). Seven probands were homozygous for the deletion, and 7 carried the mutation in heterozygosity. Two of the families were not of known Ashkenazi Jewish descent, but carried the common haplotype identified in Ashkenazi Jews. The findings were consistent with a founder effect.
INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Myopathic facies \- Facial muscle weakness \- Long philtrum (severe form) Ears \- Low-set ears (severe form) Eyes \- Hypertelorism (severe form) Mouth \- High-arched palate \- Cleft palate (severe form) Neck \- Neck flexor muscle weakness RESPIRATORY \- Respiratory insufficiency due to muscle weakness \- Absence of spontaneous respiration (severe form) CHEST External Features \- Chest deformities ABDOMEN Gastrointestinal \- Poor feeding \- Dysphagia SKELETAL \- Joint contractures \- Joint deformities (may develop over time) \- Arthrogryposis (severe form) Spine \- Hyperlordosis \- Scoliosis (onset around puberty) \- Rigid spine Hands \- Clenched hands (severe form) Feet \- Talipes (severe form) MUSCLE, SOFT TISSUES \- Hypotonia, neonatal \- Muscle weakness, generalized \- Bulbar muscle weakness \- Facial muscle weakness \- Neck muscle weakness \- Proximal limb muscle weakness initially \- Distal limb muscle weakness occurs later \- Distal limb muscle weakness initially (in some patients) \- 'Waddling' gait \- Inability to run \- Inability to walk on heels \- Frequent falls \- Myopathic changes early in disease seen on EMG \- Neurogenic changes later in disease seen on EMG \- Nemaline bodies (rods) on Gomori trichrome staining \- Nemaline bodies are usually subsarcolemmal or sarcoplasmic \- Nemaline bodies are rarely intranuclear \- Nonspecific myopathic changes without dystrophic or inflammatory changes seen on muscle biopsy \- Cores with lack of oxidative activity and mitochondrial depletion may also be found and extend along length of fiber \- Type 1 muscle fiber predominance \- Decreased muscle density on imaging \- Increased fatty infiltration \- Absence of spontaneous activity at birth (severe form) NEUROLOGIC Central Nervous System \- Delayed motor development \- Failure to achieve sitting or walking (severe form) \- Absent gag reflex \- Hyporeflexia \- Areflexia \- Slow gross motor activity \- Normal fine motor activity PRENATAL MANIFESTATIONS Movement \- Decreased fetal movement (severe form) Amniotic Fluid \- Polyhydramnios (severe form) \- Fetal hydrops (severe form) LABORATORY ABNORMALITIES \- Normal or mildly increased serum creatine kinase MISCELLANEOUS \- Extraocular muscles are not involved \- Onset in infancy \- Highly variable severity, ranging from 'typical' to 'severe' disease \- Slowly progressive or nonprogressive course \- Many adults with typical form remain ambulatory \- Death at birth or within first 2 years of life (severe form) MOLECULAR BASIS \- Caused by mutation in the nebulin gene (NEB, 161650.0001 ) ▲ Close
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*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| NEMALINE MYOPATHY 2 | c0546125 | 4,468 | omim | https://www.omim.org/entry/256030 | 2019-09-22T16:24:27 | {"doid": ["0110928"], "mesh": ["D017696"], "omim": ["256030"], "orphanet": ["171439", "171430", "171436", "171433"], "genereviews": ["NBK1288"]} |
Duroziez's disease
SpecialtyCardiology
Duroziez's disease is a congenital variant of mitral stenosis. It was described in 1877 by Paul Louis Duroziez.[1]
## References[edit]
1. ^ Duroziez' disease at Who Named It?
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Congenital heart defects
Heart septal defect
Aortopulmonary septal defect
* Double outlet right ventricle
* Taussig–Bing syndrome
* Transposition of the great vessels
* dextro
* levo
* Persistent truncus arteriosus
* Aortopulmonary window
Atrial septal defect
* Sinus venosus atrial septal defect
* Lutembacher's syndrome
Ventricular septal defect
* Tetralogy of Fallot
Atrioventricular septal defect
* Ostium primum
Consequences
* Cardiac shunt
* Cyanotic heart disease
* Eisenmenger syndrome
Valvular heart disease
Right
* pulmonary valves
* stenosis
* insufficiency
* absence
* tricuspid valves
* stenosis
* atresia
* Ebstein's anomaly
Left
* aortic valves
* stenosis
* insufficiency
* bicuspid
* mitral valves
* stenosis
* regurgitation
Other
* Underdeveloped heart chambers
* right
* left
* Uhl anomaly
* Dextrocardia
* Levocardia
* Cor triatriatum
* Crisscross heart
* Brugada syndrome
* Coronary artery anomaly
* Anomalous aortic origin of a coronary artery
* Ventricular inversion
This article about a medical condition affecting the circulatory system is a stub. You can help Wikipedia by expanding it.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Duroziez's disease | c0158618 | 4,469 | wikipedia | https://en.wikipedia.org/wiki/Duroziez%27s_disease | 2021-01-18T18:38:11 | {"wikidata": ["Q5316720"]} |
A rare acquired endocrine disease related to excessive production of growth hormone (GH) and characterized by progressive somatic disfigurement (mainly involving the face and extremities) and systemic manifestations.
## Epidemiology
Worldwide, the prevalence is 1/7,500 to 1/35,800. The annual incidence is 1/91,000 to 1/526,000.
## Clinical description
Due to its insidious onset and slow progression, acromegaly is often diagnosed from four to more than ten years after its onset, and is most often diagnosed in middle age (average age 40-50 years). The main clinical features are broadened extremities (hands and feet), widened, thickened and stubby fingers, and thickened soft tissue. The facial aspect is characteristic and includes a widened and thickened nose, prominent cheekbones, forehead bulges, thick lips and marked facial lines. The forehead and overlying skin is thickened, sometimes leading to frontal bossing. There is a tendency towards mandibular overgrowth with prognathism, maxillary widening, tooth separation and jaw malocclusion. The disease also has rheumatologic, cardiovascular, respiratory and metabolic consequences which determine its prognosis.
## Etiology
In the majority of cases, acromegaly is related to a pituitary adenoma, either purely GH-secreting (60%) or mixed. In very rare cases, acromegaly is due to ectopic secretion of growth hormone-releasing hormone (GHRH), responsible for pituitary hyperplasia. The gene aryl hydrocarbon receptor interacting protein, AIP (11q13.3), has been identified as a major susceptibility factor, particularly when acromegaly begins in childhood or adolescence. Acromegaly may also be part of multiple endocrine neoplasia syndromes such as MEN1 (MEN1; gene MEN1, 11q13), Carney complex (gene PRKAR1A , 17q24.2) or familial isolated pituiatary adenoma (FIPA; gene AIP, 11q13.2). Very rarely it may be secondary to Xq26.3 chromosomal microduplications, responsible for X-linked acrogigantism due to Xq26 microduplication (XLAG), a very early-onset gigantism syndrome. Acromegaly may also be part of McCune-Albright syndrome.
## Diagnostic methods
The clinical diagnosis is confirmed biochemically by detection of increased serum of insulin-like growth factor-I (IGF-I) concentrations (screening test) and an increased serum GH concentration not suppressed following an oral glucose tolerance test (OGTT; confirmation test). Assessment of tumor volume and extension is based on imaging studies. Echocardiography and sleep apnea testing are used to determine the clinical impact of acromegaly.
## Differential diagnosis
Differential diagnosis includes other causes of acromegaly (FIPA, MEN1, Carney complex and XLAG) as well as pachydermoperiostosis and acromegaloid features of severe insulin resistance.
## Genetic counseling
This form of acromegaly is sporadic; a causal genetic mutation has not been identified.
## Management and treatment
Treatment is aimed at correcting (or preventing) tumor compression by excising the disease-causing lesion, and at reducing GH and IGF-I levels to normal values. Transsphenoidal surgery is often the first-line treatment. When surgery fails to correct GH/IGF-I hypersecretion, medical treatment with dopamine agonists and/or somatostatin analogs is proposed. The GH antagonist (pegvisomant) is used in patients that are resistant to somatostatin analogs. Radiotherapy may be discussed as a third line of treatment in cases of medical treatment failure.
## Prognosis
Adequate hormonal disease control is achieved in most cases, allowing a life expectancy similar to that of the general population. However, even if patients are cured or well-controlled, sequelae (joint pain, deformities and altered quality of life) often remain.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Acromegaly | c0001206 | 4,470 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=963 | 2021-01-23T18:45:56 | {"gard": ["5725"], "mesh": ["D000172"], "omim": ["102200", "300943"], "umls": ["C0001206"], "icd-10": ["E22.0"]} |
Blastomycosis is a rare infection that may develop when people inhale a fungus called Blastomyces dermatitidis, a fungus that is found in moist soil, particularly where there is rotting vegetation. The fungus enters the body through the lungs, infecting them. The fungus then spreads to other areas of the body. The infection may affect the skin, bones and joints, and other areas. The disease usually affects people with weakened immune systems, such as those with HIV or who have had an organ transplant.
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*[AA]: Adrenergic agonist
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*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[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
| Blastomycosis | c0005716 | 4,471 | gard | https://rarediseases.info.nih.gov/diseases/5931/blastomycosis | 2021-01-18T18:01:46 | {"mesh": ["D001759"], "synonyms": ["North American blastomycosis", "Gilchrist's disease"]} |
Leukocyte adhesion deficiency type I (LAD-I) is a form of LAD (see this term) characterized by life-threatening, recurrent bacterial infections.
## Epidemiology
LAD-I affects 1 individual per million.
## Clinical description
Usually the first signs occur in infancy or early childhood. Patients present recurrent, life-threatening bacterial infections of the skin, mouth, and respiratory tract. Delayed umbilical cord separation is common. Skin infections may evolve into large ulcers. Severe periodontitis is often present later in life and leads to early tooth loss. A lack of swelling, redness, heat, or pus is observed in the area of infection.
## Etiology
LAD-I is caused by mutations in the ITGB2 gene (21q22.3), encoding the beta-2-integrin, CD18, which is essential for firm adhesion of leukocytes to the endothelium. Severity of the disease correlates with the degree of CD18 deficiency.
## Diagnostic methods
Diagnosis is based on complete blood counts revealing neutrophilic leukocytosis. Flow cytometric analyses reveal reduced CD18 expression on leukocytes. Genetic analyses of mutations in the ITGB2 gene confirm the diagnosis.
## Differential diagnosis
Differential diagnoses include IRAK-4 deficiency, autosomal dominant hyper IgE syndrome, chronic granulomatous disease, other primary immunodeficiencies (see these terms) and a leukemoid reaction.
## Antenatal diagnosis
Antenatal diagnosis is possible through biochemical or molecular analysis of chorionic villus cells or amniocytes in affected families for which the mutation has been identified. Flow cytometry can be performed at 20 weeks of gestation.
## Genetic counseling
Transmission is autosomal recessive.
## Management and treatment
Management should focus on controlling infections and includes antibiotics. Hematopoietic cell transplantation represents the only cure for LAD-I, but gene therapy may be available in the future.
## Prognosis
Prognosis depends on the severity of the disease. Without hematopoietic stem cell transplantation, death in patients with severe LAD-I occurs from infection within the first 2 years of life, whereas patients with a moderate form of the disease have abetter chance of surviving into adulthood. Survival rate after bone marrow transplantation is 75%.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Leukocyte adhesion deficiency type I | c0398738 | 4,472 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99842 | 2021-01-23T18:24:47 | {"gard": ["6893"], "mesh": ["C535887"], "omim": ["116920"], "umls": ["C0398738"], "icd-10": ["D84.8"], "synonyms": ["LAD-I"]} |
Clitoridectomy
Other namesClitorectomy
Specialtygynecology
[edit on Wikidata]
Clitoridectomy or clitorectomy is the surgical removal, reduction, or partial removal of the clitoris.[1] It is rarely used as a therapeutic medical procedure, such as when cancer has developed in or spread to the clitoris. It is often performed on intersex newborns. Commonly, non-medical removal of the clitoris is performed during female genital mutilation (FGM).[2]
## Contents
* 1 Medical uses
* 1.1 Malignancies
* 1.2 Intersexuality and other conditions
* 2 Technique
* 3 Society and culture
* 3.1 General
* 3.2 Human rights concerns
* 4 See also
* 5 References
## Medical uses[edit]
### Malignancies[edit]
A clitoridectomy is often done to remove malignancy or necrosis of the clitoris. This is sometimes done along with a radical complete vulvectomy. Surgery may also become necessary due to therapeutic radiation treatments to the pelvic area.[3]
Removal of the clitoris may be due to malignancy or trauma.[3][4]
### Intersexuality and other conditions[edit]
Female infants born with a 46,XX genotype but have genitalia affected by congenital adrenal hyperplasia and are treated surgically with vaginoplasty that often reduces the size of the clitoris without its total removal. The atypical size of the clitoris is due to an endocrine imbalance in utero.[1][5] Other reasons for the surgery include issues involving a microphallus and those who have Mayer-Rokitansky-Kustner disorder. Treatments on children raise human rights concerns.[citation needed]
## Technique[edit]
Clitoridectomy surgical techniques are used to remove an invasive malignancy that extends to the clitoris. Standard surgical procedures are followed in these cases. This includes evaluation and biopsy. Other factors that will affect the technique selected are age, other existing medical conditions, and obesity. Other considerations are the probability of extended hospital care and the development of infection at the surgical site.[3] The surgery proceeds with the use of general anesthesia, and prior to the vulvectomy/clitoridectomy an inguinal lymphyadenectomy is first done. The extent of the surgical site extends one to two centimeters beyond the boundaries of malignancy. Superficial lymph nodes may also need to be removed. If the malignancy is present in muscular tissue in the region, it is also removed. In some cases, the surgeon is able to preserve the clitoris though the malignancy may be extensive. The cancerous tissue is removed and the incision is closed.[3]
Post operative care may employ the use of suction drainage to allow the deeper tissues to heal toward the surface. Follow up after surgery includes the stripping of the drainage device to prevent blockage. A typical hospital stay can be up to two weeks. The site of the surgery is left unbandaged to allow for frequent examination.[3] Complications can be the development of lymphedema though not removing the saphenous vein during the surgery will help prevent this. In some instances, foot elevation, diuretic medication and compression stockings can reduce the build up of fluid.[3]
In a clitoridectomy for intersex infants, the clitoris is often reduced instead of removed. The surgeon cuts the shaft of the elongated phallus and sews the glans and preserved nerves back onto the stump. In a less common surgery called clitoral recession, the surgeon hides the clitoral shaft under a fold of skin so only the glans remains visible.[6]
## Society and culture[edit]
### General[edit]
While much feminist scholarship has described clitoridectomy as a practice aimed at controlling women's sexuality, the historic emergence of the practice in ancient European and Middle Eastern cultures may have possibly derived from ideas about intersex people and the policing of boundaries between the sexes. In the seventeenth century, anatomists remained divided on whether a clitoris was a normal female organ, with some arguing that only intersex people had one and that, if large enough to be visible, it should always be removed at birth.[7] In the 19th century, a clitoridectomy was thought by some to curb female masturbation.[8] Isaac Baker Brown (1812–1873), an English gynaecologist who was president of the Medical Society of London believed that the "unnatural irritation" of the clitoris caused epilepsy, hysteria, and mania, and he worked "to remove [it] whenever he had the opportunity of doing so", according to his obituary in the Medical Times and Gazette. Peter Lewis Allen writes that Brown's views caused outrage, and he died penniless after being expelled from the Obstetrical Society.[9]
Occasionally, in American and English medicine of the nineteenth century, circumcision was done as a cure for insanity. Some believed that mental and emotional disorders were related to female reproductive organs and that removing the clitoris would cure the neurosis. This treatment was discontinued in 1867.[10]
Aesthetics may determine clitoral norms. A lack of ambiguity of the genitalia is seen as necessary in the assignment of a sex to infants and therefore whether a child's genitalia is normal, but what is ambiguous or normal can vary from person to person.[11]
Sexual behavior is another reason for clitoridectomies. Author Sarah Rodriguez stated that the history of medical textbooks has indirectly created accepted ideas about the female body. Medical and gynecological textbooks are also at fault in the way that the clitoris is described in comparison to a male's penis. The importance and originality of a female's clitoris is underscored because it is seen as "a less significant organ, since anatomy texts compared the penis and the clitoris in only one direction." Rodriguez said that a male's penis created the framework of the sexual organ.[12]
Not all historical examples of clitoral surgeries should be assumed to be clitoridectomy (removal of the clitoris). In the nineteen thirties, the French psychoanalyst Marie Bonaparte studied African clitoral surgical practices and showed that these often involved removal of the clitoral hood, not the clitoris. She also had a surgery done to her own clitoris by the Viennese surgeon Dr Halban, which entailed cutting the suspensory ligament of the clitoris to permit it to sit closer to her vaginal opening. These sorts of clitoral surgeries, contrary to reducing women's sexual pleasure, actually appear aimed at making coitus more pleasurable for women, though it is unclear if that is ever their actual outcome.[13]
### Human rights concerns[edit]
Further information: Female genital mutilation and Intersex human rights
Clitoridectomies are the most common form of female genital mutilation. The World Health Organization (WHO) estimates that clitordectomies have been performed on 200 million girls and women that are currently alive. The regions that most clitoridectomies take place are Asia, the Middle East and west, north and east Africa. The practice also exists in migrants originating from these regions. Most of the surgeries are for cultural or religious reasons.[14]
Clitoridectomy of women with intersex conditions is controversial when it takes place during childhood or under duress. Intersex women exposed to such treatment have spoken of their loss of physical sensation, and loss of autonomy.[15][16] In recent years, multiple human rights institutions have criticized early surgical management of such characteristics.[17][18][19]
In 2013, it was disclosed in a medical journal that four unnamed elite female athletes from developing countries were subjected to gonadectomies and partial clitoridectomies after testosterone testing revealed that they had an intersex condition.[20][21] In April 2016, the United Nations Special Rapporteur on health, Dainius Pūras, condemned this treatment as a form of female genital mutilation "in the absence of symptoms or health issues warranting those procedures."[22]
## See also[edit]
* List of surgeries by type
* Medicine portal
* Vaginoplasty
* Genital mutilation
* Hypersexuality
## References[edit]
1. ^ a b Hiort, O. (2014). Understanding differences and disorders of sex development (DSD). Basel: Karger. ISBN 9783318025583.
2. ^ "New study shows female genital mutilation exposes women and babies to significant risk at childbirth" (Press release). World Health Organization. 2006-06-02.
3. ^ a b c d e f Hoffman, Barbara (2012). Williams gynecology. New York: McGraw-Hill Medical. ISBN 9780071716727.
4. ^ Horbach, Sophie E.R.; Bouman, Mark-Bram; Smit, Jan Maerten; Özer, Müjde; Buncamper, Marlon E.; Mullender, Margriet G. (2015). "Outcome of Vaginoplasty in Male-to-Female Transgenders: A Systematic Review of Surgical Techniques". The Journal of Sexual Medicine. 12 (6): 1499–1512. doi:10.1111/jsm.12868. ISSN 1743-6095. PMID 25817066.
5. ^ Gundeti, Mohan (2012). Pediatric Robotic and Reconstructive Urology a Comprehensive Guide. City: Wiley-Blackwell. ISBN 9781444335538; Access provided by the University of Pittsburgh
6. ^ Fausto-Sterling, Anne (2000). Sexing the body : gender politics and the construction of sexuality (1. ed., [Nachdr.] ed.). New York, NY: Basic Books. p. 48. ISBN 978-0-465-07714-4.
7. ^ Alison M. Moore, Victorian Medicine Was Not Responsible for Repressing the Clitoris: Rethinking Homology in the Long History of Women’s Genital Anatomy. Signs: The Journal of Women in Culture and Society 44 (1) August 2018, 53-81. DOI: 10.1086/698277.
8. ^ Duffy, John (October 19, 1963). "Masturbation and Clitoridectomy: A Nineteenth-Century View". JAMA. 186 (3): 246–248. doi:10.1001/jama.1963.63710030028012. PMID 14057114.
9. ^ Allen, Peter Lewis. The Wages of Sin: Sex and Disease, Past and Present. University of Chicago Press, 2000, p. 106.
* For the obituary, see J.F.C. "Isaac Baker Brown, F.R.C.S.", Medical Times and Gazette, 8 February 1873.
* Also see Brown, Isaac Baker. On the Curability of Certain Forms of Insanity, Epilepsy, Catalepsy, and Hysteria in Females. Robert Hardwicke, 1866.
10. ^ Atoki, Morayo (August 1995). "Should female circumcision continue to be banned?". Feminist Legal Studies. 3 (2): 229. doi:10.1007/BF01104114. S2CID 144198914; Access provided by the University of Pittsburgh.
11. ^ Kessler, Suzanne J. (2000). Lessons from the intersexed (2. Paperback printing. ed.). New Brunswick, NJ [u.a.]: Rutgers Univ. Press. p. 43. ISBN 978-0813525297.
12. ^ Rodriguez, Sarah (2014). Female Circumcision and Clitoridectomy in the United States: A History of Medical Treatment. University of Rochester Press.
13. ^ Relocating Marie Bonaparte’s Clitoris. Australian Feminist Studies 24 (60), April 2009, 149-165.
14. ^ "Female genital mutilation". World Health Organization. February 2016. Retrieved 2016-03-26.
15. ^ Holmes, Morgan. "Is Growing up in Silence Better Than Growing up Different?". Intersex Society of North America. Retrieved 2016-08-26.
16. ^ Bastien-Charlebois, Janik (August 9, 2015). "My coming out: The lingering intersex taboo". Montreal Gazette. Retrieved 2016-08-26.
17. ^ Méndez, Juan (February 2013). "Report of the Special Rapporteur on torture and other cruel, inhuman or degrading treatment or punishment, Juan E. Méndez, A.HRC.22.53" (PDF).
18. ^ Council of Europe; Commissioner for Human Rights (April 2015), Human rights and intersex people, Issue Paper
19. ^ Asia Pacific Forum of National Human Rights Institutions (June 2016). Promoting and Protecting Human Rights in relation to Sexual Orientation, Gender Identity and Sex Characteristics. Asia Pacific Forum of National Human Rights Institutions. ISBN 978-0-9942513-7-4.
20. ^ Fénichel, Patrick; Paris, Françoise; Philibert, Pascal; et al. (June 2013). "Molecular Diagnosis of 5α-Reductase Deficiency in 4 Elite Young Female Athletes Through Hormonal Screening for Hyperandrogenism". The Journal of Clinical Endocrinology & Metabolism. 98 (6): –1055–E1059. doi:10.1210/jc.2012-3893. ISSN 0021-972X. PMID 23633205.
21. ^ Jordan-Young, R. M.; Sonksen, P. H.; Karkazis, K. (April 2014). "Sex, health, and athletes". BMJ. 348 (apr28 9): –2926–g2926. doi:10.1136/bmj.g2926. ISSN 1756-1833. PMID 24776640. S2CID 2198650.
22. ^ Pūras, Dainius; Special Rapporteur on the right of everyone to the enjoyment of the highest attainable standard of physical and mental health (April 4, 2016), Sport and healthy lifestyles and the right to health. Report A/HRC/32/33, United Nations
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*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: 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
| Clitoridectomy | None | 4,473 | wikipedia | https://en.wikipedia.org/wiki/Clitoridectomy | 2021-01-18T18:31:30 | {"wikidata": ["Q1707435"]} |
Chiba and Miura (1977, 1979) described a mother and son with hypoplastic thumbs and alopecia. Short stature was marked in the child and moderate in the mother; both were reported to be mentally retarded. Winter et al. (1988) reported a similar condition in 4 generations of a family. The affected members studied were a mother and 3 sons. A main distinguishing feature was the presence of a single central upper incisor (147250) in the mother and 1 son of the family reported by Winter et al. (1988). Mental retardation and marked short stature were not found in their family. In the family of Winter et al. (1988), the mother and 1 son showed increased pigmentation in the groin with areas of raindrop depigmentation. One son showed the same thing.
Limbs \- Hypoplastic thumbs Neuro \- Mental retardation Inheritance \- Autosomal dominant Teeth \- Single central upper incisor Hair \- Alopecia Growth \- Short stature Skin \- Increased groin pigmentation with raindrop depigmentation ▲ Close
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*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| THUMB DEFORMITY AND ALOPECIA | c2931366 | 4,474 | omim | https://www.omim.org/entry/188150 | 2019-09-22T16:32:44 | {"mesh": ["C536904"], "omim": ["188150"], "orphanet": ["2251"]} |
## Summary
The purpose of this overview is to increase the awareness of clinicians regarding the genetics of Parkinson disease and related genetic counseling issues.
The following are the goals of this overview:
### Goal 1.
Describe the clinical characteristics of Parkinson disease.
### Goal 2.
Review the causes of Parkinson disease.
### Goal 3.
Provide an evaluation strategy to identify the genetic cause of Parkinson disease in a proband.
### Goal 4.
Inform genetic counseling for family members of an individual with Parkinson disease.
### Goal 5.
Provide information on targeted therapeutic clinical trials.
## Diagnosis
## Clinical Characteristics
## Differential Diagnosis
## Management
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Parkinson Disease Overview | None | 4,475 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1223/ | 2021-01-18T21:04:45 | {"synonyms": []} |
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (September 2015)
Benign nephrosclerosis refers to the renal changes most commonly occurring in association with long-standing hypertension. It is termed benign because it rarely progresses to clinically significant chronic kidney disease or kidney failure.[1]
## Morphology[edit]
The kidneys appear symmetrically atrophic and there is a reduced nephron mass.[1] The kidneys have a surface of diffuse, fine granularity that resembles grain leather. Microscopically, the basic anatomic change consists of hyaline thickening of the walls of the small arteries and arterioles (hyaline arteriolosclerosis). Under a microscope, this appears as a homogeneous, pink hyaline thickening at the expense of the vessel lumina, with loss of underlying cellular detail. The narrowing of the lumen restricts blood flow, resulting in ischemia. All structures of the kidney can show ischemic atrophy although glomerular ischemic atrophy may be patchy.[1] In advanced cases of benign nephrosclerosis the glomerular tufts may become globally sclerosed. Diffuse tubular atrophy and interstitial fibrosis are present. Often there is a scant interstitial lymphocytic infiltrate. The larger blood vessels (interlobar and arcuate arteries) show reduplication of internal elastic lamina along with fibrous thickening of the media (fibroelastic hyperplasia) and the subintima.[1]
## Clinical Course[edit]
Benign nephrosclerosis alone hardly ever causes severe damage to the kidney, except in susceptible populations, such as African Americans, where it may lead to uremia and death. However, all persons with this disease usually show some functional impairment, such as loss of concentration or a variably diminished GFR. A mild degree of proteinuria is a frequent finding.[2]
## References[edit]
1. ^ a b c d Robert W. Schrier (2010). Renal and Electrolyte Disorders. Lippincott Williams & Wilkins. pp. 296–. ISBN 978-1-60831-072-2.
2. ^ Robbins, Stanley L.; Kumar, Vinay (2007). Robbins basic pathology. Saunders/Elsevier. ISBN 978-0-8089-2366-4.
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*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Benign nephrosclerosis | c3273254 | 4,476 | wikipedia | https://en.wikipedia.org/wiki/Benign_nephrosclerosis | 2021-01-18T18:41:35 | {"wikidata": ["Q4887969"]} |
Clinical variety of lepromatous leprosy
The diffuse leprosy of Lucio and Latapí, also known as diffuse lepromatous leprosy or "pretty leprosy" is a clinical variety of lepromatous leprosy. It was first described by Lucio and Alvarado in 1852 and re-identified by Latapí in 1936. It is common in Mexico (23% leprosy cases) and in Costa Rica and very rare in other countries.
## Contents
* 1 History
* 2 Clinical features
* 3 Pathology
* 4 Treatment
* 5 References
## History[edit]
The spotted or lazarine leprosy was first described by Ladislao de la Pascua in 1844.[1] Lucio and Alvarado published a description of the disease with the same names in 1852. Latapí re-described it in 1938 and reported it as 'spotted' leprosy of Lucio in 1948. It was named the diffuse leprosy of Lucio and Latapí in 1963 by Frenken.
The underlying pathology was explained by Chévez-Zamora as a diffuse generalised cutaneous infiltration. He named it pure and primitive diffuse lepromatosis, upon which necrotising lesions develop. He proposed the name Fenómeno de Lucio or erythema necrotisans for these lesions.
## Clinical features[edit]
This condition is characterized by:[2]
* a diffuse infiltration of all the skin which never transforms into nodule
* a complete alopecia of eyebrows and eyelashes and body hair
* an anhydrotic and dysesthesic zones of the skin
* a peculiar type of lepra reaction named Lucio's phenomenon or necrotic erythema
Lucio's phenomenon consists of well-shaped erythematous spots which later become necrotic with scabs, ulcerations and scars. These lesion usually on the lower extremities and may be extensive They are frequently painful. Rarely it may be fatal.
## Pathology[edit]
The main pathological features of this disease are a vasculitis affecting all cutaneous vessels.
There are by five characteristic features:[1]
* colonisation of endothelial cells by acid-fast bacilli
* endothelial proliferation and marked thickening of vessel walls to the point of obliteration
* angiogenesis
* vascular ectasia
* thrombosis of the superficial and mid-dermal blood vessels
The likely pathogenesis is endothelial cell injury due to colonization/invasion followed by proliferation, angiogensis, thrombosis and vessel ectasia.
## Treatment[edit]
Lucio's phenomenon is treated by anti-leprosy therapy (dapsone, rifampin, and clofazimine), optimal wound care, and treatment for bacteremia including antibiotics. In severe cases exchange transfusion may be helpful.[3]
## References[edit]
1. ^ a b Vargas-Ocampo F (2007) Diffuse leprosy of Lucio and Latapí: a histologic study. Lepr. Rev. 78(3):248-260
2. ^ Saúl A, Novales J (1983) Lucio-Latapí leprosy and the Lucio phenomenon. Acta Leprol. 1(3):115-132
3. ^ Kasper DL, Braunwald E, Fauci AS, et al. Harrison's Principles of Internal Medicine. 16th edition. McGraw-Hill. 2005. Vol I. p.971.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Diffuse leprosy of Lucio and Latapí | None | 4,477 | wikipedia | https://en.wikipedia.org/wiki/Diffuse_leprosy_of_Lucio_and_Latap%C3%AD | 2021-01-18T18:43:56 | {"wikidata": ["Q5275417"]} |
Deletion 6q16 syndrome is a Prader-Willi like syndrome characterized by obesity, hyperphagia, hypotonia, small hands and feet, eye/vision anomalies, and global developmental delay.
## Epidemiology
The disease has been described in five patients.
## Etiology
Deletion 6q16 syndrome is due to an interstitial deletion located at 6q16.1q16.2. It is hypothesized that genes SIM1, GRIK2, POPDC3 and MCHR2 located in this region are associated with obesity, autism, cardiac disorders, and hyperphagia and metabolism disorders respectively.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| 6q16 microdeletion syndrome | None | 4,478 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=171829 | 2021-01-23T19:06:54 | {"icd-10": ["Q93.5"], "synonyms": ["Del(6)(q16)", "Monosomy 6q16", "Prader-Willi-like syndrome due to microdeletion 6q16"]} |
1q21.1 deletion syndrome
Other names1q21.1 (recurrent) microdeletion
SpecialtyMedical genetics
1q21.1 deletion syndrome is a rare aberration of chromosome 1. A human cell has one pair of identical chromosomes on chromosome 1. With the 1q21.1 deletion syndrome, one chromosome of the pair is not complete, because a part of the sequence of the chromosome is missing. One chromosome has the normal length and the other is too short.
In 1q21.1, the '1' stands for chromosome 1, the 'q' stands for the long arm of the chromosome and '21.1' stands for the part of the long arm in which the deletion is situated.
The syndrome is a form of the 1q21.1 copy number variations, and it is a deletion in the distal area of the 1q21.1 part. The CNV leads to a very variable phenotype, and the manifestations in individuals are quite variable. Some people who have the syndrome can function in a normal way, while others have symptoms of mental retardation and various physical anomalies.
1q21.1 microdeletion is a very rare chromosomal condition. Only 46 individuals with this deletion have been reported in medical literature as of August 2011.[1]
## Contents
* 1 Symptoms and signs
* 2 Cause
* 3 Genetics
* 3.1 The structure of 1q21.1
* 3.2 Typing
* 3.3 Related genes
* 4 Diagnostics
* 5 Management
* 6 Prevalence
* 7 Research
* 8 References
* 9 Further reading
* 10 External links
## Symptoms and signs[edit]
Recognised symptoms are:[citation needed]
* Only one set of genes on the two chromosomes function (haploinsufficiency)
* Thrombocytopenia-absent radius (TAR syndrome), in case of a class II-deletion
* Neurological-psychiatric problems: schizophrenia;[2][3] epilepsy; learning problems; cognitive disabilities — mild to moderate; developmental delay — mild to moderate (milestones like sitting, standing and walking; come at a later period in childhood); children show an ataxic gait and fall down a lot
* Dysmorphism: slightly unusual facial appearance; disturbed growth; skeletal malformations; small head (microcephaly); prominent forehead; bulbous nose; deep-set eyes; broad thumbs; broad toes; squint; very flexible joints; clavicular pseudoarthrosis[4] (the collarbone doesn't develop normally) (class II-deletion); an extra transverse crease of the fifth finger[4] (class II-deletion)); problems with the development of the vagina (Müllerian aplasia)
* Eyes: cataracts
* Heart abnormalities and cardiovascular anomalies (30% of the cases): anomalous origin of the coronary artery[4] (Class II-deletion)
* Kidneys: missing kidney or floating kidneys
* Cancer: neuroblastoma[5]
* Sleep disturbances
It is not clear whether the list of symptoms is complete. Very little information is known about the syndrome. The syndrome can have completely different effects on members of the same family.
A common deletion is between 1.0–1.9Mb. Mefford states that the standard for a deletion is 1.35Mb.[6] The largest deletion seen on a living human is over 5 Mb.
## Cause[edit]
Meiosis is the process of dividing cells in humans. In meiosis, the chromosome pairs split and a representative of each pair goes to one daughter cell. In this way the number of chromosomes will be halved in each cell, while all the parts on the chromosome (genes) remain, after being randomized. Which information of the parent cell ends up in the daughter cell is purely decided by chance. Besides this random process, there is a second random process. In this second random process the DNA will be scrambled in a way that pieces are omitted (deletion), added (duplication), moved from one place to another (translocation) and inverted (inversion). This is a common process, which leads to about 0.4% variation in the DNA.[citation needed]
A problem of the second random process is that genetic mistakes can occur. Because of the deletion and duplication process, the chromosomes that come together in a new cell may be shorter or longer. The result of this spontaneous change in the structure of DNA is a so-called copy number variation. Due to the copy number variation chromosomes of different sizes can be combined in a new cell. If this occurs around conception, the result will be a first cell of a human with a genetic variation. This can be either positive or negative. In positive cases this new human will be capable of a special skill that is assessed positively, for example, in sports or science. In negative cases, you have to deal with a syndrome or a severe disability, as in this case the 1q21.1 deletion syndrome.[citation needed]
Based on the meiotic process, the syndrome may occur in two ways.
1. a spontaneous deviation (a 'de novo' situation): two chromosomes come together of which one has a copy number variation as a result of the meiosis process.
2. a parent is unknowingly the carrier of a chromosome with a copy number variation and passes it at conception to the child, with different consequences for the child.
Due to this genetic misprint, the embryo may experience problems in the development during the first months of pregnancy. Approximately 20 to 40 days after fertilization, something goes wrong in the construction of the body parts and brain, which leads to a chain reaction.[7]
## Genetics[edit]
The structure of 1q21.1
### The structure of 1q21.1[edit]
The structure of 1q21.1 is complex. The area has a size of approximately 6 Megabase (Mb) (from 141.5 Mb to 147.9 Mb). Within 1q21.1 there are two areas where the CNVs can be found: the proximal area or TAR area (144.1 to 144.5) and the distal area (144.7 to 145.9). The 1q21.1 deletion syndrome will commonly be found in the distal area, but an overlap with the TAR-area is possible. 1q21.1 has multiple repetitions of the same structure (areas with the same color in the picture have equal structures) Only 25% of the structure is not duplicated. There are several gaps in the sequence. There is no further information available about the DNA-sequence in those areas up till now. The gaps represent approximately 700 Kilobase. New genes are expected in the gaps. Because the gaps are still a topic of research, it is hard to find the exact start and end markers of a deletion. The area of 1q21.1 is one of the most difficult parts of the human genome to map.[citation needed]
Because of the repetitions in 1q21.1, there is a larger chance of an unequal crossing-over during meiosis. CNVs occur due to non-allelic homologous recombination mediated by low copy repeats (sequentially similar regions).[citation needed]
### Typing[edit]
A common deletion is restricted to the distal area. This is a Class I-deletion.[citation needed]
In some cases the deletion is so large that the proximal area is involved as well, the so-called Class II-deletion. There are some complex cases in which both the proximal area and the distal area are affected, while the area in between is normal. There are also some a-typical variants.
### Related genes[edit]
Genes related to 1q21.1 deletion in the distal area are PDE4DIP, HYDIN2, PRKAB2, PDIA3P, FMO5, CHD1L, BCL9, ACP6, GJA5, GJA8, NBPF10, GPR89B, GPR89C, PDZK1P1 and NBPF11.[citation needed]
## Diagnostics[edit]
A 'de novo'-situation appears in about 75% of the cases. In 25% of the cases, one of the parents is carrier of the syndrome, without any effect on the parent. Sometimes adults have mild problems with the syndrome. To find out whether either of the parents carries the syndrome, both parents have to be tested. In several cases, the syndrome was identified with the child, because of a developmental disorder or another problem, and later it appeared that the parent was affected as well. In families where both parents have tested negative for the syndrome, chances of a second child with the syndrome are extremely low. If the syndrome was found in the family, chances of a second child with the syndrome are 50%, because the syndrome is autosomal dominant. The effect of the syndrome on the child cannot be predicted[citation needed]
The syndrome can be detected with fluorescence in situ hybridization.For parents with a child with the syndrome, it is advisable to consult a physician before another pregnancy.
## Management[edit]
Treatment of cause: Due to the genetic cause, no treatment of the cause is possible.[citation needed]
Treatment of manifestations: routine treatment of ophthalmologic, cardiac, and neurologic findings; speech, occupational, and physical therapies as appropriate; specialized learning programs to meet individual needs; antiepileptic drugs or antipsychotic medications as needed.[citation needed]
Surveillance: routine pediatric care; routine developmental assessments; monitoring of specific identified medical issues.
## Prevalence[edit]
As of October 2012, Unique, an international rare chromosome disorder group and registry, has 64 genetically-confirmed cases of this deletion worldwide.[8]
## Research[edit]
On several locations in the world people are studying on the subject of 1q21.1 deletion syndrome. The syndrome was identified for the first time with people with heart abnormalities. The syndrome has later been found in patients with schizophrenia. Research is done on patients with a symptom of the syndrome, to find more patients with the syndrome.[citation needed]
There may be a relation between autism and schizophrenia. Literature shows that nine locations have been found on the DNA where the syndromes related to autism or schizophrenia can be found, the so-called "hotspots": 1q21.1, 3q29, 15q13.3, 16p11.2, 16p13.1, 16q21, 17p12, 21q11.2 and 21q13.3. With a number of hotspots, either autism and schizophrenia were observed depending on the copy-number variation (CNV) at that location.[citation needed]
Statistical research showed that schizophrenia is more common in combination with 1q21.1 deletion syndrome. On the other side, autism is significantly more common with 1q21.1 duplication syndrome. Further research confirmed that the odds on a relation between schizophrenia and deletions at 1q21.1, 3q29, 15q13.3, 22q11.21 en Neurexin 1 (NRXN1) and duplications at 16p11.2 are at 7.5% or higher.[9][10]
Observed relation within 1q21.1
Common variations in the BCL9 gene, which is in the distal area, confer risk of schizophrenia and may also be associated with bipolar disorder and major depressive disorder.[11]
Research is done on 10–12 genes on 1q21.1 that produce DUF1220-locations. DUF1220 is an unknown protein, which is active in the neurons of the brain near the neocortex. Based on research on apes and other mammals, it is assumed that DUF1220 is related to cognitive development (man: 212 locations; chimpanzee: 37 locations; monkey: 30 locations; mouse: 1 location). It appears that the DUF1220-locations on 1q21.1 are in areas that are related to the size and the development of the brain. The aspect of the size and development of the brain is related to autism (macrocephaly) and schizophrenia (microcephaly). It has been proposed that a deletion or duplication of a gene that produces DUF1220-areas might cause growth and development disorders in the brain [12]
Another relation between macrocephaly with duplications and microcephaly with deletions has been seen in research on the HYDIN Paralog or HYDIN2. This part of 1q21.1 is involved in the development of the brain. It is assumed to be a dosage-sensitive gene. When this gene is not available in the 1q21.1 area, it leads to microcephaly. HYDIN2 is a recent duplication (found only in humans) of the HYDIN gene found on 16q22.2.[13] Research on the genes CHD1L and PRKAB2 within lymphoblast cells [14] lead to the conclusion that anomalies appear with the 1q21.1-deletion syndrome:
* CHD1L is an enzyme which is involved in untangling the chromatides and the DNA repair system. With 1q21.1 deletion syndrome a disturbance occurs, which leads to increased DNA breaks. The role of CHD1L is similar to that of helicase with the Werner syndrome
* PRKAB2 is involved in maintaining the energy level of cells. With 1q21.1-deletion syndrome this function was attenuated.
GJA5 has been identified as the gene that is responsible for the phenotypes observed with congenital heart diseases on the 1q21.1 location. In case of a duplication of GJA5 tetralogy of Fallot is more common. In case of a deletion other congenital heart diseases than tetralogy of Fallot are more common.[15]
## References[edit]
1. ^ "Overview: 1q21.1 microdeletion syndrome". Genetic and Rare Diseases Information Center (GARD). Office of Rare Diseases Research • U.S. National Institutes of Health. 8 August 2011. Retrieved 9 September 2013.
2. ^ Stefansson H, Rujescu D, Cichon S, et al. (September 2008). "Large recurrent microdeletions associated with schizophrenia". Nature. 455 (7210): 232–6. Bibcode:2008Natur.455..232S. doi:10.1038/nature07229. PMC 2687075. PMID 18668039.
3. ^ The International Schizophrenia Consortium (September 2008). "Rare chromosomal deletions and duplications increase risk of schizophrenia". Nature. 455 (7210): 237–41. Bibcode:2008Natur.455..237S. doi:10.1038/nature07239. PMC 3912847. PMID 18668038.
4. ^ a b c Velinov M, Dolzhanskaya N (2010). "Clavicular pseudoarthrosis, anomalous coronary artery and extra crease of the fifth finger-previously unreported features in individuals with class II 1q21.1 microdeletions". Eur J Med Genet. 53 (4): 213–6. doi:10.1016/j.ejmg.2010.05.005. PMID 20573555.
5. ^ Diskin SJ, Hou C, Glessner JT, et al. (2009). "Copy number variation at 1q21.1 associated with neuroblastoma". Nature. 459 (7249): 987–991. Bibcode:2009Natur.459..987D. doi:10.1038/nature08035. PMC 2755253. PMID 19536264.
6. ^ Mefford HC, Sharp AJ, Baker C, et al. (October 2008). "Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes". N. Engl. J. Med. 359 (16): 1685–99. doi:10.1056/NEJMoa0805384. hdl:2066/71235. PMC 2703742. PMID 18784092.
7. ^ A. Ploeger; 'Towards an integration of evolutionary psychology and developmental science: New insights from evolutionary developmental biology'
8. ^ "Chromosome 1 - 1q21.1 microdeletion" (PDF). rarechromo.org. Unique. 2012. Archived from the original (PDF) on 2010-11-21. Retrieved 9 September 2013.
9. ^ Levinson DF, Duan J, Oh S, et al. (March 2011). "Copy number variants in schizophrenia: confirmation of five previous findings and new evidence for 3q29 microdeletions and VIPR2 duplications". Am J Psychiatry. 168 (3): 302–16. doi:10.1176/appi.ajp.2010.10060876. PMC 4441324. PMID 21285140.
10. ^ Ikeda M, Aleksic B, Kirov G, et al. (February 2010). "Copy number variation in schizophrenia in the Japanese population". Biol. Psychiatry. 67 (3): 283–6. doi:10.1016/j.biopsych.2009.08.034. PMID 19880096. S2CID 26047827.
11. ^ Li J, Zhou G, Ji W, et al. (March 2011). "Common variants in the BCL9 gene conferring risk of schizophrenia". Arch. Gen. Psychiatry. 68 (3): 232–40. doi:10.1001/archgenpsychiatry.2011.1. PMID 21383261.
12. ^ e.g.: Dumas L, Sikela JM (2009). "DUF1220 domains, cognitive disease, and human brain evolution". Cold Spring Harb. Symp. Quant. Biol. 74: 375–82. doi:10.1101/sqb.2009.74.025. PMC 2902282. PMID 19850849.
13. ^ Doggett NA, Xie G, Meincke LJ, et al. (Dec 2006). "A 360-kb interchromosomal duplication of the human HYDIN locus". Genomics. 88 (6): 762–71. doi:10.1016/j.ygeno.2006.07.012. PMID 16938426.
14. ^ Harvard C (2011). "Understanding the impact of 1q21.1 copy number variant". Orphanet Journal of Rare Diseases. 6: 54. doi:10.1186/1750-1172-6-54. PMC 3180300. PMID 21824431.
15. ^ Soemedi, R.; et al. (2011). "DPhenotype-Specific Effect of Chromosome 1q21.1 Rearrangements and GJA5 Duplications in 2436 Congenital Heart Disease Patients and 6760 Controls". Hum. Mol. Genet. 21 (7): 1513–1520. doi:10.1093/hmg/ddr589. PMC 3298277. PMID 22199024.
## Further reading[edit]
* Genetics of Mental Retardation, Karger. Knight S. (ed) Chapter One: 'A Parent's' Perspective' contains description and photos of female with 1q21.1 microdeletion
* Brunet A, Armengol L, Heine D, et al. (2009). "BAC array CGH in patients with Velocardiofacial syndrome-like features reveals genomic aberrations on chromosome region 1q21.1". BMC Med. Genet. 10: 144. doi:10.1186/1471-2350-10-144. PMC 2805625. PMID 20030804.
* Brunetti-Pierri N, Berg JS, Scaglia F, Belmont J, Bacino CA, Sahoo T, et al. (2008). "Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities". Nat Genet. 40 (12): 1466–71. doi:10.1038/ng.279. PMC 2680128. PMID 19029900.
* Crespi B, Stead P, Elliot M (2010). "Evolution in health and medicine Sackler colloquium: Comparative genomics of autism and schizophrenia". Proc Natl Acad Sci U S A. 107 (Suppl 1): 1736–41. Bibcode:2010PNAS..107.1736C. doi:10.1073/pnas.0906080106. PMC 2868282. PMID 19955444.
## External links[edit]
* DECIPHER database entry for 1q21.1 deletion syndrome
* 1q21.1 deletion, GeneReviews NCBI Bookshelf
* Orpha.net
Classification
D
* ICD-10: Q93.5
* OMIM: 612474
External resources
* MedlinePlus: 1q211-microdeletion
* v
* t
* e
Chromosome abnormalities
Autosomal
Trisomies/Tetrasomies
* Down syndrome
* 21
* Edwards syndrome
* 18
* Patau syndrome
* 13
* Trisomy 9
* Tetrasomy 9p
* Warkany syndrome 2
* 8
* Cat eye syndrome/Trisomy 22
* 22
* Trisomy 16
Monosomies/deletions
* (1q21.1 copy number variations/1q21.1 deletion syndrome/1q21.1 duplication syndrome/TAR syndrome/1p36 deletion syndrome)
* 1
* Wolf–Hirschhorn syndrome
* 4
* Cri du chat syndrome/Chromosome 5q deletion syndrome
* 5
* Williams syndrome
* 7
* Jacobsen syndrome
* 11
* Miller–Dieker syndrome/Smith–Magenis syndrome
* 17
* DiGeorge syndrome
* 22
* 22q11.2 distal deletion syndrome
* 22
* 22q13 deletion syndrome
* 22
* genomic imprinting
* Angelman syndrome/Prader–Willi syndrome (15)
* Distal 18q-/Proximal 18q-
X/Y linked
Monosomy
* Turner syndrome (45,X)
Trisomy/tetrasomy,
other karyotypes/mosaics
* Klinefelter syndrome (47,XXY)
* XXYY syndrome (48,XXYY)
* XXXY syndrome (48,XXXY)
* 49,XXXYY
* 49,XXXXY
* Triple X syndrome (47,XXX)
* Tetrasomy X (48,XXXX)
* 49,XXXXX
* Jacobs syndrome (47,XYY)
* 48,XYYY
* 49,XYYYY
* 45,X/46,XY
* 46,XX/46,XY
Translocations
Leukemia/lymphoma
Lymphoid
* Burkitt's lymphoma t(8 MYC;14 IGH)
* Follicular lymphoma t(14 IGH;18 BCL2)
* Mantle cell lymphoma/Multiple myeloma t(11 CCND1:14 IGH)
* Anaplastic large-cell lymphoma t(2 ALK;5 NPM1)
* Acute lymphoblastic leukemia
Myeloid
* Philadelphia chromosome t(9 ABL; 22 BCR)
* Acute myeloblastic leukemia with maturation t(8 RUNX1T1;21 RUNX1)
* Acute promyelocytic leukemia t(15 PML,17 RARA)
* Acute megakaryoblastic leukemia t(1 RBM15;22 MKL1)
Other
* Ewing's sarcoma t(11 FLI1; 22 EWS)
* Synovial sarcoma t(x SYT;18 SSX)
* Dermatofibrosarcoma protuberans t(17 COL1A1;22 PDGFB)
* Myxoid liposarcoma t(12 DDIT3; 16 FUS)
* Desmoplastic small-round-cell tumor t(11 WT1; 22 EWS)
* Alveolar rhabdomyosarcoma t(2 PAX3; 13 FOXO1) t (1 PAX7; 13 FOXO1)
Other
* Fragile X syndrome
* Uniparental disomy
* XX male syndrome/46,XX testicular disorders of sex development
* Marker chromosome
* Ring chromosome
* 6; 9; 14; 15; 18; 20; 21, 22
* 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 inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| 1q21.1 deletion syndrome | c2675897 | 4,479 | wikipedia | https://en.wikipedia.org/wiki/1q21.1_deletion_syndrome | 2021-01-18T18:55:24 | {"gard": ["10813"], "mesh": ["C567291"], "umls": ["C2675897"], "orphanet": ["250989"], "wikidata": ["Q209049"]} |
Lysosomal storage disease
Micrograph of Gaucher disease, with cells that have the characteristic crumpled tissue paper-like cytoplasm. H&E stain.
SpecialtyEndocrinology
Lysosomal storage diseases (LSDs; /ˌlaɪsəˈsoʊməl/) are a group of about 50 rare inherited metabolic disorders that result from defects in lysosomal function.[1] Lysosomes are sacs of enzymes within cells that digest large molecules and pass the fragments on to other parts of the cell for recycling. This process requires several critical enzymes. If one of these enzymes is defective due to a mutation, the large molecules accumulate within the cell, eventually killing it.[2]
Lysosomal storage disorders are caused by lysosomal dysfunction usually as a consequence of deficiency of a single enzyme required for the metabolism of lipids, glycoproteins (sugar-containing proteins), or so-called mucopolysaccharides. Individually, LSDs occur with incidences of less than 1:100,000; however, as a group, the incidence is about 1:5,000 – 1:10,000.[3][4] Most of these disorders are autosomal recessively inherited such as Niemann–Pick disease, type C, but a few are X-linked recessively inherited, such as Fabry disease and Hunter syndrome (MPS II).
The lysosome is commonly referred to as the cell's recycling center because it processes unwanted material into substances that the cell can use. Lysosomes break down this unwanted matter by enzymes, highly specialized proteins essential for survival. Lysosomal disorders are usually triggered when a particular enzyme exists in too small an amount or is missing altogether. When this happens, substances accumulate in the cell. In other words, when the lysosome does not function normally, excess products destined for breakdown and recycling are stored in the cell.
Like other genetic disorders, individuals inherit lysosomal storage diseases from their parents. Although each disorder results from different gene mutations that translate into a deficiency in enzyme activity, they all share a common biochemical characteristic – all lysosomal disorders originate from an abnormal accumulation of substances inside the lysosome.
LSDs affect mostly children and they often die at a young age, many within a few months or years of birth.
## Contents
* 1 Classification
* 1.1 Standard classification
* 1.2 By type of defect protein
* 1.3 Lysosomal storage disorders
* 2 Signs and symptoms
* 3 Diagnosis
* 4 Treatment
* 5 History
* 6 See also
* 7 References
* 8 External links
## Classification[edit]
### Standard classification[edit]
The LSDs are generally classified by the nature of the primary stored material involved, and can be broadly broken into the following: (ICD-10 codes are provided where available)
* (E75) Lipid storage disorders
* Sphingolipidoses, including Gaucher's and Niemann–Pick diseases (E75.0-E75.1)
* Gangliosidosis (including Tay–Sachs disease (E75.2)
* Leukodystrophies
* (E76.0) Mucopolysaccharidoses, including Hunter syndrome and Hurler disease
* (E77) Glycoprotein storage disorders
* (E77.0-E77.1) Mucolipidoses
Also, glycogen storage disease type II (Pompe disease) is a defect in lysosomal metabolism as well,[5] although it is otherwise classified into E74.0 in ICD-10. Cystinosis is an LSD characterized by the abnormal accumulation of the amino acid cystine.
### By type of defect protein[edit]
Alternatively to the protein targets, LSDs may be classified by the type of protein that is deficient and is causing buildup.
Type of defect protein Disease examples Deficient protein
Lysosomal enzymes primarily Tay–Sachs disease, I-cell disease,[6] Sphingolipidoses (e.g., Krabbe disease, gangliosidosis: Gaucher, Niemann–Pick disease and glycolipids: Metachromatic leukodystrophy), Lysosomal acid lipase deficiency Various
Posttranslational modification of enzymes Multiple sulfatase deficiency Multiple sulfatases
Membrane transport proteins Mucolipidosis type II and IIIA N-acetylglucosamine-1-phosphate transferase
Enzyme protecting proteins Galactosialidosis Cathepsin A
Soluble nonenzymatic proteins GM2-AP deficiency, variant AB, Niemann–Pick disease, type C2 GM2-AP, NPC2
Transmembrane proteins SAP deficiency Sphingolipid activator proteins
Niemann–Pick disease, type C1 NPC1
Salla disease Sialin
Unless else specified in boxes, then the applicable reference is:[7]
### Lysosomal storage disorders[edit]
These are LSDs:
* Sphingolipidoses
* Ceramidase
* Farber disease
* Krabbe disease
* Infantile onset
* Late onset
* Galactosialidosis
* Gangliosides: gangliosidoses
* Alpha-galactosidase
* Fabry disease (alpha-galactosidase A)
* Schindler disease (alpha-galactosidase B)
* Beta-galactosidase / GM1 gangliosidosis
* Infantile
* Juvenile
* Adult / chronic
* GM2 gangliosidosis
* AB variant
* Activator deficiency
* Sandhoff disease
* Infantile
* Juvenile
* Adult onset
* Tay–Sachs
* Juvenile hexosaminidase A deficiency
* Chronic hexosaminidase A deficiency
* Glucocerebroside
* Gaucher disease
* Type I
* Type II
* Type III
* Sphingomyelinase
* Lysosomal acid lipase deficiency
* Early onset
* Late onset
* Niemann–Pick disease
* Type A
* Type B
* Sulfatidosis
* Metachromatic leukodystrophy
* Saposin B deficiency
* Multiple sulfatase deficiency
Mucopolysaccharidoses
* Type I
* MPS I Hurler syndrome
* MPS I S Scheie syndrome
* MPS I H-S Hurler–Scheie syndrome
* Type II (Hunter syndrome)
* Type III (Sanfilippo syndrome)
* MPS III A (Type A)
* MPS III B (Type B)
* MPS III C (Type C)
* MPS III D (Type D)
* Type IV (Morquio)
* MPS IVA (Type A)
* MPS IVB (Type B)
* Type VI (Maroteaux–Lamy syndrome)
* Type VII (Sly syndrome)
* Type IX (hyaluronidase deficiency)
Mucolipidosis
* Type I (sialidosis)
* Type II (I-cell disease)
* Type III (pseudo-Hurler polydystrophy / phosphotransferase deficiency)
* Type IV (mucolipidin 1 deficiency)
Lipidoses
* Niemann–Pick disease
* type C
* Type D
* Neuronal ceroid lipofuscinoses
* Type 1 Santavuori–Haltia disease / infantile NCL (CLN1 PPT1)
* Type 2 Jansky–Bielschowsky disease / late infantile NCL (CLN2/LINCL TPP1)
* Type 3 Batten–Spielmeyer–Vogt disease / juvenile NCL (CLN3)
* Type 4 Kufs disease / adult NCL (CLN4)
* Type 5 Finnish Variant / late infantile (CLN5)
* Type 6 Late infantile variant (CLN6)
* Type 7 CLN7
* Type 8 Northern epilepsy (CLN8)
* Type 8 Turkish late infantile (CLN8)
* Type 9 German/Serbian late infantile (unknown)
* Type 10 Congenital cathepsin D deficiency (CTSD)
* Wolman disease
Oligosaccharide
* Alpha-mannosidosis
* Beta-mannosidosis
* Aspartylglucosaminuria
* Fucosidosis
Lysosomal transport diseases
* Cystinosis
* Pycnodysostosis
* Salla disease / sialic acid storage disease
* Infantile free sialic acid storage disease
Glycogen storage diseases
* Type II Pompe disease
* Type IIb Danon disease [8]
Other
* Cholesteryl ester storage disease
Lysosomal disease
## Signs and symptoms[edit]
The symptoms of LSD vary depending on the particular disorder and other variables such as the age of onset, and can be mild to severe. They can include developmental delay, movement disorders, seizures, dementia, deafness, and/or blindness. Some people with LSD have enlarged livers or spleens, pulmonary and cardiac problems, and bones that grow abnormally.[9]
## Diagnosis[edit]
The majority of patients are initially screened by enzyme assay, which is the most efficient method to arrive at a definitive diagnosis.[9] In some families where the disease-causing mutations are known, and in certain genetic isolates, mutation analysis may be performed. In addition, after a diagnosis is made by biochemical means, mutation analysis may be performed for certain disorders.
## Treatment[edit]
No cures for lysosomal storage diseases are known, and treatment is mostly symptomatic, although bone marrow transplantation and enzyme replacement therapy (ERT) have been tried with some success.[10][11] ERT can minimize symptoms and prevent permanent damage to the body.[12] In addition, umbilical cord blood transplantation is being performed at specialized centers for a number of these diseases. In addition, substrate reduction therapy, a method used to decrease the production of storage material, is currently being evaluated for some of these diseases. Furthermore, chaperone therapy, a technique used to stabilize the defective enzymes produced by patients, is being examined for certain of these disorders. The experimental technique of gene therapy may offer cures in the future.[13]
Ambroxol has recently been shown to increase activity of the lysosomal enzyme glucocerebrosidase, so it may be a useful therapeutic agent for both Gaucher disease and Parkinson's disease.[14][15] Ambroxol triggers the secretion of lysosomes from cells by inducing a pH-dependent calcium release from acidic calcium stores.[16] Hence, relieving the cell from accumulating degradation products is a proposed mechanism by which this drug may help.
## History[edit]
Tay–Sachs disease was the first of these disorders to be described, in 1881, followed by Gaucher disease in 1882. In the late 1950s and early 1960s, de Duve and colleagues, using cell fractionation techniques, cytological studies, and biochemical analyses, identified and characterized the lysosome as a cellular organelle responsible for intracellular digestion and recycling of macromolecules. This was the scientific breakthrough that would lead to the understanding of the physiological basis of the LSDs. Pompe disease was the first disease to be identified as an LSD in 1963, with L. Hers reporting the cause as a deficiency of α-glucosidase. Hers also suggested that other diseases, such as the mucopolysaccharidosis, might be due to enzyme deficiencies.
## See also[edit]
* Mannosidosis
* Molecular chaperone therapy
## References[edit]
1. ^ Winchester B, Vellodi A, Young E (2000). "The molecular basis of lysosomal storage diseases and their treatment". Biochem. Soc. Trans. 28 (2): 150–4. doi:10.1042/bst0280150. PMID 10816117.
2. ^ Reece, Jane; Campbell, Neil (2002). Biology. San Francisco: Benjamin Cummings. pp. 121–122. ISBN 0-8053-6624-5.
3. ^ Meikle, P. J.; Hopwood, J. J.; Clague, A. E.; Carey, W. F. (20 January 1999). "Prevalence of lysosomal storage disorders". JAMA. 281 (3): 249–254. doi:10.1001/jama.281.3.249. ISSN 0098-7484. PMID 9918480.
4. ^ M, Fuller; PJ, Meikle; JJ, Hopwood (1 January 2006). "Epidemiology of lysosomal storage diseases: an overview". PMID 21290699. Cite journal requires `|journal=` (help)
5. ^ eMedicine Specialties > Neurology > Pediatric Neurology > Lysosomal Storage Disease Author: Noah S Scheinfeld, MD, JD, FAAD. Coauthor(s): Rowena Emilia Tabamo, MD; Brian Klein, MD. Updated: Sep 25, 2008
6. ^ Medical Physiology (2nd Edition) – W. Boron & E. Boulpaep, Saunders Press
7. ^ Table 7-6 in:Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (2007). Robbins Basic Pathology. Philadelphia: Saunders. ISBN 978-1-4160-2973-1. 8th edition.
8. ^ "Danon disease".
9. ^ a b Navarrete-Martínez, Juana Inés; Limón-Rojas, Ana Elena; Gaytán-García, Maria de Jesús; Reyna-Figueroa, Jesús; Wakida-Kusunoki, Guillermo; Delgado-Calvillo, Ma. del Rocío; Cantú-Reyna, Consuelo; Cruz-Camino, Héctor; Cervantes-Barragán, David Eduardo (May 2017). "Newborn screening for six lysosomal storage disorders in a cohort of Mexican patients: Three-year findings from a screening program in a closed Mexican health system". Molecular Genetics and Metabolism. 121 (1): 16–21. doi:10.1016/j.ymgme.2017.03.001. PMID 28302345.
10. ^ Clarke JT, Iwanochko RM (2005). "Enzyme replacement therapy of Fabry disease". Mol. Neurobiol. 32 (1): 043–050. doi:10.1385/MN:32:1:043. PMID 16077182.
11. ^ Bruni S, Loschi L, Incerti C, Gabrielli O, Coppa GV (2007). "Update on treatment of lysosomal storage diseases". Acta Myol. 26 (1): 87–92. PMC 2949325. PMID 17915580.
12. ^ "Enzyme Replacement Therapy for Gaucher Disease". National Gaucher Foundation. Retrieved 2017-06-08.
13. ^ Ponder KP, Haskins ME (2007). "Gene therapy for mucopolysaccharidosis". Expert Opin Biol Ther. 7 (9): 1333–1345. doi:10.1517/14712598.7.9.1333. PMC 3340574. PMID 17727324.
14. ^ McNeill, Alisdair; Magalhaes, Joana; Shen, Chengguo; Chau, Kai-Yin; Hughes, Derralyn; Mehta, Atul; Foltynie, Tom; Cooper, J. Mark; Abramov, Andrey Y. (2014-05-01). "Ambroxol improves lysosomal biochemistry in glucocerebrosidase mutation-linked Parkinson disease cells". Brain. 137 (5): 1481–1495. doi:10.1093/brain/awu020. ISSN 0006-8950. PMC 3999713. PMID 24574503.
15. ^ Albin, Roger L.; Dauer, William T. (2014-05-01). "Magic shotgun for Parkinson's disease?". Brain. 137 (5): 1274–1275. doi:10.1093/brain/awu076. ISSN 0006-8950. PMID 24771397.
16. ^ Fois, Giorgio; Hobi, Nina; Felder, Edward; Ziegler, Andreas; Miklavc, Pika; Walther, Paul; Radermacher, Peter; Haller, Thomas; Dietl, Paul (2015). "A new role for an old drug: Ambroxol triggers lysosomal exocytosis via pH-dependent Ca2+ release from acidic Ca2+ stores". Cell Calcium. 58 (6): 628–637. doi:10.1016/j.ceca.2015.10.002. PMID 26560688.
## External links[edit]
Classification
D
* ICD-10: E75-E77
* MeSH: D016464
* v
* t
* e
Lysosomal storage diseases: Inborn errors of lipid metabolism (Lipid storage disorders)
Sphingolipidoses
(to ceramide)
From ganglioside
(gangliosidoses)
* Ganglioside: GM1 gangliosidoses
* GM2 gangliosidoses (Sandhoff disease
* Tay–Sachs disease
* AB variant)
From globoside
* Globotriaosylceramide: Fabry's disease
From sphingomyelin
* Sphingomyelin: phospholipid: Niemann–Pick disease (SMPD1-associated
* type C)
* Glucocerebroside: Gaucher's disease
From sulfatide
(sulfatidoses
* leukodystrophy)
* Sulfatide: Metachromatic leukodystrophy
* Multiple sulfatase deficiency
* Galactocerebroside: Krabbe disease
To sphingosine
* Ceramide: Farber disease
NCL
* Infantile
* Jansky–Bielschowsky disease
* Batten disease
Other
* Cerebrotendineous xanthomatosis
* Cholesteryl ester storage disease (Lysosomal acid lipase deficiency/Wolman disease)
* Sea-blue histiocytosis
* v
* t
* e
Lysosomal storage diseases: Inborn errors of carbohydrate metabolism (Mucopolysaccharidoses)
Catabolism
* MPS I
* Hurler Syndrome, Hurler-Scheie Syndrome, Scheie Syndrome
* MPS II: Hunter Syndrome
* MPS III: Sanfilippo Syndrome
* MPS IV: Morquio Syndrome
* MPS VI: Maroteaux-Lamy Syndrome
* MPS VII: Sly Syndrome
* MPS IX: Hyaluronidase deficiency
* v
* t
* e
Lysosomal storage diseases: Inborn errors of carbohydrate metabolism (Glycoproteinoses)
Anabolism
* Dolichol kinase deficiency
* Congenital disorder of glycosylation
Post-translational modification
of lysosomal enzymes
* Mucolipidosis: I-cell disease (ML II)
* Pseudo-Hurler polydystrophy (ML III)
Catabolism
* Aspartylglucosaminuria
* Fucosidosis
* mannosidosis
* Alpha-mannosidosis
* Beta-mannosidosis
* Sialidosis
* Schindler disease
Other
* solute carrier family (Salla disease)
* Galactosialidosis
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Lysosomal storage disease | c0085078 | 4,480 | wikipedia | https://en.wikipedia.org/wiki/Lysosomal_storage_disease | 2021-01-18T18:48:20 | {"mesh": ["D016464"], "umls": ["C0085078"], "icd-10": ["E75", "E77"], "orphanet": ["68366"], "wikidata": ["Q675010"]} |
A number sign (#) is used with this entry because of evidence that atrioventricular septal defect-4 (AVSD4) is caused by heterozygous mutation in the GATA4 gene (600576) on chromosome 8p23.
Description
The term 'atrioventricular septal defect' (AVSD) covers a spectrum of congenital heart malformations characterized by a common atrioventricular junction coexisting with deficient atrioventricular septation. In ostium primum atrial septal defect (ASD) there are separate atrioventricular valvar orifices despite a common junction, whereas in complete AVSD the valve itself is also shared (summary by Craig, 2006).
AVSD, also designated endocardial cushion defect or atrioventricular canal defect (AVCD), is known to occur in either a nonsyndromic (isolated) form or, more commonly, as part of a malformation syndrome. The 2 syndromes most frequently associated with AVSD are Down syndrome (190685), in which AVSD is the most frequent congenital heart defect, and Ivemark syndrome (208530) (summary by Carmi et al., 1992).
For a discussion of genetic heterogeneity of atrioventricular septal defects, see AVSD1 (606215).
Molecular Genetics
Rajagopal et al. (2007) analyzed the GATA4 gene (600576) in 107 patients with congenital heart defects in the spectrum of Gata4-mutant mice and identified heterozygous missense mutations in 4 patients, including 2 (4.8%) of 43 patients with endocardial cushion defects (600576.0007; 600576.0008). Both patients had a primum atrial septal defect and cleft mitral valve, and both had a reportedly unaffected parent who also carried the mutation.
Zhang et al. (2008) screened 486 Han Chinese pediatric patients with congenital heart defects for mutations in the GATA4 gene, and identified heterozygosity for the previously identified P163S mutation (600576.0007) in a 1-year-old girl with a Rastelli type A endocardial cushion defect.
INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Atrial septal defect, primum type \- Cleft mitral valve \- Rastelli type A endocardial cushion defect (in some patients) MOLECULAR BASIS \- Caused by mutation in the GATA-binding protein-4 gene (GATA4, 600576.0007 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| ATRIOVENTRICULAR SEPTAL DEFECT 4 | c1389018 | 4,481 | omim | https://www.omim.org/entry/614430 | 2019-09-22T15:55:19 | {"doid": ["0050651"], "mesh": ["C562831"], "omim": ["614430"], "orphanet": ["98722"]} |
Sheldon-Hall syndrome (SHS) is a rare multiple congenital contracture syndrome characterized by contractures of the distal joints of the limbs, triangular face, downslanting palpebral fissures, small mouth, and high arched palate.
## Epidemiology
Epidemiological data for the prevalence of SHS are not available, but less than 100 cases have been reported in the literature.
## Clinical description
Other common clinical features of SHS include prominent nasolabial folds, high arched palate, attached earlobes, mild cervical webbing, short stature, severe camptodactyly, ulnar deviation, and vertical talus and/or talipes equinovarus. Typically, the contractures are most severe at birth and non-progressive.
## Etiology
Mutations in either MYH3, TNNI2, or TNNT3 have been found in about 50% of cases. These genes encode proteins of the contractile apparatus of fast twitch skeletal muscle fibers.
## Diagnostic methods
The diagnosis of SHS is based on clinical criteria.
## Differential diagnosis
Mutation analysis is useful to distinguish SHS from arthrogryposis syndromes with similar features (e.g. distal arthrogryposis 1 and Freeman-Sheldon syndrome; see these terms).
## Antenatal diagnosis
Prenatal diagnosis by ultrasonography is feasible at 18-24 weeks of gestation. If the family history is positive and the mutation is known in the family, prenatal molecular genetic diagnosis is possible.
## Genetic counseling
SHS is inherited in an autosomal dominant pattern but about half the cases are sporadic.
## Management and treatment
There is no specific therapy for SHS. However, patients benefit from early intervention with occupational and physical therapy, serial casting, and/or surgery.
## Prognosis
Life expectancy and cognitive abilities are normal.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Sheldon-Hall syndrome | c1834523 | 4,482 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1147 | 2021-01-23T18:19:42 | {"mesh": ["C538400"], "omim": ["601680", "616266"], "umls": ["C1834523"], "icd-10": ["Q68.8"], "synonyms": ["Distal arthrogryposis type 2B", "Freeman-Sheldon syndrome variant"]} |
Spinal shock was first explored by Whytt in 1750 as a loss of sensation accompanied by motor paralysis with initial loss but gradual recovery of reflexes, following a spinal cord injury (SCI) – most often a complete transection. Reflexes in the spinal cord below the level of injury are depressed (hyporeflexia) or absent (areflexia), while those above the level of the injury remain unaffected. The 'shock' in spinal shock does not refer to circulatory collapse, and should not be confused with neurogenic shock, which is life-threatening. The term “spinal shock” was introduced more than 150 years ago in an attempt to distinguish arterial hypotension due to a hemorrhagic source from arterial hypotension due to loss of sympathetic tone resulting from spinal cord injury. Whytt, however, may have discussed the same phenomenon a century earlier, although no descriptive term was assigned.[1]
## Phases of spinal shock[edit]
Phase Time Physical exam finding Underlying physiological event
1 0–1d Areflexia/Hyporeflexia Loss of descending facilitation
2 1–3d Initial reflex return Denervation supersensitivity
3 1–4w Hyperreflexia (initial) Axon-supported synapse growth
4 1–12m Hyperreflexia, Spasticity Soma-supported synapse growth
Ditunno et al. proposed a four-phase model for spinal shock in 2004 as follows:[2]
Phase 1 is characterized by a complete loss—or weakening—of all reflexes below the SCI. This phase lasts for a day. The neurons involved in various reflex arcs normally receive a basal level of excitatory stimulation from the brain. After an SCI, these cells lose this input, and the neurons involved become hyperpolarized and therefore less responsive to stimuli.
Phase 2 occurs over the next two days, and is characterized by the return of some, but not all, reflexes below the SCI. The first reflexes to reappear are polysynaptic in nature, such as the bulbocavernosus reflex. Monosynaptic reflexes, such as the deep tendon reflexes, are not restored until Phase 3. Restoration of reflexes is not rostral to caudal as previously (and commonly) believed, but instead proceeds from polysynaptic to monosynaptic. The reason reflexes return is the hypersensitivity of reflex muscles following denervation – more receptors for neurotransmitters are expressed and are therefore easier to stimulate.
Phases 3 and 4 are characterized by hyperreflexia, or abnormally strong reflexes usually produced with minimal stimulation. Interneurons and lower motor neurons below the SCI begin sprouting, attempting to re-establish synapses. The first synapses to form are from shorter axons, usually from interneurons – this categorizes Phase 3. Phase 4 on the other hand, is soma-mediated, and will take longer for the soma to transport various growth factors, including proteins, to the end of the axon.[3]
## Autonomic effects[edit]
In spinal cord injuries above T6, neurogenic shock may occur, from the loss of autonomic innervation from the brain. Parasympathetic is preserved but the synergy between sympathetic and parasympathetic system is lost in cervical and high thoracic SCI lesions. Sacral parasympathetic loss may be encountered in lesions below T6 or T7. Cervical lesions cause total loss of sympathetic innervation and lead to vasovagal hypotension and bradyarrhythmias – which resolve in 3–6 weeks. Autonomic dysreflexia is permanent, and occurs from Phase 4 onwards. It is characterized by unchecked sympathetic stimulation below the SCI (from a loss of cranial regulation), leading to often extreme hypertension, loss of bladder or bowel control, sweating, headaches, and other sympathetic effects.
## References[edit]
1. ^ Atkinson, Patty Pate; Atkinson, John L.D. (April 1996). "Spinal Shock". Mayo Clinic Proceedings v. 71(4): 384-389. doi:10.4065/71.4.384. Retrieved 3 August 2020.
2. ^ Ditunno, JF; Little, JW; Tessler, A; Burns, AS (2004). "Spinal shock revisited: a four-phase model". Spinal Cord. 42 (7): 383–95. doi:10.1038/sj.sc.3101603. PMID 15037862.
3. ^ Tufts University, Boston, USA – Case Study: 10 patients with SCI, traumatic spinal cord injury UJUS 2009, Retrieved April 20, 2010
* v
* t
* e
Shock
Distributive
* Septic shock
* Neurogenic shock
* Anaphylactic shock
* Toxic shock syndrome
Obstructive
* Abdominal compartment syndrome
Low volume
* Hemorrhage
* Hypovolemia
* Osmotic shock
Other
* Spinal shock
* Cryptic shock
* Vasodilatory shock
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Spinal shock | c0597503 | 4,483 | wikipedia | https://en.wikipedia.org/wiki/Spinal_shock | 2021-01-18T18:31:31 | {"gard": ["7680"], "umls": ["C0597503", "CL495135"], "wikidata": ["Q2298453"]} |
A rare skin disease that is the most common form of porokeratosis characterized by the presence of several small annular plaques with a distinctive keratotic rim found most commonly on sun-exposed areas of the skin, particularly the extremities.
## Epidemiology
Disseminated superficial actinic porokeratosis (DSAP) prevalence is not precisely known, although DSAP is the most common form of porokeratosis. It is more frequently seen in women, probably because they more readily seek advice for cosmetic concerns.
## Clinical description
The disease usually starts during the third to fourth decade of life (only rarely during childhood). DSAP is characterized by several small (0.5-1 cm), round, pink-brownish plaques, surrounded by a distinctive keratotic rim, corresponding microscopically to the cornoid lamella. They are painless, but pruritus is reported in one third of patients. The lesions appear on skin that is exposed to sunlight (usually the extremities) but never on the palms or soles. They usually appear in summer and may improve or disappear during winter. DSAP is usually a benign disease, although squamous cell carcinoma can very rarely develop within the lesions.
## Etiology
Mutations in the mevalonate kinase (MVK) gene, located to chromosome 12q24, have been found in up to one third of DSAP cases. MVK encodes an enzyme in the mevalonate pathway, which is thought to be crucial for the biosynthesis of cholesterol and isoprenoid as well as the regulation of calcium-induced keratinocyte differentiation. More recently, pathogenic mutations in the SLC17A9 gene (20q13.33) were also found in DSAP patients. Risk factors for DSAP include exposure to ultraviolet light and immunosuppression.
## Diagnostic methods
Histopathological examination of a cutaneous biopsy confirms the clinical diagnosis of DSAP. The characteristic feature is the presence of a cornoid lamella, i.e. a vertical stack of parakeratotic corneocytes within the horny layer, seated on a shallow depression of the underlying epidermis that is devoid of a granular layer. Molecular genetic testing for a mutation in the MVK gene can also confirm diagnosis.
## Differential diagnosis
Differential diagnoses include (pre)neoplastic or hyperplastic keratotic skin lesions as well as other forms of porokeratosis, such as porokeratosis of Mibelli or superficial disseminated porokeratosis (similar to DSAP but not triggered by sunlight).
## Genetic counseling
DSAP often follows an autosomal dominant pattern of inheritance, but sporadic cases have also been reported.
## Management and treatment
There is no standard treatment for DSAP. Topical imiquimod 5% cream, topical 5-fluorouracil (5-FU) and topical vitamin D-analogues (tacalcitol, calcipotriol) have shown to be beneficial in treating the lesions of DSAP in some patients. Cryotherapy, electrodessication, laser ablation and photodynamic therapy have been tested with varying results. DSAP patients should limit their exposure to sun.
## Prognosis
DSAP has a good prognosis as it very rarely progresses to carcinoma. However the disease may cause cosmetic concern and thereby exerts a negative effect on a patient's quality of life.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Disseminated superficial actinic porokeratosis | c0265970 | 4,484 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79152 | 2021-01-23T18:20:00 | {"gard": ["10983"], "mesh": ["D017499"], "omim": ["175900", "607728", "612293", "612353", "614714", "616063", "616631"], "umls": ["C0265970"], "icd-10": ["Q82.8"]} |
Hereditary persistence of alpha-fetoprotein is a benign genetic condition characterized by persistence of high alpha-fetoprotein (AFP) levels throughout life, with no associated clinical disability and thus no need for specific therapy
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Hereditary persistence of alpha-fetoprotein | c1863080 | 4,485 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=168615 | 2021-01-23T17:52:43 | {"omim": ["615970"]} |
Galton et al. (1977) reported clinical, metabolic and autopsy findings in a 6-year-old microcephalic child with the paradoxical combination of triglyceride storage in peripheral adipose tissue and gross emaciation. The authors found no increase in glycerol or cyclic AMP in peripheral adipose tissue on incubation with isoprenaline and postulated a defect in adenyl cyclase or catecholamine receptor. No information bearing on the genetics was available.
Head \- Microcephaly Growth \- Gross emaciation Lab \- Triglyceride storage in peripheral adipose tissue \- Poor stimulation of adenyl cyclase in tissues by noradrenaline Inheritance \- No information on genetics ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| TRIGLYCERIDE STORAGE DISEASE, TYPE I | c1860821 | 4,486 | omim | https://www.omim.org/entry/190420 | 2019-09-22T16:32:24 | {"mesh": ["C566031"], "omim": ["190420"]} |
Summitt (1969) described 2 brothers with craniosynostosis and syndactyly which was severe in one and mild in the other. Both were obese. Intelligence was normal. The skull was towered, as in Carpenter syndrome (201000). The parents were first cousins. Obesity was the presenting complaint, at age 6.5 years, in the sporadic case of Sells et al. (1979). Cohen et al. (1987) concluded that Summitt syndrome and Goodman syndrome (201020) are variants of Carpenter syndrome.
Head \- Craniosynostosis Growth \- Obesity Neuro \- Normal intelligence \- Tower skull Limbs \- Syndactyly Inheritance \- Autosomal recessive \- ? variant of Carpenter syndrome ▲ Close
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*[t]: Discuss this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| SUMMITT SYNDROME | c1802405 | 4,487 | omim | https://www.omim.org/entry/272350 | 2019-09-22T16:21:58 | {"mesh": ["C538142"], "omim": ["272350"], "orphanet": ["3210"]} |
Inflammation of hair follicles due to fungal infection
Not to be confused with Majocchi's disease.
Majocchi's granuloma
SpecialtyDermatology
Majocchi's granuloma is a skin condition characterized by deep, pustular plaques, and is a form of tinea corporis. It is a localized form of fungal folliculitis. Lesions often have a pink and scaly central component with pustules or folliculocentric papules at the periphery.[1] The name comes from Professor Domenico Majocchi, who discovered the disorder in 1883.[2] Majocchi was a professor of dermatology at the University of Parma and later the University of Bologna.[2] The most common dermatophyte is called Trichophyton rubrum.
## Contents
* 1 Symptoms
* 2 Causes
* 3 Mechanisms
* 4 Diagnosis
* 5 Treatment
* 6 Research
* 7 See also
* 8 References
* 9 External links
## Symptoms[edit]
Majocchi's granuloma often presents as pink scaly patches with pustules at the periphery. It is most common on skin exposed to mechanical abuse—wear and tear—such as the upper and lower extremities. Patients experience papules, pustules, or even plaques and nodules at the infection site.[3] The white to red papules and pustules often have a perifollicular location. Hair shafts can be easily removed from the pustules and papules.[3] Itching is common.
Firm or fluctuant subcutaneous nodules or abscesses represent a second form of MG that is generally observed in immunosuppressed hosts. Nodules may develop in any hair-bearing part of the body, but are most often observed on the forearms, hands, and legs of infected individuals. Involvement of the scalp and face is rarely observed. Lesions start as solitary or multiple well-circumscribed perifollicular papulopustules and nodules with or without background erythema and scaling. In rare circumstances, the lesions may have keloidal features.[4]
## Causes[edit]
Majocchi's granuloma is caused by a common group of fungi called dermatophytes. Unlike traditional tinea corporis (commonly known as ringworm) that resides in the top layer of the skin, Majocchi's granuloma contains dermatophytes that invade the hair follicle and/or dermis. The invasion of the hair follicule leads to the clinically evident papules and pustules at the periphery. The most common form, the superficial perifollicular form, occurs predominately on the legs of otherwise healthy young women who repeatedly shave their legs and develop hair follicle occlusions that directly or indirectly disrupt the follicle and allow for passive introduction of the organism into the dermis.[5] Hence, the physical barrier of the skin is important because it prevents the penetration of microorganisms. Physical factors that play a major role in inhibiting dermal invasion include the interaction among keratin production, the rate of epidermal turnover, the degree of hydration and lipid composition of the stratum corneum, CO2 levels, and the presence or absence of hair.[4] Keratin and/or necrotic material can be introduced into the dermis with an infectious organism to exacerbate the problem. Majocchi granuloma also can occur as a result of the use of potent topical steroids on unsuspected tinea.[2]
## Mechanisms[edit]
Historically, many types of dermatophytes were known to cause the condition. Trichophyton violaceum used to be one of the most common species of dermatophytes to cause this disease. Today, however, Trichophyton rubrum is the main culprit in most cases. These fungi are keratinophilic and colonize or infect the superficial keratinized tissues (the skin, nails, and hair) of humans and animals. The organisms are usually restricted to the non-living cornified layer of the epidermis and do not invade beyond the epidermis. The fungi are usually unable to penetrate into viable tissues in an immunocompetent host and therefore the infection incidence is higher in immune compromised individuals. The two forms of MG are:[6]
* small, perifollicular papular form, which is a localized dermal infection that usually occurs in healthy individuals
* deep subcutaneous plaque/nodular lesion form that occurs in immunosuppressed hosts. Tinea corporis is the name of the subset of this disease that remains restricted to the stratum corneum. Otherwise, the atypical deeper involvement is known as Majocchi's granuloma.[7] Because keratinophilic dermatophytes digest keratin, the introduction of keratin into the dermis may also act as a medium for continued growth of the organism.
## Diagnosis[edit]
Primary diagnosis starts with a thorough physical exam and evaluation of medical history. Often, the condition is readily apparent to a medical practitioner and no further testing is required. If not readily apparent, a skin biopsy test or fungal culture may be ordered. This pathological examination of the skin biopsy helps to arrive at the correct diagnosis via a fungal culture (mycology). In severe or recurrent cases, further workup may be required.
This disease commonly affects both immunocompetent and immunocompromised hosts. However, immunocompromised individuals have a higher risk.
## Treatment[edit]
Oral antifungal medications are the standard of care. Due to the location of the dermatophytes within the hair follicle, treatment with topical antifungals is often unsatisfactory. In patients with tinea pedis or onychomycosis, re-inoculation and recurrence is common. In individuals with recurrent outbreaks, inoculation sources should be identified and treated appropriately. Historical therapies include oral potassium iodide, mildly filtered local X-radiation, and topical applications of Asterol as a fungicide in both tincture and ointment forms.[4] In modern medicine, systemic antifungals, such as griseofulvin, ketoconazole, and itraconazole, are the standard. Therapy extends over at least 4–8 weeks, and treatment continues until all lesions are cleared.[4] Currently, no data about relapse rates or the complications of not treating Majocchi granuloma exist.[5]
## Research[edit]
The review article, "Majocchi’s granuloma: a symptom complex caused by fungal pathogens"[8] concludes that the Tzanck smear method is a rapid and easy diagnostic test. In addition, histopathologic examinations reveal granulomatous folliculitis in patients with MG. It found that systemic antifungals given at an adequate dose and for an appropriate duration are the drugs of choice; in general, topical antifungals alone do not clear the fungal infections.[4]
In "Majocchi's granumloma - Case report",[7] the authors discuss the case of a three-year-old child who presented with lesions around her jaw. It was reported that she had been using a combination of topical corticoids, anti-fungals and antibiotics during this period. The use of these products was ineffective. Drugs were suspended after 15 days of use and followed by cutaneous biopsy and histopathological examination. Mycological examination showed the presence of hyphae and spores compatible with MG. The patient was treated with griseofulvin for 8 weeks and went into remission.
The article "Tinea Corporis Gladiatorum Presenting as a Majocchi Granuloma"[9]discussed the importance of differential diagnosis. It includes a case report involving a 20-year-old male H who had been a part of schools wrestling team for the past six years. H presented with a 4-year history of follicular papules and pustules on his right forearm. This lesion had the typical clinical appearance. A skin biopsy showed an acute deep folliculitis compatible with a Majocchi granuloma, but fungal stainings with a Grocott stain was negative. This was the first reported case that showed that tinea corporis gladiatorum can present as a Majocchi granuloma. Thus, dermatologists must consider a Majocchi granuloma in the differential diagnosis of persistent skin lesions in wrestlers.
## See also[edit]
* Domenico Majocchi
* List of cutaneous conditions
## References[edit]
1. ^ Bolognia, Jean.; Jorizzo, Joseph L.Schaffer.; Julie V. (Eds.); et al. (2012). Dermatology. Elsevier Saunders. ISBN 978-0723435716.CS1 maint: extra text: authors list (link)
2. ^ a b c "Majocchi Granuloma: Background, Pathophysiology, Epidemiology". 2017-07-14. Cite journal requires `|journal=` (help)
3. ^ a b "Majocchi's Granuloma (Granuloma trichophyticum)". www.mdedge.com. Retrieved 2017-12-11.
4. ^ a b c d e İLkit, Macit; Durdu, Murat; Karakaş, Mehmet (2012-07-01). "Majocchi's granuloma: a symptom complex caused by fungal pathogens". Medical Mycology. 50 (5): 449–457. doi:10.3109/13693786.2012.669503. ISSN 1369-3786. PMID 22435879.
5. ^ a b "Majocchi Granuloma: Background, Pathophysiology, Epidemiology". 2017-11-17. Cite journal requires `|journal=` (help)
6. ^ Fu-qiu, Li (2014). "Majocchi's Granuloma after Topical Corticosteroids Therapy". Case Reports in Dermatological Medicine. 2014: 3 pages.
7. ^ a b Soligo Kanaan, Izabel Cristina (2015). "Majocchi's granuloma- Case report". Anais Brasileiros de Dermatologia. 90 (2): 251–253. doi:10.1590/abd1806-4841.20153115. PMC 4371678. PMID 25830999.
8. ^ Ilkit, M (2012). "Majocchi's granuloma: a symptom complex caused by fungal pathogens". Medical Mycology. 50 (5): 449–457. doi:10.3109/13693786.2012.669503. PMID 22435879.
9. ^ Kurian, Anil (2011). "Tinea Corporis Gladiatorum Presenting as a Majocchi Granuloma". ISRN Dermatology. 2011: 767589. doi:10.5402/2011/767589. PMC 3262549. PMID 22363858.
## External links[edit]
Classification
D
* DiseasesDB: 33948
External resources
* eMedicine: article/1092601
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Fungal folliculitis | c1279621 | 4,488 | wikipedia | https://en.wikipedia.org/wiki/Fungal_folliculitis | 2021-01-18T19:00:20 | {"umls": ["C1279621"], "wikidata": ["Q5509166"]} |
Schmorl's nodes
Other namesIntraosseous disk herniation, Schmorl's nodules
X-ray image of Schmorl's nodes in the lumbar spine
SpecialtyRheumatology
Schmorl's nodes are protrusions of the nucleus pulposus of the intervertebral disc through the vertebral body endplate and into the adjacent vertebra.[1]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Diagnosis
* 4 Management
* 5 Eponym
* 6 References
* 7 Further reading
* 8 External links
## Signs and symptoms[edit]
These are protrusions of disc material into the surface of the vertebral body, which may contact the marrow of the vertebra and lead to inflammation. The protrusions are also associated with necrosis of the vertebral bone and the question of whether these protrusions and inflammation cause the necrosis, or whether the cartilage migrates into areas that have become necrotic due to other conditions, is under investigation.
They may or may not be symptomatic, and their link to back pain is controversial. Williams and colleagues note that this relationship may be due to lumbar disc disease, as the two commonly occur simultaneously.[2]
## Causes[edit]
Schmorl's nodes are fairly common, especially with minor degeneration of the aging spine, but they are also seen in younger spines. Schmorl's nodes often cause no symptoms, but may simply reflect that "wear and tear" of the spine has occurred over time; they may also reflect that bone strength was at one time somewhat compromised, perhaps due to a vitamin D deficiency although this has yet to be confirmed with studies, or if heavy lifting is done at a young age before the vertebral bodies are completely ossified such as in young farm workers. There is also a strong heritability of Schmorl's Nodes (>70%).[2] While often non-complicating, Schmorl's nodes also tend to occur more often in cases of spinal deformity, specifically Scheuermann's disease. These defects are caused when the vertebra loses its normal function and is not moving/hypomobile/subluxated. During this time the forces normally distributed by the nucleus pulposus (the incompressible gelatinous center of the intervertebral disc) are concentrated in a certain area causing endplates to deform in a concave manner.[3]
## Diagnosis[edit]
CT scan in the sagittal plane of two Schmorl's nodes. The small Schmorl's node at the inferior endplate of the L3 vertebral body (arrow) has typical features, being broad-based at the endplate, with well-defined contours and thin marginal sclerosis. A large and less typical Schmorl's node (arrowhead) is observed at the superior endplate of L4.[4]
Schmorl's nodes can be detected with X-rays, although they can be imaged better by CT or MRI. They are considered to be vertical disc herniations through the cartilaginous vertebral body endplates. Schmorl's nodes can sometimes be seen radiographically, however they are more often seen on MRI, even when not visible on plain X-rays. They may or may not be symptomatic, and their etiological significance for back pain is controversial. In a study in Spine by Hamanishi, et al., Schmorl's nodes were observed on MRI in 19% of 400 patients with back pain, and in only 9% of an asymptomatic control group. The authors concluded that Schmorl's nodes are areas of "vertical disc herniation" through areas of weakness in the endplate.[5]
## Management[edit]
Painful Schmorl's node can be diagnosed by discography, which demonstrates an intravertebral disc herniation with concomitant back pain. Surgical treatment should be considered in a patient with persistent disabling back pain. When surgical treatment is indicated, eradication of the intervertebral disc including Schmorl's node and segmental fusion are preferable.[6]
## Eponym[edit]
Schmorl's nodes are named after German pathologist Christian Georg Schmorl (1861–1932).[7]
## References[edit]
1. ^ Can an Incidental Schmorl’s Node Be a Cause for Low Backache? – Enigma Resolved By a First Ever Prospective Case Control Study in A South Indian Town Population Authors Saraswathi S1, Adaikkapan M2, Senthilnathan A3, Sivakolunthu M4
* 1Post graduate, Department of Radiodiagnosis, Rajah Muthiah Medical College and Hospital, Chidambaram – 608002, Tamilnadu, India
2Professor and Head, Department of Radiodiagnosis, Rajah Muthiah Medical College and Hospital, Chidambaram – 608002, Tamilnadu, India 3Professor and Head, Department of Orthopaedics, Rajah Muthiah Medical College and Hospital, Chidambaram – 608002, Tamilnadu, India 4Lecturer, Department of Radiodiagnosis, Rajah Muthiah Medical College and Hospital, Chidambaram – 608002, Tamilnadu, India CONCLUSIONS The prevalence of Schmorl’s nodes in subjects with low backache in our present study representing a South Indian town population is 84%, majority of whom were males (65.4%) with male: female ratio of 1.8:1. the occurrence of Schmorl’s node was highest in superior end plates of upper lumbar vertebrae. The occurrences of schmorl’s nodes were very high in cases (84%) than in controls (7.4%). Schmorl’s nodes occurrence is significantly higher in cases than in controls, thereby establishing a causative role. Hence, Schmorl’snodes does cause low backache.synd/2377 at Who Named It?
2. ^ a b Williams, F. M. K.; Manek, N. J.; Sambrook, P. N.; Spector, T. D.; MacGregor, A. J. (2007). "Schmorl's nodes: Common, highly heritable, and related to lumbar disc disease". Arthritis & Rheumatism. 57 (5): 855–860. doi:10.1002/art.22789. PMID 17530687.
3. ^ HunterNovakDC(2015)[full citation needed]
4. ^ Nogueira-Barbosa, Marcello Henrique; Crema, Michel Daoud; Herrero, Carlos Fernando Pereira da Silva; Pasqualini, Wagner; Defino, Helton Luiz Aparecido (2015). "THE SEVERAL FACES OF SCHMORL'S NODE: PICTORIAL ESSAY". Coluna/Columna. 14 (4): 320–323. doi:10.1590/S1808-185120151404151248. ISSN 1808-1851.
5. ^ Hamanishi, Chiaki; Kawabata, Tutomu; Yosii, Takeo; Tanaka, Seisuke (1994). "Schmorlʼs Nodes on Magnetic Resonance Imaging". Spine. 19 (4): 450–3. doi:10.1097/00007632-199402001-00012. PMID 8178234.
6. ^ Hasegawa, K; Ogose, A; Morita, T; Hirata, Y (2004). "Painful Schmorl's node treated by lumbar interbody fusion". Spinal Cord. 42 (2): 124–8. doi:10.1038/sj.sc.3101506. PMID 14765146.
7. ^ MedFriendly.com: Schmorl’s nodule
## Further reading[edit]
* Plomp, Kimberly A; Viðarsdóttir, Una Strand; Weston, Darlene A; Dobney, Keith; Collard, Mark (2015). "The ancestral shape hypothesis: An evolutionary explanation for the occurrence of intervertebral disc herniation in humans". BMC Evolutionary Biology. 15: 68. doi:10.1186/s12862-015-0336-y. PMC 4410577. PMID 25927934. Lay summary – BBC News (27 April 2015).
* McFadden, K D; Taylor, J R (1989). "End-Plate Lesions of the Lumbar Spine". Spine. 14 (8): 867–9. doi:10.1097/00007632-198908000-00017. PMID 2781398.
* Peng, B; Wu, W; Hou, S; Shang, W; Wang, X; Yang, Y (2003). "The pathogenesis of Schmorl's nodes". The Journal of Bone and Joint Surgery. British Volume. 85 (6): 879–82. doi:10.1302/0301-620X.85B6.13555. PMID 12931811.
* Takahashi, K.; Miyazaki, T.; Ohnari, H.; Takino, T.; Tomita, K. (1995). "Schmorl's nodes and low-back pain". European Spine Journal. 4 (1): 56–9. doi:10.1007/bf00298420. PMID 7749909.
## External links[edit]
Classification
D
* ICD-10: M51.4
* ICD-9-CM: 722.30
* DiseasesDB: 32386
Wikimedia Commons has media related to Schmorl's nodes.
* 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]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Schmorl's nodes | c0410632 | 4,489 | wikipedia | https://en.wikipedia.org/wiki/Schmorl%27s_nodes | 2021-01-18T18:46:36 | {"icd-9": ["722.30"], "icd-10": ["M51.4"], "wikidata": ["Q1524867"]} |
Infant acute respiratory distress syndrome is a lung disorder that affects premature infants caused by developmental insufficiency of surfactant production and structural immaturity of the lungs. The symptoms usually appear shortly after birth and may include tachypnea, tachycardia, chest wall retractions (recession), expiratory grunting, nasal flaring and cyanosis during breathing efforts.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Infant acute respiratory distress syndrome | c0035220 | 4,490 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=70587 | 2021-01-23T18:18:40 | {"mesh": ["D012127"], "omim": ["267450"], "umls": ["C0020192", "C0035220", "C0852283"], "icd-10": ["P22.0"], "synonyms": ["Hyaline membrane disease", "Infant ARDS", "Infant respiratory distress syndrome", "Neonatal respiratory distress syndrome"]} |
Alternating hemiplegia of childhood
Other namesAHC
SpecialtyNeurology
Alternating hemiplegia of childhood is an ultra-rare neurological disorder named for the transient episodes, often referred to as "attacks", of hemiplegia from which those with the disorder suffer. It typically presents before the age of 18 months. These hemiplegic attacks can cause anything from mild weakness to complete paralysis on one or both sides of the body, and they can vary greatly in duration. Attacks may also alternate from one side of the body to the other, or alternate between affecting one or both sides during a single attack. Besides hemiplegia, symptoms of the disorder include an extremely broad range of neurological and developmental impairments which are not well understood. Normally, hemiplegia and other associated symptoms cease completely with sleep, but they may recur upon waking.[1]
Most frequently AHC is caused by a spontaneous mutation in the ATP1A3 gene.[2][3][4][5] It is an extremely rare disorder – approximately 1 in 1,000,000 people have AHC. It was only recently discovered, having first been characterized in 1971.[4][6]
## Contents
* 1 Signs and symptoms
* 1.1 Hemiplegic attacks
* 1.2 Paroxysmal symptoms
* 1.3 Non-paroxysmal symptoms
* 1.4 Epilepsy
* 2 Cause
* 3 Diagnosis
* 4 Treatments
* 4.1 Management strategies
* 4.2 Flunarizine
* 4.3 Sodium oxybate
* 5 References
* 6 External links
## Signs and symptoms[edit]
AHC patients exhibit a wide range of symptoms in addition to hemiplegic attacks.[1] These can be further characterized as paroxysmal and non-paroxysmal symptoms. Paroxysmal symptoms are generally associated with hemiplegic attacks and may occur suddenly with hemiplegia or on their own. Paroxysmal symptoms may last for variable amounts of time. Non-paroxysmal symptoms tend to be side effects of AHC which are present at all times, not just during episodes or attacks. Epilepsy, which is also considered a paroxysmal symptom, plays an important role in the progression and diagnosis of AHC.[citation needed]
### Hemiplegic attacks[edit]
Chronologically, hemiplegic attacks are not always the first symptom of AHC, but they are the most prominent symptom, as well as the symptom for which the disorder is named. Hemiplegic attacks may affect one or both sides of the body, and attacks which affect both sides of the body may be referred to as either bilateral or quadriplegic attacks. One of the unique characteristics of AHC is that hemiplegic attacks, as well as other symptoms which may co-occur with hemiplegia, cease immediately upon sleep. During strong attacks, the symptoms may reoccur upon waking.[4][7] Hemiplegic attacks can occur suddenly or gradually, and the severity of an attack can vary over its duration.[7] The attacks may alternate from one side of the body to another, though this is rare.[8] The length of attacks may also vary from minutes to weeks,[4] though length of attacks varies more greatly between people than between attacks for one person.[7] Both bilateral and hemiplegic attacks are associated with pseudobulbar features such as dysphagia, dysarthria, and respiratory difficulty.[4][7][8] Paralysis is also often accompanied by changes in skin color and temperature, sweating, restlessness, tremor, screaming, and the appearance of pain.[7] Hemiplegic attacks happen irregularly and can occur with speech, eating, and swallowing impairment. Patients with AHC are frequently underweight due to these side effects.[8] The average age of onset for hemiplegic episodes has been found to be 6–7 months of age.[4] This early onset gives the name of this disorder the slightly misleading ending "of childhood". AHC is not exclusively limited to childhood – attacks in some cases become milder after the first ten years of life, but they never completely disappear.[8]
### Paroxysmal symptoms[edit]
AHC patients have exhibited various paroxysmal symptoms which manifest to different degrees in each person.[7] Paroxysmal symptoms include tonic, tonic-clonic, or myoclonic limb movements,[9] dystonic posturing, choreoathetosis, occular nystagmus, and various other ocular motor abnormalities.[1][7] Almost half of all people have dystonic symptoms prior to experiencing hemiplegia.[4] These symptoms generally begin before 8 months of age.[9] Ocular motor abnormalities occur early, and these are the most frequent early symptoms of AHC, particularly nystagmus.[4][7] Almost 1/3 of people with this disorder had episodic ocular motor features within 1–2 days of birth. Many also experienced hemiplegia and dystonia before 3 months of age.[4] A final symptom that may be considered paroxysmal is a temporary change in behavior - some patients will become unreasonable, demanding, and aggressive either before or after an attack[10]
Not all patients have all of these symptoms, and it is not known whether they are caused by AHC.[1] Symptoms usually manifest in the first 3 months of the child's life, with an average onset of 2.5 months. Frequently, some of these symptoms will manifest in the neonatal period. These paroxysmal symptoms are often used to help diagnose AHC, since there is no simple test for it.[citation needed]
In some cases, EEGs taken during these paroxysmal events were characterized by a generalized background slowing.[4][9] Overall however, EEG during episodes and other investigative methods such as brain MRI, TACs, angiographic MRIs and CFS have normal results.[11]
### Non-paroxysmal symptoms[edit]
In the long term, many paroxysmal symptoms occur along with AHC, and while these symptoms vary in strength depending on the person, they are consistent features of AHC.[12] It is thought that some of these symptoms are brought on or worsened by hemiplegic attacks, though it is not known for certain. Patients suffer persistent motor, movement (ataxia), and cognitive deficits.[4][7][8] These deficits become more apparent over time and include developmental delays, social problems, and retardation.[1] It is rare for someone with AHC not to have cognitive deficits, but a study in Japan did find two patients who met all of the diagnostic criteria for AHC but who were not mentally impaired.[13] It is not known whether AHC is a progressive disease, but severe attacks are suspected to cause damage which result in permanent loss of function.[8] 100% of children studied in the USA have had some form of mental impairment, which is usually described as mild to moderate,[4] but varies greatly among individuals.
### Epilepsy[edit]
At least 50% of AHC sufferers also suffer from epilepsy,[4] and AHC is often misdiagnosed as epilepsy because of this.[8] These epileptic events are distinguished from other episodes by an alteration of consciousness, as well as frequent tonic or tonic-clonic activity. Epileptic episodes are generally rare, though they do increase with age. Due to the rarity of epileptic episodes, there are few EEG confirmations of them.[citation needed]
## Cause[edit]
Recent research suggests that AHC is caused by a de novo (spontaneous) genetic mutation in the ATP1A3 gene[14][15][2] on chromosome 19 (locus 19q13.31) which encodes enzyme ATP1A3. A small number of cases seem to be caused by a mutation in the ATP1A2 gene.[15] Where the mutation is inherited, it has the autosomal dominant pattern of inheritance.[15]
Previously AHC was thought to be a form of complicated migraine because of strong family histories of migraine reported in AHC cases.[4] AHC has also been considered to be a movement disorder or a form of epilepsy. Suggested causes have included channelopathy, mitochondrial dysfunction, and cerebrovascular dysfunction.[10] The disorder most closely related to AHC is familial hemiplegic migraine which is caused by a mutation in a gene for calcium channel receptors. It was thus thought that AHC may be caused by a similar channelopathy.[13]
## Diagnosis[edit]
As of 1993 only approximately 30 people with AHC had been described in scientific literature.[7] Due to the rarity and complexity of AHC, it is not unusual for the initial diagnosis to be incorrect, or for diagnosis to be delayed for several months after the initial symptoms become apparent.[8] The average age of diagnosis is just over 36 months.[4] Diagnosis of AHC is not only difficult because of its rarity, but because there is no diagnostic test, making this a diagnosis of exclusion. There are several generally accepted criteria which define this disorder, however other conditions with a similar presentation, such as HSV encephalitis, must first be ruled out. Due to these diagnostic difficulties, it is possible that the commonness of the disease is underestimated.[citation needed]
The following descriptions are commonly used in the diagnosis of AHC. The initial four criteria for classifying AHC were that it begins before 18 months of age, includes attacks of both hemiplegia on either side of the body, as well as other autonomic problems such as involuntary eye movement (episodic monocular nystagmus), improper eye alignment, choreoathetosis, and sustained muscle contractions (dystonia).[4][7] Finally, patients suffer from intellectual disabilities, delayed development, and other neurological abnormalities.[8][10] These diagnostic criteria were updated in 1993 to include the fact that all of these symptoms dissipate immediately upon sleeping. Diagnostic criteria were also expanded to include episodes of bilateral hemiplegia which shifted from one side of the body to the other.[10]
Recent criteria have been proposed for screening for AHC early, in order to improve the diagnostic timeline. These screening criteria include focal or unilateral paroxysmal dystonia in the first 6 months of life, as well as the possibility of flaccid hemiplegia either with or separate from these symptoms. Paroxysmal ocular movements should also be considered, and these should include both binocular and monocular symptoms which show in the first 3 months of life.[4]
## Treatments[edit]
Overall outcomes for AHC are generally poor, which is contributed to by AHC's various diagnostic and management challenges. In the long term, AHC is debilitating due to both the hemiplegic attacks and permanent damage associated with AHC. This damage can include cognitive impairment, behavioral and psychiatric disorders, and various motor impairments.[8] There is, however, not yet any conclusive evidence that AHC is fatal or that it shortens life expectancy, but the relatively recent discovery of the disorder makes large data for this type of information unavailable. Treatment for AHC has not been extremely successful, and there is no cure.[1] There are several drugs available for treatment, as well as management strategies for preventing and dealing with hemiplegic attacks.[citation needed]
### Management strategies[edit]
Hemiplegic attacks can be brought on by particular triggers, and management of AHC often centers around avoiding common or known triggers. While triggers vary greatly from person to person, there are also some common ones which are prevalent in many patients. Common triggers include temperature changes, water exposure, bright lights, certain foods, emotional stress, and physical activity. While avoiding triggers may help, it cannot prevent all hemiplegic episodes because many occur without being triggered. Because attacks and other associated symptoms end with sleep, various sedatives can be used to help patients sleep.[4][8]
### Flunarizine[edit]
The most common drug used to treat AHC is flunarizine. Flunarizine functions by acting as a calcium channel blocker. Other drugs, in order of frequency of use are benzodiazepines, carbamazapine, barbiturates, and valproic acid. Flunarizine is prescribed for the purpose of reducing the severity of AHC attacks and the number of episodes, though it rarely stops attacks altogether.[4] Minimizing the attacks may help reduce damage to the body from hemiplegic attacks and improve long-term outcomes as far as mental and physical disabilities are concerned.[1][13]
Experts differ in their confidence in flunarizine's effectiveness.[7][13] Some studies have found it to be very effective in reducing the duration, severity, and frequency of hemiplegic attacks.[13] It is generally considered the best treatment available, but this drug is thought by some to be of little benefit to AHC patients. Many patients suffer adverse effects without seeing any improvement.[7] Flunarizine also causes problems because it is difficult for patients to obtain, as it is not readily available in the United States.[citation needed]
### Sodium oxybate[edit]
Current research at the University of Utah is investigating whether sodium oxybate, also known as Gamma-Hydroxybutyric acid is an effective treatment for AHC.[16] Thus far, only a small number of patients have been sampled, and no conclusive results are yet available. While some success has been had thus far with the drug, AHC patients have been known to respond well initially to other drugs, but then the effectiveness will decline over time. Currently, sodium oxybate is used as a narcolepsy-cataplexy treatment, though in the past it has been used controversially in nutritional supplements. This drug was chosen to test because of a possible link between the causes of narcolepsy-cataplexy and AHC.[citation needed]
## References[edit]
1. ^ a b c d e f g Alternating Hemiplegia of Childhood Foundation. "What is AHC?". Archived from the original on 10 November 2010. Retrieved 2010-11-29.
2. ^ a b 2.Heinzen EL, Swoboda KJ, Hitomi Y, et al. (2012). "De novo mutations in ATP1A3 cause alternating hemiplegia of childhood". Nat Genet. 44 (9): 1030–4. doi:10.1038/ng.2358. PMC 3442240. PMID 22842232.
3. ^ Roswich H, Thiele H, Ohlenbusch A, et al. (2012). "Heterozygous de-novo mutations in ATP1A3 in patients with alternating hemiplegia of childhood: a whole-exome sequencing gene-identification study". Lancet Neurol. 11 (9): 764–73. doi:10.1016/S1474-4422(12)70182-5. PMID 22850527.
4. ^ a b c d e f g h i j k l m n o p q r s Sweney MT, Silver K, Gerard-Blanluet M, et al. (March 2009). "Alternating hemiplegia of childhood: early characteristics and evolution of a neurodevelopmental syndrome". Pediatrics. 123 (3): e534–41. doi:10.1542/peds.2008-2027. PMID 19254988.
5. ^ Heinzen, Erin L; Swoboda, Kathryn J; Hitomi, Yuki; Gurrieri, Fiorella; Nicole, Sophie; Vries, Boukje de; Tiziano, F Danilo; Fontaine, Bertrand; Walley, Nicole M (2012). "De novo mutations in ATP1A3 cause alternating hemiplegia of childhood". Nature Genetics. 44 (9): 1030–1034. doi:10.1038/ng.2358. PMC 3442240. PMID 22842232.
6. ^ Verret S, Steele JC (April 1971). "Alternating hemiplegia in childhood: a report of eight patients with complicated migraine beginning in infancy" (PDF). Pediatrics. 47 (4): 675–80. PMID 5089756.
7. ^ a b c d e f g h i j k l m Silver K, Andermann F (January 1993). "Alternating hemiplegia of childhood: a study of 10 patients and results of flunarizine treatment". Neurology. 43 (1): 36–41. doi:10.1212/WNL.43.1_Part_1.36. PMID 8423908.
8. ^ a b c d e f g h i j k Neville BG, Ninan M (October 2007). "The treatment and management of alternating hemiplegia of childhood". Dev Med Child Neurol. 49 (10): 777–80. doi:10.1111/j.1469-8749.2007.00777.x. PMID 17880649.
9. ^ a b c Saito Y, Inui T, Sakakibara T, Sugai K, Sakuma H, Sasaki M (August 2010). "Evolution of hemiplegic attacks and epileptic seizures in alternating hemiplegia of childhood". Epilepsy Res. 90 (3): 248–58. doi:10.1016/j.eplepsyres.2010.05.013. PMID 20580529.
10. ^ a b c d Haffejee S, Santosh PJ (January 2009). "Treatment of alternating hemiplegia of childhood with aripiprazole". Dev Med Child Neurol. 51 (1): 74–7. doi:10.1111/j.1469-8749.2008.03192.x. PMID 19087103.
11. ^ Mulas F, Smeyers P, Barbero P, Pitarch I, Velasco RP (2002). "Alternating hemiplegia in young babies". Rev Neurol (in Spanish). 34 (2): 157–62. PMID 11988911.
12. ^ Vigevano F, Andermann F, Aicardi J (1995). Alternating hemiplegia of childhood. New York: Raven Press. pp. 207–212. ISBN 978-0-7817-0163-1.
13. ^ a b c d e Sasaki M, Sakuragawa N, Osawa M (August 2001). "Long-term effect of flunarizine on patients with alternating hemiplegia of childhood in Japan". Brain Dev. 23 (5): 303–5. doi:10.1016/S0387-7604(01)00229-7. PMID 11504600.
14. ^ Reference, Genetics Home. "Alternating hemiplegia of childhood". Genetics Home Reference. Retrieved 2019-03-21.
15. ^ a b c "Alternating hemiplegia of childhood | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2019-03-21.
16. ^ University of Utah School of Medicine. Pediatric Motor Disorders Research Program. "University of Utah AHC Sodium Oxybate Trial". Retrieved 30 December 2015.
## External links[edit]
Classification
D
* OMIM: 104290
* MeSH: C536589
* DiseasesDB: 33595
* SNOMED CT: 230466004
External resources
* eMedicine: neuro/219
* Orphanet: 2131
* Alternating Hemiplegia Information Page at NINDS
* v
* t
* e
Genetic disorder, membrane: ATPase disorders
ATP1
* ATP1A2 (Alternating hemiplegia of childhood)
ATP2
* ATP2A1 (Brody myopathy)
* ATP2A2 (Darier's disease, Acrokeratosis verruciformis)
* ATP2C1 (Hailey–Hailey disease)
ATP7
* ATP7A (Menkes disease)
* ATP7B (Wilson's disease)
ATP13
* ATP13A2 (Kufor–Rakeb syndrome)
Other
* Osteopetrosis B1
see also ATPase
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Alternating hemiplegia of childhood | c3549447 | 4,491 | wikipedia | https://en.wikipedia.org/wiki/Alternating_hemiplegia_of_childhood | 2021-01-18T18:43:11 | {"gard": ["11"], "mesh": ["C536589"], "umls": ["C3549447"], "orphanet": ["2131"], "wikidata": ["Q2632848"]} |
For a discussion of genetic heterogeneity of quantitative trait loci for stature (STQTL), see STQTL1 (606255).
Mapping
Kimura et al. (2008) performed a genomewide association study with 23,465 microsatellite markers, applying selective genotyping to extremely tall and extremely short individuals from the Khalkh-Mongolian population. The most significant association was observed with SNP rs2220456 on chromosome 8q21.13 (p = 0.000016; corrected p = 0.0008). The authors noted that an approximately 300-kb region in the vicinity of the SNP had no coding sequence according to NCBI build 36.2.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| STATURE QUANTITATIVE TRAIT LOCUS 15 | c2675490 | 4,492 | omim | https://www.omim.org/entry/612578 | 2019-09-22T16:01:14 | {"omim": ["612578"]} |
Caudal appendage-deafness syndrome is characterized by caudal appendage, short terminal phalanges, deafness, cryptorchidism, intellectual deficit, short stature and dysmorphism. It has been described in monozygotic twin boys.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Caudal appendage-deafness syndrome | c2931593 | 4,493 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1123 | 2021-01-23T18:43:34 | {"gard": ["1163"], "mesh": ["C537713"], "umls": ["C2931593"], "synonyms": ["Caudal appendage-hearing loss syndrome", "Lynch-Lee-Murday syndrome"]} |
Neuroendocrine tumor
Micrograph of a neuroendocrine tumor. H&E stain
SpecialtyEndocrine oncology
Neuroendocrine tumors (NETs) are neoplasms that arise from cells of the endocrine (hormonal) and nervous systems. They most commonly occur in the intestine, where they are often called carcinoid tumors, but they are also found in the pancreas, lung and the rest of the body.
Although there are many kinds of NETs, they are treated as a group of tissue because the cells of these neoplasms share common features, such as looking similar, having special secretory granules, and often producing biogenic amines and polypeptide hormones.[1]
## Contents
* 1 Classification
* 1.1 WHO
* 1.2 Anatomic distribution
* 1.3 Grading
* 1.4 Staging
* 2 Signs and symptoms
* 2.1 Gastroenteropancreatic
* 2.1.1 Carcinoid tumors
* 2.1.2 Pancreatic neuroendocrine tumors
* 2.2 Other
* 2.3 Familial syndromes
* 3 Pathophysiology
* 4 Diagnosis
* 4.1 Markers
* 4.2 Imaging
* 4.3 Histopathology
* 4.3.1 Features in common
* 4.3.2 Argentaffin and hormone secretion
* 5 Treatment
* 5.1 Surgery
* 5.2 Symptomatic relief
* 5.3 Chemotherapy
* 5.3.1 Gastrointestinal neuroendocrine tumors
* 5.3.2 PanNETs
* 5.4 Radionuclide therapy
* 5.5 Hepatic artery
* 5.6 Other therapies
* 6 Epidemiology
* 7 History
* 8 References
* 9 External links
## Classification[edit]
### WHO[edit]
The World Health Organization (WHO) classification scheme places neuroendocrine tumors into three main categories, which emphasize the tumor grade rather than the anatomical origin:[2][3]
* well-differentiated neuroendocrine tumours, further subdivided into tumors with benign and those with uncertain behavior
* well-differentiated (low grade) neuroendocrine carcinomas with low-grade malignant behavior
* poorly differentiated (high grade) neuroendocrine carcinomas, which are the large cell neuroendocrine and small cell carcinomas.
Additionally, the WHO scheme recognizes mixed tumors with both neuroendocrine and epithelial carcinoma features, such as goblet cell cancer, a rare gastrointestinal tract tumor.[4]
Placing a given tumor into one of these categories depends on well-defined histological features: size, lymphovascular invasion, mitotic counts, Ki-67 labelling index, invasion of adjacent organs, presence of metastases and whether they produce hormones.[2][3]
### Anatomic distribution[edit]
Traditionally, neuroendocrine tumors have been classified by their anatomic site of origin. NETs can arise in many different areas of the body, and are most often located in the intestine, pancreas or the lungs. The various kinds of cells that can give rise to NETs are present in endocrine glands and are also diffusely distributed throughout the body, most commonly Kulchitsky cells or similar enterochromaffin-like cells, that are relatively more common in the gastrointestinal and pulmonary systems.[5]
NETs include certain tumors of the gastrointestinal tract and of the pancreatic islet cells,[1] certain thymus and lung tumors, and medullary carcinoma of the parafollicular cells of the thyroid.[1] Tumors with similar cellular characteristics in the pituitary, parathyroid, and adrenomedullary glands are sometimes included[6] or excluded.[1]
Within the broad category of neuroendocrine tumors there are many different tumor types:[7] this outline is presented to facilitate retrieving information. Neuroendocrine tumors are uncommon in many of these areas, and frequently represent only a very small proportion of the tumors or cancers at these locations.
* Pituitary gland: Neuroendocrine tumor of the anterior pituitary
* Thyroid gland: Neuroendocrine thyroid tumors, particularly medullary carcinoma
* Parathyroid tumors
* Thymus and mediastinal carcinoid tumors[8][9]
* Pulmonary neuroendocrine tumors[10][11]
* bronchus[9]
* pulmonary carcinoid tumors: typical carcinoid (TC; low-grade); atypical carcinoid (AC; intermediate-grade)
* small-cell lung cancer (SCLC)
* large cell neuroendocrine carcinoma of the lung (LCNEC)[12]
* Extrapulmonary small cell carcinomas (ESCC or EPSCC)
* Gastroenteropancreatic neuroendocrine tumors (GEP-NET)[13][14]
* Foregut GEP-NET (foregut tumors can conceptually encompasses not only NETs of the stomach and proximal duodenum, but also the pancreas, and even thymus, lung and bronchus)[citation needed]
* Pancreatic endocrine tumors (if considered separately from foregut GEP-NET)[15]
* Midgut GEP-NET (from distal half of 2nd part of the duodenum to the proximal two-thirds of the transverse colon)
* appendix,[16] including well differentiated NETs (benign); well differentiated NETs (uncertain malignant potential); well differentiated neuroendocrine carcinoma (with low malignant potential); mixed exocrine-neuroendocrine carcinoma (goblet cell carcinoma, also called adenocarcinoid and mucous adenocarcinoid)
* Hindgut GEP-NET[17][18]
* Liver[19][20][21] and gallbladder[22]
* Adrenal tumors, particularly adrenomedullary tumors
* Pheochromocytoma
* Peripheral nervous system tumors, such as:
* Schwannoma
* paraganglioma
* neuroblastoma
* Breast[23]
* Genitourinary tract
* urinary tract carcinoid tumor and neuroendocrine carcinoma[24][25]
* ovary
* neuroendocrine tumor of the cervix[26]
* Prostate tumor with neuroendocrine differentiation[27][28]
* testes
* Merkel cell carcinoma of skin (trabecular cancer)
* Several inherited conditions:[29]
* multiple endocrine neoplasia type 1 (MEN1)
* multiple endocrine neoplasia type 2 (MEN2)
* von Hippel-Lindau (VHL) disease[29]
* neurofibromatosis type 1[30][31]
* tuberous sclerosis[31][32]
* Carney complex[33][34]
### Grading[edit]
Neuroendocrine lesions are graded histologically according to markers of cellular proliferation, rather than cellular polymorphism. The following grading scheme is currently recommended for all gastroenteropancreatic neuroendocrine neoplasms by the World Health Organization:[35]
Mitoses in a neuroendocrine tumor.
G Mitotic count (per 10 HPF) Ki-67 index (%)
GX Grade cannot be assessed
G1 < 2 < 3%
G2 2 to 20 3–20%
G3 > 20 > 20%
If mitotic count and Ki-67 are discordant, the figure which gives the highest grade is used.
G1 and G2 neuroendocrine neoplasms are called neuroendocrine tumors (NETs) – formerly called carcinoid tumours. G3 neoplasms are called neuroendocrine carcinomas (NECs).
It has been proposed that the current G3 category be further separated into histologically well-differentiated and poorly-differentiated neoplasms to better reflect prognosis.[36]
### Staging[edit]
Lymph node metastasis of a neuroendocrine tumor.
Currently there is no one staging system for all neuroendocrine neoplasms. Well differentiated lesions generally have their own staging system based on anatomical location, whereas poorly differentiated and mixed lesions are staged as carcinomas of that location. For example, gastric NEC and mixed adenoneuroendocrine cancers are staged as a primary carcinoma of the stomach.[37]
TNM staging of gastroenteropancreatic Grade 1 and Grade 2 neuroendocrine tumors is as follows:
Stomach[38] Primary Tumor (T)
T Category Tumor Criteria
TX Primary tumour cannot be assessed
T0 No evidence of primary tumour
T1 Invades the lamina propria or submucosa, and less than or equal to 1 cm in size
T2 Invades the muscularis propria, or greater than 1 cm in size
T3 Invades through the muscularis propria into subserosal tissue without penetration of overlying serosa
T4 Invades visceral peritoneum (serosal) or other organs or adjacent structures
Regional Lymph Node (N)
N Category N Criteria
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
Distant Metastasis (M)
M Category M Criteria
M0 No distant metastasis
M1 Distant metastasis
M1a Metastasis confined to liver
M1b Metastasis in at least one extra-hepatic site
M1c Both hepatic and extra-hepatic metastases
AJCC Prognostic Stage Groups
Stage Criteria
I T1, N0, M0
II T2 or T3, N0, M0
III Any T, N1, M0; T4, N0, M0
IV Any T, any N, M1
Duodenum / Ampulla of Vater[39] Primary Tumor (T)
T Category Tumor Criteria
TX Primary tumour cannot be assessed
T1 Invades the mucosa or submucosa only, and less than or equal to 1 cm in size (duodenal tumors)
Confined within the sphincter of Oddi, and less than or equal to 1 cm in size (ampullary tumors)
T2 Invades the muscularis propria, or is > 1 cm (duodenal)
Invades through sphincter into duodenal submucosa or muscularis propria, or is > 1 cm (ampullary)
T3 Invades the pancreas or peripancreatic adipose tissue
T4 Invades visceral peritoneum (serosal) or other organs
Regional Lymph Node (N)
N Category N Criteria
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
Distant Metastasis (M)
M Category M Criteria
M0 No distant metastasis
M1 Distant metastasis
M1a Metastasis confined to liver
M1b Metastasis in at least one extra-hepatic site
M1c Both hepatic and extra-hepatic metastases
AJCC Prognostic Stage Groups
Stage Criteria
I T1, N0, M0
II T2 or T3, N0, M0
III T4, N0, M0; Any T, N1, M0
IV Any T, any N, M1
Jejunum and Ileum[40] Primary Tumor (T)
T Category Tumor Criteria
TX Primary tumour cannot be assessed
T0 No evidence of primary tumour
T1 Invades the lamina propria or submucosa, and less than or equal to 1 cm in size
T2 Invades the muscularis propria, or greater than 1 cm in size
T3 Invades through the muscularis propria into subserosal tissue without penetration of overlying serosa
T4 Invades visceral peritoneum (serosal) or other organs or adjacent structures
Regional Lymph Node (N)
N Category N Criteria
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis less than 12 nodes
N2 Large mesenteric masses (> 2 cm) and / or extensive nodal deposits (12 or greater), especially those that encase the superior mesenteric vessels
Distant Metastasis (M)
M Category M Criteria
M0 No distant metastasis
M1 Distant metastasis
M1a Metastasis confined to liver
M1b Metastasis in at least one extra-hepatic site
M1c Both hepatic and extra-hepatic metastases
AJCC Prognostic Stage Groups
Stage Criteria
I T1, N0, M0
II T2 or T3, N0, M0
III Any T, N1 or N2, M0; T4, N0, M0;
IV Any T, any N, M1
Appendix[41] Primary Tumor (T)
T Category Tumor Criteria
TX Primary tumour cannot be assessed
T0 No evidence of primary tumour
T1 2 cm or less in greatest dimension
T2 Tumor more than 2 cm but less than or equal to 4 cm
T3 Tumor more than 4 cm or with subserosal invasion or involvement of the mesoappendix
T4 Perforates the peritoneum or directly invades other organs or structures (excluding direct mural extension to adjacent subserosa of adjacent bowel)
Regional Lymph Node (N)
N Category N Criteria
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
Distant Metastasis (M)
M Category M Criteria
M0 No distant metastasis
M1 Distant metastasis
M1a Metastasis confined to liver
M1b Metastasis in at least one extra-hepatic site
M1c Both hepatic and extra-hepatic metastases
AJCC Prognostic Stage Groups
Stage Criteria
I T1, N0, M0
II T2 or T3, N0, M0
III Any T, N1, M0; T4, N1, M0
IV Any T, any N, M1
Colon and Rectum[42] Primary Tumor (T)
T Category Tumor Criteria
TX Primary tumour cannot be assessed
T0 No evidence of primary tumour
T1 Invades the lamina propria or submucosa, and less than or equal to 2 cm
T1a Less than 1 cm in greatest dimension
T1b 1–2 cm in greatest dimension
T2 Invades the muscularis propria, or greater than 2 cm in size with invasion of the lamina propria or submucosa
T3 Invades through the muscularis propria into subserosal tissue without penetration of overlying serosa
T4 Invades visceral peritoneum (serosal) or other organs or adjacent structures
Regional Lymph Node (N)
N Category N Criteria
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
Distant Metastasis (M)
M Category M Criteria
M0 No distant metastasis
M1 Distant metastasis
M1a Metastasis confined to liver
M1b Metastasis in at least one extra-hepatic site
M1c Both hepatic and extra-hepatic metastases
AJCC Prognostic Stage Groups
Stage Criteria
I T1, N0, M0
IIA T2, N0, M0
IIB T3, N0, M0
IIIA T4, N0, M0
IIIB Any T, N1, M0
IV Any T, any N, M1
Pancreas[43] Primary Tumor (T)
T Category Tumor Criteria
TX Primary tumour cannot be assessed
T1 Limited to the pancreas, less than or equal to 2 cm in size
T2 Limited to the pancreas, 2–4 cm in size
T3 Limited to the pancreas, > 4 cm; or invading the duodenum or bile duct
T4 Invading adjacent organs or the wall of large vessels
Regional Lymph Node (N)
N Category N Criteria
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node involvement
N1 Regional lymph node involvement
Distant Metastasis (M)
M Category M Criteria
M0 No distant metastasis
M1 Distant metastasis
M1a Metastasis confined to liver
M1b Metastasis in at least one extra-hepatic site
M1c Both hepatic and extra-hepatic metastases
AJCC Prognostic Stage Groups
Stage Criteria
I T1, N0, M0
II T2 or T3, N0, M0
III Any T, N1, M0; T4, N0, M0
IV Any T, any N, M1
## Signs and symptoms[edit]
### Gastroenteropancreatic[edit]
Conceptually, there are two main types of NET within the gastroenteropancreatic neuroendocrine tumors (GEP-NET) category: those which arise from the gastrointestinal (GI) system and those that arise from the pancreas. In usage, the term "carcinoid" has often been applied to both, although sometimes it is restrictively applied to NETs of GI origin (as herein), or alternatively to those tumors which secrete functional hormones or polypeptides associated with clinical symptoms, as discussed.[citation needed]
#### Carcinoid tumors[edit]
Main article: Carcinoid
Carcinoids most commonly affect the small bowel, particularly the ileum, and are the most common malignancy of the appendix. Many carcinoids are asymptomatic and are discovered only upon surgery for unrelated causes. These coincidental carcinoids are common; one study found that one person in ten has them.[44] Many tumors do not cause symptoms even when they have metastasized.[45] Other tumors even if very small can produce adverse effects by secreting hormones.[46]
Ten per cent (10%)[47] or less of carcinoids, primarily some midgut carcinoids, secrete excessive levels of a range of hormones, most notably serotonin (5-HT) or substance P,[48] causing a constellation of symptoms called carcinoid syndrome:
* flushing
* diarrhea
* asthma or wheezing
* congestive heart failure (CHF)
* abdominal cramping
* peripheral edema
* heart palpitations
A carcinoid crisis with profound flushing, bronchospasm, tachycardia, and widely and rapidly fluctuating blood pressure[1] can occur if large amounts of hormone are acutely secreted,[48] which is occasionally triggered by factors such as diet,[48] alcohol,[48] surgery[1][48] chemotherapy,[48] embolization therapy or radiofrequency ablation.[1]
Chronic exposure to high levels of serotonin causes thickening of the heart valves, particularly the tricuspid and the pulmonic valves, and over a long period can lead to congestive heart failure.[48] However, valve replacement is rarely needed.[49] The excessive outflow of serotonin can cause a depletion of tryptophan leading to niacin deficiency, and thus pellagra,[1] which is associated with dermatitis, dementia, and diarrhea. Many other hormones can be secreted by some of these tumors, most commonly growth hormone that can cause acromegaly, or cortisol, that can cause Cushing's syndrome.[citation needed]
Occasionally, haemorrhage or the effects of tumor bulk are the presenting symptoms. Bowel obstruction can occur, sometimes due to fibrosing effects of NET secretory products[46] with an intense desmoplastic reaction at the tumor site, or of the mesentery.
#### Pancreatic neuroendocrine tumors[edit]
Main article: Pancreatic neuroendocrine tumor
Pancreatic neuroendocrine tumors (PanNETs) are often referred to as "islet cell tumors",[50][51] or "pancreatic endocrine tumors"[2]
The PanNET denomination is in line with current WHO guidelines. Historically, PanNETs have also been referred to by a variety of terms, and are still often called "islet cell tumors" or "pancreatic endocrine tumors".[52] originate within the pancreas. PanNETs are quite distinct from the usual form of pancreatic cancer, adenocarcinoma, which arises in the exocrine pancreas. About 95 percent of pancreatic tumors are adenocarcinoma; only 1 or 2% of clinically significant pancreas neoplasms are GEP-NETs.[citation needed]
Well or intermediately differentiated PanNETs are sometimes called islet cell tumors; neuroendocrine cancer (NEC) (synonymous with islet cell carcinoma) is more aggressive. Up to 60% of PanNETs are nonsecretory or nonfunctional, which either don’t secrete, or the quantity or type of products such as pancreatic polypeptide (PPoma), chromogranin A, and neurotensin do not cause a clinical syndrome, although blood levels may be elevated.[29] Functional tumors are often classified by the hormone most strongly secreted by the pancreatic neuroendocrine tumor, as discussed in that main article.
### Other[edit]
In addition to the two main categories of GEP-NET, there are rarer forms of neuroendocrine tumors that arise anywhere in the body, including within the lung, thymus and parathyroid. Bronchial carcinoid can cause airway obstruction, pneumonia, pleurisy, difficulty with breathing, cough, and hemoptysis, or may be associated with weakness, nausea, weight loss, night sweats, neuralgia, and Cushing's syndrome. Some are asymptomatic.[citation needed]
Animal neuroendocrine tumors include neuroendocrine cancer of the liver in dogs, and devil facial tumor disease in Tasmanian devils.[53][54][55]
### Familial syndromes[edit]
Most pancreatic NETs are sporadic.[50] However, neuroendocrine tumors can be seen in several inherited familial syndromes, including:[29]
* multiple endocrine neoplasia type 1 (MEN1)
* multiple endocrine neoplasia type 2 (MEN2)
* von Hippel-Lindau (VHL) disease[29]
* neurofibromatosis type 1[30]
* tuberous sclerosis[31][32]
* Carney complex[33][34]
Given these associations, recommendations in NET include family history evaluation, evaluation for second tumors, and in selected circumstances testing for germline mutations such as for MEN1.[1]
## Pathophysiology[edit]
NETs are believed to arise from various neuroendocrine cells whose normal function is to serve at the neuroendocrine interface. Neuroendocrine cells are present not only in endocrine glands throughout the body that produce hormones, but are found in all body tissues.[56]
## Diagnosis[edit]
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### Markers[edit]
Symptoms from secreted hormones may prompt measurement of the corresponding hormones in the blood or their associated urinary products, for initial diagnosis or to assess the interval change in the tumor. Secretory activity of the tumor cells is sometimes dissimilar to the tissue immunoreactivity to particular hormones.[57]
Synaptophysin immunohistochemistry of neuroendocrine tumor, staining positively.
Given the diverse secretory activity of NETs there are many other potential markers, but a limited panel is usually sufficient for clinical purposes.[1] Aside from the hormones of secretory tumors, the most important markers are:
* chromogranin A (CgA), present in 99% of metastatic carcinoid tumors[58]
* urine 5-hydroxyindoleacetic acid (5-HIAA)
* neuron-specific enolase (NSE, gamma-gamma dimer)
* synaptophysin (P38)
Newer markers include N-terminally truncated variant of Hsp70 is present in NETs but absent in normal pancreatic islets.[59] High levels of CDX2, a homeobox gene product essential for intestinal development and differentiation, are seen in intestinal NETs. Neuroendocrine secretory protein-55, a member of the chromogranin family, is seen in pancreatic endocrine tumors but not intestinal NETs.[59]
### Imaging[edit]
For morphological imaging, CT-scans, MRIs, sonography (ultrasound), and endoscopy (including endoscopic ultrasound) are commonly used. Multiphase CT and MRI are typically used both for diagnostics and for evaluation of therapy. The multiphase CT should be performed before and after an intravenous injection of an iodine-based contrast agent, both in the late arterial phase and in the portal venous phase (triple-phase study). While MRI is generally superior to CT, both for detection of the primary tumor and for evaluation of metastases, CECT is more widely available, even at academic institutions. Therefore, multiphase CT is often the modality of choice.[3][60]
Advances in nuclear medicine imaging, also known as molecular imaging, has improved diagnostic and treatment paradigms in patients with neuroendocrine tumors. This is because of its ability to not only identify sites of disease but also characterize them. Neuronedocrine tumours express somatostatin receptors providing a unique target for imaging. Octreotide is a synthetic modifications of somatostatin with a longer half-life.[citation needed] OctreoScan, also called somatostatin receptor scintigraphy (SRS or SSRS), utilizes intravenously administered octreotide that is chemically bound to a radioactive substance, often indium-111, to detect larger lesions with tumor cells that are avid for octreotide.[citation needed]
Somatostatin receptor imaging can now be performed with positron emission tomography (PET) which offers higher resolution, three-dimensional and more rapid imaging. Gallium-68 receptor PET-CT is much more accurate than an OctreoScan.[61]
Imaging with fluorine-18 fluorodeoxyglucose (FDG) PET may be valuable to image some neuroendocrine tumors.[62] This scan is performed by injected radioactive sugar intravenously. Tumors that grow more quickly use more sugar. Using this scan, the aggressiveness of the tumor can be assessed.[citation needed]
Functional imaging with Gallium-labelled somatostatin analog and 18F-FDG PET tracers ensures better staging and prognostication of neuroendocrine neoplasms.[63]
The combination of somatostatin receptor and FDG PET imaging is able to quantify somatostatin receptor cell surface (SSTR) expression and glycolytic metabolism, respectively.[62] The ability to perform this as a whole body study is highlighting the limitations of relying on histopathology obtained from a single site. This is enabling better selection of the most appropriate therapy for an individual patient.[64]
### Histopathology[edit]
Small intestinal neuroendocrine tumor at bottom third of image, showing the typical intramural (within the wall) location, and overlying intact epithelium. H&E stain
#### Features in common[edit]
Neuroendocrine tumors, despite differing embryological origin, have common phenotypic characteristics. NETs show tissue immunoreactivity for markers of neuroendocrine differentiation (pan-neuroendocrine tissue markers) and may secrete various peptides and hormones. There is a lengthy list of potential markers in neuroendocrine tumors; several reviews provide assistance in understanding these markers.[65][57] Widely used neuroendocrine tissue markers are various chromogranins, synaptophysin and PGP9.5. Neuron-specific enolase (NSE) is less specific.[1][5] The nuclear neuroendocrine marker insulinoma-associated protein-1 (INSM1) has proven to be sensitive as well as highly specific for neuroendocrine differentiation.[66]
NETs are often small, yellow or tan masses, often located in the submucosa or more deeply intramurally, and they can be very firm due to an accompanying intense desmoplastic reaction. The overlying mucosa may be either intact or ulcerated. Some GEP-NETs invade deeply to involve the mesentery.[citation needed] Histologically, NETs are an example of "small blue cell tumors," showing uniform cells which have a round to oval stippled nucleus and scant, pink granular cytoplasm. The cells may align variously in islands, glands or sheets. High power examination shows bland cytopathology. Electron microscopy can identify secretory granules. There is usually minimal pleomorphism but less commonly there can be anaplasia, mitotic activity, and necrosis.[citation needed]
Some neuroendocrine tumor cells possess especially strong hormone receptors, such as somatostatin receptors and uptake hormones strongly. This avidity can assist in diagnosis and may make some tumors vulnerable to hormone targeted therapies.[citation needed]
#### Argentaffin and hormone secretion[edit]
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NETs from a particular anatomical origin often show similar behavior as a group, such as the foregut (which conceptually includes pancreas, and even thymus, airway and lung NETs), midgut and hindgut; individual tumors within these sites can differ from these group benchmarks:
* Foregut NETs are argentaffin negative. Despite low serotonin content, they often secrete 5-hydroxytryptophan (5-HTP), histamine, and several polypeptide hormones. There may be associated atypical carcinoid syndrome, acromegaly, Cushing disease, other endocrine disorders, telangiectasia, or hypertrophy of the skin in the face and upper neck.[67] These tumors can metastasize to bone.
* Midgut NETs are argentaffin positive, can produce high levels of serotonin 5-hydroxytryptamine (5-HT), kinins, prostaglandins, substance P (SP), and other vasoactive peptides, and sometimes produce corticotropic hormone (previously adrenocorticotropic hormone [ACTH]). Bone metastasis is uncommon.
* Hindgut NETs are argentaffin negative and rarely secrete 5-HT, 5-HTP, or any other vasoactive peptides. Bone metastases are not uncommon.
## Treatment[edit]
Several issues help define appropriate treatment of a neuroendocrine tumor, including its location, invasiveness, hormone secretion, and metastasis. Treatments may be aimed at curing the disease or at relieving symptoms (palliation). Observation may be feasible for non-functioning low grade neuroendocrine tumors. If the tumor is locally advanced or has metastasized, but is nonetheless slowly growing, treatment that relieves symptoms may often be preferred over immediate challenging surgeries.[citation needed]
Intermediate and high grade tumors (noncarcinoids) are usually best treated by various early interventions (active therapy) rather than observation (wait-and-see approach).[68]
Treatments have improved over the past several decades, and outcomes are improving.[46] In malignant carcinoid tumors with carcinoid syndrome, the median survival has improved from two years to more than eight years.[69]
Detailed guidelines for managing neuroendocrine tumors are available from ESMO,[70] NCCN[71] and a UK panel.[1] The NCI has guidelines for several categories of NET: islet cell tumors of the pancreas,[72] gastrointestinal carcinoids,[73] Merkel cell tumors[74] and pheochromocytoma/paraganglioma.[75]
### Surgery[edit]
Even if the tumor has advanced and metastasized, making curative surgery infeasible, surgery often has a role in neuroendocrine cancers for palliation of symptoms and possibly increased lifespan.[68]
Cholecystectomy is recommended if there is a consideration of long-term treatment with somatostatin analogs.[76]:46
### Symptomatic relief[edit]
In secretory tumors, somatostatin analogs given subcutaneously or intramuscularly alleviate symptoms by blocking hormone release. A consensus review has reported on the use of somatostatin analogs for GEP-NETs.[77]
These medications may also anatomically stabilize or shrink tumors, as suggested by the PROMID study (Placebo-controlled prospective randomized study on the antiproliferative efficacy of Octreotide LAR in patients with metastatic neuroendocrine MIDgut tumors): at least in this subset of NETs, average tumor stabilization was 14.3 months compared to 6 months for placebo.[78]
The CLARINET study (a randomized, double-blind, placebo-controlled study on the antiproliferative effects of lanreotide in patients with enteropancreatic neuroendocrine tumors) further demonstrated the antiproliferative potential of lanreotide, a somatostatin analog and recently approved FDA treatment for GEP-NETS. In this study, lanreotide showed a statistically significant improvement in progression-free survival, meeting its primary endpoint. The disease in sixty five percent of patients treated with lanreotide in the study had not progressed or caused death at 96 weeks, the same was true of 33% of patients on placebo. This represented a 53% reduction in risk of disease progression or death with lanreotide based on a hazard ratio of .47.[79]
Lanreotide is the first and only FDA approved antitumor therapy demonstrating a statistically significant progression-free survival benefit in a combined population of patients with GEP-NETS.[citation needed]
Other medications that block particular secretory effects can sometimes relieve symptoms.[49]
### Chemotherapy[edit]
Interferon is sometimes used to treat GEP-NETs.[80] Its effectiveness is somewhat uncertain, but low doses can be titrated within each person, often considering the effect on the blood leukocyte count;[80] Interferon is often used in combination with other agents, especially somatostatin analogs such as octreotide.[citation needed]
#### Gastrointestinal neuroendocrine tumors[edit]
Most gastrointestinal carcinoid tumors tend not to respond to chemotherapy agents,[49] showing 10 to 20% response rates that are typically less than 6 months. Combining chemotherapy medications has not usually been of significant improvement[49] showing 25 to 35% response rates that are typically less than 9 months.
The exceptions are poorly differentiated (high-grade or anaplastic) metastatic disease, where cisplatin with etoposide may be used[49] and Somatostatin Receptor Scintigraphy (SSRS) negative tumors which had a response rate in excess of 70% compared to 10% in strongly positive SRSS carcinoid tumors.[1]
#### PanNETs[edit]
Main article: Pancreatic neuroendocrine tumor § Treatment
Targeted therapy with everolimus (Afinitor) and sunitinib (Sutent) is approved by the FDA in unresectable, locally advanced or metastatic PanNETs. Some PanNETs are more responsive to chemotherapy than gastroenteric carcinoid tumors. Several agents have shown activity[49] and combining several medicines, particularly doxorubicin with streptozocin and fluorouracil (5-FU or f5U), is often more effective. Although marginally effective in well-differentiated PETs, cisplatin with etoposide is active in poorly differentiated neuroendocrine cancers (PDNECs).[49]
### Radionuclide therapy[edit]
Peptide receptor radionuclide therapy (PRRT) is a type of radioisotope therapy (RIT)[6] in which a peptide or hormone conjugated to a radionuclide or radioligand is given intravenously, the peptide or neuroamine hormone previously having shown good uptake of a tracer dose, using Somatostatin receptor imaging as detailed above. This type of radiotherapy is a systemic therapy and will impact somatostatin positive disease.[81] The peptide receptor may be bound to lutetium-177, yttrium-90, indium-111 and other isotopes including alpha emitters.[82] This is a highly targeted and effective therapy with minimal side effects in tumors with high levels of somatostatin cell surface expression, because the radiation is absorbed at the sites of the tumor, or excreted in the urine. The radioactively labelled hormones enter the tumor cells which, together with nearby cells, are damaged by the attached radiation. Not all cells are immediately killed; cell death can go on for up to two years.[citation needed]
PRRT was initially used for low grade NETs. It is also very useful in more aggressive NETs such as Grade 2 and 3 NETs[83][84] provided they demonstrate high uptake on SSTR imaging to suggest benefit.
### Hepatic artery[edit]
Main article: Hepatic artery embolization
Metastases to the liver can be treated by several types of hepatic artery treatments based on the observation that tumor cells get nearly all their nutrients from the hepatic artery, while the normal cells of the liver get about 70–80 percent of their nutrients and 50% their oxygen supply from the portal vein, and thus can survive with the hepatic artery effectively blocked.[46][85]
* Hepatic artery embolization (HAE) occludes the blood flow to the tumors, achieving significant tumor shrinkage in over 80%.[48] In hepatic artery chemotherapy, the chemotherapy agents are given into the hepatic artery, often by steady infusion over hours or even days. Compared with systemic chemotherapy, a higher proportion of the chemotherapy agents are (in theory) delivered to the lesions in the liver.[85]
* Hepatic artery chemoembolization (HACE), sometimes called transarterial chemoembolization (TACE), combines hepatic artery embolization with hepatic artery chemoinfusion: embospheres bound with chemotherapy agents, injected into the hepatic artery, lodge in downstream capillaries. The spheres not only block blood flow to the lesions, but by halting the chemotherapy agents in the neighborhood of the lesions, they provide a much better targeting leverage than chemoinfusion provides.[citation needed]
* Selective internal radiation therapy (SIRT)[86] for neuroendocrine metastases to the liver[87] delivers radioactive microsphere therapy (RMT) by injection into the hepatic artery, lodging (as with HAE and HACE) in downstream capillaries. In contrast to hormone-delivered radiotherapy, the lesions need not overexpress peptide receptors. The mechanical targeting delivers the radiation from the yttrium-labeled microspheres selectively to the tumors without unduly affecting the normal liver.[88] This type of treatment is FDA approved for liver metastases secondary to colorectal carcinoma and is under investigation for treatment of other liver malignancies, including neuroendocrine malignancies.[86]
### Other therapies[edit]
Radiofrequency ablation (RFA) is used when a patient has relatively few metastases.[citation needed] In RFA, a needle is inserted into the center of the lesion and current is applied to generate heat; the tumor cells are killed by cooking.[citation needed]
Cryoablation is similar to RFA; an endothermic substance[citation needed] is injected into the tumors to kill by freezing. Cryoablation has been less successful for GEP-NETs than RFA.[citation needed]
AdVince, a type of gene therapy using a genetically modified oncolytic adenovirus[89] and supported by the crowdfunding campaign iCancer[90] was used in a Phase 1 trial against NET in 2016.[91]
## Epidemiology[edit]
Although estimates vary, the annual incidence of clinically significant neuroendocrine tumors is approximately 2.5–5 per 100,000;[92] two thirds are carcinoid tumors and one third are other NETs.
The prevalence has been estimated as 35 per 100,000,[92] and may be considerably higher if clinically silent tumors are included. An autopsy study of the pancreas in people who died from unrelated causes discovered a remarkably high incidence of tiny asymptomatic NETs. Routine microscopic study of three random sections of the pancreas found NETs in 1.6%, and multiple sections identified NETs in 10%.[93] As diagnostic imaging increases in sensitivity, such as endoscopic ultrasonography, very small, clinically insignificant NETs may be coincidentally discovered; being unrelated to symptoms, such neoplasms may not require surgical excision.[citation needed]
## History[edit]
Small intestinal neuroendocrine tumors were first distinguished from other tumors in 1907.[94][45] They were named carcinoid tumors because their slow growth was considered to be "cancer-like" rather than truly cancerous.[45]
However, in 1938 it was recognized that some of these small bowel tumors could be malignant.[94][45] Despite the differences between these two original categories, and further complexities due to subsequent inclusion of other NETs of pancreas and pulmonary origin, all NETs are sometimes (incorrectly) subsumed into the term "carcinoid".[citation needed]
Enterochromaffin cells, which give rise to carcinoid tumors, were identified in 1897 by Nikolai Kulchitsky and their secretion of serotonin was established in 1953[94] when the "flushing" effect of serotonin had become clinically recognized. Carcinoid heart disease was identified in 1952, and carcinoid fibrosis in 1961.[94]
Neuroendocrine tumors were sometimes called APUDomas because these cells often show amine precursor (L-DOPA and 5-hydroxytryptophan) uptake and decarboxylation to produce biogenic amines such as catecholamines and serotonin. Although this behavior was also part of the disproven hypothesis that these cells might all embryologically arise from the neural crest,[56][68][69] neuroendocrine cells sometimes produce various types of hormones and amines,[69] and they can also have strong receptors for other hormones to which they respond.
There have been multiple nomenclature systems for these tumors,[2] and the differences between these schema have often been confusing. Nonetheless, these systems all distinguish between well-differentiated (low and intermediate-grade) and poorly differentiated (high-grade) NETs. Cellular proliferative rate is of considerable significance in this prognostic assessment.[2]
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86. ^ a b Welsh, J.; Kennedy, A.; Thomadsen, B. (2006). "Selective internal radiation therapy (SIRT) for liver metastases secondary to colorectal adenocarcinoma". International Journal of Radiation OncologyBiologyPhysics. 66 (2): S62–S73. doi:10.1016/j.ijrobp.2005.09.011. PMID 16979443.
87. ^ Van De Wiele, C.; Defreyne, L.; Peeters, M.; Lambert, B. (2009). "Yttrium-90 labelled resin microspheres for treatment of primary and secondary malignant liver tumors". The Quarterly Journal of Nuclear Medicine and Molecular Imaging. 53 (3): 317–24. PMID 19521311.
88. ^ Salem, R.; Thurston, K.; Carr, B.; Goin, J.; Geschwind, J. (2002). "Yttrium-90 microspheres: Radiation therapy for unresectable liver cancer". Journal of Vascular and Interventional Radiology. 13 (9 Pt 2): S223–S229. doi:10.1016/S1051-0443(07)61790-4. PMID 12354840.
89. ^ Masters, Alexander (2014-10-14). "A plutocratic proposal". Mosaic. The Wellcome Trust. Archived from the original on 2016-05-29. Retrieved 2016-07-03.
90. ^ "iCancer web site". icancer.org.uk. Archived from the original on 2016-07-14. Retrieved 2016-07-03.
91. ^ Masters, Alexander (2016-07-02). "Can crowdfunding really cure cancer? Alexander Masters investigates a pioneering new project". The Telegraph. Archived from the original on 2016-07-03. Retrieved 2016-07-03.
92. ^ a b Öberg, K.; Castellano, D. (2011). "Current knowledge on diagnosis and staging of neuroendocrine tumors". Cancer and Metastasis Reviews. 30: 3–7. doi:10.1007/s10555-011-9292-1. PMID 21311954. S2CID 29720754.
93. ^ Kimura, W.; Kuroda, A.; Morioka, Y. (1991). "Clinical pathology of endocrine tumors of the pancreas". Digestive Diseases and Sciences. 36 (7): 933–42. doi:10.1007/BF01297144. PMID 2070707. S2CID 20567425.
94. ^ a b c d Modlin, I.M.; Shapiro, M.D.; Kidd, M. (2004). "Siegfried oberndorfer: Origins and perspectives of carcinoid tumors". Human Pathology. 35 (12): 1440–51. doi:10.1016/j.humpath.2004.09.018. PMID 15619202.
## External links[edit]
Wikimedia Commons has media related to Neuroendocrine tumors.
* The Neuroendocrine Cancer Awareness Network (NCAN)
* Neuroendocrine tumor at Curlie
* Neuroendocrine Tumor Research Foundation
Classification
D
* ICD-10-CM: C7A.0-C7A.8, C7B.0-C7B.8
* ICD-9-CM: 209
* ICD-O: M8013/3, M8041/3, M8246/3, M8247/3, M8574/3
* MeSH: D018358
* v
* t
* e
Glandular and epithelial cancer
Epithelium
Papilloma/carcinoma
* Small-cell carcinoma
* Combined small-cell carcinoma
* Verrucous carcinoma
* Squamous cell carcinoma
* Basal-cell carcinoma
* Transitional cell carcinoma
* Inverted papilloma
Complex epithelial
* Warthin's tumor
* Thymoma
* Bartholin gland carcinoma
Glands
Adenomas/
adenocarcinomas
Gastrointestinal
* tract: Linitis plastica
* Familial adenomatous polyposis
* pancreas
* Insulinoma
* Glucagonoma
* Gastrinoma
* VIPoma
* Somatostatinoma
* Cholangiocarcinoma
* Klatskin tumor
* Hepatocellular adenoma/Hepatocellular carcinoma
Urogenital
* Renal cell carcinoma
* Endometrioid tumor
* Renal oncocytoma
Endocrine
* Prolactinoma
* Multiple endocrine neoplasia
* Adrenocortical adenoma/Adrenocortical carcinoma
* Hürthle cell
Other/multiple
* Neuroendocrine tumor
* Carcinoid
* Adenoid cystic carcinoma
* Oncocytoma
* Clear-cell adenocarcinoma
* Apudoma
* Cylindroma
* Papillary hidradenoma
Adnexal and
skin appendage
* sweat gland
* Hidrocystoma
* Syringoma
* Syringocystadenoma papilliferum
Cystic, mucinous,
and serous
Cystic general
* Cystadenoma/Cystadenocarcinoma
Mucinous
* Signet ring cell carcinoma
* Krukenberg tumor
* Mucinous cystadenoma / Mucinous cystadenocarcinoma
* Pseudomyxoma peritonei
* Mucoepidermoid carcinoma
Serous
* Ovarian serous cystadenoma / Pancreatic serous cystadenoma / Serous cystadenocarcinoma / Papillary serous cystadenocarcinoma
Ductal, lobular,
and medullary
Ductal carcinoma
* Mammary ductal carcinoma
* Pancreatic ductal carcinoma
* Comedocarcinoma
* Paget's disease of the breast / Extramammary Paget's disease
Lobular carcinoma
* Lobular carcinoma in situ
* Invasive lobular carcinoma
Medullary carcinoma
* Medullary carcinoma of the breast
* Medullary thyroid cancer
Acinar cell
* Acinic cell carcinoma
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Neuroendocrine tumor | c0206754 | 4,494 | wikipedia | https://en.wikipedia.org/wiki/Neuroendocrine_tumor | 2021-01-18T18:58:08 | {"gard": ["13445"], "mesh": ["D018358"], "umls": ["C0206754"], "wikidata": ["Q1981276"]} |
## Description
HSR1 was originally identified as a noncoding eukaryotic RNA involved in activation of heat shock factor-1 (HSF1; 140580) (Shamovsky et al., 2006). However, more recent evidence suggests a bacterial origin for HSR1 (Kim et al., 2010).
Cloning and Expression
Shamovsky et al. (2006) identified HSR1 as an unknown component required for activation of heat-shock factor-1 (HSF1; 140580). HSR1 RNA migrated at approximately 2 kb on denaturing polyacrylamide gel electrophoresis. Shamovsky et al. (2006) cloned HSR1 from BHK (Syrian hamster) and HeLa cells and found it to be a noncoding RNA about 600 nucleotides long without a poly(A) tail. Sequence comparison of HSR1 from BHK and HeLa cells revealed a high degree of homology, with only a 4-nucleotide difference. Northern blot analysis showed that HSR1 was constitutively expressed in BHK and HeLa cells, and its level seemed unaffected by heat shock.
Kim et al. (2010) found no HSR1 sequences by exhaustive searches of eukaryotic nucleotide sequence databases. Instead, they found that HSR1 shows strong sequence similarity to the 5-prime flanking region and part of the coding region of bacterial chloride channel proteins. They hypothesized that HSR1 was derived from a bacterial genome fragment either by horizontal gene transfer or bacterial infection.
Gene Function
Activation of HSF1 by heat and other stress stimuli involves trimerization and acquisition of a site-specific DNA-binding activity, which is negatively regulated by interaction with certain heat-shock proteins. Shamovsky et al. (2006) showed that HSF1 activation by heat shock is an active process that is mediated by a ribonucleoprotein complex containing translation elongation factor eEF1A (130590) and the noncoding RNA HSR1. Both HSR1 isolated from heat-shocked BHK or HeLa cells, and in vitro synthesized HSR1, activated HSF1 when added together with purified eEF1A, demonstrating that homologs of HRS1 are functionally interchangeable. Antisense oligonucleotides or short interfering RNA against HSR1 impaired the heat-shock response in vivo, rendering cells thermosensitive. Shamovsky et al. (2006) suggested that the central role of HSR1 during heat shock implies that targeting this RNA could serve as a therapeutic model for cancer, inflammation, and other conditions associated with HSF1 deregulation.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| HEAT-SHOCK RNA 1 | c1857801 | 4,495 | omim | https://www.omim.org/entry/610157 | 2019-09-22T16:05:00 | {"omim": ["610157"], "synonyms": ["Alternative titles", "HSR1"]} |
CLN4 disease is a condition that primarily affects the nervous system, causing problems with movement and intellectual function that worsen over time. The signs and symptoms of CLN4 disease typically appear around age 30, but they can develop anytime between adolescence and late adulthood.
People with CLN4 disease often develop seizures and uncontrollable muscle jerks (myoclonic epilepsy), a decline in intellectual function (dementia), problems with coordination and balance (ataxia), tremors or other involuntary movements (motor tics), and speech difficulties (dysarthria). The signs and symptoms of CLN4 disease worsen over time, and affected individuals usually survive about 15 years after the disorder begins.
CLN4 disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs), which may also be collectively referred to as Batten disease. (The adult forms of NCLs, which includes CLN4 disease, are sometimes known as Kufs disease.) All the NCLs affect the nervous system and typically cause worsening problems with vision, movement, and thinking ability. The different NCLs are distinguished by their genetic cause. Each disease type is given the designation "CLN," meaning ceroid lipofuscinosis, neuronal, and then a number to indicate its subtype.
## Frequency
CLN4 disease is a rare disorder, but its prevalence is unknown. Collectively, all forms of NCL affect an estimated 1 in 100,000 individuals worldwide.
## Causes
Mutations in the DNAJC5 gene cause CLN4 disease. The DNAJC5 gene provides instructions for making a protein called cysteine string protein alpha (CSPα). This protein is found in the brain, where it plays a role in the transmission of nerve impulses, helping nerve cells communicate with each other. Specifically, CSPα is involved in recycling certain proteins that are involved in nerve impulse transmission by refolding misshapen proteins so that they can be used in additional transmissions.
DNAJC5 gene mutations lead to the production of an altered CSPα protein. The altered protein cannot perform its function, which reduces protein recycling, causing a shortage (deficiency) of functional proteins needed for impulse transmission. Without normal communication between nerve cells, neurological functions are impaired, contributing to the features of CLN4 disease.
CLN4 disease, like other NCLs, is characterized by the accumulation of proteins and other substances in lysosomes, which are compartments in the cell that digest and recycle materials. These accumulations occur in cells throughout the body; however, nerve cells seem to be particularly vulnerable to their effects. The accumulations can cause cell damage leading to cell death. The progressive death of nerve cells in the brain and other tissues contributes to the decline of neurological function in CLN4 disease. However, it is unclear how mutations in the DNAJC5 gene are involved in the buildup of substances in lysosomes.
### Learn more about the gene associated with CLN4 disease
* DNAJC5
## Inheritance Pattern
This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
Some cases of this condition result from new (de novo) mutations in the gene that occur during the formation of reproductive cells (eggs or sperm) in an affected individual’s parent or in early embryonic development. These cases occur in people with no history of the disorder in their family.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| CLN4 disease | c1834207 | 4,496 | medlineplus | https://medlineplus.gov/genetics/condition/cln4-disease/ | 2021-01-27T08:24:55 | {"gard": ["10973"], "mesh": ["D009472"], "omim": ["162350"], "synonyms": []} |
A number sign (#) is used with this entry because CK syndrome is caused by hemizygous mutation in the NSDHL gene (300275) on chromosome Xq28.
Description
CK syndrome (CKS) is an X-linked recessive disorder characterized by mild to severe cognitive impairment, seizures, microcephaly, cerebral cortical malformations, dysmorphic facial features, and thin body habitus. It is named after the first identified patient (summary by McLarren et al., 2010).
CHILD syndrome (308050) is an allelic disorder with a different phenotype.
Clinical Features
Du Souich et al. (2009) reported a 5-generation family of Russian-Doukhobor descent with an X-linked recessive mental retardation syndrome. Affected boys had onset of seizures in the neonatal period and delayed psychomotor development associated with behavioral abnormalities, including hyperactivity, aggression, and irritability. Mental retardation ranged from mild to severe. Brain imaging of 2 affected individuals showed polymicrogyria and/or pachygyria. Other features included hypotonia, hyperextensible joints, and a thin body habitus with long limbs and digits. Dysmorphic features included microcephaly, long, narrow face, almond-shaped eyes, epicanthal folds, upslanting palpebral fissures, high nasal bridge, high-arched palate, crowded teeth, posteriorly rotated ears, micrognathia/retrognathia, and malar hypoplasia. Carrier females were unaffected. A second affected 3-generation family with similar features was reported by Tarpey et al. (2009) and McLarren et al. (2010). Laboratory studies showed that cholesterol levels in serum and cerebrospinal fluid were normal in affected individuals and carrier females.
Inheritance
McLarren et al. (2010) showed that inheritance in the family with CK syndrome reported by du Souich et al. (2009) and the family reported by Tarpey et al. (2009) was consistent with an X-linked recessive pattern. Obligate female carriers were unaffected.
Molecular Genetics
In affected members of a 3-generation family with X-linked mental retardation, Tarpey et al. (2009) identified a 1-bp duplication in the NSDHL gene (300275.0007). In affected members of the original family with CK syndrome reported by du Souich et al. (2009), McLarren et al. (2010) identified a hemizygous truncating mutation in the NSDHL gene (300275.0008). In vitro functional expression studies showed that both mutations acted as temperature-sensitive hypomorphic alleles, resulting in a less severe phenotype than that observed with mutations associated with CHILD syndrome. Cells and cerebrospinal fluid from an affected individual showed increased methylsterol levels. McLarren et al. (2010) suggested that the phenotype resulted mainly from the accumulation of toxic methylsterols, not necessarily from cholesterol deficiency.
INHERITANCE \- X-linked recessive GROWTH Weight \- Thin body habitus \- Asthenic build HEAD & NECK Head \- Microcephaly Face \- Long, narrow face \- Micrognathia \- Retrognathia \- Malar hypoplasia Ears \- Posteriorly rotated ears Eyes \- Upslanting palpebral fissures \- Almond-shaped eyes \- Epicanthal folds \- Strabismus Nose \- High nasal bridge Mouth \- High-arched palate Teeth \- Crowded teeth SKELETAL \- Hyperextensible joints Spine \- Scoliosis \- Kyphosis \- Lordosis Limbs \- Long limbs Hands \- Long digits Feet \- Long digits MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Mental retardation \- Seizures, infantile onset \- Speech delay \- Sleeping difficulties \- Cortical malformation \- Pachygyria \- Polymicrogyria Behavioral Psychiatric Manifestations \- Hyperactivity \- Aggression \- Irritability LABORATORY ABNORMALITIES \- Normal serum cholesterol MISCELLANEOUS \- Onset of seizures in infancy \- Allelic disorder to CHILD syndrome ( 308050 ) MOLECULAR BASIS \- Caused by mutation in the NAD(P)H steroid dehydrogenase-like protein (NSDHL, 300275.0007 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| CK SYNDROME | c3151781 | 4,497 | omim | https://www.omim.org/entry/300831 | 2019-09-22T16:19:32 | {"omim": ["300831"], "orphanet": ["251383"], "synonyms": ["Alternative titles", "X-linked intellectual disability-microcephaly-cortical malformation-thin habitus syndrome", "MENTAL RETARDATION, X-LINKED, WITH THIN BODY HABITUS AND CORTICAL MALFORMATION"], "genereviews": ["NBK51754"]} |
X-linked intellectual disability-retinitis pigmentosa syndrome is characterized by moderate intellectual deficit and severe, early-onset retinitis pigmentosa. It has been described in five males spanning three generations of one family. Some patients also had microcephaly. It is transmitted as an X-linked 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 inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| X-linked intellectual disability-retinitis pigmentosa syndrome | c0795873 | 4,498 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=85332 | 2021-01-23T17:56:10 | {"gard": ["8360"], "mesh": ["C537046"], "omim": ["300578"], "umls": ["C0795873"], "icd-10": ["H35.5"], "synonyms": ["Aldred syndrome", "Retinitis pigmentosa and intellectual disability due to Xp11.3 microdeletion", "Retinitis pigmentosa and intellectual disability due to del(X)(p11.3)", "Retinitis pigmentosa and intellectual disability due to monosomy Xp11.3"]} |
Epithelial basement membrane corneal dystrophy (EBMD), also called map-dot-fingerprint dystrophy, is an eye condition that affects the cornea. The epithelium is the cornea’s outermost layer, and the basement membrane is the layer that the epithelium attaches to. EBMD occurs when the epithelial basement membrane develops abnormally, resulting in folds in the tissue. It is sometimes called map-dot-fingerprint dystrophy because when viewed with a special eye test called a slit-lamp exam, the folds form patches that resemble continents on a map, or sometimes, small fingerprints. There may also be clusters of dots around the patches.
Most people with EBMD do not have symptoms and may not be aware they have EBMD. Those who do have symptoms may have mild to severe blurry vision and pain, sensitivity to light, excessive tearing, and a feeling that something is in the eye. The main cause of symptoms is recurring development of erosions in the cornea. Pain from an erosion may occur at any time but is most often experienced upon waking in the morning or during sleep. The pain can range from mild and short-lived to severe, lasting hours or longer. Severe pain may develop if nerve endings in the tissue become exposed. In most cases, symptoms will come and go over several years before going away, without causing permanent vision loss. EBMD usually affects both eyes.
EBMD usually is not inherited, occurring randomly in people with no family history of EBMD. However, familial cases with autosomal dominant inheritance have been reported. In some people with EBMD, a mutation in the TGFBI gene has been identified as the cause. However in most cases, the cause remains unknown.
Treatment options depend on the symptoms and severity in each person, and results differ from person to person. People with no symptoms or mild symptoms may not need treatment. Treatment options may include sodium chloride eye drops or ointment, wearing an eye patch, and using bandage contact lenses to protect the cornea and facilitate healing. If pain or vision loss cannot be improved with these options, outpatient eye surgery may be recommended. Unfortunately, even after treatment, recurrences are common. Using a lubricating ointment at bedtime may help to prevent repeated corneal erosions.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
| Epithelial basement membrane corneal dystrophy | c0521723 | 4,499 | gard | https://rarediseases.info.nih.gov/diseases/9732/epithelial-basement-membrane-corneal-dystrophy | 2021-01-18T18:00:40 | {"mesh": ["C535477"], "omim": ["121820"], "synonyms": ["Corneal dystrophy, anterior basement membrane", "Microcystic dystrophy of the cornea", "Cogan corneal dystrophy", "Map-dot-fingerprint dystrophy of cornea"]} |
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